Medicina, Volume 62, Issue 7 (July 2026) – 217 articles

Background and Objectives: Radial nerve palsy is one of the most clinically important neurological complications associated with humeral shaft fractures. This study aimed to evaluate the incidence of radial nerve palsy in adult humeral shaft fractures and to investigate recovery patterns and functional outcomes in surgically treated patients. Materials and Methods: This single-center retrospective observational study included adult patients with humeral shaft fractures treated between November 2022 and January 2025. All adult humeral shaft fractures during the study period were screened to determine the overall rate of radial nerve palsy. The final functional analysis included surgically treated patients with radial nerve palsy. Demographic data, fracture characteristics, injury energy, fracture type, timing of radial nerve palsy, treatment modality, operative time, radial nerve exploration, additional surgery, time to nerve recovery, and QuickDASH scores were evaluated. Conservatively managed patients with radial nerve palsy were included in the calculation of overall incidence and recovery rates but were not included in the final functional analyses. Results: A total of 469 adult patients with humeral shaft fractures were evaluated. Radial nerve palsy was identified in 77 patients, corresponding to an overall rate of 16.4%. The rate was 46.4% in open fractures and 14.5% in closed fractures. Among the 77 patients with radial nerve palsy, 49 underwent surgical treatment and constituted the final analysis cohort, whereas 28 were managed conservatively. Recovery was observed in 25 of 28 conservatively managed patients (89.3%) and in 35 of 49 surgically treated patients (71.4%). Overall, radial nerve function recovered in 60 of 77 patients (77.9%). New-onset postoperative radial nerve palsy developed in 29 of 129 surgically treated patients without preoperative palsy (22.5%); however, recovery occurred in 22 of these 29 patients (75.9%), and the rate of persistent postoperative palsy was 5.4% among patients without preoperative palsy. In the surgical cohort, open fracture, longer operative time, and higher initial Cobb angle were associated with non-recovery. Recovery of radial nerve function was the only factor independently associated with better QuickDASH scores. Conclusions: Radial nerve palsy was more frequent in open humeral shaft fractures. Although recovery was high among conservatively managed patients, surgically treated cases showed a lower recovery rate, likely reflecting greater injury complexity. New-onset postoperative radial nerve palsy was relatively frequent, but most cases recovered. Recovery of radial nerve function was strongly associated with better upper extremity functional outcomes. Full article

Background and objectives: Optimal oxygen administration during delivery room resuscitation remains a major challenge in very preterm infants. While both hypoxemia and excessive oxygen exposure have been associated with adverse outcomes, the prognostic value of early oxygenation parameters remains unclear. This study aimed to evaluate the association between preductal SpO₂ at 5 min of life and early respiratory and neurological outcomes in preterm infants born at or below 32 weeks of gestation. Materialsandmethods: This retrospective single-centre study included 31 preterm infants born at ≤32 weeks of gestation, identified from 34 consecutive eligible births. Demographic, delivery room, respiratory, laboratory, and neuroimaging data were collected from medical records. The primary outcome was intraventricular hemorrhage (IVH), graded by the Papile classification, during the first week of life. Secondary outcomes included respiratory support requirements, surfactant administration, and capillary blood gas parameters at two hours of life. Associations were evaluated using Spearman rank correlation; because SpO₂@5 and delivery room FiO₂ were strongly related to gestational age, partial correlations controlling for gestational age were additionally performed, together with a group comparison for IVH. Exact two-sided p values are reported. Results: The median gestational age was 28 weeks + 4 days (range: 22 weeks + 1 day to 31 weeks + 5 days), and the median birth weight was 1120 g. IVH of any grade occurred in 20 infants (64.5%), including severe (grade III–IV) IVH in 10 (32.3%). Median delivery room FiO₂ was 35% (IQR 30–50%), and median SpO₂ at 5 min of life was 83% (IQR 75–90%). Lower SpO₂ at 5 min of life was associated with an increased number of surfactant doses (rs = −0.46, p = 0.010), lower capillary pH at two hours of life (rs = 0.39, p = 0.032), and a higher grade of IVH (rs = −0.39, p = 0.030); median SpO₂@5 was 80% in infants with IVH versus 90% in those without (p = 0.057). Higher delivery room FiO₂ was associated with increased use of DuoPAP (rs = 0.36, p = 0.045), mechanical ventilation (rs = 0.41, p = 0.021), and surfactant administration (rs = 0.56, p < 0.001), as well as lower pH (rs = −0.55, p = 0.002) and higher lactate levels (rs = 0.37, p = 0.044) at two hours of life. Because SpO₂@5 and FiO₂ were both strongly correlated with gestational age (rs = 0.54 and −0.76, respectively), all associations were re-examined controlling for gestational age. The associations of SpO₂@5 with IVH grade (partial rs = −0.22, p = 0.247), surfactant doses (partial rs = −0.08, p = 0.678) and 2 h pH (partial rs = 0.19, p = 0.335) were attenuated and no longer significant, as were those of FiO₂ with mechanical ventilation (partial rs = −0.04, p = 0.817) and surfactant doses (partial rs = −0.01, p = 0.945); only the association between FiO₂ and 2 h pH persisted (partial rs = −0.37, p = 0.048). Conclusions: In preterm infants born at or below 32 weeks of gestation, lower SpO₂ at 5 min and higher delivery room oxygen requirements were associated with less favorable respiratory and metabolic outcomes, as well as with IVH. However, apart from the association between FiO₂ and 2 h pH, none of these associations remained statistically significant after adjustment for gestational age, and these findings, from a small and heterogeneous single-centre cohort, should be considered hypothesis-generating. Early oxygenation parameters are best viewed as simple bedside markers of cardiopulmonary adaptation and overall illness severity in very preterm infants, rather than as independent predictors of clinical outcomes. Further prospective studies are needed to confirm these associations and define clinically relevant threshold values. Full article

Background and Objectives: Acute myeloid leukemia (AML) is characterized not only by its heterogeneity but also by its high relapse rate. This results in limited treatment options, especially in elderly or therapy-refractory patients. It is known that inhibiting anti-apoptotic BCL-2 family proteins can be effective; however, cellular resistance mechanisms often limit the efficacy of this treatment. We studied the effects of the BCL-2 inhibitor ABT-737, the MCL-1 inhibitor S63845, and their combination on AML cell lines and primary AML patient cells. Materials and Methods: To analyze the effects of ABT-737 and S63845 treatment on cells, cell energy phenotype, apoptosis, and cell cycle were assessed, and gene expression by RT-qPCR and protein levels by Western blot analysis were measured. Results: Treatment with the BCL-2 inhibitor ABT-737, the MCL-1 inhibitor S63845, and their combination reduced AML cell viability and induced apoptosis. Dual treatment also altered the expression of epigenetic regulators, as the levels of DNMT1, EZH2, SUZ12, and HDAC1 were reduced, while histone acetylation was increased. An increase in pro-apoptotic markers (PARP cleavage, caspase-9) was observed, and the expression of oncogenes (MYC, WT1) was reduced in model cell lines and primary AML patient cells. Conclusions: BCL-2 and MCL-1 inhibition, alone or in combination, induced apoptosis and altered the expression of epigenetic regulators and oncogenes in AML cell lines and primary patient cells, with no consistent advantage of combined treatment over single agents. BCL-2/MCL-1 inhibition remains a promising approach for AML, and further work should clarify which patients or disease subtypes are most likely to benefit from combined versus single-agent treatment. Full article

