Journal of Clinical Medicine doi: 10.3390/jcm15134970

Authors: Magdalena Hagner-Derengowska Bartłomiej Kacprzak Anna Michalska Agnieszka Połaniecek Carla Gonçalves Robert Trybulski

Objective: To determine whether contrast therapy improves recovery after climbing-specific forearm fatigue in amateur climbers. Methods: In a randomized repeated-measures trial, 40 climbers were allocated to passive recovery (n = 20) or Game Ready contrast therapy (n = 20). Both groups completed a fixed-task intermittent fingerboard protocol on a 20 mm edge using a half-crimp grip, with 7 s of work and 3 s of rest for five sets; the load was not individualized to climbing-specific maximal finger-flexor force. The intervention group received bilateral forearm treatment consisting of alternating 1 min cold (3 °C) and heat (45 °C) phases combined with pneumatic compression ranging from 15 to 75 mmHg. Sessions lasted 20 min and were administered immediately after post-fatigue testing, at 24 h and 48 h, and then three times weekly on alternate days for 8 weeks, for a total of 27 sessions. Outcomes were assessed at baseline, immediately after fatigue, at 24 h and 48 h, and after 8 weeks. Outcomes included perfusion, reactive hyperemia, stiffness, pressure pain threshold, grip strength, perceived recovery, creatine kinase, and interleukin-6. Results: Immediate post-fatigue responses were comparable. Contrast therapy produced greater 24 h and 48 h resting perfusion responses (+7.28 percentage points, 95% CI 6.58 to 7.98; +7.62, 95% CI 6.94 to 8.31; both adjusted p < 0.001). At week 8, peak hyperemic perfusion improved more with contrast therapy (+6.21 PU, 95% CI 5.62 to 6.79; p < 0.001). Recovery favored contrast therapy for stiffness at 48 h (−71.7 N/m, 95% CI −75.6 to −67.8), pressure pain threshold at week 8 (+8.1 N/cm2, 95% CI 7.3 to 8.8), and grip strength at 48 h (+7.8 kgf, 95% CI 7.3 to 8.3; all p < 0.001). CK and IL-6 differences were transient, and no serious adverse events or intervention-related discontinuations were recorded. Conclusions: Contrast therapy was associated with more favorable cutaneous perfusion, post-occlusive reactive hyperemia-derived, and neuromechanical recovery outcomes, whereas biochemical differences were limited and time-dependent. The vascular findings do not establish improved endothelial function or nitric-oxide-mediated vasodilation because these mechanisms were not directly assessed. Trial registration: ISRCTN49499065 on 23 June 2025.

Journal of Clinical Medicine doi: 10.3390/jcm15134969

Authors: Anton Bermont Daniel L. Cohen Daniela Malkin Ariel Ben Shimol Shay Matalon Haim Shirin Sergei Vosko

Background and Aims: Bleeding and post-procedural pain are common adverse events after endoscopic mucosal resection (EMR) of large colorectal lesions. Epinephrine is frequently added to submucosal injectates, although its benefit for delayed bleeding is inconsistent and associated with post-procedural pain. Tranexamic acid (TXA), an antifibrinolytic agent used to prevent bleeding in several medical conditions, has not been evaluated during colorectal EMR. We compared TXA with epinephrine for bleeding outcomes, safety, and post-procedural pain. Methods: In this prospective, double-blind, randomized controlled pilot trial, adults undergoing EMR for colorectal lesions ≥20 mm were randomized 1:1 to receive a TXA-containing or epinephrine-containing submucosal injectate. Primary outcomes were intraprocedural bleeding severity and delayed bleeding. Secondary outcomes included post-procedural pain, post-polypectomy syndrome, and thromboembolic events. Results: The study included 121 patients (TXA, n = 60; epinephrine, n = 61). Intraprocedural bleeding rates and severity were similar between groups, and hemostasis was achieved endoscopically in all cases. Delayed bleeding occurred in 8.3% of patients in the TXA group and 11.5% in the epinephrine group (p = 0.762); clinically significant delayed bleeding occurred in 6.7% and 6.6%, respectively. Lesion size was the only independent predictor of delayed bleeding. Post-procedural pain was significantly less frequent with TXA (5.0% vs. 39.3%; p < 0.001), and no TXA-treated patients required opioid analgesia compared with 18% in the epinephrine group (p < 0.001). No major adverse events were observed in the TXA group. Conclusions: In this pilot study, TXA achieved bleeding outcomes comparable to epinephrine while significantly reducing post-procedural pain in large colorectal EMR procedures, warranting further evaluation in larger trials.

Journal of Clinical Medicine doi: 10.3390/jcm15134968

Authors: Syed Ilyas Munzir Daniel Hier Michael D. Carrithers

Background/Objectives: Our prior epigenome-wide association study (EWAS) on multiple sclerosis (MS) identified myeloid-associated methylation signatures and an association with enhancer regions. Here we compared differential DNA methylation across three central nervous system inflammatory disorders: MS, neuromyelitis optica (NMO), and neurologic post-acute sequelae of COVID-19 (neuro-PASC). Methods: Whole-blood DNA was profiled on Infinium MethylationEPIC arrays. Analyses included EWAS at the CpG level, differentially methylation region (DMR) analysis, and gene regulatory-element enrichment using Locus Overlap Analysis (LOLA). Limma linear models were adjusted for race, EPIC array version, age, sex, disease-modifying treatment class, and blood cell composition. Results: All three diseases were associated with broad CpG-level differential methylation. The most robust findings were disease-specific DMR signatures in gene regulatory regions. All three diseases shared Lamin B1-anchored chromatin states as an architectural genomic feature but differed in immune regulatory transcription factor binding sites (TFBS), RNA polymerase (Pol II) occupancy, and DNase accessibility. MS was enriched for TFBS in myeloid CEBPB and SPI1/PU.1 and lymphocyte-associated RUNX3, EBF1, and BATF. MS hypomethylated DMRs were concentrated at active enhancers and myeloid TFBS, suggestive of chronic myeloid activation. NMO showed the clearest promoter and B lymphocyte associated profile. Neuro-PASC was associated with hematopoietic DNase accessibility and TFBS for BATF and EBF1. Conclusions: These results suggest that DNA methylation in MS, NMO, and neuro-PASC differ meaningfully in regulatory architecture rather than conforming to a single shared disease-associated methylation model. A long-term goal is to develop immune therapies for newly recognized diseases such as neuro-PASC.

