Journal of Clinical Medicine doi: 10.3390/jcm15228933

Authors: Zihao Li Wuyuan Tan Yingying Xiao Yanli Xie Yuming Sun

Background: Vitamin D metabolic disorders are a critical prognostic factor in patients with chronic kidney disease (CKD). However, the dose–response association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and all-cause mortality in the CKD population remains controversial. This study aimed to quantify this association and explore a preliminary reference serum 25(OH)D range for CKD patients. Methods: We systematically searched PubMed, EMBASE, Web of Science, and Cochrane Library databases up to 10 March 2026, for prospective cohort studies investigating the association between serum 25(OH)D and all-cause mortality in CKD patients. Summary hazard ratios (HRs) were pooled using a random-effects model. Generalized least squares regression models were applied to assess the quantitative dose–response association of serum 25(OH)D with all-cause mortality. Results: A total of 17 prospective cohort studies involving 33,550 CKD patients were included. Higher serum 25(OH)D levels are significantly associated with a lower risk of all-cause mortality (pooled HR = 0.58, 95% CI: 0.53–0.64, p < 0.001; I2 = 52.7%). Dialysis status (p = 0.005) and follow-up duration (p = 0.006) were significant effect modifiers of this association. Dose–response analysis revealed a significant non-linear association with a potential U-shaped pattern (p for non-linearity < 0.001). Conclusions: Serum 25(OH)D suggests a U-shaped association with mortality in CKD; the upward risk at higher concentrations may reflect confounding, with 25(OH)D likely a marker of health status rather than a modifiable risk factor. Findings are constrained by the observational design and moderate between-study heterogeneity; future trials are warranted to validate these results and elucidate relevant mechanisms.

Journal of Clinical Medicine doi: 10.3390/jcm15228935

Authors: Ana-Maria Casapu Tatiana Dramba Diana Tatarciuc Oana Irina Gavril Diana-Elena David Cringuta Mariana Paraschiv Irina Mihaela Esanu

Background/Objectives: Malnutrition, inflammation, muscle loss, and frailty often coexist in older patients with acute coronary syndrome (ACS); we assessed their prognostic value. Methods: Following PRISMA 2020 (PROSPERO CRD420261512821), PubMed, Scopus, and Web of Science were searched on 20 September 2026 and supplemented on 1 November 2026. Observational studies of older patients with ACS (mean, median, or minimum age ≥65 years) relating nutritional, inflammatory, muscle-related, or frailty measures to mortality or major adverse cardiovascular events (MACE) were included. Risk of bias and certainty were assessed with the Newcastle–Ottawa Scale and GRADE. Results: We included 162 reports from 121 cohorts. Clinical Frailty Scale-defined frailty was associated with all-cause mortality (8 cohorts; HR 2.69, 95% CI 2.14–3.39; moderate certainty). Administrative frailty scores showed consistent but heterogeneous associations. Low Geriatric Nutritional Risk Index (HR 2.81, 95% CI 1.40–5.61) and higher CONUT scores (HR 1.29 per point, 95% CI 1.11–1.51) were associated with mortality and MACE, respectively, but not after Hartung–Knapp adjustment (very low certainty). Inflammatory indices were mostly associated with mortality but heterogeneous; muscle-related data were sparse; no study assessed ventricular remodeling. Conclusions: Frailty, and to a lesser extent malnutrition, are associated with adverse outcomes; their added value for risk stratification remains unproven.

Journal of Clinical Medicine doi: 10.3390/jcm15228934

Authors: Jyoti Jain Rahul Karna Tanveer ud din Mian Adeel Nasrullah Palash Asawa Laith Alhuneafat Pushan Aggarwal Amresh Raina Briana DiSilvio Hayah Kassis-George

Obesity and pulmonary hypertension (PH) frequently coexist, but obesity is not a distinct PH group. This narrative review of the literature published through 27 September 2026 appraises the evidence by PH group. Obesity is most clearly linked to PH through intermediate conditions, particularly heart failure with preserved ejection fraction, obstructive sleep apnea, and obesity hypoventilation syndrome, and it can complicate hemodynamic classification because elevated intrathoracic pressure may raise the measured pulmonary arterial wedge pressure. Experimental studies suggest direct pulmonary vascular effects through adipokine imbalance, inflammation, altered estrogen metabolism, oxidative stress, and insulin resistance; however, an independent causal role of obesity in human pulmonary arterial hypertension has not been established. Small, mostly observational studies report lower estimated pulmonary pressures after bariatric surgery, but a benefit of intentional weight loss on invasive hemodynamics or clinical PH outcomes is unproven. Incretin-based therapies produce substantial weight loss and improve symptoms in obesity-related heart failure with preserved ejection fraction; acute human hemodynamic data are emerging, but long-term efficacy in PH has not been tested. Higher body mass index has been associated with lower observed mortality in several PH cohorts, possibly reflecting confounding and reverse causation. We distinguish established findings from hypotheses and highlight research priorities.

Journal of Clinical Medicine doi: 10.3390/jcm15228931

Authors: Saud Aljohani Osama Alarwi Thabat Aljohani Abdullah Alharbi Yusra AlAbbasi Shahad Aloufi Hazim AlAhmadi Mujtaba Almadani Omar Alshammari

Background/Objectives: Endothelin receptor antagonists (ERAs) lower albuminuria in chronic kidney disease (CKD) but cause dose-dependent fluid retention, which natriuretic sodium–glucose cotransporter-2 inhibitors (SGLT2is) may offset. We compared ERA plus SGLT2i therapy with either class alone in adults with proteinuric CKD. Methods: PubMed/MEDLINE, Web of Science and CENTRAL were searched up to 26 September 2026, with citation searching and a supplementary PubMed search on 5 November 2026 (PROSPERO CRD420261340145). Proteinuria was pooled as ratios of geometric means (random effects) and adverse events as Mantel–Haenszel risk ratios (RRs); risk of bias was assessed with RoB 2 and ROBINS-I, and certainty with GRADE. Results: Nine studies (seven randomized; 1043 participants) were included. Compared with an SGLT2i alone, adding an ERA lowered albuminuria or proteinuria by a further 29.8% (ratio of geometric means 0.70; 95% CI 20.4–38.1%; six trials, 509 participants; I2 = 0%; moderate certainty, surrogate outcome). Fluid-retention events were numerically more frequent with the combination (RR 1.69, 0.91–3.16; low certainty) and more frequent with higher-dose zibotentan (RR 2.33, 1.29–4.20; moderate certainty); peripheral edema and discontinuation estimates were model-dependent. Compared with an ERA alone, the combination reduced fluid-retention events (RR 0.38, 0.20–0.72; low certainty). In one exploratory 64-participant stratum, eGFR declined more slowly with atrasentan over 2.5 years (very low certainty). Conclusions: Adding an ERA to an SGLT2i lowers albuminuria or proteinuria, a surrogate outcome, by about 30%, and SGLT2i co-therapy may reduce ERA-related fluid retention; safety evidence is short-term and excludes heart failure, so trials with kidney and heart-failure outcomes are needed.

Journal of Clinical Medicine doi: 10.3390/jcm15228932

Authors: Xiaoyu Zhou Qianzhi Sun Yunxi Zheng Ting Wang Yun Chen Jingyao Ruan Panpan Zhang Qi Tian Lu Li Junjie Xing Kaikai Chang Jiangnan Wu Xiaofang Yi

Objectives: The reproductive impact of bowel involvement in deep endometriosis (DE) after fertility-preserving surgery remains controversial. We aimed to determine whether bowel endometriosis (BE) is independently associated with postoperative pregnancy and live birth and to clarify its influence on conception pathways. Methods: This retrospective cohort study was conducted at a tertiary referral center between 2017 and 2024. Women aged 18–45 years who underwent laparoscopic fertility-preserving surgery for histologically confirmed DE and wished to conceive were included. Primary outcomes were postoperative pregnancy and live birth. The secondary outcome was conception mode, classified as spontaneous conception or medically assisted reproduction (MAR). Results: A total of 202 women were analyzed (127 without bowel involvement; 75 with BE). During follow-up, 140 women achieved pregnancy and 119 had a live birth. Pregnancy occurred in 64.0% of women with BE and 72.4% without bowel involvement (adjusted hazard ratio [aHR], 0.88; 95% confidence interval [CI], 0.60–1.28). Live birth occurred in 50.7% and 63.8%, respectively (aHR, 0.87; 95% CI, 0.57–1.32). BE was associated with lower cumulative incidence of spontaneous pregnancy (adjusted subdistribution hazard ratio, 0.53; 95% CI, 0.30–0.94) and higher MAR pregnancy (adjusted subdistribution hazard ratio, 1.72; 95% CI, 1.01–2.92). An inverse age–pregnancy association above 30 years in women with BE was an exploratory finding. Conclusions: BE was not significantly associated with reduced pregnancy or live birth after fertility-preserving surgery for DE. Given the limited precision of the estimates, clinically meaningful differences in pregnancy and live birth cannot be excluded. However, its association with a shift in conception pathway, characterized by fewer spontaneous conceptions and greater reliance on MAR, supports individualized fertility counselling.

Journal of Clinical Medicine doi: 10.3390/jcm15228929

Authors: Žiga Godicelj Matevž Uršič Samo Karel Fokter

Background/Objectives: Cemented total knee arthroplasty (cTKA) remains the most widely used fixation strategy, while cementless TKA (clTKA) has gained interest with advances in implant design and biomaterials. This systematic review compared survivorship, radiographic, and clinical outcomes of cemented and cementless primary TKA based exclusively on randomized controlled trials (RCTs). Methods: PubMed, MEDLINE, Scopus, Cochrane CENTRAL, and Web of Science were searched in July 2026 for RCTs published from January 2021 to July 2026 with ≥2 years of follow-up. Risk of bias was assessed using RoB 2, and findings were synthesized qualitatively due to substantial heterogeneity. Results: Six RCTs including 1295 TKAs were analyzed, with 1200 (92.7%) available at final relevant follow-up. Most survivorship, radiographic, and clinical outcomes showed no significant differences between fixation strategies. One RCT reported greater 10-year survivorship free of any revision and less aseptic tibial loosening with cementless fixation, while some studies reported fewer radiolucent lines. Functional outcomes were similar between groups. Conclusions: Most outcomes showed no statistically significant differences between cemented and cementless TKA. Favorable findings for cementless fixation were inconsistent and may be implant-specific. Given the limited number of RCTs, low event rates, and implant heterogeneity, current evidence does not establish superiority, equivalence, or non-inferiority of either fixation strategy.

Journal of Clinical Medicine doi: 10.3390/jcm15228928

Authors: Aariez Khalid Szymon Matejuk Alexis Parks Christopher M. Malozzi Brian E. Persing

FMS-like tyrosine kinase 3 (FLT3) inhibitors improve outcomes in FLT3-mutated acute myeloid leukemia (AML), but interpreting cardiovascular events is complicated by prior or concurrent anthracycline exposure, hematopoietic stem cell transplantation, infection, electrolyte disturbances, and multiple supportive-care medications. We conducted a targeted narrative review of PubMed/MEDLINE, ClinicalTrials.gov, current U.S. and European product information, professional guidance, and primary regulatory and clinical reports through 5 November 2026. For randomized comparisons with exact counts, we calculated unadjusted within-trial risk differences and risk ratios; heterogeneous data were neither pooled nor compared across agents. The strongest drug-specific evidence concerns QT prolongation and label-directed electrocardiographic monitoring, particularly for quizartinib and gilteritinib. Evidence for heart failure and myocardial or pericardial injury remains less certain and is largely observational or case-based. We organize monitoring and management by agent and treatment phase and distinguish label requirements from guideline-based or pragmatic recommendations. FLT3-specific approaches to imaging, biomarkers, treatment interruption, and rechallenge still require prospective study.

Journal of Clinical Medicine doi: 10.3390/jcm15228930

Authors: Qiyuan Cao Yaolin Li Jiaqi Xu Jinquan Zhang Kexin Zhou Wenjing Li Yan Zhang Xuehua Huang Yuanyuan Li Lijun Jiang

Background/Objectives: Symptoms and daily-life outcomes after psychiatric discharge may differ from those near discharge. We compared these assessments in children and adolescents with recorded depressive-disorder discharge diagnoses. Methods: This retrospective cohort linked admission assessments, clinical records and electronic follow-up questionnaires from West China Hospital, China, during May 2025–August 2026. Participants were aged 9–18 years. Random-intercept linear mixed-effects models adjusted for age, sex and the corresponding admission score; paired analyses estimated within-person differences. Results: Of 333 participants, 243 contributed 400 observations to the main model. Among 265 participants with a fully elapsed day-30 window, 132 (49.8%) had a selected questionnaire. Only 81 of 333 participants had both peridischarge and day-30 assessments. The adjusted day-30 local Beck Depression Inventory (BDI)-based score was 7.10 points higher than peridischarge (95% confidence interval [CI], 4.37–9.83); the complete-pair mean difference was 6.54 points (95% CI, 3.25–9.84). Six secondary contrasts had false-discovery-rate-adjusted p values below 0.05; the functional-impact CI included zero. Conclusions: Scores were less favorable at approximately one month in available assessments, including higher depressive-symptom scores among observed pairs. Selective questionnaire availability limits generalization to the entire cohort. Without validated meaningful-change thresholds for the local measures, statistically significant score differences do not establish clinically important deterioration or diagnostic relapse.

Journal of Clinical Medicine doi: 10.3390/jcm15228927

Authors: Gizem Akçın Yusuf Karancı Fulya Çiyiltepe

Background/Objectives: The Sepsis Tracheostomy early Prediction (STeP) score was developed in Japan to predict tracheostomy within 14 days in mechanically ventilated patients with sepsis and has not been tested elsewhere. We evaluated the score in a United States database and, as a secondary aim, compared it with machine learning models from the same cohort. Methods: In the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, we included adults with Sepsis-3 who received invasive mechanical ventilation within 24 h of intensive care unit (ICU) admission. As in the derivation study, the primary cohort excluded patients with viral pneumonia and those who died in the ICU without tracheostomy. The full cohort included them. Discrimination was assessed with the area under the curve (AUC) and calibration with the observed to expected (O/E) ratio. Ten machine learning algorithms were tested with nested cross-validation and temporal validation. Results: Of 4585 patients in the primary cohort, 276 (6.0%) underwent tracheostomy. The AUC of the STeP score was 0.632 vs. 0.73 in the Japanese cohort. Tracheostomy rates in the low-, moderate-, and high-risk groups were 3.3%, 6.4%, and 10.6% (O/E ratio, 0.48). The O/E ratio rose to 0.84 when the 43% of tracheostomies performed after day 14 were counted. In the full cohort, the AUC was 0.617 and the O/E ratio 0.35. In cross-validation, the AUC was 0.737 for penalized logistic regression and 0.742 for gradient boosting (0.704 and 0.710 with the 46 predictors verifiable within 24 h), but in temporal validation the models were not significantly better than the STeP score. Conclusions: The STeP score showed moderate discrimination and overestimated the risk of tracheostomy, partly because many tracheostomies were performed after day 14, and should be recalibrated before use in another health care system. The models discriminated better in cross-validation, but they were derived and tested in a single database and have not been validated externally.

Journal of Clinical Medicine doi: 10.3390/jcm15228926

Authors: Mustafa Harı Banu Kara Merve Akan Durgay Mustafa Yılmaz Muhteşem Erol Yayla

Background and aims: Sleep disturbances and psychological symptoms are common in inflammatory bowel disease (IBD). We compared sleep outcomes in IBD and non-IBD outpatients and explored associations with disease activity. Methods: This cross-sectional study included 155 patients with IBD and 149 non-IBD controls (March–May 2026). Sleep quality, insomnia severity, and psychological symptoms were assessed using the PSQI, ISI, and HADS. Multivariable and sensitivity analyses assessed associations with IBD. Results: Poor sleep quality (PSQI > 5) and moderate-to-severe insomnia (ISI ≥ 15) were more frequent in IBD than controls (50.3% vs. 36.2%, p = 0.015; and 20.0% vs. 8.1%, p = 0.003). However, median PSQI (6 vs. 4; p = 0.056) and ISI (8 vs. 7; p = 0.097) scores did not differ significantly, nor did ISI ≥ 8 prevalence (52.3% vs. 45.6%; p = 0.248). Anxiety (HADS-A ≥ 8: 39.4% vs. 27.5%; p = 0.029) and depressive symptoms (HADS-D ≥ 8: 42.6% vs. 17.4%; p < 0.001) were more frequent in IBD. In primary adjusted models, IBD was associated with poor sleep (aOR 2.00, 95% CI 1.23–3.24) and ISI ≥ 15 (aOR 3.40, 95% CI 1.61–7.18). Sensitivity analyses additionally adjusting for diabetes, hypertension, alcohol use, and BMI supported these associations; continuous-score models identified higher PSQI (β = 1.13; p = 0.008) and ISI (β = 1.52; p = 0.021) scores. Further HADS adjustment yielded nonsignificant, imprecise IBD associations. Continuous disease activity indices were not significantly correlated with sleep outcomes. Conclusions: IBD was associated with more frequent poor sleep and moderate-to-severe insomnia despite nonsignificant median and ISI ≥ 8 comparisons. Disease-activity findings were exploratory; causality cannot be inferred.

Journal of Clinical Medicine doi: 10.3390/jcm15228925

Authors: Ricardo G. Figueiredo Isis Costa Théo Queiroz Caila Silva Márcio Carvalho Karla Robles-Velasco Oscar Calderon-Llosa Juan Carlos Calderón Tanja Hildenbrand Ivan Chérrez-Ojeda

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common, disabling inflammatory airway disease marked by persistent sinonasal symptoms, impaired quality of life, and frequent comorbidities such as asthma and aspirin-exacerbated respiratory disease. Standard treatment relies on intranasal corticosteroids, systemic corticosteroids, and endoscopic sinus surgery; however, recurrence is common, and many patients develop corticosteroid dependence or require repeated surgery, raising concerns about long-term safety and disease control. Advances in understanding CRSwNP immunopathogenesis have identified type 2 (T2) inflammation as a central driver, characterized by eosinophilic infiltration and cytokine signaling mediated by interleukin (IL)-4, IL-5, IL-13, and epithelial alarmins such as thymic stromal lymphopoietin (TSLP), leading to targeted biologic therapies that modulate these pathways. This narrative review summarizes current evidence on biologic agents approved or in advanced clinical development for CRSwNP. Data from pivotal randomized controlled trials and real-world studies show that these biologics reduce nasal polyp size, improve sinonasal symptoms and olfactory function, enhance quality of life, and decrease the need for systemic corticosteroids and revision surgery, with benefits particularly pronounced in patients with coexisting asthma. Overall, biologic therapy represents a paradigm shift in managing severe CRSwNP, enabling personalized treatment while highlighting the need for long-term data, head-to-head comparisons, and cost-effectiveness analyses.

Journal of Clinical Medicine doi: 10.3390/jcm15228924

Authors: Flavio Spoto Martina Roman Giulia Vinco Leonardo Monterubbiano Emanuele Demozzi Giuseppe Sala Carmelo Cicciò Chiara Longo Luca Ordofendi Andrea Santovito Martina Castellan Sofia Maria Avesani Nicolò Cardobi Riccardo De Robertis Mirko D’Onofrio Giovanni Foti

Background/Objectives: Photon-counting CT (PCCT) spectral fat maps allow fat quantification on routine scans. We quantified the fat fraction (FF) in the liver, spleen, pancreas, and psoas, assessed determinants and regional heterogeneity, and compared spectral FF with an attenuation-derived PDFF estimate (HU-PDFF). Methods: In total, 270 consecutive patients underwent abdominal PCCT. On the unenhanced acquisition, 14 ROIs per patient were placed, recording spectral FF and 70 keV attenuation; no external reference standard was available. Agreement was assessed via ICC and Bland–Altman analysis. Results: Mean FF was 4.2% (liver), 12.3% (spleen), 23.1% (pancreas), and 15.2% (psoas); 34.8% had hepatic steatosis (FF ≥ 5%). In exploratory analyses, BMI was the main independent correlate of hepatic and pancreatic FF, and psoas FF was associated with BMI, age, and male sex; splenic FF was unrelated to BMI and age. Hepatic FF showed no systematic supra-/infra-portal difference (ICC 0.97); the pancreatic tail was leaner than the body and head. Spectral FF and attenuation correlated strongly in the liver, pancreas, and psoas (r = −0.82 to −0.92), but spectral FF was 4.6 points lower than HU-PDFF in the liver and 2.7–3.4 points higher in the pancreas and psoas; liver attenuation ≤ 58.7 HU corresponded to FF ≥ 5% (AUC 0.93; cross-validated sensitivity and specificity 86%). Conclusions: PCCT fat maps are feasible for multi-organ fat measurement. Spectral FF and HU-PDFF are highly correlated but not interchangeable because of organ-specific offsets, whose source and absolute accuracy must be established against MRI-PDFF.

Journal of Clinical Medicine doi: 10.3390/jcm15228923

Authors: Tomasz Tykocki

Extent of resection (EOR) is an established prognostic factor in glioblastoma (GBM). Neoadjuvant immune checkpoint inhibition (ICI) aims to strengthen antitumor immunity before surgery, but its effect on the surgical and radiological variables that define EOR has received little scrutiny. This narrative review examines the four neoadjuvant-ICI trials in GBM. Only one reported resection metrics: presurgical and postsurgical tumor volume, percent resection, and gross total resection did not differ between arms, and none was selected as a survival predictor in an elastic-net regression. The other three trials reported no resection data. No trial tested whether neoadjuvant ICI changes the achievable resection margin, the reliability of the early postoperative MRI used to calculate EOR, or the prognostic value of EOR. Evidence on ICI-associated pseudoprogression concerns later, longitudinal imaging, and the only dedicated GBM cohort found no pseudoprogression attributable to ICI monotherapy. Future neoadjuvant-ICI trials should prespecify EOR as an endpoint using a standardized classification such as RANO resect, standardize postoperative MRI timing, adjudicate the early postoperative scan separately from response-assessment imaging, and include newly diagnosed patients. These gaps should be read against the broader record of immunotherapy in GBM, where checkpoint inhibitors, vaccines, and gene or viral therapies have not yet improved survival in randomized trials.

Journal of Clinical Medicine doi: 10.3390/jcm15228922

Authors: Muna H. Akasha Samah F. Al-Shatnawi Tareq L. Mukattash Rana K. Abu-Farha Mohammad S. Khalifeh

Background: Type 1 diabetes mellitus (T1DM) is a chronic condition that commonly affects children and requires lifelong insulin treatment. The demands of diabetes management and its associated psychosocial burden may increase the risk of depressive symptoms among children with T1DM. Objective: The objective of this study was to assess the prevalence and severity of depressive symptoms and their association with selected sociodemographic and clinical factors among children with T1DM in Jordan. Methods: A cross-sectional study was conducted among 150 children aged 8–14 years with T1DM attending the outpatient diabetes clinic at the Royal Medical Services (RMS) Queen Rania Al Abdullah Hospital for Children. Sociodemographic and clinical data were collected using a structured questionnaire, and depressive symptoms were assessed using the Arabic version of the Children’s Depression Inventory (CDI). Associations between depressive symptoms status and selected factors were assessed using appropriate statistical tests. Statistical significance was set at p < 0.05. Results: Of the 150 children with T1DM, 73 (48.7%) had depressive symptoms. Among these, 13 (17.8%) had mild, 37 (50.7%) had moderate, and 23 (31.5%) had severe depressive symptoms. In the multivariable logistic regression analysis, family income above JD 500 (AOR = 0.168, 95% CI: 0.050–0.564, p = 0.004) and controlled glycemic status (AOR = 0.078, 95%CI: 0.015–0.399, p = 0.002) were significantly associated with lower odds of depressive symptoms, whereas a higher frequency of hypoglycemic episodes in the previous month was associated with higher odds of depressive symptoms (AOR = 1.766, 95% CI: 1.199–2.600, p = 0.004). No other variables in the adjusted model were significantly associated with depressive symptoms (p > 0.05). Conclusions: Depressive symptoms were highly prevalent among children with T1DM in Jordan, with most affected children having moderate or severe symptoms. Routine screening and appropriate psychological support should be considered as part of the comprehensive follow-up of children with T1DM.

