Journal of Clinical Medicine doi: 10.3390/jcm15187092

Authors: Dănuț Visarion Caimac Anca Maria Amzolini Simona Patru Carmen Daniela Neagoe Miruna Andreiana Matei Klejda Tani Adina Mitrea Diana Clenciu Amelia Valentina Genunche-Dumitrescu Mihai Cealîcu Paraschiva Postolache Ana Maria Bumbea

Background: Cerebral palsy is associated with complex motor impairments, including spasticity, reduced joint mobility, and functional limitations. Longitudinal data describing changes during sustained rehabilitation remain limited. Objective: We evaluated longitudinal changes in muscle tone, joint mobility, and gross motor function in children with spastic diplegic cerebral palsy participating in a structured 12-month rehabilitation program. Methods: This prospective, uncontrolled observational study included 94 children aged 5–10 years, selected from 116 children screened for eligibility. Assessments were performed at baseline (T0), 6 months (T1), and 12 months (T2). Outcomes included muscle tone (Modified Ashworth Scale, MAS), joint mobility (goniometry), and gross motor function (GMFM-88). Longitudinal changes were assessed using the Friedman test, followed by Bonferroni-adjusted post hoc pairwise comparisons between T0–T1, T0–T2, and T1–T2. Associations were assessed using Spearman’s rank correlation coefficient (ρ). Results: Significant longitudinal differences were observed across the evaluated outcomes (overall Friedman tests, p < 0.0001). Median MAS scores decreased from 3 at T0 to 2 at T2 across the evaluated muscle groups. Hip abduction increased, knee extension deficit decreased, and ankle dorsiflexion improved over the study period. GMFM-88 scores also increased longitudinally. Moderate-to-strong associations were observed between muscle spasticity and joint mobility parameters (ρ = −0.881 to 0.682). Conclusions: Favorable longitudinal changes in muscle tone, joint mobility, and gross motor function were observed during participation in the 12-month rehabilitation program. Given the uncontrolled observational design, these changes cannot be attributed exclusively to the rehabilitation intervention.

Journal of Clinical Medicine doi: 10.3390/jcm15187091

Authors: Filippo Calanna Silvia De Martinis Leonardo Clausetti Alessia Invernizzi Luca Tanel Roberto Viganò Alessandra Menon Alessio Maione Riccardo Compagnoni Paolo Ferrua Pietro S. Randelli

Background: Total knee arthroplasty (TKA) is an established treatment for end-stage rheumatoid arthritis (RA). Although cemented fixation has traditionally been preferred because of concerns regarding poor bone quality, advances in implant design and osseointegration have renewed interest in cementless fixation. This study evaluated the long-term clinical and radiological outcomes of cementless TKA in patients with RA. Methods: A retrospective single-center study included adult patients with RA who underwent primary cementless TKA between 2004 and 2021 using the same cruciate retaining implant. Clinical outcomes were assessed using range of motion (ROM), Visual Analog Scale (VAS), Oxford Knee Score (OKS), and patient satisfaction. Radiographic evaluation assessed implant fixation, while implant survivorship was analyzed using bilateral clustering via a Marginal Cox model analysis. Results: Seventy-five cementless TKAs performed in 52 patients were analyzed after a mean clinical follow-up of 10.8 ± 3.8 years. Mean ROM was 101° ± 26.5°, mean VAS score was 0.88 ± 1.84, and mean OKS was 40.3 ± 7.1. Overall, patients were satisfied or very satisfied in 89.6% of implants. Radiographic assessment showed no evidence of progressive radiolucent lines, osteolysis, implant subsidence, aseptic loosening, or malalignment. Only one revision was required because of periprosthetic joint infection, resulting in an implant survivorship of 98.3% at long-term follow-up. Conclusions: Cementless TKA demonstrated excellent long-term implant survival, durable radiographic fixation, and favorable clinical and functional outcomes in patients with rheumatoid arthritis. These findings support modern cementless fixation as a reliable and effective alternative to cemented TKA in carefully selected RA patients.

Journal of Clinical Medicine doi: 10.3390/jcm15187090

Authors: Oana Ciobănescu Anda Elena Crișan Răzvan Marian Bălan Virgil Pătrașcu Andrada-Nemesis Crișan Cristiana-Iulia Dumitrescu Mădălin-Cristian Moraru Suzana Măceș Mihai Popescu Daniela Dumitrescu

Background/Objectives: Squamous cell carcinoma (SCC) of the lip occupies an ambiguous position between cutaneous and oral-cavity oncology and lacks dedicated radiotherapy guidelines, resulting in considerable practice variability. We systematically reviewed the reported radiotherapy practices, clinical outcomes and gaps in consensus at this site. Methods: Following PRISMA 2020 and prospectively registered in PROSPERO (CRD420261349994), we searched PubMed/MEDLINE, Scopus, the Cochrane Library (Trials) and ClinicalTrials.gov (20 March 2026). Studies of at least ten patients with lip SCC treated with external beam radiotherapy or brachytherapy were eligible. Risk of bias was assessed with ROBINS-I; the synthesis was narrative, following the Synthesis Without Meta-analysis (SWiM) reporting framework. Results: Nine studies (approximately 3904 patients; 1964–2021; six countries) met the criteria. Interstitial brachytherapy was the dominant modality (seven studies), with high local control (approximately 93–97% in modern actuarial series), favourable toxicity and good functional/aesthetic outcomes; external beam radiotherapy served mainly as adjuvant treatment. Doses, fractionation, nodal management and outcome reporting were markedly heterogeneous, and eight of nine studies were at serious risk of bias. Conclusions: Radiotherapy—in the identified literature, in effect, largely historical interstitial brachytherapy—appears to be an effective, organ-preserving option in early-stage lip SCC; no conclusions can be drawn for modern external beam techniques such as IMRT. The limited, brachytherapy-dominated evidence warrants cautious interpretation and justifies protocol standardisation, a core outcome set with validated quality-of-life instruments, and multi-institutional prospective registries.

Journal of Clinical Medicine doi: 10.3390/jcm15187089

Authors: Aneta Miszewska Olga Sobczak Piotr Góralczyk Jacek Kot

Background: Mechanically ventilated intensive care patients receiving hyperbaric oxygen therapy (HBOT) are uncommon and resource-intensive. We assessed temporal changes over 11 years in diagnostic composition, HBOT treatment activity, organ-support requirements, and in-hospital mortality at an academic centre. Methods: This single-centre retrospective cohort included mechanically ventilated ICU patients receiving HBOT during the period 2013–2023. Diagnoses were grouped as carbon monoxide (CO) poisoning, clostridial myonecrosis/gas gangrene, non-clostridial necrotising soft-tissue infections (NSTIs), or other indications. Annual patient and HBOT patient-session volumes and the annual number and proportion of nocturnal sessions were summarised descriptively. Calendar-time associations were estimated using exploratory univariable logistic regression with calendar year entered as a continuous predictor and are reported as odds ratios (ORs) per one-year increase with 95% confidence intervals (CIs). Results: Of 6410 HBOT-treated patients, 176 mechanically ventilated ICU patients (2.7%) underwent 1381 sessions; 781 (56.6%) were nocturnal. Annual volumes ranged from 10 to 22 patients and from 66 to 190 sessions, without a monotonic increase. The estimated OR per one-year increase was 0.85 (95% CI: 0.76–0.95) for CO poisoning, 0.85 (95% CI: 0.76–0.96) for clostridial myonecrosis/gas gangrene, 1.23 (95% CI: 1.11–1.36) for non-clostridial NSTIs, and 1.17 (95% CI: 1.04–1.31) for catecholamine infusion. Conclusions: Diagnostic composition shifted towards non-clostridial NSTIs. Catecholamine infusion was more frequent in the later calendar years, whereas the CVVHDF estimate was small and imprecise and the mortality estimate was near null. Persistent nocturnal activity supports ICU-capable infrastructure and flexible staffing for emergency HBOT.

Journal of Clinical Medicine doi: 10.3390/jcm15187087

Authors: Donghyeon Joo Jeong Tae Byoun Jae Young Cho Sungho Jo Kyeong Ho Yun

Background/Objectives: Contemporary drug-eluting stents (DES) differ in antiproliferative drug, strut geometry, polymer, alloy, and drug release kinetics, and the independent association between the eluted drug and clinical outcomes remains uncertain. We compared outcomes among contemporary sirolimus-, zotarolimus-, and everolimus-eluting stents. Methods: This single-center retrospective cohort included 1940 patients who underwent percutaneous coronary intervention (PCI) between 2012 and 2021 with sirolimus- (n = 537), zotarolimus- (n = 400), or everolimus-eluting stents (n = 1003). The primary endpoint was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction (MI), or target vessel revascularization (TVR). The secondary endpoint was major adverse cardiovascular events (MACE), a composite of all-cause death, MI, or any revascularization. Stabilized inverse probability of treatment weighting (IPTW) based on pretreatment covariates and PCI era was used to address baseline and temporal differences; follow-up was censored at two years. Results: During a median follow-up of 731 days, weighted TVF rates were 5.4%, 7.7%, and 6.5% in the sirolimus, zotarolimus, and everolimus groups, respectively. Compared with sirolimus, TVF did not differ with zotarolimus (hazard ratio [HR] 1.38; 95% confidence interval [CI] 0.74–2.58) or everolimus (HR 1.19; 95% CI 0.70–2.02; overall p = 0.458). MACE also did not differ (overall p = 0.517). In complex PCI, TVF was higher with zotarolimus and everolimus than with sirolimus; however, event counts were small and the analyses were exploratory. Conclusions: In this observational cohort, no significant differences in mid-term outcomes were observed among the three drug-defined groups. Because drug type is closely intertwined with stent platform design, these findings should not be extrapolated to individual stent platforms. The exploratory complex-PCI subgroup finding requires confirmation in larger studies.

Journal of Clinical Medicine doi: 10.3390/jcm15187084

Authors: Baihui Wu Zhaoyan Chen Fangyuan Tian

Background: Potentially inappropriate medication (PIM) use among older people is a serious public health problem associated with increased adverse drug events. PIM refers to medications where the adverse risks outweigh the potential benefits. Identifying the risk factors for PIM is essential for optimizing prescription practices and improving patient safety. Objectives: To establish a risk prediction model for potentially inappropriate medications (PIMs) in older patients with depression, providing guidance to optimize medication plans, reduce adverse drug reactions, and improve treatment outcomes and quality of life. Methods: Prescriptions for depression patients among all hospitals in the Chengdu area were taken as an example. A significant factor influencing PIM risk was identified through univariate and multivariate logistic regression analyses, and a nomogram was constructed. The discrimination and calibration of the model were evaluated via receiver operating characteristic (ROC) curves. Results: According to the analysis of the nomogram drawn from the prescriptions of patients with depression, it can be found that the department name, reimbursement, hospital grade, age, number of diseases, sleep disorders, hypertension, cerebrovascular disease and so on each have p < 0.05 for PIM. Data from the Chengdu area (n = 4629) were divided into a training set (n = 3548) and an internal validation set (n = 1081), with Zhengzhou data (n = 1620) used as the external validation set. ROC curve analysis revealed that the area under the curve (AUC) for the training set was 0.721, that for the internal validation set was 0.668, and that for the external validation set was 0.663. Conclusions: The prediction model based on these factors has predictive value for PIM use in older patients with depression, It shows some discriminatory ability, but its external performance is moderate and its calibration is insufficient. Nevertheless, it can be used for preliminary judgment of patients’ medication and as an auxiliary screening tool. Further optimization and prospective validation are still needed.

Journal of Clinical Medicine doi: 10.3390/jcm15187086

Authors: Eduardo Guzmán-Muñoz Exal Garcia-Carrillo Antonio Castillo-Paredes Felipe Montalva-Valenzuela Iván Molina-Márquez Jose Jairo Narrea Vargas Rodrigo Villaseca-Vicuña Emilio Jofré-Saldía Rodrigo Yáñez-Sepúlveda Dario Barrera-González

Background/Objectives: Elastic resistance bands are widely used in rehabilitation, injury prevention, and athletic conditioning because they are portable, inexpensive, and adaptable to multiple movement planes. However, their mechanical behavior and training dose are often insufficiently characterized. This structured narrative review aimed to synthesize current evidence on the neuromuscular mechanisms, prescription principles, and functional applications of elastic resistance bands in sports medicine and rehabilitation. Methods: PubMed, Scopus, Web of Science, and ScienceDirect were searched from inception to 31 May 2026. Peer-reviewed human studies and reviews were included when they addressed mechanical, neuromuscular, biomechanical, prescriptive, rehabilitative, injury-prevention, or performance-related aspects of elastic resistance exercise. Evidence was synthesized narratively to link mechanical configuration, neuromuscular responses, exercise prescription, and functional outcomes. Results: Elastic bands provide an ascending, position- and configuration-dependent resistance profile determined by band properties and exercise configuration. When effort and exercise configuration are controlled, elastic resistance can elicit muscle activation and strength adaptations comparable to conventional resistance, while supporting improvements in balance, functional capacity, power, sprint performance, change-of-direction ability, and selected sport-specific outcomes. Its directional versatility and capacity for gradual load adjustment support applications from early rehabilitation to return-to-sport and performance training. Nevertheless, prescription based on band color alone is inadequate, and inconsistent reporting limits reproducibility and study comparisons. Conclusions: Elastic resistance is a scalable and clinically relevant loading modality rather than an inherently low-load alternative. Evidence is more established for improvements in muscular strength and functional performance than for direct reductions in injury incidence or successful return-to-sport outcomes. Its effectiveness depends on explicit load quantification, individualized progression, appropriate exercise configuration, and transparent reporting of intervention parameters.

Journal of Clinical Medicine doi: 10.3390/jcm15187085

Authors: Mateusz Krzysztof Mateuszczyk Magdalena Łyko Joanna Maj

Background: Scabies is a World Health Organization–designated neglected tropical disease of rising incidence with increasingly reported treatment failure, making objective verification of cure important. Dermoscopy is well established for diagnosis, but its role in assessing treatment response has never been mapped. Objectives: To map how dermoscopy assesses treatment response in scabies—which markers, timepoints and cure definitions are applied, and how it relates to clinical and microscopic standards. Methods: A scoping review following PRISMA-ScR searched PubMed/MEDLINE, Web of Science, EBSCO and Scopus (2016–2026, English) using a two-concept strategy (scabies × dermoscopy); eligibility required baseline dermoscopy plus at least one further, separately reported dermoscopic assessment during or after therapy. Two reviewers screened independently, supplemented by citation searching. Results: Ten studies were included. The same mite structure appeared under at least four names; assessment timepoints (day 2 to beyond day 28) and cure definitions were inconsistent. Dermoscopy was the genuine object of investigation in few studies; only one used ultraviolet-induced fluorescence to track response. Conclusions: Despite the disease’s recognised importance, dermoscopic monitoring of scabies remains a declared rather than a designed research aim. No standardised marker, timepoint or cure definition exists; consensus standards analogous to the 2020 IACS diagnostic criteria are needed.

Journal of Clinical Medicine doi: 10.3390/jcm15187083

Authors: Song Han Mingjing Yu Ruonan Zhang Ling Xin Yu Qiao Tao Yan

Background/Objectives: Overlapping clinical and imaging features complicate the early differentiation between spontaneous spinal cord infarction (SCI) and seronegative acute myelitis (SAM). We aimed to compare the clinical and laboratory characteristics of SCI and SAM and, as an exploratory analysis, to develop and internally validate multivariable diagnostic models evaluating whether routinely available laboratory parameters provide additional discriminatory information beyond selected clinical features. Methods: We retrospectively analyzed 75 patients (34 SCI, 41 SAM) treated between January 2017 and June 2025. Between-group laboratory comparisons were adjusted for multiple testing using the Benjamini–Hochberg false-discovery-rate procedure. Penalized logistic regression analyses were performed using clinical variables, laboratory variables, and their combination, with candidate variables defined on clinical and data-quality grounds rather than by univariate statistical significance. Model discrimination was evaluated using repeated nested cross-validation. Bootstrap optimism correction was additionally performed for the full-data combined model, and decision curve analysis was conducted as an exploratory secondary analysis. Results: SCI patients were older, more often male, and had higher prevalence of hypertension and diabetes. Radicular pain was markedly more common in SCI. After Benjamini–Hochberg correction, five laboratory parameters remained significantly different between groups: CRP, triglycerides, monocyte percentage, and absolute monocyte count were higher in SCI, whereas HDL cholesterol was lower. In the combined penalized analysis, age, hypertension, radicular pain, CRP, triglycerides, absolute monocyte count, and absolute eosinophil count were retained. The clinical, laboratory, and combined models yielded AUCs of 0.821 (95% CI 0.718–0.910), 0.756 (95% CI 0.633–0.865), and 0.871 (95% CI 0.776–0.947), respectively. Compared with the clinical model, the combined model showed a modest increase in discrimination (ΔAUC 0.050, 95% CI 0.005–0.101, p = 0.030). Bootstrap internal validation of the full-data combined model yielded an optimism-corrected AUC of 0.902, compared with an apparent AUC of 0.937, with a mean optimism of 0.035. Exploratory decision curve analysis showed a potential net benefit of the combined model across a range of threshold probabilities. Conclusions: Spontaneous SCI and SAM showed distinct clinical and laboratory profiles in this retrospective cohort. Routine laboratory parameters provided modest additional discriminatory information beyond clinical features, and the combined model maintained discrimination during internal validation. These findings are exploratory and require validation in larger, independent cohorts before clinical application.

Journal of Clinical Medicine doi: 10.3390/jcm15187081

Authors: Ruoran Xia Evgeniy Tarabrin Sergey Muraviev Milena Ivanova Zelimkhan Berikkhanov

Background/Objectives: Prolonged air leak (PAL) remains one of the most common and costly complications after lung resection. A growing body of evidence implicates the residual pleural space (RPS) as a central pathogenetic link between recognized risk factors and persistence of the alveolopleural fistula. This review synthesizes evidence on RPS pathogenesis and compares six interventions that reduce RPS by acting on the diaphragm for PAL prevention. Methods: A narrative literature search was performed in PubMed, Google Scholar, Web of Science, eLibrary.ru, and China National Knowledge Infrastructure (CNKI), covering clinical and experimental studies, systematic reviews, and classic physiological work relevant to intrapleural pressure (IPP), RPS, and diaphragmatic control. Results: RPS and PAL are reciprocally linked, and major, upper-lobe, and right-sided resection independently predict both. RPS is accompanied by excess negative IPP, reduced lung compliance, and disproportionate wall stress at the resection margin. Six methods for reducing RPS volume through diaphragmatic control are described. Conclusions: RPS is the mechanistic link connecting established PAL risk factors to fistula persistence. Among the six methods, chemical denervation with botulinum toxin type A (BTX-A) is, in principle, the only method combining full reversibility, dose-dependent control, and no need for dedicated equipment. However, this conclusion rests on a single pilot animal study in a lower-lobectomy model, and translating it to upper-lobe, low-reserve patients, who carry the greatest PAL burden, requires dedicated dose-ranging and safety work before a clinical trial can be considered.

Journal of Clinical Medicine doi: 10.3390/jcm15187082

Authors: Kübra Orman Hanifi Korkmaz Sevilay Hançer Tecimer Pınar Tekin Sibel Çıplak Hadeel Alsaleh Monira I. Aldhahi

Background/Objectives: Persistent postural–perceptual dizziness (PPPD) and anxiety disorder (AD) share overlapping clinical features that make differentiation with conventional assessments challenging. This study examined whether virtual reality (VR)-based vestibular assessment and immersive phobic scenarios can reveal distinct response profiles between these conditions. Methods: In this preliminary, single-center, cross-sectional study, 32 participants (PPPD: n = 15, AD: n = 17) underwent joint otorhinolaryngological/audiological and psychiatric evaluation, including the Clinical Test of Sensory Interaction and Balance-VR (CTSIB-VR), Limits of Stability (LOS), Dizziness Handicap Inventory (DHI), Beck Anxiety Inventory (BAI), and two immersive VR scenarios (CrowdVR and Supermarket Scrolling). Symptom onset latency, maximum tolerated intensity, avoidance behavior, and post-scenario Simulator Sickness Questionnaire (SSQ) scores were recorded after each scenario. Results: Groups did not differ on any LOS parameter. CTSIB-VR Visual Preference was significantly higher in the PPPD group (74.07 ± 7.44 vs. 60.82 ± 2.46, p < 0.001). SSQ Disorientation scores during the CrowdVR and Supermarket Scrolling scenarios were significantly elevated in PPPD (p = 0.004 and p = 0.002, respectively); at baseline VR exposure, SSQ Disorientation showed the same directional pattern but did not reach significance (p = 0.069), and the SSQ Total Severity score at baseline was numerically higher in PPPD (51.61 ± 17.62 vs. 41.13 ± 11.83) at a trend level (p = 0.055). BAI Total was markedly higher in the AD group (29.82 ± 4.86 vs. 19.27 ± 6.43, p < 0.001). Symptom onset latency during CrowdVR exposure was longer in PPPD (median 5.36 vs. 3.10 min, p = 0.007), whereas avoidance behavior was more pronounced in the AD group (p = 0.027). Conclusions: PPPD and AD showed divergent, exploratory VR-based response profiles: PPPD was marked by visual dependence, prolonged tolerance, and greater disorientation, while AD showed higher anxiety burden and earlier avoidance. These preliminary, hypothesis-generating findings suggest scenario-based VR assessment may merit further study as an adjunct in differentiating PPPD from anxiety disorder, pending diagnostic-accuracy validation in larger, multicenter cohorts.

Journal of Clinical Medicine doi: 10.3390/jcm15187080

Authors: Paulina Wais Maia Stanisławska-Kubiak Elżbieta Niechciał Piotr Fichna Andrzej Kędzia Ewa Mojs Katarzyna Anna Majewska

Background/Objectives: Subtle cognitive alterations have been described in children with type 1 diabetes (T1D), but the association between cognition and real-time glycemia during cognitive testing remains unclear. This study aimed to investigate whether blood glucose level (BGL) measured immediately before the MOXO Continuous Performance Test (MOXO-CPT) is associated with cognitive performance and modified by clinical factors. Methods: A total of 117 children with T1D (aged 6–18 years) completed the MOXO-CPT assessing sustained attention, timeliness, impulsivity, and hyperactivity. Participants were stratified by BGL measured immediately before testing (<200 mg/dL [<11.1 mmol/L] vs. ≥200 mg/dL [≥11 mmol/L]). Group comparisons were performed using the Mann–Whitney U test. Multivariable linear regression models examined associations between BGL and cognitive outcomes, adjusting for HbA1c, age, sex, treatment modality and diabetes duration. Interaction analyses were also conducted. Results: In unadjusted group comparisons, participants with BGL ≥ 200 mg/dL demonstrated nominally higher sustained attention (p = 0.036) and timeliness scores (p = 0.040) than those with BGL < 200 mg/dL. However, these differences did not remain statistically significant after Benjamini–Hochberg correction and were not confirmed after adjustment for relevant covariates. No differences were observed in impulsivity or hyperactivity. In multivariable models, higher BGLs were independently associated with higher impulsivity scores (B = 0.013, p = 0.007), with higher scores indicating better impulse-control performance. A significant BGL–sex interaction was observed for timeliness. Sex-stratified analyses showed that higher BGLs were associated with better attention and timeliness in girls, whereas the association with impulsivity observed in boys was not confirmed using robust analysis. No significant interactions between BGL and HbA1c, age, treatment modality, or diabetes duration were observed after robust analysis. Conclusions: Real-time glycemia during cognitive testing was associated with subtle, domain-specific differences in cognitive performance in children with T1D. These findings do not establish causality or indicate that higher glucose levels improve cognitive performance. Concurrent glucose levels may be worth considering when interpreting cognitive assessments, although this should be confirmed in prospective studies.

Journal of Clinical Medicine doi: 10.3390/jcm15187079

Authors: Sinan Pektaş Çağatay Küçükbingöz

Background: Epidural blood patch (EBP) remains the standard procedural treatment for post-dural puncture headache (PDPH) persisting after conservative care; whereas, the evidence for greater occipital nerve block (GONB) is limited. This study describes pain trajectories during GONB-based management and factors associated with repeated GONB. Methods: Single-centre retrospective observational cohort of all consecutive patients treated for PDPH between January 2016 and January 2018. Eligible patients met the current ICHD-3 criteria after spinal anaesthesia, had a Numerical Rating Scale (NRS) score ≥ 4 and had persistent symptoms after ≥24 h of conservative management. Bilateral landmark-guided GONB (2.5 mL bupivacaine HCl 5 mg/mL per side) was repeated when the NRS remained ≥4 at a 24 h assessment, so group membership reflected the response to treatment. Results: Sixty-two patients were analysed (mean age 33.9 ± 15.1 years; 64.5% women). NRS decreased over seven days (Friedman χ2 = 262.6, p < 0.001; Kendall’s W = 0.847); on day 7, 57 patients (91.9%; 95% CI 82.5–96.5%) had absent-to-mild pain. Thirty-eight patients (61.3%; 95% CI 48.8–72.4%) received one block. In an exploratory Firth penalised model, baseline NRS (OR 2.41, 95% CI 1.55–4.15) and orthopaedic surgery (OR 5.02, 95% CI 1.36–21.56) were associated with repeated GONB. No GONB-related complications and no EBP were documented. Conclusions: NRS scores decreased during a strategy comprising one or more GONB sessions with concomitant conservative care, but these uncontrolled observations cannot separate any effect of GONB from spontaneous recovery, regression to the mean or concomitant treatment. They are hypothesis-generating and require prospective randomised confirmation.

