Medicina Latest open access articles published in Medicina at https://www.mdpi.com/journal/medicina https://www.mdpi.com/journal/medicina MDPI en Creative Commons Attribution (CC-BY) MDPI support@mdpi.com Medicina, Vol. 62, Pages 1809: Predictors of Hospital Admission and Cardiac Diagnosis in Children Presenting with Chest Pain: The Role of Recurrent Presentation and Inflammatory Markers https://www.mdpi.com/1648-9144/62/9/1809 Background and Objectives: Pediatric chest pain is usually benign, but identifying children who require admission or have a cardiac diagnosis remains challenging. We aimed to identify factors associated with these outcomes, with a focus on recurrent presentation and the combined value of C-reactive protein (CRP) and predefined red-flag findings. Materials and Methods: This retrospective cohort included children aged 0–18 years presenting with chest pain to a tertiary pediatric emergency department between January 2021 and January 2026; visits with insufficient documentation were excluded. Red-flag findings were predefined as effort-related chest pain, syncope, palpitations, dyspnea, fever, or a family history of sudden cardiac death. Independent predictors were assessed using multivariable Firth logistic regression, and cluster-robust standard errors were used in a sensitivity analysis to account for recurrent visits. Results: Of 1703 visits (1435 patients), 452 (26.5%) were recurrent presentations. Admission occurred in 64 visits (3.8%), and 91 (5.3%) had a cardiac diagnosis. Red-flag findings (OR, 5.15), abnormal ECG (OR, 4.00), CRP > 5 mg/L (OR, 3.71), male sex (OR, 2.13), and recurrent presentation (OR, 2.51) were independently associated with admission (all p ≤ 0.009). Recurrent presentation was not associated with a cardiac or psychogenic diagnosis. Admission and cardiac diagnosis rates increased from 1.4%/2.2% in children with neither elevated CRP nor red-flag findings to 22.2%/24.8% in those with both. Routine ECG, troponin, and chest radiography had low diagnostic yields (2.1–6.0%), whereas echocardiography performed selectively yielded abnormal findings in 79.7%. Conclusions: Red-flag findings, abnormal ECG, elevated CRP, and recurrence were associated with admission, whereas recurrence was not associated with diagnosis. Combining CRP with red flags may improve risk stratification, though prospective validation is needed. 2026-09-19 Medicina, Vol. 62, Pages 1809: Predictors of Hospital Admission and Cardiac Diagnosis in Children Presenting with Chest Pain: The Role of Recurrent Presentation and Inflammatory Markers

Medicina doi: 10.3390/medicina62091809

Authors: Şule Demir Murat Ayar Ayşe Nilsu Doğan Aykut Çağlar

Background and Objectives: Pediatric chest pain is usually benign, but identifying children who require admission or have a cardiac diagnosis remains challenging. We aimed to identify factors associated with these outcomes, with a focus on recurrent presentation and the combined value of C-reactive protein (CRP) and predefined red-flag findings. Materials and Methods: This retrospective cohort included children aged 0–18 years presenting with chest pain to a tertiary pediatric emergency department between January 2021 and January 2026; visits with insufficient documentation were excluded. Red-flag findings were predefined as effort-related chest pain, syncope, palpitations, dyspnea, fever, or a family history of sudden cardiac death. Independent predictors were assessed using multivariable Firth logistic regression, and cluster-robust standard errors were used in a sensitivity analysis to account for recurrent visits. Results: Of 1703 visits (1435 patients), 452 (26.5%) were recurrent presentations. Admission occurred in 64 visits (3.8%), and 91 (5.3%) had a cardiac diagnosis. Red-flag findings (OR, 5.15), abnormal ECG (OR, 4.00), CRP > 5 mg/L (OR, 3.71), male sex (OR, 2.13), and recurrent presentation (OR, 2.51) were independently associated with admission (all p ≤ 0.009). Recurrent presentation was not associated with a cardiac or psychogenic diagnosis. Admission and cardiac diagnosis rates increased from 1.4%/2.2% in children with neither elevated CRP nor red-flag findings to 22.2%/24.8% in those with both. Routine ECG, troponin, and chest radiography had low diagnostic yields (2.1–6.0%), whereas echocardiography performed selectively yielded abnormal findings in 79.7%. Conclusions: Red-flag findings, abnormal ECG, elevated CRP, and recurrence were associated with admission, whereas recurrence was not associated with diagnosis. Combining CRP with red flags may improve risk stratification, though prospective validation is needed.

]]> Predictors of Hospital Admission and Cardiac Diagnosis in Children Presenting with Chest Pain: The Role of Recurrent Presentation and Inflammatory Markers Şule Demir Murat Ayar Ayşe Nilsu Doğan Aykut Çağlar doi: 10.3390/medicina62091809 Medicina 2026-09-19 Medicina 2026-09-19 62 9 Article 1809 10.3390/medicina62091809 https://www.mdpi.com/1648-9144/62/9/1809 Medicina, Vol. 62, Pages 1808: An Eleven-Point Ultrasound-Guided Fascia Hydrorelease Protocol for Non-Odontogenic Toothache and Orofacial Pain: A Clinical Protocol https://www.mdpi.com/1648-9144/62/9/1808 Background and Objectives: Non-odontogenic toothache often persists without an identifiable dental cause and may lead to unnecessary pulpectomy or tooth extraction. It may also result in long-term combined use of psychotropic medications, forming a recurrent clinical pattern. Ultrasound-guided fascia hydrorelease (US-FHR) targeting fascia-derived pathology has been applied to non-odontogenic toothache; however, treatment regions have not been systematically described. This article presents a proposed eleven-point US-FHR protocol for non-odontogenic toothache and related orofacial pain. Materials and Methods: This is an experience-based clinical protocol; it is not an efficacy study and does not include a new prospective study on human participants. The protocol was organized on the basis of long-term clinical experience at Kimura Pain Clinic and a focused literature search. Results: The protocol comprises 11 POINTs distributed across six anatomical regions: (1) three POINTs in the masticatory muscle region, (2) three POINTs in the medial pterygoid and capsular region, (3) one POINT in the parotid region, (4) two POINTs in the cervical region, (5) one POINT in the facial-artery region, and (6) one POINT in the upper posterior cervical region. For each POINT, the anatomical rationale, referred-pain pattern, procedural concept, and safety considerations are described. Conclusions: The proposed eleven-point protocol represents an expanded and structured development of the earlier four-region approach. Prospective, ideally controlled, studies are needed to evaluate its clinical effectiveness. 2026-09-19 Medicina, Vol. 62, Pages 1808: An Eleven-Point Ultrasound-Guided Fascia Hydrorelease Protocol for Non-Odontogenic Toothache and Orofacial Pain: A Clinical Protocol

Medicina doi: 10.3390/medicina62091808

Authors: Hiroaki Kimura Tadashi Kobayashi Ryoya Asaka Hideaki Obata

Background and Objectives: Non-odontogenic toothache often persists without an identifiable dental cause and may lead to unnecessary pulpectomy or tooth extraction. It may also result in long-term combined use of psychotropic medications, forming a recurrent clinical pattern. Ultrasound-guided fascia hydrorelease (US-FHR) targeting fascia-derived pathology has been applied to non-odontogenic toothache; however, treatment regions have not been systematically described. This article presents a proposed eleven-point US-FHR protocol for non-odontogenic toothache and related orofacial pain. Materials and Methods: This is an experience-based clinical protocol; it is not an efficacy study and does not include a new prospective study on human participants. The protocol was organized on the basis of long-term clinical experience at Kimura Pain Clinic and a focused literature search. Results: The protocol comprises 11 POINTs distributed across six anatomical regions: (1) three POINTs in the masticatory muscle region, (2) three POINTs in the medial pterygoid and capsular region, (3) one POINT in the parotid region, (4) two POINTs in the cervical region, (5) one POINT in the facial-artery region, and (6) one POINT in the upper posterior cervical region. For each POINT, the anatomical rationale, referred-pain pattern, procedural concept, and safety considerations are described. Conclusions: The proposed eleven-point protocol represents an expanded and structured development of the earlier four-region approach. Prospective, ideally controlled, studies are needed to evaluate its clinical effectiveness.

]]> An Eleven-Point Ultrasound-Guided Fascia Hydrorelease Protocol for Non-Odontogenic Toothache and Orofacial Pain: A Clinical Protocol Hiroaki Kimura Tadashi Kobayashi Ryoya Asaka Hideaki Obata doi: 10.3390/medicina62091808 Medicina 2026-09-19 Medicina 2026-09-19 62 9 Article 1808 10.3390/medicina62091808 https://www.mdpi.com/1648-9144/62/9/1808 Medicina, Vol. 62, Pages 1807: DAMPs and PAMPs in the Perioperative Period: Danger Signaling, Immune Dysfunction, and Oncologic Implications https://www.mdpi.com/1648-9144/62/9/1807 Background and Objectives: The perioperative period is characterized by marked biological stress responses that extend beyond direct tissue injury. Innate immune activation during surgery is largely driven by molecular danger signals. Surgical trauma, ischemia–reperfusion injury, blood transfusions, mechanical ventilation, and perioperative infections are critical events that result in the release of danger signals: damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). This narrative review examines perioperative DAMP and PAMP sources, their molecular recognition pathways, and their clinical and oncological significance. Materials and Methods: A literature search was conducted across PubMed/MEDLINE, Scopus, and Web of Science databases for English-language articles published up to July 2026. Search terms included DAMPs, PAMPs, perioperative, surgical stress, cancer surgery, innate immunity, PRRs, TLRs, inflammasome, HMGB1, mtDNA, perioperative immunosuppression, and anesthesia. Results: Danger signals interact with pattern-recognition receptors, including Toll-like receptors and inflammasome pathways, driving sterile inflammation, immune dysregulation, and postoperative organ injury. Rather than initiating these cascades, anesthetics and opioids act as modulators. In cancer surgery, heightened danger signaling and temporary immunosuppression may compromise host defenses during a vulnerable window. Conclusions: Circulating DAMPs and potentially selected PAMP-related markers warrant further investigation as biomarkers for perioperative risk stratification. Overcoming translational barriers will require standardized assays, validation of biomarker signatures, and integration of artificial intelligence-driven molecular profiling to advance personalized onco-anesthesia strategies. 2026-09-19 Medicina, Vol. 62, Pages 1807: DAMPs and PAMPs in the Perioperative Period: Danger Signaling, Immune Dysfunction, and Oncologic Implications

Medicina doi: 10.3390/medicina62091807

Authors: Hector Katifelis Theofania Lappa Sofia Poulopoulou Maria Gazouli

Background and Objectives: The perioperative period is characterized by marked biological stress responses that extend beyond direct tissue injury. Innate immune activation during surgery is largely driven by molecular danger signals. Surgical trauma, ischemia–reperfusion injury, blood transfusions, mechanical ventilation, and perioperative infections are critical events that result in the release of danger signals: damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). This narrative review examines perioperative DAMP and PAMP sources, their molecular recognition pathways, and their clinical and oncological significance. Materials and Methods: A literature search was conducted across PubMed/MEDLINE, Scopus, and Web of Science databases for English-language articles published up to July 2026. Search terms included DAMPs, PAMPs, perioperative, surgical stress, cancer surgery, innate immunity, PRRs, TLRs, inflammasome, HMGB1, mtDNA, perioperative immunosuppression, and anesthesia. Results: Danger signals interact with pattern-recognition receptors, including Toll-like receptors and inflammasome pathways, driving sterile inflammation, immune dysregulation, and postoperative organ injury. Rather than initiating these cascades, anesthetics and opioids act as modulators. In cancer surgery, heightened danger signaling and temporary immunosuppression may compromise host defenses during a vulnerable window. Conclusions: Circulating DAMPs and potentially selected PAMP-related markers warrant further investigation as biomarkers for perioperative risk stratification. Overcoming translational barriers will require standardized assays, validation of biomarker signatures, and integration of artificial intelligence-driven molecular profiling to advance personalized onco-anesthesia strategies.

]]> DAMPs and PAMPs in the Perioperative Period: Danger Signaling, Immune Dysfunction, and Oncologic Implications Hector Katifelis Theofania Lappa Sofia Poulopoulou Maria Gazouli doi: 10.3390/medicina62091807 Medicina 2026-09-19 Medicina 2026-09-19 62 9 Review 1807 10.3390/medicina62091807 https://www.mdpi.com/1648-9144/62/9/1807 Medicina, Vol. 62, Pages 1806: The Cerebroplacental–Renal Ratio as a Novel Doppler-Based Marker of Adverse Perinatal Outcome in Pregnancy-Induced Hypertension https://www.mdpi.com/1648-9144/62/9/1806 Background/Objectives: To evaluate the association between the newly defined cerebroplacental–renal ratio (CPRR) and adverse perinatal outcome (APO) in pregnancy-induced hypertension (PIH), and to compare its discriminative performance with the cerebroplacental ratio (CPR) and cerebroplacental–uterine ratio (CPUR). Methods: This prospective, single-center cohort study included 105 women with PIH (preeclampsia, n = 63; gestational hypertension, n = 42). Doppler assessment was performed at ≥34 + 0 weeks and within 7 days before delivery. CPR was calculated as middle cerebral artery pulsatility index (PI)/umbilical artery PI, CPUR as CPR/mean uterine artery PI, and CPRR as CPR/right renal artery PI. APO was defined by the presence of any of the following: non-reassuring fetal status, a 5 min Apgar score <7, neonatal intensive care unit admission, or neonatal death. Receiver operating characteristic analysis and multivariable logistic regression adjusted for gestational age at ultrasound assessment and diagnosis group were performed. Results: APO occurred in 37 pregnancies (35.2%). CPUR and CPRR were significantly lower in the APO group, whereas CPR did not differ significantly. CPRR showed a higher apparent AUC for APO than CPR and CPUR (AUC 0.786, 95% CI 0.698–0.875), with significantly higher AUCs on pairwise DeLong comparisons. After adjustment, CPRR was the only Doppler index independently associated with APO (adjusted OR 1.423 per 0.1-unit decrease; 95% CI 1.162–1.743; p = 0.001). Conclusions: CPRR was independently associated with APO in PIH and showed higher discriminative performance than CPR and CPUR; however, these findings require validation in independent, multicenter studies before clinical application. 2026-09-19 Medicina, Vol. 62, Pages 1806: The Cerebroplacental–Renal Ratio as a Novel Doppler-Based Marker of Adverse Perinatal Outcome in Pregnancy-Induced Hypertension

Medicina doi: 10.3390/medicina62091806

Authors: Yücel Kaya Kübra Kurt Bilirer Aybekcan Batman Burcu Çiçek İlteriş Yaman Ali Selçuk Yeniocak Can Tercan Karolin Ohanoglu Cetinel Damla Yasemin Yenliç Kaya Gülseren Polat

Background/Objectives: To evaluate the association between the newly defined cerebroplacental–renal ratio (CPRR) and adverse perinatal outcome (APO) in pregnancy-induced hypertension (PIH), and to compare its discriminative performance with the cerebroplacental ratio (CPR) and cerebroplacental–uterine ratio (CPUR). Methods: This prospective, single-center cohort study included 105 women with PIH (preeclampsia, n = 63; gestational hypertension, n = 42). Doppler assessment was performed at ≥34 + 0 weeks and within 7 days before delivery. CPR was calculated as middle cerebral artery pulsatility index (PI)/umbilical artery PI, CPUR as CPR/mean uterine artery PI, and CPRR as CPR/right renal artery PI. APO was defined by the presence of any of the following: non-reassuring fetal status, a 5 min Apgar score <7, neonatal intensive care unit admission, or neonatal death. Receiver operating characteristic analysis and multivariable logistic regression adjusted for gestational age at ultrasound assessment and diagnosis group were performed. Results: APO occurred in 37 pregnancies (35.2%). CPUR and CPRR were significantly lower in the APO group, whereas CPR did not differ significantly. CPRR showed a higher apparent AUC for APO than CPR and CPUR (AUC 0.786, 95% CI 0.698–0.875), with significantly higher AUCs on pairwise DeLong comparisons. After adjustment, CPRR was the only Doppler index independently associated with APO (adjusted OR 1.423 per 0.1-unit decrease; 95% CI 1.162–1.743; p = 0.001). Conclusions: CPRR was independently associated with APO in PIH and showed higher discriminative performance than CPR and CPUR; however, these findings require validation in independent, multicenter studies before clinical application.

]]> The Cerebroplacental–Renal Ratio as a Novel Doppler-Based Marker of Adverse Perinatal Outcome in Pregnancy-Induced Hypertension Yücel Kaya Kübra Kurt Bilirer Aybekcan Batman Burcu Çiçek İlteriş Yaman Ali Selçuk Yeniocak Can Tercan Karolin Ohanoglu Cetinel Damla Yasemin Yenliç Kaya Gülseren Polat doi: 10.3390/medicina62091806 Medicina 2026-09-19 Medicina 2026-09-19 62 9 Article 1806 10.3390/medicina62091806 https://www.mdpi.com/1648-9144/62/9/1806 Medicina, Vol. 62, Pages 1805: Effects of Exercise-Based Interventions on Depressive Symptoms in Adults with Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials https://www.mdpi.com/1648-9144/62/9/1805 Background and Objectives: Exercise is increasingly used in supportive care for lung cancer, but its effects on depressive symptoms remain uncertain. This systematic review and meta-analysis synthesized randomized evidence. Materials and Methods: Four electronic databases were searched for reports published from January 2000 to July 2026. Eligible studies enrolled adults with lung cancer and compared a structured exercise-based intervention with usual care or an eligible active rehabilitation comparator. One depression result per independent trial was selected using documented rules for assessment time, outcome format, and multiple intervention arms. A random-effects model used REML with Hartung–Knapp inference. Results: Seventeen studies met the eligibility criteria; 15 independent trials (1041 participants) contributed to the primary synthesis. The pooled effect favored exercise (Hedges’ g = −0.75, 95% CI −1.18 to −0.32; p = 0.002), but heterogeneity was considerable (τ2 = 0.4582; τ = 0.6769; I2 = 87.1%; H2 = 7.76; Q(14) = 74.11, p < 0.001) and the 95% prediction interval crossed the null (−2.27 to 0.76). The direction remained favorable in all sensitivity analyses, although exclusion of two influential studies attenuated the pooled effect to −0.49 and reduced I2 to approximately 0%. Exploratory subgroup and study-level moderator analyses did not identify a stable explanation for heterogeneity. Certainty was very low after downgrading for risk of bias, inconsistency, and indirectness. Conclusions: Exercise-based interventions may reduce depressive symptom scores in some adults with lung cancer, but confidence in the magnitude and transferability of the average effect is limited. The evidence does not establish efficacy for major depressive disorder or identify an optimal modality, dose, or delivery format. 2026-09-19 Medicina, Vol. 62, Pages 1805: Effects of Exercise-Based Interventions on Depressive Symptoms in Adults with Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Medicina doi: 10.3390/medicina62091805

Authors: Mesut Süleymanoğulları Zarife Pancar

Background and Objectives: Exercise is increasingly used in supportive care for lung cancer, but its effects on depressive symptoms remain uncertain. This systematic review and meta-analysis synthesized randomized evidence. Materials and Methods: Four electronic databases were searched for reports published from January 2000 to July 2026. Eligible studies enrolled adults with lung cancer and compared a structured exercise-based intervention with usual care or an eligible active rehabilitation comparator. One depression result per independent trial was selected using documented rules for assessment time, outcome format, and multiple intervention arms. A random-effects model used REML with Hartung–Knapp inference. Results: Seventeen studies met the eligibility criteria; 15 independent trials (1041 participants) contributed to the primary synthesis. The pooled effect favored exercise (Hedges’ g = −0.75, 95% CI −1.18 to −0.32; p = 0.002), but heterogeneity was considerable (τ2 = 0.4582; τ = 0.6769; I2 = 87.1%; H2 = 7.76; Q(14) = 74.11, p < 0.001) and the 95% prediction interval crossed the null (−2.27 to 0.76). The direction remained favorable in all sensitivity analyses, although exclusion of two influential studies attenuated the pooled effect to −0.49 and reduced I2 to approximately 0%. Exploratory subgroup and study-level moderator analyses did not identify a stable explanation for heterogeneity. Certainty was very low after downgrading for risk of bias, inconsistency, and indirectness. Conclusions: Exercise-based interventions may reduce depressive symptom scores in some adults with lung cancer, but confidence in the magnitude and transferability of the average effect is limited. The evidence does not establish efficacy for major depressive disorder or identify an optimal modality, dose, or delivery format.

]]> Effects of Exercise-Based Interventions on Depressive Symptoms in Adults with Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Mesut Süleymanoğulları Zarife Pancar doi: 10.3390/medicina62091805 Medicina 2026-09-19 Medicina 2026-09-19 62 9 Systematic Review 1805 10.3390/medicina62091805 https://www.mdpi.com/1648-9144/62/9/1805 Medicina, Vol. 62, Pages 1804: Integrated First-Trimester Assessment of Placental Biomarkers, Metabolic Indices, and IGF-1/IGFBP-5 in Relation to Subsequent Gestational Diabetes Mellitus: A Prospective Cohort Study https://www.mdpi.com/1648-9144/62/9/1804 Background and Objectives: Gestational diabetes mellitus (GDM) is usually diagnosed at 24–28 gestational weeks, although metabolic and placental alterations may emerge considerably earlier. This study evaluated whether routinely available first-trimester placental biomarkers, metabolic indices, and insulin-like growth factor (IGF)-axis components are associated with GDM diagnosed later in pregnancy and whether these markers provide complementary information across distinct biological domains. Materials and Methods: Of 200 women completing the 75-g OGTT (34 with GDM and 166 normoglycemic), deferred IGF-1 and IGFBP-5 assays were performed in a complete-biomarker analytic cohort of 90 participants with complete clinical follow-up and available stored specimens (30 GDM and 60 controls). At 11+0–13+6 weeks, pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (free β-hCG), IGF-1, IGF-binding protein-5 (IGFBP-5), fasting glucose, insulin, and lipid parameters were assessed. HOMA-IR, the triglyceride–glucose (TyG) index, TG/HDL-C, and LDL/HDL-C were calculated. GDM was diagnosed using a 75-g oral glucose tolerance test at 24–28 weeks. Group comparisons, correlation analyses, and logistic regression were performed. Results: Compared with controls, women who later developed GDM had higher first-trimester insulin, HOMA-IR, triglycerides, VLDL-C, TyG, and TG/HDL-C and lower HDL-C, free β-hCG, PAPP-A, PAPP-A MoM, and IGF-1 (all p < 0.05). Birth weight was also higher in the GDM group. Correlation patterns differed between groups, suggesting distinct relationships among placental, metabolic, and IGF-related markers. In the four-variable adjusted model, higher HOMA-IR (OR 2.123, 95% CI 1.089–4.137; p = 0.027) and TyG (OR 3.747, 95% CI 1.010–13.894; p = 0.048) were associated with increased GDM odds, whereas free β-hCG MoM (OR 0.325, 95% CI 0.115–0.920; p = 0.034) and IGF-1 (OR 0.856, 95% CI 0.748–0.980; p = 0.024) showed inverse associations. Conclusions: Pregnancies that subsequently developed GDM showed detectable first-trimester differences across metabolic, placental, and IGF-related pathways. The combined pattern supports further evaluation of multidomain early-risk assessment, although clinical predictive utility requires validation in larger independent cohorts. 2026-09-19 Medicina, Vol. 62, Pages 1804: Integrated First-Trimester Assessment of Placental Biomarkers, Metabolic Indices, and IGF-1/IGFBP-5 in Relation to Subsequent Gestational Diabetes Mellitus: A Prospective Cohort Study

Medicina doi: 10.3390/medicina62091804

Authors: Soner Gök Berfin Can Gök Esin Avcı Çiçek Hande Senol

Background and Objectives: Gestational diabetes mellitus (GDM) is usually diagnosed at 24–28 gestational weeks, although metabolic and placental alterations may emerge considerably earlier. This study evaluated whether routinely available first-trimester placental biomarkers, metabolic indices, and insulin-like growth factor (IGF)-axis components are associated with GDM diagnosed later in pregnancy and whether these markers provide complementary information across distinct biological domains. Materials and Methods: Of 200 women completing the 75-g OGTT (34 with GDM and 166 normoglycemic), deferred IGF-1 and IGFBP-5 assays were performed in a complete-biomarker analytic cohort of 90 participants with complete clinical follow-up and available stored specimens (30 GDM and 60 controls). At 11+0–13+6 weeks, pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (free β-hCG), IGF-1, IGF-binding protein-5 (IGFBP-5), fasting glucose, insulin, and lipid parameters were assessed. HOMA-IR, the triglyceride–glucose (TyG) index, TG/HDL-C, and LDL/HDL-C were calculated. GDM was diagnosed using a 75-g oral glucose tolerance test at 24–28 weeks. Group comparisons, correlation analyses, and logistic regression were performed. Results: Compared with controls, women who later developed GDM had higher first-trimester insulin, HOMA-IR, triglycerides, VLDL-C, TyG, and TG/HDL-C and lower HDL-C, free β-hCG, PAPP-A, PAPP-A MoM, and IGF-1 (all p < 0.05). Birth weight was also higher in the GDM group. Correlation patterns differed between groups, suggesting distinct relationships among placental, metabolic, and IGF-related markers. In the four-variable adjusted model, higher HOMA-IR (OR 2.123, 95% CI 1.089–4.137; p = 0.027) and TyG (OR 3.747, 95% CI 1.010–13.894; p = 0.048) were associated with increased GDM odds, whereas free β-hCG MoM (OR 0.325, 95% CI 0.115–0.920; p = 0.034) and IGF-1 (OR 0.856, 95% CI 0.748–0.980; p = 0.024) showed inverse associations. Conclusions: Pregnancies that subsequently developed GDM showed detectable first-trimester differences across metabolic, placental, and IGF-related pathways. The combined pattern supports further evaluation of multidomain early-risk assessment, although clinical predictive utility requires validation in larger independent cohorts.

]]> Integrated First-Trimester Assessment of Placental Biomarkers, Metabolic Indices, and IGF-1/IGFBP-5 in Relation to Subsequent Gestational Diabetes Mellitus: A Prospective Cohort Study Soner Gök Berfin Can Gök Esin Avcı Çiçek Hande Senol doi: 10.3390/medicina62091804 Medicina 2026-09-19 Medicina 2026-09-19 62 9 Article 1804 10.3390/medicina62091804 https://www.mdpi.com/1648-9144/62/9/1804 Medicina, Vol. 62, Pages 1803: Prognostic Value of the Richmond Agitation-Sedation Scale for Mortality and Admission in Older Emergency Department Patients https://www.mdpi.com/1648-9144/62/9/1803 Background: Altered arousal may provide rapid prognostic information in older emergency department (ED) patients. Originally developed to monitor agitation and sedation in critically ill patients, the Richmond Agitation-Sedation Scale (RASS) provides a rapid measure of arousal. However, its prognostic value relative to the Glasgow Coma Scale (GCS) in older ED patients remains uncertain. We evaluated whether RASS was associated with clinical outcomes and provided information beyond GCS. Methods: This study was a single-center retrospective cohort study of nontraumatic ED patients aged ≥ 65 years from January 2024 through October 2025. Only the first ED visit per patient was included. The primary outcome was in-hospital mortality; secondary outcomes were hospital and intensive care unit (ICU) admission. RASS was modeled categorically to preserve deviations in both directions from 0. Multivariable logistic regression and DeLong AUC comparisons were performed. Results: Among 10,208 patients, 352 (3.4%) died, 2301 (22.5%) were hospitalized, and 856 (8.4%) were admitted to the ICU. Mortality increased from 2.2% at RASS 0 to 59.4% at −5 and 45.5% at +3. Hospital and ICU admission rates also increased in both directions from RASS 0 (all trend p < 0.001). After adjustment for age, sex, vital signs, and GCS, both reduced arousal (RASS ≤ −4: aOR, 4.93; 95% CI, 2.10–11.61) and agitation (RASS ≥ +2: aOR, 5.16; 95% CI, 2.46–10.85) remained associated with mortality. RASS and GCS had similar discrimination for mortality (AUC, 0.683 vs. 0.679; p = 0.72), whereas their combination improved discrimination (AUC, 0.712; both comparisons p < 0.001). Among patients with GCS 15, mortality was 9.9% with abnormal RASS versus 1.9% with RASS 0. Conclusions: RASS demonstrated a bidirectional association with adverse outcomes and provided prognostic information comparable to and complementary to GCS. Its rapid assessment may help identify high-risk older ED patients, including those with GCS 15. 2026-09-19 Medicina, Vol. 62, Pages 1803: Prognostic Value of the Richmond Agitation-Sedation Scale for Mortality and Admission in Older Emergency Department Patients

Medicina doi: 10.3390/medicina62091803

Authors: Secdegül Coşkun Yaş Mehmet Ali Aslaner

Background: Altered arousal may provide rapid prognostic information in older emergency department (ED) patients. Originally developed to monitor agitation and sedation in critically ill patients, the Richmond Agitation-Sedation Scale (RASS) provides a rapid measure of arousal. However, its prognostic value relative to the Glasgow Coma Scale (GCS) in older ED patients remains uncertain. We evaluated whether RASS was associated with clinical outcomes and provided information beyond GCS. Methods: This study was a single-center retrospective cohort study of nontraumatic ED patients aged ≥ 65 years from January 2024 through October 2025. Only the first ED visit per patient was included. The primary outcome was in-hospital mortality; secondary outcomes were hospital and intensive care unit (ICU) admission. RASS was modeled categorically to preserve deviations in both directions from 0. Multivariable logistic regression and DeLong AUC comparisons were performed. Results: Among 10,208 patients, 352 (3.4%) died, 2301 (22.5%) were hospitalized, and 856 (8.4%) were admitted to the ICU. Mortality increased from 2.2% at RASS 0 to 59.4% at −5 and 45.5% at +3. Hospital and ICU admission rates also increased in both directions from RASS 0 (all trend p < 0.001). After adjustment for age, sex, vital signs, and GCS, both reduced arousal (RASS ≤ −4: aOR, 4.93; 95% CI, 2.10–11.61) and agitation (RASS ≥ +2: aOR, 5.16; 95% CI, 2.46–10.85) remained associated with mortality. RASS and GCS had similar discrimination for mortality (AUC, 0.683 vs. 0.679; p = 0.72), whereas their combination improved discrimination (AUC, 0.712; both comparisons p < 0.001). Among patients with GCS 15, mortality was 9.9% with abnormal RASS versus 1.9% with RASS 0. Conclusions: RASS demonstrated a bidirectional association with adverse outcomes and provided prognostic information comparable to and complementary to GCS. Its rapid assessment may help identify high-risk older ED patients, including those with GCS 15.

]]> Prognostic Value of the Richmond Agitation-Sedation Scale for Mortality and Admission in Older Emergency Department Patients Secdegül Coşkun Yaş Mehmet Ali Aslaner doi: 10.3390/medicina62091803 Medicina 2026-09-19 Medicina 2026-09-19 62 9 Article 1803 10.3390/medicina62091803 https://www.mdpi.com/1648-9144/62/9/1803 Medicina, Vol. 62, Pages 1802: Preclinical Evaluation of Labetalol for Cutaneous Melanoma Drug Repurposing: Cytotoxic Activity in A375 Cells and Mitochondria-Associated Apoptotic Signaling https://www.mdpi.com/1648-9144/62/9/1802 Background and Objectives: Drug repurposing provides an opportunity to identify anticancer activities among established pharmacological agents. Labetalol (LB), an α1- and non-selective β-adrenergic receptor antagonist, has been insufficiently investigated in melanoma. This study evaluated the potential anti-melanoma activity of LB in A375 human melanoma cells, compared its effects with those observed in HaCaT immortalized non-tumoral keratinocytes, and investigated the cellular mechanisms associated with LB-induced cytotoxicity. Materials and Methods: A375 and HaCaT cells were exposed to 75–500 μM LB for 24 h. Cell viability and lysosomal dye retention were assessed using MTT and NRU assays. A DMSO-only concentration series (0.075–0.50% v/v) was additionally evaluated by MTT in both cell lines. Mitochondrial membrane potential, mitochondrial staining patterns, nuclear morphology, cytoskeletal organization, caspase-3/7 and caspase-9 activities, and plasma membrane integrity were evaluated using JC-1, MitoTracker Red CMXRos, immunofluorescence, luminescence-based caspase assays, and AO/PI staining. The acute irritation potential of 500 μM LB was assessed using the HET-CAM assay. Results: DMSO alone did not significantly reduce viability over the investigated concentration range in either cell line. LB reduced A375 cell viability in a concentration-dependent manner, with a 24 h IC50 of 422.5 μM and a viability of 33.61% at 500 μM. Under the same experimental conditions, HaCaT viability remained at 89.01% at 500 μM, and an IC50 was not reached within the investigated concentration range. At the highest concentration, neutral red uptake and the JC-1 aggregate/monomer ratio decreased to approximately 33% and 24% of the corresponding control values, respectively. The apoptotic index increased from approximately 3% in control cells to 31%, while caspase-3/7 and caspase-9 activities increased to approximately 482% and 324% of the control. Qualitative imaging demonstrated mitochondrial staining redistribution, cytoskeletal disorganization, apoptosis-associated morphology, and loss of plasma membrane integrity at higher concentrations. In the HET-CAM assay, 500 μM LB produced a mean irritation score of 0.71 ± 0.27, within the non-irritant range. Conclusions: LB displayed concentration-dependent in vitro cytotoxicity in A375 melanoma cells, whereas HaCaT keratinocytes showed limited changes under the investigated conditions. LB treatment was also associated with mitochondria-associated apoptotic signaling in A375 cells. These findings provide preliminary evidence supporting further investigation of LB within a melanoma-directed drug-repurposing strategy. Additional studies are required to establish receptor dependence, achievable local exposure, safety, and translational relevance. 2026-09-19 Medicina, Vol. 62, Pages 1802: Preclinical Evaluation of Labetalol for Cutaneous Melanoma Drug Repurposing: Cytotoxic Activity in A375 Cells and Mitochondria-Associated Apoptotic Signaling

Medicina doi: 10.3390/medicina62091802

Authors: Richard Dahma Elena-Alina Moacă Iasmina-Alexandra Predescu Ana-Cristiane Dragomir Oana-Andrada Iftode Stela Iurciuc Diana Haj Ali Ioana Macaşoi Maria Sala-Cîrtog Iulia-Najette Crintea Alina-Doina Tănase Marilena Dinuţi

Background and Objectives: Drug repurposing provides an opportunity to identify anticancer activities among established pharmacological agents. Labetalol (LB), an α1- and non-selective β-adrenergic receptor antagonist, has been insufficiently investigated in melanoma. This study evaluated the potential anti-melanoma activity of LB in A375 human melanoma cells, compared its effects with those observed in HaCaT immortalized non-tumoral keratinocytes, and investigated the cellular mechanisms associated with LB-induced cytotoxicity. Materials and Methods: A375 and HaCaT cells were exposed to 75–500 μM LB for 24 h. Cell viability and lysosomal dye retention were assessed using MTT and NRU assays. A DMSO-only concentration series (0.075–0.50% v/v) was additionally evaluated by MTT in both cell lines. Mitochondrial membrane potential, mitochondrial staining patterns, nuclear morphology, cytoskeletal organization, caspase-3/7 and caspase-9 activities, and plasma membrane integrity were evaluated using JC-1, MitoTracker Red CMXRos, immunofluorescence, luminescence-based caspase assays, and AO/PI staining. The acute irritation potential of 500 μM LB was assessed using the HET-CAM assay. Results: DMSO alone did not significantly reduce viability over the investigated concentration range in either cell line. LB reduced A375 cell viability in a concentration-dependent manner, with a 24 h IC50 of 422.5 μM and a viability of 33.61% at 500 μM. Under the same experimental conditions, HaCaT viability remained at 89.01% at 500 μM, and an IC50 was not reached within the investigated concentration range. At the highest concentration, neutral red uptake and the JC-1 aggregate/monomer ratio decreased to approximately 33% and 24% of the corresponding control values, respectively. The apoptotic index increased from approximately 3% in control cells to 31%, while caspase-3/7 and caspase-9 activities increased to approximately 482% and 324% of the control. Qualitative imaging demonstrated mitochondrial staining redistribution, cytoskeletal disorganization, apoptosis-associated morphology, and loss of plasma membrane integrity at higher concentrations. In the HET-CAM assay, 500 μM LB produced a mean irritation score of 0.71 ± 0.27, within the non-irritant range. Conclusions: LB displayed concentration-dependent in vitro cytotoxicity in A375 melanoma cells, whereas HaCaT keratinocytes showed limited changes under the investigated conditions. LB treatment was also associated with mitochondria-associated apoptotic signaling in A375 cells. These findings provide preliminary evidence supporting further investigation of LB within a melanoma-directed drug-repurposing strategy. Additional studies are required to establish receptor dependence, achievable local exposure, safety, and translational relevance.

]]> Preclinical Evaluation of Labetalol for Cutaneous Melanoma Drug Repurposing: Cytotoxic Activity in A375 Cells and Mitochondria-Associated Apoptotic Signaling Richard Dahma Elena-Alina Moacă Iasmina-Alexandra Predescu Ana-Cristiane Dragomir Oana-Andrada Iftode Stela Iurciuc Diana Haj Ali Ioana Macaşoi Maria Sala-Cîrtog Iulia-Najette Crintea Alina-Doina Tănase Marilena Dinuţi doi: 10.3390/medicina62091802 Medicina 2026-09-19 Medicina 2026-09-19 62 9 Article 1802 10.3390/medicina62091802 https://www.mdpi.com/1648-9144/62/9/1802 Medicina, Vol. 62, Pages 1800: Intralesional Epidermal Growth Factor and Its Association with Reamputation and Level-Up Amputation in Diabetic Foot Patients with Post-Amputation Flap Necrosis: Clinical Outcomes and Macrophage Dynamics https://www.mdpi.com/1648-9144/62/9/1800 Background and Objectives: Post-amputation flap necrosis in diabetic foot patients is associated with a high risk of reamputation, level-up amputation, and limb loss. Intralesional epidermal growth factor (iEGF) has been shown to promote wound healing in diabetic foot ulcers; however, its role in the management of post-amputation tissue defects and flap necrosis remains unclear. This study aimed to evaluate the association between iEGF use and clinical outcomes in diabetic foot patients with post-amputation flap necrosis and to characterize longitudinal changes in wound macrophage-associated cell populations. Materials and Methods: This single-center observational cohort study, with retrospective identification of eligible patients and longitudinal follow-up, included 164 diabetic foot patients who developed flap necrosis, wound-healing disorders, or tissue defects following transmetatarsal, Lisfranc, Chopart, or below-knee amputations. Eighty-four patients received an iEGF-containing multidisciplinary limb-salvage strategy, while 80 patients received a multidisciplinary limb-salvage strategy without iEGF. The primary endpoint was treatment success, defined as preservation of the original amputation level without reamputation or proximal level-up amputation, together with satisfactory wound healing at the last available clinical follow-up. Secondary endpoints included mortality during follow-up and, in a flow cytometry sub-study of 12 iEGF-treated patients with available paired wound samples, changes in CD38+ and CD209+ cell proportions within the CD45+CD14+ macrophage-enriched population in paired wound-tissue samples. Results: Overall treatment success was 68.3% (112/164), and the observed crude cumulative mortality proportion was 21.3% (35/164). Treatment success was higher in the iEGF group than in the control group (95.2% [80/84] vs. 40.0% [32/80], p < 0.001), whereas the observed crude cumulative mortality proportion was lower (2.4% [2/84] vs. 41.3% [33/80], p < 0.001). In the flow-cytometry sub-study (n = 12), CD38+ cell proportions within the CD45+CD14+ macrophage-enriched population increased from 10.8% to 20.3%, whereas CD209+ cell proportions increased from 14.5% to 25.7% in paired samples collected before and after the iEGF treatment cycle (both p < 0.001). Conclusions: In this observational cohort of high-risk diabetic foot patients with post-amputation flap necrosis, wound-healing disorders, or tissue defects, iEGF administered as part of a multidisciplinary limb-salvage strategy was associated with higher treatment success, while a lower crude cumulative mortality proportion was also observed in the iEGF group. The mortality difference represents a crude cumulative comparison and should not be interpreted as evidence of a time-adjusted or treatment-associated survival benefit. Given the non-randomized treatment allocation, differences in vascular management and adjunctive therapies, and the potential for residual confounding, these findings should be interpreted as associative rather than causal. The paired tissue substudy demonstrated pre–post changes in CD38+ and CD209+ cell populations; these exploratory findings do not establish macrophage polarization or a causal biological mechanism. 2026-09-18 Medicina, Vol. 62, Pages 1800: Intralesional Epidermal Growth Factor and Its Association with Reamputation and Level-Up Amputation in Diabetic Foot Patients with Post-Amputation Flap Necrosis: Clinical Outcomes and Macrophage Dynamics

Medicina doi: 10.3390/medicina62091800

Authors: Ali Murat Basak Kubra Canarslan Demir Adile Begum Bahcecioglu Munire Kubra Ozgok Kangal Yasin Hatipoglu Hamdullah Yanik Omer Levent Karadamar Yasin Gulap Mehmet Mert Hidiroglu Simay Akyuz Kerim Bora Yilmaz

Background and Objectives: Post-amputation flap necrosis in diabetic foot patients is associated with a high risk of reamputation, level-up amputation, and limb loss. Intralesional epidermal growth factor (iEGF) has been shown to promote wound healing in diabetic foot ulcers; however, its role in the management of post-amputation tissue defects and flap necrosis remains unclear. This study aimed to evaluate the association between iEGF use and clinical outcomes in diabetic foot patients with post-amputation flap necrosis and to characterize longitudinal changes in wound macrophage-associated cell populations. Materials and Methods: This single-center observational cohort study, with retrospective identification of eligible patients and longitudinal follow-up, included 164 diabetic foot patients who developed flap necrosis, wound-healing disorders, or tissue defects following transmetatarsal, Lisfranc, Chopart, or below-knee amputations. Eighty-four patients received an iEGF-containing multidisciplinary limb-salvage strategy, while 80 patients received a multidisciplinary limb-salvage strategy without iEGF. The primary endpoint was treatment success, defined as preservation of the original amputation level without reamputation or proximal level-up amputation, together with satisfactory wound healing at the last available clinical follow-up. Secondary endpoints included mortality during follow-up and, in a flow cytometry sub-study of 12 iEGF-treated patients with available paired wound samples, changes in CD38+ and CD209+ cell proportions within the CD45+CD14+ macrophage-enriched population in paired wound-tissue samples. Results: Overall treatment success was 68.3% (112/164), and the observed crude cumulative mortality proportion was 21.3% (35/164). Treatment success was higher in the iEGF group than in the control group (95.2% [80/84] vs. 40.0% [32/80], p < 0.001), whereas the observed crude cumulative mortality proportion was lower (2.4% [2/84] vs. 41.3% [33/80], p < 0.001). In the flow-cytometry sub-study (n = 12), CD38+ cell proportions within the CD45+CD14+ macrophage-enriched population increased from 10.8% to 20.3%, whereas CD209+ cell proportions increased from 14.5% to 25.7% in paired samples collected before and after the iEGF treatment cycle (both p < 0.001). Conclusions: In this observational cohort of high-risk diabetic foot patients with post-amputation flap necrosis, wound-healing disorders, or tissue defects, iEGF administered as part of a multidisciplinary limb-salvage strategy was associated with higher treatment success, while a lower crude cumulative mortality proportion was also observed in the iEGF group. The mortality difference represents a crude cumulative comparison and should not be interpreted as evidence of a time-adjusted or treatment-associated survival benefit. Given the non-randomized treatment allocation, differences in vascular management and adjunctive therapies, and the potential for residual confounding, these findings should be interpreted as associative rather than causal. The paired tissue substudy demonstrated pre–post changes in CD38+ and CD209+ cell populations; these exploratory findings do not establish macrophage polarization or a causal biological mechanism.

]]> Intralesional Epidermal Growth Factor and Its Association with Reamputation and Level-Up Amputation in Diabetic Foot Patients with Post-Amputation Flap Necrosis: Clinical Outcomes and Macrophage Dynamics Ali Murat Basak Kubra Canarslan Demir Adile Begum Bahcecioglu Munire Kubra Ozgok Kangal Yasin Hatipoglu Hamdullah Yanik Omer Levent Karadamar Yasin Gulap Mehmet Mert Hidiroglu Simay Akyuz Kerim Bora Yilmaz doi: 10.3390/medicina62091800 Medicina 2026-09-18 Medicina 2026-09-18 62 9 Article 1800 10.3390/medicina62091800 https://www.mdpi.com/1648-9144/62/9/1800 Medicina, Vol. 62, Pages 1801: Translation and Assessment of Structural Validity and Internal Consistency of the Polish Health Literacy Questionnaire (HLQ) in Health Professions Students https://www.mdpi.com/1648-9144/62/9/1801 Background and Objectives: Assessing health literacy requires valid measurement tools that capture its multidimensional nature. The nine-scale Health Literacy Questionnaire (HLQ) is globally used for this purpose. This study reports on the initial psychometric assessment of the Polish version of the HLQ. Materials and Methods: The HLQ was translated using the developers’ Translation Integrity Procedure and administered to 918 health professions students in a cross-sectional survey. Confirmatory factor analyses (CFA) and reliability tests were conducted. Results: One-factor CFAs generally supported the intended structure of the individual HLQ scales, although some variation in model fit was observed across scales. A full, restrictive nine-factor CFA supported the original nine-factor model, with good fit indices: χ2WLSMV (866 df) = 1752.08, p < 0.0001, CFI = 0.973, TLI = 0.970, SRMR = 0.045, RMSEA = 0.035. Factor loadings were generally acceptable (≥0.50), with only two items below the threshold. Internal consistency of scales was good to acceptable in all but one domain marginally lower than desired: “Appraisal of health information” (Cronbach’s α = 0.69, composite reliability 0.68). Conclusions: The findings provide initial evidence supporting structural validity and internal consistency of the Polish HLQ in this sample. Further testing in other Polish populations is recommended. 2026-09-18 Medicina, Vol. 62, Pages 1801: Translation and Assessment of Structural Validity and Internal Consistency of the Polish Health Literacy Questionnaire (HLQ) in Health Professions Students

Medicina doi: 10.3390/medicina62091801

Authors: Agnieszka Lipiak Monika Karasiewicz Barbara Gawłowska Rafał Staszewski Sylwia Wiśniewska-Leśków Melanie Hawkins Richard H. Osborne Ewelina Chawłowska

Background and Objectives: Assessing health literacy requires valid measurement tools that capture its multidimensional nature. The nine-scale Health Literacy Questionnaire (HLQ) is globally used for this purpose. This study reports on the initial psychometric assessment of the Polish version of the HLQ. Materials and Methods: The HLQ was translated using the developers’ Translation Integrity Procedure and administered to 918 health professions students in a cross-sectional survey. Confirmatory factor analyses (CFA) and reliability tests were conducted. Results: One-factor CFAs generally supported the intended structure of the individual HLQ scales, although some variation in model fit was observed across scales. A full, restrictive nine-factor CFA supported the original nine-factor model, with good fit indices: χ2WLSMV (866 df) = 1752.08, p < 0.0001, CFI = 0.973, TLI = 0.970, SRMR = 0.045, RMSEA = 0.035. Factor loadings were generally acceptable (≥0.50), with only two items below the threshold. Internal consistency of scales was good to acceptable in all but one domain marginally lower than desired: “Appraisal of health information” (Cronbach’s α = 0.69, composite reliability 0.68). Conclusions: The findings provide initial evidence supporting structural validity and internal consistency of the Polish HLQ in this sample. Further testing in other Polish populations is recommended.

]]> Translation and Assessment of Structural Validity and Internal Consistency of the Polish Health Literacy Questionnaire (HLQ) in Health Professions Students Agnieszka Lipiak Monika Karasiewicz Barbara Gawłowska Rafał Staszewski Sylwia Wiśniewska-Leśków Melanie Hawkins Richard H. Osborne Ewelina Chawłowska doi: 10.3390/medicina62091801 Medicina 2026-09-18 Medicina 2026-09-18 62 9 Article 1801 10.3390/medicina62091801 https://www.mdpi.com/1648-9144/62/9/1801 Medicina, Vol. 62, Pages 1799: Combined Antegrade–Retrograde Cardioplegia for Myocardial Protection During Coronary Artery Bypass Grafting in Patients with Left Main Coronary Artery Disease: The CARDIOPROTECT-LMCAD Randomised Trial https://www.mdpi.com/1648-9144/62/9/1799 Background and Objectives: Myocardial protection during on-pump coronary artery bypass grafting (CABG) limits ischaemic injury, particularly in patients with left main coronary artery disease (LMCAD), in whom severe proximal stenosis may compromise antegrade cardioplegia delivery. We investigated whether combined antegrade–retrograde blood cardioplegia reduces postoperative high-sensitivity cardiac troponin I (hs-cTnI) concentrations, a marker of perioperative myocardial injury. Materials and Methods: We conducted a prospective, single-centre, randomised trial involving 60 adults undergoing elective isolated on-pump CABG for significant LMCAD. Patients were assigned (1:1) to antegrade-only or combined antegrade–retrograde blood cardioplegia. Cardiac biomarkers were measured after induction and at 4, 12, 24, and 48 h after ICU admission. The primary endpoint was peak hs-cTnI within 48 h; key secondary endpoints included the hs-cTnI area under the concentration–time curve, CK-MB, immediate myocardial electrical recovery and 30-day outcomes. Results: All patients received the assigned cardioplegia strategy, with no crossover. Peak hs-cTnI did not differ significantly between the antegrade-only and combined groups (median 529.1 [IQR 829.9] vs. 394.1 [503.4] ng/L; p = 0.21), nor did the hs-cTnI area under the concentration–time curve from 4 to 48 h (12,910.6 [23,127.4] vs. 8112.2 [11,686.2] ng·h/L; p = 0.16). Serial hs-cTnI, CK-MB, total creatine kinase, serum creatinine, immediate myocardial electrical recovery, and 30-day outcomes also did not differ significantly. No deaths, coronary sinus injuries, or other cardioplegia-related complications occurred. Conclusions: In patients undergoing isolated on-pump CABG for significant LMCAD, combined antegrade–retrograde blood cardioplegia did not significantly decrease peak hs-cTnI levels compared to the antegrade-only method. The combined approach was feasible with no cardioplegia-related complications, suggesting that an individualised strategy may be preferable to a routine one. Larger prospective studies are needed to determine whether higher-risk patients may derive greater benefit. 2026-09-18 Medicina, Vol. 62, Pages 1799: Combined Antegrade–Retrograde Cardioplegia for Myocardial Protection During Coronary Artery Bypass Grafting in Patients with Left Main Coronary Artery Disease: The CARDIOPROTECT-LMCAD Randomised Trial

Medicina doi: 10.3390/medicina62091799

Authors: Jelena Lesanovic Milan Milojevic Djordje Nikolic Ivan Soldatovic Dragana Unic-Stojanovic Igor Zivkovic Miroslav Milicic Petar Vukovic Ivana Petrovic Sinisa Jagodic Milovan Bojic Slobodan Micovic

Background and Objectives: Myocardial protection during on-pump coronary artery bypass grafting (CABG) limits ischaemic injury, particularly in patients with left main coronary artery disease (LMCAD), in whom severe proximal stenosis may compromise antegrade cardioplegia delivery. We investigated whether combined antegrade–retrograde blood cardioplegia reduces postoperative high-sensitivity cardiac troponin I (hs-cTnI) concentrations, a marker of perioperative myocardial injury. Materials and Methods: We conducted a prospective, single-centre, randomised trial involving 60 adults undergoing elective isolated on-pump CABG for significant LMCAD. Patients were assigned (1:1) to antegrade-only or combined antegrade–retrograde blood cardioplegia. Cardiac biomarkers were measured after induction and at 4, 12, 24, and 48 h after ICU admission. The primary endpoint was peak hs-cTnI within 48 h; key secondary endpoints included the hs-cTnI area under the concentration–time curve, CK-MB, immediate myocardial electrical recovery and 30-day outcomes. Results: All patients received the assigned cardioplegia strategy, with no crossover. Peak hs-cTnI did not differ significantly between the antegrade-only and combined groups (median 529.1 [IQR 829.9] vs. 394.1 [503.4] ng/L; p = 0.21), nor did the hs-cTnI area under the concentration–time curve from 4 to 48 h (12,910.6 [23,127.4] vs. 8112.2 [11,686.2] ng·h/L; p = 0.16). Serial hs-cTnI, CK-MB, total creatine kinase, serum creatinine, immediate myocardial electrical recovery, and 30-day outcomes also did not differ significantly. No deaths, coronary sinus injuries, or other cardioplegia-related complications occurred. Conclusions: In patients undergoing isolated on-pump CABG for significant LMCAD, combined antegrade–retrograde blood cardioplegia did not significantly decrease peak hs-cTnI levels compared to the antegrade-only method. The combined approach was feasible with no cardioplegia-related complications, suggesting that an individualised strategy may be preferable to a routine one. Larger prospective studies are needed to determine whether higher-risk patients may derive greater benefit.

]]> Combined Antegrade–Retrograde Cardioplegia for Myocardial Protection During Coronary Artery Bypass Grafting in Patients with Left Main Coronary Artery Disease: The CARDIOPROTECT-LMCAD Randomised Trial Jelena Lesanovic Milan Milojevic Djordje Nikolic Ivan Soldatovic Dragana Unic-Stojanovic Igor Zivkovic Miroslav Milicic Petar Vukovic Ivana Petrovic Sinisa Jagodic Milovan Bojic Slobodan Micovic doi: 10.3390/medicina62091799 Medicina 2026-09-18 Medicina 2026-09-18 62 9 Article 1799 10.3390/medicina62091799 https://www.mdpi.com/1648-9144/62/9/1799 Medicina, Vol. 62, Pages 1798: Nasal Cavity Dimensions and Pharyngeal Airway Space in Simple Snoring: A Cross-Sectional CT-Based Study https://www.mdpi.com/1648-9144/62/9/1798 Background and Objectives: The anatomical relationship between nasal cavity dimensions and the pharyngeal airway space (PAS) in simple snoring remains poorly defined. We investigated the association between nasal cavity dimensions and the PAS in adults with simple snoring using computed tomography (CT), focusing on anatomical correlations. Materials and Methods: This cross-sectional study included 83 adults with simple snoring and nasal obstruction and a confirmed apnea–hypopnea index (AHI) < 2, enrolled between 2007 and 2022. Polysomnography and CT were performed to measure nasal and pharyngeal airway dimensions. The minimum cross-sectional areas (mCSAs) of three nasal cavity segments and pharyngeal airway dimensions were measured on awake CT images. Multivariable linear regression, adjusted for age, sex, and BMI, was used to evaluate the association between the nasal and pharyngeal airway dimensions. Results: A larger bilateral narrowest nasal cross-sectional area was significantly associated with a larger PAS mCSA in the full cohort (standardized β = 0.26, p = 0.012), after adjustment for age, sex, and BMI. A 10-mm2 larger nasal area corresponded to a 3.6% larger PAS mCSA (95% CI, 0.8–6.5%), and the model explained a modest share of the variance (adjusted R2 = 0.17). The association did not differ by sex (interaction p = 0.25), indicating no evidence of effect modification. Conclusions: In individuals with simple snoring, smaller nasal cavity dimensions were associated with a narrower PAS on static CT imaging, although this association was modest and explained only a small fraction of the variation in pharyngeal calibre. These findings reflect anatomical associations and should not be interpreted as evidence of functional airway collapse or disease progression. 2026-09-18 Medicina, Vol. 62, Pages 1798: Nasal Cavity Dimensions and Pharyngeal Airway Space in Simple Snoring: A Cross-Sectional CT-Based Study

Medicina doi: 10.3390/medicina62091798

Authors: Jeong-Whun Kim Sung-Woo Cho Hyun Jung Kim

Background and Objectives: The anatomical relationship between nasal cavity dimensions and the pharyngeal airway space (PAS) in simple snoring remains poorly defined. We investigated the association between nasal cavity dimensions and the PAS in adults with simple snoring using computed tomography (CT), focusing on anatomical correlations. Materials and Methods: This cross-sectional study included 83 adults with simple snoring and nasal obstruction and a confirmed apnea–hypopnea index (AHI) < 2, enrolled between 2007 and 2022. Polysomnography and CT were performed to measure nasal and pharyngeal airway dimensions. The minimum cross-sectional areas (mCSAs) of three nasal cavity segments and pharyngeal airway dimensions were measured on awake CT images. Multivariable linear regression, adjusted for age, sex, and BMI, was used to evaluate the association between the nasal and pharyngeal airway dimensions. Results: A larger bilateral narrowest nasal cross-sectional area was significantly associated with a larger PAS mCSA in the full cohort (standardized β = 0.26, p = 0.012), after adjustment for age, sex, and BMI. A 10-mm2 larger nasal area corresponded to a 3.6% larger PAS mCSA (95% CI, 0.8–6.5%), and the model explained a modest share of the variance (adjusted R2 = 0.17). The association did not differ by sex (interaction p = 0.25), indicating no evidence of effect modification. Conclusions: In individuals with simple snoring, smaller nasal cavity dimensions were associated with a narrower PAS on static CT imaging, although this association was modest and explained only a small fraction of the variation in pharyngeal calibre. These findings reflect anatomical associations and should not be interpreted as evidence of functional airway collapse or disease progression.

]]> Nasal Cavity Dimensions and Pharyngeal Airway Space in Simple Snoring: A Cross-Sectional CT-Based Study Jeong-Whun Kim Sung-Woo Cho Hyun Jung Kim doi: 10.3390/medicina62091798 Medicina 2026-09-18 Medicina 2026-09-18 62 9 Article 1798 10.3390/medicina62091798 https://www.mdpi.com/1648-9144/62/9/1798 Medicina, Vol. 62, Pages 1797: Hemoglobin-to-Red Cell Distribution Width Ratio Independently Predicts Survival in Non-Metastatic Gastric Cancer: A Retrospective Cohort Study https://www.mdpi.com/1648-9144/62/9/1797 Background and Objectives: Gastric cancer is one of the most common malignancies worldwide and continues to be associated with high mortality. The hemoglobin-to-red cell distribution width (HGB/RDW) ratio has emerged as a promising hematological prognostic biomarker in various cancers. However, its prognostic significance in patients with curative-intent resection of non-metastatic gastric cancer remains insufficiently investigated. This study aimed to evaluate the association between the pretreatment HGB/RDW ratio and progression-free survival (PFS) as well as overall survival (OS) in patients with non-metastatic gastric cancer. Materials and Methods: In this multicenter study, a total of 175 patients with non-metastatic gastric cancer who received perioperative FLOT chemotherapy (four preoperative and four postoperative cycles) and underwent curative-intent surgical resection were retrospectively analyzed. A cut-off value for the HGB/RDW ratio was calculated using receiver operating characteristic (ROC) curve analysis. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), were analyzed using the Kaplan–Meier method. Multivariate Cox proportional hazards regression analysis was performed to identify independent prognostic factors. Results: Patients with an HGB/RDW ratio > 0.85 demonstrated significantly superior 2-year and 5-year OS rates (76.2% vs. 59.6% and 51.6% vs. 27.7%, respectively; p = 0.003) and PFS rates (69.4% vs. 49.6% and 53.7% vs. 36.4%, respectively; p = 0.047) compared to those with HGB/RDW ≤ 0.85. Multivariate analysis identified HGB/RDW ≤ 0.85 as an independent predictor of both increased mortality risk (HR: 1.88, 95% CI: 1.16–3.06; p = 0.011) and disease progression risk (HR: 1.79, 95% CI: 1.18–2.72; p = 0.006). Conclusions: The pretreatment HGB/RDW ratio is an independent prognostic factor for OS and PFS in patients with curative-intent resection of non-metastatic gastric cancer and may be considered a practical marker that could contribute to treatment planning in this patient population. 2026-09-18 Medicina, Vol. 62, Pages 1797: Hemoglobin-to-Red Cell Distribution Width Ratio Independently Predicts Survival in Non-Metastatic Gastric Cancer: A Retrospective Cohort Study

Medicina doi: 10.3390/medicina62091797

Authors: Sevgi Bilmez Altay İlker Nihat Ökten Çağlar Köseoğlu Ertürk Yiğit Mehmet Uzun Oğuzhan Kesen

Background and Objectives: Gastric cancer is one of the most common malignancies worldwide and continues to be associated with high mortality. The hemoglobin-to-red cell distribution width (HGB/RDW) ratio has emerged as a promising hematological prognostic biomarker in various cancers. However, its prognostic significance in patients with curative-intent resection of non-metastatic gastric cancer remains insufficiently investigated. This study aimed to evaluate the association between the pretreatment HGB/RDW ratio and progression-free survival (PFS) as well as overall survival (OS) in patients with non-metastatic gastric cancer. Materials and Methods: In this multicenter study, a total of 175 patients with non-metastatic gastric cancer who received perioperative FLOT chemotherapy (four preoperative and four postoperative cycles) and underwent curative-intent surgical resection were retrospectively analyzed. A cut-off value for the HGB/RDW ratio was calculated using receiver operating characteristic (ROC) curve analysis. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), were analyzed using the Kaplan–Meier method. Multivariate Cox proportional hazards regression analysis was performed to identify independent prognostic factors. Results: Patients with an HGB/RDW ratio > 0.85 demonstrated significantly superior 2-year and 5-year OS rates (76.2% vs. 59.6% and 51.6% vs. 27.7%, respectively; p = 0.003) and PFS rates (69.4% vs. 49.6% and 53.7% vs. 36.4%, respectively; p = 0.047) compared to those with HGB/RDW ≤ 0.85. Multivariate analysis identified HGB/RDW ≤ 0.85 as an independent predictor of both increased mortality risk (HR: 1.88, 95% CI: 1.16–3.06; p = 0.011) and disease progression risk (HR: 1.79, 95% CI: 1.18–2.72; p = 0.006). Conclusions: The pretreatment HGB/RDW ratio is an independent prognostic factor for OS and PFS in patients with curative-intent resection of non-metastatic gastric cancer and may be considered a practical marker that could contribute to treatment planning in this patient population.

