Journal of Clinical Medicine doi: 10.3390/jcm15166237

Authors: Haoyu Chen Louis Arnould Andrzej Grzybowski

The integration of artificial intelligence (AI) into ophthalmology represents one of the most transformative technological developments in modern medicine [...]

Journal of Clinical Medicine doi: 10.3390/jcm15166235

Authors: Sinan Mersin Pelin Aytan Seher Yontar Mahmut Bakır Koyuncu Aycan Erkenekli Esin Oğuz Kozan Enver Tekin Eyüp Naci Tiftik

Background/Objectives: Therapeutic leukapheresis is widely used to manage hyperleukocytosis in hematologic malignancies, yet the factors determining its efficacy remain incompletely defined. We aimed to identify clinical, biochemical, and procedural determinants of leukapheresis efficacy in a single-center cohort. Methods: We retrospectively analyzed 125 leukapheresis procedures performed in adult patients with hematologic malignancies between March 2012 and June 2026. At our institution, emergency leukapheresis is performed before the initiation of cytoreductive therapy, so all first procedures were treatment-naïve (repeat procedures could follow cytoreductive therapy). The primary endpoint was the white blood cell (WBC) reduction rate (%). Secondary endpoints were ≥30% and ≥50% reduction. Predictors of reduction were identified using univariate tests and multivariable regression, with within-patient correlation accounted for using cluster-robust standard errors, and pre- versus post-procedure biochemical changes were assessed for paired samples. Results: The median WBC reduction was 47.9%; ≥30% and ≥50% reduction were achieved in 75% and 42% of procedures, respectively. Reduction differed significantly by diagnosis (p < 0.001), being highest in ALL (57.4%) and lowest in CML (18.6%). In multivariable analysis, processed volume (β = 0.004, p < 0.001), inlet rate (β = −0.43, p < 0.001), acute leukemia (β = 10.4, p = 0.040), and baseline platelet count (β = −0.03, p = 0.036) were independent predictors. Leukapheresis significantly reduced LDH and uric acid levels (both p < 0.001). Conclusions: Leukapheresis efficacy is determined by disease subtype and modifiable procedural parameters. Higher processed volume and acute leukemia diagnosis were associated with greater WBC reduction, while CML blast crisis responds poorly. These findings support procedure optimization to maximize cytoreduction.

Journal of Clinical Medicine doi: 10.3390/jcm15166236

Authors: Adam J. Wells Abhiram D. Hiwase Ivan Timofeev Peter J. A. Hutchinson

The management of traumatic brain injury remains one of the greatest challenges in modern medicine. Determining whom to treat, when to intervene, and how aggressively to proceed and persist continues to define the central dilemma of neurotrauma care. While the injured brain possesses only limited regenerative capacity, substantial opportunity remains to mitigate the cascade of secondary brain injury. Previous technological and scientific advances have progressively challenged the therapeutic nihilism historically associated with severe neurotrauma, and the accelerating pace of innovation is invigorating efforts to push the boundaries of care. Contemporary neurotrauma research increasingly seeks to reduce the incidence of injury through prevention, enable ultra-early diagnosis and intervention, biologically subclassify heterogeneous injury patterns, and integrate multimodal neuromonitoring into precision-guided therapeutic strategies. Advances in artificial intelligence, computational modelling, imaging, biomarker science, and neurocritical care now build upon decades of foundational work established by prior generations of clinicians and scientists. Together, these developments may enable increasingly individualised approaches to neurotrauma management, with the aim of preserving meaningful neurological function, quality of life, and human potential on a global scale. Although many challenges remain, modern neurotrauma increasingly stands at the threshold of such transformation. This narrative review explores the emerging technologies, evolving paradigms, and future directions that may shape the next era of neurotrauma care.

Journal of Clinical Medicine doi: 10.3390/jcm15166233

Authors: Gianluca Giannarini Eleonora Bovolenta Giuliana Lista Luca Di Gianfrancesco Jeanlou Collavino Clara Ermacora Carmine Franzese Afrovita Kungulli Davide Minardi Marco Rinaldi Emma Segalla Sasa Sekulovic Fabio Traunero Matteo Alberto Maniero Francesco Claps Maria Abbinante Gioacchino De Giorgi Antonio Amodeo Angelo Porreca Alessandro Crestani

Background: Robot-assisted partial nephrectomy (RAPN) has become the preferred surgical approach for localized renal tumours, yet the optimal surgical technique remains uncertain. Ongoing refinements aim to reduce morbidity while maximizing renal function preservation. In this study, we compared perioperative outcomes, postoperative complications, and early renal function between the no-touch adaptive RAPN technique, designed to minimize vascular and parenchymal trauma, and the conventional approach. Methods: We retrospectively analyzed 387 consecutive patients undergoing RAPN for localized renal tumours between June 2017 and February 2026 at a single tertiary referral centre. Patients were treated with either the no-touch adaptive (n = 178) or conventional (n = 209) technique. The no-touch approach consisted of sutureless off-clamp simple tumour enucleation with incremental haemostasis and on-demand conversion to arterial clamping, tumour enucleoresection, or renorrhaphy when required. The conventional technique consisted of an on-clamp minimal enucleoresection with double-layer renorrhaphy. Completion rate of a fully no-touch procedure was assessed in the study group, and perioperative outcomes, 90-day complications, and renal function at 3 months were compared between the groups. Exploratory multivariable logistic regression identified predictors of postoperative complications. Absolute and relative changes in estimated glomerular filtration rate (eGFR) from baseline were analyzed, and a linear regression model adjusted for baseline eGFR was used to compare postoperative renal function between the groups. Results: Among the 175 evaluable patients after excluding three immediate conversions to radical nephrectomy before tumour excision, a fully no-touch procedure was completed in 153 (87.4%). Compared with conventional RAPN, the no-touch group had a significantly shorter hospital stay (3 vs. 5 days, p < 0.01), lower 90-day readmission rate (0% vs. 4.3%, p = 0.01), fewer overall complications (16.3% vs. 40.7%, p < 0.01), and fewer major complications (3.9% vs. 11%, p = 0.02), with no cases of delayed vascular bleeding. Low tumour complexity and the no-touch technique independently predicted a lower risk of postoperative complications. The median decline in eGFR from baseline to 3 months was significantly smaller in the no-touch group, which also showed a lower rate of clinically meaningful renal function deterioration (eGFR decline ≥ 30%; 1.1% vs. 5.7%, p = 0.03). After adjustment for baseline eGFR, the no-touch adaptive technique was associated with a 5.4 mL/min/1.73 m2 higher 3-month eGFR than the conventional technique (95% CI 3.6–7.2; p < 0.001). Conclusions: Within the limitations of this retrospective comparative study, the no-touch adaptive technique for RAPN was associated with lower perioperative morbidity and better preservation of early renal function than the conventional approach. These findings support further prospective multicentre studies to determine the reproducibility, durability, and clinical relevance of this surgical strategy.

Journal of Clinical Medicine doi: 10.3390/jcm15166234

Authors: Murat Haksever Deniz Taşdemir Selim Kandemir Bekir Kahveci Refaettin Şahin Alp Koray Kinter Savaş Özdemir Atakan Tanaçan Ismet Hortu

Background/Objectives: Preeclampsia is a heterogeneous hypertensive disorder of pregnancy, and accessible hematologic indices may reflect maternal physiologic differences before the clinical syndrome becomes evident. This study evaluated whether the first-trimester hemoglobin-to-red cell distribution width (Hb/RDW) ratio was associated with later documented preeclampsia and assessed its discrimination, relation to disease severity, and association with maternal–neonatal outcomes in a tertiary-care cohort. Methods: This retrospective cohort study included 224 singleton pregnancies managed at a tertiary referral center between January 2024 and December 2025. Data extraction, anonymization, and analysis were performed after ethics approval (Approval No. 72; 2 March 2026). Participants were categorized as preeclampsia-negative (n = 131) or preeclampsia-positive (n = 93). Preeclampsia and severe features were defined according to American College of Obstetricians and Gynecologists criteria. The Hb/RDW ratio was calculated from routine first-trimester complete blood count parameters obtained before clinical diagnosis or final outcome classification. ROC analysis, multivariable logistic regression, multicollinearity assessment, events-per-variable evaluation, calibration testing, and exploratory incremental discrimination analyses were performed. Results: The first-trimester Hb/RDW ratio was higher in pregnancies later complicated by preeclampsia. Single-marker ROC analysis showed moderate discrimination (AUC = 0.687; bootstrap 95% CI: 0.618–0.755). At the 0.63 cut-off, sensitivity was 89.2%, specificity 47.3%, positive predictive value 54.6%, and negative predictive value 86.1%. In the primary multivariable model, Hb/RDW remained associated with later preeclampsia (adjusted OR per 0.1-unit increase = 1.45; 95% CI: 1.22–1.72; p < 0.001). However, Hb/RDW was not independently associated with severe preeclampsia among affected patients, fetal growth restriction, or composite maternal morbidity. VIF values ranged from 1.00 to 1.07. Secondary models for fetal growth restriction and composite maternal morbidity had borderline events-per-variable values and were interpreted as exploratory. Conclusions: First-trimester Hb/RDW was associated with later documented preeclampsia in this retrospective tertiary-care cohort, but its single-marker performance was modest and specificity was limited. The ratio should be interpreted as an inexpensive research marker of hematologic phenotype rather than a stand-alone screening, diagnostic, or management tool. Prospective multicenter validation with standardized first-trimester sampling and adjustment for hematinic and nutritional variables is required before clinical implementation.

Journal of Clinical Medicine doi: 10.3390/jcm15166232

Authors: Aslı Bozdemir Sibel Hacıoğlu Gülsüm Akgün Çağlıyan Nevin Alayvaz Aslan Süleyman Utku Uzun Kayıhan Kara Utku Iltar Orhan Kemal Yücel Ünal Ataş Selin Arslan Kirezli Ali İhsan Gemici İnci Alacacıoğlu Mustafa Kemal Yeniay Oktay Bilgir Zehra Narlı Özdemir Handan Haydaroğlu Şahin Ayşe Uysal Zekeriya Aksöz Zeynep Tuğba Güven Kemal Aygün Atakan Tekinalp Mehmet Yılmaz Cansu Atmaca Mutlu Gökhan Pektaş Ozan Salim Nil Güler

Background: Elranatamab, a bispecific antibody targeting BCMA and CD3, has demonstrated clinical activity in relapsed/refractory multiple myeloma. Real-world evidence regarding infectious complications and supportive care remains limited. We evaluated the early clinical activity, safety profile, infectious complications, and supportive care practices associated with relapsed/refractory multiple myeloma (RRMM). This study represents one of the first multicenter real-world evaluations of elranatamab in Türkiye. Methods: This multicenter retrospective study included 87 patients with relapsed/refractory multiple myeloma treated with elranatamab. Clinical characteristics, treatment responses, immune-mediated toxicities, infectious complications, and supportive care practices were assessed. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. Multivariable analyses were performed to identify factors associated with treatment response and clinical outcomes. Results: At 3 months, ORR was 47.1% in the ITT population, 54.7% in the mITT population, and 83.7% among evaluable patients; corresponding 6-month ORRs were 31.0%, 42.2%, and 81.8%, respectively. The high proportion of patients without landmark response assessments primarily reflected insufficient follow-up, early death, or disease progression. Elevated LDH remained independently associated with lower response probability and inferior clinical outcomes. Cytokine release syndrome (CRS) occurred in 69% of patients, with grade ≥ 3 events in 5.7%, whereas immune effector cell-associated neurotoxicity syndrome (ICANS) was infrequent (4.6%) and no grade ≥ 3 events occurred. Grade ≥ 3 infections occurred in 39% of patients, including CMV events requiring antiviral treatment in 24.1%. No HBV reactivation occurred among patients receiving antiviral prophylaxis. Median PFS and OS were 8.1 and 10.6 months, respectively. Conclusions: Elranatamab demonstrated early clinical activity and a manageable safety profile in a heavily pretreated real-world RRMM population. Infectious complications, including CMV events, remained clinically relevant, emphasizing the importance of supportive care. Longer follow-up is needed to characterize long-term outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15166231

Authors: Ji Seong Park Byung Ki Cho Tae Kyun Kim Chan Kang Gi Soo Lee Jae Hwang Song

Background/Objectives: Ankle fracture–dislocation is associated with prolonged recovery, posttraumatic osteoarthritis, and poor functional outcomes. However, the structural factors responsible for ankle fracture–dislocation remain incompletely understood. This study aimed to identify the injury characteristics associated with ankle fracture–dislocation and compare radiographic outcomes between patients with and without dislocation. Methods: A retrospective review was performed on 130 patients who underwent operative treatment for ankle fractures. Patients were divided into dislocation (n = 26) and non-dislocation (n = 104) groups. Demographic characteristics, injury mechanism, trauma energy, fracture morphology, posterior malleolar fracture classification, syndesmotic injury, and deltoid ligament injury were evaluated. Independent risk factors were identified using multivariate logistic regression analysis. Bone union time and postoperative osteoarthritis were also compared. Results: Haraguchi type II posterior malleolar fracture (p < 0.001) and syndesmotic injury (p = 0.017) were independently associated with ankle fracture–dislocation. Bone union took significantly longer in the dislocation group than in the non-dislocation group (7.04 ± 3.75 vs. 5.29 ± 3.48 months; p = 0.026). Postoperative osteoarthritis occurred more frequently in the dislocation group (42.3% vs. 24.0%), although the difference was not statistically significant (p = 0.063). Conclusions: Haraguchi type II posterior malleolar fracture morphology and syndesmotic injury were associated with ankle fracture–dislocation. These findings suggest that posteromedial structural disruption and syndesmotic instability play important roles in ankle fracture–dislocation. Furthermore, ankle fracture–dislocation was associated with delayed bone union, indicating a more severe injury pattern.

Journal of Clinical Medicine doi: 10.3390/jcm15166230

Authors: Beining Wang Bei Wang Hui Sun Mengyun Zhu Fengjuan Yao Wen Lu Shun Wang Jun Wang Yunqi Shi Mingxing Xie Ying Yang Wei Ma

Background: Contemporary data on the clinical detection rate and profile of phenotypical hypertrophic cardiomyopathy (HCM) in major Chinese healthcare settings are limited. This multicenter study aimed to determine the detection rate and echocardiographic features of the HCM phenotype in a large Chinese cohort. Methods: This cross-sectional study analyzed echocardiography databases from nine medical centers across China, including adult patients examined during 2023. HCM phenotype was defined as end-diastolic wall thickness ≥15 mm in the left ventricle. Patients with moderate to severe aortic stenosis were excluded. Subcategories included phenotypes of obstructive HCM and apical hypertrophy. Results: Among 655,383 examinations, 2610 patients met the criteria of the HCM phenotype, yielding a detection rate of 0.40% (≈1 in 250). The mean age was 60.2 years with male predominance (70.3%). Asymmetric septal hypertrophy was present in 53.3% of patients. The most commonly involved site with maximal wall thickness was the interventricular septum (57.6%), followed by the apex (20.9%) and the basal septum (17.7%). The overall intra-left ventricular obstruction rate was 16.2%; left ventricular outflow tract obstruction (LVOTO) accounted for 12.1%. LVOTO patients had greater septal thickness, smaller left ventricular diastolic dimensions, and more mitral regurgitation. Female sex was associated with a significantly higher LVOTO rate than males (18.2% vs. 9.6%, p < 0.001). Pure apical hypertrophy was identified in 4.5% of patients, with an increasing detection rate in older age groups. Conclusions: This large-scale, multicenter study confirms a high clinical detection rate for the HCM phenotype (≈1 in 250) in major Chinese centers. Substantial phenotypic heterogeneity across age and sex, coupled with the identification of key factors associated with LVOTO, highlights the need for sex- and age-specific diagnostic strategies and therapeutic planning in clinical practice.

Journal of Clinical Medicine doi: 10.3390/jcm15166229

Authors: Goran Rakic Aleksandar Djuricin Nikolina Maric Mirka Lukic Sarkanović Maja Stefanovic Biljana Draskovic Srdjan Gavrilovic Milena Joksic Zelic Velibor Vasovic Radojka Joksic-Mazinjanin

Background/Objectives: This study aimed to evaluate the incidence and outcomes of emergency medical service (EMS)-treated out-of-hospital cardiac arrest (OHCA) and to determine whether predictors of outcomes differed across the pre-pandemic, pandemic, and post-pandemic periods. Methods: A retrospective observational study was conducted over a six-year period and included 1150 patients with EMS-treated OHCA. Patients were categorized into three groups according to the study period. Results: The incidence of EMS-treated OHCA differed significantly across the three study periods (χ2 = 15.184, p = 0.001), with the highest number of cases observed during the pandemic. The rate of return of spontaneous circulation (ROSC) also varied significantly between periods (p = 0.035). Although the highest overall mortality was observed during the pandemic period (97.5%), differences in overall mortality across the study periods did not reach statistical significance (p = 0.079). Variables independently associated with ROSC were EMS response time, initial cardiac rhythm, and the administration of adrenaline and atropine. Age and initial cardiac rhythm were independently associated with mortality. No significant interactions were observed between study period and the identified predictors of ROSC or mortality. Conclusions: The COVID-19 pandemic was associated with a significant increase in EMS-treated OHCA incidence and poorer patient outcomes, including lower ROSC and survival rates. Although outcomes improved in the post-pandemic period, multivariable analysis demonstrated that the pandemic period itself was not independently associated with ROSC or mortality after adjustment for relevant clinical factors. Instead, outcome differences were primarily explained by established clinical predictors, including patient age, initial cardiac rhythm, EMS response time, and resuscitation-related factors. Prospective studies incorporating more detailed data on patient characteristics, the quality of resuscitation, and organizational characteristics of the healthcare system may enable more accurate outcome modeling.

Journal of Clinical Medicine doi: 10.3390/jcm15166228

Authors: Teodora Anghel Adriana Cojocaru Lavinia Hogea Iuliana Costea Amalia Marinca Raluca Dumache Laura Nussbaum Iuliana-Anamaria Trăilă

Background/Objectives: Psilocybin-assisted therapy has progressed from early proof-of-concept work to a substantially expanded evidence base, with four pivotal studies published in 2025–2026 that were not incorporated into earlier reviews. This review synthesizes the pharmacological and neurobiological foundations of psilocybin and appraises clinical evidence across major depressive disorder (MDD), treatment-resistant depression (TRD), post-traumatic stress disorder (PTSD), cancer-related distress, and substance use disorders, emphasizing long-term durability, expanding indications, and methodological limitations. Methods: A narrative review was conducted using a targeted search of PubMed/MEDLINE, Embase, Scopus, and Web of Science (January 2000–April 2026), emphasizing 2025–2026 publications. Predefined eligibility principles prioritized randomized controlled trials, long-term follow-up studies, and systematic reviews; formal PRISMA procedures were not applied, consistent with the narrative design. Results: Four 2025–2026 studies extend the evidence base: a 52-week follow-up confirming dose-dependent maintenance of antidepressant benefit after a single 25 mg psilocybin session; the first pilot study in Veterans with severe TRD, reporting a 60% response rate at three weeks; the first safety trial in PTSD, where symptom improvement tracked self-transcendent experience intensity but worsened with session anxiety; and a living review of 15 randomized trials confirming a meaningful antidepressant effect while identifying functional unblinding as a substantial threat to effect estimates. Conclusions: Evidence supports psilocybin-assisted therapy as mechanistically distinct and clinically promising, most strongly in MDD and TRD, with preliminary support in PTSD and Veterans. Functional unblinding, small open-label designs, narrow safety populations, and absent SSRI-integration protocols constrain the current conclusions.

Journal of Clinical Medicine doi: 10.3390/jcm15166227

Authors: Jerzy Roch Kolasinski

Background: Severe burn injuries involving the face and scalp have profound physical and psychosocial consequences, and represent the greatest reconstructive challenge in plastic surgery. One comprehensive solution involves the sequential application of autologous fat grafting, follicular unit excision (FUE) hair transplantation, and scalp micropigmentation (SMP); however, the long-term outcomes of this approach have rarely been documented. Methods: A male patient sustained catastrophic methane explosion burns at age 27, involving 79% total body surface area (TBSA) with full-thickness involvement of the face and scalp (Revised Baux Score 123; estimated mortality risk 50–80%). Following 65 reconstructive procedures at external institutions over six years, he was referred to our center at age 30. He presented with extensive facial and scalp scarring, complete absence of eyebrow, beard, and mustache hair, and widespread scalp alopecia. Over an eight-year period, the patient received 11 sessions of autologous FUE hair transplantation (7180 follicular units to the eyebrows, beard, and scalp), four sessions of structural fat grafting using the Coleman technique, and five sessions of SMP. Results: The patient achieved complete reconstruction of facial hair, a natural scalp hairline, and significant scar quality improvement. Conclusions: Our findings demonstrate that systematic, long-term multimodal reconstruction, i.e., combining fat grafting, FUE transplantation, and SMP, can yield clinically meaningful esthetic and psychosocial outcomes, even after the most catastrophic burn injuries.

Journal of Clinical Medicine doi: 10.3390/jcm15166226

Authors: Matko Prtorić Armin Atić Bojan Jelaković Željko Kaštelan Nikolina Bašić-Jukić

Background: Balkan nephropathy (BEN), caused by chronic dietary exposure to aristolochic acid (AA), is a tubulointerstitial kidney disease strongly associated with upper-tract urothelial carcinoma (UTUC). Patient and graft survival, the cumulative incidence and timing of post-transplant UTUC, and the burden of non-urothelial malignancy after kidney transplantation remain poorly defined. Methods: We retrospectively analyzed all patients with BEN as the primary cause of end-stage kidney disease transplanted at University Hospital Center Zagreb between October 1973 and December 2023. Outcomes included patient and graft survival, the incidence and timing of post-transplant UTUC, and burden of non-urothelial malignancies. Results: Of 2282 kidney transplants performed in the study period, 44 (2%) were in patients with BEN. The median age at transplantation was 56 years, and the median dialysis vintage was 3.7 years. After 10 years (median) of follow up, among 34 patients with adequate follow-up, 16 (47%) developed a de novo malignancy: eight (24%) UTUC, one renal cell carcinoma, four other solid tumors, and three hematological. UTUC was diagnosed between 6 months and 15 years post-transplant (median 7 years); five of eight patients died within one year of diagnosis. Five- and ten-year patient survival rates were 82% and 54.5%. Conclusions: Kidney transplantation in patients with BEN carries a lifelong cancer risk dominated by UTUC. Prophylactic bilateral nephroureterectomy should be the default management strategy when feasible, with lifelong surveillance extending beyond the urothelium.

Journal of Clinical Medicine doi: 10.3390/jcm15166225

Authors: Liang Xu Kaixi Qiu Weiliang Wu Xiaofeng Zhu Jiang Chen

Background: This study aimed to develop and evaluate a deep learning (DL) algorithm based on magnetic resonance imaging (MRI) for the classification of temporomandibular joint degenerative joint disease (TMJDJD), thereby exploring its potential role in assisting cone-beam computed tomography (CBCT) examinations and minimizing patient radiation exposure. Methods: A retrospective analysis was conducted on 104 patients who had undergone both MRI and CBCT examinations of the temporomandibular joint. A total of 1769 sagittal and 1448 coronal MRI images were collected. After image preprocessing, the datasets were grouped according to different imaging features. Three DL frameworks—ResNet101, DenseNet201, and MobileNetV2—were developed to classify TMJDJD using various MRI image categories. The classification performance of these models was evaluated using accuracy, precision, recall, F1 score, Matthews correlation coefficient (MCC), and the results were compared with classifications made by two senior clinical experts in a blinded image-level reader experiment. Results: DenseNet201 achieved the best performance in the sagittal (Sg) group, with an accuracy of 80.11%, precision of 80.26%, recall of 75.31%, and an MCC of 0.60. DenseNet201 achieved the best performance among the evaluated DL models, with higher overall performance metrics than ResNet101 and MobileNetV2. In a constrained image-level reader comparison, DenseNet201 demonstrated comparable overall agreement metrics to the two experts, although one expert achieved higher recall and a lower false-negative rate. t-Distributed Stochastic Neighbor Embedding (t-SNE) and training curve analyses confirmed that DenseNet201 demonstrated superior feature extraction capability and a more stable training process. Grouping MRI images, however, did not improve model accuracy. Conclusions: DenseNet201 showed preliminary potential for MRI-based TMJDJD classification, particularly on sagittal images. Based on image-level classification results, the model may provide preliminary support for identifying MRI findings associated with TMJDJD and assisting decisions regarding further CBCT evaluation.