Background and Objectives: Lung adenocarcinoma (LUAD) is a clinically heterogeneous malignancy, and reliable prognostic biomarkers are still needed. Kinesin family members 4A and 4B (KIF4A and KIF4B) are mitosis-related motor proteins with potential functional overlap as paralogs. However, their coordinated prognostic significance in LUAD has not been systematically investigated. Materials and Methods: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) were analyzed to evaluate the expression patterns, clinicopathologic associations, and prognostic significance of KIF4A and KIF4B in LUAD. Correlation analysis, Kaplan–Meier survival analysis, and Cox proportional hazards regression analyses were performed. In addition, a combined paralog score and four-group expression model were evaluated. An independent LUAD cohort from the Gene Expression Omnibus (GEO; GSE81089) was analyzed for external validation. Results: KIF4A and KIF4B expression showed a strong positive correlation (r = 0.767, p < 0.001), and both genes were positively correlated with EGFR, KRAS, BRAF, MKI67, and PCNA expression. High KIF4A expression was significantly associated with age, sex, smoking status, pathologic stage, N stage, and T stage, whereas high KIF4B expression was significantly associated with age and pathologic stage. Kaplan–Meier analysis demonstrated that high expression of both KIF4A and KIF4B was associated with poorer overall survival. In Cox regression analyses, elevated expression of both genes remained significantly associated with unfavorable overall survival in univariable and multivariable models. However, when both genes were simultaneously included in the same Cox model, their individual prognostic effects were attenuated, suggesting substantial overlap in prognostic information. By contrast, the combined paralog score remained independently associated with poor overall survival. In four-group analysis, only patients with concurrent high expression of both KIF4A and KIF4B showed significantly worse overall survival compared with the low/low group. External validation demonstrated generally consistent survival patterns, although the prognostic associations were attenuated after multivariable adjustment. Conclusions: KIF4A and KIF4B expression showed substantial prognostic overlap in LUAD, and their concurrent high expression was associated with poorer overall survival. These findings suggest that KIF4A/KIF4B co-expression may serve as a candidate prognostic indicator that warrants validation in independent clinical cohorts and functional studies. Full article

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease of the nasal and paranasal sinus mucosa, associated with significant impairment in quality of life, frequent postoperative recurrence, and repeated need for systemic glucocorticosteroid therapy. Despite the availability of biologics targeting IL-4/IL-13, IL-5, and IgE, a subset of patients shows incomplete or insufficient clinical response. In this context, upstream targeting of epithelial alarmins, particularly thymic stromal lymphopoietin (TSLP), has emerged as a potential therapeutic strategy. To critically review current evidence on the role of TSLP in CRSwNP and to evaluate available data on the mechanism of action, clinical efficacy, and therapeutic potential of tezepelumab in severe and recurrent disease. Materials and Methods: A narrative review was conducted using PubMed, Scopus, and Web of Science. Studies published between 2016 and 2026 were included, comprising experimental research, phase II–III clinical trials, systematic reviews, and international guidelines. Results: TSLP functions as an epithelial alarmin that initiates and amplifies type 2 inflammation via dendritic cell activation, Th2 polarization, and activation of type 2 innate lymphoid cells (ILC2). Data suggests that tezepelumab, a monoclonal antibody targeting TSLP, may reduce inflammation and regulate the immune system. Evidence from asthma populations and relevant CRSwNP subgroups indicates potential improvements in nasal polyp score, congestion, olfactory function and quality of life. It is our understanding that the safety profile appears comparable to placebo, with no new safety concerns having been identified in long-term studies. Conclusions: Tezepelumab is a promising biologic that targets inflammation in CRSwNP. It may benefit severe, recurrent, treatment-resistant disease by modulating immune pathways. However, evidence is indirect and limited, and more trials are needed to define its efficacy, identify biomarkers, and clarify its role in treatment algorithms. Full article

Background and Objectives: Acute heart failure (AHF) has heterogeneous clinical profiles and considerable short-term mortality. Bedside evaluation of congestion and peripheral perfusion may help identify clinically relevant risk groups. This study aimed to evaluate the relationship between a non-invasive congestion–perfusion classification and in-hospital mortality in patients hospitalized with AHF and to explore the prognostic relevance of clinical, biological, and right-heart variables within the phenotypes. Materials and Methods: We performed an observational study that analyzed 790 patients hospitalized with AHF. Patients were classified at presentation into four predefined congestion–perfusion phenotypes: non-congested/preserved perfusion, congested/preserved perfusion, non-congested/impaired perfusion, and congested/impaired perfusion. Congestion was defined using pulmonary and systemic markers, whereas impaired perfusion was defined by the presence of at least two predefined criteria of hypoperfusion. Clinical, biological, and echocardiographic parameters were analyzed according to phenotype and in-hospital mortality. Discriminative performance was evaluated using ROC curve analysis, and logistic regression models were constructed within the congestive phenotypes to investigate the prognostic value of combined clinical and biological markers, with bootstrap internal validation in the combined models. Results: 78 patients died during hospitalization, with different rates across phenotypes; 2.9% in non-congested/preserved perfusion, 3.0% in non-congested/impaired perfusion, 8.0% in congested/preserved perfusion, and 19.5% in congested/impaired perfusion. In congestive phenotypes, several adverse markers were identified. Exploratory combined models demonstrated discriminatory performance in the congested/preserved perfusion phenotype (AUC 0.731) and in the congested/impaired perfusion phenotype (AUC 0.838); bootstrap optimism-corrected AUCs were 0.693 and 0.785, respectively. Right ventricular parameters were more strongly associated with mortality in the congested/impaired perfusion phenotype. LVEF showed limited discrimination within individual phenotypes. Conclusions: The highest in-hospital mortality was observed in the congestive/impaired perfusion phenotype, with a more adverse clinical, biological, and echocardiographic profile. Within the congestive phenotypes, exploratory prognostic marker patterns were partially overlapping, while LVEF showed limited discrimination. Full article

Background and Objectives: Persistent COVID-19 sequelae, often referred to as “long COVID”, still constitute a major global medical challenge. In particular, general fatigue is the most widely reported, serious symptom. In the framework of Japanese traditional (Kampo) medicine (JTM), post-infection fatigue is frequently considered a “Qi deficiency”, a significant loss of vital energy. In JTM, accurately diagnosing Qi deficiency is essential for determining the appropriate treatment. However, one challenge in JTM diagnosis is that mastering traditional diagnostic techniques takes time. We sought to validate the “Qi deficiency score”, a quantitative patient-reported outcome measure designed to assess Qi deficiency in patients suffering from long COVID. Materials and Methods: This was a methodological study. We conducted a cross-sectional study of 237 patients who sought treatment at the post-COVID-19 clinic (COVID-19 Aftercare Clinic) at Okayama University Hospital. The patient population was randomly split into two cohorts: one for Exploratory Factor Analysis (EFA, n = 122) and another for Confirmatory Factor Analysis (CFA, n = 115). The simple Qi-deficiency score comprises eight items derived from Terasawa’s diagnostic criteria, with a total range of 0–56. We evaluated internal consistency using Cronbach’s α/McDonald’s ω and examined structural validity. Convergent validity was established by examining correlations between the simple Qi deficiency score and the Fatigue Assessment Scale (FAS), the Self-rating Depression Scale (SDS), and Quality of Life (QOL) metric. Results: The score’s internal consistency (α = 0.64 and ω = 0.63) was considered modest for screening traditional clinical syndromes. EFA showed major factors representing Qi deficiency symptoms. CFA supported a one-factor model with modest fit indices (CFI = 0.87; RMSEA = 0.079; SRMR = 0.077; TLI = 0.82). Factor loadings revealed that “Body feels tired (now)” (0.98) and “Tires easily (tendency)” (0.73) were the most significant symptoms. Convergent validity showed a strong positive correlation with the FAS (r = 0.61, ρ = 0.60) and a moderate correlation with the SDS (r = 0.55, ρ = 0.55). A significant negative correlation was found with QOL scores (r = −0.42, ρ = −0.43). Conclusions: The simple Qi deficiency score may be useful for evaluating Qi deficiency in patients with post-COVID-19 condition. Full article