]]> Hemoglobin-to-Red Cell Distribution Width Ratio Independently Predicts Survival in Non-Metastatic Gastric Cancer: A Retrospective Cohort Study Sevgi Bilmez Altay İlker Nihat Ökten Çağlar Köseoğlu Ertürk Yiğit Mehmet Uzun Oğuzhan Kesen doi: 10.3390/medicina62091797 Medicina 2026-09-18 Medicina 2026-09-18 62 9 Article 1797 10.3390/medicina62091797 https://www.mdpi.com/1648-9144/62/9/1797 Medicina, Vol. 62, Pages 1796: Psoriasis and Chronic Viral Infections (HIV, HBV, and HCV): Therapeutic Approach and Safety https://www.mdpi.com/1648-9144/62/9/1796 Background and Objectives: Psoriasis is a chronic immune-mediated inflammatory disease that often requires long-term systemic therapy. Coexisting human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection complicates treatment selection because clinicians must balance control of skin and joint inflammation against risks of opportunistic infection, viral replication or reactivation, hepatotoxicity, and drug interactions. Materials and Methods: This narrative review summarizes evidence from guidelines, systematic reviews, cohort studies, case series, expert recommendations, and regulatory sources. Results: In patients with suppressed HIV RNA, stable or reconstituted CD4 counts, no active opportunistic infection, and reliable follow-up, selected systemic agents, including biologics, may be considered after individualized risk assessment. In HBV infection, reactivation prevention through antiviral prophylaxis or close monitoring is central. In HCV infection, fibrosis stage, active hepatitis, drug interactions, and timing of direct-acting antivirals should guide management. Conclusions: Chronic viral infection should not be regarded as an absolute barrier to modern psoriasis therapy. 2026-09-18 Medicina, Vol. 62, Pages 1796: Psoriasis and Chronic Viral Infections (HIV, HBV, and HCV): Therapeutic Approach and Safety

Medicina doi: 10.3390/medicina62091796

Authors: Gustavo Almeida-Silva Diogo Couto-Sousa Inês Tribolet-Abreu Filipe Monteiro João Ferreira Joana Antunes Paulo Filipe

Background and Objectives: Psoriasis is a chronic immune-mediated inflammatory disease that often requires long-term systemic therapy. Coexisting human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection complicates treatment selection because clinicians must balance control of skin and joint inflammation against risks of opportunistic infection, viral replication or reactivation, hepatotoxicity, and drug interactions. Materials and Methods: This narrative review summarizes evidence from guidelines, systematic reviews, cohort studies, case series, expert recommendations, and regulatory sources. Results: In patients with suppressed HIV RNA, stable or reconstituted CD4 counts, no active opportunistic infection, and reliable follow-up, selected systemic agents, including biologics, may be considered after individualized risk assessment. In HBV infection, reactivation prevention through antiviral prophylaxis or close monitoring is central. In HCV infection, fibrosis stage, active hepatitis, drug interactions, and timing of direct-acting antivirals should guide management. Conclusions: Chronic viral infection should not be regarded as an absolute barrier to modern psoriasis therapy.

]]> Psoriasis and Chronic Viral Infections (HIV, HBV, and HCV): Therapeutic Approach and Safety Gustavo Almeida-Silva Diogo Couto-Sousa Inês Tribolet-Abreu Filipe Monteiro João Ferreira Joana Antunes Paulo Filipe doi: 10.3390/medicina62091796 Medicina 2026-09-18 Medicina 2026-09-18 62 9 Review 1796 10.3390/medicina62091796 https://www.mdpi.com/1648-9144/62/9/1796 Medicina, Vol. 62, Pages 1795: Prospective Evaluation of Peripheral Arterial Intervention Using Air Plethysmography https://www.mdpi.com/1648-9144/62/9/1795 Background and Objectives: Air plethysmography (APG), also referred to as pulse volume recording, provides a physiological assessment of lower-extremity perfusion, but its role in contemporary surveillance after peripheral arterial revascularization remains uncertain. This prospective study aimed to evaluate the ability of APG to monitor hemodynamic recovery and predict procedural failure after open and endovascular interventions. Materials and Methods: Consecutive patients undergoing infrainguinal revascularization for symptomatic peripheral arterial disease were prospectively enrolled and followed for 24 months. Standardized clinical assessment, ankle–brachial index, Duplex ultrasonography, and APG were performed preoperatively and at 1, 6, 12, and 24 months. Longitudinal hemodynamic changes, diagnostic accuracy for restenosis, patency, and predictors of procedural failure were analyzed. Results: A total of 120 patients were included, of whom 108 (90.0%) completed a 24-month follow-up. Mean pulse volume amplitude increased from 5.8 ± 2.3 mm preoperatively to 14.6 ± 4.1 mm at one month (p < 0.001) and remained significantly improved throughout follow-up. Systolic upstroke time decreased from 192 ± 31 to 128 ± 24 ms (p < 0.001), while waveform morphology also improved substantially. Longitudinal analysis demonstrated a significant effect of time (p < 0.001) and group-by-time interaction (p = 0.031). Among secondary outcomes, APG deterioration preceded fulfillment of the predefined Duplex criteria for significant restenosis in 26 of 34 failures, with a mean observed interval of 3.8 ± 1.2 months. A ≥25% reduction in pulse volume amplitude showed good discrimination for restenosis, while APG deterioration was independently associated with procedural failure (HR = 2.80, 95% CI 1.65–5.37; p < 0.001). Conclusions: APG is a reproducible, non-invasive surveillance adjunct that objectively reflects hemodynamic recovery and may identify physiological deterioration before fulfillment of predefined Duplex criteria for significant restenosis. These findings support further evaluation of APG as a complementary physiological modality within structured surveillance following lower-extremity revascularization. 2026-09-18 Medicina, Vol. 62, Pages 1795: Prospective Evaluation of Peripheral Arterial Intervention Using Air Plethysmography

Medicina doi: 10.3390/medicina62091795

Authors: Anastasios G. Potouridis Dimitrios A. Chatzelas Apostolos G. Pitoulias Maria D. Velikoudi Georgios A. Pitoulias

Background and Objectives: Air plethysmography (APG), also referred to as pulse volume recording, provides a physiological assessment of lower-extremity perfusion, but its role in contemporary surveillance after peripheral arterial revascularization remains uncertain. This prospective study aimed to evaluate the ability of APG to monitor hemodynamic recovery and predict procedural failure after open and endovascular interventions. Materials and Methods: Consecutive patients undergoing infrainguinal revascularization for symptomatic peripheral arterial disease were prospectively enrolled and followed for 24 months. Standardized clinical assessment, ankle–brachial index, Duplex ultrasonography, and APG were performed preoperatively and at 1, 6, 12, and 24 months. Longitudinal hemodynamic changes, diagnostic accuracy for restenosis, patency, and predictors of procedural failure were analyzed. Results: A total of 120 patients were included, of whom 108 (90.0%) completed a 24-month follow-up. Mean pulse volume amplitude increased from 5.8 ± 2.3 mm preoperatively to 14.6 ± 4.1 mm at one month (p < 0.001) and remained significantly improved throughout follow-up. Systolic upstroke time decreased from 192 ± 31 to 128 ± 24 ms (p < 0.001), while waveform morphology also improved substantially. Longitudinal analysis demonstrated a significant effect of time (p < 0.001) and group-by-time interaction (p = 0.031). Among secondary outcomes, APG deterioration preceded fulfillment of the predefined Duplex criteria for significant restenosis in 26 of 34 failures, with a mean observed interval of 3.8 ± 1.2 months. A ≥25% reduction in pulse volume amplitude showed good discrimination for restenosis, while APG deterioration was independently associated with procedural failure (HR = 2.80, 95% CI 1.65–5.37; p < 0.001). Conclusions: APG is a reproducible, non-invasive surveillance adjunct that objectively reflects hemodynamic recovery and may identify physiological deterioration before fulfillment of predefined Duplex criteria for significant restenosis. These findings support further evaluation of APG as a complementary physiological modality within structured surveillance following lower-extremity revascularization.

]]> Prospective Evaluation of Peripheral Arterial Intervention Using Air Plethysmography Anastasios G. Potouridis Dimitrios A. Chatzelas Apostolos G. Pitoulias Maria D. Velikoudi Georgios A. Pitoulias doi: 10.3390/medicina62091795 Medicina 2026-09-18 Medicina 2026-09-18 62 9 Article 1795 10.3390/medicina62091795 https://www.mdpi.com/1648-9144/62/9/1795 Medicina, Vol. 62, Pages 1794: Vitamin D Deficiency in Hip Fracture Patients: Outcome-Specific Associations and Post-Fracture Management—A Narrative Review https://www.mdpi.com/1648-9144/62/9/1794 Background and Objectives: Vitamin D deficiency is common in older adults with hip fracture and has been associated with adverse postoperative outcomes. However, heterogeneity in deficiency thresholds, outcome definitions, and patient populations has complicated the interpretation and clinical application of existing evidence. This narrative review aimed to summarize current evidence regarding perioperative vitamin D status, its associations with postoperative complications, mortality, functional recovery, and secondary fracture, and the role of vitamin D supplementation after hip fracture. Materials and Methods: Relevant studies were identified through PubMed searches and manual screening of reference lists. Cohort studies, randomized controlled trials, systematic reviews, meta-analyses, and clinical guidelines addressing vitamin D status, supplementation, hip fracture outcomes, fracture prevention, or postoperative recovery in older adults were narratively synthesized. Results: Low serum 25-hydroxyvitamin D was associated with selected early medical complications, mortality, impaired functional recovery, and secondary hip fracture, although these associations varied across outcomes. The strongest prognostic associations with mobility were observed in patients with severe deficiency (approximately ≤10–12 ng/mL), whereas mild insufficiency showed less consistent associations. Heterogeneity among studies reflected differences in deficiency thresholds, sampling timing, outcome definitions, follow-up duration, study populations, and adjustment for frailty and comorbidity. Vitamin D supplementation consistently increased serum 25-hydroxyvitamin D concentrations but did not consistently improve gait, postoperative complications, mortality, or recurrent fracture. Favorable outcomes reported with exercise- and nutrition-based multimodal interventions could not be attributed to vitamin D supplementation alone. Conclusions: Vitamin D deficiency should be interpreted within the broader context of frailty, nutritional status, muscle function, and skeletal health after hip fracture. Vitamin D assessment and correction should be integrated into comprehensive post-fracture care alongside osteoporosis treatment, adequate calcium and protein intake, rehabilitation, and fall prevention. However, clinical benefits of supplementation beyond correction of deficiency remain uncertain, and future studies should focus on patients with severe deficiency and clinically meaningful, patient-centered outcomes. 2026-09-17 Medicina, Vol. 62, Pages 1794: Vitamin D Deficiency in Hip Fracture Patients: Outcome-Specific Associations and Post-Fracture Management—A Narrative Review

Medicina doi: 10.3390/medicina62091794

Authors: Hannah Lee Jaehee Lee Yejun Lee Suk-Kyoon Song

Background and Objectives: Vitamin D deficiency is common in older adults with hip fracture and has been associated with adverse postoperative outcomes. However, heterogeneity in deficiency thresholds, outcome definitions, and patient populations has complicated the interpretation and clinical application of existing evidence. This narrative review aimed to summarize current evidence regarding perioperative vitamin D status, its associations with postoperative complications, mortality, functional recovery, and secondary fracture, and the role of vitamin D supplementation after hip fracture. Materials and Methods: Relevant studies were identified through PubMed searches and manual screening of reference lists. Cohort studies, randomized controlled trials, systematic reviews, meta-analyses, and clinical guidelines addressing vitamin D status, supplementation, hip fracture outcomes, fracture prevention, or postoperative recovery in older adults were narratively synthesized. Results: Low serum 25-hydroxyvitamin D was associated with selected early medical complications, mortality, impaired functional recovery, and secondary hip fracture, although these associations varied across outcomes. The strongest prognostic associations with mobility were observed in patients with severe deficiency (approximately ≤10–12 ng/mL), whereas mild insufficiency showed less consistent associations. Heterogeneity among studies reflected differences in deficiency thresholds, sampling timing, outcome definitions, follow-up duration, study populations, and adjustment for frailty and comorbidity. Vitamin D supplementation consistently increased serum 25-hydroxyvitamin D concentrations but did not consistently improve gait, postoperative complications, mortality, or recurrent fracture. Favorable outcomes reported with exercise- and nutrition-based multimodal interventions could not be attributed to vitamin D supplementation alone. Conclusions: Vitamin D deficiency should be interpreted within the broader context of frailty, nutritional status, muscle function, and skeletal health after hip fracture. Vitamin D assessment and correction should be integrated into comprehensive post-fracture care alongside osteoporosis treatment, adequate calcium and protein intake, rehabilitation, and fall prevention. However, clinical benefits of supplementation beyond correction of deficiency remain uncertain, and future studies should focus on patients with severe deficiency and clinically meaningful, patient-centered outcomes.

]]> Vitamin D Deficiency in Hip Fracture Patients: Outcome-Specific Associations and Post-Fracture Management—A Narrative Review Hannah Lee Jaehee Lee Yejun Lee Suk-Kyoon Song doi: 10.3390/medicina62091794 Medicina 2026-09-17 Medicina 2026-09-17 62 9 Review 1794 10.3390/medicina62091794 https://www.mdpi.com/1648-9144/62/9/1794 Medicina, Vol. 62, Pages 1793: Patterns of Care in the Final Week of Life: A Comparative Analysis of Aggressive Treatment Versus Comfort-Centered Care Across Healthcare Settings https://www.mdpi.com/1648-9144/62/9/1793 Background and Objectives: End-of-life care in oncology demands a holistic, multidisciplinary framework that pivots clinical priorities from disease-directed therapies toward symptom optimization, comfort, and patient dignity. Within this context, the present study investigated care delivery patterns among advanced cancer patients during their final week of life. Materials and Methods: A retrospective medical record review was conducted, comparing an oncology ward, an intensive care unit, an inpatient palliative unit, and a home-based palliative care setting. We analyzed aggressive interventions, end-of-life care pathways, symptom management, medication use and rationalization, and transitions between care settings. Results: Among the 306 patients studied, diagnostic testing and artificial hydration were universally administered in the oncology and intensive care unit (p < 0.001), where prescriptions focused primarily on pain management. Conversely, palliative care settings addressed a wider range of terminal symptoms. The rationalization of non-essential medications took place between 1.8 and 2.9 days before death, varying significantly across medication classes and clinical settings (p < 0.001). Additionally, intensive care unit admissions were more prevalent among patients with advanced cancer, while home-based patients underwent the greatest number of care transitions. Conclusions: These findings highlight substantial differences in care across settings, emphasizing the need for coordinated planning, continuity, and patient-centered approaches to ensure comfort and dignity in the final week of life. 2026-09-17 Medicina, Vol. 62, Pages 1793: Patterns of Care in the Final Week of Life: A Comparative Analysis of Aggressive Treatment Versus Comfort-Centered Care Across Healthcare Settings

Medicina doi: 10.3390/medicina62091793

Authors: Camelia Ancuta Nicoleta Mitrea Mariana Sporis Flavia Hurducas Daniela Mosoiu

Background and Objectives: End-of-life care in oncology demands a holistic, multidisciplinary framework that pivots clinical priorities from disease-directed therapies toward symptom optimization, comfort, and patient dignity. Within this context, the present study investigated care delivery patterns among advanced cancer patients during their final week of life. Materials and Methods: A retrospective medical record review was conducted, comparing an oncology ward, an intensive care unit, an inpatient palliative unit, and a home-based palliative care setting. We analyzed aggressive interventions, end-of-life care pathways, symptom management, medication use and rationalization, and transitions between care settings. Results: Among the 306 patients studied, diagnostic testing and artificial hydration were universally administered in the oncology and intensive care unit (p < 0.001), where prescriptions focused primarily on pain management. Conversely, palliative care settings addressed a wider range of terminal symptoms. The rationalization of non-essential medications took place between 1.8 and 2.9 days before death, varying significantly across medication classes and clinical settings (p < 0.001). Additionally, intensive care unit admissions were more prevalent among patients with advanced cancer, while home-based patients underwent the greatest number of care transitions. Conclusions: These findings highlight substantial differences in care across settings, emphasizing the need for coordinated planning, continuity, and patient-centered approaches to ensure comfort and dignity in the final week of life.

]]> Patterns of Care in the Final Week of Life: A Comparative Analysis of Aggressive Treatment Versus Comfort-Centered Care Across Healthcare Settings Camelia Ancuta Nicoleta Mitrea Mariana Sporis Flavia Hurducas Daniela Mosoiu doi: 10.3390/medicina62091793 Medicina 2026-09-17 Medicina 2026-09-17 62 9 Article 1793 10.3390/medicina62091793 https://www.mdpi.com/1648-9144/62/9/1793 Medicina, Vol. 62, Pages 1792: Retzius-Sparing Robot-Assisted Radical Prostatectomy: Analysis of Functional and Oncological Outcomes https://www.mdpi.com/1648-9144/62/9/1792 Background and Objectives: Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) has emerged as an alternative surgical approach designed to preserve pelvic anatomical structures involved in urinary continence. This study aimed to evaluate the perioperative, pathological, functional, and early postoperative oncological findings of RS-RARP in patients with clinically localized prostate cancer. Materials and Methods: This retrospective single-cohort study included 132 consecutive patients who underwent RS-RARP at a single institution between January 2017 and February 2020. Demographic, perioperative, pathological, functional, and postoperative oncological data were retrospectively collected. The primary functional outcome was postoperative urinary continence recovery. Pathological outcomes included final ISUP Grade Group and positive surgical margin status, while postoperative prostate-specific antigen (PSA) measurements and treatment-related oncological follow-up data were evaluated where available. Results: The median operative time was 170 min (IQR, 160–200), and the median estimated blood loss was 100 mL (IQR, 70–150). Blood transfusion was required in one patient (0.8%), and no Clavien–Dindo grade ≥ III complications were observed. Final pathological examination demonstrated ISUP Grade Group 2 disease in 64.9% of patients, and the overall positive surgical margin rate was 33.6%. The median time to both social continence (0–1 pad/day) and complete continence (0 pad/day) was 30 days. Among 130 patients with available current pad-use data, 108 (83.1%) were completely pad-free, 13 (10.0%) required one safety pad per day, and 9 (6.9%) required two or more pads per day. The median oncological follow-up was 12 months. Follow-up data were available for 131 patients; postoperative PSA measurements were available for 79 patients and last PSA measurements for 122 patients. No salvage therapy or biochemical recurrence was documented in the available clinical records. However, incomplete longitudinal PSA data precluded reliable assessment of biochemical recurrence-free survival. Conclusions: In this retrospective single-cohort study, RS-RARP was associated with low perioperative morbidity, acceptable pathological outcomes, and favorable early urinary continence recovery. However, the absence of a conventional RARP comparator group, the relatively short follow-up period, and incomplete longitudinal PSA and recurrence-related data preclude conclusions regarding comparative effectiveness and long-term oncological efficacy. Prospective multicenter comparative studies with standardized functional assessment, systematic PSA monitoring, and longer oncological follow-up are warranted. 2026-09-17 Medicina, Vol. 62, Pages 1792: Retzius-Sparing Robot-Assisted Radical Prostatectomy: Analysis of Functional and Oncological Outcomes

Medicina doi: 10.3390/medicina62091792

Authors: Fırat Akdeniz Sıtkı Ün Uğur Boylu Aylin Köseler

Background and Objectives: Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) has emerged as an alternative surgical approach designed to preserve pelvic anatomical structures involved in urinary continence. This study aimed to evaluate the perioperative, pathological, functional, and early postoperative oncological findings of RS-RARP in patients with clinically localized prostate cancer. Materials and Methods: This retrospective single-cohort study included 132 consecutive patients who underwent RS-RARP at a single institution between January 2017 and February 2020. Demographic, perioperative, pathological, functional, and postoperative oncological data were retrospectively collected. The primary functional outcome was postoperative urinary continence recovery. Pathological outcomes included final ISUP Grade Group and positive surgical margin status, while postoperative prostate-specific antigen (PSA) measurements and treatment-related oncological follow-up data were evaluated where available. Results: The median operative time was 170 min (IQR, 160–200), and the median estimated blood loss was 100 mL (IQR, 70–150). Blood transfusion was required in one patient (0.8%), and no Clavien–Dindo grade ≥ III complications were observed. Final pathological examination demonstrated ISUP Grade Group 2 disease in 64.9% of patients, and the overall positive surgical margin rate was 33.6%. The median time to both social continence (0–1 pad/day) and complete continence (0 pad/day) was 30 days. Among 130 patients with available current pad-use data, 108 (83.1%) were completely pad-free, 13 (10.0%) required one safety pad per day, and 9 (6.9%) required two or more pads per day. The median oncological follow-up was 12 months. Follow-up data were available for 131 patients; postoperative PSA measurements were available for 79 patients and last PSA measurements for 122 patients. No salvage therapy or biochemical recurrence was documented in the available clinical records. However, incomplete longitudinal PSA data precluded reliable assessment of biochemical recurrence-free survival. Conclusions: In this retrospective single-cohort study, RS-RARP was associated with low perioperative morbidity, acceptable pathological outcomes, and favorable early urinary continence recovery. However, the absence of a conventional RARP comparator group, the relatively short follow-up period, and incomplete longitudinal PSA and recurrence-related data preclude conclusions regarding comparative effectiveness and long-term oncological efficacy. Prospective multicenter comparative studies with standardized functional assessment, systematic PSA monitoring, and longer oncological follow-up are warranted.

]]> Retzius-Sparing Robot-Assisted Radical Prostatectomy: Analysis of Functional and Oncological Outcomes Fırat Akdeniz Sıtkı Ün Uğur Boylu Aylin Köseler doi: 10.3390/medicina62091792 Medicina 2026-09-17 Medicina 2026-09-17 62 9 Article 1792 10.3390/medicina62091792 https://www.mdpi.com/1648-9144/62/9/1792 Medicina, Vol. 62, Pages 1791: Ultrasound Sliding Sign Assessed by Transvaginal or Transrectal Route for Predicting Complete Pouch of Douglas Obliteration in Patients with Ovarian Endometriomas: An Exploratory Retrospective Study https://www.mdpi.com/1648-9144/62/9/1791 Background and Objective: The ultrasound sliding sign dynamically assesses pouch of Douglas (POD) obliteration in suspected endometriosis. Transvaginal (TVS) and transrectal (TRS) ultrasound are used in patients with and without a self-reported history of vaginal intercourse, respectively, and thus in clinically distinct populations. We evaluated sliding sign performance for predicting surgically confirmed complete POD obliteration in patients with ovarian endometriomas and described findings in route-defined TVS and TRS groups. Materials and Methods: This retrospective cohort study enrolled 318 patients with surgically and pathologically confirmed ovarian endometriomas; intraoperative POD status was evaluable in 309. Patients with and without a self-reported history of vaginal intercourse underwent TVS (n = 247) and TRS (n = 71), respectively. A negative sliding sign (absent movement between the uterus and rectum) was the positive index test result for complete POD obliteration. The unadjusted full-cohort diagnostic accuracy analysis was the primary analysis. Because no parous patient underwent TRS (a lack of overlap in examination-route assignment among parous patients), exploratory adjusted analyses were restricted to nulliparous patients, using overlap weighting (principal adjusted analysis) and 1:1 propensity score matching (sensitivity analysis). Results: In the primary unadjusted analysis of the full cohort (n = 309), the negative sliding sign showed limited to moderate discriminative ability (sensitivity 0.71, 95% CI 0.63–0.78; specificity 0.60, 95% CI 0.52–0.67; PLR 1.78, 95% CI 1.44–2.20; NLR 0.48, 95% CI 0.36–0.64) and was associated with complete POD obliteration (p < 0.001). The between-route sensitivity difference was inconclusive (0.19, 95% CI −0.01 to 0.38). In the exploratory overlap-weighted analysis of nulliparous patients (n = 217), the association remained significant (weighted OR = 2.80, 95% CI 1.17–6.69; p = 0.021), without significant sliding sign-by-route interaction (p = 0.302); findings were consistent in the matching sensitivity analysis (66 pairs). Conclusions: The sliding sign was associated with surgically confirmed complete POD obliteration in patients with ovarian endometriomas, but evidence that this association differed between route-defined groups was inconclusive. Route-specific findings are exploratory because the examination route was determined by sexual history rather than randomization. Whether TRS offers performance comparable to TVS remains undetermined, because the two techniques were not evaluated in the same population and TRS feasibility was not formally assessed. 2026-09-17 Medicina, Vol. 62, Pages 1791: Ultrasound Sliding Sign Assessed by Transvaginal or Transrectal Route for Predicting Complete Pouch of Douglas Obliteration in Patients with Ovarian Endometriomas: An Exploratory Retrospective Study

Medicina doi: 10.3390/medicina62091791

Authors: Dong Liu Huanli He Yuebo Yang Qingjian Ye

Background and Objective: The ultrasound sliding sign dynamically assesses pouch of Douglas (POD) obliteration in suspected endometriosis. Transvaginal (TVS) and transrectal (TRS) ultrasound are used in patients with and without a self-reported history of vaginal intercourse, respectively, and thus in clinically distinct populations. We evaluated sliding sign performance for predicting surgically confirmed complete POD obliteration in patients with ovarian endometriomas and described findings in route-defined TVS and TRS groups. Materials and Methods: This retrospective cohort study enrolled 318 patients with surgically and pathologically confirmed ovarian endometriomas; intraoperative POD status was evaluable in 309. Patients with and without a self-reported history of vaginal intercourse underwent TVS (n = 247) and TRS (n = 71), respectively. A negative sliding sign (absent movement between the uterus and rectum) was the positive index test result for complete POD obliteration. The unadjusted full-cohort diagnostic accuracy analysis was the primary analysis. Because no parous patient underwent TRS (a lack of overlap in examination-route assignment among parous patients), exploratory adjusted analyses were restricted to nulliparous patients, using overlap weighting (principal adjusted analysis) and 1:1 propensity score matching (sensitivity analysis). Results: In the primary unadjusted analysis of the full cohort (n = 309), the negative sliding sign showed limited to moderate discriminative ability (sensitivity 0.71, 95% CI 0.63–0.78; specificity 0.60, 95% CI 0.52–0.67; PLR 1.78, 95% CI 1.44–2.20; NLR 0.48, 95% CI 0.36–0.64) and was associated with complete POD obliteration (p < 0.001). The between-route sensitivity difference was inconclusive (0.19, 95% CI −0.01 to 0.38). In the exploratory overlap-weighted analysis of nulliparous patients (n = 217), the association remained significant (weighted OR = 2.80, 95% CI 1.17–6.69; p = 0.021), without significant sliding sign-by-route interaction (p = 0.302); findings were consistent in the matching sensitivity analysis (66 pairs). Conclusions: The sliding sign was associated with surgically confirmed complete POD obliteration in patients with ovarian endometriomas, but evidence that this association differed between route-defined groups was inconclusive. Route-specific findings are exploratory because the examination route was determined by sexual history rather than randomization. Whether TRS offers performance comparable to TVS remains undetermined, because the two techniques were not evaluated in the same population and TRS feasibility was not formally assessed.

]]> Ultrasound Sliding Sign Assessed by Transvaginal or Transrectal Route for Predicting Complete Pouch of Douglas Obliteration in Patients with Ovarian Endometriomas: An Exploratory Retrospective Study Dong Liu Huanli He Yuebo Yang Qingjian Ye doi: 10.3390/medicina62091791 Medicina 2026-09-17 Medicina 2026-09-17 62 9 Article 1791 10.3390/medicina62091791 https://www.mdpi.com/1648-9144/62/9/1791 Medicina, Vol. 62, Pages 1790: Augmented Reality, Mixed Reality, Computer Vision, and Three-Dimensional Modeling in Fertility-Preserving Minimally Invasive Gynecologic Surgery: A Scoping Review with Narrative Synthesis https://www.mdpi.com/1648-9144/62/9/1790 Background and Objectives: Augmented reality (AR), mixed reality (MR), computer vision, artificial intelligence (AI), and three-dimensional (3D) modeling may be particularly relevant in fertility-preserving gynecologic surgery, where disease must be treated while uterine architecture, reproductive anatomy, and future fertility potential are preserved. This scoping review mapped and appraised the current evidence, with emphasis on myomectomy, adenomyomectomy, and endometriosis surgery. Materials and Methods: A scoping review with narrative synthesis was conducted and reported according to the PRISMA Extension for Scoping Reviews (PRISMA-ScR). PubMed/MEDLINE, Scopus, and Google Scholar were searched from database inception to 16 May 2026. Records were appraised with design-appropriate instruments: Joanna Briggs Institute (JBI) principles, Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I), randomized-trial risk-of-bias domains, and structured feasibility criteria. Results: Of 528 records identified, 20 were included. Eleven involved application of the technology in the care of patients; of these, only two were comparative—one retrospective matched case–control study of AR-assisted myomectomy and adenomyomectomy, and one single-center randomized controlled trial of 3D-printed model-assisted myomectomy. The remaining nine were enabling technologies validated on image datasets, operative video, ex vivo models, or animal models. Only one study reported a reproductive outcome—pregnancy rates in a retrospective matched series of 34 patients, which did not differ between groups—and no study reported live birth, obstetric, or long-term reproductive-safety outcomes. Conclusions: Current evidence supports technical feasibility and preoperative planning value but does not demonstrate improvement in reproductive outcomes; here “fertility-preserving” denotes the clinical context of the surgery rather than a demonstrated reproductive benefit. Adequately powered controlled studies reporting fertility-relevant endpoints are required. 2026-09-17 Medicina, Vol. 62, Pages 1790: Augmented Reality, Mixed Reality, Computer Vision, and Three-Dimensional Modeling in Fertility-Preserving Minimally Invasive Gynecologic Surgery: A Scoping Review with Narrative Synthesis

Medicina doi: 10.3390/medicina62091790

Authors: Eleni Karatrasoglou Alexandros Rodolakis Themistoklis Grigoriadis Athanasios Protopapas

Background and Objectives: Augmented reality (AR), mixed reality (MR), computer vision, artificial intelligence (AI), and three-dimensional (3D) modeling may be particularly relevant in fertility-preserving gynecologic surgery, where disease must be treated while uterine architecture, reproductive anatomy, and future fertility potential are preserved. This scoping review mapped and appraised the current evidence, with emphasis on myomectomy, adenomyomectomy, and endometriosis surgery. Materials and Methods: A scoping review with narrative synthesis was conducted and reported according to the PRISMA Extension for Scoping Reviews (PRISMA-ScR). PubMed/MEDLINE, Scopus, and Google Scholar were searched from database inception to 16 May 2026. Records were appraised with design-appropriate instruments: Joanna Briggs Institute (JBI) principles, Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I), randomized-trial risk-of-bias domains, and structured feasibility criteria. Results: Of 528 records identified, 20 were included. Eleven involved application of the technology in the care of patients; of these, only two were comparative—one retrospective matched case–control study of AR-assisted myomectomy and adenomyomectomy, and one single-center randomized controlled trial of 3D-printed model-assisted myomectomy. The remaining nine were enabling technologies validated on image datasets, operative video, ex vivo models, or animal models. Only one study reported a reproductive outcome—pregnancy rates in a retrospective matched series of 34 patients, which did not differ between groups—and no study reported live birth, obstetric, or long-term reproductive-safety outcomes. Conclusions: Current evidence supports technical feasibility and preoperative planning value but does not demonstrate improvement in reproductive outcomes; here “fertility-preserving” denotes the clinical context of the surgery rather than a demonstrated reproductive benefit. Adequately powered controlled studies reporting fertility-relevant endpoints are required.

]]> Augmented Reality, Mixed Reality, Computer Vision, and Three-Dimensional Modeling in Fertility-Preserving Minimally Invasive Gynecologic Surgery: A Scoping Review with Narrative Synthesis Eleni Karatrasoglou Alexandros Rodolakis Themistoklis Grigoriadis Athanasios Protopapas doi: 10.3390/medicina62091790 Medicina 2026-09-17 Medicina 2026-09-17 62 9 Review 1790 10.3390/medicina62091790 https://www.mdpi.com/1648-9144/62/9/1790 Medicina, Vol. 62, Pages 1789: Individualizing Perioperative Analgesia: Patient-Specific Determinants of Postoperative Pain and Opioid-Related Outcomes https://www.mdpi.com/1648-9144/62/9/1789 Background and Objectives: Postoperative pain and opioid requirements can vary widely, even among patients undergoing similar procedures. This narrative review examines how biological sex, age, frailty, chronic pain, preoperative opioid exposure, and psychological factors may affect postoperative pain, opioid response, and recovery. Materials and Methods: PubMed and Google Scholar were searched from database inception through 18 June 2026. Relevant systematic reviews, meta-analyses, clinical guidelines, randomized trials, and observational studies involving adult surgical patients were included, with a focus on postoperative pain, opioid use, adverse effects, persistent pain, and functional recovery. Human perioperative evidence was prioritized, while experimental and preclinical evidence was used selectively to explain relevant biological mechanisms. Results: The available evidence was heterogeneous across patient populations, surgical procedures, analgesic techniques, and outcome definitions. No single patient characteristic consistently predicts postoperative pain or opioid requirements. Female sex is associated with a greater risk of postoperative nausea and vomiting, but reported differences in pain and opioid efficacy are inconsistent. Older and frail patients may be more susceptible to sedation, respiratory depression, delirium, and other opioid-related adverse effects. Patients with chronic pain or prior opioid exposure often have more difficult postoperative pain control because of tolerance, dependence, or possible opioid-induced hyperalgesia. Anxiety, depression, and pain catastrophizing may also contribute to greater pain and poorer recovery, although their relationship with opioid consumption is less consistent. Conclusions: Perioperative analgesia should be based on the patient’s overall clinical picture rather than any single risk factor. The proposed framework is conceptual and has not been clinically validated. Considering these characteristics together may help clinicians select appropriate multimodal treatments, anticipate analgesic needs, monitor for adverse effects, and support recovery. 2026-09-17 Medicina, Vol. 62, Pages 1789: Individualizing Perioperative Analgesia: Patient-Specific Determinants of Postoperative Pain and Opioid-Related Outcomes

Medicina doi: 10.3390/medicina62091789

Authors: Sarah Kazemeini Ryan Shih Sunny Zhang Raphael Cohen Nathaniel LaBarre Moonis Ghani George Tsao

Background and Objectives: Postoperative pain and opioid requirements can vary widely, even among patients undergoing similar procedures. This narrative review examines how biological sex, age, frailty, chronic pain, preoperative opioid exposure, and psychological factors may affect postoperative pain, opioid response, and recovery. Materials and Methods: PubMed and Google Scholar were searched from database inception through 18 June 2026. Relevant systematic reviews, meta-analyses, clinical guidelines, randomized trials, and observational studies involving adult surgical patients were included, with a focus on postoperative pain, opioid use, adverse effects, persistent pain, and functional recovery. Human perioperative evidence was prioritized, while experimental and preclinical evidence was used selectively to explain relevant biological mechanisms. Results: The available evidence was heterogeneous across patient populations, surgical procedures, analgesic techniques, and outcome definitions. No single patient characteristic consistently predicts postoperative pain or opioid requirements. Female sex is associated with a greater risk of postoperative nausea and vomiting, but reported differences in pain and opioid efficacy are inconsistent. Older and frail patients may be more susceptible to sedation, respiratory depression, delirium, and other opioid-related adverse effects. Patients with chronic pain or prior opioid exposure often have more difficult postoperative pain control because of tolerance, dependence, or possible opioid-induced hyperalgesia. Anxiety, depression, and pain catastrophizing may also contribute to greater pain and poorer recovery, although their relationship with opioid consumption is less consistent. Conclusions: Perioperative analgesia should be based on the patient’s overall clinical picture rather than any single risk factor. The proposed framework is conceptual and has not been clinically validated. Considering these characteristics together may help clinicians select appropriate multimodal treatments, anticipate analgesic needs, monitor for adverse effects, and support recovery.

]]> Individualizing Perioperative Analgesia: Patient-Specific Determinants of Postoperative Pain and Opioid-Related Outcomes Sarah Kazemeini Ryan Shih Sunny Zhang Raphael Cohen Nathaniel LaBarre Moonis Ghani George Tsao doi: 10.3390/medicina62091789 Medicina 2026-09-17 Medicina 2026-09-17 62 9 Review 1789 10.3390/medicina62091789 https://www.mdpi.com/1648-9144/62/9/1789 Medicina, Vol. 62, Pages 1788: Post-Pancreatectomy Acute Pancreatitis in Pancreatic Cancer: A Single-Center Experience https://www.mdpi.com/1648-9144/62/9/1788 Background and Objectives: In 2022, the International Study Group of Pancreatic Surgery (ISGPS) introduced a definition of postoperative acute pancreatitis (PPAP). This study aimed to assess the perioperative factors associated with clinically relevant PPAP (CR-PPAP) after pancreatoduodenectomy (PD) due to pancreatic ductal adenocarcinoma (PDAC) and to present the real-world treatment strategies for this complication. Materials and Methods: We performed a retrospective single-center analysis of 282 patients who underwent pancreatoduodenectomy for PDAC between 2010 and 2023. Results: CR-PPAP was diagnosed in 13.1% of patients. This group had significantly higher CRP (219 vs. 42 mg/L) and more frequently elevated drain amylase activity (97.3% vs. 18%). CR-PPAP was associated with significantly higher rates of reoperation (37.8% vs. 3.3%), delayed gastric emptying (73% vs. 16.3%), hemorrhage (21.6% vs. 0.8%) and pancreatic fistula (97.3% vs. 0.8%), as well as longer hospitalization (15 vs. 13 days). Antibiotics were administered significantly more often in the CR-PPAP group (86.5% vs. 6.5%), while somatostatin was used in all CR-PPAP patients and octreotide in 62.2%. Thirty-day mortality did not differ significantly between groups. In multivariate analysis, a small main pancreatic duct was the only independent factor associated with CR-PPAP. Conclusions: PPAP, as defined by the ISGPS 2022 criteria, is a relatively common complication following PD for malignancy, with a small pancreatic duct being a major risk factor. PPAP is strongly associated with other major postoperative complications and prolonged hospitalization, but not with increased mortality. Despite the frequent use of antibiotics, octreotide, and somatostatin in clinical practice, evidence-based treatment recommendations for CR-PPAP remain lacking, highlighting the need for management guidelines. 2026-09-16 Medicina, Vol. 62, Pages 1788: Post-Pancreatectomy Acute Pancreatitis in Pancreatic Cancer: A Single-Center Experience

Medicina doi: 10.3390/medicina62091788

Authors: Ewa Grudzińska Magdalena Gajda Karolina Majewska Wojciech Dubaj Sławomir Mrowiec

Background and Objectives: In 2022, the International Study Group of Pancreatic Surgery (ISGPS) introduced a definition of postoperative acute pancreatitis (PPAP). This study aimed to assess the perioperative factors associated with clinically relevant PPAP (CR-PPAP) after pancreatoduodenectomy (PD) due to pancreatic ductal adenocarcinoma (PDAC) and to present the real-world treatment strategies for this complication. Materials and Methods: We performed a retrospective single-center analysis of 282 patients who underwent pancreatoduodenectomy for PDAC between 2010 and 2023. Results: CR-PPAP was diagnosed in 13.1% of patients. This group had significantly higher CRP (219 vs. 42 mg/L) and more frequently elevated drain amylase activity (97.3% vs. 18%). CR-PPAP was associated with significantly higher rates of reoperation (37.8% vs. 3.3%), delayed gastric emptying (73% vs. 16.3%), hemorrhage (21.6% vs. 0.8%) and pancreatic fistula (97.3% vs. 0.8%), as well as longer hospitalization (15 vs. 13 days). Antibiotics were administered significantly more often in the CR-PPAP group (86.5% vs. 6.5%), while somatostatin was used in all CR-PPAP patients and octreotide in 62.2%. Thirty-day mortality did not differ significantly between groups. In multivariate analysis, a small main pancreatic duct was the only independent factor associated with CR-PPAP. Conclusions: PPAP, as defined by the ISGPS 2022 criteria, is a relatively common complication following PD for malignancy, with a small pancreatic duct being a major risk factor. PPAP is strongly associated with other major postoperative complications and prolonged hospitalization, but not with increased mortality. Despite the frequent use of antibiotics, octreotide, and somatostatin in clinical practice, evidence-based treatment recommendations for CR-PPAP remain lacking, highlighting the need for management guidelines.

]]> Post-Pancreatectomy Acute Pancreatitis in Pancreatic Cancer: A Single-Center Experience Ewa Grudzińska Magdalena Gajda Karolina Majewska Wojciech Dubaj Sławomir Mrowiec doi: 10.3390/medicina62091788 Medicina 2026-09-16 Medicina 2026-09-16 62 9 Article 1788 10.3390/medicina62091788 https://www.mdpi.com/1648-9144/62/9/1788 Medicina, Vol. 62, Pages 1787: Left Atrial Strain as an Integrative Marker of Diastolic Dysfunction and Atrial Fibrillation in Hypertrophic Cardiomyopathy: A Retrospective Cross-Sectional Study https://www.mdpi.com/1648-9144/62/9/1787 Background and Objectives: Echocardiographic assessment of left ventricular diastolic dysfunction (LVDD) in hypertrophic cardiomyopathy (HCM) is challenging, as conventional parameters correlate poorly with left ventricular filling pressure. Emerging evidence suggests that left atrial (LA) strain is associated with atrial fibrillation (AF). This study aimed to compare LA reservoir strain (LASr)-based and conventional LVDD grading, evaluate associations between LA strain and clinical and echocardiographic parameters, and explore its relationship with AF. Materials and Methods: This retrospective cross-sectional single-center study included 109 adult HCM patients with comprehensive echocardiographic data. LVDD was graded using conventional echocardiographic parameters and LASr-based thresholds (≥35% (grade 0), ≥24% to <35% (grade 1), ≥19% to <24% (grade 2), and <19% (grade 3)). Results: LASr-based grading revealed a significantly greater prevalence of advanced LVDD compared with conventional assessment (grade 3: 39% vs. 3%, p < 0.001), with poor intermethod agreement (κ = 0.07). Overall, approximately 45% of patients were reclassified into higher LVDD grades using LASr, particularly among nonobstructive HCM patients. Higher LASr-based LVDD grades were associated with worse conventional diastolic indices, reduced biventricular strain parameters, and higher natriuretic peptide levels. Reduced LA reservoir and conduit strain were independently associated with documented AF after adjustment for age, LA volume index, and left ventricular mass index. Conclusions: LASr provides additional information on diastolic dysfunction in HCM patients and is associated with documented AF. LASr-based grading assigned more patients to advanced LVDD grades than conventional assessment. The observed association with AF requires prospective validation before LA strain can be used for risk stratification. 2026-09-16 Medicina, Vol. 62, Pages 1787: Left Atrial Strain as an Integrative Marker of Diastolic Dysfunction and Atrial Fibrillation in Hypertrophic Cardiomyopathy: A Retrospective Cross-Sectional Study

Medicina doi: 10.3390/medicina62091787

Authors: Eglė Tamulėnaitė-Stuokė Joana Ažukaitė Marius Šukys Eglė Ereminienė

Background and Objectives: Echocardiographic assessment of left ventricular diastolic dysfunction (LVDD) in hypertrophic cardiomyopathy (HCM) is challenging, as conventional parameters correlate poorly with left ventricular filling pressure. Emerging evidence suggests that left atrial (LA) strain is associated with atrial fibrillation (AF). This study aimed to compare LA reservoir strain (LASr)-based and conventional LVDD grading, evaluate associations between LA strain and clinical and echocardiographic parameters, and explore its relationship with AF. Materials and Methods: This retrospective cross-sectional single-center study included 109 adult HCM patients with comprehensive echocardiographic data. LVDD was graded using conventional echocardiographic parameters and LASr-based thresholds (≥35% (grade 0), ≥24% to <35% (grade 1), ≥19% to <24% (grade 2), and <19% (grade 3)). Results: LASr-based grading revealed a significantly greater prevalence of advanced LVDD compared with conventional assessment (grade 3: 39% vs. 3%, p < 0.001), with poor intermethod agreement (κ = 0.07). Overall, approximately 45% of patients were reclassified into higher LVDD grades using LASr, particularly among nonobstructive HCM patients. Higher LASr-based LVDD grades were associated with worse conventional diastolic indices, reduced biventricular strain parameters, and higher natriuretic peptide levels. Reduced LA reservoir and conduit strain were independently associated with documented AF after adjustment for age, LA volume index, and left ventricular mass index. Conclusions: LASr provides additional information on diastolic dysfunction in HCM patients and is associated with documented AF. LASr-based grading assigned more patients to advanced LVDD grades than conventional assessment. The observed association with AF requires prospective validation before LA strain can be used for risk stratification.

]]> Left Atrial Strain as an Integrative Marker of Diastolic Dysfunction and Atrial Fibrillation in Hypertrophic Cardiomyopathy: A Retrospective Cross-Sectional Study Eglė Tamulėnaitė-Stuokė Joana Ažukaitė Marius Šukys Eglė Ereminienė doi: 10.3390/medicina62091787 Medicina 2026-09-16 Medicina 2026-09-16 62 9 Article 1787 10.3390/medicina62091787 https://www.mdpi.com/1648-9144/62/9/1787 Medicina, Vol. 62, Pages 1786: Initial Experience with Standalone Thoracoscopic Left Atrial Appendage Occlusion Using AtriClip Pro2: A Single-Center Retrospective Cohort Study in Latvia https://www.mdpi.com/1648-9144/62/9/1786 Background and Objectives: Left atrial appendage (LAA) closure is an established strategy for stroke prevention in selected patients with atrial fibrillation (AF), particularly when long-term oral anticoagulation (OAC) is contraindicated. Thoracoscopic epicardial LAA occlusion using the AtriClip Pro2 device provides a minimally invasive surgical approach; however, evidence for standalone use remains limited. This study aimed to describe the initial feasibility and early clinical outcomes of standalone thoracoscopic LAA occlusion using AtriClip Pro2 in Latvia. Materials and Methods: We performed a single-center retrospective observational study including all consecutive patients who underwent standalone thoracoscopic LAA occlusion at the Department of Cardiac Surgery, Pauls Stradins Clinical University Hospital, between December 2024 and March 2026. Baseline characteristics, procedural outcomes, perioperative complications, rehospitalizations, and antithrombotic therapy status were assessed. LAA closure was assessed by transesophageal echocardiography (TEE). Results: Fourteen patients were included. Mean age was 63.6 ± 16.7 years (median 67.0; IQR 54.8–76.8), and 64.3% were female. Thoracoscopic completion was achieved in 13/14 patients (92.9%; 95% CI 68.5–98.7%); one patient (7.1%) required conversion to median sternotomy because of intraoperative bleeding. Complete LAA exclusion without residual flow or stump was documented in all 14 patients (100%; 95% CI 78.5–100%). No perioperative stroke or mortality occurred. At three months, follow-up data were available for all patients, and antithrombotic therapy had been discontinued in 12/14 patients (85.7%). Conclusions: This small, heterogeneous, single-center series supports the technical feasibility of standalone thoracoscopic AtriClip Pro2 implantation in selected patients. These encouraging early findings warrant further evaluation in larger cohorts with longer clinical follow-up and standardized postoperative imaging. 2026-09-16 Medicina, Vol. 62, Pages 1786: Initial Experience with Standalone Thoracoscopic Left Atrial Appendage Occlusion Using AtriClip Pro2: A Single-Center Retrospective Cohort Study in Latvia

Medicina doi: 10.3390/medicina62091786

Authors: Diāna Kalniņa Kaspars Kupics Renāta Rimdjonoka Inga Urtāne Daniels Siļčonoks Andrejs Ērglis Pēteris Stradiņš

Background and Objectives: Left atrial appendage (LAA) closure is an established strategy for stroke prevention in selected patients with atrial fibrillation (AF), particularly when long-term oral anticoagulation (OAC) is contraindicated. Thoracoscopic epicardial LAA occlusion using the AtriClip Pro2 device provides a minimally invasive surgical approach; however, evidence for standalone use remains limited. This study aimed to describe the initial feasibility and early clinical outcomes of standalone thoracoscopic LAA occlusion using AtriClip Pro2 in Latvia. Materials and Methods: We performed a single-center retrospective observational study including all consecutive patients who underwent standalone thoracoscopic LAA occlusion at the Department of Cardiac Surgery, Pauls Stradins Clinical University Hospital, between December 2024 and March 2026. Baseline characteristics, procedural outcomes, perioperative complications, rehospitalizations, and antithrombotic therapy status were assessed. LAA closure was assessed by transesophageal echocardiography (TEE). Results: Fourteen patients were included. Mean age was 63.6 ± 16.7 years (median 67.0; IQR 54.8–76.8), and 64.3% were female. Thoracoscopic completion was achieved in 13/14 patients (92.9%; 95% CI 68.5–98.7%); one patient (7.1%) required conversion to median sternotomy because of intraoperative bleeding. Complete LAA exclusion without residual flow or stump was documented in all 14 patients (100%; 95% CI 78.5–100%). No perioperative stroke or mortality occurred. At three months, follow-up data were available for all patients, and antithrombotic therapy had been discontinued in 12/14 patients (85.7%). Conclusions: This small, heterogeneous, single-center series supports the technical feasibility of standalone thoracoscopic AtriClip Pro2 implantation in selected patients. These encouraging early findings warrant further evaluation in larger cohorts with longer clinical follow-up and standardized postoperative imaging.

]]> Initial Experience with Standalone Thoracoscopic Left Atrial Appendage Occlusion Using AtriClip Pro2: A Single-Center Retrospective Cohort Study in Latvia Diāna Kalniņa Kaspars Kupics Renāta Rimdjonoka Inga Urtāne Daniels Siļčonoks Andrejs Ērglis Pēteris Stradiņš doi: 10.3390/medicina62091786 Medicina 2026-09-16 Medicina 2026-09-16 62 9 Article 1786 10.3390/medicina62091786 https://www.mdpi.com/1648-9144/62/9/1786 Medicina, Vol. 62, Pages 1785: Perioperative Hydrogen Inhalation and Postoperative Pain After Endoscopic Discectomy: A Pilot Non-Randomized Clinical Study with Exploratory Murine Data https://www.mdpi.com/1648-9144/62/9/1785 Background/Objectives: Postoperative pain after endoscopic discectomy may reflect acute surgical nociception superimposed on pre-existing radicular symptoms. Molecular hydrogen (H2) has antioxidant and anti-inflammatory properties, but clinical evidence for perioperative analgesia is limited. We evaluated the association between perioperative H2 inhalation and postoperative pain and analgesic requirements. Methods: This open-label, non-randomized pilot study enrolled 37 patients in two consecutive periods (H2, n = 25; control, n = 12). Because original outcome records for 12 H2-period participants could no longer be retrieved at the time of manuscript preparation, the complete-case clinical analysis included 25 source-verifiable participants (H2, n = 13; control, n = 12). H2 was delivered via nasal cannula as a 66.7% H2/33.3% O2 source gas at 2 L/min (estimated inspired H2 approximately 4%). Pain was evaluated with a numerical rating scale (NRS) preoperatively, at post-anesthesia care unit (PACU) arrival, at 1, 6, 12, and 24 h, and at 1 month. Longitudinal scores were analyzed using generalized estimating equations with Holm-adjusted comparisons. A parallel exploratory murine chronic constriction injury (CCI) experiment (n = 6/group) assessed mechanical allodynia over 14 days of daily H2 inhalation. Results: The group-by-time interaction was significant (Wald χ2(6) = 56.68, p < 0.001). After Holm adjustment, pain scores were lower with H2 at PACU arrival (difference, −3.21; adjusted p = 0.002), 1 h (−2.42; adjusted p = 0.004), and 1 month (−3.45; adjusted p < 0.001). Intraoperative fentanyl use and rescue analgesic use were also lower in the H2 group; no adverse events were documented in the analyzed cohort. In the murine CCI experiment, H2-treated mice showed higher ipsilateral paw withdrawal thresholds than air-exposed controls. Conclusions: Perioperative H2 inhalation was associated with lower pain scores at selected time points and reduced analgesic requirements. These preliminary findings require confirmation in randomized trials. Trial registration: ClinicalTrials.gov NCT05476575. 2026-09-16 Medicina, Vol. 62, Pages 1785: Perioperative Hydrogen Inhalation and Postoperative Pain After Endoscopic Discectomy: A Pilot Non-Randomized Clinical Study with Exploratory Murine Data

Medicina doi: 10.3390/medicina62091785

Authors: Chao-Hsien Sung Wen-Chin Ko Chia-Chi Kung Chi-Feng Hung

Background/Objectives: Postoperative pain after endoscopic discectomy may reflect acute surgical nociception superimposed on pre-existing radicular symptoms. Molecular hydrogen (H2) has antioxidant and anti-inflammatory properties, but clinical evidence for perioperative analgesia is limited. We evaluated the association between perioperative H2 inhalation and postoperative pain and analgesic requirements. Methods: This open-label, non-randomized pilot study enrolled 37 patients in two consecutive periods (H2, n = 25; control, n = 12). Because original outcome records for 12 H2-period participants could no longer be retrieved at the time of manuscript preparation, the complete-case clinical analysis included 25 source-verifiable participants (H2, n = 13; control, n = 12). H2 was delivered via nasal cannula as a 66.7% H2/33.3% O2 source gas at 2 L/min (estimated inspired H2 approximately 4%). Pain was evaluated with a numerical rating scale (NRS) preoperatively, at post-anesthesia care unit (PACU) arrival, at 1, 6, 12, and 24 h, and at 1 month. Longitudinal scores were analyzed using generalized estimating equations with Holm-adjusted comparisons. A parallel exploratory murine chronic constriction injury (CCI) experiment (n = 6/group) assessed mechanical allodynia over 14 days of daily H2 inhalation. Results: The group-by-time interaction was significant (Wald χ2(6) = 56.68, p < 0.001). After Holm adjustment, pain scores were lower with H2 at PACU arrival (difference, −3.21; adjusted p = 0.002), 1 h (−2.42; adjusted p = 0.004), and 1 month (−3.45; adjusted p < 0.001). Intraoperative fentanyl use and rescue analgesic use were also lower in the H2 group; no adverse events were documented in the analyzed cohort. In the murine CCI experiment, H2-treated mice showed higher ipsilateral paw withdrawal thresholds than air-exposed controls. Conclusions: Perioperative H2 inhalation was associated with lower pain scores at selected time points and reduced analgesic requirements. These preliminary findings require confirmation in randomized trials. Trial registration: ClinicalTrials.gov NCT05476575.

]]> Perioperative Hydrogen Inhalation and Postoperative Pain After Endoscopic Discectomy: A Pilot Non-Randomized Clinical Study with Exploratory Murine Data Chao-Hsien Sung Wen-Chin Ko Chia-Chi Kung Chi-Feng Hung doi: 10.3390/medicina62091785 Medicina 2026-09-16 Medicina 2026-09-16 62 9 Article 1785 10.3390/medicina62091785 https://www.mdpi.com/1648-9144/62/9/1785 Medicina, Vol. 62, Pages 1784: Clinical Outcomes of Ultrasound-Guided Stellate Ganglion Block in Highly Treatment-Resistant Chronic Migraine: A 6-Month Prospective Single-Group Interventional Study https://www.mdpi.com/1648-9144/62/9/1784 Background and Objectives: Chronic migraine (CM) remains a major cause of neurological disability, and a subset of patients remains highly treatment-resistant despite previous preventive and interventional treatments. Stellate ganglion block (SGB) has been proposed as a sympathetic neuromodulatory intervention, but evidence in this population remains limited. This study evaluated 6-month clinical outcomes and tolerability after a structured ultrasound-guided SGB protocol. Materials and Methods: This prospective, single-center, uncontrolled, single-group interventional study enrolled 42 adults with CM who had experienced insufficient benefit from prior preventive migraine treatment and previous interventional headache procedures. After an initial ultrasound-guided SGB to assess anatomical suitability and procedural tolerability, all participants proceeded to four additional weekly ultrasound-guided SGB sessions using 5 mL of 1% lidocaine, for five protocol-defined sessions in total. The primary outcome was the change in monthly headache days (MHD) from baseline to 6 months. Results: All 42 participants (mean age: 44.4 ± 7.4 years) completed the 6-month follow-up. Median MHD decreased from 29.0 days at baseline to 6.0 days at 6 months (Kendall’s W = 0.643, p < 0.001), corresponding to a median within-participant reduction of 17.0 days (BCa 95% CI: 13.0–19.0). A ≥50% reduction in MHD was achieved by 73.8% of participants (95% CI: 58.9–84.7) at 6 months, whereas 14.3% (95% CI: 6.7–27.8) achieved a ≥50% reduction in mean pain intensity. HIT-6 and MIDAS scores also improved significantly (p < 0.001). Six participants (14.3%) reported mild, self-limited adverse effects; no serious adverse events were documented. Conclusions: Ultrasound-guided SGB was associated with sustained reductions in headache frequency, analgesic use, and migraine-related disability over 6 months. Because this was an uncontrolled single-group study, the findings should be considered preliminary and hypothesis-generating. The frequency-dominant pattern of improvement and favorable tolerability support further controlled evaluation of SGB as a potential adjunctive neuromodulatory strategy in highly treatment-resistant CM. 2026-09-16 Medicina, Vol. 62, Pages 1784: Clinical Outcomes of Ultrasound-Guided Stellate Ganglion Block in Highly Treatment-Resistant Chronic Migraine: A 6-Month Prospective Single-Group Interventional Study

Medicina doi: 10.3390/medicina62091784

Authors: Sukriye Dadali Emel Basar Ulku Sabuncu Gulcin Babaoglu Ali Costu Erkan Yavuz Akcaboy

Background and Objectives: Chronic migraine (CM) remains a major cause of neurological disability, and a subset of patients remains highly treatment-resistant despite previous preventive and interventional treatments. Stellate ganglion block (SGB) has been proposed as a sympathetic neuromodulatory intervention, but evidence in this population remains limited. This study evaluated 6-month clinical outcomes and tolerability after a structured ultrasound-guided SGB protocol. Materials and Methods: This prospective, single-center, uncontrolled, single-group interventional study enrolled 42 adults with CM who had experienced insufficient benefit from prior preventive migraine treatment and previous interventional headache procedures. After an initial ultrasound-guided SGB to assess anatomical suitability and procedural tolerability, all participants proceeded to four additional weekly ultrasound-guided SGB sessions using 5 mL of 1% lidocaine, for five protocol-defined sessions in total. The primary outcome was the change in monthly headache days (MHD) from baseline to 6 months. Results: All 42 participants (mean age: 44.4 ± 7.4 years) completed the 6-month follow-up. Median MHD decreased from 29.0 days at baseline to 6.0 days at 6 months (Kendall’s W = 0.643, p < 0.001), corresponding to a median within-participant reduction of 17.0 days (BCa 95% CI: 13.0–19.0). A ≥50% reduction in MHD was achieved by 73.8% of participants (95% CI: 58.9–84.7) at 6 months, whereas 14.3% (95% CI: 6.7–27.8) achieved a ≥50% reduction in mean pain intensity. HIT-6 and MIDAS scores also improved significantly (p < 0.001). Six participants (14.3%) reported mild, self-limited adverse effects; no serious adverse events were documented. Conclusions: Ultrasound-guided SGB was associated with sustained reductions in headache frequency, analgesic use, and migraine-related disability over 6 months. Because this was an uncontrolled single-group study, the findings should be considered preliminary and hypothesis-generating. The frequency-dominant pattern of improvement and favorable tolerability support further controlled evaluation of SGB as a potential adjunctive neuromodulatory strategy in highly treatment-resistant CM.