Journal of Clinical Medicine doi: 10.3390/jcm15166224

Authors: Bernardo A. Cedeno-Veloz Juan Erviti Marta Gutiérrez-Valencia Leire Leache Luis Carlos Saiz Alba M. Rodríguez García Nicolás Martínez-Velilla

Background: Evidence on the real-world effectiveness of antiresorptive therapy for hip fracture prevention in very old women remains limited. We aimed to assess the association between antiresorptive use and incident hip fracture among age ≥ 75 older women with osteoporosis. Methods: We conducted a population-based nested case–control study using the Base de Datos para la Investigación Farmacoepidemiológica en Ámbito Público (BIFAP), a Spanish research database. Women aged 75 years or older with osteoporosis and no previous antiresorptive use at cohort entry were followed from 2010 to 2022. Incident hip fracture cases were matched to risk-set controls by age, autonomous region, and calendar year of database registration. Antiresorptive exposure was classified as current, recent, past, or never use. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) and confidence intervals. Results: The study included 2057 incident hip fracture cases and 19,275 matched controls. Compared with never users, current antiresorptive users had lower odds of hip fracture (aOR 0.76; 0.65–0.87), whereas past users had higher odds (aOR 1.91; 1.57–2.33). Ever use was not associated with hip fracture risk compared with never use (aOR 1.01; 0.90–1.13). Conclusions: In this real-world nested case–control study of women aged ≥75 years with osteoporosis, current antiresorptive use was associated with lower odds of hip fracture, whereas past use was associated with higher odds. Because treatment initiation, persistence, and discontinuation are strongly influenced by baseline fracture risk, osteoporosis severity, frailty, and clinical surveillance, these findings should be interpreted as associations rather than causal treatment effects.

Journal of Clinical Medicine doi: 10.3390/jcm15166223

Authors: Andrea Lopez-Lopez Estefanía Rivas Vázquez Margarita Regueiro-Abel Carmen Cristina Álvarez-Suárez Charigan Abou Johk-Casas Juliana Elices-Teja Ramón Ríos Vázquez Germán Santamarina-Pernas Carlos González-Juanatey

Background/Objectives: Traditionally, risk stratification in heart failure with reduced ejection fraction (HFrEF) patients has been a static process. This study aims to identify clinical predictors and causes of mortality at different stages of the disease, distinguishing between early mortality (≤1 year) and late mortality (>1 year), as well as cardiovascular and non-cardiovascular causes. Methods: This is an observational, longitudinal study of a cohort of 1510 patients with HFrEF followed up in a specialist heart failure unit between 2011 and 2023. Patients were categorized into three groups: alive (n = 1093), early mortality (n = 55) and late mortality (n = 362). Multivariate Cox regression models were used to identify mortality independent predictors in each period. Results: During the first year, cardiovascular and non-cardiovascular mortality showed a relatively balanced distribution, with a slight predominance of non-cardiovascular causes (52.8%). Progression of heart failure remained the leading individual cause of early death (38.2%). Independent predictors of early cardiovascular death included ischemic etiology (HR 2.78; 95% CI: 1.20–6.40; p = 0.01), NYHA functional class (HR 4.38; 95% CI: 2.18–8.81; p < 0.001) and renal function (HR 0.60; 95% CI: 0.44–0.84; p = 0.002). In contrast, late mortality (>1 year) was predominantly due to non-cardiovascular causes (59.7%), notably cancer (24.3%) and infections (7.5%). Late all-cause mortality was independently associated with age (HR 1.35; 95% CI: 1.17–1.56; p < 0.001), hypertension (HR 1.38; 95% CI: 1.06–1.81; p = 0.015) and ischemic etiology (HR 1.45; 95% CI: 1.16–1.80; p < 0.001). In the follow-up, the improvement of left ventricular ejection fraction (LVEF) emerged as a protective factor against long-term all-cause mortality (HR 0.77; 95% CI: 0.63–0.94; p = 0.01) and, even more markedly, against late cardiovascular mortality (HR 0.47; 95% CI: 0.33–0.66; p < 0.001), whereas baseline LVEF at diagnosis lacked significant predictive value in either model. Conclusions: Mortality in HFrEF is a dynamic process. Early survival is determined by hemodynamic stability, renal function and functional severity, whilst late survival is predominantly driven by non-cardiovascular comorbidities, biological aging, and ventricular remodeling trajectory. The improvement of LVEF during follow-up is a more reliable prognostic marker than the baseline measurement, suggesting that clinical management should shift from early pharmacological optimization towards a multidisciplinary approach focused on long-term non-cardiovascular risk.

Journal of Clinical Medicine doi: 10.3390/jcm15166222

Authors: Loizos Hadjigeorgiou Melina Yerolatsite Nanteznta Torounidou George Zarkavelis Dimitrios Schizas Vasileios Tatsis Stefano Rausei Konstantinos Vlachos Georgios D. Lianos

Circulating tumor DNA (ctDNA) is a promising non-invasive biomarker for detecting minimal residual disease (MRD) and predicting recurrence after curative treatment, yet evidence in esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric cancer has largely been examined within individual tumor types. In this scoping review, we mapped this evidence across all three malignancies and clarified key methodological and clinical considerations. Following the PRISMA-ScR guidelines, we searched PubMed, Scopus, and the Cochrane Library (3 April 2026) for studies linking ctDNA to disease-free, recurrence-free, or overall survival after curative-intent treatment. Twenty-seven studies (1746 patients; 10 ESCC, 4 EAC, 8 gastric, and 5 mixed) were included. Across every tumor type, postoperative ctDNA MRD was the most informative timepoint, with independent multivariable hazard ratios for disease-free, recurrence-free, or event-free survival of 2.8 to 21.8, whereas preoperative ctDNA was seldom prognostic. Serial monitoring further improved performance and flagged recurrence 78 to 278 days before imaging. Tumor-informed assays showed higher sensitivity than tumor-agnostic ones (80% vs. 35%), though direct comparisons were limited; correction for clonal hematopoiesis was essential for tumor-agnostic assays, and blood-based assays performed poorly in diffuse-type and peritoneal disease. Postoperative ctDNA MRD is a consistent, independent prognostic biomarker across upper gastrointestinal cancers that adds prognostic information beyond conventional staging and pathological response, supporting prospective interventional trials of ctDNA-guided management.

Journal of Clinical Medicine doi: 10.3390/jcm15166221

Authors: Rozeta Sokou Alexandra Lianou Vasiliki Mougiou Andreas G. Tsantes Stefanos Bonovas Argirios E. Tsantes Nicoletta Iacovidou

Neonatal thromboembolic (TE) disease is an increasingly recognized clinical entity, driven by the physiological uniqueness of developmental hemostasis, improved survival of preterm infants, and the widespread use of invasive supportive technologies. Most neonatal thrombotic events are associated with central venous and arterial catheterization which are considered the most significant modifiable risk factors. The clinical spectrum encompasses catheter-related thrombosis, perinatal stroke and site-specific entities such as renal vein and portal vein thrombosis. Each condition presents distinct challenges such as neurological complications, chronic organ dysfunction and portal hypertension. Diagnosis relies primarily on Doppler ultrasonography, though its sensitivity is limited in deep-vessel scenarios, often requiring advanced modalities like magnetic resonance imaging (MRI) or magnetic resonance angiography (MRA). Therapeutic interventions remain controversial due to a lack of high-quality evidence, with current guidelines largely based on observational data. Ultimately, managing neonatal TE requires a nuanced, individualized approach that balances the risk of thrombus extension against the inherent hemorrhagic vulnerability of the neonate. This review aims to provide a comprehensive and up-to-date overview of neonatal TE, emphasizing major clinical entities and diagnostic strategies. It highlights current evidence gaps and outlines future directions, including the need for standardized management protocols and high-quality prospective research.

Journal of Clinical Medicine doi: 10.3390/jcm15166220

Authors: Eiman Shalabna Amy Goh Deepa Gopinath Chen Nahshon Esther Maor-Sagie Rinat Gabbay-Benziv

Objective: We aimed to evaluate the association between intrapartum febrile morbidity and maternal birth trauma among women undergoing vaginal delivery, with stratification by parity. Methods: This retrospective cohort study included women with singleton, cephalic, vaginal deliveries at a university-affiliated medical center between 2018 and 2024, excluding multiple gestations and cesarean deliveries. The primary exposure was intrapartum febrile morbidity, defined as maternal intrapartum temperature ≥38.0 °C, with or without clinical chorioamnionitis. The primary outcome was maternal birth trauma, including first- through fourth-degree perineal lacerations, cervical lacerations, or episiotomy. Multivariable logistic regression models were used to assess the independent association between intrapartum febrile morbidity and birth trauma. Analyses were additionally stratified by parity. Results: Among 21,736 women with vaginal deliveries included in the study, birth trauma occurred in 41.8% of deliveries (9075/21,736). Intrapartum febrile morbidity was more common among women with birth trauma compared with those delivering with an intact perineum (4.2% vs. 1.8%, p < 0.001). After adjustment for confounders, intrapartum febrile morbidity remained independently associated with birth trauma in the overall cohort (adjusted odds ratio [aOR], 1.5; 95% CI, 1.1–1.8). In parity-stratified analyses, the association persisted among multiparous women (aOR 1.8; 95% CI, 1.2–2.9) but was not statistically significant among nulliparous women (aOR, 1.3; 95% CI, 0.9–1.7). Nulliparity and operative vaginal delivery were the strongest predictors of birth trauma. Conclusions: These findings suggest that intrapartum febrile morbidity may identify women at increased risk of lower genital tract trauma beyond established mechanical risk factors.

Journal of Clinical Medicine doi: 10.3390/jcm15166219

Authors: Phi Dinh Truong Hoai Thu Thi Nguyen Quang Ngoc Nguyen Linh Huynh Dinh Nguyet Minh Thi Giap Thai Quoc Nguyen Minh Nhat Pham Than Xuan Le Long Phi Ngo Trang Ngoc Nguyen Hue Minh Thi Bui Thanh Van Nguyen Olivier Morel Hung Manh Pham

Background/Objectives: Leaflet thrombosis after transcatheter aortic valve replacement (TAVR), typically identified as hypoattenuated leaflet thickening (HALT) on multidetector computed tomography (MDCT), is increasingly recognized as an early manifestation of bioprosthetic valve dysfunction. However, factors associated with early HALT in Southeast Asian populations remain poorly characterized. The objective of this study was to characterize MDCT features of leaflet thrombosis and identify factors independently associated with early HALT after TAVR. Methods: In this two-center observational study, patients undergoing MDCT 1–3 months after TAVR were evaluated. Leaflet thrombosis was defined as HALT. Leaflet involvement, thrombus severity, anatomical distribution, and post-implantation geometric parameters were analyzed. Multivariable logistic regression identified factors associated with early HALT. Results: Among 65 patients, HALT was detected in 30.8%, predominantly as subclinical leaflet thrombosis (29.2%), whereas clinical valve thrombosis was rare (1.5%). Most cases involved one or two leaflets, with preferential involvement of the non-coronary cusp. Patients with HALT showed greater increases in transvalvular peak gradients, and a peak gradient increase ≥10 mmHg was more frequent than in patients without HALT (30.0% vs. 4.4%; p = 0.008). Severe RCA ostial eccentricity (grade 3–4) combined with a neo-sinus–RCA distance > 13 mm was independently associated with HALT (adjusted OR 5.52; p = 0.006). Lack of left ventricular ejection fraction improvement after TAVR was also independently associated with HALT (adjusted OR 4.44; p = 0.018), though given the limited number of HALT events (n = 20), these multivariable associations should be regarded as exploratory and hypothesis-generating. Conclusions: Early post-TAVR leaflet thrombosis is common and predominantly subclinical. CT-derived neo-sinus geometry and impaired ventricular recovery were independently associated with HALT, supporting the hypothesis that altered neo-sinus washout contributes to thrombus formation.

Journal of Clinical Medicine doi: 10.3390/jcm15166216

Authors: Renata Martinelli Luca Massimi

Background: Idiopathic syringomyelia (IS) is defined by exclusion: an intramedullary fluid-filled cavity without Chiari malformation, spinal trauma, tumor, infection, or other identifiable cause. Growing evidence suggests IS is a progressively shrinking category as advanced imaging and intraoperative exploration uncover occult arachnoid or hydrodynamic substrates. To the best of our knowledge, no systematic reviews of the literature have been published on this topic. The authors aim to map operational definitions of IS, summarize proposed pathogenetic mechanisms, characterize diagnostic strategies and their yield, describe management approaches and outcomes, and identify pediatric–adult differences. Methods: A scoping review was conducted in accordance with PRISMA-ScR. PubMed and Scopus were searched from inception to May 2026. Eligible sources were original studies of any design addressing IS in pediatric or adult patients, in English. Studies on syringomyelia secondary to Chiari malformation, trauma, tumor, or infection were excluded. Data were extracted across five domains and synthesized narratively. Results: Eighteen studies (365 patients; five case reports, nine retrospective cohorts, two morphometric studies, one cine-MRI case–control, one technical note) were included. Operational definitions were markedly heterogeneous. Four pathogenetic mechanisms emerged: subarachnoid CSF obstruction with abnormal intramedullary pulse pressure, occult arachnoid pathology, posterior fossa morphometric variants overlapping with the Chiari spectrum, and persistent central canal as a developmental variant. In the four largest pediatric series (n = 214), 91–95% of children remained stable or improved on conservative management at up to 7-year follow-up, with no concordance between syrinx size change and clinical course. In symptomatic adults, targeted arachnoid lysis or web excision yielded clinical improvement in 87% of IS-occult arachnoid web patients; syringo-subarachnoid shunting was occasionally effective but risked neurological deterioration without prior substrate identification. Conclusions: The idiopathic label reflects the current limits of diagnostic investigation rather than a fixed nosological entity, since occult arachnoid or hydrodynamic substrates are identified in most adult IS cases when advanced imaging and intraoperative exploration are systematically deployed. Pathogenesis converges on a unified model of subarachnoid CSF obstruction generating abnormal intramedullary pulse pressure. Management should be driven by clinical, not radiological, evolution: arachnolysis or web excision is the primary strategy when an operable substrate is identified, while conservative management remains best supported in clinically stable patients, particularly children.

Journal of Clinical Medicine doi: 10.3390/jcm15166218

Authors: Carolin Schröder Sheila Bonilla Moran Verena Kirn Andree Faridi Philipp Meyer-Wilmes Laila Najjari Fabinshy Thangarajah Sebastian Hentsch Christian Kurbacher Laura Tascón Padrón Lucia A. Otten Eva K. Egger Alexander Mustea Dominique Koensgen

Background/Objectives: Women with breast cancer (BC) and gynaecological cancer (GC) often undergo extensive oncological treatment, which can lead to pelvic floor disorders (PFD). However, there is still limited evidence regarding their real-world treatment practices, patient counselling, and prevalence. This study aims to systematically evaluate the prevalence of PFD and current treatment approaches, identify unmet needs, and improve future care. Methods: This observational multicentre survey was conducted at four university hospitals and one gynaecological oncology outpatient clinic in Germany. Women with BC and GC, who had undergone at least one oncological treatment, completed anonymously a study-specific questionnaire and the validated German Pelvic Floor Questionnaire. Recruitment was undertaken over a period of nine months, reflecting real-world daily care. Results: A total of 246 patients were included (median age 57 years, range 30–88); 74% were postmenopausal, and 52% had at least one vaginal delivery. BC was the most common diagnosis (63.8%). The most common symptoms were urinary incontinence (22.3% in BC, 38.1% in GC) and urgency (32.5% in BC, 35.7% in GC). Pelvic radiotherapy was significantly associated with increased urgency symptoms (p = 0.017), pelvic surgery with urgency symptoms (p = 0.048) and dyspareunia (p = 0.045), and antihormonal therapy with vaginal dryness (p = 0.028). The combination of chemotherapy and antihormonal therapy was associated with significantly higher rates of vaginal dryness in women with GC, whereas no such association was observed in women with BC (p = 0.036). Among the 108 patients classified as having new-onset symptoms, 51 (47.2%) reported symptom onset within one year of the cancer diagnosis. Overall, 34.1% of patients reported impairment in more than one patient-reported domain, including daily life, social life, sexual well-being, and psychological well-being. The median study-specific impact rating for the most bothersome pelvic floor symptom was 5/10. Only 28.0% of patients received prior counselling on PFD, and 19.9% were actively asked about symptoms. In total, 26.0% received urogynaecological treatment, whereas 15.4% reported unmet treatment needs. Conclusions: PFD is highly prevalent in women with BC and GC. Symptoms are clinically relevant but underestimated in routine care. Despite the availability of effective treatment options, significant gaps exist in patient counselling, early detection, and access to specialised care.

Journal of Clinical Medicine doi: 10.3390/jcm15166217

Authors: Dae-Woong Kim Eui-Dong Yeo Ki Jin Jung Chang Hwa Hong Sung Hyun Lee Jae Young Ji Dhong-Won Lee Woo-Jong Kim

Background: In high-grade syndesmotic injuries involving combined disruption of the anterior inferior tibiofibular ligament (AITFL) and posterior inferior tibiofibular ligament (PITFL), most suture-tape augmentation techniques have focused on the AITFL alone. This study evaluated the clinical and radiologic outcomes of a suture-tape-only anterior and posterior (A-P) augmentation technique, with a primary focus on technical feasibility and maintenance of syndesmotic reduction. Methods: We retrospectively reviewed consecutive patients who underwent A-P syndesmotic augmentation using nonabsorbable suture tape, based on clinical and radiologic data available from January 2022 through April 2026. Complete disruption of both the AITFL and PITFL was confirmed arthroscopically and by direct visualization. Clinical outcomes were assessed using the Olerud–Molander Ankle Score (OMAS) and visual analog scale (VAS) preoperatively and at the 1-year postoperative assessment. Syndesmotic reduction was evaluated on bilateral computed tomography (CT) scans obtained 1 year postoperatively using the direct anterior difference (DAD), direct posterior difference (DPD), fibular translation (FT), and fibular rotation (FR), with the uninjured contralateral ankle serving as the reference. Results: Seven patients (mean age, 35.1 years; mean follow-up, 26.3 months) were included. At the 1-year postoperative assessment, the mean OMAS increased from 1.4 ± 3.8 to 86.4 ± 5.6, whereas the mean VAS score decreased from 8.1 ± 0.7 to 0.3 ± 0.5 (both p = 0.016), with preoperative scores obtained in the acute injury setting. For both observers, no individual absolute side-to-side difference exceeded the predefined malreduction threshold for any of the four CT parameters. Bony union was achieved in all cases. One patient developed a superficial wound complication, and no reoperations were required. Conclusions: In this small, selected case series, A-P suture-tape augmentation was technically feasible, and syndesmotic reduction was maintained at 1 year postoperatively in patients with combined AITFL and PITFL injuries. These preliminary findings warrant further evaluation in larger comparative studies.

Journal of Clinical Medicine doi: 10.3390/jcm15166215

Authors: Qing Guo Hong Luan Xiaohong Chen Xi Zhao Mouhsun Chiang Ling Wu Xixi Tan Xue Min Xiaolin Feng Bo Xiao Mi Chen Jialin Lin Zhenying Zhang

Background/Objectives: Psoriatic arthritis (PsA) affects up to 30% of psoriasis patients but remains underdiagnosed due to heterogeneous early manifestations. Existing tools rely on advanced imaging or biomarkers, limiting feasibility. This study aimed to develop a simple nomogram, using routinely available clinical features to identify patients with likely PsA. Methods: This multicenter cross-sectional study enrolled adult psoriasis patients from two tertiary hospitals (training: n = 884; validation: n = 690). PsA was diagnosed using the Classification Criteria for Psoriatic Arthritis (CASPAR) by rheumatologists and dermatologists who were blinded to each other’s assessments. Thirteen candidate predictors, including demographics, disease history, and lesion characteristics, were prespecified. Independent predictors were selected using least absolute shrinkage and selection operator (LASSO) regression, followed by multivariable logistic regression. Internal validation used 1000 bootstrap resamples, followed by temporal–geographic validation. Performance was assessed using area under the curve (AUC), calibration plots, the Hosmer–Lemeshow test, decision curve analysis (DCA), and clinical impact curves (CIC). Sensitivity analyses included E-value analysis for unmeasured confounding and alternative model specifications. Results: Five independent predictors were identified: uveitis (odds ratio (OR): 5.23, 95% confidence interval (CI): 1.94–14.10), inverse lesions (OR: 1.65, 95% CI: 1.09–2.48), scalp lesions (OR: 2.97, 95% CI: 1.45–6.10), nail lesions (OR: 5.98, 95% CI: 3.69–9.68), and arthralgia (OR: 20.23, 95% CI: 13.14–31.13). The nomogram showed good discrimination (AUC: 0.885 training, 0.874 validation), with good calibration and clinical utility confirmed by DCA and CIC. Conclusions: This nomogram, integrating five clinically accessible predictors, offers a practical tool to identify psoriasis patients with likely PsA, supporting timely referral in tertiary dermatology outpatient settings.

Journal of Clinical Medicine doi: 10.3390/jcm15166211

Authors: Alessio Barrancotto Simone Di Cola Fabio Melandro Lucia Lapenna Anthony Vignone Antonio Bencivenga Arianna Brancati Pierleone Lucatelli Mario Corona Stefania Gioia Silvia Nardelli

Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment for complications of portal hypertension, but hepatic encephalopathy (HE), liver dysfunction, rebleeding, and mortality remain difficult to predict in otherwise eligible candidates. However, predicting post-TIPS outcomes remains challenging using conventional risk scores such as MELD 3.0 and Child–Turcotte–Pugh. This narrative review critically evaluates how clinical, biochemical, procedural, conventional imaging, handcrafted radiomics, and deep-learning features can be integrated for personalized post-TIPS risk prediction, supplemented by backward and forward reference checking. Thirty-two original post-TIPS studies met the core inclusion criteria: 18 focused primarily on clinical, biochemical, hemodynamic, microbiome, or procedural predictors and 14 on imaging, body composition, radiomics, or multimodal models. AI, ML, and radiomics models, by the aim of logistic regression, tree-based ensembles, support vector machines, artificial neural networks, and hybrid deep-learning models, able to capture non-linear interactions, have consistently demonstrated improved predictive performance compared with conventional scores, particularly for HE, with reported incidences of approximately 20–47%, mortality, and liver dysfunction. Their advantage lies in the ability to model complex, non-linear relationships and integrate heterogeneous data sources, including laboratory parameters, ammonia levels, hemodynamic variables, and imaging-derived features. Radiomics and deep learning approaches further enhance predictive accuracy. CT is currently the principal imaging substrate, while direct post-TIPS radiomics evidence for MRI and ultrasound remains sparse. Studies of liver and spleen morphology, portal-vein geometry, muscle and adipose tissue, and radiomic texture suggest incremental information beyond conventional scores, particularly when clinical and imaging features are combined; however, negative volumetric findings show that additional image features do not automatically improve prediction. However, most studies are retrospective, single-center, and lack external validation and no validated transformer-based or other sequence model has yet been established for post-TIPS outcomes. Standardization issues in radiomics and limited model interpretability remain significant barriers. Future directions should lead to prospective multicenter cohort validation, increasing sample sizes, harmonized imaging and endpoint definitions, locked external validation with recalibration, and the development of clinically interpretable tools to make it easier to identify those patients suitable for TIPS and their post-procedural management.