Background and Objectives: Diabetes mellitus is a major systemic modifier of oral infection, periodontal inflammation, and tissue healing. Persistent hyperglycemia may intensify oxidative stress, immune dysfunction, dysbiotic biofilm activity, and advanced glycation end-product/receptor signaling, thereby reducing the predictability of periapical and periodontal healing. In patients with endo-periodontal lesions, these mechanisms may interact with pulpal infection and periodontal breakdown, complicating diagnosis, prognosis, and therapeutic sequencing. This review summarizes current evidence on diabetes, glycated hemoglobin (HbA1c), and endo-periodontal outcomes and proposes an HbA1c-guided clinical framework for risk stratification and treatment planning. Materials and Methods: A structured narrative review with an expert-informed clinical framework was conducted using the literature published between January 2016 and December 2025. Eligible sources included consensus reports, clinical practice guidelines, systematic reviews, meta-analyses, umbrella reviews, randomized and non-randomized clinical studies, observational studies, and selected mechanistic studies or contemporary narrative reviews with direct relevance to the framework. Case reports, animal studies, and in vitro investigations without direct relevance to the clinical framework were excluded from the main synthesis. Results: Diabetes is associated with increased periodontal severity, impaired periodontal treatment response, a higher prevalence of radiolucent periapical lesions in root-filled teeth, delayed periapical healing, and increased non-retention of endodontically treated teeth. Periodontal therapy is safe in diabetic patients and may be associated with modest reductions in HbA1c, especially when baseline metabolic control is poor. Conclusions: HbA1c should complement, not replace, pulpal testing, periodontal charting, and radiographic assessment. The proposed framework prioritizes endodontic infection control when pulpal necrosis or active intracanal infection is present, adapts periodontal intervention to metabolic risk, and postpones elective surgical or regenerative procedures in poorly controlled diabetes until medical stabilization is achieved. Full article

Background and Objectives: The Ankura stent graft was introduced in Europe in 2015 for the endovascular repair of infrarenal abdominal aortic aneurysms (AAAs). Evidence regarding its long-term efficacy remains limited. This study presents eight years of clinical experience with the Ankura endograft for endovascular aneurysm repair (EVAR) at a tertiary university vascular center. Materials and Methods: This single-center retrospective study included patients who underwent elective EVAR with the Ankura endograft between January 2015 and January 2023. All patients were anatomically suitable according to the instructions for use (IFU). Computed tomography angiography was performed at 1 and 12 months and annually thereafter during follow-up; the surveillance protocol was subsequently modified to use duplex ultrasound. Primary outcomes were categorized as early (technical success, clinical success, and 30-day mortality and morbidity) or late (aneurysm-related and non-aneurysm-related mortality). Results: A total of 220 patients were included (211 men [95.9%]); the mean age was 71.41 years (range, 49–87 years); and the mean aneurysm diameter was 59.15 mm (range, 32–109 mm). Primary and secondary technical success rates were 97.3% and 100%, respectively, and the clinical success rate was 96.8%. Thirty-day morbidity and mortality rates were 6.3% and 0%, respectively. No perioperative conversions occurred. The mean follow-up duration was 51.76 months (range, 1–131 months). Freedom from reintervention at 24, 36, 48, and 72 months was 98.2%, 97.7%, 97.2%, and 95.9%, respectively. Iliac limb patency was 99.5%. Aneurysm-related and non-aneurysm-related mortality during follow-up were 2.2% and 20.45%, respectively. Conclusions: In this study, the Ankura AAA stent graft demonstrated durable efficacy, with a high iliac limb patency rate, a low reintervention rate, and low aneurysm-related mortality during follow-up. Its long-term efficacy and safety should be evaluated in larger studies. Full article

Background and Objectives: Accurate preoperative assessment of lymph node metastasis is essential for surgical staging and treatment planning in endometrial carcinoma. Magnetic resonance imaging (MRI) is widely used for local staging; however, its nodal performance is limited by reliance on morphologic criteria. 18F-FDG PET/CT provides whole-body functional assessment and may support decision-making when sentinel lymph node (SLN) mapping is unavailable. This study compared MRI and 18F-FDG PET/CT for preoperative detection of pelvic and paraaortic nodal metastases across pragmatic histologic risk groups. Materials and Methods: This retrospective diagnostic-accuracy study included 255 consecutive surgically treated patients with histologically confirmed endometrial carcinoma who underwent both preoperative pelvic MRI and whole-body 18F-FDG PET/CT at a tertiary gynecologic oncology center between December 2023 and December 2025. All patients underwent pelvic lymphadenectomy, 111 patients (43.5%) also underwent paraaortic lymphadenectomy, and SLN mapping was not performed. Patients were categorized as Group 1 (Grade 1–2 endometrioid adenocarcinoma) or Group 2 (Grade 3 endometrioid or non-endometrioid/aggressive histology). Diagnostic estimates were reported with 95% confidence intervals, paired comparisons were performed using exact McNemar tests, and multivariable bias-reduced logistic regression was used to assess independent imaging associations with nodal metastasis. Results: Any nodal metastasis was documented in 24 patients (9.4%). 18F-FDG PET/CT showed higher sensitivity than MRI for patient-level nodal detection (91.7%, 95% CI 74.2–97.7 vs. 37.5%, 95% CI 21.2–57.3), with similarly high specificity (97.0%, 95% CI 93.9–98.5 vs. 97.8%, 95% CI 95.0–99.1). The NPV of 18F-FDG PET/CT was 99.1% (95% CI 96.8–99.8), compared with 93.8% (95% CI 90.0–96.2) for MRI. MRI sensitivity was particularly low in Group 1 (18.2%, 95% CI 5.1–47.7), whereas PET/CT retained high sensitivity in both groups, though the perfect performance observed in Group 2 had wide confidence limits. Conclusions: 18F-FDG PET/CT demonstrated superior sensitivity and NPV compared with MRI for preoperative nodal assessment in endometrial carcinoma. These results support the selective use of PET/CT as an adjunctive staging tool in settings without SLN mapping, but they should not be interpreted as evidence that PET/CT can replace histologic nodal staging. Full article

