Journal of Clinical Medicine doi: 10.3390/jcm15218645

Authors: Farzad Salehpour Francisco Gonzalez-Lima

Background: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder that can persist across the lifespan and is associated with substantial clinical, economic, and psychosocial burden. This narrative review examines the clinical and economic burdens of ADHD on individuals and families, encompassing direct medical costs, including assessment and treatment expenditures, alongside non-medical costs, educational and occupational disruption, caregiving demands, and adverse mental health outcomes among family members. It synthesizes evidence across developmental stages and geographic regions and considers the clinical implications of these interconnected burdens. Methods: A structured search of PubMed, Scopus, Web of Science, and Embase, supplemented by reference-list screening, identified English-language publications from January 2000 through June 2026. Evidence was synthesized narratively across direct medical, non-medical, and family-related burdens, prioritizing large population-based and administrative claims studies, longitudinal investigations, systematic reviews, and meta-analyses. Interpretation considered study design, confounding factors, economic perspectives, and differences in cost estimation. Results: ADHD is associated with substantial healthcare, non-medical, and family-related economic costs. Reported costs encompass diagnostic assessment, treatment, comorbidity, and adverse events, alongside educational support, occupational losses, accidents, and criminal justice involvement. Families experience reduced occupational productivity, elevated caregiving demands, greater healthcare utilization, and increased depression, anxiety, and stress. Conclusions: Clinically, these findings support assessing functional and family-level burden alongside symptoms, identifying and managing comorbidities, maintaining treatment during transitions to adult services, and monitoring tolerability. Integrating these burden domains into routine assessment and treatment planning may help identify modifiable drivers of impairment and guide more comprehensive care across the lifespan for patients and their families.

Journal of Clinical Medicine doi: 10.3390/jcm15218640

Authors: Carlo Biz Assunta Pozzuoli Giacomo Maso Elisa Belluzzi Pietro Ruggieri

Background/Objectives: Cemented femoral stems are a well-established treatment option for femoral neck fractures (FNFs) in elderly patients. This study evaluated mid-term clinical and radiographic outcomes and safety profile in patients undergoing hemiarthroplasty with the CL TRAUMA cemented femoral stem (LimaCorporate) for FNF. Methods: The single-center observational Post-Market Clinical Investigation identified 474 patients who underwent hip arthroplasty between 2017 and 2023. Of these, 54 (11.4%) who were alive, contactable, willing, and physically able to attend were included in the mid-term follow-up (FU) assessment. Perioperative, discharge, and 1-month FU data were collected retrospectively, while mid-term clinical and radiographic FU was performed prospectively after a minimum of 2 years. The primary endpoint was satisfactory status, defined as a Harris Hip Score (HHS) ≥ 80. Secondary endpoints included patient satisfaction assessed using Visual Analogue Scale (VAS), radiographic outcomes, and documented serious adverse events (SAEs). Results: The 54 evaluated patients (54/474; 11.4% of the implanted population) included 49 females and 5 males, with a mean age at surgery of 77.1 ± 9.1 years and a mean FU of 4.4 ± 0.8 years. All patients underwent hemiarthroplasty for FNF. Mean HHS was 80.6 ± 16.9, with 33 patients (61.1%) achieving the primary endpoint. Mean VAS satisfaction was 76.4 ± 29.3. At mid-term FU, RLLs were observed in 38.9% of patients, predominantly of limited thickness. Distal stem migration was observed in one case (1.9%), and bone remodeling in three patients (5.6%). Eleven SAEs occurred in 10 patients (18.5%); three events were related and two possibly related to the surgical procedure, whereas none was considered related to the device. No femoral stem revisions were documented among the 54 evaluated patients during the available FU. Conclusions: Among the selected patients who survived and completed mid-term follow-up after bipolar hemiarthroplasty with the CL TRAUMA cemented femoral stem, satisfactory functional status and patient satisfaction were observed, together with generally stable stem-specific radiographic findings. No SAEs were considered related to the femoral stem, and no femoral stem revisions were documented. These findings should be interpreted cautiously and cannot be extrapolated to the entire implanted population.

Journal of Clinical Medicine doi: 10.3390/jcm15218641

Authors: Nagihan Kolkıran Atike Pınar Erdoğan Mustafa Şahbazlar Gözde Mütevelizade Ferhat Ekinci

Background/Objectives: Despite the established benefits of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, survival outcomes remain heterogeneous among patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer. We developed the Metabolic–Muscle Reserve Index (MMRI), integrating tumor metabolic activity, biochemical status, and skeletal muscle quantity, and investigated its relationship with progression-free survival (PFS) and overall survival (OS). Methods: We conducted a retrospective study involving 168 patients with HR+/HER2− metastatic breast cancer who were treated with CDK4/6 inhibitors. MMRI incorporated baseline PET/CT-derived maximum standardized uptake value (SUVmax), serum lactate dehydrogenase (LDH), albumin, and CT-derived psoas volume index (PVI). Receiver operating characteristic (ROC) analysis identified an exploratory MMRI cut-off. We examined survival using Kaplan–Meier analysis and Cox regression. Results: ROC analysis identified an MMRI cut-off of 10.68 for mortality discrimination, with an AUC of 0.642 (95% CI: 0.563–0.716). Patients with MMRI > 10.68 had shorter median PFS (14.1 vs. 28.1 months; p < 0.001) and OS (29.7 months vs. not reached; p < 0.001) than those with MMRI ≤ 10.68. In multivariable Cox analysis, higher MMRI was associated with shorter PFS (HR: 1.857, 95% CI: 1.329–2.596; p = 0.0003) and OS (HR: 1.974, 95% CI: 1.368–2.846; p = 0.0003). Conclusions: Patients with higher MMRI values experienced shorter PFS and OS during CDK4/6 inhibitor treatment for HR+/HER2− metastatic breast cancer. Given its modest discriminative performance, these findings remain exploratory and require prospective external validation before clinical application.

Journal of Clinical Medicine doi: 10.3390/jcm15218643

Authors: Karolina Kędzierska-Kapuza Judyta Samul-Jastrzębska Monika Cygler Magdalena Jerzak Edward Franek

Background: Lipedema is a chronic adipose tissue disorder characterized by disproportionate lower-limb fat accumulation, pain, and resistance to conventional weight-loss strategies. Tirzepatide produces substantial weight loss, but evidence in lipedema is limited. Methods: This single-center ambispective pilot case series described a 22–25-week routine clinical course in 2025. During the first 8–9 weeks, all participants received only a low-carbohydrate Mediterranean diet and recommendations for aerobic and resistance exercise; no participant received tirzepatide during this phase. After completion of the 8–9-week non-pharmacological phase, four participants started tirzepatide (2.5–7.5 mg once weekly) and continued it for the remaining 14–16 weeks, whereas one participant declined pharmacotherapy. After approval by the Bioethics Committee (Resolution No. 12/2026, 4 February 2026), the 2025 data were analyzed retrospectively; participants gave verbal consent to further follow-up in March–April 2026 and were followed up prospectively, and all signed written consent for publication of their data and photographs in October 2026. Anthropometric, ultrasound, biochemical, pain, and quality-of-life outcomes were summarized descriptively for each case. Where available, changes are reported separately for the diet-and-exercise phase (T1–T2) and the tirzepatide phase (T2–T3). Results: Weight loss among the five completers ranged from 7.7 to 17.1 kg. Body fat percentage decreased in four of five participants, whereas skeletal muscle mass decreased numerically in all four tirzepatide-treated participants. Lower-limb circumferences and subcutaneous adipose tissue thickness generally decreased, although the magnitude and distribution of changes differed between participants. Fasting glucose and HOMA-IR decreased in most cases, whereas lipid changes were mixed. Patient-reported SF-36 scores (assessed only at T2 and T3) generally improved among the four participants receiving tirzepatide, particularly for bodily pain, while pressure pain threshold responses (T2 to T3) were heterogeneous. No adverse events, gastrointestinal symptoms, dose reductions, treatment interruptions, discontinuations, or serious adverse events were reported by the four tirzepatide-treated participants; the study was not designed to assess safety. Conclusions: This ambispective pilot case series provides preliminary, hypothesis-generating observations on a multimodal intervention that included tirzepatide in four of five women with lipedema and excess body weight. The observed changes cannot be attributed to tirzepatide or interpreted as a lipedema-specific effect because all participants received concurrent dietary, exercise, and supplementation interventions, and the participant who declined pharmacotherapy was not a comparator or control.

Journal of Clinical Medicine doi: 10.3390/jcm15218644

Authors: Nurullah Duger Burak Dagtekin Furkan Talo Melek Atille Aydin Mucahit Karaduman Muhammed Yildirim Tuba Talo Yildirim Tolga Fikret Tozum

Background/Objectives: Early diagnosis of periodontal disease is critical to prevent tissue destruction and tooth loss. This study evaluates six modern deep learning architectures for four-class radiographic periodontal bone loss grading on panoramic radiographs. Methods: This retrospective study analyzed 1053 images. Two periodontologists independently classified each image according to the most severely affected tooth into four bone loss categories: Healthy, Mild (<25%), Moderate (25–50%), and Severe (>50%). Six convolutional, transformer, and hybrid backbones (ConvNeXt-Tiny, MaxViT-Tiny, EfficientViT-B1, FocalNet-Tiny, CAFormer-S18, and DaViT-Tiny) were trained on a 70/10/20 stratified split using an NVIDIA Tesla T4 GPU, the AdamW optimizer, Cosine Annealing, and early stopping. Performance was assessed using standard classification metrics, Matthews Correlation Coefficient, Cohen’s and Quadratic Weighted Kappa, Expected Calibration Error, Area Under the Curve (AUC), McNemar’s test, and bootstrap 95% confidence intervals. Results: FocalNet-Tiny achieved the highest numerical scores among the tested models, reaching 83.41% accuracy, 84.70% balanced accuracy, 83.50% macro-F1, and 0.9610 OvR AUC. The p-values obtained from the comparisons of the models were all above 0.05, indicating that the classification performances of the evaluated models are quite similar. Bootstrap analysis confirmed stable prediction metrics for the top-scoring model. Conclusions: This study provides a controlled benchmark of modern deep learning backbones for four-class radiographic periodontal bone loss grading. FocalNet-Tiny achieved the highest numerical metrics and stable bootstrap estimates, yet performed comparably to other contemporary architectures such as ConvNeXt-Tiny. Direct radiographic classification shows promise for automated radiographic pre-screening; however, multi-center external validation and integration with clinical periodontal parameters are required before clinical implementation.

Journal of Clinical Medicine doi: 10.3390/jcm15218642

Authors: Yahya A. Alzahrani Maan H. Harbi

Background/Objectives: Narcolepsy type 1 (NT1) results from loss of hypothalamic orexin neurons. Selective orexin-2 receptor (OX2R) agonists now permit direct receptor-level restoration of deficient signaling, but recent broad reviews do not fully integrate the post-approval, trial-specific efficacy, prescribing, and safety evidence. This review asks what benefits and risks are supported by current data, which toxicities appear class-related versus molecule-specific, and how OX2R agonism should be positioned clinically. Methods: We performed a targeted narrative review of peer-reviewed human studies, major guidelines, trial registries, and regulatory documents updated through 16 October 2026. Peer-reviewed trials and regulatory sources were prioritized; conference- or sponsor-reported data were used only when peer-reviewed evidence was unavailable and were identified as provisional. Results: In the pivotal phase 3 trials, oveporexton produced placebo-adjusted improvements in MWT sleep latency of 13.8–20.1 min, ESS reductions of 8.0–9.8 points, and weekly cataplexy incidence-rate ratios of 0.25–0.38. Clinically important safety considerations include insomnia, urinary frequency/urgency, CPK elevations, CYP3A interactions, and measurable abuse potential. Alixorexton phase 2 data support OX2R agonism as a developing drug class, whereas firazorexton illustrates molecule-specific hepatotoxic risk. Conclusions: OX2R agonists are best described as mechanism-based pharmacological restoration of orexin signaling, not proven disease-modifying therapy. Their comparative clinical position remains uncertain because head-to-head trials with established therapies are lacking.

Journal of Clinical Medicine doi: 10.3390/jcm15218638

Authors: Hany Kayed Mohamed I. Soltane Svetlana Hetjens Florian Rehberger Thomas Walter Dominik Nörenberg Stefan O. Schoenberg Fabian Siegel Johann S. Rink

Background/Objectives: Early diagnosis and therapy stratification represent central factors in the management of critically ill patients, today often assisted by clinical scores, which also include laboratory testing results. The aim of this study was to further characterize computed tomography-detected abnormal esophageal widening, which we often observe in critically ill patients in our emergency department when reading CT examinations. We expect this factor to be potentially meaningful for clinical evaluation and prognosis of critically ill patients. Methods: In this retrospective observational study, critically ill patients receiving CT trauma room imaging in our hospital’s emergency department were included. In the first part of the analysis, esophageal diameter at four anatomical landmarks were compared between patients who survived and those who died within 28 days in all critically ill patients presenting with AEW. In the second exploratory part of the study, the relevance of the laboratory parameters and AEW in predicting mortality were analyzed. In part three, the correlation between the 28-day mortality of all critically ill patients and the presence of esophageal widening was assessed. Results: Esophageal widening was detected in 98 of all 1683 included patient examinations. Nineteen of these patients have died (19.4%), and ten of them (52.6%) suffered primarily from a cerebrovascular event. In the group of patients with AEW, cervical AEW was more frequent among deceased patients (63.2% vs. 27.8%; p = 0.0064), and mean maximal esophageal diameter was also greater among deceased patients (19.2 vs. 16.4 mm; p = 0.0392). Multiple laboratory parameters were also found to correlate with mortality in all patients with AEW. No significant correlation of AEW alone with 28-day mortality in all critically ill patients that received ED-CT could be demonstrated in our retrospective sample. Conclusions: Esophageal widening, especially in the upper segment, was found in a substantial proportion of critically ill patients, with increased width correlating with mortality risk in the group of patients with AEW. Future studies should include much larger patient cohorts and a prospective design to evaluate if AEW might be a candidate to serve as a potential parameter of clinical scores which aim at early patient stratification.

Journal of Clinical Medicine doi: 10.3390/jcm15218639

Authors: Nerea Sanfeliu Garces Ahmed Alsinbili Lucas Costa Tracy Barnfather Lynne Cooley Barbara Kardos Mike Pashler Attila Kardos

Background: As part of the National Health Service England new chest pain pathway implementation project, we tested the impact of an artificial intelligence (AI)-based, CariHeart risk score-based new pathway (NP) compared with the current pathway (CP). Methods: One hundred and thirty-five consecutive patients referred to the Rapid Access Chest Pain Clinic who underwent Cardiac Computed Tomography Angiography (CCTA) for the assessment of suspected coronary artery disease (CAD) were included. CCTA images were analysed for qualitative plaque characterisation and grading of coronary artery stenosis and CariHeart risk score (derived from the perivascular fat attenuation index (FAI) score, plaque burden and clinical risk factors) as part of this analysis. We assessed the proportion of patients with non-obstructive CAD classified as high-risk by CariHeart and the differences between the pathways in initiation/intensification and de-escalation of cardiovascular preventive therapy (CVPT; statin, aspirin, ezetimibe and colchicine). CP was based on nurse assessment and CCTA with subsequent cardiologist recommendation and the NP was based on the same in addition to the CariHeart risk assessment-based management. Results: The average age was 61 years, with 47% female and 82% Caucasian. CCTA showed that 83% of patients had non-obstructive CAD (no or <50% stenosis), 16% had moderate CAD (50–69% stenosis), and 1.5% had severe or chronic total occlusion. The CariHeart score indicated low risk (<1% risk) in 3%, intermediate risk (1–5%) in 38%, and high risk (>5%) in 59% of patients. Based on the CariHeart risk score, 54% of patients with non-obstructive CAD were classified as high-risk, whereas 17% of patients with obstructive (≥50%) CAD were classified as intermediate-risk and none as low-risk. Among 133 patients with recommendations under both pathways, escalation of CVPT was recommended for 30% with the CP and 84% with the NP (McNemar p < 0.0001); the rest continued their existing therapy. Under the CP, escalation was more frequent in patients with higher FAI score centiles and higher CariHeart risk; under the NP, escalation rates were high in all categories. No de-escalation of medication was recommended in either of the pathways. In patients with no or mild CAD on the local CCTA report, escalation was recommended more often with the NP than with the CP (86% vs. 25%). Conclusions: Incorporating the AI-based CariHeart risk score into the chest pain pathway classified a high proportion of patients with non-obstructive CAD as high-risk and was associated with a higher rate of recommended escalation of CVPT than the CP. Whether this improves clinical outcomes requires prospective evaluation.

Journal of Clinical Medicine doi: 10.3390/jcm15218637

Authors: Soon Il Jeong Un Hyo Baek Hyun Seok Bang Dae Yun Seo

Sarcopenia complicates cardiovascular disease, but diagnostic definitions and outcome selection can substantially alter the interpretation of exercise rehabilitation. This critical review examines how these differences affect the translation of muscle biology into clinical assessment and treatment, with heart failure as the principal clinical setting. Targeted literature retrieval prioritized recent consensus statements, clinical studies, and intervention trials, while experimental evidence was considered separately. Human biopsy studies associate inflammatory and mitochondrial abnormalities with muscle dysfunction; causal manipulation of muscle-derived signaling remains predominantly experimental. European and Asian consensus frameworks differ in their thresholds and the diagnostic role of physical performance. These distinctions matter because trials frequently enroll patients with frailty or exercise intolerance without confirming sarcopenia. Resistance and combined interventions improve selected measures of strength or physical performance, whereas muscle quantity, diagnostic status, and clinical events may respond differently. A small coronary artery disease trial provides direct, short-term evidence in confirmed sarcopenia, but durability remains uncertain. Rehabilitation should therefore link an explicit diagnostic framework to individualized exercise, nutritional assessment, and repeated measurement of the intended outcomes. Future trials should establish whether improvements in defining muscle components persist and translate into sustained independence and fewer clinical events.

Journal of Clinical Medicine doi: 10.3390/jcm15218636

Authors: Anna Annunziata Angela Irene Mirizzi Antonietta Coppola Maria Rosaria Valentino Rosa Saggio Pasqualina Gaglione Gianfranco Gaglione Gennaro Calafiore Cristina Liguori Giuseppe Fiorentino

Background: DMD causes progressive respiratory muscle weakness and chronic alveolar hypoventilation requiring ventilatory support. While nocturnal non-invasive ventilation (NIV) is the standard care, daytime ventilation is often provided with prolonged use of nasal–oronasal masks. These interfaces can cause skin injury, air leaks, and reduced adherence. Mouthpiece ventilation (MPV) provides on-demand pressure support without an interface and may be an alternative for intermittent daytime ventilation. Objective: To assess the feasibility, safety, and clinical impact of MPV as an adjunct to nocturnal NIV in patients with DMD. Methods: Six patients with DMD and chronic respiratory failure on nocturnal NIV were enrolled in a 30-day observational pilot study. After training, participants used MPV during daytime. Clinical assessment, arterial blood gases, and quality of life evaluated with the S3-NIV questionnaire were performed at baseline (T0) and after 30 days (T1). Results: All patients tolerated MPV well, with mean daily use of >16 h. PaCO2 decreased in all patients (from 49.7 ± 7.1 to 43.5 ± 5.7 mmHg; p = 0.031); 4/6 were normocapnic at T1, whereas hypercapnia persisted in two. S3-NIV scores improved from 2.53 ± 0.69 at T0 to 4.87 ± 0.91 at T1 (p = 0.031). Patients reported improved performance of daily activities and better psychological well-being. No MPV-related adverse events occurred. Conclusions: MPV was feasible, safe, and well tolerated as an adjunct to nocturnal NIV in this small series of patients with DMD over 30 days. Given the small sample and short follow-up, no firm conclusions can be drawn; larger studies with longer follow-up are needed to confirm these findings and define the optimal role of MPV in DMD respiratory management.

Journal of Clinical Medicine doi: 10.3390/jcm15218633

Authors: Takafumi Tanei Satoshi Yamashita Satoshi Maesawa Tomotaka Ishizaki Takahiro Suzuki Shun Yamamoto Satoshi Shinoda Toshihiko Wakabayashi Ryuta Saito

Background/Objectives: Although calcitonin gene-related peptide monoclonal antibodies (CGRP-mAbs) have improved migraine prevention, some patients continue to experience inadequate response or re-worsening during treatment. This study evaluated the effectiveness of add-on Kampo therapy in migraine patients receiving CGRP-mAb treatment. Methods: This retrospective observational study included 39 migraine patients who received add-on Kampo therapy during ongoing CGRP-mAb treatment, contributing 55 treatment episodes. The primary endpoint was the change in monthly headache days (MHD) from baseline to 1 month after Kampo initiation. Secondary outcomes included migraine frequency, headache-related disability, quality of life, acute medication use, and work productivity. A responder was defined as achieving a ≥30% reduction in MHD at 1 month. Results: The study population was highly refractory, with chronic migraine present in 79.5% of patients and medication-overuse headache in 56.4%. Among treatment episodes, 72.7% experienced re-worsening after an initial response to CGRP-mAb treatment. Median MHD was 14.0 days after CGRP-mAb treatment and subsequently increased to 16.0 days before Kampo initiation. After Kampo initiation, median MHD decreased to 10.0 days at 1 month. Significant improvements were also observed at 1 month in headache-related disability, quality of life, acute medication use, and presenteeism. The ≥30% and ≥50% responder rates at 1 month were 41.8% and 12.7%, respectively. Re-worsening after an initial CGRP-mAb response showed an exploratory association with treatment response in the Firth penalized logistic regression model. Conclusions: Add-on Kampo therapy was associated with improvements in headache burden, quality of life, acute medication use, and work productivity in patients with inadequate response or re-worsening during CGRP-mAb treatment. These hypothesis-generating findings suggest a potential role for add-on Kampo therapy as a treatment optimization strategy and warrant confirmation in prospective controlled studies.

Journal of Clinical Medicine doi: 10.3390/jcm15218635

Authors: Inho Yoon Junsung Suh Jin Kim Min Young Kwak Hye Ah Joo

Background: Current clinical guidelines for pediatric otitis media with effusion (OME) advise watchful waiting and strongly discourage systemic antibiotic use. This study evaluated the rate of pre-referral antibiotic use among children with persistent OME requiring ventilation tube (VT) insertion and analyzed the bacterial culture positivity of middle ear effusion. Methods: We retrospectively reviewed 38 children (56 ears) aged 3 months to 12 years with persistent OME (≥3 months) who underwent first-time VT insertion between March 2025 and August 2026 at a secondary referral center. Prior antibiotic history from primary care clinics was investigated, and antibiotics were discontinued upon referral. Middle ear effusion samples were aseptically aspirated during VT insertion for bacterial direct culture and susceptibility testing. Results: Among the 38 children, 78.9% had received antibiotics prescribed by primary care clinics for OME before referral. Following a mean antibiotic-free interval of 27.34 days, direct bacterial cultures of middle ear effusion yielded positive growth in only 10 of 56 ears (17.9%). The most commonly isolated organisms were coagulase-negative staphylococci (CoNS; 80%, 8/10), of which 75% (6/8) showed methicillin resistance. Prior antibiotic exposure was not significantly associated with bacterial culture positivity (18.2% vs. 16.7%, Fisher’s exact test, p = 1.000). Conclusions: Despite guideline recommendations, pre-referral antibiotic use remains common among children with OME requiring VT insertion in South Korea. Given the observational design, small sample size, and culture sensitivity limits, these findings support adherence to existing clinical guidelines. Educational initiatives and guidance are needed to promote evidence-based prescribing in primary care.