Journal of Clinical Medicine doi: 10.3390/jcm15228916

Authors: Kentaro Yamane Wataru Narita Shinichiro Takao Hisakazu Shitozawa Kazuhiro Takeuchi Shinnosuke Nakahara

Background/Objectives: Conventional open-door cervical laminoplasty involves extensive paraspinal muscle stripping linked to axial pain. Whether a short-incision, limited-exposure variant can be adopted by surgeons with different levels of prior experience, and whether any tissue-sparing benefit survives adjustment for operated level, is unclear. Methods: In a single-centre retrospective cohort, 90 consecutive exoscopic minimally invasive cervical laminoplasty (ExLAP) procedures (senior surgeon, n = 68; junior surgeon, n = 22) were compared with same-institution conventional Hirabayashi laminoplasty, and the primary comparison was restricted to the two surgeons who performed both techniques (n = 67). Learning curves were assessed by operative-time cumulative sum (CUSUM) analysis. Acute tissue-trauma surrogates were incision length, estimated blood loss (EBL), day-1 haemoglobin decline, day-1 creatine kinase (CK) rise and C-reactive protein (CRP). Level-matched and propensity-score-matched sensitivity analyses were performed. Results: Descriptive CUSUM change points occurred at case 11 (junior) and case 24 (senior), with operative-time reductions of 37.6% and 14.0%. Compared to same-surgeon conventional laminoplasty, ExLAP had a shorter incision (34.3 vs. 90.7 mm), lower EBL (10 vs. 50 mL; non-measurable in 40.0% vs. 11.9%) and lower day-1 CRP (1.34 vs. 3.16 mg/dL) (all p < 0.001), together with a lower day-1 CK rise (160 vs. 230 U/L; p = 0.015). After level matching and propensity-score matching, the incision, EBL and day-1 CRP differences persisted, but the CK difference lost significance (p = 0.09 and p = 0.16). Complications did not differ. Conclusions: ExLAP was implemented by both surgeons, with a descriptive operative-time change point at approximately 11 cases in the junior surgeon, and reduced incision length, blood loss and early systemic inflammation. The CK reduction was not robust to operated level, so the data support a limited-exposure rather than a proven muscle-sparing benefit.

Journal of Clinical Medicine doi: 10.3390/jcm15228921

Authors: Mauro Podda Raimondo Sanna Marcello Pisano Adolfo Pisanu

Background/Objectives: Malignant gastric outlet obstruction (GOO) is a clinically relevant complication of advanced pancreatic cancer. Conventional gastroenterostomy may be limited by delayed gastric emptying (DGE) and delayed recovery of oral intake. Gastric partitioning has been proposed to improve postoperative gastric emptying. This study compared early postoperative and functional outcomes after conventional gastroenterostomy (GEA) and gastroenterostomy with gastric partitioning (GEAP) in patients with metastatic pancreatic cancer and locally advanced primary tumors causing GOO. Methods: This single-center retrospective comparative cohort included consecutive patients undergoing surgical palliation between January 2021 and June 2026. Outcomes included operative time, time to resumption of oral intake, Gastric Outlet Obstruction Scoring System (GOOSS) at discharge, postoperative length of stay, DGE, 30-day complications, and mortality. Results: Twenty patients were included, with 10 in each group. Median operative time was 127.5 min (IQR 95–140) after GEA and 80 min (IQR 67.75–93.75) after GEAP (p = 0.052). All patients resumed oral intake, with a median time of 4.5 days (IQR 2.25–9.25) after GEA versus 1.5 days (IQR 0.25–3) after GEAP (p = 0.063). Among patients discharged alive (GEA, N = 7; GEAP, N = 10), median postoperative length of stay was 11 days (IQR 9.5–11.5) versus 8 days (IQR 6.25–11.5) (p = 0.364), while median discharge GOOSS was 3 (IQR 2–3) in both groups (p = 1.000). DGE occurred in 40% after GEA and 10% after GEAP (OR 0.17, 95% CI 0.01–1.88; p = 0.303), with grade C DGE observed only after GEA. Thirty-day postoperative complications occurred in 90% versus 60% (p = 0.303), and mortality was 30% versus 10% (p = 0.582). Conclusions: GEAP showed favorable early postoperative outcomes, particularly regarding resumption of oral intake and DGE. However, given the small sample size, retrospective design, and absence of statistically significant differences, these findings remain preliminary and hypothesis-generating and do not establish superiority over conventional GEA. Larger prospective studies are warranted.

Journal of Clinical Medicine doi: 10.3390/jcm15228920

Authors: Serkan Uysal Ayse Ali Hasan Ulas Kumbasar

Background/Objectives: Thoracic outlet syndrome (TOS) is a heterogeneous neurovascular compression disorder in which operative planning depends on the compressed structure and the anatomy at risk. This study evaluated the technical feasibility and the surgical execution of anatomy-driven paraclavicular decompression in patients with complex TOS, while secondarily reporting documented clinical response. Methods: We retrospectively reviewed patients who underwent paraclavicular TOS decompression at Hacettepe University Faculty of Medicine between June 2021 and March 2025. The dominant TOS subtype was assigned using available clinical, radiological, electrophysiological, and operative data. Outcomes were analyzed separately at the patient level and procedure level. Statistical analysis was descriptive. Results: Twelve patients were included; 9 were female, and median age at first operation was 29.0 years (range, 16–63). The dominant phenotype was arterial TOS in 6 patients, neurogenic in 3, venous in 2, and mixed vascular-neurogenic in 1. Cervical rib was documented in 9 patients, broad first-rib anatomy in 6, embolic history in 6, and prior vascular intervention in 4. The 12 patients contributed 15 operative episodes: 12 primary/index decompressions, 2 staged contralateral decompressions, and 1 redo decompression. All procedures used a paraclavicular approach. Among 14 primary or staged contralateral decompressions, first-rib resection and scalenectomy were performed in all procedures, cervical-rib resection in 10, and subclavius muscle resection in 9. Adjunct vascular procedures were performed in 6 of 15 operative episodes. Three hematoma-related explorations occurred, and one PTFE graft thrombosis responded to anticoagulation. Clinical response was evaluable in 8 patients; complete response was documented in 4 and partial response in 4. Conclusions: In this small retrospective series, paraclavicular decompression demonstrated high technical feasibility and reliable surgical execution across a complex TOS cohort with manageable intraoperative safety profiles. While clinical response was evaluated secondarily in available cases, the findings do not establish clinical superiority or proven clinical benefit over other approaches and should be interpreted as a descriptive evaluation of surgical execution rather than comparative effectiveness. Separate patient-level and procedure-level reporting improved interpretability.

Journal of Clinical Medicine doi: 10.3390/jcm15228919

Authors: Elena-Emanuela Rusu Teodor Căluşi Bogdan Marian Sorohan Dorina-Beatrice Tacu Corina Țincu Ruxandra-Oana Jurcuț Robert Adam Adriana Mursă Diana-Silvia Zilişteanu Bogdan Stănciulescu Sonia Bălănică Bogdan Obrişcă Vlad Ştefănescu Filip Mureşan Mihaela Gherghiceanu Cristina Bucşa Paula Vizireanu Cătălin Baston Constantin Gîngu Silviu Guler-Margaritis Gener Ismail

Background/Objectives: Fabry disease (FD) is a rare, X-linked, lysosomal storage multisystemic disorder that may lead to kidney failure, making kidney transplantation (KT) necessary. Data on long-term kidney allograft outcomes and the evolution of systemic FD under disease-specific therapy after KT remain limited. Methods: We retrospectively evaluated six kidney transplant recipients (KTRs) with FD, who were followed in our center for a median time of 7 years after KT (range, 4–13). Results: Of these, five patients (83.3%) were male and five had a classic Fabry phenotype. At the last follow-up appointment, patient survival was 100% and five out of six KTRs had a functional kidney graft; the median change in the estimated glomerular filtration rate from 1 year to the last follow-up was +3.3 mL/min/1.73 m2 (range, −50.7 to +10.5). Proteinuria remained low. One patient developed late antibody-mediated rejection with de novo donor-specific antibodies and graft loss at 8 years post-transplantation. Five KTRs were receiving enzyme replacement therapy at the time of KT. Three patients were subsequently switched to migalastat and two later returned to enzyme replacement therapy. Lyso-Gb3 and cardiac structural parameters showed heterogenous longitudinal trajectories, although kidney graft function was generally preserved. No cardiovascular events occurred during follow-up. Conclusions: These findings indicate that KT is an effective renal replacement therapy in FD and highlight the need for continuous Fabry-specific treatment and multidisciplinary surveillance post-transplantation.

Journal of Clinical Medicine doi: 10.3390/jcm15228918

Authors: Noemi Maria Vitale Abdulnaser Fakhrou Noemi Licitra Alessia Sangiorgio Giulia Schilirò Carlotta Catania Beatrice Eleonora De Leo Eleonora Uccelli Giorgia Farruggio Simona Maria Frischetto Idria Verduzzo Pasquale Caponnetto

Background/Objectives: Body dysmorphic disorder (BDD) is characterized by a persistent and intrusive preoccupation with a perceived defect in physical appearance, associated with significant psychosocial impairment. Individuals with BDD frequently seek aesthetic and cosmetic procedures to correct the perceived flaw, yet cosmetic treatment has traditionally been regarded as a relative contraindication in this population, often associated with unsatisfactory outcomes and symptom exacerbation. However, more recent evidence has been heterogeneous, keeping the relationship between BDD and aesthetic treatment outcomes controversial. This scoping review aimed to map the literature of the last decade on the clinical, psychological, and behavioral outcomes of surgical and non-surgical aesthetic procedures performed on individuals with BDD. Methods: This review was conducted according to the Joanna Briggs Institute (JBI) methodology for scoping reviews and reported in accordance with the PRISMA extension for Scoping Reviews (PRISMA-ScR). PubMed, Scopus, and EBSCOhost were searched for studies published between 2016 and February 2026 reporting clinical, psychological, or behavioral outcomes of aesthetic procedures (surgical or minimally invasive) in samples with a formal BDD diagnosis or a positive screening result. Study selection and data charting were performed independently by two reviewers. Results: Of 419 records identified, 17 primary studies published between 2016 and 2026 met the inclusion criteria. The included studies varied considerably in design, sample size, BDD assessment methods, aesthetic procedures, outcome measures, and follow-up duration. Several studies reported improvements in BDD-related measures, changes in screening classification, or favorable postoperative satisfaction, whereas others reported less favorable findings. Psychological and behavioral outcomes were assessed inconsistently, and broader psychiatric safety outcomes were rarely investigated. The heterogeneity of the available evidence limited direct comparisons and prevented conclusions regarding treatment effectiveness or psychological safety. Conclusions: The available evidence is limited and highly heterogeneous in study design, populations, procedures, outcome measures, and follow-up duration, and most samples were identified through screening instruments rather than diagnostic interviews. Although several studies reported postoperative improvement and satisfaction in some individuals with BDD symptoms, these findings do not establish the efficacy of aesthetic treatment for BDD and should be interpreted with caution. Future research should jointly examine preoperative BDD severity and treatment expectations as potential predictors of postoperative outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15228914

Authors: Mustafa Boz Serap Boz Hande Selvi Öztorun Rana Tuna Dogrul Ahmet Tuğrul Zeytin Güneş Eken Kamile Sılay

Methods: This prospective observational study included 152 adults aged ≥65 years evaluated and discharged from the Emergency Department of Bilecik Training and Research Hospital between April 2025 and April 2026. We assessed nutritional status using the Mini Nutritional Assessment—Short Form (MNA-SF) and Global Leadership Initiative on Malnutrition (GLIM) criteria. We recorded comprehensive geriatric assessment, anthropometric, clinical, and laboratory data. We evaluated emergency department (ED) revisits and mortality during the first month and separately during months 2–3 after discharge. We examined associations using conventional logistic regression models adjusted for age, sex, and Charlson Comorbidity Index. Firth-penalized logistic regression was used for mortality during months 2–3 because of separation and for additional sensitivity analyses incorporating frailty, functional status, dementia, and inflammatory burden. Results: Among 152 participants, 81 (53.3%) had GLIM-defined malnutrition. These participants were older and had poorer anthropometric, functional, and cognitive measures, along with a higher prevalence of frailty. In exploratory expanded models, GLIM-defined malnutrition remained associated with ED revisits during the first month (adjusted OR 2.99, 95% CI 1.03–9.13; p = 0.045) and months 2–3 (adjusted OR 5.15, 95% CI 1.28–22.32; p = 0.022). Associations with mortality were attenuated after adjustment for geriatric characteristics. The confidence intervals included the null for both first-month mortality (adjusted OR 4.76, 95% CI 0.69–52.70; p = 0.115) and mortality during months 2–3 (adjusted OR 11.63, 95% CI 0.85–1684.51; p = 0.068). Conclusions: GLIM-defined malnutrition was common among older adults discharged from the ED and was associated with subsequent ED revisits after adjustment for measured geriatric characteristics. Mortality findings were imprecise and sensitive to adjustment for functional status. GLIM assessment may help characterize nutritional and geriatric vulnerability, but larger studies are needed to confirm its additional prognostic contribution.

Journal of Clinical Medicine doi: 10.3390/jcm15228915

Authors: Ece Sahin Hafizoglu Faruk Recep Ozalp Ferhat Ekinci Huseyin Salih Semiz Mustafa Sahbazlar Atike Pinar Erdogan

Objective: This study aimed to compare the real-world outcomes of second-line nivolumab with those of other second-line systemic therapies in patients with metastatic renal cell carcinoma (mRCC) who progressed after first-line systemic therapy. Materials and Methods: Data from 147 mRCC patients followed up across two centers between January 2015 and June 2025 were retrospectively analyzed. Patients were grouped according to their second-line regimen into the nivolumab group (n = 73) and the other therapies group (n = 74; predominantly axitinib and everolimus). The primary endpoint was overall survival (OS), and the secondary endpoint was progression-free survival (PFS). Associations were evaluated using Cox regression models with covariates prespecified on clinical grounds, and robustness was assessed in sensitivity analyses addressing treatment era, subsequent therapy, histology, and the PFS definition. Results: Median OS was 22 months in the nivolumab group and 17 months in the other therapies group; this unadjusted difference was not statistically significant (log-rank p = 0.051), nor was the difference in restricted mean survival time up to 60 months (6.0 months, p = 0.118). Median PFS was 10.0 and 6.4 months, respectively (p = 0.011). In the primary multivariable model, receipt of other second-line therapies was associated with worse OS (HR: 1.694, 95% CI: 1.105–2.597) and PFS (HR: 1.972, 95% CI: 1.320–2.946) compared with nivolumab. The OS association was consistent in direction in sensitivity analyses, including an analysis restricted to patients who started second-line therapy from 2018 onward (HR: 2.081, 95% CI: 1.080–4.007), but was attenuated and no longer statistically significant when subsequent therapy was modelled as a time-dependent covariate (HR: 1.416, 95% CI: 0.949–2.112). In the comparator group, 21.6% of patients subsequently received nivolumab. Conclusions: In this real-world cohort, second-line nivolumab was associated with lower adjusted hazards of death and progression than other second-line systemic therapies, although the unadjusted OS difference was not statistically significant. Given the observational design, the strong association between second-line treatment and treatment era, and differences in subsequent therapy, these findings should be interpreted as associations rather than causal treatment effects. They are most relevant to settings in which first-line TKI monotherapy remains in use.

Journal of Clinical Medicine doi: 10.3390/jcm15228917

Authors: Lea Rupert Chiedozie Kenneth Ugwoke Thierry Girard Tatjana Stopar Pintarič

Background and Objectives: Obstetric hemorrhage encompasses heterogeneous processes in which hypofibrinogenemia may develop through different mechanisms and at different stages. Materials and Methods: Two contrasting cases, discussed in the context of current evidence, illustrate how the timing, evolution, and treatment response of fibrinogen abnormalities may inform clinical interpretation. Results: Placental abruption at 20 weeks’ gestation was associated with profound early coagulopathy, including thrombocytopenia, prolonged clotting times, and impaired fibrin-based clot formation, despite limited externally apparent bleeding. Rotational thromboelastometry-guided hemostatic treatment enabled induction of labor and vaginal delivery. In placenta accreta spectrum, massive uterine hemorrhage was accompanied by persistent severe hypofibrinogenemia despite fibrinogen replacement, transfusion, balloon tamponade, and uterine artery embolization. Hemostasis and recovery of fibrinogen concentrations and clot firmness followed emergency hysterectomy and continued resuscitation. Conclusions: These trajectories suggest that fibrinogen is both a therapeutic target and a dynamic, context-dependent hemostatic indicator. We propose an interpretive framework integrating obstetric context, bleeding progression, hemodynamics, serial laboratory or viscoelastic findings, administered treatment, and source control. Its practical emphasis is early assessment in conditions prone to coagulopathy and repeated clinical reassessment when hypofibrinogenemia persists or recurs. This hypothesis-generating framework complements existing protocols and requires prospective evaluation against standard clinical assessment before use as a validated decision tool.

Journal of Clinical Medicine doi: 10.3390/jcm15228913

Authors: Takahiko Nobuoka Megumi Nobuoka Makoto Harada Koji Hashimoto Yuji Kamijo

Background/Objectives: Avacopan-associated liver injury is an emerging safety concern in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), particularly in Japan. We investigated its clinical characteristics and association with cytomegalovirus (CMV) antigenemia. Methods: We retrospectively analyzed 29 patients with AAV who initiated avacopan between June 2022 and April 2026. The primary outcome was clinically adjudicated avacopan-associated liver injury, based on suspected rather than confirmed drug causality, within 6 months of initiation. An exploratory Firth penalized logistic regression analysis was performed, adjusting for the Birmingham Vasculitis Activity Score (BVAS) at diagnosis. Results: Clinically adjudicated avacopan-associated liver injury occurred in 7 of 29 patients (24%). Among 22 patients evaluable for CMV antigenemia, CMV antigenemia was more frequent in patients with liver injury than in those without (86% vs. 7%). The association persisted after BVAS adjustment (adjusted odds ratio, 27.94; 95% confidence interval, 3.22–625.09; p = 0.002). In some patients with CMV antigenemia, liver injury developed after documented clearance of antigenemia. Liver biopsies from three patients showed cholestasis and bile duct injury without CMV-positive cells. Conclusions: CMV antigenemia was associated with clinically adjudicated avacopan-associated liver injury. However, the small sample size, nonuniform CMV testing, potential confounding, and sensitivity to outcome definition limit the interpretation of this association. These findings are hypothesis-generating and require validation in larger studies.

Journal of Clinical Medicine doi: 10.3390/jcm15228912

Authors: Krystian Mania Anna Pieczyńska Katarzyna Hojan

Background/Objectives: Surgical treatment for non-small cell lung cancer (NSCLC) presents risks of cancer-related cognitive impairment (CRCI) and postoperative cognitive dysfunction (POCD), which are further exacerbated by cancer-related fatigue. While multimodal prehabilitation improves physical performance, its effect on neurological outcomes remains largely unexamined. This study aimed to evaluate the impact of a comprehensive multimodal prehabilitation program on cognitive function and fatigue levels in lung cancer patients undergoing elective surgery. Methods: In this prospective randomized controlled trial, 77 eligible NSCLC patients were randomized to either a two-week multimodal prehabilitation program (individualized physical exercise, respiratory training, nutritional guidance, and psychological support) or standard preoperative care. Cognitive function was evaluated using Addenbrooke’s Cognitive Examination-III (ACE-III), and subjective fatigue was assessed using the Fatigue Assessment Scale (FAS) at baseline (T0), in the early postoperative period (T1), and at two months post-surgery (T2). Between-group differences and longitudinal recovery trajectories were evaluated using linear mixed-effects models adjusted for age, sex, and education. Results: Postoperatively, the prehabilitation group achieved significantly higher ACE-III total scores (83.8 ± 9.4 vs. 78.5 ± 10.5; p = 0.049) and language scores (p = 0.015) compared to controls, with total ACE-III benefits maintained at two months (86.8 ± 8.8 vs. 81.9 ± 9.7; p = 0.050). Mixed-effects modeling confirmed significant additional effects of prehabilitation on the recovery trajectories of ACE-III total (β = 3.14, p < 0.001), memory (β = 0.86, p = 0.007), and language (β = 1.19, p < 0.001). Furthermore, the prehabilitation group demonstrated significantly lower total fatigue (β = −5.82, p< 0.001), mental fatigue (β = −2.27, p < 0.001) and physical fatigue (β = −4.31, p< 0.001) immediately following surgery, although fatigue levels converged between cohorts by two months. Conclusions: Comprehensive multimodal prehabilitation significantly attenuates early postoperative cognitive decline, supports cognitive preservation through two months post-surgery, particularly in memory and language, and reduces postoperative fatigue in patients undergoing lung cancer surgery. Trial Registration: ISRCTN15332421 (retrospectively registered on 5 February 2026).

Journal of Clinical Medicine doi: 10.3390/jcm15228911

Authors: Oliver Czech Katarzyna Siewierska Aleksandra Kowaluk Agnieszka Staniak Paweł Kiper Iwona Malicka

Background: Haematological malignancies are associated with fatigue, reduced functional capacity, and limitations in daily activities. This systematic review and meta-analysis evaluated the effects of exercise-based interventions on physical function and health-related quality of life in adults with haematological malignancies, irrespective of cancer subtype or treatment phase. Methods: PubMed, Web of Science, Scopus, Embase, and the Cochrane Library were searched in May 2026, and the search was updated in September 2026. Methodological quality was assessed using the Cochrane Risk of Bias 2 tool. Random-effects meta-analyses were conducted in Review Manager 5.4, and the review was registered in PROSPERO (CRD420251019321). Results: Nineteen randomised controlled trials involving 1355 participants were included in the systematic review; 16 studies contributed to quantitative synthesis. Exercise-based interventions improved VO2peak (SMD = 0.32; 95% CI [0.09, 0.54]), upper-limb strength (SMD = 0.26; 95% CI [0.01, 0.51]), and lower-limb strength (SMD = 0.38; 95% CI [0.19, 0.56]). The pooled effect on the six-minute walk test was not statistically significant (SMD = 0.21; 95% CI [−0.03, 0.44]). A significant effect was also observed for stair-test performance (SMD = 0.71; 95% CI [0.27, 1.14]), whereas the pooled effect on health-related quality of life was not statistically significant (SMD = 0.15; 95% CI [−0.01, 0.31]). Conclusions: Exercise-based rehabilitation may improve selected domains of physical function, particularly cardiorespiratory fitness and muscle strength. Effects on six-minute walk distance and quality of life remain uncertain. These findings support considering individualised exercise within multidisciplinary haemato-oncology care, while further high-quality research is needed.