Background and Objectives: Left atrial appendage (LAA) closure is a Class I recommendation in patients with atrial fibrillation to reduce the risk of cardioembolic stroke. Achieving reliable and complete LAA exclusion during minimally invasive mitral valve surgery via right minithoracotomy remains technically challenging. We report here to our knowledge the largest series of a novel technique for LAA exclusion using an epicardial clip device applied via right minithoracotomy during minimally invasive mitral valve surgery. Materials and Methods: Between June 2023 and May 2026, 40 patients with atrial fibrillation underwent minimally invasive mitral valve surgery via right minithoracotomy with concomitant LAA exclusion. Cardiopulmonary bypass was established via percutaneous femoral cannulation. Following completion of the intracardiac procedure and prior to aortic cross-clamp removal, a suture was placed around the LAA base via the transverse sinus and used to guide clip deployment under direct vision. Successful closure was confirmed by intraoperative transesophageal echocardiography. Results: Mean patient age was 66.6 ± 8.0 years; 21 patients (53%) were female. Mitral valve repair was performed in 36 patients (90%) and replacement in 4 (10%). Concomitant cryoablation for AF was performed in 31 patients (78%). Successful LAA clip deployment was achieved in all 40 patients (100%). The 35 mm clip was used in 36 patients (90%), the 40 mm clip in 3 patients (8%), and the 45 mm clip in 1 patient (2%). Mean total operative time was 183 ± 58 min; mean CPB time was 134 ± 42 min; mean aortic cross-clamp time was 70 ± 27 min. In-hospital mortality was 0%. One patient (3%) required re-thoracotomy for bleeding, one developed a postoperative stroke, and two required ECMO support. Median hospital stay was 9 days. At discharge, 18 patients (45%) were in sinus rhythm; among the 31 who underwent concomitant cryoablation, 16 (52%) were discharged in sinus rhythm. Conclusions: Minimally invasive LAA exclusion is feasible and safe when performed via right minithoracotomy during minimally invasive mitral valve surgery. The technique achieves high rates of successful deployment and avoids the need for additional incisions or access sites. This approach represents a valuable addition to the armamentarium of concomitant stroke prevention strategies in patients with AF undergoing minimally invasive valvular surgery. Full article

Background and Objectives: Coronary computed tomography angiography (CCTA) has become a central non-invasive imaging modality for the evaluation of suspected chronic coronary syndromes. Nevertheless, referral patterns and sex-related differences in real-world CCTA utilization may vary according to demographic structure, healthcare accessibility, and regional clinical practice. The present study aimed to evaluate age- and sex-related patterns in CCTA referrals and coronary atherosclerotic burden within a real-world Eastern European single-center CCTA referral cohort. Materials and Methods: We performed a retrospective analysis of 2742 consecutive CCTA examinations at a tertiary center in Sibiu, Romania, between March 2019 and January 2025. The demographic profile of the referral cohort was compared with the adult population structure of Sibiu County. Subsequently, an age- and sex-stratified proportional subsample of 397 cases was selected from the CCTA cohort for detailed analysis of sex-related differences regarding coronary artery calcium score (CACS), significant coronary stenoses, and significant cardiovascular event risk. Results: The age distribution of the CCTA referral cohort differed significantly from that of the adult county population (p < 0.01), with referrals concentrated predominantly between 55 and 79 years of age. Female patients were overall more frequently represented within the referral cohort compared with the underlying county population; however, males demonstrated significantly higher coronary artery calcium scores, a greater prevalence of significant coronary stenoses, and higher revascularization risk compared with females—particularly between 50 and 79 years of age—within the stratified proportional subsample. In contrast, patients younger than 40 years demonstrated very low rates of significant coronary disease regardless of sex. Conclusions: This study provides a real-world perspective on age- and sex-related patterns in CCTA utilization and coronary atherosclerotic burden within an Eastern European imaging center. The findings highlight the interaction between demographic structure, guideline-directed diagnostic strategies, and coronary imaging utilization in routine clinical practice. Full article

Background and Objectives: Risk stratification is an important tool for guiding clinical decision-making in patients with non-ST-segment elevation myocardial infarction (NSTEMI), yet mortality remains considerable despite contemporary therapeutic advances. Endothelial Activation and Stress Index (EASIX), calculated using lactate dehydrogenase, serum creatinine, and platelet count, is a readily available composite prognostic index that has demonstrated prognostic value across various cardiovascular settings. However, its role in NSTEMI has not been fully established. We therefore evaluated the association between EASIX and 1-year mortality and examined whether it provides incremental prognostic information beyond the GRACE risk score. Materials and Methods: We retrospectively evaluated 624 consecutive patients with NSTEMI who underwent invasive coronary angiography. EASIX was calculated from laboratory parameters obtained at admission. The prognostic significance of EASIX was evaluated using Cox proportional hazards models, Kaplan–Meier survival analysis, restricted cubic spline modelling, and incremental performance metrics. Results: During 1-year follow-up, 75 patients (12.0%) died. Admission EASIX values were higher among non-survivors than survivors (p < 0.001). Mortality increased progressively across EASIX tertiles (p < 0.001). In multivariable analyses, log₂(EASIX) remained independently associated with mortality both in the clinical model (HR 1.381, p = 0.002) and after adjustment for the GRACE score (HR 1.315, p = 0.005). Restricted cubic spline analyses supported a graded relationship between EASIX and mortality risk. Addition of EASIX to the GRACE score improved discrimination (ΔAUC = 0.015, p = 0.032) and risk reclassification (continuous NRI = 0.385, p = 0.020). Conclusions: Admission EASIX emerged as an independent predictor of 1-year mortality among patients with NSTEMI. Furthermore, it provides incremental prognostic information beyond the GRACE risk score and may represent a simple, inexpensive, and readily available tool for risk stratification in contemporary NSTEMI practice. Full article

Background and Objectives: The aim of this study was to use a modified lateral lumbar approach developed by the authors for single-level lumbar decompression and interbody fusion using intervertebral implants. Materials and Methods: A total of 38 patients with single-level L1–L5 degenerative disc disease who underwent lumbar interbody fusion were included in this study. The procedure was performed using the modified lateral lumbar surgical approach. Clinical outcomes included the assessment of functional status using the Karnofsky Performance Scale and Oswestry Disability Index (ODI), quality of life using the EuroQol Visual Analogue Scale (EQ-VAS), and pain intensity using Visual Analogue Scale (VAS). Preoperative and postoperative radiographic parameters assessed on magnetic resonance imaging (MRI) were compared. Results: Significant improvement in functional status, quality of life, and pain reduction was observed in all patients. Radiographic outcomes also improved significantly. Mean disc height increased from 8.2 mm preoperatively to 12.2 mm postoperatively (p < 0.05). The cross-sectional area of the spinal canal increased significantly following surgery. Furthermore, a reduction in disc herniation width and enlargement of the intervertebral foramina were observed. No neurovascular complications occurred, and endplate injury with cage subsidence was noted in 5% of patients. Conclusions: Lateral lumbar discectomy and interbody fusion increase spinal canal area, enlarge the neuroforamina, and restore intervertebral disc height. Most patients experienced substantial functional improvement and pain reduction. No neurological or vascular complications were observed, which may be due to the modified approach. The confirmation of this hypothesis requires further research and a longer follow-up period. Full article