Journal of Clinical Medicine doi: 10.3390/jcm15218634

Authors: Hirsh D. Trivedi

Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most common chronic liver disease in the world [...]

Journal of Clinical Medicine doi: 10.3390/jcm15218632

Authors: Esther Méndez Elvira Bisbe Misericordia Basora Adrián Vizoso Albert García-Casanovas Maria J. Colomina

Background/Objectives: Sex-specific anemia criteria classify women with hemoglobin (Hb) 12.0–12.9 g/dL as non-anemic. We assessed whether World Health Organization (WHO) criteria underrecognize red blood cell (RBC) transfusion risk compared with a uniform patient blood management (PBM) threshold of Hb <13.0 g/dL in elective open cardiac valve surgery (CVS). Methods: This nationwide retrospective cohort included adults undergoing elective open CVS in 40 Spanish centers (2016–2024), 32 of which reported preoperative Hb. Hb was modeled continuously and in three strata (<12.0, 12.0–12.9, ≥13.0 g/dL). The primary outcome was RBC transfusion; secondary outcomes were postoperative complications, length of stay, and in-hospital mortality within 30 days. Mixed-effects models adjusted for age, comorbidity burden, surgical complexity, valve position, year of surgery, and center. Results: Among 29,757 eligible patients, 20,017 had available Hb measurements; 9247 (46.2%) were women, including 2333 (25.2%) with Hb 12.0–12.9 g/dL. In this stratum, 68.0% of women and 52.7% of men received RBC transfusions. The adjusted between-sex probability difference was 15.1 percentage points (95% CI, 11.4–18.9; adjusted odds ratio, 1.85; 95% CI, 1.59–2.16). The categorical sex × Hb interaction was significant (p < 0.001), whereas the continuous interaction was not (p = 0.486). Sex did not significantly modify the Hb associations with complications or in-hospital mortality within 30 days. Conclusions: Women with Hb 12.0–12.9 g/dL had substantial transfusion risk despite being classified as non-anemic by the WHO criteria. Hb <13.0 g/dL may be a pragmatic sex-inclusive trigger for perioperative risk recognition and etiologic evaluation, not a proven therapeutic target.

Journal of Clinical Medicine doi: 10.3390/jcm15218628

Authors: Dimitrios Argyropoulos Arian Arjomandi Rad Antonios Kourliouros Dionysios Pavlopoulos Ioannis Toumpoulis Dimitrios Angouras

Background: Coronary artery bypass grafting (CABG) is the most common adult cardiac surgical procedure worldwide. Although survival and graft patency are well characterised, health-related quality of life (HRQoL) is increasingly recognised as a patient-centred outcome that may be modifiable. Existing syntheses have summarised global HRQoL change after CABG but have not consistently focused on the patient-, surgery- and recovery-level factors associated with that change. Methods: PubMed/MEDLINE, Embase, Cochrane CENTRAL and CINAHL were searched from 1 January 2010 to 31 March 2025. Eligible studies were primary investigations (prospective or retrospective cohort, cross-sectional analytical, or randomised controlled trial) of adults (≥18 years) undergoing isolated CABG that reported HRQoL with a validated multidimensional instrument and assessed at least one candidate factor. Two reviewers independently screened records, extracted data and assessed risk of bias using the Newcastle–Ottawa Scale for observational studies and the Cochrane Risk of Bias 2 tool for randomised trials. Certainty of evidence was rated using the GRADE approach as adapted for prognostic-factor questions. Owing to heterogeneity in instruments, factor definitions and follow-up, results were synthesised narratively; no meta-analysis was performed. Results: Of 1220 records identified, six studies met the inclusion criteria, three prospective cohorts, two cross-sectional analytical studies and one randomised controlled trial, together contributing analysable HRQoL data on 1271 patients. Follow-up ranged from the end of post-operative cardiac rehabilitation to 10 years. Four different instruments were used: the SF-36 in three studies, the SF-36 with the SF-12 in one, the SF-12v2 in one and the disease-specific MacNew questionnaire in one. Risk of bias was low in two cohort studies and moderate in the remaining three observational studies, and low overall for the randomised trial. No factor was examined by more than five of the six studies, and most were reported by only one or two; findings are therefore described by the number of supporting studies rather than as consistent. Diabetes mellitus and post-operative complications were each independently associated with poorer physical HRQoL in two studies. Female sex, older age, lower pre-operative HRQoL, repeat percutaneous coronary intervention, heart failure or dyspnoea, social support, cardiac self-efficacy, marital status and unemployment were each supported by a single study. Depressive symptoms were not confirmed as an independent factor in the only study modelling them separately, and cardiac rehabilitation could not be evaluated because every patient received it wherever it was delivered. The sole randomised comparison showed that exercise-based prehabilitation improved pre-operative functional capacity and quality of life, but by less than the minimal clinically important difference and with no significant post-operative effect. Conclusions: Factors associated with HRQoL after CABG cluster into non-modifiable demographic and comorbidity factors, potentially modifiable psychosocial and behavioural factors, and recovery-related factors emerging post-operatively. The evidence base is nevertheless small, clinically and methodologically heterogeneous, and almost entirely observational. The factors identified are candidate targets requiring confirmation in prospective studies with pre-operative measurement and, thereafter, in randomised trials; they are not established causal determinants. Persistent heterogeneity of HRQoL instruments and factor definitions argues for standardised reporting in future studies of cardiac surgical recovery.

Journal of Clinical Medicine doi: 10.3390/jcm15218631

Authors: Ching-Yao Cheng Jaw-Horng Liou Kao Tz Wei Shang-Feng Tsai

Background: Direct real-world comparisons of empagliflozin and canagliflozin regarding renal outcomes in patients with type 2 diabetes mellitus (T2DM) remain limited. This study compared longitudinal changes in the estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR). Methods: This retrospective observational cohort study included 215 adults with type 2 diabetes mellitus who received either empagliflozin (n = 115) or canagliflozin (n = 100) at a tertiary medical center. Renal outcomes, including estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), were evaluated over 18 months. Between-group differences in renal outcomes were assessed using multivariable regression models adjusted for relevant baseline clinical characteristics. Linear mixed-effects models were additionally employed to account for repeated measurements and evaluate differences in longitudinal trajectories between treatment groups. A reduction in UACR of ≥30% from baseline was evaluated as a clinically meaningful albuminuria response using multivariable logistic regression. Subgroup analyses were performed according to age and baseline UACR. Results: In multivariable linear regression analysis, the 18-month change in eGFR did not differ significantly between canagliflozin and empagliflozin (adjusted β, −0.43 mL/min/1.73 m2; 95% confidence interval [CI], −4.12 to 3.26; p = 0.819). Consistently, linear mixed-effects models showed no significant treatment-by-time interaction for eGFR (p for interaction = 0.356) or log-transformed UACR (p for interaction = 0.104). In the adjusted logistic regression analysis, canagliflozin was associated with lower odds of achieving a ≥30% reduction in UACR at 12 months compared with empagliflozin (adjusted odds ratio [OR], 0.40; 95% CI, 0.20–0.79; p = 0.008). However, this association was not statistically significant at 18 months (adjusted OR, 0.62; 95% CI, 0.32–1.18; p = 0.147). Subgroup interaction analyses did not demonstrate significant effect modification by age or baseline UACR (p for interaction = 0.859 and 0.626, respectively). Conclusions: In this real-world cohort of patients with type 2 diabetes mellitus, empagliflozin and canagliflozin showed comparable longitudinal eGFR and UACR trajectories over 18 months. Although a difference in the likelihood of achieving a ≥30% reduction in UACR was observed at 12 months, this finding was not sustained at 18 months and should be interpreted cautiously. Overall, our findings do not establish the superiority of either SGLT2 inhibitor in terms of renal outcomes. Further studies with larger populations and prospective designs are warranted.

Journal of Clinical Medicine doi: 10.3390/jcm15218629

Authors: Selen Topalel Mehmet Özkılıç

Background/Objectives: Shock index (SI) and modified shock index (MSI) are simple hemodynamic indices derived from routinely available vital signs, but their perioperative prognostic relevance in coronary artery bypass grafting (CABG) remains incompletely characterized. This study evaluated perioperative changes in SI, MSI, and their age-adjusted derivatives and explored their associations with in-hospital mortality and postoperative outcomes after elective isolated CABG. Methods: This retrospective single-center study included 245 adults who underwent elective isolated CABG between 1 January 2023, and 1 May 2025. SI, MSI, Age-SI, and Age-MSI were calculated at seven perioperative time points. The primary outcome was in-hospital mortality; prespecified secondary outcomes included AKI, stroke, ICU length of stay, and mechanical ventilation duration, while additional postoperative morbidity outcomes were explored. Discrimination was assessed using receiver operating characteristic analysis. Exploratory models evaluated post-cardiopulmonary bypass (post-CPB) SI and MSI in combination with EuroSCORE II, with Firth penalized regression and bootstrap internal validation used as sensitivity analyses because of the limited number of deaths. Results: In-hospital mortality occurred in 12/245 patients (4.9%). Post-CPB measurements were available in 243 patients, including 10 non-survivors. Among the evaluated time points, the strongest observed mortality discrimination occurred post-CPB: SI had an AUC of 0.798 (95% CI 0.621–0.974) and MSI an AUC of 0.793 (95% CI 0.606–0.980). After adjustment for EuroSCORE II, both post-CPB SI (OR 1.30 per 0.1-unit increase, 95% CI 1.09–1.56; p = 0.004) and MSI (OR 1.23 per 0.1-unit increase, 95% CI 1.07–1.41; p = 0.003) remained associated with mortality. Addition of either index increased the apparent AUC from 0.798 to 0.830 and improved model fit; however, the absolute increase in discrimination was modest, and bootstrap confidence intervals for ΔAUC included zero. Firth penalized regression yielded similar effect estimates, and optimism-corrected AUCs were 0.824 for EuroSCORE II + SI and 0.829 for EuroSCORE II + MSI. Age-adjusted indices showed exploratory associations with several postoperative morbidity outcomes. Conclusions: Post-CPB SI and MSI were associated with in-hospital mortality among patients who reached the post-CPB assessment point and remained associated after adjustment for EuroSCORE II. Although their addition improved model fit, incremental improvement in discrimination was modest and uncertain. These readily available indices may serve as supportive markers of perioperative hemodynamic instability rather than standalone prognostic tools. Given the limited number of mortality events, these findings should be considered exploratory and require external validation.

Journal of Clinical Medicine doi: 10.3390/jcm15218630

Authors: Michał Grabala Piotr Kowalski Krzysztof Zakrzewski Jakub Kowalski Paweł Grabala

Background: Advances in spinal deformity surgery have expanded treatment options for pediatric and adolescent patients, but neurological complications remain among the most serious adverse events. Intraoperative neuromonitoring (IONM) enables early detection of spinal cord dysfunction, while preservation of adequate spinal cord perfusion remains an important component of perioperative neurological protection. Objective: This narrative review examines current evidence regarding neurological protection during complex spinal deformity surgery, with emphasis on spinal cord perfusion, IONM interpretation, hemodynamic management, and the potential interaction between mechanical and autonomic factors. An illustrative case of recurrent IONM deterioration associated with profound hemodynamic instability is included. Methods: A narrative review of contemporary literature was conducted, focusing on spinal cord perfusion, mechanisms of neurological injury, IONM, perioperative blood pressure management, corrective strategies, and postoperative neurological surveillance. Pediatric deformity studies were prioritized, while adult and mixed-population studies were included when relevant mechanistic or technical information was provided. The clinical case was analyzed separately from the literature synthesis. Results: Current evidence supports maintaining adequate systemic perfusion and promptly evaluating reversible physiological and mechanical contributors when IONM deterioration occurs. Blood pressure augmentation may restore signals in a subset of patients, but IONM changes cannot be assumed to be purely ischemic, and improved perfusion may not overcome persistent mechanical compromise. In the illustrative case, recurrent IONM signal loss occurred during corrective maneuvers and was associated with profound hypotension and bradycardia during a subsequent correction attempt. Motor and somatosensory evoked potentials were comparable to baseline by the end of surgery after release of corrective forces, hemodynamic management, and vasopressor support; they had recovered to 50% of baseline immediately before correction was resumed. Because these interventions were performed concurrently, the relative contribution of mechanical release, improved systemic perfusion, and possible autonomic mechanisms could not be determined. Motor and sensory function remained intact postoperatively, although she later reported sweating and temperature asymmetry during follow-up. Conclusions: Neurological protection during complex spinal deformity correction requires an integrated perioperative approach combining individualized surgical strategy, multimodal IONM, hemodynamic optimization, and postoperative surveillance. When IONM deterioration occurs, mechanical, hemodynamic, anesthetic, and technical causes should be assessed concurrently. The presented case supports consideration of a possible autonomic contribution to severe intraoperative hemodynamic instability, but does not establish a specific autonomic syndrome or causal pathway.

Journal of Clinical Medicine doi: 10.3390/jcm15218625

Authors: Carlotta Liberale Arianna Burato Livio Presutti Giuseppe Mercante Giulia Molinari

Background/Objectives: To describe the technical feasibility of fully exoscopic management of an unusually extensive external auditory canal cholesteatoma (EACC). Methods: We report a 26-year-old man with advanced right EACC and a history of ipsilateral myringoplasty approximately 15 years previously; a postoperative origin was suspected but could not be established. Clinical, radiological, surgical, and follow-up findings are described. Results: Imaging revealed extensive erosion of the superior EAC and adjacent temporal bone with mass effect on the right temporal lobe. The ORBEYE™ 4K three-dimensional exoscope was used throughout the operation, including dissection along exposed dura and hearing-preserving reconstruction. An intraoperative cerebrospinal fluid leak occurred at the middle cranial fossa dura and was controlled during surgery, without persistent postoperative leakage. The patient was discharged on postoperative day 4. Based on the reported four-frequency pure-tone averages, the calculated air–bone gap decreased from 18.5 to 8.5 dB HL. Diffusion-weighted MRI at 18 months showed no evidence of residual or recurrent disease, and clinical examination at 24 months showed a patent, epithelialized canal. Conclusions: This case illustrates the technical feasibility of a fully exoscopic, hearing-preserving approach to complex EACC. Comparative studies are required before conclusions about superiority or generalizable safety relative to conventional visualization can be drawn.

Journal of Clinical Medicine doi: 10.3390/jcm15218627

Authors: Yunxiao Zhang Wanpu Yan Jin Wei Jing Wang You Wan Fengyu Liu Jiheng Chen

Background: We aimed to clarify (1) the analgesic efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with general anesthesia during minimally invasive lung cancer surgery and (2) exploratory neural network correlates of acupuncture–drug combined anesthesia. Methods: Eligible patients receiving general anesthesia for minimally invasive lung cancer surgery were randomly allocated to perioperative TEAS or sham-TEAS in this randomized, patient- and assessor-blinded, sham-controlled trial. Postoperative patient-controlled intravenous analgesia (PCIA) was administered. Outcome measures included postoperative visual analog scale (VAS) pain scores, sufentanil consumption via PCIA, and total/effective PCIA pump presses. Perioperative electroencephalography (EEG) was acquired using a 22-lead recorder, and brainwave power spectra were analyzed using Fourier transform. Repeated-measures analysis of variance (RM-ANOVA) was applied to serial postoperative VAS scores at 6, 24 and 48 h. Independent-samples t-tests compared cumulative sufentanil consumption at 6, 24 and 48 h postoperatively. Post hoc simple-effect comparisons were performed as exploratory analyses without multiplicity adjustment. The EEG sub-study was exploratory; false-discovery-rate (FDR) correction was used to control multiple comparisons across electrodes and frequency bands. Results: In total, 109 patients were randomized. A significant group-by-time interaction was detected for postoperative VAS scores (F(1.599,171.124) = 68.287, p < 0.001). Simple-effect analyses revealed lower VAS scores in the TEAS group at postoperative 6 h (mean difference −1.900, 95%CI −2.181 to −1.619, p < 0.001) and 24 h (mean difference −1.391, 95%CI −1.645 to −1.138, p < 0.001), with no between-group difference at 48 h (mean difference −0.066, 95%CI −0.320 to 0.187, p = 0.605). The TEAS group also exhibited reduced PCIA sufentanil consumption at 6, 24 and 48 h postoperatively, alongside fewer total and effective PCIA pump presses. After FDR correction, exploratory EEG analysis identified potential dipole-related power differences in the prefrontal, occipital, parietal (postcentral gyrus), temporal and diencephalic regions, predominantly within beta-band oscillations (14–35 Hz). Conclusions: These exploratory findings suggest that TEAS combined with general anesthesia may reduce postoperative pain and analgesic requirement. This potential benefit may arise from TEAS-mediated modulation of pain-related neural networks; however, the observed intraoperative EEG oscillatory differences are exploratory neurophysiological correlates and do not confirm causal mechanisms.

Journal of Clinical Medicine doi: 10.3390/jcm15218626

Authors: Tuna Sumer Nihat Akbulut

Background/Objectives: Dental implants are an established treatment for functional and aesthetic rehabilitation of partially or completely edentulous patients. This in vitro study evaluates the effects of dental implant design, diameter, length, and bone density on primary implant stability using Osstell ISQ and Penguin Resonance Frequency Analysis (RFA) devices. Materials and Methods: A total of 96 dental implants were included in this study. Combinations of two implant designs (T6 Standard and T6 Torq), two implant diameters (3.5 mm and 5.0/4.8 mm), and two implant lengths (8 mm and 14 mm) were placed into synthetic bone blocks with densities of PCF15 and PCF30. Implant stability was measured twice from two different directions using Osstell ISQ and Penguin RFA devices. The data were statistically analyzed. Results: Both RFA devices demonstrated high measurement reproducibility. When all measurements were evaluated collectively, the intraclass correlation coefficient (ICC) reached 0.999 for both devices. Bone density was identified as the most influential factor affecting primary implant stability. Significantly higher ISQ values were obtained in the high-density bone model (p < 0.001). Increases in implant length and diameter significantly enhanced primary stability (p < 0.001). T6 Torq implants exhibited significantly higher ISQ values than T6 Standard implants in low-density bone and small-dimension implant combinations (p < 0.001). Conclusions: Under the present experimental conditions, bone density showed the greatest influence on primary implant stability, followed by implant length and implant diameter. In low-density bone, particularly with short and narrow implants, more aggressive implant macrodesigns may contribute to higher primary stability. However, the clinical relevance of these findings requires further investigation.

Journal of Clinical Medicine doi: 10.3390/jcm15218624

Authors: Noriko Aramaki-Hattori Satoru Sasaki Naoki Murao Taiki Nozaki Akihiro Fujino Ayato Hayashi Michio Ozeki Saori Endo Shimpei Akiyama Tadashi Nomura Shunsuke Sakakibara Yoshihisa Kawakami Ai Morita Junko Ochi Motoki Akamatsu Sadanori Akita

Background/Objectives: Slow-flow vascular malformations, including venous malformation (VM), lymphatic malformation (LM), and Klippel–Trenaunay syndrome (KTS), are rare, symptomatic disorders with limited treatment options. This study evaluated the efficacy and safety of serabelisib, an orally available selective phosphoinositide 3-kinase α inhibitor, in these patients. Methods: This phase 3, multicenter, single-arm, confirmatory study was conducted in Japan (September 2023–June 2025). Patients aged ≥2 years received oral serabelisib once daily (100 mg for body weight ≥ 40 kg; 60 mg/m2 for <40 kg) for up to 52 weeks. The primary endpoint was the response rate at the final evaluation (≥24 weeks), defined as the proportion of patients achieving a ≥20% reduction from baseline in target lesion volume on blinded, centrally reviewed magnetic resonance imaging. The response rate was compared with a natural history-based null rate of 6.7% (exact binomial test). Trial registration: jRCT2041230064. Results: Thirty-six patients received serabelisib. The response rate was 30.6% (11/36; 95% confidence interval, 16.3–48.1%; p < 0.001) and remained significant in post hoc sensitivity analyses for null rates of up to 16%. Response rates were 19.0% (VM), 33.3% (LM), and 50.0% (KTS). Quality of life did not improve consistently. Adverse drug reactions (ADRs) occurred in 52.8% of patients (grade 3 or 4, 22.2%), most commonly hyperinsulinemia (13.9%), nausea (11.1%), and liver function test abnormal (11.1%); most hepatic ADRs (13 of 15 events) resolved after dose interruption or discontinuation. One death (tubulointerstitial nephritis) was judged unrelated to treatment. Conclusions: Serabelisib produced radiological responses exceeding a natural history benchmark in refractory VM, LM, and KTS, with hepatic toxicity requiring monitoring. Larger controlled studies with longer follow-up are needed to confirm its clinical benefit and long-term safety.

Journal of Clinical Medicine doi: 10.3390/jcm15218623

Authors: Meihong Xia Xingyue Su Jing Liu Di Lv Jianning Guo Qin Hui Fang Ye Yuanmei Chen Chao Wang Lijuan Tang Qi Zhang

Severe pneumonia requires repeated assessment, but anatomical abnormalities, oxygenation, and regional ventilation may follow different recovery trajectories. This narrative review examines chest computed tomography (CT), electrical impedance tomography (EIT), and digital lung sounds as complementary sources of structural, ventilation, and acoustic information, with lung ultrasound (LUS) considered as an important bedside comparator. Focused searches and source verification were conducted in October 2026, with an evidence publication cutoff of 15 July 2026. CT characterizes whole-lung anatomy and complications when clinically indicated; EIT tracks regional ventilation-related changes; and digital auscultation provides stored recordings for serial and remote review. LUS supports bedside assessment of accessible peripheral lesions, pleural abnormalities, and reaeration. Small pneumonia studies support the measurement of regional ventilation trends, and selected controlled studies report favorable short-term findings. Acoustic evidence is concentrated in pediatric populations, with limited adult severe-pneumonia validation. Findings from ARDS and ventilator-weaning studies provide additional physiological context. The proposed longitudinal framework brings these complementary signals together across early assessment, treatment response, ICU transitions, and recovery. Prospective studies should establish its reproducibility, incremental clinical value, resource requirements, and effects on patient-important outcomes before routine implementation.

Journal of Clinical Medicine doi: 10.3390/jcm15218622

Authors: Özgür Akkaya Izatullah Jalalzai Ümit Arslan

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Journal of Clinical Medicine doi: 10.3390/jcm15218620

Authors: Abdulmecit Oktem İlayda Gercik Arzik Mukremin Ceylan Zübeyde Emiralioglu Cakir Orhan Nural Atalay Ekin

Background/Objectives: To identify the clinical factors associated with a multidisciplinary fetal council’s recommendation for termination of pregnancy in fetuses with renal anomalies, to describe how often families followed this recommendation, and to describe outcomes among continued pregnancies. Methods: This retrospective cohort study included 103 singleton pregnancies with a prenatally diagnosed renal or urinary tract anomaly discussed at a tertiary fetal council between December 2023 and July 2026. Renal severity, gestational age at diagnosis, amniotic fluid status, associated fetal abnormalities, and genetic evaluation were examined in relation to the council recommendation. Independent associations were assessed using multivariable logistic regression, Poisson regression with robust variance estimation, and Firth penalized logistic regression. Postnatal outcomes were summarized for pregnancies that continued. Results: A termination recommendation was issued in 59 of 103 pregnancies (57.3%). Of these, 43 families (72.9%) accepted it and the pregnancy was terminated, whereas 16 (27.1%) continued the pregnancy. Later diagnosis and moderate or low renal severity were independently associated with a lower likelihood of a termination recommendation. The presence of an additional fetal anomaly (adjusted odds ratio [aOR] 8.24, 95% confidence interval [CI] 1.59–42.65) and completion of genetic testing (aOR 4.53, 95% CI 1.45–14.15) were independently associated with a higher likelihood of such a recommendation. Among 60 continued pregnancies, 11 intrauterine or neonatal/postnatal deaths occurred (18.3%); mortality was 42.9% in the high-severity group and 5.3% in the low-severity group. The prenatal renal finding was confirmed postnatally in 22 cases, while renal-specific follow-up was unavailable in 18. Conclusions: Termination recommendations issued after prenatal detection of a renal anomaly were shaped by the timing of diagnosis, expected renal prognosis, the wider fetal phenotype, and the availability of genetic information. The observed difference between the council recommendation and the parental decision, together with substantial variation in postnatal outcomes, supports individualized counseling within a multidisciplinary framework.