Journal of Clinical Medicine doi: 10.3390/jcm15134966

Authors: Kellina Maduray Jingquan Zhong

Background: Metabolic reprogramming in critical illness and the physiological stress of general hospitalization represent fundamentally different states, yet it remains unknown if ketosis acts as a protective shield or a maladaptive metabolic response in the development of atrial fibrillation (AF) across these contexts. We examined urine and serum β-hydroxybutyrate measurements to understand the metabolic association among intensive care unit (ICU) and general hospital populations. Methods: This retrospective cohort study utilized the MIMIC-IV v3.1 database. Patients with preexisting AF or flutter were excluded. Ketosis was defined as urine ketone positivity (≥20 mg/dL) or serum β-hydroxybutyrate (≥1.0 mmol/L). The final analytic cohort included a general ward cohort (n = 13,641) and an ICU cohort (n = 10,251). Multivariable logistic regression, propensity score matching and subgroup analyses were performed. Results: In the ICU cohort, urine ketone positivity and elevated serum β-hydroxybutyrate were associated with lower incidence of AF (5.2% vs. 6.8%, p = 0.001; 3.1% vs. 9.4%, p = 0.034). After adjustment, urine ketone positivity remained independently associated with reduced odds of incident AF (adjusted OR 0.79, 95% CI 0.64–0.98, p = 0.032). Propensity-matched analyses demonstrated protective associations for urine ketones (OR 0.68, 95% CI 0.52–0.88, p = 0.004) and β-hydroxybutyrate (OR 0.24, 95% CI 0.08–0.70, p = 0.003). In contrast, urine ketone positivity in the general ward cohort was associated with higher incident AF (0.9% vs. 0.5%, p = 0.019) and increased adjusted odds (OR 2.62, 95% CI 1.03–6.66, p = 0.044). Urinary ketosis was associated with lower mortality and reduced inflammatory marker profiles across both the ICU and general ward cohorts. Subgroup analyses revealed directionally consistent ketone-AF associations across biological sex with no significant interaction effects. Conclusions: Endogenous ketones demonstrated a context-dependent association with incident AF across clinical acuity levels. These findings highlight ketone metabolism as a potential target for both arrhythmia monitoring and prevention.

Journal of Clinical Medicine doi: 10.3390/jcm15134967

Authors: Michał Pomorski Tomasz Fuchs Anna Kryza-Ottou Joanna Budny-Wińska Jakub Śliwa Adam Pomorski

Apical pelvic organ prolapse (POP) is characterized by descent of the uterus or post-hysterectomy vaginal vault resulting from failure of level I pelvic support and represents a major contributor to pelvic floor dysfunction and recurrent prolapse surgery. Loss of apical support is frequently associated with anterior and posterior compartment defects, leading to vaginal bulge symptoms, pelvic pressure, urinary and bowel dysfunction, sexual dysfunction, and reduced quality of life. This narrative review summarizes current knowledge on POP, from molecular mechanisms and emerging biomarkers to contemporary surgical management, with particular emphasis on sacrocolpopexy and robotic-assisted approaches. A literature search of PubMed, Scopus, Google Scholar, and Consensus identified peer-reviewed studies published up to February 2026. Evidence demonstrates that POP has a multifactorial and polygenic background involving extracellular matrix remodeling, connective tissue integrity, smooth muscle dysfunction, and altered level of protein expression. Several candidate biomarkers, including single-nucleotide polymorphisms, circulating proteins, metabolites, and imaging-based parameters, show potential for risk prediction and earlier diagnosis, although routine clinical implementation remains limited. Sacrocolpopexy remains the gold standard for apical prolapse repair because of superior anatomical outcomes, low recurrence, and significant quality-of-life improvement. Laparoscopic and robotic-assisted sacrocolpopexy provide comparable efficacy with reduced blood loss, shorter hospitalization, and faster recovery. The objective success rate is usually over 90%. Complications are very rare and typically include mesh erosion in 2–4% of cases and the need for reoperation in 6% of cases. Our own experience shows that, for a group of surgeons, the learning curve for the laparoscopic approach reached a plateau after a total of 30 operations. Robotic platforms may facilitate complex pelvic dissection and shorten the learning curve, although higher procedural costs remain a major limitation.

Journal of Clinical Medicine doi: 10.3390/jcm15134965

Authors: Uri Hochberg Adi Lichtenstein Wisam Zbede Ahmad Taher Jesus de Santiago Silviu Brill Morsi Khashan

Background/Objectives: Cervical radiculopathy is a frequent cause of pain, often leading to disability, reduced quality of life, and significant healthcare utilization. Cervical epidural steroid injections are widely used, though safety concerns have been reported. Ultrasound-guided cervical retrolaminar block (RLCB) is a potential alternative. The purpose of this study was to evaluate the long-term clinical trajectory after ultrasound-guided cervical retrolaminar block, including pain outcomes, patient-reported improvement, and the rate of subsequent cervical spine surgery. Methods: This is a retrospective cohort analysis that was conducted at the Pain and Spine Surgery units in a single center. : We included 121 patients with cervical radiculopathy treated between January 2020 and September 2022 (mean age 49.4 ± 11.1 years; 51.2% male). All patients underwent RLCB. s: Primary outcome measures were subsequent cervical decompressive surgery and composite pain response (≥2-point absolute and ≥50% relative NRS reduction). Secondary outcome measures included recurrence, analgesic use, global rating of change (GRC), satisfaction, willingness to repeat, and safety. Baseline data was extracted from records; structured follow-up interviews were conducted at two years. Results: At two years, 9.1% required surgery, and 57.9% achieved composite pain response; 74.4% reported ≥2-point NRS reduction. GRC scores showed improvement (mean 5.0 ± 3.4), with 37% reporting “very much better.” Satisfaction was high, with 70.2% willing to repeat. Pain recurred in 71.1% but persisted in 28.9%. No major complications occurred; minor events were reported in 6.6%. Outcomes were less favorable in patients with pre-injection pain duration ≥1 year. p. Conclusions: In this retrospective cohort, cervical RLCB was associated with sustained patient-reported improvement, high satisfaction, and a 9.1% observed subsequent surgery rate at two years. These findings are hypothesis-generating and require confirmation in prospective controlled studies.

Journal of Clinical Medicine doi: 10.3390/jcm15134964

Authors: Oguz Kaan Kaya Veli Umut Turgut

Background: Cerebral aneurysms and aneurysmal subarachnoid hemorrhage (aSAH) may induce cardiac electrical instability through autonomic dysregulation and an exaggerated neurohumoral stress response. Electrocardiographic (ECG) abnormalities, including QT/QTc prolongation, QTc dispersion, and P-wave dispersion, are recognized markers of ventricular repolarization heterogeneity and atrial conduction abnormalities associated with arrhythmogenic risk. However, data regarding the reversibility of these electrophysiological alterations following definitive aneurysm treatment remain limited. Methods: This retrospective, single-center study included 39 patients with cerebral aneurysms who underwent microsurgical clipping between January 2025 and May 2026 and 35 age- and sex-matched healthy controls. Standard 12-lead ECGs were evaluated at baseline (preoperative) and one month after surgery in the aneurysm group. QT interval, corrected QT (QTc) interval, QTc dispersion, and P-wave dispersion were assessed using standardized methods. Baseline transthoracic echocardiographic parameters, including left ventricular ejection fraction and left atrial diameter, were evaluated to minimize potential confounding related to structural cardiac abnormalities. Between-group and within-group comparisons were performed using appropriate statistical analyses. Results: Baseline demographic and echocardiographic characteristics were comparable between the aneurysm and control groups. Patients with cerebral aneurysms demonstrated significantly higher baseline QT interval, QTc interval, QTc dispersion, and P-wave dispersion compared with healthy controls. Following microsurgical treatment, significant reductions in QT interval, QTc interval, QTc dispersion, and P-wave dispersion were observed at one month compared with preoperative values, whereas PR interval and QRS duration remained unchanged. These findings suggest a partial normalization of cardiac electrical heterogeneity after definitive aneurysm treatment. Conclusions: Cerebral aneurysms are associated with increased ventricular repolarization and atrial conduction heterogeneity, reflecting autonomic-mediated cardiac electrical instability. The significant reduction in QTc dispersion and P-wave dispersion following microsurgical treatment suggests that these electrophysiological abnormalities may be at least partially reversible after aneurysm repair. ECG-derived markers such as QTc dispersion and P-wave dispersion may represent practical and non-invasive tools for monitoring cardiac electrical instability and recovery in patients with cerebral aneurysms.