]]> Clinical Outcomes of Ultrasound-Guided Stellate Ganglion Block in Highly Treatment-Resistant Chronic Migraine: A 6-Month Prospective Single-Group Interventional Study Sukriye Dadali Emel Basar Ulku Sabuncu Gulcin Babaoglu Ali Costu Erkan Yavuz Akcaboy doi: 10.3390/medicina62091784 Medicina 2026-09-16 Medicina 2026-09-16 62 9 Article 1784 10.3390/medicina62091784 https://www.mdpi.com/1648-9144/62/9/1784 Medicina, Vol. 62, Pages 1783: Artificial Intelligence for Precision Antiarrhythmic Drug Therapy in Atrial Fibrillation: From Recurrence Prediction to Comparative Treatment Selection https://www.mdpi.com/1648-9144/62/9/1783 Rhythm control therapy has an important role in atrial fibrillation (AF) management, and antiarrhythmic drugs (AADs) remain essential for pharmacological cardioversion, maintenance of sinus rhythm, reduction in AF burden, and treatment before or after catheter ablation. However, their efficacy varies substantially among patients, while proarrhythmia, organ toxicity, drug interactions, and treatment discontinuation frequently limit their use. Current drug selection therefore relies mainly on safety-based exclusion based on structural heart disease, ventricular function, coronary disease, renal or hepatic function, and baseline conduction and repolarization characteristics, rather than on individualized prediction of comparative therapeutic benefit. This narrative review examines the potential role of artificial intelligence (AI), machine learning (ML), computational electrophysiology, and cardiac digital twins across the AAD treatment pathway. Particular attention is given to patient selection, comparative drug choice, prediction of cardioversion success and sinus-rhythm maintenance, dose optimization, proarrhythmia assessment, extracardiac toxicity, and longitudinal safety surveillance. AI can potentially integrate clinical, electrocardiographic (ECG), imaging, wearable, genomic, and pharmacological data to estimate patient-specific efficacy and toxicity. ML models have already demonstrated the feasibility of predicting drug-induced QT prolongation from electronic health records and detecting ECG signatures associated with drug-induced arrhythmic risk. Moreover, patient-specific AF digital twins have been used to simulate electrophysiological responses to amiodarone and identify patients with different subsequent rhythm outcomes. Nevertheless, most available applications remain retrospective, single-center, non-comparative, or proof-of-concept, and few directly support selection among alternative AADs. Most are prognostic, estimate outcomes under observed care, or predict drug-specific toxicity; models that estimate outcomes under alternative AADs remain the essential missing element. AI-supported antiarrhythmic therapy represents a promising transition from population-based prescribing toward individualized estimation of efficacy, toxicity, and monitoring requirements. Its clinical adoption will require multicenter external validation, causal treatment-effect modeling, prospective workflow evaluation, randomized impact trials, transparent uncertainty reporting, and continued clinician oversight. 2026-09-16 Medicina, Vol. 62, Pages 1783: Artificial Intelligence for Precision Antiarrhythmic Drug Therapy in Atrial Fibrillation: From Recurrence Prediction to Comparative Treatment Selection

Medicina doi: 10.3390/medicina62091783

Authors: Alina Scridon Vasile-Bogdan Halațiu Dan-Alexandru Cozac

Rhythm control therapy has an important role in atrial fibrillation (AF) management, and antiarrhythmic drugs (AADs) remain essential for pharmacological cardioversion, maintenance of sinus rhythm, reduction in AF burden, and treatment before or after catheter ablation. However, their efficacy varies substantially among patients, while proarrhythmia, organ toxicity, drug interactions, and treatment discontinuation frequently limit their use. Current drug selection therefore relies mainly on safety-based exclusion based on structural heart disease, ventricular function, coronary disease, renal or hepatic function, and baseline conduction and repolarization characteristics, rather than on individualized prediction of comparative therapeutic benefit. This narrative review examines the potential role of artificial intelligence (AI), machine learning (ML), computational electrophysiology, and cardiac digital twins across the AAD treatment pathway. Particular attention is given to patient selection, comparative drug choice, prediction of cardioversion success and sinus-rhythm maintenance, dose optimization, proarrhythmia assessment, extracardiac toxicity, and longitudinal safety surveillance. AI can potentially integrate clinical, electrocardiographic (ECG), imaging, wearable, genomic, and pharmacological data to estimate patient-specific efficacy and toxicity. ML models have already demonstrated the feasibility of predicting drug-induced QT prolongation from electronic health records and detecting ECG signatures associated with drug-induced arrhythmic risk. Moreover, patient-specific AF digital twins have been used to simulate electrophysiological responses to amiodarone and identify patients with different subsequent rhythm outcomes. Nevertheless, most available applications remain retrospective, single-center, non-comparative, or proof-of-concept, and few directly support selection among alternative AADs. Most are prognostic, estimate outcomes under observed care, or predict drug-specific toxicity; models that estimate outcomes under alternative AADs remain the essential missing element. AI-supported antiarrhythmic therapy represents a promising transition from population-based prescribing toward individualized estimation of efficacy, toxicity, and monitoring requirements. Its clinical adoption will require multicenter external validation, causal treatment-effect modeling, prospective workflow evaluation, randomized impact trials, transparent uncertainty reporting, and continued clinician oversight.

]]> Artificial Intelligence for Precision Antiarrhythmic Drug Therapy in Atrial Fibrillation: From Recurrence Prediction to Comparative Treatment Selection Alina Scridon Vasile-Bogdan Halațiu Dan-Alexandru Cozac doi: 10.3390/medicina62091783 Medicina 2026-09-16 Medicina 2026-09-16 62 9 Review 1783 10.3390/medicina62091783 https://www.mdpi.com/1648-9144/62/9/1783 Medicina, Vol. 62, Pages 1782: Management and Clinical Outcomes of Liver Hemangiomas: A Retrospective Comparative Study of Transcatheter Arterial Embolization and Surgery https://www.mdpi.com/1648-9144/62/9/1782 Background and Objectives: Hemangiomas are the most common benign tumors of the liver. Surgical options such as enucleation, segmentectomy, and hepatectomy are the primary treatment choices, though the morbidity and complication rates remain high. Transcatheter arterial embolization (TAE) has emerged as a safe and effective alternative treatment option that has gained popularity in recent years. Materials and Methods: We retrospectively evaluated data from patients who underwent either surgical intervention (n = 19) or transarterial embolization (62 lesions in 61 patients; analyses performed per treated lesion) for liver hemangioma between 2003 and 2021. Outcomes were assessed separately for each modality without a composite efficacy endpoint: clinical success (relief of the presenting symptoms, assessed in patients symptomatic at baseline), technical success and radiological response for embolization, treatment-related complications, length of hospital stay, and the need for reintervention. Results: There was no significant difference in the pretreatment size of the lesions between the TAE and surgery groups (median of 10.0 [IQR 7.8–13.9] versus 10.0 [IQR 9.0–17.0] cm; p = 0.100). The length of hospital stay was shorter in the TAE group (median of 1 versus 6 days; p < 0.001), although era-related differences in perioperative care may contribute to this difference, and follow-up was longer in surgically treated patients, reflecting the later adoption of embolization at our institution. Postoperative mortality did not occur in either group. In the embolization group, there were significant reductions in lesion size and volume and the complication rate was low, with no serious complications, supporting the safety profile of TAE. Conclusions: In this retrospective, non-randomized, single-center series, transarterial embolization was found to be a safe and effective minimally invasive treatment for liver hemangiomas and was associated with a shorter hospital stay. Because treatment allocation was not randomized, we cannot establish therapeutic equivalence between the two modalities, and the comparison should be regarded as descriptive; TAE represents an effective minimally invasive treatment option in appropriately selected patients and may be considered within a multidisciplinary treatment strategy, while surgery remains necessary in selected cases such as embolization failure, complicated lesion vascularization, or localization. 2026-09-16 Medicina, Vol. 62, Pages 1782: Management and Clinical Outcomes of Liver Hemangiomas: A Retrospective Comparative Study of Transcatheter Arterial Embolization and Surgery

Medicina doi: 10.3390/medicina62091782

Authors: Sefa Ergün Fadime Kutluk Rauf Hamid Yasemin Pekmezci Seyfullah Halit Karagöz Mehmet Velidedeoğlu Server Sezgin Uludağ Ahmet Baş Fatih Gülşen Salih Pekmezci

Background and Objectives: Hemangiomas are the most common benign tumors of the liver. Surgical options such as enucleation, segmentectomy, and hepatectomy are the primary treatment choices, though the morbidity and complication rates remain high. Transcatheter arterial embolization (TAE) has emerged as a safe and effective alternative treatment option that has gained popularity in recent years. Materials and Methods: We retrospectively evaluated data from patients who underwent either surgical intervention (n = 19) or transarterial embolization (62 lesions in 61 patients; analyses performed per treated lesion) for liver hemangioma between 2003 and 2021. Outcomes were assessed separately for each modality without a composite efficacy endpoint: clinical success (relief of the presenting symptoms, assessed in patients symptomatic at baseline), technical success and radiological response for embolization, treatment-related complications, length of hospital stay, and the need for reintervention. Results: There was no significant difference in the pretreatment size of the lesions between the TAE and surgery groups (median of 10.0 [IQR 7.8–13.9] versus 10.0 [IQR 9.0–17.0] cm; p = 0.100). The length of hospital stay was shorter in the TAE group (median of 1 versus 6 days; p < 0.001), although era-related differences in perioperative care may contribute to this difference, and follow-up was longer in surgically treated patients, reflecting the later adoption of embolization at our institution. Postoperative mortality did not occur in either group. In the embolization group, there were significant reductions in lesion size and volume and the complication rate was low, with no serious complications, supporting the safety profile of TAE. Conclusions: In this retrospective, non-randomized, single-center series, transarterial embolization was found to be a safe and effective minimally invasive treatment for liver hemangiomas and was associated with a shorter hospital stay. Because treatment allocation was not randomized, we cannot establish therapeutic equivalence between the two modalities, and the comparison should be regarded as descriptive; TAE represents an effective minimally invasive treatment option in appropriately selected patients and may be considered within a multidisciplinary treatment strategy, while surgery remains necessary in selected cases such as embolization failure, complicated lesion vascularization, or localization.

]]> Management and Clinical Outcomes of Liver Hemangiomas: A Retrospective Comparative Study of Transcatheter Arterial Embolization and Surgery Sefa Ergün Fadime Kutluk Rauf Hamid Yasemin Pekmezci Seyfullah Halit Karagöz Mehmet Velidedeoğlu Server Sezgin Uludağ Ahmet Baş Fatih Gülşen Salih Pekmezci doi: 10.3390/medicina62091782 Medicina 2026-09-16 Medicina 2026-09-16 62 9 Article 1782 10.3390/medicina62091782 https://www.mdpi.com/1648-9144/62/9/1782 Medicina, Vol. 62, Pages 1780: Beyond Pain Intensity: Central Sensitization and Psychosocial Symptom Burden in Women with Rheumatoid Arthritis https://www.mdpi.com/1648-9144/62/9/1780 Background and Objectives: Persistent pain in rheumatoid arthritis (RA) may reflect mechanisms not fully captured by systemic inflammatory markers. This study estimated the frequency of elevated Central Sensitization Inventory (CSI) scores in women with RA and examined associations with pain, fatigue, depressive symptoms, function, inflammatory markers, and disease activity. Materials and Methods: This prospective single-center observational cohort included 97 female inpatients who completed a standardized three-week rehabilitation program. The CSI was used as a symptom-based screening instrument. Pain, function, fatigue, and depressive symptoms were assessed with the Visual Analog Scale (VAS), Health Assessment Questionnaire (HAQ), FACIT-Fatigue scale, and Beck Depression Inventory-II (BDI-II), respectively. Results: Fifty-seven participants (58.8%) had CSI scores ≥ 40. Higher CSI scores were associated with greater pain, more depressive symptoms, more fatigue, and higher DAS28-CRP scores, but not with ESR, CRP, IL-6, or disease duration. In adjusted baseline models, the association with VAS pain was statistically significant but modest (unstandardized beta = 0.024 per CSI point; standardized beta = 0.273). Across the three-week follow-up, VAS pain decreased by 2.53 points; mean FACIT-Fatigue and HAQ changes were smaller than commonly cited clinically important thresholds, and CSI changed only modestly. In adjusted multivariable models, higher CSI scores remained independently associated with VAS pain, FACIT-Fatigue, and BDI-II scores, whereas no significant association was found with HAQ. CSI was not associated with CRP, IL-6, or disease duration. Conclusions: In this cohort of women with RA, elevated CSI scores identified a greater self-reported symptom burden and were independently associated with pain, fatigue, and depressive symptoms after adjustment, though the pain association remained modest in magnitude. No meaningful association was found with functional disability. The uncontrolled, single-arm design and restricted inflammatory-marker range preclude causal conclusions or proof that symptoms were independent of inflammation. 2026-09-16 Medicina, Vol. 62, Pages 1780: Beyond Pain Intensity: Central Sensitization and Psychosocial Symptom Burden in Women with Rheumatoid Arthritis

Medicina doi: 10.3390/medicina62091780

Authors: Maja Vučković Dragana Kožul Tamara Popović Ivan Soldatović Sandra Trivunović Tatjana Nožica Radulović Daria Ćupurdija Snežana Tomašević Todorović

Background and Objectives: Persistent pain in rheumatoid arthritis (RA) may reflect mechanisms not fully captured by systemic inflammatory markers. This study estimated the frequency of elevated Central Sensitization Inventory (CSI) scores in women with RA and examined associations with pain, fatigue, depressive symptoms, function, inflammatory markers, and disease activity. Materials and Methods: This prospective single-center observational cohort included 97 female inpatients who completed a standardized three-week rehabilitation program. The CSI was used as a symptom-based screening instrument. Pain, function, fatigue, and depressive symptoms were assessed with the Visual Analog Scale (VAS), Health Assessment Questionnaire (HAQ), FACIT-Fatigue scale, and Beck Depression Inventory-II (BDI-II), respectively. Results: Fifty-seven participants (58.8%) had CSI scores ≥ 40. Higher CSI scores were associated with greater pain, more depressive symptoms, more fatigue, and higher DAS28-CRP scores, but not with ESR, CRP, IL-6, or disease duration. In adjusted baseline models, the association with VAS pain was statistically significant but modest (unstandardized beta = 0.024 per CSI point; standardized beta = 0.273). Across the three-week follow-up, VAS pain decreased by 2.53 points; mean FACIT-Fatigue and HAQ changes were smaller than commonly cited clinically important thresholds, and CSI changed only modestly. In adjusted multivariable models, higher CSI scores remained independently associated with VAS pain, FACIT-Fatigue, and BDI-II scores, whereas no significant association was found with HAQ. CSI was not associated with CRP, IL-6, or disease duration. Conclusions: In this cohort of women with RA, elevated CSI scores identified a greater self-reported symptom burden and were independently associated with pain, fatigue, and depressive symptoms after adjustment, though the pain association remained modest in magnitude. No meaningful association was found with functional disability. The uncontrolled, single-arm design and restricted inflammatory-marker range preclude causal conclusions or proof that symptoms were independent of inflammation.

]]> Beyond Pain Intensity: Central Sensitization and Psychosocial Symptom Burden in Women with Rheumatoid Arthritis Maja Vučković Dragana Kožul Tamara Popović Ivan Soldatović Sandra Trivunović Tatjana Nožica Radulović Daria Ćupurdija Snežana Tomašević Todorović doi: 10.3390/medicina62091780 Medicina 2026-09-16 Medicina 2026-09-16 62 9 Article 1780 10.3390/medicina62091780 https://www.mdpi.com/1648-9144/62/9/1780 Medicina, Vol. 62, Pages 1781: Improvements in Gait Function Following Integrative Korean–Western Medicine Treatment in Older Adults with Chronic Stroke: A Retrospective Exploratory Study https://www.mdpi.com/1648-9144/62/9/1781 Background and Objectives: Patients with chronic stroke aged 65 years or older and who are more than 6 months post-onset are generally considered to have reached a rehabilitation plateau, beyond which further functional improvement is difficult to achieve. This study aimed to evaluate changes in gait function before and after integrative Korean–Western medicine treatment in older adults with chronic stroke. Materials and Methods: In this single-center, retrospective, single-group pre–post observational study, we analyzed the medical records of 15 patients with chronic stroke aged ≥65 years who received integrative Korean–Western medicine treatment five times per week for 4 weeks. The primary outcome was the step length ratio, reflecting gait symmetry. Secondary outcomes included walking velocity, lateral symmetry, center of pressure (COP)-related parameters, manual muscle test (MMT) scores, and Fugl-Meyer Assessment (FMA) scores. Results: The step length ratio increased significantly from 0.61 [0.50–0.70] before treatment to 0.86 [0.62–0.94] after treatment (p = 0.009, r = 0.675). Walking velocity (p = 0.006, r = 0.715) and mean COP velocity (p = 0.007, d = −0.822) also improved significantly. In contrast, no significant changes were observed in MMT or FMA scores, and no treatment-related adverse events were recorded. Conclusions: In this retrospective, uncontrolled, single-group study, significant improvements in gait symmetry, walking velocity, and postural control were observed following integrative Korean–Western medicine treatment in older adults with chronic stroke. The improvement in gait function without a corresponding change in FMA-based motor function—although both MMT and FMA scores were relatively high at baseline, potentially limiting sensitivity to detect further motor improvement—raises the hypothesis that other mechanisms, potentially including enhanced sensorimotor integration, may have contributed to these changes; however, this mechanistic interpretation remains speculative and was not directly tested. Randomized controlled trials with appropriate control groups are warranted to further verify these findings. 2026-09-16 Medicina, Vol. 62, Pages 1781: Improvements in Gait Function Following Integrative Korean–Western Medicine Treatment in Older Adults with Chronic Stroke: A Retrospective Exploratory Study

Medicina doi: 10.3390/medicina62091781

Authors: Hyangyu Park Yeonghun Wi Cheol-Hyun Kim

Background and Objectives: Patients with chronic stroke aged 65 years or older and who are more than 6 months post-onset are generally considered to have reached a rehabilitation plateau, beyond which further functional improvement is difficult to achieve. This study aimed to evaluate changes in gait function before and after integrative Korean–Western medicine treatment in older adults with chronic stroke. Materials and Methods: In this single-center, retrospective, single-group pre–post observational study, we analyzed the medical records of 15 patients with chronic stroke aged ≥65 years who received integrative Korean–Western medicine treatment five times per week for 4 weeks. The primary outcome was the step length ratio, reflecting gait symmetry. Secondary outcomes included walking velocity, lateral symmetry, center of pressure (COP)-related parameters, manual muscle test (MMT) scores, and Fugl-Meyer Assessment (FMA) scores. Results: The step length ratio increased significantly from 0.61 [0.50–0.70] before treatment to 0.86 [0.62–0.94] after treatment (p = 0.009, r = 0.675). Walking velocity (p = 0.006, r = 0.715) and mean COP velocity (p = 0.007, d = −0.822) also improved significantly. In contrast, no significant changes were observed in MMT or FMA scores, and no treatment-related adverse events were recorded. Conclusions: In this retrospective, uncontrolled, single-group study, significant improvements in gait symmetry, walking velocity, and postural control were observed following integrative Korean–Western medicine treatment in older adults with chronic stroke. The improvement in gait function without a corresponding change in FMA-based motor function—although both MMT and FMA scores were relatively high at baseline, potentially limiting sensitivity to detect further motor improvement—raises the hypothesis that other mechanisms, potentially including enhanced sensorimotor integration, may have contributed to these changes; however, this mechanistic interpretation remains speculative and was not directly tested. Randomized controlled trials with appropriate control groups are warranted to further verify these findings.

]]> Improvements in Gait Function Following Integrative Korean–Western Medicine Treatment in Older Adults with Chronic Stroke: A Retrospective Exploratory Study Hyangyu Park Yeonghun Wi Cheol-Hyun Kim doi: 10.3390/medicina62091781 Medicina 2026-09-16 Medicina 2026-09-16 62 9 Article 1781 10.3390/medicina62091781 https://www.mdpi.com/1648-9144/62/9/1781 Medicina, Vol. 62, Pages 1779: Recurrence of Benign Vocal Fold Lesions: Risk Factors and an Exploratory Comparison of Cold-Instrument and CO2 Laser Surgery in a Retrospective Cohort https://www.mdpi.com/1648-9144/62/9/1779 Background and Objectives: Benign vocal fold lesions (BVFLs) are common causes of persistent dysphonia, but recurrence estimates are influenced by lesion type, outcome definition, and follow-up. We evaluated recurrence after documented lesion resolution and explored clinical factors and surgical technique. Materials and Methods: We performed a single-center retrospective cohort study of 214 adults with a first documented BVFL diagnosis between January 2022 and December 2024. Clinical records were reviewed through January 2026. Recurrence was defined as lesion reappearance after documented resolution at the initial post-treatment laryngeal assessment; persistent lesions were classified separately. Results: Follow-up was documented in 142 patients (66.4%). Initial lesion resolution was documented in 135 patients, of whom 23 developed recurrence (17.0%); 7 patients had persistent disease at the initial post-treatment assessment. No evaluated demographic or clinical factor was significantly associated with recurrence in univariate analyses. In the secondary exploratory surgical analysis, recurrence occurred in 7/29 patients treated with cold instruments (24.1%) and 3/27 treated with CO2 laser (11.1%; OR 2.55, 95% CI 0.58–11.08; Fisher exact p = 0.299). Conclusions: Documented recurrence after initial lesion resolution occurred in 17.0% of patients. The surgical technique comparison was underpowered and unadjusted and does not establish superiority of either technique. Variable follow-up and differential attrition should be considered when interpreting the recurrence proportion. 2026-09-16 Medicina, Vol. 62, Pages 1779: Recurrence of Benign Vocal Fold Lesions: Risk Factors and an Exploratory Comparison of Cold-Instrument and CO2 Laser Surgery in a Retrospective Cohort

Medicina doi: 10.3390/medicina62091779

Authors: Alexandru Vlase Octavian Dragos Palade Dragoș Munteanu Ionut Andrei Roman Stefan Moscalu Ana Doina Roxana Andreea Rusescu Ruxandra Oana Aliuș Catalina Voiosu

Background and Objectives: Benign vocal fold lesions (BVFLs) are common causes of persistent dysphonia, but recurrence estimates are influenced by lesion type, outcome definition, and follow-up. We evaluated recurrence after documented lesion resolution and explored clinical factors and surgical technique. Materials and Methods: We performed a single-center retrospective cohort study of 214 adults with a first documented BVFL diagnosis between January 2022 and December 2024. Clinical records were reviewed through January 2026. Recurrence was defined as lesion reappearance after documented resolution at the initial post-treatment laryngeal assessment; persistent lesions were classified separately. Results: Follow-up was documented in 142 patients (66.4%). Initial lesion resolution was documented in 135 patients, of whom 23 developed recurrence (17.0%); 7 patients had persistent disease at the initial post-treatment assessment. No evaluated demographic or clinical factor was significantly associated with recurrence in univariate analyses. In the secondary exploratory surgical analysis, recurrence occurred in 7/29 patients treated with cold instruments (24.1%) and 3/27 treated with CO2 laser (11.1%; OR 2.55, 95% CI 0.58–11.08; Fisher exact p = 0.299). Conclusions: Documented recurrence after initial lesion resolution occurred in 17.0% of patients. The surgical technique comparison was underpowered and unadjusted and does not establish superiority of either technique. Variable follow-up and differential attrition should be considered when interpreting the recurrence proportion.

]]> Recurrence of Benign Vocal Fold Lesions: Risk Factors and an Exploratory Comparison of Cold-Instrument and CO2 Laser Surgery in a Retrospective Cohort Alexandru Vlase Octavian Dragos Palade Dragoș Munteanu Ionut Andrei Roman Stefan Moscalu Ana Doina Roxana Andreea Rusescu Ruxandra Oana Aliuș Catalina Voiosu doi: 10.3390/medicina62091779 Medicina 2026-09-16 Medicina 2026-09-16 62 9 Article 1779 10.3390/medicina62091779 https://www.mdpi.com/1648-9144/62/9/1779 Medicina, Vol. 62, Pages 1778: Treatment Gaps in Women Aged 65 Years and Older with Stress or Stress-Predominant Mixed Urinary Incontinence: Age-Stratified Patterns of Active Therapy, Containment Use, Frailty, and Anxiety https://www.mdpi.com/1648-9144/62/9/1778 Background and Objectives: Older women with stress or stress-predominant mixed urinary incontinence may rely on pads or diapers despite bothersome symptoms. We examined age-stratified treatment patterns and whether age remained associated with a treatment gap after accounting for frailty and symptom burden. Materials and Methods: This single-center observational study combined record review (December 2023–April 2026) with a questionnaire assessment (19 June–3 August 2026). Within the 65–74, 75–84, and ≥85-year strata, 185, 182, and 183 women were screened; after 25, 22, and 23 exclusions or incomplete assessments, respectively, 160 evaluable women remained in each stratum. The treatment gap required International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) score ≥ 8, daily pad/diaper use, pad/diaper-only management, and no active treatment in the previous 12 months. Frailty and anxiety were assessed with the fatigue, resistance, ambulation, illnesses, and loss of weight (FRAIL) scale and Geriatric Anxiety Inventory. Results: Treatment-gap prevalence was 33.8%, 44.4%, and 55.0%. Supervised pelvic floor muscle training declined from 55.0% to 40.0% and 25.0%; recent active treatment from 50.0% to 35.0% and 20.0%; and previous continence surgery from 30.0% to 18.1% and 8.1%. After adjustment, age was not independently associated. Higher ICIQ-UI SF scores [adjusted odds ratio (aOR) 1.10 per point, 95% confidence interval (CI) 1.02–1.19] and stress-predominant mixed incontinence (aOR 1.53, 95% CI 1.03–2.25) remained associated. Conclusions: Containment dependence increased and active-treatment exposure decreased with age, but symptom burden and phenotype explained more adjusted risk than age. Regular reassessment may distinguish appropriate containment from remediable under-treatment. 2026-09-16 Medicina, Vol. 62, Pages 1778: Treatment Gaps in Women Aged 65 Years and Older with Stress or Stress-Predominant Mixed Urinary Incontinence: Age-Stratified Patterns of Active Therapy, Containment Use, Frailty, and Anxiety

Medicina doi: 10.3390/medicina62091778

Authors: Doğucan Nuri Uğur Kadir Böcü

Background and Objectives: Older women with stress or stress-predominant mixed urinary incontinence may rely on pads or diapers despite bothersome symptoms. We examined age-stratified treatment patterns and whether age remained associated with a treatment gap after accounting for frailty and symptom burden. Materials and Methods: This single-center observational study combined record review (December 2023–April 2026) with a questionnaire assessment (19 June–3 August 2026). Within the 65–74, 75–84, and ≥85-year strata, 185, 182, and 183 women were screened; after 25, 22, and 23 exclusions or incomplete assessments, respectively, 160 evaluable women remained in each stratum. The treatment gap required International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) score ≥ 8, daily pad/diaper use, pad/diaper-only management, and no active treatment in the previous 12 months. Frailty and anxiety were assessed with the fatigue, resistance, ambulation, illnesses, and loss of weight (FRAIL) scale and Geriatric Anxiety Inventory. Results: Treatment-gap prevalence was 33.8%, 44.4%, and 55.0%. Supervised pelvic floor muscle training declined from 55.0% to 40.0% and 25.0%; recent active treatment from 50.0% to 35.0% and 20.0%; and previous continence surgery from 30.0% to 18.1% and 8.1%. After adjustment, age was not independently associated. Higher ICIQ-UI SF scores [adjusted odds ratio (aOR) 1.10 per point, 95% confidence interval (CI) 1.02–1.19] and stress-predominant mixed incontinence (aOR 1.53, 95% CI 1.03–2.25) remained associated. Conclusions: Containment dependence increased and active-treatment exposure decreased with age, but symptom burden and phenotype explained more adjusted risk than age. Regular reassessment may distinguish appropriate containment from remediable under-treatment.

]]> Treatment Gaps in Women Aged 65 Years and Older with Stress or Stress-Predominant Mixed Urinary Incontinence: Age-Stratified Patterns of Active Therapy, Containment Use, Frailty, and Anxiety Doğucan Nuri Uğur Kadir Böcü doi: 10.3390/medicina62091778 Medicina 2026-09-16 Medicina 2026-09-16 62 9 Article 1778 10.3390/medicina62091778 https://www.mdpi.com/1648-9144/62/9/1778 Medicina, Vol. 62, Pages 1777: Current Diabetes Self-Management and the Number of Documented Complications in Adults with Type 2 Diabetes: A Cross-Sectional Study https://www.mdpi.com/1648-9144/62/9/1777 Background and Objectives: Current self-management behavior may not reflect the long-term exposures that led to established complications in people with type 2 diabetes (T2D). To assess whether Diabetes Self-Management Questionnaire (DSMQ) scores were associated with the number of documented diabetes-related and cardiovascular conditions and whether the finding was robust to alternative outcome constructions. Materials and Methods: This single-center cross-sectional reanalysis included 262 adults with T2D. The DSMQ was re-calculated from item-level responses. The primary outcome was an unweighted count of seven database-recorded conditions. Spearman correlation and multivariable Poisson regression with HC3 robust standard errors were used. Sensitivity analyses excluded heart failure, separated microvascular and cardiovascular counts, and substituted estimated glomerular filtration rate <60 mL/min/1.73 m2 for the recorded chronic kidney disease field. Results: Median DSMQ Sum Scale was 5.10 (IQR 3.13–7.08), and median condition count was 3 (IQR 2–3). No evidence of an unadjusted association was identified (ρ = −0.056; p = 0.368). In the adjusted model (n = 260), the DSMQ estimate was IRR 0.988 per point (95% CI 0.962–1.014; p = 0.355). The result remained nonsignificant after excluding heart failure (IRR 0.993; 95% CI 0.960–1.027), for the microvascular count (IRR 0.993; 95% CI 0.964–1.024), and for the cardiovascular count including heart failure (IRR 0.980; 95% CI 0.945–1.015). Pearson dispersion was 0.587, providing no evidence of overdispersion. Conclusions: No evidence of an association between current DSMQ-measured self-management and the number of recorded conditions was identified in this cohort. The result does not demonstrate equivalence and does not imply that sustained self-management is unrelated to long-term complication risk. In practice, contemporary DSMQ scores should guide cur-rent education and support needs, not be used as a proxy for historical com-plication exposure. 2026-09-16 Medicina, Vol. 62, Pages 1777: Current Diabetes Self-Management and the Number of Documented Complications in Adults with Type 2 Diabetes: A Cross-Sectional Study

Medicina doi: 10.3390/medicina62091777

Authors: Paula-Alexandra Popovici Andreea Diana Igna Bianca-Lăcrimioara Petca Timea Claudia Ghitea Mihaela Simona Popoviciu

Background and Objectives: Current self-management behavior may not reflect the long-term exposures that led to established complications in people with type 2 diabetes (T2D). To assess whether Diabetes Self-Management Questionnaire (DSMQ) scores were associated with the number of documented diabetes-related and cardiovascular conditions and whether the finding was robust to alternative outcome constructions. Materials and Methods: This single-center cross-sectional reanalysis included 262 adults with T2D. The DSMQ was re-calculated from item-level responses. The primary outcome was an unweighted count of seven database-recorded conditions. Spearman correlation and multivariable Poisson regression with HC3 robust standard errors were used. Sensitivity analyses excluded heart failure, separated microvascular and cardiovascular counts, and substituted estimated glomerular filtration rate <60 mL/min/1.73 m2 for the recorded chronic kidney disease field. Results: Median DSMQ Sum Scale was 5.10 (IQR 3.13–7.08), and median condition count was 3 (IQR 2–3). No evidence of an unadjusted association was identified (ρ = −0.056; p = 0.368). In the adjusted model (n = 260), the DSMQ estimate was IRR 0.988 per point (95% CI 0.962–1.014; p = 0.355). The result remained nonsignificant after excluding heart failure (IRR 0.993; 95% CI 0.960–1.027), for the microvascular count (IRR 0.993; 95% CI 0.964–1.024), and for the cardiovascular count including heart failure (IRR 0.980; 95% CI 0.945–1.015). Pearson dispersion was 0.587, providing no evidence of overdispersion. Conclusions: No evidence of an association between current DSMQ-measured self-management and the number of recorded conditions was identified in this cohort. The result does not demonstrate equivalence and does not imply that sustained self-management is unrelated to long-term complication risk. In practice, contemporary DSMQ scores should guide cur-rent education and support needs, not be used as a proxy for historical com-plication exposure.

]]> Current Diabetes Self-Management and the Number of Documented Complications in Adults with Type 2 Diabetes: A Cross-Sectional Study Paula-Alexandra Popovici Andreea Diana Igna Bianca-Lăcrimioara Petca Timea Claudia Ghitea Mihaela Simona Popoviciu doi: 10.3390/medicina62091777 Medicina 2026-09-16 Medicina 2026-09-16 62 9 Article 1777 10.3390/medicina62091777 https://www.mdpi.com/1648-9144/62/9/1777 Medicina, Vol. 62, Pages 1776: Sex-Related Differences in Clinical Characteristics and Outcomes Among Patients Clinically Managed for Suspected Bacterial Infection in the Emergency Department https://www.mdpi.com/1648-9144/62/9/1776 Background and Objectives: Suspected bacterial infection is one of the leading presentations to the Emergency Department (ED) and is still associated with considerable morbidity and mortality. There is increasing evidence that biological sex may influence host immune responses, disease manifestations, therapeutic requirements, and clinical outcomes in infectious diseases. However, sex-specific differences among patients clinically managed for suspected bacterial infection in ED remain incompletely defined. This study, therefore, aimed to assess demographic characteristics, clinical presentation, and clinical management as well as short-term outcomes related to sex among these patients. Materials and Methods: This retrospective single-center observational study included consecutive adults presenting with suspected bacterial infection to the ED between 1 June and 31 August 2025. Demographic, clinical, laboratory, treatment, infection-source, and outcome data were extracted from medical records. Between-group comparisons were followed by planned age-adjusted analyses and multivariable logistic regression. Results: A total of 213 patients were included, comprising 100 women (46.9%) and 113 men (53.1%). Women were older than men (median 77.0 vs. 67.0 years, p < 0.001), had lower diastolic blood pressure (70 vs. 75 mmHg, p = 0.004), and lower hemoglobin concentrations (11.79 vs. 12.45 g/dL, p = 0.004). Cardiovascular disease was more frequent among women than men (72.0% vs. 52.2%, p = 0.003), although this difference was attenuated and no longer significant after adjustment for age. A documented urinary source of infection was more frequent among women (51.0% vs. 34.5%, p = 0.015) and remained significantly associated with female sex after age adjustment (OR 2.14, 95% CI 1.20–3.81, p = 0.010; Benjamini–Hochberg-adjusted p = 0.039). No significant difference was detected in Emergency Department treatment: supplemental oxygen, vasopressors and broad-spectrum antibiotics were given with similar frequency to women and men (all p ≥ 0.139). Direct intensive care unit (ICU) admission from the ED occurred in 14 of 100 women (14.0%) and 21 of 113 men (18.6%; OR 0.71, 95% CI 0.34–1.49), and in-hospital mortality in 7 women (7.0%) and 9 men (8.0%; OR 0.87, 95% CI 0.31–2.43). After adjustment, female sex was not independently associated with direct ICU admission (OR 0.64, 95% CI 0.29–1.39; p = 0.257) or in-hospital mortality (OR 0.80, 95% CI 0.27–2.35; p = 0.690). Conclusions: In this single-center retrospective cohort of adults clinically managed for suspected bacterial infection in the emergency department, women were older and more frequently had a documented urinary source of infection. After adjustment for age, female sex remained associated with a documented urinary source of infection. The study did not provide precise evidence that sex was independently associated with direct ICU admission or in-hospital mortality; however, the confidence intervals were wide and clinically relevant differences cannot be excluded. Larger prospective multicenter studies with standardized diagnostic criteria, microbiological confirmation, and adequate outcome-event numbers are needed. 2026-09-16 Medicina, Vol. 62, Pages 1776: Sex-Related Differences in Clinical Characteristics and Outcomes Among Patients Clinically Managed for Suspected Bacterial Infection in the Emergency Department

Medicina doi: 10.3390/medicina62091776

Authors: Daian-Ionel Popa Larysa Alexandra Bălulescu Ovidiu Alexandru Mederle Codrina Mihaela Levai Tiberiu Buleu Anca Tudor Ion Petre Raluca Ibănescu Carmen Gabriela Williams Dumitru Sutoi Dragos Fortofoiu Cătălina Băzăvan Adelin Ciudoiu Răzvan Roșca Florina Buleu

Background and Objectives: Suspected bacterial infection is one of the leading presentations to the Emergency Department (ED) and is still associated with considerable morbidity and mortality. There is increasing evidence that biological sex may influence host immune responses, disease manifestations, therapeutic requirements, and clinical outcomes in infectious diseases. However, sex-specific differences among patients clinically managed for suspected bacterial infection in ED remain incompletely defined. This study, therefore, aimed to assess demographic characteristics, clinical presentation, and clinical management as well as short-term outcomes related to sex among these patients. Materials and Methods: This retrospective single-center observational study included consecutive adults presenting with suspected bacterial infection to the ED between 1 June and 31 August 2025. Demographic, clinical, laboratory, treatment, infection-source, and outcome data were extracted from medical records. Between-group comparisons were followed by planned age-adjusted analyses and multivariable logistic regression. Results: A total of 213 patients were included, comprising 100 women (46.9%) and 113 men (53.1%). Women were older than men (median 77.0 vs. 67.0 years, p < 0.001), had lower diastolic blood pressure (70 vs. 75 mmHg, p = 0.004), and lower hemoglobin concentrations (11.79 vs. 12.45 g/dL, p = 0.004). Cardiovascular disease was more frequent among women than men (72.0% vs. 52.2%, p = 0.003), although this difference was attenuated and no longer significant after adjustment for age. A documented urinary source of infection was more frequent among women (51.0% vs. 34.5%, p = 0.015) and remained significantly associated with female sex after age adjustment (OR 2.14, 95% CI 1.20–3.81, p = 0.010; Benjamini–Hochberg-adjusted p = 0.039). No significant difference was detected in Emergency Department treatment: supplemental oxygen, vasopressors and broad-spectrum antibiotics were given with similar frequency to women and men (all p ≥ 0.139). Direct intensive care unit (ICU) admission from the ED occurred in 14 of 100 women (14.0%) and 21 of 113 men (18.6%; OR 0.71, 95% CI 0.34–1.49), and in-hospital mortality in 7 women (7.0%) and 9 men (8.0%; OR 0.87, 95% CI 0.31–2.43). After adjustment, female sex was not independently associated with direct ICU admission (OR 0.64, 95% CI 0.29–1.39; p = 0.257) or in-hospital mortality (OR 0.80, 95% CI 0.27–2.35; p = 0.690). Conclusions: In this single-center retrospective cohort of adults clinically managed for suspected bacterial infection in the emergency department, women were older and more frequently had a documented urinary source of infection. After adjustment for age, female sex remained associated with a documented urinary source of infection. The study did not provide precise evidence that sex was independently associated with direct ICU admission or in-hospital mortality; however, the confidence intervals were wide and clinically relevant differences cannot be excluded. Larger prospective multicenter studies with standardized diagnostic criteria, microbiological confirmation, and adequate outcome-event numbers are needed.

]]> Sex-Related Differences in Clinical Characteristics and Outcomes Among Patients Clinically Managed for Suspected Bacterial Infection in the Emergency Department Daian-Ionel Popa Larysa Alexandra Bălulescu Ovidiu Alexandru Mederle Codrina Mihaela Levai Tiberiu Buleu Anca Tudor Ion Petre Raluca Ibănescu Carmen Gabriela Williams Dumitru Sutoi Dragos Fortofoiu Cătălina Băzăvan Adelin Ciudoiu Răzvan Roșca Florina Buleu doi: 10.3390/medicina62091776 Medicina 2026-09-16 Medicina 2026-09-16 62 9 Article 1776 10.3390/medicina62091776 https://www.mdpi.com/1648-9144/62/9/1776 Medicina, Vol. 62, Pages 1775: Myocardial Injury and Predictors of In-Hospital Mortality in Severe or Critical COVID-19: A Single-Center Observational Cohort Study https://www.mdpi.com/1648-9144/62/9/1775 Background and Objectives: In-hospital mortality remains high among patients with severe or critical COVID-19. This study aimed to identify independent predictors of in-hospital mortality and assess the prognostic value of myocardial injury in this high-risk population. Materials and Methods: This single-center observational cohort study included 172 adults hospitalized with severe or critical COVID-19 across multiple pandemic waves. Mortality-associated factors were assessed using logistic regression and receiver operating characteristic curve analysis. Myocardial injury was defined as hs-cTnT > 14 ng/L, measured on days 3–5 after admission. Results: Of 172 patients, 60 died during hospitalization (34.9%). In the primary multivariable model, based on 126 complete cases and 37 deaths, age (aOR = 2.55 per 10-year increase; 95% CI, 1.55–4.22), pre-existing cardiovascular disease (aOR = 3.06; 95% CI, 1.03–9.07), LDH (aOR = 6.31 per doubling; 95% CI, 2.70–14.78), and CT pulmonary involvement (aOR = 1.34 per 10% increase; 95% CI, 1.01–1.80), were independently associated with in-hospital mortality. In a separate analysis of 121 patients with 35 deaths, myocardial injury remained independently associated with mortality after adjustment for age, cardiovascular disease, and pulmonary involvement (aOR = 5.19; 95% CI, 1.82–14.77). Among 131 patients with complete phenotype data, mortality was 6.7% (2/30) in patients with neither component, 19.6% (11/56) with isolated respiratory involvement, 50.0% (3/6) with isolated myocardial injury, and 56.4% (22/39) with both components. The primary multivariable model had an apparent AUC of 0.898 (95% CI, 0.828–0.968). Conclusions: Age, LDH, and myocardial injury were independently associated with in-hospital mortality, while the associations of cardiovascular disease and CT involvement were attenuated in the multiple-imputation sensitivity analysis. Combined assessment of clinical, pulmonary, and cardiac factors may improve risk stratification, but these findings require validation in independent cohorts. 2026-09-16 Medicina, Vol. 62, Pages 1775: Myocardial Injury and Predictors of In-Hospital Mortality in Severe or Critical COVID-19: A Single-Center Observational Cohort Study

Medicina doi: 10.3390/medicina62091775

Authors: Valentina Negrea Septimiu Toader Voidazan Adina Huțanu Vlad Adrian Pop Anca Meda Văsieșiu

Background and Objectives: In-hospital mortality remains high among patients with severe or critical COVID-19. This study aimed to identify independent predictors of in-hospital mortality and assess the prognostic value of myocardial injury in this high-risk population. Materials and Methods: This single-center observational cohort study included 172 adults hospitalized with severe or critical COVID-19 across multiple pandemic waves. Mortality-associated factors were assessed using logistic regression and receiver operating characteristic curve analysis. Myocardial injury was defined as hs-cTnT > 14 ng/L, measured on days 3–5 after admission. Results: Of 172 patients, 60 died during hospitalization (34.9%). In the primary multivariable model, based on 126 complete cases and 37 deaths, age (aOR = 2.55 per 10-year increase; 95% CI, 1.55–4.22), pre-existing cardiovascular disease (aOR = 3.06; 95% CI, 1.03–9.07), LDH (aOR = 6.31 per doubling; 95% CI, 2.70–14.78), and CT pulmonary involvement (aOR = 1.34 per 10% increase; 95% CI, 1.01–1.80), were independently associated with in-hospital mortality. In a separate analysis of 121 patients with 35 deaths, myocardial injury remained independently associated with mortality after adjustment for age, cardiovascular disease, and pulmonary involvement (aOR = 5.19; 95% CI, 1.82–14.77). Among 131 patients with complete phenotype data, mortality was 6.7% (2/30) in patients with neither component, 19.6% (11/56) with isolated respiratory involvement, 50.0% (3/6) with isolated myocardial injury, and 56.4% (22/39) with both components. The primary multivariable model had an apparent AUC of 0.898 (95% CI, 0.828–0.968). Conclusions: Age, LDH, and myocardial injury were independently associated with in-hospital mortality, while the associations of cardiovascular disease and CT involvement were attenuated in the multiple-imputation sensitivity analysis. Combined assessment of clinical, pulmonary, and cardiac factors may improve risk stratification, but these findings require validation in independent cohorts.

]]> Myocardial Injury and Predictors of In-Hospital Mortality in Severe or Critical COVID-19: A Single-Center Observational Cohort Study Valentina Negrea Septimiu Toader Voidazan Adina Huțanu Vlad Adrian Pop Anca Meda Văsieșiu doi: 10.3390/medicina62091775 Medicina 2026-09-16 Medicina 2026-09-16 62 9 Article 1775 10.3390/medicina62091775 https://www.mdpi.com/1648-9144/62/9/1775 Medicina, Vol. 62, Pages 1774: Predictive Value of On-Treatment Alpha-Fetoprotein Change for Lenvatinib Response in Patients with Hepatocellular Carcinoma: A Real-World Retrospective Study in Vietnam https://www.mdpi.com/1648-9144/62/9/1774 Background and Objectives: Changes in alpha-fetoprotein (AFP) after initiating lenvatinib may reflect response in patients with hepatocellular carcinoma (HCC), but the optimal assessment time point and AFP decline threshold remain unstandardized. This study evaluated the association between AFP change at the first post-treatment measurement and imaging response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Materials and Methods: This retrospective study included 191 patients with HCC treated with lenvatinib. The primary analysis population comprised patients with pretreatment AFP ≥ 20 ng/mL and ≥1 post-treatment AFP measurement. AFP response was defined as a ≥40% decrease from pretreatment levels. The primary endpoints were the objective response rate (ORR) and disease control rate (DCR) according to mRECIST; progression-free survival (PFS) and overall survival (OS) were exploratory. Associations were assessed using multivariable logistic regression adjusted for AFP timing, albumin–bilirubin (ALBI) score, macrovascular invasion, and tumor number ≥ 5. Sensitivity and 2-month landmark analyses were also performed. Results: Of 124 patients, 47 (37.9%) achieved an AFP response. ORR was 44.7% versus 6.5% in the non-response group (OR 11.36; 95% confidence interval [CI] 3.68–42.67; p < 0.001); DCR was 83.0% versus 57.1% (OR 3.62; 95% CI 1.42–10.19; p = 0.003). After adjustment, AFP response remained independently associated with ORR (aOR 12.96; 95% CI 3.85–43.66; p < 0.001) and DCR (aOR 5.76; 95% CI 1.95–17.00; p = 0.002); findings were unchanged when restricted to cycle-1 measurements (aOR 12.27). In exploratory analyses, median PFS was 8.51 versus 4.30 months and median OS 18.53 versus 10.15 months; landmark analysis gave concordant estimates (PFS HR 0.38; OS HR 0.45). Conclusions: A ≥40% AFP decline at the first post-treatment measurement was independently associated with ORR and DCR according to mRECIST in patients with HCC and pretreatment AFP ≥ 20 ng/mL. These findings are hypothesis-generating and require confirmation in prospective, multicenter studies with independent validation before AFP kinetics can be considered in routine practice. 2026-09-16 Medicina, Vol. 62, Pages 1774: Predictive Value of On-Treatment Alpha-Fetoprotein Change for Lenvatinib Response in Patients with Hepatocellular Carcinoma: A Real-World Retrospective Study in Vietnam

Medicina doi: 10.3390/medicina62091774

Authors: Ngoc-Tan Hoang Van-Quang Le Thang Tran Thi-Que Pham Thi-Dung Nguyen Thi-Cuc Hoang Thanh-Phuong Pham Thi-Hoa Nguyen

Background and Objectives: Changes in alpha-fetoprotein (AFP) after initiating lenvatinib may reflect response in patients with hepatocellular carcinoma (HCC), but the optimal assessment time point and AFP decline threshold remain unstandardized. This study evaluated the association between AFP change at the first post-treatment measurement and imaging response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Materials and Methods: This retrospective study included 191 patients with HCC treated with lenvatinib. The primary analysis population comprised patients with pretreatment AFP ≥ 20 ng/mL and ≥1 post-treatment AFP measurement. AFP response was defined as a ≥40% decrease from pretreatment levels. The primary endpoints were the objective response rate (ORR) and disease control rate (DCR) according to mRECIST; progression-free survival (PFS) and overall survival (OS) were exploratory. Associations were assessed using multivariable logistic regression adjusted for AFP timing, albumin–bilirubin (ALBI) score, macrovascular invasion, and tumor number ≥ 5. Sensitivity and 2-month landmark analyses were also performed. Results: Of 124 patients, 47 (37.9%) achieved an AFP response. ORR was 44.7% versus 6.5% in the non-response group (OR 11.36; 95% confidence interval [CI] 3.68–42.67; p < 0.001); DCR was 83.0% versus 57.1% (OR 3.62; 95% CI 1.42–10.19; p = 0.003). After adjustment, AFP response remained independently associated with ORR (aOR 12.96; 95% CI 3.85–43.66; p < 0.001) and DCR (aOR 5.76; 95% CI 1.95–17.00; p = 0.002); findings were unchanged when restricted to cycle-1 measurements (aOR 12.27). In exploratory analyses, median PFS was 8.51 versus 4.30 months and median OS 18.53 versus 10.15 months; landmark analysis gave concordant estimates (PFS HR 0.38; OS HR 0.45). Conclusions: A ≥40% AFP decline at the first post-treatment measurement was independently associated with ORR and DCR according to mRECIST in patients with HCC and pretreatment AFP ≥ 20 ng/mL. These findings are hypothesis-generating and require confirmation in prospective, multicenter studies with independent validation before AFP kinetics can be considered in routine practice.

]]> Predictive Value of On-Treatment Alpha-Fetoprotein Change for Lenvatinib Response in Patients with Hepatocellular Carcinoma: A Real-World Retrospective Study in Vietnam Ngoc-Tan Hoang Van-Quang Le Thang Tran Thi-Que Pham Thi-Dung Nguyen Thi-Cuc Hoang Thanh-Phuong Pham Thi-Hoa Nguyen doi: 10.3390/medicina62091774 Medicina 2026-09-16 Medicina 2026-09-16 62 9 Article 1774 10.3390/medicina62091774 https://www.mdpi.com/1648-9144/62/9/1774 Medicina, Vol. 62, Pages 1773: A Common Language for Post-Transplant Anastomotic Biliary Strictures: Standardized Endoscopic Outcome Definitions and a Failure-Mode Roadmap https://www.mdpi.com/1648-9144/62/9/1773 Background and Objectives: Anastomotic biliary stricture (AS) is the most frequent biliary complication after duct-to-duct liver transplantation (LT) and a leading indication for post-transplant endoscopic retrograde cholangiopancreatography (ERCP). Because inconsistent outcome definitions hamper cross-study comparisons, we also propose standardized outcome definitions and a minimum reporting dataset. Materials and Methods: This narrative review covers pathogenesis and risk factors, diagnosis and timing, balloon dilation and stenting, the management of treatment failure, procedure-related safety, and graft outcomes. Results: ERCP is the established first-line treatment and achieves durable resolution in most patients. Randomized evidence shows comparable resolution with multiple plastic stents (MPS) and fully covered self-expandable metal stents (FCSEMS), the latter reducing procedures and treatment duration at the cost of migration and possible recurrence. Evidence is weaker for recurrent or refractory strictures, sequential stent addition versus complete exchange, and Roux-en-Y anatomy or a completely obstructed anastomosis. We define technical success, treatment success, recurrence, refractory disease, and durable stent-free resolution, and organize advanced management as a roadmap matching four modes of endoscopic failure to salvage techniques. Conclusions: Endoscopic therapy is central to graft-preserving management of post-transplant AS; adopting these harmonized definitions should make outcomes comparable and rescue algorithms evidence-based. 2026-09-15 Medicina, Vol. 62, Pages 1773: A Common Language for Post-Transplant Anastomotic Biliary Strictures: Standardized Endoscopic Outcome Definitions and a Failure-Mode Roadmap

Medicina doi: 10.3390/medicina62091773

Authors: Daniele Balducci Michele Montori Marco Marzioni Giuseppe Tarantino Antonio Benedetti Gianluca Svegliati-Baroni Emanuele Bendia Enrico Palmeri Matteo Ghisa Luca Maroni

Background and Objectives: Anastomotic biliary stricture (AS) is the most frequent biliary complication after duct-to-duct liver transplantation (LT) and a leading indication for post-transplant endoscopic retrograde cholangiopancreatography (ERCP). Because inconsistent outcome definitions hamper cross-study comparisons, we also propose standardized outcome definitions and a minimum reporting dataset. Materials and Methods: This narrative review covers pathogenesis and risk factors, diagnosis and timing, balloon dilation and stenting, the management of treatment failure, procedure-related safety, and graft outcomes. Results: ERCP is the established first-line treatment and achieves durable resolution in most patients. Randomized evidence shows comparable resolution with multiple plastic stents (MPS) and fully covered self-expandable metal stents (FCSEMS), the latter reducing procedures and treatment duration at the cost of migration and possible recurrence. Evidence is weaker for recurrent or refractory strictures, sequential stent addition versus complete exchange, and Roux-en-Y anatomy or a completely obstructed anastomosis. We define technical success, treatment success, recurrence, refractory disease, and durable stent-free resolution, and organize advanced management as a roadmap matching four modes of endoscopic failure to salvage techniques. Conclusions: Endoscopic therapy is central to graft-preserving management of post-transplant AS; adopting these harmonized definitions should make outcomes comparable and rescue algorithms evidence-based.

]]> A Common Language for Post-Transplant Anastomotic Biliary Strictures: Standardized Endoscopic Outcome Definitions and a Failure-Mode Roadmap Daniele Balducci Michele Montori Marco Marzioni Giuseppe Tarantino Antonio Benedetti Gianluca Svegliati-Baroni Emanuele Bendia Enrico Palmeri Matteo Ghisa Luca Maroni doi: 10.3390/medicina62091773 Medicina 2026-09-15 Medicina 2026-09-15 62 9 Review 1773 10.3390/medicina62091773 https://www.mdpi.com/1648-9144/62/9/1773 Medicina, Vol. 62, Pages 1772: Diagnostic Efficacy of Clinico-Pathological Parameters in Predicting Nodal Positivity in Oral Cavity Squamous Cell Carcinoma: A Multivariate Risk Assessment https://www.mdpi.com/1648-9144/62/9/1772 Background and Objectives: This study investigated clinicopathological factors associated with occult cervical lymph node metastasis in clinically node-negative oral cavity squamous cell carcinoma (OCSCC). Materials and Methods: This retrospective study included 108 patients who underwent primary tumor resection and elective neck dissection. Depth of invasion (DOI), lymphovascular invasion (LVI), perineural invasion, and histological grade were evaluated. Receiver operating characteristic analysis and multivariable logistic regression were used to assess associations with pathological nodal positivity. Results: Occult nodal metastasis was identified in 27 patients (25%). The cohort-derived DOI threshold was 8.5 mm, with an area under the curve of 0.841. LVI and histological grade were associated with nodal positivity in the multivariable analysis, although the adjusted estimates were imprecise. Conclusions: Histopathological characteristics were associated with occult nodal metastasis in this selected surgical cohort. However, the limited number of nodal events and the postoperative availability of key variables restrict clinical applicability. These exploratory findings require independent validation and should not be used to determine whether elective neck dissection can be omitted. 2026-09-15 Medicina, Vol. 62, Pages 1772: Diagnostic Efficacy of Clinico-Pathological Parameters in Predicting Nodal Positivity in Oral Cavity Squamous Cell Carcinoma: A Multivariate Risk Assessment

Medicina doi: 10.3390/medicina62091772

Authors: Deniz Baklacı Gökhan Furkan Kılıç Hüseyin Işık Aleyna Şivetoğlu Duygu Erdem

Background and Objectives: This study investigated clinicopathological factors associated with occult cervical lymph node metastasis in clinically node-negative oral cavity squamous cell carcinoma (OCSCC). Materials and Methods: This retrospective study included 108 patients who underwent primary tumor resection and elective neck dissection. Depth of invasion (DOI), lymphovascular invasion (LVI), perineural invasion, and histological grade were evaluated. Receiver operating characteristic analysis and multivariable logistic regression were used to assess associations with pathological nodal positivity. Results: Occult nodal metastasis was identified in 27 patients (25%). The cohort-derived DOI threshold was 8.5 mm, with an area under the curve of 0.841. LVI and histological grade were associated with nodal positivity in the multivariable analysis, although the adjusted estimates were imprecise. Conclusions: Histopathological characteristics were associated with occult nodal metastasis in this selected surgical cohort. However, the limited number of nodal events and the postoperative availability of key variables restrict clinical applicability. These exploratory findings require independent validation and should not be used to determine whether elective neck dissection can be omitted.