Journal of Clinical Medicine doi: 10.3390/jcm15228910

Authors: Omar Hamodat Sana Najjar Alyamama Alnamous Muhammed Ali Najah Rama Karima Deemah Al-Qaisi Marwan Abdulkadder Ahmad Holeihel

Background/Objectives: Acute appendicitis is the leading cause of emergency abdominal surgery in children. Although appendectomy remains the standard treatment, antibiotic-based nonoperative management (NOM) is an alternative for selected patients. We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs) comparing these strategies in pediatric uncomplicated acute appendicitis. Methods: PubMed, MEDLINE via Ovid, Scopus, and CINAHL were searched through 15 July 2026; CENTRAL and ClinicalTrials.gov were searched on 13 October 2026 (PROSPERO: CRD420261447254). Pediatric RCTs were included. RoB 2 and GRADE were used. Random-effects pooling required compatible outcomes. Results: Eight RCTs involving 1920 children were included. Both one-year comparative trials favored appendectomy, but their different composite endpoints were not pooled. NOM avoided appendectomy at one year in 62.5–70.0% in three trials. Clinical complications were uncertain (RR 1.61, 95% CI 0.63–4.13; I2 = 54.9%). No significant pooled difference was found in hospital stay or return to normal activities. Recurrence and school outcomes were reported separately. Conclusions: Appendectomy provides more reliable definitive treatment. NOM can avoid surgery in selected children but carries a risk of subsequent failure or recurrence. Comparative safety and recovery remain uncertain. Families should be informed of these trade-offs and the limitations of the pooled evidence.

Journal of Clinical Medicine doi: 10.3390/jcm15228908

Authors: Zulfiya Zhankalova Balday Issenova Zhansila Ismet Gulnara Myrzabayeva Rimma Suatbayeva Akmaral Izbassarova Anel Zhumabek Balzhan Lakanova Mukhtar Kulimbet Almat Turysbekuly Ulbobek Artykbayeva

Background/Objectives: To critically review the effectiveness, safety and implementation of fully remote, hybrid and digitally supported cardiac rehabilitation (CR) in adults after coronary revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), distinguishing direct from indirect evidence. Methods: This structured narrative review drew on searches of MEDLINE (PubMed), Embase, the Cochrane Library, Scopus and Web of Science, supplemented by reference list and citation searching and by guidance from major cardiology societies. Randomized and non-randomized comparative studies, economic evaluations, qualitative studies and systematic reviews were selected purposively, appraised qualitatively for methodological limitations, and synthesized narratively by outcome, comparator, intervention comprehensiveness and directness of evidence for revascularized patients. Results: Compared with usual care, digital CR improved short-term exercise capacity; compared with center-based CR, it produced broadly similar exercise capacity and short- to intermediate-term quality of life. Lower odds of all-cause readmission with digital CR in one meta-analysis (OR 0.37, 95% CI 0.25–0.56) were based on only seven heterogeneous studies (n = 859) and are not corroborated by the 2023 Cochrane review; effects on major adverse cardiovascular events and mortality remain uncertain. Economic evaluations were generally favorable. Serious exercise-related adverse events were rarely reported in the selected, predominantly lower-risk participants studied, but surveillance was inconsistent, and safety after CABG and in higher-risk patients has not been established. Reimbursement, workforce capacity, interoperability and digital exclusion were the main implementation barriers. Conclusions: Comprehensive remote or hybrid CR is a reasonable option for appropriately assessed, clinically stable, lower-risk patients, particularly after PCI, and a promising way to reach those who would otherwise receive no rehabilitation; patients in the early period after CABG or at higher risk should start with supervised center-based or hybrid care. Digital CR should widen access to multidisciplinary rehabilitation rather than replace supervised programs, and adequately powered trials with long-term clinical and standardized safety outcomes are needed.

Journal of Clinical Medicine doi: 10.3390/jcm15228909

Authors: Lina De Paola Gabriele Napoletano Elisabetta Pelagatti Miriam Ottaviani Susanna Marinelli Simona Meneghini Bruno Cirillo

Background and Objectives: New psychoactive substances (NPS) are characterized by continuous growth in the market and constant evolution in their chemical structures, representing an emerging challenge for forensic medicine and toxicology. The rapid spread of NPS has led to an increase in poisoning cases, with serious implications for public health and criminal justice. These substances are often difficult to detect using traditional analytical methods due to the frequent alterations in their chemical composition, and many of them are not yet regulated or formally recognized under existing legislation. As a result, advanced analytical techniques such as chromatography and mass spectrometry are essential for the accurate identification and quantification of NPS. Materials and Methods: We conducted a comprehensive literature review covering the last five years, aiming to explore current analytical methodologies and their clinical and forensic implications, while emphasizing the critical need for ongoing research to effectively address the challenges posed by NPS. Results: These advanced approaches are crucial for timely and accurate diagnosis in both clinical and forensic settings, improving the management of poisoning cases and supporting subsequent legal investigations. Combined analytical techniques represent a significant advancement in forensic science, particularly in the identification of isomers and novel psychoactive compounds. Conclusions: This progress enhances the collaboration between clinicians, toxicologists, and forensic pathologists, raising the level of interdisciplinary knowledge required to tackle these emerging threats more effectively.

Journal of Clinical Medicine doi: 10.3390/jcm15228907

Authors: Maedeh Mirasheh Zahra Shahabinia Mai Abdel Haleem A. Abusalah Afrooz Mazidimoradi Leila Allahqoli Hamid Salehiniya Do-Youn Lee

Background: Gynecological cancers, particularly ovarian, endometrial, and cervical cancers, have a high disease burden in terms of incidence and mortality, and their diagnosis and treatment remain challenging. AI-based multi-omics approaches integrate multilayer data, enabling comprehensive modeling and clinical decision-making. This narrative review aimed to critically examine the current and prospective applications of these approaches in three common gynecological cancers and to evaluate their clinical potential. Methods: In this narrative review, following searches of PubMed, Web of Science, Scopus, and Google Scholar and screening of 1254 records, 51 original studies were included and synthesized qualitatively and descriptively. Relevant systematic reviews and meta-analyses were consulted only for contextualization and were not included in the primary evidence synthesis. Results: AI-based multi-omics approaches in gynecological cancers may help distinguish cancer from healthy tissue, benign from malignant conditions, and early from advanced stages; identify molecular subgroups; predict survival and recurrence; predict responses to chemotherapy and immunotherapy; and discover therapeutic targets. Minimally invasive biofluids and machine learning models showed better performance than CA125 and HE4 in some studies. Factors such as the tumor microenvironment, immunity, LDHA, and ITGA1 were associated with drug resistance in computational or preclinical studies, whereas HRD and TP53 alterations are clinically validated determinants of platinum response. In cervical cancer, the evidence was more limited and heterogeneous. Overall, the findings are promising but preliminary, and further extensive clinical validation is needed. Conclusions: AI-based multi-omics approaches may contribute to early diagnosis, molecular classification, prognostic assessment, and treatment selection in gynecological cancers; however, they remain at the proof-of-concept and initial validation stages. Prospective, multicenter, standardized studies with external validation are necessary for clinical application. These tools may serve as complementary approaches to current diagnostic pathways.

Journal of Clinical Medicine doi: 10.3390/jcm15228906

Authors: Tao Chen Chuan Zhou Yifan Wang Lubomir M. Hadjiiski Qian Dong Matthias Wilms

Background/Objectives: Multiple myeloma (MM) remains incurable, with most patients eventually experiencing relapse/progression despite advances in treatment. This preliminary study evaluated the prognostic value of longitudinal changes in vertebral magnetic resonance imaging (MRI) patterns using a two-stage machine learning (2S-ML) framework. Methods: The study included 62 patients with paired spinal MRI scans acquired before and after autologous stem cell transplantation (ASCT). First, a pre-trained ResNet-18 was fine-tuned to classify vertebrae into four marrow infiltration patterns. Second, 12 handcrafted temporal descriptors were extracted to characterize longitudinal changes in MRI patterns. Ridge-penalized Cox proportional hazards regression was employed as the primary model to predict time to progression (TTP) and overall survival (OS). A random forest classifier was retained as a secondary analysis for fixed-horizon outcome prediction, and model performance was evaluated using patient-level leave-one-case-out cross-validation (LOCO-CV). Results: The 4MRI-P model achieved an average AUC of 0.8905 ± 0.0054 across 1208 vertebral MRI annotations. In the primary Cox analysis, adding longitudinal MRI features to clinical variables modestly improved the C-index for TTP (0.6950 to 0.7301) and OS (0.6801 to 0.6924). The secondary random forest analysis achieved time-dependent AUCs of 0.8291 ± 0.0844 for TTP at 36 months and 0.7396 ± 0.0776 for OS at 60 months. Kaplan–Meier analyses showed significant separation between risk groups for both outcomes (both p < 0.001). Conclusions: These preliminary findings suggest that AI-driven analysis of longitudinal vertebral MRI patterns may provide prognostic value for survival risk stratification in MM.

Journal of Clinical Medicine doi: 10.3390/jcm15228905

Authors: Eline A. Breuking Karlijn J. P. van Wessem Bart J. M. Vlaminckx Frederique J. C. van Eerten Dominique B. Buck Leo Koenderman Jetske Ruiterkamp Falco Hietbrink Kim E. M. Benders

Background: Crush injuries are associated with extensive soft tissue damage leading to a high risk of complications. Differences between pediatric and adult patients remain poorly studied. This study aimed to compare outcomes after crush injury in pediatric and adult patients and to identify predictors of viability-related complications (VRCs). It was hypothesized that children sustained fewer complications than adults following extremity crush injuries. Methods: A retrospective comparative cohort study was conducted at a level-1 trauma center. Pediatric patients (<16 years) treated between 2017 and 2024 and adult patients (≥16 years) treated between 2019 and 2023 were included. Patients with crush injury not involving extremities were excluded. VRCs were defined as (secondary) tissue necrosis, infection (related to impaired tissue viability), or both. The primary outcome was incidence of VRC in pediatric patients compared to adult patients. Group comparisons were performed using Chi-square testing. Logistic regression analyses were performed to identify independent predictors of VRC. Results: A total of 116 patients were included, of whom 36 were pediatric patients and 80 were adult patients. VRC occurred in 13.9% of children, compared to 56.3% of adults (p < 0.001). Isolated necrosis did not occur in pediatric patients within the cohort. Multivariable logistic regression identified age, degloving injury and open fracture as independent predictors of VRC. ISS and fasciotomy were not associated with VRC. The risk of VRC increased progressively with age, with a 2.5% increase in odds per additional year of age. Conclusions: Pediatric patients had a substantially lower incidence of viability-related complications after crush injury than adults. The results of this study suggest the presence of age-related differences in tissue viability after trauma, which may warrant corresponding surgical approaches. An increased understanding of age-related differences will contribute to more individualized treatment strategies in complex traumatic injury.

Journal of Clinical Medicine doi: 10.3390/jcm15228903

Authors: Maria Luiza Băean Cosmin Medar Oana Nicu-Canareica Diana Zamfir Radu-Adrian Popescu Alexandru Scafa-Udriște

Guidelines list stress perfusion cardiovascular magnetic resonance (CMR) and myocardial perfusion scintigraphy (MPS) side by side for chronic coronary syndromes, with the same class of recommendation; in practice, availability decides. The comparative literature is less settled than that parity suggests. In CE-MARC, CMR reached an area under the curve of 0.89 against 0.74 for single-photon emission computed tomography (SPECT); a same-patient meta-analysis against invasive angiography gives sensitivity of 72% against 63% and specificity of 77% against 78%, with heterogeneity above 90%; when tested by randomisation in CE-MARC 2, unnecessary angiography occurred in 7.5% of CMR-guided and 7.1% of MPS-guided patients. This narrative review examines ten open questions: whether absolute flow quantification is ready to guide decisions when positron emission tomography supplies validated thresholds, whether ischaemia without obstructive disease is an imaging or an invasive diagnosis, whether viability testing still changes management after STICH and REVIVED-BCIS2, and whether cost-effectiveness estimates computed under assumed availability apply where 56% of Eastern European respondents report no formal CMR training. For each, we set out the competing positions and the study that could resolve it, identify areas of consensus, propose a framework for modality selection, and outline the head-to-head comparison the field still lacks.

Journal of Clinical Medicine doi: 10.3390/jcm15228904

Authors: Claudiu Avram Maria-Laura Craciun Ana-Maria Pah Iasmina Isacov Adina Octavia Duse Cristiana Adina Avram

Background/Objectives: Obstructive sleep apnea (OSA) may complicate fatigue and cardiovascular risk assessment in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA). We evaluate the strength and clinical applicability of disease-specific evidence. Methods: This expert narrative review uses a documented PubMed/MEDLINE update through 28 October 2026, supplemented by reference-list checking, general OSA trials, and professional guidance. Evidence is appraised qualitatively by ascertainment, selection, adjustment, and directness. Results: RA has the largest but most heterogeneous evidence base: pooled OSA prevalence was 29.8% (95% confidence interval [CI], 15.2–46.7%; I2 = 99.6%), with mixed definitions. In PsA, 21/42 polysomnography (PSG)-tested volunteers had OSA (50%; descriptive 95% CI, 35.5–64.5%), whereas 22/247 clinic patients had a recorded diagnosis (8.9%; 95% CI, 6.0–13.1%). These estimates are not interchangeable. Ankylosing spondylitis (AS) findings differ between matched objective testing and administrative cohorts. Adiposity, demographics, medication, and surveillance constrain interpretation. Positive airway pressure has established sleep-related indications; improvements in arthritis activity or arthritis-specific cardiovascular events remain unproven. Tirzepatide evidence concerns adults with obesity and moderate-to-severe OSA. Conclusions: PsA and axSpA evidence remains limited. Shared biology supports a conceptual hypothesis rather than a demonstrated causal axis. Targeted case finding should lead to guideline-concordant objective diagnosis; universal asymptomatic rheumatology screening and disease-modifying effects of OSA treatment are not established.

Journal of Clinical Medicine doi: 10.3390/jcm15228898

Authors: Arash Ghoroghi Christopher M. B. Stewart Sirat Gandhi Charlotte V. E. Carpenter Sandeep Ghokale Zayd Jawad Simon Humphry Clare Carpenter

Background/Objectives: Cast wedging is a simple, non-operative technique for correcting residual angulation of a fractured limb held within a cast. Evidence quantifying how effectively it reduces angular deformity in paediatric diaphyseal tibial fractures is limited. We aimed to quantify the immediate change in absolute coronal and sagittal angular deformity achieved by wedging, to describe whether the correction was maintained to the final follow-up radiograph, and to describe the cases where wedging did not achieve definitive management. Methods: We retrospectively identified 53 children (aged 3–15 years) who underwent cast wedging for a diaphyseal tibial fracture at a single centre between 2005 and 2025, from 338 paediatric tibial shaft fractures managed during the period. Coronal (CAD) and sagittal (SAD) angular deformity were each measured independently by two clinicians (mean used) before wedging, immediately after wedging and on the final radiograph. Paired absolute deformity was compared with the Wilcoxon signed-rank test and Hodges–Lehmann median differences; paired proportions with McNemar’s test. A sensitivity analysis was restricted to the 47 children managed by wedging alone. Results: Wedging reduced absolute coronal deformity from a median of 8.0° (interquartile range [IQR] 6.0–10.0) to 3.5° (IQR 2.0–5.0) (Hodges–Lehmann median reduction 4.0°, 95% confidence interval [CI] 3.0–5.0; p < 0.001) and sagittal deformity from 5.0° (IQR 3.0–7.0) to 3.0° (IQR 1.0–7.0) (median reduction 1.5°, 95% CI 0.5–2.3; p = 0.002). The proportion within accepted coronal alignment (<5°) rose from 21% (95% CI 12–33) to 68% (95% CI 55–79; McNemar p < 0.001), and within sagittal alignment (<10°) from 81% to 94% (p = 0.046); no child was over-corrected in the coronal plane. Forty-seven of 53 children (88.7%) were managed by wedging alone, and 49 (92.5%) did not undergo surgical fixation. Among the 47, the proportion within 5° coronally fell from 74% immediately after wedging to 55% at a median of 89 days, indicating partial loss of correction; six children required further intervention (two repeat manipulations, four fixations). Conclusions: In paediatric diaphyseal tibial fractures, cast wedging produced a significant immediate reduction in absolute angular deformity, most marked in the coronal plane, and most children did not undergo surgical fixation. The findings are short-term and radiographic, and part of the immediate correction was not maintained to final follow-up. Wedging appears most useful for purely angular malalignment, whereas shortening, translation and comminution were features of the children in whom it was insufficient.

Journal of Clinical Medicine doi: 10.3390/jcm15228902

Authors: Aleksandra Budzisz

Background/Objectives: Disordered-eating risk among athletes may be associated with demographic and sport-related characteristics as well as with how athletes evaluate the appearance and functionality of their bodies. This study examined the prevalence and correlates of disordered eating risk and investigated the associations of functional and aesthetic body-image dimensions with eating attitudes in competitive athletes. Methods: The sample comprised 739 competitive athletes representing 20 sports or track-and-field event groups. Participants completed the Eating Attitudes Test-26 and the Embodied Image Scale. Differences according to sport and training characteristics were examined using multivariate analyses, while hierarchical linear and logistic regression models assessed associations between body-image dimensions and continuous EAT-26 scores and positive screening status. Results: Overall, 17.6% of athletes were identified as being at risk of disordered eating (95% CI [15.0%, 20.5%]). Positive screening was more frequent among women and younger athletes but did not differ across sports disciplines or training characteristics. Sport discipline differentiated primarily functional investment and functional satisfaction, with the observed effects concentrated largely in the basketball subgroup. The final linear regression model explained 8.6% of the variance in EAT-26 scores, with body-image dimensions contributing an additional 6.4% beyond age and sex. Greater aesthetic value and investment were associated with higher EAT-26 scores, whereas greater aesthetic satisfaction was associated with lower scores. A similar pattern was observed for positive screening status; functional investment was additionally inversely associated with screening risk. Conclusions: Disordered-eating risk was present across diverse sports rather than concentrated within particular disciplines. Aesthetic body-image dimensions were more consistently associated with eating attitudes than functional dimensions, supporting the relevance of multidimensional body-image assessment in athlete screening and prevention.

Journal of Clinical Medicine doi: 10.3390/jcm15228901

Authors: Yusuke Morishita Yuki Yamanashi Yukio Nakamura Kentaro Nagatani Kohei Hashimoto Takuya Okamoto Akira Kato Masataka Deie Nobunori Takahashi

Background/Objectives: Meniscal healing after repair concomitant with anterior cruciate ligament (ACL) reconstruction may vary by lesion characteristics. We evaluated second-look arthroscopic healing rates and factors associated with partial or non-healing, particularly vascular zone. Methods: This retrospective cohort included 109 patients (131 repaired menisci) undergoing second-look arthroscopy at least 12 months after ACL reconstruction with meniscal repair (mean interval, 16.3 ± 6.3 months). Healing was classified as complete, partial, or non-healing. Associations were examined using multivariable logistic generalized estimating equations (GEE) accounting for within-patient clustering. Results: Complete, partial, and non-healing occurred in 73 (55.7%), 34 (26.0%), and 24 (18.3%) menisci, respectively. Complete healing occurred in 41/62 red-red (66.1%) and 32/69 red-white zone tears (46.4%). Higher body mass index (BMI) (per kg/m2: adjusted odds ratio [aOR], 1.11; 95% confidence interval [CI], 1.00–1.22; p = 0.04), red-white versus red-red zone location (aOR, 3.29; 95% CI, 1.31–8.23; p = 0.01), and more sutures (per suture: aOR, 1.41; 95% CI, 1.08–1.83; p = 0.01) were associated with partial or non-healing in the primary analysis. However, sensitivity analyses showed less consistent associations for BMI and vascular zone, whereas the association with suture number was more consistent. Conclusions: Complete structural healing was observed in selected red-white zone tears. The association between suture number and partial or non-healing was comparatively consistent across analyses, although suture number may reflect tear extent and repair complexity rather than a causal effect. Associations with BMI and vascular zone should be interpreted cautiously.

Journal of Clinical Medicine doi: 10.3390/jcm15228900

Authors: Esra Akaydın Gültürk

Background/Objectives: Whether Shapley-based explanations of machine learning survival models are transported to new populations is rarely tested. We assessed the geographic and temporal transportability of the performance and time-dependent SurvSHAP(t) explanations of survival models in breast cancer. Methods: Cox, random survival forest (RSF), gradient-boosted survival (GBSA), DeepSurv and DeepHit models for recurrence-free survival were developed in Rotterdam (n = 2982) and applied without updating to a geographic (German Breast Cancer Study Group [GBSG], n = 686) and a temporal cohort (Duke, 2000–2014, n = 888). Explanation shift was assessed with classifier two-sample tests and density-ratio decomposition; agreement with local reference models refitted in each external cohort was tested with a 500-refit bootstrap null and Holm correction. Results: Discrimination was preserved (Uno’s C at 0.64–0.68 in GBSG; 0.71–0.73 in Duke), but the three-year risk was overestimated about three-fold in Duke (observed/expected at 0.28–0.35); a true decline in risk could not be separated from differences in event ascertainment. Explanations shifted in both cohorts (classifier area under the curve [AUC] at 0.75–0.90), yet nodal category ranked first in all 15 model–cohort pairs. Disagreement with the local reference model was detected only for RSF in GBSG (Holm-adjusted p = 0.032); elsewhere, and particularly in Duke, non-detection does not establish agreement because power was limited. Local models gave more weight to endocrine therapy in Duke (+0.07 to +0.22; +0.04 to +0.24 across imputations). Conclusions: Preserved discrimination did not prevent marked miscalibration in a later cohort, and preserved importance rankings did not guarantee that transported explanations matched those of locally trained models. Explanations should be evaluated externally alongside, and separately from, predictive performance.

Journal of Clinical Medicine doi: 10.3390/jcm15228899

Authors: Robert Balan Parwis Massoudy Marius Mihai Harpa Klara Brînzaniuc Jonah Schwarz

Background: Minimally invasive and endoscopic techniques have expanded the surgical options for tricuspid valve repair. Conventional approaches often require manual snaring of the venae cavae, which can increase procedural complexity, especially in advanced heart failure settings. This study describes a snare-free totally endoscopic approach to tricuspid valve repair utilizing percutaneous venous self-expanding cannulation. Methods: Between 2020 and 2025, 32 patients with severe tricuspid regurgitation (TR) underwent totally endoscopic tricuspid valve repair using a standardized snare-free technique. Venous drainage was achieved via predominantly percutaneous femoral cannulation with a self-expanding venous cannula, providing central venous decompression without external tourniquets or loops. All clinical, intraoperative, and early postoperative parameters were collected and analyzed using descriptive statistical methodology. Results: Snare-free cannulation was performed in all 32 patients (100.0%, 95% CI: 89.1–100.0%). Pure snare-free endoscopic repair was completed in 31 patients (96.9%, 95% CI: 83.8–99.9%), with one patient (3.1%) requiring conversion to full median sternotomy and manual caval snaring. The mean cardiopulmonary bypass (CPB) time was 145.9 ± 35.8 min, and the mean aortic cross-clamp duration was 92.4 ± 24.5 min. All-cause 30-day mortality was 3.1% (n = 1/32), and no cases of clinically documented hemolysis were observed (0.0%, 95% CI: 0.0–10.9%). The mean intensive care unit stay was 6.0 ± 4.9 days (n = 31), and the mean postoperative hospital length of stay was 15.3 ± 9.6 days (n = 30). Quantitative predischarge residual TR grades and transvalvular gradients were not systematically recorded; therefore, endoscopic completion in this cohort establishes cannulation feasibility rather than definitive valve-repair efficacy. Conclusion: Snare-free totally endoscopic tricuspid valve repair using percutaneous self-expanding venous cannulation appeared technically feasible and was associated with acceptable early clinical outcomes in this selected single-center cohort.