Journal of Clinical Medicine doi: 10.3390/jcm15134963

Authors: Chun-Fu Lin Chen-Chih Chung Jia-Hung Chen Nai-Fang Chi Chaur-Jong Hu Hung-En Huang Chih-Chung Chen Tu-Hsueh Yeh James Cheng-Chung Wei Hsun-Hua Lee

Background: OnabotulinumtoxinA and calcitonin gene-related peptide (CGRP) monoclonal antibodies are widely used for chronic migraine prevention, but comparative real-world evidence on healthcare utilization remains limited. This study aimed to compare the association of onabotulinumtoxinA versus CGRP monoclonal antibodies with acute triptan prescription and migraine-related return visits in patients with chronic migraine. Methods: We conducted a retrospective cohort study using the TriNetX global federated electronic health record database from 2018 to 2024. Adults with chronic migraine who initiated onabotulinumtoxinA or a CGRP monoclonal antibody were matched 1:1 by propensity score. The primary outcomes were time to acute triptan prescription and time to first migraine-related return visit during follow-up. Results: After propensity score matching, 10,140 patients were included in each treatment group. OnabotulinumtoxinA was associated with a lower hazard of acute triptan prescription than CGRP monoclonal antibodies (hazard ratio 0.513, 95% confidence interval 0.481–0.546; p < 0.001), whereas migraine-related return visits were similar between groups (hazard ratio 1.008, 95% confidence interval 0.977–1.039; p = 0.69). Conclusions: In this multicenter real-world analysis, onabotulinumtoxinA was associated with a lower hazard of acute triptan prescription than CGRP monoclonal antibodies, while migraine-related return visits were comparable. These findings reflect treatment-related healthcare utilization patterns in routine practice and should be interpreted considering the limitations of retrospective electronic health record data.

Journal of Clinical Medicine doi: 10.3390/jcm15134962

Authors: Andrea Braga Maurizio Serati Alessandro Ferdinando Ruffolo Giorgio Treglia Giorgio Caccia Vita Zacesta Giorgia Tenani Marco Torella Matteo Frigerio Marco Soligo Stefano Salvatore Andrea Papadia Greta Codoni

Background: Although routine use of episiotomy is widely discouraged in spontaneous vaginal deliveries, the use of episiotomy in operative vaginal delivery (OVD) remains highly debated. This systematic review and meta-analysis evaluated the current evidence on the safety of episiotomy in preventing obstetric anal sphincter injuries (OASIS) during OVD. Methods: A systematic literature search was conducted on PubMed/MEDLINE and CENTRAL databases with a cut-off date of November 2025. The protocol was registered in PROSPERO. We included studies which encompassed the incidence of OASIS when episiotomy (median or medio-lateral) was performed during vacuum or forceps delivery and when episiotomy was not performed. Randomized controlled trials (RCTs), prospective or retrospective cohort studies and observational studies were considered appropriate study designs. A meta-analysis using risk ratio as the outcome measure was performed to compare the presence of the event (OASIS) in patients with or without episiotomy. Results: A total of 15 studies were analyzed to evaluate the role of medio-lateral episiotomy (MLE) in OVD. The results demonstrated a statistically significant lower rate of severe perineal trauma in the experimental group (pooled RR 0.5; 95% CI: 0.30–0.84). A statistically significant difference in support of the use of MLE was found in two further subgroup analyses, comprising 14 studies focusing on the role of MLE during vacuum delivery (VD) and 9 studies considering the role of MLE during forceps delivery (FD). Conclusions: This study highlights that the use of MLE in nulliparous women undergoing OVD is associated with a significantly decreased risk of OASIS.

Journal of Clinical Medicine doi: 10.3390/jcm15134961

Authors: Nejc Piko Sebastjan Bevc Franjo Husam Naji Robert Ekart

Background: Hyperhomocysteinemia (homocysteine [Hcy] ≥15 μmol/L) is frequently observed in patients with impaired kidney function and has been associated with vascular remodeling and increased cardiovascular risk. We aimed to evaluate the relationship between Hcy, arterial stiffness, coronary artery disease (CAD), peripheral arterial disease, and biomarkers of kidney injury in patients undergoing elective coronary angiography. Methods: In this prospective observational study, 133 patients undergoing elective coronary angiography were stratified according to serum Hcy levels (Hcy <15 vs. Hcy ≥15 μmol/L). CAD severity was assessed angiographically. Arterial stiffness was evaluated using carotid–femoral pulse wave velocity (cfPWV), while peripheral arterial disease was assessed using ankle–brachial index (ABI). Kidney function was evaluated using serum creatinine, estimated glomerular filtration rate (eGFR), cystatin C, and urinary albumin-to-creatinine ratio (UACR). Correlation, multivariable regression, logistic regression, and receiver operating characteristic (ROC) analyses were performed. Results: Patients with hyperhomocysteinemia demonstrated significantly worse kidney function, including higher serum creatinine, cystatin C, and UACR levels, and lower eGFR (all p < 0.01). Patients with elevated Hcy levels also exhibited significantly higher cfPWV values (11.4 ± 3.3 vs. 9.7 ± 2.1 m/s, p < 0.001). Hcy correlated positively with cystatin C, creatinine, UACR, and cfPWV, and inversely with eGFR. In multivariable linear regression analysis, Hcy remained independently associated with increased cfPWV after adjustment for age, sex, and eGFR (β = 0.137, 95% CI 0.047–0.226, and p = 0.003). This association remained significant in sensitivity analyses incorporating hypertension, diabetes mellitus, LDL cholesterol, and statin therapy (β = 0.124, 95% CI 0.032–0.216, and p = 0.008). No independent associations were observed between Hcy and angiographic CAD severity or ABI values. ROC analysis demonstrated modest discrimination for elevated arterial stiffness (AUC = 0.66, 95% CI 0.56–0.76) and good discrimination for impaired kidney function (AUC = 0.82, 95% CI 0.69–0.92). Conclusions: Elevated Hcy levels were independently associated with impaired kidney function and increased central arterial stiffness, but not with angiographic CAD severity or peripheral arterial disease. These findings suggest that hyperhomocysteinemia may reflect cardiorenal vascular dysfunction and diffuse vascular remodeling rather than focal obstructive atherosclerotic disease. Further studies are needed to determine its clinical utility and prognostic value.