Journal of Clinical Medicine doi: 10.3390/jcm15166214

Authors: Adnan Arslan Aytekin Dikici Ferhat Danışman Yunus Can Ünal Ömer Faruk Yıldırım Şehmuz Kaya

Background/Objectives: Plain radiography is the first-line imaging modality for acute foot and ankle trauma; however, computed tomography (CT) may provide additional information in selected patients with persistent clinical suspicion, equivocal radiographic findings, or a need for detailed fracture characterization. We hypothesized that the CT-confirmed fracture proportion would be higher among patients with suspicious radiographs than among those with normal radiographs and that CT would identify additional fractures in a clinically selected cohort. Methods: This retrospective single-center selected-cohort study included 1000 adult patients with isolated foot and/or ankle trauma who underwent both plain radiography and CT during the same clinical encounter. Plain radiographs were categorized as normal, suspicious for fracture, or definite fracture on the basis of original radiology reports and available imaging records. A CT-confirmed fracture was defined as the presence of an acute fracture on CT. Analyses focused primarily on CT-confirmed fracture proportions and conditional diagnostic yield within the selected CT cohort. Conditional apparent diagnostic performance was evaluated as a supplementary sensitivity analysis and was not intended to estimate population-level diagnostic accuracy. Results: Plain radiographs were categorized as normal in 628 patients, suspicious in 283, and definite fracture in 89. CT detected acute fractures in 386 patients (38.6%). The CT-confirmed fracture proportions were 14.8% in the normal radiograph group, 72.1% in the suspicious radiograph group, and 100.0% in the definite fracture group. The proportion of patients without a definite fracture on plain radiography but with an acute fracture on CT was 29.7%. Fracture-pattern classification was unavailable in 85 of 386 cases with CT-confirmed fractures (22.0%); therefore, fracture-pattern analyses were considered exploratory. Conclusions: In this selected CT cohort, CT identified additional acute fractures in a subset of adult isolated foot and ankle trauma cases that could not be definitively classified as fractures on plain radiography. Because CT was not systematically performed in all trauma patients, the findings represent selected-cohort CT yield rather than true population-level diagnostic accuracy.

Journal of Clinical Medicine doi: 10.3390/jcm15166213

Authors: Robert Jan Łuczyk Kamil Sikora Agnieszka Zawada Marta Łuczyk Dorota Weber Anna Charuta

Background: Stress is regarded as one of the natural and unavoidable elements of human life and, at the same time, one of the key determinants of physical and mental health. Stress is not a new phenomenon; it has accompanied human beings since the beginning of life as a reaction to everyday challenges. This study aimed to assess the prevalence and severity of stress, as well as stress-coping strategies, in a group of patients treated for oncological reasons. Methods: The study included 108 patients hospitalized at the Independent Public Clinical Hospital No. 1 in Lublin, Poland, in the following departments: the 2nd Department of General, Gastroenterological and Gastrointestinal Oncological Surgery; the Department of Oncological Surgery; and the Department of Hemato-Oncology and Bone Marrow Transplantation. Three standardized questionnaires were used: the Perceived Stress Scale (PSS-10), the Type D Personality Scale (DS-14), and the “How Do I Cope” Inventory (JSR). Statistical analysis was performed with IBM SPSS Statistics, version 25; statistical significance was set at α < 0.05. Results: Patients treated for oncological reasons constitute a group exceptionally exposed to stress, which accompanies them at every stage of the disease, from diagnosis, through treatment, to the terminal phase. In patients whose treatment resulted in remission, stress related to the possibility of recurrence accompanies every follow-up examination and every worrying symptom. Given the range of situations that provoke stress, the overall level of stress in this group can be regarded as high. Stress-coping strategies among oncological patients are shaped by multiple factors, including selected sociodemographic characteristics; taking into account the diversity of these factors, coping strategies varied considerably across the sample. The level of coping strategies was not associated with age or sex but was significantly associated with educational attainment. Conclusions: Oncological patients experience a high and pervasive level of stress that persists throughout diagnosis, treatment, and follow-up. Stress-coping strategies are heterogeneous, are not determined by age or sex, but are shaped by education, indicating a need for individualized psychosocial and educational support integrated into routine oncological care.

Journal of Clinical Medicine doi: 10.3390/jcm15166212

Authors: Min Seok Kim Hahn Jin Jung Soo Kyoung Park Seung Hyuk Yang Shin Hyuk Yoo Ji-Hun Mo

Objectives: Factors influencing outcomes of endoscopic dacryocystorhinostomy (DCR) for primary acquired nasolacrimal duct obstruction remain unclear. We evaluated clinical factors associated with surgical success. Methods: We retrospectively reviewed patients who underwent endoscopic DCR for this indication (2012–2022). Allergic rhinitis, obstruction level and type, canalicular intubation stent (CIS) insertion, and adjunctive procedures were analyzed against surgical success, epiphora scores, and SNOT-22 change using multivariate logistic regression. Results: Among 300 eyes (259 patients), the success rate was 82.0%. Epiphora scores improved from 7.6 ± 1.3 to 4.0 ± 2.3 and SNOT-22 from 17.3 ± 19.1 to 11.1 ± 14.2 (both p < 0.001). Sac-level and duct–sac junction obstructions had higher success than canalicular obstruction, and allergic rhinitis was associated with less epiphora improvement. CIS insertion was associated with lower success; however, this was confined to functional (42.0% vs. 92.0%) and canalicular-level (53.3% vs. 77.6%) obstruction—where CIS was selectively used—and absent in drainage-level obstruction (85.3% vs. 85.7%), indicating confounding by indication. Conclusions: Endoscopic DCR yields favorable outcomes with significant epiphora and quality-of-life improvement. Obstruction level, allergic rhinitis, and CIS insertion were associated with surgical outcomes; the CIS association, however, likely reflects confounding by indication rather than a direct adverse effect, as CIS was selectively used in functional and canalicular-level obstruction.

Journal of Clinical Medicine doi: 10.3390/jcm15166210

Authors: Abdullah Raizah

Objectives: To determine whether concomitant polytrauma is independently associated with worse in-hospital outcomes among fall-related proximal humerus fracture (PHF) patients and whether fracture subtype is associated with heterogeneity in this association. Methods: Retrospective cohort study using the American College of Surgeons Trauma Quality Program Participant Use File (ACS TQP-PUF; 2019–2022). Adults with PHF and a fall mechanism were included. Multivariable logistic regression adjusted for age, sex, the five mFI-5 components, anticoagulant use, and calendar year. Non-home discharge (NHD) was restricted to survivors. Sensitivity analyses used 1:1 PSM (all primary covariates in propensity model; post-matching SMDs assessed) and restriction to ground-level falls. Results: Among 63,995 fall-related PHF patients (70.5% female; 75.8% aged ≥65 years), 3884 (6.1%) met polytrauma criteria (ISS ≥ 16); polytrauma patients were more often male (45.1% vs. 28.5%) and slightly younger (mean age 69.3 vs. 72.0 years). Polytrauma was independently associated with in-hospital mortality (aOR 7.05, 95% CI 6.14–8.09) and non-home discharge among survivors (aOR 1.95, 95% CI 1.79–2.12; crude 72.0% vs. 64.6%). ICU utilization (aOR 13.25, 95% CI 12.34–14.22) and any complication (aOR 3.41, 95% CI 3.07–3.79) are reported as descriptive markers subject to triage and ascertainment bias, respectively. The ICD-10 subtype-stratified mortality aORs ranged from 3.36 to 8.28 across five strata (exploratory; no formal interaction test performed). PSM (3884 pairs; n = 7768) and ground-level fall restriction produced estimates consistent with the primary analyses. Conclusions: Concomitant polytrauma was independently associated with substantially higher in-hospital mortality and non-home discharge after fall-related PHF, identifying a high-risk subgroup that warrants closer clinical attention.

Journal of Clinical Medicine doi: 10.3390/jcm15166209

Authors: Nicola Rizzieri Luca Dall’Asta Maris Ozolinš

Objectives: The purpose of this study was to evaluate the ability of computer vision models to detect myopia from standard colour fundus photographs and to compare their diagnostic performance with that of experienced ophthalmologists. Methods: A previously published dataset of 324 retinal fundus images labelled as myopic or non-myopic based on cycloplegic refraction as used for model training and internal validation. Images were acquired using a non-mydriatic 45° fundus camera. Final model evaluation was performed on an independent test set of 50 images from different patients who were not included in the original dataset. YOLOv8 and YOLOv11 variants were trained for binary classification. Internal validation used patient-level cluster bootstrap confidence intervals, whereas image-level bootstrap confidence intervals were estimated for the independent test set. Pairwise model comparisons were adjusted using the Holm–Bonferroni correction. Five experienced ophthalmologists independently classified the test set, and their consensus was compared with the selected YOLO models using DeLong’s and exact McNemar tests. Results: Internal validation identified YOLOv8-m and YOLOv11-n as the best-performing models according to a predefined composite score used exclusively for model selection. On the independent test set, YOLOv11-n achieved the highest area under the curve (AUC = 0.889), followed by YOLOv8-m (0.806), although the difference was not statistically significant (DeLong test, p > 0.05). The clinical consensus achieved an AUC of 0.832, with no significant difference compared with either model. Exact McNemar testing likewise revealed no statistically significant differences in paired classification outcomes between either AI model and the clinical consensus. Limitations include the small, single-centre, class- and age-imbalanced dataset and the limited number of expert observers. Conclusions: Although neither YOLOv8-m nor YOLOv11-n showed statistically significant differences from the clinical consensus on this independent test set, these findings should be interpreted cautiously given the relatively small, single-centre study population. Larger multicentre studies with independent external validation are warranted to confirm the generalisability, robustness, and potential role of clinician-driven computer vision models as decision support tools for myopia screening.

Journal of Clinical Medicine doi: 10.3390/jcm15166208

Authors: Piotr Morasiewicz Anna Robinson Łukasz Tomczyk Krystian Kazubski Marta Laszkowska Morasiewicz Paweł Leyko

Background: Achilles tendon contracture is a prevalent issue in pediatric populations, often leading to complications such as toe walking and limited ankle dorsiflexion. This study aims to compare the clinical outcomes of two surgical techniques for Achilles tendon lengthening—conventional percutaneous lengthening and Z-plasty—in children with idiopathic Achilles tendon contracture, while assessing the adequacy of a six-week postoperative immobilization period. Methods: A retrospective analysis was conducted on 60 pediatric patients (ages 5–17) who underwent Achilles tendon lengthening at our institution between 2021 and 2025. Patients were divided into two groups: 25 receiving percutaneous lengthening and 35 undergoing Z-plasty. Inclusion criteria encompassed idiopathic contracture with a follow-up of over 12 months. Outcomes measured included ankle dorsiflexion, time to resume normal activities, length of hospital stay, duration of cast immobilization, complications, the likelihood of choosing the same treatment method again, taking analgesics, AOFAS score, and patient/guardian satisfaction. Results: Both surgical methods resulted in significant improvements in ankle dorsiflexion and functional outcomes. The percutaneous group demonstrated a mean increase of 30° in dorsiflexion, while the Z-plasty group showed a mean increase of 32.5°. The time from surgery to resuming normal activities in the Z-plasty group ranged from 6 to 11 weeks, which was significantly higher than the range of 6 to 7 weeks in the percutaneous lengthening group, p = 0.024. Guardian and patient satisfaction was high in both groups, with 94.3% of patients from the Z-plasty group and 100% of patients from the percutaneous group expressing willingness to choose the same treatment again. Four patients (11.4%) from the Z-plasty group and one patient (4%) from the percutaneous lengthening group developed complications. Conclusions: The period of cast immobilization of six weeks helped achieve good outcomes and caused few complications in children from both study groups. The conventional percutaneous approach to Achilles tendon lengthening in children helps achieve substantial correction of ankle dorsiflexion with a low risk of complications. Due to the risk of selection bias, the results should be interpreted with caution.

Journal of Clinical Medicine doi: 10.3390/jcm15166207

Authors: Yuntao Wang Jihong Zhang Xiaopeng Liu Xibing Zhuang Qi Zhang

Background: Distant metastatic relapse remains a major problem after treatment for lung cancer. We examined the association between pre-treatment neutrophil-to-lymphocyte ratio (NLR) and newly documented distant metastasis within 2 years among patients without distant metastasis at baseline. Methods: We retrospectively screened 527 consecutive unique patients with a hospital diagnosis of lung cancer who were managed between 1 January and 31 December 2022; follow-up continued for 24 months after initial treatment (administrative cutoff, 31 December 2024). After hierarchical exclusions, 186 complete cases remained. The primary analysis included 148 patients with stage I–III disease and used record-based incident distant metastasis within 24 months, determined by comprehensive clinical assessment. Logistic regression estimated the association between continuous NLR and the endpoint before and after adjustment for age, sex, and clinical stage. Stage IV patients were retained only in a secondary analysis of the original heterogeneous composite endpoint. Results: Thirty-one out of 148 patients with stage I–III disease (20.9%) developed distant metastasis within 2 years. Mean pre-treatment NLR was 2.83 in patients with an event and 2.07 in those without an event. Each one-unit increase in NLR was associated with higher odds of distant metastasis in the unadjusted model (odds ratio [OR] 2.71, 95% confidence interval [CI] 1.65–4.45; p < 0.001) and after adjustment for age, sex, and stage (adjusted OR 2.70, 95% CI 1.60–4.57; p < 0.001). In the secondary full-cohort analysis, 49 of 186 patients met the heterogeneous composite endpoint. Conclusions: Higher pre-treatment NLR was associated with 2-year incident distant metastasis in this stage I–III cohort. The result does not establish causality or a clinically actionable cut point and requires prospective external validation.

Journal of Clinical Medicine doi: 10.3390/jcm15166205

Authors: Aishah Ibrahim Albakr Alia Alokley Feras AlSulaiman Mustafa Ahmed Alqarni Saud A. Alnaaim Ali Hafiz Alhashim Mohammed Alshurem Abrar J. Alwaheed Safi G. Alqatari Erum Sharif Azra Zafar Kawther Mohammed Hadhiah Foziah Jabbar Alshamrani Rizwana Shahid Ammar S. Bukhamsin Fahad Hammad F. Alrayes Rahaf Marhoom Alsaadi Farah Abdullah Alsaqr

Background/Objectives: Young-onset ischemic stroke shows substantial etiologic heterogeneity. However, the value and diagnostic yield of advanced cardiac and autoimmune evaluations in young adults remain uncertain. Methods: Patients aged 25–55 years admitted with acute ischemic stroke to King Fahd University Hospital in Saudi Arabia between January 2020 and December 2025 were included. Evaluation followed a multidisciplinary young-stroke pathway, incorporating neurovascular imaging, cardiac assessment, and targeted autoimmune and rheumatologic investigations. A Clinically Meaningful Diagnostic Yield (CMDY) was defined as a diagnostic finding that resulted in etiologic reclassification, management modification, or changes to secondary prevention strategy. Results: A total of 480 patients were included (median age, 40 years; 67.7% men). CMDY was observed in 200 (41.7%) patients. Among 79 patients initially classified as having embolic stroke of an undetermined source, 35 (44.3%) were assigned a determined etiologic mechanism following evaluation and follow-up. Patients with undetermined stroke etiology decreased from 16.5% after first-pass evaluation to 9.2% after diagnostic completion. Patent foramen ovale/atrial septal defect-associated stroke mechanisms were identified in 61 patients (12.7%), autoimmune/inflammatory stroke mechanisms in 26 patients (5.4%), and atrial fibrillation-related cardioembolic stroke in 18 patients (3.8%). Clinically relevant mechanisms were identified in 169 patients (35.2%) whose primary etiologic classification remained unchanged. Independent predictors of CMDY were hypertension, prior stroke or transient ischemic attack, multi-territory infarction, and cortical infarction. Conclusions: Etiologic evaluation yielded clinically meaningful findings in over two-fifths of young adults with ischemic stroke and influenced etiologic assessment, treatment, and secondary prevention. Diagnostic yield was greatest among patients with prior cerebrovascular events and cortical or multi-territory infarctions, supporting a selective, phenotype-driven approach that warrants prospective multicenter validation.

Journal of Clinical Medicine doi: 10.3390/jcm15166206

Authors: Mitri K. Khoury R. Trey Rogers Hasan Aldailami Tiziano Tallarita Shiv Patel

Background/Objectives: Endovascular repair (EVAR) is the default for most abdominal aortic aneurysms (AAAs), yet open repair (OR) remains necessary, and the decision hinges on fitness for open surgery. No standardized preoperative tool defines who is “unfit” for OR. We derived and validated a preoperative risk score for severe major adverse events (MAE) after elective OR and examined whether high-risk patients had fewer perioperative events with EVAR. Methods: Using the Vascular Quality Initiative (VQI) Open AAA registry, we identified 9833 elective AAA OR patients without prior aortic surgery. Severe MAE was a 30-day composite of death, myocardial infarction (MI), stroke, new dialysis, or bowel ischemia. A multivariable model was converted to an integer score, validated, and benchmarked against the Revised Cardiac Risk Index (RCRI), E-PASS, and a Vascular Quality Initiative Frailty Index. High-risk (score ≥ 7) OR patients were propensity score matched 1:1 to elective EVAR patients and outcomes were compared. Results: Severe MAE occurred in 10.8% of OR patients. The 0–18-point score had an optimism-corrected C-statistic of 0.67 and calibration slope of 0.96, and it outperformed RCRI (C 0.57), E-PASS (C 0.61), and a Vascular Quality Initiative Frailty Index (C 0.63) (all ΔAUC p < 0.001). Severe MAE rose across low (4%), intermediate (9%), and high (20%) tiers; performance was stable on temporal validation (AUC 0.67, slope 0.94). Among 2357 matched high-risk pairs, severe MAE was 20.3% (OR) vs. 4.4% (EVAR) (risk difference +15.9 percentage points; relative risk 4.6), with the largest absolute benefit in the highest-risk patients. Conclusions: A simple preoperative score stratifies perioperative risk for elective open AAA repair and outperforms generic indices. High-risk patients would have had markedly fewer perioperative adverse outcomes if treated with EVAR. These associational findings can inform shared decision-making.

Journal of Clinical Medicine doi: 10.3390/jcm15166201

Authors: Alejandro José Gonzalez-Ochoa Juliana de Miranda Vieira Paola Ortiz Joana Storino Konstantinos Kavallieros Takaya Murayama Nicole Marie Yuja Valle Joana Margarida Magalhães Ferreira Windsor Ting

Acute deep vein thrombosis (DVT) continues to represent a significant global contributor to morbidity and mortality. Although multiple international societies have published evidence-based clinical practice guidelines, important differences persist. This structured narrative review compares contemporary international guidance to identify areas of consensus, methodological divergence, evidence gaps, and priorities for future research. Recommendations were compared across diagnostic evaluation, anticoagulant selection, treatment duration, outpatient management, compression therapy, endovascular intervention, and special populations. Broad agreement was identified regarding clinical pretest probability assessment, D-dimer testing, compression ultrasonography, and direct oral anticoagulants as first-line therapy for most eligible patients with acute DVT. Clinically important differences remain, however, in the management of isolated distal DVT, anticoagulation duration, catheter-directed interventions, compression therapy, and selected high-risk populations. These discrepancies primarily reflect differences in publication timing, methodological frameworks, interpretation of emerging evidence, and healthcare-system context rather than fundamentally conflicting evidence. Contemporary international guidance therefore demonstrates substantial convergence on the core principles of acute DVT management while continuing to differ in areas supported by limited or evolving evidence. Future harmonization will require high-quality randomized trials, broader international collaboration, and the integration of precision medicine, validated risk-prediction models, biomarkers, and emerging anticoagulant strategies into guideline development.

Journal of Clinical Medicine doi: 10.3390/jcm15166204

Authors: Jinhu Chen Cheng Zhang Ligang Zhang Hexi Du Changsheng Zhan

Background: Retroperitoneoscopic laparoscopic adrenalectomy (RLA) is widely adopted for benign adrenal lesions due to its direct access and minimal bowel interference. However, expanding indications to larger tumors and complex anatomies increase technical difficulty because of the confined retroperitoneal space and obscured hilar landmarks. Current predictive models mainly focus on transperitoneal approaches and lack specificity for RLA. This study aimed to develop and internally validate a preoperative nomogram for predicting RLA-specific surgical difficulty. Methods: All patients undergoing RLA from April 2024 to February 2025 at a single center were included. Operative time and postoperative hemoglobin (Hb) reduction were used as surrogate markers of difficulty. Patients were classified into high- and standard-risk groups. Univariate and multivariate analyses were performed to identify predictors of difficult RLA and develop a composite difficulty score. Results: Tumor position (between the upper renal pole and renal pedicle: OR 8.819, 95% CI 3.981–21.462, p < 0.001) and pheochromocytoma (PHEO) pathology (OR 34.881, 95% CI 3.841–4719.428, p < 0.001) were the strongest independent predictors of high surgical difficulty, whereas tumor size (≥40 mm: OR 3.926, p = 0.071) showed limited predictive value. The composite score demonstrated excellent discrimination, with an optimism-corrected area under the curve (AUC) of 0.828 (95% CI 0.796–0.835). The nomogram showed robust calibration, and a cutoff score ≥ 2 yielded a negative predictive value of 0.940. Conclusions: This study developed an RLA-specific nomogram incorporating tumor size, position, and pathology. The tumor–renal pedicle relationship was more predictive of surgical difficulty than tumor size alone, providing risk stratification to guide surgical planning, optimize patient selection, and enhance safety as RLA indications expand. External validation is required to confirm its generalizability.

Journal of Clinical Medicine doi: 10.3390/jcm15166202

Authors: Luca Schwarzenbacher Belma Strugalioska Gregor S. Reiter Lorenz Wassermann Sandra Rezar-Dreindl Stefan Sacu Eva Stifter

Objectives: To evaluate temporal trends in ocular biometrics, patient demographics and surgical strategies for intraocular lens (IOL) localization in pediatric cataracts. Methods: This retrospective study included 291 eyes of 148 pediatric patients operated at a tertiary referral center between 2019 and 2025, comprising 219 operated eyes and 72 unaffected fellow eyes serving as intra-individual controls. Eyes were stratified into three chronological cohorts (2019–2020, 2021–2022, 2023–2025). Axial length (AL), white-to-white (WTW) diameter and central corneal thickness were analyzed in relation to the anatomical IOL placement. A generalized linear mixed model with a random intercept per patient accounted for the within-patient correlation between fellow eyes. Results: Mean AL increased from 18.91 ± 2.83 mm to 20.32 ± 3.19 mm (p = 0.004), whereas the increase in WTW diameter was not significant (p = 0.450). The age at surgery increased significantly across the periods (median 1.08, 1.33 and 3.13 years; p < 0.001), a general temporal effect that was not modified by the site of implantation (p = 0.32). Underlying etiology strongly influenced the approach: all eyes with Marfan syndrome received an iris-fixated IOL, whereas 90% of uveitic eyes remained aphakic. Femtosecond laser-assisted cataract surgery (FLACS) was used in 13 eyes and confined to the most recent period. Conclusions: Pediatric cataract surgery shows a progressive increase in the age at surgery that is not specific to any IOL localization, while the surgical approach is frequently determined by the underlying etiology. The increasing use of FLACS represents an institutional trend; the small number of cases and absence of outcome data preclude conclusions regarding its safety or feasibility.

Journal of Clinical Medicine doi: 10.3390/jcm15166203

Authors: Vincenzo Schiavone Gennaro Giulio Melone Pierpaolo Castagliuolo Giuseppe Sgarlato Alessandro Costa Rossana Alloni Gianluca Mascianà Enrico Davoli

Background: Primary plantar hyperhidrosis is a disabling condition characterized by excessive plantar sweating and impaired quality of life. Lumbar sympathectomy is reserved for patients with symptoms refractory to conservative treatment, but minimally invasive techniques remain technically heterogeneous. This study describes a modified retroperitoneoscopic lumbar sympathectomy and reports its preliminary perioperative outcomes. Methods: A single-center case series included consecutive patients who underwent modified retroperitoneoscopic lumbar sympathectomy for primary plantar hyperhidrosis between June 2019 and May 2024. The technique combined ultrasound-guided retroperitoneal access, indocyanine green (ICG)-assisted creation of the retroperitoneal working space, and temporary selective clamping of the lumbar sympathetic trunk with an intraoperative assessment of plantar temperature and perfusion before definitive clipping. Results: Forty-five patients underwent 81 procedures, including 35 bilateral procedures (70 sides), 10 unilateral procedures, and one unilateral reoperation for recurrent symptoms. All patients resumed oral intake and ambulation on the day of surgery and were discharged within 24 h according to institutional protocol. No intraoperative or postoperative complications were observed and resolution of plantar sweating in subsequent follow-ups was achieved. Conclusions: Modified retroperitoneoscopic lumbar Sympathetic Chain Selective Clamping appears to be a feasible and safe technique for the surgical treatment of primary plantar hyperhidrosis. These technical refinements may facilitate retroperitoneal access and intraoperative confirmation of the target sympathetic level. Larger comparative studies with standardized outcomes and longer follow-up are needed to confirm the durability and clinical value of this approach.