Journal of Clinical Medicine doi: 10.3390/jcm15228897

Authors: Ali Fuat Gürbüz Melek Karakurt Eryılmaz Cengiz Kadıyoran İsmail Beypınar Oğuzhan Yıldız Bahattin Engin Kaya Talat Aykut Murat Araz Mehmet Artaç

Background/Objectives: Regorafenib is a multikinase inhibitor approved for refractory metastatic colorectal cancer (mCRC). VEGF-pathway inhibition may also cause structural changes in normal organs, including pancreatic volume loss. We evaluated pancreatic volume changes during regorafenib therapy and their association with treatment exposure and clinical outcomes. Methods: We retrospectively analyzed 85 of 115 screened patients with mCRC treated with regorafenib at a single center who had contrast-enhanced CT before treatment and at the first response evaluation. Pancreatic atrophy was defined a priori as a ≥10% volume reduction from baseline. Survival was analyzed with a 12-week landmark approach; for OS, landmark and time-dependent Cox models were added. Results: Median pancreatic volume decreased from 54.22 to 50.00 mL (median paired change −5.8%, 95% CI −9.1 to −4.2; p < 0.001), and atrophy developed in 31 patients (36.5%). Atrophy was associated with longer treatment duration (median 149 vs. 92 days; p = 0.001) and higher disease control (58.6% vs. 17.3%; p < 0.001). The conventional PFS comparison favored the atrophy group (5.26 vs. 3.29 months; p = 0.003) but is confounded by guarantee-time bias. In the 12-week landmark population (n = 65), median PFS was 2.50 vs. 1.28 months (log-rank p = 0.046); however, atrophy was not independently associated with PFS (HR 0.68, 95% CI 0.39–1.20; p = 0.181). Median OS was 11.30 vs. 6.74 months (p = 0.271), and atrophy was not independently associated with OS in conventional (HR 0.99, 95% CI 0.60–1.64), landmark (HR 1.05, 95% CI 0.62–1.76), or time-dependent (HR 1.16, 95% CI 0.69–1.94) models. Conclusions: Regorafenib-associated pancreatic atrophy is a measurable imaging finding linked to longer treatment exposure and concurrent disease control. After accounting for guarantee-time bias, it was not independently associated with PFS or OS and should not be regarded as a prognostic biomarker.

Journal of Clinical Medicine doi: 10.3390/jcm15228896

Authors: Yasin Taşkın Ahmet Tuğrul Şahin

Background/Objectives: Large language models (LLMs) are increasingly used to obtain medical information, but the quality of their responses to complex, time-sensitive neurovascular questions requires disease-specific evaluation. We compared the expert-rated response quality of five publicly accessible LLM systems using standardized questions on aneurysmal subarachnoid hemorrhage (aSAH). Methods: Thirty standardized Turkish-language questions covering aneurysm treatment, vasospasm and related complications, and neurocritical care and follow-up (10 questions per domain) were submitted to ChatGPT, Gemini, Claude, DeepSeek, and Microsoft Copilot through public web interfaces in July 2026. Each question was submitted once per system in a separate chat session, generating 150 responses. Five senior neurosurgeons independently rated each response on a 1–10 scale for coverage, relevance, comprehensibility, clinical applicability, and overall quality. Inter-rater reliability was assessed using intraclass correlation coefficients (ICCs). Repeated-measures linear mixed models, Bonferroni-adjusted pairwise comparisons, and Friedman sensitivity analyses were performed. Results: The evaluation comprised 3750 expert score observations without missing data. Inter-rater reliability was good to excellent (ICC 0.835–0.911). AI system was significantly associated with all five evaluation dimensions (all p < 0.001). Adjusted overall scores were highest for ChatGPT (7.68), followed by Gemini (6.97), Claude (6.69), DeepSeek (5.92), and Copilot (4.75). Neither the clinical-topic main effect nor the model-by-topic interaction was statistically significant (all p > 0.05). Friedman analyses also identified between-model differences across all dimensions (all p < 0.001). Conclusions: Publicly accessible LLM systems differed significantly in expert-rated response quality when answering standardized Turkish-language aSAH questions. These differences were observed within the study’s specific question set and evaluation protocol and should not be interpreted as evidence of differences in real-world clinical outcomes. The absence of statistically significant model-by-topic interactions does not establish equivalent performance across clinical domains. Model-specific validation, assessment of clinically important errors, and continued expert oversight are needed before considering LLM-generated information for clinical decision support.

Journal of Clinical Medicine doi: 10.3390/jcm15228895

Authors: Rustam Omarbayev Yerbol Iskakov Aliya Orassay Rinat Nugumanov Saule Paizullayeva Manarbek Askarov

Background/Objectives: Regenerative therapies are increasingly used for organic erectile dysfunction (ED), but their effects on erectile function and clinically meaningful response remain uncertain. We evaluated erectile-function scores, penile hemodynamics, and responder outcomes. Methods: We searched PubMed, Scopus, and Cochrane CENTRAL from January 1999 to June 2026. Controlled, active-comparator, and uncontrolled studies were analysed separately. Random-effects models synthesised continuous and responder outcomes by follow-up period. We assessed risk of bias using RoB 2 and ROBINS-I and rated certainty of evidence using GRADE. Results: We included 46 study reports comprising 18 randomized trials and 28 non-randomized studies. In controlled comparisons, mean International Index of Erectile Function (IIEF) scores favored treatment at short-term follow-up (≤12 weeks; Hedges’ g = 1.08, 95% CI 0.64–1.52). The mid-term estimate was less precise (13–24 weeks; g = 0.49, 95% CI −0.02 to 1.01). Controlled Erection Hardness Score estimates were also imprecise. Risk ratios for study-defined clinically meaningful improvement in the IIEF erectile function domain were 2.51 (95% CI 0.76–8.31), 2.62 (0.56–12.36), and 2.67 (0.58–12.22) at 4, 12, and 24 weeks, respectively. Exploratory within-group analyses showed post-treatment changes in erectile function and peak systolic velocity, with substantial heterogeneity across several analyses. Conclusions: Controlled studies favored regenerative therapies for short-term improvement in mean erectile-function scores. Whether more patients achieve a clinically meaningful response, how long any benefit lasts, and which therapies are most effective remain uncertain. The review was registered with PROSPERO (CRD420261421415).

Journal of Clinical Medicine doi: 10.3390/jcm15228894

Authors: Milan Bogojevic Natasa Miketic Elvira Strujic Dragana Pravilovic Lutovac Slavica Pavlov Dolijanovic Lorenzo Dagna Marco Matucci-Cerinic Rifat Medjedovic Milica Markovic

Clinical development of conventional JAK, selective TYK2, and dual TYK2/JAK1 inhibitors has expanded beyond inflammatory arthritis, but evidence across systemic rheumatic diseases varies substantially and the agents are not pharmacologically interchangeable. We conducted a structured narrative review of PubMed/MEDLINE and ClinicalTrials.gov with an initial search in May 2026 and targeted updates through 9 November 2026, prioritizing randomized trials and interpreting observational studies and case reports as exploratory. Findings were organized by the highest direct clinical evidence and the practical conclusions that evidence can support. Upadacitinib for giant cell arteritis and brepocitinib for adult dermatomyositis now have phase 3 evidence and regulatory approval in the United States; upadacitinib is also approved for giant cell arteritis in the European Union. In the 52-week VALOR trial, brepocitinib 30 mg improved mean Total Improvement Score versus placebo (46.5 vs. 31.2; p < 0.001), while serious infections were more frequent (10% vs. 1%). Evidence in systemic lupus erythematosus remains mixed, and phase 3 programs are ongoing. A randomized baricitinib trial in Sjögren disease has a promising conference-abstract result, but full peer-reviewed data are not yet available. Evidence in polymyalgia rheumatica, systemic sclerosis, other vasculitides, VEXAS, and monogenic inflammatory diseases remains less mature. Clinical use should follow disease-specific evidence, regulatory status, and individualized safety assessment; pathway plausibility alone does not establish efficacy or predict response.

Journal of Clinical Medicine doi: 10.3390/jcm15228890

Authors: Yuki Motokawa Hiroaki Takaya Tadashi Namisaki Yui Osaki Tomihiro Iwata Hiroki Kachi Hitoshi Mori Takashi Inoue Akihiko Shibamoto Satoshi Iwai Yuki Tsuji Yukihisa Fujinaga Shinya Sato Koh Kitagawa Norihisa Nishimura Akira Mitoro Kiyoshi Asada Hitoshi Yoshiji

Aim: Sarcopenia is prevalent in patients with liver cirrhosis (LC) and associated with increased mortality and poor outcomes. However, readily available, noninvasive biomarkers for sarcopenia screening remain limited. This study evaluated the clinical utility of the von Willebrand factor (VWF)/a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13 (ADAMTS13) ratio as a biomarker for sarcopenia in patients with LC. Methods: We retrospectively analyzed 321 patients with LC. Sarcopenia was diagnosed according to the Japan Society of Hepatology criteria using computed tomography-derived skeletal muscle index and handgrip strength. ADAMTS13 and VWF levels were measured by enzyme-linked immunosorbent assay. Multivariate analyses identified factors associated with sarcopenia and overall survival. Results: Sarcopenia was diagnosed in 71 patients (22.1%). Patients with sarcopenia were older and had lower body mass index and hemoglobin levels. The VWF/ADAMTS13 ratio was significantly higher in patients with sarcopenia and negatively correlated with skeletal muscle index and handgrip strength. Multivariable logistic regression identified the VWF/ADAMTS13 ratio as an independent factor associated with sarcopenia (odds ratio 2.75, 95% confidence interval [CI]: 1.29–5.87, p < 0.01). A combined model including age, body mass index, hemoglobin, and VWF/ADAMTS13 ratio achieved an optimism-corrected area under the curve of 0.790 (95% CI: 0.730–0.850). Cox proportional hazards analysis demonstrated that an elevated VWF/ADAMTS13 ratio independently predicted poor overall survival (hazard ratio 1.67, 95% CI: 1.07–2.61, p < 0.05). Conclusions: The VWF/ADAMTS13 ratio was significantly associated with sarcopenia and may serve as a useful biomarker for its screening and identification in patients with LC.

Journal of Clinical Medicine doi: 10.3390/jcm15228893

Authors: Chi Hyun Lee Hee Tae Jung Ju Heon An Su Hee Kim Hyun Seung Lee Joo Hyoung Kim

Porous polycaprolactone (PCL) scaffolds are used in reconstructive applications because they can provide prolonged structural support while permitting tissue infiltration, yet their contribution to bone regeneration remains context-dependent. We report a 10-year-old boy with a congenital dermoid cyst of the forehead that was firmly adherent to the frontal bone and associated with focal outer-table erosion. After complete excision, a biodegradable PCL mesh was placed over the residual partial-thickness osseous defect to support the frontal contour. Serial computed tomography demonstrated progressive restoration of osseous continuity and thickness during follow-up, without implant-related complications. Prior experimental and clinical studies indicate that bone formation around PCL-based scaffolds varies with scaffold design, defect characteristics, and the local biological environment. In this biologically favorable pediatric partial-thickness defect, the porous PCL mesh may have functioned primarily as a space-maintaining structural scaffold that permitted progressive osseous remodeling from adjacent tissues. This case suggests that PCL mesh may provide a useful structural scaffold in selected pediatric cranial defects with preserved surrounding osteogenic potential.

Journal of Clinical Medicine doi: 10.3390/jcm15228892

Authors: Jonatan Vuković Josipa Radić Mislav Radić Tina Bečić Ivana Jukić

Adequate bowel preparation remains essential for high-quality colonoscopy, yet patients with diabetes mellitus consistently experience higher rates of inadequate bowel cleansing. Although diabetes is well established as a risk factor, treating it as a simple binary variable may no longer be sufficient. Diabetes is a heterogeneous disease, and the probability of inadequate bowel preparation likely varies substantially according to individual clinical characteristics. Evidence suggests that diabetes-related autonomic neuropathy may contribute to gastrointestinal dysmotility, including gastroparesis and impaired colonic transit, while chronic constipation may also arise through other mechanisms. These conditions, together with other diabetes-related complications, glycemic characteristics, medication exposure and longer disease duration, may contribute to or identify increased vulnerability to inadequate bowel preparation. Recent findings linking longer diabetes duration to clinically inadequate bowel preparation further highlight the need to investigate risk heterogeneity within the diabetic population. However, diabetes duration should be regarded as a candidate risk marker rather than a causal factor or stand-alone criterion for intensified preparation. We propose that research now move beyond repeatedly demonstrating diabetes as a risk factor and toward developing and prospectively validating diabetes-specific risk-stratification approaches. These approaches should subsequently be evaluated in intervention trials to determine whether targeted modifications of bowel preparation improve cleansing quality, metabolic safety and patient adherence. The next step is therefore not simply diabetes-specific preparation but risk-adapted preparation for patients with diabetes.

Journal of Clinical Medicine doi: 10.3390/jcm15228888

Authors: Dragoș Forțofoiu Ancuța-Ramona Boicea Camen Lidia Boldeanu Cosmin Vasile Obleaga Mihail Virgil Boldeanu Mohamed-Zakaria Assani Rodica Pădureanu Ioana-Gabriela Dragne Vlad Pădureanu Isabela Siloși Cristin-Constantin Vere

Colorectal cancer (CRC) is associated with psychological, metabolic, inflammatory, and endocrine disturbances that may influence patient well-being and clinical outcomes. Psychological distress and circadian disruption can affect hypothalamic–pituitary–adrenal (HPA) axis activity, whereas systemic inflammation, nutritional deterioration, disease burden, and anticancer therapies may alter hypothalamic–pituitary–thyroid (HPT) axis function. This narrative review critically examines the clinical and translational evidence linking psychological stress, neuroendocrine regulation, systemic thyroid function, and tumor-specific thyroid hormone signaling in CRC. A structured PubMed/MEDLINE search prioritized studies published between January 2020 and July 2026, supplemented by selected earlier landmark studies. Available evidence supports the clinical relevance of psychological distress and suggests that cortisol dynamics and allostatic load may provide complementary information on systemic stress adaptation. Reduced free triiodothyronine (FT3) concentrations and altered FT3/FT4 ratios have been associated with unfavorable outcomes in selected CRC populations, although these associations are influenced by non-thyroidal illness syndrome, inflammation, nutritional status, disease severity, and treatment exposure. Importantly, circulating thyroid hormone parameters do not directly reflect thyroid hormone signaling within the tumor microenvironment, where local hormone metabolism, receptor-mediated pathways, and interactions with stromal and immune cells may contribute to tumor biology. Emerging evidence also implicates neuropeptide signaling in neuroendocrine–tumor communication, although its clinical significance remains uncertain. Collectively, these findings support an integrated approach to assessing psychological, circadian, inflammatory, nutritional, and endocrine alterations in CRC while highlighting the limitations of interpreting isolated biomarkers. Prospective longitudinal studies incorporating standardized neuroendocrine assessments, treatment-related variables, and matched tumor analyses are needed to establish whether integrated neuroendocrine profiles offer prognostic or predictive value beyond established clinicopathological factors.

Journal of Clinical Medicine doi: 10.3390/jcm15228891

Authors: Abdurrahman Şeramet Serkan Sönmez Özer Gazioğlu Volkan Burak Taban

Background/Objectives: Inflammatory–nutritional indices have been proposed as predictors of arteriovenous fistula (AVF) failure. We examined whether six routine indices measured around the time of AVF creation are associated with AVF failure, reflecting access biology, or with all-cause mortality, reflecting patient vulnerability. Methods: In this single-centre retrospective cohort (2020–2026), the Controlling Nutritional Status (CONUT) score, prognostic nutritional index, C-reactive protein-to-albumin ratio, modified Glasgow Prognostic Score and neutrophil- and platelet-to-lymphocyte ratios were calculated from laboratory data obtained within 30 days of surgery. Mortality (n = 185; confirmed deaths) was analysed with Cox models adjusted for age, heart failure and diabetes, and AVF failure in a selected subcohort (n = 70) with cause-specific and Fine–Gray models. Results: During a median follow-up of 25.3 months, 30 patients (16.2%) died. Each one-point CONUT increase was associated with higher mortality hazard (adjusted hazard ratio [HR] 1.27, 95% confidence interval [CI] 1.09–1.48), and CONUT ≥5 with a threefold hazard versus CONUT 0–1 (HR 3.24, 95% CI 1.15–9.12). Adding CONUT improved model fit, but the gain in discrimination was uncertain (optimism-corrected C-index 0.593 to 0.676), and CONUT did not discriminate better than albumin alone. In the subcohort, 31 AVFs failed; no index was significantly associated with failure, but estimates were imprecise (subdistribution HR for CONUT ≥5 vs. <5 1.63, 95% CI 0.53–5.01). Conclusions: In this exploratory cohort, perioperative inflammatory–nutritional burden was associated with mortality after AVF creation. These indices reflect group-level risk rather than individual outcomes and may help identify patients warranting comprehensive nutritional assessment.

Journal of Clinical Medicine doi: 10.3390/jcm15228889

Authors: Matej Chren Milan Špánik Tamás Kristóf Kis Szymon Kuliś

Background: Competitive DanceSport imposes substantial cardiovascular demands, yet heart rate (HR) responses to pair and solo performance of Standard dances have rarely been examined within the same dancers. This study compared mean HR (HRmean) and peak HR (HRpeak) between a solo session and a subsequent pair session across the five Standard dances. Methods: Sixteen competitive Standard dancers (eight established couples; performance class A–S, Slovak Dance Sport Federation; age 22.5 ± 2.6 years) completed two simulated competition finals one week apart, first individually and then with their regular partner; condition was therefore confounded with session order. Each final comprised Waltz, Tango, Viennese Waltz, Slow Foxtrot, and Quickstep, performed for 90 s at competition-prescribed tempos. HR was recorded with Polar H10 chest straps. Overall effects were analyzed with linear mixed models accounting for repeated observations within dancers and potential dependence within couples; pair–solo differences within dances were estimated with paired t tests, and distribution-free and couple-level analyses served as sensitivity analyses. Results: HRmean was higher in the pair session by 8.9 beats·min−1 (95% CI 5.0–12.8; p < 0.001) and HRpeak by 7.5 beats·min−1 (95% CI 3.8–11.2; p < 0.001). In exploratory dance-specific comparisons (Condition × Dance, Greenhouse–Geisser-corrected: HRmean p = 0.008; HRpeak p < 0.001), differences ranged from 11.1 (Tango) to 5.8 beats·min−1 (Quickstep) for HRmean and from 10.9 (Waltz) to 3.9 beats·min−1 (Quickstep) for HRpeak. For HRpeak in Quickstep, the paired estimate was 3.9 beats·min−1 (95% CI 1.0–6.7; Holm-adjusted p = 0.014), whereas the mixed model with a pooled residual variance gave a 95% CI of −0.01 to 7.76 (p = 0.0504). Couple-level analyses and distribution-free tests supported the overall findings. Conclusions: HRmean and HRpeak were higher in the pair session than in the preceding solo session; the variation across dances was exploratory. Because condition was confounded with session order, these differences cannot be attributed to partner interaction.

Journal of Clinical Medicine doi: 10.3390/jcm15228887

Authors: Pamela Maslowski Anna Paradowska-Stolarz Marcin Mikulewicz Edward Kijak Katarzyna Skośkiewicz-Malinowska

Objectives: To systematically review the current evidence on orthodontic treatment in adults aged 65 years and older. Materials and Methods: This review followed the PRISMA 2020 reporting guidelines. The Medline PubMed, Scopus, and supplementary Google Scholar databases were searched. Based on the predefined inclusion and exclusion criteria, five studies were included out of 3533 records identified. However, all five studies meeting the eligibility criteria were case reports and were therefore included in the final qualitative synthesis. PROSPERO registration number: CRD420261421719. Results: The included case reports describe improvements in dental esthetics and oral function in selected elderly patients following orthodontic treatment. However, these findings should be interpreted cautiously, as the available evidence is limited to individual case reports. Successful treatment often requires interdisciplinary collaboration among dental specialists. Age-related biological changes, particularly periodontal considerations, present challenges that should be addressed during treatment planning. Conclusions: The included case reports describe orthodontic treatment as a potentially feasible option for selected patients aged 65 years and older, particularly when careful diagnosis, individualized treatment planning, and appropriate interdisciplinary management are implemented. However, since the available evidence is derived exclusively from case reports, its certainty is very low, and the reported outcomes cannot be generalized to the broader elderly population. Further well-designed clinical studies are needed to provide stronger evidence. Clinical Relevance: As interest in orthodontic treatment among older adults continues to grow, clinicians should carefully consider age-related biological changes and periodontal status when planning treatment. Advanced chronological age alone should not necessarily be considered a contraindication to orthodontic treatment; however, decisions should be individualized according to each patient’s oral health, periodontal condition, and overall clinical circumstances. The available case reports provide preliminary clinical insights, but further comparative studies are needed to better establish treatment outcomes in this population.

Journal of Clinical Medicine doi: 10.3390/jcm15228886

Authors: Pantelie Nicolcescu Aurel Nechita Manuela Arbune Mădălina-Nicoleta Matei Gabriel Valeriu Popa Maria Filofteia Mercuț

Background: Fournier’s gangrene (FG) is a necrotizing soft-tissue infection with substantial mortality. Objective: To critically compare prognostic determinants and scoring systems according to intended purpose, measurement timing, validation, and clinical applicability. Methods: This narrative review used searches of PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar, with the final database search on 27 July 2026. Four authors independently selected publications and extracted data; two authors adjudicated disagreements. The documented selection retained 94 publications. Diagnostic accuracy, mortality association, and prognostic-model performance were considered separately. Results: Mortality was 19.8% in a 6152-case literature synthesis and 16.1% in a Spanish national cohort. A 40-study meta-analysis reported pooled areas under the receiver operating characteristic curve (AUCs) of 0.90 for the Fournier’s Gangrene Severity Index (FGSI), 0.94 for its Uludag modification (UFGSI), and 0.84 for its simplified form (SFGSI), derived from different subsets of 9, 6, and 3 studies, respectively. These estimates do not establish comparative superiority. SFGSI requires fewer laboratory variables; FGSI includes broader physiology; UFGSI additionally incorporates age and anatomical extent. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) primarily supports diagnosis of necrotizing fasciitis. Neutrophil-to-lymphocyte ratio (NLR) thresholds show mortality associations but lack established external validation. General organ-dysfunction and comorbidity instruments address different domains. The Fournier’s Gangrene Mortality Index (FGMI) has limited external validation, whereas its platelet- and arterial-carbon-dioxide-augmented model (FGMI-2P) remains in model development. Conclusions: Instrument choice should reflect the clinical question, available data, and stage of care. The proposed framework has not been shown to improve decisions or outcomes beyond clinical assessment. Prognostic calculation must not delay resuscitation, antimicrobial treatment, or surgical source control.

Journal of Clinical Medicine doi: 10.3390/jcm15228883

Authors: Loredana Elena Stoica Smaranda-Adelina Bugala Dana Maria Albulescu Loredana Elena Selaru Cristina Maria Comanescu Gabriel Sebastian Petrescu Ancuta-Ramona Boicea Camen Dragos Cadea

Background/Objectives: Salivary inflammatory biomarkers may provide a minimally invasive summary of oral inflammatory burden, but a composite score requires biologically grounded construction and precise validation claims before clinical interpretation. We evaluated an equally weighted six-biomarker salivary inflammatory score, internally confirmed its one-factor structure, and examined cross-sectional associations with gingival, plaque and Community Periodontal Index (CPI) screening measures in children. Methods: This multicenter cross-sectional study included 1345 children aged 6–12 years from three Romanian counties. IL-6, IL-1β, TNF-α, IL-8, MRP-8/14, and CRP were measured in duplicate. The sample was split before standardization into derivation (n = 1076) and internal test (n = 269) subsets; derivation-set parameters were applied unchanged to the test subset. Exploratory factor analysis was conducted in the derivation subset, and the prespecified one-factor model was assessed in the internal test subset. Adjusted GI and CPI associations used all 1345 participants; because 54 archived participant-level PI values exceeded the stated 0–3 scale and could not be adjudicated from unavailable surface-level source records, the primary PI analyses used the 1291 records within the valid 0–3 range. Results: One factor explained 89.6% of biomarker variance in the derivation subset and showed excellent fit in the internal test subset (robust χ2 = 9.422, df = 9, p = 0.399; RMSEA = 0.013; SRMR = 0.007). Each one-derivation-set-standard-deviation increase in the score was associated with higher GI (B = 0.649, 95% CI 0.626–0.673; R2 = 0.898; n = 1345) and PI (B = 0.696, 95% CI 0.672–0.719; R2 = 0.914; n = 1291). Adjusted odds ratios were 33.29 (95% CI 19.57–56.62) for CPI 1 versus CPI 0 and 442.17 (95% CI 226.14–864.58) for CPI 2 versus CPI 0. Conclusions: The study supports internal structural confirmation of a dominant one-factor biomarker construct and strong cross-sectional associations after adjustment for measured covariates. It does not establish temporal stability, between-laboratory reproducibility, diagnostic accuracy or added clinical value beyond routine periodontal examination.