Journal of Clinical Medicine doi: 10.3390/jcm15187078

Authors: Doris H. Fuertinger Felix J. Meigel Aiyuan Wang Sabrina Casper Sheng-Han Yueh Kevin Ho

Background: Ultrafiltration (UF) during hemodialysis is typically prescribed as a fixed treatment goal and delivered using a largely constant ultrafiltration rate throughout the session. We evaluated whether Adaptive Ultrafiltration (Adaptive UF), a physiological closed-loop control strategy guided by continuous relative blood volume (RBV) monitoring, could improve RBV target attainment while individualizing fluid removal within predefined treatment constraints. Methods: We performed a paired patient-specific in silico study using 119,472 historical hemodialysis treatments from 11,246 U.S. patients. Treatment-specific plasma refill rate profiles were derived from recorded RBV and ultrafiltration data. For each historical treatment, a corresponding Adaptive UF treatment was simulated and compared with the corresponding originally delivered treatment. Outcomes included the percentage of time within a predefined favorable RBV target region, UF delivery, and operational performance. Results: Mean time within the RBV target region increased from 36.3% with historically delivered treatments to 56.4% with Adaptive UF, showing an absolute improvement of 20.2 percentage points (95% CI, 19.9–20.5); target attainment improved in 90.0% of patients. Mean area outside the target range decreased from 280.7 to 139.5 RBV %–minutes. Mean achieved UF volume increased by 296.4 mL, although treatment-level UF delivery was bidirectional, increasing in 83.1% and decreasing in 16.9% of treatments. UF rates remained below 13 mL/kg/h in all simulations, and 99.4% of treatments remained within predefined UF volume limits. Conclusions: Adaptive UF improved intradialytic RBV target attainment and individualized UF delivery within predefined treatment constraints. Prospective studies are required to determine whether these physiological improvements translate into clinical benefit.

Journal of Clinical Medicine doi: 10.3390/jcm15187077

Authors: Annette M. Goulak Sophie Z. Gu Andres Serrano Teja M. Kapoor Gal Antman Sharon P. Keh Stephen L. Trokel Leejee H. Suh

Objectives: To investigate tear film characteristics in patients with Sjögren’s syndrome (SS) and dry eye disease (DED) using the Tear Film Imager (TFI), focusing on comparisons to a matched control group and correlations between TFI parameters and clinical characteristics. Methods: This pilot cross-sectional study enrolled 15 patients with confirmed SS and DED and compared them to 15 age-matched healthy controls. Both groups underwent tear film imaging with the TFI. SS participants also completed clinical evaluations including the Ocular Surface Disease Index (OSDI), Schirmer’s test, tear osmolarity, and tear breakup time (TBUT). TFI parameters included muco-aqueous layer thickness (MALT), muco-aqueous layer thinning rate (MALTR), lipid layer thickness (LLT), lipid map uniformity (LMU), lipid breakup time (LBUT), and interblink interval (IBI). Results: The study included 15 participants with SS (mean age 53.4 ± 15.1 years; 86.7% female) and 15 controls (mean age 52.3 ± 15.5 years; 73.3% female). SS participants exhibited significantly higher LMU (136.6 nm2 vs. 62.7 nm2; p = 0.034). Other parameters did not differ significantly. 60% of SS participants qualified for lipid-related DED versus 20% of controls. Schirmer’s test scores positively correlated with MALT (ρ = 0.61, p < 0.05), while shorter IBIs correlated with greater symptom severity on the OSDI (ρ = −0.75, p < 0.05) amongst the SS group. Conclusions: Lipid layer heterogeneity, as measured by LMU, appears to be a key feature of SS-associated DED. Future studies should validate these findings and investigate lipid-targeted therapies.

Journal of Clinical Medicine doi: 10.3390/jcm15187076

Authors: Chaitanyanand B. Koppiker Aijaz Ul Noor Rupa Mishra Vaibhav Jain Priya Sivadasan Sneha Bhandari Namrata Athavale Vishesha Lulla Sanika Limaye Mugdha Pai Chetan Deshmukh Mansi Munshi Beenu Varghese Upendra Dhar Sneha Joshi

Background: Centrally located breast tumors (CLBTs) present unique challenges in surgical management, requiring a delicate balance between oncological outcomes and cosmetic preservation. Oncoplastic techniques have emerged as a promising solution, allowing larger excisions while maintaining cosmetic appearance and function. This study aims to evaluate the surgical management of CLBT using oncoplastic breast surgery (OBS) treated at a single surgeon center in India. Methods: Among 138 patients with CLBT who underwent OBS, diagnosis and staging adhered to NCCN guidelines, with treatment decisions made via a multidisciplinary tumor board and patient counseling. Intraoperative ultrasound, specimen mammography, and frozen-section evaluation guided resection margins and axillary staging. Results: The median patient age was 52.7 years. Seventy-three percent of patients had unifocal disease, with 67% presenting at the cT2–cT3 stage, and 50% being clinically node-positive. Level 1 OBS was used in 21.73% of cases, Level 2 in 42.75%, and Level 3 in 35%, with 28% qualifying as extreme oncoplasty. Post-surgical complications were observed in 13% cases. Cosmetic outcomes were good to excellent in 94% of cases. At a median follow-up of 57 months, overall survival (OS) was 91.93%, and disease-free survival (DFS) was 88.17%. The BREAST-Q PROM response rate was 94%, with high satisfaction across all domains. Conclusions: This study highlights the safety and efficacy of OBS in CLBT. Key factors such as multidisciplinary management, meticulous surgical planning, and rigorous intraoperative rad-path assessment contributed to its success. These findings highlight the potential of OBS to optimize outcomes and enhance quality of life, even in difficult cases and resource-limited settings.

Journal of Clinical Medicine doi: 10.3390/jcm15187075

Authors: Sang Hyun Na So Hyun Ahn

Background/Objectives: Schatzker type is assigned early, usually from the anteroposterior (AP) radiograph. A single benchmark accuracy cannot say whether a model read the fracture, the anatomy around it, the annotation, or how the archive was assembled. We ran four inexpensive controls to separate those contributions. Methods: We benchmarked a ResNet-50 on PlaTiF, a 2026 public release built for artificial-intelligence research that pairs 421 AP knee radiographs from 186 patients with expert Schatzker labels and per-image tibial segmentations. Evaluation used stratified group five-fold cross-validation grouped by patient, five seeds and balanced accuracy. Inputs were cropped to the expert tibial segmentation shipped with the dataset, an oracle localisation unavailable at deployment. Four controls ran on identical folds: a regression given no pixel content; ablation of the tibial pixels with its complement; a regression on the expert mask alone; and an augmentation audit for label-erasing invariances. Results: Among the 128 fracture patients the network reached 0.345 ± 0.030 six-class balanced accuracy, +0.168 over a non-anatomical baseline fitted on the same folds and the same labels (95% CI +0.106 to +0.230, p = 0.002). Recall was graded: 0.72 for Schatzker VI, 0.11 for V and 0.04 for IV, the last two below chance (0.167). Erasing the tibial pixels left 0.257 ± 0.025, read on its own as the target bone being unused; its complement, the tibia with everything else removed, reached 0.367 ± 0.012, and the whole radiograph, which carries both, only 0.297 ± 0.032 (+0.071 for the tibia alone, 95% CI +0.031 to +0.111, p = 0.008). A regression on the expert mask alone reached 0.213 ± 0.034 and was not distinguishable from the erased model. On fracture versus no classifiable fracture the network reached 0.833 ± 0.028 against 0.814 ± 0.016 for a model given no pixels (p = 0.264), and a coronal computed tomography section accompanied 126 of 128 fracture patients but 24 of 58 others (p = 2.9 × 10−19). Conclusions: Each headline number admitted an explanation other than the fracture in the target bone. An ablation reported without its complement misstated where the signal lay, and an augmentation audit overturned our own explanation for the failure of type IV. Controls of this kind cost minutes, and this study illustrates why they can be informative when a benchmark is built on a retrospective clinical archive.

Journal of Clinical Medicine doi: 10.3390/jcm15187074

Authors: Toshiro Hirai Yuka Abe Ranko Kawata Yuriko Kusumoto Haruka Sako Takashi Matsumoto Deepesh Kumar Gupta Kazuyoshi Baba

Background/Objectives: Impaired masticatory function may compromise nutritional status in older adults wearing removable dentures, but its associations with nutritional risk indices remain unclear. This study aimed to examine associations between masticatory performance and risk defined by the Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT) score. Methods: This cross-sectional study included 179 outpatients aged ≥60 years wearing removable dentures. Masticatory performance was quantified by glucose concentration after chewing a gummy jelly. GNRI-defined risk was the prespecified primary outcome; PNI- and CONUT-defined risk were secondary. Logistic regression used Model 1 adjusted for age, sex, and comorbidity and an exploratory Model 2 with additional oral, dietary, and socioeconomic covariates. Results: Mean age was 74.1 ± 6.9 years, and 60.9% were female. Nutritional risk was identified in 21.8%, 48.6%, and 31.3% using the GNRI, PNI, and CONUT, respectively. Higher masticatory performance, indicated by higher glucose concentration, was associated with lower odds of GNRI-defined nutritional risk in both the primary parsimonious model (OR per 10 mg/dL increase, 0.89; 95% CI, 0.82–0.95; p = 0.001) and the exploratory additionally adjusted model (OR, 0.89; 95% CI, 0.82–0.96; p = 0.002). Associations with PNI- and CONUT-defined risk were not consistent across models. Conclusions: Lower masticatory performance was consistently associated with higher GNRI-defined risk, whereas comparable associations were not consistently observed for PNI- or CONUT-defined risk. Objective assessment of masticatory performance may provide clinically relevant information regarding GNRI-defined nutritional risk in older removable denture wearers.

Journal of Clinical Medicine doi: 10.3390/jcm15187073

Authors: Anton Uhlen Omar A. Oudit Darshan Patel Niraj Shah Lena Delorenzo Shreya Vuchula

Background: Telomeres are repetitive DNA sequences at chromosome ends that maintain genomic stability and shorten with age. Mutations in genes such as DKC1, TERC, TERT, NOP10, TINF2 and NHP2 cause Telomere Spectrum Disorders (TSD), leading to shortened telomeres. Acquired TSDs arise from environmental or occupational exposures and commonly affect veterans, truck drivers, and industrial workers. These exposures generate reactive oxygen species associated with cancer, liver disease, pulmonary disease, and bone marrow complications. Idiopathic Pulmonary Fibrosis (IPF) is most common pulmonary manifestation, followed by hepatic fibrosis/cirrhosis, hematologic disorders (e.g., aplastic anemia, MDS), and rarely gastrointestinal findings. This case describes a Gulf War veteran with suspected acquired short telomeres and multisystem involvement (idiopathic cirrhosis, pulmonary fibrosis, cytopenias) and uniquely found to have gastrointestinal (Gastric Antral Vascular Ectasia, GAVE), a potential unsuspected manifestation of TSD. Methods/Case: A 76-year-old male with atrial fibrillation (post-Watchman), cryptogenic cirrhosis, COPD, IPF, diabetes, and anemia presented with severe shortness of breath and hypoxia. Admitted for Sepsis and Acute Hypoxic Respiratory Failure. Treated with AVAPS, IV Zosyn, IV Lasix, steroids, bronchodilators, and diuretics. His condition improved, and he was discharged on baseline 3L O2. His Gl history included GAVE, an unsuspected bleeding complication causing chronic iron-deficiency anemia. Hematologic findings included chronic anemia, thrombocytopenia, and a hypocellular bone marrow with 12% atypical NK cells. Discussion/Results: The patient's Gulf War exposure to oil fire pollutants (benzene, toluene, PAHs, lead, cadmium, and particulate matter) likely contributed to telomere shortening and TSD-related multisystem disease. Given his shortened telomeres, testing for TERC and TERT mutations is warranted. GAVE (“watermelon stomach”) is a rare cause of GI bleeding characterized by dilated gastric vessels and chronic anemia and has been linked to TSD but no current reports have documented this association. Its occurrence in this patient suggests an unrecognized gastrointestinal manifestation of TSD as the patient does not have known history of portal hypertension. Conclusions: This represents an potentially underreported manifestation of acquired TSD presenting with combined hepatic, pulmonary, hematologic, and gastrointestinal (GAVE) involvement.

Journal of Clinical Medicine doi: 10.3390/jcm15187072

Authors: Jaeik Jang Myung Jin Jang Kang Kook Choi Soon Ki Min Wu Seong Kang Gil Jae Lee Seung Hwan Lee Jayun Cho Byungchul Yu

Background/Objectives: Traumatic bladder rupture often accompanies pelvic fracture, making it uncertain whether differences between extraperitoneal bladder rupture (EPBR) and intraperitoneal bladder rupture (IPBR) reflect the rupture site itself or overall trauma burden. Prior multi-institutional evidence has focused on EPBR. We therefore examined whether rupture site was associated with hospital length of stay after accounting for concomitant pelvic fracture and injury severity. Methods: We retrospectively reviewed 46 adults with definite traumatic bladder rupture treated at a single regional trauma center from January 2014 through December 2024. Rupture site was the primary exposure, hospital length of stay was the primary outcome, and intensive care unit (ICU) length of stay was the secondary outcome. Parsimonious exploratory log-linear models included rupture site, concomitant pelvic fracture, and Injury Severity Score (ISS). Results: Twenty-one patients had IPBR, 25 had EPBR, and 26 had concomitant pelvic fracture. In the adjusted primary-outcome analysis, rupture site was not clearly associated with hospital length of stay (EPBR versus IPBR adjusted ratio, 1.02; 95% CI, 0.59–1.76). The secondary adjusted analysis likewise showed no clear association with ICU length of stay (adjusted ratio for ICU days + 1, 1.31; 95% CI, 0.77–2.21). In unadjusted comparisons, pelvic fracture was observed more frequently with EPBR (72.0% versus 38.1%; p = 0.021; FDR q = 0.078), and EPBR was associated with longer hospital stay (median, 44.0 versus 24.0 days; p = 0.024; FDR q = 0.078) and ICU stay (8.0 versus 4.0 days; p = 0.007; FDR q = 0.037). Among 42 surgically treated patients, EPBR was associated with a longer admission-to-repair interval (adjusted ratio for days + 1, 2.21; 95% CI, 1.28–3.82). Conclusions: After adjustment for concomitant pelvic fracture and ISS, rupture site was not clearly associated with hospital or ICU length of stay. The conditional admission-to-repair finding may reflect complex trauma-care pathways rather than diagnostic delay. The frequent coexistence of bladder rupture and pelvic fracture reinforces the clinical importance of careful bladder assessment in patients with severe pelvic trauma.

Journal of Clinical Medicine doi: 10.3390/jcm15187071

Authors: Aliyah Abdulmohsen Alabdulqader Suliman Alkhudairy Abdulelah Saeed Mohammed Alwahabi Renad Ibrahim Alsulaiman Hassan A. Alzubaidi Reem T. Alshammari Lilian Mazen Abu Dabat Nawaf Abdullah Alqahtani Maha Jassim Alhamdan Ali Bakr Hesham Alshaikh

Background/Objectives: To systematically evaluate and compare the clinical efficacy and safety of non-cryotherapy modalities versus standard liquid nitrogen cryotherapy for the treatment of plantar warts, while exploring the influence of specific cryotherapy procedural parameters and intervention-related subgroup characteristics on treatment outcomes. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted according to PRISMA guidelines. We searched four major databases from inception until 1 July 2026. The primary outcome was complete clearance. Secondary outcomes included partial clearance, recurrence, and treatment-related adverse events. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using random-effects models. Results: Thirty-one RCTs involving 2313 patients were included. No statistically significant difference was detected between non-cryotherapy modalities and cryotherapy in complete clearance rates (RR = 1.09, 95% CI: 0.98–1.20; p = 0.10; I2 = 0.00%) or recurrence outcomes (RR = 0.90, 95% CI: 0.56–1.44; p = 0.66). Partial clearance significantly favored cryotherapy (RR = 0.65, 95% CI: 0.44–0.95; p = 0.03), particularly in subgroup analyses using two freeze–thaw cycles and treatment intervals of every two weeks. Regarding safety, topical therapies demonstrated significantly lower erythema rates than cryotherapy, while no statistically significant differences were observed in blistering, scarring, or secondary bacterial infection. Conclusions: No statistically significant difference was detected between non-cryotherapy modalities and cryotherapy regarding complete clearance or recurrence of plantar warts. Cryotherapy may offer better partial clearance under optimized treatment parameters, whereas topical therapies may be better tolerated in selected patients.

Journal of Clinical Medicine doi: 10.3390/jcm15187070

Authors: Mario Bonomini Lucia Del Vecchio Roberto Minutolo Vittorio Sirolli Francesco Locatelli

Anemia is a common complication of chronic kidney disease (CKD) and is associated with CKD progression and other adverse outcomes, which can result in increased rates of cardiovascular events and mortality. The search for the most effective and at the same time safe therapy for anemia in patients with CKD has always been a focus for nephrologists. The traditional treatment of CKD-dependent anemia is a combination of iron supplementation (oral and intravenous) and erythropoiesis-stimulating agents (ESA). Clinical practice data on the management of anemia in CKD patients highlight that anemia treatment is still suboptimal, and treatment is frequently omitted or underused due to a high rate of therapeutic inertia in initiating and increasing doses of anemia drugs. Moreover, ESA therapy has been associated with a risk of cardiovascular events, particularly in hypo responder patients requiring high doses or at high Hb targets. More recently, a class of oral drugs (hypoxia-inducible factor prolyl hydroxylase inhibitors) has been developed based on the modulation of the mechanisms underlying HIF oxygen sensing, leading to a simultaneous stimulation of endogenous erythropoietin production and improved iron metabolism. Unexpectedly, they went from a theoretical physiological superiority to a substantial non-inferiority, and remain largely underused likely because of the questionable concerns of their long-term safety. The landscape of the management of CKD anemia is evolving, including potential therapeutic erythropoietic strategies that are available in clinical practice and new approaches under clinical development, which can be employed as standalone approaches or eventually combined with conventional anemia treatments. We review here the most recent developments in investigational strategies for increasing erythropoiesis and improving the management of CKD anemia.

Journal of Clinical Medicine doi: 10.3390/jcm15187069

Authors: Oğuzhan Elçi Ali Benian

Background/Objectives: Most evidence on SARS-CoV-2 infection in pregnancy comes from hospitalised or symptomatic cohorts sampled early in the pandemic. We described maternal and neonatal outcomes in an unselected cohort of PCR-confirmed infections ending in live birth, identified characteristics associated with neonatal intensive care unit (NICU) admission and with prolonged maternal hospitalisation, and benchmarked event rates against national data. Methods: A retrospective cohort of all pregnant women with a positive nasopharyngeal SARS-CoV-2 RT-PCR result at a Turkish tertiary centre between March 2020 and May 2023. Of 151 women identified, 133 had retrievable records; eight pregnancies did not end in a live birth, leaving 125. Prespecified subgroups (NICU admission; maternal stay >3 days) were compared using Mann–Whitney U and χ2/Fisher exact tests, and cohort proportions with 2024 Turkish national rates by one-sample exact binomial tests. Results: The mean maternal age was 29.9 ± 5.5 years and gestational age at delivery was 38.0 ± 2.0 weeks; 19 women (15.2%) delivered preterm and 76 (60.8%) were diagnosed in the third trimester. Sixteen neonates (12.8%) required NICU care and two mothers (1.6%) intensive care; there were no maternal deaths or stillbirths. NICU admission was associated with preterm birth (56.2% vs. 9.2%, p < 0.001) and lower Apgar scores, and prolonged maternal stay with preterm birth, pregnancy-related comorbidity, and caesarean delivery (all p ≤ 0.001). Neither the trimester of infection nor vaccination status was associated with either outcome. Caesarean (64.0%) and preterm birth (15.2%) rates did not exceed national values (p = 0.58 and p = 0.42). Conclusions: Adverse outcomes clustered with preterm delivery and pre-existing pregnancy complications rather than with the timing of infection. Without a matched control group, and with power limited to large effects, these descriptive findings cannot exclude a clinically important effect of SARS-CoV-2.

Journal of Clinical Medicine doi: 10.3390/jcm15187068

Authors: Renè Tezze Cristina Rizza Ludovica Rita Vocale Giorgio Sciaramenti Alberto Sarti Giovanni Camaiti Pierpaolo Cioci Kristi Hoxha Isabella Maccaferri Francesco Paparazzo Federico Marchini Gianluca Campo Rita Pavasini

Left atrial appendage closure has emerged as an established nonpharmacological strategy for stroke prevention in selected patients with atrial fibrillation, particularly those in whom long-term oral anticoagulation is problematic. Its contemporary role, however, is defined by a central tension between procedural precision and clinical uncertainty. Advances in multimodality imaging, including transesophageal echocardiography, cardiac computed tomography, three-dimensional echocardiography, fusion imaging, and emerging computational tools, now allow highly accurate assessment of left atrial appendage anatomy, device sizing, intraprocedural guidance, and postprocedural surveillance. These techniques are essential to minimize peri-device leak, device-related thrombus, and other procedure-related complications in a structure characterized by marked interindividual variability. At the same time, the randomized evidence base remains nuanced. Early warfarin-era trials established the feasibility of LAAC, whereas contemporary comparisons with direct oral anticoagulants and best available medical therapy have yielded more heterogeneous results, reflecting differences in patient selection, comparator regimens, and endpoint design. Taken together, the available data support LAAC as a reasonable option in carefully selected patients at elevated bleeding risk or with limited tolerance for chronic anticoagulation, but not as a universal substitute for oral anticoagulant therapy. Future progress will depend on more refined phenotyping, standardized imaging pathways, and longer-term comparative data to better define which patients derive the greatest net clinical benefit from LAAC.

Journal of Clinical Medicine doi: 10.3390/jcm15187067

Authors: Saide Elif Güllülü Boz Fazıl Çağrı Hunutlu Esra Çelik Abdullah İbrahim Çalışır Halime Soyak Kabaca Cuma Bülent Gül Abdülmecit Yıldız Alparslan Ersoy Mustafa Güllülü Ayşegül Oruç

Background/Objectives: Rituximab (RTX) is an established treatment for primary membranous nephropathy (PMN); however, real-world data on predictors of response and the influence of previous treatment status remain limited. We evaluated outcomes and predictors of treatment failure in PMN patients treated with RTX. Methods: This retrospective cohort study included 58 adults with biopsy-proven PMN who received RTX between 2013 and 2023. Clinical remission at 6 and 9 months, treatment failure (persistent non-response or relapse after remission), and failure-free survival were evaluated. Outcomes were compared according to baseline anti-phospholipase A2 receptor (anti-PLA2R) antibody levels and previous treatment status. Results: Clinical remission increased significantly from 60.3% at 6 months to 72.4% (42/58) at 9 months (p < 0.001). Patients with baseline anti-PLA2R levels ≤ 150 RU/mL achieved significantly higher remission rates at both time points. The pattern of treatment failure also differed, with persistent refractory disease predominating at higher antibody levels and relapse after remission at lower levels. Baseline serum albumin was the only variable independently associated with treatment failure (odds ratio 0.18, 95% confidence interval 0.04–0.61; p = 0.010). Outcomes were comparable among treatment-naive, relapsing, and treatment-refractory patients at the predefined 9-month assessment. Infections occurred in 7 patients (12.1%). Conclusions: RTX achieved favorable clinical outcomes in PMN, with remission continuing to improve beyond 6 months. Baseline anti-PLA2R antibody levels and serum albumin provided complementary prognostic information. Previous treatment status was not associated with remission or treatment failure at the predefined 9-month assessment and was not independently associated with failure-free survival after adjustment for baseline serum albumin, although this finding should be interpreted cautiously given the limited sample size and unequal follow-up.