Journal of Clinical Medicine doi: 10.3390/jcm15134959

Authors: Alexandre Genoud Ines Portugal Nicolas Murith Jean-Francois Deux Tornike Sologashvili Christoph Huber Mustafa Cikirikcioglu

Coronary artery anomalies (CAAs) are a rare but clinically significant group of congenital abnormalities that are associated with myocardial ischaemia, malignant arrhythmias and sudden cardiac death, particularly in young people and athletes. Despite increasing recognition of these conditions and advances in cardiovascular imaging, there are still significant challenges regarding their classification, risk stratification and management, particularly with respect to surgical indications. This review provides a comprehensive overview of the current evidence on the classification, pathophysiology, diagnosis and management of CAAs, with a particular focus on surgical decision-making and contemporary guideline recommendations. A systematic literature search was conducted up to February 2025 using PubMed and Google Scholar. Priority was given to international guidelines, consensus statements, systematic reviews, meta-analyses and large observational studies. CAAs encompass a broad spectrum of anatomical variants and clinical presentations. Among these, anomalies of coronary origin are the most extensively studied. Surgical management is well established for coronary arteries arising from the pulmonary artery, particularly for anomalous left coronary artery from the pulmonary artery (ALCAPA). Substantial advances have also been made in the diagnosis, risk stratification, and treatment of anomalous aortic origin of a coronary artery (AAOCA), which has become a major focus of contemporary guideline recommendations. For patients with AAOCA, surgical correction, including unroofing, coronary reimplantation or coronary artery bypass grafting, is recommended for individuals with symptoms and/or high-risk anatomical features. In contrast, the diagnosis and management of myocardial bridging, coronary artery fistulas, and coronary artery ectasia remain controversial, with considerable variability in the indications for medical, percutaneous, and surgical treatment. The management of CAAs is an evolving field. While there is consensus for a limited number of anomalies, most cases still require individualised decision-making. It is essential to develop standardised diagnostic frameworks, improved risk stratification tools and outcome-based management criteria. A multidisciplinary, evidence-based approach involving cardiologists, cardiac imagers, interventional cardiologists and cardiac surgeons is crucial in order to optimise patient outcomes and reduce the risk of adverse cardiovascular events, including sudden cardiac death.

Journal of Clinical Medicine doi: 10.3390/jcm15134960

Authors: Akihiro Hasegawa Ehsan Rojhani Ahmed Hashem Fathallah Rodrigo Ruano Alireza Abdollah Shamshirsaz

Advances in fetal diagnosis and molecular medicine have opened new opportunities for in utero molecular-targeted drug therapy, shifting fetal treatment from purely procedural interventions toward pharmacologic strategies that address disease mechanisms before irreversible organ damage occurs. In this review, we highlight recent advances in in utero drug therapy, focusing on molecular-targeted approaches with emerging clinical or trial-level evidence. Early clinical experience and ongoing trials have demonstrated the feasibility of achieving therapeutically relevant fetal drug exposure, although the strength of evidence varies considerably across therapeutic classes. However, significant challenges remain, including optimization of fetal drug delivery, characterization of fetal pharmacokinetics and pharmacodynamics, long-term safety assessment, and ethical considerations. The current evidence base ranges from single case reports to ongoing Phase 3 clinical trials, underscoring both the promise of prenatal molecular therapeutics and the need for further prospective evaluation. Continued integration of fetal imaging, genomics, ethics and pharmacology will be essential to advance safe and effective prenatal precision therapies.

Journal of Clinical Medicine doi: 10.3390/jcm15134958

Authors: Damian Romańczuk Sandra Lange Wioletta Mędrzycka-Dąbrowska Grzegorz Cichowlas

Background: The administration of intravenous contrast media using automated power injectors is fundamental for high-quality computed tomography (CT), particularly in CT angiography (CTA). The selection of an appropriate vascular access device (VAD) and adherence to technical safety standards are critical for ensuring diagnostic efficacy and patient safety. This systematic review aims to synthesize current scientific literature regarding the efficacy and safety of contrast media infusion across various vascular access routes, including peripheral intravenous cannulas (PIVC), central venous catheters (CVC), and totally implantable venous access devices (TIVAD). Methods: The review followed PRISMA 2020 guidelines. A comprehensive search was conducted in PubMed, CINAHL, Web of Science, and Scopus for studies published between 2000 and 2026. A total of 19 studies—including randomized controlled trials (RCTs), cohort studies, and systematic reviews—were analyzed. Methodological quality was assessed using Joanna Briggs Institute (JBI) appraisal tools. Results: Modern PIVCs utilizing diffuser technology (side holes) significantly reduce distal jet pressure, minimizing vessel wall damage during high-flow injections. For patients with difficult vascular access, “power-injectable” certified devices (e.g., PICCs or TIVADs) serve as a safe alternative. Standard, non-power-injectable central lines must be avoided due to the risk of catheter rupture. The selection of an appropriate vascular access device is particularly challenging in patients of older age or those with chronic conditions, such as peripheral vascular disease, obesity, or chemotherapy-related venous damage, which often lead to difficult intravenous access (DIVA). Conclusions: Utilizing certified power-injectable devices and advanced cannula designs improves the safety of high-pressure contrast administration. Adherence to technical protocols and the identification of high-risk patients are essential for mitigating complications such as contrast extravasation.

Journal of Clinical Medicine doi: 10.3390/jcm15134956

Authors: Yulia Lutokhina Andrei Nartov Valeriia Nartova Olga Pavlova Vsevolod Sedov Nina Gagarina Olga Blagova

Introduction: Giant sinus of Valsalva aneurysms (SVA) represent a rare cardiovascular pathology that may remain asymptomatic for an extended period. However, they are associated with a high risk of life-threatening complications, including compression of adjacent structures and aneurysm rupture. Case presentation: We report a clinical case of a 71-year-old female patient with a long-standing history of arterial hypertension and cardiac arrhythmias, in which echocardiography revealed aneurysmal dilatation of the right coronary sinus. Cardiac computed tomography (CT) confirmed the presence of a giant aneurysm of the right sinus of Valsalva measuring 70 × 51 × 49 mm, compressing the outflow tracts of both ventricles (right—up to 7 mm, left—up to 8 mm) and the left inferior pulmonary vein (up to 3 mm), which clinically manifested as dyspnoea, lower-extremity oedema, and rhythm disturbances. The patient successfully underwent complex reconstructive surgery, including aortic root replacement and valve repair. Despite the technical success of the operation, the patient died from pneumonia three months postoperatively. Discussion: This observation underscores the critical role of imaging modalities (echocardiography and CT) in verifying this pathology. The use of multimodal imaging facilitated both a timely diagnosis and a detailed three-dimensional evaluation of the aneurysm’s relationship with adjacent structures. This information, in turn, guided personalised surgical planning. Conclusions: This case highlights the necessity of considering giant SVA in the differential diagnostic workup of patients who present with unexplained symptoms of heart failure.