Background and Objectives: Immune checkpoint inhibitors (ICIs) improve survival in advanced non-small-cell lung cancer (NSCLC), yet treatment responses vary. The potential influence of proton pump inhibitors (PPIs), metformin, statins, and nonsteroidal anti-inflammatory drugs (NSAIDs) on immunotherapy efficacy has gained increasing attention. This study aimed to evaluate the associations of these medications with survival outcomes. Materials and Methods: This retrospective cohort study included 179 patients with advanced NSCLC who received second-line nivolumab. The use of PPIs, metformin, statins, and NSAIDs was assessed within a ±30-day exposure window around nivolumab initiation. Sensitivity analyses were performed including all four studied medications. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and Cox regression models. Results: Median follow-up was 19 months, and 52.5% of patients used PPIs. In univariable analysis, PPI use was significantly associated with worse PFS (HR = 2.01; p < 0.001), while PD-L1 ≥ 50% expression was associated with improved PFS (HR = 0.57; p = 0.034). In multivariable analysis, PPI use remained independently associated with worse PFS (HR = 2.22; p < 0.001), and male sex was associated with improved PFS (HR = 0.56; p = 0.013). For OS, PPI use (HR = 1.53; p = 0.043), ECOG ≥ 2 (HR = 2.09; p = 0.001), and male sex (HR = 0.53; p = 0.008) were significant factors in univariable analysis. In multivariable analysis, PPI use (HR = 2.01; p = 0.002) and ECOG ≥ 2 (HR = 2.21; p = 0.001) were independent adverse prognostic factors, while male sex was independently associated with improved OS (HR = 0.41; p = 0.001). Median PFS was 5 months in PPI users versus 9 months in non-users (p < 0.001); median OS was 9 versus 14 months (p = 0.036). The use of metformin, statins, and NSAIDs showed no significant relationship with PFS or OS. Sensitivity analyses supported an association between PPI use and worse outcomes. Conclusions: PPI use was associated with worse PFS and OS in patients with advanced NSCLC receiving second-line nivolumab. These findings suggest that unnecessary PPI use should be carefully reassessed during immunotherapy. Full article

Background and Objectives: Stress urinary incontinence (SUI) is a common condition among women and is frequently associated with impaired sexual function and increased sexual distress. Pelvic floor muscle training (PFMT) is considered a first-line conservative treatment for SUI; however, its effects on female sexual function remain incompletely understood. The present study aimed to evaluate the impact of PFMT on sexual function, sexual distress, and pelvic floor muscle performance in women with SUI. Materials and Methods: This prospective controlled observational study included sexually active women with clinically confirmed SUI and female sexual dysfunction. Participants were allocated either to a control group (Group A) or to a supervised 12-week PFMT program (Group B). Sexual function and distress were assessed using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale–Revised (FSDS-R), respectively. Pelvic floor muscle performance was evaluated using Peritron perineometry, including peak vaginal squeeze pressure, endurance, and resting tone. Objective severity of SUI was assessed using the one-hour pad test. Results: A total of 102 women completed the study, including 44 in the control group and 58 in the PFMT group. After 12 weeks, women undergoing PFMT demonstrated significant improvements in urinary continence, pelvic floor muscle strength, and sexual function compared with controls (all p < 0.01). Mean FSFI total score increased from 21.5 ± 2.5 to 26.6 ± 3.3, while the proportion of women with clinically significant sexual distress decreased from 100% to 58.6%. Peak vaginal squeeze pressure and endurance also improved significantly following PFMT. Conclusions: PFMT significantly improves sexual function, reduces sexual distress, and enhances pelvic floor muscle performance in women with SUI. These findings support the integration of PFMT into the comprehensive management of women with SUI and associated sexual dysfunction. Full article

Background/Objectives: Glaucoma is one of the leading causes of irreversible blindness worldwide. Open-angle glaucoma (OAG) predominates in East Asian populations, with normal-tension glaucoma accounting for the majority of cases. Although intraocular pressure remains the most established risk factor, non-pressure-dependent mechanisms, including ocular vascular dysregulation, warrant further investigation. Cold extremities, a hallmark of Flammer syndrome reflecting primary vascular dysregulation, and underweight (body mass index [BMI] < 18.5 kg/m²) are each independently associated with OAG; however, their combined effect has not been examined at the population level. Materials and Methods: Using nationally representative data from the Korea National Health and Nutrition Examination Survey 2008–2012 (n = 8135; controls 7418, OAG 717), participants aged ≥ 50 years with measured intraocular pressure within the normal range (5–21 mmHg) at the time of examination were classified into four groups: non-underweight without cold extremities (N-N, reference), cold extremities only (CEO), underweight only (UWO), and underweight with cold extremities (UW+CE). Complex sample logistic regression was adjusted for sex, age, diabetes mellitus, mean arterial pressure, intraocular pressure, and spherical equivalent. Results: UW+CE was associated with significantly higher odds of OAG than N-N (adjusted odds ratio [OR] = 2.10, 95% confidence interval: 1.14–3.88, p = 0.018), whereas neither CEO (OR = 1.10, p = 0.431) nor UWO (OR = 1.54, p = 0.170) was significantly associated individually. This association with UW+CE remained robust across alternative BMI thresholds and after further adjustment for socioeconomic, lifestyle, and cardiometabolic variables. Conclusions: Co-occurring cold extremities and underweight status were associated with a combined hemodynamic risk profile for OAG, suggesting their potential utility as clinically accessible noninvasive markers for the early identification of highly vulnerable individuals and informing proactive glaucoma screening strategies. Full article

Background and Objectives: Ultrasound-guided sciatic and saphenous nerve blocks are widely used as analgesic alternatives for multimodal analgesia. However, how to objectively quantify the opioid- and anaesthetic-sparing effects of an additional peripheral nerve block in patients undergoing ankle fracture surgery under general anaesthesia remains unclear. This study aimed to evaluate their efficacy in managing postoperative pain and opioid-sparing effects following ankle fracture surgery. Materials and Methods: Patients scheduled for ankle fracture surgery were randomly assigned to the nerve block (n = 30) or control group (n = 30). The primary outcome was the postoperative numeric rating scale (NRS) score. The secondary outcomes included the total doses of remifentanil and propofol, Quality of Recovery-40 Korean (QoR-40K) scores, and self-reported patient satisfaction. Results: The NRS score immediately after surgery was significantly lower in the nerve block group compared with that in the control group (2.6 ± 2.5 vs. 6.2 ± 2.6; p < 0.001). The total remifentanil dose required during surgery was also significantly lower in the nerve block group than in the control group (1148.1 ± 391.8 vs. 1487.4 ± 798.8; p = 0.041). However, the patient satisfaction scale (3 [IQR, 2–4] vs. 3 [IQR, 2–4]; p = 0.206) and QoR-40K score 24 h after surgery (169 [IQR, 155–184] vs. 175 [IQR, 154–165]; p = 0.324) did not differ significantly between the two groups. Conclusions: Ultrasound-guided sciatic and saphenous nerve blocks significantly reduced immediate postoperative pain and intraoperative remifentanil consumption under qNOX (quantitative nociception index)-guided general anaesthesia during ankle fracture surgery. Full article