Journal of Clinical Medicine doi: 10.3390/jcm15166200

Authors: Tomaz Velnar Katarina Salobir Bruno Splavski Borut Prestor Senta Frol Ulf Jensen-Kondering Matija Zupan

Background: Intracerebral haemorrhage (ICH) requires rapid multidisciplinary assessment, yet access to neurological and neurosurgical expertise may be uneven. Although telemedicine is established in acute ischaemic stroke (AIS), evidence regarding its role in ICH remains limited. This review describes the organisational framework of the Slovenian TeleKap network and examines its potential application to ICH care. Methods: PubMed/MEDLINE, Scopus, and Google Scholar were searched for literature concerning telemedicine, telestroke, ICH, neurosurgery, acute stroke care, and the Slovenian TeleKap network. Relevant guidelines, reviews, clinical studies, and publications describing telemedicine implementation were narratively synthesised, with emphasis on organisational workflow and neurosurgical consultation. Results: TeleKap connects regional hospitals with tertiary neurological and neurosurgical centres through audiovisual consultation and remote access to clinical and imaging data. In ICH, it provides an organisational mechanism for specialist input into assessment, triage, transfer decisions, preoperative planning, local management, and continuity of care. These functions constitute organisational capabilities rather than clinically validated benefits. They may support more standardised workflows and multidisciplinary coordination; however, no TeleKap-specific ICH registry, consecutive cohort, or comparative study has demonstrated shorter treatment times, more appropriate transfers, improved resource utilisation, or better clinical outcomes. Published evidence of telestroke effectiveness relates predominantly to AIS and cannot be extrapolated directly to ICH. Conclusions: TeleKap represents a national implementation of established telemedicine principles within the Slovenian healthcare system, but its clinical effectiveness, cost-effectiveness, and transferability remain to be established. Further development should prioritise registry-based quality monitoring, standardised protocols, and interoperability, with locally validated AI-supported imaging considered as a subsequent step.

Journal of Clinical Medicine doi: 10.3390/jcm15166199

Authors: Yau Ching Yun Laura S. Kraemer John R. Hallsten James Friend Ann Gaffey

Background/Objectives: Chronic limb-threatening ischemia (CLTI) is the end stage of peripheral arterial disease (PAD) and leads to severe morbidity and mortality. With an increase in diabetes mellitus (DM) and an aging population, tibial artery CLTI is becoming more prevalent. Conventional endovascular devices are often limited by both length and size, highlighting the need for improved endovascular microcatheters. Methods: Here we provide a narrative review of CLTI in tibial disease and current treatment options, highlighting current endovascular techniques, the mechanics and challenges of current catheters, and call attention to the need for novel micro-steerable catheters. Results: Although PAD endovascular treatments have advanced over the past several decades, active tip steering for tibial and intrahospital microcatheters remains limited and without prospective clinical outcome data despite broader advances in peripheral endovascular therapy and catheter tip steering for larger vessels. Challenges in developing steerable microcatheters include the geometry and mechanics of the catheter’s tip on a microscale (50 µm–900 µm). Micro-fabrication methods have shown early promise in creating intricate microstructures; however, challenges remain in precise fabrication and assembly. Further research and development of novel microcatheters for the treatment of tibial disease is needed, as larger steerable catheters have been shown to improve patient outcomes with decreased procedure time, fluoroscopy time, required contrast, and procedural complications. Conclusions: The refinement of steerable micro catheters in tibial vessel intervention would expand current endovascular treatment and diagnostic capabilities, likely improving patient outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15166198

Authors: Manuel A. Rodríguez-Cigala Daniela Velázquez-Aréstegui Silvestre Fuentes-Figueroa Carlos A. Guzmán-Martín

Background: Pediatric tibial lengthening requires prolonged treatment and may be complicated by adverse events that affect both achievement of the planned correction and biological treatment efficiency. Evidence regarding these complementary dimensions in children treated with monolateral external fixation remains limited. Methods: We conducted a retrospective cohort study of pediatric patients who underwent tibial lengthening with a monolateral external fixator between June 2018 and June 2023 at a tertiary pediatric orthopedic center. Planned and achieved lengthening, treatment duration, distraction, maturation, and healing indices, and postoperative complications were evaluated. Complications were analyzed according to overall occurrence, cumulative burden, and pin-site severity. Associations were explored using nonparametric comparisons, Spearman correlations, logistic regression, and robust linear regression. Results: Thirty-nine patients were included; the median age was 14 years (interquartile range [IQR], 11–16), and 69.2% were male. Median distraction, maturation, and healing indices were 0.60 mm/day (IQR, 0.46–0.78), 4.48 days/mm (IQR, 3.03–6.50), and 6.29 days/mm (IQR, 4.90–9.00), respectively. Patients who failed to achieve the planned correction had greater planned lengthening targets. After adjustment for overall complication status, each additional millimeter of planned lengthening was associated with approximately 7% higher odds of failure to achieve the planned goal (odds ratio, 1.07; 95% confidence interval, 1.01–1.16; p = 0.046). Postoperative complications were associated with longer distraction and healing periods and higher healing indices. In robust models adjusted for achieved lengthening, any complication was associated with an approximately 41% higher healing index (p = 0.010), while each increase in pin-site severity was associated with an approximately 22% higher healing index (p = 0.009). Increasing complication burden showed a progressive pattern of prolonged healing. Conclusions: Pediatric tibial lengthening outcomes may be understood through two complementary dimensions. Greater planned lengthening was associated with a lower probability of fully achieving the intended correction, whereas postoperative complications primarily affected treatment efficiency and duration. Careful planning and early complication control may therefore represent complementary strategies for reducing treatment burden.

Journal of Clinical Medicine doi: 10.3390/jcm15166197

Authors: Johannes Bernhard Johanna Ebner Lukas Galli Bea Goessinger Harald Gabriel Lore Schrutka Patrick Haider Christian Hengstenberg Konstantin A. Krychtiuk Stefan Greisenegger Walter S. Speidl

Background: Elevated levels of lipoprotein(a) [Lp(a)] are an independent risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). However, there is only limited data investigating the role of elevated Lp(a) levels in patients with patent foramen ovale (PFO)-associated embolic stroke of undetermined source (ESUS). Methods: We included 266 patients with PFO-associated ESUS who underwent percutaneous PFO closure and had Lp(a) measurements available. These patients were matched according to age, sex and previously documented statin treatment to 947 hospital controls without stroke. Results: Median age was 51 years (IQR 43–59) and 40% were female. Median Lp(a) levels were higher in cases (24 IQR 12–88 nmol/L) than in controls (21 IQR 7–75 nmol/L; p = 0.003). This association appeared more pronounced in men than in women. In males, patients with Lp(a) in the second tertile had an odds ratio (OR) of 1.64 (95% CI, 1.03–2.62) and patients with Lp(a) in the third tertile had an odds ratio of 2.18 (95% CI 1.38–3.44) independent of age, statin use, HbA1c and eGFR. In contrast, in females the second (OR 2.08 [95% CI 1.22–3.54]) but not the third tertile (OR 0.88 [95% CI 0.49–1.59]) of Lp(a) was associated with case status. Conclusions: In this retrospective matched case–control study, higher Lp(a) concentrations were associated with case status in a selected cohort of patients with PFO-associated ESUS, particularly in men. These findings should be considered hypothesis-generating and require confirmation in prospective studies with more representative comparison cohorts.

Journal of Clinical Medicine doi: 10.3390/jcm15166196

Authors: Anwen Davies Andrew Bentley Andras Bikov

Background: Amyotrophic lateral sclerosis (ALS), the most common type of motor neurone disease (MND), is a devastating diagnosis that often leads to mortality within 2–5 years of symptom onset. Respiratory failure and aspiration pneumonia both associated with respiratory muscle weakness are the most common causes of death. Difficult to diagnose and devastating in its prognosis, much research has aimed to identify a reliable biomarker to diagnose ALS, prognosticate and improve enrolment into clinical trials to further research efforts. Over the last few decades, neurofilaments (NFs) have emerged as promising biomarkers, especially neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH). This review aims to summarise the current evidence for use of NFs as biomarkers in ALS. Current Evidence: Higher levels of NFL and pNFH are measured in CSF than in serum, and levels in CSF and serum are correlated. High CSF NFL, serum NFL and CSF pNFH levels could differentiate patients with ALS from healthy controls, other neurological disease, neurodegenerative controls (without MND), other MND subtypes and ALS disease mimics; however, studies reported a high degree of heterogeneity irrespective of which media or NFs have been used. The number of studies examining NFs to predict respiratory failure in patients with ALS is low. Conclusions and Future Directions: Despite numerous studies consistently reporting higher NF levels in ALS compared to various controls, their clinical value is limited due to high heterogeneity of the results and inconsistencies in proving its prognostic value. Further understanding the relationship between NF levels and respiratory failure is paramount to improve the quality of life of patients with ALS and increase survival.

Journal of Clinical Medicine doi: 10.3390/jcm15166195

Authors: Jolene Zhuo Lin Ng Angela Makris Renuka Shanmugalingam

Background/Objectives: Home blood pressure monitoring (HBPM) is increasingly used in pregnancy, but evidence regarding its safety and clinical utility in women with hypertensive disorders of pregnancy (HDPs) remains limited. We aimed to compare maternal and fetal outcomes and healthcare use with HBPM versus clinic-based blood pressure monitoring. Methods: Cochrane, MEDLINE, Embase and PubMed were searched for randomized controlled trials published from January 1970 to December 2022; this review was undertaken to inform guideline development of hypertension in pregnancy in Australia and New Zealand. Two reviewers independently screened studies, extracted data and assessed risk of bias using RoB. Outcomes reported by at least two clinically comparable trials were pooled and heterogeneity was summarized using I2. Outcomes reported by a single trial are presented as individual study estimates and were not meta-analyzed. Certainty of evidence was assessed using GRADE. Results: Four randomized trials involving 3533 participants were included. HBPM was not associated with a statistically significant difference in preeclampsia, adverse maternal composite outcomes, severe hypertension (≥160/110 mmHg), emergency delivery for hypertension, stillbirth, small-for-gestational-age birth or neonatal mortality. A single trial also found no statistically significant difference in preterm birth before 34 weeks. Serious fetal outcomes were uncommon and confidence intervals were wide. In one pilot trial, HBPM was associated with fewer antenatal visits and a longer duration of blood pressure monitoring. Conclusions: In structured care pathways with clinician oversight and predefined escalation protocols, HBPM was not associated with evidence of increased maternal or fetal risk and may be a useful adjunct to standard antenatal care. The small number of United Kingdom trials, sparse serious events and limited evidence in established or severe preeclampsia preclude conclusions of equivalence or definitive safety.

Journal of Clinical Medicine doi: 10.3390/jcm15166194

Authors: Phuc Nhon Nguyen Anna Ramos Henri Marret

Background: To evaluate whether the methods of induction of labor (IOL) used for pregnancies complicated with fetal growth restriction (FGR) have different impacts on materno-fetal outcomes. Methods: This was a single-center, retrospective cohort study conducted over a one-year period, from January 2024 to December 2024, in the maternity ward of the Orléans University Hospital, France. The clinical data related to maternal–fetal characteristics and IOL outcomes were recorded. The results were comparable between the Cook® balloon and Prostaglandin groups. Results: A total of 47 patients met the inclusion criteria; 27 cases underwent the Cook® balloon and 20 cases received prostaglandin for IOL. There were no substantial differences between Cook balloon and prostaglandin on maternal–fetal characteristics and outcome of IOL. However, the duration of latent labor-delivery phase and duration of onset of labor induction and delivery were longer in the Cook® balloon group compared with the prostaglandin group (30.05 ± 10.81 versus 22.29 ± 11.94 (hours) and 7.33 ± 3.96 versus 3.74 ± 4.77 (hours), respectively, p < 0.05). The success rate according to criterion 1 (Bishop score greater than 7 after IOL) was approximately 60% (28/47 cases). However, if using criterion 2 (success by vaginal birth), after the application of two or three methods of cervical ripening with amniotomy ± use of oxytocin, the success rate increased by more than 20%, up to 80.85% (38/47 cases). Conclusions: IOL with Cook® balloon and prostaglandin may both be acceptable methods for pregnancies complicated by FGR. In addition, IOL did not differ in terms of materno-neonatal outcomes between two groups. However, the duration time from IOL to delivery and the duration from latent phase of labor to delivery were longer in the Cook® balloon group compared with the prostaglandin group.

Journal of Clinical Medicine doi: 10.3390/jcm15166193

Authors: Neng-Jun Wang Wei-Song Zhang Lin Liu Bin-Fei Zhang

Objective: To explore the associations of preoperative waiting time with the incidence of intraoperative blood transfusion and transfusion volume among older patients with hip fracture, to inform perioperative blood management and optimize surgical timing. Methods: Older patients aged ≥65 years who underwent hip fracture surgery at a tertiary trauma center in Northwest China between 1 January 2015 and 30 September 2019 were included. The primary exposure variable was preoperative waiting time. The outcome indicators included intraoperative transfusion status and total transfusion volume. Logistic regression was used for binary transfusion outcomes, and general linear regression was applied for continuous transfusion volume. Multivariate regression models were established to adjust for confounders after univariate screening, and stratified analyses were performed to explore population heterogeneity. Results: A total of 2836 eligible patients were included in this study. The mean age of all participants was 79.52 ± 6.68 years, including 2100 cases of intertrochanteric fracture and 736 cases of femoral neck fracture. Intraoperative blood transfusion was administered in 1415 patients (49.9%). Fully adjusted analyses revealed that each one-day increase in preoperative waiting time was associated with a 6% higher odds of intraoperative transfusion (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.02–1.10, p = 0.0007) and a 0.03-unit increase in transfusion volume (β = 0.03, 95%CI: 0.02–0.05, p < 0.0001). However, no independent association was observed for massive transfusion. The associations were generally consistent across strata despite apparent numerical differences (p for interaction tests > 0.05). Conclusions: Among older patients undergoing hip fracture surgery, longer waiting time was associated with higher transfusion risk. These findings highlight the critical importance of optimizing perioperative pathways to minimize surgical delays. Because residual confounding and inability to distinguish medical from administrative delay remain important limitations, these findings should be interpreted as an association rather than proof that surgical delay causes increased transfusion requirements.

Journal of Clinical Medicine doi: 10.3390/jcm15166192

Authors: Bartłomiej Gromadzki Michał Wiciński Zygmunt Siedlecki Rafał Porzych Igor Pisarski

Background/Objectives: Extracellular matrix remodeling, cellular stress responses, and blood–brain/blood–tumor barrier-related alterations are important processes involved in brain tumor biology. This exploratory cross-sectional pilot study evaluated circulating circulating protein disulfide isomerase A4 (PDIA4), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and claudin-2 (CLDN2) concentrations in vitamin D-deficient patients with different brain tumor entities and aimed to provide preliminary effect-size estimates for future studies. Methods: A total of 62 vitamin D-deficient participants were included, comprising patients with glioblastoma (GBM; n = 15), brain metastases (n = 20), and meningioma (n = 8) and surgical controls with degenerative spine disease (n = 19). Serum biomarker concentrations were measured using enzyme-linked immunosorbent assays. Global between-group effect sizes were estimated using η2, while exploratory pairwise comparisons and associations with tumor size were assessed using non-parametric methods. Effect-size estimates were prioritized, with p-values reported to provide complementary inferential context. Results: The largest global between-group effect-sizes were observed for CLDN2 (η2 = 0.35) and MMP-2 (η2 = 0.22), whereas the estimated effects were small for MMP-9 (η2 = 0.05) and negligible for PDIA4 (η2 = 0.00). Exploratory pairwise comparisons indicated lower serum MMP-2 concentrations in patients with GBM than in surgical controls and lower CLDN2 concentrations in patients with GBM and brain metastases than in controls. Positive exploratory associations were observed between tumor size and PDIA4 concentration in the GBM group (Spearman’s rho = 0.56; 95% CI: 0.02–0.90) and between tumor size and MMP-2 concentration in patients with brain metastases (rho = 0.46; 95% CI: 0.01–0.90). Conclusions: These preliminary effect-size estimates, together with the exploratory correlations with tumor size, may inform biomarker selection and sample-size planning in future prospective studies. The findings should not be interpreted as robust diagnostic or prognostic evidence and require validation in larger, independent, and well-controlled cohorts.

Journal of Clinical Medicine doi: 10.3390/jcm15166191

Authors: Caris M. Smith Shawn A. Hallett Jeremie O. Piña

The paradigm of craniomaxillofacial (CMF) reconstruction is shifting from traditional bone grafting and biochemical adjuncts toward a nucleomechanical framework that leverages the cell nucleus as a mechanosensitive organelle. By utilizing computer-aided design and computer-aided manufacturing (CAD/CAM)-derived scaffolds with 10 µm micropillar arrays and specific interfacial stiffness (25–40 kPa), surgeons can physically manipulate the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex to achieve a nuclear aspect ratio above 2.5. This structural deformation mechanically expands nuclear pores to trigger cytoskeletal and molecular responses, such as Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) translocation. Resultantly, this physical tension pulls open chromatin fibers to activate master osteogenic regulators like RUNX2, effectively bypassing the risks and limitations associated with supraphysiologic growth factor delivery (e.g., rhBMP-2). Clinically, translating these principles involves moving away from absolute rigid internal fixation toward advanced resorbable biomaterials that permit controlled micro-motions (100–200 µm) under functional masticatory loads. This review provides a structured synthesis of the field, outlining deterministic topographic criteria, clinical boundary conditions, and the potential strategies needed to overcome age-related mechanosensory blockades. Ultimately, we establish a multidisciplinary framework that bridges precision bioengineering with native oral and maxillofacial surgical realities to drive living, biophysically mediated bone repair.

Journal of Clinical Medicine doi: 10.3390/jcm15166190

Authors: Ayako Eno Kuo-Chung Chang Tetsuro Oshika

Background/Objective: Whereas conventional flanged intrascleral fixation is limited to 3-piece intraocular lenses (IOLs), we developed and evaluated a novel haptic-extended flange technique for single-piece acrylic IOLs, including presbyopia-correcting and toric lenses. Methods: In this technique, a 6-0 polypropylene suture is secured along the lateral aspect of the single-piece IOL haptic to extend its length, followed by intrascleral flange fixation. Uncorrected visual acuity (UCVA) from far to near, corrected distance visual acuity (CDVA), and refraction were evaluated at 1 month postoperatively. IOL tilt and decentration were assessed using anterior segment optical coherence tomography. Results: This study included a consecutive series of 10 eyes of 10 patients (mean age: 58.3 ± 16.2 years), comprising 5 eyes with multifocal IOL, 2 eyes with multifocal toric IOL, 2 eyes with enhanced monofocal IOL, and 1 eye with monofocal IOL. All IOLs were securely fixed; the mean IOL tilt was 5.74 ± 2.93° and the mean decentration was 0.35 ± 0.19 mm. All eyes achieved CDVA of 20/20 or better, and all eyes with multifocal IOLs achieved UCVA at 40 cm of 20/25 or better. No early postoperative complications attributable to the surgical procedure were observed. In a case associated with atopic dermatitis, retinal detachment occurred 4 months after surgery. Conclusions: In this preliminary case series, haptic-extended flange fixation enabled early stabilization of selected single-piece acrylic IOLs with favorable short-term visual and anatomic outcomes. Larger studies with longer follow-up are needed to confirm long-term safety, durability and comparative effectiveness.

Journal of Clinical Medicine doi: 10.3390/jcm15166189

Authors: Luigi Angelo Vaira Hareem Qadeer Sebastiano Stellino Jerome R. Lechien Antonino Maniaci Fabio Maglitto Giuseppe Consorti Giulio Cirignaco Łukasz Woźniak Carlos Navarro-Cuéllar Bożena Antonowicz Jan Borys Giovanni Salzano Giacomo De Riu

Objectives: To systematically review the evidence on horse-related maxillofacial trauma, with emphasis on horse-kick injuries, anatomical patterns, associated injuries, management, outcomes, and prevention. Methods: This systematic review followed the PRISMA 2020 statement. PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library were searched for original clinical studies reporting facial, craniofacial, orbital, dental, or maxillofacial injuries related to horse-associated activities. Data were extracted on study characteristics, demographics, mechanism, mounted/unmounted status, anatomical site, associated injuries, treatment, complications, outcomes, mortality, and protective equipment. Due to substantial heterogeneity in study design, denominators, and outcome reporting, a structured narrative synthesis was performed without formal meta-analysis. Results: Twenty-eight original clinical studies were included. Maxillofacial-specific series consistently identified horse kicks as a major mechanism, especially among unmounted individuals. Injuries most frequently involved the midface, orbit, zygomaticomaxillary complex, mandible, nasal region, and dentoalveolar structures. Severe presentations included optic nerve avulsion, orbitocranial penetrating trauma, naso-orbito-ethmoid and frontal sinus fractures, airway compromise, intracranial injury, and multisystem trauma. Management ranged from conservative treatment to operative fixation, orbital reconstruction, soft tissue repair, advanced airway management, and multidisciplinary care. Helmet use was often absent or poorly documented, particularly during unmounted activities. Conclusions: Horse kicks represent a distinct localized high-energy mechanism of maxillofacial trauma. Prevention should extend beyond riding and include facial protection, protective eyewear, and safety protocols for ground-based horse handling.

Journal of Clinical Medicine doi: 10.3390/jcm15166188

Authors: Qianfeng Xiao Xin Wei Ying Xu Si Wang

Background: Right-to-left shunting through a patent foramen ovale (PFO) is an underrecognized yet potentially reversible cause of refractory hypoxemia, particularly in patients with right ventricular dysfunction. This case report describes heart-rate-dependent right-to-left shunting through a PFO causing refractory hypoxemia in a patient with inflammatory cardiomyopathy and severe right ventricular dysfunction, presumably arising from biventricular output mismatch. Case Presentation: We report the case of a 41-year-old male with inflammatory cardiomyopathy and a recently implanted single-chamber pacemaker (VVI mode, lower rate limit 50 bpm), admitted for decompensated heart failure. After initial clinical improvement with guideline-directed therapy, the patient’s intrinsic heart rate declined, and ventricular pacing at 50 bpm became the dominant rhythm. He subsequently developed refractory hypoxemia unresponsive to mechanical ventilation. Systematic hemodynamic assessment was performed using transthoracic echocardiography and thoracic electrical bioimpedance (TEB) monitoring at different pacing rates. Results: Echocardiographic evaluation revealed dynamic interatrial shunting through a PFO with the following characteristics: left-to-right at a pacing rate of 80 bpm and right-to-left at 50 bpm. Hemodynamic and echocardiographic data suggested that bradycardia induced biventricular output mismatch—left ventricular outflow tract velocity–time integral (VTI) increased by approximately 38% (from 17.5 cm to 24.1 cm), whereas right ventricular outflow tract VTI increased by only approximately 4% (13.3 cm vs. 13.8 cm). This mismatch likely resulted in relative elevation of right atrial pressure, thereby driving right-to-left shunting through the PFO. Increasing the pacing rate to 80 bpm reversed the shunt direction, normalized oxygenation, and facilitated successful extubation. Conclusions: This case suggests that in patients with severe right ventricular dysfunction, bradycardia may induce biventricular output mismatch with substantially greater left than right ventricular stroke volume augmentation, and presumably relative elevation of right atrial pressure, potentially leading to dynamic right-to-left shunting through a PFO. For such patients with unexplained hypoxemia, the possibility of dynamic PFO shunting should be considered. Appropriately increasing the pacing rate may help restore biventricular output matching, reverse shunt direction, and improve oxygenation; individualized heart rate management strategies warrant clinical consideration.