Journal of Clinical Medicine doi: 10.3390/jcm15187066

Authors: Murat Karamanlıoğlu Murat Yıldız Oral Menteş Suzan Şahan Maşide Arı Suna Kavurgacı Deniz Çelik Ezgi Gürel Akan

Background/Objectives: Acute hypercapnic respiratory failure is associated with significant morbidity and mortality despite advances in non-invasive mechanical ventilation (NIMV) therapy. The frontal QRS-T angle is a simple electrocardiographic marker reflecting ventricular depolarization–repolarization heterogeneity and has been associated with adverse cardiovascular outcomes. However, the relationship between dynamic changes in frontal QRS-T angle and NIMV treatment response in acute hypercapnic respiratory failure remains unclear. This study aimed to evaluate the association between frontal QRS-T angle changes after NIMV treatment and clinical outcomes in patients with acute hypercapnic respiratory failure. Methods: This retrospective observational cohort study included 186 adult patients hospitalized with acute hypercapnic respiratory failure and treated with bilevel positive airway pressure between January 2024 and December 2025. Frontal QRS-T angle values were obtained from standard 12-lead electrocardiograms recorded before NIMV initiation (T0) and at the 24th hour of treatment (T24). Clinical, laboratory, arterial blood gas, and electrocardiographic parameters were analyzed. Receiver operating characteristic (ROC) analysis, Kaplan–Meier survival analysis, correlation analysis, and multivariable logistic regression analysis were performed to evaluate the prognostic significance of frontal QRS-T angle. Results: Successful NIMV treatment was achieved in 143 patients (76.9%), whereas 43 patients (23.1%) experienced NIMV failure. Patients with failed NIMV treatment had significantly higher baseline frontal QRS-T angle values compared with the successful group [128° (94–156) vs. 71° (48–101), p < 0.001]. Frontal QRS-T angle significantly decreased after treatment in the successful NIMV group but not in the failed group. A significant positive correlation was observed between ΔPaCO2 and Δfrontal QRS-T angle (r = 0.624, p < 0.001). ROC analysis demonstrated that baseline frontal QRS-T angle predicted NIMV failure with an AUC of 0.842 (95% CI: 0.773–0.898) and in-hospital mortality with an AUC of 0.811 (95% CI: 0.735–0.873). Kaplan–Meier analysis showed significantly lower survival rates in patients with frontal QRS-T angle >90° (log-rank p < 0.001). Multivariable logistic regression analysis identified frontal QRS-T angle >90° as an independent predictor of in-hospital mortality (OR: 3.617, 95% CI: 1.484–8.813, p = 0.005). Conclusions: Baseline frontal QRS-T angle was associated with NIMV failure and in-hospital mortality, while its 24-h change was associated with physiological response among patients with paired T0–T24 measurements. These findings are hypothesis-generating and do not establish the utility of frontal QRS-T angle monitoring for immediate escalation or intubation decisions.

Journal of Clinical Medicine doi: 10.3390/jcm15187065

Authors: Alper Koç Nesibe Aydoğdu Elif Suyanı

Objectives: Hospital-acquired anemia (HAA) is an important clinical problem that can adversely affect outcomes, particularly in critically ill patients. This study aimed to determine the incidence of hospital-acquired anemia in adult ICU patients and to evaluate its relation with diagnostic phlebotomy procedures and other etiologic factors. Methods: Data from 1170 adult ICU admissions between 1 January and 31 December 2024 were retrospectively reviewed and 321 patients were included in the analysis. The median age of the study cohort was 72 years (range: 18–102), with 45.2% females (n = 145) and 54.8% males (n = 176). The median ICU length of stay was 6 days (range: 3–29). Results: HAA developed in 35.8% of patients, while a decrease in hemoglobin levels was observed in 80.4%. Patients who developed HAA had significantly longer ICU stays and higher ferritin, CRP, and diagnostic phlebotomy (DP) volumes, while admission hemoglobin levels were lower compared with those without HAA (all p < 0.05). In multivariate analysis, a longer ICU stay, higher ferritin levels, lower admission hemoglobin levels and greater DP volumes were independently associated with the development of HAA. Conclusions: HAA was common in critically ill patients and was associated with several clinical and laboratory factors, including inflammatory burden, baseline hemoglobin level, ICU length of stay, and diagnostic phlebotomy volume. These findings suggest that HAA is a multifactorial process, with ICU length of stay, inflammatory status, baseline hemoglobin levels, and diagnostic phlebotomy volume all potentially contributing to its development.

Journal of Clinical Medicine doi: 10.3390/jcm15187064

Authors: Soner Kumcu Eren Oral Kalbisağde Burak Toprak

Background: Despite advances in surgical and perioperative care, early mortality and postoperative complications after isolated coronary artery bypass grafting (CABG) remain clinically relevant. Conventional risk models primarily reflect baseline clinical and operative characteristics and may not fully capture the dynamic immune-inflammatory response to cardiopulmonary bypass and surgical trauma. Hematologic indices derived from routine complete blood counts may provide a practical and low-cost assessment of this perioperative inflammatory burden. Methods: This single-center retrospective observational study included 650 adult patients who underwent isolated CABG between 2020 and 2024. Preoperative and postoperative monocyte-to-lymphocyte ratio (MLR), pan-immune-inflammation value (PIV), and delta neutrophil index (DNI) were evaluated. The primary outcome was in-hospital mortality, and the secondary outcome was a composite postoperative adverse event comprising prolonged mechanical ventilation, prolonged intensive care unit stay, prolonged inotropic support, pneumonia, or sepsis. Results: In-hospital mortality occurred in 52 patients (8.0%), and composite postoperative adverse events occurred in 221 patients (34.0%). Non-survivors were older and had higher clinical risk scores, lower ejection fraction, longer cardiopulmonary bypass and aortic cross-clamp times, and less favorable renal and inflammatory profiles. Preoperative and postoperative MLR, PIV, and DNI were significantly higher in non-survivors after false discovery rate correction. In univariable analyses, DNI showed the strongest associations with mortality; however, none of the immune-inflammatory indices remained independently associated with mortality or composite postoperative adverse events after multivariable adjustment. Among individual biomarkers, postoperative DNI showed the highest discrimination for in-hospital mortality (AUC 0.765, 95% CI 0.692–0.838), followed by preoperative DNI (AUC 0.738). Addition of postoperative DNI to the clinical mortality model increased the AUC from 0.805 to 0.815, although the incremental improvement was not statistically significant. Conclusions: Although perioperative MLR, PIV, and DNI were associated with adverse outcomes in unadjusted analyses, none remained independently associated with in-hospital mortality or composite postoperative adverse events after multivariable adjustment. Postoperative DNI showed the strongest individual discrimination for mortality; however, its addition to the clinical model resulted in only a small and statistically non-significant improvement in AUC. These findings indicate limited incremental prognostic value of the evaluated immune-inflammatory indices beyond established clinical and operative risk factors and do not support their use as stand-alone predictors after isolated CABG.

Journal of Clinical Medicine doi: 10.3390/jcm15187063

Authors: David Erren Franziska A. Meister Karsten Große Tony Bruns Naomi Gestels Oliver Beetz Felix Oldhafer Martin W. von Websky Thomas Vogel Florian W. R. Vondran Iakovos Amygdalos

Background/Objectives: Recipient-related factors continue to influence long-term outcomes after deceased-donor liver transplantation (DDLT). This study evaluated the prognostic value of the preoperative C-reactive protein-to-albumin ratio (CAR) for recipient survival (RS) and graft survival (GS). Methods: Adult patients undergoing DDLT between 2010 and 2023 were retrospectively analyzed. Re-transplantations, split or domino transplants, patients who died within 90 days and patients with early allograft dysfunction were excluded. Primary endpoints were 3-year RS and GS. Receiver operating characteristic analysis was used to determine the optimal CAR cut-off. Survival was assessed using Kaplan–Meier analysis and Cox regression. Results: A total of 330 patients were included. Mean RS and GS were 112 months (95%CI 106–119) and 110 months (95%CI 103–116), respectively. Preoperative CAR demonstrated the strongest predictive value for 3-year RS (AUC = 0.70, p < 0.001) and GS (AUC = 0.71, p < 0.001). A CAR cut-off of 41% provided optimal discrimination. Patients with CAR > 41% had significantly reduced 3-year RS (31 vs. 34 months, p < 0.001) and GS (30 vs. 34 months, p < 0.001). CAR > 41% was independently associated with increased risk of 3-year mortality (HR 2.101, 95%CI 1.277–3.456, p = 0.003) and graft loss (HR 3.666, 95%CI 1.804–7.449, p < 0.001). Similar results were observed for 5-year outcomes. Conclusions: Elevated preoperative CAR is independently associated with inferior patient and graft survival and may enhance risk stratification after DDLT.

Journal of Clinical Medicine doi: 10.3390/jcm15187062

Authors: Mihaela-Camelia Tîrnovanu Ștefan-Dragoș Tîrnovanu Elena Cojocaru Monica Holicov Vlad-Constantin Donica Roxana-Ana Covali Awad Dmour Norin Forna Paul-Dan Sîrbu Alin Ciubotaru

Background: Cerebral endometriosis is an exceptionally rare manifestation of extrapelvic endometriosis and remains a diagnostic challenge because its clinical and imaging features may mimic more common neurological, inflammatory, vascular, or neoplastic disorders. Catamenial neurological symptoms may provide an important diagnostic clue, but histological confirmation is rarely available. Case presentation: We report the case of a 48-year-old woman with epilepsy beginning at 41 years of age, associated with short-term memory loss and a catamenial pattern of seizures. She had no typical symptoms of pelvic endometriosis, including dysmenorrhea, dyspareunia, or cyclic pelvic pain. Neuropsychological test for memory had normal scores. Brain magnetic resonance imaging (MRI) revealed a right hippocampal lesion with T2/FLAIR hyperintensity and later pseudonodular contrast enhancement, raising suspicion of focal cortical dysplasia, infection, tumor infiltration, or a hippocampal tumor. Magnetic resonance spectroscopy (MRS) was inconclusive and did not provide clear support for tumor-like infiltration. Because of the temporal association between symptoms and menstruation, cerebral endometriosis was considered. The patient received hormonal therapy with progestins, including desogestrel and dienogest, after which antiepileptic therapy was discontinued. Neurological symptoms resolved completely. Follow-up MRI demonstrated marked regression or disappearance of the previously described right hippocampal hyperintense lesion, with preserved bilateral hippocampal morphology. Conclusions: This case highlights the importance of considering cerebral endometriosis in women of reproductive or perimenopausal age presenting with catamenial epilepsy and unexplained intracranial lesions, even in the absence of pelvic endometriosis symptoms. Recognition of menstrual cyclicity, careful neuroimaging follow-up, and multidisciplinary evaluation may support diagnosis and guide individualized treatment. The favorable clinical and radiological response to progestin therapy in this case adds to the limited evidence regarding conservative management of presumed cerebral endometriosis. Cerebral endometriosis is a very rare condition, and only eight case reports were found in the literature.

Journal of Clinical Medicine doi: 10.3390/jcm15187061

Authors: Sophia Tsokkou Paraskevi Chatzikomnitsa Menelaos Papakonstantinou Areti Danai Gkaitatzi Eftychia Liampou Georgia Kolympa Antonios Fantakis Evdokia Toutziari Dimitrios Giakoustidis Theodora Papamitsou Vasileios N. Papadopoulos Alexandros Giakoustidis

Colorectal cancer (CRC) remains one of the most frequently diagnosed malignancies worldwide and a leading indication for major abdominal surgery, with a rising incidence among younger adults. Because CRC resection is a physiologically demanding procedure performed in a frequently comorbid, often anemic and malnourished population, the preoperative period represents a decisive window in which laboratory and diagnostic testing shapes staging, risk stratification, and optimization. This narrative review is deliberately confined to the preoperative window—from histological diagnosis to the day of elective, curative-intent colon or rectal resection—and synthesizes evidence retrieved from PubMed/MEDLINE, Scopus, and ScienceDirect together with current society guidelines. It is organized around four themes: (i) the core laboratory workup, including the complete blood count and preoperative anemia, iron studies, metabolic and hepatic panels, coagulation testing, and carcinoembryonic antigen (CEA); (ii) the diagnostic and staging workup, encompassing complete colonic evaluation, contrast-enhanced computed tomography, pelvic magnetic resonance imaging for rectal cancer, and the selective role of positron emission tomography; (iii) risk stratification and preoperative optimization, spanning patient blood management, nutritional assessment and albumin, computed-tomography-defined low skeletal muscle mass, frailty, functional capacity, prehabilitation, and glycemic control; and (iv) molecular characterization, distinguishing mismatch-repair/microsatellite-instability (MMR/MSI) testing—an established, widely recommended component of CRC evaluation—from genuinely emerging biomarkers such as circulating tumor DNA (ctDNA) and systemic inflammatory and prognostic nutritional indices. Differences between colon and rectal cancer, elective and emergency presentation, and upfront versus post-neoadjuvant surgery are signposted throughout. We further integrate these elements within contemporary guideline and Enhanced Recovery After Surgery (ERAS) frameworks, including the 2025 ERAS Society recommendations for elective colorectal surgery, and distill them into a practical, evidence-based preoperative checklist specifying thresholds, timing, interventions, and strength of supporting evidence. We emphasize that the prognostic power of postoperative ctDNA does not yet translate into ctDNA-guided treatment decisions outside clinical trials. The central message is that preoperative testing in CRC should be purposeful and stage- and risk-adapted rather than reflexive: each investigation should refine staging, modify perioperative management, or enable measurable optimization. Each risk domain is paired with the intervention it should trigger, the criteria identifying candidates for extended thromboprophylaxis are specified, and the systemic inflammatory indices are framed as a trigger for optimization rather than as prognostic commentary.

Journal of Clinical Medicine doi: 10.3390/jcm15187060

Authors: Ekrem Akdeniz Mücahid Uğur Ömer Dağlar Reha Ordulu Emrah Küçük Muhammed Esad Kayhan Mesut Şengül Muhammed Bahattin Ulu Mahmut Ulubay Mustafa Kemal Atilla

Background: This study aimed to describe the long-term clinical trajectory, stone burden changes, and secondary endourological reintervention outcomes in patients presenting with residual stone fragments (RSFs) > 4.0 mm confined to the lower pole following percutaneous nephrolithotomy (PCNL). Methods: We retrospectively reviewed a single-center cohort of 29 consecutive patients who underwent index-PCNL for isolated lower pole calculi and presented with RSFs > 4.0 mm on routine non-contrast computed tomography (NCCT) at 3 months postoperatively (defined as study baseline and time zero), followed for a minimum of 12 months. Demographic data, baseline and terminal stone burden, stone-related clinical events, procedural complications, and secondary endourological interventions were analyzed. Results: Twenty-nine patients (20 males, 9 females; mean age: 50.1 ± 12.0 years) were analyzed. Preoperative median two-dimensional (2D) stone burden was 332.0 mm2 (IQR: 282.0–386.0 mm2). At the 3-month baseline NCCT, median residual 2D stone burden was 24.0 mm2 (IQR: 13.0–33.0 mm2). Over a median follow-up of 36.0 months (IQR: 18.0–48.0 months), four patients (13.8%, 95% CI: 3.9–31.7%) achieved spontaneous stone passage, 15 patients (51.7%, 95% CI: 32.5–70.6%) required secondary reintervention due to interval enlargement or symptoms, and 10 patients (34.5%, 95% CI: 17.9–54.3%) remained on active surveillance. Across the cohort, median stone burden on the last positive scan prior to clinical events or the final surveillance visit increased to 57.0 mm2 (IQR: 38.0–104.0 mm2). Conclusions: In this selected single-center cohort of 29 patients with lower-pole residual fragments > 4.0 mm at 3-month NCCT after PCNL, 15 patients underwent secondary intervention and four experienced documented spontaneous passage during variable follow-up. Because interval monitoring and intervention criteria were individualized, these findings are descriptive and do not establish the optimal timing of treatment. Larger prospective studies with standardized imaging protocols are required to better define management strategies.

Journal of Clinical Medicine doi: 10.3390/jcm15187059

Authors: Ahmad Alenezi Masoud Garashi Satish Panchadar Gautam Biswas

Background/Objectives: Rubidium-82 (82Rb) PET myocardial perfusion imaging (MPI) yields, in a single study, quantitative absolute myocardial blood flow (MBF, mL/min/g), myocardial flow reserve (MFR), and gated left ventricular (LV) function (LVEF, EDV, ESV, SV). These quantitative values depend on the tracer, scanner, kinetic model, software, and underlying population and have been characterised almost exclusively in North American and European cohorts. The Arabian Gulf, where Kuwait has among the highest age-standardised diabetes prevalence worldwide (25.6%), is essentially unstudied, so the distribution and behaviour of these parameters in such a real-world cardiometabolic population are unknown. To evaluate the distribution of the quantitative 82Rb PET parameter set in a real-world Arabian Gulf cohort and, within a small clinically defined normal subgroup, to describe sex- and age-related patterns in absolute MBF, MFR, and LV function. Given the limited size of the normal subgroup, these values are presented as exploratory, hypothesis-generating observations rather than definitive population reference norms. Methods: Retrospective single-centre study of 330 consecutive 82Rb PET/CT studies (analytic cohort n = 292 after exclusion of repeat studies and those with incomplete quantitative output; mean age 63.1 ± 12.1 years) who underwent adenosine-stress 82Rb PET/CT MPI. The clinically defined normal subgroup, normal perfusion (C1), normal global MFR (≥2.0), normal resting LVEF, and no documented cardiac history, comprised 44 patients (25 female, 19 male). Reference values are reported as sex- and age-stratified centiles (5th, 25th, median, 95th percentiles), with the 5th percentile reported for each parameter. Sex differences used Mann–Whitney U with rank-biserial r and Cohen’s d (95% CI); age was examined across broad bands. All analyses followed APA 7 standards with Bonferroni correction. Results: In the clinically defined normal subgroup, median global stress MBF was 2.94 mL/min/g (5th percentile 2.03) and median global MFR was 2.72 (5th percentile 2.06); every value satisfied the C1 definition (MFR ≥ 2.0) by construction, so these limits describe the preselected subgroup and cannot independently validate the 2.0 threshold. Women had higher resting MBF than men (median 1.07 vs. 0.90 mL/min/g; p = 0.007), with numerically lower global MFR that did not survive correction for multiple comparisons (2.57 vs. 2.98; p = 0.022); stress MBF did not differ by sex (3.00 vs. 2.91; p = 0.522). LV volumes were smaller in women, while LVEF was similar between sexes. The 5th percentile for stress LVEF was 54% (women) and 53% (men). These absolute-flow reference values are lower than those reported for Western low-risk cohorts (stress MBF ~3.25 mL/min/g; MFR ~3.18), consistent with the higher cardiometabolic burden of this population. Conclusions: In this exploratory single-centre evaluation, quantitative 82Rb PET flow values in a small clinically defined normal Arabian Gulf subgroup were lower than Caucasian-derived values, while sex-related differences in resting flow were evident and age-related differences were numerically consistent with previously reported trends. Because the normal subgroup is small, these findings are hypothesis-generating and require confirmation in larger, prospectively screened cohorts before use as population reference values; they nonetheless indicate that population- and pipeline-specific calibration is needed when quantitative 82Rb thresholds derived elsewhere are applied locally.

Journal of Clinical Medicine doi: 10.3390/jcm15187057

Authors: Agata Śmiłowska Magdalena Stania Małgorzata Gajda Justyna Niesporek Anna Polak Jolanta Grabowska-Markowska Agnieszka Opala-Berdzik

Background: Art-based interventions, including music therapy, are increasingly used in palliative care to support symptom management and improve quality of life in patients with advanced cancer. This systematic review and meta-analysis aimed to evaluate their efficacy in adults with advanced cancer receiving palliative care. Methods: The review protocol was registered in PROSPERO (CRD42025636049). A systematic search of PubMed, MEDLINE (Ovid), and Embase was conducted from database inception to 17 December 2024 (PubMed), 21 December 2024 (MEDLINE (Ovid)), and 10 January 2025 (Embase), and was updated in February 2026. Additional searches were conducted in ClinicalTrials.gov, WHO ICTRP, Cochrane CENTRAL, and Google Scholar in August 2026. Studies comparing art-based interventions with standard care or active control interventions were included. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence using the GRADE approach. Results: Eleven reports with 9 RCTs (involving 675 patients) met the inclusion criteria, all evaluating music-based interventions. Music-based interventions in addition to routine palliative care were associated with a statistically significant reduction in pain intensity compared with control conditions (SMD = −0.51; 95%CI: −0.98 to −0.03; p = 0.04; k = 3; n =224), although high between-study heterogeneity was observed (I2 = 67.69%). They were also associated with higher quality-of-life scores (SMD = 0.92; 95%CI: 0.59 to 1.24; p < 0.0001; k = 2; n = 168; I2 = 0%); however, the certainty of evidence was very low, making this effect highly uncertain. Conclusions: Evidence for music-based interventions remains very uncertain, precluding firm conclusions regarding clinical benefit. Further high-quality trials, including other forms of art-based interventions, are needed.

Journal of Clinical Medicine doi: 10.3390/jcm15187058

Authors: Nouf Shawqi Alwaseah Abdulwahab Binjomah Rimah Abdullah Saleem Muhammad Raihan Sajid Hani Tamim Maria Imtiaz Ashna Majid

Background: Transfusion-transmitted infections (TTIs) continue to threaten the safety of blood supply systems worldwide. This study aimed to estimate the prevalence of malaria, HTLV I/II, and syphilis among blood donors at the Riyadh Regional Laboratory and Blood Bank from 2018 to 2022, and to assess associations with gender, age, nationality, and the ABO/RhD blood group. Methods: We conducted a retrospective analysis of 217,543 blood donations. Demographic and serological records were extracted from the blood bank’s electronic database and analyzed in SPSS v28. Chi-square, Fisher’s exact tests and multivariate logistic regression were used as appropriate, with significance set at p < 0.05. Results: Male donors accounted for 97% of the cohort, and 52% were non-Saudi nationals. Malaria was rare (0.03%; n = 58); all 58 cases were detected in 2018, and none were recorded in subsequent years. HTLV I/II antibodies were observed in 464 donors (0.21%), with the highest annual share in 2019 (39.7%). Syphilis was the most common TTI, identified in 1143 donors (0.52%), and showed a significant increasing trend over the study period (Cochran–Armitage test p < 0.001; Poisson regression IRR 1.21, 95% CI 1.15–1.28, p < 0.001). In multivariable logistic regression, non-Saudi nationality was independently associated with syphilis positivity (aOR 1.48, 95% CI 1.31–1.67), and ages 46–65 was associated with higher odds of all three TTIs. ABO and RhD blood groups were not significantly associated with TTI positivity in univariate or multivariable analyses. Conclusions: Current screening practices appear to maintain low TTI prevalence in the central region, but the rising syphilis trend and the clustering of malaria positivity among non-Saudi donors point to the need for closer surveillance and targeted donor counseling. The study also highlights the need for more granular demographic data collection, including specific country of origin and duration of residence, to enable more effective risk stratification and intervention targeting.

Journal of Clinical Medicine doi: 10.3390/jcm15187056

Authors: Jihyuk Chung Jeong-Am Ryu

Background/Objectives: Elevated intracranial pressure (ICP) drives secondary brain injury and poor outcome. The pressure reactivity index (PRx), the reference marker of cerebral autoregulation, requires high-frequency waveforms unavailable in many centers. We examined whether routinely charted hourly ICP and cerebral perfusion pressure (CPP) can stratify prognosis without the PRx. Methods: In a retrospective cohort of 990 adults with invasive ICP monitoring at a tertiary neurosurgical ICU (a predominantly non-traumatic case mix), we derived from hourly ICP the mean, variability (within-patient standard deviation), and peak burden (time above 22 mmHg), and from CPP the low-perfusion burden (time below 60 mmHg). Each metric (per 1 SD) was related to 28-day mortality and poor neurological outcome (Glasgow Outcome Scale 1–3), adjusted for age, sex, APACHE II, GCS, diagnosis, and mean ICP, with incremental value and sensitivity analyses. Results: In total, 86 of 990 patients died within 28 days. ICP variability was associated with both mortality and poor neurological outcome and, unlike peak burden, remained independent after adjustment for mean ICP. Peak burden lost significance once mean and variability were known. For CPP, hypoperfusion burden, but not CPP variability, was associated with mortality. CPP variability did not survive joint modeling with ICP variability. Excess risk was confined to low CPP, with no harm at high CPP. ICP variability added incremental value beyond a clinical model, robust to sensitivity analyses. Conclusions: Routinely available ICP variability and CPP hypoperfusion burden carry prognostic information beyond mean pressure. ICP variability predicted both outcomes, whereas hypoperfusion burden predicted mortality. These summaries may offer a pragmatic alternative where the PRx is unavailable, pending validation.

Journal of Clinical Medicine doi: 10.3390/jcm15187055

Authors: Ki Young Lee Jung-Hee Lee Kyung-Chung Kang Hong-Sik Park Woo-Jae Jang Eugene J. Park

Background: Determining the appropriate magnitude of lumbar lordosis (LL) correction in adult spinal deformity (ASD) remains controversial. The fused spinopelvic angle (FSPA), a posture-independent parameter, may provide a geometric measure of fused-construct orientation associated with proximal junctional kyphosis (PJK) risk. Methods: This retrospective single-center study included 258 patients aged ≥65 years with ASD and pure sagittal malalignment associated with lumbar degenerative kyphosis/drop body syndrome who underwent long-segment fixation from T10 to the sacrum with sacropelvic fixation. Patients were divided into non-PJK (n = 135) and PJK (n = 123) groups. Adjusted nested logistic regression models, receiver operating characteristic (ROC) analysis, and DeLong comparison were used to evaluate the association of FSPA with PJK and its incremental value beyond postoperative pelvic incidence–lumbar lordosis (PI-LL). Results: Postoperative FSPA was lower in the PJK group (p < 0.001) and remained independently associated with PJK in the fully adjusted model including postoperative PI-LL (adjusted OR = 0.910 per degree; 95% CI, 0.866–0.957; p < 0.001). FSPA showed greater discriminatory ability than postoperative PI-LL (AUC, 0.694 vs. 0.596; difference, 0.099; 95% CI, 0.035–0.162; DeLong p = 0.002). Adding FSPA to the clinical model containing postoperative PI-LL significantly improved model fit (likelihood-ratio p < 0.001). The cohort-derived FSPA threshold of 2.38° yielded 64.2% sensitivity and 63.7% specificity. Conclusions: Higher postoperative FSPA was independently associated with lower odds of radiographic PJK and provided additional predictive information beyond postoperative PI-LL. The identified threshold of 2.38° may serve as a preliminary reference for postoperative alignment in this selected cohort.