]]> Diagnostic Efficacy of Clinico-Pathological Parameters in Predicting Nodal Positivity in Oral Cavity Squamous Cell Carcinoma: A Multivariate Risk Assessment Deniz Baklacı Gökhan Furkan Kılıç Hüseyin Işık Aleyna Şivetoğlu Duygu Erdem doi: 10.3390/medicina62091772 Medicina 2026-09-15 Medicina 2026-09-15 62 9 Article 1772 10.3390/medicina62091772 https://www.mdpi.com/1648-9144/62/9/1772 Medicina, Vol. 62, Pages 1771: Beyond Sequencing: Integrating MLPA Reveals Hidden Structural PKD2 Variants and Enhances Mutation Detection in a Highly Selected ADPKD Greek Cohort https://www.mdpi.com/1648-9144/62/9/1771 Background and Objectives: The genetic architecture of late-onset autosomal dominant polycystic kidney disease (ADPKD) remains incompletely defined. Pathogenic mutations in two genes that encode polycystin proteins, PKD1 and PKD2, prevail among these patients. Detection of PKD1 alterations by a sequencing method is challenging as this is a large gene with high GC content and multiple pseudogenes. Although next-generation sequencing (NGS) has become the cornerstone of molecular diagnosis, its limited availability in several settings and its limited sensitivity for structural variants may create a diagnostic blind spot, particularly for PKD2. Because PKD2-associated ADPKD follows a milder clinical course with delayed progression to end-stage renal disease (ESRD), its contribution to late-onset disease may be systematically underestimated. We hypothesized that a phenotype-driven strategy integrating copy number analysis would uncover clinically relevant PKD2 variants overlooked by DNA sequencing methods. Materials and Methods: Six well-characterized consecutive ADPKD patients that entered KRT (kidney replacement therapy) above 70 years old underwent targeted PKD2 analysis using bidirectional Sanger DNA sequencing of all coding exons and exon–intron boundaries, complemented by multiplex ligation-dependent probe amplification (MLPA) for copy number variant detection. Results: Pathogenic PKD2 variants were identified in 33% of the patients in this limited cohort. These included the recurrent nonsense variant p.Arg872Ter and a previously undescribed multi-exonic deletion encompassing exons 1–9 that was detectable exclusively by MLPA. Additionally a novel variant of unknown significance (VUS) (p.Leu273Gln) was detected. The high diagnostic yield in this phenotypically highly enriched cohort highlights the value of targeted structural variant analysis. Conclusions: Our findings identify structural PKD2 variation as an under-recognized cause of genetically unresolved late-onset ADPKD and demonstrate that phenotype-guided incorporation of copy number analysis can overcome limitations of NGS alone. A combined sequencing–MLPA approach may therefore provide a more complete and clinically informative molecular diagnosis, particularly in carefully selected patients with late-onset ADPKD. 2026-09-15 Medicina, Vol. 62, Pages 1771: Beyond Sequencing: Integrating MLPA Reveals Hidden Structural PKD2 Variants and Enhances Mutation Detection in a Highly Selected ADPKD Greek Cohort

Medicina doi: 10.3390/medicina62091771

Authors: Akrivi Papachristopoulou Angeliki Margoni Aimilios Christos Simoudis Aristea Mylona Olga-Irini Kroupi Petros Nikolopoulos Athanasios G. Papavassiliou Demetrios V. Vlahakos Christos Kroupis

Background and Objectives: The genetic architecture of late-onset autosomal dominant polycystic kidney disease (ADPKD) remains incompletely defined. Pathogenic mutations in two genes that encode polycystin proteins, PKD1 and PKD2, prevail among these patients. Detection of PKD1 alterations by a sequencing method is challenging as this is a large gene with high GC content and multiple pseudogenes. Although next-generation sequencing (NGS) has become the cornerstone of molecular diagnosis, its limited availability in several settings and its limited sensitivity for structural variants may create a diagnostic blind spot, particularly for PKD2. Because PKD2-associated ADPKD follows a milder clinical course with delayed progression to end-stage renal disease (ESRD), its contribution to late-onset disease may be systematically underestimated. We hypothesized that a phenotype-driven strategy integrating copy number analysis would uncover clinically relevant PKD2 variants overlooked by DNA sequencing methods. Materials and Methods: Six well-characterized consecutive ADPKD patients that entered KRT (kidney replacement therapy) above 70 years old underwent targeted PKD2 analysis using bidirectional Sanger DNA sequencing of all coding exons and exon–intron boundaries, complemented by multiplex ligation-dependent probe amplification (MLPA) for copy number variant detection. Results: Pathogenic PKD2 variants were identified in 33% of the patients in this limited cohort. These included the recurrent nonsense variant p.Arg872Ter and a previously undescribed multi-exonic deletion encompassing exons 1–9 that was detectable exclusively by MLPA. Additionally a novel variant of unknown significance (VUS) (p.Leu273Gln) was detected. The high diagnostic yield in this phenotypically highly enriched cohort highlights the value of targeted structural variant analysis. Conclusions: Our findings identify structural PKD2 variation as an under-recognized cause of genetically unresolved late-onset ADPKD and demonstrate that phenotype-guided incorporation of copy number analysis can overcome limitations of NGS alone. A combined sequencing–MLPA approach may therefore provide a more complete and clinically informative molecular diagnosis, particularly in carefully selected patients with late-onset ADPKD.

]]> Beyond Sequencing: Integrating MLPA Reveals Hidden Structural PKD2 Variants and Enhances Mutation Detection in a Highly Selected ADPKD Greek Cohort Akrivi Papachristopoulou Angeliki Margoni Aimilios Christos Simoudis Aristea Mylona Olga-Irini Kroupi Petros Nikolopoulos Athanasios G. Papavassiliou Demetrios V. Vlahakos Christos Kroupis doi: 10.3390/medicina62091771 Medicina 2026-09-15 Medicina 2026-09-15 62 9 Article 1771 10.3390/medicina62091771 https://www.mdpi.com/1648-9144/62/9/1771 Medicina, Vol. 62, Pages 1770: Clinical Outcomes and Factors Associated with Response to Fluoroscopy-Guided Cervical Medial Branch Pulsed Radiofrequency in Chronic Cervical Facet Joint Pain: A Retrospective Cohort Study https://www.mdpi.com/1648-9144/62/9/1770 Background and Objectives: Pulsed radiofrequency (PRF) of the cervical medial branches is a non-destructive neuromodulatory option for chronic cervical facet joint pain, yet evidence regarding the durability of clinical response and factors associated with sustained benefit remains limited. This study aimed to characterize the 6-month trajectory of pain and disability after fluoroscopy-guided cervical medial branch PRF and to explore baseline factors associated with meaningful pain relief (MPR). Materials and Methods: In this retrospective single-center cohort study, 75 patients with chronic cervical facet joint pain who achieved ≥50% temporary pain relief following a diagnostic medial branch block underwent fluoroscopy-guided cervical medial branch PRF, followed by injection of local anesthetic and corticosteroid at the treated levels. Numeric Rating Scale (NRS) and Neck Disability Index (NDI) scores were evaluated at baseline and at 1, 3, and 6 months. MPR was defined as ≥50% reduction in NRS from baseline. Global Perceived Effect (GPE) and changes in analgesic medication use were assessed as complementary clinical outcomes. An exploratory multivariable logistic regression analysis was performed to examine factors independently associated with MPR at 6 months. Results: Median NRS scores decreased from 7.0 at baseline to 4.0, 4.0, and 5.0 at 1, 3, and 6 months, respectively, while median NDI scores decreased from 30.0 to 14.0, 16.0, and 20.0 (both overall p < 0.001). Despite sustained improvement relative to baseline, MPR progressively declined from 57.3% at 1 month to 49.3% at 3 months and 36.0% at 6 months (overall p < 0.001). Favorable GPE and reduced analgesic medication use showed parallel declines, supporting attenuation of overall clinical benefit over time. In the exploratory multivariable model, fibromyalgia was independently associated with 75% lower odds of 6-month MPR (OR = 0.25, 95% CI: 0.088–0.709; p = 0.009). Age, sex, and baseline NRS were not significantly associated with 6-month MPR. No serious acute periprocedural adverse events were documented during the 2 h observation period. Conclusions: Fluoroscopy-guided cervical medial branch PRF, combined with post-procedural corticosteroid and local anesthetic administration, was associated with clinically meaningful improvements in both pain and neck-related disability, with the greatest benefit during the first 3 months and partial attenuation by 6 months. The progressive decline across pain response, patient-reported global improvement, and analgesic-use outcomes highlights the time-dependent nature of the benefit associated with the combined intervention. Fibromyalgia was independently associated with substantially lower odds of 6-month MPR in this exploratory analysis; this association should be interpreted cautiously and requires prospective validation before it can inform patient selection, although it may be relevant when counseling patients regarding the durability of response. 2026-09-15 Medicina, Vol. 62, Pages 1770: Clinical Outcomes and Factors Associated with Response to Fluoroscopy-Guided Cervical Medial Branch Pulsed Radiofrequency in Chronic Cervical Facet Joint Pain: A Retrospective Cohort Study

Medicina doi: 10.3390/medicina62091770

Authors: Nevcihan Şahutoğlu Bal Şükriye Dadalı Ali Çoştu Gülçin Babaoğlu Ülkü Sabuncu Emel Başar Erkan Yavuz Akçaboy

Background and Objectives: Pulsed radiofrequency (PRF) of the cervical medial branches is a non-destructive neuromodulatory option for chronic cervical facet joint pain, yet evidence regarding the durability of clinical response and factors associated with sustained benefit remains limited. This study aimed to characterize the 6-month trajectory of pain and disability after fluoroscopy-guided cervical medial branch PRF and to explore baseline factors associated with meaningful pain relief (MPR). Materials and Methods: In this retrospective single-center cohort study, 75 patients with chronic cervical facet joint pain who achieved ≥50% temporary pain relief following a diagnostic medial branch block underwent fluoroscopy-guided cervical medial branch PRF, followed by injection of local anesthetic and corticosteroid at the treated levels. Numeric Rating Scale (NRS) and Neck Disability Index (NDI) scores were evaluated at baseline and at 1, 3, and 6 months. MPR was defined as ≥50% reduction in NRS from baseline. Global Perceived Effect (GPE) and changes in analgesic medication use were assessed as complementary clinical outcomes. An exploratory multivariable logistic regression analysis was performed to examine factors independently associated with MPR at 6 months. Results: Median NRS scores decreased from 7.0 at baseline to 4.0, 4.0, and 5.0 at 1, 3, and 6 months, respectively, while median NDI scores decreased from 30.0 to 14.0, 16.0, and 20.0 (both overall p < 0.001). Despite sustained improvement relative to baseline, MPR progressively declined from 57.3% at 1 month to 49.3% at 3 months and 36.0% at 6 months (overall p < 0.001). Favorable GPE and reduced analgesic medication use showed parallel declines, supporting attenuation of overall clinical benefit over time. In the exploratory multivariable model, fibromyalgia was independently associated with 75% lower odds of 6-month MPR (OR = 0.25, 95% CI: 0.088–0.709; p = 0.009). Age, sex, and baseline NRS were not significantly associated with 6-month MPR. No serious acute periprocedural adverse events were documented during the 2 h observation period. Conclusions: Fluoroscopy-guided cervical medial branch PRF, combined with post-procedural corticosteroid and local anesthetic administration, was associated with clinically meaningful improvements in both pain and neck-related disability, with the greatest benefit during the first 3 months and partial attenuation by 6 months. The progressive decline across pain response, patient-reported global improvement, and analgesic-use outcomes highlights the time-dependent nature of the benefit associated with the combined intervention. Fibromyalgia was independently associated with substantially lower odds of 6-month MPR in this exploratory analysis; this association should be interpreted cautiously and requires prospective validation before it can inform patient selection, although it may be relevant when counseling patients regarding the durability of response.

]]> Clinical Outcomes and Factors Associated with Response to Fluoroscopy-Guided Cervical Medial Branch Pulsed Radiofrequency in Chronic Cervical Facet Joint Pain: A Retrospective Cohort Study Nevcihan Şahutoğlu Bal Şükriye Dadalı Ali Çoştu Gülçin Babaoğlu Ülkü Sabuncu Emel Başar Erkan Yavuz Akçaboy doi: 10.3390/medicina62091770 Medicina 2026-09-15 Medicina 2026-09-15 62 9 Article 1770 10.3390/medicina62091770 https://www.mdpi.com/1648-9144/62/9/1770 Medicina, Vol. 62, Pages 1768: Ocular Surface Symptoms, Objective Redness, and Intraocular Pressure After a Switch from Fixed Dorzolamide/Timolol to Netarsudil in Latanoprost-Treated Glaucoma and Ocular Hypertension: A Prospective Real-World Cohort Study https://www.mdpi.com/1648-9144/62/9/1768 Background and Objectives: Conjunctival hyperemia is common with netarsudil, but redness may not reflect the overall patient experience when treatment burden is reduced. We evaluated ocular surface symptoms, objective redness, tear-film parameters, intraocular pressure (IOP), and treatment preference after a routine-care switch from twice-daily fixed dorzolamide/timolol to once-daily netarsudil 0.02%, while continuing latanoprost. Materials and Methods: This prospective, single-center observational cohort included 30 consecutive adults with primary open-angle glaucoma or ocular hypertension and controlled IOP. Outcomes were assessed at baseline and months 1 and 2. The primary outcome was the Ocular Surface Disease Index (OSDI). Continuous eye-level outcomes were analyzed using mixed-effects models accounting for fellow-eye and repeated-measures correlation; grade ≥ 2 hyperemia was analyzed using participant-clustered logistic regression. Results: Twenty-seven participants (54 eyes) completed evaluable 2-month follow-up. Median OSDI decreased from 7.50 at baseline to 6.25 at month 1 and 5.00 at month 2 (Friedman p = 0.0015). The mean baseline-to-month 2 change was −2.95 points (95% CI, −4.80 to −1.10), and 6/27 participants (22.2%) improved by at least 7 points. Serle grade ≥ 2 hyperemia increased from 7.4% of eyes at baseline to 51.9% at month 1 and 44.4% at month 2. Estimated mean bulbar redness index increased from 1.57 to 2.14 (p < 0.0001), tear meniscus height increased modestly, and non-invasive keratograph break-up time showed no significant longitudinal change. Estimated mean IOP changed from 14.50 to 13.65 mmHg (p = 0.0083), with no eye showing an increase of at least 4 mmHg. Burning improved after multiplicity adjustment, and 17/27 participants with available month-2 preference data (63.0%) preferred netarsudil. Conclusions: The switch was associated with modest OSDI improvement and maintained short-term IOP control despite increased objective redness. Patient preference appeared to reflect factors beyond redness alone. 2026-09-15 Medicina, Vol. 62, Pages 1768: Ocular Surface Symptoms, Objective Redness, and Intraocular Pressure After a Switch from Fixed Dorzolamide/Timolol to Netarsudil in Latanoprost-Treated Glaucoma and Ocular Hypertension: A Prospective Real-World Cohort Study

Medicina doi: 10.3390/medicina62091768

Authors: Virginia Zanutigh Celina Logioco Leila Galetto Franco Perrone Noelia Podesta Florencia Valvecchia

Background and Objectives: Conjunctival hyperemia is common with netarsudil, but redness may not reflect the overall patient experience when treatment burden is reduced. We evaluated ocular surface symptoms, objective redness, tear-film parameters, intraocular pressure (IOP), and treatment preference after a routine-care switch from twice-daily fixed dorzolamide/timolol to once-daily netarsudil 0.02%, while continuing latanoprost. Materials and Methods: This prospective, single-center observational cohort included 30 consecutive adults with primary open-angle glaucoma or ocular hypertension and controlled IOP. Outcomes were assessed at baseline and months 1 and 2. The primary outcome was the Ocular Surface Disease Index (OSDI). Continuous eye-level outcomes were analyzed using mixed-effects models accounting for fellow-eye and repeated-measures correlation; grade ≥ 2 hyperemia was analyzed using participant-clustered logistic regression. Results: Twenty-seven participants (54 eyes) completed evaluable 2-month follow-up. Median OSDI decreased from 7.50 at baseline to 6.25 at month 1 and 5.00 at month 2 (Friedman p = 0.0015). The mean baseline-to-month 2 change was −2.95 points (95% CI, −4.80 to −1.10), and 6/27 participants (22.2%) improved by at least 7 points. Serle grade ≥ 2 hyperemia increased from 7.4% of eyes at baseline to 51.9% at month 1 and 44.4% at month 2. Estimated mean bulbar redness index increased from 1.57 to 2.14 (p < 0.0001), tear meniscus height increased modestly, and non-invasive keratograph break-up time showed no significant longitudinal change. Estimated mean IOP changed from 14.50 to 13.65 mmHg (p = 0.0083), with no eye showing an increase of at least 4 mmHg. Burning improved after multiplicity adjustment, and 17/27 participants with available month-2 preference data (63.0%) preferred netarsudil. Conclusions: The switch was associated with modest OSDI improvement and maintained short-term IOP control despite increased objective redness. Patient preference appeared to reflect factors beyond redness alone.

]]> Ocular Surface Symptoms, Objective Redness, and Intraocular Pressure After a Switch from Fixed Dorzolamide/Timolol to Netarsudil in Latanoprost-Treated Glaucoma and Ocular Hypertension: A Prospective Real-World Cohort Study Virginia Zanutigh Celina Logioco Leila Galetto Franco Perrone Noelia Podesta Florencia Valvecchia doi: 10.3390/medicina62091768 Medicina 2026-09-15 Medicina 2026-09-15 62 9 Article 1768 10.3390/medicina62091768 https://www.mdpi.com/1648-9144/62/9/1768 Medicina, Vol. 62, Pages 1769: Rhabdomyolysis Reported in Association with SARS-CoV-2 Infection and COVID-19 Vaccination: A Systematic Review https://www.mdpi.com/1648-9144/62/9/1769 Background and Objectives: The association between SARS-CoV-2 infection, COVID-19 vaccination, and the development of rhabdomyolysis remains unclear. This systematic review aimed to comprehensively synthesize and analyze the available evidence on the occurrence of rhabdomyolysis in the context of SARS-CoV-2 infection and COVID-19 vaccination. Materials and Methods: A literature search was conducted in PubMed, Scopus, EMBASE, and Web of Science. The review followed PRISMA 2020 guidelines, assessing methodological quality. Statistical analyses were performed using STATA v18. Results: A total of 133 patients with rhabdomyolysis associated with SARS-CoV-2 infection were identified from 93 case reports and 7 case series; the median age was 45.5 years (IQR: 24–62), with a predominance of males (72.9%). Additionally, 13 observational studies comprising 818 patients with rhabdomyolysis associated with SARS-CoV-2 infection were included. Among cases associated with SARS-CoV-2 vaccination, 20 patients were identified from 20 case reports; the median age was 52.5 years (IQR: 22.5–76.5), with a predominance of males (75%). These cases were primarily associated with mRNA-based vaccines, particularly Pfizer-BioNTech BNT162b2 (50%) and Moderna (20%), and occurred predominantly after the first and second doses. The most frequent clinical manifestations in both groups were fever, myalgia, and dark urine. Clinical outcomes were favorable in most patients, both among infection-associated cases (72.2%) and vaccination-associated cases (80%). Conclusions: Rhabdomyolysis has been documented during SARS-CoV-2 infection, although its true frequency remains uncertain, whereas cases following COVID-19 vaccination do not establish causality or platform-specific risks. 2026-09-15 Medicina, Vol. 62, Pages 1769: Rhabdomyolysis Reported in Association with SARS-CoV-2 Infection and COVID-19 Vaccination: A Systematic Review

Medicina doi: 10.3390/medicina62091769

Authors: Fernando M. Runzer-Colmenares Nelson Luis Cahuapaza-Gutierrez Cielo Cinthya Calderon-Hernandez Mariam Miyanay Umeres-Bravo Ruth Angélica Rojas-De la Cruz Tatiana Vanessa Villavicencio-Escudero Renzo Pajuelo-Vasquez Nathaly Enciso

Background and Objectives: The association between SARS-CoV-2 infection, COVID-19 vaccination, and the development of rhabdomyolysis remains unclear. This systematic review aimed to comprehensively synthesize and analyze the available evidence on the occurrence of rhabdomyolysis in the context of SARS-CoV-2 infection and COVID-19 vaccination. Materials and Methods: A literature search was conducted in PubMed, Scopus, EMBASE, and Web of Science. The review followed PRISMA 2020 guidelines, assessing methodological quality. Statistical analyses were performed using STATA v18. Results: A total of 133 patients with rhabdomyolysis associated with SARS-CoV-2 infection were identified from 93 case reports and 7 case series; the median age was 45.5 years (IQR: 24–62), with a predominance of males (72.9%). Additionally, 13 observational studies comprising 818 patients with rhabdomyolysis associated with SARS-CoV-2 infection were included. Among cases associated with SARS-CoV-2 vaccination, 20 patients were identified from 20 case reports; the median age was 52.5 years (IQR: 22.5–76.5), with a predominance of males (75%). These cases were primarily associated with mRNA-based vaccines, particularly Pfizer-BioNTech BNT162b2 (50%) and Moderna (20%), and occurred predominantly after the first and second doses. The most frequent clinical manifestations in both groups were fever, myalgia, and dark urine. Clinical outcomes were favorable in most patients, both among infection-associated cases (72.2%) and vaccination-associated cases (80%). Conclusions: Rhabdomyolysis has been documented during SARS-CoV-2 infection, although its true frequency remains uncertain, whereas cases following COVID-19 vaccination do not establish causality or platform-specific risks.

]]> Rhabdomyolysis Reported in Association with SARS-CoV-2 Infection and COVID-19 Vaccination: A Systematic Review Fernando M. Runzer-Colmenares Nelson Luis Cahuapaza-Gutierrez Cielo Cinthya Calderon-Hernandez Mariam Miyanay Umeres-Bravo Ruth Angélica Rojas-De la Cruz Tatiana Vanessa Villavicencio-Escudero Renzo Pajuelo-Vasquez Nathaly Enciso doi: 10.3390/medicina62091769 Medicina 2026-09-15 Medicina 2026-09-15 62 9 Systematic Review 1769 10.3390/medicina62091769 https://www.mdpi.com/1648-9144/62/9/1769 Medicina, Vol. 62, Pages 1767: Prognostic Value of Preoperative Inflammatory, Hematological, and Metabolic Blood Indices in Endometrioid-Type Endometrial Cancer: A Retrospective Cohort Study https://www.mdpi.com/1648-9144/62/9/1767 Background and Objectives: Peripheral blood indices have been proposed as prognostic biomarkers in endometrial cancer, but most reports include mixed histological subtypes, do not control for benign uterine pathology that independently alters hematological profiles, and evaluate these indices in isolation. We evaluated all three categories head-to-head in a histologically homogeneous endometrioid cohort and formally tested whether they add prognostic information beyond established clinicopathological variables. Materials and Methods: Of 195 patients operated for endometrioid-type endometrial cancer between 2018 and 2024, 142 were included; adenomyosis or leiomyoma on final histopathology, active infection and hematological disease were exclusion criteria. Fourteen preoperative blood-derived indices spanning the three categories were analyzed as continuous variables. A pre-specified clinical model (age category, grade, FIGO stage) was compared with models adding the biomarkers using likelihood-ratio tests, Harrell’s concordance index, time-dependent areas under the curve, bootstrap internal validation, and influence diagnostics. Results: Median follow-up was 52.5 months; 34 patients (23.9%) died and 5-year overall survival was 74.1%. None of the conventional inflammatory ratios were associated with survival (SII p = 0.893; all others p ≥ 0.26). In the multivariable model, histologic grade and NRBC% remained associated with survival (NRBC% HR 3.30 per 1%, 95% CI 1.09–9.97, p = 0.034). Adding NRBC% to the clinical model improved fit (likelihood-ratio p = 0.039) but not discrimination (ΔC 0.006, 95% CI −0.041 to 0.053, p = 0.814), and no index retained significance after Benjamini–Hochberg adjustment. The NRBC% association disappeared on dichotomization at the detection limit and could not be estimated once the five patients with values above 0.30% were excluded. Conclusions: In a predominantly early-stage endometrioid endometrial cancer cohort, preoperative blood-derived indices added no measurable discriminatory information beyond established pathological variables. The NRBC% association rests on very few observations at the upper end of its distribution and is hypothesis-generating only. 2026-09-14 Medicina, Vol. 62, Pages 1767: Prognostic Value of Preoperative Inflammatory, Hematological, and Metabolic Blood Indices in Endometrioid-Type Endometrial Cancer: A Retrospective Cohort Study

Medicina doi: 10.3390/medicina62091767

Authors: Gorkem Ulger Kasim Akay Hamza Yildiz Pelin Aytan Sevki Goksun Gokulu Tolgay Tuyan Ilhan

Background and Objectives: Peripheral blood indices have been proposed as prognostic biomarkers in endometrial cancer, but most reports include mixed histological subtypes, do not control for benign uterine pathology that independently alters hematological profiles, and evaluate these indices in isolation. We evaluated all three categories head-to-head in a histologically homogeneous endometrioid cohort and formally tested whether they add prognostic information beyond established clinicopathological variables. Materials and Methods: Of 195 patients operated for endometrioid-type endometrial cancer between 2018 and 2024, 142 were included; adenomyosis or leiomyoma on final histopathology, active infection and hematological disease were exclusion criteria. Fourteen preoperative blood-derived indices spanning the three categories were analyzed as continuous variables. A pre-specified clinical model (age category, grade, FIGO stage) was compared with models adding the biomarkers using likelihood-ratio tests, Harrell’s concordance index, time-dependent areas under the curve, bootstrap internal validation, and influence diagnostics. Results: Median follow-up was 52.5 months; 34 patients (23.9%) died and 5-year overall survival was 74.1%. None of the conventional inflammatory ratios were associated with survival (SII p = 0.893; all others p ≥ 0.26). In the multivariable model, histologic grade and NRBC% remained associated with survival (NRBC% HR 3.30 per 1%, 95% CI 1.09–9.97, p = 0.034). Adding NRBC% to the clinical model improved fit (likelihood-ratio p = 0.039) but not discrimination (ΔC 0.006, 95% CI −0.041 to 0.053, p = 0.814), and no index retained significance after Benjamini–Hochberg adjustment. The NRBC% association disappeared on dichotomization at the detection limit and could not be estimated once the five patients with values above 0.30% were excluded. Conclusions: In a predominantly early-stage endometrioid endometrial cancer cohort, preoperative blood-derived indices added no measurable discriminatory information beyond established pathological variables. The NRBC% association rests on very few observations at the upper end of its distribution and is hypothesis-generating only.

]]> Prognostic Value of Preoperative Inflammatory, Hematological, and Metabolic Blood Indices in Endometrioid-Type Endometrial Cancer: A Retrospective Cohort Study Gorkem Ulger Kasim Akay Hamza Yildiz Pelin Aytan Sevki Goksun Gokulu Tolgay Tuyan Ilhan doi: 10.3390/medicina62091767 Medicina 2026-09-14 Medicina 2026-09-14 62 9 Article 1767 10.3390/medicina62091767 https://www.mdpi.com/1648-9144/62/9/1767 Medicina, Vol. 62, Pages 1766: Current Evidence on Endoscopic Biliary Drainage in the Era of Surgically Altered Anatomy: A Narrative Review https://www.mdpi.com/1648-9144/62/9/1766 Endoscopic retrograde cholangiopancreatography (ERCP) remains the reference standard for biliary drainage, yet it fails in up to 15% of cases, most notably when a surgically altered anatomy (SAA) is present. The expanding use of bariatric and oncologic gastrointestinal surgery has increased the number of patients in whom the papilla is displaced, unreachable, or replaced by a biliodigestive anastomosis, making conventional access difficult or impossible. This narrative review appraises the current evidence on endoscopic biliary drainage in SAA, focusing on procedural efficacy, anatomical peculiarities, adverse-event profiles and technical considerations to guide clinical decision-making. Available strategies include luminal techniques, duodenoscope-assisted ERCP, forward-viewing (cap-assisted colonoscope) ERCP, and enteroscope-assisted ERCP, as well as endoscopic ultrasound-guided biliary drainage (EUS-BD), encompassing EUS-guided hepaticogastrostomy, EUS-guided antegrade stenting, EUS-guided rendezvous and EUS-directed transgastric/transenteric ERCP (EDGE/EDEE), and laparoscopic-assisted ERCP (LA-ERCP). No single approach is universally superior and available comparative data is mainly retrospective and affected by major selection bias. Technique selection should be tailored to the reconstruction type, indication (benign vs. malignant), limb length, expected survival, and local expertise, ideally within a multidisciplinary, high-volume setting. Adequately powered randomized trials incorporating quality-of-life and cost-effectiveness endpoints are still needed to define the optimal first-line strategy. This literature review encompasses the multiple strategies to achieve biliary drainage in surgically altered anatomy, highlighting strengths and weaknesses of each technique, as well as the preferred approach for each type of anatomical reconstruction. 2026-09-14 Medicina, Vol. 62, Pages 1766: Current Evidence on Endoscopic Biliary Drainage in the Era of Surgically Altered Anatomy: A Narrative Review

Medicina doi: 10.3390/medicina62091766

Authors: Davide Scalvini Carlo Ciccioli Angelo Bruni Marco Valvano Gianmaria La Rosa Michele Dota Alessandro Cappellini Giulio Massetti Guglielmo Aprile Francesca Torello Viera Letizia Veronese Gianluca Franchellucci Stefano Mazza Aurelio Mauro Marco Bardone Alessandro Fugazza Marco Spadaccini Alessandro Repici Andrea Anderloni

Endoscopic retrograde cholangiopancreatography (ERCP) remains the reference standard for biliary drainage, yet it fails in up to 15% of cases, most notably when a surgically altered anatomy (SAA) is present. The expanding use of bariatric and oncologic gastrointestinal surgery has increased the number of patients in whom the papilla is displaced, unreachable, or replaced by a biliodigestive anastomosis, making conventional access difficult or impossible. This narrative review appraises the current evidence on endoscopic biliary drainage in SAA, focusing on procedural efficacy, anatomical peculiarities, adverse-event profiles and technical considerations to guide clinical decision-making. Available strategies include luminal techniques, duodenoscope-assisted ERCP, forward-viewing (cap-assisted colonoscope) ERCP, and enteroscope-assisted ERCP, as well as endoscopic ultrasound-guided biliary drainage (EUS-BD), encompassing EUS-guided hepaticogastrostomy, EUS-guided antegrade stenting, EUS-guided rendezvous and EUS-directed transgastric/transenteric ERCP (EDGE/EDEE), and laparoscopic-assisted ERCP (LA-ERCP). No single approach is universally superior and available comparative data is mainly retrospective and affected by major selection bias. Technique selection should be tailored to the reconstruction type, indication (benign vs. malignant), limb length, expected survival, and local expertise, ideally within a multidisciplinary, high-volume setting. Adequately powered randomized trials incorporating quality-of-life and cost-effectiveness endpoints are still needed to define the optimal first-line strategy. This literature review encompasses the multiple strategies to achieve biliary drainage in surgically altered anatomy, highlighting strengths and weaknesses of each technique, as well as the preferred approach for each type of anatomical reconstruction.

]]> Current Evidence on Endoscopic Biliary Drainage in the Era of Surgically Altered Anatomy: A Narrative Review Davide Scalvini Carlo Ciccioli Angelo Bruni Marco Valvano Gianmaria La Rosa Michele Dota Alessandro Cappellini Giulio Massetti Guglielmo Aprile Francesca Torello Viera Letizia Veronese Gianluca Franchellucci Stefano Mazza Aurelio Mauro Marco Bardone Alessandro Fugazza Marco Spadaccini Alessandro Repici Andrea Anderloni doi: 10.3390/medicina62091766 Medicina 2026-09-14 Medicina 2026-09-14 62 9 Review 1766 10.3390/medicina62091766 https://www.mdpi.com/1648-9144/62/9/1766 Medicina, Vol. 62, Pages 1765: Bailout Stenting After Drug-Coated Balloon Angioplasty: Clinical Outcomes and Implications for Contemporary PCI—A Systematic Review and Meta-Analysis https://www.mdpi.com/1648-9144/62/9/1765 Background and Objectives: Drug-coated balloon (DCB) angioplasty represents an established stentless strategy in percutaneous coronary intervention (PCI), although bailout stenting (BOS) is frequently required in the presence of suboptimal angiographic results. The clinical impact of BOS following DCB remains incompletely defined. Materials and Methods: We performed a systematic review and single-arm meta-analysis of studies reporting clinical outcomes after BOS following DCB angioplasty, with quantitative synthesis restricted to studies reporting BOS-specific clinical outcomes. Pooled event rates for cardiac death, myocardial infarction (MI), target vessel revascularization (TVR), and target lesion revascularization (TLR) were estimated using random-effects models. Heterogeneity was assessed using standard heterogeneity statistics. Results: Five studies were included in the systematic review; four studies reporting BOS-specific clinical outcomes contributed to the quantitative synthesis, whereas REC-CAGEFREE I was retained as strategy-level supportive evidence. BOS after DCB angioplasty was associated with low pooled rates of cardiac death (1%), MI (3%), TLR (5%) and TVR (5%), with minimal or moderate heterogeneity across analyses. Overall, pooled outcomes were within the range reported in contemporary drug-eluting stent (DES) trials. Conclusions: BOS following DCB angioplasty was associated with generally low short- to mid-term event rates that were broadly consistent with selected historical DES benchmarks. However, because these comparisons are indirect, comparable safety or efficacy cannot be inferred. BOS may therefore be considered a pragmatic contingency within DCB-based strategies rather than necessarily representing procedural failure. 2026-09-14 Medicina, Vol. 62, Pages 1765: Bailout Stenting After Drug-Coated Balloon Angioplasty: Clinical Outcomes and Implications for Contemporary PCI—A Systematic Review and Meta-Analysis

Medicina doi: 10.3390/medicina62091765

Authors: Marcello Marchetta Branislav Crnomarković Lucio Giuseppe Granata Giuseppe Massimo Sangiorgi Mila Kovačević

Background and Objectives: Drug-coated balloon (DCB) angioplasty represents an established stentless strategy in percutaneous coronary intervention (PCI), although bailout stenting (BOS) is frequently required in the presence of suboptimal angiographic results. The clinical impact of BOS following DCB remains incompletely defined. Materials and Methods: We performed a systematic review and single-arm meta-analysis of studies reporting clinical outcomes after BOS following DCB angioplasty, with quantitative synthesis restricted to studies reporting BOS-specific clinical outcomes. Pooled event rates for cardiac death, myocardial infarction (MI), target vessel revascularization (TVR), and target lesion revascularization (TLR) were estimated using random-effects models. Heterogeneity was assessed using standard heterogeneity statistics. Results: Five studies were included in the systematic review; four studies reporting BOS-specific clinical outcomes contributed to the quantitative synthesis, whereas REC-CAGEFREE I was retained as strategy-level supportive evidence. BOS after DCB angioplasty was associated with low pooled rates of cardiac death (1%), MI (3%), TLR (5%) and TVR (5%), with minimal or moderate heterogeneity across analyses. Overall, pooled outcomes were within the range reported in contemporary drug-eluting stent (DES) trials. Conclusions: BOS following DCB angioplasty was associated with generally low short- to mid-term event rates that were broadly consistent with selected historical DES benchmarks. However, because these comparisons are indirect, comparable safety or efficacy cannot be inferred. BOS may therefore be considered a pragmatic contingency within DCB-based strategies rather than necessarily representing procedural failure.

]]> Bailout Stenting After Drug-Coated Balloon Angioplasty: Clinical Outcomes and Implications for Contemporary PCI—A Systematic Review and Meta-Analysis Marcello Marchetta Branislav Crnomarković Lucio Giuseppe Granata Giuseppe Massimo Sangiorgi Mila Kovačević doi: 10.3390/medicina62091765 Medicina 2026-09-14 Medicina 2026-09-14 62 9 Systematic Review 1765 10.3390/medicina62091765 https://www.mdpi.com/1648-9144/62/9/1765 Medicina, Vol. 62, Pages 1764: Association Between Toe Walking and Repetitive Behaviors in Children with Autism Spectrum Disorder: A Cross-Sectional Phenotypic Analysis https://www.mdpi.com/1648-9144/62/9/1764 Background and Objectives: Toe walking (TW) is frequently observed in children with Autism Spectrum Disorder (ASD), yet its clinical significance remains incompletely understood. While previous studies have linked TW to ASD severity and multisystem involvement, its relationship with the behavioral phenotype of repetitive behaviors has not been systematically explored. Materials and Methods: This study analyzed a cohort of 289 children with ASD who underwent comprehensive clinical assessment, including motor evaluation, sleep assessment using the Sleep Disturbance Scale for Children (SDSC), feeding behavior using the Brief Autism Mealtime Behavior Inventory (BAMBI), and detailed behavioral characterization through the Repetitive Behavior Scale-Revised (RBS-R) at the item level. Statistical analyses included non-parametric group comparisons, Spearman correlation analyses, and multivariable regression models. Results: TW was observed in 27.3% of participants. Children with TW showed significantly higher scores in stereotyped behaviors (7.71 ± 2.09 vs. 4.26 ± 2.06, r = 0.756, pFDR < 0.001), ritualistic/sameness behaviors (11.78 ± 3.21 vs. 7.05 ± 3.03, r = 0.709, pFDR < 0.001), and total RBS-R scores (25.52 ± 4.51 vs. 15.88 ± 4.64, r = 0.867, pFDR < 0.001). Correlation analyses revealed a strong association between TW and stereotyped behaviors (ρ = 0.588, p < 0.001) and a moderate association with ritualistic/sameness behaviors (ρ = 0.549, p < 0.001). RBS-R total scores were also correlated with sleep disturbances (ρ = 0.532, p < 0.001). In the multivariate linear model, TW was associated with an adjusted mean increase of 7.77 points in the RBS-R Total Score (B = 7.771, 95% CI 6.603–8.939, p < 0.001, β = 0.551). In the multivariate logistic model, the combined Ritualistic/Sameness behavior domain independently predicted the presence of TW (OR = 1.549, 95% CI 1.366–1.757, p < 0.001). Conclusions: In children with ASD, TW was associated with specific domains of repetitive behavior, particularly stereotyped and ritualistic/sameness patterns. These cross-sectional findings suggest a phenotypic association between motor and behavioral features, without establishing specificity, causality, or a shared underlying mechanism. This multidimensional perspective may support future studies investigating the clinical and biological correlates of TW in ASD. 2026-09-13 Medicina, Vol. 62, Pages 1764: Association Between Toe Walking and Repetitive Behaviors in Children with Autism Spectrum Disorder: A Cross-Sectional Phenotypic Analysis

Medicina doi: 10.3390/medicina62091764

Authors: Martina Gnazzo Giuditta Bargiacchi Beatrice Gallai Giulia Spoto Gabriella Di Rosa Valentina Baldini Lucia Parisi Agata Maltese Michele Roccella Eva Germanò Maria Esposito Marco Carotenuto

Background and Objectives: Toe walking (TW) is frequently observed in children with Autism Spectrum Disorder (ASD), yet its clinical significance remains incompletely understood. While previous studies have linked TW to ASD severity and multisystem involvement, its relationship with the behavioral phenotype of repetitive behaviors has not been systematically explored. Materials and Methods: This study analyzed a cohort of 289 children with ASD who underwent comprehensive clinical assessment, including motor evaluation, sleep assessment using the Sleep Disturbance Scale for Children (SDSC), feeding behavior using the Brief Autism Mealtime Behavior Inventory (BAMBI), and detailed behavioral characterization through the Repetitive Behavior Scale-Revised (RBS-R) at the item level. Statistical analyses included non-parametric group comparisons, Spearman correlation analyses, and multivariable regression models. Results: TW was observed in 27.3% of participants. Children with TW showed significantly higher scores in stereotyped behaviors (7.71 ± 2.09 vs. 4.26 ± 2.06, r = 0.756, pFDR < 0.001), ritualistic/sameness behaviors (11.78 ± 3.21 vs. 7.05 ± 3.03, r = 0.709, pFDR < 0.001), and total RBS-R scores (25.52 ± 4.51 vs. 15.88 ± 4.64, r = 0.867, pFDR < 0.001). Correlation analyses revealed a strong association between TW and stereotyped behaviors (ρ = 0.588, p < 0.001) and a moderate association with ritualistic/sameness behaviors (ρ = 0.549, p < 0.001). RBS-R total scores were also correlated with sleep disturbances (ρ = 0.532, p < 0.001). In the multivariate linear model, TW was associated with an adjusted mean increase of 7.77 points in the RBS-R Total Score (B = 7.771, 95% CI 6.603–8.939, p < 0.001, β = 0.551). In the multivariate logistic model, the combined Ritualistic/Sameness behavior domain independently predicted the presence of TW (OR = 1.549, 95% CI 1.366–1.757, p < 0.001). Conclusions: In children with ASD, TW was associated with specific domains of repetitive behavior, particularly stereotyped and ritualistic/sameness patterns. These cross-sectional findings suggest a phenotypic association between motor and behavioral features, without establishing specificity, causality, or a shared underlying mechanism. This multidimensional perspective may support future studies investigating the clinical and biological correlates of TW in ASD.

]]> Association Between Toe Walking and Repetitive Behaviors in Children with Autism Spectrum Disorder: A Cross-Sectional Phenotypic Analysis Martina Gnazzo Giuditta Bargiacchi Beatrice Gallai Giulia Spoto Gabriella Di Rosa Valentina Baldini Lucia Parisi Agata Maltese Michele Roccella Eva Germanò Maria Esposito Marco Carotenuto doi: 10.3390/medicina62091764 Medicina 2026-09-13 Medicina 2026-09-13 62 9 Article 1764 10.3390/medicina62091764 https://www.mdpi.com/1648-9144/62/9/1764 Medicina, Vol. 62, Pages 1763: Determinants of Chemical Pleurodesis Recurrence in Malignant Pleural Effusion: Mechanical Apposition or Systemic Inflammation? A Retrospective Cohort Study https://www.mdpi.com/1648-9144/62/9/1763 Background and Objectives: Malignant pleural effusion (MPE) severely impairs quality of life; chemical pleurodesis is the standard palliative modality, but the relative contributions of systemic inflammation, tube caliber, and mechanical pleural apposition to failure remain controversial. This study evaluated independent determinants of pleurodesis recurrence, hospital length of stay, and 30-day mortality using causal inference and mediation modeling. Materials and Methods: We conducted a retrospective cohort study of 140 patients undergoing chemical pleurodesis for symptomatic MPE. Pre-procedural inflammatory biomarkers, including the Neutrophil-to-Lymphocyte Ratio (NLR), tube caliber, administration method (bedside slurry vs. Video-Assisted Thoracoscopic Surgery [VATS] poudrage), and lung re-expansion status were recorded. Multivariable logistic regression with nomogram construction, 1:1 propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and bootstrap structural equation modeling (SEM) mediation analysis were performed. Results: Pleurodesis recurrence occurred in 28.6% (n = 40) and 30-day mortality in 16.4% (n = 23) of patients. Non-expandable lung (adjusted odds ratio [aOR] = 9.89, 95% CI: 3.98–26.29, p < 0.001) and suboptimal catheter position (aOR = 3.80, 95% CI: 1.11–14.84, p = 0.407) were the strongest independent predictors of recurrence (C-index = 0.851); non-expandable lung also increased mortality 5.21-fold (p = 0.036). Large-bore tubes reduced matched odds of catheter malposition (OR = 0.096) and recurrence (OR = 0.405, p = 0.493) in the propensity-matched cohort, and VATS poudrage shortened hospital stay by 6.40 days (p = 0.074) versus slurry after weighting. Exploratory mediation analysis showed NLR’s direct effect on recurrence was non-significant (β = 0.0147, p = 0.5897); although summed indirect pathways accounted for a numerically larger share of the total effect, the bootstrap confidence interval for the total indirect effect crossed zero (β = 0.0330, 95% CI: −0.0155 to 0.0742), with only the pathway via catheter malposition individually excluding zero (β = 0.0126, 95% CI: 0.0014–0.0416), suggesting a plausible but unconfirmed mechanical-mediation trend. Patients with no comorbidities unexpectedly had higher mortality than those with multiple comorbidities (25.0% vs. 7.1%, p = 0.19), reflecting younger age and greater cachexia (albumin 28.14 ± 4.54 g/L) rather than comorbidity itself. Conclusions: Pleurodesis efficacy in MPE appears to be governed primarily by mechanical visceroparietal apposition; systemic inflammation showed no significant direct effect on recurrence, and its possible indirect, mechanically mediated contribution should be regarded as hypothesis-generating pending prospective confirmation. Clinicians managing high-risk patients (elevated NLR, non-expandable lung, or cachexia) should prioritize mechanical optimization—large-bore drainage, VATS poudrage, or early indwelling pleural catheter placement. 2026-09-13 Medicina, Vol. 62, Pages 1763: Determinants of Chemical Pleurodesis Recurrence in Malignant Pleural Effusion: Mechanical Apposition or Systemic Inflammation? A Retrospective Cohort Study

Medicina doi: 10.3390/medicina62091763

Authors: Caner İşevi Mehmet Gökhan Pirzirenli Eren Yılmaz Yavuz Karaca Burçin Çelik Yasemin Büyükkarabacak

Background and Objectives: Malignant pleural effusion (MPE) severely impairs quality of life; chemical pleurodesis is the standard palliative modality, but the relative contributions of systemic inflammation, tube caliber, and mechanical pleural apposition to failure remain controversial. This study evaluated independent determinants of pleurodesis recurrence, hospital length of stay, and 30-day mortality using causal inference and mediation modeling. Materials and Methods: We conducted a retrospective cohort study of 140 patients undergoing chemical pleurodesis for symptomatic MPE. Pre-procedural inflammatory biomarkers, including the Neutrophil-to-Lymphocyte Ratio (NLR), tube caliber, administration method (bedside slurry vs. Video-Assisted Thoracoscopic Surgery [VATS] poudrage), and lung re-expansion status were recorded. Multivariable logistic regression with nomogram construction, 1:1 propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and bootstrap structural equation modeling (SEM) mediation analysis were performed. Results: Pleurodesis recurrence occurred in 28.6% (n = 40) and 30-day mortality in 16.4% (n = 23) of patients. Non-expandable lung (adjusted odds ratio [aOR] = 9.89, 95% CI: 3.98–26.29, p < 0.001) and suboptimal catheter position (aOR = 3.80, 95% CI: 1.11–14.84, p = 0.407) were the strongest independent predictors of recurrence (C-index = 0.851); non-expandable lung also increased mortality 5.21-fold (p = 0.036). Large-bore tubes reduced matched odds of catheter malposition (OR = 0.096) and recurrence (OR = 0.405, p = 0.493) in the propensity-matched cohort, and VATS poudrage shortened hospital stay by 6.40 days (p = 0.074) versus slurry after weighting. Exploratory mediation analysis showed NLR’s direct effect on recurrence was non-significant (β = 0.0147, p = 0.5897); although summed indirect pathways accounted for a numerically larger share of the total effect, the bootstrap confidence interval for the total indirect effect crossed zero (β = 0.0330, 95% CI: −0.0155 to 0.0742), with only the pathway via catheter malposition individually excluding zero (β = 0.0126, 95% CI: 0.0014–0.0416), suggesting a plausible but unconfirmed mechanical-mediation trend. Patients with no comorbidities unexpectedly had higher mortality than those with multiple comorbidities (25.0% vs. 7.1%, p = 0.19), reflecting younger age and greater cachexia (albumin 28.14 ± 4.54 g/L) rather than comorbidity itself. Conclusions: Pleurodesis efficacy in MPE appears to be governed primarily by mechanical visceroparietal apposition; systemic inflammation showed no significant direct effect on recurrence, and its possible indirect, mechanically mediated contribution should be regarded as hypothesis-generating pending prospective confirmation. Clinicians managing high-risk patients (elevated NLR, non-expandable lung, or cachexia) should prioritize mechanical optimization—large-bore drainage, VATS poudrage, or early indwelling pleural catheter placement.

]]> Determinants of Chemical Pleurodesis Recurrence in Malignant Pleural Effusion: Mechanical Apposition or Systemic Inflammation? A Retrospective Cohort Study Caner İşevi Mehmet Gökhan Pirzirenli Eren Yılmaz Yavuz Karaca Burçin Çelik Yasemin Büyükkarabacak doi: 10.3390/medicina62091763 Medicina 2026-09-13 Medicina 2026-09-13 62 9 Article 1763 10.3390/medicina62091763 https://www.mdpi.com/1648-9144/62/9/1763 Medicina, Vol. 62, Pages 1762: Salivary Melatonin and MMP-9 Levels in Stage III Periodontitis: A Pilot Study Using Standardized Pre-Sleep Saliva Collection https://www.mdpi.com/1648-9144/62/9/1762 Background and Objectives: Periodontitis is a chronic multifactorial inflammatory disease characterized by progressive destruction of the tooth-supporting tissues. Although periodontal diagnosis is primarily based on clinical and radiographic parameters, salivary biomarkers may provide additional biological information on inflammatory activity and host-response regulation. Matrix metalloproteinase-9 (MMP-9) is involved in extracellular matrix degradation and periodontal tissue destruction, whereas melatonin is a circadian-related molecule with antioxidant, anti-inflammatory, and immunomodulatory properties. However, evidence regarding the simultaneous assessment of salivary MMP-9 and melatonin using standardized pre-sleep saliva collection remains limited. This pilot study aimed to evaluate salivary melatonin and MMP-9 concentrations in periodontal health and stage III periodontitis, to assess their interrelationship, and to explore their preliminary in-sample ability to distinguish periodontal health from stage III periodontitis. Materials and Methods: This cross-sectional pilot study included 18 systemically healthy non-smoking adults: 9 periodontally healthy participants and 9 patients with stage III periodontitis. Pre-sleep unstimulated saliva was collected between 23:00 and 24:00 h or immediately before sleep, following a standardized protocol. Salivary MMP-9 and melatonin concentrations were determined using enzyme-linked immunosorbent assay. Periodontal diagnosis was established according to the 2017 World Workshop classification. Group comparisons, correlation analyses, and receiver operating characteristic curve analyses were performed as exploratory analyses. Results: Salivary melatonin concentrations were significantly lower in patients with stage III periodontitis than in periodontally healthy participants (p = 0.019), with a large effect size (Hedges’ g = 1.261). Salivary MMP-9 concentrations were higher in the periodontitis group, but the difference was not statistically significant (p = 0.465). No significant correlation was found between salivary melatonin and MMP-9 levels. Receiver operating characteristic analysis suggested preliminary in-sample discriminatory ability for melatonin (AUC = 0.827; p = 0.019), whereas MMP-9 showed limited and non-significant discriminatory ability (AUC = 0.593; p = 0.508). Conclusions: In this pilot sample, lower pre-sleep salivary melatonin levels were associated with stage III periodontitis, whereas MMP-9 showed limited standalone discriminatory ability. These findings should be interpreted as preliminary and hypothesis-generating. The present study does not establish a clinically applicable diagnostic cut-off or validated diagnostic utility for salivary melatonin. Larger, independently validated studies are needed to confirm these observations. 2026-09-13 Medicina, Vol. 62, Pages 1762: Salivary Melatonin and MMP-9 Levels in Stage III Periodontitis: A Pilot Study Using Standardized Pre-Sleep Saliva Collection

Medicina doi: 10.3390/medicina62091762

Authors: Ivan Ivanov Emilia Naseva Antoaneta Mlachkova Velitchka Dosseva-Panova Zdravka Pashova-Tasseva Hristina Maynalovska Boyan Kirilov Viktoria Petrova Nikolay Ishkitiev Sonia Apostolova

Background and Objectives: Periodontitis is a chronic multifactorial inflammatory disease characterized by progressive destruction of the tooth-supporting tissues. Although periodontal diagnosis is primarily based on clinical and radiographic parameters, salivary biomarkers may provide additional biological information on inflammatory activity and host-response regulation. Matrix metalloproteinase-9 (MMP-9) is involved in extracellular matrix degradation and periodontal tissue destruction, whereas melatonin is a circadian-related molecule with antioxidant, anti-inflammatory, and immunomodulatory properties. However, evidence regarding the simultaneous assessment of salivary MMP-9 and melatonin using standardized pre-sleep saliva collection remains limited. This pilot study aimed to evaluate salivary melatonin and MMP-9 concentrations in periodontal health and stage III periodontitis, to assess their interrelationship, and to explore their preliminary in-sample ability to distinguish periodontal health from stage III periodontitis. Materials and Methods: This cross-sectional pilot study included 18 systemically healthy non-smoking adults: 9 periodontally healthy participants and 9 patients with stage III periodontitis. Pre-sleep unstimulated saliva was collected between 23:00 and 24:00 h or immediately before sleep, following a standardized protocol. Salivary MMP-9 and melatonin concentrations were determined using enzyme-linked immunosorbent assay. Periodontal diagnosis was established according to the 2017 World Workshop classification. Group comparisons, correlation analyses, and receiver operating characteristic curve analyses were performed as exploratory analyses. Results: Salivary melatonin concentrations were significantly lower in patients with stage III periodontitis than in periodontally healthy participants (p = 0.019), with a large effect size (Hedges’ g = 1.261). Salivary MMP-9 concentrations were higher in the periodontitis group, but the difference was not statistically significant (p = 0.465). No significant correlation was found between salivary melatonin and MMP-9 levels. Receiver operating characteristic analysis suggested preliminary in-sample discriminatory ability for melatonin (AUC = 0.827; p = 0.019), whereas MMP-9 showed limited and non-significant discriminatory ability (AUC = 0.593; p = 0.508). Conclusions: In this pilot sample, lower pre-sleep salivary melatonin levels were associated with stage III periodontitis, whereas MMP-9 showed limited standalone discriminatory ability. These findings should be interpreted as preliminary and hypothesis-generating. The present study does not establish a clinically applicable diagnostic cut-off or validated diagnostic utility for salivary melatonin. Larger, independently validated studies are needed to confirm these observations.

]]> Salivary Melatonin and MMP-9 Levels in Stage III Periodontitis: A Pilot Study Using Standardized Pre-Sleep Saliva Collection Ivan Ivanov Emilia Naseva Antoaneta Mlachkova Velitchka Dosseva-Panova Zdravka Pashova-Tasseva Hristina Maynalovska Boyan Kirilov Viktoria Petrova Nikolay Ishkitiev Sonia Apostolova doi: 10.3390/medicina62091762 Medicina 2026-09-13 Medicina 2026-09-13 62 9 Article 1762 10.3390/medicina62091762 https://www.mdpi.com/1648-9144/62/9/1762 Medicina, Vol. 62, Pages 1761: Full-Endoscopic Unilateral Laminotomy for Bilateral Decompression Under Surgeon-Directed Local Anesthesia in Older Patients with Lumbar Spinal Stenosis https://www.mdpi.com/1648-9144/62/9/1761 Background and Objectives: Older patients with lumbar spinal stenosis often have comorbidities and limited physiological reserve that complicate conventional decompression under general anesthesia. This study aimed to evaluate the surgical technique and preliminary 1-year clinical outcomes of full-endoscopic unilateral laminotomy for bilateral decompression (FE-ULBD) performed under surgeon-directed local anesthesia. Materials and Methods: This retrospective cohort study included 24 consecutive patients aged ≥ 75 years who underwent FE-ULBD under surgeon-directed local anesthesia for symptomatic central lumbar spinal stenosis between March 2024 and April 2025. Clinical outcomes were evaluated using the visual analog scale (VAS) for leg pain, Oswestry Disability Index (ODI), and modified MacNab criteria. Additionally, perioperative outcomes and complications were analyzed. Results: The mean age of patients was 80.5 ± 3.8 years. The mean VAS scores improved from 8.46 ± 0.72 preoperatively to 2.08 ± 0.83 at 12 months, while ODI scores improved from 68.83% ± 8.07% to 18.34% ± 13.74% (both p < 0.001). Of the 24 patients, 21 (87.5%) achieved excellent or good outcomes. Procedure-related complications included an incidental dural tear in one patient (4.2%) and transient postoperative dysesthesia in 4 patients (16.7%). No major anesthesia-related complications or revision surgeries were observed. Conclusions: FE-ULBD under surgeon-directed local anesthesia was feasible and associated with improvements in pain and function at 12 months in carefully selected older patients. These preliminary findings warrant confirmation in larger prospective studies with a comparator cohort of older patients receiving general anesthesia. 2026-09-12 Medicina, Vol. 62, Pages 1761: Full-Endoscopic Unilateral Laminotomy for Bilateral Decompression Under Surgeon-Directed Local Anesthesia in Older Patients with Lumbar Spinal Stenosis

Medicina doi: 10.3390/medicina62091761

Authors: Yong Ahn Sungsoo Bae Jae-Ouk Lee

Background and Objectives: Older patients with lumbar spinal stenosis often have comorbidities and limited physiological reserve that complicate conventional decompression under general anesthesia. This study aimed to evaluate the surgical technique and preliminary 1-year clinical outcomes of full-endoscopic unilateral laminotomy for bilateral decompression (FE-ULBD) performed under surgeon-directed local anesthesia. Materials and Methods: This retrospective cohort study included 24 consecutive patients aged ≥ 75 years who underwent FE-ULBD under surgeon-directed local anesthesia for symptomatic central lumbar spinal stenosis between March 2024 and April 2025. Clinical outcomes were evaluated using the visual analog scale (VAS) for leg pain, Oswestry Disability Index (ODI), and modified MacNab criteria. Additionally, perioperative outcomes and complications were analyzed. Results: The mean age of patients was 80.5 ± 3.8 years. The mean VAS scores improved from 8.46 ± 0.72 preoperatively to 2.08 ± 0.83 at 12 months, while ODI scores improved from 68.83% ± 8.07% to 18.34% ± 13.74% (both p < 0.001). Of the 24 patients, 21 (87.5%) achieved excellent or good outcomes. Procedure-related complications included an incidental dural tear in one patient (4.2%) and transient postoperative dysesthesia in 4 patients (16.7%). No major anesthesia-related complications or revision surgeries were observed. Conclusions: FE-ULBD under surgeon-directed local anesthesia was feasible and associated with improvements in pain and function at 12 months in carefully selected older patients. These preliminary findings warrant confirmation in larger prospective studies with a comparator cohort of older patients receiving general anesthesia.

]]> Full-Endoscopic Unilateral Laminotomy for Bilateral Decompression Under Surgeon-Directed Local Anesthesia in Older Patients with Lumbar Spinal Stenosis Yong Ahn Sungsoo Bae Jae-Ouk Lee doi: 10.3390/medicina62091761 Medicina 2026-09-12 Medicina 2026-09-12 62 9 Article 1761 10.3390/medicina62091761 https://www.mdpi.com/1648-9144/62/9/1761 Medicina, Vol. 62, Pages 1760: Prognostic Value of Temporalis Muscle Thickness for Predicting Mortality in Patients with Emergency Department Cardiac Arrest https://www.mdpi.com/1648-9144/62/9/1760 Background and Objectives: Temporalis muscle thickness (TMT) has emerged as an imaging-based morphometric surrogate associated with reduced muscle mass and frailty; however, its prognostic value in emergency department cardiac arrest (EDCA) remains unclear. This study aimed to evaluate the association between TMT and emergency department mortality in patients with EDCA who had cranial CT imaging available during the same emergency department encounter and to investigate its association with in-hospital mortality. Materials and Methods: This study included 129 adult patients who experienced cardiac arrest in the emergency department between 1 June 2022 and 31 May 2025, and had eligible cranial CT imaging available during the same emergency department encounter. TMT was measured on non-contrast brain computed tomography images. The association between TMT and mortality outcomes, including emergency department and in-hospital mortality, was statistically analyzed. Results: TMT was significantly lower in patients who died in the emergency department compared with survivors (median 3.29 mm [Q1–Q3: 2.63–3.95] vs. 4.69 mm [Q1–Q3: 3.70–5.65], p < 0.001). Similarly, patients who died in an in-hospital setting had lower TMT values than survivors (median 4.06 mm [Q1–Q3: 3.26–5.34] vs. 5.00 mm [Q1–Q3: 4.21–5.85], p = 0.040). ROC analysis demonstrated the moderate discriminative ability of TMT for predicting emergency department mortality (AUC = 0.763, 95% CI 0.671–0.856). Logistic regression analysis identified that, after adjustment for age, sex, and CPR duration, TMT remained associated with emergency department mortality (adjusted OR 0.34, 95% CI 0.133–0.886; p = 0.027). Conclusions: Among patients with EDCA who had eligible cranial CT imaging during the same emergency department encounter, lower temporalis muscle thickness was associated with increased emergency department mortality, whereas its association with in-hospital mortality was weaker. Given the retrospective design and limited number of outcome events, these findings should be considered exploratory and require validation in larger independent cohorts. 2026-09-12 Medicina, Vol. 62, Pages 1760: Prognostic Value of Temporalis Muscle Thickness for Predicting Mortality in Patients with Emergency Department Cardiac Arrest

Medicina doi: 10.3390/medicina62091760

Authors: Ahmet Öztürk Serkan Günay Erdal Komut Hakan Özerol Mert Barındık Serdal Ateş Seval Komut Yavuz Yiğit

Background and Objectives: Temporalis muscle thickness (TMT) has emerged as an imaging-based morphometric surrogate associated with reduced muscle mass and frailty; however, its prognostic value in emergency department cardiac arrest (EDCA) remains unclear. This study aimed to evaluate the association between TMT and emergency department mortality in patients with EDCA who had cranial CT imaging available during the same emergency department encounter and to investigate its association with in-hospital mortality. Materials and Methods: This study included 129 adult patients who experienced cardiac arrest in the emergency department between 1 June 2022 and 31 May 2025, and had eligible cranial CT imaging available during the same emergency department encounter. TMT was measured on non-contrast brain computed tomography images. The association between TMT and mortality outcomes, including emergency department and in-hospital mortality, was statistically analyzed. Results: TMT was significantly lower in patients who died in the emergency department compared with survivors (median 3.29 mm [Q1–Q3: 2.63–3.95] vs. 4.69 mm [Q1–Q3: 3.70–5.65], p < 0.001). Similarly, patients who died in an in-hospital setting had lower TMT values than survivors (median 4.06 mm [Q1–Q3: 3.26–5.34] vs. 5.00 mm [Q1–Q3: 4.21–5.85], p = 0.040). ROC analysis demonstrated the moderate discriminative ability of TMT for predicting emergency department mortality (AUC = 0.763, 95% CI 0.671–0.856). Logistic regression analysis identified that, after adjustment for age, sex, and CPR duration, TMT remained associated with emergency department mortality (adjusted OR 0.34, 95% CI 0.133–0.886; p = 0.027). Conclusions: Among patients with EDCA who had eligible cranial CT imaging during the same emergency department encounter, lower temporalis muscle thickness was associated with increased emergency department mortality, whereas its association with in-hospital mortality was weaker. Given the retrospective design and limited number of outcome events, these findings should be considered exploratory and require validation in larger independent cohorts.