Journal of Clinical Medicine doi: 10.3390/jcm15218621

Authors: Ahmad Kharoufeh Ahmad Omari Bassam Awad Mohamedanas Mohamedfaruk Patni Shadha Nasser BaHutair Haidy Alzaghal Hammad Alqedrh Ashfaq Ahmad Shah Bukhari Hafiz Ahmad

Background/Objectives: Pulmonary arterial hypertension (PAH) management is evolving beyond conventional vasoactive therapies toward strategies targeting pathways implicated in pulmonary vascular remodeling. Despite advances in combination therapy, substantial residual risk persists. The clinical introduction of sotatercept, targeting activin signaling, has expanded the therapeutic landscape. This narrative review critically evaluates the evidence supporting remodeling-directed treatment and examines how established recommendations, individualized therapeutic considerations, and investigational strategies can be distinguished within risk-guided PAH management. Methods: Clinical, translational, and mechanistic evidence was narratively synthesized, prioritizing randomized controlled trials, prospective investigations, major guidelines, and relevant mechanistic studies. Particular attention was given to differences in trial populations, endpoints, background treatment, safety, and evidence maturity. Results: Sotatercept has demonstrated incremental clinical benefits across functional, hemodynamic, and clinical-outcome measures in studied PAH populations, although trial heterogeneity limits indirect comparisons and long-term disease modification remains unproven. Other remodeling-directed approaches, including growth-factor inhibition, BMPR2 restoration, immune modulation, and metabolic targeting, remain investigational, with variable and frequently preliminary evidence. The proposed synthesis distinguishes guideline-supported therapeutic escalation from individualized clinical considerations and research hypotheses, emphasizing residual risk, treatment tolerability, and demonstrated incremental benefit. Conclusions: Remodeling-directed therapy expands the treatment options for PAH but does not replace established vasoactive treatment or risk-based escalation. Future priorities include defining optimal therapeutic sequencing, identifying responsive patient populations, and determining whether sustained clinical improvements translate into modification of disease progression.

Journal of Clinical Medicine doi: 10.3390/jcm15218617

Authors: Barbara Lipka Małgorzata Kępa Maciej Łopaciński Aleksandra Warakomska Maciej Dobrzyński Marek Ziętek Dariusz Skaba Rafał Wiench

Background: Denture stomatitis, the most common form of oral candidiasis among denture wearers, remains highly prevalent, and antifungal resistance is an emerging concern. Essential oils and plant-derived volatile compounds show broad-spectrum antifungal activity in vitro, generating interest as complementary therapies. This review evaluated the clinical efficacy, mycological efficacy, and safety of these compounds versus conventional antifungals or placebo, based solely on randomized controlled trials (RCTs). Methods: Following PRISMA 2020 guidelines and PROSPERO registration (CRD420261473618), PubMed, Embase, Scopus, and Cochrane CENTRAL were searched on 20 July 2026 for English-language RCTs published up to 30 June 2026 and evaluating topical essential oils or volatile compounds against a conventional antifungal or placebo comparator in oral candidiasis. Two reviewers independently conducted screening, extraction and RoB 2 risk-of-bias assessment. Due to heterogeneity, findings were synthesized narratively. Results: Eight RCTs (347 participants), all in denture stomatitis patients, met inclusion criteria, evaluating oils from Zataria multiflora, Cinnamomum zeylanicum, Melaleuca alternifolia, Pelargonium graveolens, Satureja hortensis, Artemisia sieberi, and clove/cinnamon extracts. In active-comparator trials, no statistically significant differences in clinical outcomes were detected, but these trials were small and underpowered and none defined a non-inferiority margin; mycological efficacy varied, sometimes favoring nystatin or miconazole. Both placebo-controlled trials favored essential oil gels for clinical and mycological recovery. Adverse effects were inconsistently and mostly non-systematically reported; one trial reported vertigo, nausea and vomiting in the essential-oil group. Overall risk of bias was low in three trials and raised some concerns in five for both outcomes. Conclusions: The evidence for essential oils in denture stomatitis is preliminary and insufficient to support replacing conventional antifungal therapy; the findings cannot be extrapolated to other forms of oral candidiasis. Safety data are insufficient to draw firm conclusions. Standardized formulations and larger, well-designed RCTs with longer follow-up and safety assessment are needed.

Journal of Clinical Medicine doi: 10.3390/jcm15218618

Authors: Jessica Mondaca Urrutia Rodrigo Yáñez-Sepúlveda Paz Pezoa-Fuentes Yeny Concha-Cisternas Eduardo Guzmán-Muñoz Carlos Abraham Herrera-Amante Lawrence W. Judge Claudio Farías-Valenzuela Pablo Valdés-Badilla Bastian Parada-Flores Jordan Hernandez-Martínez Exal Garcia-Carrillo

Background: Slow gait, weak handgrip strength, and impaired balance are common functional deficits in aging populations that predict adverse health outcomes. Accurate, scalable prediction tools are needed for community-based screening in low-resource settings. Objectives: To benchmark nine machine learning (ML) classifiers for predicting the presence of ≥1 functional deficit using cardiometabolic and anthropometric predictors; to assess calibration, generalization, and clinical utility; to quantify the incremental value of these predictors over age and sex; and to characterize the stability of SHAP-based feature importance. Methods: We analyzed cross-sectional data from the Mexican Health and Aging Study 2012 (MHAS 2012) biomarker sub-study (N = 1961; mean age 61.9 ± 10.5 years; 59.8% women). The outcome was ≥1 of slow gait (<0.8 m/s), weak handgrip (EWGSOP2 sex-specific cut-points), or inability to sustain a 10-s one-leg stance (prevalence 78.7%). Twenty cardiometabolic and anthropometric predictors were used, excluding the functional measures used in outcome construction. Performance was estimated with nested, repeated stratified 10-fold cross-validation (5 × 10 outer folds; inner 5-fold hyperparameter tuning), with all preprocessing confined to training folds. Results: Logistic Regression (LR) achieved the highest discrimination (AUC-ROC 0.751, 95% CI 0.724–0.779), with good calibration (scaled Brier 0.125; calibration slope 0.96) and a small overfit gap (0.011); no classifier outperformed it (ET: AUC 0.745). An age–sex model alone reached AUC 0.734; all other predictors added ΔAUC = +0.018 (95% CI 0.004–0.031), almost entirely through anthropometry, whereas blood biomarkers and blood pressure added no measurable discrimination. SHAP identified age, sex, height, body weight, and BMI × Age as the most influential features; BMI ranked 12th of 20 (bootstrap 95% rank interval 8–20). Conclusions: Cardiometabolic and anthropometric predictors identify middle-aged and older Mexican people with ≥1 functional deficit with moderate accuracy (AUC ≈ 0.75), but most of the signal is carried by age, sex, and simple anthropometry. This reproducible, circularity- and leakage-free framework supports risk stratification rather than diagnosis, and requires external and temporal validation before clinical implementation.

Journal of Clinical Medicine doi: 10.3390/jcm15218619

Authors: Marco Bonsano Barbara Iacoviello Giorgio Berlot

Several extracorporeal blood purification techniques are used to treat septic shock and other conditions characterized by the release of inflammatory mediators and bacterial toxins, notably lipopolysaccharide (endotoxin), which account for the cardiovascular, coagulation and metabolic derangements. Each technique has advantages and drawbacks, including, for most devices, the need for circuit anticoagulation and the possible removal of antibiotics. High-quality randomized trials remain scarce, and their heterogeneity in populations, techniques, dose and timing, together with the enrollment of biologically unselected patients, limits firm conclusions. In this narrative review, we describe the available techniques, critically appraise the clinical evidence for each modality against the 2026 Surviving Sepsis Campaign guidelines, and outline the phenotype-guided direction of ongoing research. The 2026 Surviving Sepsis Campaign guidelines suggest against the use of blood purification techniques in adults with sepsis or septic shock (conditional recommendation, very low certainty of evidence) and, specifically, against polymyxin-B hemoperfusion (conditional recommendation, low certainty of evidence). In the phenotype-enriched Tigris trial, polymyxin-B hemoadsorption showed a high posterior probability of mortality benefit in endotoxic septic shock; given the small sample, the imprecise primary estimate and the informative prior, this promising finding requires independent confirmation. Outside clinical trials, routine blood purification is not supported.

Journal of Clinical Medicine doi: 10.3390/jcm15218616

Authors: Doğuş Hemşinli Sedat Ozan Karakişi Atilla Topçu Oğuzhan Okcu İbrahim Yel Fatih Eren

Background/Objectives: Experimental animal models are fundamental to developing and translating strategies for preventing postoperative mediastinal adhesions. Rabbits are widely used in adhesion research; however, the anatomical and technical suitability of the rabbit median sternotomy model for reproducing conditions relevant to human redo sternotomy remains incompletely characterized. This study aimed to characterize the rabbit sternum and assess the feasibility and translational suitability of the rabbit median sternotomy model for mediastinal adhesion research. Methods: An acute, non-survival observational feasibility study was performed in two adult female New Zealand White rabbits. Median sternotomy was performed using 22 cm surgical scissors with ball-tipped blades, following a previously described technique with a technical modification. Macroscopic assessments included sternal morphology, the technical feasibility of midline division, pleural and peritoneal integrity, the apparent adequacy of the remaining sternal bone for re-approximation, and the relationships between the sternum and underlying mediastinal structures. Sternal closure was not attempted. Results: The rabbit sternum exhibited a narrow, highly segmented, and flexible configuration, with an elongated xiphoid process extending beyond the thoracic cavity. Median sternotomy proved technically challenging because of the limited width of the sternum. During the procedure, the surgical scissors deviated laterally, resulting in fragmentation of the sternal segments. Under the surgical conditions evaluated in this study, macroscopic assessment indicated that the remaining sternal bone was insufficient to permit stable re-approximation comparable to that required in humans; therefore, no closure attempt was made. Conclusions: These characteristics limited reproduction of the retrosternal conditions encountered during human median sternotomy. In this two-animal feasibility assessment, the rabbit median sternotomy model demonstrated anatomical and technical limitations that may reduce its translational fidelity for studies specifically intended to reproduce the retrosternal conditions of human redo sternotomy.

Journal of Clinical Medicine doi: 10.3390/jcm15218615

Authors: Gabriele Melegari Andrea Tognù Eros Pilia Domenico Santonastaso Elisabetta Bertellini Alberto Barbieri

Background: Gram-negative bacterial infections represent an increasingly relevant challenge in orthopedic surgery, particularly in complex patients exposed to major trauma, revision procedures, prolonged hospitalization, previous antimicrobial therapy, and intensive care. Although Gram-positive organisms remain predominant in prosthetic joint infections (PJIs) and fracture-related infections (FRIs), the emergence of multidrug-resistant (MDR) Gram-negative pathogens has important implications for perioperative management, antimicrobial prophylaxis, and treatment. Objective: This narrative review examines the epidemiology, pathogenesis, antimicrobial resistance, and management of Gram-negative orthopedic infections, with particular emphasis on issues relevant to anesthesiologists and intensive care physicians. Methods: A structured narrative literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science from database inception to July 2026, according to the principles of the Scale for the Assessment of Narrative Review Articles (SANRA). Original studies, systematic reviews, meta-analyses, guidelines, consensus statements, and relevant narrative reviews addressing Gram-negative infections in orthopedic surgery were considered. Results: Gram-negative pathogens account for a minority of orthopedic infections but become increasingly relevant in complex PJIs, FRIs, open fractures, revision surgery, and patients with substantial healthcare exposure. Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii are among the principal pathogens involved. Their clinical relevance is amplified by biofilm formation and increasingly complex antimicrobial resistance mechanisms. Perioperative antibiotic prophylaxis should remain individualized in patients colonized or previously infected with MDR Gram-negative organisms, avoiding indiscriminate broad-spectrum prophylaxis. Once infection is established, management requires adequate microbiological sampling, surgical source control, and susceptibility-guided antimicrobial therapy. New β-lactam/β-lactamase inhibitor combinations and cefiderocol have expanded therapeutic options against resistant Gram-negative pathogens; however, evidence specifically supporting cefiderocol for bone and joint infections remains limited. Conclusions: Gram-negative orthopedic infections represent an emerging challenge at the intersection of orthopedic surgery, infectious diseases, anesthesiology, and critical care. Early recognition of high-risk patients, individualized perioperative strategies, effective source control, resistance-guided antimicrobial therapy, and multidisciplinary management are essential.

Journal of Clinical Medicine doi: 10.3390/jcm15218613

Authors: Pawel Jaworski Mateusz Wityk Piotr Major Wiesław Tarnowski Natalia Dowgiałło-Gornowicz

Introduction: Driven by impaired insulin secretion and insulin resistance, type 2 diabetes mellitus (T2DM) stands as a chronic metabolic disorder. While metabolic bariatric surgery (MBS) is highly effective, data on older populations remain limited. The objective of this study is to assess the long-term outcomes and clinical predictors of T2DM remission in patients aged 60 and older following sleeve gastrectomy. Materials and Methods: This retrospective cohort study evaluates data retrieved from the medical records of 129 patients aged ≥60 years with T2DM who underwent primary laparoscopic sleeve gastrectomy between 2008 and 2022. Baseline demographic characteristics, body mass index (BMI), T2DM duration, and treatment modalities were extracted. Metabolic outcomes, including total weight loss (%TWL) and excess weight loss (%EWL), were evaluated over a median follow-up of 6.0 years. Results: The cohort had a median age of 66 years, with females accounting for 62% of the population. At the final follow-up, the median %TWL was 19.4%, and the median %EWL was 47.8%. Overall, T2DM remission was achieved in 80 (62.0%) patients, whereas 16 (12.4%) patients experienced no clinical changes. Duration of T2DM of more than 10 years was associated with a lower likelihood of remission of T2DM (p = 0.007). Conclusions: Our findings demonstrate that a substantial proportion of patients aged 60 years and older achieved T2DM remission at the last available follow-up following sleeve gastrectomy. A decreased likelihood of remission correlated with longer preoperative T2DM duration, which highlights the clinical value of offering metabolic surgery early to eligible older patients.

Journal of Clinical Medicine doi: 10.3390/jcm15218612

Authors: Christos Kourek Serge Sicouri Alexandros Briasoulis Dimitrios E. Magouliotis Andrew Xanthopoulos Ioannis Paraskevaidis Basel Ramlawi

Background/Objectives: Atrial fibrillation (AF) after intracerebral hemorrhage (ICH) creates a therapeutic conflict: withholding oral anticoagulation may increase ischemic stroke risk, whereas resumption of anticoagulation may increase recurrent ICH. Left atrial appendage occlusion (LAAO) offers a nonpharmacologic alternative, but isolated stroke or bleeding rates do not describe the overall benefit–harm balance. This focused review examines net clinical benefit (NCB) as a decision framework for LAAO after ICH and presents a secondary benchmark-adjusted analysis derived from our prior systemaatic review and meta-analysis. Methods: Thirteen endocardial LAAO cohorts with complete data for ischemic stroke, recurrent ICH, major bleeding, and all-cause death contributed to the analysis. The component event data and prespecified severity weights were carried forward from the prior meta-analysis; the external benchmark comparison, study-level benchmark-adjusted NCB synthesis, and benchmark-sensitivity analyses were not part of that report and constitute the distinct secondary analysis presented here. Results: Prespecified external benchmark rates were 8.0, 2.0, 3.0, and 6.0 events per 100 patient-years, respectively. Unweighted and severity-weighted NCB were evaluated using both pooled-rate and study-level Hartung–Knapp random-effects approaches. Study-level pooled NCB was 12.20 events per 100 patient-years (95% CI, 8.61–15.79; I2 = 96%), and weighted NCB was 14.39 (95% CI, 8.84–19.94; I2 = 94%). Additional two-component analyses using PRESTIGE-AF reference rates yielded unweighted NCB estimates of 5.65 and 2.06 events per 100 patient-years for no-OAC and DOAC comparator scenarios, respectively. Excluding all-cause mortality from the original model yielded an unweighted NCB of 8.41. These exploratory results highlight the sensitivity of NCB estimates to comparator selection and endpoint composition. Conclusions: Contemporary randomized evidence, including PRESTIGE-AF, CLOSURE-AF, and CHAMPION-AF, reinforces that benefit–harm balance is population-, comparator-, endpoint-, and time-horizon-dependent. Accordingly, these NCB estimates should be interpreted as decision-analytic and hypothesis-generating rather than causal treatment effects. ICH-specific randomized comparisons remain essential.

Journal of Clinical Medicine doi: 10.3390/jcm15218611

Authors: Ahmet Atasever Sinan Efe Yazici Yildiray Yuzer

Background/Objectives: Tumor size and number do not fully capture the risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation. We examined whether the pretransplant tumor-to-liver maximum standardized uptake value (SUV) ratio on 18F-FDG PET/CT is associated with recurrence, and assessed the previously reported cutoff of 1.43 in an independent cohort. Methods: We retrospectively analyzed 227 adults who underwent liver transplantation for HCC between July 2004 and November 2024 and had pretransplant FDG PET/CT. The primary endpoint was time to recurrence (TTR). The SUV ratio was analyzed as a continuous, log2-transformed variable in Cox models adjusted for age, MELD-Na, alpha-fetoprotein (AFP), and Milan status; the 1.43 cutoff was a secondary analysis. Death without recurrence was treated as a competing event. Results: Over a median follow-up of 80 months, 43 patients developed recurrence and 86 died. Each doubling of the SUV ratio was associated with a higher recurrence rate (adjusted HR 6.68; 95% CI 3.58–12.47) and higher mortality (HR 2.79; 95% CI 1.72–4.53). The 5-year cumulative incidence of recurrence was 44.7% with a ratio >1.43 and 7.5% with a ratio ≤1.43. Only 2 of 51 non-FDG-avid tumors recurred. The ratio added prognostic information to Milan criteria and AFP (likelihood ratio χ2 28.5; p < 0.001) and stratified risk within the Milan criteria (5-year cumulative incidence of recurrence, 26.4% vs. 5.2%). Conclusions: A high pretransplant tumor-to-liver SUV ratio was strongly associated with recurrence independently of Milan status and AFP. External validation with standardized PET protocols is needed before clinical use.

Journal of Clinical Medicine doi: 10.3390/jcm15218614

Authors: Grzegorz Procyk Adam Sukiennik Jakub Michal Zimodro

Background/Objectives: Low-density lipoprotein cholesterol (LDL-C) measurements include cholesterol carried by lipoprotein(a) [Lp(a)], which may influence the clinical classification of familial hypercholesterolemia (FH). We aimed to systematically review the available evidence and estimate the pooled proportion of individuals reclassified to a lower FH diagnostic category after correction of LDL-C for estimated Lp(a)-cholesterol. Methods: Embase, PubMed, and Scopus were searched from inception through 9 October 2026. We included observational studies with cross-sectional analyses of adults aged ≥18 years evaluated for suspected FH using the Dutch Lipid Clinic Network (DLCN) criteria before and after LDL-C correction for Lp(a)-cholesterol. Lp(a)-cholesterol was estimated as 30% of Lp(a) mass. The primary endpoint was reclassification to a lower DLCN diagnostic category among participants with possible, probable, or definite FH at baseline. Random-effects models were used to estimate pooled proportions. Risk of bias was assessed using the JBI critical appraisal tool for cross-sectional studies. Results: Four studies comprising 2970 individuals were included. The primary analysis included 2793 participants with possible, probable, or definite FH at baseline. After LDL-C correction for estimated Lp(a)-cholesterol, 19.8% (95% CI, 15.9–24.5) were reclassified to a lower DLCN diagnostic category. Conclusions: Correction of LDL-C for estimated Lp(a)-cholesterol resulted in downward DLCN reclassification in approximately one in five adults with at least possible FH from selected referral populations. The clinical utility of this adjustment, including its consequences for genetic testing and missed FH diagnoses, needs to be investigated.

Journal of Clinical Medicine doi: 10.3390/jcm15218610

Authors: Anar Mammadli Erdem Diker

Background/Objectives: Hemoglobin may identify differences in prognosis among patients with advanced chronic kidney disease (CKD) and documented myocardial ischemia. We examined the shape of its association with clinical outcomes in ISCHEMIA-CKD. Methods: This exploratory observational secondary analysis included 758 randomized participants with baseline hemoglobin. The primary endpoint was the parent-trial composite of all-cause death or myocardial infarction (MI). Adjusted Cox regression with restricted cubic splines characterized the hemoglobin association. Mortality and pooled nonfatal MI were examined using Cox and competing-risk models. Results: Median hemoglobin was 11.1 g/dL; 247 participants experienced the primary endpoint. The adjusted association departed from log-linearity (p = 0.015), with higher hazard at lower hemoglobin and an uncertain upper limb. Relative to 11.1 g/dL, the hazard ratio (HR) at 8 g/dL was 1.98 (95% confidence interval [CI] 1.26–3.10). As a linear summary, the HR per 1 g/dL lower hemoglobin was 1.13 (95% CI 1.04–1.23) for the primary endpoint. Corresponding mortality associations were present, whereas pooled nonfatal MI showed no clear association (subdistribution HR 1.03, 95% CI 0.89–1.21). Exploratory treatment interaction tests provided no convincing evidence of effect modification (linear p = 0.059; spline p = 0.124). Conclusions: Among selected, clinically stable participants with advanced CKD and moderate-to-severe ischemia, lower baseline hemoglobin was associated with adverse prognosis. Nonlinearity and uncertainty at higher values argue against a single summary estimate or an inferred optimal target. These potentially confounded findings neither establish benefit from hemoglobin correction nor support hemoglobin-based selection of invasive versus conservative management.