Journal of Clinical Medicine doi: 10.3390/jcm15166187

Authors: Jisu Park Moon Jong Chang Minji Han Jung-Wee Park Tae Woo Kim Young-Kyun Lee Chong Bum Chang Seung-Baik Kang

Background/Objectives: Thrombocytopenia increases bleeding tendency and may complicate perioperative management in total knee arthroplasty (TKA), yet data on both in-hospital burden and post-discharge adverse events are limited. This study evaluated the association between preoperative platelet count and outcomes after primary TKA. Methods: In total, 3474 primary TKAs performed for osteoarthritis at a single institution (2008–2023) were retrospectively reviewed. Patients were classified as Normal, Mild, Moderate, or Severe by preoperative platelet count; the Severe group (N = 6) was excluded from comparative analyses and reported descriptively. Inverse probability of treatment weighting (IPTW) balanced baseline covariates. In-hospital outcomes were red blood cell (RBC) transfusion, intensive care unit (ICU) admission, and length of stay; follow-up outcomes were 30-day readmission, 1-year periprosthetic joint infection (PJI), and 1-year mortality. Results: After IPTW, the RBC transfusion rate rose with lower platelet count (Normal, 14.0%; Mild, 27.0%; Moderate, 32.5%; p < 0.001), and transfusion volume peaked in the Moderate group. ICU admission was more frequent (Moderate, 6.0%; Normal, 0.7%; Mild, 0.4%; p = 0.002), and length of stay increased with severity (p = 0.008). Readmission, 1-year PJI, and mortality were comparable across groups. In multivariable analysis, moderate thrombocytopenia was independently associated with RBC transfusion (adjusted odds ratio [aOR], 3.26; 95% confidence interval [CI], 1.51–6.59; p < 0.001) and ICU admission (aOR, 5.46; 95% CI, 1.37–17.41; p = 0.008), but not PJI or mortality. Conclusions: Preoperative thrombocytopenia—particularly in the mild-to-moderate range evaluated in this study—increased perioperative burden after TKA, with higher RBC transfusion and ICU utilization, but was not associated with a significant increase in major postoperative adverse events during 1-year follow-up. Even if not causally responsible, a low preoperative platelet count is a routinely available marker that may flag patients requiring closer perioperative attention. As the associated burden appears largely limited to the hospitalization period, such attentive in-hospital management may allow these patients to achieve favorable outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15166186

Authors: Burak Bahadır Nur Hürsoy Fatma Betül Saylak Eda Aslanbaba Bahadır Orhan Beger

Objective: To characterize age- and sex-related differences in maxillary strut (MS) morphometry, shape, and pneumatization in children using computed tomography (CT). Methods: Cranial CT examinations from 180 children aged 1–18 years were retrospectively evaluated. After one participant with a rudimentary unilateral MS was excluded, the primary bilateral complete-case analyses included 179 children and 358 MSs (179 right and 179 left). The anteroposterior diameter (MS-AP), area (MS-A), and mediolateral diameter (MS-ML) were measured bilaterally. Each side was classified as trapezoidal or hourglass-shaped, yielding bilateral trapezoidal, bilateral hourglass-shaped, or asymmetric participant-level patterns. Results: All morphometric parameters were higher in males than in females (MS-AP and MS-ML, p < 0.001; MS-A, p = 0.008), with no significant right–left differences. All parameters differed across chronological age strata and age groups (all p < 0.001). Age-by-sex interactions were significant for MS-AP (p < 0.001) and MS-A (p = 0.001), but not for MS-ML (p = 0.257). Bilateral trapezoidal, bilateral hourglass-shaped, and asymmetric patterns occurred in 40.8%, 30.2%, and 29.1% of participants, respectively. Shape pattern was associated with sex (p = 0.003), but not with age group (p = 0.359), and the right–left shape distributions did not differ significantly (p = 0.070). Pneumatization was unilateral in 4 out of 179 participants (2.2%; exact 95% confidence interval: 0.6–5.6%). Conclusions: Pediatric MS dimensions vary with age and sex, while shape shows a sex-related distribution and pneumatization is uncommon. These CT-based findings provide baseline anatomical data on pediatric MS development and may inform future radiological and surgical research.

Journal of Clinical Medicine doi: 10.3390/jcm15166185

Authors: Ming-Hsun Wen Tzu-Ang Chen Tzu-Han Li Wei-Chen Hung Ping-Chia Cheng Chih-Ming Chang Wu-Chia Lo Po-Wen Cheng Po-Hsuan Wu Li-Jen Liao

Background: Postoperative bleeding and prolonged drainage after head and neck surgery may delay drainage tube removal and hospital discharge, increasing complication risk and resource utilization. Optimizing intra and postoperative hemostasis is essential to facilitate early recovery and support enhanced recovery after surgery (ERAS) pathways. This study aimed to identify factors associated with postoperative drainage and length of hospital stay, with particular focus on energy-based device and fibrin sealant use. Methods: Adult patients who underwent neck surgery under general anesthesia with inpatient admission at a tertiary medical center between January 2024 and December 2025 were retrospectively analyzed. Surgical procedures included thyroidectomy (n = 99), parotidectomy (n = 43), submandibular gland excision (n = 25), neck dissection (n = 27) and other procedures (n = 22). Clinical variables, surgical factors, use of energy-based device, hemostatic agents, postoperative drainage volume, and length of hospital stay were collected. Logistic regression analysis was performed to evaluate predictors of early discharge (defined as discharge on postoperative day 1). Results: A total of 216 patients were included. Surgical procedure type was strongly associated with operative duration, postoperative day 1 drainage volume, and length of hospital stay. Neck dissection and total thyroidectomy were associated with increased drainage and prolonged hospitalization. The use of fibrin sealants was independently associated with lower postoperative drainage volume, shorter hospital stay, and a significantly higher likelihood of early discharge (adjusted odds ratio: 4.43, 95% CI 1.92–10.23, p < 0.001). Energy-based device use and patient-controlled analgesia were not associated with early discharge. Conclusions: Incorporating fibrin sealant into perioperative management may facilitate safer and earlier discharge, improve patient turnover, and optimize resource utilization within ERAS-based care pathways.

Journal of Clinical Medicine doi: 10.3390/jcm15166184

Authors: Giulia Ciccarese Francesco Drago Gloria Hoxhallari Domenico Bonamonte Aurora De Marco Alexandre Raphael Meduri Rossana Spadavecchia Paolo Romita Francesca Ambrogio Caterina Foti

Dermatological practice frequently encounters infections of the skin and mucous membranes, ranging from primary viral and bacterial infections to the reactivation of latent viral pathogens [...]

Journal of Clinical Medicine doi: 10.3390/jcm15166183

Authors: Nikola Martić Jovana Jančić Slobodan Spasojević Nemanja Martić Aleksandar Rašković Marko Krstić Milica Paut Kusturica

Background/Objectives: The main objective of this study was to describe the prevalence and prescribing patterns of off-label and unlicensed medication use in a tertiary neonatal intensive care unit in Serbia and to evaluate differences according to gestational age. Methods: This retrospective single-center cohort study included 257 neonates hospitalized in a tertiary neonatal intensive care unit between January and December 2023. Medication prescriptions were classified as off-label or unlicensed according to the approved Summary of Product Characteristics in Serbia. Clinical and prescribing data were analyzed descriptively, with predefined patient-level outcomes compared across gestational-age groups using non-parametric analyses. Results: A total of 1919 distinct medication prescription records were identified, of which 1642/1919 (85.6%) were classified as off-label and 27/1919 (1.4%) as unlicensed. At the patient level, 252/257 neonates (98.1%) were exposed to at least one off-label medication, whereas 26/257 (10.1%) were exposed to at least one unlicensed medication. Anti-infectives for systemic use accounted for the largest therapeutic-class prescription count. Off-label prescribing was primarily related to age and dosing recommendations. Medication utilization varied across gestational age groups; however, extremely preterm neonates also had substantially longer hospitalizations, and the observed differences should therefore be interpreted as unadjusted prescribing patterns rather than an independent effect of gestational age. Conclusions: Off-label prescribing was highly prevalent in this Serbian tertiary neonatal intensive care unit, whereas patient exposure to unlicensed medications was relatively uncommon. The observed differences across gestational age groups should be interpreted in the context of differences in hospitalization duration and clinical complexity. These findings characterize prescribing patterns and regulatory gaps in neonatal pharmacotherapy and identify areas requiring further neonatal-specific clinical research.

Journal of Clinical Medicine doi: 10.3390/jcm15166182

Authors: Ji-Sun Kim Gulnaz Stybayeva Se Hwan Hwang

Background/Objectives: The objective of this study was to evaluate age-specific effects of intraoperative platelet-rich plasma (PRP) administration on postoperative pain, wound healing, and bleeding after tonsillectomy. Methods: PubMed, Embase, Scopus, Google Scholar, and Cochrane databases were searched from inception to October 2025. Randomized controlled trials comparing intraoperative PRP with placebo or no treatment in patients undergoing tonsillectomy were included. Data on postoperative pain, wound healing, and bleeding were extracted and analyzed using standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analyses were performed by age (adults versus children) and by postoperative day. Results: Nine randomized controlled trials comprising 442 participants were included. In adults, PRP significantly reduced postoperative pain (SMD = −1.26 [−1.70 to −0.81]) and improved wound healing (SMD = −1.43 [−2.65 to −0.22]). The analgesic effect was greatest during the early recovery period (postoperative days 0–5) and diminished thereafter. There were no significant differences in primary postoperative bleeding (OR = 0.49 [0.04 to 5.61]) or secondary postoperative bleeding (OR = 0.23 [0.02 to 2.16]) between the PRP and control groups. In children, PRP did not significantly affect pain or bleeding outcomes. Conclusions: Intraoperative PRP may reduce early postoperative pain and may promote mucosal recovery in adults. However, its clinical efficacy in children remains unclear. Further well-designed, age-stratified trials are warranted to clarify the role of PRP in enhancing postoperative recovery.

Journal of Clinical Medicine doi: 10.3390/jcm15166181

Authors: Nandini Nair Dongping Du Aiswarya J. Pillai Swarna Mahesh Mrudula R. Munagala Howard J. Eisen Balakrishnan Mahesh

Background: Heart failure (HF) represents the final common pathway of diverse cardiovascular disorders, including coronary artery disease, primary myocardial pathology, and abnormalities of cardiac conduction. These conditions arise from an interplay of genetic, environmental, and psychosocial influences, making it essential to understand these determinants to improve risk prediction and prevention. Multiple biological pathways of inflammation, fibrosis, coagulation, oxidative stress, lipid dysregulation, endothelial dysfunction, and metabolic disturbances are shaped by inherited susceptibility and modifiable exposures. Together, these mechanisms drive HF development and progression, though their relative contributions vary across populations. Methods: PubMed and Google Scholar were searched for clinical, biomedical, and interdisciplinary studies published between 1 January 2000, and 31 December 2025. Keywords included “Asian,” “adult,” “India,” “heart failure,” “risk assessment,” “prognosis,” and “predictive value.” Studies were included if they focused on South Asian Indian adults, with priority given to original research, systematic reviews, and meta-analyses. Pediatric studies and those centered on other ethnic groups were excluded. Results: Among South Asian Indians, cardiovascular disease burden remains disproportionately high compared with Western populations. Unique genetic architecture, environmental exposures, and sociocultural factors appear to contribute to earlier onset and more aggressive disease. Identifying population-specific genetic variants, clarifying psychosocial influences, and addressing environmental risks may help reduce these disparities. Conclusions: This qualitative review highlights key gaps in current knowledge. A deeper understanding of these determinants could refine HF risk stratification, guide targeted prevention strategies, and reduce the growing cardiovascular burden in South Asian Indians. There is an urgent need for South Asian specific HF risk prediction models.

Journal of Clinical Medicine doi: 10.3390/jcm15166180

Authors: Selcuk Candan Okan Kati Oguz Kagan Bakkaloglu Tugce Eskazan Ali İbrahim Hatemi Ahmet Merih Dobrucalı Billur Canbakan

Background: Colorectal neoplasia in adults younger than 50 years has attracted increasing clinical attention because of the rising incidence of early-onset colorectal cancer. However, the clinicopathological characteristics of colorectal lesions detected in younger adults remain incompletely described. This study aimed to characterize the clinical, anatomical, and histopathological features of colorectal neoplasia in adults younger than 50 years undergoing colonoscopy. Methods: This retrospective single-center study included adults aged 18–49 years who underwent complete colonoscopy between January 2018 and December 2023. After exclusion of individuals with normal colonoscopy findings, 152 patients with at least one colorectal lesion were included. Lesions were classified as benign, advanced, or malignant according to established histopathological criteria. Demographic, endoscopic, and pathological characteristics were analyzed and compared across lesion categories. Results: Among 152 patients, 83 (54.6%) had benign lesions, 64 (42.1%) had advanced neoplasia, and 5 (3.3%) had malignant lesions. Advanced lesions were observed predominantly in individuals aged 40–49 years. Most lesions were detected in symptomatic patients undergoing clinically indicated colonoscopy. Histopathological evaluation demonstrated a higher frequency of villous/tubulovillous adenomas, sessile serrated lesions, and high-grade dysplasia among advanced lesions. Larger lesion size was strongly associated with advanced pathological features (p < 0.001). In multivariable analysis, patients aged 30–39 years had significantly lower odds of advanced or malignant neoplasia than those aged 40–49 years, whereas no independent associations were observed for sex, smoking status, alcohol use, family history of colorectal cancer, or lesion location. Conclusions: In this selected cohort of adults younger than 50 years with detected colorectal lesions undergoing clinically indicated colonoscopy, advanced neoplasia represented a substantial proportion of cases. These findings should not be extrapolated to the general population of adults younger than 50 years or to screening cohorts.

Journal of Clinical Medicine doi: 10.3390/jcm15166179

Authors: Gokhan Burul Hasan Göze Isa Yalcınkaya Tahir Alper Cinli Mesut Ayer İstemi Serin

Background/Objectives: Malnutrition adversely affects the clinical course of acute myeloid leukemia (AML), yet comparative data on objective nutritional indices remain limited. Methods: This study evaluated the prognostic performance of four indices—Controlling Nutritional Status (CONUT), Simple CONUT, Prognostic Nutritional Index (PNI), and Nutritional Risk Index (NRI)—on overall survival (OS) alongside the European LeukemiaNet (ELN) 2022 risk classification. Pre-treatment parameters of 236 newly diagnosed AML patients were retrospectively analyzed using Receiver Operating Characteristic (ROC) curves and multivariate Cox regression models. Results: In ROC analysis, only NRI demonstrated significant discriminative performance in predicting OS (Area Under the Curve = 0.637, p < 0.001), whereas CONUT, Simple CONUT, and PNI lacked statistical significance. Patients with low NRI scores had significantly worse survival than the high NRI group (median OS: 16.8 months versus not reached, p = 0.004), particularly within the ELN favorable risk category (2-year OS: 59.6% versus 93.5%, p = 0.022). Multivariate analysis established NRI as an independent predictor of mortality (Hazard Ratio = 0.967, p = 0.009) alongside age and ELN risk. Conclusions: In conclusion, NRI outperforms other nutritional indices and serves as an independent prognostic factor in AML, offering a more holistic and effective approach to clinical risk stratification.

Journal of Clinical Medicine doi: 10.3390/jcm15166178

Authors: Huazhang Liu Minghui Pan Liming Jin Guangjie Chen Chang Tao Xiang Yan

Objective: Our objective was to compare clinical safety and postoperative efficacy between transvesicoscopic Politano–Leadbetter (TPL) and laparoscopic Lich–Gregoir (LLG) ureteral reimplantation in infants and toddlers under 36 months diagnosed with primary obstructive megaureter (POM). Methods: This was a single-center retrospective cohort study of pediatric patients with POM who underwent ureteral reimplantation between January 2018 and April 2025. Patients were stratified into TPL and LLG groups by surgical approach. Baseline characteristics, perioperative outcomes, perioperative complications, imaging findings, renal functional outcomes, and long-term complications were collected and analyzed. Primary group comparisons were unadjusted, with additional multivariable linear regression performed for operative duration. Results: We enrolled 65 children: 30 in the TPL group and 35 in the LLG group. Baseline characteristics showed no statistically significant differences across the two study cohorts. There were no open conversions in either group. Total operative duration did not differ significantly between the TPL and LLG groups (145.8 ± 30.6 min vs. 136.9 ± 25.2 min; mean difference, 8.9 min; 95% CI, −4.9 to 22.7; p = 0.210). In multivariable linear regression, TPL showed a non-significant trend toward longer operative time after adjustment for age, preoperative ureteral diameter, and surgery year (B = 10.4 min; 95% CI, −3.7 to 24.4; p = 0.141). Time to postoperative oral intake was slightly shorter in the TPL group (6.1 ± 2.3 h vs. 8.2 ± 2.9 h; mean difference, −2.1 h; 95% CI, −3.4 to −0.8; p = 0.002). No statistically significant differences were detected in estimated blood loss, ureteral tapering rate, double-J stent placement rate, postoperative pain score, acetaminophen use, urinary catheterization duration, or length of hospital stay. Perioperative complications occurred in 3 patients in the TPL group and 5 patients in the LLG group (10.0% vs. 14.3%; risk difference, −4.3%; 95% CI, −20.1% to 11.5%; p = 0.716). No Clavien–Dindo grade III or higher complications occurred in either group. During follow-up, both groups showed reductions in anteroposterior pelvic diameter (APD) and ureteral diameter (UD), with preserved differential renal function (DRF). Low-grade postoperative vesicoureteral reflux (VUR) was detected in two LLG patients, including one grade I case at 4 months and one grade II case at 6 months after surgery; both were managed conservatively. Neither group experienced recurrent ureterovesical junction obstruction (UVJO) nor required reoperation during follow-up. Conclusions: In this single-center retrospective cohort of infants and toddlers with POM, no statistically significant differences were detected in the main perioperative and follow-up outcomes between TPL and LLG. TPL enables intravesical reconstruction and better preserves the natural anatomical course of the ureter and may serve as an alternative minimally invasive option for this patient population.

Journal of Clinical Medicine doi: 10.3390/jcm15166177

Authors: Attila Nemes Barbara Bordács Nóra Ambrus Csaba Lengyel

Background/Objectives: During the cardiac cycle, the left ventricle (LV) exhibits not only a complex contraction–relaxation pattern, but also a wringing-like motion known as LV twist or rotational mechanics. Concurrently, the aortic valve and its annulus (AVA), representing the LV outlet, undergo spatial displacement throughout the cycle, which can be quantified as AVA plane systolic excursion (AAPSE). While three-dimensional speckle-tracking echocardiography (3DSTE) enables the simultaneous assessment of these functional parameters, the relationship between AAPSE and basal/apical LV rotation—particularly across different ranges of these values—remains poorly characterized in healthy subjects. Therefore, the present study aimed to characterize this relationship in detail. Methods: This study included 110 apparently healthy adult volunteers (mean age: 35.1 ± 11.9 years; 68 males). All subjects underwent two-dimensional Doppler echocardiography and 3DSTE, with the latter enabling simultaneous quantification of LV rotational parameters and AAPSE. Results: A tendency toward increased basal LV rotation and decreased apical LV rotation was observed in healthy subjects with mean AAPSE, while LV twist remained preserved compared to those with lower- or higher-than-mean AAPSE. AAPSE tended to be higher in healthy subjects with mean basal LV rotation compared with those with lower- or higher-than-mean values. Furthermore, AAPSE was significantly increased in subjects with elevated apical LV rotation. AAPSE did not correlate with any LV rotational parameters, including basal LV rotation (r = −0.008, p = 0.932), apical LV rotation (r = 0.065, p = 0.593), LV twist (r = 0.061, p = 0.632), and LV twist time (r = 0.181, p = 0.073). Conclusions: There are no significant correlations between AAPSE and LV rotational parameters, but the trends observed in subgroup analyses could serve as hypothesis-generating observations for future studies.

Journal of Clinical Medicine doi: 10.3390/jcm15166176

Authors: Ben T. Daxon William M. LeTourneau Brendan T. Wanta Mariah L. Bennett Abier M. Dawood Rylee N. Stewart Pia P. McEleney

Background/Objectives: Retained airway secretions are a common complication of mechanical ventilation and a major contributor to ventilator-associated pneumonia. Airway Pressure Release Ventilation following a Time-Controlled Adaptive Ventilation protocol (APRV-TCAV) has been anecdotally observed to improve secretion clearance, but the mechanism is not well established. Because TCAV sets the release time (TLow) from each patient’s own expiratory flow decay, we hypothesized that the resulting expiratory-dominant flow profile would generate a net antegrade force on secretions. This bench study compared secretion movement between APRV-TCAV and conventional Volume-Control Continuous Mandatory Ventilation (VC-CMV), with and without an in-line oscillatory device. Methods: A critical care ventilator was connected to a 3 L test lung via a 7 mm endotracheal tube (ETT). Simulated mucus (1% guar gum) was instilled into the ETT, and secretion movement was measured under VC-CMV (positive end-expiratory pressure (PEEP) 5, 10, 15 cmH2O) and APRV-TCAV (PHigh 20, 25, 30 cmH2O; PLow 0 cmH2O). Each condition was repeated with an in-line oscillatory device. Results: All VC-CMV settings produced retrograde secretion movement toward the test lung; all APRV-TCAV settings produced antegrade movement. The largest antegrade movement was observed at the widest PHigh-to-PLow differential. Adding the oscillatory device raised peak expiratory flow above peak inspiratory flow in every condition, yet abolished antegrade movement under APRV-TCAV. Conclusions: In this bench study, APRV-TCAV reversed the direction of secretion movement within the ETT, with larger antegrade movement at wider PHigh-to-PLow differentials. This suggests a potential mechanism by which the ventilator flow profile itself may influence secretion movement. The directional effect depended on the intact release-phase waveform and was abolished by in-line oscillatory therapy despite preserved peak flow asymmetry.

Journal of Clinical Medicine doi: 10.3390/jcm15166175

Authors: John Carlos McDearman John Attelah Ali Nourbakhsh

Traumatic spinal cord injury (SCI) is a catastrophic condition associated with profound neurologic disability, psychosocial disruption, high long-term healthcare utilization, and reduced life expectancy. Globally, SCI remains a major cause of morbidity, most commonly resulting from traumatic mechanisms such as motor vehicle collisions and falls, with a bimodal age distribution affecting both younger adults and older individuals. This narrative review provides a comprehensive, clinically oriented overview of SCIs with emphasis on classification, initial evaluation, imaging, and contemporary management strategies. The review highlights the dual-phase pathophysiology of SCIs—primary mechanical insult followed by secondary injury cascades—underscoring the rationale for rapid stabilization and timely, injury-specific interventions. Initial care is framed around immobilization and trauma resuscitation principles, with cervical spine clearance guided by validated decision tools and early, appropriate imaging acquisition. We discuss adjunctive imaging considerations and address the ongoing debate regarding MRI use in obtunded patients with negative initial studies. Acute inpatient management priorities include prevention of secondary complications, hemodynamic optimization, respiratory support, and vigilant surveillance for autonomic dysfunction. Pharmacologic neuroprotection with high-dose methylprednisolone remains controversial; current guideline recommendations are reviewed. Finally, we outline operative decision-making and evidence supporting early decompression in selected patients, as well as common surgical approaches and their indications. This review consolidates foundational concepts and current standards to support practical, evidence-informed SCI evaluation and management.

Journal of Clinical Medicine doi: 10.3390/jcm15166174

Authors: Shiloh Plaut

This perspective paper addresses five methodological concerns in clinical investigations across the field of pain research and the paradigm of central sensitization. The first is the conflation of the phenomenon and the measurement tool: a patient reported outcome questionnaire called “Central Sensitization Inventory” is given as an example. Second, instruments that are used for measuring central sensitization (and its severity) are not validated to measure the phenomenon of central sensitization. The third is conceptual ambiguity regarding the theoretical framework of central sensitization and nociplastic pain, perpetuating the perception of central sensitization/nociplastic pain as both a phenomenon and a mechanism at the same time. The fourth is the conflation of clinical reasoning with scientific thinking, where in the former jumping from the mechanism to the phenomenon and vice versa is natural. The fifth is terminology issues such as “central-sensitivity syndromes” and “central sensitization-associated symptoms” when referring to fibromyalgia and similar conditions. In summary, by clinician-researchers confusing empirics with theory and theory with empirics and using clinical reasoning instead of scientific thinking, central sensitization becomes an axiom instead of a paradigm to be investigated according to hypothesis-driven studies. The failure to be aware of and clearly distinguish between these cognitive frameworks can lead to flawed research designs, inappropriate interpretations of findings, groundless mechanistic conclusions, and ultimately compromised clinical decision making.