]]> Prognostic Value of Temporalis Muscle Thickness for Predicting Mortality in Patients with Emergency Department Cardiac Arrest Ahmet Öztürk Serkan Günay Erdal Komut Hakan Özerol Mert Barındık Serdal Ateş Seval Komut Yavuz Yiğit doi: 10.3390/medicina62091760 Medicina 2026-09-12 Medicina 2026-09-12 62 9 Article 1760 10.3390/medicina62091760 https://www.mdpi.com/1648-9144/62/9/1760 Medicina, Vol. 62, Pages 1759: Association of Postoperative Drainage Strategy with Persistent Urinary Leakage and Clinical Outcomes Following Percutaneous Nephrolithotomy https://www.mdpi.com/1648-9144/62/9/1759 Background and Objectives: Persistent postoperative urinary leakage may delay recovery after percutaneous nephrolithotomy (PCNL). This study evaluated the association between postoperative drainage strategy, persistent urinary leakage, and clinical outcomes following prone PCNL. Materials and Methods: This retrospective, non-randomized cohort analysis included 606 consecutive eligible patients undergoing prone PCNL between 2015 and 2026 from a prospectively maintained institutional database. Patients received either an external ureteral catheter (n = 529) or primary antegrade double-J (DJ) stent (n = 77). Perioperative outcomes were compared, and factors associated with persistent urinary leakage were evaluated in the ureteral-catheter group. Results: Operative and nephroscopy times were longer in the DJ-stent group (110.4 ± 47.2 vs. 100.6 ± 37.9 min, p = 0.041; 50.0 vs. 40.0 min, p = 0.002). Persistent urinary leakage occurred in 39 patients (7.4%) with ureteral catheters and in none with primary DJ stents (p = 0.006). After stabilized IPTW, the risk difference for primary DJ stenting versus ureteral-catheter drainage was −7.45 percentage points (95% bootstrap CI, −9.77 to −5.33). The distributions of nephrostomy tube removal time and hospital stay differed between the drainage groups (DJ stent vs. ureteral catheter: 2.0 [IQR, 2.0–2.0] vs. 2.0 [IQR, 2.0–2.5] days, p = 0.028; and 3.0 [IQR, 2.0–3.0] vs. 3.0 [IQR, 3.0–4.0] days, p = 0.004, respectively), although the corresponding Hodges–Lehmann estimated differences were small (0 days [95% CI, 0 to 0] and 0 days [95% CI, 0 to 1], respectively). In multivariable analysis, residual stone presence was associated with higher odds of persistent urinary leakage (adjusted OR 2.16, 95% CI 1.09–4.28; p = 0.027). Conclusions: Primary antegrade DJ stenting was associated with lower urinary leakage rates. Although the distributions of nephrostomy tube removal time and hospital stay also favored the DJ-stent group, the absolute between-group differences were small. Residual stone presence remained independently associated with higher odds of persistent urinary leakage. 2026-09-12 Medicina, Vol. 62, Pages 1759: Association of Postoperative Drainage Strategy with Persistent Urinary Leakage and Clinical Outcomes Following Percutaneous Nephrolithotomy

Medicina doi: 10.3390/medicina62091759

Authors: Anıl Eker Kemal Züngün Muhammet Bilal Nart Muhammet Halil Dağaşan Serkan Yarımoğlu Murat Şahan İbrahim Halil Bozkurt Tansu Değirmenci

Background and Objectives: Persistent postoperative urinary leakage may delay recovery after percutaneous nephrolithotomy (PCNL). This study evaluated the association between postoperative drainage strategy, persistent urinary leakage, and clinical outcomes following prone PCNL. Materials and Methods: This retrospective, non-randomized cohort analysis included 606 consecutive eligible patients undergoing prone PCNL between 2015 and 2026 from a prospectively maintained institutional database. Patients received either an external ureteral catheter (n = 529) or primary antegrade double-J (DJ) stent (n = 77). Perioperative outcomes were compared, and factors associated with persistent urinary leakage were evaluated in the ureteral-catheter group. Results: Operative and nephroscopy times were longer in the DJ-stent group (110.4 ± 47.2 vs. 100.6 ± 37.9 min, p = 0.041; 50.0 vs. 40.0 min, p = 0.002). Persistent urinary leakage occurred in 39 patients (7.4%) with ureteral catheters and in none with primary DJ stents (p = 0.006). After stabilized IPTW, the risk difference for primary DJ stenting versus ureteral-catheter drainage was −7.45 percentage points (95% bootstrap CI, −9.77 to −5.33). The distributions of nephrostomy tube removal time and hospital stay differed between the drainage groups (DJ stent vs. ureteral catheter: 2.0 [IQR, 2.0–2.0] vs. 2.0 [IQR, 2.0–2.5] days, p = 0.028; and 3.0 [IQR, 2.0–3.0] vs. 3.0 [IQR, 3.0–4.0] days, p = 0.004, respectively), although the corresponding Hodges–Lehmann estimated differences were small (0 days [95% CI, 0 to 0] and 0 days [95% CI, 0 to 1], respectively). In multivariable analysis, residual stone presence was associated with higher odds of persistent urinary leakage (adjusted OR 2.16, 95% CI 1.09–4.28; p = 0.027). Conclusions: Primary antegrade DJ stenting was associated with lower urinary leakage rates. Although the distributions of nephrostomy tube removal time and hospital stay also favored the DJ-stent group, the absolute between-group differences were small. Residual stone presence remained independently associated with higher odds of persistent urinary leakage.

]]> Association of Postoperative Drainage Strategy with Persistent Urinary Leakage and Clinical Outcomes Following Percutaneous Nephrolithotomy Anıl Eker Kemal Züngün Muhammet Bilal Nart Muhammet Halil Dağaşan Serkan Yarımoğlu Murat Şahan İbrahim Halil Bozkurt Tansu Değirmenci doi: 10.3390/medicina62091759 Medicina 2026-09-12 Medicina 2026-09-12 62 9 Article 1759 10.3390/medicina62091759 https://www.mdpi.com/1648-9144/62/9/1759 Medicina, Vol. 62, Pages 1758: Periostitis of the Pubic Symphysis in Inguinal and Femoral Hernia: An Uninterpreted Source of Chronic Groin Pain https://www.mdpi.com/1648-9144/62/9/1758 Background and Objectives: Severe chronic postoperative inguinal pain (CPIP) affects 2–5% of patients after hernia repair, yet most published explanations remain neuropathic. The pubic periosteum, including the tubercle and adjacent symphyseal zone, lies within the operative field and may be engaged by medial mesh fixation. Its contribution to CPIP has not been tested. This narrative review brings together anatomical, imaging and clinical evidence and defines a hypothesis that can be examined prospectively. Materials and Methods: PubMed/MEDLINE, Embase and the Cochrane Library were searched without date restriction, with the final search run in April 2026. Thirty-three publications met the eligibility criteria. Evidence was classified using the 2011 OCEBM Levels of Evidence, with indirectness recorded when the population, exposure or outcome did not match the review question. The review was narrative, so no PRISMA flow diagram or formal risk-of-bias assessment was undertaken. Results: Direct evidence is limited. Among 1633 patients in one retrospective study, six underwent reoperation for severe late pain, and two had a staple placed in the periosteum. Pain resolved after staple removal. Two further cases of MRI-confirmed osteitis pubis followed laparoscopic repair with a titanium tacker. CT found pubic spurs in 17 of 20 patients, although their clinical meaning was uncertain. Fixation trials, CPIP reviews and groin-pain imaging studies repeatedly examined adjacent outcomes but did not define a periosteal endpoint. Conclusions: Pubic periosteal pathology is a plausible and testable pain generator, not an established cause of CPIP. Prospective studies should pair preoperative MRI and standardised pain mapping with explicit recording of fixation at the pubic tubercle. This design would show whether periosteal findings identify a distinct pain phenotype and whether penetrating fixation modifies its course. 2026-09-12 Medicina, Vol. 62, Pages 1758: Periostitis of the Pubic Symphysis in Inguinal and Femoral Hernia: An Uninterpreted Source of Chronic Groin Pain

Medicina doi: 10.3390/medicina62091758

Authors: Sergey Yu. Muraviev Zakhar A. Akulov Maria A. Sukhanova Miroslava O. Pilipenko Evgeniy A. Tarabrin Zelimkhan G. M. Berikkhanov Aleksey G. Kotelnikov Andrey M. Nikolaev Vadim S. Razumovsky Milena Yu. Ivanova Sara Nourmahal Ruoran Xia Vladislav S. Rakintsev Alexey L. Shestakov

Background and Objectives: Severe chronic postoperative inguinal pain (CPIP) affects 2–5% of patients after hernia repair, yet most published explanations remain neuropathic. The pubic periosteum, including the tubercle and adjacent symphyseal zone, lies within the operative field and may be engaged by medial mesh fixation. Its contribution to CPIP has not been tested. This narrative review brings together anatomical, imaging and clinical evidence and defines a hypothesis that can be examined prospectively. Materials and Methods: PubMed/MEDLINE, Embase and the Cochrane Library were searched without date restriction, with the final search run in April 2026. Thirty-three publications met the eligibility criteria. Evidence was classified using the 2011 OCEBM Levels of Evidence, with indirectness recorded when the population, exposure or outcome did not match the review question. The review was narrative, so no PRISMA flow diagram or formal risk-of-bias assessment was undertaken. Results: Direct evidence is limited. Among 1633 patients in one retrospective study, six underwent reoperation for severe late pain, and two had a staple placed in the periosteum. Pain resolved after staple removal. Two further cases of MRI-confirmed osteitis pubis followed laparoscopic repair with a titanium tacker. CT found pubic spurs in 17 of 20 patients, although their clinical meaning was uncertain. Fixation trials, CPIP reviews and groin-pain imaging studies repeatedly examined adjacent outcomes but did not define a periosteal endpoint. Conclusions: Pubic periosteal pathology is a plausible and testable pain generator, not an established cause of CPIP. Prospective studies should pair preoperative MRI and standardised pain mapping with explicit recording of fixation at the pubic tubercle. This design would show whether periosteal findings identify a distinct pain phenotype and whether penetrating fixation modifies its course.

]]> Periostitis of the Pubic Symphysis in Inguinal and Femoral Hernia: An Uninterpreted Source of Chronic Groin Pain Sergey Yu. Muraviev Zakhar A. Akulov Maria A. Sukhanova Miroslava O. Pilipenko Evgeniy A. Tarabrin Zelimkhan G. M. Berikkhanov Aleksey G. Kotelnikov Andrey M. Nikolaev Vadim S. Razumovsky Milena Yu. Ivanova Sara Nourmahal Ruoran Xia Vladislav S. Rakintsev Alexey L. Shestakov doi: 10.3390/medicina62091758 Medicina 2026-09-12 Medicina 2026-09-12 62 9 Review 1758 10.3390/medicina62091758 https://www.mdpi.com/1648-9144/62/9/1758 Medicina, Vol. 62, Pages 1757: Incidence of Malignant Oral Cavity Tumors in the Republic of Serbia: Trend Analysis (1999–2020) and Projections to 2040 https://www.mdpi.com/1648-9144/62/9/1757 Background and Objectives: Malignant tumors of the oral cavity are an important and growing component of the global cancer burden, with well-documented sex disparities in incidence. This study aimed to characterize temporal trends in the incidence of these tumors in the Republic of Serbia between 1999 and 2020, overall and by sex, and to forecast incidence through 2040. Materials and Methods: All histopathologically verified cases (ICD-10: C01–C06, excluding the lip) reported to the Cancer Registry of the Republic of Serbia (excluding the Autonomous Province of Kosovo and Metohija, for which data are unavailable) were analyzed retrospectively. Age-standardized incidence rates (ASRs; world standard population) were calculated, and joinpoint regression estimated the annual percentage change (APC) with 95% confidence intervals (CI). Autoregressive Integrated Moving Average (ARIMA) models projected incidence to 2040, with sensitivity analyses for the 2016 extension of Registry coverage. Results: A total of 5695 cases were registered (3872 men, 1823 women). Restricted to the population under consistent Registry coverage (Central Serbia, 1999–2015), incidence did not change significantly in either sex (men: APC = −0.30%, 95% CI: −1.63, 1.06; women: APC = −3.31%, 95% CI: −7.41, 0.96). Over the full 1999–2020 series, which includes the 2016 extension of coverage to Vojvodina, incidence appeared to rise among men (APC = 1.71%; 95% CI: 0.47, 2.96; p = 0.009), with an apparent acceleration after 2013 (APC = 8.39%; p = 0.002); a level-shift model and a formal comparison of competing trend descriptions both attributed this apparent rise to the 2016 coverage change rather than to a genuine trend (+50.7%; p < 0.001). Male incidence was about twice that in women (mean ASR 3.63 versus 1.64). Under an unchanged-coverage scenario, ARIMA models projected a flat mean incidence through 2040 (2.6 per 100,000 overall; 4.7 in men, with a 95% prediction interval widening from 3.6–5.8 in 2021 to 1.2–8.2 in 2040), with a considerably less precise and less reliable forecast for women. Conclusions: Oral cavity cancer incidence in Central Serbia was stable from 1999 to 2015, with a persistent male excess. The apparent post-2013 rise is attributable to the 2016 extension of registry coverage rather than to a genuine trend, and a counterfactual estimate suggests considerably higher incidence in Vojvodina. Region-stratified reporting is needed before national trends can be interpreted reliably. 2026-09-11 Medicina, Vol. 62, Pages 1757: Incidence of Malignant Oral Cavity Tumors in the Republic of Serbia: Trend Analysis (1999–2020) and Projections to 2040

Medicina doi: 10.3390/medicina62091757

Authors: Vojkan Lazić Vladimir Videnović Andrija Ćosić Milan Miladinović Marko Matvijenko Aleksandar Šubarić Aleksandra Ilić Vladimir Matvijenko Dejan Perić Goran Videnović

Background and Objectives: Malignant tumors of the oral cavity are an important and growing component of the global cancer burden, with well-documented sex disparities in incidence. This study aimed to characterize temporal trends in the incidence of these tumors in the Republic of Serbia between 1999 and 2020, overall and by sex, and to forecast incidence through 2040. Materials and Methods: All histopathologically verified cases (ICD-10: C01–C06, excluding the lip) reported to the Cancer Registry of the Republic of Serbia (excluding the Autonomous Province of Kosovo and Metohija, for which data are unavailable) were analyzed retrospectively. Age-standardized incidence rates (ASRs; world standard population) were calculated, and joinpoint regression estimated the annual percentage change (APC) with 95% confidence intervals (CI). Autoregressive Integrated Moving Average (ARIMA) models projected incidence to 2040, with sensitivity analyses for the 2016 extension of Registry coverage. Results: A total of 5695 cases were registered (3872 men, 1823 women). Restricted to the population under consistent Registry coverage (Central Serbia, 1999–2015), incidence did not change significantly in either sex (men: APC = −0.30%, 95% CI: −1.63, 1.06; women: APC = −3.31%, 95% CI: −7.41, 0.96). Over the full 1999–2020 series, which includes the 2016 extension of coverage to Vojvodina, incidence appeared to rise among men (APC = 1.71%; 95% CI: 0.47, 2.96; p = 0.009), with an apparent acceleration after 2013 (APC = 8.39%; p = 0.002); a level-shift model and a formal comparison of competing trend descriptions both attributed this apparent rise to the 2016 coverage change rather than to a genuine trend (+50.7%; p < 0.001). Male incidence was about twice that in women (mean ASR 3.63 versus 1.64). Under an unchanged-coverage scenario, ARIMA models projected a flat mean incidence through 2040 (2.6 per 100,000 overall; 4.7 in men, with a 95% prediction interval widening from 3.6–5.8 in 2021 to 1.2–8.2 in 2040), with a considerably less precise and less reliable forecast for women. Conclusions: Oral cavity cancer incidence in Central Serbia was stable from 1999 to 2015, with a persistent male excess. The apparent post-2013 rise is attributable to the 2016 extension of registry coverage rather than to a genuine trend, and a counterfactual estimate suggests considerably higher incidence in Vojvodina. Region-stratified reporting is needed before national trends can be interpreted reliably.

]]> Incidence of Malignant Oral Cavity Tumors in the Republic of Serbia: Trend Analysis (1999–2020) and Projections to 2040 Vojkan Lazić Vladimir Videnović Andrija Ćosić Milan Miladinović Marko Matvijenko Aleksandar Šubarić Aleksandra Ilić Vladimir Matvijenko Dejan Perić Goran Videnović doi: 10.3390/medicina62091757 Medicina 2026-09-11 Medicina 2026-09-11 62 9 Article 1757 10.3390/medicina62091757 https://www.mdpi.com/1648-9144/62/9/1757 Medicina, Vol. 62, Pages 1756: Antimicrobial Resistance and Stewardship in Surgical Departments: A Three-Year Single-Center Study https://www.mdpi.com/1648-9144/62/9/1756 Background and Objectives: Antimicrobial resistance represents an important patient-safety concern in surgical departments, where empirical therapy, invasive procedures, intensive-care exposure, and healthcare-associated infections may contribute to adverse outcomes. This study aimed to describe temporal changes in institutional surveillance indicators related to microbiological testing coverage, selected antimicrobial-resistance phenotypes among clinical isolates, selected-antibiotic use profiles, and infection-related patient-safety outcomes in surgical departments and the intensive care unit of a Romanian tertiary clinical emergency hospital. Materials and Methods: A retrospective, longitudinal, single-center observational study was conducted from January 2023 to December 2025. Data were extracted from four institutional sources: microbiology laboratory records, pharmacy antimicrobial-use data, the infection prevention and control registry, and the clinical-administrative hospital information system. Microbiological testing coverage, the selected resistance phenotypes and healthcare-associated infection indicators were analyzed at semester level, with selected-antibiotic DDD profiles being analyzed at department level. Statistical analyses included descriptive statistics, Cochran–Armitage trend testing, Fisher’s exact test, and exploratory Spearman correlation. Results: The hospital-wide microbiological testing intensity index based on 1892 antibiogram events among 8141 antibiotic-treated patient records increased significantly from 18.05% (Semester I 2023) to 28.20% (Semester II 2025). When expressed as proportions of clinical isolates, E. coli MDR decreased from 10/136 isolates (7.4%) in Semester II 2023 to 0/122 isolates (0.0%) in Semester II 2025, and S. aureus MRSA+MLSB decreased from 11/36 isolates (30.6%) to 0/22 isolates (0.0%) over the same interval. Undetected several semesters, P. aeruginosa XDR/PDR accounted for 4/25 clinical isolates (16.0%) in the final semester. Selected-antibiotic DDD profiles differed across departments, with General Surgery and ICU accounting for the largest selected-antibiotic totals. Preoperative bacteriological screening increased from 48 tests in Semester I 2024 to 329 tests in Semester II 2025, MRSA-positive screening results decreasing from 10/48 (20.8%) to 2/329 (0.6%) over this interval, this finding being interpreted descriptively because the screened population and screening protocol could not be fully standardized retrospectively. Among 46 validated cases of healthcare or Clostridioides difficile infections, the overall mean length of stay was 15.35 days, peaking at 20.80 days in surgical departments. Conclusions: Routinely collected hospital data can generate useful institutional surveillance signals related to antimicrobial resistance, antimicrobial use, and infection-related patient safety. Increased microbiological testing coverage and lower proportions of selected MDR/MRSA phenotypes were observed during the study period, while late detection of XDR/PDR P. aeruginosa highlighted the need for sustained microbiological surveillance and department-specific stewardship review. 2026-09-11 Medicina, Vol. 62, Pages 1756: Antimicrobial Resistance and Stewardship in Surgical Departments: A Three-Year Single-Center Study

Medicina doi: 10.3390/medicina62091756

Authors: Adriana Grindean Mihaela Elvira Cîmpianu Elena Maria Domsa Adrian Popentiu

Background and Objectives: Antimicrobial resistance represents an important patient-safety concern in surgical departments, where empirical therapy, invasive procedures, intensive-care exposure, and healthcare-associated infections may contribute to adverse outcomes. This study aimed to describe temporal changes in institutional surveillance indicators related to microbiological testing coverage, selected antimicrobial-resistance phenotypes among clinical isolates, selected-antibiotic use profiles, and infection-related patient-safety outcomes in surgical departments and the intensive care unit of a Romanian tertiary clinical emergency hospital. Materials and Methods: A retrospective, longitudinal, single-center observational study was conducted from January 2023 to December 2025. Data were extracted from four institutional sources: microbiology laboratory records, pharmacy antimicrobial-use data, the infection prevention and control registry, and the clinical-administrative hospital information system. Microbiological testing coverage, the selected resistance phenotypes and healthcare-associated infection indicators were analyzed at semester level, with selected-antibiotic DDD profiles being analyzed at department level. Statistical analyses included descriptive statistics, Cochran–Armitage trend testing, Fisher’s exact test, and exploratory Spearman correlation. Results: The hospital-wide microbiological testing intensity index based on 1892 antibiogram events among 8141 antibiotic-treated patient records increased significantly from 18.05% (Semester I 2023) to 28.20% (Semester II 2025). When expressed as proportions of clinical isolates, E. coli MDR decreased from 10/136 isolates (7.4%) in Semester II 2023 to 0/122 isolates (0.0%) in Semester II 2025, and S. aureus MRSA+MLSB decreased from 11/36 isolates (30.6%) to 0/22 isolates (0.0%) over the same interval. Undetected several semesters, P. aeruginosa XDR/PDR accounted for 4/25 clinical isolates (16.0%) in the final semester. Selected-antibiotic DDD profiles differed across departments, with General Surgery and ICU accounting for the largest selected-antibiotic totals. Preoperative bacteriological screening increased from 48 tests in Semester I 2024 to 329 tests in Semester II 2025, MRSA-positive screening results decreasing from 10/48 (20.8%) to 2/329 (0.6%) over this interval, this finding being interpreted descriptively because the screened population and screening protocol could not be fully standardized retrospectively. Among 46 validated cases of healthcare or Clostridioides difficile infections, the overall mean length of stay was 15.35 days, peaking at 20.80 days in surgical departments. Conclusions: Routinely collected hospital data can generate useful institutional surveillance signals related to antimicrobial resistance, antimicrobial use, and infection-related patient safety. Increased microbiological testing coverage and lower proportions of selected MDR/MRSA phenotypes were observed during the study period, while late detection of XDR/PDR P. aeruginosa highlighted the need for sustained microbiological surveillance and department-specific stewardship review.

]]> Antimicrobial Resistance and Stewardship in Surgical Departments: A Three-Year Single-Center Study Adriana Grindean Mihaela Elvira Cîmpianu Elena Maria Domsa Adrian Popentiu doi: 10.3390/medicina62091756 Medicina 2026-09-11 Medicina 2026-09-11 62 9 Article 1756 10.3390/medicina62091756 https://www.mdpi.com/1648-9144/62/9/1756 Medicina, Vol. 62, Pages 1755: Transition from Pediatric to Adult Endocrine Care in Patients with Congenital Adrenal Hyperplasia: A Single-Center Retrospective Analysis https://www.mdpi.com/1648-9144/62/9/1755 Background and Objectives: The transition from pediatric to adult endocrine care represents a vulnerable period for patients with congenital adrenal hyperplasia (CAH), given the risk of loss to follow-up and the evolving physiological and healthcare requirements associated with the transition to adulthood. This study aimed to compare structured and non-structured transition pathways in patients with CAH, focusing on the continuity of adult endocrine care and disease-specific hormonal, clinical, and treatment-related outcomes. Materials and Methods: This single-center, retrospective, observational study included patients with CAH who transitioned from pediatric to adult endocrine care and met predefined pediatric and adult follow-up eligibility criteria. Patients were classified according to whether the transition occurred through a structured multidisciplinary transition program or without participation in the structured program. Outcomes were evaluated during predefined observation periods before and after transfer and included continuity-of-care measures, 17-hydroxyprogesterone (17-OHP) and androstenedione concentrations, achievement of predefined hormonal targets, body mass index (BMI), glucocorticoid and mineralocorticoid treatment, and CAH-related clinical outcomes. Results: Among 67 patients assessed for eligibility, 29 were included: 20 in the structured transition group and 9 in the non-structured transition group. Overall, 62.1% of the study population was female. No significant between-group differences were observed in continuity-of-care measures, including the pediatric-to-adult care gap, first-year adult visit frequency, maximum visit-free interval, first-year loss to follow-up, or active adult endocrine follow-up at the study cutoff. Pre-transition and post-transfer 17-OHP and androstenedione concentrations and achievement of predefined hormonal targets did not differ significantly between groups. No significant longitudinal changes in hormonal outcomes, BMI, or body-surface-area-adjusted hydrocortisone-equivalent glucocorticoid doses were observed within either group. At the study cutoff, 85.0% of patients in the structured group and 77.8% in the non-structured group remained under active adult endocrine follow-up. Conclusions: In this small single-center cohort, no significant differences in the continuity of adult endocrine follow-up or disease-specific outcomes were observed between structured and non-structured transition pathways. Most patients remained engaged with adult endocrine care, and hormonal control showed no evident deterioration following transfer in either group. Given the small sample size and high overall retention, these findings should not be interpreted as evidence of equivalence between the two transition approaches. 2026-09-11 Medicina, Vol. 62, Pages 1755: Transition from Pediatric to Adult Endocrine Care in Patients with Congenital Adrenal Hyperplasia: A Single-Center Retrospective Analysis

Medicina doi: 10.3390/medicina62091755

Authors: Filiz Mercan Sarıdaş Kadircan Karatoprak Hatice Nursoy Erhan Hocaoğlu Müge Yaşar Yasemin Denkboy Öngen Soner Cander Erdinç Ertürk Özen Öz Gül Erdal Eren Canan Ersoy

Background and Objectives: The transition from pediatric to adult endocrine care represents a vulnerable period for patients with congenital adrenal hyperplasia (CAH), given the risk of loss to follow-up and the evolving physiological and healthcare requirements associated with the transition to adulthood. This study aimed to compare structured and non-structured transition pathways in patients with CAH, focusing on the continuity of adult endocrine care and disease-specific hormonal, clinical, and treatment-related outcomes. Materials and Methods: This single-center, retrospective, observational study included patients with CAH who transitioned from pediatric to adult endocrine care and met predefined pediatric and adult follow-up eligibility criteria. Patients were classified according to whether the transition occurred through a structured multidisciplinary transition program or without participation in the structured program. Outcomes were evaluated during predefined observation periods before and after transfer and included continuity-of-care measures, 17-hydroxyprogesterone (17-OHP) and androstenedione concentrations, achievement of predefined hormonal targets, body mass index (BMI), glucocorticoid and mineralocorticoid treatment, and CAH-related clinical outcomes. Results: Among 67 patients assessed for eligibility, 29 were included: 20 in the structured transition group and 9 in the non-structured transition group. Overall, 62.1% of the study population was female. No significant between-group differences were observed in continuity-of-care measures, including the pediatric-to-adult care gap, first-year adult visit frequency, maximum visit-free interval, first-year loss to follow-up, or active adult endocrine follow-up at the study cutoff. Pre-transition and post-transfer 17-OHP and androstenedione concentrations and achievement of predefined hormonal targets did not differ significantly between groups. No significant longitudinal changes in hormonal outcomes, BMI, or body-surface-area-adjusted hydrocortisone-equivalent glucocorticoid doses were observed within either group. At the study cutoff, 85.0% of patients in the structured group and 77.8% in the non-structured group remained under active adult endocrine follow-up. Conclusions: In this small single-center cohort, no significant differences in the continuity of adult endocrine follow-up or disease-specific outcomes were observed between structured and non-structured transition pathways. Most patients remained engaged with adult endocrine care, and hormonal control showed no evident deterioration following transfer in either group. Given the small sample size and high overall retention, these findings should not be interpreted as evidence of equivalence between the two transition approaches.

]]> Transition from Pediatric to Adult Endocrine Care in Patients with Congenital Adrenal Hyperplasia: A Single-Center Retrospective Analysis Filiz Mercan Sarıdaş Kadircan Karatoprak Hatice Nursoy Erhan Hocaoğlu Müge Yaşar Yasemin Denkboy Öngen Soner Cander Erdinç Ertürk Özen Öz Gül Erdal Eren Canan Ersoy doi: 10.3390/medicina62091755 Medicina 2026-09-11 Medicina 2026-09-11 62 9 Article 1755 10.3390/medicina62091755 https://www.mdpi.com/1648-9144/62/9/1755 Medicina, Vol. 62, Pages 1754: Temporomandibular Joint Defects: Etiology and Reconstruction Strategy: A Narrative Review https://www.mdpi.com/1648-9144/62/9/1754 Temporomandibular joint (TMJ) defects primarily arise from congenital malformations, bony ankylosis, and radical tumor resection. As a pivotal structure for regulating maxillofacial development and maintaining stomatognathic homeostasis, the anatomical restoration and functional reconstruction of the TMJ are essential for rehabilitating the dentofacial complex. Distinct from standard mandibular reconstruction, TMJ reconstruction is inherently more complex, with treatment heavily dependent on etiology, age, defect extent, and coexisting dentofacial deformities—factors that invariably require patient-specific protocols. This review systematically evaluates current reconstructive paradigms, including free bone grafting (costochondral and coronoid process grafting, vertical ramus osteotomy), vascularized free flaps (vascularized fibula, vascularized medial femoral condyle, and deep circumflex iliac artery flaps), mandibular ramus distraction osteogenesis, and total joint replacement. We provide a critical analysis of their respective clinical indications, advantages, and limitations, while discussing emerging trends and future perspectives in the field. 2026-09-11 Medicina, Vol. 62, Pages 1754: Temporomandibular Joint Defects: Etiology and Reconstruction Strategy: A Narrative Review

Medicina doi: 10.3390/medicina62091754

Authors: Hengyu Zou Bimeng Jie Haoliang Chen Yang He Shuo Chen

Temporomandibular joint (TMJ) defects primarily arise from congenital malformations, bony ankylosis, and radical tumor resection. As a pivotal structure for regulating maxillofacial development and maintaining stomatognathic homeostasis, the anatomical restoration and functional reconstruction of the TMJ are essential for rehabilitating the dentofacial complex. Distinct from standard mandibular reconstruction, TMJ reconstruction is inherently more complex, with treatment heavily dependent on etiology, age, defect extent, and coexisting dentofacial deformities—factors that invariably require patient-specific protocols. This review systematically evaluates current reconstructive paradigms, including free bone grafting (costochondral and coronoid process grafting, vertical ramus osteotomy), vascularized free flaps (vascularized fibula, vascularized medial femoral condyle, and deep circumflex iliac artery flaps), mandibular ramus distraction osteogenesis, and total joint replacement. We provide a critical analysis of their respective clinical indications, advantages, and limitations, while discussing emerging trends and future perspectives in the field.

]]> Temporomandibular Joint Defects: Etiology and Reconstruction Strategy: A Narrative Review Hengyu Zou Bimeng Jie Haoliang Chen Yang He Shuo Chen doi: 10.3390/medicina62091754 Medicina 2026-09-11 Medicina 2026-09-11 62 9 Review 1754 10.3390/medicina62091754 https://www.mdpi.com/1648-9144/62/9/1754 Medicina, Vol. 62, Pages 1753: Contemporary Evidence on Interhospital Neonatal Transport as a Potentially Sepsis-Relevant Care Interval: A Scoping Review https://www.mdpi.com/1648-9144/62/9/1753 Background and Objectives: Neonatal sepsis is time-sensitive, yet the role of interhospital transport in its early care pathway is poorly characterised. This scoping review systematically identified and classified contemporary neonatal transport variables, interventions, and organisational practices potentially relevant to early sepsis care, examined the evidentiary proximity of the available literature to neonatal sepsis, and identified priorities for direct investigation. Materials and Methods: PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library were searched for English-language, peer-reviewed reports published from 1 January 2020 to 30 June 2026. Google Scholar, an academic search engine, and backward citation searching supplemented the database search. Two reviewers independently screened records; a third author charted data using a predefined matrix. Findings were reported according to PRISMA-ScR and synthesised descriptively because the mapping question and non-comparable concepts and outcomes did not support a pooled estimate. Results: Thirty-nine sources of evidence were included. They covered system organisation; respiratory and procedural stabilisation; haemodynamic, metabolic, and thermal management; medication and fluid use; adverse events; environmental exposures; and communication. Evidence was predominantly indirect: 24 sources were classified as indirect clinical, seven as indirect organisational, four as indirect technical, one as indirect experiential, and three as direct transport-process/indirect sepsis-outcome evidence. Few reports addressed infection-related processes, and none established that a transport intervention independently improved sepsis-specific outcomes. Antimicrobial timing, culture status, perfusion trajectories, and structured sepsis handover were rarely reported. Conclusions: Contemporary neonatal transport research identifies measurable care processes that may matter when sepsis is suspected, but the sepsis-specific effect of transport remains unproven. Prospective multicentre studies should directly link transport-phase processes with infection-defined populations and outcomes. 2026-09-11 Medicina, Vol. 62, Pages 1753: Contemporary Evidence on Interhospital Neonatal Transport as a Potentially Sepsis-Relevant Care Interval: A Scoping Review

Medicina doi: 10.3390/medicina62091753

Authors: Roni Octavian Damian Lidia Boldeanu Mihai Gabriel Cucu Mirela Anişoara Siminel Mihai Alexandru Butoi Vlad Ionut Belghiru Monica Iuliana Puticiu Raluca Mihaela Tat Bogdan Oprita Mohamed-Zakaria Assani Virginia Maria Radulescu Cristiana Geormaneanu Mihail Virgil Boldeanu Luciana Teodora Rotaru

Background and Objectives: Neonatal sepsis is time-sensitive, yet the role of interhospital transport in its early care pathway is poorly characterised. This scoping review systematically identified and classified contemporary neonatal transport variables, interventions, and organisational practices potentially relevant to early sepsis care, examined the evidentiary proximity of the available literature to neonatal sepsis, and identified priorities for direct investigation. Materials and Methods: PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library were searched for English-language, peer-reviewed reports published from 1 January 2020 to 30 June 2026. Google Scholar, an academic search engine, and backward citation searching supplemented the database search. Two reviewers independently screened records; a third author charted data using a predefined matrix. Findings were reported according to PRISMA-ScR and synthesised descriptively because the mapping question and non-comparable concepts and outcomes did not support a pooled estimate. Results: Thirty-nine sources of evidence were included. They covered system organisation; respiratory and procedural stabilisation; haemodynamic, metabolic, and thermal management; medication and fluid use; adverse events; environmental exposures; and communication. Evidence was predominantly indirect: 24 sources were classified as indirect clinical, seven as indirect organisational, four as indirect technical, one as indirect experiential, and three as direct transport-process/indirect sepsis-outcome evidence. Few reports addressed infection-related processes, and none established that a transport intervention independently improved sepsis-specific outcomes. Antimicrobial timing, culture status, perfusion trajectories, and structured sepsis handover were rarely reported. Conclusions: Contemporary neonatal transport research identifies measurable care processes that may matter when sepsis is suspected, but the sepsis-specific effect of transport remains unproven. Prospective multicentre studies should directly link transport-phase processes with infection-defined populations and outcomes.

]]> Contemporary Evidence on Interhospital Neonatal Transport as a Potentially Sepsis-Relevant Care Interval: A Scoping Review Roni Octavian Damian Lidia Boldeanu Mihai Gabriel Cucu Mirela Anişoara Siminel Mihai Alexandru Butoi Vlad Ionut Belghiru Monica Iuliana Puticiu Raluca Mihaela Tat Bogdan Oprita Mohamed-Zakaria Assani Virginia Maria Radulescu Cristiana Geormaneanu Mihail Virgil Boldeanu Luciana Teodora Rotaru doi: 10.3390/medicina62091753 Medicina 2026-09-11 Medicina 2026-09-11 62 9 Review 1753 10.3390/medicina62091753 https://www.mdpi.com/1648-9144/62/9/1753 Medicina, Vol. 62, Pages 1752: Acute Respiratory Infections Hospitalizations and In-Hospital Mortality in Ecuador: Differences in Patterns Between Pediatric and Adult Populations https://www.mdpi.com/1648-9144/62/9/1752 Background and Objectives: Acute respiratory infections (ARIs) remain a leading cause of hospitalization and preventable in-hospital mortality. This study aimed to characterize ARI hospitalizations and mortality in Ecuador and to identify factors associated with mortality across age groups. Materials and Methods: A cross-sectional study was conducted using national hospital data for 2015–2023. Crude hospitalization and in-hospital mortality rates were estimated by year and province. Age-adjusted temporal trends were evaluated using Joinpoint regression to obtain annual percentage change (APC). Univariable and multivariable logistic regression analyses were used to assess factors associated with in-hospital mortality in the overall, pediatric and adult populations. Results: A total of 576,195 ARI hospitalizations were analyzed: 51.24% were pediatric and 48.76% adult admissions. Although children accounted for most hospitalizations, in-hospital mortality was substantially higher among adults (14.04%) than among children (0.53%) and increased progressively with age. Age-adjusted rates had a significant annual increase among adults from 2015 to 2021 (APC 30.08% for hospitalization and 55.10% for mortality) and declined significantly from 2021 to 2023 (APC: −53.09% and −72.90%, respectively), whereas pediatric trends showed no significant changes. Lower respiratory tract infections, including bacterial pneumonia, viral pneumonia, and COVID-19, showed the highest odds of in-hospital death. Bronchiolitis was associated with increased odds of death in both pediatric and adult populations, with markedly stronger associations among adults. Rural residence and ethnicity showed age-specific associations with mortality, potentially reflecting differences in access to hospital care. During 2020–2021, COVID-19 accounted for 70.71% of ARI hospitalizations and nearly 87.17% of in-hospital deaths, with ARI hospitalization rates remaining above pre-pandemic levels thereafter. Conclusions: ARIs impose a substantial and unequal burden on Ecuador’s health system. Mortality patterns may reflect age-related vulnerability, disease severity, and structural barriers to care rather than hospitalization volume alone, supporting the need for age-differentiated and equity-oriented public health strategies. 2026-09-11 Medicina, Vol. 62, Pages 1752: Acute Respiratory Infections Hospitalizations and In-Hospital Mortality in Ecuador: Differences in Patterns Between Pediatric and Adult Populations

Medicina doi: 10.3390/medicina62091752

Authors: German Josuet Lapo-Talledo Andrés Ramírez Jorge Andrés Talledo-Delgado Karime Montes Escobar Pedro Muñoz-Arteaga Vanessa Quito-Calle Lorena Cañizares-Jarrín Andrea Margot Moreira Toscano

Background and Objectives: Acute respiratory infections (ARIs) remain a leading cause of hospitalization and preventable in-hospital mortality. This study aimed to characterize ARI hospitalizations and mortality in Ecuador and to identify factors associated with mortality across age groups. Materials and Methods: A cross-sectional study was conducted using national hospital data for 2015–2023. Crude hospitalization and in-hospital mortality rates were estimated by year and province. Age-adjusted temporal trends were evaluated using Joinpoint regression to obtain annual percentage change (APC). Univariable and multivariable logistic regression analyses were used to assess factors associated with in-hospital mortality in the overall, pediatric and adult populations. Results: A total of 576,195 ARI hospitalizations were analyzed: 51.24% were pediatric and 48.76% adult admissions. Although children accounted for most hospitalizations, in-hospital mortality was substantially higher among adults (14.04%) than among children (0.53%) and increased progressively with age. Age-adjusted rates had a significant annual increase among adults from 2015 to 2021 (APC 30.08% for hospitalization and 55.10% for mortality) and declined significantly from 2021 to 2023 (APC: −53.09% and −72.90%, respectively), whereas pediatric trends showed no significant changes. Lower respiratory tract infections, including bacterial pneumonia, viral pneumonia, and COVID-19, showed the highest odds of in-hospital death. Bronchiolitis was associated with increased odds of death in both pediatric and adult populations, with markedly stronger associations among adults. Rural residence and ethnicity showed age-specific associations with mortality, potentially reflecting differences in access to hospital care. During 2020–2021, COVID-19 accounted for 70.71% of ARI hospitalizations and nearly 87.17% of in-hospital deaths, with ARI hospitalization rates remaining above pre-pandemic levels thereafter. Conclusions: ARIs impose a substantial and unequal burden on Ecuador’s health system. Mortality patterns may reflect age-related vulnerability, disease severity, and structural barriers to care rather than hospitalization volume alone, supporting the need for age-differentiated and equity-oriented public health strategies.

]]> Acute Respiratory Infections Hospitalizations and In-Hospital Mortality in Ecuador: Differences in Patterns Between Pediatric and Adult Populations German Josuet Lapo-Talledo Andrés Ramírez Jorge Andrés Talledo-Delgado Karime Montes Escobar Pedro Muñoz-Arteaga Vanessa Quito-Calle Lorena Cañizares-Jarrín Andrea Margot Moreira Toscano doi: 10.3390/medicina62091752 Medicina 2026-09-11 Medicina 2026-09-11 62 9 Article 1752 10.3390/medicina62091752 https://www.mdpi.com/1648-9144/62/9/1752 Medicina, Vol. 62, Pages 1751: Bridging the Gap in Psychogenic Erectile Dysfunction: A Narrative Review of Underexplored Therapeutic Options https://www.mdpi.com/1648-9144/62/9/1751 Background and Objectives: Psychogenic erectile dysfunction (ED) is a distinct clinical condition characterized by predominant psychological or relational factors. Despite its prevalence, diagnostic criteria remain heterogeneous and are often based on exclusion of organic causes. Current guidelines recommend cognitive behavioral therapy (CBT), eventually combined with medical therapy such as phosphodiesterase type 5 inhibitors (PDE5i), as first-line treatment. However, evidence regarding alternative conservative and surgical therapies remains limited. This narrative review aims to evaluate the available evidence on these treatments in psychogenic ED. Materials and Methods: A comprehensive literature search was conducted in PubMed, Scopus, and MEDLINE using MeSH terms and free-text keywords related to psychogenic ED and therapeutic interventions. Eligible studies included those involving human subjects, published in English, and reporting outcomes specifically for psychogenic or non-organic ED. Reviews, case reports, and non-full-text articles were excluded. Study selection and data extraction were performed independently by two authors. Due to heterogeneity, a narrative synthesis was conducted. Results: Evidence on alternative therapies is limited and heterogeneous, with many studies predating the 2000s. Vacuum erection devices (VEDs) may improve outcomes, particularly when combined with psychotherapy. Constriction rings showed promising preliminary results. Acupuncture demonstrated inconsistent efficacy, although recent randomized trials suggest potential benefits. Intracavernosal injections (ICI) showed favorable outcomes, particularly in patients refractory to first-line therapies, with some reports of restored spontaneous erections. Penile prosthesis (PP) implantation remains underexplored in contemporary literature on psychogenic ED; however, recent evidence reports good satisfaction rates. Conclusions: Beyond CBT and PDE5i, evidence for alternative treatments in psychogenic ED is scarce and methodologically limited. Selected patients may benefit from adjunctive therapies, including VED, ICI, and acupuncture, while PP can be considered a definitive treatment option. Further well-designed studies are needed to clarify their role within a structured, evidence-based management approach. 2026-09-11 Medicina, Vol. 62, Pages 1751: Bridging the Gap in Psychogenic Erectile Dysfunction: A Narrative Review of Underexplored Therapeutic Options

Medicina doi: 10.3390/medicina62091751

Authors: Marta Pezzoli Elettra Fuligni Mattia Lo Re Andrea Cocci Andrea Minervini Damien Carnicelli

Background and Objectives: Psychogenic erectile dysfunction (ED) is a distinct clinical condition characterized by predominant psychological or relational factors. Despite its prevalence, diagnostic criteria remain heterogeneous and are often based on exclusion of organic causes. Current guidelines recommend cognitive behavioral therapy (CBT), eventually combined with medical therapy such as phosphodiesterase type 5 inhibitors (PDE5i), as first-line treatment. However, evidence regarding alternative conservative and surgical therapies remains limited. This narrative review aims to evaluate the available evidence on these treatments in psychogenic ED. Materials and Methods: A comprehensive literature search was conducted in PubMed, Scopus, and MEDLINE using MeSH terms and free-text keywords related to psychogenic ED and therapeutic interventions. Eligible studies included those involving human subjects, published in English, and reporting outcomes specifically for psychogenic or non-organic ED. Reviews, case reports, and non-full-text articles were excluded. Study selection and data extraction were performed independently by two authors. Due to heterogeneity, a narrative synthesis was conducted. Results: Evidence on alternative therapies is limited and heterogeneous, with many studies predating the 2000s. Vacuum erection devices (VEDs) may improve outcomes, particularly when combined with psychotherapy. Constriction rings showed promising preliminary results. Acupuncture demonstrated inconsistent efficacy, although recent randomized trials suggest potential benefits. Intracavernosal injections (ICI) showed favorable outcomes, particularly in patients refractory to first-line therapies, with some reports of restored spontaneous erections. Penile prosthesis (PP) implantation remains underexplored in contemporary literature on psychogenic ED; however, recent evidence reports good satisfaction rates. Conclusions: Beyond CBT and PDE5i, evidence for alternative treatments in psychogenic ED is scarce and methodologically limited. Selected patients may benefit from adjunctive therapies, including VED, ICI, and acupuncture, while PP can be considered a definitive treatment option. Further well-designed studies are needed to clarify their role within a structured, evidence-based management approach.

]]> Bridging the Gap in Psychogenic Erectile Dysfunction: A Narrative Review of Underexplored Therapeutic Options Marta Pezzoli Elettra Fuligni Mattia Lo Re Andrea Cocci Andrea Minervini Damien Carnicelli doi: 10.3390/medicina62091751 Medicina 2026-09-11 Medicina 2026-09-11 62 9 Review 1751 10.3390/medicina62091751 https://www.mdpi.com/1648-9144/62/9/1751 Medicina, Vol. 62, Pages 1750: Longitudinal Visual Evoked Potential Changes Show Distinct Associations with Relapse Activity and Disability in Relapsing–Remitting Multiple Sclerosis: A Multicenter Retrospective Cohort Study https://www.mdpi.com/1648-9144/62/9/1750 Background and Objectives: Visual evoked potentials (VEPs) are established tools for detecting optic pathway involvement in multiple sclerosis (MS); however, the distinct clinical significance of longitudinal changes in latency and amplitude remains unclear. This exploratory study aimed to evaluate the clinical utility of serial VEP assessments in patients with relapsing–remitting MS (RRMS) by examining the associations between temporal changes in latency and amplitude and concurrent markers of disease activity and disability. Materials and Methods: We retrospectively analyzed 83 patients with RRMS from three centers who underwent at least two pattern-reversal VEP assessments ≥ 1 year apart. Patients with recent optic neuritis were excluded. Longitudinal changes in VEP latency and amplitude were evaluated in relation to relapse activity during the same inter-assessment interval, baseline MRI and CSF findings, and disability assessed by the Expanded Disability Status Scale (EDSS). Sensitivity analyses were stratified and adjusted for disease-modifying therapy (DMT) efficacy tier, and progression independent of relapse activity (PIRA) was examined using a formal definition. Results: Over a median follow-up of 2 years, 43.4% of patients developed P100 latency prolongation, which was independently associated with a higher annualized relapse rate during the same interval (odds ratio [OR] 2.91, p = 0.005; area under the curve (AUC) 0.72 for concurrent on-study relapse activity), an association that persisted after adjustment for DMT efficacy tier, but not with disability worsening. In contrast, 56.6% of patients exhibited amplitude reduction, which was associated with greater disability accumulation at the group level, with higher EDSS scores at follow-up despite similar baseline values (p < 0.05); the corresponding inverse correlation between amplitude decline and EDSS change was only nominally significant (ρ = −0.231, p = 0.036), did not survive correction for multiple comparisons, and was attenuated after adjustment for baseline EDSS. Formally defined PIRA events were rare (n = 3), precluding inference. Baseline magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) findings differed in the latency group, with fewer MRI lesions and a lower immunoglobulin G (IgG) index, whereas no corresponding differences were observed in the amplitude group. Conclusions: In this exploratory cohort, longitudinal prolongation of VEP latency was associated with concurrent relapse activity, whereas amplitude decline showed a weaker, group-level association with disability. These findings are consistent with, but do not demonstrate, distinct inflammatory and neurodegenerative substrates, and warrant prospective validation before serial VEP monitoring can inform individualized management in MS. 2026-09-11 Medicina, Vol. 62, Pages 1750: Longitudinal Visual Evoked Potential Changes Show Distinct Associations with Relapse Activity and Disability in Relapsing–Remitting Multiple Sclerosis: A Multicenter Retrospective Cohort Study

Medicina doi: 10.3390/medicina62091750

Authors: Samet Öncel Meral Seferoğlu Sami Ömerhoca Semanur Aksu Ertuğrul Çınar Hakan Kılıçaslan Abdulkadir Tunç Nilüfer Kale İçen

Background and Objectives: Visual evoked potentials (VEPs) are established tools for detecting optic pathway involvement in multiple sclerosis (MS); however, the distinct clinical significance of longitudinal changes in latency and amplitude remains unclear. This exploratory study aimed to evaluate the clinical utility of serial VEP assessments in patients with relapsing–remitting MS (RRMS) by examining the associations between temporal changes in latency and amplitude and concurrent markers of disease activity and disability. Materials and Methods: We retrospectively analyzed 83 patients with RRMS from three centers who underwent at least two pattern-reversal VEP assessments ≥ 1 year apart. Patients with recent optic neuritis were excluded. Longitudinal changes in VEP latency and amplitude were evaluated in relation to relapse activity during the same inter-assessment interval, baseline MRI and CSF findings, and disability assessed by the Expanded Disability Status Scale (EDSS). Sensitivity analyses were stratified and adjusted for disease-modifying therapy (DMT) efficacy tier, and progression independent of relapse activity (PIRA) was examined using a formal definition. Results: Over a median follow-up of 2 years, 43.4% of patients developed P100 latency prolongation, which was independently associated with a higher annualized relapse rate during the same interval (odds ratio [OR] 2.91, p = 0.005; area under the curve (AUC) 0.72 for concurrent on-study relapse activity), an association that persisted after adjustment for DMT efficacy tier, but not with disability worsening. In contrast, 56.6% of patients exhibited amplitude reduction, which was associated with greater disability accumulation at the group level, with higher EDSS scores at follow-up despite similar baseline values (p < 0.05); the corresponding inverse correlation between amplitude decline and EDSS change was only nominally significant (ρ = −0.231, p = 0.036), did not survive correction for multiple comparisons, and was attenuated after adjustment for baseline EDSS. Formally defined PIRA events were rare (n = 3), precluding inference. Baseline magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) findings differed in the latency group, with fewer MRI lesions and a lower immunoglobulin G (IgG) index, whereas no corresponding differences were observed in the amplitude group. Conclusions: In this exploratory cohort, longitudinal prolongation of VEP latency was associated with concurrent relapse activity, whereas amplitude decline showed a weaker, group-level association with disability. These findings are consistent with, but do not demonstrate, distinct inflammatory and neurodegenerative substrates, and warrant prospective validation before serial VEP monitoring can inform individualized management in MS.

]]> Longitudinal Visual Evoked Potential Changes Show Distinct Associations with Relapse Activity and Disability in Relapsing–Remitting Multiple Sclerosis: A Multicenter Retrospective Cohort Study Samet Öncel Meral Seferoğlu Sami Ömerhoca Semanur Aksu Ertuğrul Çınar Hakan Kılıçaslan Abdulkadir Tunç Nilüfer Kale İçen doi: 10.3390/medicina62091750 Medicina 2026-09-11 Medicina 2026-09-11 62 9 Article 1750 10.3390/medicina62091750 https://www.mdpi.com/1648-9144/62/9/1750 Medicina, Vol. 62, Pages 1749: Influence of Support Surface Stability on Changes in Quadriceps Femoris Muscle Thickness During Progressive Squat Exercise in Patients with Stroke: A Randomized Controlled Trial https://www.mdpi.com/1648-9144/62/9/1749 Background and Objectives: Stroke, a neurological disorder caused by damage to the central nervous system, is commonly accompanied by impairments in motor and sensory function and muscle strength. We compared the effects of progressive squat exercises performed under varying support-surface stability conditions on quadriceps femoris muscle thickness in patients 6 months to less than 1 year after stroke, using rehabilitative ultrasound imaging. Materials and Methods: This randomized, open-label, parallel-group controlled trial assessed 36 patients with stroke for eligibility. Four individuals were excluded before randomization; the remaining 32 participants were randomly assigned in a 1:1 ratio to either the unstable-support-surface squat exercise group (n = 16) or the stable-support-surface squat exercise group (n = 16). Both groups performed progressive squat exercises five times per week for 4 weeks. Quadriceps femoris muscle thickness was measured before and after the intervention using rehabilitative ultrasound imaging. Results: Between-group comparisons of changes from baseline showed significantly greater increases in rectus femoris and vastus medialis muscle thickness in the unstable support-surface squat exercise group than in the stable support-surface squat exercise group (p < 0.05). No significant between-group differences were observed in vastus intermedius or vastus lateralis muscle thickness (p > 0.05). Conclusions: Progressive squat exercise performed on an unstable support surface resulted in greater increases in rectus femoris and vastus medialis muscle thickness than the same exercise performed on a stable support surface. However, these findings are limited to muscle thickness and should not be interpreted as evidence of improved muscle strength or functional performance. 2026-09-11 Medicina, Vol. 62, Pages 1749: Influence of Support Surface Stability on Changes in Quadriceps Femoris Muscle Thickness During Progressive Squat Exercise in Patients with Stroke: A Randomized Controlled Trial

Medicina doi: 10.3390/medicina62091749

Authors: Hui Ju Nam Ga-Yeon Kim

Background and Objectives: Stroke, a neurological disorder caused by damage to the central nervous system, is commonly accompanied by impairments in motor and sensory function and muscle strength. We compared the effects of progressive squat exercises performed under varying support-surface stability conditions on quadriceps femoris muscle thickness in patients 6 months to less than 1 year after stroke, using rehabilitative ultrasound imaging. Materials and Methods: This randomized, open-label, parallel-group controlled trial assessed 36 patients with stroke for eligibility. Four individuals were excluded before randomization; the remaining 32 participants were randomly assigned in a 1:1 ratio to either the unstable-support-surface squat exercise group (n = 16) or the stable-support-surface squat exercise group (n = 16). Both groups performed progressive squat exercises five times per week for 4 weeks. Quadriceps femoris muscle thickness was measured before and after the intervention using rehabilitative ultrasound imaging. Results: Between-group comparisons of changes from baseline showed significantly greater increases in rectus femoris and vastus medialis muscle thickness in the unstable support-surface squat exercise group than in the stable support-surface squat exercise group (p < 0.05). No significant between-group differences were observed in vastus intermedius or vastus lateralis muscle thickness (p > 0.05). Conclusions: Progressive squat exercise performed on an unstable support surface resulted in greater increases in rectus femoris and vastus medialis muscle thickness than the same exercise performed on a stable support surface. However, these findings are limited to muscle thickness and should not be interpreted as evidence of improved muscle strength or functional performance.

]]> Influence of Support Surface Stability on Changes in Quadriceps Femoris Muscle Thickness During Progressive Squat Exercise in Patients with Stroke: A Randomized Controlled Trial Hui Ju Nam Ga-Yeon Kim doi: 10.3390/medicina62091749 Medicina 2026-09-11 Medicina 2026-09-11 62 9 Article 1749 10.3390/medicina62091749 https://www.mdpi.com/1648-9144/62/9/1749 Medicina, Vol. 62, Pages 1748: Physicians’ Judgments About Off-Label Medical Narcotic Use and Dose Reduction Responses: A South Korean Cross-Sectional Survey https://www.mdpi.com/1648-9144/62/9/1748 Background and Objectives: Off-label medical narcotic use may be classified as misuse and abuse, but this classification need not coincide with judgments about how broadly medical narcotic use should be permitted. We examined the association and discordance between these judgments, as well as how each was related to three dose-reduction-related responses. Materials and Methods: We analyzed cross-sectional web-based survey data from 300 physicians specializing in neurology, psychiatry, or anesthesiology and pain medicine in South Korea. Strict classification of all off-label use as misuse and abuse and a restrictive view of how broadly medical narcotic use should be permitted were entered simultaneously into logistic regression models for prior recommendation of dose reduction or discontinuation, belief that dose reduction would be helpful, and future intention to attempt dose reduction. Models were adjusted for age, sex, practice type, and specialty, with false-discovery rate (FDR) adjustment across six primary associations. Results: Strict classification was selected by 42 physicians (14.0%), and a restrictive view by 107 (35.7%). The two judgments were positively associated (adjusted odds ratio [aOR], 4.99; 95% confidence interval [CI], 2.38–10.46), but 92 of 297 physicians (31.0%) gave discordant responses. After FDR adjustment, strict classification was associated with prior recommendation (aOR, 3.06; 95% CI, 1.37–6.83) and the belief that dose reduction would be helpful (aOR, 4.51; 95% CI, 1.91–10.67). A restrictive view was associated with the same belief (aOR, 3.59; 95% CI, 2.12–6.10) and future intention (aOR, 2.89; 95% CI, 1.55–5.40). Conclusions: These findings indicate that physicians’ broad judgments about off-label medical narcotic use and the permitted scope of medical narcotic use are related but distinct and show different patterns of association with three dose-reduction-related responses. They support the view that tapering decisions should be guided by individualized clinical assessment rather than by legal and regulatory frameworks alone. 2026-09-10 Medicina, Vol. 62, Pages 1748: Physicians’ Judgments About Off-Label Medical Narcotic Use and Dose Reduction Responses: A South Korean Cross-Sectional Survey

Medicina doi: 10.3390/medicina62091748

Authors: Yongsoo Lee Yang-Ki Minn Jung Eun Kim

Background and Objectives: Off-label medical narcotic use may be classified as misuse and abuse, but this classification need not coincide with judgments about how broadly medical narcotic use should be permitted. We examined the association and discordance between these judgments, as well as how each was related to three dose-reduction-related responses. Materials and Methods: We analyzed cross-sectional web-based survey data from 300 physicians specializing in neurology, psychiatry, or anesthesiology and pain medicine in South Korea. Strict classification of all off-label use as misuse and abuse and a restrictive view of how broadly medical narcotic use should be permitted were entered simultaneously into logistic regression models for prior recommendation of dose reduction or discontinuation, belief that dose reduction would be helpful, and future intention to attempt dose reduction. Models were adjusted for age, sex, practice type, and specialty, with false-discovery rate (FDR) adjustment across six primary associations. Results: Strict classification was selected by 42 physicians (14.0%), and a restrictive view by 107 (35.7%). The two judgments were positively associated (adjusted odds ratio [aOR], 4.99; 95% confidence interval [CI], 2.38–10.46), but 92 of 297 physicians (31.0%) gave discordant responses. After FDR adjustment, strict classification was associated with prior recommendation (aOR, 3.06; 95% CI, 1.37–6.83) and the belief that dose reduction would be helpful (aOR, 4.51; 95% CI, 1.91–10.67). A restrictive view was associated with the same belief (aOR, 3.59; 95% CI, 2.12–6.10) and future intention (aOR, 2.89; 95% CI, 1.55–5.40). Conclusions: These findings indicate that physicians’ broad judgments about off-label medical narcotic use and the permitted scope of medical narcotic use are related but distinct and show different patterns of association with three dose-reduction-related responses. They support the view that tapering decisions should be guided by individualized clinical assessment rather than by legal and regulatory frameworks alone.