Background and Objectives: Environmental exposure to endocrine-disrupting chemicals (EDCs) is increasingly recognized as a potential contributor to cancer-related biological variability; however, human biomonitoring data in oncology populations remain limited. The present study aimed to assess urinary concentrations of selected phenolic EDCs and their associations with cardiometabolic, hematological, inflammatory, and survival-related parameters in patients with advanced lung cancer. Materials and Methods: A total of 190 patients diagnosed with stage IIIB/IV lung cancer were included in this study. Urinary concentrations of bisphenol A (BPA), bisphenol S (BPS), triclosan (TCS), and resorcinol (RCO) were determined using validated analytical methods. Associations between exposure biomarkers and clinical laboratory parameters were evaluated using sex-stratified statistical analyses and regression models adjusted for age and body mass index. Results: TCS was the most frequently quantified compound (29.47%), followed by BPS (27.37%), RCO (11.58%), and BPA (7.89%). Higher odds of TCS quantification were observed in patients with lung adenocarcinoma and a higher probability of BPA quantification in patients with squamous-cell carcinoma. Sex-specific exposure patterns were observed, with higher BPA and BPS concentrations measured among female patients. Exposure to phenolic EDCs was associated with alterations in kidney function biomarkers, liver enzyme activity, inflammatory cell profiles, and anthropometric indicators. In particular, BPA and BPS showed associations with renal function markers and systemic inflammatory parameters, while TCS exposure was related to reduced leukocyte subpopulations. Survival analysis demonstrates borderline associations for BPA between exposure groups. Conclusions: These findings provide novel human biomonitoring evidence linking exposure to phenolic endocrine-disrupting chemicals with systemic metabolic and inflammatory variability in patients with advanced lung cancer. The observed associations support the biological plausibility that environmental endocrine disruptors may contribute to interindividual heterogeneity in cancer-related physiological responses. Full article

Background and Objectives: The prediction of difficult laryngoscopic view remains an important component of preoperative airway assessment. Conventional bedside tests are widely used, but their diagnostic performance may be limited by subjectivity and interobserver variability. Focused upper airway ultrasonography may provide objective anatomical information and complement standard clinical evaluation. This study aimed to evaluate the diagnostic accuracy of focused upper airway ultrasonographic and conventional anthropometric measurements for predicting difficult laryngoscopic view in adult patients scheduled for tracheal intubation. Materials and Methods: This single-center, prospective, observational study included 212 adult patients with American Society of Anesthesiologists physical status I–III who were scheduled for elective surgery under general anesthesia requiring tracheal intubation. Preoperative airway assessment included the Modified Mallampati classification, upper lip bite test, mouth opening, thyromental distance, and sternomental distance. Focused ultrasonographic measurements included hyoid–skin distance and epiglottis–skin distance. Difficult laryngoscopic view was defined as a Cormack–Lehane grade III–IV view recorded during the initial direct laryngoscopic assessment. Diagnostic performance was evaluated using receiver operating characteristic curve analysis, and independent predictors were assessed using multivariable logistic regression. Results: Difficult laryngoscopic view was identified in 44 of 212 patients (20.8%). Patients with difficult laryngoscopic view had significantly higher body weight and body mass index, smaller mouth opening, and greater hyoid–skin distance. Hyoid–skin distance was significantly greater in patients with difficult laryngoscopic view than in those without difficult laryngoscopic view (12.00 ± 2.79 mm vs. 10.33 ± 3.16 mm; p = 0.002). Mouth opening was significantly smaller in patients with difficult laryngoscopic view (4.39 ± 0.72 cm vs. 4.74 ± 0.99 cm; p = 0.030). Epiglottis–skin distance did not differ significantly between groups. In receiver operating characteristic analysis, hyoid–skin distance showed an area under the curve of 0.682, with a cut-off value of ≥12.05 mm, sensitivity of 47.73%, and specificity of 83.33%. In multivariable logistic regression analysis, body mass index and hyoid–skin distance were independently associated with difficult laryngoscopic view, whereas greater mouth opening had a protective effect. The combined multivariable model showed an area under the curve of 0.734; however, at a probability cut-off value of 0.5, its sensitivity was low at 15.9%, despite high specificity of 97.0%. Conclusions: Focused upper airway ultrasonography may provide complementary objective information when used together with conventional preoperative airway assessment. Hyoid–skin distance was independently associated with difficult laryngoscopic view and demonstrated relatively high specificity; however, its discriminatory performance was modest and its sensitivity was limited. Therefore, hyoid–skin distance and the combined model should not be interpreted as standalone screening tools for excluding difficult laryngoscopic view. Their main clinical value may be as adjunctive parameters that support risk stratification and advance airway management planning in selected patients. Full article

Background and Objectives: The method of femoral canal opening during intramedullary fixation may influence the biological response to surgery. The aim of this study was to compare the early biological responses associated with mechanical canal opening and manual canal opening during Proximal Femoral Nail Antirotation (PFNA) fixation in patients with pertrochanteric femoral fractures, with a particular focus on inflammation, coagulation, organ dysfunction, and bone metabolism. Materials and Methods: This single-centre prospective randomised study consisted of 60 participants (50 women) with a mean age of 80.33 ± 11.13 years, who were randomly assigned to either manual femoral canal opening (n = 30) or mechanical canal opening (n = 30). Outcomes were assessed preoperatively and postoperatively during a 72 h follow-up period. This study was registered at ClinicalTrials.gov (ClinicalTrials.gov ID NCT07648719; registration date: 15 June 2026; study start: 1 March 2025). Results: Across all participants, surgery was associated with a significant decrease in haemoglobin levels, calcium, and estimated glomerular filtration rate, while fibrinogen, urea, creatinine, CRP (C-reactive protein), and NT-proBNP (N-terminal pro-B-type natriuretic peptide) significantly increased postoperatively. Patients in the mechanical canal opening group demonstrated significantly higher postoperative levels of leukocytes (p = 0.002), CRP (p = 0.001), NT-proBNP (p = 0.002), fibrinogen (p = 0.026), activated partial thromboplastin time (p = 0.035), urea (p = 0.001), and creatinine (p = 0.018), as well as greater reductions in haemoglobin (p < 0.001), compared with the manual canal opening group. Bone turnover markers also differed between groups: postoperative bone-specific alkaline phosphatase levels were significantly higher in the mechanical canal opening group (p = 0.001), whereas the increase in total procollagen type 1 N-terminal propeptide was more pronounced in the manual canal opening group (p = 0.045). Conclusions: The method of femoral canal opening during PFNA fixation significantly influences early postoperative systemic inflammation, coagulability, organ stress, and bone turnover dynamics. Manual opening of the femoral canal was associated with lower early systemic and bone stress biomarker responses compared with mechanical canal opening. Whether these differences translate into improved clinical outcomes, particularly in elderly patients with limited physiological reserve, remains to be determined. Full article

Background and Objectives: Renal sinus fat accumulation affects many diabetic processes, including blood pressure. The aim of this study was to find out if there is a link between the amount of fat in the renal sinus and the blood pressure that changes throughout the day in adults with non-alcoholic fatty liver disease (NAFLD). Materials and Methods: This retrospective analysis involved 55 adult patients diagnosed with non-alcoholic fatty liver disease (NAFLD) based on abdominal computed tomography (CT) and who had undergone 24 h ambulatory blood pressure monitoring (ABPM). According to standard ABPM criteria, individuals whose night-time systolic blood pressure decreased by ≥10% compared to daytime values were classified as “dippers,” whereas those with a reduction of <10% were classified as “non-dippers”. Results: The non-dipper group had a significantly higher leukocyte count (p = 0.012). Renal sinus fat volume (RSFV) was significantly larger in the non-dipper group (6.41 ± 3 mL) than the dipper group (4.12 ± 2.26 mL; p = 0.005). In the ROC curve analysis showing the role of RSFV in predicting the non-dipper blood pressure pattern, the threshold value for RSFV in our cohort was determined as ≥3.7 mL with a positive predictive value of 72.2%. Conclusions: Our findings indicated that RSFV plays a significant role in predicting the non-dipper blood pressure profile among individuals diagnosed with NAFLD. Participants with an RSFV of 3.7 mL or more in our cohort were more likely to exhibit a non-dipping blood pressure pattern. Future studies are needed to validate these findings in larger cohorts. Full article