Journal of Clinical Medicine doi: 10.3390/jcm15187054

Authors: Ilja Osthoff Monica Soare Franz-Josef Vogl JoEllen Welter Alexander Dullenkopf

Background/Objectives: Remifentanil may be useful during general anesthesia for cesarean delivery, although the amount administered before delivery using target-controlled infusion (TCI) at different effect-site targets has not been well quantified. This pharmacokinetic study investigated how much remifentanil would be delivered before birth at different initial effect-site targets. Methods: This retrospective simulation study used demographic data from 50 women undergoing cesarean delivery. Remifentanil TCI (Minto model) was simulated with initial effect-site targets of 1, 2, 4, and 6 ng/mL. One minute after the simulated plasma peak, the target was reduced to 1 ng/mL (t0). Doses before t0, duration of the infusion pause, and total dose before delivery were calculated. Simulated dosing patterns were summarized overall and stratified by elective and emergency procedures. Results: Infusion pauses after target reduction lasted 175, 346, and 503 s after initial targets of 2, 4, and 6 ng/mL, respectively. Delivery occurred during these pauses in 16%, 46%, and 72% of cases (19%, 71%, and 90% in emergency cases). Mean remifentanil dose at delivery was 33.7, 43.0, 70.0, and 101.0 μg for initial targets of 1, 2, 4, and 6 ng/mL, respectively. Following target reduction, the additional remifentanil administered before delivery decreased from a mean of 17.0 μg with an initial effect-site target of 1 ng/mL to 0.9 μg with an initial target of 6 ng/mL. Conclusions: This simulation demonstrated that only modest additional doses of remifentanil would be delivered to the mother between induction and delivery during target-controlled infusion for cesarean delivery, with the exact amount depending on the initial effect-site target concentration.

Journal of Clinical Medicine doi: 10.3390/jcm15187053

Authors: Konstantinos Chaidas Maria Zisoglou Chrysovalantis Stylianou Dimitrios Askitis Hippokrates Moschouris Michael Katotomichelakis

Background/Objectives: Ultrasound-guided microwave ablation (MWA) has emerged as an effective minimally invasive treatment for benign thyroid nodules, but practical guidance regarding implementation of the technique within otorhinolaryngology practice remains limited. This study aimed to describe the implementation of ultrasound-guided MWA for benign thyroid nodules in a tertiary ENT center, with emphasis on technical considerations, procedural safety, and early clinical outcomes. Methods: A retrospective analysis of prospectively collected data included consecutive patients seen at the ENT outpatient clinic between March 2024 and July 2025. All procedures were performed by a single ENT surgeon, and technical aspects were described. Procedural characteristics, pain, complications, nodule volume reduction, compressive symptoms, cosmetic outcomes, and thyroid function were evaluated through 3-month follow-up. Results: Twenty-five patients underwent ultrasound-guided MWA for 30 benign thyroid nodules. All procedures were successfully completed under local anesthesia. No major complications occurred; two patients developed minor, self-limiting ecchymosis. Median nodule volume decreased from 12.77 mL (IQR, 4.13–17.74) at baseline to 3.81 mL (IQR, 1.31–7.60) at 3 months, corresponding to a mean volume reduction ratio of 63.8%. Significant improvements in compressive symptoms and cosmetic scores were observed (p < 0.001). All patients remained euthyroid, with no cases of new-onset hypothyroidism. Conclusions: This early experience supports the feasibility and short-term procedural safety of ultrasound-guided MWA for selected benign thyroid nodules within an ENT setting. Careful patient selection, meticulous technique, and structured operator training appear to be key components for successful implementation. Beyond its favorable early clinical outcomes, this study provides a practical framework for centers seeking to establish thyroid MWA programs.

Journal of Clinical Medicine doi: 10.3390/jcm15187052

Authors: Jarosław Kabaciński Michał Murawa

Background/Objectives: The My Jump Lab app can be used to examine inter-limb asymmetry during the countermovement jump (CMJ), both in healthy athletes and in athletes undergoing rehabilitation post-injury. However, the correct assessment of jump height (JH) using this application requires high measurement accuracy, similar to the method of double integration of vertical ground reaction force values. This study aimed to determine the validity and reliability of the My Jump Lab app for estimating jump height (JH) during the single-leg countermovement jump (CMJ). Methods: Twenty-two healthy male adults performed single-leg CMJs for the dominant lower extremity (D) and non-dominant lower extremity (ND). The AMTI force platform and an iPhone 13 smartphone were used. JH during the CMJ was estimated based on the displacement of the jumper’s center of mass (force platform), the jumper’s flight time (smartphone and My Jump Lab), and the flight time of the reflective marker placed on the jumper’s sacrum (smartphone and My Jump Lab-M). Results: The assessment of the concurrent validity showed (1) poor agreement between the My Jump Lab and the force platform for the ND and D (p < 0.001) and (2) moderate (ND) and good (D) agreement between the My Jump Lab-M and the force platform (p < 0.001). Conclusions: The results of the single-leg CMJ height estimation revealed the greater accuracy of the My Jump Lab-M method compared with the My Jump Lab method. However, due to the good agreement between My Jump Lab-M and the gold standard, this new method may not provide an objective assessment of the height in this vertical jump. Therefore, the most accurate method of double integration of vertical ground reaction force values is recommended for the single-leg CMJ test.

Journal of Clinical Medicine doi: 10.3390/jcm15187051

Authors: Wiktor Szatkowski Aleksandra Dudek Katarzyna Franczyk Małgorzata Nowak-Jastrząb Tomasz Kluz Małgorzata Cieślak-Steć Magdalena Śliwińska Paweł Blecharz

Background/Objectives: Advanced endometrial cancer (FIGO III–IV) is characterised by poor prognosis and a heterogeneous biological profile, and molecular classification enables treatment personalisation by identifying subtypes with distinct therapeutic targets. We aimed to characterise the molecular and histopathological features of FIGO III–IV cases in a Polish multicentre cohort and to discuss the resulting treatment implications. Methods: This retrospective multicentre study included 915 consecutive patients with endometrial cancer operated on between April 2022 and May 2025 at three oncology centres in south-eastern Poland. Molecular subtyping (POLEmut, p53abn, dMMR/MSI-H, NSMP) was performed using immunohistochemistry (IHC) and next-generation sequencing (NGS). FIGO stage was assigned according to the FIGO 2009 classification. Results: Among 888 patients with a known molecular subtype, FIGO III–IV cases accounted for 15.9% (n = 141). The p53abn subtype predominated (35.5%), followed by dMMR/MSI-H (26.2%), NSMP (24.1%), and POLEmut (5.7%). The proportion of p53abn increased with stage (I–II vs. III–IV, p < 0.001), whereas dMMR/MSI-H remained stable regardless of stage (p = 0.83). POLEmut was absent in FIGO IV (0/16; 95% CI 0.0–19.4%), which should be regarded as an exploratory observation requiring prospective validation. Conclusions: The molecular profile of advanced endometrial cancer may inform treatment strategy; the therapeutic implications presented here are descriptive and hypothesis-generating, as the study did not include survival data. The dMMR/MSI-H subtype identifies patients who may benefit from immunotherapy in accordance with current clinical indications, supporting routine MMR testing regardless of disease stage. Conversely, p53abn tumours point to the need for a more intensive treatment strategy, in line with current guidelines. The absence of POLEmut in FIGO IV is an exploratory observation requiring prospective validation. Treatment de-escalation in POLEmut FIGO IIIC remains subject to further clinical validation and requires individualised assessment after complete staging.

Journal of Clinical Medicine doi: 10.3390/jcm15187050

Authors: Giuseppe Biondi-Zoccai Giovanni Vincenzo Biondi-Zoccai Ambra Cerri Francesco Burzotta Carlo Trani Enrico Romagnoli Arturo Giordano Nicola Corcione Salvatore Giordano Martino Pepe Carlo Cicerone Domenico Tavella Luigi Spadafora Marco Bernardi Attilio Lauretti Francesco Versaci Simone Calcagno Fabrizio D’Ascenzo

Background: Artificial intelligence (AI) is increasingly being integrated into cardiovascular medicine, with potential applications across image analysis, procedural planning, risk stratification, decision support, and workflow optimization. However, its adoption in interventional cardiology remains heterogeneous and may be influenced by several factors. We aimed to conduct a nationwide survey to assess attitudes towards AI among Italian interventional cardiologists. Methods: We conducted a nationwide, cross-sectional, web-based survey of Italian interventional cardiologists. A structured questionnaire collected information on professional characteristics, familiarity with and current use of AI, perceived clinical applications, expected benefits, trust, implementation barriers, and training needs. Conditional branching was used to obtain additional details from respondents who reported current use of AI-based tools, while all responses were collected voluntarily and analyzed in anonymized, aggregate form. Categorical variables and Likert-scale responses were summarized using descriptive statistics, with exploratory comparisons performed across prespecified professional and institutional subgroups. Results: Among 129 respondents, 70.5% reported at least moderate familiarity with AI and 77.5% reported some current use, although only 60.5% reported regular or occasional professional use, and applications were concentrated mainly in research, education, and information synthesis rather than direct procedural support. Nearly half (48.1%) expected AI to become standard in many procedures within 5 years, while 69.0% anticipated either routine use or particular value in complex cases. Attitudes were broadly favorable, with 85.3% agreeing that AI could improve diagnostic and procedural precision, 86.8% expressing strong interest in future use, and 76.7% stating that AI should support rather than replace physician judgment. The leading barriers were medico-legal uncertainty (45.0%), poor integration with existing clinical systems (34.9%), and cultural resistance or operator distrust (29.5%), whereas preservation of physician control was the most frequently cited requirement for adoption (58.9%). Greater AI familiarity was independently associated with current AI use (p < 0.001) and good or high trust (p < 0.001). Compared with no prior training, one and multiple AI training experiences were independently associated with good or high familiarity (both p < 0.05). Conclusions: Italian interventional cardiologists showed substantial exposure to AI, strong interest in future adoption, and generally favorable expectations regarding its contribution to diagnostic precision, workflow, and procedural support. Acceptance remained conditional on physician oversight, stronger clinical validation, reliable interoperability, and clear medico-legal governance, and previous AI-focused education appeared independently associated with greater familiarity.

Journal of Clinical Medicine doi: 10.3390/jcm15187049

Authors: Silvia Proietti Cristian Axel Hernandez Gaytan Jorge Augusto Alcacio-Mendoza Franco Gaboardi Guido Giusti

Background & Objectives: Laser lithotripsy is the standard energy source for mini-percutaneous nephrolithotomy (mini-PCNL). Although Holmium:YAG (Ho:YAG), Thulium Fiber Laser (TFL), and pulsed Thulium:YAG (p-Tm:YAG) are currently available for clinical use, direct comparisons among all three laser technologies are lacking. This study aimed to compare the efficacy, safety, and procedural performance of Ho:YAG, TFL, and p-Tm:YAG during mini-PCNL. The primary endpoint was the stone-free rate (SFR). Secondary outcomes included complications, operative time, lasing time, total energy delivered, and laser-related procedural metrics. Methods: Consecutive patients treated with p-Tm:YAG during mini-PCNL for renal stones were prospectively enrolled and compared with two cohorts from our institutional database treated with Ho:YAG or TFL. All procedures were performed using the same mini-PCNL technique and predefined laser settings selected to achieve the closest technically feasible match among the three platforms. Results: Ninety patients were included (30 per group). No significant differences in SFR were observed among Ho:YAG, TFL, and p-Tm:YAG (p = 0.93), or in overall complication rates (p = 0.93). After adjusting for stone volume, density, composition, and location, the laser platform was not independently associated with SFR, whereas stone volume was the only independent predictor of stone-free status. TFL exhibited a significantly longer operative time than Ho:YAG and a longer lasing time than both Ho:YAG and p-Tm:YAG, and was associated with greater total energy delivery, lower ablation efficiency, and lower ablation speed. Conversely, p-Tm:YAG demonstrated a significantly shorter lasing time than TFL and an ablation efficiency similar to that of Ho:YAG, with lasing time and ablation speed values between those observed with Ho:YAG and TFL under the evaluated settings. Laser efficacy did not differ significantly among the three groups. Conclusions: No significant differences in stone-free or safety outcomes were observed among the three laser platforms in mini-PCNL. Although significant differences were observed in lasing time, ablation speed, and energy utilization, p-Tm:YAG demonstrated an intermediate procedural profile under the operating parameters evaluated in this study. Overall, the present findings suggest that p-Tm:YAG represents a feasible treatment option for mini-PCNL, although larger randomized studies are needed before firm conclusions regarding relative platform performance can be drawn.

Journal of Clinical Medicine doi: 10.3390/jcm15187048

Authors: Heather R. M. Connor Luke X. Chong Kingsley Chung Brooke Daws Monica Hanna Monique Jankovski Minh Luu Sarah Mawdsley Madi Pollock Cameron Skinner Jessie Whiley Jessica Xu Amanda K. Edgar

Background: Measurement of anterior chamber depth (ACD) is an important screening method for angle-closure glaucoma risk. We aimed to determine the precision and agreement of a smartphone-based method for measuring ACD when compared with anterior segment optical coherence tomography (AS-OCT) and Smith’s technique. Methods: A total of 43 participants (22 female, 21 male) were recruited. The mean age ± standard deviation of participants was 21.9 ± 2.1 years (range = 19–27 years). Three measurements were taken on each participant’s right eye in a random order for each technique. For this comparative study, differences in ACD, test–retest variability of a given method, and Bland–Altman level of agreement were computed to compare differences in performance between all three methods. Results: Smith’s technique over-estimated ACD, while smartphone photography under-estimated ACD, when compared to the reference AS-OCT. There was proportional bias between all three techniques. Smith’s technique had the largest degree of variability, whereas there was no statistically significant difference in test–retest variability between AS-OCT and smartphone photography. Conclusions: Zamir’s smartphone photography technique could be used for measuring ACD. Although there are some limitations compared to other established approaches, smartphone photography may have potential as a low-cost screening tool for estimating ACD in settings where specialised equipment is not available. Further studies are required to establish diagnostic performance for angle-closure screening in clinically relevant populations.

Journal of Clinical Medicine doi: 10.3390/jcm15187047

Authors: Mehul Mittal Rishi Jain Joshua M. Tennyson Divy Kumar Pranav M. Bajaj Samuel G. Reyes Wellington K. Hsu Alpesh A. Patel Srikanth N. Divi

Background/Objectives: Posterior cervical decompression and fusion (PCDF) carry perioperative risks and increases postoperative healthcare utilization (HU). Traditional prediction models emphasize comorbidities and surgical factors, yet social determinants of health (SDHs) are known to also affect clinical outcomes. We applied machine learning (ML) to integrate SDHs and clinical variables in predicting 90-day readmission and HU after PCDF. Methods: We conducted a retrospective, single-institution machine learning analysis of adult patients undergoing single or multilevel PCDF (2003–2023). Models were designed using 88 clinical variables and five census-derived Social Vulnerability Index (SVI) scores. Outcomes were 90-day readmission and HU (the unweighted sum of 18 post-discharge components including urgent visits, invasive procedures, non-routine testing, and imaging). Models were trained on 50 repeated 80/20 train–test splits with training-only preprocessing and hyperparameter tuning. Results: Among 1015 patients (mean age of 64.7, 59.0% male, 97.2% with multilevel fusions), 90-day readmission was 15.5% and mean HU score was 13.6 ± 9.0. Regarding readmission, the clinical-only logistic regression model was the best predictor (AUROC 0.65). For HU, clinical-only random forest performed best (MAE: 4.80, R2: 0.326). Adding SVI to the matched clinical-plus-SDH models did not improve prediction for either 90-day readmission or healthcare utilization. Length of stay, year of surgery, and several SVI measures were prominent contributors across both SHAP analyses. Conclusions: ML models integrating SDH and clinical factors available by index discharge modestly predicted readmission and HU after PCDF. However, adding SVI did not meaningfully increase their overall performance, and the models require external validation before clinical use.

Journal of Clinical Medicine doi: 10.3390/jcm15187045

Authors: Zofia Maria Kiestrzyn Tatiana Antczak Jakub Dyś Maciej Wilczak Karolina Chmaj-Wierzchowska

Background/Objectives: Endometrial polyps (EPs) are common benign intrauterine lesions associated with abnormal uterine bleeding, infertility, recurrent implantation failure, and recurrent pregnancy loss. Although traditionally considered hormone-dependent lesions, increasing evidence suggests that chronic endometritis (CE) may contribute to their development and recurrence. This review summarizes current evidence regarding the relationship between CE and EPs, focusing on pathophysiological mechanisms, diagnostic approaches, and clinical implications. Methods: This narrative review was conducted according to the Scale for the Assessment of Narrative Review Articles (SANRA). A literature search was performed using PubMed/MEDLINE, Scopus, and Google Scholar to identify original studies, systematic reviews, meta-analyses, and consensus statements addressing CE, EPs, infertility, endometrial microbiota, and polyp recurrence. Results: Current evidence demonstrates a consistent association between CE and EPs, with approximately half of premenopausal women with EPs showing histological evidence of CE. Chronic inflammation may promote polyp formation through immune activation, inflammatory cytokine signaling, abnormal angiogenesis, extracellular matrix remodeling, dysregulated apoptosis, and alterations in the endometrial microbiome. CE has also been identified as an independent predictor of EP recurrence after hysteroscopic polypectomy and may impair endometrial receptivity. Histopathological examination with CD138 immunohistochemistry remains the diagnostic reference standard. Conclusions: Emerging evidence supports an inflammatory component in the pathogenesis of endometrial polyps and suggests that CE may represent a potentially modifiable risk factor for recurrence and reproductive failure. Incorporating assessment of CE into the evaluation of selected women with recurrent polyps or infertility may improve individualized management. However, prospective studies are needed before routine screening and treatment can be universally recommended.

Journal of Clinical Medicine doi: 10.3390/jcm15187044

Authors: Małgorzata Godala Ewelina Gaszyńska Izabela Materek-Kuśmierkiewicz Ewa Małecka-Wojciesko

Background/Objectives: Vitamin D deficiency may increase the risk of IBD and be associated with disease activity. The aim of the study was to assess vitamin D levels, their association with disease activity in patients with IBD. Methods: A total of 231 subjects took part in the cross-sectional comparative study, including 129 patients with IBD and 102 healthy individuals Disease Activity Index and the Montreal classification were used to assess disease activity in patients with CD. For patients with UC, the Partial Mayo Score and the Montreal classification were applied. To determine total 25(OH)D chemiluminescent immunoassay (CLIA) technology was used. Results: The concentration of 25(OH)D was significantly lower in the group of patients with IBD compared to the control group (25.5 ng/mL vs. 28.8 ng/mL, p = 0.0027). Differences in 25(OH)D concentrations depended on IBD activity, with significantly higher vitamin D concentrations found in patients in remission compared to those with active IBD (28.9 ± 7.2 ng/mL vs. 22.3 ± 6.1 ng/mL, p = 0.0022). This association was confirmed for both UC and CD patients. A multivariate adaptive regression model using spline curves revealed a relationship between serum 25(OH)D concentrations in patients with IBD and total dietary vitamin D intake, including vitamin D supplementation, consumption of one serving of fish per week, and disease remission. Conclusions: Serum 25(OH)D levels in IBD patients may serve as an additional, useful, and non-invasive marker of disease activity.

Journal of Clinical Medicine doi: 10.3390/jcm15187046

Authors: Krzysztof Dobrzeniecki Monika Kacprzak Dobrochna Stachecka Kornelia Sarnowska Witold Włodzimierz Kędzia Małgorzata Mizgier Magdalena Pisarska-Krawczyk Katarzyna Plagens-Rotman Witold Mirosław Kędzia Justyna Opydo-Szymaczek Grażyna Jarząbek-Bielecka

Background: Premenstrual disorders (PMDs), including premenstrual syndrome and premenstrual dysphoric disorder, are common conditions that may substantially affect adolescents’ physical and psychological well-being. However, their presentation and management during adolescence are complicated by reproductive-axis maturation, overlap with other medical conditions, and limited adolescent-specific evidence. This review aimed to provide an interdisciplinary perspective on PMDs in adolescents, integrating biological, psychological, developmental, clinical, and sociocultural aspects. Methods: A structured narrative review was conducted. Publications addressing the neuroendocrine and developmental mechanisms, clinical manifestations, psychosocial consequences, diagnosis, and treatment of PMDs were considered, with adolescent-specific evidence prioritized where available. Results: Current evidence suggests that PMDs are associated with altered sensitivity to physiological ovarian steroid fluctuations and their neuroactive effects rather than abnormal circulating hormone concentrations alone. In adolescents, PMDs may present with diverse somatic, affective, cognitive, and behavioral symptoms and are associated with impaired quality of life, school functioning, interpersonal relationships, and psychological well-being. Diagnostic assessment remains challenging because symptoms may overlap with normal pubertal changes and psychiatric disorders. Prospective monitoring of symptom cyclicity and functional impairment is therefore essential. Pharmacological treatments, particularly selective serotonin reuptake inhibitors and selected combined oral contraceptives, represent important therapeutic options, while psychological, lifestyle, physical activity, and physiotherapeutic interventions may provide additional benefits. However, most treatment evidence is derived from adult populations. Conclusions: PMDs in adolescents should be conceptualized as multidimensional conditions requiring an interdisciplinary approach integrating gynecological, psychiatric, psychological, endocrinological, primary care, and lifestyle perspectives. Greater recognition and developmentally appropriate assessment may facilitate earlier diagnosis and individualized management. Further prospective, adolescent-specific research is needed to clarify the biological and psychosocial determinants of PMDs and establish evidence-based strategies for their multidisciplinary management.

Journal of Clinical Medicine doi: 10.3390/jcm15187039

Authors: Athanasios Zikopoulos Efthalia Moustakli Anastasios Potiris Vasilios Sebastian Paraschos Ariadni Theodora Katopodi Nikolaos Kathopoulis Ismini Anagnostaki Ioannis Tsakiridis Themistoklis Dagklis Eriketi Kokkosi Angeliki Sarella Konstantinos Zikopoulos Sofoklis Stavros

Background: Recurrent implantation failure (RIF) remains one of the most challenging presentations in assisted reproductive technology and is characterized by failure to achieve clinical pregnancy despite the transfer of multiple good-quality embryos. Advances in embryo selection and preimplantation genetic testing have highlighted the contribution of endometrial factors to a substantial proportion of otherwise unexplained implantation failures. Methods: This narrative review summarizes current evidence regarding endometrial receptivity, the principal endometrial mechanisms implicated in RIF, contemporary diagnostic approaches, and available therapeutic strategies. Electronic literature searches were conducted using PubMed/MEDLINE, Scopus, ScienceDirect, and the Cochrane Library for publications available up to June 2026. Results: Anatomical, inflammatory, temporal, hormonal, immunological, and vascular endometrial causes of RIF can all be broadly categorized. Progesterone resistance, impaired decidualization, chronic endometritis, microbiome dysbiosis, displacement of the window of implantation, and immune dysregulation represent proposed mechanisms contributing to implantation failure in selected patients. Diagnostic evaluation is most effective when performed using a stepwise approach that prioritizes clinically actionable findings and avoids indiscriminate testing. Management primarily focuses on optimizing hormonal support, whereas immunomodulatory and antithrombotic therapies should be reserved for carefully selected patients. Emerging approaches, including granulocyte colony-stimulating factor, platelet-rich plasma, and microbiome-directed therapies, have shown promising preliminary results in selected patient populations; however, further validation is required. Conclusions: RIF is best regarded as a heterogeneous clinical outcome rather than a single disease entity, reflecting multiple disturbances in endometrial receptivity. Overall, current evidence supports a mechanism-informed approach that integrates targeted diagnostics with individualized, evidence-based therapeutic strategies.