Journal of Clinical Medicine doi: 10.3390/jcm15218609

Authors: Ivan Levaj Ivan Bojanić Ana Pilipović Jan Homolak Dinko Nizić Marko Šimunović Josip Vlaić Mislav Jelić Mario Josipović

Background/Objectives: To compare the morphological and biomechanical properties of a quadrupled gracilis (4GR) graft with two standard hamstring grafts for anterior cruciate ligament (ACL) reconstruction: a quadrupled semitendinosus (4ST) graft and a doubled semitendinosus–gracilis (2ST2GR) graft. Methods: Tendon specimens were obtained from 30 cadaveric donors (mean age, 42.6 years; range, 21–56 years). Tendon and graft dimensions were measured before biomechanical testing. Grafts underwent standardized preconditioning followed by load-to-failure testing at a displacement rate of 20 mm/min. Differences between graft types were analyzed using a generalized linear mixed-effects model, with results expressed as estimated marginal means with 95% confidence intervals (CI). Results: The mean 4GR graft length was 64.7 (95% CI, 61.6–67.8) mm, with 80% exceeding 60 mm. Graft diameter was greatest in the 4ST group, intermediate in the 2ST2GR group, and smallest in the 4GR group (7.98 [95% CI, 7.67–8.29], 7.41 [95% CI, 7.12–7.70], and 6.12 [95% CI, 5.89–6.36] mm, respectively). The 4ST graft demonstrated significantly greater maximum force than both the 4GR and 2ST2GR grafts, whereas no significant difference was observed between the 4GR and 2ST2GR grafts. In contrast, tensile strength was significantly higher in the 4GR grafts than in both the 4ST and 2ST2GR grafts. Stiffness was significantly higher in the 4ST grafts than in the 4GR grafts, whereas Young’s modulus was significantly higher in the 4GR grafts than in the 4ST grafts. Conclusions: The 4GR graft provided sufficient length for all-inside ACL reconstruction in most specimens. Despite its smaller diameter and lower absolute load-bearing capacity than 4ST, the 4GR graft demonstrated higher tensile strength and Young’s modulus, indicating favorable intrinsic mechanical properties. These findings may help inform graft selection in selected reconstructive procedures.

Journal of Clinical Medicine doi: 10.3390/jcm15218608

Authors: Roman Sonkin Anna Khalemsky Carmi Bartal

Background/Objectives: Whether influenza increases the risk of newly diagnosed atrial fibrillation (NDAF) beyond the effect of acute illness is uncertain. We examined whether viral etiology and prior influenza vaccination (exposures) were associated with NDAF within one year (primary outcome), and whether NDAF was associated with one-year all-cause mortality (secondary outcome), in hospitalized adults. Methods: This retrospective cohort study included 21,653 adults hospitalized in Clalit Health Services facilities (2012–2020) who underwent respiratory-virus PCR testing: influenza A (n = 2829), influenza B (n = 992), other respiratory viruses (n = 561), and PCR-negative concurrent controls (n = 17,271). NDAF within 365 days was analyzed with cause-specific Cox and Fine–Gray models, including time windows; mortality with time-dependent Cox models; and vaccination with propensity score matching. Results: NDAF was recorded in 1228 patients (5.7%), 56% of them on the day of admission. Compared with PCR-negative patients, no viral etiology was associated with a higher hazard of NDAF (influenza A: HR 0.87, 95% CI 0.73–1.04; influenza B: HR 0.73, 95% CI 0.53–1.00), including within 30 days and after excluding day-0 events. NDAF was associated with higher one-year mortality (HR 1.68, 95% CI 1.52–1.87), especially when recorded after discharge (HR 3.04). Influenza vaccination was not associated with NDAF (HR 0.97, 95% CI 0.85–1.10). Conclusions: Among hospitalized adults tested for respiratory viruses, neither influenza nor prior vaccination was associated with NDAF compared with PCR-negative inpatients, who were not necessarily of similar acute illness severity. NDAF marked a higher hazard of one-year mortality.

Journal of Clinical Medicine doi: 10.3390/jcm15218607

Authors: Güray Ceylan Muammer Bilici Ünzile Işıl Yüce

Background/Objectives: Hashimoto’s thyroiditis (HT) is associated with autoimmune thyroid inflammation, but its systemic inflammatory, immunonutritional, and atherogenic lipid profile across thyroid functional groups remains insufficiently characterized. This study aimed to evaluate routinely available inflammatory, immunonutritional, and atherogenic indices across the HT spectrum and to examine their relationships with thyroid function and autoimmunity. Methods: This retrospective study included newly diagnosed, untreated adult patients with HT and healthy controls without documented comorbidities. After exclusions and propensity score matching for age, sex, and body mass index, 148 patients with HT and 74 controls were analyzed. Patients with HT were classified as euthyroid HT (EH, n = 62), subclinical hypothyroidism (SCH, n = 47), or overt hypothyroidism (OH, n = 39). A total of 44 demographic, thyroid-related, hematologic, biochemical, lipid, inflammatory, immunonutritional, and atherogenic variables were evaluated. Elastic Net–penalized logistic regression, multivariable logistic regression, correlation analysis, and receiver operating characteristic curve analysis were performed. Results: HT was associated with a distinct systemic profile characterized by higher inflammatory and atherogenic indices and alterations in immunonutritional indices. Across the control, EH, SCH, and OH groups, systemic inflammation response index (SIRI; 0.5 vs. 0.8 vs. 1.0 vs. 1.4, p < 0.001) and atherogenic index of plasma (AIP; 0.1 vs. 0.3 vs. 0.5 vs. 0.8, p < 0.001) showed an ascending pattern, whereas prognostic nutritional index (PNI; 56.0 ± 3.2 vs. 50.2 ± 6.0 vs. 46.8 ± 5.5 vs. 40.6 ± 7.0, p < 0.001) showed a descending pattern. In multivariable models, SIRI and AIP were independently associated with EH compared with controls, whereas SIRI, AIP, and PNI were independently associated with SCH compared with EH and with OH compared with SCH. SIRI and AIP showed strong positive correlations with thyroid-stimulating hormone and negative correlations with free thyroxine, while PNI showed the opposite pattern. These indices also differed significantly according to anti-thyroid peroxidase and anti-thyroglobulin antibody status. Conclusions: Distinct inflammatory, immunonutritional, and atherogenic lipid profiles were observed across HT groups. SIRI and AIP may reflect systemic alterations even in EH, whereas lower PNI may reflect immunonutritional alterations associated with SCH or OH.

Journal of Clinical Medicine doi: 10.3390/jcm15218605

Authors: Nikodem Kuczyński Mariusz Sowa Mariola Głowacka Edyta Zomkowska Dawid Pilewski

Chronic subdural hematoma (cSDH) is an increasingly common neurological disorder in older adults and may present with cognitive decline, gait instability, recurrent falls, and loss of independence rather than overt focal deficits. Because these symptoms overlap with dementia, delirium, parkinsonism, and frailty, diagnosis may be delayed despite the potential for meaningful recovery after treatment. This narrative review summarizes evidence on clinical recognition, treatment, early mobilization, rehabilitation, and patient-centered recovery in older adults with cSDH. A targeted search of PubMed/MEDLINE, Scopus, and Web of Science identified randomized trials, observational studies, systematic reviews, meta-analyses, guidelines, and consensus statements available through July 2026. Surgical decompression may improve cognition and mobility, but the magnitude and durability of recovery vary. Premorbid cognitive and functional status, frailty, malnutrition, postoperative delirium, and complications are associated with outcomes, although causal effects are incompletely established. Postoperative drainage reduces recurrence; selected randomized trials suggest that middle meningeal artery embolization reduces recurrence or treatment failure, whereas evidence for independent cognitive and gait benefits remains limited. Early mobilization may reduce medical complications. Evidence specific to cSDH remains insufficient to prescribe a standardized exercise dose or progression. Multidimensional follow-up and prospective trials using cognitive, gait, quality-of-life, and participation outcomes are needed to determine whether successful hematoma treatment translates into restored independence and meaningful daily function.

Journal of Clinical Medicine doi: 10.3390/jcm15218606

Authors: Haengjin Ohe Jinhee Hwang Suk Ran Kim Seonwoo Kim Sun Cheol Park

Background/Objectives: Intermittent claudication (IC) secondary to peripheral artery disease (PAD) causes exertional leg pain and discomfort, which limits functional walking capacity. The clinical efficacy of Ginkgo biloba extract (GBE) as a therapeutic agent for IC is debatable. This systematic review and meta-analysis evaluated the efficacy and safety of GBE compared with a placebo in patients with IC due to PAD. Methods: Databases including PubMed, Embase, the Cochrane Library, and CINAHL were searched until 24 April 2026. Eligible studies included randomized, double-blind, controlled trials (RCTs) comparing placebo. Primary outcome was absolute claudication distance (ACD) at the end of the study. Secondary outcomes were initial claudication distance (ICD), ankle-brachial index (ABI), ankle pressure, and adverse events. Walking outcomes across various treadmill protocols were standardized to estimate caloric expenditure (kcal). A random-effects model was used to pool the effect estimates across trials. Risk of bias was assessed using the Cochrane risk-of-bias tool (RoB 2). Results: A total of 14 RCTs comprising 893 participants represent the total number randomized were included. GBE was associated with a statistically significant but modest improvement in ACD compared with placebo (mean difference [MD], 3.50 kcal; 95% CI, 0.02 to 6.98; p = 0.049). This benefit was significant in trials with a 24-week duration (MD, 4.67 kcal; 95% CI, 2.26 to 7.08; p < 0.001) but not in 12–16 weeks trials (MD, 1.35 kcal; 95% CI, −2.39 to 5.09; p = 0.48). No significant changes were observed for ICD or resting ABI/ankle pressure. GBE was well tolerated, with an overall adverse event incidence comparable to placebo. Conclusions: In patients with IC due to PAD, GBE therapy improves absolute walking performance, with a significant effect observed in trials evaluating 24 weeks of treatment. Given its favorable safety and tolerability profile, GBE can represent a clinically relevant and well-tolerated therapeutic option to support functional walking capacity, particularly for patients unable to tolerate or use conventional pharmacological agents.

Journal of Clinical Medicine doi: 10.3390/jcm15218604

Authors: Kyoung-Sim Jung Jin-Hwa Jung Hwi-Young Cho Tae-Sung In

Objectives: Carpal tunnel syndrome (CTS) is associated with impaired hand sensorimotor function, but wrist and thumb kinematics during sustained smartphone use remain unclear. This study compared joint posture, angular velocity, and time-related kinematic changes during a 30-min smartphone typing task between patients with CTS and healthy controls. Methods: Thirteen patients with CTS and 14 healthy controls completed a standardized 30-min two-handed smartphone typing task. Three-dimensional wrist and thumb kinematics were recorded, and mean joint angles and root mean square (RMS) angular velocities were calculated for wrist extension, wrist ulnar deviation, thumb metacarpophalangeal (MCP) flexion, MCP abduction, and interphalangeal (IP) flexion. Outcomes were analyzed over the entire task and across three 10-min intervals. Results: The CTS group showed greater wrist extension than the healthy control group (39.27 ± 9.31° vs. 27.99 ± 9.92°, p = 0.005) and less thumb MCP flexion (25.94 ± 8.43° vs. 32.66 ± 6.50°, p = 0.028). No significant between-group differences were found for the other joint angles or RMS angular velocities. No significant time effects or group × time interactions were observed. Conclusions: Patients with CTS demonstrated greater wrist extension and reduced thumb MCP flexion during sustained smartphone typing. These findings suggest that CTS-related kinematic differences may be more apparent in specific joint postures than in overall movement velocity.

Journal of Clinical Medicine doi: 10.3390/jcm15218603

Authors: Katsuaki Kanbe Ayako Kubota

Background/Objectives: Ozoralizumab, a tumor necrosis factor (TNF) blocker, was launched in Japan in 2022. However, there is no evidence to determine whether this biological agent is the best choice for patients with rheumatoid arthritis (RA). To investigate the clinical factors related to the efficacy of ozoralizumab, we analyzed 100 patients treated with ozoralizumab in real-world practice. Methods: 100 patients with RA treated with ozoralizumab (female, n = 87; male, n = 13), with a mean age of 61.8 years, and a mean disease duration of 10.7 years. Methotrexate (MTX) and prednisolone (PSL) were used by 49% and 10% of patients, respectively. The cohort included biologic-naïve patients (n = 39) and patients who switched from another biologic agent (n = 61). Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) positivity rates were 91% and 74%, respectively. We analyzed clinical factors associated with Disease Activity Score 28 C-reactive protein (DAS28-CRP) at 24 weeks and assessed remission, treatment continuation, and adverse-event rates. Results: DAS28-CRP decreased from 4.38 at baseline to 2.59 at 24 weeks. The remission rate was 59% at 24 weeks. DAS28-CRP at 24 weeks correlated with the anti-CCP titer in the MTX-positive group. Disease duration was correlated with DAS28-CRP at 24 weeks in the MTX-negative and biologic-naïve groups. Remission at 24 weeks was correlated with disease duration. Adverse events occurred in 9% of patients, and all cases improved. Conclusions: The efficacy and safety of ozoralizumab were confirmed in 100 patients with RA. Anti-CCP and disease duration are clinical factors that may predict the efficacy of ozoralizumab in RA. Therefore, a high anti-CCP titer or early RA may indicate the efficacy of ozoralizumab in real-world RA practice.

Journal of Clinical Medicine doi: 10.3390/jcm15218602

Authors: Dong Eun Lee Jong Kun Kim Min-Seong Kwak Kyung-Woo Lee Sin-Youl Park

Background/Objectives: Initial classification of skin lesions in the emergency department (ED) is difficult when dermatology consultations are limited. This study externally validated a deep learning (DL) algorithm for classifying three common ED skin lesions and explored whether algorithmic pre-classification was associated with changes in the classification performance of medical staff. Methods: A ResNet-50-based algorithm was developed using 6000 clinical images from 4815 patients. For external validation, 100 images from an independent institution were classified by the algorithm and nine medical staff members (three emergency medicine specialists, three residents, and three physician assistant [PA] nurses). Fifteen days later, the staff reclassified the same randomly reordered images with the algorithmic pre-classification provided. Results: In external validation, the algorithm showed an overall accuracy of 0.96 (95% confidence interval [CI], 0.90–0.99), lesion-specific balanced accuracies of 0.95–0.96, and a macro-average area under the receiver operating characteristic curve of 0.98 (95% CI, 0.95–1.00). Unassisted, the three PA nurses differed significantly from the algorithm for urticaria and herpes zoster (all p < 0.01, McNemar’s exact test). After receiving algorithmic assistance, all medical staff showed a balanced accuracy of 0.97 or higher for all three lesions. In the mixed-effects model, assistance was associated with higher odds of correct classification (odds ratio 25.9, 95% CI 11.7–57.2), and inter-rater agreement (Fleiss’ κ) increased from 0.70 to 0.97. Conclusions: The algorithm demonstrated high classification performance on independent external validation, and algorithmic assistance was associated with improved classification performance, with the largest absolute gains among medical staff with lower unassisted accuracy. As these findings are exploratory, they should be confirmed in randomized prospective studies.

Journal of Clinical Medicine doi: 10.3390/jcm15218601

Authors: Abdullah Saleh Almutairi Osama Mansour Alnoodaly Sulaiman Mohammed Alrasheed Salman Tarique Ansari Shaul Hameed Kolarkodi

Background/Objectives: Digital guidance of tooth autotransplantation, using cone beam computed tomography (CBCT)-based planning with three-dimensionally (3D) printed donor tooth replicas, surgical guides, navigation or robotics, aims to shorten extra-alveolar time and improve positioning. This systematic review synthesised the clinical, radiographic and operative outcomes of digitally guided autotransplantation and compared them with conventional technique. Methods: Following PRISMA 2020 and PROSPERO registration CRD420261434791, MEDLINE (PubMed and Ovid), Embase, Scopus, Web of Science, CENTRAL and ClinicalTrials.gov were searched from inception to August 2026, with Google Scholar and reference-list screening. Clinical studies of at least five digitally guided transplanted teeth or patients were eligible. Two reviewers independently screened, extracted data and assessed risk of bias (RoB 2, ROBINS-I or the JBI case-series checklist); certainty was rated with GRADE. Results: Twenty-five studies reported in 33 publications (2012–2026; one randomised, eight comparative non-randomised, sixteen single-arm; approximately 1300 patients) were included. All used CBCT- or CT-derived 3D-printed replicas, eleven with printed guides; none used navigation or robotics. In guided arms, survival was 92–100% and success 86–100% at 6 months to 5 years. Extra-alveolar time was under one minute in eleven reports, most donor teeth fitted at the first attempt, and positional deviation from the plan was about 1–2 mm. Compared with the conventional technique, guidance shortened surgical time by 13–15 min in two studies (low certainty) and was associated with higher survival and success and less root resorption in retrospective cohorts at serious risk of bias, whereas the registered controlled trial and a prospective paediatric cohort found no significant clinical difference (very low certainty). Conclusions: Digital guidance improves the operative efficiency and positional control of autotransplantation. Clinical superiority over conventional technique remains unproven; randomised trials with standardised outcomes and follow-up beyond two years are needed.

Journal of Clinical Medicine doi: 10.3390/jcm15218600

Authors: Seung Hee Jeon Jeong Ah Shin Young-Jung Roh

Central serous chorioretinopathy (CSC) is increasingly understood within the pachychoroid disease spectrum, with choroidal abnormalities playing a central pathogenic role. Nevertheless, the retinal pigment epithelium (RPE) remains critical to outer blood–retinal barrier function and subretinal fluid (SRF) homeostasis, and represents a potentially modifiable therapeutic target. RPE-targeted laser therapies employ biologically distinct approaches, ranging from sublethal RPE modulation with subthreshold micropulse laser and nondamaging retinal laser therapy to selective RPE injury followed by repair with selective retina therapy. We reviewed their laser–tissue interactions, dosimetry, clinical outcomes, and safety in CSC, focusing on how different RPE responses contribute to fluid resolution. Experimental and clinical observations provide a biological basis for considering how sublethal RPE modulation and selective RPE injury followed by repair may contribute to restoration of the RPE barrier and fluid homeostasis through distinct biological responses. Nevertheless, the mechanisms linking these RPE responses to SRF resolution remain incompletely understood. RPE-targeted laser therapies represent both potential therapeutic approaches and a means of gaining mechanistic insight into the contribution of RPE dysfunction to CSC. However, despite their distinct biological rationales, the clinical evidence supporting these modalities remains heterogeneous and insufficient to establish their comparative efficacy. Optimal treatment parameters, patient selection, and the long-term efficacy and safety of repeated treatment remain to be established.

Journal of Clinical Medicine doi: 10.3390/jcm15218599

Authors: Yusuf Ozlulerden Duran Duzgun Sinan Celen Mesut Berkan Duran Kursat Kucuker Aykut Akinci Aykut Baser Ahmet Baki Yagci

Background: Preservation of sexual function has become a central goal in the surgical management of benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS), yet the impact of treatment on the patient’s partner has rarely been examined. Transperineal laser ablation (TPLA) is an emerging, explicitly ejaculation-sparing technique with a favorable reported sexual function profile. Objective: In this retrospective, single-center, single-arm cohort study, we aimed to longitudinally evaluate erectile function, ejaculatory function and bother, and partner sexual function from the first postoperative week to 12 months after TPLA. Materials and Methods: This retrospective study was based on prospectively collected outcome data from 36 consecutive sexually active men who underwent ultrasound-guided TPLA (SoracteLite™/EchoLaser™) for moderate-to-severe LUTS/BPH, with assessments at postoperative weeks 1 and 2 and months 1, 3, 6, 9, and 12. Erectile function (IIEF-5), ejaculatory function and bother (MSHQ-EjD), and partner sexual function (Female Sexual Function Index, FSFI) were assessed longitudinally alongside IPSS, Qmax, post-void residual volume, and prostate volume. Results: Median baseline IPSS was 31 and prostate volume was 70 mL. IIEF-5 declined transiently at weeks 1 and 2 (both p < 0.001), returned to baseline by month 1, and did not differ significantly from baseline thereafter, consistent with preservation of erectile function. MSHQ-EjD function scores likewise declined transiently in the early postoperative period before rising modestly above baseline from month 3 onward (all p < 0.001, months 3–12), with a parallel change in the bother domain over the same period. Partner FSFI scores followed a similar temporal pattern, declining transiently during the first postoperative month, normalizing by month 3, and was slightly higher than baseline at month 12 (p < 0.05). IPSS improved from 31 to 8 and prostate volume decreased by a median of 52.5% at 12 months (both p < 0.001). No Clavien–Dindo grade ≥II complication occurred. Conclusions: In this retrospective single-arm cohort, TPLA was followed by substantial relief of severe LUTS. The findings are compatible with preservation of erectile function and a small increase in ejaculatory function scores, with partner sexual function following a parallel, non-causal trajectory. In the absence of a comparator group, these later changes cannot be attributed to TPLA itself and may partly reflect urinary symptom relief, medication changes, regression to the mean, or expectation effects. Controlled studies incorporating partner-reported outcomes are needed to determine whether TPLA confers couple-level sexual benefit.

Journal of Clinical Medicine doi: 10.3390/jcm15218597

Authors: Ayse Sena Sisman Ugur Onal Busra Calisir Emel Yilmaz Esra Kazak Yasemin Heper Guven Ozkaya Remzi Iscimen Cuneyt Ozakin Beyza Ener Halis Akalin

Background/Objectives: The risk factors for the severe presentation (severe sepsis or septic shock) are not fully understood in ICU-acquired candidaemia. The primary objective of this study was to evaluate risk factors for the severe presentation (severe sepsis or septic shock) and mortality in patients with candidaemia in ICUs. Secondarily, we compared 28-day mortality between patients treated with fluconazole and those treated with an echinocandin. Methods: A retrospective cohort design was employed in a single-center ICU setting, encompassing a study period from 2004 to 2023. Adult patients who had Candida growth in blood cultures taken 48 h after admission to the ICU were included in the study. Risk factors for the severe presentation (severe sepsis and septic shock) and mortality were evaluated in the 141 patients included in the study. The treatment comparison between fluconazole and echinocandins was performed in 113 patients (with 48-h rules) and 125 patients (without 48-h rules). Results: Among 141 patients, 77 (54.6%) died within 28 days. We found that in the multivariable model, APACHE II score, TPN use, steroid use, and concomitant bacteremia were associated with severe presentation. Each one-point increase in APACHE II score was associated with higher risk of severe presentation (adjusted OR 1.146, 95% CI 1.056–1.242; p = 0.001). TPN use and steroid use were also associated with higher risk (adjusted OR 3.297, 95% CI 1.265–8.590; p = 0.015; and adjusted OR 6.067, 95% CI 1.486–24.768; p = 0.012, respectively). Concomitant bacteraemia was associated with lower odds of severe presentation. Patients with severe presentation (severe sepsis or septic shock) had a higher risk of 28-day mortality than patients with sepsis (adjusted OR 8.06, 95% CI 2.60–25.00; p < 0.001). In the primary cohort (n = 113; overlap weights), 28-day mortality was 49.2% with fluconazole and 52.1% with echinocandin (OR 1.12, 95% CI 0.37–3.45; p = 0.838). Results were consistent in the 125-patient cohort without the 48-h rule (OR 1.40, 95% CI 0.51–3.81; p = 0.508). Conclusions: Each one-point increase in APACHE II score on admission, TPN use, and steroid use was associated with severe presentation in ICU-acquired candidaemia. The severity of the clinical presentation at the onset of candidaemia (presence of severe sepsis or septic shock) was strongly associated with 28-day mortality. No difference in 28-day mortality was detected between fluconazole and echinocandin treatment, but this comparison was imprecise and cannot inform antifungal choice.