Journal of Clinical Medicine doi: 10.3390/jcm15134957

Authors: Sameh A. Ahmed Osama M. Alhadramy Lobna S. Hazman Hussein M. Ismail

Background/Objectives: Heart failure (HF) classification based on left ventricular ejection fraction (LVEF) provides an incomplete representation of disease complexity, as it does not fully integrate functional impairment, structural remodeling, and clinical severity within a unified framework. Although N-terminal pro-B-type natriuretic peptide (NT-proBNP) is widely used for diagnosis and risk stratification, prior studies have primarily evaluated its role in isolation or within individual HF phenotypes, leaving its phenotype-specific distribution and integrative capacity across the HF spectrum insufficiently defined. This study aimed to address this gap by systematically evaluating NT-proBNP across HF phenotypes and assessing its potential as an integrative biomarker linking ventricular dysfunction, structural remodeling, and clinical severity. Methods: A cross-sectional study was conducted including 125 participants, comprising 65 clinically stable HF patients and 60 age- and sex-matched controls. HF patients were stratified according to LVEF into HF with reduced EF (HFrEF) (n = 28), (HFmrEF) (n = 20), and HF with preserved EF (HFpEF) (n = 17). Serum NT-proBNP concentrations were measured using a standardized electrochemiluminescence immunoassay. Clinical and echocardiographic parameters, including LVEF, left ventricular end diastolic diameter (LVEDD), left atrial diameter (LAD), and New York Heart Association (NYHA) functional class, were recorded and analyzed. Results: NT-proBNP levels were significantly higher in HF patients compared with controls (1845 ± 620 vs. 95.7 ± 40.5 pg/mL; p < 0.001) and demonstrated a clear stepwise increase across phenotypes (HFrEF: 2850.6 ± 710.4; HFmrEF: 1620.8 ± 480.2; HFpEF: 920.9 ± 310.3 pg/mL; p < 0.001). NT-proBNP showed a strong inverse correlation with LVEF (r = −0.68, p < 0.001) and significant positive correlations with LVEDD (r = 0.61, p < 0.001) and LAD (r = 0.57, p < 0.001). Higher levels were associated with more advanced NYHA functional class (III–IV vs. II: 2510 ± 680 vs. 980 ± 340 pg/mL; p < 0.001). ROC analysis demonstrated robust discriminatory performance across HF phenotypes, with the highest accuracy observed in HFrEF. Conclusions: NT-proBNP exhibits a phenotype-dependent gradient and consistently reflects ventricular dysfunction, adverse structural remodeling, and clinical severity across the HF spectrum. These findings support its role as an integrative biomarker that captures the multidimensional nature of HF, with potential implications for phenotype-based risk stratification and more precise clinical decision making.

Journal of Clinical Medicine doi: 10.3390/jcm15134955

Authors: Mengmeng Ji Dema Yaseen Alsabbagh Siobhan Sutcliffe Massini Merzkani Krista L. Lentine Bekir Tanriover Su-Hsin Chang Tarek Alhamad

Background: During the COVID-19 pandemic, uncertainty regarding the safety of kidneys from COVID-19-positive donors led to a reduction in kidney transplants and increased organ non-use in the United States. This study aims to evaluate whether donor COVID-19 positivity is associated with one-year post-transplant estimated glomerular filtration rate (eGFR) among kidney transplant recipients. Methods: This retrospective cohort study used data from the United States Organ Procurement and Transplantation Network (OPTN) 2020–2024. Donor COVID-19 status was determined by the SARS-CoV-2 nucleic acid amplification technique (NAT) and antibody test results. The main outcome was recipients’ one-year eGFR, estimated by the CKD-EPI 2021 formula. Linear regression models were used to compare the mean one-year eGFR among donor COVID-19 groups, adjusted by inverse probability of treatment weights. Interaction terms of donor acute kidney injury status and race were assessed to evaluate effect modification. Results: Among 38,199 included kidney transplant recipients, 1090 (2.9%) received kidneys from donors with active COVID-19 infection, 423 (1.1%) from donors with resolved infection, and 36,686 (96.0%) from COVID-19-negative donors. After weighting and adjustment, there was no significant difference in one-year eGFR for recipients of kidneys from donors with active COVID-19 (mean difference, 0.05 [95% CI, −1.08 to 1.18]) or resolved infection (mean difference, −0.27 [95% CI, −2.19 to 1.64]) compared with COVID-19-negative donors. Neither donor AKI nor donor race modified the association between donor COVID-19 status and one-year eGFR. Conclusions: This study suggests that kidneys from COVID-19-positive donors may be a viable option without compromising short-term allograft function as measured by 1-year eGFR.

Journal of Clinical Medicine doi: 10.3390/jcm15134954

Authors: Vikas Chauhan

Moyamoya disease is a progressive steno-occlusive cerebrovascular disorder in which cerebral perfusion may become highly dependent on systemic arterial pressure, arterial carbon dioxide tension, and collateral flow. Encephaloduroarteriosynangiosis (EDAS) is an indirect revascularization procedure that promotes neovascularization over weeks to months but does not immediately augment cerebral blood flow intraoperatively. Anesthetic management therefore requires preservation of cerebral oxygen delivery during a period of persistent physiologic vulnerability. This narrative review presents a practical perioperative framework for EDAS anesthesia, emphasizing maintenance of mean arterial pressure near baseline or modestly above baseline, avoidance of hypotension and hypovolemia, normoxia, normothermia, and careful regulation of carbon dioxide. Hyperventilation should be avoided because hypocapnia can reduce cerebral blood flow through vasoconstriction, while excessive hypercapnia may contribute to regional maldistribution or steal physiology. Raw electroencephalography may provide cortical ischemia surveillance where available, whereas somatosensory evoked potentials, motor evoked potentials, near-infrared spectroscopy, and transcranial Doppler should be considered adjunctive and institution-dependent. A structured algorithm that integrates hemodynamics, ventilation, oxygen delivery, anesthetic depth, neuromonitoring, and surgical communication may support the timely recognition and correction of intraoperative hypoperfusion.

Journal of Clinical Medicine doi: 10.3390/jcm15134953

Authors: Abdullah Alqarni Hassan Ahmed Assiri Ali Hassan Asiri Sami Ali Humaidi Hassan Abdulrhman Alshehri Yousef S. Otayfi Omar Saleh Aljughuli Zaher Saleh Aljughuli Abdulaziz Abdullah Alqahtani Mohammad Shahul Hameed

Background: Elongated styloid processes and ossifications of the stylohyoid chain can be observed on dental imaging modalities. In this study, we assessed the performance of artificial intelligence (AI) in identifying elongated styloid processes and ossifications of the stylohyoid chain. Methods: We performed a systematic review of relevant studies published between April 2020 and April 2026 on PubMed, Scopus, and Web of Science. Relevant data were extracted using predefined criteria. We assessed the risk of bias using categories derived from QUADAS-2, CLAIM and STARD-AI. Results: Four original studies met the inclusion criteria. Of these, only two specifically addressed elongated styloid processes on panoramic images (OPGs). For one study that utilized ML algorithms, both logistic regression and neural networks achieved 100% performance, while naive Bayes demonstrated substantially lower performance than either model. Another study using deep learning algorithms observed accuracy rates of 97.49% and 84.11%, and area under the curve values of 0.9825 and 0.8943 for EfficientNetB5 and InceptionV3 models. A broader study using OPG anomaly detection reported target-level data for stylohyoid ligament ossification. The fourth study used cone-beam computed tomography images, including stylohyoid ligament ossification as part of a multi-class soft tissue calcification/ossification detection task. Due to significant variability in target definitions, imaging modalities, validation methods, and performance metrics across studies, a meta-analysis was not feasible. Conclusions: The use of AI-based systems for detecting elongated styloid processes and stylohyoid chain ossification shows potential for future clinical utility; however, current evidence is insufficient to support independent clinical practice. Future research should incorporate larger-scale prospective multicenter validations as well as external validation on a patient-by-patient basis when possible. Additional research into the clinical implications associated with both false-positive and false-negative results is warranted.