Journal of Clinical Medicine doi: 10.3390/jcm15187043

Authors: Toshimi Sato Tomoyuki Morisawa Masakazu Saitoh Kentaro Iwata Michitaka Kato Koji Sakurada Yuji Kono Daisuke Suzuki Tetsuya Takahashi

Background/Objectives: Evidence regarding the prognostic impact of outpatient physical therapy (PT) initiated shortly after discharge in older patients with chronic kidney disease (CKD) hospitalized for worsening heart failure (HF) is limited. We evaluated the association between outpatient PT initiation within 30 days of discharge and the primary endpoint of all-cause mortality within 1 year after discharge. Methods: In this retrospective multicenter cohort study, we applied a 30-day post-discharge landmark design. Patients who died or were rehospitalized within 30 days after discharge were excluded, and 6359 eligible 30-day event-free survivors were included in the analysis. Of these, 244 (3.8%) underwent outpatient PT within 30 days of discharge, and the remaining patients had no documented outpatient PT within that period. Propensity scores were estimated from prespecified covariates and used for 1:1 matching. We assessed associations with 1-year all-cause mortality, cardiovascular (CV)-related rehospitalization, and their composite using Cox proportional hazards models in the propensity score-matched cohorts and pooled estimates across the 50 imputed and matched datasets using Rubin’s rules. Results: Within 1 year of discharge, 1099 participants died, 1586 were rehospitalized for CV-related reasons, and 2325 experienced either event. In pooled Cox regression analyses, outpatient PT initiation within 30 days was associated with lower all-cause mortality (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.22–0.97; p = 0.042) and the composite outcome (HR, 0.67; 95% CI, 0.48–0.94; p = 0.021), but not CV-related rehospitalization alone (HR, 0.78; 95% CI, 0.55–1.10; p = 0.178). Conclusions: Among patients with HF and study-defined CKD who were alive and free from CV rehospitalization at the 30-day landmark, early outpatient PT participation was associated with a lower risk of subsequent all-cause mortality. Given the observational design, treatment selection, and residual confounding, this finding does not establish a causal effect and requires confirmation in prospective controlled studies.

Journal of Clinical Medicine doi: 10.3390/jcm15187041

Authors: Rehab Alhasani Lujain Almutairi Reyof Alshahrani Seham Almutairi Amal Alharbi Remas Aldamok Monira I. Aldhahi

Background/Objectives: Auditory sensory stimulation, particularly binaural beats, affects neural oscillations and may improve cognitive and motor functions. Nevertheless, there is a paucity of research examining the concurrent effects of 40 Hz gamma binaural beats on postural control, motor coordination, and cognitive function in healthy adults. To evaluate the effects of 40 Hz gamma binaural beat auditory stimulation on postural control, motor coordination, and cognitive function in healthy adults. Methods: A pre–post quasi-experimental study was conducted among healthy adults who received 20 min of daily 40 Hz gamma binaural beat stimulation for two weeks. Outcomes included static balance, dynamic balance, upper-limb coordination, and cognitive function. Results: Thirty-two participants (mean age: 22.28 ± 2.43 years; 96.9% female) completed the study. Significant improvements were observed in dynamic balance (p < 0.001; d = 0.85), upper limb coordination (p < 0.001; d = 0.92), and PROMIS cognitive function scores (p < 0.001; d = 0.96). Static balance outcomes showed limited changes, except for the eyes-open Stability Index (p = 0.0005; d = −0.68). Conclusions: In this single-arm exploratory pilot study, 40 Hz gamma binaural beat stimulation was associated with improvements in selected sensorimotor and cognitive outcomes; however, in the absence of a sham or acoustically matched control condition, these findings should be interpreted as hypothesis-generating effect-size estimates rather than evidence of stimulation-specific efficacy, pending confirmation in controlled trials.

Journal of Clinical Medicine doi: 10.3390/jcm15187042

Authors: Adam Rafał Nowiński Wojciech Jelski Marta Skrodzka Barbara Mroczko Mariusz Gryko Karolina Orywal

Background: Prostate cancer (PCa) remains one of the most frequently diagnosed cancers in men worldwide, and there is growing interest in the role of metabolic reprogramming in its development. Key metabolic pathways include alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are enzymes involved in the oxidation of alcohols and aldehydes, the detoxification of xenobiotics, and the regulation of cell proliferation and the oxidative stress response. Despite well-documented changes in enzyme activity in other malignancies, their activity in prostate tissue has not yet been thoroughly investigated. This study aimed to evaluate the activity of total ADH and its isoenzymes (classes I–IV), and ALDH classes I and III, in prostate cancer tissue compared with benign prostatic hyperplasia (BPH). Methods: Enzyme activities were determined using spectrophotometric and fluorometric methods in prostate tissue obtained from 48 patients with PCa (26 with low-risk and 22 with intermediate-risk disease) and from 42 patients with benign prostatic hyperplasia (BPH). The study groups were compared using non-parametric statistical tests, with p < 0.05 considered statistically significant. Results: The isoenzyme ADH class III showed the highest activity in both studied groups. The activity of ADH class I was significantly higher in PCa tissue compared with BPH (p = 0.0499), while ALDH I and III activity was also significantly higher in PCa tissue than in BPH (p = 0.0007). No significant differences were observed in total ADH or its other isoenzymes. Significant correlations were found among some ADH isoenzymes, but not with ALDH. Conclusions: Increased activity of class I ADH and ALDH enzymes in prostate cancer tissue may reflect disease-related metabolic changes and suggest their potential significance in the biology of prostate cancer. These findings provide new insights into metabolic reprogramming in prostate cancer and support the need for further studies to determine the biological and potential clinical significance of these enzymes.

Journal of Clinical Medicine doi: 10.3390/jcm15187040

Authors: Mark Stanworth Thomas Peukert Joanne Marley Clare Puddifoot Andrew McDowell Elaine Murray Shu-Dong Zhang

Background/Objectives: Migraine is a neurological disorder with a heterogeneous presentation; however, compounds perceived as effective by migraine sufferers are often underrepresented in research. This study adopts a novel exploratory approach to determine whether pharmacodynamic data from such compounds can be used to prioritise candidate migraine-related genes and biological pathways for future investigation, and to generate hypotheses regarding migraine pathophysiology. Methods: A structured internet search identified 181 compounds perceived as effective for migraine, of which 148 had at least one supportive report identified in the PubMed literature. Following DrugBank-based exclusions for insufficient interaction data, 137 compounds remained for analysis. A gene list was extrapolated from compound–protein interactions, followed by analyses identifying significantly enriched tissues and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. Unique genes from enriched tissue-specific sublists were considered targets of interest, and those not previously directly associated with migraine in the databases and literature searches used were deemed candidate migraine target genes. Results: A total of 32 compounds affected the products of 21 targets of interest. CHRM3, CHRNA4, and SCN2B emerged as prioritised candidate genes that had not previously been directly associated with migraine in the databases examined. Enrichment analysis of the pharmacodynamically derived gene set identified tissue-enrichment signals involving skeletal muscle (q = 6.01 × 10−5), prefrontal cortex (q = 5.36 × 10−3), cerebellar peduncles (q = 1.28 × 10−2) and cerebellum (q = 4.79 × 10−2). Nine compounds interacting with established Familial Hemiplegic Migraine (FHM) genes may warrant future investigation. No conclusions regarding therapeutic efficacy are drawn from these data. Conclusions: This exploratory pipeline prioritised CHRM3, CHRNA4, and SCN2B as candidate genes for further investigation, alongside enriched tissues and pathways. These findings should be regarded as hypothesis-generating rather than evidence of causality or therapeutic utility. More broadly, variations of this prioritisation framework may prove useful for exploring other disorders.

Journal of Clinical Medicine doi: 10.3390/jcm15187037

Authors: Leonie F. Keidel Charlotte Engelmann Michael Hafner Miranda Gehrke Lara Buhl Siegfried G. Priglinger Marc J. Mackert

Background/Objectives: Our objective was to compare clinical outcomes of the Hydrus® Microstent implantation combined with cataract surgery in eyes with pseudoexfoliation glaucoma (PXG) and primary open angle glaucoma (POAG). Methods: This retrospective, single-center comparative cohort study included eyes with POAG or PXG undergoing combined cataract surgery and Hydrus® Microstent implantation between June 2021 and December 2025 at the University Eye Hospital of the Ludwig Maximilian University in Munich, Germany. Clinical outcomes were evaluated until 8–14 months after surgery. Results: A total of 74 eyes were included, comprising 49 POAG eyes and 25 PXG eyes. After cataract surgery plus Hydrus® Microstent, IOP decreased significantly in both groups from baseline to the final 8–14-month follow-up (POAG: 17.6 ± 3.9 to 13.8 ± 2.3 mmHg, p < 0.0001; PXG: 19.2 ± 4.3 to 14.6 ± 2.7 mmHg, p < 0.0001). The magnitude of IOP reduction did not differ between groups (p = 0.410). Meanwhile, the number of IOP-lowering medications decreased significantly in both groups with no between-group difference (POAG: −1.20 medications; PXG group −1.09 medications, p = 0.724). Surgical success rates were comparable. Conclusions: Hydrus® Microstent implantation combined with cataract surgery showed comparable surgical outcomes in POAG and PXG eyes. Regardless of the more aggressive disease characteristics of PXG, no significant differences were observed between PXG and POAG eyes regarding IOP reduction, medication burden, BCVA, surgical success, complications or safety outcomes. These findings suggest that combined cataract surgery and Hydrus® Microstent implantation may be a useful treatment option in selected patients with PXG.

Journal of Clinical Medicine doi: 10.3390/jcm15187038

Authors: Yusuke Murakami Yoshiaki Minakata Yasushi Tanimoto Keisuke Miki Shinji Tamaki Toshiyuki Kita

Background/Objectives: Reduced physical activity (PA) and increased sedentary behavior (SB) are associated with adverse outcomes in chronic obstructive pulmonary disease (COPD), but the factors underlying their long-term change are unclear; we investigated the baseline factors associated with these changes. Methods: Japanese outpatients with stable COPD co-enrolled in the SPACE (baseline) and E-PAC (follow-up) studies were analyzed retrospectively. Twenty-nine baseline clinical variables were assessed. PA and SB were measured with a waist-worn triaxial accelerometer and expressed in metabolic equivalents (METs). Annualized percentage changes (per year, relative to baseline) were analyzed by Spearman’s rank correlation and multiple linear regression. Results: Thirty-two participants (all men; median age 71.0 years; median follow-up 5.0 years) were analyzed. Lower baseline body weight, BMI, upper arm circumference, FEV1.0, FEV1.0/FVC, and lowest percutaneous oxygen saturation (SpO2) during the 6 min walk test (6MWT) were correlated with greater annualized declines in PA. For SB, the annualized change was correlated only with the lowest SpO2 during the 6MWT, FEV1.0/FVC, and the hemoglobin concentration. In multivariable models adjusted for FEV1.0 %pred and the lowest SpO2 during the 6MWT, BMI remained associated with the declines in total PA and in the duration at ≥3.0 METs; the models for the step count and SB were not significant. Conclusions: In this exploratory analysis, nutrition-related anthropometric measures, poorer pulmonary function, and exercise-induced desaturation were associated with the long-term decline in PA, and a lower BMI remained associated after adjustment. For the change in SB, associations were found only in unadjusted correlation analysis and were not supported by the multivariable model. These hypothesis-generating findings require confirmation in a larger cohort.

Journal of Clinical Medicine doi: 10.3390/jcm15187036

Authors: Ha Young Yu Chang-Ok Seo Yun Gi Kim Jong-Il Choi Joo Hee Jeong Jaemin Shim Seong-Mi Park Young-Hoon Kim

Background/Objectives: Left atrial (LA) low-voltage area quantification is time-consuming and threshold-dependent. We investigated whether mean left atrial bipolar voltage, as a marker of atrial cardiomyopathy, is associated with prior ischemic stroke and compared its performance with low-voltage area percentage (LVA%). Methods: In this single-center retrospective cross-sectional study, 259 consecutive patients with atrial fibrillation (AF) undergoing radiofrequency catheter ablation were enrolled. Mean LA voltage was calculated as the arithmetic mean of all bipolar voltage points acquired during electroanatomic mapping. LVA% was defined as the proportion of LA surface area with voltage < 0.5 mV. Associations with prior ischemic stroke were assessed using Firth’s penalized logistic regression. Results: The median age was 67 years and 31.7% were women. Twenty-nine patients (11.2%) had prior ischemic stroke. Patients with prior stroke had significantly lower mean LA voltage (0.5 [0.4–0.8] vs. 1.0 [0.6–1.3] mV, p < 0.001). After adjustment for CHA2DS2-VASc components, mean LA voltage remained independently associated with prior stroke (odds ratio 0.12, 95% confidence interval 0.03–0.38; p < 0.001). Mean LA voltage and LVA% showed comparable discrimination (area under the curve 0.743 vs. 0.717; p = 0.392), but adding mean LA voltage to the LVA%-only model improved model fit (likelihood ratio test p = 0.024). Conclusions: In this cross-sectional cohort, lower mean LA voltage was independently associated with prior ischemic stroke and may better reflect the extent of underlying atrial remodeling than LVA%.

Journal of Clinical Medicine doi: 10.3390/jcm15187035

Authors: José Manuel Ramia Belén Hernández-Roca Juan Jesús Rubio-García Daniel Aparicio-López Juli Busquets Luis Secanella Nuria Peláez Maialen Alkorta Itziar de Ariño-Hervás María del Mar Achalandabaso Enrique Toledo Fernando Rotellar Pablo Martí-Cruchaga Miguel Ángel Gómez-Bravo Gonzalo Suárez Marina Garcés-Albir Luis Sabater Gabriel García Francisco Javier Alcalá Enrique Asensio David Pacheco Esteban Cugat Francisco Espín María Galófre Belinda Sánchez Julio Santoyo Jorge Calvo Carmelo Loinaz María Isabel García-Domingo Santiago Sánchez-Cabús Belén Martín Gerardo Blanco-Fernández Isabel Jaén-Torrejimeno Carlos Domingo Carmen Payá Carmen González Sandra Ruiz Rafael López-Andújar Cristina Ballester Ana Belén Vico Natalia Zambudio Sergio Estévez Manuel Nogueira-Sixto José Ignacio Miota Belén Conde Miguel Ángel Suárez Jorge Roldán de la Rúa Angélica Blanco Manuel González Pilar Elena González Betsabé Reyes Santiago López-Ben Berta Tió Javier Mínguez Inmaculada Lasa Alberto Miyar Lorena Solar Fernando Burdío Benedetto Ielpo Alberto Carabias María Paloma Sanz-Muñoz Alfredo Escartín Fulthon Vela Elia Marqués Adelino Pérez Gloria Palomares Antonio Calvo José Tomás Castell María Jesús Castro María del Carmen Manzanares Enrique Artigues Juan Luis Blas Luis Díez Alicia Calero José E. Quiñones Mario Rodríguez Mario Serradilla-Martín Cándido F. Alcázar-López Celia Villodre

Background: Whether tumor functional status influences postoperative outcomes after left pancreatectomy (LP) for pancreatic neuroendocrine tumors (pNETs) remains unknown. We evaluated the association between functional status, perioperative management, and postoperative outcomes in a prospective nationwide cohort of patients undergoing LP for pNET. Methods: This prespecified analysis of the prospective multicenter SPANDISPAN study included consecutive patients undergoing elective LP at 41 Spanish hospitals between February 2022 and January 2023. Of 98 patients with pNET, functional status was available in 88 (14 functioning and 74 non-functioning tumors). Perioperative characteristics, spleen preservation, and postoperative outcomes were compared according to tumor functional status. Results: Spleen preservation was performed in 28.6% of functioning and 18.9% of non-functioning tumors (p = 0.472; risk difference 9.7 percentage points, 95% CI [confidence interval] −15.6 to 34.9). Patients with functioning tumors had lower rates of clinically relevant postoperative pancreatic fistula (7.1% vs. 36.5%; p = 0.032; risk difference −29.3 percentage points, 95% CI −46.7 to −12.0), shorter length of hospital stay (median 4 vs. 7 days; p = 0.036), and no 90-day readmissions (0% vs. 31.1%; p = 0.017; risk difference −31.1 percentage points, 95% CI −41.6 to −20.5). Tumor functional status was not significantly associated with the use of spleen-preserving resection. Conclusions: Functional status is associated with clinically relevant differences in postoperative outcomes after LP for pNET. Patients with functioning tumors experienced lower postoperative morbidity than those with non-functioning tumors, whereas no statistically significant association was detected between tumor functional status and spleen preservation. These exploratory findings suggest that tumor functional status may warrant consideration as an additional factor in perioperative risk stratification and patient counseling, pending confirmation in larger, adequately powered studies; spleen preservation should continue to be guided by established oncological criteria.

Journal of Clinical Medicine doi: 10.3390/jcm15187034

Authors: Michał Bohdan Anna Kowalczys Alicja Radtke-Łysek Wioletta Raczyńska Alicja Fedyczkowska Aleksandra Gutowska Anna Borzyszkowska Sławomir Żegleń Marcin Gruchała

Background/Objectives: Body composition may influence functional capacity and long-term outcomes after thoracic organ transplantation. However, direct comparisons of body composition patterns between heart transplant (HTx) and lung transplant (LTx) recipients remain limited. This study compared body composition parameters and their relationship with time since transplantation in HTx and LTx recipients using bioelectrical impedance analysis (BIA). Methods: This cross-sectional study included 79 clinically stable transplant recipients (38 HTx and 41 LTx) with a median time of 9 months after transplantation (range, 1 month–9 years). Body composition was assessed using the SECA mBCA 515 analyzer. Absolute fat mass (AFM), relative fat mass (RFM), fat-free mass (FFM), skeletal muscle mass (SMM), phase angle (PA), and extracellular water-to-total body water ratio (ECW/TBW) were measured. Associations between body composition parameters and time since transplantation were modelled using adjusted generalized additive models with separate smooth functions for HTx and LTx recipients. Results: Positive cross-sectional associations between AFM and time since transplantation were observed during the 3–9-month post-transplant interval in both groups (HTx: 0.72 kg/month, p = 0.042; LTx: 0.83 kg/month, p = 0.021). In contrast, significant positive associations between SMM and time since transplantation were observed exclusively among LTx recipients during the 1–3-month (0.59 kg/month, p = 0.039) and 3–9-month (0.49 kg/month, p = 0.003) intervals, whereas no significant associations were observed after HTx. In LTx recipients, ECW/TBW was negatively associated and PA positively associated with time since transplantation during the 3–9-month interval. Conclusions: HTx and LTx recipients exhibited different cross-sectional patterns of body composition according to time since transplantation. HTx recipients were characterized by greater adiposity without a significant association between SMM and time since transplantation, whereas LTx recipients showed positive associations between SMM and time since transplantation during the early post-transplant intervals.

Journal of Clinical Medicine doi: 10.3390/jcm15187033

Authors: Hajime Matsumura Miki Fujii

Whilst early debridement and autologous skin grafting remain the cornerstones of treatment for deep burns, there has been a shift towards a more selective and regenerative medicine-oriented approach in the topical management of burn wounds. The most critical issue is whether the wound can achieve epithelialization within approximately 2 to 3 weeks. This timeframe is of clinical significance due to the strong association between delayed epithelialization and hypertrophic scarring, which can result in contractures and functional impairment. However, given that the likelihood of epithelialization is influenced by factors such as the mechanism of injury, anatomical location and skin thickness at that site, age, and blood flow, its prediction remains incomplete and relies heavily on experience. The second challenge is to remove necrotic tissue while preserving as much healthy tissue as possible, thereby creating a wound bed with an adequately controlled microbial burden. Excessive excision should be avoided. The cytotoxic effects of several topical antimicrobial agents can inhibit the migration of keratinocytes, fibroblasts and other cells, as well as damaging the extracellular matrix. In order to address these issues, a range of methods are employed, including enzymatic debridement. The third challenge pertains to the reconstruction of the dermis in full-thickness burns, and the role of dermal and matrix-based materials is expanding. In addition to conventional artificial dermis, acellular fish skin matrices, synthetic biodegradable temporary matrices, and recombinant biomaterials are now being used. These materials can be regarded not solely as wound dressings, but also as instruments for preserving or re-establishing a biologically functional dermal matrix prior to epithelialization. Once these conditions are achieved, autologous skin cell suspension or cultured epidermal autografting may become appropriate options in selected wounds. This Perspective proposes a framework for precision-oriented local burn wound care structured around four sequential but iterative objectives.

Journal of Clinical Medicine doi: 10.3390/jcm15187032

Authors: Evgenia Mela Maximos Frountzas Nefeli Tomara Dimitrios Damaskos Nektaria Karangeli Adam Mylonakis Markos Despotidis Aristeidis Sourgiadakis Nikoletta Dimitriou George Tribonias Dimitrios Schizas

Background/Objectives: Boerhaave’s syndrome (BS) is a rare, life-threatening condition associated with high mortality. This systematic review aimed to summarize the clinical presentation, management, and outcomes of adult patients with BS. Methods: PubMed and Scopus were searched through 12 June 2026 for case reports and case series reporting individual patient-level data. Demographic, clinical, diagnostic, therapeutic, and outcome data were extracted. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist, and factors associated with in-hospital mortality were explored using logistic regression. Results: A total of 427 studies comprising 694 patients were included. Mean age was 57.1 years and 523 patients (80.6%) were male. Vomiting (79.5%) and chest pain (60.7%) were the most common symptoms, while 263 patients (67.6%) met SIRS criteria at diagnosis. The distal esophagus was involved in 83.5% of cases, and computed tomography was the predominant diagnostic modality (55.5%). Surgery was the most common first-line treatment (62.8%). In-hospital and 30-day mortality were 18.2% and 15.4%, respectively. In exploratory analyses, increasing age and SIRS were associated with in-hospital mortality. Risk of bias assessment identified methodological concerns across studies predominantly due to selective and incomplete outcome reporting. Certainty of evidence for in-hospital mortality was very low according to GRADE. Conclusions: BS remains associated with substantial morbidity and mortality. Surgery remains the most frequently applied treatment, while conservative and endoscopic strategies are used in selected patients. Case-based evidence precludes reliable comparative assessment of treatment effectiveness. The association between SIRS and mortality remains hypothesis-generating.

Journal of Clinical Medicine doi: 10.3390/jcm15187031

Authors: Ekrem Solmaz Gokce Yildiran Zeliha Fazliogullari Zekeriya Tosun

Background/Objectives: Microtia is frequently associated with temporal bone malformations, but the extent to which external ear phenotype reflects underlying CT-defined anatomy remains uncertain. This study aimed to compare the relationships of Marx severity grading and Nagata morphological classification with temporal bone anatomy in patients with microtia. Methods: This retrospective study included 26 patients with 27 affected ears who had both preoperative external ear photographs and temporal bone computed tomography (CT) examinations. Each affected ear was classified according to the Marx and Nagata systems, and temporal bone anatomy was assessed using the modified Jahrsdoerfer CT scoring system. Associations were evaluated using Spearman rank correlation and permutation-based Jonckheere–Terpstra analysis, with an additional patient-level sensitivity analysis. Results: Considerable variation in Jahrsdoerfer scores was observed within external ear phenotypic categories, with substantial overlap between Marx Grades II and III and lower scores concentrated in Grade IV. The inverse association between Marx grade and Jahrsdoerfer score did not reach conventional statistical significance (ρ = −0.380, p = 0.051), whereas the Jonckheere–Terpstra test identified an overall decreasing trend (permutation p = 0.025). This trend no longer reached statistical significance in the patient-level sensitivity analysis. Nagata classification did not significantly discriminate CT-based radiological severity. Conclusions: Greater external auricular severity may be associated with less favorable temporal bone anatomy, but the relationship was not uniform across successive Marx grades. Marx and Nagata classifications provide complementary phenotypic information, but neither consistently reflected the extent of underlying temporal bone malformation. These preliminary findings emphasize phenotype–CT variability and support individualized CT-based anatomical assessment when imaging is clinically indicated.

Journal of Clinical Medicine doi: 10.3390/jcm15187030

Authors: Panagiotis Korovessis Vasileios Syrimpeis Georgios Vlachopoulos Dimitrios Ntourantonis George Sakellaropoulos

Background/Objectives: The optimal surgical approach for Percutaneous KyphoPlasty (PKP) in patients with recent single-level Osteoporotic Vertebral Compression Fractures (OVCFs) remains controversial. Most available previous meta-analyses included studies with variable heterogeneity, often mixing unilateral and bilateral MIS approaches, differing surgical techniques, and various fracture patterns, which limited the reliability of their conclusions. This meta-analysis aimed to compare the efficacy and safety of unilateral versus bilateral PKP exclusively in patients with recent single-level OVCFs only. Methods: A systematic review was conducted according to the PRISMA 2020 guidelines. PubMed, Scopus, Cochrane Library, and ScienceDirect were searched for comparative studies published between 2000 and 2025. Randomized Controlled Trials (RCTs), prospective, and retrospective comparative studies comparing unilateral and bilateral PKP for recent single-level OVCFs were included. Clinical and radiological outcomes as well as perioperative complications and safety outcomes were analyzed using random-effects meta-analysis. Predefined subgroup analyses according to study design and sensitivity analyses were performed. Results: Eleven studies involving 1374 patients (705 unilateral and 669 bilateral PKP) met the inclusion criteria. No significant differences were observed between the two surgical approaches regarding short- or long-term pain relief, cement leakage, number of adjacent vertebral fractures, or overall clinical outcomes. Bilateral PKP demonstrated statistically significant, but clinically negligible, advantages in anterior vertebral body height restoration and kyphosis correction. Unilateral PKP required an insignificantly lower cement volume. For operative time, the overall pooled estimate favored unilateral PKP by approximately 10 min but showed extreme heterogeneity (I2 = 98.5%). Importantly, the two RCTs showed no statistically significant between-group difference (MD = +1.2 min, 95% CI −4.5 to +6.8), indicating that the apparent overall effect was largely driven by observational evidence. Similar discrepancies between randomized and retrospective studies were observed for several other outcomes, underscoring the importance of considering study design when interpreting the results. Conclusions: Current evidence does not demonstrate clinically meaningful superiority of either unilateral or bilateral PKP for the treatment of recent single-level OVCFs. Bilateral PKP may provide small advantages in selected radiographic outcomes, whereas unilateral PKP uses modestly less bone cement; however, the relevance of these differences remains clinically uncertain. Surgical approach selection may therefore be individualized according to vertebral morphology, pedicle anatomy, fracture characteristics, surgeon experience, and technical feasibility rather than expectations of superior clinical outcomes. Further adequately powered randomized trials with standardized outcome reporting and long-term follow-up are warranted.