Journal of Clinical Medicine doi: 10.3390/jcm15166173

Authors: Pelin İsmailoğlu Alp Bayramoğlu Tuğba Yemiş Muhammed Sadıkzade Nevnihal Akbaytürk Özlem Çelebi Erdivanlı

Background/Objectives: This study aimed to characterize the three-dimensional morphology of the aerated maxillary sinus using CT-based air-cavity reconstruction and to evaluate its relationship with selected morphometric parameters, septa characteristics, bilateral symmetry, and dental root extension. Methods: This retrospective study included 125 paranasal computed tomography (CT) examinations from 61 males, 64 females (mean age 37.04 ± 15.37 years), corresponding to 250 maxillary sinuses. Three-dimensional air-cavity segmentation was performed using Mimics software following a standardized Hounsfield unit-based thresholding protocol. Morphological patterns of the aerated cavity were classified according to internal compartmentalization and associated morphological features. Morphometric measurements, including ostium-to-sinus-floor distance, axial sinus dimensions, multiplanar septal characteristics, and dental root extension, were recorded and statistically analyzed. Results: Unilocular morphology represented the predominant configuration on both sides (right: 55.2%; left: 53.6%), whereas bilocular and multilocular patterns were less common. Morphologically more complex configurations demonstrated a higher frequency of coronal and axial septa than simple unilocular cavities. Side-to-side differences were identified for ostium-to-sinus-floor distance (p = 0.050), axial longitudinal sinus length (p = 0.027), and pole measurements (p < 0.001). Dental root extension was more frequent on the left side (16.0%) than on the right (6.4%; p = 0.002). Male participants exhibited greater ostium-to-sinus-floor distances and larger axial sinus dimensions than females (all p < 0.05), whereas age showed only a weak negative correlation with left axial transverse sinus length (ρ = −0.191, p = 0.032). Inter-observer agreement for the proposed 18-category three-dimensional morphological classification was substantial (Cohen’s κ = 0.726 for the right side and κ = 0.717 for the left side; both p < 0.001). Conclusions: CT-based three-dimensional air-cavity reconstruction enabled detailed evaluation of the internal morphology of the aerated maxillary sinus. The observed variability in morphological patterns, septa distribution, and selected morphometric characteristics suggests that assessment of the aerated cavity may complement conventional morphometric evaluation of the maxillary sinus. These findings provide a descriptive anatomical reference that may support future radiological, anatomical, and computational investigations of maxillary sinus morphology.

Journal of Clinical Medicine doi: 10.3390/jcm15166172

Authors: Giacomo Allegrini Giulia Acconci Gianna Musettini Luigi Coltelli Chiara Finale Samanta Cupini Linda Bartalini Paola Orlandi Guido Bocci

Cyclin-Dependent Kinase 4/6 inhibitors (CDK 4/6i) represented a paradigm shift in the treatment of patients with metastatic hormone-receptor-positive (HR+), HER2-negative (HER2-) breast cancer patients. When disease progression occurs and further hormonal manipulations or target therapies fail, chemotherapy remains a therapeutic choice. For these reasons, resources should be invested in redesigning the best treatment strategy with the current chemotherapy drugs available. Nevertheless, the preferred strategy typically remains a planned sequence of single chemotherapeutic agents. This approach endeavors to extend overall survival and maintain quality of life. Within this complex and evolving therapeutic scenario, where the necessity for effective and treatment options is crucial, we explore in the present paper a perspective for a hypothetical new role of bevacizumab combined with paclitaxel for patients with metastatic HR+, HER2- breast cancer patients resistant to hormone therapy. Recent findings from our preliminary published pharmacogenetic studies, could suggest the efficacy of bevacizumab as linked to a well-defined genomic profile of genes implicated in the process of neoangiogenesis (e.g., favorable profile: VEGF-A rs833061/VEGFR-2 rs1870377: CT/AT, CT/AA, TT/AA, TT/TT, CC/TT), concluding the present perspective underlying the fact that bevacizumab combined with paclitaxel will be reconsidered with this new potential use only if well-designed prospective trials confirm what has been observed from our retrospective data.

Journal of Clinical Medicine doi: 10.3390/jcm15166171

Authors: İsa Kılıç Abdülmecit Yıldız

Background/Objectives: We aimed to analyse the development of acute kidney injury (AKI), its association with mortality, and mortality-associated factors in patients admitted to the intensive care unit (ICU) with sepsis. Methods: This retrospective cohort study was conducted on adult patients with sepsis admitted to the ICU of a tertiary-care hospital between January 2023 and December 2023. Demographic, clinical, and laboratory data within the first 24 h of admission to the ICU were recorded. These data were compared between patients with and without sepsis-associated acute kidney injury (SA-AKI). Results: Among 1163 admissions, 185 met the study criteria, and the incidence of SA-AKI was 45.4%. The overall 28-day mortality was 38.4%. Patients with SA-AKI had significantly higher mortality than those without SA-AKI (63.1% vs. 17.8%, p < 0.001). In the multivariable Cox regression analysis, SA-AKI was independently associated with a higher risk of 28-day mortality (HR = 2.87, 95% CI 1.51–5.45, p = 0.001). Among patients with SA-AKI, elevated lactate showed a borderline association with mortality (HR = 1.06 per mmol/L, 95% CI 1.00–1.13, p = 0.053); first-day vasopressor use was not independently associated with mortality after adjustment for illness severity. Conclusions: SA-AKI was independently associated with higher 28-day mortality. Within the SA-AKI subgroup, lactate showed only a borderline association with mortality, whereas first-day vasopressor use appeared to reflect illness severity.

Journal of Clinical Medicine doi: 10.3390/jcm15166170

Authors: Hamza Idrees Liviu-Coriolan Misca Rehan Gul

Background/Objectives: First metatarsophalangeal (MTP) joint arthritis is a debilitating condition often treated with arthrodesis or joint replacement. However, the effectiveness of MTP joint replacement has not been thoroughly researched. This study aimed to evaluate functional outcomes and complication rates following first MTP joint replacement over a maximum seven-year follow-up period. Methods: A retrospective cohort study of 60 patients (68 toes) who underwent MTP joint replacement was performed. Data were extracted from medical records and anonymised prior to analysis. The primary outcomes measured included functional improvement and pain relief (AOFAS). Results: Findings indicate significant improvement in mean active and passive range of motion (ROM), with a mean active ROM of 35 degrees and a mean passive ROM of 45 degrees from a pre-op ROM of 0–10 degrees. The overall complication rate was 20.58%, with 10 cases of persistent stiffness but no pain and four cases of continued post-operative pain that necessitated MTP arthrodesis. Patients reported a mean post-operative AOFAS Hallux MTP-IP score of 88, improving from a pre-op score of 35. Conclusions: Results suggest that first MTP joint replacement is associated with significant pain relief and functional improvement with acceptable complication rates over the study period.

Journal of Clinical Medicine doi: 10.3390/jcm15166169

Authors: Shuo Wang Yuwen Wang Fang Li Xuemei Luo Hong Cai Runmei Zou Cheng Wang

Objectives: Clinically feasible simple methods for prognostic assessment of cardioinhibitory vasovagal syncope (VVS) are rare. This study investigated the predictive utility of head-up tile test (HUTT) data among cardioinhibitory VVS children with non-pharmacological therapy. Methods: A retrospective analysis was conducted on the clinical data of 403 children with VVS who had cardioinhibitory responses induced by HUTT. The children were aged 4–18 years old, including 178 males and 225 females. After the non-pharmacological interventions and follow-up, they were divided into the good prognosis group (233 cases) and the poor prognosis group (170 cases). Results: (1) Comparison between groups: Compared with the good prognosis group, the baseline heart rate (HR0) in the poor prognosis group was lower, and the proportion of sublingual nitroglycerin-provoked HUTT (SNHUT) was higher (p < 0.05). (2) Univariate analysis: Univariate analysis showed that HR0 was a protective factor on the prognosis of VVS, while SNHUT was a risk factor for the prognosis of VVS. (3) Multivariate analysis: HR0 was an independent protective factor on the prognosis of VVS. That is, for every 1 bpm increase in HR0, the risk of poor prognosis of VVS decreased by 3%. SNHUT was an independent risk factor for the prognosis of VVS, and the risk of poor prognosis of VVS increased by 3.34 times compared with basic HUTT (BHUT). (4) Evaluation of diagnostic tests: The combination of HR0 and HUTT mode had a good prognostic prediction effect for VVS (AUC = 0.71, p < 0.001). Conclusions: The combination of HR0 and HUTT mode demonstrates robust prognostic predictive value for non-pharmacological interventions in pediatric patients with VVS exhibiting cardioinhibitory responses during HUTT.

Journal of Clinical Medicine doi: 10.3390/jcm15166168

Authors: Anna Cieślińska Natalia Krzykowska Dominika Rozmus Ewa Fiedorowicz Patrycja Kuklo Janusz Płomiński Andrzej Grzybowski

Background/Objectives: Glaucoma is a progressive optic neuropathy and one of the leading causes of irreversible blindness worldwide. Despite the important role of elevated intraocular pressure in disease development, genetic factors such as polymorphisms in the angiotensin-converting enzyme 2 (ACE2) gene may contribute to disease susceptibility. This study aims to evaluate the correlation between the rs879922 polymorphism in the ACE2 gene and glaucoma risk, as well as to assess its relationship with serum ACE2 protein levels. Methods: Patients diagnosed with glaucoma and healthy individuals were enrolled in this study. The rs879922 polymorphism was tested using the PCR-RFLP method. Serum ACE2 concentrations were measured using the ELISA method and expressed as mean ± standard deviation. Results: The rs879922 polymorphism was significantly associated with glaucoma in the allelic (OR = 2.04, p = 0.01) and recessive (OR = 2.63, p = 0.01) models, but not in the dominant model (OR = 1.80, p = 0.21). Genotype distributions deviated from Hardy–Weinberg equilibrium in both groups. Mean serum ACE2 levels were higher in glaucoma patients in comparison to controls (5.23 vs. 3.29 ng/mL). Genotype-stratified analysis revealed that in controls, the GG genotype was associated with the highest ACE2 levels, whereas in glaucoma patients, the CC genotype showed the highest concentrations. Conclusions: The rs879922 polymorphism in the ACE2 gene may be associated with glaucoma susceptibility and influences serum ACE2 levels. The relationship between genotype and ACE2 concentration appears to differ between glaucoma patients and healthy individuals, suggesting a potential interaction between genetic variation and disease status.

Journal of Clinical Medicine doi: 10.3390/jcm15166167

Authors: Aura Vîjîiac Ioana Petre Sebastian Onciul Alina Scărlătescu Diana Zamfir Radu Gabriel Vătășescu

Background: Atrial stiffness can be estimated non-invasively using speckle-tracking echocardiography (STE) and has recently emerged as an outcome predictor. We aimed to assess left atrial (LA) and right atrial (RA) phasic function; the LA stiffness index (LASI), the RA stiffness index (RASI) and their sum; and the biatrial stiffness index (BASI) in dilated cardiomyopathy (DCM), and to test whether combining the two atria adds prognostic information over either index alone. Methods: A total of 121 patients with non-ischaemic DCM in sinus rhythm were followed prospectively for a composite endpoint of all-cause death, non-fatal cardiac arrest, or hospitalisation for heart failure decompensation. LASI was defined as the mitral E/e′ ratio divided by LA reservoir strain, RASI as the tricuspid Et/e′t ratio divided by RA reservoir strain, and BASI as the sum of the two. Cox models were adjusted for NYHA class, LV ejection fraction (LVEF), maximal LA volume (LAVmax) and pulmonary artery systolic pressure (PASP). Results: After 19 ± 11 months, 55 patients reached the endpoint. LA reservoir and contraction strain, all three components of RA strain and all three stiffness indices were significantly impaired in patients with events. All stiffness indices were independent outcome predictors in multivariable Cox regression (HR 2.79 [95% CI, 1.35–5.75], p = 0.006 for LASI, HR 1.84 [95% CI, 1.02–3.29], p = 0.04 for RASI and HR 2.74 [95% CI, 1.36–5.51], p = 0.005 for BASI). BASI showed the greatest increase in risk prediction (Δ likelihood ratio χ2 test = 10.3, p = 0.001) over NYHA class, left ventricular ejection fraction, LA maximal volume and pulmonary artery systolic pressure. BASI showed the highest discrimination (AUC = 0.73); however, it was not significantly better than LASI or RASI alone. Conclusions: Left and right atrial stiffness are both associated with adverse outcome in DCM and add prognostic information to an LV-centred risk model. Their unweighted sum performs at least as well as either component and offers a single parsimonious measure, whose incremental clinical value remains to be established in larger, externally validated cohorts.

Journal of Clinical Medicine doi: 10.3390/jcm15166166

Authors: Kadir Cetinkaya Yasar Ünsal Mert Yığıt Erva Eser Mehmet Özgür Özates Atilla Kazancı

Objective: The objective was to evaluate longitudinal changes in health-related quality of life (HRQoL) following surgical resection of brain metastases and investigate the prognostic value of the Graded Prognostic Assessment (GPA) score in predicting HRQoL improvement. Methods: This prospective observational study included 42 consecutive adult patients undergoing microsurgical resection for histopathologically confirmed brain metastases. HRQoL was assessed using the EuroQol Five-Dimension Five-Level questionnaire (EQ-5D-5L) questionnaire and EuroQol Visual Analogue Scale (EQ-VAS) preoperatively and at 1 and 6 months postoperatively. Patients were stratified according to their preoperative GPA scores, and longitudinal changes in HRQoL were analyzed using non-parametric statistical methods. Results: Mean EQ-VAS scores exhibited a significant postoperative increase from 38.3 ± 19.3 at baseline to 77.6 ± 19.3 at one month and 75.7 ± 16.7 at six months (p < 0.001). Significant improvements were observed across all five EQ-5D-5L dimensions (all p < 0.001). Patients with favorable GPA scores (3.0–4.0) demonstrated greater improvements in EQ-VAS than those in lower GPA categories at one month (p = 0.035) and six months (p = 0.013). Higher baseline GPA scores were positively correlated with HRQoL improvement at both follow-up time points (ρ = 0.51 and ρ = 0.50, respectively; both p < 0.001). Changes in clinician-rated Karnofsky Performance Status (KPS) did not differ significantly across GPA categories (p = 0.731). Conclusions: Surgical resection of brain metastases significantly improves patient-reported HRQoL. The GPA score is a significant predictor of postoperative HRQoL gain, whereas traditional clinician-rated scales like KPS may lack the sensitivity to capture these patient-centered improvements. However, the findings regarding GPA subgroups should be considered exploratory due to the limited number of patients in certain tiers.

Journal of Clinical Medicine doi: 10.3390/jcm15166165

Authors: Hisham Abdulrahman Aloshaywan Rimah Abdullah Saleem Muhammad Raihan Sajid Hani Tamim Salman Aldosari Hibba Siraj Anas M. Alkhabaz Lara M. Samhan Momo Arai Abdulwahab Binjomah

Background/Objectives: Blood group antigen frequencies vary across ethnic populations and are critical for safe transfusion practice, inventory management, and alloimmunization prevention. This study aimed to determine ABO blood group, extended Rh phenotype (D, C, c, E, e), and K antigen frequencies among blood donors at the Riyadh Regional Blood Bank, and to examine their associations with donor ethnicity. Methods: This retrospective cross-sectional study analyzed 10,463 blood donors (January–December 2021) using the Immucor NEO Iris fully automated immunohematology analyzer. Donors were classified into five ethnic groups. Chi-square tests assessed associations (p < 0.05), the primary scientific contribution is the descriptive frequency data, with hypothesis testing presented as secondary and exploratory. Results: Most donors were male (95.2%). Blood group O+ was most prevalent (31.6%); AB− was rarest (0.9%). Rh D-positivity was 84.7%, lowest among Saudis (81.1%). The most frequent Rh phenotypes were CcDee (24.2%), ccDee (19.9%), and CCDee (17.7%). K antigen positivity was 13.7%. Significant associations were found between D antigen and ethnicity (p < 0.001), Rh phenotype and ethnicity (p = 0.003), and ABO and ethnicity (p < 0.001). A hypothesis-generating association between Rh phenotype and K antigen (p = 0.019) did not meet the Bonferroni-corrected threshold and is considered exploratory. Conclusions: This study provides, to our knowledge, one of the largest ethnically stratified blood group datasets from Riyadh to date. The high D-negativity among Saudi donors (18.9%) has direct implications for extended phenotyping protocols and rare donor registry development. The association between Rh phenotype and K antigen requires molecular confirmation before any biological or clinical conclusions can be drawn.

Journal of Clinical Medicine doi: 10.3390/jcm15166164

Authors: Rukiye Çiftçi İpek Atik Neşe Bülbül Özgür Eken Monira I. Aldhahi

Background/Objectives: Anthropometric machine-learning models may approximate body-composition classifications, but performance can be inflated by inconsistent preprocessing, non-independent validation records, and incomplete calibration reporting. This study evaluated a sex-specific bioelectrical impedance analysis (BIA)-defined high-adiposity phenotype using simple anthropometric variables in adults with and without hypertension. Methods: Of 583 prespecified records, 11 with invalid placeholder-coded values in required anthropometric or body-composition fields were excluded, leaving 572 participants (385 normotensive and 187 hypertensive). A high-adiposity phenotype was defined as BIA-derived body fat ≥ 25% in males or ≥35% in females. Predictors were sex, height, body weight, waist circumference, and hypertension status; body mass index and body-fat percentage were excluded. Eight algorithms were assessed using 10 repetitions of stratified five-fold group cross-validation, with identical predictor profiles kept within the same fold. Continuous predictors were standardized within training folds. Performance was estimated from averaged out-of-fold probabilities with 2000 stratified bootstrap confidence intervals, calibration measures, and SHAP analysis. Results: A high-adiposity phenotype was present in 441 participants (77.1%). Random forest achieved the highest discrimination (ROC AUC = 0.959, PR AUC = 0.980). Gradient boosting provided the strongest threshold-dependent performance (accuracy = 0.937, balanced accuracy = 0.895, sensitivity = 0.973, specificity = 0.817, precision = 0.947, F1 score = 0.960, MCC = 0.817) and the lowest Brier score (0.057), but its calibration slope was 0.462, indicating overconfident probabilities. SHAP analysis identified waist circumference as the largest attribution within the fitted gradient-boosting model; this result must be interpreted jointly with the ablation analysis because sex, height, and body weight are inputs to the proprietary Tanita equation. Conclusions: Simple anthropometric variables classified the prespecified Tanita BIA-derived high-adiposity threshold with strong internal performance after duplicate-aware validation. Sex, height, and body weight alone achieved a ROC AUC of 0.920; adding waist circumference produced a small and uncertain increase in discrimination (ΔROC AUC = 0.0054, 95% CI −0.0060 to 0.0153), whereas hypertension status added a negligible value. The findings represent internal validation of a device-defined outcome, not prediction of an independent biological reference, and require external validation against criterion body-composition methods before clinical application.

Journal of Clinical Medicine doi: 10.3390/jcm15166163

Authors: Maria-Emilia Cerghedean-Florea Cosmin Adrian Teodoru Horațiu Dura Adrian Hașegan Adrian Boicean Paul Șiancu Denisa Tănăsescu Mihaela Laura Vică Horia Stanca Tudor Călinici Valeria Coviltir Ciprian Tănăsescu

Background/Objectives: To evaluate macular structural changes after uncomplicated phacoemulsification using optical coherence tomography (OCT) and to investigate whether cardiometabolic disease influences the early postoperative retinal response. Methods: This retrospective observational study included 111 eyes from 111 patients undergoing uncomplicated phacoemulsification with intraocular lens implantation. Macular OCT parameters were evaluated preoperatively and at postoperative days 1, 7, and 30. Patients were stratified according to the presence of cardiometabolic disease, and retinal changes were compared between groups. Results: Exploratory visit-specific comparisons produced nominal differences in average retinal thickness and macular volume at several assessments; however, none remained statistically significant after Holm adjustment across the 16 parameter-by-visit comparisons. The adjusted models provided no statistically significant evidence that postoperative changes from baseline differed according to cardiometabolic status. Model-derived interaction contrasts at days 1, 7, and 30 were small and their 95% confidence intervals included zero for all OCT outcomes. Accordingly, no statistically significant differences in postoperative change from baseline were detected between groups; equivalence was not assessed. Conclusions: Although nominal differences were observed in exploratory visit-specific comparisons, none remained statistically significant after multiplicity adjustment. Furthermore, the adjusted analyses did not detect statistically significant differences in postoperative change from baseline according to cardiometabolic status after adjustment for baseline retinal structure and relevant demographic and surgical confounders. No statistically significant evidence of different postoperative OCT trajectories was detected between groups; equivalence was not assessed.

Journal of Clinical Medicine doi: 10.3390/jcm15166161

Authors: Claudio Marasca Domenico D’Amico Claudia Giofrè Viviana Lora

Background/Objectives: Patients with a clinical diagnosis of severe psoriasis complicated by comorbidities such as cardiovascular disease, obesity, metabolic syndrome and/or with the involvement of high-impact areas constitute a clinical challenge. Tildrakizumab is a monoclonal antibody targeting the IL-23/Th17 axis with a proven record of efficacy and safety in these patients. Methods: Here we present four cases of patients with severe psoriasis and comorbidities including cardiovascular disease (Case 1), obesity (Cases 2 and 3), metabolic syndrome (Case 3), and/or high-impact areas (Cases 2–4). Three patients (Cases 1–3) had previously received biologics but developed secondary failure or loss of efficacy; one patient was bio-naïve (Case 4). Results: The treatment with tildrakizumab in all four patients led to a quick onset (by Week 4 in all cases) of complete and lasting (1 year in Case 1, 4 years in Case 2 and 2 years in Cases 3 and 4) remission with no adverse events reported. Conclusions: Tildrakizumab is a valuable therapeutic option for patients with psoriasis and complex clinical situations, and in particular, in cases with obesity and difficult-to-treat lesion locations such as hands, scalp and genitals. Therapeutic success is often linked to an improvement in patients’ quality of life.

Journal of Clinical Medicine doi: 10.3390/jcm15166162

Authors: Mete Hakan Karalök Bağnu Dündar Ayhan Parmaksız Asiye Gök Yurttaş

Background/Objectives: Human papillomavirus (HPV) is the leading cause of cervical cancer and anogenital malignancies, yet its clinical presentation, genotype distribution, co-infection patterns, and viral load are poorly characterised in tertiary-care referrals. This study aimed to identify predictors of HPV positivity and describe genotype, co-infection, and relative viral copy number (Cq values) in this setting. Methods: A retrospective case–control study of 234 patients (97 HPV-positive, 137 HPV-negative) used a 37-genotype qPCR platform at a tertiary-care hospital between January-December 2025. Demographic data, clinical diagnosis categories, genotype profiles, co-infection patterns, and cycle quantification (Cq) values were recorded, and multivariable logistic regression identified independent predictors of HPV positivity. Results: HPV positivity was 41.5% (97/234). Only the clinical diagnosis category independently predicted HPV status. Compared with non-specific presentations, patients with anogenital or viral warts (aOR: 4.25; 95% CI: 1.49–12.14; p = 0.007) and vaginal or vulvar inflammation (aOR: 2.08; 95% CI: 1.19–3.63; p = 0.010) had higher odds of positivity. High-risk genotypes were the second most frequently detected category (40.00% of detections), after low-risk genotypes (48.21%), with HPV-16 leading among high-risk types. Co-infection occurred in 44.3% of HPV-positive patients, mostly involving mixed-risk genotypes. Patients with anogenital warts had lower Cq values than those with urinary tract complaints (p = 0.011), reflecting higher relative viral copy numbers per swab. Conclusions: HPV positivity and relative viral copy number (as approximated by Cq values) tracked more closely with clinical presentation than with demographic background. The dominance of low-risk and high-risk genotypes and the prevalence of mixed-risk co-infections were consistent with the symptomatic profile of the cohort. These findings support interpreting HPV results in light of clinical presentation and extended genotyping with relative viral copy number quantification in tertiary settings.

Journal of Clinical Medicine doi: 10.3390/jcm15166160

Authors: Andrea Tedeschi Federico Barocelli Luigi Gerra Federico Breviario Francesco Sbarra Gianluca Pagnoni Giuseppe Marasacchia Francesco Marangi Susan Darroudi Francesco Di Spigno Francesca Coppi Annalisa Arcari Giulia Losi Daniele Vallisa Giampaolo Niccoli Daniela Aschieri Alessandro Navazio Luigi Tarantini

Bruton tyrosine kinase inhibitors have transformed the management of chronic lymphocytic leukemia and other B-cell malignancies, but their clinical use is increasingly influenced by cardiovascular safety. In contemporary practice, patients receiving these therapies are typically older and characterized by a high burden of comorbidities, including cardiovascular disease, metabolic disorders, and renal impairment. In this setting, cardiovascular complications should not be interpreted as isolated adverse events, but rather as clinical expressions of underlying patient vulnerability and frailty. Atrial fibrillation and arterial hypertension represent the most frequent complications, while heart failure, ventricular arrhythmias, and bleeding, although less common, may carry significant prognostic implications. Importantly, these events often arise from the interaction between drug exposure and pre-existing comorbidities, and may lead to treatment interruption, dose reduction, or discontinuation, ultimately compromising the long-term benefit of otherwise highly effective therapies. This review provides a comprehensive overview of the clinical burden, mechanisms, and management of cardiovascular complications associated with these agents, and proposes a practical, patient-centered framework to guide clinical decision-making. A structured approach based on risk assessment, early detection, and proactive management is essential to prevent complications, optimize treatment continuity, and preserve the long-term benefit of therapy in a complex and vulnerable population.