Background and Objectives: Sepsis is a life-threatening condition characterized by organ dysfunction due to a dysregulated host response to infection. Blood cultures (BCs) remain the gold standard for diagnosing bloodstream infections, yet their positivity rate is limited and culture-negative sepsis remains poorly characterized. This study aimed to identify clinical and laboratory predictors of BC positivity in patients with suspected sepsis and to evaluate the prognostic implications of BC results on 28-, 90-, and 365-day survival. Materials and Methods: We retrospectively analyzed adult patients admitted to the Emergency Department of Policlinico di Bari (March 2023–December 2025) with sepsis or septic shock (Sepsis-3 criteria). After excluding contaminated cultures, 912 patients were included (602 culture-positive; 310 culture-negative) with a 1-year follow up. Predictors of BC positivity were assessed using logistic regression and ROC analysis; survival was evaluated with Kaplan–Meier curves and Cox models adjusted for age and Sequential Organ Failure Assessment (SOFA) score. We also evaluated time-to-positivity (TTP) for all blood culture isolates. Results: Culture-positive patients presented with greater initial severity, including higher rates of septic shock, elevated procalcitonin, CRP, lactate, and SOFA scores, and more frequent thrombocytopenia. Procalcitonin showed good discriminatory ability (AUC (area under the ROC curve) 0.785; cutoff 0.85 ng/mL; sensitivity 59.8%; specificity 83.8%). Key laboratory thresholds included a procalcitonin cutoff of 0.85 ng/mL, while CRP and platelet count did not show meaningful discriminatory cutoffs beyond their significant differences between culture-positive and culture-negative patients. Survival was consistently lower in culture-positive patients at 28 days (72.9% vs. 85.9%), 90 days (57.5% vs. 71.8%), and 365 days (44.3% vs. 61.2%). However, in adjusted Cox regression, BC positivity was not independently associated with 1-year mortality (HR 1.46; p = 0.092), whereas age and SOFA score remained significant predictors. Conclusions: Blood culture positivity identifies patients with greater initial severity, explaining their poorer unadjusted survival. However, culture positivity itself is not an independent predictor of long-term mortality, as age and organ dysfunction remain the main determinants of outcome. Procalcitonin showed solid discriminatory ability for true bacteremia. Full article

Background and Objectives: Sarcoidosis is a multisystem inflammatory disorder associated with significant oxidative stress. This study aimed to evaluate dynamic thiol-disulfide homeostasis (TDH)-a systemic redox status indicator-in patients with sarcoidosis. Materials and Methods: This cross-sectional study enrolled 58 sarcoidosis patients (diagnosed via ATS/ERS/WASOG criteria) and 53 healthy controls. Concentrations of native thiol (NT) and total thiol (TT) were determined utilizing an automated spectrophotometric technique. Disulfide (DS) levels and proportional indices were calculated, and the association of TDH parameters with the presence of sarcoidosis (patients vs. healthy controls) was examined using receiver operating characteristic (ROC) and Cohen’s d analysis. Results: Patients exhibited significantly reduced serum NT and TT levels compared to the control group (p = 0.003 and p = 0.009, respectively), whereas DS and the DS/NT ratio were elevated (p = 0.011 and p < 0.001). All parameters showed medium effect sizes. ROC analysis indicated that TDH parameters demonstrate an association with the presence of sarcoidosis, with AUC values ranging from 0.625 to 0.664. Among these, the DS/NT ratio showed the highest observed association with the disease group (AUC = 0.664), yielding 75.8% sensitivity and 60.3% specificity at a 5.7% cut-off. Conclusions: Our findings indicate that TDH is significantly altered in sarcoidosis, reflecting a systemic shift toward an oxidative state. These parameters appear to be exploratory biochemical indicators of systemic redox imbalance. To better understand their involvement in disease pathophysiology, future large-scale, prospective clinical trials might provide further insights. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the hepatic manifestation of systemic metabolic dysfunction and has become one of the leading causes of chronic liver disease worldwide. Although obesity is a major determinant of MASLD, the metabolic and lifestyle context in which the disease develops may vary across different geographical and dietary environments. The present study aimed to evaluate the prevalence of MASLD among adults with metabolic dysfunction from two European cohorts, to compare the clinical, metabolic, lifestyle, and psychological characteristics of participants with MASLD from Romania and Italy, and to explore differences according to MASLD status within each cohort. In addition, intestinal permeability was exploratorily assessed in a subgroup of the Italian cohort. Methods: This prospective multicentre observational study included 132 adults undergoing metabolic and hepatic evaluation in Romania (n = 52) and Italy (n = 80). Hepatic steatosis was assessed using SteatoTest in the Romanian cohort and ultrasonography in the Italian cohort. Anthropometric and metabolic parameters were recorded in all participants. Dietary quality was evaluated using the MEDI-LITE questionnaire, physical activity using the International Physical Activity Questionnaire (IPAQ), depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9), and health-related quality of life using the 36-Item Short Form Health Survey (SF-36). Intestinal permeability was evaluated in the Italian cohort using the lactulose/mannitol absorption test. Results: MASLD was identified in 80.8% of participants from the Romanian cohort and in 66.3% of participants from the Italian cohort. Among patients with MASLD, Italian participants exhibited significantly higher body mass index, waist circumference, fasting insulin, total cholesterol, LDL cholesterol, and diastolic blood pressure compared with Romanian participants, whereas HDL cholesterol levels were significantly higher in the Romanian cohort. Sex-stratified analyses revealed significant sex-related differences in anthropometric and metabolic parameters within both cohorts. In both geographical populations, participants with MASLD demonstrated lower adherence to the Mediterranean diet, lower physical activity levels, higher depressive symptom burden, and less favorable quality-of-life indicators compared with participants without MASLD. Exploratory analyses of intestinal permeability in the Italian cohort did not reveal significant differences according to MASLD or obesity status. Conclusions: MASLD was highly prevalent in both Romanian and Italian adults with metabolic dysfunction. Patients with MASLD exhibited distinct metabolic and lifestyle profiles across the two geographical cohorts, supporting the potential contribution of environmental and lifestyle-related factors to MASLD heterogeneity. Lower adherence to the Mediterranean diet, reduced physical activity, and increased psychological burden were consistently associated with MASLD in both populations. Exploratory intestinal permeability analyses did not demonstrate significant differences according to MASLD or obesity status in the Italian cohort. Full article