Journal of Clinical Medicine doi: 10.3390/jcm15187029

Authors: Danyan Yang Boren Tan Rong Li Qifeng Zhu Huajun Li Yue Mao

Background: Percutaneous intramyocardial septal radiofrequency ablation (PIMSRA), also known as the Liwen procedure, is an emerging septal reduction therapy for obstructive hypertrophic cardiomyopathy (OHCM), but standardized early rehabilitation pathways after PIMSRA are lacking. We aimed to develop an enhanced recovery after surgery (ERAS)-informed, risk-stratified stepwise rehabilitation pathway after PIMSRA, describe its documented early inpatient implementation in selected clinically stable patients, report preliminary in-hospital safety observations, and explore its associations with hospitalization outcomes. Methods: This exploratory single-center retrospective cohort study included 102 patients with OHCM who underwent first-time PIMSRA between 1 July 2023 and 3 August 2025 and met the same predefined post-PIMSRA rehabilitation eligibility criteria. Patients were classified according to the care pathway actually received: usual care (n = 53) or early inpatient implementation of the ERAS-informed rehabilitation pathway plus usual care (n = 49). The planned pathway incorporated rehabilitation eligibility screening, risk stratification, staged early mobilization, structured physiological monitoring with predefined stop criteria, multidisciplinary coordination, and patient education. Pathway selection was nonrandomized and reflected patient- or family-related preferences and implementation or logistical factors. Results: The ERAS-informed group had a shorter ICU length of stay than the usual-care group in the primary analysis [20.0 (5.8–26.6) h vs. 23.0 (17.1–45.5) h; Hodges–Lehmann difference, −6.0 h; 95% CI, −16.51 to −0.53; p = 0.022]. Three ICU stays > 100 h occurred in the usual-care group and none in the ERAS-informed group; after excluding these observations, the comparison was attenuated (p = 0.060). The total hospital length of stay was shorter in the ERAS-informed group [8.0 (7.0–11.0) d vs. 9.0 (8.0–13.0) d; difference, −1.0 d; 95% CI, −2.02 to −0.03; p = 0.029], whereas the post-PIMSRA length of stay did not differ significantly (p = 0.058). The admission-to-PIMSRA interval was also not significantly different (p = 0.309). No rehabilitation-related adverse events were recorded in the ERAS-informed group during hospitalization (0/49; exact binomial 95% CI, 0.0–7.3%). Conclusions: Among selected clinically stable patients after PIMSRA, early inpatient implementation of pathway components was achievable, primarily during the period corresponding to planned stages 1–2. No rehabilitation-related adverse events were recorded, providing preliminary patient-level in-hospital safety observations. Fidelity, adherence, completion, and reproducibility of the complete four-stage, risk-stratified pathway were not established. Length-of-stay associations were exploratory and should not be interpreted causally.

Journal of Clinical Medicine doi: 10.3390/jcm15187028

Authors: Antonella Meloni Laura Pistoia Paolo Ricchi Filomena Longo Lorenza Torti Valerio Cecinati Elisabetta Corigliano Michela Zerbini Luigi Barbuto Priscilla Fina Stefania Renne Vincenzo Positano Andrea Barison

Objectives: This multicenter cross-sectional study investigated the relationship between age and organ-specific iron burden and characterized multi-organ iron phenotypes across different age groups in adults with non-transfusion-dependent thalassemia (NTDT). Methods: We retrospectively evaluated 96 adults with NTDT enrolled in the multicenter Italian Extension-Myocardial Iron Overload in Thalassemia network. Hepatic, pancreatic, and cardiac iron burden were assessed by quantitative magnetic resonance imaging (MRI). Results: The median age was 41.64 (36.08–53.92) years. Hepatic iron overload (IO) was present in 59.4% of patients and pancreatic IO in 29.2%, whereas no patient exhibited myocardial IO. Age was not associated with liver iron concentration (LIC) or cardiac R2*. A weak positive correlation was observed between age and pancreatic R2* (R = 0.215, p = 0.035), although this association was no longer significant after the exclusion of one extreme value. LIC and pancreatic R2* were not correlated. Across age groups (<40, 40–59, and ≥60 years), the prevalence of pancreatic IO increased (22.9%, 28.6%, and 50.0%, respectively), whereas hepatic IO remained stable. Isolated hepatic IO was the most common phenotype overall, while combined hepatic and pancreatic IO was more frequent among patients aged ≥60 years. Conclusions: In adults with NTDT, age was not associated with greater hepatic or cardiac iron burden, whereas older patients showed a higher prevalence of pancreatic iron accumulation and combined hepatic–pancreatic iron involvement. These findings highlight the organ-specific heterogeneity of iron distribution in NTDT and support the role of multi-organ MRI assessment beyond LIC evaluation, particularly in older patients.

Journal of Clinical Medicine doi: 10.3390/jcm15187027

Authors: Speranta Iacob Teresa Antonini Maria Cristina Morelli Sara Pasquato Liz Schick Heiner Wedemeyer Fabien Zoulim Giacomo Germani

Background/Objectives: Liver transplantation (LT) is life-saving, yet its long-term impact on quality of life (QoL) remains complex and incompletely characterized. A standardized, transplant-specific patient-reported outcome measure (PROM) for routine use in European LT recipients is currently lacking. Methods: This descriptive, cross-sectional survey assessed QoL among 794 adult LT recipients across 22 European countries using a purpose-built, 48-item transplant-specific questionnaire developed within the European Society for Organ Transplantation (ESOT) Patient Inclusion Initiative. The instrument has not undergone psychometric validation and was used as an exploratory research survey. Respondents were grouped by time since LT (0–5, 6–12, and ≥13 years). Group comparisons used chi-square tests with Benjamini–Hochberg correction, followed by multivariable analyses adjusted for relevant sociodemographic factors. Results: Median time since LT was 6 years (IQR 3–12). After multiple-testing correction, alcohol consumption (q < 0.001), feeling that life is worth living (q = 0.029), and changes in social life (q = 0.029) differed between groups. In multivariable analysis, only alcohol consumption remained independently associated with time since LT, with progressively higher odds at 6–12 years (aOR 4.18, 95% CI 2.56–6.82) and ≥13 years (aOR 7.09, 95% CI 4.27–11.77) compared with 0–5 years. Physical health, emotional functioning, sexual health, satisfaction with care and medication adherence did not differ between groups. Conclusions: This large European survey provides hypothesis-generating information on self-reported well-being after LT. Alcohol consumption was the only outcome independently associated with time since transplantation. These findings support prospective studies using psychometrically validated patient-reported measures.

Journal of Clinical Medicine doi: 10.3390/jcm15187025

Authors: Kamil Nelke Agnieszka Kotela Zuzanna Majchrzak Marzena Laszczyńska Tomasz Horodniczy Kamil Wesołek Agata Małyszek Jacek Matys Maciej Dobrzyński

Objective: This systematic review evaluated the clinical application of autologous tissue grafts for chin augmentation performed with or without genioplasty. The primary outcomes included clinical and aesthetic improvement, graft stability and integration, resorption, complications, patient satisfaction, and the need for secondary procedures. Methods: The review was prospectively registered in OSF and conducted in accordance with the PRISMA 2020 statement. PubMed, Scopus, Embase, Web of Science, and WorldCat were searched using terms related to genioplasty, chin advancement, and autologous grafting materials, including bone, adipose tissue, cartilage, dermal tissue, and tooth-derived grafts. Eligible studies included original clinical publications involving human patients and reporting outcomes following chin augmentation with an autologous tissue graft, with or without genioplasty. Study selection and data extraction were conducted independently according to predefined eligibility criteria. Methodological quality was assessed using the appropriate Joanna Briggs Institute critical appraisal tools. Because of substantial clinical and methodological heterogeneity across the included studies, no meta-analysis was performed, and the findings were instead synthesized qualitatively. Results: Seventeen publications were included, comprising predominantly retrospective studies, case series, case reports, and technique-oriented clinical reports, with only one prospective randomized comparative trial; the overall level of evidence was therefore low, and comparative data across graft types remained limited. The evaluated materials comprised autologous adipose tissue, dermal grafts, iliac crest bone, costal cartilage and costochondral grafts, coronoid process bone, external oblique line corticocancellous bone, mandibular bone harvested during orthognathic surgery, a third-molar tooth graft, and an osteocartilaginous nasal hump graft. Most studies reported improvements in chin projection, facial profile, symmetry, or lower facial proportions. The available evidence suggests that autologous bone and cartilage grafts may provide integration and structural support, with limited clinically evident resorption reported; however, these observations derive from limited and heterogeneous evidence. Soft-tissue grafts improved chin contour but showed less predictable volume maintenance. Dermal graft resorption reached approximately 35% after 12 months, while fat grafting was associated with soft-tissue relapse and occasional secondary lipofilling. Serious graft-related complications were not frequently reported; however, adverse-event reporting was inconsistent, preventing reliable estimation of their incidence. Reported events included infections, temporary sensory disturbances, contour irregularities, and isolated graft removals. The certainty of the findings was limited by heterogeneous study designs, predominantly small or uncontrolled samples, variable outcome measures, and inconsistent follow-up. Conclusions: Autologous tissue grafts represent potentially effective options for chin augmentation when the graft source and surgical technique are selected according to the type and extent of the deformity. The available evidence suggests that bone and cartilage grafts may provide structural support, whereas adipose and dermal tissues may be considered for moderate soft-tissue augmentation; however, these conclusions are based on limited and heterogeneous evidence. However, the available evidence does not establish the superiority of autologous grafts over sliding genioplasty or alloplastic implants. Registration: Open Science Framework.

Journal of Clinical Medicine doi: 10.3390/jcm15187026

Authors: Orly Tamir Dor Hadida Barzilai Havi Murad Nirit Agai Leah Borovoi Avraham Karasik Ariel Israel Eugene Merzon

Background: Obesity is a heterogeneous chronic disease, yet it is still commonly defined and managed using body mass index alone. Identifying clinically meaningful subgroups may support more efficient, precise and practical care. Objective: To identify and characterize population-level heterogeneity among adults with obesity in a large Israeli healthcare cohort. Methods: In this cross-sectional study, we analyzed deidentified electronic health record data from the Leumit Obesity Registry. Adults with obesity who had at least one documented weight measurement and height or BMI record during 2024 were included. Demographic, socioeconomic, lifestyle, clinical, and treatment variables were analyzed using K-prototypes cluster analysis to identify subgroups within a mixed-data population. Results: The study included 68,203 adults with obesity. Five distinct patient clusters were identified: metabolically healthy young adults, 19% of the cohort; adults with low comorbidity, 18%; middle-aged adults with moderate comorbidity, 23%; multimorbid seniors with socioeconomic disadvantage, 24%; and higher socioeconomic status advanced age with high clinical burden, 16%. The clusters differed substantially in age, comorbidity burden, socioeconomic status, and obesity-treatment utilization. GLP-1 use was most common in the older multimorbid clusters, particularly among low SES. Dietitian use was lower in the oldest and sickest cluster, despite high disease burden. Bariatric surgery was overall relatively rare and was concentrated mainly in the younger clusters. Conclusions: Adults with obesity in this large population-based registry did not represent a single clinical group, but rather several distinct phenotypes with different clinical and treatment patterns. These findings support a shift toward more phenotype-informed obesity care and resource planning.

Journal of Clinical Medicine doi: 10.3390/jcm15187024

Authors: Murtaja Ahmad Alramahy Batol Ahmad Alramahy Jakob Benedict Seidelin Panu Wetwittayakhlang Jacob Tveiten Bjerrum Mohamed Attauabi

Background/Objectives: Postoperative endoscopic recurrence is common after intestinal resection for Crohn’s disease (CD), making surveillance essential. We performed a systematic review and meta-analysis evaluating the diagnostic performance of intestinal ultrasonography (IUS) for postoperative endoscopic recurrence and the prognostic association of IUS findings with surgical outcomes in the overall CD population. Methods: MEDLINE (PubMed) and Embase were searched from inception through 1 July 2026, for prospective studies evaluating postoperative IUS in CD. Diagnostic accuracy was analyzed using random-effects bivariate meta-analysis to estimate pooled sensitivity, specificity, likelihood ratios, summary receiver operating characteristic (SROC) curves, and diagnostic odds ratios (DORs). Results: Twenty-six prospective studies were included, comprising 797 patients evaluated for postoperative endoscopic recurrence and 1060 patients evaluated for associations between IUS findings and subsequent intestinal surgery. A bowel-wall thickness (BWT) threshold of >3.0 mm demonstrated high diagnostic accuracy for detecting any postoperative endoscopic recurrence (Rutgeerts ≥ i1), with pooled sensitivity of 85%, specificity of 83%, DOR of 30.8, and SROC AUC of 0.91, positive likelihood ratio of 5.3, and negative likelihood ratio of 0.19. For postoperative endoscopic recurrence (Rutgeerts ≥ i2), pooled sensitivity and specificity were lower at 79% and 67%, respectively (DOR 8.3; SROC AUC 0.76). A BWT threshold of >5.0 mm identified severe endoscopic recurrence (Rutgeerts i3–i4) with sensitivity of 79% and specificity of 81%, while a threshold of ≥7.0 mm was associated with increased risk of intestinal resections in the overall CD population. Conclusions: IUS demonstrated high diagnostic performance for postoperative endoscopic recurrence of CD with balanced sensitivity and specificity, and favourable likelihood ratios, although performance varied according to the definition and severity of recurrence. Evidence regarding diagnostic accuracy for modified Rutgeerts scores remains limited. Overall, these findings support IUS as a complementary modality to ileocolonoscopy, enabling repeated postoperative monitoring and risk stratification for endoscopic recurrence and surgery.

Journal of Clinical Medicine doi: 10.3390/jcm15187023

Authors: Gulcin Yilmaz Gunes Hikmet Çoban Fuat Erel Merve Akış Yılmaz Nurhan Sarioglu Mustafa Colak Merve Yumrukuz Senel

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) may progress despite antifibrotic therapy, highlighting the need for biomarkers of early treatment-associated biological changes. This study aimed to assess the potential role of hepcidin in monitoring treatment response by evaluating pre- and post-treatment serum hepcidin levels in patients with IPF receiving antifibrotic therapy. Methods: This prospective observational cohort study included 38 clinically stable patients diagnosed with IPF according to the 2022 American Thoracic Society/European Respiratory Society (ATS/ERS)criteria between January and July 2025. Serum hepcidin was measured by ELISA at antifibrotic therapy initiation and month 3. Demographic data, pulmonary function tests, diffusing capacity for carbon monoxide (DLCO), and 6 min walk test results were recorded. Analyses were performed using SPSS 25.0. Results: Mean serum hepcidin decreased from 33.00 ± 16.74 to 24.41 ± 12.42 ng/mL (p < 0.001), with reductions observed in 30 of 38 patients (78.9%). Mean forced vital capacity (FVC) increased from 73.83 ± 18.10% predicted to 77.74 ± 15.70% predicted (p < 0.001). Median DLCO increased from 68.50 (51.00–80.50)% predicted to 72.50 (60.00–83.75)% predicted (p < 0.001). Six-minute walk distance did not change significantly (p = 0.078), nor did hemoglobin, C-reactive protein, or erythrocyte sedimentation rate. The change in hepcidin did not differ between the pirfenidone and nintedanib groups (p = 0.817). Although FVC and DLCO increased over three months, these short-term functional changes should be interpreted cautiously, as test familiarization, measurement variability, and regression to the mean cannot be excluded; therefore, they should not be considered evidence of fibrosis reversal or a direct treatment effect. Conclusions: Our study provides the first real-world data demonstrating a significant decrease in serum hepcidin following antifibrotic treatment in patients with IPF. These findings suggest that serum hepcidin may have potential clinical utility as a biomarker for assessing response to antifibrotic therapy in IPF.

Journal of Clinical Medicine doi: 10.3390/jcm15187022

Authors: Daniela-Vasilica Serban Diana-Maria Mateescu Daniela Crainic Nina Ivanovic Roxana Manuela Fericean Florina Maria Bojin Ana-Olivia Toma Elena Daniela Jurj Emilia Clej Virgil Paunescu

Background/Objectives: General cardio-oncology guidance describes cardiovascular toxicity from BRAF/MEK inhibitors and immune checkpoint inhibitors (ICIs), but it does not resolve how treatment decisions should change when heart failure (HF) is already present. This critical narrative review separates direct HF-specific evidence from indirect evidence and proposes an HF-centered framework for systemic melanoma. Methods: MEDLINE/PubMed, Embase, and the Cochrane Library were searched for English-language sources published from January 2015 to April 2026, with targeted guideline, prescribing-information, interaction, and geriatric-oncology updates through July 2026. Sources were classified as direct, indirect, or extrapolated. This review follows SANRA principles but does not claim systematic-review conduct, pooled estimates, formal risk-of-bias assessment, or GRADE certainty. Results: Only case-level evidence directly describes systemic melanoma treatment in established HF; most cardiotoxicity rates are derived from selected longitudinal and real-world cohorts. We therefore organize decisions across four domains: HF phenotype and current stability; oncological urgency and alternatives; treatment-specific toxicity phenotype; and detectability, reversibility, and patient priorities. Each domain is graded ordinally and generates its own decision output, and explicit precedence rules resolve situations in which several domains are simultaneously abnormal; the pathway from assessment to documented output is presented as a decision flowchart and applied to illustrative clinical cases. This approach modifies interpretation of symptoms, biomarkers, ventricular function, surveillance, drug interactions, treatment interruption, and rechallenge. Every actionable statement is labeled as guideline-supported or author-proposed, therapy-specific baseline and follow-up monitoring are tabulated separately for each treatment class, and heart failure with preserved ejection fraction is addressed as a phenotype in which clinical deterioration may occur without any change in ejection fraction. Patient-level priorities in older adults—survival, quality of life, avoidance of hospitalization, tolerance of frequent monitoring, oral versus infusion treatment, and functional expectation—are specified as items to be recorded rather than inferred. Conclusions: Stable HF is not an automatic contraindication to effective melanoma therapy, whereas recent or active decompensation requires stabilization or monitored treatment when oncological delay is unsafe. The proposed framework operationalizes guideline principles for an understudied population while making the limits of the evidence explicit. It makes a procedural rather than an empirical claim: it is a transparent structure for documenting a decision that must be made anyway, not an algorithm derived from or validated against outcome data.

Journal of Clinical Medicine doi: 10.3390/jcm15187020

Authors: Giovanni Perricone Raffaella Viganò Chiara Mazzarelli Chiara Becchetti Giulia Dispinzieri Adelaide Panariello Paola Prandoni Sara Conti Paolo Angelo Cortesi Mario Camozzi Gianpaola Monti Andrea Lauterio Stefano Di Sandro Luca Saverio Belli

Background/Objectives: Severe alcohol-associated hepatitis (SAH) is a complication of alcoholic liver disease associated with high mortality. Effective identification of factors predicting the course, outcome, and need for early liver transplantation (eLT) in patients with SAH is crucial. Acute-on-chronic liver failure (ACLF), a syndrome characterized by an acute decompensation of cirrhosis, failure of one or more organs, and high short-term mortality, can occur in SAH, and its impact on management, prognostication, and need for eLT should be clarified. Methods: This is a single-center, retrospective study of patients with SAH admitted to the ASST GOM Niguarda in Milan between April 2016 and May 2023. Results: One hundred patients were included. Median Maddrey’s discriminant function (MDF) was 72.1 (IQR 51.6–101.3), and the median model for end-stage liver disease—sodium (MELD-Na) score was 28.5 (IQR 25.0–32.5). At presentation, 57 patients (57%) had ACLF 0–1 (54 ACLF 0—no organ failure [OF] or single non-renal OF with serum creatinine < 1.5 mg/dl and no hepatic encephalopathy; 3 ACLF 1—defined by the presence of at least renal failure or any other single OF if associated with renal dysfunction and/or grade I–II hepatic encephalopathy), and 43 patients (43%) had ACLF 2–3 (31 ACLF 2—defined by the presence of two OFs, 12 ACLF 3—defined by the presence of three or more OFs). In the latter group, circulatory failure was present in two (4.65%) and respiratory failure in three (6.98%). SAH was the only precipitating factor in 3 (100%) and 39 (90.7%) patients with ACLF 1 and ACLF 2–3, respectively, with infection being an associated factor in 5 (11.63%) and GI bleeding in 2 (4.65%) of subjects with ACLF 2–3. Non-response to medical treatment (MT) was significantly higher in patients with ACLF 2–3 (38/43, 88.4%) than in those with ACLF 0–1 (25/57, 43.8%). ACLF 2–3 was associated with a corresponding higher need for eLT (ACLF 2–3: 15/43, 34.9% vs. ACLF 0–1: 10/57, 17.54%%; p = 0.0474). ACLF status at presentation (ACLF 2–3 vs. ACLF 0–1) has a similar predictive accuracy of outcome (death or liver transplantation [LT]) to MELD-Na (as a 1-unit increase) (3.261 [1.999; 5.318], concordance index 0.702 vs. 1.154 [1.094; 1.217], concordance index 0.708). Conclusions: ACLF 2–3 is a frequent presentation of SAH, 43% of the cases. Given that most of these patients do not respond to MT (approximately 90%), fast-track evaluation for LT is advised for patients with a favorable psycho-social profile.

Journal of Clinical Medicine doi: 10.3390/jcm15187021

Authors: Hui Lu Shanshan Cheng Xingzi Liu Meiling Jin Fang Sun Qianmei Sun

Background: Intradialytic hypotension (IDH) is a common complication of hemodialysis (HD) and is associated with an increased risk of poor prognosis. This study investigated the factors associated with IDH in HD patients and explored the value of brain natriuretic peptide (BNP) in predicting IDH. Methods: Participants were divided into two groups according to the occurrence of IDH. Differences in clinical data between the IDH and no-IDH groups were analyzed, and the influencing factors of IDH were analyzed using logistic regression. A receiver operating characteristic (ROC) curve was applied to identify the optimal critical value of BNP for the occurrence of IDH in HD patients. Results: A total of 123 HD patients were included, in which the percentage of IDH was 30.9%. In patients with IDH, the levels of BNP (224.4 vs. 464.7 pg/mL, p = 0.001), pre-HD systolic blood pressure (SBP) (153.0 vs. 162.0 mmHg, p = 0.002), pre-HD diastolic blood pressure (DBP) (75.7 vs. 84.1 mmHg, p = 0.001), post-HD SBP (134.2 vs. 154.2 mmHg, p < 0.001) and DBP (72.8 vs. 84.0 mmHg, p < 0.001) were significantly lower than those in the non-IDH group, and the level of ejection fraction (66.5 vs. 64.1%, p = 0.039) was significantly higher. Univariate analysis showed that BNP [odds ratio (OR) = 0.999, p = 0.015], pre-HD SBP (OR = 0.960, p = 0.001), and DBP (OR = 0.944, p = 0.001) were associated with IDH. Multivariate analysis revealed that lower BNP levels (OR = 0.999, p = 0.030), lower pre-HD DBP levels (OR = 0.928, p = 0.009), and higher body mass index (BMI) (OR = 1.133, p = 0.032) were independently correlated with IDH. BNP had a predictive value for the occurrence of IDH. Conclusions: BNP showed predictive value for IDH and may serve as a useful predictor of this complication. Its independent association with IDH supported its potential utility in clinical decision-making.