Journal of Clinical Medicine doi: 10.3390/jcm15166159

Authors: Lukman Amanov Sadeq Ali-Hasan-Al-Saegh Arian Arjomandi Rad Jawad Salman Fabio Ius Stefan Rümke Khalil Aburahma Jan Dieter Schmitto Bastian Schmack Arjang Ruhparwar Alina Zubarevich Alexander Weymann

Background: Minimally invasive approaches for multivalve surgery have attracted increasing interest; however, data on combined aortic and mitral valve replacement or repair using via right anterior minithoracotomy remain quite limited. This study aimed to evaluate the feasibility, safety, and early outcomes of minimally invasive concomitant aortic and mitral valve replacement or repair using this approach. Methods: This retrospective study included 24 patients who underwent simultaneous aortic and mitral valve procedures via right anterior minithoracotomy. We collected preoperative, intraoperative, and postoperative data, assessing echocardiographic parameters. Early clinical outcomes, complications, and mortality rates were analyzed, with correlations between EuroSCORE II and outcomes explored. Results: The median follow-up was 412 days. All procedures were completed successfully without conversion to sternotomy. Postoperative echocardiography demonstrated a significant reduction in transvalvular gradients, with aortic mean pressure gradient decreasing from 51.3 ± 23.0 mmHg to 6.7 ± 1.7 mmHg (p < 0.001) and mitral mean pressure gradient from 19.3 ± 26.7 mmHg to 4.0 ± 1.4 mmHg (p < 0.001), while left ventricular ejection fraction remained unchanged (p = 0.67). During the study period, one patient died from a non-cardiac cause. EuroSCORE II showed a moderate positive correlation with intensive care unit length of stay (p = 0.011) but not with hospital stay or operative times. Conclusions: Minimally invasive aortic and mitral valve replacement or repair via right anterior minithoracotomy is feasible and was associated with favorable early hemodynamic and clinical outcomes in this single-center cohort.

Journal of Clinical Medicine doi: 10.3390/jcm15166158

Authors: Shoa-Lin Lin Jia-Ying Hu Wei-Cheng Lin Jun-Hao Wei Chi-Li Lee Chih-Neng Hsu

Objective: Vitamin D deficiency is a global concern, but its prevalence in critically ill patients in high-sunlight tropical regions is limited. This study evaluated the prevalence of vitamin D deficiency in intensive care unit (ICU) patients in southern Taiwan and identified which variables correlate with deficiency and in-hospital mortality. Methods: We prospectively enrolled 221 critically ill patients, categorizing them by serum 25(OH)D levels as follows: Group A (sufficient, ≥30 ng/mL), Group B (insufficient, 20.0–29.9 ng/mL), and Group C (deficient, ≤19.9 ng/mL). Clinical variables, laboratory parameters, and outcomes were analyzed. Results: Despite the tropical climate, 33.5% of patients were vitamin D-deficient, and 47.1% were insufficient. Group C patients were significantly younger than other groups (p = 0.049). Significant differences between Groups C and A were observed in ICU length of stay (p = 0.036) and total hospital stay (p = 0.004). Multivariable analysis confirmed that only younger age (OR 0.968, p = 0.008) and low albumin level (OR 0.171, p < 0.001) were independently associated with vitamin D deficiency. Only serum albumin (p = 0.001) and C-reactive protein (CRP) levels (p = 0.015) were significantly associated with in-hospital mortality. Conclusions: Vitamin D deficiency is highly prevalent among critically ill patients in southern Taiwan, challenging the assumption that tropical ultraviolet exposure is naturally protective. Younger age and hypoalbuminemia are independent predictors of vitamin D deficiency. However, vitamin D levels were not independently associated with in-hospital mortality, which was instead predicted by albumin and CRP levels. These findings highlight a high rate of hypovitaminosis D in ICU but do not support its role as an independent predictor of mortality.

Journal of Clinical Medicine doi: 10.3390/jcm15166157

Authors: Musa Çalışkan Tahir Yurttaş Selim Doğan Ufuk İdiz Kenan Büyükaşık Taşkın Rakıcı Mert Sevinç

Background/Objectives: Acute mesenteric ischemia (AMI) resembles non-vascular intestinal ischemia (NSII) and non-specific abdominal pain (NSAP) at presentation yet carries 50–80% mortality. We tested how well admission data separate these conditions and predict in-hospital mortality, the primary endpoint. Methods: We studied 197 consecutive adults (2015–2021): AMI (n = 61), NSII (n = 62), and NSAP controls (n = 74). Admission demographics, comorbidities, laboratory markers, the Mannheim Peritonitis Index (MPI), and APACHE-II were compared by ROC/DeLong analysis and multivariable logistic regression (STROBE). Results: AMI had more atrial fibrillation, thromboembolism, chronic kidney disease (CKD), and dyslipidemia (p ≤ 0.028) and higher in-hospital mortality than NSII (47.5% vs. 16.1%; p < 0.001). Inflammatory ratios, lactate, and albumin separated AMI from NSAP well (AUC up to 0.93) but from NSII modestly (lactate, 0.672). APACHE-II (AUC 0.861) and MPI (0.810) predicted in-hospital death and improved combined (0.897; DeLong p = 0.014). Independent predictors were MPI (adjusted odds ratio 1.14, 95% CI 1.06–1.23), CKD (3.72, 1.25–12.10), and arterial lactate (1.20, 1.03–1.45). Conclusions: A composite admission panel was internally consistent but hypothesis-generating, not a triage tool ready for clinical use. CT angiography remains essential, since these markers cannot separate vascular from non-vascular ischemia; prospective external validation is required.

Journal of Clinical Medicine doi: 10.3390/jcm15166156

Authors: Niels Rahe-Meyer Justyna Bartoszko Jerrold H. Levy

Fibrinogen is an essential component of hemostasis and clot formation that stabilizes the platelet-dependent primary hemostatic process. Low fibrinogen levels can be primary (congenital) or secondary (acquired). Acquired hypofibrinogenemia may result from chronic diseases (e.g., liver, autoimmune diseases, and malignancies) or major hemorrhage (e.g., trauma, surgery). Low fibrinogen levels are both a symptom and a precipitating factor for coagulopathy and ongoing bleeding. Fibrinogen repletion with fibrinogen-containing products is important for managing coagulopathic bleeding with suspected or documented hypofibrinogenemia. Different available fibrinogen sources include fibrinogen concentrate, cryoprecipitate, and frozen plasma and vary based on multiple factors including fibrinogen content, purity, other clotting or non-clotting proteins (e.g., immunomodulating proteins or proteins of unknown function), preparation time, safety, volumes, and availability. Fibrinogen replacement strategies have been studied in trauma but also in patients undergoing spine, cytoreductive, and cardiac surgery. In this review, we discuss the physiological actions of fibrinogen, strategies for control of coagulopathic bleeding related to hypofibrinogenemia, and the therapeutic, logistical, and economic factors that influence treatment decisions. In addition, current guidelines and clinical studies were considered regarding the formation of evidence-based treatment strategies that can be individualized at the patient’s bedside.

Journal of Clinical Medicine doi: 10.3390/jcm15166155

Authors: Antonio Musolino Alessandra Marchesi Giovanni Antonelli Livia Gargiullo Flavio Storelli Giovanni Orso Benedetta Benelli Marta Ventura Ludovica Ariaudo Giulia Cafiero Giulio Calcagni Benedetta Leonardi Michele Lioncino Aurelio Secinaro Riccardo Babini Alberto Villani

Introduction: Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired pediatric heart disease in high-income countries. Coronary artery aneurysms (CAA) represent the most severe complication and drive long-term cardiovascular risk. Despite improved outcomes with early intravenous immunoglobulin therapy, follow-up strategies remain heterogeneous, particularly for patients showing CAA regression. Dynamic risk stratification based on coronary Z-scores has been proposed, but long-term real-world data are still needed to optimize surveillance. Methods: We conducted a single-center, retrospective study including pediatric patients (age 1 month–18 years) with KD complicated by CAA, followed at Bambino Gesù Children’s Hospital (Rome) between 1999 and 2024. Coronary involvement was assessed using Boston Z-scores of the right coronary artery, left main coronary artery, and left anterior descending artery. CAA severity over time was analyzed using a composite MAX SCORE (highest Z-score among coronary branches) along with the 1-YEAR MAX SCORE (highest MAX SCORE reached within the 1 year of disease). The distribution and timing of cardiac computed tomography angiography (CCTA) and exercise stress testing (EST) during follow-up were analyzed in relation to coronary severity. Results: Among 502 KD patients, 122 (24.3%) developed CAA; 113 were included in the analysis. Mean age at diagnosis was 24.6 months (M/F 3.5:1). Multivessel involvement was observed in 72%, most frequently affecting the left anterior descending artery. Long-term follow-up ≥10 years was available for 31.9% of patients. Most changes in coronary severity occurred within the first year after disease onset, with complete CAA regression in 76.1% of patients. Conversely, 53% of patients affected by giant aneurysms at 12 months showed persistent severe disease at last follow-up. EST (164 tests in 40 patients) was almost universally negative for inducible ischemia (163/164), whereas CCTA (47 exams in 35 patients) was preferentially performed early and in higher-risk patients. Test prescription correlated more closely with 1-YEAR MAX SCORE than with contemporaneous severity. Echocardiography showed systematic differences compared with CCTA for right coronary and left anterior descending artery Z-scores. Discussion: In our experience, early coronary status was closely associated with the intensity of long-term surveillance strategies in KD. The 1-YEAR MAX SCORE was associated with subsequent patterns of coronary evolution, and the continuous 1-year Maximum Z-score showed good discriminatory ability for persistent CAA on ROC analysis, pending external validation. While the low rate of positive findings on EST raises questions about its diagnostic yield in real-world practice, CCTA provided detailed anatomical characterization. Overall, these findings suggest that early coronary severity may help inform individualized, severity-driven follow-up strategies, warranting confirmation in prospective multicenter studies.

Journal of Clinical Medicine doi: 10.3390/jcm15166154

Authors: Mateusz Mazurek Zygmunt Domagała Rafał Matkowski

Background: Objective breast assessment is relevant in aesthetic, reconstructive, and oncoplastic breast surgery. Smartphones and tablets are widely available devices that may offer an accessible means for three-dimensional (3D) breast surface imaging, with potential relevance for preoperative assessment, surgical planning, and outcome evaluation. However, the available evidence is heterogeneous, and the validity of different devices, applications, and workflows remains unclear. This narrative review aimed to summarize the evidence on smartphone-based 3D surface imaging. Methods: A structured literature search was conducted in PubMed, Embase, Web of Science, and EBSCOhost. Only original studies that used smartphone- or tablet-based breast assessment were included. Data extraction included devices, software, population/material, outcomes, comparators, validation metrics, and limitations. Reporting completeness was assessed using an adapted GRRAS-based appraisal. Results: A total of 9 studies representing approximately 7 independent datasets were included. Only two studies assessed volumetry as one of the primary aims. The evidence base was small and heterogeneous. Most studies were patient-based, while the remaining studies used phantom or model-based designs. Feasibility was demonstrated for selected device–application–workflow combinations, predominantly involving iPhones and the 3D Scanner App, but these findings were not generalizable to smartphone-based 3D breast imaging as a whole. Evidence was more favorable for selected linear anthropometric measurements than for volumetry. Key limitations included breast ptosis, inframammary fold (IMF) geometry, posterior boundary definition, software, and operator dependence. Three of the included reports had potentially overlapping cohorts. Due to substantial heterogeneity in devices, applications, comparators, outcomes, and validation metrics, meta-analysis was not performed. Conclusions: Current evidence is limited to a small number of heterogeneous, predominantly single-center datasets and supports only workflow-specific feasibility for selected anthropometric and surface-based measurements. These findings should not be generalized across smartphone devices, applications, or reconstruction workflows. Breast volumetry remains insufficiently validated and is supported by only two non-comparable studies. Future studies should provide more detailed reporting that focuses on objective characteristics of the workflow and outcomes, including predefined analyses of agreement and measurement error.

Journal of Clinical Medicine doi: 10.3390/jcm15166153

Authors: Daniel Wolder Luka Velemir Clémentin Castel Anna Błażuk-Fortak Agata Michalska Katarzyna Kwas-Sarnacka Grzegorz Świercz Israel Hendler

Background: This systematic review aimed to evaluate the safety and outcomes of extraperitoneal cesarean section (EPCS), including the French Ambulatory Cesarean Section (FAUCS), by comparing them to those of transperitoneal cesarean section (TCS). Data Sources: The search was conducted using the following electronic bibliographic databases: PubMed, Web of Science, and Scopus. Studies were included if they were observational or interventional and investigated EPCS, including FAUCS, as the primary intervention. Exclusion criteria were animal studies, reviews, editorials, and conference abstracts. Methods: Two reviewers independently assessed the risk of bias using RoB 2 for RCTs and ROBINS-I for retrospective studies. Studies were grouped into comparable categories, and data were synthesized in summary tables and by comparative descriptive analysis. Results: In comparative studies, EPCS was associated with significantly lower rates of postoperative complications, such as fever (4% vs. 16% for TCS) and elevated C-reactive protein or leukocytosis (0% vs. 16–20%). EPCS reduced postoperative pain, with lower VAS scores at 24 h (e.g., 2.5 vs. 4.0 in TCS, p < 0.001) and shorter analgesic use. Time to return of bowel function was faster in EPCS and modified EPCS (6–8 h vs. 18–24 h in TCS, p < 0.01). Hospital stays were shorter after EPCS (4.15 ± 0.89 days vs. 4.82 ± 1.34 days, p = 0.027). FAUCS enabled early discharge within 24–48 h in 86–93% of cases and reduced morphine use (0.8% vs. 38% in TCS). Neonatal outcomes, including Apgar scores and cord pH, were similar across all groups. Conclusions: EPCS offers several potential advantages over TCS, including less postoperative pain, faster recovery, and shorter hospital stays. EPCS and its FAUCS variant are also associated with quicker return of bowel function and lower analgesic needs. TCS, while enabling faster fetal delivery, is linked to greater postoperative discomfort and slower recovery. However, current evidence is limited, and further high-quality trials are needed to confirm these benefits and assess long-term outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15166151

Authors: María Isabel Uriarte-Ayestarán Alicia Gutiérrez-Misis María Victoria Castell-Alcalá José M. Mostaza Carlos Lahoz Paula Lorenzana-Honorato Francisco Javier San Andrés-Rebollo Juan Cárdenas-Valladolid Pilar Vich-Pérez Paula Regueiro-Toribio Miguel Ángel Salinero-Fort

Background: Chronic kidney disease (CKD) is highly prevalent in older adults, yet distinguishing pathological CKD from age-related decline in kidney function remains challenging. KDIGO guidelines recommend combined assessment of estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR), but implementation in primary care is uncertain. We evaluated CKD screening patterns, KDIGO risk categories, and the prognostic value of eGFR and albuminuria for all-cause mortality in adults aged ≥75 years. Methods: We conducted a retrospective population-based cohort study of 587,603 community-dwelling adults aged ≥75 years using Primary Care electronic records. Complete CKD screening was defined as at least two eGFR and two uACR measurements ≥ 3 months apart during 2015–2019. CKD prevalence, KDIGO risk categories, and 40-month all-cause mortality were assessed. Multivariable Cox regression models evaluated the independent and joint associations of eGFR and albuminuria with mortality. Results: Only 19.0% of participants underwent complete KDIGO-recommended screening, mainly because of limited albuminuria testing. Among screened individuals, CKD prevalence was 25.7%, with over half classified as high or very high KDIGO risk. Mortality increased progressively with declining eGFR, increasing albuminuria, and worsening KDIGO risk. Macroalbuminuria (HR 1.87, 95% CI 1.75–2.00) and eGFR < 30 mL/min/1.73 m2 (HR 1.91, 95% CI 1.79–2.04) were independently associated with mortality. Conclusions: Complete KDIGO-recommended screening was performed in only one in five adults aged ≥75 years, identifying a major implementation gap in primary care. Albuminuria provided prognostic information beyond eGFR, improving identification of older adults at highest risk of death. These findings support systematic combined eGFR–uACR assessment to improve risk stratification, guide kidney-protective management, and inform healthcare planning for ageing populations.

Journal of Clinical Medicine doi: 10.3390/jcm15166152

Authors: Maria Grandinetti Gabriele Mazzenga Piergiorgio Bruno Giovanni Alfonso Chiariello Annalisa Pasquini Maria Calabrese Nicola Testa Marialisa Nesta Monica Filice Rosa Lillo Federico Cammertoni Natalia Pavone Francesco Burzotta Massimo Massetti

Objectives: Functional tricuspid regurgitation (TR) recurrence after concomitant mitral–tricuspid surgery remains associated with adverse long-term outcomes, while reintervention on the isolated tricuspid valve carries substantial operative risk. Despite increasing awareness of the prognostic importance of functional TR, concomitant tricuspid valve repair remains inconsistently adopted in contemporary practice, particularly in technically demanding procedures. We sought to identify predictors of recurrent TR and develop an individualized prediction model to support patient-tailored surgical planning. Methods: This single-center ambispective study included 178 consecutive patients undergoing concomitant mitral–tricuspid surgery between January 2012 and June 2019. Baseline clinical, echocardiographic and operative variables were retrospectively collected, whereas long-term clinical and echocardiographic follow-up was prospectively completed after Ethics Committee approval. Clinical, echocardiographic and operative variables were first evaluated by univariable Cox proportional hazards analysis. Based on their univariable association with recurrent TR, biological plausibility and clinical relevance, candidate predictors were subsequently entered into a multivariable Cox proportional hazards model while limiting model complexity according to the number of available outcome events. Internal validation was performed by bootstrap resampling, and regression coefficients were transformed into an exploratory individualized perioperative nomogram estimating 5-year tricuspid regurgitation recurrence-free survival. Results: Univariable analysis identified female sex, dyslipidemia, left ventricular ejection fraction < 45%, severe pre-operative TR, indexed tricuspid annular diameter and suture-based annuloplasty as predictors of recurrent TR. Multivariable analysis identified surgical repair strategy as the only independent predictor associated with recurrent TR, with suture-based annuloplasty showing a significantly higher recurrence risk than prosthetic ring annuloplasty. These variables were integrated into an exploratory individualized prediction model estimating 5-year recurrence-free survival: the FuTURe nomogram. Conclusions: Our findings confirm the association between prosthetic ring annuloplasty and a lower risk of recurrent TR, consistent with current evidence supporting ring implantation as the preferred repair strategy. Beyond identifying predictors of recurrence, the FuTURe study proposes an exploratory perioperative individualized prediction model intended to complement current guideline recommendations. Consistent with its acronym, the FuTURe study shifts the focus from immediate procedural success to the patient’s future clinical trajectory, highlighting the value of individualized recurrence-risk assessment from a lifetime management perspective.

Journal of Clinical Medicine doi: 10.3390/jcm15166150

Authors: Beatrice Trabalza Marinucci Federica Palmeri Damiano Caruso Massimiliano Mancini Giorgia Piccioni Fabiana Messa Anna Maria Ciccone Giulio Maurizi Erino Angelo Rendina Mohsen Ibrahim

Background/Objectives: Reliable preoperative assessment of treatment response after neoadjuvant chemoimmunotherapy in locally advanced non-small-cell lung cancer (NSCLC) remains challenging because conventional imaging may not accurately distinguish viable tumour from treatment-related fibrosis or immune-mediated changes. This study investigated whether CT-derived radiomic features combined with machine learning could improve the identification of patients achieving pathological complete response (pCR). Methods: Twenty-nine consecutive patients with stage III NSCLC who underwent surgical resection following neoadjuvant chemoimmunotherapy were retrospectively analysed. Radiomic features were extracted from preoperative CT scans and used to develop supervised machine-learning models based on Random Forest, Support Vector Machine, K-Nearest Neighbors, Multi-Layer Perceptron, and Logistic Regression algorithms. Histopathological findings after surgery served as the reference standard. Feature distributions were compared between patients with and without pCR using the Mann–Whitney U test with Bonferroni correction. Results: Surgical procedures included 19 lobectomies, 2 bilobectomies, 3 pneumonectomies, and 5 complex major resections. Pathological complete response was observed in 9 of 29 patients (31%). The proposed radiomics-based model achieved an area under the ROC curve of 0.92 (95% CI, 0.81–1.00), with 91% accuracy, 90% sensitivity, and 92% specificity (p < 0.05). All patients classified by the model as complete responders were confirmed to have pathological complete response at postoperative histological examination. Conclusions: CT-based radiomics combined with machine learning demonstrated promising performance for the preoperative prediction of pathological response after neoadjuvant chemoimmunotherapy in stage III NSCLC. Although these findings require external validation in larger prospective cohorts, this approach may support preoperative treatment assessment and surgical decision-making.

Journal of Clinical Medicine doi: 10.3390/jcm15166149

Authors: Anna Pitsillidi Laura Vona Stefano Bettocchi Sven Schiermeier Günter Karl Noé

Background/Objective: Anterior compartment prolapse is commonly described as cystocele or anterior vaginal wall descent, although these terms do not identify the underlying mechanism of support failure. Similar POP-Q findings may result from different anatomical defects, including central cystocele, paravaginal support loss, apical descent, levator ani injury, hiatal ballooning, or combined abnormalities. Pelvic floor ultrasound may improve anatomical characterization, but its role in defect-specific phenotyping remains unclear. Our objective was to map the current evidence on the use of pelvic floor ultrasound for anatomical phenotyping of anterior compartment prolapse beyond POP-Q staging. Methods: A scoping review was conducted according to PRISMA-ScR guidelines. PubMed/MEDLINE, Scopus, and Web of Science were searched through May 2026. Studies evaluating anterior compartment prolapse using pelvic floor ultrasound were included. Non-ultrasound anatomical, clinical, and MRI studies were considered only as contextual literature and were not included in the evidence synthesis. Results: Twelve ultrasound-based studies were included. Most studies focused on lateral/paravaginal support abnormalities, while fewer investigated central cystocele configuration, apical-related anterior prolapse, levator-related abnormalities, and hiatal ballooning. Ultrasound techniques were heterogeneous and included transabdominal, introital, transvaginal, and translabial/transperineal approaches, frequently using three-dimensional and four-dimensional imaging. Conclusions: The available evidence suggests that anterior compartment prolapse represents a heterogeneous anatomical condition rather than a single entity defined by POP-Q descent alone. Pelvic floor ultrasound may complement clinical examination by providing dynamic information on different components of anterior compartment support, including cystocele configuration, levator ani integrity, and hiatal dimensions. However, the clinical interpretation of several phenotypes remains limited by heterogeneous terminology, variable imaging protocols, and the lack of standardized diagnostic criteria, particularly for paravaginal defects and the apical contribution to anterior wall descent. Future research should focus on harmonized ultrasound definitions, reproducible acquisition protocols, and prospective validation against anatomical and clinical outcomes to determine the role of ultrasound-based phenotyping in individualized management.

Journal of Clinical Medicine doi: 10.3390/jcm15166148

Authors: Toshiyuki Kawai Yaichiro Okuzu Yusuke Takaoka Daichi Natsume Shuichi Matsuda

Hip fractures are among the most devastating fragility fractures, associated with excess mortality, disability, loss of independence, and substantial healthcare costs. Although age-standardized incidence has declined in several high-income countries, absolute case numbers continue to rise because of population aging. This review summarizes contemporary PubMed-indexed evidence on the epidemiology, risk stratification, and prevention of proximal femoral fractures, with emphasis on hip-fracture outcomes rather than vertebral or composite endpoints alone. We discuss secular trends, FRAX-based case findings and screening, non-pharmacologic strategies, pharmacologic therapy, and health-system interventions relevant to both primary and secondary prevention. Among non-pharmacologic measures, long-term balance-challenging and resistance-based exercise has the most consistent evidence for reducing falls and likely contributes to fracture prevention, whereas multifactorial interventions, home hazard modification, calcium/vitamin D supplementation, and hip protectors are best targeted to selected high-risk populations and care settings. Among medications, bisphosphonates, denosumab, and romosozumab-based sequential strategies show the strongest evidence for reducing hip-fracture risk, while teriparatide and abaloparatide have important roles in very-high-risk patients despite less direct hip-fracture evidence. Menopausal hormone therapy reduces hip fractures in younger postmenopausal women but is limited by extra-skeletal risk, and selective estrogen receptor modulators are primarily vertebral-fracture agents. A major message of this review is that effective prevention depends not only on drug efficacy but also on implementation. Fracture liaison services, orthogeriatric co-management, prompt treatment after fragility fracture, and sustained adherence support are essential to close persistent care gaps. Preventing hip fractures therefore requires an integrated, risk-stratified approach that combines skeletal protection, falls prevention, and reliable health-system delivery.