Journal of Clinical Medicine doi: 10.3390/jcm15218598

Authors: Benjamin Treichl Mirjam Bachler Jennifer Gebetsberger Philipp Martin Lichtenberger Pia Tscholl Johannes Bösch Daniel Niederbrunner Daniel Stürzel Michael Rauscher Dietmar Fries

Background/Objectives: Early fluid resuscitation is a cornerstone of trauma care, but the relationship between resuscitation strategies and acute kidney injury (AKI) remains insufficiently characterized. This study aimed to evaluate whether administration of 4% succinylated gelatin is associated with the development of AKI in critically ill trauma patients during the first seven days of intensive care unit (ICU) treatment. Methods: We conducted an observational retrospective single-center cohort study including 215 adult trauma patients admitted to the ICU at a tertiary care center between 2015 and 2020. Gelatin exposure, kidney function, and clinical outcomes were assessed from the pre-ICU phase through the first ICU week. The primary outcome was the development of AKI, at stage ≥ 2 of the Kidney Disease: Improving Global Outcomes (KDIGO) staging. We used mixed-effects models, competing-risk analyses, correlation analyses and exploratory unsupervised clustering to explore associations between gelatin use and renal outcomes. Results: AKI occurred in 17% of patients and was associated with older age, higher Simplified Acute Physiology Score 3 (SAPS3), pre-existing comorbidities, and early signs of hemodynamic and metabolic compromise. Gelatin doses of ≥10 mL/kg/day were not associated with a consistent rise in serum creatinine or progression of AKI over time. Multivariable regression models revealed no independent association between gelatin and worsening AKI. Instead, KDIGO stage worsening was primarily associated with AKI present at ICU admission and with crystalloid volume. Clustering analysis identified a high-risk phenotype with increased gelatin exposure, but this cluster also showed pronounced shock and inflammation, suggesting confounding by indication. In a competing-risk analysis, gelatin was not associated with new-onset AKI, whereas higher gelatin doses were associated with a lower rate of ICU discharge. Conclusions: In this retrospective cohort of critically ill trauma patients, succinylated gelatin administration showed no statistically significant association with KDIGO-defined AKI progression across unadjusted and adjusted models. Gelatin doses of ≥10 mL/kg/day were more frequently administered in patients with greater hemodynamic instability, suggesting that gelatin use primarily reflected underlying illness severity rather than acting as a direct nephrotoxic agent. These findings provide no evidence of an independent nephrotoxic effect of gelatin when used as part of balanced trauma resuscitation strategies.

Journal of Clinical Medicine doi: 10.3390/jcm15218596

Authors: George Apostolidis Petroula Nana Giuseppe Panuccio José I. Torrealba Daour Yousef al Sarhan Nils Zabel Christian-Alexander Behrendt Tilo Kölbel

Objective: Different endovascular techniques are available for type II endoleak management. This scoping review aimed to summarize the available evidence on the use of N-Butyl cyanoacrylate (NBCA) for type II endoleak management. Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). A protocol was registered on Open Science Framework. A systematic search using the PCC (Population, Concept, Context) framework was performed in PubMed, Scopus and Cochrane Library. Findings were systematically presented using structured tables summarizing NBCA techniques, efficacy and safety outcomes. Results: Following full-text assessment, 65 studies were included, comprising cohort and comparative studies, case reports, technical reports and preclinical studies. Single-arm cohort studies reported technical success rates of 90–100%, complication rates of 0–40% and variable durability outcomes, with clinical success ranging from 88 to 100%, endoleak resolution from 40 to 100% and aneurysm sac increase from 13 to 50%. Comparative studies reported improved outcomes with ethanol addition to the NBCA-ethiodized oil mixture compared with NBCA-ethiodized oil alone, shorter procedure times with direct puncture versus intra-arterial approach and more durable mid-term outcomes with selective embolization of contributing branches. Individually reported complications highlighted embolization risks and technical reports focused on catheter utilization. Pre-emptive embolization showed favorable outcomes on sac diameter reduction and endoleak type II occurrence. Conclusions: NBCA demonstrated technical feasibility for type II endoleak management, with variable durability. Considerable heterogeneity existed in access techniques, mixture ratios and outcome reporting. Preventive use demonstrated promising outcomes. Given the retrospective designs, limited sample sizes and heterogenous outcomes, adequately powered prospective studies are warranted.

Journal of Clinical Medicine doi: 10.3390/jcm15218595

Authors: Vitaliy Koikov Gulmira Derbissalina Zhanar Balmukhamedova Ayagoz Umbetzhanova Zhanagul Bekbergenova Natalya Zemlyanskaya Viktor Zemlyanskiy

Background: The menopausal transition is associated with cardiovascular remodeling, but it remains unclear whether regional alterations in left ventricular (LV) myocardial mechanics are present despite preserved global systolic function. This study investigated myocardial deformation and diastolic function in women during the menopausal transition, with particular attention to the effects of chronological age and cardiometabolic factors. Methods: This cross-sectional study included 153 women aged 45–55 years, comprising 93 perimenopausal and 60 menopausal women. Menopausal status was determined using menstrual history and hormonal assessment. Conventional echocardiography and two-dimensional speckle-tracking echocardiography were performed to assess LV structure, diastolic function, global longitudinal strain (GLS), and regional longitudinal strain. Multivariable regression models were adjusted for age, body mass index, and low-density lipoprotein cholesterol. Results: GLS was similar in menopausal and perimenopausal women (−19.62 ± 2.08% vs. −19.50 ± 1.96%; p = 0.723), whereas mean basal longitudinal strain was less negative in menopausal women (−18.14 ± 2.19% vs. −19.11 ± 2.22%; p = 0.009). This association persisted after multivariable adjustment (β = 1.07, 95% CI 0.27–1.88; p = 0.009). The largest segmental difference occurred in the basal inferior segment, which was considered an exploratory finding. Basal inferior strain was associated with LV diastolic dysfunction (OR 1.13 per 1 percentage-point shift toward less negative strain, 95% CI 1.01–1.26; p = 0.038). Its addition to the clinical model increased the apparent AUC from 0.619 to 0.667 (likelihood-ratio p = 0.035), although the difference between AUCs was not statistically significant by the paired DeLong test (p = 0.167). This finding should be considered exploratory and hypothesis-generating. Conclusions: Menopause was associated with a selective shift toward less negative basal LV longitudinal deformation and less favorable diastolic function despite preserved LVEF and GLS. In an exploratory analysis, basal inferior longitudinal strain was associated with LV diastolic dysfunction, although its apparent incremental discriminative value was modest. Regional longitudinal strain may provide complementary information on subclinical cardiac functional alterations associated with menopausal status, but its clinical utility requires validation in independent cohorts.

Journal of Clinical Medicine doi: 10.3390/jcm15218594

Authors: Duygu Genç Albayrak Duygu İnan Osman Uzman Ahmet Çağdaş Yumurtaş Ufuk Yıldız Burcu Aggül Emir Renda Funda Özlem Pamuk Can Yücel Karabay Ahmet İlker Tekkeşin

Background/Objectives: In patients with non-ST-segment elevation myocardial infarction (NSTEMI), contrast-associated acute kidney injury (CA-AKI) is a clinically important complication of coronary angiography. Whether the Fibrosis-4 (FIB-4) index and aspartate aminotransferase-to-platelet ratio index (APRI) relate to CA-AKI in this setting is unclear. We compared the associations of both indices with CA-AKI. Methods: We retrospectively analyzed 771 patients with NSTEMI who underwent coronary angiography from May 2020 to May 2025. CA-AKI was identified from changes in serum creatinine 48–72 h after contrast administration. Both indices were derived from admission laboratory values. Associations were evaluated using separate multivariable logistic regression models. Discrimination was compared using the paired DeLong test, and the incremental performance of FIB-4 beyond the Mehran score was explored. Results: Overall, 97 patients (12.6%) developed CA-AKI. In the primary adjusted model, FIB-4 was associated with CA-AKI (odds ratio 1.19, 95% confidence interval 1.04–1.36; p = 0.013), but APRI was not. FIB-4 showed modest discrimination but a significantly higher area under the receiver operating characteristic curve (AUC) than APRI (0.614 versus 0.535; DeLong p < 0.001). Adding FIB-4 to the Mehran score improved model fit (likelihood-ratio p = 0.009), but the increase in AUC from 0.646 to 0.666 was not statistically significant (DeLong p = 0.100). Sensitivity analyses showed that the association varied with covariate adjustment. Conclusions: FIB-4 was associated with CA-AKI in the primary adjusted model and showed higher discrimination than APRI. These findings support further investigation of FIB-4 as a potential adjunct to renal risk assessment, although its modest discrimination and uncertain incremental clinical value require independent validation.

Journal of Clinical Medicine doi: 10.3390/jcm15218590

Authors: Chol Min Kang Hyung June Ku Hyung Hwan Moon Seong-Eun Kim Ji Hoon Jo Young Il Choi Dong Hoon Shin

The journal retracts the article titled “Predicting Safe Liver Resection Volume for Major Hepatectomy Using Artificial Intelligence” [...]

Journal of Clinical Medicine doi: 10.3390/jcm15218593

Authors: Nicola Ortalli Alberto Civolani Simone Aldo Lari Emanuela Vargiu Erika Meleddu Maria Maddalena Angioni Alberto Floris Sara Onali Matteo Piga Massimo Claudio Fantini Alessandra Vacca Alberto Cauli

Background/Objectives: This study aimed to evaluate whether liver stiffness (LS), as assessed by transient elastography (TE), is increased in patients with systemic sclerosis (SSc) and to identify the factors associated with LS. Methods: In this exploratory cross-sectional study, the LS value and the prevalence of LS ≥ 5.3 and LS ≥ 7.5 kPa in 94 SSc patients and 50 healthy controls (HCs) were compared by univariate and multivariate analyses (adjusted for age and sex). TE was performed using FibroScan® and LS values were expressed in kPa. Clinical and laboratory variables were analysed as factors potentially associated with LS, LS ≥ 5.3 kPa and LS ≥ 7.5 kPa, in exploratory analyses adjusted for a pre-specified set of confounders. Results: Among the 94 SSc patients, 79 (84%) were female; median age was 59 (49–70) years, and median disease duration was 8 (3–13) years. LS was significantly higher in SSc patients than in HCs in both univariate (5.12 ± 1.95 vs. 4.18 ± 0.98 kPa, p < 0.001) and multivariate analyses (β = 0.289, p = 0.001), with a higher prevalence of LS ≥ 5.3 kPa (40.4% vs. 10.0%, adjOR 6.85, p = 0.001) and LS ≥ 7.5 kPa (11.7% vs. 0%, p = 0.009). Only a limited number of factors were associated with LS abnormalities: telangiectasias (β = 0.222, p = 0.044) and glutamic–oxaloacetic transaminase (GOT) (β = 0.278, p = 0.012) for LS, and GOT (adjOR 1.082, p = 0.020) and anti-centromere antibodies (adjOR 4.09, p = 0.017) for LS ≥ 5.3 kPa. In univariate analysis, LS ≥ 7.5 kPa was associated with pulmonary hypertension (p = 0.049), pre-capillary pulmonary hypertension (p = 0.011), and GOT (p = 0.032); no multivariate model was fitted because of the few events. Conclusions: SSc patients show increased LS values and a higher prevalence of both LS ≥ 5.3 kPa and LS ≥ 7.5 kPa than HCs, easily detectable by TE. These findings are exploratory and require confirmation in larger cohorts to determine whether increased LS in SSc reflects hepatic fibrosis and whether it carries clinical and prognostic implications.

Journal of Clinical Medicine doi: 10.3390/jcm15218592

Authors: Giorgia Sbarra Paolo Antonio Danza Nicoletta Cassano Gino Antonio Vena Alexandre Raphael Meduri Francesca Ambrogio Giuseppe Demichele Aurora De Marco Domenico Bonamonte Antonio Facciorusso Giulia Ciccarese Caterina Foti

Background: Multiple options exist for the treatment of viral warts, but there is not yet a treatment capable of inducing a complete sustained response in all cases. The aim of this narrative review was to evaluate the efficacy and safety of KOH solution in cutaneous and anogenital warts. Methods: A literature search was conducted using the PubMed, Ovid Medline, Google Scholar, Scopus and Embase electronic databases and focusing on articles published in English that described the effects of monotherapy with KOH solution on different wart types. Results: We selected 24 studies involving 2083 patients, of whom 1423 were recruited in KOH groups. The heterogeneity in study designs, patient populations, outcomes and intervention characteristics (e.g., concentration of KOH, frequency of application, and treatment duration) precluded the possibilities of performing a meta-analysis and making direct comparisons among the studies. In many studies, there were small patient samples and short follow-up periods. However, despite such limitations, the available results regarding the use of KOH solution for warts seem to show efficacy rates comparable to those of established therapies, including TCA solution and cryotherapy. Side effects were generally described as mild and transient. KOH-related adverse events include burning sensation, erythema, dyspigmentation, and superficial erosions. Conclusions: Preliminary data suggest the potential clinical utility of KOH solution for the treatment of warts, although more data are needed to obtain definite conclusions and to optimize treatment protocols. Further research should include high-quality studies with extended follow-up periods and standardized outcome measures.

Journal of Clinical Medicine doi: 10.3390/jcm15218588

Authors: Bianca Rocca Javier Solsona-Caravaca Martin Roncaglia Nuria Vallejo Víctor González Fernández Pablo E. Tobías-Castillo Gisela Teixidó-Tura Ruper Oliveró-Soldevila Guillem Casas Filipa Valente Oro Aran Ignacio Ferreira-González José Rodríguez-Palomares Laura Galian-Gay

Tricuspid regurgitation (TR) is associated with adverse clinical outcomes, highlighting the need for echocardiographic assessment beyond conventional severity grading. This narrative review examines the prognostic value and clinical applicability of established and emerging echocardiographic parameters. TR phenotype influences prognosis and response to transcatheter intervention, with more favourable outcomes in atrial than ventricular functional TR. The five-grade TR classification improves risk stratification, with massive or torrential TR associated with worse outcomes despite comparable procedural success. Right ventricular–pulmonary arterial coupling provides valuable prognostic information and may help identify an optimal therapeutic window for transcatheter intervention, particularly in patients with intermediate coupling values. The GLIDE score helps predict anatomical suitability and procedural success for transcatheter edge-to-edge repair, whereas high TRI-SCORE values (≥6) identify patients in whom a significant survival benefit from repair has not been demonstrated. Treatment decisions should therefore integrate symptoms, overall clinical status, procedural feasibility, and expected benefit through individualized Heart Team assessment. Following intervention, the severity of residual TR, ideally mild or less, remains a key determinant of procedural success.

Journal of Clinical Medicine doi: 10.3390/jcm15218591

Authors: Radha Bansal Shezan Fouzdar Swechha Bhatt Shiv Patel Vanessa Sauer Aseman Bagheri Sheshdeh Prajakta Lokhande Shaidah Deghan Anahita Dua

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve cardiovascular outcomes in patients with type 2 diabetes and have emerging relevance in peripheral artery disease (PAD), but their association with platelet function after lower-extremity revascularization is uncertain. We evaluated whether active GLP-1RA exposure was associated with thromboelastography with platelet mapping (TEG-PM) and global hemostatic parameters in patients with diabetes and PAD. Methods: We retrospectively analyzed prospectively collected serial TEG data from adults with diabetes and PAD undergoing lower-extremity revascularization between December 2022 and December 2025. GLP-1RA exposure was defined as active use at each blood draw and treated as time-varying. Platelet outcomes were analyzed using linear mixed-effects models adjusted for nonlinear elapsed time, insulin, aspirin, clopidogrel, ticagrelor, age, sex, body mass index, renal function, coronary artery disease, and hypertension. False discovery rate (FDR) correction was applied within prespecified ADP and arachidonic acid (AA) outcome families. Results: The cohort included 178 patients contributing 462 scheduled measurements; 20 patients contributed 47 GLP-1RA-exposed measurements. At baseline, 13 of 169 patients were receiving a GLP-1RA. Adjusted GLP-1RA-associated differences were −1.98 percentage points for ADP aggregation (95% CI, −10.9 to 6.89; FDR-adjusted p = 0.815), −0.64 mm for ADP maximum amplitude (MA) (95% CI, −6.06 to 4.77; FDR-adjusted p = 0.815), −0.45 percentage points for AA aggregation (95% CI, −13.5 to 12.6; FDR-adjusted p = 0.947), and −1.63 mm for AA-MA (95% CI, −8.28 to 5.03; FDR-adjusted p = 0.947). Global TEG outcomes and GLP-1RA-by-insulin interactions were not significant. The strongest time interaction was observed for ADP-MA (omnibus p = 0.072; FDR-adjusted p = 0.145). Conclusions: No statistically significant associations were detected between active GLP-1RA exposure and pathway-specific platelet reactivity or global hemostatic parameters in this longitudinal PAD cohort. Estimates remained imprecise, and effects of potentially clinically relevant magnitude could not be excluded. The descriptive ADP-mediated temporal pattern warrants prospective evaluation in larger cohorts.

Journal of Clinical Medicine doi: 10.3390/jcm15218589

Authors: Theodoros Chrelias Evangelos Dimakakos Konstantinos Samiotis Kalliopi Varaki Margarita Toumanidou Kyriaki Cholidou Urska Bregar Peter Marschang Chris Manu Nikolaos Michalopoulos Nikolaos Arkadopoulos Nikolaos Papadopoulos

Background: Lymphedema is a chronic condition for which accurate imaging evaluation of the lymphatic system can contribute to diagnosis, disease assessment, and treatment planning. Non-contrast magnetic resonance lymphangiography (NCMRL) is an imaging technique that enables morphological visualization of lymphatic abnormalities without contrast agent administration. This technical report aims to describe the NCMRL protocol routinely implemented at our institution, with particular emphasis on lower-extremity imaging. Methods: The institutional NCMRL workflow performed on a 3 Tesla (3T) magnetic resonance imaging (MRI) system is described, including patient positioning, three-station anatomical coverage, pulse sequence selection, acquisition parameters, geometric alignment, and image post-processing using segmental and panoramic maximum intensity projection (MIP) reconstructions. Results: The report documents the acquisition and post-processing workflow and illustrates its imaging output through representative clinical images. No systematic assessment of diagnostic accuracy, quantitative image quality, or examination success rates was performed. Conclusions: This technical report provides a structured description of an existing institutional NCMRL workflow for lower-extremity imaging. The documented approach may serve as a reference for future protocol optimization and standardization, while its reproducibility and broader clinical applicability require further evaluation.

Journal of Clinical Medicine doi: 10.3390/jcm15218587

Authors: Ng Kaiwen Aaron Qi Yang Goh Bryan Xiangrong Sim Sri Yudah Pauline Poh Lin Chan Hla Myint Htoon Audrey Wei Lin Chia

Aim: In this retrospective audit, Atropine 0.025% eyedrops were evaluated in a clinical setting. Method: Children aged 4–16 years, who were started on Atropine 0.025% with at least 6 months of follow-up, were included. A total of 588 eyes (299 children) were classified as treatment-naïve eyes started on Atropine 0.025% daily (Group A, n146), eyes progressing on Atropine 0.01% daily increased to 0.025% daily (Group B, n287) or combined with myopia control glasses (Group C, n66), and those stable on Atropine 0.01% twice daily converted to Atropine 0.025% daily (Group D, n89). Spherical equivalent (SE) and axial length (AL) were recorded from 6 months before treatment to 24 months after treatment began. Result: Group A children were younger (8.4 ± 1.5 years), while Group D children were older (10.6 ± 1.59 years). Progression in the first 6 m was significantly less than that in 6 m prior in Groups A-C. At 1 year, a change in AL < 0.15 mm was noted in 41%, 49%, 50% and 35%, and a change in AL ≥ 0.30 mm was observed in 38%, 18%, 32% and 23% of eyes in Groups A, B, C and D, respectively. Treatment was increased in 37%, 34%, 12% and 41% of eyes over 2 years in Groups A, B, C and D, respectively. Mean progression at 2 years was −0.63 ± 0.86 D or 0.44 ± 0.31 mm, −0.39 ± 0.59 D or 0.30 ± 0.26 mm, −0.30 ± 0.48 D or 0.36 ± 0.40 mm, and −0.48 ± 0.54 D or 0.33 ± 0.22 mm in Groups A, B, C and D, respectively. Multivariate analysis suggested that progression was mainly associated with younger age. Conclusions: Atropine 0.025% was a useful addition to myopia control, with some eyes requiring further modification in treatment.

Journal of Clinical Medicine doi: 10.3390/jcm15218585

Authors: Dimitrios E. Magouliotis Beatrice Bacchi Arian Arjomandi Rad Andrew Xanthopoulos Tulio Caldonazo Michele D’Alonzo Massimo Baudo Francesco Cabrucci Francesca Maria di Muro

Frozen elephant trunk (FET) stabilizes the arch and proximal descending aorta, but complete distal remodeling is achieved in only a subset of patients with aortic dissection. Persistent false lumen perfusion, aortic growth, and distal stent graft-induced new entry lead to secondary thoracic endovascular aortic repair (TEVAR), and reported distal reintervention rates range from about 13% at 5 years in pooled data to 33% in a center with routine staging. This narrative review examines the indications for and timing of secondary TEVAR after FET. PubMed was searched to September 2026, and 97 publications were included. Evidence obtained in patients treated with FET is distinguished from evidence extrapolated from primary type B dissection and from the authors’ interpretation. We summarize the predictors of incomplete remodeling, including stent graft length, residual re-entry location, chronicity, aortic diameter at the distal stent level, early remodeling trajectory, and heritable aortopathy, and we contrast planned completion with surveillance-based reactive TEVAR, including technical aspects and spinal cord protection. Direct evidence on timing after FET is limited to retrospective series and one pilot randomized trial of TEVAR 1 to 3 months after type I repair; most data on the time-dependent loss of flap plasticity come from primary type B dissection. No universal timing rule is supported. We propose a phenotype-driven approach, not yet validated, in which timing is referenced to dissection onset and individualized to aortic anatomy, disease progression, and clinical condition.

Journal of Clinical Medicine doi: 10.3390/jcm15218586

Authors: Jonathan Wong Ryan Wong Zachary Hamilton Luke Wang

Background/Objectives: The role of radical cystectomy (RC) in clinically metastatic (cM+) bladder cancer is unclear. This study aimed to identify national clinical practice patterns, factors associated with receipt of RC, and survival outcomes among patients with cM+ bladder cancer before the immunotherapy and antibody–drug conjugate era. Methods: In this retrospective cohort study, 18,360 patients with cM+ bladder cancer were identified from the National Cancer Database between 2006 and 2016. Demographics, comorbidities, cancer stage, and surgical outcomes were compared between patients who received RC and those managed without cystectomy (No RC). Multivariable logistic regression was used to identify factors associated with receiving RC, and overall survival was evaluated with Kaplan–Meier analysis and a multivariable Cox model with time measured from diagnosis, adjusted for age, sex, race, Charlson Comorbidity Index (CCI) score, clinical T stage, and histology. Results: Among the 18,360 patients with cM+ bladder cancer, 987 (5.4%) underwent RC. Patients who underwent RC were significantly younger, more likely to be White, and had lower CCI scores. Utilization of RC remained stable throughout the study period. On multivariable logistic regression, increasing age, Black race, and CCI score ≥ 3 were associated with lower odds of receiving RC, whereas cT3/4 disease and urothelial histology were predictors of receiving RC. Kaplan–Meier analysis demonstrated higher overall survival in the RC group. Postoperative mortality was 4.6% at 30 days and 23.6% at 90 days. Conclusions: Radical cystectomy was infrequently performed among patients with cM+ bladder cancer and was concentrated among younger, healthier patients. The survival difference between groups reflects selection and cannot be interpreted as a causal survival benefit from RC, since surgical intent, metastatic burden, and postoperative disease status are unavailable. Our findings provide a descriptive, population-level reference for comparison with future studies of RC in the current treatment era.