Journal of Clinical Medicine doi: 10.3390/jcm15187019

Authors: Ahmet Yiğitbay Erim Can Demircan Muhammed Fatih Civan Alev Kural Cemal Kural Ali Can Koluman Nezih Ziroğlu

Background and Objectives: Femoral arterial calcification (FAC) on routine hip radiographs may provide opportunistic vascular information within orthogeriatric assessment. We evaluated the associations of FAC and the Atherogenic Index of Plasma (AIP) with 1-year mortality after hip-fracture surgery. Materials and Methods: This retrospective single-centre cohort included 229 patients aged 65 years or older. FAC was graded from 0 to 3 on preoperative radiographs using an exploratory semiquantitative classification. AIP was calculated as log10(TG/HDL-C). Logistic regression and complementary survival analyses were partially adjusted for age, sex, FAC, and AIP. Incremental discrimination was assessed using nested age + sex, age + sex + FAC, and age + sex + FAC + AIP models. Results: Thirty-eight patients (16.6%) died within 1 year. Interobserver agreement for FAC grading was almost perfect (κ = 0.87). Each one-grade increase in FAC was associated with mortality in the partially adjusted logistic (OR = 1.44, 95% CI 1.09–1.91) and Cox models (HR = 1.36, 95% CI 1.07–1.73). AIP was not significantly associated with mortality. AUCs were 0.726 for age + sex, 0.757 for age + sex + FAC, and 0.761 for age + sex + FAC + AIP; neither incremental increase was significant. Conclusions: Radiographic FAC was associated with 1-year mortality but did not demonstrate significant incremental discrimination beyond age and sex. FAC may serve as an opportunistic marker within multidisciplinary orthogeriatric assessment, not as a stand-alone prognostic tool. AIP findings remain inconclusive because sampling occurred during acute admission without standardised fasting. Prospective multicentre validation with comprehensive geriatric covariates is required.

Journal of Clinical Medicine doi: 10.3390/jcm15187018

Authors: Özge Öztürk Recep Taha Ağaoğlu Gunel Aliyeva Mesut Şimşek Kadriye Yakut Yücel

Background/Objectives: To investigate maternal serum Isthmin-1 (ISM1) levels in pregnancies complicated by fetal growth restriction (FGR) and to evaluate its potential discriminatory performance for FGR. Methods: This prospective cross-sectional study included 44 pregnant women with late-onset FGR and 43 gestational age-matched healthy controls. FGR was diagnosed according to one of two criteria: (1) estimated fetal weight (EFW) below the 3rd percentile, or (2) EFW between the 3rd and 10th percentile with at least one abnormal Doppler finding (Umbilical Artery Pulsatility Index (UA-PI), Middle Cerebral Artery Pulsatility Index (MCA-PI), or Cerebroplacental Ratio (CPR). Maternal serum ISM1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Ultrasonographic parameters, Doppler indices, and perinatal outcomes were compared between groups. Correlation and receiver operating characteristic (ROC) analyses were performed to assess diagnostic performance. Results: Maternal ISM1 levels were significantly lower in the FGR group compared with controls [10.63 (9.95–12.10) vs. 12.40 (10.75–13.25) ng/mL, p = 0.003]. ISM1 correlated negatively with FGR presence (r = −0.318, p = 0.003) and positively with EFW percentile (r = 0.235, p = 0.028). ROC analysis showed moderate diagnostic accuracy Area Under the Curve (AUC) = 0.684, 95% CI: 0.575–0.779) with 70.5% sensitivity and 72.1% specificity at a cut-off ≤11.5 ng/mL. No significant association was found between ISM1 and composite adverse perinatal outcomes. Conclusions: Levels of ISM1 in maternal serum were found to be significantly lower in pregnancies complicated by FGR, supporting a potential association between ISM1 and impaired fetal growth. However, its moderate diagnostic performance and lack of association with adverse perinatal outcomes indicate that ISM1 should currently be regarded as a promising exploratory biomarker rather than a standalone diagnostic or prognostic marker. Further studies are needed to validate these findings and to determine whether ISM1 provides additional value when combined with established Doppler and angiogenic markers.

Journal of Clinical Medicine doi: 10.3390/jcm15187016

Authors: Omer Erdogan Omur Memik Mustafa Gunes Oguz Ozden Cebeci Murat Ustuner Ahmed Omer Halat Ali Kemal Uslubas Taha Erseckin

Background: This study aimed to investigate the association between metabolic and atherogenic indices and erectile dysfunction (ED) severity, and to compare their diagnostic performance in predicting severe ED. Methods: This retrospective study included 221 men with ED between January 2025 and January 2026. ED severity was assessed using the International Index of Erectile Function-5 (IIEF-5). The triglyceride–glucose (TyG) index, atherogenic index of plasma (AIP), Castelli Risk Index-1 and -2, and atherogenic coefficient (AC) were calculated from routine laboratory parameters. Correlation, logistic regression, and ROC analyses were performed. Results: Patients with severe ED (n = 57) had significantly higher triglyceride, fasting glucose, TyG, and AIP levels and lower high-density lipoprotein cholesterol (HDL) levels than those with mild-to-moderate ED (all p < 0.05). TyG (ρ = 0.369, p < 0.001) and AIP (ρ = 0.359, p < 0.001) were positively correlated with severe ED. In the multivariable model, the TyG index remained associated with severe ED after adjustment for AIP, age, BMI, total testosterone, and the TyG-by-testosterone interaction (OR: 4.354, 95% CI: 1.668–11.364; p = 0.003). Total testosterone was not independently associated with severe ED (p = 0.510), and the TyG-by-testosterone interaction was not significant (p = 0.281). ROC analysis showed that TyG had the best predictive performance (AUC: 0.743). Conclusions: The TyG index showed discrimination for IIEF-5-defined severe ED and may have value as a complementary metabolic risk-stratification parameter.

Journal of Clinical Medicine doi: 10.3390/jcm15187017

Authors: Samantha H. Collins Igor Matushansky

Osteosarcoma clinical presentation, treatment tolerance, and treatment delivery differ across the age spectrum. Adult cohorts are more heterogeneous, with higher proportions of axial and secondary osteosarcoma and greater variation in comorbidity and treatment intensity. Furthermore, emerging genomic studies suggest age-associated differences in tumor complexity and stress-response pathways, whereas direct age-stratified epigenomic and immune-microenvironment data remain limited. These molecular observations are hypothesis-generating and data currently do not support age-specific treatment selection. This narrative review summarizes clinical and biological evidence across age groups, distinguishes prognostic associations from predictive treatment effects, and identifies major confounders and evidence gaps. The available evidence supports age-inclusive prospective trials that model age explicitly, incorporate biomarker-stratified analyses, and report delivered dose intensity, toxicity, and host factors.

Journal of Clinical Medicine doi: 10.3390/jcm15187015

Authors: Emir Baskovski Halil Gulyigit Omer Akyurek Timucin Altin Eralp Tutar

Atrial fibrillation (AF) is a major cause of cardioembolic stroke, and oral anticoagulation (OAC) remains the standard of care for thromboembolic prophylaxis. Because the left atrial appendage (LAA) is the dominant source of thrombus in AF, percutaneous LAA occlusion (LAAO) has been developed as a mechanical alternative for patients in whom long-term anticoagulation is problematic. Randomized trials against warfarin established non-inferiority for the composite endpoint, though not consistently across coprimary endpoints, and more recent trials against direct oral anticoagulants (DOACs) have extended this comparison to post-ablation and lower-risk populations. Across these studies a consistent pattern emerges: the clinical advantage of LAAO derives largely from a reduction in non-procedural bleeding rather than from superior ischemic protection, and recent meta-analyses diverge mainly according to how the thromboembolic endpoint is composed. At the extreme of stroke and bleeding risk, LAAO failed to demonstrate non-inferiority to physician-directed medical care. This review synthesizes the randomized evidence, examines methodological differences in endpoint construction and patient selection that complicate cross-trial comparison, and discusses determinants of procedural success including peridevice leak, device endothelialization, and device-related thrombus. Remaining evidence gaps are outlined, particularly for patients who experience ischemic stroke despite adequate anticoagulation.

Journal of Clinical Medicine doi: 10.3390/jcm15187013

Authors: Piotr S. Liberski Krzysztof Żerdziński Michał Gałuszewski Michał Skrzypek Łukasz J. Krzych

Background: Severity-of-illness scores and registry-derived risk models assume that the association between a baseline characteristic and death is stable over time. Methods: A retrospective analysis of 25,344 admissions (2010–2020) to 34 intensive care units in the Silesian Registry of Anaesthesiology and Intensive Care, with unchanged variable definitions and intra-ICU death as the outcome, was conducted. For each of 48 characteristics, a characteristic-by-time interaction was tested by likelihood ratio under four implementations of time-chronological quintiles, fixed calendar periods, linear and spline continuous time, each independently Benjamini–Hochberg corrected. Results: Twenty-two of 48 characteristics showed significant heterogeneity in the primary quintile analysis (q < 0.05), with 11 under all four. Adjustment for centre left 12 significant, 6 of which also survived adjustment for case mix. An adjusted model retained discrimination out of period but over-predicted risk in the final quintile. Conclusions: For nearly half of the characteristics, the crude association with intra-ICU death is not temporally stable, although most of the movement tracks a changing population. Out of period, a fixed model loses the level of predicted risk, not the weighting of its predictors-level rather than structural drift. Multi-year registry analyses should test temporal homogeneity rather than assume it.

Journal of Clinical Medicine doi: 10.3390/jcm15187014

Authors: Junfeng Tang Chenggang Wang Xianfa Yuan Qing Gao Yuchen Hu Yusheng Sun Xiaofeng Liu Wen Jin Liangye Sun

Objectives: To compare the clinical efficacy of the modified multi-strand Nice knot suture construct combined with suture anchor fixation versus conventional Kirschner wire tension band fixation for inferior patellar pole fractures. Methods: This retrospective chart review enrolled 108 consecutive patients with inferior patellar pole fractures treated surgically at our institution between January 2019 and January 2024. Patients were allocated to two groups based on the fixation method used: 52 patients underwent the modified suture construct fixation (modified suture fixation group, MSFG), and 56 received conventional Kirschner wire tension band fixation (conventional tension band fixation group, CTBFG). The primary outcomes included anterior knee pain VAS score, knee ROM, and complication rate; secondary outcomes comprised operative time, Bostman, Lysholm and Kujala scores, elective and symptomatic implant removal rates, time to fracture union, Insall–Salvati index, patellar length, and hospitalization costs. Results: All surgical procedures were completed uneventfully. Baseline demographic and clinical characteristics were comparable between groups (all p > 0.05), with a mean follow-up of 25.5 ± 6.0 months (range, 22–36 months). Operative time did not differ significantly between cohorts (p = 0.230). Although the MSFG exhibited statistically lower anterior knee pain VAS scores (0.82 ± 0.6 vs. 1.26 ± 0.8, p = 0.003) and slightly greater knee ROM (132.7° ± 9.8° vs. 128.8° ± 8.1°, p = 0.027), the magnitude of these differences was below the recognized minimal clinically important difference. At the final follow-up, Bostman, Lysholm and Kujala scores were similar between groups (all p > 0.05). Of critical importance, the MSFG had markedly lower rates of implant-related complications and any secondary surgery (both p < 0.001). In the CTBFG, 40 patients (71.4%) underwent secondary surgery: 10 for symptomatic hardware irritation and 30 as entirely elective asymptomatic removals. By contrast, no patient in the MSFG required any form of reoperation. No revision surgeries for fixation failure were required in either group. Radiographically, fracture union time and patellar length were comparable (all p > 0.05). While the Insall–Salvati index was statistically lower in the MSFG (0.96 ± 0.1 vs. 1.02 ± 0.1, p = 0.006), all values remained within the normal physiological range and no functional impairment was observed. Subgroup analysis of comminuted fractures with osteoporosis demonstrated that the MSFG eliminated the implant failure complications seen in the CTBFG (0% vs. 28.6%). Conclusions: The modified multi-strand Nice knot suture construct combined with suture anchor fixation provides functional outcomes equivalent to conventional Kirschner wire tension band fixation. However, it offers two distinct advantages: the complete absence of hardware-related complications and the elimination of the need for secondary implant removal. These findings suggest that the modified suture construct may offer particular advantages for patients with comminuted or osteoporotic inferior patellar pole fractures, although further prospective studies are warranted to confirm these observations.

Journal of Clinical Medicine doi: 10.3390/jcm15187012

Authors: Andreea Veronica Stavăr Cristina Octaviana Daia Brindușa Ilinca Mitoiu Madalina Codruta Verenca

Background/Objectives: Electrotherapy encompasses diverse therapeutic modalities used in Physical and Rehabilitation Medicine, but pediatric evidence varies substantially across modality–indication pairs. This structured narrative review mapped the available pediatric clinical evidence and provided a clinically structured synthesis of clinical applications, treatment parameters, reported therapeutic outcomes, safety, and evidence gaps in pediatric rehabilitation. Methods: PubMed, Scopus, and Web of Science were searched for publications from 1 January 2000 to 17 July 2026. Evidence was synthesized by electrotherapy modality and clinical indication and classified using Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence. Formal methodological quality and risk-of-bias appraisal using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) and Risk of Bias 2 (RoB 2) was performed for the evidence underpinning OCEBM Level 1 classifications; no formal GRADE certainty-of-evidence assessment was performed. Results: A comparatively more developed pediatric evidence base was identified for radial extracorporeal shock wave therapy (rESWT) in cerebral palsy-related spasticity; transcutaneous electrical nerve stimulation (TENS) and interferential current therapy (IFC) in bladder and bowel dysfunction; and neuromuscular electrical stimulation (NMES)/functional electrical stimulation (FES), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) for selected motor rehabilitation outcomes. Photobiomodulation (PBM)/low-level laser therapy (LLLT), pulsed electromagnetic field therapy (PEMF), and high-intensity laser therapy (HILT) showed promising but indication-specific evidence, whereas Transfer of Energy Capacitive and Resistive (TECAR) had preliminary adjunctive evidence. Therapeutic ultrasound and Deep Oscillation Therapy were supported by insufficient pediatric clinical evidence, while several modalities lacked eligible pediatric clinical studies. Short-term tolerability was generally favorable, but long-term safety data remain limited. Conclusions: Electrotherapy has an adjunctive role in selected pediatric rehabilitation indications, but prescription should be based on specific modality–indication pairs. The available evidence does not support comparative effectiveness conclusions between modalities. Standardized multicenter trials and long-term safety studies are required.

Journal of Clinical Medicine doi: 10.3390/jcm15187009

Authors: Tan Van Nguyen Le Thi Ho Linh Khanh Thi Vu Huy Quang Nguyen

Background/Objectives: Osteoporosis and coronary artery disease coronary artery disease (CAD) share common risk factors and biological pathways, yet their relationship in older adults with chronic coronary syndrome (CCS) remains incompletely understood. This study investigated the association between dual-energy X-ray absorptiometry (DXA)-defined osteoporosis and angiographic CAD burden in older adults with CCS. Methods: This two-center cross-sectional study included 451 consecutive adults aged ≥60 years with CCS who underwent DXA and invasive coronary angiography between July 2023 and June 2024. Osteoporosis was defined according to the World Health Organization criteria. CAD burden was assessed by disease extent (≥2-vessel or left main disease and ≥3-vessel or left main disease) and angiographic severity using the Gensini score. Multivariable logistic regression was performed after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, chronic kidney disease, and smoking history. Results: Osteoporosis was identified in 151 participants (33.5%). Compared with participants without osteoporosis, those with osteoporosis had significantly higher prevalences of ≥2-vessel or left main disease (79.5% vs. 55.7%, p < 0.001), ≥3-vessel or left main disease (66.9% vs. 33.3%, p < 0.001), and severe CAD (Gensini score > 54; 29.0% vs. 15.0%, p = 0.022). After multivariable adjustment, osteoporosis remained independently associated with ≥2-vessel or left main disease (adjusted odds ratio [OR] 3.97, 95% confidence interval [CI] 2.31–6.81), ≥3-vessel or left main disease (adjusted OR 5.07, 95% CI 3.06–8.41), and severe CAD (adjusted OR 3.08, 95% CI 1.50–6.36; all p ≤ 0.002). Conclusions: DXA-defined osteoporosis was independently associated with a substantially greater angiographic burden of coronary artery disease in older adults with CCS. These findings suggest that osteoporosis may serve as a marker of more advanced coronary atherosclerosis and support closer cardiovascular risk assessment in this high-risk population.

Journal of Clinical Medicine doi: 10.3390/jcm15187011

Authors: Abduljaleel Samad Omed Shihab Fedil Yalda Jodal Ahmed Azhin Raza

Background/Objectives: Severe posterior mandibular atrophy presents anatomical challenges for implant rehabilitation because of reduced residual bone volume and the close relationship between the mental foramen, its anatomical variations, and the surrounding alveolar bone. Among these variations, the anterior loop may further influence the available lingual bone adjacent to the mental foramen. Despite the clinical importance of this region, quantitative three-dimensional anatomical information regarding lingual bone availability remains limited. Therefore, the aim of this retrospective cone-beam computed tomography (CBCT)-based study was to quantitatively evaluate the availability of lingual bone adjacent to the mental foramen in posterior atrophied mandibles and to assess the influence of the anterior loop on these anatomical dimensions, thereby providing quantitative anatomical information about this region. Methods: In a retrospective CBCT-based anatomical study, 110 CBCT scans of adult patients with atrophied mandibles were analyzed using standardized cross-sectional views perpendicular to the dental arch; linear measurements were obtained from the lingual cortical plate to the mesial (Point A), middle (Point B), and distal (Point C) borders of the mental foramen. The presence of the anterior loop was recorded. Descriptive statistics and independent-samples t-tests were performed to compare measurements between loop and no-loop groups (α = 0.05). Results: The mean measurements of the lingual bone were 7.22 ± 1.65 mm at Point A, 6.18 ± 1.55 mm at Point B, and 4.82 ± 1.38 mm at Point C, showing a gradual decrease from mesial to distal. An anterior loop was found in 26.4% of the cases. Significantly thinner dimensions of the lingual bone were observed with an anterior loop at all three measurement points (p < 0.01). Conclusions: The present CBCT-based anatomical study measured the amount of lingual bone available adjacent to the mental foramen in posterior atrophied mandibles and observed a significant correlation between the presence of an anterior loop and reduced lingual bone dimensions. These findings add to the knowledge of the anatomy of this area and could serve as the basis for future clinical studies to investigate the potential for a mental foramen bypass concept.

Journal of Clinical Medicine doi: 10.3390/jcm15187010

Authors: Daniel K. Fahim Aimen Vanood Lee-Onn Chieng Andrew Ragheb Wissam El-Fallal

Background/Objectives: When performing a vertebrectomy in the thoracic spine for metastatic disease with a pathological fracture, traditionally, surgeons include two vertebral levels above and below in the instrumented fusion. We evaluated the safety and feasibility of an alternative method involving short-segment instrumentation after a posterior transpedicular thoracic vertebrectomy and reconstruction with pedicle screw fixation at only one level above and below. Methods: We retrospectively reviewed our series of thirty consecutive patients treated for non-junctional (T2 to T11), single-level thoracic spinal metastasis via vertebrectomy and reconstruction with posterior short-segment instrumented fusion. The primary outcome was a need for reoperation due to construct failure. The secondary outcomes included local tumor recurrence, neurological function, pain scores, operative time, estimated blood loss, post-operative wound complications, and length of stay. Results: All patients had a minimum Bilsky Grade of 2 and a minimum SINS (Spinal Instability Neoplastic Score) of 10. Two patients suffered perioperative complications, but there was no construct failure or need for revision surgery at any time during the follow-up period. No patients experienced worsening neurological function, and an overall improvement in pain was seen postoperatively (7.67 versus 2.77; p < 0.001; 95% CI: 4.28–5.52). The mean intraoperative blood loss was 605 mL (range, 50–1200 mL; SD, 314.7 mL), and the mean operative time was 260.73 min (range, 169 to 442 min; SD, 64.4 min). The average length of stay was six days. The median length of the follow-up was 24 months (range, 1–65 months; IQR, 12–42 months). Three patients in this cohort had local tumor recurrence (two of these patients suffered from a radioresistant tumor pathology). Conclusions: Our results support the safety and feasibility of this less invasive technique in the management of patients suffering from metastatic disease requiring single-level vertebrectomy and reconstruction in the non-junctional thoracic spine.

Journal of Clinical Medicine doi: 10.3390/jcm15187003

Authors: Corina Porr Valentin-Cristian Iovin Anca Vidrighin Emi M. Preda Gabriela Mariana Iancu Dana M. Harris Cosmina Diaconu

Background: Interleukin-17 (IL-17) contributes to persistent airway inflammation, neutrophil recruitment, and inflammatory pathways extending beyond classical type 2 immunity. However, the distribution of circulating IL-17 across clinically distinct upper- and lower-airway disease phenotypes remains incompletely characterized. This study compared serum IL-17 concentrations in allergic rhinitis, non-allergic asthma, allergic asthma associated with allergic rhinitis, and healthy controls. Methods: This retrospective single-center observational study included 88 adults: allergic rhinitis (n = 31), non-allergic asthma (n = 15), allergic asthma associated with allergic rhinitis (n = 22), and healthy controls (n = 20). Serum IL-17 concentrations were measured using a quantitative sandwich enzyme-linked immunosorbent assay. Overall group differences were assessed using the Kruskal–Wallis test, followed by Holm-adjusted pairwise Mann–Whitney U tests. Results: Serum IL-17 concentrations differed significantly across the four groups (Kruskal–Wallis H = 12.981, p = 0.0047). Median IL-17 concentrations were 126.21 pg/mL in non-allergic asthma, 50.97 pg/mL in allergic rhinitis, 54.72 pg/mL in allergic asthma associated with allergic rhinitis, and 0.00 pg/mL in healthy controls. Each disease group had significantly higher IL-17 than controls after Holm correction (adjusted p = 0.0103, 0.0172, and 0.0196, respectively), whereas the three disease phenotypes did not differ significantly from one another. Conclusions: Circulating IL-17 concentrations were higher in allergic rhinitis, non-allergic asthma, and allergic asthma associated with allergic rhinitis than in healthy controls. However, the substantial overlap among disease phenotypes and the absence of statistically significant between-phenotype differences should not be interpreted as evidence of equivalence or a shared biological mechanism. These findings should be considered exploratory and require confirmation in larger, prospectively characterized cohorts.

Journal of Clinical Medicine doi: 10.3390/jcm15187005

Authors: Joanna Wojciula Marcin Bartoszewicz Magdalena Wojciula Piotr Sienkiewicz Grzegorz Szewczyk Piotr Fiedor

Background/Objectives: Persistent infection with high-risk HPV genotypes accounts for the development of a substantial portion of anogenital and oropharyngeal malignancies. Patients with primary and secondary immunodeficiency or those receiving immunosuppressive therapy, including transplant recipients and patients affected by rare diseases, are vulnerable to particularly severe clinical manifestations of infection. While HPV vaccination constitutes primary prevention, patients with HPV-associated disease remain at risk of reinfection or subsequent infection with alternative genotypes following surgical treatment and may benefit from peri-operative vaccination regimens. This study aimed to evaluate long-term outcomes of HPV vaccination following surgical management of condyloma acuminata in patients with concurrent high-risk genotype infection. Methods: 350 patients with condyloma acuminata and HPV-16 or -18 co-infection confirmed by histopathological examination and PCR genotyping (oral cavity, vulva, vagina, penis, anoderma), including a subgroup with primary or acquired immunodeficiency or chronic immunosuppressive regimens, underwent surgical treatment, receiving simultaneous immunization with the first dose (subsequent completion of full regimen over 12 months) of the bivalent Cervarix vaccine (170 patients) or the quadrivalent Gardasil vaccine (180 patients). A follow-up examination, including HPV genotyping (16/18/31/35), was performed after 6 and 12 months following regimen completion. After 36 months, a standard clinical examination was performed, and in doubtful cases, supplemented with genotyping and biopsy/cytology. Observation was continued in subsequent years (5, 10, and >15 years). Results: Condyloma acuminata requiring removal were observed in 5% of the patients in follow-up at 36 months, with no significant statistical difference between vaccine groups. No cellular atypia or malignant transformation in the form of squamous cell carcinoma was observed. Genotyping did not detect HPV-16/18/31/35 infection in the follow-up examinations. Conclusions: In this uncontrolled, single-arm cohort, peri-operative initiation of either the bivalent or quadrivalent HPV vaccine was associated with a low rate of clinically apparent condyloma acuminata recurrence and no detectable HPV-16/18/31/35 infection during follow-up.

Journal of Clinical Medicine doi: 10.3390/jcm15187008

Authors: Robert Jan Łuczyk Dorota Weber Agata Wiśnios Marta Łuczyk Kamil Sikora Anna Charuta

Background/Objectives: A cancer diagnosis forces a rapid, often unwelcome reorganization of a patient’s sense of self, routines, and future plans, and patients vary considerably in how far they progress toward accepting that new reality. Personality is a candidate explanation for this variability, and although the Five-Factor Model has been linked to cancer-related distress and coping in several large cohorts, its relationship to illness acceptance specifically, alongside disease duration, treatment self-assessment, and perceived social support, has not been jointly examined in a single, diagnostically broad oncology sample. Methods: We surveyed 114 outpatients with a confirmed malignant tumor diagnosis, combining a study-specific questionnaire with the NEO-Five-Factor Inventory (NEO-FFI) and the Acceptance of Illness Scale (AIS). Because several study variables were non-normally distributed and the study-specific measures were ordinal, associations were examined using Spearman’s correlation, the Kruskal–Wallis H test, and the Mann–Whitney U test. Results: Illness acceptance was moderate on average (mean [M] = 26.55, standard deviation [SD] = 7.34); 22 patients (19.30%) were classified as having low acceptance, 76 (66.67%) as average acceptance, and 16 (14.04%) as high acceptance. All five personality domains correlated with acceptance, led by a strong negative association with neuroticism (ρ = −0.632, p < 0.001) and moderate positive associations with extraversion, agreeableness, conscientiousness, and openness to experience (all p < 0.001). Longer disease duration and a more favorable self-rated treatment outcome were both associated with higher acceptance, and patients who felt supported by close relatives scored higher than those who found support difficult to gauge. Conclusions: Personality traits, particularly neuroticism, were associated with illness acceptance. Brief psychosocial assessment may help identify patients reporting greater difficulties in psychological adjustment to cancer.