Journal of Clinical Medicine doi: 10.3390/jcm15134952

Authors: Małgorzata Elżbieta Poniatowska-Roszkowska Tabea Troschke Bożena Birkenfeld Hanna Piwowarska-Bilska

Background: Neuroendocrine tumors—are relatively rare but increasingly diagnosed malignancies originating from diffuse neuroendocrine cells, most commonly affecting the gastroenteropancreatic system. Due to their long asymptomatic development and low incidence, pose a diagnostic and therapeutic challenge for physicians. Recently, the role of nuclear medicine has been growing not only in the diagnostic stage but also in treatment. Systemic radionuclide therapy using somatostatin analogs labelled with the radioisotope lutetium-177 is becoming increasingly common in patients with advanced-stage disease. Currently, most patients receive a standard activity of therapeutic radiopharmaceuticals. Recent clinical studies provide increasing evidence of a close relationship between the absorbed radiation dose in pathological lesions and the therapeutic effect of radioisotope therapy. Internal dosimetry is used to measure the doses of ionising radiation absorbed by the patient after administration of the radiopharmaceutical. The lack of individual internal dosimetry prior to therapy means that only a small fraction of patients receive optimal doses of radioactivity, which is markedly different from external beam radiotherapy planning. Methods: A narrative literature review was conducted using the PubMed/MEDLINE and Embase databases, focusing primarily on publications from the last years. The search strategy included combinations of keywords related to peptide receptor radionuclide therapy and dosimetry, such as “Lutetium-177”, “neuroendocrine tumors”, “dosimetry”, “PRRT”, “systemic radionuclide therapy” and “artificial intelligence”. Particular emphasis was placed on recent prospective clinical studies, multicenter investigations, systematic reviews and consensus documents published by major nuclear medicine societies, including the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). Seminal earlier publications considered essential for understanding the development of dosimetry concepts and clinical implementation were also included. Results: This study confirms the existence of a clinically significant dose-response relationship in 177Lu-PRRT. Higher absorbed doses to tumour lesions are associated with longer progression-free survival. The lack of individualized internal dosimetry prior to therapy means that only a small proportion of patients receive optimal radiation doses. Simplified dosimetric approaches with a reduced number of imaging time points, together with emerging artificial intelligence–based tools, appear promising for reducing the complexity of the dosimetry process. Conclusions: The aim of this study was to analyse the current literature on the role of internal dosimetry in the treatment of neuroendocrine tumors using the radioisotope lutetium-177. Available data support the clinical relevance of individualized dosimetry and highlight its potential to optimize both therapeutic efficacy and treatment safety.

Journal of Clinical Medicine doi: 10.3390/jcm15134951

Authors: Claudio Tirelli Ornella Rondinone Fausta Alfano Jacopo Cefalo Giulia Nalesso Matteo Ciracì Carmine Salerni Monica Rosa Miozzo Stefano Centanni Michele Mondoni

The pathogenesis of interstitial lung diseases (ILDs) is significantly influenced by genetic factors, yet lack of consensus on the optimal timing for genetic testing and precise patient selection could hinder clinical practice. Position papers currently suggest testing patients presenting with a suspect of Familial Pulmonary Fibrosis (FPF) and with extra-pulmonary syndromic features (i.e., premature graying, cytopenias, liver cirrhosis) for genetic screening. Diagnostics rely on next-generation sequencing (NGS) to identify pathogenic/likely pathogenic variants in telomere-related and surfactant-related genes. A specialized genetic consultation is essential in the correct interpretation of test results, especially when variants of uncertain significance (VUS) are detected. Adoption of other tests, such as polygenic risk scores, could further support precision medicine in ILD care. Future research might address the knowledge gap regarding early test prescription and the role of therapy, including lung transplant stratification and antifibrotic therapy, in FPF.

Journal of Clinical Medicine doi: 10.3390/jcm15134950

Authors: Jiazheng Sun Yanjie Lin Hong Zhao

Introduction: Ado-trastuzumab emtansine (T-DM1) is a targeted agent for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which combines the anti-tumor activity of trastuzumab with the cytotoxic effect of DM1, a microtubule inhibitor. Although T-DM1 has improved outcomes in patients with HER2-positive breast cancer, portal hypertension may occur during treatment in the absence of overt cirrhosis on liver biopsy. These clinical and pathological features are consistent with porto-sinusoidal vascular disorder (PSVD). This study aimed to summarize the reported clinical, biochemical, imaging, histological, therapeutic, and prognostic features of T-DM1-associated PSVD. Methods: PubMed and Web of Science were searched for published cases of T-DM1-associated PSVD. Given the evolving terminology of PSVD, related terms, including non-cirrhotic portal hypertension and nodular regenerative hyperplasia, were also included in the search strategy. If the patient has a recorded history of T-DM1 exposure and the liver biopsy results meet PSVD criteria, the case is included regardless of whether there is clinical, endoscopic, or imaging evidence of portal hypertension. Cases without liver biopsy or with features suggestive of overt cirrhosis were excluded. Patient-level data were extracted and descriptively summarized, including demographic characteristics, clinical manifestations, biochemical indicators, imaging examination results, liver biopsy results, treatment methods, and prognosis. Unreported data were considered missing values and were not imputed. Results: Seven eligible articles comprising eight patients were identified. All patients were female, with a mean age of 60.38 years and a median age of 62.50 years. The interval from T-DM1 initiation to PSVD diagnosis ranged from 6 to 30 months. When reported, the mean interval from treatment initiation to symptom onset was 18.3 months. Thrombocytopenia and splenomegaly were observed in 7 of 8 patients. Mild elevations in alanine aminotransferase and aspartate aminotransferase were observed in all patients. Liver biopsy showed thinned and disorganized hepatic plates accompanied by nodular regeneration of hepatocytes in six patients. Clinical improvement was observed after discontinuation or modification of T-DM1 in most cases. Conclusions: T-DM1-associated PSVD is a rare but clinically significant complication that may develop months after treatment initiation. It commonly presents with thrombocytopenia, splenomegaly, gastrointestinal bleeding, or mild liver biochemical abnormalities in the absence of overt cirrhosis. Early recognition of unexplained platelet decline, splenic enlargement, or portal hypertension-related findings during T-DM1 therapy may facilitate timely diagnosis and individualized management. Withdrawal or modification of the suspected drug may contribute to clinical improvement, although further studies are needed to clarify the mechanism and optimal management strategy.

Journal of Clinical Medicine doi: 10.3390/jcm15134947

Authors: Marilena Recupero Raffaele Ferri Serafino Buono

Background: EEG neurofeedback has been proposed as a non-pharmacological approach to enhance attention and cognitive performance in neurodevelopmental conditions. However, its efficacy in individuals with intellectual disability (ID) remains limited. Methods: We conducted a systematic review of treatment studies evaluating EEG-based neurofeedback targeting attention and executive function outcomes in participants with ID. Searches were performed in Embase, Web of Science, Scopus, PubMed, and the Cochrane Library from inception to 12 March 2026. Two reviewers independently completed screening, eligibility assessment, data extraction, and risk-of-bias appraisal, with disagreements resolved by a third reviewer. Due to heterogeneity in study designs, neurofeedback protocols, participant characteristics, and outcome measures, data were synthesized narratively. Results: Six studies met the inclusion criteria, comprising small randomized or controlled experimental studies, case series, and single-case reports. Several studies suggested improvements in attention-related neuropsychological performance and behavioral or task-based outcomes, and in some cases were accompanied by parallel EEG changes. Nevertheless, the overall body of evidence was constrained by small sample sizes, heterogeneous populations, limited blinding, infrequent sham or active controls, variable follow-up durations, and incomplete effect-size reporting. Conclusions: EEG neurofeedback appears to confer benefits for attention-related outcomes in individuals with ID, but current findings are preliminary and warrant larger, well-controlled trials with standardized protocols and reporting.