Journal of Clinical Medicine doi: 10.3390/jcm15218584

Authors: Francisco José Rodríguez-Velasco José Alberto Becerra-Mejías Luis Miguel Lara-Godoy María Yuste-Domínguez Julio Carmona-Blesa Guadalupe Gil-Fernández

Background: Cardiac rehabilitation (CR) reduces cardiovascular mortality and improves quality of life in coronary patients. Risk stratification at program onset is essential for individualizing exercise prescription. Phase angle (PhA), derived from bioelectrical impedance analysis, is an index of cell membrane integrity that has emerged as a functional biomarker in various clinical populations. Its utility at the onset of a phase II CR program has not been explored in the Spanish context. This study evaluated the association of PhA with CR risk category, functional capacity and quality of life, its change during the program, and its incremental value over the Duke Treadmill Score (DTS) and clinical variables for risk classification in patients beginning phase II CR. Methods: This was an exploratory prospective longitudinal observational study with repeated measures. A total of 109 patients with ischemic heart disease (86.2% male; mean age: 60.2 ± 7.6 years) enrolled in an 8-week phase II CR program (Badajoz, Spain) were included. Phase angle was measured with a multifrequency bioimpedance analyzer (TANITA MC-780MA) under standardized conditions at baseline and program completion. Non-parametric tests (Wilcoxon, Mann–Whitney U, and Spearman correlation), multivariable models adjusted for potential confounders, receiver operating characteristic (ROC) analysis with incremental-value metrics, and a classification and regression tree (CART) evaluated with standard, repeated and nested stratified cross-validation were applied. Results: Baseline PhA was significantly higher in the low-risk group than in the high-risk group (5.43 ± 0.65° vs. 4.98 ± 0.81°; U = 1568.5; p = 0.002; rank-biserial r = 0.38). PhA correlated positively with the Duke Treadmill Score (r_s = +0.268; p = 0.005), physical functioning (r_s = +0.291; p = 0.002), vitality (r_s = +0.265; p = 0.005) and grip strength (r_s = +0.196; p = 0.041), and inversely with age (r_s = −0.288; p = 0.002) and the comorbidity index (r_s = −0.198; p = 0.039). High-risk status remained associated with lower PhA after adjustment for age, sex, BMI, comorbidity, LVEF, diabetes, revascularization type and time since the event (β = −0.49°; p = 0.002). PhA alone showed moderate discrimination (AUC = 0.689; 95% CI: 0.574–0.803); adding PhA to the DTS did not improve discrimination (ΔAUC = +0.004; p = 0.748); and a CART model combining DTS, PhA and grip strength (cross-validated accuracy: 85.2%) classified patients identically to the DTS alone. Without the DTS, adding PhA to a clinical model improved model fit and reclassification (likelihood-ratio p = 0.003; NRI = 0.64) without a significant AUC gain (+0.067; p = 0.106). After 8 weeks, PhA increased slightly (5.27 → 5.33°; p = 0.016); the mean change was small (95% CI: 0.01–0.10°) and was not associated with functional changes, and its clinical relevance is uncertain because repeatability data were not available. Conclusions: Phase angle is lower in high-risk CR patients independently of age, sex, body composition and comorbidity and correlates weakly to moderately with functional capacity and quality of life. However, it did not add discriminative value to the DTS, and the clinical relevance of its small mean change during the program is uncertain. These exploratory findings show associations only: neither the standalone use of PhA nor its added value over the DTS for risk stratification has been established, and its use for monitoring the response to rehabilitation has not been validated.

Journal of Clinical Medicine doi: 10.3390/jcm15218583

Authors: Peter Direr Marta Gibas-Stanek Robin Bruggink Petra Kaminkova Mette Kuijpers Thomas Maal Piotr S. Fudalej

Background/Objectives: Most healthy faces are mildly asymmetric, but how this asymmetry changes during growth and relates to facial size is unclear. We examined whether whole-face soft-tissue asymmetry increases as children grow and whether any increase simply reflects facial growth. Methods: We analysed 1014 three-dimensional facial scans of 377 children aged 6.0–18.8 years, followed for up to 3.2 years (median 2.0); the primary asymmetry analysis included 1003 scans of 376 children, after whole-face values with an isolated extreme point were set to missing. Asymmetry was the mean absolute perpendicular distance between the facial surface and its mirror image. Mixed-effects models separated within-child change from between-child differences. Repeat-capture reliability was not assessed. Results: Asymmetry increased by 3.2% per year within children entering at 11 years (95% confidence interval [CI], 2.2–4.1); older entrants were 2.7% more asymmetric per year of age (95% CI, 1.6–3.8). After adjustment for imaging session, the estimate was similar but imprecise (3.4%; 95% CI, −1.4 to 8.5). Facial size increased by 1.5% per year and asymmetry relative to size by 1.6%. Within children, asymmetry rose by about 1.7% for each 1% increase in facial size (exponent 1.73; 95% CI, 1.28–2.19); after adjustment for age this association was imprecise (0.89; 95% CI, −0.13 to 1.91), so the contributions of facial size and age could not be separated. Boys had 6.5% greater asymmetry; relative to facial size, 3.1% (95% CI, −2.0 to 8.6). Conclusions: On average, facial asymmetry increased modestly as children grew and increased relative to facial size over the observation period; whether this reflects facial enlargement itself or other age-related changes could not be determined. The estimated annual increase (about 0.013 mm) was below the residual variability between scans (about 0.04 mm); these population-level findings suggest that change cannot be detected in individual children, and individual monitoring and diagnostic thresholds require validated measurement.

Journal of Clinical Medicine doi: 10.3390/jcm15218582

Authors: Isidro Olavide Pablo Montero-López Marc Vives

Cardiac surgery is increasingly performed in older, frailer patients with multimorbidity, making postoperative recovery dependent not only on technical success but also on the quality of perioperative care. Enhanced Recovery After Surgery (ERAS) programs address this challenge through coordinated preoperative optimization, attenuation of surgical stress, organ protection, opioid-sparing analgesia, early mobilization, and structured discharge. This narrative review critically appraises ERAS in cardiac surgery and organizes the evidence across the perioperative pathway. Available studies associate complete ERAS programs with modest reductions in intensive care and hospital length of stay and possible reductions in overall complications, but evidence certainty is limited by heterogeneous bundles, single-center designs, and predominance of observational studies. Component-level evidence is strongest or clinically most relevant for frailty assessment, Patient Blood Management, multimodal analgesia, oxygen delivery-guided perfusion, delirium prevention, and early mobilization, although universal thresholds and isolated technologies should be avoided. Successful implementation depends on multidisciplinary governance, explicit responsibilities, adherence measurement, audit, and patient-centered outcomes. Future development should retain a standardized core while allowing transparent adaptation to baseline risk and observed response. Precision perioperative approaches remain hypothesis-generating and require external validation, clinical impact evaluation, assessment of equity, and demonstration of cost-effectiveness before routine adoption.

Journal of Clinical Medicine doi: 10.3390/jcm15218581

Authors: Mervenur Gizem Öztürk Öznur Demiroluk Mehmet Timuçin Aydın Arzu Yıldırım Ar

We thank Akdogan and colleagues for their valuable comments [...]

Journal of Clinical Medicine doi: 10.3390/jcm15218580

Authors: Mihaela Dana Pogan Rahela Tabita Moca Diana Berechet Raluca Iurcov Abel Emanuel Moca Ruxandra Ilinca Matei

Background/Objectives: Polymethyl methacrylate (PMMA)-based acrylic materials are widely used in dentistry, but they are not completely biologically inert and have been associated with hypersensitivity and allergic reactions in both patients and dental personnel. This narrative review aimed to synthesize the available evidence on (meth)acrylate-related hypersensitivity reactions in dentistry, with an emphasis on clinical manifestations, immunological mechanisms, and risk factors. Methods: A structured literature search was conducted in PubMed, Web of Science, and Scopus (15 August–1 September 2026), following the SANRA (Scale for the Assessment of Narrative Review Articles) guideline. After screening 408 records, 17 core articles were selected and grouped into four thematic categories: prevalence and clinical relevance, molecular and immunological mechanisms, clinical manifestations in patients, and occupational sensitization in dental personnel. Results: Confirmed (meth)acrylate sensitization ranges from 1.4% to 8% depending on population and testing methodology, remaining lower than metal allergy but clinically relevant. Haptenization through covalent binding of electrophilic monomers to host proteins underlies sensitization, while sublethal HEMA (2-hydroxyethyl methacrylate) exposure can induce measurable cellular stress independent of overt cytotoxicity. Patient presentations range from localized contact stomatitis to acute facial swelling, whereas dental personnel, particularly dental technicians, show disproportionately high occupational incidence rates. Testing restricted to HEMA alone may miss a substantial proportion of sensitized individuals. Conclusions: (Meth)acrylate hypersensitivity, although relatively uncommon, warrants increased diagnostic vigilance, broader patch-test panels, and improved occupational preventive measures. The current literature remains methodologically heterogeneous, underscoring the need for standardized testing series and larger prospective studies.

Journal of Clinical Medicine doi: 10.3390/jcm15218579

Authors: Dominika Biernaczyk Marcin Polok

Background: This study aimed to evaluate the effectiveness of percutaneous internal ring suturing (PIRS) for pediatric inguinal hernia. While previous reviews have addressed pediatric laparoscopic hernia repair more broadly, the present review specifically focuses on PIRS, with particular emphasis on recurrence rates. Methods: We searched PubMed, Web of Science, and Scopus for studies evaluating PIRS in children. The database searches were conducted between May 2025 and July 2026. Studies were eligible if they included at least 50 pediatric patients with inguinal hernia, reported a minimum follow-up of 6 months, and provided recurrence rates. Of 206 articles screened, 10 studies met the inclusion criteria; study characteristics and outcomes were summarized descriptively. Risk of bias was assessed using JBI tools and RoB 2, as appropriate. Results: The included studies comprised 1934 patients undergoing 2405 PIRS procedures. Overall, 80 complications (3.33%) were reported, including 39 recurrences (1.62%). Other complications included hematomas, iliac vessel punctures, granulomas, and transient hydroceles. One patient developed adhesive ileus with bowel strangulation, which required resection of a part of the ileum. Intraoperative assessment identified 190 additional bilateral hernias, increasing the rate of bilateral cases from 11.92% to 18.88%. Among the 1061 patients with available contralateral patent processus vaginalis (CPPV) data, CPPV was identified in 194 (18.28%). One case of complete androgen insensitivity syndrome (CAIS) was identified during PIRS. The weighted mean age reported across eight studies was 3.05 years. Mean operative time ranged from 8.48 to 26.5 min for unilateral and 18.0 to 33.9 min for bilateral procedures. Conclusions: PIRS appears to be an effective minimally invasive technique for pediatric inguinal hernia repair, with a low reported recurrence and complication rate. The possibility of closing the inguinal canal on the opposite side and assessing the gonads in girls during the procedure seems to provide an advantage over open techniques.

Journal of Clinical Medicine doi: 10.3390/jcm15218578

Authors: Iván Julián-Rochina Mateo López-Moral Esther García-Morales Marta Izquierdo-Renau José David Piñeiro-Ramos José Luis Lázaro-Martínez

Diabetic foot syndrome (DFS) is a severe complication affecting millions of people worldwide, yet its clinical management remains predominantly reactive, focusing on established ulcers rather than early preventive measures. Although the role of the cutaneous microbiome in chronic wounds is recognized, longitudinal ecological shifts in the skin of the foot throughout the progression of diabetes mellitus remain underexplored. This structured narrative review evaluates transitional microbial dynamics from intact skin through to active ulceration and explores emerging microbiome-targeted therapies. Based on a structured literature search of PubMed, Scopus, and Web of Science, complemented by citation searching, and a narrative synthesis of 32 selected publications, current evidence suggests that diabetes-associated changes in the cutaneous microbiome involve heterogeneous alterations in microbial diversity and composition, which vary according to microbial community, anatomical location, and clinical status. DFS progression involves a profound ecological collapse, characterized by depletion of protective commensals (e.g., Staphylococcus epidermidis) and the predominance of virulent Staphylococcus aureus lineages alongside Gram-negative anaerobes. Consequently, precision interventions such as topical probiotics, synbiotics, and bacteriophage therapy have substantial potential to disrupt recalcitrant biofilms and reprogram host immunity toward pro-regenerative phenotypes. Ultimately, recognizing the skin as a primary target organ in diabetes mellitus highlights the need to shift DFS management toward a proactive framework. Validating these microbiome-modulating therapies through standardized clinical trials is crucial to restoring host-microbiota symbiosis and ultimately preventing lower-extremity amputations.

Journal of Clinical Medicine doi: 10.3390/jcm15218574

Authors: Torben Sonneck Michaela Barnikel Paola Arnold Gabriela Leuschner Amanda Tufman Jürgen Behr

Background/Objectives: Patients with pulmonary arterial hypertension (PAH) may display obstructive ventilatory defects outside of defined obstructive lung disease. However, its pathogenesis and prognostic relevance remain unknown. Similar data have emerged for patients with chronic thromboembolic pulmonary hypertension (CTEPH), but there is no description in a real-world European cohort. Methods: We performed a single-center, retrospective, cross-sectional study of patients with PAH (n = 46) and CTEPH (n = 45) at an academic PH center. Data were collected on pulmonary function tests, DLCO, right heart catheterization results, pre-existing diagnoses of asthma and chronic obstructive pulmonary disease (COPD), current medications, and adverse outcomes. Results: Patients with PAH and CTEPH showed a reduced FVC (81% for both groups), FEV1 (74 and 75%) and DLCO (54 and 53%). A previous diagnosis of COPD was documented in 11% of patients, and asthma in 11% of patients with PAH and 4.5% of patients with CTEPH respectively. Even after excluding patients with asthma or COPD, ventilatory obstruction was still present in at least 22% of patients and 16% were being treated with long-acting bronchodilators or inhaled corticosteroids. Of these patients, those who had adverse outcomes (active listing for lung transplantation, lung transplantation or death) had a significantly lower FVC (68 vs. 83%, p = 0.026), FEV1 (61 vs. 79%, p = 0.01) and MEF50 (38 vs. 59%, p = 0.021). All patients with adverse outcomes had a mean expiratory flow at 50% vital capacity (MEF50) < 60%, as opposed to 57% of those without an adverse event, however MEF50 did not predict adverse outcomes after adjusting for FVC. Conclusions: Ventilatory obstruction is common in patients with PAH and CTEPH even when excluding patients with asthma/COPD or a history of smoking. Symptomatic treatment with bronchodilators is common even without these comorbidities. Patients with adverse outcomes had lower FEV1, FVC and MEF50, but the functional relevance of the latter remains to be explored.

Journal of Clinical Medicine doi: 10.3390/jcm15218577

Authors: Paweł Skowronek Adam Smolik Filip Skowronek Łukasz Dutka Maria R. Skowronek Klaudia Joniak Michał J. Skowronek

Medial unicompartmental knee arthroplasty (UKA) is a bone- and ligament-preserving alternative to total knee arthroplasty (TKA) for selected patients with isolated medial compartment osteoarthritis, but it carries a consistently higher revision rate. The assumption that a failed UKA converts easily to a primary-standard TKA has not survived registry scrutiny, and conversion is now best regarded as a formal revision procedure. This contemporary narrative review, which is not a systematic review, evaluates revision strategies after failed medial UKA. Sources were identified through targeted literature searches and reference-list screening, and the strength of evidence was graded by level of evidence. Three pathways are considered: revision within the medial compartment, including bearing and single-component exchange; retention of a well-fixed, well-positioned medial UKA with addition of a patellofemoral arthroplasty or a lateral UKA; and conversion to TKA. Evidence quality differs sharply between pathways. Conversion to TKA is supported by registry and comparative cohort data, and medial UKA-to-UKA revision mainly by evidence of its high failure rate. Compartmental addition rests on one small dedicated series, one small multicentre comparative study, one descriptive multicentre series, one expert consensus and indirect data from primary bicompartmental arthroplasty. A four-step framework is proposed (failure mechanism, compartmental mapping, bone and ligament assessment, patient and centre factors); it is evidence-informed but not validated.

Journal of Clinical Medicine doi: 10.3390/jcm15218575

Authors: Doralisa Morrone Richa Chhabra Eva-Maria Fronk Jose Souza Paulus Kirchhof Raffaele De Caterina on behalf of the ETNA-AF-Europe Investigators

Background/Objectives: ETNA-AF-Europe was a post-authorization, prospective, non-interventional study evaluating edoxaban in atrial fibrillation (AF). Here, we assessed annualized rates of intracranial haemorrhage, haemorrhagic stroke, and ischaemic stroke in subpopulations of edoxaban-treated patients with AF. Methods: We assessed overall annualized adjudicated event rates over 4 years, including subpopulations stratified by age, renal/hepatic impairment, chronic concomitant anti-platelet use, and CHA2DS2-VASc score. Results: Overall, 13,164 patients were included, with a median (interquartile range) age of 75.0 (68.0, 80.0) years. Overall annualized intracranial haemorrhage rates were 0.18%/year and remained ≤0.24%/year in high-risk subpopulations, with minor rate increases observed with age (<65 years: 0.07%/year, ≥65–<75 years: 0.16%/year, ≥75 years: 0.23%/year) and CHA2DS2-VASc score (0–1: 0.04%/year, 2–4: 0.19%/year, >4: 0.24%/year). Overall annualized haemorrhagic stroke rates were 0.08%/year and remained ≤0.10%/year in high-risk subpopulations, with minor rate increases observed with age (<65 years: 0.06%/year, ≥65–<75 years: 0.08%/year, ≥75 years: 0.09%/year) and CHA2DS2-VASc score (0–1: 0.00%/year, 2–4: 0.09%/year, >4: 0.10%/year). Overall annualized ischaemic stroke rates were 0.49%/year and remained ≤1.05%/year in high-risk subpopulations; however, rates increased notably with age (<65 years: 0.21%/year, ≥65–<75 years: 0.34%/year, ≥75 years: 0.68%/year) and CHA2DS2VASc score (0–1: 0.15%/year, 2–4: 0.43%/year, >4: 1.05%/year). Conclusions: Annualized intracranial haemorrhage, haemorrhagic stroke, and ischaemic stroke rates in ETNA-AF-Europe were low and demonstrated no meaningful increases with renal/hepatic impairment and chronic concomitant antiplatelet use. Minor rate increases observed with higher CHA2DS2-VASc scores and increasing age were much less steep for haemorrhagic stroke than for ischaemic stroke.

Journal of Clinical Medicine doi: 10.3390/jcm15218576

Authors: Katharina Theresa Obermeier Anusha Abdullah Felix Kramer Ina Dewenter Wenko Smolka Michael Roßkopf

Restless Head Syndrome (RHS) and Burning Mouth Syndrome (BMS) are rare, underrecognized causes of orofacial discomfort that are frequently misdiagnosed. This review maps the available literature on both conditions, examines their proposed relationship to restless leg syndrome (RLS) and to each other, and appraises the role of dopaminergic therapy. A literature search was conducted in PubMed and ScienceDirect for publications from January 2000 to December 2024 describing the clinical presentation, diagnosis, or treatment of RHS, BMS, or craniofacial variants of RLS. The evidence consisted predominantly of case reports and small case series. RHS and other craniofacial RLS variants presented with rest-associated, evening-predominant discomfort that was relieved by movement and responded to dopaminergic agents. Only one small case series described patients with BMS who also fulfilled RLS criteria. The evidence supports clinical similarities rather than a confirmed association or shared pathophysiology. Clinicians should consider atypical RLS variants in the differential diagnosis of unexplained orofacial sensory symptoms; prospective studies are needed before firm diagnostic or therapeutic conclusions can be drawn.

Journal of Clinical Medicine doi: 10.3390/jcm15218573

Authors: Michał Grabala Piotr Kowalski Justyna Walczak Joanna Suszczyńska Krzysztof Zakrzewski Paweł Grabala

Background: Posterior spinal fusion (PSF) is an established treatment for progressive adolescent idiopathic scoliosis (AIS) requiring surgery. Thoracic and abdominal complications range from transient postoperative findings to uncommon emergencies. This narrative review examines their reported frequency, recognition, prevention, and management. Methods: Literature published between January 2000 and June 2026 was reviewed using PubMed/MEDLINE and Google Scholar, supplemented by reference-list screening. AIS-specific evidence was prioritized. Reports involving other deformities or surgical approaches and general management guidelines were used as explicitly identified contextual evidence. No pooled incidence estimates were calculated. Results: Reported frequencies depended strongly on outcome definitions, imaging protocols, surgical approach, and follow-up. Two retrospective AIS studies detected pleural effusion in 71.0% and 76.3% of patients on computed tomography approximately one week after PSF; in the latter study, all effusions were asymptomatic and required no treatment. These findings should not be equated with clinically significant pulmonary complications. Postoperative ileus was reported in 13.2% of one 318-patient AIS cohort aged 10–20 years, whereas superior mesenteric artery syndrome, chylothorax, hemothorax, and implant-related vascular injury were supported largely by small series or case reports. Enhanced recovery pathways were consistently associated with shorter hospitalization, but evidence that they prevent individual rare complications was limited. Accurate instrumentation, appropriate blood conservation, individualized nutritional assessment, opioid-sparing analgesia, and symptom-directed investigation support perioperative care. Conclusions: Thoracic and abdominal complications after PSF for AIS require separate interpretation of radiographic findings, clinically diagnosed events, and events requiring intervention. Persistent vomiting, progressive abdominal distension, respiratory deterioration, unexplained anemia, or hemodynamic instability warrant prompt reassessment. Management should follow the suspected diagnosis, patient physiology, and relevant pediatric or multidisciplinary guidance.

Journal of Clinical Medicine doi: 10.3390/jcm15218571

Authors: Frederique J. C. van Eerten Steven Ferree Jan-Hendrik Venhuizen Mark C. H. de Groot Saskia Haitjema Falco Hietbrink

Background: Trauma care is inherently complex due to wide variability in patients, injury patterns, possible treatment strategies, and achievable outcomes that dynamically interact and influence the risk of complications and long-term functional recovery. Mortality-focused research insufficiently reflects this complexity and the evolving goals of trauma care. A Learning Healthcare System offers an opportunity to learn from routine clinical care by integrating data and translating findings into feedback. Objective: This paper proposes a comprehensive framework for continuous evaluation and improvement of trauma care that integrates patient and injury characteristics with care processes, complications, and outcomes beyond mortality, and describes an institutional data infrastructure that can support this framework. Approach: A conceptual framework based on routine care data is described, together with an institutional example combining the Dutch National Trauma Registry, the Utrecht Patient-Oriented Database, and a specialty complication registry. No new patient-level data were created or analyzed, and the effectiveness of the integrated infrastructure was not evaluated. Maintaining these databases requires dedicated professionals, data managers, structured documentation, multidisciplinary collaboration, and continuous quality control. Conclusions: Linking complementary registries provides a foundation for a Learning Healthcare System in complex trauma care. Combining established mortality and morbidity reviews with the opportunities offered by large, integrated databases may facilitate the implementation of a Learning Healthcare System in trauma care.