]]> Physicians’ Judgments About Off-Label Medical Narcotic Use and Dose Reduction Responses: A South Korean Cross-Sectional Survey Yongsoo Lee Yang-Ki Minn Jung Eun Kim doi: 10.3390/medicina62091748 Medicina 2026-09-10 Medicina 2026-09-10 62 9 Article 1748 10.3390/medicina62091748 https://www.mdpi.com/1648-9144/62/9/1748 Medicina, Vol. 62, Pages 1747: A Comparison of 18-Gauge and 20-Gauge Short Peripheral Catheters in Terms of Pain and Procedural Difficulty: A Randomized Controlled Trial in the Emergency Department https://www.mdpi.com/1648-9144/62/9/1747 Background and Objectives: Clinicians often default to the narrower short peripheral catheter (SPC), believing wider catheters to be more painful and harder to insert. One previous randomized trial found no difference, but it neither selected patients by measured access risk nor interpreted the result against a prespecified threshold of clinical importance. We conducted a confirmatory trial addressing both, comparing 18-gauge and 20-gauge SPCs in adult emergency department patients at low-to-moderate risk of difficult access. Materials and Methods: In a single-center, parallel-group superiority randomized controlled trial with 1:1 allocation (ClinicalTrials.gov NCT07629427), adults with an Adult Difficult Intravenous Access (A-DIVA) score from 0 to 3 were allocated to an 18-gauge or a 20-gauge SPC by block randomization. Patients were blinded by goggles until dressing, and the data analyst was also blinded. Co-primary outcomes were patient-reported pain and nurse-reported procedural difficulty on 100 mm visual analog scales immediately after the first attempt; first-attempt success was secondary. The trial was powered for a 13 mm difference in pain. Results: In total, 204 patients were randomized, 102 per group. Median pain was 32.5 vs. 30.5 mm (median difference 1 mm, 95% CI −4 to 6; p = 0.65) and median procedural difficulty was 12.0 vs. 15.0 mm (−1 mm, 95% CI −4 to 1; p = 0.28). The first attempt succeeded in 92.2% and 90.2% of patients (absolute risk difference 2.0 percentage points, 95% CI −5.8 to 9.7; p = 0.62); no prespecified subgroup showed a treatment interaction. Conclusions: In adults at low-to-moderate risk of difficult intravenous access, we did not detect a difference between 18-gauge and 20-gauge SPCs in terms of insertion pain, procedural difficulty, or first-attempt success, and the confidence interval for pain lay well within the minimum clinically important difference. Formal equivalence was not tested; the trial was designed to detect superiority. SPC size can therefore be chosen on the anticipated therapy rather than the expected discomfort. 2026-09-10 Medicina, Vol. 62, Pages 1747: A Comparison of 18-Gauge and 20-Gauge Short Peripheral Catheters in Terms of Pain and Procedural Difficulty: A Randomized Controlled Trial in the Emergency Department

Medicina doi: 10.3390/medicina62091747

Authors: Erhan Altunbas Emir Unal Onatcan Ozogul Cigdem Ozpolat Sinan Karacabey

Background and Objectives: Clinicians often default to the narrower short peripheral catheter (SPC), believing wider catheters to be more painful and harder to insert. One previous randomized trial found no difference, but it neither selected patients by measured access risk nor interpreted the result against a prespecified threshold of clinical importance. We conducted a confirmatory trial addressing both, comparing 18-gauge and 20-gauge SPCs in adult emergency department patients at low-to-moderate risk of difficult access. Materials and Methods: In a single-center, parallel-group superiority randomized controlled trial with 1:1 allocation (ClinicalTrials.gov NCT07629427), adults with an Adult Difficult Intravenous Access (A-DIVA) score from 0 to 3 were allocated to an 18-gauge or a 20-gauge SPC by block randomization. Patients were blinded by goggles until dressing, and the data analyst was also blinded. Co-primary outcomes were patient-reported pain and nurse-reported procedural difficulty on 100 mm visual analog scales immediately after the first attempt; first-attempt success was secondary. The trial was powered for a 13 mm difference in pain. Results: In total, 204 patients were randomized, 102 per group. Median pain was 32.5 vs. 30.5 mm (median difference 1 mm, 95% CI −4 to 6; p = 0.65) and median procedural difficulty was 12.0 vs. 15.0 mm (−1 mm, 95% CI −4 to 1; p = 0.28). The first attempt succeeded in 92.2% and 90.2% of patients (absolute risk difference 2.0 percentage points, 95% CI −5.8 to 9.7; p = 0.62); no prespecified subgroup showed a treatment interaction. Conclusions: In adults at low-to-moderate risk of difficult intravenous access, we did not detect a difference between 18-gauge and 20-gauge SPCs in terms of insertion pain, procedural difficulty, or first-attempt success, and the confidence interval for pain lay well within the minimum clinically important difference. Formal equivalence was not tested; the trial was designed to detect superiority. SPC size can therefore be chosen on the anticipated therapy rather than the expected discomfort.

]]> A Comparison of 18-Gauge and 20-Gauge Short Peripheral Catheters in Terms of Pain and Procedural Difficulty: A Randomized Controlled Trial in the Emergency Department Erhan Altunbas Emir Unal Onatcan Ozogul Cigdem Ozpolat Sinan Karacabey doi: 10.3390/medicina62091747 Medicina 2026-09-10 Medicina 2026-09-10 62 9 Article 1747 10.3390/medicina62091747 https://www.mdpi.com/1648-9144/62/9/1747 Medicina, Vol. 62, Pages 1746: Intragraft FOXP3+ Cells and Continuous Banff Indices in T Cell-Mediated Kidney Allograft Rejection https://www.mdpi.com/1648-9144/62/9/1746 Background and Objectives: FOXP3+ (Forkhead box P3) regulatory T cells contribute to immune tolerance after kidney transplantation, but their role in T cell-mediated rejection (TCMR) remains controversial. This study investigated the association between intragraft FOXP3+ cells and the recently introduced Banff-derived activity (AI) and chronicity index (CI) in biopsy-proven TCMR. Materials and Methods: This retrospective cross-sectional study included 119 kidney allograft biopsies diagnosed as acute or chronic active TCMR according to the Banff classification. FOXP3+ cells were assessed by immunohistochemistry and expressed as cortical cell density (cells/mm2). Associations between FOXP3+ cell density, Banff-derived indices, inflammatory cell densities, and clinical parameters were analyzed using non-parametric statistical methods. Results: FOXP3+ cells were detected in 17.6% of biopsies. FOXP3+ cell density was univariately associated with higher CI values (ρ = 0.228, p = 0.013) and chronic lesions interstitial fibrosis (ci) (ρ = 0.284, p = 0.002) and tubular atrophy (ct) (ρ = 0.246, p = 0.008). No association was observed with AI or activity lesions, except for a weak negative correlation with interstitial inflammation (i) (ρ = −0.209, p = 0.025). In multivariable analysis, FOXP3 positivity was not significantly associated with CI after adjustment for transplantation–biopsy interval (B = 0.568, 95% CI −0.741–1.876, p = 0.391). FOXP3+ cell density positively correlated with cluster of diferentiation (CD)4+ (ρ = 0.350, p < 0.001), CD8+ (ρ = 0.229, p = 0.018), and CD163+ (ρ = 0.207, p = 0.047) cell densities. No association with short-term graft outcome was observed. Conclusions: FOXP3+ cell infiltration was associated with chronic histological changes in unadjusted analyses, but this association did not remain statistically significant after adjustment for transplantation-to-biopsy interval. These preliminary findings suggest that FOXP3+ cell accumulation and chronic histological changes may represent parallel time-dependent phenomena and require confirmation in larger cohorts. 2026-09-10 Medicina, Vol. 62, Pages 1746: Intragraft FOXP3+ Cells and Continuous Banff Indices in T Cell-Mediated Kidney Allograft Rejection

Medicina doi: 10.3390/medicina62091746

Authors: Petar Đolonga Petar Šenjug Anja Stadnik Ana Dunatov Huljev Lada Zibar Sandra Zekić Tomaš Danica Galešić Ljubanović Merica Glavina Durdov

Background and Objectives: FOXP3+ (Forkhead box P3) regulatory T cells contribute to immune tolerance after kidney transplantation, but their role in T cell-mediated rejection (TCMR) remains controversial. This study investigated the association between intragraft FOXP3+ cells and the recently introduced Banff-derived activity (AI) and chronicity index (CI) in biopsy-proven TCMR. Materials and Methods: This retrospective cross-sectional study included 119 kidney allograft biopsies diagnosed as acute or chronic active TCMR according to the Banff classification. FOXP3+ cells were assessed by immunohistochemistry and expressed as cortical cell density (cells/mm2). Associations between FOXP3+ cell density, Banff-derived indices, inflammatory cell densities, and clinical parameters were analyzed using non-parametric statistical methods. Results: FOXP3+ cells were detected in 17.6% of biopsies. FOXP3+ cell density was univariately associated with higher CI values (ρ = 0.228, p = 0.013) and chronic lesions interstitial fibrosis (ci) (ρ = 0.284, p = 0.002) and tubular atrophy (ct) (ρ = 0.246, p = 0.008). No association was observed with AI or activity lesions, except for a weak negative correlation with interstitial inflammation (i) (ρ = −0.209, p = 0.025). In multivariable analysis, FOXP3 positivity was not significantly associated with CI after adjustment for transplantation–biopsy interval (B = 0.568, 95% CI −0.741–1.876, p = 0.391). FOXP3+ cell density positively correlated with cluster of diferentiation (CD)4+ (ρ = 0.350, p < 0.001), CD8+ (ρ = 0.229, p = 0.018), and CD163+ (ρ = 0.207, p = 0.047) cell densities. No association with short-term graft outcome was observed. Conclusions: FOXP3+ cell infiltration was associated with chronic histological changes in unadjusted analyses, but this association did not remain statistically significant after adjustment for transplantation-to-biopsy interval. These preliminary findings suggest that FOXP3+ cell accumulation and chronic histological changes may represent parallel time-dependent phenomena and require confirmation in larger cohorts.

]]> Intragraft FOXP3+ Cells and Continuous Banff Indices in T Cell-Mediated Kidney Allograft Rejection Petar Đolonga Petar Šenjug Anja Stadnik Ana Dunatov Huljev Lada Zibar Sandra Zekić Tomaš Danica Galešić Ljubanović Merica Glavina Durdov doi: 10.3390/medicina62091746 Medicina 2026-09-10 Medicina 2026-09-10 62 9 Article 1746 10.3390/medicina62091746 https://www.mdpi.com/1648-9144/62/9/1746 Medicina, Vol. 62, Pages 1745: Perioperative H-FABP and Its Association with Postoperative Morbidity Following Pancreatic Resection: A Prospective Observational Study https://www.mdpi.com/1648-9144/62/9/1745 Background and Objectives: Postoperative morbidity presents a significant challenge in pancreatic surgery. Biomarkers that enable early detection of complications could enhance postoperative monitoring and allow for timely intervention. This study aimed to assess whether perioperative concentrations of heart-type fatty acid–binding protein (H-FABP) are linked to severe postoperative complications and pancreas-specific morbidity following pancreatic resection. Materials and Methods: Serum H-FABP levels were measured preoperatively and on postoperative days 2, 4, and 6. Results: Among the 53 patients (33 women [62.3%]) included in the final analysis, those with malignant disease exhibited significantly higher preoperative H-FABP concentrations (median, 1320 vs. 630 ng/L; p = 0.015), as did patients classified as ASA III (median, 1309 vs. 620 ng/L; p = 0.025) and aged 70 years or older (median = 1431 vs. 550 ng/L; p < 0.001). Elevated postoperative H-FABP levels were associated with severe complications, with notable increases observed on postoperative day (POD) 2 (p = 0.026), POD4 (p = 0.022), and POD6 (p = 0.015). Exploratory ROC analysis indicated moderate discrimination for severe complications (AUC, 0.70, 0.71, and 0.73, respectively). No significant differences in postoperative H-FABP levels were found among patients with clinically relevant postoperative pancreatic fistula, postpancreatectomy acute pancreatitis and postpancreatectomy hemorrhage. Conclusions: Exploratory comparisons at individual time points showed higher postoperative concentrations of H-FABP in patients with severe complications; however, the main longitudinal analysis using a mixed-effects model did not reveal a statistically significant group effect or an interaction between group and time. Larger prospective multicenter studies are required to validate its clinical utility. 2026-09-10 Medicina, Vol. 62, Pages 1745: Perioperative H-FABP and Its Association with Postoperative Morbidity Following Pancreatic Resection: A Prospective Observational Study

Medicina doi: 10.3390/medicina62091745

Authors: Danaja Plevel Ana Kalamutova Aleš Jerin Mihajlo Đokić Aleš Tomažič Blaž Trotovšek Miha Petrič

Background and Objectives: Postoperative morbidity presents a significant challenge in pancreatic surgery. Biomarkers that enable early detection of complications could enhance postoperative monitoring and allow for timely intervention. This study aimed to assess whether perioperative concentrations of heart-type fatty acid–binding protein (H-FABP) are linked to severe postoperative complications and pancreas-specific morbidity following pancreatic resection. Materials and Methods: Serum H-FABP levels were measured preoperatively and on postoperative days 2, 4, and 6. Results: Among the 53 patients (33 women [62.3%]) included in the final analysis, those with malignant disease exhibited significantly higher preoperative H-FABP concentrations (median, 1320 vs. 630 ng/L; p = 0.015), as did patients classified as ASA III (median, 1309 vs. 620 ng/L; p = 0.025) and aged 70 years or older (median = 1431 vs. 550 ng/L; p < 0.001). Elevated postoperative H-FABP levels were associated with severe complications, with notable increases observed on postoperative day (POD) 2 (p = 0.026), POD4 (p = 0.022), and POD6 (p = 0.015). Exploratory ROC analysis indicated moderate discrimination for severe complications (AUC, 0.70, 0.71, and 0.73, respectively). No significant differences in postoperative H-FABP levels were found among patients with clinically relevant postoperative pancreatic fistula, postpancreatectomy acute pancreatitis and postpancreatectomy hemorrhage. Conclusions: Exploratory comparisons at individual time points showed higher postoperative concentrations of H-FABP in patients with severe complications; however, the main longitudinal analysis using a mixed-effects model did not reveal a statistically significant group effect or an interaction between group and time. Larger prospective multicenter studies are required to validate its clinical utility.

]]> Perioperative H-FABP and Its Association with Postoperative Morbidity Following Pancreatic Resection: A Prospective Observational Study Danaja Plevel Ana Kalamutova Aleš Jerin Mihajlo Đokić Aleš Tomažič Blaž Trotovšek Miha Petrič doi: 10.3390/medicina62091745 Medicina 2026-09-10 Medicina 2026-09-10 62 9 Article 1745 10.3390/medicina62091745 https://www.mdpi.com/1648-9144/62/9/1745 Medicina, Vol. 62, Pages 1744: Necrotizing Fasciitis of the Extremities: Microbial Spectrum, Antimicrobial Resistance, and Clinical Outcomes in a 7-Year Retrospective Cohort Study https://www.mdpi.com/1648-9144/62/9/1744 Background and Objectives: Necrotizing fasciitis (NF) is characterized by rapid and aggressive infection of the subcutaneous tissue and fascia, and a high risk of death in case of delay in diagnosis and treatment. Materials and Methods: This 7-year retrospective study (May 2017–May 2024) evaluated 38 patients with upper- and lower-limb NF admitted to the surgery clinic at the County Emergency Hospital in Craiova, Romania. Results: 21.8% of the confirmed NF cases were monomicrobial; Gram-positive strains were predominant, but Gram-negative strains were also involved. The mortality rate was 28.9%; acute kidney injury appears as the only independent risk factor associated with mortality, although in univariate analysis, septic shock and high NLR and INR values were also factors associated with mortality. An increased resistance rate to antibiotics was recorded, with a 32.7% MDR rate; moderate to high resistance to piperacillin + tazobactam, most cephalosporins, most carbapenems (for Gram-negative strains), and quinolones was noted. Conclusions: Multidisciplinary management, comprising intensive medical support, prompt targeted antibiotic therapy, and immediate surgical intervention, was critical for achieving favorable patient outcomes. Increasing antibiotic resistance may alter the prognosis in patients with NF. 2026-09-10 Medicina, Vol. 62, Pages 1744: Necrotizing Fasciitis of the Extremities: Microbial Spectrum, Antimicrobial Resistance, and Clinical Outcomes in a 7-Year Retrospective Cohort Study

Medicina doi: 10.3390/medicina62091744

Authors: Cosmin Vasile Obleaga Polliana Mihaela Leru Sergiu Marian Cazacu Alexandru Marin Pascu Livia Dragonu Andreea Doriana Stanculescu Dragos George Popa Florin-Liviu Gherghina Dragos Marian Popescu Ion Vasile Lidia Boldeanu

Background and Objectives: Necrotizing fasciitis (NF) is characterized by rapid and aggressive infection of the subcutaneous tissue and fascia, and a high risk of death in case of delay in diagnosis and treatment. Materials and Methods: This 7-year retrospective study (May 2017–May 2024) evaluated 38 patients with upper- and lower-limb NF admitted to the surgery clinic at the County Emergency Hospital in Craiova, Romania. Results: 21.8% of the confirmed NF cases were monomicrobial; Gram-positive strains were predominant, but Gram-negative strains were also involved. The mortality rate was 28.9%; acute kidney injury appears as the only independent risk factor associated with mortality, although in univariate analysis, septic shock and high NLR and INR values were also factors associated with mortality. An increased resistance rate to antibiotics was recorded, with a 32.7% MDR rate; moderate to high resistance to piperacillin + tazobactam, most cephalosporins, most carbapenems (for Gram-negative strains), and quinolones was noted. Conclusions: Multidisciplinary management, comprising intensive medical support, prompt targeted antibiotic therapy, and immediate surgical intervention, was critical for achieving favorable patient outcomes. Increasing antibiotic resistance may alter the prognosis in patients with NF.

]]> Necrotizing Fasciitis of the Extremities: Microbial Spectrum, Antimicrobial Resistance, and Clinical Outcomes in a 7-Year Retrospective Cohort Study Cosmin Vasile Obleaga Polliana Mihaela Leru Sergiu Marian Cazacu Alexandru Marin Pascu Livia Dragonu Andreea Doriana Stanculescu Dragos George Popa Florin-Liviu Gherghina Dragos Marian Popescu Ion Vasile Lidia Boldeanu doi: 10.3390/medicina62091744 Medicina 2026-09-10 Medicina 2026-09-10 62 9 Article 1744 10.3390/medicina62091744 https://www.mdpi.com/1648-9144/62/9/1744 Medicina, Vol. 62, Pages 1743: Effects of Maternal Cigarette Smoking on Pulmonary Function, Respiratory Muscle Strength, Functional Exercise Capacity, and Skeletal Muscle Oxygenation During the Second Trimester of Pregnancy https://www.mdpi.com/1648-9144/62/9/1743 Background and Objectives: Cigarette smoking during pregnancy may adversely affect maternal respiratory function and exercise performance. This study aimed to compare pulmonary function, respiratory muscle strength, functional exercise capacity, and quadriceps muscle oxygenation between smoking and non-smoking women during the second trimester of pregnancy. Materials and Methods: In this prospective cross-sectional study, 110 women in the second trimester of pregnancy (55 smokers and 55 non-smokers) underwent pulmonary function testing, respiratory muscle strength assessment, a six-minute walk test (6MWT), and quadriceps muscle oxygenation measurement using near-infrared spectroscopy (NIRS). Results: Baseline demographic and obstetric characteristics were comparable between the groups (all p > 0.05). Compared with non-smokers, pregnant smokers had significantly lower forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), including % predicted values and z-scores, as well as a lower FEV1/FVC ratio (all p < 0.001). Smokers also had lower maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) (both p < 0.001) and a shorter six-minute walk distance (6MWD) (p < 0.001). In addition, smokers exhibited lower resting and end-exercise quadriceps muscle oxygen saturation (SmO2), together with a greater exercise-induced decline in SmO2 (ΔSmO2) (all p < 0.001). In multivariable regression analysis, pack-years (β = −0.512, p < 0.001) and gestational age (β = −0.217, p = 0.006) were independent predictors of ΔSmO2. Conclusions: Maternal smoking during the second trimester is associated with modest reductions in pulmonary function, respiratory muscle weakness, reduced exercise capacity, and compromised skeletal muscle oxygenation. These findings suggest that the physiological effects of smoking extend beyond the lungs to peripheral muscle oxygen utilization and further emphasize the importance of early smoking cessation during pregnancy. 2026-09-10 Medicina, Vol. 62, Pages 1743: Effects of Maternal Cigarette Smoking on Pulmonary Function, Respiratory Muscle Strength, Functional Exercise Capacity, and Skeletal Muscle Oxygenation During the Second Trimester of Pregnancy

Medicina doi: 10.3390/medicina62091743

Authors: Ramazan Bülbül Buğra Kerget Ayşegül Evren Dilmaç Zehra Deniz Zor Aksakal Alperen Aksakal

Background and Objectives: Cigarette smoking during pregnancy may adversely affect maternal respiratory function and exercise performance. This study aimed to compare pulmonary function, respiratory muscle strength, functional exercise capacity, and quadriceps muscle oxygenation between smoking and non-smoking women during the second trimester of pregnancy. Materials and Methods: In this prospective cross-sectional study, 110 women in the second trimester of pregnancy (55 smokers and 55 non-smokers) underwent pulmonary function testing, respiratory muscle strength assessment, a six-minute walk test (6MWT), and quadriceps muscle oxygenation measurement using near-infrared spectroscopy (NIRS). Results: Baseline demographic and obstetric characteristics were comparable between the groups (all p > 0.05). Compared with non-smokers, pregnant smokers had significantly lower forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), including % predicted values and z-scores, as well as a lower FEV1/FVC ratio (all p < 0.001). Smokers also had lower maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) (both p < 0.001) and a shorter six-minute walk distance (6MWD) (p < 0.001). In addition, smokers exhibited lower resting and end-exercise quadriceps muscle oxygen saturation (SmO2), together with a greater exercise-induced decline in SmO2 (ΔSmO2) (all p < 0.001). In multivariable regression analysis, pack-years (β = −0.512, p < 0.001) and gestational age (β = −0.217, p = 0.006) were independent predictors of ΔSmO2. Conclusions: Maternal smoking during the second trimester is associated with modest reductions in pulmonary function, respiratory muscle weakness, reduced exercise capacity, and compromised skeletal muscle oxygenation. These findings suggest that the physiological effects of smoking extend beyond the lungs to peripheral muscle oxygen utilization and further emphasize the importance of early smoking cessation during pregnancy.

]]> Effects of Maternal Cigarette Smoking on Pulmonary Function, Respiratory Muscle Strength, Functional Exercise Capacity, and Skeletal Muscle Oxygenation During the Second Trimester of Pregnancy Ramazan Bülbül Buğra Kerget Ayşegül Evren Dilmaç Zehra Deniz Zor Aksakal Alperen Aksakal doi: 10.3390/medicina62091743 Medicina 2026-09-10 Medicina 2026-09-10 62 9 Article 1743 10.3390/medicina62091743 https://www.mdpi.com/1648-9144/62/9/1743 Medicina, Vol. 62, Pages 1742: Cardiovascular–Kidney–Metabolic Syndrome and Its Hepatic Dimension: A Narrative Review https://www.mdpi.com/1648-9144/62/9/1742 Metabolic syndrome came to the attention of the scientific community several decades ago, and its definition has undergone multiple changes over time. It is currently defined by the coexistence of hypertension, central obesity, dyslipidemia, and impaired glucose metabolism, with insulin resistance, chronic inflammation, and oxidative stress representing important underlying pathophysiological mechanisms. The latter two processes are major promoters of the onset and progression of atherosclerosis. In parallel, many individuals develop metabolic dysfunction-associated steatotic liver disease (MASLD), formerly called non-alcoholic fatty liver disease (NAFLD). Growing evidence indicates that MASLD may interact bidirectionally with cardiovascular, renal, and metabolic dysfunction and may contribute to cardiometabolic risk. These observations have prompted proposals for a broader cardio–reno–hepato–metabolic axis. However, MASLD is not currently included in the established cardiovascular-kidney-metabolic (CKM) definition or staging system, and its incorporation remains an evolving conceptual extension. Prediabetes is a reversible condition characterized by abnormal glucose levels that do not meet the diagnostic criteria for diabetes. The American Diabetes Association defines prediabetes as glycated hemoglobin (HbA1c) = 5.7–6.4%, fasting plasma glucose = 100–125 mg/dL, or two-hour plasma glucose during an oral glucose tolerance test = 140–199 mg/dL. This comprehensive review examines traditional and genetic risk determinants, shared pathophysiological mechanisms, diagnostic strategies, clinical manifestations, emerging phenotypes, circulating microRNAs as non-invasive biomarkers, complications, and the principal therapeutic strategies, including diet, exercise, and pharmacotherapy. Particular attention is given to the recent approvals of resmetirom and semaglutide for metabolic dysfunction-associated steatohepatitis and to the expanding roles of sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists and non-steroidal mineralocorticoid receptor antagonists. Cardiovascular, renal, metabolic, and hepatic disorders are frequently present in the same patient. Other individuals may develop this high-risk cluster over time. The aim of this article is to define the interplay between different metabolic conditions and to outline the best approach to diagnosis, monitoring, and effective integrated therapy. 2026-09-10 Medicina, Vol. 62, Pages 1742: Cardiovascular–Kidney–Metabolic Syndrome and Its Hepatic Dimension: A Narrative Review

Medicina doi: 10.3390/medicina62091742

Authors: Vasilica Enache Dan-Cristian Popescu Bogdan Marcu Mara Diaconu Alexandru-Cristian Nechita

Metabolic syndrome came to the attention of the scientific community several decades ago, and its definition has undergone multiple changes over time. It is currently defined by the coexistence of hypertension, central obesity, dyslipidemia, and impaired glucose metabolism, with insulin resistance, chronic inflammation, and oxidative stress representing important underlying pathophysiological mechanisms. The latter two processes are major promoters of the onset and progression of atherosclerosis. In parallel, many individuals develop metabolic dysfunction-associated steatotic liver disease (MASLD), formerly called non-alcoholic fatty liver disease (NAFLD). Growing evidence indicates that MASLD may interact bidirectionally with cardiovascular, renal, and metabolic dysfunction and may contribute to cardiometabolic risk. These observations have prompted proposals for a broader cardio–reno–hepato–metabolic axis. However, MASLD is not currently included in the established cardiovascular-kidney-metabolic (CKM) definition or staging system, and its incorporation remains an evolving conceptual extension. Prediabetes is a reversible condition characterized by abnormal glucose levels that do not meet the diagnostic criteria for diabetes. The American Diabetes Association defines prediabetes as glycated hemoglobin (HbA1c) = 5.7–6.4%, fasting plasma glucose = 100–125 mg/dL, or two-hour plasma glucose during an oral glucose tolerance test = 140–199 mg/dL. This comprehensive review examines traditional and genetic risk determinants, shared pathophysiological mechanisms, diagnostic strategies, clinical manifestations, emerging phenotypes, circulating microRNAs as non-invasive biomarkers, complications, and the principal therapeutic strategies, including diet, exercise, and pharmacotherapy. Particular attention is given to the recent approvals of resmetirom and semaglutide for metabolic dysfunction-associated steatohepatitis and to the expanding roles of sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists and non-steroidal mineralocorticoid receptor antagonists. Cardiovascular, renal, metabolic, and hepatic disorders are frequently present in the same patient. Other individuals may develop this high-risk cluster over time. The aim of this article is to define the interplay between different metabolic conditions and to outline the best approach to diagnosis, monitoring, and effective integrated therapy.

]]> Cardiovascular–Kidney–Metabolic Syndrome and Its Hepatic Dimension: A Narrative Review Vasilica Enache Dan-Cristian Popescu Bogdan Marcu Mara Diaconu Alexandru-Cristian Nechita doi: 10.3390/medicina62091742 Medicina 2026-09-10 Medicina 2026-09-10 62 9 Review 1742 10.3390/medicina62091742 https://www.mdpi.com/1648-9144/62/9/1742 Medicina, Vol. 62, Pages 1741: Prognostic Value of Inflammatory and Nutritional Indices in Patients Undergoing Permanent Pacemaker Implantation for Degenerative Complete Atrioventricular Block https://www.mdpi.com/1648-9144/62/9/1741 Background and Objectives: Systemic inflammation and nutritional impairment may influence outcomes after permanent pacemaker implantation, but the prognostic value of composite indices in degenerative complete atrioventricular block remains unclear. We evaluated the associations of routinely available inflammatory and nutritional indices with long-term all-cause mortality in this population. Materials and Methods: This retrospective, single-center study included 272 patients who underwent permanent pacemaker implantation for isolated complete atrioventricular block attributed to degenerative conduction system disease between August 2020 and July 2024. Baseline laboratory values were used to calculate the prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, systemic immune-inflammation index, systemic inflammation response index, and pan-immune-inflammation value. The primary endpoint was all-cause mortality during follow-up. Discriminatory performance was assessed using receiver operating characteristic (ROC) analysis, and independent associations were evaluated using multivariable Cox regression. Results: During a mean follow-up of 27.8 ± 16.6 months, 69 patients (25.4%) died. Compared with survivors, non-survivors were older and had lower hemoglobin, lymphocyte count, albumin, estimated glomerular filtration rate, GNRI, LMR, and PNI values, whereas C-reactive protein, NLR, and SIRI values were higher. PNI had the numerically highest AUC for mortality prediction (AUC: 0.720, 95% CI: 0.648–0.793; p < 0.001), corresponding to moderate discriminatory performance, whereas GNRI showed fair discrimination (AUC: 0.677, 95% CI: 0.589–0.766; p < 0.001). In multivariable Cox regression, PNI remained independently associated with mortality (HR: 0.945, 95% CI: 0.909–0.982; p = 0.004). Conclusions: Among the evaluated inflammatory and nutritional indices, PNI demonstrated the numerically highest discriminatory performance and remained independently associated with long-term all-cause mortality. PNI may therefore serve as a readily available adjunct to clinical risk stratification in patients undergoing permanent pacemaker implantation for degenerative complete atrioventricular block; however, external validation is required. 2026-09-10 Medicina, Vol. 62, Pages 1741: Prognostic Value of Inflammatory and Nutritional Indices in Patients Undergoing Permanent Pacemaker Implantation for Degenerative Complete Atrioventricular Block

Medicina doi: 10.3390/medicina62091741

Authors: Murat Erdem Alp Cemal Ozanalp Güngör İlayda Bostancı Alp Merve Kertmen Eyüp Özkan Veli Polat Süleyman Barutçu Taylan Akgün

Background and Objectives: Systemic inflammation and nutritional impairment may influence outcomes after permanent pacemaker implantation, but the prognostic value of composite indices in degenerative complete atrioventricular block remains unclear. We evaluated the associations of routinely available inflammatory and nutritional indices with long-term all-cause mortality in this population. Materials and Methods: This retrospective, single-center study included 272 patients who underwent permanent pacemaker implantation for isolated complete atrioventricular block attributed to degenerative conduction system disease between August 2020 and July 2024. Baseline laboratory values were used to calculate the prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, systemic immune-inflammation index, systemic inflammation response index, and pan-immune-inflammation value. The primary endpoint was all-cause mortality during follow-up. Discriminatory performance was assessed using receiver operating characteristic (ROC) analysis, and independent associations were evaluated using multivariable Cox regression. Results: During a mean follow-up of 27.8 ± 16.6 months, 69 patients (25.4%) died. Compared with survivors, non-survivors were older and had lower hemoglobin, lymphocyte count, albumin, estimated glomerular filtration rate, GNRI, LMR, and PNI values, whereas C-reactive protein, NLR, and SIRI values were higher. PNI had the numerically highest AUC for mortality prediction (AUC: 0.720, 95% CI: 0.648–0.793; p < 0.001), corresponding to moderate discriminatory performance, whereas GNRI showed fair discrimination (AUC: 0.677, 95% CI: 0.589–0.766; p < 0.001). In multivariable Cox regression, PNI remained independently associated with mortality (HR: 0.945, 95% CI: 0.909–0.982; p = 0.004). Conclusions: Among the evaluated inflammatory and nutritional indices, PNI demonstrated the numerically highest discriminatory performance and remained independently associated with long-term all-cause mortality. PNI may therefore serve as a readily available adjunct to clinical risk stratification in patients undergoing permanent pacemaker implantation for degenerative complete atrioventricular block; however, external validation is required.

]]> Prognostic Value of Inflammatory and Nutritional Indices in Patients Undergoing Permanent Pacemaker Implantation for Degenerative Complete Atrioventricular Block Murat Erdem Alp Cemal Ozanalp Güngör İlayda Bostancı Alp Merve Kertmen Eyüp Özkan Veli Polat Süleyman Barutçu Taylan Akgün doi: 10.3390/medicina62091741 Medicina 2026-09-10 Medicina 2026-09-10 62 9 Article 1741 10.3390/medicina62091741 https://www.mdpi.com/1648-9144/62/9/1741 Medicina, Vol. 62, Pages 1740: The Epigenetic Architecture of Classical Hodgkin Lymphoma: Lineage Erasure, Immune Escape, and Therapeutic Reprogramming https://www.mdpi.com/1648-9144/62/9/1740 Classical Hodgkin lymphoma (cHL) is distinguished by a rare population of Hodgkin and Reed–Sternberg (HRS) cells that has largely extinguished its germinal center (GC) B-cell identity while maintaining survival, immune escape, and dependence on a highly organized tumor microenvironment (TME). This narrative review examines how interacting epigenetic mechanisms construct and stabilize this malignant state and evaluates whether it can be therapeutically reprogrammed. The relevant mechanistic and clinical literature available through 2026 was synthesized, encompassing lineage factor disruption, DNA methylation, histone modifications, Polycomb repression, chromatin-remodeling lesions, non-coding RNAs, antigen presentation, immune checkpoint regulation, and epigenetic therapies in cHL. Lineage erasure appears to be an actively maintained program produced by promoter hypermethylation, histone deacetylation, Polycomb-associated repression, altered histone demethylase activity, transcription factor antagonism, and somatic lesions affecting chromatin regulators. These mechanisms coexist with structural and transcriptional alterations involving antigen presentation and programmed death ligand 1/programmed death ligand 2 (PD-L1/PD-L2), while non-coding RNAs and extracellular vesicles provide an additional regulatory layer connecting HRS cells with immune and stromal components of the TME. Epigenetic repression is heterogeneous in its reversibility: partially methylated or deacetylated loci may remain pharmacologically responsive, whereas densely methylated, Polycomb-associated, or genetically entrenched states are less likely to be restored through isolated interventions. Histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors can nevertheless alter tumor- and immune-related programs, supporting combinations with PD-1 blockade. Complete restoration of a physiological B-cell epigenome is unlikely; however, the HRS state remains therapeutically modifiable. Epigenetic therapy may therefore be most effective when used to reduce state stability and increase immune visibility rather than to achieve complete lineage reconstitution. 2026-09-09 Medicina, Vol. 62, Pages 1740: The Epigenetic Architecture of Classical Hodgkin Lymphoma: Lineage Erasure, Immune Escape, and Therapeutic Reprogramming

Medicina doi: 10.3390/medicina62091740

Authors: Matei Seleusan Diana Cenariu Adrian-Bogdan Țigu Diana Gulei Mădălina Nistor Ximena Maria Muresan Mihnea Zdrenghea

Classical Hodgkin lymphoma (cHL) is distinguished by a rare population of Hodgkin and Reed–Sternberg (HRS) cells that has largely extinguished its germinal center (GC) B-cell identity while maintaining survival, immune escape, and dependence on a highly organized tumor microenvironment (TME). This narrative review examines how interacting epigenetic mechanisms construct and stabilize this malignant state and evaluates whether it can be therapeutically reprogrammed. The relevant mechanistic and clinical literature available through 2026 was synthesized, encompassing lineage factor disruption, DNA methylation, histone modifications, Polycomb repression, chromatin-remodeling lesions, non-coding RNAs, antigen presentation, immune checkpoint regulation, and epigenetic therapies in cHL. Lineage erasure appears to be an actively maintained program produced by promoter hypermethylation, histone deacetylation, Polycomb-associated repression, altered histone demethylase activity, transcription factor antagonism, and somatic lesions affecting chromatin regulators. These mechanisms coexist with structural and transcriptional alterations involving antigen presentation and programmed death ligand 1/programmed death ligand 2 (PD-L1/PD-L2), while non-coding RNAs and extracellular vesicles provide an additional regulatory layer connecting HRS cells with immune and stromal components of the TME. Epigenetic repression is heterogeneous in its reversibility: partially methylated or deacetylated loci may remain pharmacologically responsive, whereas densely methylated, Polycomb-associated, or genetically entrenched states are less likely to be restored through isolated interventions. Histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors can nevertheless alter tumor- and immune-related programs, supporting combinations with PD-1 blockade. Complete restoration of a physiological B-cell epigenome is unlikely; however, the HRS state remains therapeutically modifiable. Epigenetic therapy may therefore be most effective when used to reduce state stability and increase immune visibility rather than to achieve complete lineage reconstitution.

]]> The Epigenetic Architecture of Classical Hodgkin Lymphoma: Lineage Erasure, Immune Escape, and Therapeutic Reprogramming Matei Seleusan Diana Cenariu Adrian-Bogdan Țigu Diana Gulei Mădălina Nistor Ximena Maria Muresan Mihnea Zdrenghea doi: 10.3390/medicina62091740 Medicina 2026-09-09 Medicina 2026-09-09 62 9 Review 1740 10.3390/medicina62091740 https://www.mdpi.com/1648-9144/62/9/1740 Medicina, Vol. 62, Pages 1739: Self-Reported Post-COVID-19 Condition and Associated Factors Using Machine Learning Techniques: A Cross-Sectional Study https://www.mdpi.com/1648-9144/62/9/1739 Background and Objectives: Post-COVID-19 condition (PCC) is a commonly reported disorder that has gained attention from the World Health Organization (WHO). Several studies have examined factors associated with PCC; however, relatively few have combined statistical and machine-learning approaches. Therefore, this study used statistical analysis to identify factors associated with PCC and machine-learning methods to evaluate the relative importance of these factors and their contributions to model predictions of PCC. Materials and Methods: This study employed a cross-sectional observational design in which 963 eligible individuals who had tested positive for COVID-19 were enrolled. Participants were asked about the presence of persistent symptoms lasting for at least 2 months and occurring 3 months after COVID-19 infection, as well as the specific symptoms experienced. The WHO Global COVID-19 Clinical Platform Case Report Form for PCC was used to classify persistent symptoms. Demographic information and medical factors were examined using Poisson regression and machine-learning techniques. Results: A total of 209 (22%) out of 963 reported having PCC with fatigue (45%), followed by bone/joint/muscle pain (34%), one neurological symptom (24%), one pulmonary/respiratory symptom (23%), and one mental health symptom (16%) were the most common persistent symptoms. Modified Poisson regression showed that having exactly two chronic conditions, and experiencing two or more previous COVID-19 infections were significantly associated with the prevalence of PCC. The SHAP beeswarm plot indicated that sex, age, time since last COVID-19 infection, number of chronic conditions, and BMI had the greatest influence on the support vector machine (SVM) predictions. Within the fitted model, female sex, age, a longer time since last COVID-19 infection, the presence of chronic conditions, and higher BMI generally shifted predictions toward the PCC category. Conclusions: Approximately 22% of participants reported persistent symptoms, with fatigue being the most frequently reported, followed by musculoskeletal pain and symptoms affecting other body systems. In the modified Poisson regression analysis, having exactly two chronic conditions and multiple previous COVID-19 infections were significantly associated with higher prevalence of PCC. However, the machine-learning models demonstrated limited discriminative performance. 2026-09-09 Medicina, Vol. 62, Pages 1739: Self-Reported Post-COVID-19 Condition and Associated Factors Using Machine Learning Techniques: A Cross-Sectional Study

Medicina doi: 10.3390/medicina62091739

Authors: Alaa A. Alghwiri Ziad Hawamdeh Abrar F. AlAbed Alhaq Dania F. Naser Alia A. Alghwiri

Background and Objectives: Post-COVID-19 condition (PCC) is a commonly reported disorder that has gained attention from the World Health Organization (WHO). Several studies have examined factors associated with PCC; however, relatively few have combined statistical and machine-learning approaches. Therefore, this study used statistical analysis to identify factors associated with PCC and machine-learning methods to evaluate the relative importance of these factors and their contributions to model predictions of PCC. Materials and Methods: This study employed a cross-sectional observational design in which 963 eligible individuals who had tested positive for COVID-19 were enrolled. Participants were asked about the presence of persistent symptoms lasting for at least 2 months and occurring 3 months after COVID-19 infection, as well as the specific symptoms experienced. The WHO Global COVID-19 Clinical Platform Case Report Form for PCC was used to classify persistent symptoms. Demographic information and medical factors were examined using Poisson regression and machine-learning techniques. Results: A total of 209 (22%) out of 963 reported having PCC with fatigue (45%), followed by bone/joint/muscle pain (34%), one neurological symptom (24%), one pulmonary/respiratory symptom (23%), and one mental health symptom (16%) were the most common persistent symptoms. Modified Poisson regression showed that having exactly two chronic conditions, and experiencing two or more previous COVID-19 infections were significantly associated with the prevalence of PCC. The SHAP beeswarm plot indicated that sex, age, time since last COVID-19 infection, number of chronic conditions, and BMI had the greatest influence on the support vector machine (SVM) predictions. Within the fitted model, female sex, age, a longer time since last COVID-19 infection, the presence of chronic conditions, and higher BMI generally shifted predictions toward the PCC category. Conclusions: Approximately 22% of participants reported persistent symptoms, with fatigue being the most frequently reported, followed by musculoskeletal pain and symptoms affecting other body systems. In the modified Poisson regression analysis, having exactly two chronic conditions and multiple previous COVID-19 infections were significantly associated with higher prevalence of PCC. However, the machine-learning models demonstrated limited discriminative performance.

]]> Self-Reported Post-COVID-19 Condition and Associated Factors Using Machine Learning Techniques: A Cross-Sectional Study Alaa A. Alghwiri Ziad Hawamdeh Abrar F. AlAbed Alhaq Dania F. Naser Alia A. Alghwiri doi: 10.3390/medicina62091739 Medicina 2026-09-09 Medicina 2026-09-09 62 9 Article 1739 10.3390/medicina62091739 https://www.mdpi.com/1648-9144/62/9/1739 Medicina, Vol. 62, Pages 1738: Effects of Two Different Multicomponent Cognitive–Motor Training Protocols on EEG Spectral Activity, Cognitive–Motor Interference, and Gait Performance in Individuals with Chronic Stroke: A Randomized Controlled Trial https://www.mdpi.com/1648-9144/62/9/1738 Background and Objectives: This trial examined whether two task-complexity gait training protocols differentially affect EEG spectral activity, cognitive–motor interference, and gait performance in chronic stroke. Materials and Methods: Forty-four participants were randomly allocated to Progressive Task-Complexity Gait Training (PTCGT; n = 22) or Constant Task-Complexity Gait Training (CTCGT; n = 22). Both groups trained for 4 weeks using the same auditory-feedback walker. PTCGT progressed from obstacle avoidance to rhythmic auditory cueing plus obstacle avoidance, followed by a verbal fluency dual-task. CTCGT maintained rhythmic auditory cueing plus obstacle avoidance. Outcomes included EEG theta, SMR, mid-beta, Concentration Index, SEF-50, DTC%, and GAITRite gait parameters. Results: Significant group-by-time interactions were observed for EEG and gait measures. DTC showed a significant interaction in repeated-measures ANOVA (p = 0.041), but not in mixed-effects sensitivity analysis (p = 0.088). PTCGT showed greater pre–post changes in EEG and gait outcomes, whereas the DTC difference was less robust. Conclusions: PTCGT was associated with greater changes in EEG spectral characteristics and gait performance than CTCGT. However, these differences cannot be attributed specifically to the progressive task-complexity protocol because PTCGT also involved additional cognitive-task exposure and greater task complexity. In addition, because cognitive-task performance was not quantitatively assessed, improvements in dual-task ability or cognitive–motor integration cannot be established. 2026-09-09 Medicina, Vol. 62, Pages 1738: Effects of Two Different Multicomponent Cognitive–Motor Training Protocols on EEG Spectral Activity, Cognitive–Motor Interference, and Gait Performance in Individuals with Chronic Stroke: A Randomized Controlled Trial

Medicina doi: 10.3390/medicina62091738

Authors: Shin-Young Park Si-A Lee

Background and Objectives: This trial examined whether two task-complexity gait training protocols differentially affect EEG spectral activity, cognitive–motor interference, and gait performance in chronic stroke. Materials and Methods: Forty-four participants were randomly allocated to Progressive Task-Complexity Gait Training (PTCGT; n = 22) or Constant Task-Complexity Gait Training (CTCGT; n = 22). Both groups trained for 4 weeks using the same auditory-feedback walker. PTCGT progressed from obstacle avoidance to rhythmic auditory cueing plus obstacle avoidance, followed by a verbal fluency dual-task. CTCGT maintained rhythmic auditory cueing plus obstacle avoidance. Outcomes included EEG theta, SMR, mid-beta, Concentration Index, SEF-50, DTC%, and GAITRite gait parameters. Results: Significant group-by-time interactions were observed for EEG and gait measures. DTC showed a significant interaction in repeated-measures ANOVA (p = 0.041), but not in mixed-effects sensitivity analysis (p = 0.088). PTCGT showed greater pre–post changes in EEG and gait outcomes, whereas the DTC difference was less robust. Conclusions: PTCGT was associated with greater changes in EEG spectral characteristics and gait performance than CTCGT. However, these differences cannot be attributed specifically to the progressive task-complexity protocol because PTCGT also involved additional cognitive-task exposure and greater task complexity. In addition, because cognitive-task performance was not quantitatively assessed, improvements in dual-task ability or cognitive–motor integration cannot be established.

]]> Effects of Two Different Multicomponent Cognitive–Motor Training Protocols on EEG Spectral Activity, Cognitive–Motor Interference, and Gait Performance in Individuals with Chronic Stroke: A Randomized Controlled Trial Shin-Young Park Si-A Lee doi: 10.3390/medicina62091738 Medicina 2026-09-09 Medicina 2026-09-09 62 9 Article 1738 10.3390/medicina62091738 https://www.mdpi.com/1648-9144/62/9/1738 Medicina, Vol. 62, Pages 1737: Evaluation of the Effect of Coronal Flaring on SWEEPS Laser-Activated Irrigation in Root Canals with Different Curvatures: A Confocal Laser Scanning Microscopy Study https://www.mdpi.com/1648-9144/62/9/1737 Background and Objectives: The aim of this study was to evaluate the penetration of laser-activated irrigation solutions into dentinal tubules in root canals with different degrees of curvature and different coronal flaring. Materials and Methods: Seventy-six maxillary first molar teeth previously extracted for various reasons were included in the present study. The specimens were divided into two main groups according to distal root canal curvature, determined using the Schneider method: straight (<10°) and curved (20–40°). These groups were further classified into two subgroups according to whether a coronal flaring procedure was performed (n = 19). Following root canal preparation of all specimens, final irrigation was performed using a laser activation method and an irrigation solution prepared with the fluorescent dye Rhodamine B. Horizontal apical, middle, and coronal sections of 1 ± 0.1 mm thickness were obtained from the specimens at 2 mm, 5 mm, and 8 mm from the apical foramen, respectively. The effect of the irrigation solution on dentinal tubule penetration in the root canals was evaluated in the obtained sections using confocal laser scanning microscopy. Following evaluation, the mean and maximum penetration distances into the dentinal tubules were measured. The obtained data were statistically analyzed using Generalized Estimating Equations and Bonferroni correction for multiple comparisons, with the significance level set at p < 0.05. Results: The analysis revealed that only the region factor had a statistically significant effect on mean penetration values (p < 0.001), whereas canal curvature (p = 0.010), coronal flaring (p = 0.002), and region (p < 0.001) had statistically significant effects on maximum penetration values. However, none of the two-way or three-way interactions were significant (p > 0.05). Conclusions: Coronal flaring did not affect mean dentinal tubule penetration but increased maximum penetration depth. Maximum penetration was higher in straight canals than in curved canals, while both mean and maximum penetration were significantly affected by the root canal region. 2026-09-09 Medicina, Vol. 62, Pages 1737: Evaluation of the Effect of Coronal Flaring on SWEEPS Laser-Activated Irrigation in Root Canals with Different Curvatures: A Confocal Laser Scanning Microscopy Study

Medicina doi: 10.3390/medicina62091737

Authors: İbrahim Sevinç Esma Dinger

Background and Objectives: The aim of this study was to evaluate the penetration of laser-activated irrigation solutions into dentinal tubules in root canals with different degrees of curvature and different coronal flaring. Materials and Methods: Seventy-six maxillary first molar teeth previously extracted for various reasons were included in the present study. The specimens were divided into two main groups according to distal root canal curvature, determined using the Schneider method: straight (<10°) and curved (20–40°). These groups were further classified into two subgroups according to whether a coronal flaring procedure was performed (n = 19). Following root canal preparation of all specimens, final irrigation was performed using a laser activation method and an irrigation solution prepared with the fluorescent dye Rhodamine B. Horizontal apical, middle, and coronal sections of 1 ± 0.1 mm thickness were obtained from the specimens at 2 mm, 5 mm, and 8 mm from the apical foramen, respectively. The effect of the irrigation solution on dentinal tubule penetration in the root canals was evaluated in the obtained sections using confocal laser scanning microscopy. Following evaluation, the mean and maximum penetration distances into the dentinal tubules were measured. The obtained data were statistically analyzed using Generalized Estimating Equations and Bonferroni correction for multiple comparisons, with the significance level set at p < 0.05. Results: The analysis revealed that only the region factor had a statistically significant effect on mean penetration values (p < 0.001), whereas canal curvature (p = 0.010), coronal flaring (p = 0.002), and region (p < 0.001) had statistically significant effects on maximum penetration values. However, none of the two-way or three-way interactions were significant (p > 0.05). Conclusions: Coronal flaring did not affect mean dentinal tubule penetration but increased maximum penetration depth. Maximum penetration was higher in straight canals than in curved canals, while both mean and maximum penetration were significantly affected by the root canal region.

]]> Evaluation of the Effect of Coronal Flaring on SWEEPS Laser-Activated Irrigation in Root Canals with Different Curvatures: A Confocal Laser Scanning Microscopy Study İbrahim Sevinç Esma Dinger doi: 10.3390/medicina62091737 Medicina 2026-09-09 Medicina 2026-09-09 62 9 Article 1737 10.3390/medicina62091737 https://www.mdpi.com/1648-9144/62/9/1737 Medicina, Vol. 62, Pages 1736: Clinical and Epidemiological Profile of Atrial Fibrillation in a High-Altitude Tertiary-Care Setting https://www.mdpi.com/1648-9144/62/9/1736 Background and Objectives: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a major cause of stroke, heart failure, and death. Evidence on AF in Latin American and Andean tertiary-care settings remains limited. The objective was to describe the demographic and clinical profile, documented thromboembolic and bleeding risk, in-hospital management, and outcomes of adults with AF treated at a tertiary hospital located at 2850 m above sea level. Materials and Methods: We retrospectively reviewed unique adult patient records from January 2021 through December 2023 identified by ICD-10 code I48 and explicit clinician documentation of AF. Independent electrocardiographic adjudication was not performed. Demographics, comorbidities, chart-recorded AF category, risk scores, echocardiographic findings, in-hospital treatments, and outcomes were summarized descriptively. Results: Among 238 patients, mean age was 77.9 ± 13.3 years, 55.0% were male, and 97.1% were recorded as mestizo. Hypertension (58.0%) and heart failure (22.7%) were the most frequent comorbidities. CHA2DS2-VASc and HAS-BLED scores were documented for 199 patients (83.6%); their respective means were 3.3 ± 1.4 and 2.3 ± 1.1. Any anticoagulant was administered during hospitalization to 195 patients (81.9%), but previous and discharge therapy, indications, contraindications, dosing, and temporary interruptions were not consistently available. Five patients died in hospital (2.1%). Secondary exploratory comparisons by survival status were hypothesis-generating, and none remained significant after false-discovery-rate correction. Conclusions: This cohort describes an older, comorbid population treated at a hospital situated at high altitude. The study does not establish an altitude-related AF phenotype, the appropriateness of chronic anticoagulation, or prognostic factors for mortality. Prospective multicentre studies with adjudicated AF, individual altitude exposure, oxygenation and haematologic measures, and longitudinal treatment data are warranted. 2026-09-09 Medicina, Vol. 62, Pages 1736: Clinical and Epidemiological Profile of Atrial Fibrillation in a High-Altitude Tertiary-Care Setting

Medicina doi: 10.3390/medicina62091736

Authors: Vladimir Ernesto Ullauri-Solórzano René Antonio Vicuña Mariño Diego Ricardo Egas Proaño Diana Moreira-Vera Henrry Oswaldo Jaramillo Prado Ana Gabriela Finke Barriga Gabriela Tatiana León Molina Juan José Paz y Miño Ronald Alfredo Cevallos Macías Jorge Vasconez-Gonzalez Juan S. Izquierdo-Condoy Esteban Ortiz-Prado

Background and Objectives: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a major cause of stroke, heart failure, and death. Evidence on AF in Latin American and Andean tertiary-care settings remains limited. The objective was to describe the demographic and clinical profile, documented thromboembolic and bleeding risk, in-hospital management, and outcomes of adults with AF treated at a tertiary hospital located at 2850 m above sea level. Materials and Methods: We retrospectively reviewed unique adult patient records from January 2021 through December 2023 identified by ICD-10 code I48 and explicit clinician documentation of AF. Independent electrocardiographic adjudication was not performed. Demographics, comorbidities, chart-recorded AF category, risk scores, echocardiographic findings, in-hospital treatments, and outcomes were summarized descriptively. Results: Among 238 patients, mean age was 77.9 ± 13.3 years, 55.0% were male, and 97.1% were recorded as mestizo. Hypertension (58.0%) and heart failure (22.7%) were the most frequent comorbidities. CHA2DS2-VASc and HAS-BLED scores were documented for 199 patients (83.6%); their respective means were 3.3 ± 1.4 and 2.3 ± 1.1. Any anticoagulant was administered during hospitalization to 195 patients (81.9%), but previous and discharge therapy, indications, contraindications, dosing, and temporary interruptions were not consistently available. Five patients died in hospital (2.1%). Secondary exploratory comparisons by survival status were hypothesis-generating, and none remained significant after false-discovery-rate correction. Conclusions: This cohort describes an older, comorbid population treated at a hospital situated at high altitude. The study does not establish an altitude-related AF phenotype, the appropriateness of chronic anticoagulation, or prognostic factors for mortality. Prospective multicentre studies with adjudicated AF, individual altitude exposure, oxygenation and haematologic measures, and longitudinal treatment data are warranted.

]]> Clinical and Epidemiological Profile of Atrial Fibrillation in a High-Altitude Tertiary-Care Setting Vladimir Ernesto Ullauri-Solórzano René Antonio Vicuña Mariño Diego Ricardo Egas Proaño Diana Moreira-Vera Henrry Oswaldo Jaramillo Prado Ana Gabriela Finke Barriga Gabriela Tatiana León Molina Juan José Paz y Miño Ronald Alfredo Cevallos Macías Jorge Vasconez-Gonzalez Juan S. Izquierdo-Condoy Esteban Ortiz-Prado doi: 10.3390/medicina62091736 Medicina 2026-09-09 Medicina 2026-09-09 62 9 Article 1736 10.3390/medicina62091736 https://www.mdpi.com/1648-9144/62/9/1736 Medicina, Vol. 62, Pages 1735: Sarcopenia and 24-Month All-Cause Mortality in Patients Receiving Maintenance Hemodialysis: A Prospective Observational Cohort Study Applying the Revised European Working Group on Sarcopenia in Older People Criteria https://www.mdpi.com/1648-9144/62/9/1735 Background and Objectives: Sarcopenia is common among patients receiving maintenance hemodialysis, although prevalence estimates vary according to the diagnostic approach. We assessed sarcopenia defined according to the revised European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, its baseline correlates, and its association with 24-month all-cause mortality. Materials and Methods: In this single-center prospective cohort at a tertiary nephrology center, 176 patients enrolled in December 2022 were followed for 24 months. Confirmed sarcopenia required both low handgrip strength and a low appendicular skeletal muscle index assessed by bioelectrical impedance. Physical performance was not assessed. Because the proportional-hazards assumption was not satisfied, restricted mean survival time (RMST) was used as the primary measure of the survival difference. Results: Sarcopenia was present in 46 of 176 participants (26.1%, 95% CI 20.2–33.1). Older age, lower serum albumin and phosphorus concentrations, lower Kt/V, and longer time on maintenance hemodialysis were independently associated with sarcopenia. Thirty-one participants died during follow-up, and survival was lower among those with sarcopenia (log-rank p = 0.035). The adjusted RMST difference was −3.88 months (95% CI −6.49 to −1.28; p = 0.003). A Cox sensitivity analysis yielded a hazard ratio of 2.62 (95% CI 1.06–6.45). There was no evidence of a sarcopenia-by-sex interaction in the adjusted RMST analysis (p = 0.964). Conclusions: Confirmed sarcopenia was present in approximately one quarter of patients and was associated with approximately four months shorter restricted mean survival over 24 months. EWGSOP2-based assessment may provide prognostic information in this setting; whether routine screening or management based on sarcopenia status improves clinical outcomes remains to be determined. 2026-09-09 Medicina, Vol. 62, Pages 1735: Sarcopenia and 24-Month All-Cause Mortality in Patients Receiving Maintenance Hemodialysis: A Prospective Observational Cohort Study Applying the Revised European Working Group on Sarcopenia in Older People Criteria

Medicina doi: 10.3390/medicina62091735

Authors: Zorica M. Dimitrijevic Jelena Randjelovic Danijela Tasic Karolina Paunovic Branislav Apostolovic Emina Kostic Tamara Vrecic Aleksandar Radivojevic Branka Mitic

Background and Objectives: Sarcopenia is common among patients receiving maintenance hemodialysis, although prevalence estimates vary according to the diagnostic approach. We assessed sarcopenia defined according to the revised European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, its baseline correlates, and its association with 24-month all-cause mortality. Materials and Methods: In this single-center prospective cohort at a tertiary nephrology center, 176 patients enrolled in December 2022 were followed for 24 months. Confirmed sarcopenia required both low handgrip strength and a low appendicular skeletal muscle index assessed by bioelectrical impedance. Physical performance was not assessed. Because the proportional-hazards assumption was not satisfied, restricted mean survival time (RMST) was used as the primary measure of the survival difference. Results: Sarcopenia was present in 46 of 176 participants (26.1%, 95% CI 20.2–33.1). Older age, lower serum albumin and phosphorus concentrations, lower Kt/V, and longer time on maintenance hemodialysis were independently associated with sarcopenia. Thirty-one participants died during follow-up, and survival was lower among those with sarcopenia (log-rank p = 0.035). The adjusted RMST difference was −3.88 months (95% CI −6.49 to −1.28; p = 0.003). A Cox sensitivity analysis yielded a hazard ratio of 2.62 (95% CI 1.06–6.45). There was no evidence of a sarcopenia-by-sex interaction in the adjusted RMST analysis (p = 0.964). Conclusions: Confirmed sarcopenia was present in approximately one quarter of patients and was associated with approximately four months shorter restricted mean survival over 24 months. EWGSOP2-based assessment may provide prognostic information in this setting; whether routine screening or management based on sarcopenia status improves clinical outcomes remains to be determined.