Journal of Clinical Medicine doi: 10.3390/jcm15134949

Authors: Cristina de Angelis Francesco Garifalos Davide Menafra Paolo Chiodini Giacomo Galdiero Mariangela Piscopo Tonia Romano Nunzia Verde Antonella Giarra Marco Trifuoggi Erminio Massimo Crescenzo Chiara Simeoli Mariarosaria Negri Claudia Pivonello Annamaria Colao Rosario Pivonello

Background/Objectives: The “Land of Fires” (LF) in the Campania Region has attracted considerable attention due to massive environmental contamination deriving from decades of illegal disposal, burial, and burning of urban, industrial, and toxic waste. Cadmium (Cd) has been repeatedly proven to affect male reproductive function by a plethora of endocrine and non-endocrine mechanisms. The scientific literature is almost devoid of large studies addressing semen quality in this area, particularly by directly correlating seminal parameters to objectively measured pollutant burden in biological samples. Therefore, the aim of the current study was to comprehensively evaluate semen quality of males of reproductive age living in the LF, by correlating seminal parameters to cumulative local male reproductive tract Cd burden objectively quantified in whole semen samples. Methods: The current single-center, observational, cross-sectional study evaluated semen quality in 493 males aged 14–50 (29.07 ± 7.17) years living in three LF municipalities. Moreover, the association of semen quality with whole semen Cd (sCd) levels measured by inductively coupled plasma mass spectrometry (ICP-MS) was addressed in a subgroup of participants; semen samples suitable for semen Cd measurements were available from 383/493 (77.7%) participants of the total cohort, and all analyses involving semen Cd were performed within the measured subset. Results: In the total cohort, seminal parameters were as follows: semen pH 8.32 ± 0.3, semen volume 3.13 ± 1.67 mL, sperm concentration 37.58 ± 30.18 × 106/mL, total count 111.2 ± 104 × 106/ejaculate, total motility 56.83 ± 16.09%, progressive motility 50.22 ± 16.63%, in situ motility 6.72 ± 3.43%, immotile spermatozoa 43.07 ± 15.88%, normal morphology 7.97 ± 4.02%, and viability 64.75 ± 15.34%. Prevalence of normozoospermia and pathological seminal parameters was as follows: normozoospermia 66.5% (328/493), pathological seminal parameters 33.5% (165/493), specifically, oligozoospermia 14% (69/493), cryptozoospermia 0.8% (4/493), azoospermia 2.2% (11/493), asthenozoospermia 3% (15/493), teratozoospermia 0.6% (3/493), oligo-astheno-teratozoospermia 6.1% (30/493), necrozoospermia 5.7% (28/493), and different combined seminal parameters alterations 7.1% (35/493). Whole semen Cd was below (undetectable) or above (detectable) the limit of detection (LoD) (0.2 μg/L) in 66.6% (255/383) and 33.4% (128/383) whole semen samples, respectively. In samples with detectable sCd, sCd level was below or above the median value (0.76 μg/L; min–max 0.1–5.95 μg/L) in 23.4% (30/128) and 76.6% (98/128) whole semen samples, respectively. Participants with detectable sCd levels had a significantly reduced sperm total count (93.28 ± 84.88 × 106/ejaculate vs. 113.2 ± 101.5 × 106/ejaculate; p = 0.037), and normal morphology (7.29 ± 3.71% vs. 8.23 ± 3.91%; p = 0.034), and a significantly lower prevalence of normozoospermia (60.2% vs. 72.2%; p = 0.02) and significantly higher prevalence of pathological seminal parameters (39.8% vs. 27.8%; p = 0.02), specifically, a significantly higher prevalence of oligozoospermia (21.1% vs. 12.6%; p = 0.036) than those with undetectable sCd levels. Whole semen Cd levels were significantly higher in participants with pathological seminal parameters (1.08 ± 0.84 μg/L vs. 0.93 ± 0.74 μg/L; p = 0.037) than those with normozoospermia. Participants with sCd levels above the median value (N = 98) had a significantly reduced sperm concentration (29.12 ± 24.84 × 106/mL vs. 43.62 ± 29.55 × 106/mL; p = 0.015) and displayed a trend towards reduced sperm normal morphology (6.92 ± 3.38% vs. 8.55 ± 4.49%; p = 0.057) than those with sCd levels below the median value (N = 30). Moreover, participants with sCd levels above the median value (N = 98) had a significantly reduced sperm concentration (29.12 ± 24.84 × 106/mL vs. 35.3 ± 26.29 × 106/mL; p = 0.03), total count (85.77 ± 80.52 × 106/ejaculate vs. 113.2 ± 101.5 × 106/ejaculate; p = 0.008) and normal morphology (6.92 ± 3.38% vs. 8.23 ± 3.91%; p = 0.006), and a significantly lower prevalence of normozoospermia (57.1% vs. 72.2%; p = 0.008) and significantly higher prevalence of pathological seminal (42.9% vs. 27.8%; p = 0.008), specifically, a significantly higher prevalence of oligozoospermia (23.5% vs. 12.6%; p = 0.014) than those with undetectable sCd levels. Conclusions: The results of the current study demonstrate an association between the environmental Cd exposure and the impairment of seminal parameters, with a significantly poorer semen quality in participants with detectable sCd, and, more markedly, in those with sCd level above the median value, compared to participants with undetectable sCd, although subgroups comparisons highlighted a homogeneous profile in major confounders including age, BMI, and smoking habits among subgroups of participants with different sCd burden.

Journal of Clinical Medicine doi: 10.3390/jcm15134948

Authors: Eusebi Chiner Ignacio Boira Joaquín Fernández-Serrano Mónica Llombart Violeta Esteban Paula Fernández Martínez Marian Fernández Sandra Vañes Francesco Gigliarano Sandra Navarro Sergio García Ferrer

Background/Objectives: Chronic home oxygen therapy—long-term oxygen therapy (LTOT)—improves survival and quality of life in chronic respiratory failure when used ≥15 h/day, but adherence is frequently suboptimal and specific patient-reported outcome measures (PROMs) are scarce. To develop, validate and apply a specific PROM for patients on LTOT. Methods: A prospective observational cohort study was conducted at San Juan de Alicante University Hospital (April 2024–December 2025) following a four-stage process: conceptual framework definition and expert workshop, content validation and item reduction, cognitive interviews with pilot reliability testing (n = 25), and field application to 120 consecutive chronic LTOT users. The LTOT-PROM was designed to capture the patient-perceived impact attributable to LTOT during the previous 4 weeks. Internal consistency was assessed with Cronbach’s α and test–retest reproducibility with the intraclass correlation coefficient (ICC). Results: The final instrument comprises 15 scored items in two dimensions—Daily Activity (9 items) and Adverse Effects (6 items)—plus one ambulatory-only mobility item excluded from the total score. Cronbach’s α was 0.814 (95% CI 0.681–0.906) for Daily Activity, 0.743 (95% CI 0.548–0.872) for Adverse Effects and 0.808 (95% CI 0.677–0.902) for the total scale; total ICC(A,1) was 0.890 (95% CI 0.767–0.950). Among the 120 patients (62 men, 58 women; mean age 78 ± 13 years; mean therapy duration 40 ± 32 months), 68% reported reduced effort for daily activities, 66% reported a reduction in dyspnoea and 67% reported improved self-confidence; 49% reported morning airway dryness and 7% abandoned the equipment due to nasal dryness or rhinitis. Conclusions: The LTOT-PROM is a brief, reliable and reproducible oxygen-specific instrument for assessing the recent patient-perceived impact of LTOT in routine clinical practice. Further studies should evaluate structural validity, external validity and the relationship between LTOT-PROM scores and objective adherence measures. The construct was predefined as the patient-perceived impact attributable to LTOT during a standardised 4-week recall window, and cognitive interviews confirmed that respondents interpreted the items as experienced benefit/burden during that period rather than as week-to-week symptom change.