Journal of Clinical Medicine doi: 10.3390/jcm15166147

Authors: Matei Șerban Corneliu Toader Alexandru Vlad Ciurea Leon Dănăilă Răzvan-Adrian Covache-Busuioc

Basilar trunk aneurysms (BTAs) are rare intracranial aneurysms. These aneurysms pose substantial clinical risk because they are located close to vital cranial structures and perfusion-sensitive perforating arteries. In addition, outcomes from BTA repair are dependent upon several factors, which include proximity to the brainstem, preservation of perforators, corridor access to the aneurysm, successful clipping of the aneurysm through reconstruction, the need for intraoperative rescue manoeuvres and the ability of the patient to recover from complications. Many previous studies have documented the outcomes associated with BTA repair; however, few studies have examined how the anatomy of the BTA directly relates to surgical decisions made by surgeons. Therefore, we developed an explainable AI framework for documenting surgeon reasoning regarding the open microsurgical treatment of BTAs. The primary objective was to develop and internally evaluate an explainable microsurgical intelligence framework for structuring surgeon reasoning during open microsurgical treatment of BTAs. The secondary objectives were to explore the relationships between the proposed constructs and postoperative pontine infarction, angiographic occlusion, functional outcome, hidden disability, operative difficulty, and composite technical-safety failure. Methods: We retrospectively analysed the cases of 31 adult patients who underwent open microsurgical treatment of a basilar trunk aneurysm at our hospital between October 1999 and March 2025. The cohort included 18 women (58.1%) and 13 men (41.9%), with a median age of 55 years (interquartile range, 44–63 years); 14 patients (45.2%) presented with ruptured aneurysms. A database containing more than 300 variables collected information about each patient’s imaging studies, operative strategies employed during surgery, intraoperative events encountered during surgery, intraoperative angiographic verification, occurrence of new injuries or complications resulting from surgery, and degree of recovery in each patient. Temporally separated scores were generated to quantify perforator-aware hazard, compression burden imposed by proximity to the brainstem, constraints imposed by corridors available for clipping of the BTA, burden imposed by clip reconstruction, degree of surgical precision adjusted based on the need for rescue manoeuvres, degree of dataset/model readiness, and degree of case-level learning density. The framework was evaluated internally using methods that included leave-one-out cross-validation, Firth regression modelling, Bayesian modelling, bootstrap optimism correction, calibration assessments using Brier score, decision-curve analysis, evaluations of explainability, conformal uncertainty estimation, and retrieval of similar cases. Results: Complete occlusion of the aneurysm was successfully achieved in 27 patients (87.1%), whereas residual neck or sac remained in four patients (12.9%). New pontine infarction occurred in six patients (19.4%), including four perforator-related infarctions (12.9%). A favourable last-follow-up modified Rankin Scale (mRS) score of 0–2 was achieved in 25 patients (80.6%); however, hidden disability was noted in 11 of these 25 patients (44.0%). Mortality was 6.5% and was limited to two patients with high-grade rupture. PAH-S-pre predicted pontine infarction (OR, 1.19 for every five-point increase; leave-one-out cross-validated AUC, 0.92). The composite technical-safety failure model had an ROC AUC of 0.91, optimism-corrected AUC of 0.88, calibration slope of 0.96, Brier score of 0.10, and permutation p < 0.001. Explainability indicated that PAH-S-pre, BPCI, and CCR represented the most important features. Conformal prediction resulted in abstention from prediction in four patients (12.9%). Conclusions: Expert microsurgical thought processes involved in repairing BTAs can be systematised and recorded into time-relevant and clinically meaningful measures that preserve anatomical interpretability. Clinical use will require external validation before implementation; however, this framework may provide a clinically interpretable foundation for risk-adapted planning, verification, surveillance, education, and future decision-support research for complex neurovascular surgery.

Journal of Clinical Medicine doi: 10.3390/jcm15166146

Authors: Douglas F. Lightstone Joseph W. Betz Jason W. Haas Paul A. Oakley Joseph R. Ferrantelli Ibrahim M. Moustafa Deed E. Harrison

Background: The biomedical literature assessing the reliability of mensuration of sagittal cervical spine alignment in radiographs has not been systematically evaluated. This review aims to systematically identify and assess reliability studies on biomechanical assessments of the sagittal cervical spine used in clinical practice. Methods: The study design was registered with PROSPERO (CRD42023402990). Funding was obtained from Chiropractic BioPhysics (CBP) Non-Profit (Eagle, ID, USA). Inclusion criteria involved studies in English with: human subjects, radiography of the sagittal cervical spine, and reliability analysis of biomechanical mensuration of the sagittal cervical spine. Exclusion criteria involved studies with: geometric modeling, animals, cadavers, phantom mannequins, and non-radiographic studies. PubMed, CINAHL, AltHealthWatch, and Web of Science databases were searched from inception through to 24 January 2023. The quality appraisal tool for studies of diagnostic reliability (QAREL) assessed bias risk. Results: We followed the synthesis without meta-analysis (SWiM) according to systematic review guidelines. Scrutiny of the inclusion criteria yielded 51 articles. The results were limited due to the heterogeneity of various mensuration methods (Cobb, posterior tangent, translation measures, etc.) and the incorporation of both manual and digital measured assessments. Other sources of heterogeneity included the quality and type of images used, whether digital or plain film radiographs were used, and the differences in statistical analysis and reporting (ICCs or Pearson correlation coefficients, Cohen’s kappa agreement, or Bland–Altman plots). Still, the preponderance of evidence found good-to-excellent reliability. Conclusions: This SROL discovered good-to-excellent intra-examiner reliability for the following biomechanical mensuration methods: intersegmental rotation angles, the thoracic inlet angle, the T1 slope, the C2–C7 posterior tangent method for total cervical lordosis, and the Cobb C2–C7 method for total cervical lordosis. Likewise, using these criteria, we identified good-to-excellent inter-examiner reliability for the following biomechanical mensuration methods: intersegmental rotation angles, the thoracic inlet angle, the T1 slope, translation using the sagittal vertical axis of C2–C7, the C2–C7 posterior tangent method for total cervical lordosis, and the Cobb C2–C7 method for total cervical lordosis.

Journal of Clinical Medicine doi: 10.3390/jcm15166145

Authors: Minju Kim Jiyoon Bhan Do Gyeong Lee Hyun Sik Chung

Background: Sodium–glucose co-transporter-2 (SGLT-2) inhibitors are widely prescribed for type 2 diabetes mellitus (T2DM) because of their cardiovascular and renoprotective benefits. However, their use is associated with euglycemic diabetic ketoacidosis (EDKA), a rare but potentially life-threatening complication characterized by severe ketoacidosis despite relatively normal blood glucose levels. Failure to discontinue SGLT-2 inhibitors before surgery, as recommended in current guidelines, together with perioperative fasting and surgical stress, increases the risk of EDKA. Diagnostic complexity is compounded when concurrent postoperative surgical complications provide an alternative explanation for persistent metabolic acidosis. Methods: A 71-year-old man with T2DM receiving uninterrupted empagliflozin underwent direct lateral interbody fusion under general anesthesia. On postoperative day 2, he developed severe high anion-gap metabolic acidosis (pH 7.204, HCO3− 10.1 mEq/L) with near-normal blood glucose levels (178 mg/dL). Pneumoperitoneum identified on imaging was attributed to Hemovac drain-related peritoneal injury, and emergent laparoscopic exploration was performed under a working diagnosis of surgical sepsis. Although surgical source control was successfully achieved, severe metabolic acidosis persisted postoperatively (pH 7.275). Euglycemic diabetic ketoacidosis is an uncommon diabetic complication associated with several perioperative risk factors, including prolonged fasting and surgical stress. Subsequent serum ketone analysis demonstrated markedly elevated beta-hydroxybutyrate levels (4.8 mmol/L), confirming co-existing EDKA. Results: Following empagliflozin discontinuation, targeted treatment with concurrent insulin–dextrose infusion resulted in complete resolution of acid-base imbalance within five days. Conclusions: A concurrent surgical complication appeared to mask EDKA and contributed to a delay in its recognition. In patients receiving SGLT-2 inhibitors, metabolic acidosis that persists after an apparent surgical cause has been addressed should prompt measurement of serum ketones, irrespective of the blood glucose concentration. Structured perioperative protocols for SGLT-2 inhibitor management and postoperative ketone surveillance may help to prevent similar events.

Journal of Clinical Medicine doi: 10.3390/jcm15166144

Authors: Carlos Roberto Montes-de-Oca-Saucedo José Antonio Garza-Cruz Bruno Briceño-Villardaga Ingrid Vanessa Infante-Lee Rafael Chavarría-Rojas Natalie Carled Bermejo-Valero Adolfo Soto-Domínguez Neeran Narainswami

Background/Objectives: We aimed to provide an updated synthesis of the efficacy and ocular safety of subretinal adeno-associated viral (AAV) RPGR gene therapy for retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis pigmentosa (RPGR-XLRP) and to assess the certainty of the available evidence. Methods: We performed a PROSPERO-registered (CRD420251163589), PRISMA 2020 systematic review and meta-analysis using database and trial-registry searches. The primary microperimetry synthesis was restricted to mesopic Macular Integrity Assessment (MAIA) 68-loci acquisitions; continuous-outcome syntheses were conducted at the cohort level, using observed paired-eye contrasts when available; dose levels were interpreted within clinical programs; and above-maximum-tolerated-dose and peripheral-injection cohorts were reported separately. Random-effects analyses used DerSimonian–Laird models with Hartung–Knapp–Sidik–Jonkman small-sample correction. Risk of bias and certainty were assessed with design-matched tools and Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: The quantitative synthesis included four trials reported in five publications (128 participants; AAV8, AAV5, and AAV2tYF platforms). Mesopic retinal sensitivity numerically favored treatment, but the pooled differences were not statistically significant at six months (mean difference [MD] +1.11 dB; 95% confidence interval [CI], −0.88 to +3.09) or twelve months (MD +0.97 dB; 95% CI, −3.99 to +5.94). Best-corrected visual acuity showed no statistically significant pooled difference (MD +0.94 letters; 95% CI, −4.97 to +6.85). The six-month ≥10-letter low-luminance responder estimate favored treatment, but was nonsignificant and attenuated by twelve months; no primary pooled efficacy outcome reached significance under small-sample-adjusted inference. Certainty was very low for functional outcomes and low for safety outcomes. Uncontrolled treated-eye proportions were 80.8% for intraocular inflammation, 17.0% for ocular serious adverse events, and 4.3% for central-injection retinal detachment. Conclusions: Current evidence does not establish a clinically actionable functional benefit, although a modest true effect cannot be excluded. Clinically relevant ocular safety signals were observed, but the estimates were uncontrolled and program dependent. Adequately powered randomized trials with standardized functional endpoints, optimized subretinal delivery strategies, and careful within-program dose selection are needed.

Journal of Clinical Medicine doi: 10.3390/jcm15166143

Authors: Selçuk Akan Mustafa Uğurlu Bahadır Ertürk

Background: Fibromyalgia (FM) is a complex chronic pain disorder characterized by interactions among psychological, biological, and clinical factors. Although psychiatric symptoms and sleep disturbance are recognized contributors to disease burden, their multidimensional relationships with selected biological variables and fibromyalgia severity remain incompletely understood. Objective: This study aimed to investigate multidimensional associations among psychiatric symptoms, sleep disturbance, selected biological variables, and fibromyalgia severity using complementary analytical approaches, including multiple linear regression, Classification and Regression Tree (CART) analysis, and path analysis. Methods: In this cross-sectional study, 102 women with FM and 53 healthy female controls underwent standardized clinical and laboratory assessment. Fibromyalgia severity was assessed using the Fibromyalgia Impact Questionnaire (FIQ), depressive symptoms with the Beck Depression Inventory (BDI), anxiety symptoms with the Beck Anxiety Inventory (BAI), and sleep disturbance with the Jenkins Sleep Scale (JSS). Serum thyroid-stimulating hormone (TSH) and 25-hydroxyvitamin D concentrations were measured as selected biological variables. Multiple linear regression identified independent associations with disease severity, CART analysis evaluated hierarchical classification patterns, and path analysis examined direct and indirect associations within a predefined conceptual framework. Results: Depressive symptoms, sleep disturbance, and anxiety symptoms were independently associated with greater fibromyalgia severity, whereas TSH and vitamin D showed no consistent independent associations. CART identified sleep disturbance as the primary hierarchical classifier, followed by depressive and anxiety symptoms, achieving an overall classification accuracy of 93.5% (AUC = 0.951). Within the proposed conceptual framework, path analysis demonstrated direct associations between psychological symptoms and fibromyalgia severity, whereas TSH and vitamin D exhibited distinct indirect relationships through depressive and anxiety symptoms, respectively. Conclusions: Psychological symptoms were more consistently associated with fibromyalgia severity than the selected biological variables across complementary analytical approaches. The integrated use of multiple linear regression, CART analysis, and path analysis provided a multidimensional perspective on fibromyalgia and highlighted the importance of comprehensive biopsychosocial assessment while emphasizing that the observed findings represent statistical associations rather than causal relationships.

Journal of Clinical Medicine doi: 10.3390/jcm15166142

Authors: Dania Abunaser Juhaina S. Al Maqbali Salim Al Busaidi Yousra Nomier Yousuf Al Suleimani

Objective: The prevalence and clinical impact of iron deficiency (ID) in patients with heart failure (HF) in Oman remain insufficiently characterized. This study aimed to evaluate the prevalence of ID and its association with clinical outcomes, as well as to assess the impact of iron supplementation on hospitalization and mortality among HF patients. Methods: A retrospective observational cohort study included adult patients (≥18 years) with HF who had ≥2 iron profiles; patients with end-stage renal disease were excluded. ID was defined using American Heart Association (AHA) and European Society of Cardiology (ESC) criteria. Results: Of 2246 patients screened, 211 met inclusion criteria (57.8% female; mean age 70 ± 12.7 years). ID prevalence was 68.3% (AHA) and 71.1% (ESC), with ESC criteria detecting more biochemical deficiencies. ID was associated with higher all-cause and HF-related readmissions (p < 0.01), longer length of stay (p = 0.045), and more atrial fibrillation (AF) (p < 0.01). All-cause mortality was similar, although the composite of mortality and readmission was slightly higher with ID (p = 0.052). Iron supplementation significantly increased ferritin (+32 ng/mL) and transferrin saturation (+2.8%) (p < 0.01) and was linked to fewer strokes (p = 0.049), with no major differences in other outcomes. Conclusions: The study found that ID was highly prevalent; however, systematic screening was not routinely practiced, which largely led to delayed initiation of appropriate management. Routine ESC-guided ID screening and management are recommended. However, given the retrospective, non-randomized study design, these findings should not be interpreted as evidence of a causal treatment effect and are likely influenced by confounding by indication. Prospective randomized studies are needed to confirm these observations.

Journal of Clinical Medicine doi: 10.3390/jcm15166140

Authors: Yong Hoon Kim Ae-Young Her Sunwon Kim Dong Oh Kang Chang-Bae Sohn Eun-Seok Shin

Background: Whether the comparative effectiveness of a drug-coated balloon (DCB)-based versus drug-eluting stent (DES)-only percutaneous coronary intervention (PCI) strategy differs between stable angina (SA) and acute coronary syndrome (ACS) remains uncertain. Methods: In this observational, registry-based study, we analyzed 11,522 patients (4490 with SA and 7032 with ACS) from two multicenter registry sources who had undergone PCI in routine clinical practice; the treatment strategy was not assigned by a study protocol. Within each presentation, the DCB-based and DES-only strategies were compared using propensity-score overlap weighting. Complementary within-strategy analyses compared SA with ACS. The primary outcome was the 3-year rate of major adverse cardiac and cerebrovascular events (MACCE). Results: In both presentations, a DCB-based strategy was associated with a lower 3-year risk of MACCE than a DES-only strategy, with a stronger association in SA (overlap-weighted hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.22–0.49) than in ACS (HR, 0.73; 95% CI, 0.59–0.91; p-for-interaction < 0.001). Within-strategy analyses localized this effect modification to the DCB-based group: SA was associated with a lower risk of MACCE than ACS (HR, 0.47; 95% CI, 0.31–0.69) in the DCB-based group, whereas this gradient was absent in the DES-only group. The incidence of major bleeding was lower with the DCB-based strategy in both presentations. Conclusions: A DCB-based PCI strategy was associated with lower 3-year event rates than a DES-only strategy in both SA and ACS, with the strongest relative association in SA. These observational findings are hypothesis-generating and warrant confirmation in randomized trials.

Journal of Clinical Medicine doi: 10.3390/jcm15166141

Authors: Mohammed J. Alsaadi Badr Aljabri Abdulmajeed Altoijry Abdulrahman M. Alfuraih

Background/Objectives: Proximal glue migration toward the saphenofemoral junction (SFJ) and endovenous glue-induced thrombosis are recognised concerns during cyanoacrylate ablation. This exploratory pilot study compared standard and modified ultrasound-guided compression protocols. Methods: Thirty patients with incompetent great saphenous veins (GSVs) were allocated non-randomly, in two sequential cohorts, to a standard (n = 15) or modified (n = 15) protocol. The modified protocol added a “release-and-check” duplex assessment after the initial 3 min compression, a 1 min recompression, and an extra minute for veins > 5.5 mm. The primary outcome was glue migration distance from the compression level, measured immediately postoperatively. Clinical and thromboembolic outcomes were not systematically ascertained; follow-up was one week. Results: Baseline variables were comparable (standardised differences ≤ 0.31). Mean migration distance was lower with the modified protocol (0.80 ± 0.34 vs. 1.97 ± 0.51 cm; mean difference −1.17 cm, 95% CI −1.50 to −0.85; p < 0.0001), persisting after covariate adjustment. Residual stump length was greater (4.41 ± 0.34 vs. 2.49 ± 1.27 cm; p < 0.001), although this SFJ-referenced measure is confounded by the unrecorded compression distance. Deep venous extension occurred in 3/15 standard and 0/15 modified limbs (p = 0.22); all three were asymptomatic Cho grade III events, resolved at one week. Immediate migration was recorded in 7/15 versus 0/15 limbs (p = 0.006). Conclusions: In this small, non-randomised exploratory cohort, a “release-and-check” modification was associated with shorter immediate glue migration. These hypothesis-generating findings rest on an unblinded surrogate endpoint with one-week follow-up and do not establish clinical safety, effectiveness or durability; adequately powered randomised trials with blinded assessment and adjudicated endpoints are required.

Journal of Clinical Medicine doi: 10.3390/jcm15166139

Authors: Marta Herstowska Ada Przygocka-Pieniążek Agnieszka Lejk Jacek Burzyński Małgorzata Myśliwiec Łukasz Kaska

Background/Objectives: The rising prevalence of severe adolescent obesity has increased the number of young patients referred for bariatric surgery. The psychiatric and psychosocial profiles of adolescents and of adult women undergoing this treatment remain insufficiently characterized. This study compared preoperative and postoperative psychiatric, psychosocial, and metabolic profiles of adolescents and adult women undergoing bariatric surgery. Methods: This prospective cohort study recruited 77 consecutive female patients (32 adolescents aged <18 years; 45 adult women aged 18–25 years) at a single bariatric center in Poland between December 2022 and December 2023. All participants underwent comprehensive preoperative and one-year postoperative assessments including laboratory testing, standardized psychiatric interviews, and psychometric screening with the Beck Depression Inventory (BDI) and the Patient Health Questionnaire-9 (PHQ-9). Results: Preoperatively, adolescents were more severely affected for their age (median BMI-for-age z-score 3.53) and waited longer between the first obesity clinic visit and surgery. Adolescents more frequently reported self-harm behaviors and moderate-to-severe depression on the BDI, whereas adult women more often reported psychoactive substance use. Both groups achieved comparable improvements in laboratory and comorbidity outcomes at one year, although relative weight loss was greater in adult women (median total weight loss 37.6% vs. 28.4%, p < 0.0001). Postoperatively, a greater proportion of adolescents than adult women improved with respect to social anxiety (50.0% vs. 13.3%, p = 0.0007) and BDI depression severity (53.1% vs. 24.4%, p = 0.02), whereas a greater proportion of adult women improved with respect to psychoactive substance use (46.7% vs. 12.5%, p = 0.003). Generalized anxiety and suicidal ideation declined within both groups, but the extent of improvement did not differ significantly between them. These differences persisted, and for several outcomes became larger, after adjustment for the reduction in BMI, which was smaller in adolescents. Conclusions: In this observational cohort, bariatric surgery was associated with distinct psychiatric and psychosocial outcome profiles in adolescents compared with adult women. Because the study was uncontrolled and included no non-surgical comparison group, these findings are hypothesis-generating and cannot establish a causal effect of surgery or of its timing; confirmation in larger, multicenter studies with appropriate comparison groups is required. Comprehensive multidisciplinary perioperative care and tailored postoperative psychological support appear important for both age groups.

Journal of Clinical Medicine doi: 10.3390/jcm15166138

Authors: Audrey Meier Tobias Krause Carl Alessandro Starvaggi Milan Milosevic Kai Ziebarth

Background: Epidemiological patterns vary across populations and treatment centres worldwide, with obesity consistently reported as the main risk factor. The primary aim of this study was to characterise age- and sex-adjusted body mass index (BMI) z-scores in children with slipped capital femoral epiphysis (SCFE) treated in Bern, as well as to investigate their association with clinical characteristics. A secondary aim was to compare the observed characteristics with those reported internationally. Methods: This is a single-centre, retrospective cohort study conducted at the Department of Pediatric Surgery, University Children’s Hospital, Inselspital, University of Bern, and included patients under the age of 18 who were treated for SCFE between 2005 and 2025. Demographic, clinical, and anthropometric data were collected for all patients, including sex, age at the time of surgery, slip severity using the Southwick angle, intraoperative slip stability, symptom duration, as classified by Fahey/O’Brien, affected side of the hip, as well as height and weight at the time of surgery. The primary outcome was the age- and sex-adjusted BMI z-score at the time of surgery. Analyses stratified by sex, age, and slip severity were prespecified as secondary analyses. All other subgroup analyses were exploratory and hypothesis-generating. Results: The final cohort included 90 males (69.23%) and 40 females (30.77%). BMI data were available for 114 of the 130 patients. Two-thirds of the patients (62.3%) were overweight or obese. The median BMI z-score was 1.43 (interquartile range 0.72–2.19; mean 1.31 ± 1.11) and was significantly higher than the expected reference value of 0 (p < 0.001). There was no statistically significant difference in BMI z-scores between females and males (p = 0.288). A statistically significant association was observed between age at surgery and BMI z-score. Higher age at surgery was associated with lower BMI z-scores (p = 0.007). There was a trend towards lower BMI z-scores with increasing slip severity. However, this difference did not reach statistical significance (p = 0.158). In an exploratory, hypothesis-generating analysis, patients with stable slips had significantly higher BMI z-scores than those with unstable slips (p = 0.008). This association persisted after adjustment for age and after correction for multiple testing (p_adj = 0.032). A further exploratory, hypothesis-generating analysis showed that BMI z-scores also differed significantly across symptom duration, as classified by Fahey/O’Brien (p = 0.026). The lowest values were observed in the acute-on-chronic group. However, these differences just missed the threshold for statistical significance after adjustment for age and after correction for multiple testing (p_adj = 0.052). Conclusions: In Switzerland, children diagnosed with SCFE had a significantly higher BMI compared to the reference population. Our study revealed that two-thirds of the children were classified as overweight or obese, with obesity being approximately ten times more prevalent among this group compared to the overall Swiss paediatric population. A higher relative body weight was found to be independently associated with a younger age at surgery, consistent with obesity accelerating skeletal maturation and advancing the manifestation of SCFE. We identified a trend towards lower BMI z-scores with increasing slip severity; however, this finding did not reach statistical significance. Consequently, elevated body weight should be regarded as a marker of predisposition and earlier disease onset rather than of slip severity. Childhood obesity prevention may be relevant to SCFE prevention in Switzerland.