Journal of Clinical Medicine doi: 10.3390/jcm15228885

Authors: Hao Liu Qianqian Han Yuan Ji Yi Zhu Chang Liu Fangfang Wang Jingcheng Chen Zhenyan Zhu Jiyong Ge

Background/Objectives: Incretin-based therapies have been tested in trials specifically enrolling patients with obesity-related heart failure with preserved ejection fraction (HFpEF), whereas much of the obesity-relevant evidence for sodium-glucose cotransporter 2 (SGLT2) inhibitors derives from body mass index (BMI) subgroups of broader heart-failure trials. We synthesized these evidence streams separately and evaluated their directness and certainty. Methods: PubMed, Web of Science Core Collection, and CENTRAL were searched from inception through 1 July 2026, with supplementary searches of ClinicalTrials.gov, reference lists, trial names, registration numbers, protocols, and appendices. Randomized trials and randomized trial-derived analyses were eligible if they provided obesity- or BMI-relevant data for health status, 6 min walk distance (6MWD), body weight, or heart-failure/cardiovascular-death outcomes. Risk of bias was evaluated with RoB 2 and certainty with GRADE. Drug classes and evidence strata were analyzed separately. Results: The database searches identified 5258 records; 4461 unique records were screened, 48 reports underwent full-text assessment, and 41 reports were linked to 12 randomized trial programs. Twelve reports from 10 independent trials contributed unique quantitative estimates. In obesity-specific trials, incretin-based therapy improved KCCQ-CSS by 7.38 points (95% CI 5.51 to 9.26; I2 = 0%; moderate certainty), increased 6MWD by 17.60 m (95% CI 11.86 to 23.35; I2 = 0%; moderate certainty), and reduced weight by 9.56 percentage points (95% CI −12.71 to −6.42; I2 = 95.0%; moderate certainty). SUMMIT reported fewer cardiovascular-death or worsening-heart-failure events (HR 0.62, 95% CI 0.41 to 0.95; moderate certainty). For SGLT2 inhibitors, the primary blinded functional synthesis based on two subgroup analyses favored treatment for 6MWD (16.85 m, 95% CI 5.19 to 28.50; I2 = 11.2%; low certainty), but inference was highly imprecise under t-based Hartung–Knapp analysis. Weight effects were not pooled across evidence tiers: the exact BMI ≥ 30 kg/m2 EMPEROR-Preserved estimate was −1.48 kg (95% CI −1.84 to −1.13; low certainty), while obesity-enriched trials provided supportive but indirect estimates. In BMI ≥ 30 kg/m2 strata from EMPEROR-Preserved and DELIVER, the exploratory pooled event estimate was HR 0.80 (95% CI 0.69 to 0.91; I2 = 12.5%; low certainty), whereas the modified Hartung–Knapp 95% CI was 0.33 to 1.95. Conclusions: Obesity-specific randomized evidence supports clinically relevant improvements in symptoms, functional capacity, and weight with incretin-based therapies. SGLT2 estimates in patients with obesity or high BMI generally favored treatment but were less direct and less certain because they were frequently subgroup-derived, sometimes included participants with LVEF 41–49%, and were based on few independent trials. The findings do not establish class superiority or test a phenotype-guided treatment strategy; rather, they generate a hypothesis for phenotype-informed treatment selection.

Journal of Clinical Medicine doi: 10.3390/jcm15228884

Authors: Oana Diana Preda Simona-Raluca Iacoban Florentina-Adriana Găuianu Larisa Zidaru Daniel Murariu Sânziana Barbu Camelia Dobrea Ioana Loredana Cirlan Andra Matei Bianca Constantin Bianca Tarau Andreea-Lăcrămioara Mohorea-Neata Iulia Ursuleac Daniel Coriu Sorina Nicoleta Bădelită

Background/Objectives: Hodgkin lymphoma (HL) is the most common hematological malignancy among women of reproductive age. However, data on disease outcomes and infectious complications in pregnancy-associated HL are limited. No prior study has examined patients treated exclusively in the postpartum period. Our objective was to assess whether pregnancy-associated HL is associated with poorer disease outcomes and an increased risk of infectious complications. Methods: A multicenter, retrospective matched cohort study included 13 women diagnosed with HL during pregnancy or within 12 months postpartum (pregnancy-associated, PA) and 22 matched non-pregnancy-associated (NPA) controls. Controls were matched by International Prognostic Score, Ann Arbor stage, and age (within ±5 years), with diagnoses made between 2016 and 2025. Conditional logistic regression and mixed-effects Poisson regression were used to analyze infectious episodes separately for first-line and subsequent treatments. Progression-free survival (PFS) was estimated using the Kaplan–Meier method. Results: During first-line therapy, the PA group demonstrated significantly higher odds of any infection (OR 5.47, 95% CI 1.11–26.88, p = 0.037) and a higher number of infectious episodes (IRR 3.11, 95% CI 1.73–5.62, p < 0.001). No statistically significant differences were observed during subsequent lines of treatment. Progressive disease following first-line therapy was more frequent in the PA group (38.5% vs. 9.1%, p = 0.0559). Progression-free survival (PFS) at 12 months was 52.7% (95% CI 19.0–78.2) in the PA group compared to 77.3% (95% CI 53.7–89.8) in the NPA group (log-rank p = 0.27). No deaths were reported in either group. Conclusions: Pregnancy-associated HL is linked to a higher risk of infectious complications during first-line treatment and an increased rate of primary progression. These findings support the need for closer infectious surveillance in this population and should be confirmed in larger cohorts.

Journal of Clinical Medicine doi: 10.3390/jcm15228882

Authors: Guerchouh Nawel Moulgada Abdelmadjid Zagane Mohammed El Sallah Sahli Abderahmane Boudjemaa Ismail Murat Yaylacı Şevval Öztürk Ecren Uzun Yaylacı Ali Akdoğan Yılmaz Güvercin

Background/Objectives: Lower-limb amputation presents biomechanical challenges at the residual limb–prosthetic socket interface, where uneven load transfer may generate localized stress concentrations. This study investigates the biomechanical behavior of a patient-specific transfemoral residual limb–prosthesis system with and without a structural implant positioned at the distal femur. Methods: Finite element simulations were performed for three activities: normal walking, stair descent, and stair ascent. Von Mises stress, contact pressure (CPRESS), and longitudinal shear stress (CSHEAR1) were evaluated in the residual limb and prosthetic components. Results: During normal walking, stair descent, and stair ascent, the implant reduced the maximum von Mises stress in the residual limb by 62.9%, 55.1%, and 80.2%, respectively. The maximum longitudinal shear stress in the residual limb decreased by 28.6%, 28.0%, and 41.5%, respectively. During stair descent, the maximum contact pressure at the residual limb interface decreased by 79.4%, from 173 to 35.6 kPa, while during stair ascent it decreased by 38.6%, from 95.5 to 58.6 kPa. The maximum contact pressure on the prosthetic liner decreased by 43.0% during stair descent and 33.7% during stair ascent. Similarly, the maximum longitudinal shear stress on the socket decreased by 43.3% and 33.3%, respectively. However, slight increases in some peak contact and shear stress values were observed during normal walking. These findings indicate that the biomechanical effects of the implant depend on the activity and the parameter evaluated. Conclusions: Although the numerical results demonstrate reductions in several peak stress and pressure values, clinical benefits cannot be established from the simulations alone.

Journal of Clinical Medicine doi: 10.3390/jcm15228881

Authors: Alexandros Moniakis Antonella Maria Giardina Ismail Zaed Marco Morandi Andrea Cardia Davide Milani

Intraoperative ultrasound (ioUS) provides real-time imaging during cranial surgery and may be particularly useful when the reliability of conventional neuronavigation is reduced by brain shift, tissue distortion, or registration challenges. Cottonoid patties have previously been described as echogenic markers for intraoperative orientation, but their use has remained limited. In this technical note and case series, we describe a simple technique combining cottonoids with ioUS to provide a dynamic intraoperative reference during tumor resection. By exploiting the intrinsic hyperechogenicity of cottonoids and their readily identifiable movement during gentle manipulation, the technique was used to confirm surgical trajectories, support depth perception, and assist with spatial orientation throughout the procedure. We report a consecutive series of 12 patients with intracranial tumors in different anatomical locations and surgical positions, with particular emphasis on posterior fossa and occipital lesions. Rather than introducing a novel concept, the present Technical Note extends previous proof-of-concept experience by describing the practical transferability of cottonoid-guided ioUS to an independent consecutive adult cohort and by detailing its repeated use throughout the operative workflow, from initial trajectory confirmation to resection-cavity assessment. Trajectory confirmation was estimated by the operating surgeon to require less than 30 s in all cases, and no complications attributable to the technique were observed. Gross-total resection, assessed by postoperative magnetic resonance imaging, was achieved in all patients. The series also provides practical experience with posterior fossa and prone-position procedures, settings that remain comparatively underrepresented in the published literature. Our experience suggests that cottonoid-guided ioUS is a feasible, inexpensive, and practical adjunct to conventional neuronavigation, providing a dynamic reference that reflects current intraoperative anatomy.

Journal of Clinical Medicine doi: 10.3390/jcm15228880

Authors: Diana-Georgiana Basaca Iulius Jugănaru Meda-Ada Bugi Diana Nica Niculina Mang Lucian-Ioan Cristun Mihaela Sîrbu Giorgiana-Flavia Brad Raluca Asproniu Andrei Păun Andreea Grigoriță Emil Robert Stoicescu Otilia Mărginean

Background/Objectives: The impact of SARS-CoV-2 infection on the metabolic presentation and early course of type 1 diabetes mellitus (T1DM) in children remains incompletely understood. Although an increased frequency of diabetic ketoacidosis (DKA) has been reported during the coronavirus disease 2019 (COVID-19) pandemic, it is unclear whether this reflects a direct pathogenic role of the virus or indirect effects related to healthcare access and delayed presentation. Methods: This retrospective study included children with newly diagnosed T1DM evaluated between 2021 and 2025 at a single tertiary pediatric center. Two cohorts were compared: patients with PCR-documented and serologically confirmed prior SARS-CoV-2 infection (nucleocapsid antibody-based assay) and those without. DKA severity, acid-base parameters, lipid profile, autoimmune markers, thyroid function, and metabolic indices were compared at diagnosis. HbA1c, insulin dose, and C-peptide were assessed at diagnosis and 12-month follow-up. Multivariable regression, interaction testing, sensitivity, and subgroup analyses were performed. Results: Of 134 children, 58 had confirmed prior SARS-CoV-2 infection. Median HbA1c at diagnosis was 11.02% in the COVID group versus 11.77% in the non-COVID group (p = 0.057). Insulin requirements were similar (p = 0.87). Severe DKA occurred in 39.7% versus 42.1% (p = 0.90). C-peptide levels at diagnosis and 12 months did not differ between groups. Prior SARS-CoV-2 infection was not significantly associated with HbA1c at diagnosis (β = −0.65% HbA1c, 95% CI −1.33 to 0.03; p = 0.061; additionally adjusted for DKA grade, β = −0.68%, p = 0.079). HbA1c at 12 months was similar between groups (p = 0.85); in multivariable analysis adjusted for baseline HbA1c, age, and sex, prior infection was not significantly associated with HbA1c at follow-up (adjusted β = 0.39%, 95% CI −0.06 to 0.84; p = 0.092). Conclusions: No statistically significant association was found between confirmed prior SARS-CoV-2 infection and metabolic severity at diagnosis or glycemic outcomes during the first year, although the HbA1c comparison approached significance and the sample size limited power to detect differences smaller than approximately 1.04% HbA1c. The findings do not exclude a modest effect of prior infection, and larger prospective studies are warranted.

Journal of Clinical Medicine doi: 10.3390/jcm15228879

Authors: Julien G. Cohen Louise Bondeelle David Leite-Arada Julia Langhart Federica Giannotti Sarah Morin Pierre-Alexandre Poletti Anne Bergeron

Background/Objectives: Bronchiolitis obliterans syndrome (BOS) is the only pulmonary manifestation of graft-versus-host disease recognized after allogeneic hematopoietic stem-cell transplantation (HSCT). Air trapping, a supporting diagnostic feature, requires paired inspiratory and expiratory CT, increasing radiation exposure. We compared inspiratory with expiratory CT, with and without minimum-intensity projection (MinIP), for assessing small-airway involvement. Methods: In this retrospective exploratory study, 14 patients with post-HSCT BOS underwent inspiratory and expiratory volumetric CT. Five blinded readers scored lobular hypoattenuation (inspiratory mosaic attenuation; expiratory air trapping) in six lung zones on native and MinIP reconstructions. Agreement, reproducibility and functional correlation were analyzed. Results: Native inspiratory and expiratory scores showed no systematic difference (mean difference −0.21; 95% CI, −0.96 to 0.54; within a ±2-point exploratory equivalence margin, p < 0.001) and substantial agreement (weighted κ = 0.80). Inter-reader reproducibility was moderate, highest for native inspiration (intraclass correlation coefficient, 0.57), which correlated most strongly with the forced expiratory flow at 25–75% z-score (ρ = −0.75); differences between native phases were not significant. MinIP increased scores but reduced reproducibility and functional correlation. Conclusions: In established BOS, native inspiratory CT agreed substantially with expiratory CT without systematic difference, but individual differences preclude conclusions on diagnostic interchangeability. Prospective studies including early disease are needed.

Journal of Clinical Medicine doi: 10.3390/jcm15228878

Authors: Yan Zhang Bo Wang Dan Lin Ronghua Zhou

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is frequent after pediatric cardiac surgery and is associated with adverse short- and long-term kidney outcomes. Although multiple pharmacologic and non-pharmacologic preventive strategies have been evaluated, the randomized evidence remains fragmented and their comparative effectiveness and certainty remain unclear. Methods: PubMed/MEDLINE, Embase, Web of Science, CENTRAL, and ClinicalTrials.gov were queried from inception to October 21, 2026 to identify randomized trials evaluating preventive strategies in children undergoing cardiac surgery with postoperative renal outcome data. Relative effects were synthesized using a frequentist random-effects network model and expressed as ORs with 95% CIs; confidence in the network estimates was appraised using CINeMA. Results: The analysis included 36 trials involving 6296 participants and 1274 trial-reported renal outcome events, with 21 treatment nodes linked by 22 direct comparisons. Relative to Control, the network estimates favored remote ischemic preconditioning (RIPC) (OR, 0.41; 95% CI, 0.28–0.60) and dexmedetomidine (OR, 0.51; 95% CI, 0.31–0.85), while goal-directed perfusion (GDP) showed a borderline favorable estimate (OR, 0.54; 95% CI, 0.29–0.99). Overall heterogeneity was modest (I2 = 9.9%), although greater variation was observed among the direct RIPC trials (I2 = 46.2%). CINeMA confidence was moderate for RIPC and low for dexmedetomidine. Evidence for the remaining interventions was generally limited or imprecise. Conclusions: RIPC showed the most credible association with lower odds of CSA-AKI, while dexmedetomidine was also favorable and GDP showed a less robust signal. These findings remain insufficient for practice-changing recommendations and require confirmation in larger pediatric trials using harmonized kidney outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15228877

Authors: Mehmet Çağatay Çiçek Kadir Ömür Günseren Levent Turan Abdülmecit Yıldız

Background: Kidney transplant recipients carry a substantially increased risk of malignancy. Ionizing radiation from medical imaging is a recognized but seldom-quantified contributor to this risk. We aimed to characterize cumulative exposure to ionizing radiation from medical imaging after transplantation in deceased-donor kidney transplant (DDKT) recipients. Methods: This single-center retrospective study included all DDKT recipients transplanted between June 2006 and June 2018 with at least six months of follow-up. All radiologic procedures involving ionizing radiation—direct and contrast radiography, computed tomography (CT), fluoroscopy, coronary angiography, and nuclear medicine—were retrieved from the institutional radiology database. Typical effective doses were assigned from published catalogs using International Commission on Radiological Protection (ICRP) Publication 103 tissue-weighting factors. CT-specific cumulative effective dose (CED) was computed per examination with the ImPACT CT Patient Dose Calculator v1.02 (Monte Carlo-based). Recipients were stratified into low- (0–20 mSv), moderate- (>20–50 mSv), high- (>50–100 mSv), and very-high-dose (>100 mSv) categories. Results: 350 DDKT recipients (mean age 43.9 ± 11.3 years, 43.4% female) were followed for a median of 4.8 years (interquartile range [IQR] 2.71–7.51), yielding 1861 patient-years. A total of 9636 ionizing-radiation procedures were performed; 7600 (78.9%) were plain radiographs, and 875 (9.1%) were CT scans. Mean total CED was 36.0 ± 34.5 mSv (median 24.7, IQR 10.6–50.8 mSv). Median annual CED was 5.32 mSv (IQR 1.68–14.50). CT accounted for 69.4% of the total CED. Twenty-six percent (n = 92) of recipients had a CED above 50 mSv and 6.3% (n = 22) above 100 mSv. Older recipients (above the median age of 45 years) had a significantly higher mean total CED than younger recipients (41.8 ± 36.0 vs 30.3 ± 32.0 mSv; mean difference 11.5 mSv, 95% confidence interval [CI] 4.7–18.3; p = 0.014). In multivariable analysis, delayed graft function was the only factor independently associated with higher CED (CED ratio 1.43, 95% CI 1.05–1.93) and more CT examinations, whereas recipient age was not independently associated with CED after adjustment. Conclusions: A substantial proportion of DDKT recipients are exposed to non-trivial cumulative doses of ionizing radiation after transplantation, primarily driven by CT imaging. These are descriptive exposure data: the study did not assess clinical outcomes and does not demonstrate any clinical harm attributable to imaging-related radiation, and the expected radiation-attributable cancer risk is modest in absolute terms. Therefore, clinically indicated imaging should not be curtailed; rather, care-neutral measures—tracking of cumulative dose, preferential use of non-ionizing modalities where diagnostically equivalent, and low-dose CT protocols—are reasonable, particularly in younger recipients and in those with delayed graft function.

Journal of Clinical Medicine doi: 10.3390/jcm15228876

Authors: Zain Al Abdeen Al Zuabi Chandra Pasapula Anand Karmegam Ahmed S. Elhalawany Aakanksha Shetty Adam Devany Steven Cutts

Tarsal tunnel syndrome (TTS) was first described independently by Keck and Lam in 1962 as a compressive neuropathy of the posterior tibial nerve and its branches occurring behind the medial malleolus. Symptoms include pain, paraesthesia, and sensory disturbance in the medial and plantar aspects of the foot. The condition affects women more frequently than men and, while often idiopathic, has a range of identifiable intrinsic and extrinsic causes. Recent cadaveric studies have refined understanding of tarsal tunnel anatomy, demonstrating that the flexor retinaculum is frequently an extension of the crural fascia rather than an independent structure, and that the lateral plantar nerve and the nerve to abductor digiti minimi share a common origin in the majority of cases. Diagnosis remains challenging in the absence of a single pathognomonic test. Nerve conduction studies carry a false-negative rate approaching 50%, and quantitative ultrasound has emerged as a complementary investigation, though the evidence base for each modality varies markedly in quality and is critically appraised below rather than simply catalogued. Reported surgical success rates vary widely (44–95%), and this review argues that this variability is itself informative: it reflects heterogeneous diagnostic criteria and outcome measures across a literature composed almost entirely of retrospective, uncontrolled, single-centre case series, rather than genuine disagreement about whether surgery works. Bone–nerve contact on imaging, hindfoot malalignment, and coexistent plantar fasciitis have been associated with poorer outcomes in a single retrospective series, whereas identifiable space-occupying lesions consistently predict good results. Prognostic factors, the coexistence of TTS with diabetic neuropathy, and the emerging ‘double crush’ phenomenon are discussed, alongside an explicit assessment of where the evidence is strong, where it is weak, and where clinical practice currently outruns the data.

Journal of Clinical Medicine doi: 10.3390/jcm15228874

Authors: Ciprian Cucoreanu Maria Andreea Soporan Ioana-Ecaterina Pralea Adrian-Bogdan Țigu Ximena-Maria Mureșan Radu Moldovan Alina Uifălean Maria Iacobescu George-Călin Dindelegan Cristina-Adela Iuga

Background/Objectives: Circulating proteomic changes after metabolic and bariatric surgery are often described without reference to a non-obese population. We characterized plasma-proteome remodeling following sleeve gastrectomy (SG) using a three-state reference-aware framework. Methods: This exploratory observational analysis included 61 plasma specimens from 49 participants: 26 preoperative (T0), 15 postoperative follow-up (FW), and 20 non-obese control specimens. Twelve surgical participants had matched T0–FW specimens (median sampling interval, 141 days; IQR, 114–193 days; range, 82–219 days). We assessed 408 protein groups using participant-blocked limma analysis and secondary age- and sex-adjusted reference contrasts. Results: Twenty-five proteins changed within participants (Benjamini–Hochberg q < 0.05; 15 increased and 10 decreased). Descriptive reference-aware categories were postoperative-emergent (20), reference-directed attenuation (3), reference-crossing (1), and paired-only (1). A post hoc reference-deviation score calculated from 400 complete-case proteins increased in all 12 matched participants (mean paired change, +0.165; exact sign-flip p = 0.000488). No Reactome pathway remained robust across sensitivity analyses. Conclusions: During the variable postoperative period, proteomic remodeling was heterogeneous and did not uniformly converge toward the non-obese statistical reference. These exploratory associations do not establish surgery-specific effects, clinical biomarker validity, or adverse health consequences.

Journal of Clinical Medicine doi: 10.3390/jcm15228875

Authors: Woochan Choi

Background: Left ventricular (LV) aneurysm after myocardial infarction is a recognized source of cardioembolic stroke, and anticoagulation is recommended once LV thrombus is demonstrated. When a large cerebral infarct is complicated by hemorrhagic transformation (HT), however, anticoagulation is often delayed or interrupted. Intracardiac thrombus formation during such intervals is rarely documented on serial imaging. Case Presentation: An 82-year-old man with prior non-ST-elevation myocardial infarction presented with acute ischemic stroke caused by right internal carotid artery (ICA) occlusion. Endovascular thrombectomy (EVT) achieved complete reperfusion, and initial transthoracic echocardiography and chest computed tomography showed an LV apical aneurysm without visible thrombus. Because HT developed after EVT, anticoagulation was withheld and later initiated with warfarin. An LV apical thrombus detected during subtherapeutic anticoagulation was no longer visible on imaging obtained 24 h later, coinciding with recurrent ICA occlusion after the international normalized ratio had reached the therapeutic range. After warfarin was stopped because of progression to parenchymal hematoma, a second de novo thrombus formed in the same aneurysm during the subsequent interruption. Anticoagulation was resumed with warfarin and brief intermediate-dose low-molecular-weight heparin bridging, after which the thrombus regressed without further embolic or hemorrhagic events before transfer. Conclusions: This case suggests that a post-infarction LV apical aneurysm may remain capable of forming thrombus despite preserved global systolic function and initially negative cardiac imaging. When HT necessitates delayed or interrupted anticoagulation, individualized repeat imaging may help detect newly formed LV thrombus in selected patients with a persistent LV aneurysm or regional akinesia.