]]> Sarcopenia and 24-Month All-Cause Mortality in Patients Receiving Maintenance Hemodialysis: A Prospective Observational Cohort Study Applying the Revised European Working Group on Sarcopenia in Older People Criteria Zorica M. Dimitrijevic Jelena Randjelovic Danijela Tasic Karolina Paunovic Branislav Apostolovic Emina Kostic Tamara Vrecic Aleksandar Radivojevic Branka Mitic doi: 10.3390/medicina62091735 Medicina 2026-09-09 Medicina 2026-09-09 62 9 Article 1735 10.3390/medicina62091735 https://www.mdpi.com/1648-9144/62/9/1735 Medicina, Vol. 62, Pages 1734: Oxidative Stress and Oocyte Developmental Competence: A Cell-Specific Analysis of Antioxidant Enzymes in Human Follicle Cells https://www.mdpi.com/1648-9144/62/9/1734 Background and Objectives: Granulosa (GCs) and cumulus cells (CCs) play a key supportive role in oocyte developmental competence and in antioxidant defence mechanisms triggered by endogenous reactive oxygen species production. Assisted reproductive technology (ART) procedures are an additional source of oxidative stress (OS) that somatic cells must counteract to ensure healthy embryo production. In this study, we quantified the major antioxidant enzymes (CAT, GPx1, SOD-1 and 2) in GCs and CCs retrieved from human antral follicles classified as large (>18 mm, L) or small (<18 mm, S) using ELISA. We correlated their contents with ongoing pregnancy rate (OPR). Materials and Methods: Healthy women (n = 17) undergoing ART procedures were selected for this study. During pickup, antral follicles were classified by diameter as L or S, and their somatic cells were stored separately for ELISA. After intracytoplasmic sperm injection (ICSI), embryo quality was assessed morphologically, and the OPR was evaluated. Results: Results showed that embryo quality and OPR were positively correlated with higher antioxidant enzyme levels detected in both GCs and CCs independently of follicle size. Conclusions: The data suggest that adequate levels of antioxidant enzymes in GCs and CCs are necessary not only to protect the oocyte from oxidative damage, but may also help predict embryo quality and OPR. 2026-09-09 Medicina, Vol. 62, Pages 1734: Oxidative Stress and Oocyte Developmental Competence: A Cell-Specific Analysis of Antioxidant Enzymes in Human Follicle Cells

Medicina doi: 10.3390/medicina62091734

Authors: Giovanni Ruvolo Gianna Rossi Daniele Lozzi Gerlando Cocchiara Beatrice Ermini Marta Scarcella Michele Ermini Ettore Cittadini Sandra Cecconi

Background and Objectives: Granulosa (GCs) and cumulus cells (CCs) play a key supportive role in oocyte developmental competence and in antioxidant defence mechanisms triggered by endogenous reactive oxygen species production. Assisted reproductive technology (ART) procedures are an additional source of oxidative stress (OS) that somatic cells must counteract to ensure healthy embryo production. In this study, we quantified the major antioxidant enzymes (CAT, GPx1, SOD-1 and 2) in GCs and CCs retrieved from human antral follicles classified as large (>18 mm, L) or small (<18 mm, S) using ELISA. We correlated their contents with ongoing pregnancy rate (OPR). Materials and Methods: Healthy women (n = 17) undergoing ART procedures were selected for this study. During pickup, antral follicles were classified by diameter as L or S, and their somatic cells were stored separately for ELISA. After intracytoplasmic sperm injection (ICSI), embryo quality was assessed morphologically, and the OPR was evaluated. Results: Results showed that embryo quality and OPR were positively correlated with higher antioxidant enzyme levels detected in both GCs and CCs independently of follicle size. Conclusions: The data suggest that adequate levels of antioxidant enzymes in GCs and CCs are necessary not only to protect the oocyte from oxidative damage, but may also help predict embryo quality and OPR.

]]> Oxidative Stress and Oocyte Developmental Competence: A Cell-Specific Analysis of Antioxidant Enzymes in Human Follicle Cells Giovanni Ruvolo Gianna Rossi Daniele Lozzi Gerlando Cocchiara Beatrice Ermini Marta Scarcella Michele Ermini Ettore Cittadini Sandra Cecconi doi: 10.3390/medicina62091734 Medicina 2026-09-09 Medicina 2026-09-09 62 9 Article 1734 10.3390/medicina62091734 https://www.mdpi.com/1648-9144/62/9/1734 Medicina, Vol. 62, Pages 1733: Intensive Versus Non-Intensive Therapy in Older Patients with Acute Myeloid Leukemia: A Real-World Experience https://www.mdpi.com/1648-9144/62/9/1733 Background and Objectives: The optimal treatment strategy for older patients with acute myeloid leukemia (AML) remains uncertain because treatment selection is influenced by age, comorbidity, functional status, and disease biology. This study explored real-world outcomes with intensive and non-intensive treatment strategies. Materials and Methods: We retrospectively analyzed 69 patients aged ≥ 65 years diagnosed with AML between 2012 and 2022 at a tertiary center. Treatment intensity was defined by regimen. Baseline demographic, clinical, and laboratory parameters were recorded. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method and compared using log-rank tests. Results: A total of 69 patients were included, with a median age of 71 years. Intensive and non-intensive therapies were administered in 24.2% and 75.8% of treated patients, respectively. The median PFS was 6.7 months, and the median OS was 7.8 months. One- and two-year OS rates were 29% and 9.2%, respectively. No significant differences in PFS or OS were observed between treatment intensity groups. Among response-evaluable patients, complete remission/complete remission with incomplete hematologic recovery (CR/CRi) was achieved in 58.0% of intensively treated patients and 43.3% of those receiving hypomethylating agent (HMA)-based therapy. Among the evaluated baseline variables, only Eastern Cooperative Oncology Group (ECOG) performance status was significantly associated with overall survival. Patients with an ECOG performance status ≥ 2 had significantly shorter OS than those with ECOG <2 (median OS: 4.85 vs. 8.60 months, p = 0.009). Conclusions: In this real-world cohort of older patients with AML, no statistically significant differences in PFS or OS were observed between intensive and non-intensive treatment strategies. Although CR/CRi rates were numerically higher with intensive therapy, disease progression remained frequent among patients who achieved a response. ECOG performance status was significantly associated with overall survival, highlighting the relevance of functional status in individualized treatment selection. These findings should not be interpreted as evidence of therapeutic equivalence. 2026-09-09 Medicina, Vol. 62, Pages 1733: Intensive Versus Non-Intensive Therapy in Older Patients with Acute Myeloid Leukemia: A Real-World Experience

Medicina doi: 10.3390/medicina62091733

Authors: Dila Elifsu Yuksekli Arda Bayar Ceren Uzunoglu Guren Fatma Arikan Fatma Temiz Ahmet Mert Yanik Tayfur Toptas Isik Kaygusuz Atagunduz Tulin Tuglular Asu Fergun Yilmaz

Background and Objectives: The optimal treatment strategy for older patients with acute myeloid leukemia (AML) remains uncertain because treatment selection is influenced by age, comorbidity, functional status, and disease biology. This study explored real-world outcomes with intensive and non-intensive treatment strategies. Materials and Methods: We retrospectively analyzed 69 patients aged ≥ 65 years diagnosed with AML between 2012 and 2022 at a tertiary center. Treatment intensity was defined by regimen. Baseline demographic, clinical, and laboratory parameters were recorded. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method and compared using log-rank tests. Results: A total of 69 patients were included, with a median age of 71 years. Intensive and non-intensive therapies were administered in 24.2% and 75.8% of treated patients, respectively. The median PFS was 6.7 months, and the median OS was 7.8 months. One- and two-year OS rates were 29% and 9.2%, respectively. No significant differences in PFS or OS were observed between treatment intensity groups. Among response-evaluable patients, complete remission/complete remission with incomplete hematologic recovery (CR/CRi) was achieved in 58.0% of intensively treated patients and 43.3% of those receiving hypomethylating agent (HMA)-based therapy. Among the evaluated baseline variables, only Eastern Cooperative Oncology Group (ECOG) performance status was significantly associated with overall survival. Patients with an ECOG performance status ≥ 2 had significantly shorter OS than those with ECOG <2 (median OS: 4.85 vs. 8.60 months, p = 0.009). Conclusions: In this real-world cohort of older patients with AML, no statistically significant differences in PFS or OS were observed between intensive and non-intensive treatment strategies. Although CR/CRi rates were numerically higher with intensive therapy, disease progression remained frequent among patients who achieved a response. ECOG performance status was significantly associated with overall survival, highlighting the relevance of functional status in individualized treatment selection. These findings should not be interpreted as evidence of therapeutic equivalence.

]]> Intensive Versus Non-Intensive Therapy in Older Patients with Acute Myeloid Leukemia: A Real-World Experience Dila Elifsu Yuksekli Arda Bayar Ceren Uzunoglu Guren Fatma Arikan Fatma Temiz Ahmet Mert Yanik Tayfur Toptas Isik Kaygusuz Atagunduz Tulin Tuglular Asu Fergun Yilmaz doi: 10.3390/medicina62091733 Medicina 2026-09-09 Medicina 2026-09-09 62 9 Article 1733 10.3390/medicina62091733 https://www.mdpi.com/1648-9144/62/9/1733 Medicina, Vol. 62, Pages 1732: Pretreatment CONUT Score and Overall Survival in Patients with Metastatic Pancreatic Adenocarcinoma Receiving First-Line Chemotherapy: A Retrospective Cohort Study https://www.mdpi.com/1648-9144/62/9/1732 Background and Objectives: Metastatic pancreatic adenocarcinoma is related to poor prognosis and is frequently accompanied by malnutrition, inflammation, and immune dysregulation. The Controlling Nutritional Status (CONUT) score is a composite laboratory-based index that may reflect aspects of nutritional and immune status. This study aimed to evaluate the association between pretreatment CONUT score and overall survival (OS) in patients with metastatic pancreatic adenocarcinoma receiving first-line systemic chemotherapy. Materials and Methods: In this retrospective analysis, a total of 156 patients diagnosed with metastatic pancreatic adenocarcinoma between January 2017 and July 2024 and treated with first-line systemic chemotherapy were included. Based on the conventional CONUT classification, patients were categorized a priori into normal-CONUT (scores 0–1) and elevated-CONUT (scores ≥ 2) groups, with CONUT additionally evaluated as a continuous score. OS was estimated using the Kaplan–Meier method. Univariable and multivariable Cox regression analyses were performed to evaluate the association between the CONUT score, selected clinical factors, and overall survival. Results: The cohort demonstrated a median OS of 9.1 months (95% CI: 6.6–11.6). OS was significantly better among individuals classified in normal CONUT group relative to elevated CONUT group (14.1 vs. 6.5 months, respectively, p <0.001). Higher continuous CONUT scores were also associated with shorter OS (HR 1.23 (1.14–1.32), p < 0.001). In multivariable analysis, an elevated CONUT score (HR, 2.40 (1.63–3.52); p <0.001), liver metastases (HR 1.99 (1.31–3.02); p = 0.001), and the presence of comorbidity (HR, 1.88 (1.28–2.75); p = 0.001) remained significantly associated with shorter OS. Conclusions: An elevated pretreatment CONUT score was associated with shorter overall survival in this selected chemotherapy-treated cohort. As a readily available laboratory-based index, CONUT may provide additional prognostic information; however, prospective studies are needed to determine whether it adds value beyond established clinical factors. 2026-09-09 Medicina, Vol. 62, Pages 1732: Pretreatment CONUT Score and Overall Survival in Patients with Metastatic Pancreatic Adenocarcinoma Receiving First-Line Chemotherapy: A Retrospective Cohort Study

Medicina doi: 10.3390/medicina62091732

Authors: Zeynep Alaca Topcu Serhat Demirer Tuba Baydas Mehmet Besiroglu Mahmut Gumus

Background and Objectives: Metastatic pancreatic adenocarcinoma is related to poor prognosis and is frequently accompanied by malnutrition, inflammation, and immune dysregulation. The Controlling Nutritional Status (CONUT) score is a composite laboratory-based index that may reflect aspects of nutritional and immune status. This study aimed to evaluate the association between pretreatment CONUT score and overall survival (OS) in patients with metastatic pancreatic adenocarcinoma receiving first-line systemic chemotherapy. Materials and Methods: In this retrospective analysis, a total of 156 patients diagnosed with metastatic pancreatic adenocarcinoma between January 2017 and July 2024 and treated with first-line systemic chemotherapy were included. Based on the conventional CONUT classification, patients were categorized a priori into normal-CONUT (scores 0–1) and elevated-CONUT (scores ≥ 2) groups, with CONUT additionally evaluated as a continuous score. OS was estimated using the Kaplan–Meier method. Univariable and multivariable Cox regression analyses were performed to evaluate the association between the CONUT score, selected clinical factors, and overall survival. Results: The cohort demonstrated a median OS of 9.1 months (95% CI: 6.6–11.6). OS was significantly better among individuals classified in normal CONUT group relative to elevated CONUT group (14.1 vs. 6.5 months, respectively, p <0.001). Higher continuous CONUT scores were also associated with shorter OS (HR 1.23 (1.14–1.32), p < 0.001). In multivariable analysis, an elevated CONUT score (HR, 2.40 (1.63–3.52); p <0.001), liver metastases (HR 1.99 (1.31–3.02); p = 0.001), and the presence of comorbidity (HR, 1.88 (1.28–2.75); p = 0.001) remained significantly associated with shorter OS. Conclusions: An elevated pretreatment CONUT score was associated with shorter overall survival in this selected chemotherapy-treated cohort. As a readily available laboratory-based index, CONUT may provide additional prognostic information; however, prospective studies are needed to determine whether it adds value beyond established clinical factors.

]]> Pretreatment CONUT Score and Overall Survival in Patients with Metastatic Pancreatic Adenocarcinoma Receiving First-Line Chemotherapy: A Retrospective Cohort Study Zeynep Alaca Topcu Serhat Demirer Tuba Baydas Mehmet Besiroglu Mahmut Gumus doi: 10.3390/medicina62091732 Medicina 2026-09-09 Medicina 2026-09-09 62 9 Article 1732 10.3390/medicina62091732 https://www.mdpi.com/1648-9144/62/9/1732 Medicina, Vol. 62, Pages 1731: Mortality Associated with Intensive Care Unit Admission and Mechanical Ventilation in Adults with Acute Chest Syndrome: A Systematic Review https://www.mdpi.com/1648-9144/62/9/1731 Background and Objectives: Acute chest syndrome (ACS) is the leading cause of sickle cell disease (SCD)-related mortality (~25% of deaths). A subset of patients develops severe respiratory compromise requiring intensive care unit (ICU) admission or mechanical ventilation (MV), a high-risk group with widely variable reported mortality. This review aimed to determine the mortality rates, ICU/hospital length of stay, and reported complications among adult SCD patients with ACS admitted to the ICU or placed on MV. Materials and Methods: This PRISMA 2020-compliant systematic review was prospectively registered on PROSPERO (CRD420261295111). Cochrane Library, PubMed, Web of Science, ScienceDirect, EBSCOhost, and Scopus were searched without date restriction. Due to substantial clinical and methodological heterogeneity, the pre-specified meta-analysis was replaced by a narrative synthesis. Methodological quality was assessed using the Newcastle–Ottawa Scale. Results: Eight studies were included (one multicenter prospective cohort, two national database studies, three single-center cohorts, and one before–after antimicrobial stewardship study). In-hospital mortality ranged from 0.95% to 3.8%; overall mortality including follow-up reached 12.9% in a dedicated ICU cohort, a distinct endpoint from in-hospital death. Mechanical ventilation was the strongest indicator of mortality, with odds ratios of 67.53 (MV < 96 h) and 8.73 (MV ≥ 96 h) in the largest national cohort. Tricuspid regurgitant jet velocity ≥3 m/second was associated with cor pulmonale, invasive ventilation, and all immediate hospital deaths in one severe cohort. Documented bacterial infection was uncommon (10–20% of episodes), despite frequent antibiotic use, and procalcitonin-guided discontinuation safely reduced antibiotic exposure. All eight included studies were rated high quality on the Newcastle–Ottawa Scale (score ≥ 7/9). Conclusions: Mechanical ventilation, pulmonary hypertension/cor pulmonale, and comorbidity burden are the most consistent markers of poor outcome in ACS. The findings support early recognition, severity-based respiratory support, and antimicrobial stewardship, but should be interpreted cautiously given the substitution of narrative synthesis for meta-analysis, heterogeneous populations, and the geographic concentration of the included studies. 2026-09-08 Medicina, Vol. 62, Pages 1731: Mortality Associated with Intensive Care Unit Admission and Mechanical Ventilation in Adults with Acute Chest Syndrome: A Systematic Review

Medicina doi: 10.3390/medicina62091731

Authors: Mohammed Essam Shaybah Osama Alsehli Ali Al-Harthi Nada Bajuaifer Mohammed Bafaqih Mohammed Alzhrani Abdulrhman Alasmari Abdulghafur Kashgari Omar M. Alhazmi Anas Sameer Munshi

Background and Objectives: Acute chest syndrome (ACS) is the leading cause of sickle cell disease (SCD)-related mortality (~25% of deaths). A subset of patients develops severe respiratory compromise requiring intensive care unit (ICU) admission or mechanical ventilation (MV), a high-risk group with widely variable reported mortality. This review aimed to determine the mortality rates, ICU/hospital length of stay, and reported complications among adult SCD patients with ACS admitted to the ICU or placed on MV. Materials and Methods: This PRISMA 2020-compliant systematic review was prospectively registered on PROSPERO (CRD420261295111). Cochrane Library, PubMed, Web of Science, ScienceDirect, EBSCOhost, and Scopus were searched without date restriction. Due to substantial clinical and methodological heterogeneity, the pre-specified meta-analysis was replaced by a narrative synthesis. Methodological quality was assessed using the Newcastle–Ottawa Scale. Results: Eight studies were included (one multicenter prospective cohort, two national database studies, three single-center cohorts, and one before–after antimicrobial stewardship study). In-hospital mortality ranged from 0.95% to 3.8%; overall mortality including follow-up reached 12.9% in a dedicated ICU cohort, a distinct endpoint from in-hospital death. Mechanical ventilation was the strongest indicator of mortality, with odds ratios of 67.53 (MV < 96 h) and 8.73 (MV ≥ 96 h) in the largest national cohort. Tricuspid regurgitant jet velocity ≥3 m/second was associated with cor pulmonale, invasive ventilation, and all immediate hospital deaths in one severe cohort. Documented bacterial infection was uncommon (10–20% of episodes), despite frequent antibiotic use, and procalcitonin-guided discontinuation safely reduced antibiotic exposure. All eight included studies were rated high quality on the Newcastle–Ottawa Scale (score ≥ 7/9). Conclusions: Mechanical ventilation, pulmonary hypertension/cor pulmonale, and comorbidity burden are the most consistent markers of poor outcome in ACS. The findings support early recognition, severity-based respiratory support, and antimicrobial stewardship, but should be interpreted cautiously given the substitution of narrative synthesis for meta-analysis, heterogeneous populations, and the geographic concentration of the included studies.

]]> Mortality Associated with Intensive Care Unit Admission and Mechanical Ventilation in Adults with Acute Chest Syndrome: A Systematic Review Mohammed Essam Shaybah Osama Alsehli Ali Al-Harthi Nada Bajuaifer Mohammed Bafaqih Mohammed Alzhrani Abdulrhman Alasmari Abdulghafur Kashgari Omar M. Alhazmi Anas Sameer Munshi doi: 10.3390/medicina62091731 Medicina 2026-09-08 Medicina 2026-09-08 62 9 Systematic Review 1731 10.3390/medicina62091731 https://www.mdpi.com/1648-9144/62/9/1731 Medicina, Vol. 62, Pages 1730: Ex Vivo Shear-Wave Elastography for Intraoperative Prediction of Axillary Lymph Node Metastasis in Breast Cancer https://www.mdpi.com/1648-9144/62/9/1730 Background and Objectives: Intraoperative sentinel lymph node (SLN) assessment is a pivotal step in early-stage breast cancer surgery. Frozen section (FS) analysis remains a widely utilised technique; however, its limitations, particularly in the detection of micrometastases, are well-documented. The process is both time-consuming and costly. The objective of this study was to investigate the potential of ex vivo shear-wave elastography (SWE) as a rapid and reproducible method for quantifying lymph node stiffness and predicting metastatic involvement. Materials and Methods: Between January 2022 and January 2024, 100 patients with biopsy-confirmed invasive breast cancer undergoing SLNB were enrolled in the study. A total of 384 excised axillary lymph nodes were subjected to ex vivo SWE immediately following excision, prior to the standard histopathological procedure. The mean stiffness (Emean) values were recorded, and the diagnostic performance was evaluated with the use of ROC analysis. Results: Of the 384 nodes examined, 45 (11.6%) were found to have metastases on final histopathology. It was demonstrated that Emean exhibited excellent discriminatory power, with an Area Under the Curve (AUC) value of 0.957. At the optimal cut-off of 28 kPa, the sensitivity and specificity levels were recorded as 91% and 87%, respectively. Conclusions: The findings of this study indicate that ex vivo SWE is a highly accurate and reproducible method for identifying metastatic sentinel lymph nodes. The technique has the potential to complement or selectively replace intraoperative FS, thereby reducing unnecessary tissue processing. The logical next step is multicentre validation. 2026-09-08 Medicina, Vol. 62, Pages 1730: Ex Vivo Shear-Wave Elastography for Intraoperative Prediction of Axillary Lymph Node Metastasis in Breast Cancer

Medicina doi: 10.3390/medicina62091730

Authors: Süleyman Özkan Aksoy Işıl Başara Akın Gökçe Kıran Kazancı Merih Güray Durak Canan Altay Zekai Serhan Derici Cihan Ağalar Berke Manoğlu Muhammet Berkay Sakaoğlu Erhan Tükel Pınar Balcı Ali İbrahim Sevinç

Background and Objectives: Intraoperative sentinel lymph node (SLN) assessment is a pivotal step in early-stage breast cancer surgery. Frozen section (FS) analysis remains a widely utilised technique; however, its limitations, particularly in the detection of micrometastases, are well-documented. The process is both time-consuming and costly. The objective of this study was to investigate the potential of ex vivo shear-wave elastography (SWE) as a rapid and reproducible method for quantifying lymph node stiffness and predicting metastatic involvement. Materials and Methods: Between January 2022 and January 2024, 100 patients with biopsy-confirmed invasive breast cancer undergoing SLNB were enrolled in the study. A total of 384 excised axillary lymph nodes were subjected to ex vivo SWE immediately following excision, prior to the standard histopathological procedure. The mean stiffness (Emean) values were recorded, and the diagnostic performance was evaluated with the use of ROC analysis. Results: Of the 384 nodes examined, 45 (11.6%) were found to have metastases on final histopathology. It was demonstrated that Emean exhibited excellent discriminatory power, with an Area Under the Curve (AUC) value of 0.957. At the optimal cut-off of 28 kPa, the sensitivity and specificity levels were recorded as 91% and 87%, respectively. Conclusions: The findings of this study indicate that ex vivo SWE is a highly accurate and reproducible method for identifying metastatic sentinel lymph nodes. The technique has the potential to complement or selectively replace intraoperative FS, thereby reducing unnecessary tissue processing. The logical next step is multicentre validation.

]]> Ex Vivo Shear-Wave Elastography for Intraoperative Prediction of Axillary Lymph Node Metastasis in Breast Cancer Süleyman Özkan Aksoy Işıl Başara Akın Gökçe Kıran Kazancı Merih Güray Durak Canan Altay Zekai Serhan Derici Cihan Ağalar Berke Manoğlu Muhammet Berkay Sakaoğlu Erhan Tükel Pınar Balcı Ali İbrahim Sevinç doi: 10.3390/medicina62091730 Medicina 2026-09-08 Medicina 2026-09-08 62 9 Article 1730 10.3390/medicina62091730 https://www.mdpi.com/1648-9144/62/9/1730 Medicina, Vol. 62, Pages 1728: Distribution of Non-Fermenting Gram-Negative Bacilli and Carbapenem Resistance Profiles in Intensive Care Units of a Foundation University Hospital: A 2023–2025 Retrospective Analysis https://www.mdpi.com/1648-9144/62/9/1728 Background and Objectives: Non-fermenting Gram-negative bacilli (NFGNB) are frequently recovered from respiratory specimens in intensive care units (ICUs) and are increasingly carbapenem-resistant. We described their distribution and resistance profiles in adult ICUs over three years. Materials and Methods: Respiratory specimens submitted from adult ICUs of a foundation university hospital in Istanbul between 6 January 2023 and 27 December 2025 were analysed retrospectively using laboratory information system data. Identification and susceptibility testing used the BD Phoenix M50 system with year-specific EUCAST breakpoints (v13.0–v15.0); colistin MICs were determined by broth microdilution. The number of patients contributing more than one isolate was 268. Accordingly, the primary trend analysis was performed using generalised estimating equations (GEE) accounting for within-patient clustering. Chi-square and first-isolate analyses were used as secondary and sensitivity analyses. Results: A total of 1407 isolates were recovered from 654 of 1194 patients with a respiratory culture. Acinetobacter spp. predominated (56.9% of isolates; 54.3% of patients), followed by Pseudomonas spp. (29.4%) and Stenotrophomonas maltophilia (11.1%). Carbapenem resistance in Acinetobacter spp. was 96.7% (95% CI 95.3–97.8) for imipenem and 96.6% (95.1–97.7) for meropenem, without temporal trend. In P. aeruginosa, meropenem resistance rose from 44.7% to 71.4% (GEE odds ratio per year 1.45, 95% CI 1.09–1.92, p = 0.011), whereas imipenem resistance did not change significantly. Among the agents tested, colistin was found to be the most effective (22.4% resistance in Acinetobacter spp. and 13.1% in P. aeruginosa). Ceftazidime–avibactam resistance in P. aeruginosa was 24.3%. Of the S. maltophilia isolates, 85.8% were categorised as susceptible-increased exposure to trimethoprim–sulfamethoxazole. Conclusions: Carbapenem resistance is high and stable in Acinetobacter spp. but rising for meropenem in P. aeruginosa. These data do not distinguish colonisation from infection and cannot be linked to clinical outcomes. They should therefore be used to inform local empirical-treatment policy alongside clinical assessment, rather than as evidence of treatment failure. 2026-09-08 Medicina, Vol. 62, Pages 1728: Distribution of Non-Fermenting Gram-Negative Bacilli and Carbapenem Resistance Profiles in Intensive Care Units of a Foundation University Hospital: A 2023–2025 Retrospective Analysis

Medicina doi: 10.3390/medicina62091728

Authors: Hacer Ozturk Akin Ozge Unlu

Background and Objectives: Non-fermenting Gram-negative bacilli (NFGNB) are frequently recovered from respiratory specimens in intensive care units (ICUs) and are increasingly carbapenem-resistant. We described their distribution and resistance profiles in adult ICUs over three years. Materials and Methods: Respiratory specimens submitted from adult ICUs of a foundation university hospital in Istanbul between 6 January 2023 and 27 December 2025 were analysed retrospectively using laboratory information system data. Identification and susceptibility testing used the BD Phoenix M50 system with year-specific EUCAST breakpoints (v13.0–v15.0); colistin MICs were determined by broth microdilution. The number of patients contributing more than one isolate was 268. Accordingly, the primary trend analysis was performed using generalised estimating equations (GEE) accounting for within-patient clustering. Chi-square and first-isolate analyses were used as secondary and sensitivity analyses. Results: A total of 1407 isolates were recovered from 654 of 1194 patients with a respiratory culture. Acinetobacter spp. predominated (56.9% of isolates; 54.3% of patients), followed by Pseudomonas spp. (29.4%) and Stenotrophomonas maltophilia (11.1%). Carbapenem resistance in Acinetobacter spp. was 96.7% (95% CI 95.3–97.8) for imipenem and 96.6% (95.1–97.7) for meropenem, without temporal trend. In P. aeruginosa, meropenem resistance rose from 44.7% to 71.4% (GEE odds ratio per year 1.45, 95% CI 1.09–1.92, p = 0.011), whereas imipenem resistance did not change significantly. Among the agents tested, colistin was found to be the most effective (22.4% resistance in Acinetobacter spp. and 13.1% in P. aeruginosa). Ceftazidime–avibactam resistance in P. aeruginosa was 24.3%. Of the S. maltophilia isolates, 85.8% were categorised as susceptible-increased exposure to trimethoprim–sulfamethoxazole. Conclusions: Carbapenem resistance is high and stable in Acinetobacter spp. but rising for meropenem in P. aeruginosa. These data do not distinguish colonisation from infection and cannot be linked to clinical outcomes. They should therefore be used to inform local empirical-treatment policy alongside clinical assessment, rather than as evidence of treatment failure.

]]> Distribution of Non-Fermenting Gram-Negative Bacilli and Carbapenem Resistance Profiles in Intensive Care Units of a Foundation University Hospital: A 2023–2025 Retrospective Analysis Hacer Ozturk Akin Ozge Unlu doi: 10.3390/medicina62091728 Medicina 2026-09-08 Medicina 2026-09-08 62 9 Article 1728 10.3390/medicina62091728 https://www.mdpi.com/1648-9144/62/9/1728 Medicina, Vol. 62, Pages 1729: Correction: Opincans et al. Comparison of Bilateral Rectus Sheath Block and Thoracic Epidural Analgesia for Postoperative Pain Control After Open Gastrectomy: A Randomized Controlled Trial. Medicina 2025, 61, 1695 https://www.mdpi.com/1648-9144/62/9/1729 In the original publication [...] 2026-09-08 Medicina, Vol. 62, Pages 1729: Correction: Opincans et al. Comparison of Bilateral Rectus Sheath Block and Thoracic Epidural Analgesia for Postoperative Pain Control After Open Gastrectomy: A Randomized Controlled Trial. Medicina 2025, 61, 1695

Medicina doi: 10.3390/medicina62091729

Authors: Janis Opincans Igors Ivanovs Aleksejs Miscuks Janis Pavulans Elina Zemite Agris Rudzats Zurabs Kecbaja Aleksejs Kaminskis

In the original publication [...]

]]> Correction: Opincans et al. Comparison of Bilateral Rectus Sheath Block and Thoracic Epidural Analgesia for Postoperative Pain Control After Open Gastrectomy: A Randomized Controlled Trial. Medicina 2025, 61, 1695 Janis Opincans Igors Ivanovs Aleksejs Miscuks Janis Pavulans Elina Zemite Agris Rudzats Zurabs Kecbaja Aleksejs Kaminskis doi: 10.3390/medicina62091729 Medicina 2026-09-08 Medicina 2026-09-08 62 9 Correction 1729 10.3390/medicina62091729 https://www.mdpi.com/1648-9144/62/9/1729 Medicina, Vol. 62, Pages 1727: Periprosthetic Fractures After Total Knee Arthroplasty—A Two-Center Study and Systematic Review of the Literature https://www.mdpi.com/1648-9144/62/9/1727 Background and Objectives: Periprosthetic fracture is a complex and urgent condition in orthopedic surgery. It requires an individual approach to every patient, and treatment is associated with high risk of complications. Materials and methods: Fifty-six patients treated due to periprosthetic fracture (PPF) after total knee arthroplasty were retrospectively analyzed according to surgical protocol, treatment time, and complication rate. The results were compared to the available literature. Results: Almost all patients (91%) were treated surgically—revision total knee arthroplasty or osteosynthesis. A therapeutic success was achieved in 81% of all cases. Replacement of the femoral component with the semi-constrained type of implant was performed most frequently during revision total knee arthroplasty. In PPFs of the femur, destabilization of fixation was observed mainly in type II according to the Lewis–Rorabeck classification. Conclusions: Despite the complexity of the problem, treatment of periprosthetic knee fractures can be effective. Provided that the implant remains stable, osteosynthesis is a good treatment option for PPF of the femur. In revision total knee arthroplasty, implants with a higher level of restriction are usually used to ensure better knee joint stability. 2026-09-08 Medicina, Vol. 62, Pages 1727: Periprosthetic Fractures After Total Knee Arthroplasty—A Two-Center Study and Systematic Review of the Literature

Medicina doi: 10.3390/medicina62091727

Authors: Piotr Sypień Daniel Jaglarz Jan Gralewski Ewa Tramś Witold Bołtuć Rafał Kamiński Dariusz Grzelecki

Background and Objectives: Periprosthetic fracture is a complex and urgent condition in orthopedic surgery. It requires an individual approach to every patient, and treatment is associated with high risk of complications. Materials and methods: Fifty-six patients treated due to periprosthetic fracture (PPF) after total knee arthroplasty were retrospectively analyzed according to surgical protocol, treatment time, and complication rate. The results were compared to the available literature. Results: Almost all patients (91%) were treated surgically—revision total knee arthroplasty or osteosynthesis. A therapeutic success was achieved in 81% of all cases. Replacement of the femoral component with the semi-constrained type of implant was performed most frequently during revision total knee arthroplasty. In PPFs of the femur, destabilization of fixation was observed mainly in type II according to the Lewis–Rorabeck classification. Conclusions: Despite the complexity of the problem, treatment of periprosthetic knee fractures can be effective. Provided that the implant remains stable, osteosynthesis is a good treatment option for PPF of the femur. In revision total knee arthroplasty, implants with a higher level of restriction are usually used to ensure better knee joint stability.

]]> Periprosthetic Fractures After Total Knee Arthroplasty—A Two-Center Study and Systematic Review of the Literature Piotr Sypień Daniel Jaglarz Jan Gralewski Ewa Tramś Witold Bołtuć Rafał Kamiński Dariusz Grzelecki doi: 10.3390/medicina62091727 Medicina 2026-09-08 Medicina 2026-09-08 62 9 Systematic Review 1727 10.3390/medicina62091727 https://www.mdpi.com/1648-9144/62/9/1727 Medicina, Vol. 62, Pages 1726: Endoscopic Ultrasound-Guided Gallbladder Drainage for Malignant Distal Biliary Obstruction: Current Evidence, Technical Considerations, and Future Directions https://www.mdpi.com/1648-9144/62/9/1726 Malignant distal biliary obstruction (MDBO) is most commonly managed by endoscopic retrograde cholangiopancreatography (ERCP) with self-expandable metal stent placement. When ERCP fails or is not feasible, endoscopic ultrasound-guided biliary drainage (EUS-BD) has increasingly replaced percutaneous transhepatic biliary drainage in expert centers. Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has emerged as an indirect route for biliary decompression when the cystic duct is patent. This comprehensive narrative review focuses on the anatomical rationale, patient selection, procedural technique, comparative positioning, clinical outcomes, adverse events, and unresolved issues of EUS-GBD in MDBO. The supporting evidence is predominantly observational. Published meta-analyses report technical success generally exceeding 90%, pooled clinical success of approximately 82–89%, and overall adverse event rates of approximately 10–14%; these estimates vary with study selection, outcome definitions, assessment time points, and predominantly observational study designs. Comparative studies suggest efficacy and safety similar to EUS-guided choledochoduodenostomy after failed ERCP in anatomically selected patients, although nonrandomized allocation and confounding by indication remain major limitations. A prospective study has demonstrated feasibility as primary palliation, but this strategy cannot yet be considered standard of care. Prophylactic EUS-GBD to prevent post-stenting cholecystitis represents a separate indication and should not be conflated with EUS-GBD for biliary decompression. The key determinant of physiological success is unobstructed communication between the gallbladder and the central biliary tree; therefore, cystic duct patency, tumor relationship to the cystic duct take-off, gallbladder distension, and the absence of extensive gallbladder involvement must be assessed before intervention. EUS-GBD is best positioned as a rescue option after failed ERCP when direct EUS-BD is technically impossible, unsafe, or unsuccessful. Prospective randomized trials, standardized outcome definitions, comparative cost-effectiveness analyses, and dedicated long-term stent management protocols are needed before broader adoption. 2026-09-08 Medicina, Vol. 62, Pages 1726: Endoscopic Ultrasound-Guided Gallbladder Drainage for Malignant Distal Biliary Obstruction: Current Evidence, Technical Considerations, and Future Directions

Medicina doi: 10.3390/medicina62091726

Authors: Danilo Paduano Roberto Leone Gianluca Franchellucci Francesco Auriemma Carmine Gentile Matteo Fiacca Federica Calabrese Eleonora Solida Abed Al-Lehibi Emad Aljahdali Abdulrahman Alfadda Resheed Alkhiari Ammar Alotaibi Cesare Hassan Alessandro Repici Benedetto Mangiavillano

Malignant distal biliary obstruction (MDBO) is most commonly managed by endoscopic retrograde cholangiopancreatography (ERCP) with self-expandable metal stent placement. When ERCP fails or is not feasible, endoscopic ultrasound-guided biliary drainage (EUS-BD) has increasingly replaced percutaneous transhepatic biliary drainage in expert centers. Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has emerged as an indirect route for biliary decompression when the cystic duct is patent. This comprehensive narrative review focuses on the anatomical rationale, patient selection, procedural technique, comparative positioning, clinical outcomes, adverse events, and unresolved issues of EUS-GBD in MDBO. The supporting evidence is predominantly observational. Published meta-analyses report technical success generally exceeding 90%, pooled clinical success of approximately 82–89%, and overall adverse event rates of approximately 10–14%; these estimates vary with study selection, outcome definitions, assessment time points, and predominantly observational study designs. Comparative studies suggest efficacy and safety similar to EUS-guided choledochoduodenostomy after failed ERCP in anatomically selected patients, although nonrandomized allocation and confounding by indication remain major limitations. A prospective study has demonstrated feasibility as primary palliation, but this strategy cannot yet be considered standard of care. Prophylactic EUS-GBD to prevent post-stenting cholecystitis represents a separate indication and should not be conflated with EUS-GBD for biliary decompression. The key determinant of physiological success is unobstructed communication between the gallbladder and the central biliary tree; therefore, cystic duct patency, tumor relationship to the cystic duct take-off, gallbladder distension, and the absence of extensive gallbladder involvement must be assessed before intervention. EUS-GBD is best positioned as a rescue option after failed ERCP when direct EUS-BD is technically impossible, unsafe, or unsuccessful. Prospective randomized trials, standardized outcome definitions, comparative cost-effectiveness analyses, and dedicated long-term stent management protocols are needed before broader adoption.

]]> Endoscopic Ultrasound-Guided Gallbladder Drainage for Malignant Distal Biliary Obstruction: Current Evidence, Technical Considerations, and Future Directions Danilo Paduano Roberto Leone Gianluca Franchellucci Francesco Auriemma Carmine Gentile Matteo Fiacca Federica Calabrese Eleonora Solida Abed Al-Lehibi Emad Aljahdali Abdulrahman Alfadda Resheed Alkhiari Ammar Alotaibi Cesare Hassan Alessandro Repici Benedetto Mangiavillano doi: 10.3390/medicina62091726 Medicina 2026-09-08 Medicina 2026-09-08 62 9 Review 1726 10.3390/medicina62091726 https://www.mdpi.com/1648-9144/62/9/1726 Medicina, Vol. 62, Pages 1725: Arthroscopic Anterior Cruciate Ligament Transection for Osteoarthritis Induction in Rabbits: A Pilot Feasibility and Characterization Study https://www.mdpi.com/1648-9144/62/9/1725 Background and Objectives: Traditional open anterior cruciate ligament transection (ACLT) surgical models performed through arthrotomy may introduce capsular trauma and postoperative inflammatory responses that can interfere with the interpretation of post-traumatic osteoarthritis (OA). This study aimed to evaluate the feasibility of a minimally invasive, arthroscopic ACLT rabbit model performed entirely under arthroscopic visualization, without arthrotomy, using a 2.4-mm arthroscope and 2.5-mm shaver, and to provide preliminary structural, histological, synovial, and systemic biochemical characterization of the model for future therapeutic testing. Materials and Methods: Bilateral arthroscopic ACLT was performed in three skeletally mature New Zealand rabbits, followed by a supervised 12-week exercise protocol. Joint degeneration was evaluated macroscopically and histopathologically using the standardized Pritzker-Osteoarthritis Research Society International (OARSI) grading system. Collagen matrix remodeling was assessed via Picrosirius Red staining. Local intra-articular catabolism was quantified via Enzyme-Linked Immunosorbent Assay (ELISA) for matrix metallopeptidase 13 (MMP-13) and interleukin-1β (IL-1β) from synovial fluid. Systemic oxidative stress, including lipid peroxidation biomarkers, malondialdehyde (MDA), and nitric oxide (NO), was evaluated in serum. Results: The arthroscopic approach induced osteoarthritic changes, with severity varying across the cohort. Histopathology revealed vertical matrix fissures and disruption of the normal columnar chondrocyte organization, yielding a median comprehensive Pritzker-OARSI score of 6 (range 6–10), with horizontal degradation restricted to stage 2. Synovial fluid analysis demonstrated measurable concentrations of MMP-13 (188.77 ± 93.87 ng/mL) and IL-1β (174.93 ± 95.51 pg/mL). Furthermore, serum oxidative stress parameters at the 12-week endpoint included lipid peroxidation (MDA: 1.01 ± 0.03 nmol/mL) and NO levels (82.72 ± 0.32 µmol/L), presented descriptively in the absence of a comparator group. Conclusions: This study establishes the first multifaceted pathological baseline of a minimally invasive arthroscopic ACLT rabbit model before therapeutic intervention. The arthroscopic ACLT model produced structural cartilage degeneration alongside measurable intra-articular catabolic and systemic oxidative stress changes, establishing a baseline phenotype and a starting point for future therapeutic studies. 2026-09-08 Medicina, Vol. 62, Pages 1725: Arthroscopic Anterior Cruciate Ligament Transection for Osteoarthritis Induction in Rabbits: A Pilot Feasibility and Characterization Study

Medicina doi: 10.3390/medicina62091725

Authors: Alina Otilia Adam Horea Rares Ciprian Benea Luciana-Mădălina Gherman Daniel Oltean-Dan Dragoș Apostu Dan Gheban Adrian Bogdan Tigu Andrei Ivancuta Alexandru Cristian Sabo Andrada Uhl Maria Crișan

Background and Objectives: Traditional open anterior cruciate ligament transection (ACLT) surgical models performed through arthrotomy may introduce capsular trauma and postoperative inflammatory responses that can interfere with the interpretation of post-traumatic osteoarthritis (OA). This study aimed to evaluate the feasibility of a minimally invasive, arthroscopic ACLT rabbit model performed entirely under arthroscopic visualization, without arthrotomy, using a 2.4-mm arthroscope and 2.5-mm shaver, and to provide preliminary structural, histological, synovial, and systemic biochemical characterization of the model for future therapeutic testing. Materials and Methods: Bilateral arthroscopic ACLT was performed in three skeletally mature New Zealand rabbits, followed by a supervised 12-week exercise protocol. Joint degeneration was evaluated macroscopically and histopathologically using the standardized Pritzker-Osteoarthritis Research Society International (OARSI) grading system. Collagen matrix remodeling was assessed via Picrosirius Red staining. Local intra-articular catabolism was quantified via Enzyme-Linked Immunosorbent Assay (ELISA) for matrix metallopeptidase 13 (MMP-13) and interleukin-1β (IL-1β) from synovial fluid. Systemic oxidative stress, including lipid peroxidation biomarkers, malondialdehyde (MDA), and nitric oxide (NO), was evaluated in serum. Results: The arthroscopic approach induced osteoarthritic changes, with severity varying across the cohort. Histopathology revealed vertical matrix fissures and disruption of the normal columnar chondrocyte organization, yielding a median comprehensive Pritzker-OARSI score of 6 (range 6–10), with horizontal degradation restricted to stage 2. Synovial fluid analysis demonstrated measurable concentrations of MMP-13 (188.77 ± 93.87 ng/mL) and IL-1β (174.93 ± 95.51 pg/mL). Furthermore, serum oxidative stress parameters at the 12-week endpoint included lipid peroxidation (MDA: 1.01 ± 0.03 nmol/mL) and NO levels (82.72 ± 0.32 µmol/L), presented descriptively in the absence of a comparator group. Conclusions: This study establishes the first multifaceted pathological baseline of a minimally invasive arthroscopic ACLT rabbit model before therapeutic intervention. The arthroscopic ACLT model produced structural cartilage degeneration alongside measurable intra-articular catabolic and systemic oxidative stress changes, establishing a baseline phenotype and a starting point for future therapeutic studies.

]]> Arthroscopic Anterior Cruciate Ligament Transection for Osteoarthritis Induction in Rabbits: A Pilot Feasibility and Characterization Study Alina Otilia Adam Horea Rares Ciprian Benea Luciana-Mădălina Gherman Daniel Oltean-Dan Dragoș Apostu Dan Gheban Adrian Bogdan Tigu Andrei Ivancuta Alexandru Cristian Sabo Andrada Uhl Maria Crișan doi: 10.3390/medicina62091725 Medicina 2026-09-08 Medicina 2026-09-08 62 9 Article 1725 10.3390/medicina62091725 https://www.mdpi.com/1648-9144/62/9/1725 Medicina, Vol. 62, Pages 1724: When Hemolysis Misleads: Implications for the Clinical Interpretation of Enzyme Activities in Pediatric Samples https://www.mdpi.com/1648-9144/62/9/1724 Background and Objectives: Hemolysis is one of the most frequent preanalytical interferences in clinical laboratory practice. This laboratory-based experimental study evaluated the effect of different degrees of hemolysis on plasma enzyme activities in pediatric blood samples. Materials and Methods: Twenty-six venous blood samples collected in lithium-heparin tubes were gently homogenized and divided into four equal whole-blood aliquots. One aliquot served as the untreated reference, while the remaining three aliquots were subjected to two, four, or eight aspiration–reinjection cycles through an 18-gauge needle to induce increasing degrees of erythrocyte lysis. All four aliquots were subsequently centrifuged under identical conditions and classified according to the semiquantitative hemolysis component of the analyzer-generated LIH index as non-hemolyzed, H1, H2, H3, H4, or H5. Activities of alpha-amylase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, creatine kinase, and lactate dehydrogenase, as well as potassium concentration, were measured using the same DxC 700 AU automated clinical chemistry analyzer. Statistical analysis included 26 samples and was performed using the Wilcoxon signed-rank test. Results: Hemolysis caused a progressive increase in lactate dehydrogenase, aspartate aminotransferase, creatine kinase, alanine aminotransferase, and potassium, with the strongest effects observed for lactate dehydrogenase and aspartate aminotransferase. Alpha-amylase and alkaline phosphatase showed a decreasing trend, while gamma-glutamyl transferase showed variable behavior across hemolysis groups. Conclusions: The findings confirm that even low degrees of hemolysis can substantially alter selected biochemical results, especially lactate dehydrogenase, aspartate aminotransferase, and creatine kinase. Laboratory reports from hemolyzed pediatric samples should therefore be interpreted with caution to reduce the risk of clinically misleading results. 2026-09-07 Medicina, Vol. 62, Pages 1724: When Hemolysis Misleads: Implications for the Clinical Interpretation of Enzyme Activities in Pediatric Samples

Medicina doi: 10.3390/medicina62091724

Authors: Dejan Dobrijević Kristian Pastor

Background and Objectives: Hemolysis is one of the most frequent preanalytical interferences in clinical laboratory practice. This laboratory-based experimental study evaluated the effect of different degrees of hemolysis on plasma enzyme activities in pediatric blood samples. Materials and Methods: Twenty-six venous blood samples collected in lithium-heparin tubes were gently homogenized and divided into four equal whole-blood aliquots. One aliquot served as the untreated reference, while the remaining three aliquots were subjected to two, four, or eight aspiration–reinjection cycles through an 18-gauge needle to induce increasing degrees of erythrocyte lysis. All four aliquots were subsequently centrifuged under identical conditions and classified according to the semiquantitative hemolysis component of the analyzer-generated LIH index as non-hemolyzed, H1, H2, H3, H4, or H5. Activities of alpha-amylase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, creatine kinase, and lactate dehydrogenase, as well as potassium concentration, were measured using the same DxC 700 AU automated clinical chemistry analyzer. Statistical analysis included 26 samples and was performed using the Wilcoxon signed-rank test. Results: Hemolysis caused a progressive increase in lactate dehydrogenase, aspartate aminotransferase, creatine kinase, alanine aminotransferase, and potassium, with the strongest effects observed for lactate dehydrogenase and aspartate aminotransferase. Alpha-amylase and alkaline phosphatase showed a decreasing trend, while gamma-glutamyl transferase showed variable behavior across hemolysis groups. Conclusions: The findings confirm that even low degrees of hemolysis can substantially alter selected biochemical results, especially lactate dehydrogenase, aspartate aminotransferase, and creatine kinase. Laboratory reports from hemolyzed pediatric samples should therefore be interpreted with caution to reduce the risk of clinically misleading results.

]]> When Hemolysis Misleads: Implications for the Clinical Interpretation of Enzyme Activities in Pediatric Samples Dejan Dobrijević Kristian Pastor doi: 10.3390/medicina62091724 Medicina 2026-09-07 Medicina 2026-09-07 62 9 Article 1724 10.3390/medicina62091724 https://www.mdpi.com/1648-9144/62/9/1724 Medicina, Vol. 62, Pages 1723: Custom-Made 3D-Printed Implants for Paprosky Type 3A and 3B Acetabular Defects: Early Surgical and Functional Outcomes from a Multicentre Study https://www.mdpi.com/1648-9144/62/9/1723 Background and Objectives: Reconstruction of extensive acetabular bone defects in revision total hip arthroplasty (THA) remains technically demanding and is associated with a high risk of complications. Custom-made three-dimensional (3D)-printed implants have emerged as a patient-specific option for managing severe bone loss, particularly in Paprosky type 3A and 3B defects. The aim of this multicentre study was to evaluate the early clinical, radiographic, and surgical outcomes following single-stage reconstruction using custom-made 3D-printed acetabular implants. Materials and Methods: This retrospective multicentre study included 62 patients treated between 2021 and 2024 at four orthopaedic departments. All patients had Paprosky type 3A (n = 34) or 3B (n = 28) acetabular defects and underwent reconstruction with custom-made 3D-printed implants. A minimum clinical follow-up of 6 months was required for inclusion. Preoperative computed tomography was used for implant design and surgical planning. Clinical assessment included pain using the Visual Analogue Scale, functional evaluation using the Harris Hip Score and Karnofsky Performance Scale, mobility, range of motion, and use of orthopaedic aids. Radiographic evaluation included plain radiographs and computed tomography. Standardised functional and CT outcome assessments were performed during the first 6 months after surgery, whereas the mean overall follow-up represented subsequent clinical surveillance. Mean follow-up was 27 months. Results: All patients had undergone multiple previous surgical procedures before implantation of the custom-made prosthesis. The interval between primary arthroplasty and implantation of the custom-made implant ranged from 9 to 31 years. During follow-up, improvements in pain, mobility, and functional performance were observed across the entire cohort. The reported functional and CT outcomes refer to the standardised 6-month assessment period. Radiographic evaluation demonstrated satisfactory implant positioning and restoration of hip biomechanics. Progressive radiographic findings suggestive of implant integration were observed during follow-up. The most common complications were postoperative wound-healing disorders and prosthetic dislocation, particularly in patients with more extensive bone defects. Conclusions: Single-stage reconstruction using custom-made 3D-printed implants appears to be a feasible treatment option for patients with Paprosky type 3A and 3B defects, resulting in improvements in pain, mobility, and functional performance. Radiographic assessment suggested stable implant fixation and progressive implant integration during early follow-up. However, postoperative wound-healing disorders, infection, and prosthetic dislocation remain clinically relevant complications, particularly in patients with more extensive bone defects. Further studies with longer follow-up are required to determine long-term implant durability, implant survivorship, and functional outcomes. 2026-09-07 Medicina, Vol. 62, Pages 1723: Custom-Made 3D-Printed Implants for Paprosky Type 3A and 3B Acetabular Defects: Early Surgical and Functional Outcomes from a Multicentre Study

Medicina doi: 10.3390/medicina62091723

Authors: Grzegorz Guzik Piotr Szremski Daniel Pyrka Paweł Łęgosz

Background and Objectives: Reconstruction of extensive acetabular bone defects in revision total hip arthroplasty (THA) remains technically demanding and is associated with a high risk of complications. Custom-made three-dimensional (3D)-printed implants have emerged as a patient-specific option for managing severe bone loss, particularly in Paprosky type 3A and 3B defects. The aim of this multicentre study was to evaluate the early clinical, radiographic, and surgical outcomes following single-stage reconstruction using custom-made 3D-printed acetabular implants. Materials and Methods: This retrospective multicentre study included 62 patients treated between 2021 and 2024 at four orthopaedic departments. All patients had Paprosky type 3A (n = 34) or 3B (n = 28) acetabular defects and underwent reconstruction with custom-made 3D-printed implants. A minimum clinical follow-up of 6 months was required for inclusion. Preoperative computed tomography was used for implant design and surgical planning. Clinical assessment included pain using the Visual Analogue Scale, functional evaluation using the Harris Hip Score and Karnofsky Performance Scale, mobility, range of motion, and use of orthopaedic aids. Radiographic evaluation included plain radiographs and computed tomography. Standardised functional and CT outcome assessments were performed during the first 6 months after surgery, whereas the mean overall follow-up represented subsequent clinical surveillance. Mean follow-up was 27 months. Results: All patients had undergone multiple previous surgical procedures before implantation of the custom-made prosthesis. The interval between primary arthroplasty and implantation of the custom-made implant ranged from 9 to 31 years. During follow-up, improvements in pain, mobility, and functional performance were observed across the entire cohort. The reported functional and CT outcomes refer to the standardised 6-month assessment period. Radiographic evaluation demonstrated satisfactory implant positioning and restoration of hip biomechanics. Progressive radiographic findings suggestive of implant integration were observed during follow-up. The most common complications were postoperative wound-healing disorders and prosthetic dislocation, particularly in patients with more extensive bone defects. Conclusions: Single-stage reconstruction using custom-made 3D-printed implants appears to be a feasible treatment option for patients with Paprosky type 3A and 3B defects, resulting in improvements in pain, mobility, and functional performance. Radiographic assessment suggested stable implant fixation and progressive implant integration during early follow-up. However, postoperative wound-healing disorders, infection, and prosthetic dislocation remain clinically relevant complications, particularly in patients with more extensive bone defects. Further studies with longer follow-up are required to determine long-term implant durability, implant survivorship, and functional outcomes.

]]> Custom-Made 3D-Printed Implants for Paprosky Type 3A and 3B Acetabular Defects: Early Surgical and Functional Outcomes from a Multicentre Study Grzegorz Guzik Piotr Szremski Daniel Pyrka Paweł Łęgosz doi: 10.3390/medicina62091723 Medicina 2026-09-07 Medicina 2026-09-07 62 9 Article 1723 10.3390/medicina62091723 https://www.mdpi.com/1648-9144/62/9/1723 Medicina, Vol. 62, Pages 1722: Serum Autophagy-Related Protein 5 and Clinically Defined Cognitive Status in Older Adults: A Plate-Stratified Cross-Sectional Study Across: Normal Cognition, Mild Cognitive Impairment, and Alzheimer’s Disease https://www.mdpi.com/1648-9144/62/9/1722 Background and Objectives: Impaired autophagy has been implicated in neurodegeneration, but circulating autophagy-related proteins have shown inconsistent associations with cognitive impairment. We compared serum autophagy-related protein 5 (ATG5) among older adults with normal cognition, mild cognitive impairment (MCI), and clinically diagnosed Alzheimer’s disease (AD), and examined its relationship with global cognitive performance. Materials and Methods: This single-centre cross-sectional study enrolled 164 older adults (55 with normal cognition, 55 with MCI, and 54 with clinically diagnosed AD). Cognitive status was determined through integrated clinical assessment rather than a single test cut-off. An enzyme-linked immunosorbent assay was employed to quantify serum ATG5, yielding quantifiable values for 156 participants, right-censored observations above the highest calibrator for six, and unmeasurable results for two. Since the two 96-well plates, drawn from one ELISA kit lot and processed on the same day, exhibited a substantial discrepancy in measurement scale across runs, they were analysed as distinct strata, with the principal group contrast estimated via a right-censored Tobit regression of log-transformed ATG5 within each plate, controlling for cognitive group, age and sex; a pooled plate-adjusted model also provided support. Supportive analyses used within-plate z-standardised ATG5. Associations with clinical variables were assessed using age- and sex-adjusted partial Spearman correlations with false discovery rate correction. Results: Across both analytical strata (plate 1 omnibus p = 0.293; plate 2 p = 0.264) and within the supportive pooled model (p = 0.143; AD vs. normal geometric mean ratio 0.89, 95% CI 0.73–1.09), serum ATG5 concentrations did not differ significantly between cognitive groups. Concentrations on plate 2 were 47% lower (GMR 0.53, 95% CI 0.45–0.62), a gap exceeding the inter-assay imprecision declared by the manufacturer and unexplained by the calibrator values from plate 2; since relative dispersion matched across both plates (likelihood ratio p = 0.730), the pattern suggests a multiplicative scale shift of unknown origin. Serum ATG5 levels were weakly associated with global cognitive performance assessed via the S-MMSE (partial ρ = 0.283, p < 0.001, FDR p = 0.010), an association that persisted after adjusting for education, albumin and folate and retained a similar magnitude within a linear model (β = 0.044, p = 0.014). Incorporating ATG5 into a model that included age, sex and education failed to enhance discrimination (ΔAUC +0.012 and +0.000). Conclusions: Serum ATG5 did not discriminate normal cognition, MCI, and clinically diagnosed AD. A weak rank-based association with S-MMSE was observed, but the effect was small. These findings do not support serum ATG5 as a diagnostic discriminator for clinically defined cognitive status. 2026-09-07 Medicina, Vol. 62, Pages 1722: Serum Autophagy-Related Protein 5 and Clinically Defined Cognitive Status in Older Adults: A Plate-Stratified Cross-Sectional Study Across: Normal Cognition, Mild Cognitive Impairment, and Alzheimer’s Disease

Medicina doi: 10.3390/medicina62091722

Authors: Kübra Erdoğan Cemile Biçer Rıdvan Erten Kübra Kaya Serap Boz Hatice Turgut Şahin Cemile Peker Arzu Nevin Dağdemir Büşragül Yılmaz Aslıhan Yıldırım Rana Tuna Doğrul Hande Selvi Öztorun Güneş Eken Kamile Sılay

Background and Objectives: Impaired autophagy has been implicated in neurodegeneration, but circulating autophagy-related proteins have shown inconsistent associations with cognitive impairment. We compared serum autophagy-related protein 5 (ATG5) among older adults with normal cognition, mild cognitive impairment (MCI), and clinically diagnosed Alzheimer’s disease (AD), and examined its relationship with global cognitive performance. Materials and Methods: This single-centre cross-sectional study enrolled 164 older adults (55 with normal cognition, 55 with MCI, and 54 with clinically diagnosed AD). Cognitive status was determined through integrated clinical assessment rather than a single test cut-off. An enzyme-linked immunosorbent assay was employed to quantify serum ATG5, yielding quantifiable values for 156 participants, right-censored observations above the highest calibrator for six, and unmeasurable results for two. Since the two 96-well plates, drawn from one ELISA kit lot and processed on the same day, exhibited a substantial discrepancy in measurement scale across runs, they were analysed as distinct strata, with the principal group contrast estimated via a right-censored Tobit regression of log-transformed ATG5 within each plate, controlling for cognitive group, age and sex; a pooled plate-adjusted model also provided support. Supportive analyses used within-plate z-standardised ATG5. Associations with clinical variables were assessed using age- and sex-adjusted partial Spearman correlations with false discovery rate correction. Results: Across both analytical strata (plate 1 omnibus p = 0.293; plate 2 p = 0.264) and within the supportive pooled model (p = 0.143; AD vs. normal geometric mean ratio 0.89, 95% CI 0.73–1.09), serum ATG5 concentrations did not differ significantly between cognitive groups. Concentrations on plate 2 were 47% lower (GMR 0.53, 95% CI 0.45–0.62), a gap exceeding the inter-assay imprecision declared by the manufacturer and unexplained by the calibrator values from plate 2; since relative dispersion matched across both plates (likelihood ratio p = 0.730), the pattern suggests a multiplicative scale shift of unknown origin. Serum ATG5 levels were weakly associated with global cognitive performance assessed via the S-MMSE (partial ρ = 0.283, p < 0.001, FDR p = 0.010), an association that persisted after adjusting for education, albumin and folate and retained a similar magnitude within a linear model (β = 0.044, p = 0.014). Incorporating ATG5 into a model that included age, sex and education failed to enhance discrimination (ΔAUC +0.012 and +0.000). Conclusions: Serum ATG5 did not discriminate normal cognition, MCI, and clinically diagnosed AD. A weak rank-based association with S-MMSE was observed, but the effect was small. These findings do not support serum ATG5 as a diagnostic discriminator for clinically defined cognitive status.