Epicardial adipose tissue (EAT) is a distinct form of visceral adipose tissue that lies within the pericardium and directly adjacent to the myocardium. Individuals with type 2 diabetes mellitus (T2DM) exhibit excessive and metabolically active EAT, which contributes to the development of early diabetic myocardial disease, formerly referred to as diabetic cardiomyopathy. Recent studies have demonstrated that excess EAT is characterized by a proinflammatory profile that may adversely affect the underlying myocardium, leading to impaired diastolic and systolic function. In this review, we discuss the role of excessive EAT as a source of proinflammatory and profibrotic cytokines that influence adjacent ventricular and atrial myocardium through local tissue crosstalk. In addition to metabolic alterations, enlarged EAT induces hemodynamic changes that result in pericardial constraint and enhanced ventricular interdependence, both of which are hallmarks of diabetic pericardial disease. We further analyze the interplay among T2DM, inflammation, obesity, and increased EAT on the one hand, and myocardial dysfunction characterized by myocardial stiffness, elevated filling pressures, and diastolic and systolic dysfunction on the other. We emphasize that the distinct immunometabolic activity of perivascular adipose tissue may lead to a paradigm shift in the understanding of coronary artery disease, moving from a predominantly endoluminal to an exoluminal perspective. A wide range of dietary, lifestyle, and pharmacological interventions are available within this emerging diabeto-cardiometabolic continuum, each with a potential role; however, the timing of intervention is crucial. This review also explores the potential effects of antidiabetic and other pharmacological agents that modulate EAT thickness, volume, and/or activity, and discusses directions for future mechanistic and clinical research. Full article

Background and Objectives: Oropharyngeal squamous cell carcinoma (OPSCC) is a biologically heterogeneous disease. p16 immunohistochemistry is widely used as a surrogate marker for human papillomavirus (HPV)–associated OPSCC and plays a key role in prognostication and staging. However, p16 overexpression does not invariably reflect transcriptionally active HPV infection, and the clinical significance of p16–HPV discordance remains incompletely defined, particularly in populations with high exposure to traditional carcinogens. Materials and Methods: We conducted a retrospective cohort study of patients diagnosed with OPSCC between 2016 and 2020 at a tertiary referral center in Taiwan. p16 immunohistochemistry was performed in all cases, and transcriptionally active high-risk HPV was assessed by RNA in situ hybridization in p16-positive tumors. Clinicopathologic characteristics, carcinogen exposure profiles, and survival outcomes, including overall survival (OS) and disease-free survival (DFS), were analyzed according to p16 and HPV status. Results: Among 140 patients with OPSCC, 49 (35%) were p16-positive, of whom 44 (90%) demonstrated transcriptionally active HPV. Compared with p16-negative tumors, p16-positive OPSCC was significantly associated with lymphoepithelial organ involvement, non-keratinizing morphology, lower clinical stage, and less exposure to alcohol, betel nut, and tobacco. In Kaplan–Meier and univariable analyses, p16 positivity was associated with significantly improved OS and DFS. In contrast, p16-positive/HPV RNA-negative tumors exhibited clinicopathologic features more closely resembling p16-negative OPSCC, including greater keratinization and higher carcinogen exposure. Conclusions: p16-positive/HPV RNA-negative tumors showed clinicopathologic features suggestive of biological heterogeneity; however, the small number of discordant cases precludes definitive conclusions regarding survival differences. These findings support selective HPV RNA testing in p16-positive OPSCC with atypical clinicopathologic features, particularly in carcinogen-endemic populations. Full article

Background and Objectives: The wrist is one of the most common sites of rheumatic disease. Based on the graded deformities of Larsen et al., surgery has been adapted to minimize harm while maximizing benefit to the individual. This study aims to survey the institutional experience, describing functional outcomes and patient satisfaction across several surgical approaches, without formal statistical comparison. Materials and Methods: The studies and results presented here are from one center specialized in rheumaorthopedic surgery and reflect the above concepts. The studies cover a broad spectrum of surgical techniques, which were categorized according to the Larsen stages of wrist destruction. All studies were retrospective or retrospective-like, and follow-up data were analyzed collectively. The primary endpoints were functional outcome scales and patient satisfaction, supplemented by pain relief, as well as strength and range of motion. The assessment utilized, amongst others, the QuickDASH, FFbH and Clayton score, as well as appropriate patient-reported measures such as ADL and SF-36. Radiological follow-ups were classified according to the Larsen–Dale–Eek classification; for endoprostheses/arthrodesis, carpal height was determined according to Youme. Results: Significant improvements in the Clayton score (consistently greater postoperatively than preoperatively) are evident for several procedures, particularly MPW^® (+37 points) and APW^® (+28 points). Postoperative reductions in VAS pain scores are marked for most procedures, e.g., MPW^® from 7 to 1.8. The revision rates for most procedures are around 10–13% during the follow-up periods. In addition, the tendon and soft tissue functions of the hand(s) play critical roles in these PROMs. Conclusions: The studies present the results and limitations of surgical treatment for rheumatic wrists in the prebiological era. The results of individual studies need to be examined more closely to better assess the potential and limitations of surgery for patients. Full article

Background and Objectives: Acute appendicitis is the most common surgical emergency in children. The standard of care has been appendectomy for many years. However, in recent years, studies investigating antibiotic therapy alone have increased rapidly, suggesting that non-operative management may be an effective alternative with a lower risk of complications. In this study, we compared two antibiotic regimens (ceftazidime/metronidazole and ampicillin/metronidazole) to evaluate the effectiveness of two antibacterial strategies. Materials and Methods: A total of 41 children aged 7–18 years were enrolled and randomly assigned to one of the two treatment groups, with the follow-up conducted over one year to assess recurrence. For the evaluation of antibiotic effectiveness, inflammation was assessed using leukocyte count, C-reactive protein, and the biomarkers IL-6, IL-8, and MCP-1, which were measured on each of the three days of inpatient antibiotic therapy. Results: Analysis of the collected data revealed no statistically significant difference in inflammatory markers between the two treatment groups. Conclusions: These findings suggest that both antibiotic regimens offer comparable clinical outcomes and may be used interchangeably in clinical practice. Full article

Background and Objectives: The effects of nicotine on wound healing and flap survival remain controversial. While smoking is associated with increased flap complications, emerging evidence suggests that nicotine may exert dose- and duration-dependent effects. This study aimed to investigate how short-term, low-dose nicotine affects flap survival and to evaluate its potential role in oxidative stress and ferroptosis. Materials and Methods: Twelve adult male BALB/c mice were randomly assigned to either a control group or a nicotine-treated group, with six mice in each group. Nicotine, at a dose of 2 mg/kg, was given subcutaneously for fourteen days before flap surgery. This treatment continued for seven days after the surgery. A dorsal random-pattern skin flap model was established in all animals. The flap necrosis area was assessed on postoperative day 7 using planimetric analysis. Serum and tissue glutathione peroxidase 4 (GPX4) levels and serum malondialdehyde (MDA) levels were measured. Histopathological evaluation included epithelialization, microvascular density, neovascularization, fibroblast density, and inflammatory cell infiltration. Results: Nicotine treatment significantly reduced flap necrosis compared with the control group. Histopathological analysis demonstrated significantly increased epithelialization and microvascular density in the nicotine-treated group, whereas no significant differences were observed in neovascularization, fibroblast density, or inflammatory cell infiltration. Biochemical analyses revealed no significant differences in serum or tissue GPX4 levels or serum MDA levels between the groups. Conclusions: Short-term nicotine administration enhanced flap survival, correlating with increased epithelialization and microvascular density, while not significantly affecting markers of oxidative stress or ferroptosis. These results imply that the positive impact of nicotine on flap viability might be largely attributable to vascular processes rather than pathways involving oxidative stress. Full article