Journal of Clinical Medicine doi: 10.3390/jcm15228873

Authors: Shahabeddin Yazdanpanah Hana-Joy E. Hanks Carla Guedikian Jade Dai Rowen Lin Amy Huang Ammar Bhaiji Sultan Baz Vivian Chen Nitin N. Bhatia Yu-Po Lee Emily S. Mills Hao-Hua Wu Sohaib Z. Hashmi Don Young Park

Background: Biportal endoscopic decompression for lumbar spinal stenosis (LSS) may facilitate rapid recovery, yet early minimal clinically important difference (MCID) achievement across pathology-relevant patient-reported outcome measures (PROMs) here remains insufficiently characterized. Accordingly, this study evaluates early (six-week) MCID achievement and associated factors following biportal endoscopic decompression for LSS to supplement surgeon comprehension and patient expectation-setting. Methods: A prospectively maintained, single-center/surgeon database was retrospectively queried (2021–2026) for adult patients undergoing biportal endoscopic decompression without fusion for LSS-only indications. Cases were excluded based on factors such as missing data, complicating etiologies/procedures, or insufficient follow-up. The primary outcome was literature-anchored MCID achievement, defined as an improvement of ≥2 points in the visual analog scale (VAS)-back and VAS-leg PROMs, and ≥14.9 points in the Oswestry Disability Index (ODI). Statistics included paired comparisons, exploratory multivariable logistic regressions with odds ratios (ORs), sensitivity analyses, and subgroup examinations. Results: Ninety-nine patients were included (mean age = 70.0 ± 10.0 years; body mass index [BMI] = 27.2 ± 5.1 kg/m2; follow-up = 6 ± 0 weeks; 53.5% male). VAS-back improved from 6.1 ± 2.8 to 2.0 ± 2.1, VAS-leg from 6.9 ± 2.4 to 1.4 ± 2.1, and ODI from 42.9 ± 18.6 to 21.5 ± 15.1 (all p < 0.001). Six-week MCID achievement rates were 78.8%, 88.9%, and 63.6%, respectively, with significant pairwise differences (all corrected p < 0.05). Best-case/worst-case exclusion sensitivity analyses yielded achievement ranges of 60.3–83.3% for VAS-back, 67.3–90.4% for VAS-leg, and 46.2–71.8% for ODI. Higher preoperative VAS-back (odds ratio [OR] = 1.810) and ODI (OR = 1.183) were associated with respective MCID achievement. Male sex increased (OR = 4.727) and higher BMI decreased (OR = 0.859) odds of ODI-MCID achievement (both corrected p < 0.05), though findings were statistically limited. In the subgroup with postoperative radiculitis (23.2%), which is known to affect recovery and its perception, lower six-week ODI-MCID achievement was observed (43.5% versus 69.7%, p = 0.022). Conclusions: Biportal endoscopic decompression for LSS was associated with substantial six-week MCID achievement rates, with the highest achievement rate observed for VAS-leg. While baseline symptom severity was associated with MCID achievement, these relationships warrant cautious interpretation given the use of absolute change thresholds. These findings may help to inform patient counseling and early postoperative expectation-setting.

Journal of Clinical Medicine doi: 10.3390/jcm15228872

Authors: Yana Osnytska Zuzanna Leciej Agnieszka Kempinska-Podhorodecka Agnieszka Brodowska Andrzej Starczewski Adrianna Zahorowska

Background: Advanced endometriosis substantially impairs health-related quality of life (HRQoL). This prospective cohort study assessed six-month changes in HRQoL and pain following surgical treatment and postoperative hormonal therapy and explored whether postoperative changes and adverse-effect profiles differed according to hormonal treatment. Methods: Fifty women with histologically confirmed rASRM stage III–IV endometriosis underwent surgical treatment. SF-36v2 and Numerical Rating Scale (NRS) scores were assessed preoperatively and at six months. Paired changes, correlations with pain reduction, disease-stage differences, and exploratory comparisons among dienogest, GnRH-agonist, and combined ethinylestradiol/dienogest (EE/DNG) treatment groups were analysed. Adverse effects were compared using the Fisher–Freeman–Halton exact test with Holm adjustment. Results: All eight SF-36v2 domains improved significantly (all p < 0.001; r = 0.74–0.87), and median NRS pain decreased from 8 (IQR 7–8) to 2 (IQR 1–3) (p < 0.001; r = 0.87). Pain reduction was positively associated with improvement across all SF-36v2 domains; seven of eight correlations were statistically significant before adjustment, while four remained significant after Holm correction, with the strongest association observed for Bodily Pain (ρ = 0.538). No statistically significant differences in pain or HRQoL change were detected by rASRM stage or postoperative hormonal regimen. Hot flushes differed across hormonal groups and were most frequent with GnRH-agonist therapy (56.3%; Holm-adjusted p = 0.010). Conclusions: Six months after surgery and postoperative hormonal therapy for advanced endometriosis, substantial improvements in HRQoL and pain were observed. HRQoL improvement was only partly associated with pain reduction. Exploratory comparisons among postoperative hormonal regimens did not detect differences in patient-reported improvement, whereas tolerability profiles differed, particularly with respect to hot flushes in the GnRH-agonist group. Because treatment allocation was not randomized, these findings do not establish comparative efficacy or treatment equivalence.

Journal of Clinical Medicine doi: 10.3390/jcm15228871

Authors: Rex Mawuli Kwadjo Djokoto Edward Anabila Agana Kingsley Afreh Nduroh Johnny Arthur-Komeh Opei Adarkwa Andrew Panyin Vormawor Amponsah Peprah Anthony Amanfo Ofori Victor Boachie Owusu Isaac Kofi Adu Wilfred Kwamina Junior Sam-Awortwi Augustine Tawiah Michael Adumatta Benedict Apaw Agyei

Background: Evidence from sub-Saharan Africa on obstetric and perinatal outcomes after in vitro fertilization (IVF) is limited, and Ghanaian maternal-age comparisons have largely involved general obstetric populations. We compared outcomes among singleton IVF pregnancies across younger and advanced maternal age groups at a Ghanaian fertility center. Methods: This retrospective comparative cohort included 261 singleton IVF pregnancies delivered at Oak Specialist Hospital between 2022 and 2026: 99 women aged 20–34 years and 162 aged ≥35 years. Outcomes were summarized across age groups, and adjusted prevalence ratios (aPRs) were estimated using modified Poisson regression with robust standard errors. Models used age 20–34 years as the reference and adjusted for parity, pre-existing hypertension and diabetes, number of embryos transferred, and delivery year. Results: The broad composite outcome occurred in 70/98 (71.4%) younger pregnancies and 84/161 (52.2%) pregnancies at age ≥35 years. aPRs versus age 20–34 were 0.66 (95% CI 0.51–0.86) for ages 35–39, 0.71 (0.53–0.96) for ages 40–44, and 0.63 (0.46–0.86) for ages ≥45 (global p = 0.002). The perinatal composite occurred in 67/99 (67.7%) and 84/162 (51.9%), respectively. Age group was not associated with preterm birth (global p = 0.349), while recorded NICU admission was lower in the older strata. Hypertensive disorder of pregnancy was recorded in 21/48 (43.8%) pregnancies at age ≥45 years and 13/99 (13.1%) at age 20–34 years. Conclusions: Older age groups had lower recorded composite and NICU outcomes than the younger IVF reference group, but individual perinatal outcomes did not show a consistent age gradient. These inverse findings should not be interpreted as protective effects; selection, case mix, and outcome documentation may contribute. Larger multicenter studies with verified records are needed.

Journal of Clinical Medicine doi: 10.3390/jcm15228870

Authors: Kinga Brawańska-Maśluch Katarzyna Paliszek-Saładyga Małgorzata Bukowska Paulina Dziewierz Joanna Chrzanowska Daniel Fichte Aleksander Basiak Robert Śmigiel

Leukodystrophies are a diverse group of inherited disorders affecting central nervous system white matter, with onset from infancy to adulthood. Although neurological symptoms dominate, endocrine dysfunctions are increasingly recognized as significant contributors to disease course. These can arise directly from genetic mutations or secondarily due to hypothalamic–pituitary or peripheral gland involvement. This scoping review focuses on leukodystrophies associated with hormonal abnormalities, summarizing current diagnostic approaches, preventive strategies, and treatment options. Literature from PubMed/MEDLINE and Embase (1991–May 2026) was analysed, including original research, reviews, meta-analyses, and case reports. Endocrinopathies commonly observed include adrenal insufficiency, hypogonadism, growth hormone deficiency, hypothyroidism, and diabetes mellitus. Disorders such as X-linked adrenoleukodystrophy, POLR3-related leukodystrophy, vanishing white matter disease, and Aicardi–Goutières syndrome show distinct hormonal involvement patterns. Early detection and timely hormone replacement can improve growth, development, metabolic stability, and quality of life, while preventing severe complications. Diagnosis integrates clinical evaluation, hormonal testing, neuroimaging, and advanced molecular analyses, including whole-exome or whole-genome sequencing. Effective management requires a multidisciplinary approach combining supportive care, endocrine replacement, and selected disease-modifying therapies. Understanding the interplay between neurological and endocrine features is crucial for optimizing care and improving long-term outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15228869

Authors: Mobin Mobadersani Alireza Motamedi Alanagh Ali Meshkini Homayoun Sadeghi-Bazargani

Background/Objectives: Secondary injury after acute traumatic spinal cord injury (SCI) evolves over hours to weeks; no adjunctive neuroprotective therapy is standard care. This review aimed to assess the benefits and harms of neuroprotective interventions first given within 14 days of injury. Methods: We searched PubMed, Embase, Scopus, CENTRAL and four trial registers (16–21 May 2026) for randomized trials of neuroprotective interventions versus inactive or active comparators. Synthesis was by comparison, with meta-analysis only where grouping rules allowed. Risk of bias was assessed with RoB 2 and certainty with GRADE (PROSPERO CRD420261442429). Results: Thirty-four trials (about 3700 participants) were included: 26 pharmacologic, three biologic and five physiologic or procedural. Each prespecified synthesis group held one trial, limiting pooling to four exploratory two-trial riluzole analyses. Of 40 graded estimates, one had Moderate certainty, 17 Low and 22 Very low, mainly because of imprecision. In cervical injury, riluzole may result in little to no difference in motor recovery (mean difference 3.60 points, 95% CI −1.66 to 8.86; 0.97 allowing for baseline imbalance) or mortality (risk ratio 0.83, 0.39 to 1.77) and may slightly improve functional independence (4.32 points, −2.07 to 10.70), all with Low certainty. In complete injury, autologous macrophages given on days 9–17 probably make little to no difference in motor recovery (Moderate certainty). Conclusions: No neuroprotective intervention for acute traumatic SCI has Moderate- or High-certainty evidence of benefit, and evidence on serious harms is too sparse to judge safety. Larger trials with harmonized outcomes, precise timing and complete harms reporting are needed.

Journal of Clinical Medicine doi: 10.3390/jcm15228868

Authors: Buket Yılmaz Bulbul Nuray Can Nuri Isler Burak Andac Esra Zeynep Yucesan Buse Ekici Isil Yigitbasi Seda Dogan Gamze Nur Aktas Mehmet Celik

Background/Objectives: Diagnostic criteria for non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) have changed twice since 2016, most visibly in the tolerance for true papillae and in the role of molecular findings. We evaluated historical NIFTPs under the original and subsequent frameworks and related framework-specific classification to long-term outcomes. Methods: In this single-center, retrospective cohort (surgery 2007–2016), archival slides of 79 historical NIFTPs with linked longitudinal follow-up were independently re-reviewed in 2026 by two pathologists without knowledge of long-term outcomes or molecular results; their framework-specific classifications were concordant in all cases. Reasons for failure to retain the diagnosis across all frameworks were classified as criterion-dependent, criterion-independent, or technical. Outcomes were compared with 56 infiltrative and 39 invasive encapsulated follicular-variant papillary thyroid carcinomas (FVPTCs) from the same institution. Results: Thirty-six tumors (45.6%; 95% CI, 34.3–57.2%) qualified as NIFTP under all frameworks. Retention was 47/79 (59.5%; 95% CI, 47.9–70.4%) under the original 2016 criteria, 37/79 (46.8%; 95% CI, 35.5–58.4%) under the 2018 consensus primary criteria, and 46/79 (58.2%; 95% CI, 46.6–69.2%) under WHO 2022. Ten tumors with well-formed true papillae occupying <1% qualified under 2016 and WHO 2022 but not under the 2018 criteria. One additional BRAF V600E-positive tumor had no well-formed papillae, an entirely follicular growth pattern, and a nuclear score of 3; it fulfilled the 2016 and 2018 primary morphologic criteria but was excluded under WHO 2022 because BRAF V600E was detected. Criterion-independent discordance between the historical classification and contemporary re-review accounted for 28/79 tumors (35.4%; 95% CI, 25.0–47.0%). During a median follow-up of 132 months, no incident structural events were observed among historical NIFTPs (0/64; upper 95% CI, 5.6%), and none of 36 with examined lymph nodes had nodal metastasis, whereas nodal metastasis at surgery (4/27) and the only incident structural recurrence occurred among invasive encapsulated FVPTCs. Conclusions: Framework-specific retention ranged from 46.8% to 59.5%, driven mainly by the papilla criterion and, in one molecularly discordant case, BRAF V600E status. Most diagnostic loss reflected criterion-independent discordance identified on contemporary dual-pathologist slide re-review. No incident structural events were observed among outcome-evaluable historical NIFTPs during a median follow-up of 11 years.

Journal of Clinical Medicine doi: 10.3390/jcm15228866

Authors: Mikhail Kolev Irina Naskinova Meglena Lazarova Hristo Kalinov Velin Klisurov

Small public multimodal datasets invite overstated claims that wearable signals classify attention-deficit/hyperactivity disorder (ADHD). The HYPERAKTIV dataset served as a methodological case study: 103 adult psychiatric outpatients, 51 with ADHD and 52 clinical controls, with actigraphy, heart-rate recordings, and cognitive testing. The task was differential classification, not screening. Background/Objectives: The objective is to quantify how far the reported performance depends on the evaluation protocol. Methods: The methods evaluated four nested feature blocks on 63 complete cases with one fixed model and one estimand: the mean out-of-fold area under the receiver operating characteristic curve (AUROC) over 20 fold assignments. Each block was compared with a permutation null from the identical protocol. Results: The results are that the fold assignment alone moved a single block’s AUROC by up to 0.235, and no block exceeded its null. The heart-rate-variability increment was −0.039 (percentile interval −0.153 to 0.155), inconclusive under every interval method. A bootstrap holding the fitted models fixed suggested a bounded null, and DeLong’s test made the cognitive increment significant; resampling the whole pipeline confirmed neither. On datasets with the heart-rate-variability block permuted, these two tests rejected in 18.3% and 14.7% of those datasets at a 5% level. The pre-scored ADHD Confidence Index alone reached an AUROC of 0.743, descriptively above every fitted model. Conclusions: The conclusions drawn are that small-sample studies should report a protocol-matched null and intervals that refit the whole pipeline.

Journal of Clinical Medicine doi: 10.3390/jcm15228867

Authors: Weirna Winantiningtyas Raden Besthadi Sukmono Pryambodho

Background/Objectives: Pain after nephrectomy has somatic and visceral components and usually requires opioids. We evaluated the efficacy and safety of single-shot (non-catheter) thoracic or thoracolumbar paravertebral block (TPVB) in adults undergoing unilateral nephrectomy or nephroureterectomy. Methods: The protocol was registered in PROSPERO (CRD420261499704). PubMed, Cochrane CENTRAL and ScienceDirect were searched from January 2001 to 30 September 2026 for randomized controlled trials. Two reviewers independently screened records, extracted data and assessed risk of bias with Cochrane RoB 2. Random-effects meta-analyses used DerSimonian–Laird heterogeneity estimates with Hartung–Knapp–Sidik–Jonkman (HKSJ) confidence intervals; sensitivity analyses were defined on clinical grounds (surgical approach, blinding and type of operation); certainty was graded with GRADE. Results: Six trials with 498 participants were included. TPVB was associated with lower 24 h opioid consumption (standardized mean difference −1.19, 95% CI −2.50 to 0.11; I2 = 91%) and resting pain at 24 h (mean difference −0.90, 95% CI −2.59 to 0.79; I2 = 64%); the direction was consistent, but both intervals included no effect and the magnitude is uncertain. Effects were larger against no block than against an active fascial plane block, but each subgroup contained two trials and comparator type overlapped with surgical approach and blinding. The reduction in resting pain was confined to two open-label trials of open surgery. Nausea (risk ratio 0.83, 95% CI 0.37 to 1.88), vomiting (risk ratio 0.83, 95% CI 0.20 to 3.44) and rescue analgesia (risk ratio 1.24, 95% CI 0.54 to 2.83) did not differ. Block-related complications were defined and reported inconsistently and could not be pooled. Two trials had low overall risk of bias and four had some concerns; certainty of evidence was very low for all outcomes. Conclusions: The available trials show a consistent direction of effect favoring TPVB for 24 h opioid consumption and resting pain after unilateral nephrectomy or nephroureterectomy, but the magnitude of that effect is uncertain. Any benefit applies mainly to comparisons with no block; superiority over other regional blocks is not established, and the findings should not be generalized to all analgesia for renal surgery.

Journal of Clinical Medicine doi: 10.3390/jcm15228864

Authors: Young Tae Lim Hanpyo Hong Hyewon Kim Jae Min Lee Youngjin Jung

Background/Objectives: Younger age is an established risk factor for coronary artery abnormalities (CAAs) in Kawasaki disease (KD), but nationwide data on age-related differences in treatment and antithrombotic management are limited. We characterized age-specific patterns of claims-coded CAAs, initial treatment, and antithrombotic prescribing in Korean children with KD. Methods: Using the Health Insurance Review and Assessment Service database, we analyzed 52,247 patients with KD diagnosed in 2010–2023, stratified by age (<1, 1 to <5, and 5 to <18 years). CAAs were identified by diagnostic code I25.4, which does not distinguish aneurysm from ectasia. Factors associated with claims-coded CAAs were explored using multivariable logistic regression. Results: Claims-coded CAAs were identified in 3.3% of patients, with similar proportions across age groups (3.5%, 3.1%, and 3.5%; p = 0.069). Older children (≥5 years) more frequently received initial intravenous immunoglobulin (IVIG) plus corticosteroid therapy (24.3% vs. 16.0–18.5%; p < 0.001). Among patients with claims-coded CAAs, older children more often had cumulative, not necessarily concurrent, exposure to aspirin, clopidogrel, and warfarin during follow-up (10.8% vs. 3.7–6.2%) and antithrombotic prescriptions for >12 months (40.6% vs. 25.3–25.6%). IVIG prescription on hospital Day ≥ 3 was associated with higher odds of claims-coded CAAs (adjusted odds ratio, 1.48; 95% confidence interval, 1.22–1.80). Conclusions: Although the proportion of claims-coded CAAs was similar across age groups, recorded antithrombotic prescribing among affected children differed by age; because observation time was not standardized, whether this reflects true management differences or lesion severity requires validation. KD should remain in the differential diagnosis for school-age children.

Journal of Clinical Medicine doi: 10.3390/jcm15228860

Authors: Felice Gragnano Vincenzo De Sio Antonio Capolongo Giuseppe Verde Giovanni Pio Iannotti Angelo Romano Elio Mattia Migliaccio Michelangelo Luciani Gabriele Cappiello Elisabetta Moscarella Simona Sperlongano Vincenzo Acerbo Arturo Cesaro Dobromir Dobrev Antonio Landi Diana A. Gorog Dominick J. Angiolillo Marco Valgimigli Paolo Calabrò

Dual antiplatelet therapy (DAPT) is central to the prevention of thrombotic complications after percutaneous coronary intervention (PCI). However, its optimal composition and duration are not uniform across all settings. Both ischemic and bleeding risks peak early after PCI, although their relative balance changes dynamically over time. This has shifted contemporary practice from standard DAPT regimens toward modulation of antiplatelet therapy by means of de-escalating and escalating the intensity of platelet inhibition tailored to clinical risk, procedural complexity, medication adherence, and time from PCI. In this narrative review, we examine randomized evidence on de-escalation and escalation antiplatelet strategies in patients undergoing PCI. De-escalation may be achieved through antiplatelet discontinuation, dose reduction, or switching. Among these approaches, aspirin withdrawal followed by P2Y12 inhibitor monotherapy with ticagrelor has the strongest evidence, particularly after an initial event-free period. Guided and unguided switching strategies may further refine treatment in selected patients. Conversely, escalation through increased doses, prolonged or additional antiplatelet therapy, or switching to more potent P2Y12 inhibition may be considered in patients in whom residual ischemic risk outweighs bleeding risk. Contemporary European and American guidelines increasingly reflect this risk-adapted approach. In conclusion, antiplatelet therapy following PCI should not be considered a “one size fits all” approach, but rather a strategy that needs to be tailored according to the patient’s risk profile that may need adjustments during the course of the patient’s follow-up.

Journal of Clinical Medicine doi: 10.3390/jcm15228863

Authors: Cristina Matesanz López Celia María Pinedo Sierra José Manuel Padilla Brito Sonia Pascual García Elizabeth Manuely González Revilla María Asunción Nieto Barbero

Drug-induced sarcoid-like reactions (DISRs) are uncommon granulomatous disorders that develop in temporal association with drug exposure and closely resemble sarcoidosis clinically, radiologically, and histologically. Their recognition has become increasingly relevant with the expanding use of immune-modulating and targeted therapies. Immune checkpoint inhibitors and tumor necrosis factor-alpha inhibitors are among the best-documented causes, while sarcoid-like reactions have also been reported with interferons, dupilumab, BRAF/MEK inhibitors, and other biologic and targeted agents. Thoracic involvement is particularly common and typically manifests as bilateral hilar or mediastinal lymphadenopathy, with or without pulmonary parenchymal abnormalities. In patients with cancer, these findings may mimic disease progression and lead to inappropriate modification of effective anticancer therapy. Imaging findings are not specific, and histological confirmation may therefore be necessary when the differential diagnosis would alter clinical management. Management should be individualized according to clinical severity, organ involvement, diagnostic certainty, and the importance of continuing the suspected drug. Observation or continuation of therapy may be appropriate in selected asymptomatic or limited cases, whereas drug withdrawal and systemic corticosteroids may be required in symptomatic or multisystem disease. This narrative review summarizes current evidence on DISRs, with particular emphasis on pulmonary and intrathoracic manifestations, associated drug classes, diagnostic challenges, management, and outcomes. A respiratory-focused diagnostic pathway is proposed, integrating comparison with prior imaging, targeted microbiological sampling, selective bronchoscopic or other tissue biopsy, and assessment of competing diagnoses, including malignancy and immune checkpoint inhibitor pneumonitis. The pathway also supports individualized decisions on observation, drug continuation, or withdrawal; it is not a validated diagnostic instrument.

Journal of Clinical Medicine doi: 10.3390/jcm15228862

Authors: İbrahim Halil Ural Dudu Kübra Akyol Sümeyye Akçay Burcu Akkurt

Background: Respiratory dysfunction is common after stroke, but its relationship with chronic phase walking capacity and balance is unclear. We explored associations between spirometry and walking and balance performance. Methods: In this exploratory cross-sectional study, 27 outpatients with chronic ischemic stroke underwent spirometry, including peak expiratory flow (PEF); six-minute walk test (6MWT) and Berg Balance Scale (BBS) data were available for 25. We used Spearman correlations (Bonferroni α = 0.005), rank-based partial correlations, and linear regression. Results: PEF correlated with 6MWT distance (ρ = 0.568, 95% confidence interval [0.21, 0.82], p = 0.003; B = 23.92 m per L/s, R2 = 0.297). The association persisted after adjustment for age, body mass index, and time since stroke (partial r = 0.558, p = 0.007), although adjusted analyses did not meet the Bonferroni threshold. In 13 participants with high-quality spirometry, the correlation was similar in size but not significant (ρ = 0.360, p = 0.226). No other parameter correlated with 6MWT distance, and none with BBS scores. Conclusions: Higher PEF was associated with longer walking distance in this small exploratory sample, but effort-dependent measurement error and confounding by motor impairment cannot be excluded. PEF should not replace functional assessment; larger studies are needed.