]]> Serum Autophagy-Related Protein 5 and Clinically Defined Cognitive Status in Older Adults: A Plate-Stratified Cross-Sectional Study Across: Normal Cognition, Mild Cognitive Impairment, and Alzheimer’s Disease Kübra Erdoğan Cemile Biçer Rıdvan Erten Kübra Kaya Serap Boz Hatice Turgut Şahin Cemile Peker Arzu Nevin Dağdemir Büşragül Yılmaz Aslıhan Yıldırım Rana Tuna Doğrul Hande Selvi Öztorun Güneş Eken Kamile Sılay doi: 10.3390/medicina62091722 Medicina 2026-09-07 Medicina 2026-09-07 62 9 Article 1722 10.3390/medicina62091722 https://www.mdpi.com/1648-9144/62/9/1722 Medicina, Vol. 62, Pages 1721: Association of SGLT2 Inhibitor Use with Glycosuria, Pyuria, Urinary Symptoms, and Significant Urine Culture Positivity in Adults with Type 2 Diabetes: A Prospective Cross-Sectional Study https://www.mdpi.com/1648-9144/62/9/1721 Background and Objectives: Sodium–glucose cotransporter 2 (SGLT2) inhibitors increase urinary glucose excretion, but the relationship between glycosuria and findings supporting urinary tract infection (UTI) remains unclear. We evaluated associations of SGLT2 inhibitor use with glycosuria, pyuria, UTI-compatible symptoms, and significant urine culture positivity in adults with type 2 diabetes. Materials and Methods: This prospective cross-sectional study included 251 adults who reported using every agent in their current oral antidiabetic regimen for at least three months. Blood tests, urinalysis, and midstream urine culture were obtained at a single study visit. SGLT2 inhibitor users and nonusers were compared; contaminated cultures were excluded from culture-based analyses. Multivariable logistic regression examined factors associated with glycosuria and pyuria. Results: Overall, 108 participants (43.0%) used an SGLT2 inhibitor (dapagliflozin, n = 51; empagliflozin, n = 57). Glycosuria was more frequent among users than nonusers (69.4% vs. 39.9%; OR = 3.43; 95% CI, 2.02–5.82; p < 0.001). In multivariable analysis, SGLT2 inhibitor use (adjusted OR = 3.14; 95% CI, 1.75–5.63) and each 1% increase in HbA1c (adjusted OR = 1.56; 95% CI, 1.27–1.92) were independently associated with glycosuria. Pyuria and UTI-compatible symptoms did not differ between groups. Among 217 evaluable cultures, significant culture positivity was numerically higher among users, but the estimate was imprecise (9.5% vs. 4.1%; OR = 2.45; 95% CI, 0.79–7.57; p = 0.110). Symptomatic culture positivity was similar (4.2% vs. 4.1%; p = 1.000). Conclusions: SGLT2 inhibitor use and higher HbA1c levels were independently associated with glycosuria. The small number of culture-positive events precludes firm conclusions about culture-based outcomes; these analyses are exploratory and do not demonstrate the presence or absence of an association. Glycosuria alone should not be interpreted as an indicator of UTI. 2026-09-07 Medicina, Vol. 62, Pages 1721: Association of SGLT2 Inhibitor Use with Glycosuria, Pyuria, Urinary Symptoms, and Significant Urine Culture Positivity in Adults with Type 2 Diabetes: A Prospective Cross-Sectional Study

Medicina doi: 10.3390/medicina62091721

Authors: Türkan Tüzün Ayten Eraydın

Background and Objectives: Sodium–glucose cotransporter 2 (SGLT2) inhibitors increase urinary glucose excretion, but the relationship between glycosuria and findings supporting urinary tract infection (UTI) remains unclear. We evaluated associations of SGLT2 inhibitor use with glycosuria, pyuria, UTI-compatible symptoms, and significant urine culture positivity in adults with type 2 diabetes. Materials and Methods: This prospective cross-sectional study included 251 adults who reported using every agent in their current oral antidiabetic regimen for at least three months. Blood tests, urinalysis, and midstream urine culture were obtained at a single study visit. SGLT2 inhibitor users and nonusers were compared; contaminated cultures were excluded from culture-based analyses. Multivariable logistic regression examined factors associated with glycosuria and pyuria. Results: Overall, 108 participants (43.0%) used an SGLT2 inhibitor (dapagliflozin, n = 51; empagliflozin, n = 57). Glycosuria was more frequent among users than nonusers (69.4% vs. 39.9%; OR = 3.43; 95% CI, 2.02–5.82; p < 0.001). In multivariable analysis, SGLT2 inhibitor use (adjusted OR = 3.14; 95% CI, 1.75–5.63) and each 1% increase in HbA1c (adjusted OR = 1.56; 95% CI, 1.27–1.92) were independently associated with glycosuria. Pyuria and UTI-compatible symptoms did not differ between groups. Among 217 evaluable cultures, significant culture positivity was numerically higher among users, but the estimate was imprecise (9.5% vs. 4.1%; OR = 2.45; 95% CI, 0.79–7.57; p = 0.110). Symptomatic culture positivity was similar (4.2% vs. 4.1%; p = 1.000). Conclusions: SGLT2 inhibitor use and higher HbA1c levels were independently associated with glycosuria. The small number of culture-positive events precludes firm conclusions about culture-based outcomes; these analyses are exploratory and do not demonstrate the presence or absence of an association. Glycosuria alone should not be interpreted as an indicator of UTI.

]]> Association of SGLT2 Inhibitor Use with Glycosuria, Pyuria, Urinary Symptoms, and Significant Urine Culture Positivity in Adults with Type 2 Diabetes: A Prospective Cross-Sectional Study Türkan Tüzün Ayten Eraydın doi: 10.3390/medicina62091721 Medicina 2026-09-07 Medicina 2026-09-07 62 9 Article 1721 10.3390/medicina62091721 https://www.mdpi.com/1648-9144/62/9/1721 Medicina, Vol. 62, Pages 1720: Preoperative Posterior Paraspinal Fatty Infiltration and an Exploratory Axial Muscle Imaging Phenotype in Surgically Treated Metastatic Epidural Spinal Cord Compression: A Retrospective Cohort Study https://www.mdpi.com/1648-9144/62/9/1720 Background and Objectives: Prognostic assessment in metastatic epidural spinal cord compression (MESCC) requires estimation of survival, systemic condition, and the likelihood of early functional improvement. We evaluated whether posterior paraspinal fatty infiltration and an exploratory routine-imaging axial muscle phenotype derived from preoperative L3 CT/MRI were associated with overall survival and early neurological improvement after surgery for MESCC. Materials and Methods: Consecutive adults who underwent surgery for MESCC (Bilsky grade 1C–3) between June 2020 and November 2025 were retrospectively analyzed. Psoas quantity was measured on preoperative L3 computed tomography using the psoas-to-vertebral-body ratio (PVR) and psoas muscle index. Posterior paraspinal muscle quality was graded on axial T2-weighted L3 magnetic resonance imaging using a Goutallier-style scale in the multifidus/erector spinae compartment. The primary exposure was high-grade posterior paraspinal fatty infiltration, defined as patient-level maximum Goutallier grade 3–4. An exploratory secondary phenotype combined lower PVR by sex-specific cohort median with Goutallier grade 3–4. Results: Among 133 eligible patients, PVR measurements were available in 119, Goutallier grading in 112, and complete combined phenotyping in 109. Median survival was 383 days for Goutallier 0–2 and 144.5 days for Goutallier 3–4. In the primary clinical/Katagiri-adjusted Cox model, Goutallier 3–4 was associated with worse overall survival (hazard ratio [HR] 1.80, 95% confidence interval [CI] 1.06–3.07; p = 0.029). The exploratory both-abnormalities subgroup comprised 21 patients, with median survival of 73 days, and among patients with a preoperative Frankel deficit, early Frankel improvement occurred in 2/15 (13.3%); the adjusted overall-survival HR was 2.64 (95% CI 1.15–6.03; p = 0.021), whereas binary-outcome estimates were imprecise. Conclusions: High-grade posterior paraspinal fatty infiltration was associated with inferior survival and lower early neurological improvement after surgery for MESCC. The combined phenotype identified a small high-risk subgroup but should be regarded as hypothesis-generating. These routine-imaging markers require external validation and should not be used as stand-alone surgical selection criteria. 2026-09-07 Medicina, Vol. 62, Pages 1720: Preoperative Posterior Paraspinal Fatty Infiltration and an Exploratory Axial Muscle Imaging Phenotype in Surgically Treated Metastatic Epidural Spinal Cord Compression: A Retrospective Cohort Study

Medicina doi: 10.3390/medicina62091720

Authors: Aydin Talat Baydar Muhammed Bayindir Bilal Yekeler Mairambek Murtazaev Baran Taskala

Background and Objectives: Prognostic assessment in metastatic epidural spinal cord compression (MESCC) requires estimation of survival, systemic condition, and the likelihood of early functional improvement. We evaluated whether posterior paraspinal fatty infiltration and an exploratory routine-imaging axial muscle phenotype derived from preoperative L3 CT/MRI were associated with overall survival and early neurological improvement after surgery for MESCC. Materials and Methods: Consecutive adults who underwent surgery for MESCC (Bilsky grade 1C–3) between June 2020 and November 2025 were retrospectively analyzed. Psoas quantity was measured on preoperative L3 computed tomography using the psoas-to-vertebral-body ratio (PVR) and psoas muscle index. Posterior paraspinal muscle quality was graded on axial T2-weighted L3 magnetic resonance imaging using a Goutallier-style scale in the multifidus/erector spinae compartment. The primary exposure was high-grade posterior paraspinal fatty infiltration, defined as patient-level maximum Goutallier grade 3–4. An exploratory secondary phenotype combined lower PVR by sex-specific cohort median with Goutallier grade 3–4. Results: Among 133 eligible patients, PVR measurements were available in 119, Goutallier grading in 112, and complete combined phenotyping in 109. Median survival was 383 days for Goutallier 0–2 and 144.5 days for Goutallier 3–4. In the primary clinical/Katagiri-adjusted Cox model, Goutallier 3–4 was associated with worse overall survival (hazard ratio [HR] 1.80, 95% confidence interval [CI] 1.06–3.07; p = 0.029). The exploratory both-abnormalities subgroup comprised 21 patients, with median survival of 73 days, and among patients with a preoperative Frankel deficit, early Frankel improvement occurred in 2/15 (13.3%); the adjusted overall-survival HR was 2.64 (95% CI 1.15–6.03; p = 0.021), whereas binary-outcome estimates were imprecise. Conclusions: High-grade posterior paraspinal fatty infiltration was associated with inferior survival and lower early neurological improvement after surgery for MESCC. The combined phenotype identified a small high-risk subgroup but should be regarded as hypothesis-generating. These routine-imaging markers require external validation and should not be used as stand-alone surgical selection criteria.

]]> Preoperative Posterior Paraspinal Fatty Infiltration and an Exploratory Axial Muscle Imaging Phenotype in Surgically Treated Metastatic Epidural Spinal Cord Compression: A Retrospective Cohort Study Aydin Talat Baydar Muhammed Bayindir Bilal Yekeler Mairambek Murtazaev Baran Taskala doi: 10.3390/medicina62091720 Medicina 2026-09-07 Medicina 2026-09-07 62 9 Article 1720 10.3390/medicina62091720 https://www.mdpi.com/1648-9144/62/9/1720 Medicina, Vol. 62, Pages 1719: Guilt Facets and Eating Disorder Psychopathology: An Exploratory Cross-Sectional Study Using the Moral Orientation Guilt Scale https://www.mdpi.com/1648-9144/62/9/1719 Background and Objectives: Moral emotions are increasingly implicated in the maintenance of eating disorders (EDs), yet guilt is less differentiated than shame in the ED literature. Contemporary cognitive accounts distinguish deontological guilt linked to violating internalised moral norms from altruistic guilt linked to empathic concern or perceived harm to others. This study examined associations between guilt facets, ED diagnosis, and ED psychopathology in a clinical sample. Materials and Methods: One hundred and eleven adult outpatients (≥18 years) with DSM-5 ED diagnoses (anorexia nervosa, n = 32; bulimia nervosa, n = 24; binge-eating disorder, n = 55; 92 women) were consecutively recruited at first assessment at the Eating Disorders Centre of the University of Campania “Luigi Vanvitelli” (Naples, Italy) between January 2024 and December 2025 and completed the Italian versions of the Moral Orientation Guilt Scale (MOGS) and the Eating Disorder Inventory 2 (EDI-2). Between-diagnosis differences in guilt facets were tested using Kruskal–Wallis analyses. Spearman correlations examined relationships between MOGS facets and EDI-2 subscales. An exploratory regression tested whether MOGS Empathy was associated with EDI-2 Asceticism beyond sex. Results: Significant between-diagnosis differences emerged for Moral Norm Violation (p < 0.001), Moral Dirtiness (p = 0.020), Harm (p = 0.021), and both deontological (p = 0.001) and altruistic guilt composites (p = 0.041), with binge-eating disorder showing the highest mean levels. No between-diagnosis difference emerged for Empathy (p = 0.114). The prespecified MNV–Bulimia correlation was not confirmed (ρ = 0.12, unadjusted p = 0.199; Holm-adjusted p = 0.199). Empathy was associated with Asceticism (ρ = 0.28, unadjusted p = 0.003; Holm-adjusted p = 0.008), and altruistic guilt was associated with Interpersonal Distrust (ρ = 0.24, unadjusted p = 0.010; Holm-adjusted p = 0.020). Broader exploratory correlations did not survive false discovery rate correction. In a regression model including sex, Empathy was associated with Asceticism (B = 0.263, 95% CI 0.078–0.447; standardised β = 0.26; p = 0.006), explaining approximately 7% of the variance (R2 = 0.07). Conclusions: Distinct guilt facets show selective, small-to-moderate associations with ED-related psychological traits in an adult outpatient sample. These findings are hypothesis-generating and require replication in larger and longitudinal samples that include shame, trauma, self-criticism, weight stigma, illness duration, and gender identity measures. 2026-09-07 Medicina, Vol. 62, Pages 1719: Guilt Facets and Eating Disorder Psychopathology: An Exploratory Cross-Sectional Study Using the Moral Orientation Guilt Scale

Medicina doi: 10.3390/medicina62091719

Authors: Fabiola Raffone Eugenia Barone Danilo Atripaldi Eleonora Arsenio Flavia Martinelli Serena Cruccu Marco Carfagno Vassilis Martiadis Alessio Maria Monteleone

Background and Objectives: Moral emotions are increasingly implicated in the maintenance of eating disorders (EDs), yet guilt is less differentiated than shame in the ED literature. Contemporary cognitive accounts distinguish deontological guilt linked to violating internalised moral norms from altruistic guilt linked to empathic concern or perceived harm to others. This study examined associations between guilt facets, ED diagnosis, and ED psychopathology in a clinical sample. Materials and Methods: One hundred and eleven adult outpatients (≥18 years) with DSM-5 ED diagnoses (anorexia nervosa, n = 32; bulimia nervosa, n = 24; binge-eating disorder, n = 55; 92 women) were consecutively recruited at first assessment at the Eating Disorders Centre of the University of Campania “Luigi Vanvitelli” (Naples, Italy) between January 2024 and December 2025 and completed the Italian versions of the Moral Orientation Guilt Scale (MOGS) and the Eating Disorder Inventory 2 (EDI-2). Between-diagnosis differences in guilt facets were tested using Kruskal–Wallis analyses. Spearman correlations examined relationships between MOGS facets and EDI-2 subscales. An exploratory regression tested whether MOGS Empathy was associated with EDI-2 Asceticism beyond sex. Results: Significant between-diagnosis differences emerged for Moral Norm Violation (p < 0.001), Moral Dirtiness (p = 0.020), Harm (p = 0.021), and both deontological (p = 0.001) and altruistic guilt composites (p = 0.041), with binge-eating disorder showing the highest mean levels. No between-diagnosis difference emerged for Empathy (p = 0.114). The prespecified MNV–Bulimia correlation was not confirmed (ρ = 0.12, unadjusted p = 0.199; Holm-adjusted p = 0.199). Empathy was associated with Asceticism (ρ = 0.28, unadjusted p = 0.003; Holm-adjusted p = 0.008), and altruistic guilt was associated with Interpersonal Distrust (ρ = 0.24, unadjusted p = 0.010; Holm-adjusted p = 0.020). Broader exploratory correlations did not survive false discovery rate correction. In a regression model including sex, Empathy was associated with Asceticism (B = 0.263, 95% CI 0.078–0.447; standardised β = 0.26; p = 0.006), explaining approximately 7% of the variance (R2 = 0.07). Conclusions: Distinct guilt facets show selective, small-to-moderate associations with ED-related psychological traits in an adult outpatient sample. These findings are hypothesis-generating and require replication in larger and longitudinal samples that include shame, trauma, self-criticism, weight stigma, illness duration, and gender identity measures.

]]> Guilt Facets and Eating Disorder Psychopathology: An Exploratory Cross-Sectional Study Using the Moral Orientation Guilt Scale Fabiola Raffone Eugenia Barone Danilo Atripaldi Eleonora Arsenio Flavia Martinelli Serena Cruccu Marco Carfagno Vassilis Martiadis Alessio Maria Monteleone doi: 10.3390/medicina62091719 Medicina 2026-09-07 Medicina 2026-09-07 62 9 Article 1719 10.3390/medicina62091719 https://www.mdpi.com/1648-9144/62/9/1719 Medicina, Vol. 62, Pages 1718: The Effect of Intravenous Dextrose Administration on Postoperative Nausea and Vomiting: Systematic Review and Meta-Analysis with Trial Sequential Analysis https://www.mdpi.com/1648-9144/62/9/1718 Background and Objectives: Intravenous dextrose administration is a potential nonpharmacological adjunct for preventing postoperative nausea and vomiting (PONV); however, its efficacy and optimal timing remain unclear. This systematic review and meta-analysis, including trial sequential analysis (TSA), evaluated the antiemetic effects of perioperative dextrose administration. Materials and Methods: Electronic databases were searched for randomized controlled trials (RCTs) comparing dextrose-containing fluids with dextrose-free solutions under general anesthesia. The primary outcomes were the incidence of postoperative nausea (PON) and vomiting (POV) and PONV during the early (0–6 h) and late (6–48 h) periods, as well as the overall period (defined as any assessment for which the included study did not report a specific time point). The secondary outcome was the use of rescue antiemetics. Subgroup analyses were performed according to the timing of administration (preoperative, combined preoperative-and-intraoperative, intraoperative, or postoperative). Results: Fourteen RCTs (n = 1455), predominantly derived from laparoscopic surgery, were identified as eligible for the systematic review; of these, 13 RCTs (15 sub-studies, 1334 patients) contributed to the quantitative synthesis, while one trial (Firouzian et al.) was included in the qualitative review and risk-of-bias assessment only, as it reported continuous outcome data incompatible with the binary-outcome meta-analysis. Overall, dextrose infusion significantly reduced PON (RR = 0.73; 95% CI: 0.62–0.87), early PON (RR = 0.73; 95% CI: 0.60–0.88), PONV (RR = 0.65; 95% CI: 0.51–0.86), and early PONV (RR = 0.66; 95% CI: 0.51–0.85). Dextrose also significantly reduced the overall use of rescue antiemetics (RR = 0.57; 95% CI: 0.37–0.87). Formal tests for subgroup interaction by administration timing were significant only for rescue antiemetic use (p = 0.044); interaction tests for all PON, POV, and PONV outcomes were not statistically significant (all p > 0.4), indicating that the timing-based subgroup findings for these outcomes should be considered exploratory. Conclusions: Perioperative intravenous dextrose is an effective nonpharmacological adjunct for PONV prevention, with efficacy that may vary according to the timing of administration; however, this timing-based pattern was formally supported by a significant subgroup interaction test only for the use of rescue antiemetics, not for PON, POV, or PONV, and should therefore be regarded as exploratory. In this analysis, postoperative administration was associated with reduced PON and PONV, and preoperative, combined preoperative-and-intraoperative, and postoperative administration were each associated with reduced use of rescue antiemetics, whereas intraoperative administration alone showed no significant benefit. 2026-09-07 Medicina, Vol. 62, Pages 1718: The Effect of Intravenous Dextrose Administration on Postoperative Nausea and Vomiting: Systematic Review and Meta-Analysis with Trial Sequential Analysis

Medicina doi: 10.3390/medicina62091718

Authors: Jae Hyuk Choi Pyung Gul Park Geun Joo Choi Hyun Kang

Background and Objectives: Intravenous dextrose administration is a potential nonpharmacological adjunct for preventing postoperative nausea and vomiting (PONV); however, its efficacy and optimal timing remain unclear. This systematic review and meta-analysis, including trial sequential analysis (TSA), evaluated the antiemetic effects of perioperative dextrose administration. Materials and Methods: Electronic databases were searched for randomized controlled trials (RCTs) comparing dextrose-containing fluids with dextrose-free solutions under general anesthesia. The primary outcomes were the incidence of postoperative nausea (PON) and vomiting (POV) and PONV during the early (0–6 h) and late (6–48 h) periods, as well as the overall period (defined as any assessment for which the included study did not report a specific time point). The secondary outcome was the use of rescue antiemetics. Subgroup analyses were performed according to the timing of administration (preoperative, combined preoperative-and-intraoperative, intraoperative, or postoperative). Results: Fourteen RCTs (n = 1455), predominantly derived from laparoscopic surgery, were identified as eligible for the systematic review; of these, 13 RCTs (15 sub-studies, 1334 patients) contributed to the quantitative synthesis, while one trial (Firouzian et al.) was included in the qualitative review and risk-of-bias assessment only, as it reported continuous outcome data incompatible with the binary-outcome meta-analysis. Overall, dextrose infusion significantly reduced PON (RR = 0.73; 95% CI: 0.62–0.87), early PON (RR = 0.73; 95% CI: 0.60–0.88), PONV (RR = 0.65; 95% CI: 0.51–0.86), and early PONV (RR = 0.66; 95% CI: 0.51–0.85). Dextrose also significantly reduced the overall use of rescue antiemetics (RR = 0.57; 95% CI: 0.37–0.87). Formal tests for subgroup interaction by administration timing were significant only for rescue antiemetic use (p = 0.044); interaction tests for all PON, POV, and PONV outcomes were not statistically significant (all p > 0.4), indicating that the timing-based subgroup findings for these outcomes should be considered exploratory. Conclusions: Perioperative intravenous dextrose is an effective nonpharmacological adjunct for PONV prevention, with efficacy that may vary according to the timing of administration; however, this timing-based pattern was formally supported by a significant subgroup interaction test only for the use of rescue antiemetics, not for PON, POV, or PONV, and should therefore be regarded as exploratory. In this analysis, postoperative administration was associated with reduced PON and PONV, and preoperative, combined preoperative-and-intraoperative, and postoperative administration were each associated with reduced use of rescue antiemetics, whereas intraoperative administration alone showed no significant benefit.

]]> The Effect of Intravenous Dextrose Administration on Postoperative Nausea and Vomiting: Systematic Review and Meta-Analysis with Trial Sequential Analysis Jae Hyuk Choi Pyung Gul Park Geun Joo Choi Hyun Kang doi: 10.3390/medicina62091718 Medicina 2026-09-07 Medicina 2026-09-07 62 9 Systematic Review 1718 10.3390/medicina62091718 https://www.mdpi.com/1648-9144/62/9/1718 Medicina, Vol. 62, Pages 1717: Total Temporomandibular Joint Replacement with Customized Prosthesis in Craniofacial Malformations: A Scoping Review https://www.mdpi.com/1648-9144/62/9/1717 Background: Craniofacial malformations may affect maxillomandibular growth and TMJ function. Customized total TMJ replacement has been used for reconstruction in selected patients with severe congenital TMJ deficiencies. Objectives: To map and characterize the evidence on indications, surgical and prosthetic characteristics, associated procedures, outcomes, complications, and knowledge gaps of customized total TMJ replacement in patients with craniofacial malformations. Methods: This scoping review followed PRISMA-ScR guidelines. PubMed, Embase, Scopus, and Web of Science were searched from 1994 to 7 August 2026, with complementary searches in Google Scholar and OATD. Study selection and data extraction were independently performed by two reviewers, and findings were synthesized descriptively. Results: Seven studies comprising 36 patients aged 9–59 years were included. Forty-three TMJ replacements were performed (29 unilateral and 7 bilateral), most commonly using customized TMJ Concepts prostheses. Twenty-five patients (69.4%) had undergone previous surgery. Orthognathic surgery was part of the treatment pathway in all studies. Reported outcomes included mouth opening, facial symmetry, occlusion, and mandibular function; however, outcome reporting was heterogeneous, limiting attribution of these outcomes specifically to TMJ replacement. Conclusions: Evidence remains limited and heterogeneous, precluding conclusions regarding effectiveness, safety, predictability, or superiority. Prospective studies with standardized outcomes and long-term follow-up are needed. 2026-09-07 Medicina, Vol. 62, Pages 1717: Total Temporomandibular Joint Replacement with Customized Prosthesis in Craniofacial Malformations: A Scoping Review

Medicina doi: 10.3390/medicina62091717

Authors: Bastian Abarzúa Maria Ignacia Oporto Víctor Ravelo Erick Vargas Florencio Monje-Gil Sergio Olate

Background: Craniofacial malformations may affect maxillomandibular growth and TMJ function. Customized total TMJ replacement has been used for reconstruction in selected patients with severe congenital TMJ deficiencies. Objectives: To map and characterize the evidence on indications, surgical and prosthetic characteristics, associated procedures, outcomes, complications, and knowledge gaps of customized total TMJ replacement in patients with craniofacial malformations. Methods: This scoping review followed PRISMA-ScR guidelines. PubMed, Embase, Scopus, and Web of Science were searched from 1994 to 7 August 2026, with complementary searches in Google Scholar and OATD. Study selection and data extraction were independently performed by two reviewers, and findings were synthesized descriptively. Results: Seven studies comprising 36 patients aged 9–59 years were included. Forty-three TMJ replacements were performed (29 unilateral and 7 bilateral), most commonly using customized TMJ Concepts prostheses. Twenty-five patients (69.4%) had undergone previous surgery. Orthognathic surgery was part of the treatment pathway in all studies. Reported outcomes included mouth opening, facial symmetry, occlusion, and mandibular function; however, outcome reporting was heterogeneous, limiting attribution of these outcomes specifically to TMJ replacement. Conclusions: Evidence remains limited and heterogeneous, precluding conclusions regarding effectiveness, safety, predictability, or superiority. Prospective studies with standardized outcomes and long-term follow-up are needed.

]]> Total Temporomandibular Joint Replacement with Customized Prosthesis in Craniofacial Malformations: A Scoping Review Bastian Abarzúa Maria Ignacia Oporto Víctor Ravelo Erick Vargas Florencio Monje-Gil Sergio Olate doi: 10.3390/medicina62091717 Medicina 2026-09-07 Medicina 2026-09-07 62 9 Review 1717 10.3390/medicina62091717 https://www.mdpi.com/1648-9144/62/9/1717 Medicina, Vol. 62, Pages 1716: Clinical Impact of Fingolimod-Associated Lymphopenia in Multiple Sclerosis: A Real-World Cohort Study https://www.mdpi.com/1648-9144/62/9/1716 Background and Objectives: Fingolimod, a sphingosine-1-phosphate receptor modulator, is an effective disease-modifying therapy for relapsing forms of multiple sclerosis (MS). Although lymphopenia is a well-recognized pharmacological effect, its clinical significance remains uncertain. This study evaluated the frequency and severity of fingolimod-associated lymphopenia, longitudinal hematological changes and their relationship with clinical outcomes in a real-world MS cohort. Materials and Methods: This retrospective observational study included 143 adults with MS who initiated fingolimod treatment between May 2019 and October 2020. Demographic, clinical and laboratory data were collected at baseline and at 3- and 6-month follow-up visits. Lymphopenia was graded according to the Common Terminology Criteria for Adverse Events version 4.0. Laboratory parameters and infection outcomes were compared according to lymphopenia severity. Logistic regression analysis was performed to identify factors associated with Grade 4 lymphopenia at 6 months. Results: At 6 months, lymphopenia was present in 124 patients (86.7%), including Grade 4 lymphopenia in 15 (10.5%). Leukocyte, neutrophil and lymphocyte counts decreased, whereas ALT, AST, GGT, NLR and SII increased significantly during treatment (all p < 0.001). Infection frequency did not differ among lymphopenia severity groups (p = 0.530). No statistically significant association was detected between Grade 3–4 lymphopenia and infection risk (OR, 1.41; 95% CI, 0.42–4.71; p = 0.545). Lower baseline lymphocyte count was independently associated with Grade 4 lymphopenia (adjusted OR 0.078, 95% CI 0.018–0.325; p < 0.001). Conclusions: Fingolimod-associated lymphopenia was common, with Grade 4 lymphopenia affecting approximately one-tenth of patients. No statistically significant association between lymphopenia severity and infection was detected; however, the small number of Grade 4 cases, low event rate and wide confidence interval limited the statistical power to exclude clinically meaningful differences. These findings should therefore be interpreted cautiously and do not establish the absence of infection risk associated with severe lymphopenia. Regular hematological monitoring and individualized clinical decision-making remain essential, particularly in patients with lower baseline lymphocyte counts. 2026-09-07 Medicina, Vol. 62, Pages 1716: Clinical Impact of Fingolimod-Associated Lymphopenia in Multiple Sclerosis: A Real-World Cohort Study

Medicina doi: 10.3390/medicina62091716

Authors: Murat Yeniçeri Mustafa Can Şenoymak Süleyman Baş Hasan Hakan Çoban Ayşe Gürbüz Yeniçeri Serkan Demir Alpaslan Tanoglu

Background and Objectives: Fingolimod, a sphingosine-1-phosphate receptor modulator, is an effective disease-modifying therapy for relapsing forms of multiple sclerosis (MS). Although lymphopenia is a well-recognized pharmacological effect, its clinical significance remains uncertain. This study evaluated the frequency and severity of fingolimod-associated lymphopenia, longitudinal hematological changes and their relationship with clinical outcomes in a real-world MS cohort. Materials and Methods: This retrospective observational study included 143 adults with MS who initiated fingolimod treatment between May 2019 and October 2020. Demographic, clinical and laboratory data were collected at baseline and at 3- and 6-month follow-up visits. Lymphopenia was graded according to the Common Terminology Criteria for Adverse Events version 4.0. Laboratory parameters and infection outcomes were compared according to lymphopenia severity. Logistic regression analysis was performed to identify factors associated with Grade 4 lymphopenia at 6 months. Results: At 6 months, lymphopenia was present in 124 patients (86.7%), including Grade 4 lymphopenia in 15 (10.5%). Leukocyte, neutrophil and lymphocyte counts decreased, whereas ALT, AST, GGT, NLR and SII increased significantly during treatment (all p < 0.001). Infection frequency did not differ among lymphopenia severity groups (p = 0.530). No statistically significant association was detected between Grade 3–4 lymphopenia and infection risk (OR, 1.41; 95% CI, 0.42–4.71; p = 0.545). Lower baseline lymphocyte count was independently associated with Grade 4 lymphopenia (adjusted OR 0.078, 95% CI 0.018–0.325; p < 0.001). Conclusions: Fingolimod-associated lymphopenia was common, with Grade 4 lymphopenia affecting approximately one-tenth of patients. No statistically significant association between lymphopenia severity and infection was detected; however, the small number of Grade 4 cases, low event rate and wide confidence interval limited the statistical power to exclude clinically meaningful differences. These findings should therefore be interpreted cautiously and do not establish the absence of infection risk associated with severe lymphopenia. Regular hematological monitoring and individualized clinical decision-making remain essential, particularly in patients with lower baseline lymphocyte counts.

]]> Clinical Impact of Fingolimod-Associated Lymphopenia in Multiple Sclerosis: A Real-World Cohort Study Murat Yeniçeri Mustafa Can Şenoymak Süleyman Baş Hasan Hakan Çoban Ayşe Gürbüz Yeniçeri Serkan Demir Alpaslan Tanoglu doi: 10.3390/medicina62091716 Medicina 2026-09-07 Medicina 2026-09-07 62 9 Article 1716 10.3390/medicina62091716 https://www.mdpi.com/1648-9144/62/9/1716 Medicina, Vol. 62, Pages 1715: Comparative Outcomes of Kirschner Wire Fixation Versus Locking Plate Osteosynthesis in Fifth Metacarpal Neck Fractures: A 20-Year Retrospective Analysis https://www.mdpi.com/1648-9144/62/9/1715 Background and Objectives: Fifth metacarpal neck fractures are commonly encountered in hand surgery, yet optimal surgical fixation remains debated. This study compares Kirschner wire (K-wire) fixation and locking plate osteosynthesis in terms of radiological and functional outcomes. Materials and Methods: A retrospective cohort of 30 patients (mean age 45) from 2003–2022 was reviewed. Patients underwent either antegrade K-wire fixation or dorsal/volar locking plate fixation. Outcomes assessed included union time, angular and length deformity correction, return to work, and complication rates. Results: Both groups achieved similar final angulation correction (85%, p = 0.72). K-wire fixation achieved significantly faster radiographic union (K-wire: 3.5 months; plate: 4.5 months, p = 0. 019). K-wires allowed earlier intervention (6.0 (3.0–9.0) vs. 14.0 (9.0–22.0) days to surgery, p < 0.05) but had a 6.7% malunion rate. Plating allowed earlier return to work and avoided pin-tract issues. Functional scores (QuickDASH) and grip strength restoration (>90%) were statistically similar. Conclusions: Both K-wire fixation and locking plate osteosynthesis achieved bone union and satisfactory functional recovery in this retrospective cohort. However, given the small sample size and observational nature of the study, surgical selection should be tailored to individual patient presentation and surgeon preference until larger prospective trials are available. 2026-09-07 Medicina, Vol. 62, Pages 1715: Comparative Outcomes of Kirschner Wire Fixation Versus Locking Plate Osteosynthesis in Fifth Metacarpal Neck Fractures: A 20-Year Retrospective Analysis

Medicina doi: 10.3390/medicina62091715

Authors: Sung Huang Laurent Tsai Shiny Chih-Hsuan Wu Yung-Chuan Liu Po-Ju Lai Chun-Ying Cheng

Background and Objectives: Fifth metacarpal neck fractures are commonly encountered in hand surgery, yet optimal surgical fixation remains debated. This study compares Kirschner wire (K-wire) fixation and locking plate osteosynthesis in terms of radiological and functional outcomes. Materials and Methods: A retrospective cohort of 30 patients (mean age 45) from 2003–2022 was reviewed. Patients underwent either antegrade K-wire fixation or dorsal/volar locking plate fixation. Outcomes assessed included union time, angular and length deformity correction, return to work, and complication rates. Results: Both groups achieved similar final angulation correction (85%, p = 0.72). K-wire fixation achieved significantly faster radiographic union (K-wire: 3.5 months; plate: 4.5 months, p = 0. 019). K-wires allowed earlier intervention (6.0 (3.0–9.0) vs. 14.0 (9.0–22.0) days to surgery, p < 0.05) but had a 6.7% malunion rate. Plating allowed earlier return to work and avoided pin-tract issues. Functional scores (QuickDASH) and grip strength restoration (>90%) were statistically similar. Conclusions: Both K-wire fixation and locking plate osteosynthesis achieved bone union and satisfactory functional recovery in this retrospective cohort. However, given the small sample size and observational nature of the study, surgical selection should be tailored to individual patient presentation and surgeon preference until larger prospective trials are available.

]]> Comparative Outcomes of Kirschner Wire Fixation Versus Locking Plate Osteosynthesis in Fifth Metacarpal Neck Fractures: A 20-Year Retrospective Analysis Sung Huang Laurent Tsai Shiny Chih-Hsuan Wu Yung-Chuan Liu Po-Ju Lai Chun-Ying Cheng doi: 10.3390/medicina62091715 Medicina 2026-09-07 Medicina 2026-09-07 62 9 Article 1715 10.3390/medicina62091715 https://www.mdpi.com/1648-9144/62/9/1715 Medicina, Vol. 62, Pages 1714: Classification Performance of General-Purpose Multimodal Large Language Models Across Orthodontic Radiographic Tasks: A Comparative Study of ChatGPT, Gemini, and Claude https://www.mdpi.com/1648-9144/62/9/1714 Background and Objectives: General-purpose multimodal large language models (MLLMs) can interpret radiographic images, but their classification performance across orthodontic tasks remains uncertain. This study compared the classification performance of ChatGPT, Gemini, and Claude on lateral cephalometric, hand–wrist, and panoramic radiographs. Materials and Methods: This retrospective diagnostic accuracy study included 250 individuals, each contributing one lateral cephalometric, hand–wrist, and panoramic pretreatment radiograph (750 total). Reference classifications were established by two experienced orthodontists, with disagreements resolved by consensus. Lateral cephalometric radiographs were classified as skeletal Class I, II, or III based on the ANB angle according to Steiner analysis; hand–wrist radiographs as prepubertal, pubertal, or postpubertal; and panoramic radiographs as early mixed, late mixed, or permanent dentition. Each image was evaluated once by each AI platform using identical Turkish prompts in separate chat sessions. Classification accuracy, balanced accuracy, macro-F1, class-specific metrics, and reference agreement were assessed. Generalized estimating equations (GEE) assessed platform, radiograph type, and interaction effects on correct classification. Results: ChatGPT had the highest hand–wrist accuracy (81.6%; 95% CI, 76.3–85.9), whereas Gemini had the highest panoramic accuracy (92.8%; 95% CI, 88.9–95.4). Lateral cephalometric accuracies were 70.0%, 64.4%, and 64.8% for ChatGPT, Gemini, and Claude, respectively, with no significant interplatform difference (p = 0.336). The platform × radiograph type interaction was significant (Wald χ2 = 42.52; df = 4; p < 0.001). Agreement with the reference standard was highest for ChatGPT on hand–wrist radiographs (κw = 0.758) and Gemini on panoramic radiographs (κw = 0.883). Conclusions: Classification performance was task- and platform-dependent, with no model consistently achieving the highest performance. For the predefined classification tasks, these models should not be used as standalone tools for these classification tasks. Their potential as decision-support tools requires prospective evaluation of AI-assisted clinician performance and external validation. 2026-09-06 Medicina, Vol. 62, Pages 1714: Classification Performance of General-Purpose Multimodal Large Language Models Across Orthodontic Radiographic Tasks: A Comparative Study of ChatGPT, Gemini, and Claude

Medicina doi: 10.3390/medicina62091714

Authors: Nuri Can Tanrısever Kutluhan Yılmaz Ayşegül Dilara Güvenç Tokur Merve Berika Kadıoğlu Mahmut Kadıoğlu

Background and Objectives: General-purpose multimodal large language models (MLLMs) can interpret radiographic images, but their classification performance across orthodontic tasks remains uncertain. This study compared the classification performance of ChatGPT, Gemini, and Claude on lateral cephalometric, hand–wrist, and panoramic radiographs. Materials and Methods: This retrospective diagnostic accuracy study included 250 individuals, each contributing one lateral cephalometric, hand–wrist, and panoramic pretreatment radiograph (750 total). Reference classifications were established by two experienced orthodontists, with disagreements resolved by consensus. Lateral cephalometric radiographs were classified as skeletal Class I, II, or III based on the ANB angle according to Steiner analysis; hand–wrist radiographs as prepubertal, pubertal, or postpubertal; and panoramic radiographs as early mixed, late mixed, or permanent dentition. Each image was evaluated once by each AI platform using identical Turkish prompts in separate chat sessions. Classification accuracy, balanced accuracy, macro-F1, class-specific metrics, and reference agreement were assessed. Generalized estimating equations (GEE) assessed platform, radiograph type, and interaction effects on correct classification. Results: ChatGPT had the highest hand–wrist accuracy (81.6%; 95% CI, 76.3–85.9), whereas Gemini had the highest panoramic accuracy (92.8%; 95% CI, 88.9–95.4). Lateral cephalometric accuracies were 70.0%, 64.4%, and 64.8% for ChatGPT, Gemini, and Claude, respectively, with no significant interplatform difference (p = 0.336). The platform × radiograph type interaction was significant (Wald χ2 = 42.52; df = 4; p < 0.001). Agreement with the reference standard was highest for ChatGPT on hand–wrist radiographs (κw = 0.758) and Gemini on panoramic radiographs (κw = 0.883). Conclusions: Classification performance was task- and platform-dependent, with no model consistently achieving the highest performance. For the predefined classification tasks, these models should not be used as standalone tools for these classification tasks. Their potential as decision-support tools requires prospective evaluation of AI-assisted clinician performance and external validation.

]]> Classification Performance of General-Purpose Multimodal Large Language Models Across Orthodontic Radiographic Tasks: A Comparative Study of ChatGPT, Gemini, and Claude Nuri Can Tanrısever Kutluhan Yılmaz Ayşegül Dilara Güvenç Tokur Merve Berika Kadıoğlu Mahmut Kadıoğlu doi: 10.3390/medicina62091714 Medicina 2026-09-06 Medicina 2026-09-06 62 9 Article 1714 10.3390/medicina62091714 https://www.mdpi.com/1648-9144/62/9/1714 Medicina, Vol. 62, Pages 1713: Key Inflammatory Pathways, Biomarkers, and Targeted Management Strategies in Primary Total Joint Arthroplasty: A Narrative Review https://www.mdpi.com/1648-9144/62/9/1713 Total joint arthroplasty is a surgical procedure with rising global incidence. Although a strong postoperative inflammatory response is necessary for tissue repair following primary arthroplasty, it may prove to be harmful if excessive or prolonged. This could compromise osseointegration, increase pain, and delay the detection of periprosthetic joint infection. This narrative review examines the principal inflammatory pathways activated by primary arthroplasty. Damage-associated molecular patterns produced by injury and cell death, such as High Mobility Group Box 1 Protein, cell-free DNA, extracellular ATP, histones, and heat shock proteins, trigger innate immune activation following surgical trauma. These mediators use inflammasome pathways and pattern recognition receptors to intensify inflammatory signaling. The acute-phase trajectory, characterized by increases in C-reactive protein and erythrocyte sedimentation rate, alongside the role of interleukin-6 as a precursor factor, is examined together with synovial markers to facilitate the differentiation between septic and aseptic inflammation. Cytokine signaling cascades (JAK-STAT, NF-κB, MAPK) and the RANK/RANKL/OPG axis at the bone-immune interface are also considered. This manuscript highlights relevant inflammatory pathways, clinically significant biomarkers, and pathway-guided management strategies to provide an overview of the current research on the biological mechanisms underlying perioperative inflammation in primary arthroplasty. No inflammatory biomarker has yet been validated as a predictor of aseptic loosening. 2026-09-06 Medicina, Vol. 62, Pages 1713: Key Inflammatory Pathways, Biomarkers, and Targeted Management Strategies in Primary Total Joint Arthroplasty: A Narrative Review

Medicina doi: 10.3390/medicina62091713

Authors: Adelina-Elena Moise Mihai Emanuel Gherghe Alex-Gabriel Grigore Iosif-Aliodor Timofticiuc Matei Todor Patricia Balaban Constantin-Adrian Andrei Serban Dragosloveanu Constantin Caruntu Cristian Scheau

Total joint arthroplasty is a surgical procedure with rising global incidence. Although a strong postoperative inflammatory response is necessary for tissue repair following primary arthroplasty, it may prove to be harmful if excessive or prolonged. This could compromise osseointegration, increase pain, and delay the detection of periprosthetic joint infection. This narrative review examines the principal inflammatory pathways activated by primary arthroplasty. Damage-associated molecular patterns produced by injury and cell death, such as High Mobility Group Box 1 Protein, cell-free DNA, extracellular ATP, histones, and heat shock proteins, trigger innate immune activation following surgical trauma. These mediators use inflammasome pathways and pattern recognition receptors to intensify inflammatory signaling. The acute-phase trajectory, characterized by increases in C-reactive protein and erythrocyte sedimentation rate, alongside the role of interleukin-6 as a precursor factor, is examined together with synovial markers to facilitate the differentiation between septic and aseptic inflammation. Cytokine signaling cascades (JAK-STAT, NF-κB, MAPK) and the RANK/RANKL/OPG axis at the bone-immune interface are also considered. This manuscript highlights relevant inflammatory pathways, clinically significant biomarkers, and pathway-guided management strategies to provide an overview of the current research on the biological mechanisms underlying perioperative inflammation in primary arthroplasty. No inflammatory biomarker has yet been validated as a predictor of aseptic loosening.

]]> Key Inflammatory Pathways, Biomarkers, and Targeted Management Strategies in Primary Total Joint Arthroplasty: A Narrative Review Adelina-Elena Moise Mihai Emanuel Gherghe Alex-Gabriel Grigore Iosif-Aliodor Timofticiuc Matei Todor Patricia Balaban Constantin-Adrian Andrei Serban Dragosloveanu Constantin Caruntu Cristian Scheau doi: 10.3390/medicina62091713 Medicina 2026-09-06 Medicina 2026-09-06 62 9 Review 1713 10.3390/medicina62091713 https://www.mdpi.com/1648-9144/62/9/1713 Medicina, Vol. 62, Pages 1712: Venous Thromboembolism in Neonates, Children, and Adolescents: A Comprehensive Narrative Review of Risk Factors, Diagnosis, Treatment, and Prevention https://www.mdpi.com/1648-9144/62/9/1712 Venous thromboembolism (VTE) was once considered rare in the young, but it has become an increasingly important complication of contemporary pediatric care, driven by the improved survival of children with complex chronic illness and by the expanding use of central venous catheters. This narrative review synthesizes current evidence on VTE across the entire pediatric age range, from the critically ill neonate to the injured adolescent. We first examine noncerebral VTE in children beyond the newborn period, describing an incidence that is far lower than in adults yet rising among hospitalized patients, the multifactorial risk factors dominated by central venous catheters, and the age-dependent protection conferred by developmental hemostasis. We outline a diagnostic approach centered on compression ultrasonography and computed tomography pulmonary angiography, and a treatment paradigm that increasingly favors direct oral anticoagulants and shorter, six-week courses for low-risk provoked events. Dedicated sections address the distinct biology, presentation, and management of neonatal thrombosis, including renal vein thrombosis, portal vein thrombosis, and purpura fulminans, for which low-molecular-weight heparin is preferred and warfarin is generally avoided. We review the heightened, malignancy-specific risk of cancer-associated thrombosis, the difficulty of anticoagulating the thrombocytopenic child, and the consistent evidence against routine primary thromboprophylaxis. Cerebral sinovenous thrombosis is considered in depth, emphasizing its age-dependent triggers, the central role of magnetic resonance venography, and the safety of anticoagulation. Finally, we summarize the comparatively low but age-graded risk of VTE after major pediatric trauma and the puberty-based approach to prophylaxis. Throughout, we highlight the continued reliance on extrapolated adult data, the emergence of pediatric randomized trials and multicenter registries, and the unmet need for prospectively validated risk-prediction tools. The review offers clinicians an integrated, contemporary framework for recognizing, diagnosing, treating, and preventing thrombosis from the neonate to the adolescent. 2026-09-06 Medicina, Vol. 62, Pages 1712: Venous Thromboembolism in Neonates, Children, and Adolescents: A Comprehensive Narrative Review of Risk Factors, Diagnosis, Treatment, and Prevention

Medicina doi: 10.3390/medicina62091712

Authors: Marko Bašković Jana Buzuk Bianka Dujić Danijela Jurić Kristina Jurković Karla Pehar Sara Vuković Katarina Čavka Miroslav Gjurašin Dubravko Habek Davor Bojić Darko Antičević Katarina Lohman Vuga Ivan Milas

Venous thromboembolism (VTE) was once considered rare in the young, but it has become an increasingly important complication of contemporary pediatric care, driven by the improved survival of children with complex chronic illness and by the expanding use of central venous catheters. This narrative review synthesizes current evidence on VTE across the entire pediatric age range, from the critically ill neonate to the injured adolescent. We first examine noncerebral VTE in children beyond the newborn period, describing an incidence that is far lower than in adults yet rising among hospitalized patients, the multifactorial risk factors dominated by central venous catheters, and the age-dependent protection conferred by developmental hemostasis. We outline a diagnostic approach centered on compression ultrasonography and computed tomography pulmonary angiography, and a treatment paradigm that increasingly favors direct oral anticoagulants and shorter, six-week courses for low-risk provoked events. Dedicated sections address the distinct biology, presentation, and management of neonatal thrombosis, including renal vein thrombosis, portal vein thrombosis, and purpura fulminans, for which low-molecular-weight heparin is preferred and warfarin is generally avoided. We review the heightened, malignancy-specific risk of cancer-associated thrombosis, the difficulty of anticoagulating the thrombocytopenic child, and the consistent evidence against routine primary thromboprophylaxis. Cerebral sinovenous thrombosis is considered in depth, emphasizing its age-dependent triggers, the central role of magnetic resonance venography, and the safety of anticoagulation. Finally, we summarize the comparatively low but age-graded risk of VTE after major pediatric trauma and the puberty-based approach to prophylaxis. Throughout, we highlight the continued reliance on extrapolated adult data, the emergence of pediatric randomized trials and multicenter registries, and the unmet need for prospectively validated risk-prediction tools. The review offers clinicians an integrated, contemporary framework for recognizing, diagnosing, treating, and preventing thrombosis from the neonate to the adolescent.

]]> Venous Thromboembolism in Neonates, Children, and Adolescents: A Comprehensive Narrative Review of Risk Factors, Diagnosis, Treatment, and Prevention Marko Bašković Jana Buzuk Bianka Dujić Danijela Jurić Kristina Jurković Karla Pehar Sara Vuković Katarina Čavka Miroslav Gjurašin Dubravko Habek Davor Bojić Darko Antičević Katarina Lohman Vuga Ivan Milas doi: 10.3390/medicina62091712 Medicina 2026-09-06 Medicina 2026-09-06 62 9 Review 1712 10.3390/medicina62091712 https://www.mdpi.com/1648-9144/62/9/1712 Medicina, Vol. 62, Pages 1711: Efficacy and Safety of Ozanimod in Ulcerative Colitis: A Real-World Pan-Hellenic Study https://www.mdpi.com/1648-9144/62/9/1711 Background and Objectives: Ozanimod is approved for the treatment of ulcerative colitis (UC). The aim of the present study was to evaluate the clinical, biochemical, and endoscopic outcomes. Materials and Methods: This was a retrospective, multicenter, cohort study. Clinical, biochemical, endoscopic, and safety data were collected from medical records. Τhe primary outcome was clinical response at week 12. Secondary outcomes included clinical remission, endoscopic improvement and remission, biochemical outcomes, treatment persistence, and safety. Clinical outcomes were assessed at weeks 12 and 48, while treatment persistence was evaluated over the complete 48-week follow-up period, using Kaplan–Meier analysis. Clinical response was defined as a ≥30% reduction in partial Mayo score and remission as a partial Mayo score < 3, with no individual sub-score > 1 and a rectal bleeding sub-score of 0. Clinical response and remission were primarily assessed using an observed-case approach, with an additional sensitivity analysis classifying discontinuations due to lack of efficacy as treatment failures. Results: A total of 79 patients were included (62.0% male; median age 44 years, IQR 31–56). Prior biologic exposure was recorded in 29.1%, and 64.6% were previously exposed to oral corticosteroids. Among patients with available clinical assessment at week 12 (n = 62), clinical response and clinical remission were achieved in 77.4% and 71.0%, respectively. Among patients with available data at week 12 (n = 32), endoscopic improvement was observed in 65.6%, while endoscopic remission was achieved in 15.6%. At week 48, among 26 evaluable patients, clinical response and remission rates were 96.2% and 84.6%, respectively; when discontinuations due to lack of efficacy were considered treatment failures, the corresponding rates were 52.1% and 45.8%. Treatment persistence did not differ significantly according to overall prior biologic exposure, whereas previous vedolizumab exposure was associated with lower treatment persistence over the week 48 follow-up (log-rank p = 0.037). In multivariable Cox regression, previous vedolizumab exposure remained associated with an increased hazard of treatment discontinuation (adjusted HR 3.07, 95% CI 1.23–7.67; p = 0.016). Adverse events were reported in 13.9% of patients. Conclusions: Ozanimod demonstrated good efficacy and a favorable safety profile in patients with moderate UC. 2026-09-06 Medicina, Vol. 62, Pages 1711: Efficacy and Safety of Ozanimod in Ulcerative Colitis: A Real-World Pan-Hellenic Study

Medicina doi: 10.3390/medicina62091711

Authors: Pavlos Pardalis Alexandros Ioannou Theodoros Delidis Georgios Kokkotis Georgios Leonidakis Georgios Axiaris Konstantinos Argyriou Anthia Gatopoulou Olga Giouleme Nikolaos Kalakos Pantelis Karatzas Ioanna Nefeli Mastorogianni Andreas Kapsoritakis Efrosini Laoudi Panagiotis Markopoulos Konstantinos Katsanos Georgios Michalopoulos Konstantinos Mousourakis Georgios Bamias Georgios Papatheodoridis Ioanna Papatzelou Konstantinos Soufleris Maria Tzouvala Eftychia Tsironi Ioannis Psaroudakis Angeliki Theodoropoulou Alexandra Varka Nikos Viazis Eirini Zacharopoulou Konstantinos Karmiris Ioannis Koutroubakis Spyridon Michopoulos Evanthia Zampeli

Background and Objectives: Ozanimod is approved for the treatment of ulcerative colitis (UC). The aim of the present study was to evaluate the clinical, biochemical, and endoscopic outcomes. Materials and Methods: This was a retrospective, multicenter, cohort study. Clinical, biochemical, endoscopic, and safety data were collected from medical records. Τhe primary outcome was clinical response at week 12. Secondary outcomes included clinical remission, endoscopic improvement and remission, biochemical outcomes, treatment persistence, and safety. Clinical outcomes were assessed at weeks 12 and 48, while treatment persistence was evaluated over the complete 48-week follow-up period, using Kaplan–Meier analysis. Clinical response was defined as a ≥30% reduction in partial Mayo score and remission as a partial Mayo score < 3, with no individual sub-score > 1 and a rectal bleeding sub-score of 0. Clinical response and remission were primarily assessed using an observed-case approach, with an additional sensitivity analysis classifying discontinuations due to lack of efficacy as treatment failures. Results: A total of 79 patients were included (62.0% male; median age 44 years, IQR 31–56). Prior biologic exposure was recorded in 29.1%, and 64.6% were previously exposed to oral corticosteroids. Among patients with available clinical assessment at week 12 (n = 62), clinical response and clinical remission were achieved in 77.4% and 71.0%, respectively. Among patients with available data at week 12 (n = 32), endoscopic improvement was observed in 65.6%, while endoscopic remission was achieved in 15.6%. At week 48, among 26 evaluable patients, clinical response and remission rates were 96.2% and 84.6%, respectively; when discontinuations due to lack of efficacy were considered treatment failures, the corresponding rates were 52.1% and 45.8%. Treatment persistence did not differ significantly according to overall prior biologic exposure, whereas previous vedolizumab exposure was associated with lower treatment persistence over the week 48 follow-up (log-rank p = 0.037). In multivariable Cox regression, previous vedolizumab exposure remained associated with an increased hazard of treatment discontinuation (adjusted HR 3.07, 95% CI 1.23–7.67; p = 0.016). Adverse events were reported in 13.9% of patients. Conclusions: Ozanimod demonstrated good efficacy and a favorable safety profile in patients with moderate UC.

]]> Efficacy and Safety of Ozanimod in Ulcerative Colitis: A Real-World Pan-Hellenic Study Pavlos Pardalis Alexandros Ioannou Theodoros Delidis Georgios Kokkotis Georgios Leonidakis Georgios Axiaris Konstantinos Argyriou Anthia Gatopoulou Olga Giouleme Nikolaos Kalakos Pantelis Karatzas Ioanna Nefeli Mastorogianni Andreas Kapsoritakis Efrosini Laoudi Panagiotis Markopoulos Konstantinos Katsanos Georgios Michalopoulos Konstantinos Mousourakis Georgios Bamias Georgios Papatheodoridis Ioanna Papatzelou Konstantinos Soufleris Maria Tzouvala Eftychia Tsironi Ioannis Psaroudakis Angeliki Theodoropoulou Alexandra Varka Nikos Viazis Eirini Zacharopoulou Konstantinos Karmiris Ioannis Koutroubakis Spyridon Michopoulos Evanthia Zampeli doi: 10.3390/medicina62091711 Medicina 2026-09-06 Medicina 2026-09-06 62 9 Article 1711 10.3390/medicina62091711 https://www.mdpi.com/1648-9144/62/9/1711 Medicina, Vol. 62, Pages 1710: Accuracy of Dynamic Computer-Assisted Surgery for Pterygoid Implant Placement in Fully and Partially Edentulous Maxillae: A Retrospective Comparative Study https://www.mdpi.com/1648-9144/62/9/1710 Background and Objectives: The rehabilitation of the atrophic posterior maxilla with pterygoid implant presents a significant challenge due to complex regional anatomy and limited visual access. This study aimed to compare the accuracy of a dynamic computer-assisted implant surgery system (dCAIS) for pterygoid implant placement in fully and partially edentulous maxillae using radiographic marker registration (RMR) and markerless tracing registration (MTR), respectively. Materials and Methods: Forty pterygoid implants were retrospectively evaluated in 40 patients, divided into two groups: fully edentulous (n = 20) and partially edentulous (n = 20). Implant placement was performed using a dynamic navigation system (dCAIS), utilizing either bone-anchored mini-screws or tooth-surface tracing as reference points. Accuracy was assessed by superimposing preoperative plans with postoperative cone beam computer tomography (CBCT) scans. Coronal, apical, and angular deviations were measured and analyzed using the Data Science Workbench (version 14). The level of statistical significance was set at α = 0.05 (two-tailed). Results: The mean deviations for fully and partially edentulous maxillae measured 1.24 ± 0.27 mm and 1.40 ± 0.27 mm at the coronal level (p = 0.065), 1.30 ± 0.49 mm and 1.30 ± 0.54 at the apical level (p = 0.995), and 0.72 ± 0.38° and 0.82 ± 0.43° in angular deviation (p = 0.560), respectively. No statistically significant differences were found between the two groups. Notably, mean angular deviation was remarkably low (<1°) in both groups. Conclusions: No statistically significant between-group differences in accuracy were detected in coronal, apical, and angular deviations between the markerless tracing registration method in partially edentulous patients and the bone-anchored radiographic marker registration method in fully edentulous patients. 2026-09-06 Medicina, Vol. 62, Pages 1710: Accuracy of Dynamic Computer-Assisted Surgery for Pterygoid Implant Placement in Fully and Partially Edentulous Maxillae: A Retrospective Comparative Study

Medicina doi: 10.3390/medicina62091710

Authors: Luka Plivelić Ivica Dubravica Ivan Zajc Vlatka Debeljak Ana Zulijani

Background and Objectives: The rehabilitation of the atrophic posterior maxilla with pterygoid implant presents a significant challenge due to complex regional anatomy and limited visual access. This study aimed to compare the accuracy of a dynamic computer-assisted implant surgery system (dCAIS) for pterygoid implant placement in fully and partially edentulous maxillae using radiographic marker registration (RMR) and markerless tracing registration (MTR), respectively. Materials and Methods: Forty pterygoid implants were retrospectively evaluated in 40 patients, divided into two groups: fully edentulous (n = 20) and partially edentulous (n = 20). Implant placement was performed using a dynamic navigation system (dCAIS), utilizing either bone-anchored mini-screws or tooth-surface tracing as reference points. Accuracy was assessed by superimposing preoperative plans with postoperative cone beam computer tomography (CBCT) scans. Coronal, apical, and angular deviations were measured and analyzed using the Data Science Workbench (version 14). The level of statistical significance was set at α = 0.05 (two-tailed). Results: The mean deviations for fully and partially edentulous maxillae measured 1.24 ± 0.27 mm and 1.40 ± 0.27 mm at the coronal level (p = 0.065), 1.30 ± 0.49 mm and 1.30 ± 0.54 at the apical level (p = 0.995), and 0.72 ± 0.38° and 0.82 ± 0.43° in angular deviation (p = 0.560), respectively. No statistically significant differences were found between the two groups. Notably, mean angular deviation was remarkably low (<1°) in both groups. Conclusions: No statistically significant between-group differences in accuracy were detected in coronal, apical, and angular deviations between the markerless tracing registration method in partially edentulous patients and the bone-anchored radiographic marker registration method in fully edentulous patients.

]]> Accuracy of Dynamic Computer-Assisted Surgery for Pterygoid Implant Placement in Fully and Partially Edentulous Maxillae: A Retrospective Comparative Study Luka Plivelić Ivica Dubravica Ivan Zajc Vlatka Debeljak Ana Zulijani doi: 10.3390/medicina62091710 Medicina 2026-09-06 Medicina 2026-09-06 62 9 Article 1710 10.3390/medicina62091710 https://www.mdpi.com/1648-9144/62/9/1710