Journal of Clinical Medicine doi: 10.3390/jcm15187007

Authors: Eleonora Acquisti Rodolfo Pini Enrico Gallitto Mohammad Abualhin Alessia Sonetto Marcello Lodato Stefania Caputo Antonio Cappiello Marco Mattiacci Gianluca Faggioli Mauro Gargiulo

Background: Aorto-iliac Trans-Atlantic Inter-Society Consensus II (TASC II) C and D lesions with involvement of the aortic bifurcation are complex, and their endovascular treatment with kissing stenting can be technically demanding. The aim of this study is to analyze the outcomes, risk factors and follow-up of aorto-iliac revascularization through kissing stenting. Methods: A single-center, retrospective, observational study was performed including patients treated with aorto-iliac kissing stenting from 2016 to 2025 for TASC II C and D lesions. Pre-/peri- and post-operative data were prospectively collected and retrospectively analyzed. Aorto-iliac calcification consisted of calcific lesions involving more than 70% of the aortic circumference. Technical and clinical success, primary patency and reintervention rate were analyzed. Results: Overall, 123 patients were included, 48 (39%) female; mean age was 68 ± 7 years. Sixty-nine patients (56%) had critical limb-threatening ischemia, 46 (37%) diabetes mellitus, 5 (4%) end-stage chronic kidney disease in hemodialysis and 68 (55%) aortic calcification. Femoral accesses were percutaneous in 18 (15%) and surgical in 105 (85%) cases; additional brachial access was used in 49 (40%) patients. Simultaneous femoral endarterectomy was performed in 48 (39%) cases. Stentgrafts and bare metal stents were used in 32 (26%) and 91 (74%) cases, respectively. Technical success was 100%. Primary patency at 1, 3 and 5 years was 100%, 98 ± 3% and 94 ± 5%, respectively. At a mean follow up of 39 months, 6 (5%) stent thromboses occurred. Freedom from reintervention at 1, 3 and 5 years was 99%, 93% and 81%, respectively. Calcification was associated with a higher 3-year reintervention rate: 13% vs. 0%, p = 0.037. Brachial access, additional femoral endarterectomy and use of covered stents did not affect the reintervention rate. Conclusions: Kissing stent is an effective and safe technique to provide revascularization in aorto-iliac TASC C-D lesions with involvement of the aortic bifurcation, with good outcomes in terms of technical, clinical success and primary patency. It often needs an upper limb access and/or adjunctive procedures such as femoral endarterectomy. Presence of severe calcification is associated with a higher reintervention rate.

Journal of Clinical Medicine doi: 10.3390/jcm15187006

Authors: Luigi Cianni Sara Martellini Raffaele Vitiello Alessandro El Motassime Giulio Maccauro Maristella Francesca Saccomanno

Background: Reconstruction with megaprostheses is an important limb-salvage option in cases of bone tumors and metastases, as it allows extensive bone resection while preserving the limb. However, postoperative shoulder instability remains a frequent complication. Although implant instability is one of the leading causes of treatment failure, the factors contributing to it are still not clearly defined. This study analyzes the correlation between resection length, implant type, and involvement of the deltoid and rotator cuff in relation to postoperative instability and the risk of postoperative dislocation. Methods: Twenty-five patients treated at our institution between 2014 and 2025 who underwent proximal humerus replacement with a megaprosthesis were included. Patients were divided into two groups: those with postoperative dislocation (Group A) and those without (Group B). Functional outcomes were assessed using the MSTS and DASH scores. The mean follow-up was 20.38 ± 11.87 months. Results: Of the twenty-five patients included, six (24%) experienced instability and subsequent dislocation (Group A). Rotator cuff invasion was present in 100% of Group A and 36.8% of Group B (p < 0.001), while deltoid invasion was present in 83.3% of Group A and 21% of Group B (p = 0.001). The mean resection length was 14.4 ± 2.2 cm in Group A and 13.7 ± 3.7 cm in Group B (p = 0.636). No significant differences were found between the groups in DASH and MSTS scores. Conclusions: In this cohort, rotator cuff and deltoid involvement were significantly associated with postoperative shoulder instability following proximal humerus megaprosthetic reconstruction. These findings suggest that careful preoperative assessment of rotator cuff and deltoid involvement may help identify patients at higher risk of postoperative instability and optimize surgical planning. Future studies should focus on preoperative planning and the development of a risk score to identify patients at higher risk of instability, potentially allowing for additional procedures such as latissimus dorsi flap reconstruction.

Journal of Clinical Medicine doi: 10.3390/jcm15187004

Authors: Marisa Rosso Carlos Alcaide Miguel Muñoz

Although advances in pediatric oncology have resulted in cure rates exceeding 80% among children with cancer, progress in survival outcomes has begun to plateau in recent years. Mortality in this population remains largely associated with aggressive disease features, particularly tumor resistance to chemotherapy and metastatic spread. At the same time, the growing population of childhood cancer survivors has drawn increasing attention to the persistent and potentially serious late effects associated with conventional chemotherapy. Thus, it is crucial to discover drugs with specific antitumor action, effective and safe drugs that, combined with chemotherapy or radiotherapy, could chemosensitize or radiosensitize the tumor and reduce the severe side effects of both. Substance P (SP) peptide and its Neurokinin-1 receptor (NK-1R) are known to be involved in pediatric cancer, promotion and progression. Pediatric cancer overexpresses SP/NK-1R and NK-1R is essential for viability of cancer cells and is not essential for normal non-tumor cells. SP induces mitogenesis, exerts anti-apoptotic effects, and promotes angiogenesis, invasion and migration for metastasis in cancer cells and produces inflammation. Conversely, NK-1R antagonists, such as aprepitant and similar drugs, inhibit mitogenesis and induce apoptosis in pediatric cancer cells in a concentration-dependent manner. They also inhibit angiogenesis, invasion, and migration in pediatric cancer cells and have an anti-inflammatory effect. Moreover, aprepitant in combination with chemotherapy or radiotherapy can produce chemosensitization or radiosensitisation and decreases the severe side effects of both. This review updates the role of the SP/NK-1R axis in pediatric cancers and analyzes its potential as a therapeutic target. It highlights NK-1R antagonists, particularly aprepitant, and their potential as drugs for the treatment of pediatric cancer.

Journal of Clinical Medicine doi: 10.3390/jcm15187002

Authors: Emilia Cotter Maria Araujo Alyssa Juma Jijia Wang Tiffany Graham

Background/Objectives: Previous studies regarding the efficacy of cranial remolding orthoses (CROs) have shown that earlier treatment initiation is associated with more favorable outcomes, but there are few studies utilizing 3D-printed CROs. This study evaluated the impact of treatment initiation age on the success of 3D-printed CROs in terms of morphological measurement changes and caregiver satisfaction. Methods: A total of 1054 infants who initiated treatment with a 3D-printed CRO during 2023 across six pediatric clinics in Canada were included in this retrospective cohort study. Participants were stratified by treatment initiation age (<6 months, 6–9 months, and 9–12 months) and deformational head shape: deformational plagiocephaly (DP), deformational brachycephaly (DB), or deformational asymmetric brachycephaly (DAB). Results: Relevant pre-treatment measurements for DP were CVAI = 7.98 ± 2.30, for DB were CR = 97 ± 4%, and DAB were CVAI = 7.22 ± 2.21 and CR = 95 ± 3%. All head shapes improved during treatment and overall caregiver satisfaction was high (94.4%). A total of 66.89% of participants achieved full correction of their cranial deformation (CR ≤ 90% and CVAI < 3.5), with the highest correction observed among the youngest infants for each head shape type. Cranial correction rates were highest for DP (76.85%), followed by DAB (57.73%) and DB (54.68%). The mean correction rate varied greatly between treatment initiation age and deformation type subgroups (21.74% to 82.73%). Conclusions: Treatment with 3D-printed CROs resulted in measurement improvement across all participants and caregiver satisfaction remained high. Earlier treatment initiation was associated with significantly better correction rates, supporting early referral and intervention whenever possible. These findings provide evidence to inform clinical recommendations and support caregivers in making decisions regarding treatment for cranial deformation and appear akin to the findings of studies utilizing traditionally fabricated CROs.

Journal of Clinical Medicine doi: 10.3390/jcm15187001

Authors: Monika Burzyńska Małgorzata Pikala

Background: The aim of this study was to assess long-term trends in mortality due to digestive diseases among older adults in Poland. Methods: Mortality data for the years 2000–2022 were analyzed for individuals aged ≥65 years. Age-standardized death rates (SDRs) were calculated. Particular attention was paid to liver cirrhosis-related mortality, operationalized according to the tenth revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) joined categories K70 and K74. Temporal trends were assessed using joinpoint regression to estimate annual percentage change (APC) and average annual percentage change (AAPC) stratified by sex and age groups (65–74 and ≥75 years). The total number of deaths included in the statistical analysis was 6,645,408. Results: In early old age (65–74 years), the proportion of deaths due to digestive diseases increased in both men (from 3.6% to 5.0%) and women (from 4.1% to 4.5%), while a decrease was observed in late old age (≥75 years). The combined K70/K74-coded liver disease category represented an important component of digestive disease mortality. Among women aged 65–74 years, a significant upward trend in SDR was observed after 2015 (APC 3.5%, p < 0.05), with an increase from 54.7 to 70.8. In men of the same age, SDR remained relatively stable overall (160.5 to 171.6), although mortality due to liver-related diseases increased significantly after 2015 (APC 6.7%, p < 0.05). In older age groups, declining trends were observed until the late 2010s, followed by recent non-significant increases. Conclusions: Mortality patterns for alcohol-related liver disease and hepatic fibrosis/cirrhosis showed particularly unfavorable recent trends in adults aged 65–74 years. These findings highlight the need for continued surveillance and prevention of chronic liver disease in ageing populations.

Journal of Clinical Medicine doi: 10.3390/jcm15187000

Authors: Erin Jadallah Natalie McConaghy Min-Jeong Cho Albert Chao

Breast reconstruction after mastectomy or breast-conserving surgery requires careful planning that accounts for patient preference, comorbidities, tumor characteristics, and anticipated neoadjuvant or adjuvant therapies. Advances in the treatment of breast cancer have led to evolving recommendations for these therapies, with each influencing not just the complications from surgery but also the long-term outcomes. This narrative review summarizes the current indications for these therapies and their potential impacts on breast reconstruction. Contemporary recommendations for postmastectomy radiation therapy, chemotherapy, immunotherapy, endocrine therapy, and other targeted therapies are explored, with an emphasis placed on perioperative management of systemic therapies and how they may influence reconstructive decision-making. Understanding the nuances of these therapies enables plastic surgeons to be strategic in the timing of reconstruction through individualized planning and can improve reconstructive success. As breast cancer treatment evolves, familiarity with oncologic management is essential for achieving safe, patient-centered care.

Journal of Clinical Medicine doi: 10.3390/jcm15186999

Authors: Oswaldo Antonio Caguana-Vélez Diana Badenes-Bonet Xavier Duran Flavio Zuccarino Didac Ramal Santiago Carbullanca Judit Villar-García Diego A. Rodríguez-Chiaradía Eva Balcells

Background: Organising pneumonia secondary to COVID-19 (OP-COVID-19) is a recognised inflammatory complication of SARS-CoV-2 infection. We assessed the 2-year clinical, radiological, and functional evolution of patients hospitalised with OP-COVID-19 and identified factors independently associated with long-term fibrotic-like lesions. Methods: This ambispective longitudinal study included adults consecutively hospitalised with OP-COVID-19 from March 2020 to February 2021. Diagnosis was based on clinical assessment and high-resolution computed tomography (HRCT). Patients underwent standardised follow-up at 3, 6, 12, and 24 months after hospital discharge, including clinical assessment, chest HRCT, pulmonary function tests, and the six-minute walk test. Longitudinal radiological changes were assessed using paired comparisons, and exploratory multivariable logistic regression identified factors independently associated with long-term fibrotic-like lesions. Results: OP-COVID-19 was diagnosed in 271 patients (4.9%), and 228 were included in the follow-up cohort. Inflammatory HRCT abnormalities resolved progressively, with paired comparisons showing a significant reduction in consolidations, peribronchovascular opacities, crazy-paving pattern, reversed halo sign, and perilobular opacities at 3–6 months compared with the initial HRCT (p < 0.05 for all). Among the 221 patients with an ascertainable final radiological outcome, persistent pulmonary abnormalities were observed in 14.9%, including fibrotic-like lesions in 10.4%. No statistically detectable late radiological progression was observed among patients undergoing extended imaging follow-up. The need for respiratory support during the acute phase (odds ratio [OR] 5.79, 95% confidence interval [CI] 1.81–18.52), bronchial dilatation (OR 3.50, 95% CI 1.10–11.11), and architectural distortion and/or volume loss on initial HRCT (OR 4.72, 95% CI 1.80–12.35) were independently associated with long-term fibrotic-like abnormalities. Pulmonary function was largely preserved, with mildly reduced diffusing capacity for carbon monoxide (DLCO) in the assessed subsets. Conclusions: OP-COVID-19 has a favourable long-term prognosis, with progressive resolution of inflammatory abnormalities in most patients. Fibrotic-like lesions occur in a minority of patients and are associated with greater initial disease severity and early structural abnormalities on HRCT. These findings support risk-stratified follow-up for patients with OP-COVID-19.

Journal of Clinical Medicine doi: 10.3390/jcm15186997

Authors: Alexandru Orasan Nicolae Constantin Balica Adrian Mihail Sitaru Mihaela Cristina Negru Anda Ioana Morgovan Kristine Guran Andreea Mihaela Banta Sebastian Ciurescu Mihaela-Iuliana Sirbu Eugen Horatiu Stefanescu

Background/Objectives: Management of locally advanced cervical cancer (LACC) and other gynecological malignancies aims to achieve locoregional control while avoiding morbid surgical salvage. This exploratory, hypothesis-generating study described the treatment pathways of three protocol groups and examined whether clinical, sociodemographic, and treatment-deviation variables are associated with any oncological surgery. Methods: Sixty-nine adult patients with gynecological or urogenital cancers (89.9% cervical carcinoma) treated with platinum-based chemotherapy at a Romanian tertiary center between April 2024 and April 2025 were stratified into INTERLACE-type dose-dense induction chemotherapy followed by chemoradiotherapy (Group A, n = 27), classic three-weekly neoadjuvant chemotherapy followed by chemoradiotherapy (Group B, n = 7), and no induction chemotherapy (Group C, n = 35). Associations with any oncological surgery (upfront, completion, or salvage) were explored by multivariable logistic regression with bootstrap internal validation, Firth penalized regression, and restricted sensitivity analyses. Results: Twenty-five patients (36.2%) underwent surgery (14 upfront, 8 completion, 3 salvage), and none of them were from Group A, whose median follow-up was only 8.6 months and whose allocation was confounded by diagnosis and stage. The model showed an apparent area under the curve of 0.717 (optimism-corrected 0.672), accuracy of 73.9% against a no-information rate of 63.8% (p = 0.049), sensitivity of 0.480, and specificity of 0.886. Urban provenience (OR 0.343, 95% CI 0.113–1.039, p = 0.059), Delta Target Dose (OR 1.109 per Gy, p = 0.076), and number of chemotherapy cycles (OR 1.298 per cycle, p = 0.076) showed non-significant trends whose direction was unchanged in all sensitivity analyses. Conclusions: The absence of surgery after induction chemotherapy is hypothesis-generating rather than confirmatory, and the exploratory model is not a clinical prediction tool. Geographic provenience and planning-to-delivery treatment deviation are candidate variables for prospective evaluation in a homogeneous LACC population with standardized radiotherapy parameters and mature oncological endpoints.

Journal of Clinical Medicine doi: 10.3390/jcm15186996

Authors: Osman Anil Savaş Hasan Açik Taner Kivilcim Amir Mahdi Akbari Mehrdad Sheikhvatan

Background: The discovery of non-invasive biomarkers that can predict the therapeutic response in Inflammatory Bowel Disease (IBD) is of utmost importance in the field of personalized medicine. The present prospective cohort study was designed to investigate the use of circulating levels of plasma microRNA-145 (miR-145) and microRNA-191 (miR-191) in the diagnosis and association with therapeutic response in Crohn’s disease (CD) and ulcerative colitis (UC). Methods: The present study was conducted as a retrospective observational cohort study on 183 adult IBD patients, consisting of 96 CD patients and 87 UC patients. Patient data and study parameters were obtained retrospectively from existing clinical records and available laboratory/molecular data collected during routine clinical care. A healthy control group consisting of 92 individuals was included for comparison with the patients with IBD. The circulating levels of miR-145 and miR-191 were assessed in the peripheral blood plasma at baseline using qRT PCR. The clinical response was evaluated at 12 weeks using the CDAI score for CD and the Mayo score for UC. Results: In active IBD, there was significant down-regulation of miR-145 and significant up-regulation of miR-191. Responders at 12 weeks had significantly higher levels of baseline miR-145 (2.0-fold, p < 0.001) and lower levels of miR-191 (1.8-fold, p < 0.001) compared with non-responders. Also, miR-145 negatively correlated with disease activity, and miR-191 positively correlated with acute inflammation markers. ROC curve analysis showed good discriminative values for both miR-145 and miR-191. Conclusions: The level of circulating miR-145 and miR-191 correlates with the activity of IBD. Importantly, the baseline level of miR-145 expression is a non-invasive potential biomarker associated with therapeutic response at 12 weeks.

Journal of Clinical Medicine doi: 10.3390/jcm15186998

Authors: Xuexue Wu Xiaoyuan Li Mengqian Li Zuoyu Liang Ping Zhou Chan Yang Lingping Xie Lili Jiang

Background: The relationship between acute fibrinous and organizing pneumonia (AFOP) and organizing pneumonia (OP) remains debated, and direct comparative evidence is limited. We aimed to delineate their differences across clinical, radiological, histological, and immunophenotypic dimensions. Methods: We conducted a retrospective study of 85 consecutive patients with pathologically confirmed AFOP (n = 49) or OP (n = 36). Clinical data, radiological patterns, laboratory findings, and immunohistochemical profiles of alveolar epithelial, macrophage, lymphocyte, vascular, and mesenchymal markers were comprehensively compared. Results: The two groups were comparable in demographics, clinical symptoms, and dominant radiological patterns. However, median C-reactive protein (CRP; 80.45 vs. 12.65 mg/L, p < 0.001) and neutrophil-to-lymphocyte ratio (NLR; 4.56 vs. 2.42, p = 0.013) were higher in AFOP, with CRP demonstrating an apparent area under the curve (AUC) of 0.798 for discriminating AFOP from OP in this derivation cohort. After Benjamini–Hochberg correction for multiple comparisons, CD68 was significantly higher, and CD38 was significantly lower in AFOP than in OP. Trends were also observed for CD163, surfactant protein A (SP-A), and CD34, but these did not remain statistically significant after correction. All three deaths and all cases requiring mechanical ventilation occurred in the AFOP group, though these differences were not statistically significant. Conclusions: Despite clinical and radiological overlap, AFOP and OP exhibit distinct systemic inflammatory responses and pulmonary immunophenotypes, with AFOP characterized by macrophage-predominant inflammation and qualitatively fewer CD34+ microvessels within fibrin balls. These immunophenotypic findings are descriptive and require further validation.

Journal of Clinical Medicine doi: 10.3390/jcm15186995

Authors: Ercan Yılmaz Nezihe Koker Ozer Hatice Turgut Erdem Topal Ramazan Özdemir Recep Gunakın Mehmet Aslan

Background: Children born preterm may have persistent alterations in airway function that extend into school age; however, exercise-induced bronchoconstriction (EIB) in this population remains insufficiently characterized. This study aimed to determine the prevalence of EIB in school-aged children born at ≤32 weeks of gestation and to investigate associated clinical and neonatal factors. Methods: This single-center cross-sectional study included 42 children born at ≤32 weeks of gestation who were evaluated at 7–8 years of age. Perinatal, neonatal, respiratory, and atopic characteristics were obtained from medical records and parental reports. Baseline spirometry was performed before a standardized treadmill exercise challenge. Spirometry was repeated at 5, 10, 15, and 30 min after exercise. EIB was defined as a ≥10% decrease in forced expiratory volume in one second (FEV1) from baseline at any post-exercise time point. Results: The median gestational age was 29 (25–32) weeks, and 31% had a history of bronchopulmonary dysplasia. EIB was identified in 13 of 42 children (31%). Post-exercise EIB positivity was observed at 5, 10, 15, and 30 min in 9.5%, 16.7%, 11.9%, and 9.5% of participants, respectively. Dyspnea was the most frequent exercise-related symptom (38%). No significant differences were observed between EIB-positive and EIB-negative children regarding gestational age, birth weight, bronchopulmonary dysplasia, neonatal respiratory support, baseline pulmonary function, total IgE, or peripheral eosinophil count. Conclusions: EIB was detected in approximately one-third of school-aged children born at ≤32 weeks of gestation. These findings suggest that clinically relevant exercise-related airway hyperresponsiveness may persist into school age despite relatively preserved baseline spirometry.

Journal of Clinical Medicine doi: 10.3390/jcm15186994

Authors: Andrej Belančić Ivana Mudnić

Marketing authorisation is a regulatory conclusion that, on the basis of the available evidence, the medicine has a favourable benefit–risk balance for a defined population and indication [...]

Journal of Clinical Medicine doi: 10.3390/jcm15186992

Authors: Karam Addas Ameen Aldabbagh Jana Balloura Ahmad Al Raiy Rian M. Balafkhar Lama S. Othman Kadi Aldowairej Osama Abdullah Al-Amoudi Meshari M. Alotaibi Fahad Mohammed Aldehaim Hammam Sibyani Bassam M. Alshahrani Abdulrahman Alnwiji Yasir Jasim Ayman M. A. Mohamed

Purpose: This study aimed to evaluate the effects of active transcranial direct current stimulation (tDCS) compared with sham stimulation on circulating brain-derived neurotrophic factor (BDNF), pain-related outcomes, working memory, and inflammatory and neuroplasticity biomarkers. Methods: PubMed/MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov were searched from inception to May 2026. Randomized and controlled clinical trials comparing active with sham tDCS in adults were included. The primary outcome was post-treatment BDNF concentration. Secondary outcomes included pain intensity, pain catastrophizing, pain-related disability and functional interference, working memory, and circulating inflammatory or neuroplasticity biomarkers. Risk of bias was assessed using the revised Cochrane risk-of-bias tool. Mean differences (MDs) with 95% confidence intervals (CIs) were pooled using random-effects models. Serum and plasma BDNF were analyzed separately. Results: Twenty-one studies were included in the systematic review, of which 15 contributed to at least one quantitative synthesis and 12 study comparisons contributed to the primary BDNF analyses. Active tDCS did not significantly affect serum BDNF (MD = −0.01 [−0.15, 0.13], p = 0.890) or plasma BDNF (MD = 0.02 [−0.25, 0.29], p = 0.870) compared with sham stimulation. In contrast, active tDCS was associated with lower pain intensity (MD = −1.79 [−2.34, −1.23], p < 0.00001). No statistically significant difference was observed in the PCS total score or in the helplessness, magnification, or rumination subscales, although the point estimates generally favored active tDCS. For pain-related disability and functional interference, active tDCS was associated with lower PCP:S total scores and lower emotional interference, whereas no significant differences were observed for interference with daily activities or pain frequency. No significant differences were observed for working memory, interleukins, tumor necrosis factor-alpha, glial cell line-derived neurotrophic factor, interleukin-18, or soluble tumor necrosis factor receptors. Substantial heterogeneity was present in several pain-related and inflammatory biomarker analyses. Conclusions: Active tDCS was not associated with consistent differences in circulating serum or plasma BDNF or in the assessed peripheral inflammatory and neuroplasticity biomarkers compared with sham stimulation; however, these null peripheral findings should not be interpreted as evidence of absent central neuroplastic effects, because circulating measures may not adequately capture localized or transient biological changes within the central nervous system. Active tDCS was associated with improvements in some pain-related outcomes; however, the limited number of studies, substantial heterogeneity, and low certainty of the available evidence preclude firm conclusions regarding its clinical effectiveness for pain management.

Journal of Clinical Medicine doi: 10.3390/jcm15186993

Authors: Mara Carsote Claudiu Nistor Ana-Maria Gheorghe

Endocrine care in the modern medical and surgical era is characterized in many societies by easy access to screening protocols (e [...]