Journal of Clinical Medicine doi: 10.3390/jcm15218572

Authors: Ferhat Balgetir Prabal Datta Barua Jun Shen Padmanesan Narasimhan Smitha Shivshankar Sengul Dogan Irem Tasci Burak Tasci Mehmet Baygin Turker Tuncer Makiko Kobayashi

Objective: Dementia is a prevalent neurological disorder, and accurate detection is essential for timely intervention. This study aims to design an interpretable symbolic feature engineering framework for EEG-based dementia classification and to examine how its performance depends on the validation protocol. Methods: We used a publicly available EEG dementia dataset including Alzheimer’s disease (AD), frontotemporal dementia (FD), and healthy controls. A self-organized explainable feature engineering (SOXFE) model was introduced with five phases: (i) feature extraction using Bipartite Channel Transformer (BCT) and Previous-Next Pattern (PNPat), (ii) feature selection via cumulative weight-based iterative neighborhood component analysis (CWINCA), (iii) explainable output generation using Directed Lobish (DLob), (iv) classification through an ensemble tkNN classifier, and (v) information fusion with combinational majority voting (CMV). Performance was evaluated with segment-wise 10-fold cross-validation, leave-one-subject-out (LOSO) cross-validation, and nested participant-grouped 10-fold cross-validation. Results: Segment-wise 10-fold cross-validation, which allowed segments of one participant in both training and test folds, yielded accuracies of 99.12–99.74%. Participant-independent accuracy was substantially lower: 51.19–63.81% for LOSO and 49.00–62.50% for nested participant-grouped validation at the segment level. Participant-level LOSO accuracy equaled the majority-class rate for dementia versus healthy controls (67.05%) and fell below it for AD versus FD (57.63% versus 61.02%). No exact McNemar comparison showed an accuracy advantage over the majority-class baseline. DLob outputs were produced as feature-level visualizations. Conclusions: The findings support the feasibility of interpretable, algorithm-derived symbolic feature representations. They do not establish reproducible disease-related EEG characteristics or clinical diagnostic utility. DLob outputs describe the channel transitions used by the model. Independent cohorts and stronger participant-independent performance are required before clinical application.

Journal of Clinical Medicine doi: 10.3390/jcm15218570

Authors: Munerah Hamed

Background/Objectives: Skin cancer is a largely preventable disease associated with ultraviolet radiation exposure that represents an important public health concern in Saudi Arabia. In the context of ongoing social and lifestyle changes, this study aimed to assess knowledge, attitudes, and practices regarding skin cancer and examine their associations with sociodemographic characteristics among surveyed adults residing in Saudi Arabia. Methods: This cross-sectional study used a self-administered online questionnaire distributed through social media platforms. A total of 451 participants aged ≥18 years residing in Saudi Arabia were included. Data comprised sociodemographic characteristics and knowledge, attitudes, and practices regarding skin cancer. Descriptive statistics are presented as mean ± standard deviation (SD) and median (interquartile range [IQR]) for continuous variables and frequencies and percentages for categorical variables. Non-parametric and multiple linear regression analyses were used to assess associations between sociodemographic characteristics and knowledge, attitude, and practice scores. Results: The median knowledge, attitude, and practice scores were 13.0/26 (IQR 10.0–16.0), 6.0/12 (IQR 4.0–7.0), and 5.0/16 (IQR 4.0–6.0), respectively. Sex, education level, and employment status were significantly associated with knowledge scores. Age, sex, education level, employment status, and income were associated with attitude scores. Sex, employment status, and income were associated with practice scores. Conclusions: This study identified differences in skin cancer knowledge, attitudes, and preventive practices among adults in Saudi Arabia, highlighting opportunities to strengthen preventive behaviors. Targeted public health interventions may help promote skin cancer awareness and prevention.

Journal of Clinical Medicine doi: 10.3390/jcm15218568

Authors: Perihan Perkin Derya Sarikaya Hilal Karakas Ugur Ozberk Burak Bilgin Efnan Algin Oznur Bal Didem Sener Dede Gokhan Ucar

Background/Objectives: The optimal adjuvant chemotherapy regimen remains uncertain for some patients with hormone receptor (HR)-positive/HER2-negative early breast cancer, particularly regarding the incremental benefit of anthracyclines. We compared real-world outcomes with docetaxel-plus-cyclophosphamide (TC) and anthracycline–taxane chemotherapy. Methods: This retrospective single-center cohort included patients with stage I–III HR-positive/HER2-negative breast cancer who underwent surgery and received adjuvant TC or anthracycline–taxane chemotherapy between 2019 and 2025. Patients receiving neoadjuvant systemic therapy were excluded. Disease-free survival (DFS) was the primary outcome and overall survival (OS) the secondary outcome. Propensity score overlap weighting adjusted for measured baseline differences was used; the absolute difference in weighted 3-year DFS was the primary adjusted measure. Results: Among 361 patients, 201 received TC and 160 anthracycline–taxane chemotherapy. The anthracycline–taxane group had higher baseline clinicopathologic risk. Median follow-up was 39.0 months. Twelve DFS events occurred (TC, n = 3; anthracycline–taxane, n = 9). Unadjusted 3-year DFS was 99.0% versus 96.6% (p = 0.096), and 3-year OS was 99.4% versus 99.1% (p = 0.725). The overlap-weighted analysis included 346 patients and achieved adequate covariate balance. Weighted 3-year DFS was 99.2% with TC and 96.5% with anthracycline–taxane chemotherapy, an absolute difference of 2.68 percentage points (95% CI, −1.81 to 10.03). Sensitivity analysis yielded similar results (2.70 percentage points; 95% CI, −1.76 to 9.87). Conclusions: No statistically significant difference in 3-year DFS was demonstrated after adjustment. Limited events and relatively short follow-up preclude conclusions regarding equivalence or noninferiority. These findings support individualized adjuvant chemotherapy selection and warrant confirmation in larger cohorts with longer follow-up.

Journal of Clinical Medicine doi: 10.3390/jcm15218560

Authors: Tomás Loureiro João Heitor Marques Nuno Campos Tiago Monteiro

Background/Objectives: This study aims to review the evolution of preoperative ectasia risk assessment before laser vision correction (LVC), with particular emphasis on the changing role of corneal pachymetry and its interpretation within contemporary multimodal screening strategies. Methods: A structured narrative review of the literature was conducted to examine the historical development of ectasia screening, the incorporation of pachymetric parameters into successive risk models, and the available evidence regarding refractive outcomes in constitutionally thin corneas undergoing laser vision correction. Results: Preoperative ectasia screening has evolved from reliance on isolated clinical and topographic parameters to comprehensive multimodal assessment integrating corneal tomography, biomechanics, epithelial thickness mapping, and artificial intelligence-based indices. Although corneal pachymetry remains a key component of most contemporary risk models, increasing evidence suggests that constitutionally thin corneas with otherwise normal tomographic and biomechanical profiles can achieve favourable outcomes following surface ablation. However, the available evidence remains limited by retrospective study designs, highly selected populations, and insufficient long-term follow-up. Conclusions: Corneal thickness should no longer be interpreted as an isolated indicator of ectasia risk but rather as one component of an integrated assessment of corneal susceptibility. Contemporary preoperative screening should prioritise individualised multimodal evaluation over reliance on isolated pachymetric thresholds. At the same time, further prospective studies are needed to define the long-term safety of surface ablation in constitutionally thin corneas.

Journal of Clinical Medicine doi: 10.3390/jcm15218569

Authors: Giovanni Paolino Matteo Riccardo Di Nicola Rachele Bardelli Noemi Brigenti Nicola Zerbinati Santo Raffaele Mercuri Andrea Carugno

Green pit vipers of the genus Trimeresurus are among the leading causes of snakebite envenomation across tropical and subtropical Asia, yet their clinical phenotype has been less systematically characterized than that of other medically important Asian viperids. This comprehensive review synthesizes the published clinical literature on human Trimeresurus envenomation, drawing on 70 clinical reports encompassing 4720 reported patient episodes, and integrates these data with current taxonomic and venomic evidence. Envenomations cluster in East, Southeast, and South Asia. The single most important limitation of this literature is the unreliability of species attribution: 55% of reported cases are attributed only at genus level or derive from cohorts in which two or more Trimeresurus species are reported together and cannot be separated, a figure consistent with the 56% of snakebites left unidentified in a recent 40,817-patient Chinese survey. Bites involve the extremities almost exclusively, with a predominance of the lower limb (55% versus 45%). The clinical picture is dominated by local effects (i.e., extensive edema and pain in the large majority of patients, secondary infection in approximately one in six, and cutaneous necrosis in approximately one in thirty) and by systemic hemotoxicity driven by venom-induced consumptive coagulopathy. Renal involvement is uncommon, in contrast to Daboia russelii envenomation, and severe neurotoxicity is exceptional. Documented mortality in the reviewed hospital-based literature is low (two deaths among 3387 patients in reports documenting outcome, <0.1%) but is not zero, and hospital-based series cannot capture pre-hospital deaths. Management centers on conservative wound care, serial coagulation monitoring, and selective antivenom administration; routine fasciotomy is not justified without objective evidence of compartment syndrome. Reliable species identification, standardized clinical reporting, and long-term functional follow-up remain the principal unmet needs.

Journal of Clinical Medicine doi: 10.3390/jcm15218567

Authors: Edoardo Mortato Marina Talamonti Annunziata Raimondo Viviana Lora Matteo Megna Cristina Mugheddu Gabriele Biondi Anna Balato Giacomo Caldarola Lorenzo Marcelli Serena Lembo Dario Graceffa Luca Potestio Laura Atzori Maria Antonia Montesu Eugenia Veronica Di Brizzi Eleonora De Luca Lucia Bufano Luca Bianchi Marco Galluzzo

Background/Objectives: Individualising guselkumab maintenance is increasingly considered in clinical practice, but the characteristics associated with clinicians’ decisions to modify dosing intervals remain poorly defined. We investigated the clinical profiles of patients undergoing interval extension or reduction and assessed drug survival after interval reduction in patients with psoriatic arthritis (PsA). Methods: This retrospective study included patients receiving guselkumab for psoriasis across eight Italian centres. Patients undergoing interval extension beyond every eight weeks (q8w; n = 39) were compared with those without interval extension (n = 951). Separately, patients with PsA undergoing interval reduction from q8w to every four weeks (q4w; n = 39) were compared with patients with PsA maintained on q8w (n = 184). Between-group comparisons were exploratory and unadjusted. Post-interval reduction drug survival was estimated using the Kaplan–Meier method. Results: Patients undergoing extension had less frequent palmoplantar involvement (2.6% versus 14.7%; p = 0.033), nail involvement (0% versus 13.6%; p = 0.014), and PsA (7.7% versus 23.1%; p = 0.023), and more frequent previous anti-IL-12/23 treatment (35.9% versus 18.2%; p = 0.006). Within the PsA population, interval reduction was associated with younger age (56.9 versus 62.8 years; p = 0.023) and obesity (41.0% versus 23.4%; p = 0.023). Five patients subsequently returned to standard q8w dosing following clinical improvement. All 39 patients undergoing interval reduction were included in the survival analysis, with six guselkumab discontinuations. Estimated drug survival was 97.1% at 52 weeks (95% CI 81.4–99.6%) and 84.2% at 104 weeks (95% CI 62.7–93.9%). Conclusions: Guselkumab interval modification was associated with distinct clinical profiles, suggesting that disease phenotype, joint involvement, and treatment history contribute to individualised maintenance decisions. These findings describe clinical selection in routine practice and support prospective evaluation of patient selection criteria and long-term outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15218566

Authors: Cătălin Pleșea-Condratovici Constantin-Marinel Vlase Ionuț-Silviu Vasile Aritina-Elvira Moroșanu Manuela Arbune Petruț-Ștefan Șerban Răzvan Cosmin Pană

Background: Anxiety is common among health science students, but the Balkan region is underrepresented in student mental health research and no regional synthesis exists. This systematic review and meta-analysis estimated the pooled prevalence of anxiety among medical, dental and nursing students in selected Balkan countries. Methods: Following PRISMA 2020 and a PROSPERO registration (CRD420261332221), PubMed, Scopus, and Web of Science were searched for English-language observational studies in eleven Balkan countries that assessed anxiety with a validated instrument. Two reviewers independently screened studies, extracted data and appraised quality (JBI). Prevalence was pooled with a DerSimonian-Laird random-effects model after Freeman-Tukey transformation, with prediction intervals and exploratory subgroup and sensitivity analyses. Results: Nine cross-sectional studies (N = 5177) from Croatia, Romania, Greece, Kosovo and Serbia were included. The pooled prevalence of anxiety at or above moderate severity was 27.5% (95% CI: 20.2–35.5%), with very high heterogeneity (I2 = 97.1%; 95% prediction interval 5.3–58.6%). Leave-one-out analyses (26.0–29.4%) and alternative estimators (26.9–27.5%) gave similar estimates. Subgroup analyses were exploratory. Conclusions: The pooled prevalence is an average across heterogeneous studies, not a regional benchmark. The evidence is limited to English-language studies from five of eleven countries, and the findings are preliminary. Harmonised primary research is needed.

Journal of Clinical Medicine doi: 10.3390/jcm15218565

Authors: Andrea Barbieri Giacomo Mori Filippo Bondi Alessio Bragagni Alice Parmigiani Niccolò Morisi Floriana Cannito Gaetano Alfano Gian Piero Guerrini Barbara Catellani Giuseppe Boriani Gabriele Donati

Cardiovascular assessment before kidney transplantation (KT) remains uncertain despite contemporary guidelines. Historically, many transplant centers have adopted intensive screening strategies to detect obstructive coronary artery disease (CAD), often resulting in stress testing, coronary angiography, revascularization, dual antiplatelet therapy, and potentially delayed transplantation. However, evidence that systematic detection and prophylactic treatment of stable CAD improve outcomes in asymptomatic KT candidates remains limited. Recent American, British, and European guidance increasingly supports more selective, risk-adapted assessment, yet the low level of supporting evidence leaves substantial discretion in patient and test selection, as well as wait-list surveillance. This implementation gap is particularly relevant for historically high-testing centers seeking to revise established protocols. Moreover, the cardiovascular phenotype of advanced chronic kidney disease extends beyond obstructive epicardial CAD and includes myocardial, microvascular, structural, and systemic abnormalities that may be better captured by physiological vulnerability and functional reserve. Exercise-based assessment may therefore provide prognostic information beyond ischemia detection. In this Viewpoint, we examine the evidence challenging intensive CAD-centered screening, discuss the evolving role of functional testing and risk-adapted surveillance, and illustrate how these principles were translated into a multidisciplinary local protocol revision. The emerging challenge is not simply to perform fewer tests but to identify who truly benefits from additional testing and to select the right test for the right patient at the right time.

Journal of Clinical Medicine doi: 10.3390/jcm15218564

Authors: Jędrzej Tschurl Tomasz Kotwicki Piotr Janusz Milud Shadi

Background: Fracture of newly formed bone (the regenerate) after EF (External Fixator) removal is a serious complication of bone lengthening in Congenital Femoral Deficiency (CFD). This study aimed to determine whether prophylactic intramedullary nailing (IMN) at the time of EF removal reduces the risk of femoral fractures in CFD and to evaluate its safety. Methods: This retrospective comparative study included 53 CFD patients who underwent femoral lengthening (44 in the IMN group, 9 in the historical no-IMN group). We analyzed the incidence of fractures, infections, and unplanned surgeries. The predictive value of Fischgrund principles and Li classification for fracture risk was evaluated. Results: The fracture rate was 11.3% (6/53). The IMN group had fewer fractures (6.8%) versus the no-IMN group (33.3%, p = 0.054). Surgical treatment risk for femoral fracture was significantly lower in the IMN group (2.3% vs. 33.3%, p < 0.05). Despite complications in the IMN group (4.5% infection rate, 4.5% nail malposition rate, 2.3% hip dislocation), the rate of unplanned surgery was lower than in the no-IMN group (11.4% vs. 33.3%, p = 0.12). Associations between regenerate morphology and subsequent fracture occurrence were observed only in the historical no-IMN group. Prophylactic nailing may provide mechanical support in patients with less mature regenerate. Conclusions: In this retrospective study with a historical comparison group (no-IMN), prophylactic intramedullary nailing was associated with fewer fractures requiring surgery after femoral lengthening with EF in CFD.

Journal of Clinical Medicine doi: 10.3390/jcm15218562

Authors: Nour Maalouf Mazen Abou Mrad Fiona Mankertz Reza Dehdab Isabelle Schöpper Rosa Alba Pugliesi Saif Afat Jonas C. Apitzsch

Background/Objectives: To evaluate the resource utilization, procedural costs, procedure time, and intraprocedural outcomes of interventional radiology (IR)-guided totally implantable venous access port (TIVAP) placement and contextualize these findings using institutional surgical benchmarks. Methods: We conducted a single-center study between March 2020 and March 2024 that included 93 patients requiring TIVAP placement for chemotherapy. All ports were inserted under ultrasound and fluoroscopic guidance in an angiography suite. Surgical insertions using a cephalic vein cut-down under anesthesia were used as a comparator. Data collected included number of consent forms, staffing, procedure duration, material and medication utilization, and procedural costs obtained from hospital financial records. Descriptive statistics were used to summarize outcomes. Results: IR-guided TIVAP insertion required one combined consent form and two personnel, compared with two consent forms and four personnel for the surgical workflow. The average procedural cost in the angiography suite was €168.16 versus an institutional surgical benchmark of €407.90, representing a 58.8% lower observed cost. The recorded average procedure time was 45 min for IR versus 85 min for the surgical benchmark. Material costs were comparable, except for intravenous anesthetic agents used in the operating room. No intraprocedural complications occurred among the 93 IR cases. Conclusions: IR-guided TIVAP implantation required fewer personnel and was associated with lower observed procedural costs and shorter recorded procedure times relative to institutional surgical benchmarks. The absence of a patient-level surgical comparator and long-term follow-up limits conclusions regarding comparative safety and clinical outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15218561

Authors: Pragya Rai Yu-Han Kao Xiaohan Hu Ashwini Arunachalam Andrew Song Stephen V. Liu

Background: Durvalumab is currently approved as consolidation therapy for patients with unresectable stage III non-small cell lung cancer (NSCLC) without disease progression following concurrent chemoradiotherapy (cCRT). This study described real-world characteristics, disease progression, subsequent treatment, and clinical outcomes according to durvalumab receipt. Methods: This retrospective cohort study used the N-Power Medicine database. Adults diagnosed with unresectable stage III NSCLC who initiated cCRT between February 2018 and October 2023 and subsequently received durvalumab or no durvalumab and were followed until October 2025. Baseline characteristics, disease progression, and subsequent treatment patterns were summarized descriptively. Kaplan–Meier methods were used to estimate overall survival (OS) and time to death or distant metastasis (TDDM). Results: Among 717 patients who initiated cCRT, 487 received cCRT followed by durvalumab and 230 received cCRT only. Baseline characteristics were broadly similar between cohorts. Median theoretical follow-up was 60.5 and 60.8 months, respectively. Disease progression was observed in both groups, with higher rates in the cCRT-only cohort (48.7% vs. 40.9%). TDDM was 26.7 months in the cCRT + durvalumab cohort and 5.6 months in the cCRT-only cohort. Median OS was 42.6 months and 11.4 months, and OS events occurred in 55.2% and 80.0% of patients, respectively. In the cCRT + durvalumab cohort, OS rates at 12, 36 and 60 months were 83.6%, 56.0%, and 42.8%. Conclusions: In real-world practice, approximately one-third of patients with unresectable stage III NSCLC did not receive durvalumab following cCRT. Despite consolidation therapy, a substantial proportion of patients continue to experience disease progression, highlighting ongoing unmet need in this population.

Journal of Clinical Medicine doi: 10.3390/jcm15218563

Authors: Mauro Giovanni Carta Massimo Tusconi Elisa Cantone Viviana Forte Giulia Cossu Michela Atzeni Alessandra Scano Germano Orrù Michele Fornaro Alessandra Perra

Background: The Sardinian Blue Zone is internationally recognized for exceptional longevity, particularly among men. The provinces encompassing this area also report elevated suicide mortality among older men. This paradox raises the question of whether older men recruited within the longevity area show increased depressive screening positivity or whether additional interacting mechanisms may contribute to suicide vulnerability. Objective: To examine whether the reported excess suicide mortality among older men in the provinces encompassing the Sardinian Blue Zone is accompanied by higher depressive screening positivity or PHQ-9 Item 9 scores in older men recruited within the longevity area, and to explore the distribution of subthreshold depressive symptoms. Methods: We conducted an exploratory secondary analysis of a population-based survey including Sardinian residents aged ≥60 years. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). The Blue Zone group was recruited from six municipalities within the longevity area in Nuoro and Ogliastra. Comparisons were stratified by sex and used two-sided Fisher exact tests and analysis of variance. Results: No statistically significant increase in screening positivity for probable depression or PHQ-9 Item 9 scores was observed in Blue Zone residents. Older men showed a higher prevalence of clinically relevant symptoms below the screening threshold for probable major depression (PHQ-9 5–9: 4/19 vs. 4/171; OR = 11.13; Fisher p = 0.00395). Among women, this symptom range was less frequent in the Blue Zone (5/34 vs. 77/208; Fisher p = 0.01077). Conclusions: The observed symptom distributions motivate examination of mechanisms extending beyond the prevalence of major depression alone. The male excess in subthreshold depressive symptoms, interpreted alongside independent evidence on activation, supports investigation of mood and rhythm dysregulation and culturally shaped responses to stress. The sociobiological framework generates testable hypotheses for longitudinal psychiatric and anthropological research.

Journal of Clinical Medicine doi: 10.3390/jcm15218559

Authors: Dirk Rades Stefan Janssen Laura Doehring Jan-Dirk Küter Michael von Staden Ahmed Al-Salool Julia Koeck Justus Domschikowski Christian Felix Schulz Jon Cacicedo Christine Vestergård Madsen Charlotte Kristiansen

Background/Objectives: Moderate hypo-fractionation is frequently used for irradiation of prostate cancer. Irrespective of dose fractionation, radiotherapy can lead to radiation cystitis. To reduce urinary toxicity, it is important to avoid bladder volumes < 200 mL. This may be facilitated with an app reminding patients to drink water prior to irradiation. This non-randomized multicenter REFILL-PAC-HYPO trial with external control evaluated the association between use of the reminder app and bladder filling during a radiotherapy course. Methods: Twenty-two patients receiving hypo-fractionated irradiation (20 × 3.0 Gy) were planned to be supported by the app (the prospective experimental group) and compared to 95 patients who were not supported by the app (the historical control group). The primary endpoint was the number of fractions with a bladder volume < 200 mL. Secondary objectives included satisfaction with the app and its impact on using health technology. Results: The median number of fractions with a bladder volume < 200 mL was lower in the app-supported experimental group (13; interquartile range: 6, 18 vs. 19; interquartile range: 14, 20). The Wilcoxon–Mann–Whitney test indicated a significant between-group difference (p = 0.0009) with a Hodges–Lehmann estimate of −4 fractions (95% confidence interval: −7 to −2). Supportive analyses used a multivariable negative binomial model (rate ratio: 0.71; p = 0.0018) and propensity score analysis (p = 0.012). The dissatisfaction rate was 20%; 78.9% of patients stated at least a little impact of trial participation on the use of health technology. Conclusions: Given the limitations of this study, the app was associated with fewer fractions with a bladder volume < 200 mL in this cohort. Although patient dissatisfaction was considered acceptable, further optimization of the app would be welcomed. Moreover, the findings of this study require confirmation in a randomized trial that also considers urinary toxicity.