Journal of Clinical Medicine doi: 10.3390/jcm15228865

Authors: Hannes Egli Angela Vidal Tanya Karrer Giovanni Ruggeri Diana Hoehn Michael D. Mueller Annette Kuhn Anna-Sophie Villiger

Background/Objectives: Pelvic organ prolapse (POP) is a common condition, affecting approximately 3–6% of women symptomatically and up to 50% when assessed objectively, with a lifetime surgical risk of about 13%. Sacrocolpopexy is widely regarded as the gold standard for surgical management of apical prolapse, and minimally invasive techniques have increasingly supplanted open surgery due to reduced perioperative morbidity. Although laparoscopic sacrocolpopexy (LSC) is effective, it is technically challenging and associated with a substantial learning curve. Robot-assisted sacrocolpopexy (RASC) provides enhanced three-dimensional visualization and instrument dexterity, albeit at increased costs. This study aimed to compare the efficacy, safety, perioperative outcomes, and costs of these two surgical approaches. Methods: We searched MEDLINE, Embase, Scopus, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to 2 June 2025, with an updated search performed on 19 October 2026, for comparative studies of LSC and RASC in women with apical pelvic organ prolapse. Randomized and comparative observational studies were eligible. The primary outcome was operative time; secondary outcomes included total costs, objective cure rate, complication rate, reoperation rate, total blood loss, length of stay, and mesh-related outcomes. Continuous outcomes were synthesized as mean differences and dichotomous outcomes as odds ratios with 95% confidence intervals using random-effects meta-analysis; heterogeneity was assessed using I2. Results: A total of 31 studies involving 15,783 patients (5417 LSC and 10,366 RASC) were included, comprising three randomized controlled trials and 28 non-randomized studies. RASC was associated with significantly longer operative time (MD 20.81 min, 95% CI 10.61–31.01; p < 0.001; I2 = 96%) and higher costs (USD 5583.05, 95% CI 1449.91–9716.2; p = 0.008; I2 = 94%). RASC was associated with a significantly lower intraoperative blood loss (MD −30.27 mL, 95% CI −44.12 to −16.42; p < 0.0001; I2 = 97%), although the clinical relevance of this difference is questionable. No statistically significant differences were observed in postoperative POP-Q point C (MD −0.05 cm, 95% CI −0.45 − 0.35; p = 0.32; I2 = 74%), objective cure rates (OR 0.97, 95% CI 0.28–3.39; p = 0.97; I2 = 69%), overall complications (OR 1.19, 95% CI 0.83–1.69; p = 0.71; I2 = 0%), or reoperation rates (OR 2.0, 95% CI 0.61–6.55; p = 0.25; I2 = 51%). Conclusions: No statistically significant differences in effectiveness or safety outcomes were identified between LSC and RASC. RASC was associated with longer operative time and higher costs, while the reduction in intraoperative blood loss, although statistically significant, is of uncertain clinical significance. Further high-quality studies with extended follow-up are needed to determine whether these differences translate into meaningful clinical benefits.

Journal of Clinical Medicine doi: 10.3390/jcm15228861

Authors: Nada H. Aldahlawi Mayar I. Almaslukh

Background/Objectives: The impact of diabetes mellitus (DM) on vision-related quality of life (VRQoL) in Saudi Arabia is rarely quantified. This study measured VRQoL in a convenience sample of adults with type 1 (T1DM) and type 2 (T2DM) diabetes in Riyadh and identified the factors associated with it. Methods: In this cross-sectional study, 300 adults with self-reported T1DM (n = 131) or T2DM (n = 169), recruited at a university hospital and by snowball sampling, completed the Arabic 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) online; the primary outcome was the standard composite score. Diabetes types were compared with Holm-adjusted tests, and multivariable linear regression was checked with fractional logistic and median regression. Results: The composite was high (median 88.0, interquartile range 73.4–96.0); 19% reported diabetic retinopathy (DR), 24% cataract and 9% had never had an eye examination. T1DM participants scored higher on 7 of 12 subscales (r ≤ 0.20), but diabetes type was not associated with VRQoL after adjustment (β = 0.5 points). Self-reported DR (β = −15.8), age ≥55 years (β = −18.6) and cataract/glaucoma (β = −7.9) were independently associated with a lower composite in every sensitivity analysis; smaller associations with irregular glucose levels, never having been examined and female sex were model-dependent. Conclusions: Lower VRQoL was associated with self-reported ocular complications and older age rather than with diabetes type. The findings rest on self-reported data from a non-probability sample; prospective studies with clinically graded retinopathy and objective glycaemic measures are needed before routine VRQoL assessment can be recommended.

Journal of Clinical Medicine doi: 10.3390/jcm15228859

Authors: Ingrid C. Landfald Karoline L. Landfald Łukasz Olewnik Artur Balasa Bartłomiej Szewczyk Marta Pośnik Andrzej Borowski

After surgery near the posterior hip or pelvic sidewall, a new foot drop, posterior thigh sensory loss or change in bladder function raises different questions about the site of injury. This critical narrative review examines how the operative exposure and the distribution of a deficit can guide investigation and how strongly the available evidence supports prevention. We selected human anatomical studies, clinical cohorts, trials, evidence syntheses and professional guidance identified through database searches and citation tracking. After posterior pelvic fixation, distal segmental weakness prompts review of the screw trajectory, whereas isolated abductor weakness draws attention to the entry site and abductor tendons. After proximal hamstring repair, a posterior thigh cutaneous deficit implicates a different nerve from weakness below the knee. In pelvic surgery, evidence for preservation of urinary function concerns autonomic pathways and cannot establish protection of the somatic plexus. Across these settings, baseline neurological status, the unit counted and the timing of outcome assessment materially change estimates of harm. A severe or progressive deficit requires urgent assessment for a treatable structural cause. For stable deficits, targeted imaging and serial electrodiagnosis can refine localization and prognosis. Few studies connect a technical precaution to a sustained improvement in neurological function.

Journal of Clinical Medicine doi: 10.3390/jcm15228858

Authors: Hasan Hüseyin Gökpınar Tansel Koyunoğlu Hilal Telli İsmail Saraçoğlu

Background: Greater trochanteric pain syndrome (GTPS) is a multifactorial and often underdiagnosed musculoskeletal disorder associated with substantial pain and disability. This study evaluated the effectiveness of ultrasound-guided dry needling (US-guided DN) on pain intensity, pressure pain threshold (PPT), and disability in patients with GTPS. Methods: This participant- and assessor-blinded, randomized, sham-controlled trial randomized 50 patients with GTPS (25 per group), of whom 46 completed the study (intervention n = 24; sham n = 22). Participants received three weekly sessions of either real or sham US-guided DN, along with a standardized home exercise program. The primary outcome was activity-related pain intensity measured using the Visual Analog Scale (VAS). Secondary outcomes included PPT assessed at four anatomical sites and functional disability assessed using the Oswestry Disability Index (ODI). Results: Pain intensity and functional disability decreased over time in both groups, without evidence of superior outcomes following active dry needling. For the primary outcome (VAS), the estimated between-group difference at the final assessment was 0.50 points (95% CI: −0.44 to 1.43; p = 0.301). No significant overall group × time interactions were observed for PPT at any of the four anatomical sites. However, exploratory baseline-adjusted analyses identified significantly higher PPT values at the final assessment in the intervention group at the gluteal region and iliotibial band after Holm correction for multiple comparisons. Conclusions: US-guided DN did not demonstrate superior short-term improvements in pain intensity or disability compared with sham needling in patients with GTPS. Exploratory findings of higher baseline-adjusted PPT values at selected anatomical sites suggest possible localized differences in mechanical pain sensitivity. However, these findings do not establish a definitive treatment-specific hypoalgesic effect, and their clinical relevance remains uncertain. Trial Registration: The study was conducted in accordance with the Declaration of Helsinki and approved by the Kutahya Health Sciences University Clinical Research Ethics Committee (Approval No. 2023-09/04). The trial was prospectively registered at ClinicalTrials.gov (NCT06241872).

Journal of Clinical Medicine doi: 10.3390/jcm15228857

Authors: Anna Karpouza Paraskevi Kirgou Vasiliki Sachtaridou Dimitrios Papagiannis Erasmia Rouka Foteini Malli Ioannis Pantazopoulos Ilias Papanikolaou Ourania S. Kotsiou

Background: Soluble urokinase plasminogen activator receptor (suPAR) reflects systemic immune activation. We examined associations between serum suPAR and pulmonary/internal-medicine admission in adults presenting to the emergency department (ED) with respiratory symptoms. Methods: This prospective single-centre exploratory pilot included 87 adults (54 pathway admissions; 33 ED discharges). Serum suPAR concentrations were determined using four-parameter logistic calibration of an eight-point ELISA standard curve, with correction for the fivefold serum dilution. Exploratory adjusted logistic regression and single-marker ROC analyses were performed. Results: Median serum suPAR was 3440.0 (2497.5–4535.0) pg/mL overall, 3955.0 (2979.0–5559.0) pg/mL among admitted patients and 2832.5 (2216.0–3317.5) pg/mL among discharged patients (p < 0.001). The apparent AUC for suPAR was 0.765 (95% bootstrap CI 0.663–0.856). After adjustment for age-category midpoint, sex, SpO2 and log-CRP, the odds ratio for admission per 1-SD increase in log-suPAR was 2.43 (95% CI 1.18–4.98; p = 0.015); the corresponding estimate for log-CRP was 1.69 (0.93–3.07; p = 0.084). Conclusions: Serum suPAR was associated with pathway-specific admission after adjustment for CRP and selected clinical covariates. These exploratory findings do not establish incremental clinical utility and require external validation.

Journal of Clinical Medicine doi: 10.3390/jcm15228856

Authors: Carmine Musto Luca Paolucci Michela Bonanni Francesco De Felice Giulia Nardi Giovanni Ferraiuoli Luigi Lucisano Matteo Pelliccia Massimo Mancone Christian di Russo Javier Escaned

Coronary physiological assessment refines lesion selection, but the randomized evidence addressing its clinical value differs according to the treatment comparison. This narrative review examines three distinct questions: (1) percutaneous coronary intervention (PCI) plus medical therapy versus medical therapy alone in selected chronic coronary settings; (2) PCI versus a placebo procedure for symptomatic stable angina; and (3) physiology-guided complete versus culprit-lesion-only PCI in acute coronary syndromes (ACS) with multivessel disease, with medical therapy provided in both arms. We reviewed pivotal randomized studies and follow-up publications through 31 October 2026 and considered contemporary trials comparing different physiological guidance methods separately. In chronic coronary settings, FAME 2 demonstrated a reduction in urgent revascularization, ORBITA-2 established a placebo-controlled angina benefit after withdrawal of background antianginal drugs, and NOTION-3 showed fewer myocardial infarctions and urgent revascularizations in patients undergoing transcatheter aortic-valve implantation, but included lesions eligible by either fractional flow reserve (FFR) or angiographic severity. In ACS, the results of trials comparing complete with culprit-only PCI vary; several composite benefits are driven by repeat revascularization, whereas FIRE also showed a reduction in cardiovascular death or myocardial infarction. These designs cannot isolate the benefit attributable to physiological selection from the benefit of treating additional lesions. Recent trials directly comparing angiography-derived physiology with alternative guidance strategies address a different question. FFR, non-hyperemic pressure indices, and angiography-derived measurements have distinct methodological and timing considerations, particularly after infarction. Overall, symptom relief, unplanned revascularization, and death or myocardial infarction should be interpreted separately; choice of revascularization strategy should integrate clinical presentation, anatomy, physiology, patient preferences, and optimized medical therapy.

Journal of Clinical Medicine doi: 10.3390/jcm15228855

Authors: Colomba Pessolano Marina Garofano Placido Bramanti Mariaconsiglia Calabrese Irene Cappadona Elisa Anna Contursi Francesco Corallo Federico Di Filippo Maria Pia Di Palo Andrea Marino Alessia Nunziante Maria Pagano Marianna Amboni Alessia Bramanti

Background: Cognitive impairment is one of the most disabling non-motor manifestations of Parkinson’s disease (PD), substantially affecting functional independence, quality of life, and caregiver burden. Technology-assisted cognitive rehabilitation, including computerized cognitive training, virtual reality-based interventions, digital rehabilitation platforms, and remotely delivered programmes, has emerged as a potential approach to support cognitive functioning in PD. However, evidence regarding its cognitive, psychological, and implementation outcomes remains fragmented. Methods: A systematic review was conducted following PRISMA 2020, with PROSPERO identifier CRD420261433368. PubMed/MEDLINE, Scopus, Web of Science and PsycINFO were searched, with the reported final search on 30 June 2026. Structured interventions using technology as an active cognitive therapeutic component were considered. Cognitive, psychological, patient-reported, caregiver and implementation findings were synthesized narratively, distinguishing comparative effects from uncontrolled changes. Two additional reports identified during targeted revision-stage checking were assessed and included. Results: Thirteen studies were included in the current synthesis, spanning randomized, pilot, non-randomized and uncontrolled designs. Controlled cognitive findings were inconsistent. Small studies provided signals in selected executive outcomes and in time-based and verbal-response prospective memory, while the largest randomized trial found no benefit on its primary planning-accuracy endpoint. Psychological, functional and quality-of-life effects were limited or inconsistent. Implementation findings were generally favorable in selected research cohorts, with technical barriers and transient VR symptoms reported. Conclusions: Current evidence does not establish generalized, sustained comparative cognitive efficacy or consistent patient-important benefit of technology-assisted cognitive rehabilitation in PD. Selected cognitive signals warrant independent replication. Delivery feasibility, adherence and usability are distinct from clinical effectiveness and safety. Future trials should distinguish cognitive phenotypes, prespecify clinically relevant outcomes and assess everyday function alongside cognitive performance.

Journal of Clinical Medicine doi: 10.3390/jcm15228854

Authors: Ignacio Mesina-Estarrón Olutola Akande Rachel Zhang Fernando Cotrim Gomes Aaron Yengo-Kahn

Background: A subset of patients with Chiari I malformation carries craniovertebral junction anomalies such that posterior fossa decompression alone is insufficient to address ventral brainstem compression or craniocervical instability, and occipitocervical fusion is warranted. How often this occurs, and whether extended fusion carries added early morbidity are not established. We compared early outcomes between occipitocervical constructs ending at C2 and extended constructs in pediatric patients undergoing posterior fossa decompression. Methods: We identified patients undergoing posterior fossa decompression (CPT 61343) in the ACS NSQIP-Pediatric participant use files from 2016 through 2024. Cases with concurrent occipitocervical fusion were classified by construct extent into three mutually exclusive strata: fusion to C2 alone (OCF-2), fusion with a single additional subaxial interspace (OCF-3), and fusion with multiple subaxial interspaces (OCF-M). Thirty-day unplanned reoperation, unplanned readmission, and secondary outcomes were compared. Results: Among 9056 sampled PFD episodes, 100 (1.10%) included concurrent OCF: 61 constructs ended at C2 (OCF-2), and 39 extended below it (OCF-3, n = 20; OCF-M, n = 19). Age, sex, comorbidities, and preoperative risk factors were similar between groups. Reoperation occurred in 5.1% of patients with extended constructs and 8.2% of those with OCF-2 (RD −3.1%; 95% CI −13.4 to 9.6), and readmission in 5.1% and 4.9%, respectively (RD 0.2%; 95% CI −9.1 to 12.4). Across OCF-2, OCF-3, and OCF-M, no outcome showed a graded association with the number of fused levels. Conclusions: In this cohort of pediatric Chiari I patients, extending fixation below C2 was not associated with a detectable difference in early morbidity. Rates from this multi-institutional study may provide reference values for family counseling and expected event rates for future study design. Studies with long-term follow-up that capture radiological features are needed to address confounding by indication and better characterize the trade-offs of construct length.

Journal of Clinical Medicine doi: 10.3390/jcm15228852

Authors: Cristina Monica Pantea Naomi-Adina Ciurea Nora Rat Ioana Bancila Sabrina Munteanu Ana-Maria Filip Tavaszi Anita Anca Negovan

Acute non-variceal upper gastrointestinal bleeding (NVUGIB) in patients receiving antithrombotic therapy requires bleeding control to be balanced against the thromboembolic consequences of treatment interruption or reversal. This narrative review summarizes recent gastroenterology, cardiology, and hemostasis guidance, including the 2026 European Society of Gastrointestinal Endoscopy (ESGE) update on peptic ulcer bleeding, the 2022 American College of Gastroenterology–Canadian Association of Gastroenterology guideline, recent European Society of Cardiology and American College of Cardiology/American Heart Association guidelines, and current evidence and regulatory positions on anticoagulant reversal. Endoscopic recommendations are presented as applying to peptic ulcer bleeding, from which they were derived; variceal bleeding is outside the scope of the review. The review addresses risk stratification, resuscitation, endoscopic hemostasis, management of antiplatelet and anticoagulant therapy during acute bleeding, reversal, and resumption of therapy, with separate consideration of atrial fibrillation, recent acute coronary syndrome or percutaneous coronary intervention, chronic coronary and peripheral arterial disease, mechanical valves, and frail older patients. Principal studies are reported with effect estimates and 95% confidence intervals where available, and guideline recommendations are distinguished from the authors’ proposed approach. Current evidence supports timely hemostasis, avoidance of unnecessary interruption, selective rather than routine reversal, and individualized resumption when the indication persists, although evidence on reversal-agent choice and restart timing is largely observational and of low certainty. Seven practical principles, representing the authors’ synthesis rather than formal recommendations, are proposed.

Journal of Clinical Medicine doi: 10.3390/jcm15228853

Authors: Meserret Aslan Sevil İnal Ece Nilüfer

Background/Objectives: Nipple pain and trauma may adversely affect breastfeeding comfort and continuation. Silver nipple cups are used as a supportive intervention, but their clinical effectiveness and safety remain uncertain. This systematic review aimed to synthesize evidence concerning nipple pain, nipple trauma, user experience, and safety. Methods: This systematic review followed PRISMA 2020. Six databases were searched through 23 June 2026. Four eligible studies were critically appraised using design-specific Joanna Briggs Institute tools. Findings were synthesized narratively, and certainty of evidence was assessed using GRADE. Results: Four studies involving 622 women were included: one pilot randomized controlled trial, one non-randomized comparative study, one prospective observational cohort study, and one analytical cross-sectional study. In the pilot randomized trial, complete pain resolution at day 7 occurred in 11/16 women (68.8%) using silver nipple cups and 3/14 women (21.4%) receiving standard care (RR 3.21, 95% CI 1.12–9.22). Fissure healing occurred in 68.8% and 50.0% of participants, respectively (RR 1.38, 95% CI 0.74–2.55). Observational findings suggested possible short-term benefits but were limited by methodological weaknesses and heterogeneity. No serious adverse events were directly attributed to silver nipple cup use; however, safety monitoring was limited. Conclusions: Current evidence is insufficient to establish the clinical effectiveness or safety of silver nipple cups. Preliminary findings suggesting short-term nipple pain relief require confirmation in adequately powered, methodologically rigorous randomized controlled trials.

Journal of Clinical Medicine doi: 10.3390/jcm15228851

Authors: Ren Yi Kow Yong Ng Jeremy Tze En Lim Darren Keng Jin Tay Hee Nee Pang Seng Jin Yeo Ming Han Lincoln Liow

Background: Robotic assistance may improve the precision of kinematic alignment total knee arthroplasty (KA-rTKA), but immediate recovery after imageless KA-rTKA remains insufficiently described. This study describes an early institutional experience with imageless robotic workflow for KA-rTKA and provides preliminary postoperative day 1 (POD1) recovery and six-month functional outcomes. Methods: This retrospective single-center study included 50 knees in 50 consecutive unique patients who underwent KA-rTKA, using the VELYS Robotic-Assisted Solution between January and June 2024. POD1 outcomes included range of motion (ROM), pain, and walking distance. Six-month outcomes included ROM, Knee Society Function Score (KSFS), Knee Society Knee Score (KSKS), Oxford Knee Score (OKS), and SF-36 Physical and Mental Component Summary scores (PCS and MCS). Minimum clinically important difference (MCID) attainment was assessed. Results: On POD1, mean ROM was 71.9° ± 21.8°, resting pain was 1.0 ± 1.4, movement-related pain was 3.8 ± 2.2, and walking distance was 19.0 ± 17.6 m. At six months, KSFS improved from 52.8 ± 20.9 to 72.1 ± 24.6, KSKS from 38.1 ± 15.4 to 83.3 ± 18.4, OKS (lower scores indicate better function) from 35.7 ± 9.0 to 20.1 ± 7.0, PCS from 31.7 ± 7.7 to 46.1 ± 10.2, and MCS from 51.4 ± 11.8 to 58.5 ± 9.6 (all p < 0.001). MCID achievement was high across knee-specific outcomes, at 94%, 80%, and 90% for KSKS, KSFS, and OKS respectively. Conclusions: Imageless KA-rTKA was associated with favorable immediate postoperative recovery and clinically meaningful six-month improvements in this single-arm series. Larger comparative studies with longer follow-up are required to determine whether these early improvements translate into superior long-term outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15228849

Authors: Jessica Nicolas Imad Uthman Jad Nicolas Piercarlo Sarzi Puttini Anthony Nicolas Y Van Tran Phong Van Pham Giacomo Farì Marco Antonio Narvaez Tamayo Matteo Luigi Giuseppe Leoni Giustino Varrassi

Background/Objectives: Fibromyalgia is a chronic, symptom-defined condition whose recognition and management depend on sustained access to care. Recorded utilization during crises may therefore reflect disrupted access, diagnostic recognition, and longitudinal engagement rather than disease burden. Since 2019, Lebanon has experienced overlapping financial deterioration, the COVID-19 pandemic, the Beirut port explosion, and armed conflict. We characterized recorded fibromyalgia utilization and continuity across these six years. Methods: This retrospective cohort study analyzed all outpatient encounters with fibromyalgia as the primary diagnosis in electronic health records of the American University of Beirut Medical Center, January 2019–December 2024. Monthly encounter volume was the primary utilization outcome. Recorded continuity was evaluated as time from each patient’s index encounter to a subsequent fibromyalgia-coded encounter, with 180-day return as the principal standardized comparison across cohorts. Results: We identified 4969 encounters from 3237 patients (87.5% female; mean age, 46.7 years). Monthly encounter volume fell around the 2019 financial and banking disruption and remained below the preceding nine-month level (84.3 vs. 66.8 encounters/month; rate ratio, 0.76; 95% CI, 0.61–0.94), with a further exploratory reduction in mid-2024. The 180-day probability of a subsequent encounter declined from 22.8% in the 2019 cohort to 15.6% in 2024 (hazard ratio, 0.59; 95% CI, 0.45–0.76); lower return rates emerged from the 2022 cohort onward. Conclusions: Recorded fibromyalgia utilization and recorded return for subsequent fibromyalgia-coded care within the same institution changed at different times during Lebanon’s compounding crises. These findings describe recorded care, not disease occurrence: recovering patient numbers may coexist with persistently lower recorded return within the institution, so aggregate utilization alone may incompletely describe recovery for continuity-dependent chronic conditions.

Journal of Clinical Medicine doi: 10.3390/jcm15228850

Authors: Andrea C. Vazquez-Loreto Sanjana Molleti Hanna Pawlowski Calisa G. Lee-Choi Cole S. Elsner Mina M. Sitto Gabriel N. Medina Niki C. Feiz Phillip C. Hoopes Majid Moshirfar

Background: The purpose of this study is to assess the ability of generative AI and a refractive surgeon to distinguish post-LASIK Scheimpflug tomography images based on original excimer laser ablation and to recognize untreated corneas. Methods: Corneal tomography Pentacam images from 204 eyes, which included hyperopic ablations, myopic ablations, myopic astigmatic ablations, mixed astigmatic ablations, or untreated eyes, were compiled. These were individually queried in ChatGPT-5.5 using a multiple-choice prompt to obtain a response. A refractive surgeon was also tested on the same 204 corneas. Results: The clinician obtained higher overall accuracy (85.8% [95% CI 80.2–90.3]) compared to ChatGPT, (60.3% [95% CI 53.2–67.1], p < 0.001) and was significantly more likely to answer correctly overall based on McNemar’s test. Additionally, ChatGPT underperformed in the myopia with astigmatism, mixed astigmatism, and untreated categories, with sensitivities of 38%, 6.3%, and 76%, respectively. Conclusions: The overall accuracy of ChatGPT-5.5 did not meet that of the clinician while ability to identify myopic and hyperopic ablation patterns was comparable. Both the AI model and the clinician had decreased accuracy in myopic astigmatism and mixed astigmatism ablation patterns, though the clinician still performed significantly better. Further studies involving alternative AI models, multicenter data, and standardized evaluation protocols are warranted to establish the clinical applicability of these findings.

Journal of Clinical Medicine doi: 10.3390/jcm15228847

Authors: Natalia Tomala Pola Wideł Dominik Rosik Jakub Szczepaniak Maciej Garbarz Aleksandra Królikowska Daria Kluba Oliwier Pioterek Mateusz Drążyk Zygmunt Domagała

Background: The oculomotor nerve (CN III) traverses several anatomically complex regions, including the interpeduncular cistern, cavernous sinus, superior orbital fissure, and orbit, where its relationships with adjacent neurovascular structures are of considerable clinical relevance. Although numerous anatomical studies have described individual segments of CN III, the available evidence remains fragmented. This systematic review aimed to synthesize the published literature on the origin, course, branching pattern, morphometry, and anatomical variations of the oculomotor nerve, with emphasis on clinically relevant relationships. Methods: A systematic search of PubMed, Embase, Web of Science, and Google Scholar was performed for original human studies on oculomotor nerve anatomy published up to September 2025. Two reviewers independently screened records. Eligible studies were assessed using the AQUA tool. Extracted data included nerve segment, course, branching, morphometry, anatomical relationships, and reported variations. Owing to methodological heterogeneity, the findings were synthesized qualitatively. Results: Thirty-five original studies were included in the systematic review. They used heterogeneous units of analysis, including living participants, cadavers, heads, brains, orbits, nerves, and histological specimens; therefore, aggregate sample size was not calculated. Cadaveric dissection and MRI were the most common methods of CN III presentation. The orbital segment was the best-described portion of the nerve and demonstrated the greatest branching variability, particularly within the superior and inferior divisions. The cisternal segment showed clinically important relationships with the posterior cerebral, superior cerebellar, and posterior communicating arteries, supporting the anatomical basis of neurovascular compression and oculomotor palsy. Morphometric comparisons across studies were limited by differences in methods, landmarks, and tissue preparation. Conclusions: The oculomotor nerve demonstrates segment-specific anatomical variability, with the greatest complexity in its orbital branching pattern and important neurovascular relationships along its cisternal and cavernous course. This knowledge may be of value to microsurgical, orbital, and neuroradiological practice. The evidence remains limited by methodological heterogeneity, underreporting of sex- and population-based differences, and the small number of studies addressing the intramesencephalic segment.

Journal of Clinical Medicine doi: 10.3390/jcm15228848

Authors: Shaikh B. Iqbal Sneha E. Thomas Gaurav M. Parmar

Descending thoracic aortic mural thrombi are uncommon in normal or minimally diseased aortas. Mural thrombi are commonly associated with underlying aortic pathologies such as aneurysm, dissection, aortitis, or advanced atherosclerosis. They can occasionally be idiopathic, associated with endothelial disorders, or associated with hypercoagulable states. Aortic thrombus carries risk of peripheral embolization. Evidence guiding management of descending thoracic aortic thrombus is limited. Medical management is dependent on thrombus morphology, embolic events, and bleeding risk. Ultimately, endovascular or surgical removal may be considered in recurrent embolic events.

Journal of Clinical Medicine doi: 10.3390/jcm15228846

Authors: Mariusz Stanisław Sowa Joanna Sowa Maciej Budzanowski

Background: This study aims to establish local diagnostic reference levels (DRLs) for mechanical thrombectomy performed using a low-dose imaging protocol and to assess objective image quality parameters under routine clinical conditions. Methods: This retrospective, single-center observational study included 59 consecutive patients who underwent mechanical thrombectomy for acute ischemic stroke between January 2023 and March 2026, with no exclusions. Radiation metrics, including dose-area product (DAP), reference air kerma (Ka,r), fluoroscopy time (FT), and number of images, were extracted from system-generated dose reports. Local DRLs were defined as the 75th percentile (P75) of the dose distribution. Objective image quality was assessed using quantitative parameters such as background noise, signal-to-noise ratio (SNR), absolute contrast-to-noise ratio (CNR), CNR/DAP, CNR/Ka,r, and figure-of-merit (FOM = CNR2/DAP). Results: In the overall cohort, the median and P75 values were 16.6/26.2 Gy·cm2 for DAP, 206/306 mGy for Ka,r, and 1217/1622 s for FT. The median number of images per procedure was 210, with a P75 of 285. Procedures utilizing combined biplane imaging demonstrated higher DAP and Ka,r values compared to those using single-plane imaging, while FT did not differ significantly. Objective image-quality analysis was feasible in all 59 procedures. The median background noise, SNR, and absolute CNR were 44.24, 34.47, and 26.99, respectively. Median dose-normalized values were 1.32 for CNR/DAP, 0.12 for CNR/Ka,r, and 33.21 for FOM. No procedure required escalation of the imaging protocol due to insufficient angiographic visualization. Conclusions: Mechanical thrombectomy performed under a predefined low-dose protocol yielded low absolute local dose values in this single-center cohort. ROI-based image-quality parameters remained measurable. Because no standard-dose comparator was imaged, the magnitude of dose reduction and the preservation of image quality relative to conventional settings could not be quantified.

Journal of Clinical Medicine doi: 10.3390/jcm15228845

Authors: Seulah Han Jin-Young Min

Objectives: Recent studies suggest that Staphylococcus aureus and its enterotoxins (SEs) contribute to the pathophysiology of chronic rhinosinusitis (CRS). This study investigated the clinical significance of SE-specific IgE sensitization in olfactory dysfunction in patients with CRS. Methods: Seventy-five adult patients with CRS treated between July 2020 and December 2021 were enrolled. Serum SE-specific IgE levels against SEA, SEB, and TSST-1 were measured using the ImmunoCAP assay. SE sensitization was defined as a level ≥0.1 kU/L for at least one SE. Olfactory function was assessed using the Korean Version of the Sniffin’ Sticks test II (KVSS II). Total KVSS II and threshold, discrimination, and identification scores were compared between SE-specific IgE-positive and -negative groups. Correlations between individual SE-specific IgE levels and KVSS II scores were also analyzed. The primary comparison was the total KVSS II score; all other analyses were exploratory. Results: Among the 75 patients, 29 (38.7%) were sensitized to at least one SE. Compared with SE-specific IgE-negative patients, SE-specific IgE-positive patients showed a lower total KVSS II score, although the difference did not reach statistical significance (31.7 ± 10.6 vs. 26.2 ± 13.2, p = 0.09). SE-specific IgE positivity was associated with significantly poorer olfactory threshold performance (p = 0.01). Olfactory threshold scores were also significantly correlated with serum levels of SEA (r = −0.28, p = 0.02), SEB (r = −0.34, p < 0.01), and TSST-1 (r = −0.38, p < 0.01). In exploratory multivariable analysis, higher serum TSST-1-specific IgE levels showed a nominal association with lower olfactory threshold scores (B = −1.86; 95% CI, −3.60 to −0.13; p = 0.04), which did not remain statistically significant after Holm adjustment (adjusted p = 0.12). Conclusions: In this exploratory study, SE-specific IgE sensitization was associated with poorer olfactory threshold performance, whereas the primary comparison of the total olfactory score was not statistically significant. TSST-1-specific IgE showed a preliminary association that requires confirmation in larger prospective studies.

Journal of Clinical Medicine doi: 10.3390/jcm15228844

Authors: Jian Li Lichun Zhou

Background: Higher serum bilirubin has been associated with lower left ventricular mass in hypertension, but whether the relation is nonlinear and whether reported thresholds are reproducible remain unresolved. Methods: We performed a secondary cross-sectional analysis of a publicly archived cohort of 339 untreated hypertensive patients; 327 had complete data. Left ventricular mass index (LVMI) was the primary outcome and left ventricular hypertrophy (LVH) the secondary outcome. We used multivariable regression and restricted cubic splines, and assessed change-point precision by profile likelihood and bootstrap resampling. Results: Each 1 μmol/L higher total bilirubin was associated with a 1.20 g/m2 lower LVMI (95% CI, −1.73 to −0.67; p < 0.001), and the association was nonlinear (p < 0.001), with a steeper slope below the median (p for interaction <0.001). The change point was imprecisely estimated (maximum likelihood 12.5 μmol/L; profile-likelihood interval 10.4–13.1), and the association was confined to participants at or above the median fasting glucose (q = 0.004). Adding bilirubin increased the optimism-corrected C-statistic by 0.056. Conclusions: Thresholds should be interpreted as descriptions of curve shape rather than reproducible cut points, and the present evidence does not support using bilirubin for risk stratification.

Journal of Clinical Medicine doi: 10.3390/jcm15228843

Authors: Carmen Imma Aquino Sakthipriyan Venkatesan Mohammad Mostafa Ola Pour Arianna Ligori Agnese Immacolata Volpicelli Daniela Ferrante Renzo Boldorini Raffaele Tinelli Maurizio Guida Valentino Remorgida Elena Grossini Daniela Surico

Background/Objectives: One of the most prevalent gynecological diseases in developed nations is endometrial cancer (EC), whose incidence is steadily rising. Osteopontin (OPN) is a crucial extracellular matrix molecule linked to tumors. Our main goal was to investigate the potential relationship between OPN and EC, by comparing its levels in blood and endometrial tissue in 40 patients with malignant versus 40 with benign uterine disorders. Our secondary aim was to analyze OPN (in blood and endometrial tissue) and the levels of some related molecules (Cyclin-Dependent Kinase Inhibitor 3-CDKN3 and Integrin αvβ3, in endometrial tissue), also considering established serum tumor markers. Methods: Patients undergoing hysterectomy for EC (cases) or for benign diseases (controls) at the Department of Obstetrics and Gynecology of the AOU Maggiore della Carità, Novara (Italy), were recruited for this single-center prospective observational study. Results: The mean amount of OPN in blood and endometrium was significantly higher in cases than in controls (p < 0.0001). Integrin αvβ3 and CDKN3 were significantly higher in cases (p < 0.0001); no significant connections were found considering OPN, Integrin αvβ3, CDKN3 and weight, body mass index, age, thyroid-stimulating hormone (TSH), glycated hemoglobin, specific cancer staging/grading and molecular classification. Conclusions: These preliminary findings require validation in future prospective, independent cohorts. The levels of OPN, Integrin αvβ3, and CDKN3 were significantly elevated in cases compared to controls. No major confounding has been identified in preliminary evaluations, supporting their potential utility in a future diagnostic panel, though these findings require verification in larger cohorts.

Journal of Clinical Medicine doi: 10.3390/jcm15228842

Authors: Fatih Kurt Süheyla Karadağ Erkoç Güngör Enver Özgencil Özlem Doğan Hanzade Aybüke Ünal Özer Volkan Baytaş

Background/Objectives: To compare perioperative cytokine profiles, four-month chronic pain, acute analgesia, and recovery among women receiving intrathecal morphine (ITM) or erector spinae plane block (ESPB) after elective caesarean delivery. Methods: In this prospective observational cohort, 88 women received ITM (50 μg; n = 44) or bilateral ESPB (0.25% bupivacaine, 20 mL/side; n = 44) as part of routine care. Serum IL-6, TNF-α, and IL-10 were measured at baseline, 6 h, and 24 h. Results: Clinically relevant acute pain occurred in 13/44 (29.5%) ITM versus 25/44 (56.8%) ESPB participants (unadjusted risk difference, −27.3 percentage points; 95% CI −44.9 to −6.6). No rescue analgesia was required by 21/44 (47.7%) versus 4/44 (9.1%) (risk difference, 38.6 percentage points; 95% CI 20.2 to 54.0). Mean ObsQoR-11 scores were 95.05 ± 7.49 versus 91.52 ± 6.91 (mean difference, 3.53 points; 95% CI 0.48 to 6.58). Baseline IL-6 and IL-10 concentrations differed; an exploratory baseline-adjusted analysis showed an IL-10 group-by-time interaction after Holm correction. Chronic pain occurred in 3/44 (6.8%) versus 6/44 (13.6%) (risk difference, −6.8 percentage points; 95% CI −20.6 to 6.7). Conclusions: ITM receipt was associated with lower early pain burden and fewer rescue analgesic requirements, but treatment selection was non-randomised and associated with clinician identity. Cytokine findings are exploratory; chronic pain comparisons remain inconclusive.

Journal of Clinical Medicine doi: 10.3390/jcm15228841

Authors: Vincenzo Paragliola Federico Moretti Andrea Moretti Gianluca Massaro Giuseppe Massimo Sangiorgi

Coronary imaging technologies have become cornerstones of contemporary percutaneous coronary intervention (PCI), providing anatomical and physiological information that complements angiography and supports lesion assessment, procedural planning, device selection, procedural optimization and long-term risk stratification. This comprehensive review focuses on intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), optical coherence tomography (OCT), fractional flow reserve computed tomography (FFR-CT), and the Murray law-based quantitative flow ratio (μFR), examining their current applications in modern PCI and providing a practical overview of their respective roles. These technologies are compared in terms of their technical characteristics, advantages and limitations in lesion assessment and PCI optimization. Evidence from recent major clinical trials and contemporary studies is critically reviewed alongside current guideline recommendations. The integration of anatomical, morphological and physiological information represents a key component of modern PCI, facilitating optimal device selection and procedural optimization while supporting individualized treatment strategies, particularly in patients with complex coronary artery disease (CAD).

Journal of Clinical Medicine doi: 10.3390/jcm15228840

Authors: Núria Llorach-Perucho Noelia Pérez-Romero Alexis Luna-Aufroy Sandra Montmany-Vioque Montse Adell-Trapé Ariadna Cidoncha-Secilla Christian J. Herrero-Vicente Andrea Torrecilla-Portolés Laura Mora-López

Background/Objectives: Sliding and paraesophageal/mixed hiatal hernias differ anatomically and clinically, although surgical outcomes are frequently analyzed together. This study compared postoperative functional outcomes and proton pump inhibitor (PPI) requirements according to hernia type and explored recurrence patterns as secondary outcomes. Methods: We retrospectively analyzed a prospectively maintained database of consecutive patients undergoing hiatal hernia repair at a tertiary referral center between May 2014 and September 2023. Patients were classified as sliding (type I) or paraesophageal/mixed hernias. Symptoms were assessed using an 11-item Likert questionnaire. Functional changes were evaluated using paired analyses in patients with available preoperative and postoperative assessments. Recurrence-free survival was estimated using Kaplan–Meier analysis, with exploratory Cox regression for symptomatic recurrence. Results: Seventy-seven patients were included (37 sliding; 40 paraesophageal/mixed). Sliding hernias showed a predominantly reflux-related phenotype, whereas paraesophageal/mixed hernias were characterized by more obstructive symptoms and dysphagia. Paired analyses confirmed significant improvement in reflux-related symptoms after sliding hernia repair and in obstructive symptoms and dysphagia after paraesophageal/mixed hernia repair. PPI requirements decreased significantly in both groups. Symptomatic recurrence occurred in 12 patients (15.6%) and was more frequent after paraesophageal/mixed repair (log-rank p = 0.011). In an exploratory Cox model stratified by sex and adjusted for age and American Society of Anesthesiologists (ASA) classification, paraesophageal/mixed hernia was associated with a higher hazard of symptomatic recurrence (HR 4.87, 95% CI 1.00–23.74; p = 0.050), although estimates were imprecise. Radiologically documented anatomical recurrence occurred in 15 patients (19.5%) and differed between groups over time (log-rank p < 0.001); postoperative imaging was symptom-driven and therefore did not represent systematic anatomical surveillance. Revisional surgery was required in 6.5% of patients. Conclusions: Sliding and paraesophageal/mixed hiatal hernias showed distinct clinical, surgical, and functional phenotypes. Exploratory analyses also suggested different recurrence patterns, although these findings require cautious interpretation because of the limited number of events, residual confounding, and non-systematic postoperative imaging.

Journal of Clinical Medicine doi: 10.3390/jcm15228839

Authors: Fanny Mikula Eva Karner Stephanie Springer Mina Kreter Sophie Gruber Alex Farr Greta Lisa Carlin Ricarda Heemann Florian Heinzl Veronica Falcone

Background/Objectives: Cesarean delivery, while potentially life-saving, is associated with significant short- and long-term risks. Particularly in nulliparous, singleton, cephalic pregnancies at term, unnecessary Cesarean delivery should be avoided, to prevent—among others—complications in potential subsequent pregnancies. This study aimed to identify the most common indications for Cesarean delivery in women classified as group 1 or 2 of the Robson-Ten Group Classification System and to develop a protocol for safely reducing Cesarean delivery rates in this population. Methods: We conducted a retrospective data analysis of all deliveries in Robson group 1 or 2 at the Medical University of Vienna in 2023. Based on these data, we performed a literature review to develop a narrative protocol addressing the most frequent indications for Cesarean delivery according to the selected evidence. Results: We included 890 women, 558 of whom delivered vaginally (62.7%), whereas 332 underwent Cesarean delivery (37.3%). The most frequent indications for Cesarean delivery were pathological fetal tracings, prolonged labor or labor arrest, maternal primary disease and unsuccessful induction of labor. Higher maternal age (p < 0.01) and underlying disease like hypertensive (p = 0.04) or glycemic (p = 0.01) disorders were associated with an increased risk for Cesarean delivery. Conclusions: We identified the most common indications for Cesarean delivery among women in Robson group 1 and 2 and generated a proposed framework to achieve a safe reduction in Cesarean delivery rates, based on this study’s findings and selected current evidence. Safety and effectiveness of this protocol need to be validated in prospective studies.

Journal of Clinical Medicine doi: 10.3390/jcm15228838

Authors: Onur Karakayalı Merve Akın Özdemir Ali Cankut Tatlıparmak Sarper Yılmaz

Background/Objectives: We compared eight prehospital trauma scores for discriminating recorded secondary interhospital transfer in multiply injured patients, identified factors associated with transfer, and compared a random forest with logistic regression. Methods: Retrospective cohort of Kocaeli emergency medical services records (January 2024–June 2025). Scores were evaluated with receiver operating characteristic analysis; logistic regression was adjusted for the initial receiving facility. Models were trained on a patient-level 70% sample and evaluated on the remaining 30% and by repeated grouped cross-validation. Results: Of 1194 patients, 561 (47.0%) underwent secondary transfer. The Circulation, Respiration, Abdomen, Motor, Speech (CRAMS) score had the highest discrimination (area under the curve [AUC] 0.676; 95% confidence interval [CI] 0.647–0.705). Pediatric (odds ratio [OR] 4.46; 95% CI 2.82–7.07) and elderly age (OR 2.44; 1.71–3.48) and thoracic injury (OR 1.68; 1.23–2.29) were independently associated with transfer. In the held-out set (n = 356), the random forest AUC was 0.836 (0.795–0.878) versus 0.765 for logistic regression with the same predictors (p < 0.001); its calibration slope was 1.34, indicating that predicted probabilities were compressed toward the average risk. Conclusions: Individual scores showed limited discrimination for this system-level outcome. The random forest discriminated better than regression with the same information but requires recalibration and external validation before clinical use.

Journal of Clinical Medicine doi: 10.3390/jcm15228837

Authors: Ewelina Kazimierczyk Remigiusz Kazimierczyk Mariola Kucharewicz Małgorzata Knapp Karol Kamiński Anna Lisowska

Background: Treatment of gastrointestinal cancers usually requires a combination of different chemotherapeutic drugs, predominantly fluoropyrimidines, which may result in cardiotoxicity. The main aim of the study was to assess the impact of chemotherapy on left ventricular function assessed in echocardiography. Methods: The single-center study included 63 patients [mean age of 66.4 (9.9) years, male (52.4%)], diagnosed with gastrointestinal cancer (colorectal cancer: n = 51, 81%). The most common chemotherapy regimen was FOLFOX 4 (oxaliplatin, 5-fluorouracil, levofolinic acid). Patients underwent echocardiography before the first cycle of chemotherapy and after a follow-up period of 6 months. In addition to standard echocardiographic parameters, left ventricular ejection fraction (LVEF) was measured using the 3D method and myocardial strain analysis was performed using the speckle-tracking technique (global longitudinal strain—GLS). Results: The mean LVEF of the study group was 58.9 (5.7)% and mean GLS was −17.2 (3.6)%. After the follow-up period, no statistically significant changes in LVEF, GLS, or diastolic function parameters were observed, irrespective of cancer type and chemotherapeutic drug. During follow-up, seven patients (11.1%) died due to the progression of cancer. Symptoms of possible fluoropyrimidine-induced cardiotoxicity (FIC) were observed in five cases, with cardiac arrhythmias being the most frequent manifestation (premature ventricular complexes, atrial fibrillation, and atrioventricular blocks). Conclusions: In this single-center study we showed that fluoropyrimidine-based chemotherapy was not associated with significant short-term deterioration in serial echocardiographic indices of LV systolic or diastolic function. However, clinically relevant cardiovascular events still occurred, underscoring that preserved LVEF and GLS do not exclude fluoropyrimidine-associated cardiovascular toxicity.

Journal of Clinical Medicine doi: 10.3390/jcm15228835

Authors: Daniel Muñoz-Barba Sofía Haselgruber de Francisco María Rosa Cantudo-Cuenca Manuel Sánchez-Díaz Salvador Arias-Santiago

Background/Objectives: Real-world data on the effectiveness, safety, and utilization of topical ruxolitinib in non-segmental vitiligo (NSV) remain limited. The aim of this study was to evaluate the clinical outcomes and safety of ruxolitinib cream in patients with NSV, characterize real-world treatment utilization based on pharmacy dispensing data, and explore its association with disease severity and clinical improvement. Methods: This retrospective observational study included patients with NSV treated with ruxolitinib cream for at least 24 weeks. Disease severity was assessed at baseline and after 12 and 24 weeks using total and facial body surface area (T-BSA and F-BSA) and Vitiligo Area Scoring Index (T-VASI and F-VASI). Treatment utilization was estimated from monthly pharmacy dispensing data. Results: Forty-one patients were included. Mean age was 48.3 years and 65.9% of patients were female. The mean amount of ruxolitinib cream dispensed was 151 ± 134 g/month. Significant reductions were observed in F-BSA and F-VASI (both p < 0.001), T-BSA (p = 0.02), and T-VASI (p < 0.001). No statistically significant association was detected between monthly dispensed quantity and baseline disease severity or clinical improvement at 12 or 24 weeks (all p > 0.50). Adverse events were mild and predominantly local. Conclusions: Ruxolitinib cream was associated with significant clinical improvement in real-world NSV, particularly in facial involvement. No statistically significant association was detected between dispensed quantity and clinical improvement.