Journal of Clinical Medicine doi: 10.3390/jcm15218558

Authors: Bui Hong Thien Khanh Pham Thi Cam Van Nguyen Phuc Thinh

Background/Objectives: Unrestricted kinematic alignment (KA) may produce excessive tibial varus in some knees. We evaluated a modified KA technique using conventional mechanical instruments combined with a standardized 3D-printed 2° tibial recut guide that retained calipered femoral resurfacing while selectively restricting tibial varus, comparing it with historical manual mechanical alignment (MA) controls. Methods: This single-centre comparative cohort study included 120 knees from 104 patients (66 consecutive prospective KA knees and 54 historical MA knees). Inverse probability of treatment weighting targeting the average treatment effect on the treated adjusted for age, sex, body mass index, ASA class, and preoperative hip–knee–ankle angle. Treatment-effect inference used patient-level cluster-robust standard errors across 104 patient clusters. Outcomes included the 2011 Objective Knee Society Score (Objective KSS), patient-reported outcomes, and postoperative coronal alignment. Results: The recut guide was used in 37/66 KA knees (56.1%). KA was associated with a higher Objective KSS (ATT +15.47; 95% CI 9.07–21.87; p < 0.001), driven mainly by alignment (+11.93; 95% CI 5.93–17.94; p < 0.001) and stability (+2.16; 95% CI 0.54–3.79; p = 0.009), while the Objective KSS ROM component did not differ significantly. Patient-reported outcomes were not significantly different, including WOMAC (ATT −4.16; 95% CI −8.33 to 0.02; p = 0.051), OKS (ATT −1.89; 95% CI −3.88 to 0.10; p = 0.062), FJS (ATT +10.70; 95% CI −1.31 to 22.71; p = 0.081), and total KSS (ATT +5.17; 95% CI −2.36 to 12.70; p = 0.179). KA showed less residual varus HKA (−2.03° vs. −4.61°), fewer postoperative HKA outliers beyond ±6° (6.1% vs. 38.9%), higher FMA (91.20° vs. 89.26°), and a more horizontal joint line, whereas TMA did not differ significantly (p = 0.331). Conclusions: Modified KA with selective tibial varus restriction was associated with a higher postoperative Objective KSS and more favorable coronal alignment than historical manual MA, while patient-reported outcomes were largely comparable. These findings support the technical feasibility of the approach but do not establish causal or clinical superiority over contemporary MA.

Journal of Clinical Medicine doi: 10.3390/jcm15218557

Authors: Ahmed Abu-Zaid Omar A. Alnajar Rashed A. Alasoosi Fawaz Almutairi Abdullah M. Alazemi Latifah Alyaqout Mariam Mohammad Alkandari Farah R. Alqussair Abdulaziz S. Alasfar Omar Almutairi Maryam S. AlAmrani Abdullah J. Alrashed Abdullah M. Alharran

Objective: To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing low versus high intraoperative intraocular pressure (IOP) during phacoemulsification. Methods: PubMed, Scopus, Web of Science (WoS), and CENTRAL were searched from inception through 6 July 2026, followed by a supplementary manual search conducted before data extraction on 5 August 2026, to identify any additional eligible studies. RCTs comparing low-IOP versus high-IOP strategies during phacoemulsification were included. Outcomes were categorized as intraoperative, postoperative, and safety outcomes. Data were pooled as mean differences (MDs) or risk ratios (RRs) with corresponding 95% confidence intervals (CIs) using random-effects models. Results: Twelve RCTs comprising 1051 eyes were included. Cumulative dissipated energy was comparable between low- and high-IOP strategies (MD −0.12, 95% CI −0.45 to 0.20; p = 0.42). No significant between-group differences were observed in endothelial cell density, best-corrected visual acuity, central corneal thickness, or postoperative IOP across the reported follow-up periods (all p > 0.05). Intraoperative pain, aspiration time, total case time, fluid usage, and safety outcomes were also comparable between groups. Low-IOP phacoemulsification was associated with a modest increase in total ultrasound time (MD 1.53 s, 95% CI 0.03 to 3.03; p = 0.047). Conclusions: Low-IOP phacoemulsification provides intraoperative, postoperative, and safety outcomes broadly comparable to high-IOP strategies. Despite a statistically significant but clinically negligible increase in ultrasound time of approximately 1.5 s in favor of low-IOP, no significant differences were observed in cumulative dissipated energy, endothelial cell density, best-corrected visual acuity, central corneal thickness, postoperative IOP, or safety outcomes. However, these findings should not be interpreted as definitive evidence of equivalence or non-inferiority between the two strategies.

Journal of Clinical Medicine doi: 10.3390/jcm15218556

Authors: Ercan Yılmaz Zeynep Yamancan Yılmaz

We read with great interest the review by Lan et al [...]

Journal of Clinical Medicine doi: 10.3390/jcm15218554

Authors: Mattia Pasquinucci Maria Elena Derchi Alessandra Siboldi Sara Bondanza Chiara Panicucci Federica Trucco Claudio Bruno Davide Meneghesso

Advances in respiratory care have significantly extended the life expectancy of patients with Duchenne and Becker muscular dystrophies (DMD/BMD), making progressive dilated cardiomyopathy the leading cause of mortality in this population. Historically, a conservative “watch and wait” approach was often maintained until overt systolic dysfunction became evident. However, the advent of advanced echocardiographic technologies, particularly Global Longitudinal Strain (GLS) imaging, has demonstrated that myocardial impairment begins in early childhood, long before a decline in ejection fraction occurs. This critical evidence strongly advocates for a paradigm shift toward early, proactive cardioprotective strategies. As patients progress into the transitional age and adulthood, the pediatric prophylactic approach (traditionally based on ACE inhibitors and beta-blockers) must integrate with evolving adult heart failure guidelines. This comprehensive review critically evaluates the pathophysiological continuum of dystrophic cardiomyopathy. We highlight the prognostic value of early subclinical detection (GLS) and specifically discuss the transition to modern guideline-directed medical therapies (GDMTs), exploring the emerging role of Angiotensin Receptor-Neprilysin Inhibitors (ARNI, e.g., sacubitril/valsartan) and SGLT2 inhibitors (e.g., dapagliflozin) in this specific cohort. Finally, we address the role of advanced device therapies (ICD, CRT, and left ventricular assist devices) in end-stage disease. By bridging pediatric neurology and adult cardiology, this review aims to equip clinicians with an updated, multidisciplinary framework to optimize cardiovascular outcomes in the growing population of transitional-age DMD/BMD patients.

Journal of Clinical Medicine doi: 10.3390/jcm15218555

Authors: Paulina Mizera Karol Kamil Kłosiński Joanna Maria Czyżewska Jacek Cywiński Zbigniew Włodzimierz Pasieka Mateusz Jęckowski

Background: Renal arteriovenous fistula (RAVF) and renal artery pseudoaneurysm (RAP) are rare vascular complications that may occur following renal surgery, trauma, or endovascular interventions. Delayed presentation after nephrectomy is exceptionally uncommon. Case Description: We report the case of a 59-year-old woman with a pseudoaneurysm of the left renal artery stump associated with a high-flow renal arteriovenous fistula who was diagnosed three decades after left nephrectomy performed for complicated nephrolithiasis. The patient presented with episodic left flank pain without haematuria. Computed tomography angiography (CTA) and selective angiography confirmed the presence of a pseudoaneurysm and a high-flow arteriovenous fistula. Endovascular coil embolization was initially attempted; however, the coil migrated through the high-flow fistulous tract into the peripheral left pulmonary arterial circulation. Because the patient remained asymptomatic and haemodynamically stable and the coil was located peripherally, the procedural risk of retrieval was considered to outweigh the anticipated benefit. The coil was therefore left in situ under clinical and imaging surveillance. Because substantial arteriovenous shunting persisted after the unsuccessful embolization, definitive laparoscopic ligation of the left renal artery and vein stumps was successfully performed approximately one month later. During the two-year follow-up, two CTA examinations and Doppler ultrasonography confirmed complete occlusion of the fistula and pseudoaneurysm, with no recurrent abdominal symptoms or pulmonary complications related to the migrated coil. Discussion: Although post-nephrectomy arteriovenous fistulas presenting 28 and 45 years after surgery have previously been reported, the combination of a renal artery stump pseudoaneurysm, a high-flow fistula, pulmonary coil migration, persistent arteriovenous shunting, and subsequent successful laparoscopic management is particularly unusual. This case highlights the technical challenges of endovascular treatment in high-flow fistulas and the role of surgical management following unsuccessful embolization. Conclusions: Delayed renal artery stump pseudoaneurysm associated with renal arteriovenous fistula after nephrectomy is an extremely rare condition. Although endovascular embolization remains the preferred first-line treatment, surgical management may be necessary in cases complicated by technical failure or embolization-related complications.

Journal of Clinical Medicine doi: 10.3390/jcm15218553

Authors: Egemen Cicek Cem Deniz Ayıkol

Background/Objectives: Perforated peptic ulcer (PPU) is a serious clinical condition requiring emergency surgery and continues to carry a significant risk of mortality. This study evaluated factors associated with in-hospital mortality and the discriminatory performance of admission parameters. Methods: We retrospectively studied 385 adults who underwent emergency surgery for PPU between January 1999 and December 2025. Survivors and non-survivors were compared using nonparametric tests for continuous variables. A multivariable logistic regression model included 265 complete cases (40 deaths), and selected admission variables were evaluated using receiver operating characteristic (ROC) analysis. Results: In-hospital mortality occurred in 49 patients (12.7%). Non-survivors were older (median 76.50 vs. 55.00 years; p < 0.001) and had lower hemoglobin (12.30 vs. 14.90; p < 0.001) and higher BUN levels (36.00 vs. 21.00; p < 0.001). Time from symptom onset to admission did not differ significantly between groups (median 24 vs. 16 h; p = 0.471). After adjustment, ASA class remained associated with mortality (adjusted OR 5.404; 95% CI 2.640–11.064; p < 0.001), whereas BUN did not (adjusted OR 1.010; 95% CI 0.988–1.032; p = 0.378). ROC AUC values were 0.801 for ASA, 0.788 for age, and 0.749 for BUN. Conclusions: ASA class was independently associated with in-hospital mortality in this cohort. Although BUN showed discrimination in ROC analysis, its adjusted association was not statistically significant. Findings and exploratory cut-offs require external validation.

Journal of Clinical Medicine doi: 10.3390/jcm15218552

Authors: Łukasz Turek Marcin Sadowski Łukasz Zandecki Jacek Kurzawski Marianna Janion

Background/Objectives: Whether long-term prognosis differs between patients with atrial fibrillation (AF) and those with atrial flutter (AFL) after adjustment for baseline cardiovascular characteristics remains unclear. Methods: In this prospective observational cohort study, we enrolled 656 patients meeting predefined anticoagulation eligibility criteria with AF (n = 558) or AFL (n = 98) who underwent transesophageal echocardiography (TEE) before a planned rhythm-control intervention. The primary endpoint was left atrial appendage thrombus (LAAT) detected at the index TEE. Long-term outcomes included cardiovascular death, heart failure (HF) hospitalization, ischemic stroke, transient ischemic attack, myocardial infarction, and systemic thromboembolism. Results: LAAT was detected in 14.2% of patients with AF and 10.2% of patients with AFL (p = 0.29). After multivariable adjustment, AFL versus AF was not independently associated with LAAT (adjusted odds ratio [aOR], 0.53; 95% confidence interval [CI], 0.25–1.11; p = 0.09). Median follow-up was 6.85 (3.64–8.53) years. Cardiovascular death occurred in 96 patients (14.6%; AF: n = 78, AFL: n = 18), and HF hospitalization occurred in 91 patients (13.9%; AF: n = 78, AFL: n = 13). Log-rank comparisons were not statistically significant for cardiovascular death (log-rank p = 0.42) or HF hospitalization (log-rank p = 0.73). In extended Cox models that accounted for nonproportional hazards, AFL versus AF was not independently associated with cardiovascular death (adjusted hazard ratio [aHR], 1.09; 95% CI, 0.64–1.85; p = 0.75) or HF hospitalization (aHR, 0.69; 95% CI, 0.37–1.27; p = 0.23). Conclusions: Catheter ablation was recorded in 83.7% of AFL versus 24.6% of AF patients, including index-hospitalization ablation in 46.9% versus 0%, respectively. In this selected cohort meeting predefined anticoagulation eligibility criteria referred for TEE-guided rhythm control, no statistically significant independent association was detected between index arrhythmia type (AF versus AFL) and LAAT, cardiovascular death, or HF hospitalization. Importantly, these findings describe associations under markedly different subsequent rhythm-control treatment pathways and do not establish equivalent intrinsic risks for AF and AFL. The smaller AFL group (n = 98) and wide confidence intervals limit precision; clinically meaningful differences cannot be excluded. These findings should not be extrapolated to unselected AF/AFL populations, including asymptomatic patients, those managed exclusively with rate control, or patients not receiving anticoagulation. The comparison is based on presenting arrhythmia, not a rhythm phenotype confirmed to persist throughout follow-up; incident AF among patients initially presenting with AFL was not systematically ascertained.

Journal of Clinical Medicine doi: 10.3390/jcm15218551

Authors: Fabiana Lucà Alessandro Navazio Samuela Carigi Mauro Gori Giovanna Geraci Luisa De Gennaro Concetta Di Nora Paolo Manca Maria Vittoria Matassini Vittoria Rizzello Maria Denitza Tinti Matteo Bianco Renata De Maria Vittorio Palmieri Daniela Aschieri Ilaria Battistoni Claudio Bilato Stefania Angela Di Fusco Vered Gil Ad Attilio Iacovoni Barbara Maria Teresa Mabritto Massimo Milli Pietro Scicchitano Francesco Vigorito Michele Massimo Gulizia Furio Colivicchi Fabrizio Oliva Federico Nardi Massimo Grimaldi

Background: Heart failure (HF) remains a major cause of morbidity, mortality, and healthcare resource utilisation, requiring integrated multidisciplinary care across hospital and community settings. This study aimed to describe the organisation of HF care and post-discharge management in Italy through two complementary national surveys promoted by the Italian Association of Hospital Cardiologists (ANMCO). Methods: Two complementary cross-sectional organisational surveys were conducted to describe the organisation of HF care in Italy. The Regioni 3.0 survey, performed between November 2023 and September 2024, collected 196 responses from directors of cardiology departments and HF Centers regarding organisational resources, post-discharge follow-up pathways, and integration with community healthcare services. A second survey, administered during the ANMCO Heart Failure Centers Convention in October 2024, collected 135 responses on discharge planning and outpatient follow-up practices. Results: HF outpatient clinics were available in 85.7% of Centers, whereas only 42.6% reported non-physician staff specifically assigned to HF care. Structured post-discharge follow-up pathways were reported by 91.3% of Centers, but functional links with primary care or community healthcare services were present in only 47.7%. Medication reconciliation and patient education were routinely performed in most Centers, whereas telemonitoring systems were available in approximately one-third of respondents. Conclusions: HF care in Italy is supported by a widespread network of outpatient clinics and structured post-discharge follow-up pathways. However, important organizational gaps remain in multidisciplinary staffing, hospital–community integration, and telemonitoring, highlighting the need to strengthen multidisciplinary resources, improve hospital–community integration, and expand telemonitoring to support more coordinated HF care nationwide.

Journal of Clinical Medicine doi: 10.3390/jcm15218550

Authors: Brent Musolf Carmen Nussbaum-Krammer Michael O’Neal Tobias Wuerfel Nicola Maffulli Christoph Schmitz

Background/Objectives: Chronic wounds such as diabetic foot ulcers, venous leg ulcers and burns are a major health-care burden. Extracorporeal shock wave therapy (ESWT) is a non-invasive treatment that promotes angiogenesis and tissue regeneration. This review synthesizes the clinical evidence for ESWT in wound management, and asks how contemporary reviews reflect it. Methods: PubMed and Ovid/Embase were searched from inception to 1 September 2026 according to PRISMA, regardless of wound type, study design or ESWT modality. Fifty-one clinical studies and 46 prior reviews were analyzed. Heterogeneity confined the primary synthesis to a qualitative one; an exploratory pooled analysis was performed for the one endpoint reported consistently enough to permit it. Results: None of the 46 previously published reviews covered the original evidence in its full breadth: each cited a median of 19.4% of the clinical studies available at its reference date (range 0–90.9%), and systematic reviews covered no more than narrative ones. Most studies reported improved healing across all four modalities. In seven controlled trials in diabetic foot ulcers reporting complete healing as events and denominators, the exploratory pooled risk ratio favored ESWT (1.51, 95% CI 1.22–1.87; I2 = 0%; 689 patients). Such data existed for three modalities only, resting on one trial for two, so modalities could not be compared. Conclusions: ESWT may be a useful adjunct in wound management, particularly for diabetic foot ulcers, although the evidence is heterogeneous and partly uncontrolled. Because no previous review reflected the evidence base as a whole, conclusions drawn from it should be read with caution. Head-to-head trials with matched physical dose are needed before any modality can be preferred.

Journal of Clinical Medicine doi: 10.3390/jcm15218549

Authors: Danilo Mladenović Jelena Stojanov Sanja Kostić Nevena Mićanović Marjana Gojković Miloš Petronijević Svetlana Vrzić Petronijević Jovana Bjekić Bojana Dunjić Kostić Miloš Marković

Background: Mood disorders, especially perinatal depression (PND), are a major public health concern, yet in Serbia there are no standardized screening protocols and limited data on healthcare professionals’ preparedness to recognize and manage it. Aims: To explore awareness, attitudes toward screening, self-reported familiarity, and self-reported clinical practices regarding PND among healthcare professionals in Serbia. Method: A cross-sectional, anonymous online survey was conducted in a convenience sample of 221 healthcare professionals (gynecology/obstetrics, pediatrics, psychiatry, midwifery, and community nursing) from two urban centers (Belgrade and Niš). A de novo 23-item survey was used. Group differences were tested with Fisher’s exact tests, and associations with demographic and professional characteristics were examined with penalized (Firth) logistic and ordinal regression models with psychiatry as reference category; p-values were Holm-adjusted within each family of tests. Results: Most respondents recognized pregnancy (85.5%) and the postpartum period (93.7%) as periods of increased risk for mental disorders and supported routine screening (91.0%). However, self-reported awareness of guidelines, screening timeframes, and diagnostic criteria was limited, particularly among non-psychiatric professionals. In multivariable analyses using psychiatry as the reference category, respondents working in gynecology/obstetrics had significantly lower odds of reporting awareness of national guidelines (OR = 0.120, 95% CI 0.038–0.327), international guidelines (OR = 0.176, 95% CI 0.044–0.575), recommended screening timeframes (OR = 0.053, 95% CI 0.007–0.237), and institutional clinical pathways (OR = 0.047, 95% CI 0.005–0.235). Respondents working in pediatrics also had lower odds of reporting awareness of national guidelines (OR = 0.121, 95% CI 0.043–0.297) and screening timeframes (OR = 0.032, 95% CI 0.005–0.132). Both non-psychiatric groups had higher odds of reporting poorer familiarity with ICD-10 diagnostic criteria and choosing referral to a psychiatrist rather than initiating screening themselves in the clinical vignette. All reported associations remained significant after Holm correction. Conclusions: In this convenience sample, gaps in self-reported familiarity, screening practices, and perceived institutional organization were evident, particularly outside psychiatry. Although the findings cannot be extrapolated to the national level without caution, they suggest that integrating routine screening into maternal care, targeted training, and updated national guidelines could improve the early detection and care of PND.

Journal of Clinical Medicine doi: 10.3390/jcm15218547

Authors: Nadra Elyass Elamin Dost Muhammad Halepoto Mohamed Eid Soliman Abdulrahman M. Alhowikan Laila Yousef Al-Ayadhi

Background: Soluble CD40 ligand (sCD40L) plays an important role in inflammation and autoimmune disorders, including a variety of neurological and neurodegenerative disorders. However, evidence regarding the role of sCD40L in autism spectrum disorder (ASD) is limited. Therefore, the aim of this study was to assess the clinical significance of plasma sCD40L levels in individuals with ASD and to examine their relationship with the severity of ASD, social impairments, and sensory dysfunction. Materials and Methods: Plasma levels of sCD40L were measured using an enzyme-linked immunosorbent assay (ELISA). The severity of ASD, social impairments, and sensory dysfunction was assessed in all children with ASD using the Childhood Autism Rating Scale (CARS), the Social Responsiveness Scale (SRS), and the Short Sensory Profile (SSP), respectively. Results: Plasma sCD40L levels were significantly increased in children with ASD (83.77 ± 24.76) compared with controls (68.28 ± 12.74), with p = 0.001. Plasma sCD40L levels were significantly higher in children with severe ASD-related symptoms. The mean sCD40L levels were 87.23 ± 20.93 among children with severe ASD according to the CARS, 86.45 ± 25.53 among those with greater social impairment according to the SRS, and 89.74 ± 27.22 among those with atypical sensory processing according to the SSP (p ≤ 0.05). These results indicate that sCD40L levels increased with greater severity of the symptoms. Additionally, receiver operating characteristic (ROC) curve analysis revealed significant discriminatory ability of plasma sCD40L between the two groups, with an AUC of 0.701 [95% confidence interval (CI), 0.583–0.819, p < 0.001]. Conclusions: Our study suggests that sCD40L may contribute to the pathophysiology of ASD and be associated with the severity of ASD symptoms. This association suggests that sCD40L may serve as a promising biomarker for neuroinflammatory processes associated with ASD. However, further studies with larger sample sizes are warranted to validate these findings.

Journal of Clinical Medicine doi: 10.3390/jcm15218548

Authors: Eman M. Mansory Maha A. Badawi

Background: Manual, paper-based blood donor history questionnaires require blood bank staff to cross-reference lengthy eligibility manuals, which can slow decision-making and introduce inconsistency. Staff-facing digital references have improved workflow efficiency in other healthcare settings, but their use in the Saudi blood donation process has not been explored. Objective: To assess the feasibility and staff acceptability of a searchable digital version of the DHQ eligibility manual developed with AI assistance, and to explore its association with perceived screening time and overall process rating. Methods: This was a two-center, prospective, pre-post quality improvement pilot conducted between April–August 2026: The Saudi National Donor History Questionnaire (DHQ v1.0) and its 52-item eligibility flowchart were converted into a searchable reference and a digital questionnaire that generates an eligibility output. Baseline and post-implementation staff surveys were administered and compared. Results: Twelve responses were obtained at each assessment, the baseline and post-implementation surveys (86% response rate). Perceived time efficiency improved, with 33% of participants reporting the screening process took less than 5 min using the tool, compared with none reporting the same impression before tool use. Overall process rating was unchanged. Perceived tool-specific ratings were favorable across ease of use, speed of retrieval, accuracy, workflow improvement, and satisfaction. Medication-related uncertainty fell from 75.0% to 50.0%. Conclusions: An AI-assisted digital adaptation of an existing paper-based donor eligibility manual was feasible and well accepted by staff. More staff reported shorter per-donor assessment times after implementation; however, this exploratory, self-reported finding needs confirmation in larger studies with objective measures.

Journal of Clinical Medicine doi: 10.3390/jcm15218546

Authors: Nneka Nwachukwu Manila Gaddh

Pregnancy-related venous thromboembolism (VTE) remains a leading cause of maternal morbidity and mortality. Physiologic changes in pregnancy, along with patient-specific and pregnancy-specific risk factors, increase this VTE risk. The prevention and treatment of pregnancy-related VTE is often complex and requires the careful consideration of variation in clinical guidelines, VTE risk profile, bleeding assessment, careful delivery planning and patient preference. The mainstay of treatment for an acute VTE in pregnancy is the use of low-molecular-weight heparin. In this review, we highlight three clinical cases to review clinical approaches to the prevention and treatment of VTE in pregnancy in these scenarios. Importantly, this review goes over the current understanding of the pathophysiology and clinical practice experience for pregnant patients with VTE. We also explored the variation in professional clinical guidelines on VTE prophylaxis and treatment strategies in pregnancy, and how these guidelines may be interpreted in the context of patient care for optimal outcomes.