Journal of Clinical Medicine doi: 10.3390/jcm15134946

Authors: Bosung Kim Yeong-Gwan Jeon Jung Hyun So Soonchang Hong Ji-Hyoung Park

Background/Objectives: Ultrasound-guided fascial plane blocks have emerged as opioid-sparing analgesic strategies for cardiac surgery; however, evidence regarding combined block techniques remains limited. This randomized controlled trial evaluated the analgesic efficacy of combined pectoserratus plane block (PSPB) and pecto-intercostal fascial plane block (PIFB) in patients undergoing cardiac surgery via median sternotomy. Methods: Sixty-two adult patients undergoing cardiac surgery via median sternotomy were randomized to either a block group receiving bilateral PSPB and PIFB after anesthetic induction or a control group receiving conventional analgesia alone. The primary outcome was postoperative visual analog scale (VAS) pain score at 6, 12, 24, and 48 h after surgery. Secondary outcomes included Korean version of Quality of Recovery-15 (QoR-15K) scores, total opioid consumption, rescue analgesic dose, time to first rescue analgesia, extubation time, intensive care unit (ICU) stay, hospital stay, and the incidence of postoperative nausea and vomiting. Results: Fifty-four patients were included in the final analysis. Postoperative VAS scores did not differ significantly between groups after Bonferroni correction for repeated measurements. No significant overall between-group effect was observed in repeated-measures ANOVA. ICU stay was statistically shorter in the block group, although the absolute difference was small and of uncertain clinical relevance. No significant differences were observed in the remaining secondary outcomes. Conclusions: Combined PSPB and PIFB did not reduce postoperative pain or improve recovery outcomes after cardiac surgery via median sternotomy. Early postoperative pain scores were numerically higher in the block group, although these differences were not statistically significant after correction for multiple comparisons. The incremental analgesic benefit of combined fascial plane blocks may therefore be limited in this clinical setting.

Journal of Clinical Medicine doi: 10.3390/jcm15134945

Authors: Jungmin So Moon-Ho Park

Background/Objectives: Assessment of cognitive function in patients with dementia is often hindered by functional and environmental barriers. Although caregiver reports are an alternative source, their clinical utility for estimating patients’ cognitive function remains uncertain. This study aimed to estimate cognitive function using caregiver-reported data combined with patient demographics and to evaluate its clinical utility. Methods: This retrospective cross-sectional study enrolled participants who visited a memory clinic and completed the Montreal Cognitive Assessment (MoCA) for cognitive assessment, together with caregiver-reported questionnaires for activities of daily living (ADL) and neuropsychiatric symptoms (NPS). Multivariable linear regression models were constructed to predict the MoCA score, with Model 1 including demographics, ADL, and NPS as covariates and Model 2 further incorporating clinical diagnosis. The intraclass correlation coefficient, Bland–Altman analysis, and regression error characteristic curves were assessed. Results: Among 2650 participants (56.5% women; mean age, 70.4 years), the NPS variable was excluded from both models. Model 1, which included demographics and ADL, explained 65.4% of the variance, whereas Model 2, which incorporated clinical diagnosis, explained 75.9%. Model 2 yielded an intraclass correlation coefficient of 0.853, compared to 0.778 for Model 1. At a 4-point error tolerance, Model 2 yielded an accuracy of 75.5%. Bland–Altman biases were near zero, with 95% limits of agreement of approximately ±7 points for Model 2. Conclusions: MoCA scores can be estimated using caregiver-reported ADL scores, demographics, and clinical diagnosis. NPS scores provided no additional predictive value when these factors were included. These models provide valid quantitative tools for indirect cognitive assessment when in-person testing is impossible.

Journal of Clinical Medicine doi: 10.3390/jcm15134944

Authors: Seihee Min Jiwon Han Joo Youn Oh Jeong-Hwa Seo

Background/Objectives: To evaluate whether gabapentin pretreatment modulates neuronal excitability and attenuates second-eye hyperalgesia in patients undergoing sequential bilateral cataract surgery under monitored anesthesia care with retrobulbar block. Methods: We conducted a prospective, parallel-group, randomized controlled trial with blinded outcome assessors at a tertiary university hospital. Patients aged > 60 years undergoing elective sequential bilateral cataract surgeries with a 1-week interval were enrolled. Participants were randomized 1:1 to receive gabapentin (100 mg three times daily for 1 week between surgeries) or no pretreatment. The primary outcome was the incidence of hyperalgesia, defined as greater intraoperative pain during the second-eye surgery compared to the first. Secondary outcomes included preoperative anxiety level, intraoperative and postoperative pain score, opioid rescue requirements, and surgeon/patient satisfaction for first- and second-eye surgeries. Results: Sixty-four patients (128 eyes) were included and analyzed (31 per group). Hyperalgesia was lower in the gabapentin pretreatment group than in the control group (4 [12.9%] vs. 17 [54.8%], risk ratio 0.24, 95% confidence interval 0.09–0.63, p = 0.001). Maximum intraoperative pain significantly decreased from the first to the second surgery in the gabapentin pretreatment group, whereas it increased in the control group (mean difference [standard deviation], −1.48 [2.14] vs. 0.97 [1.96], p < 0.001). Preoperative anxiety improved similarly in both groups before the second surgery. Conclusions: Gabapentin pretreatment may represent a promising strategy for reducing second-eye hyperalgesia and improving perioperative pain-related outcomes in older patients undergoing sequential bilateral cataract surgery under monitored anesthesia care with retrobulbar block.

Journal of Clinical Medicine doi: 10.3390/jcm15134943

Authors: Aditya Desai Simran Gill Aparna Manoj Naishal Mandal Haidar Hajeh Darshi Desai Haresh Gandhi Prabhdeep Sethi James Blankenship Tanawan Riangwiwat

Objectives: Severe aortic stenosis (AS) with cardiogenic shock (CS) presents a complex clinical challenge. For these patients, the optimal management strategy—either direct transcatheter aortic valve replacement (TAVR) or a staged approach with balloon aortic valvuloplasty (BAV) as a bridge to TAVR (BAV-TAVR)—is uncertain. We aimed to compare the outcomes of these two strategies. Methods: We conducted a retrospective cohort study using the TriNetX database. In this study, we identified patients with CS who underwent direct TAVR or who survived to and underwent TAVR within 30 days of balloon aortic valvuloplasty (BAV-TAVR). After matching propensity scores, 198 patients were analyzed in each group (total of 396). The primary outcome was major adverse cardiovascular events (MACE) at 30 days, 1 year, and 3 years. Results: The analysis included 396 matched patients (198 in each cohort). There was no significant difference in the primary endpoint of MACE at 30 days between the staged BAV and direct TAVR groups HR 1.14 (95% CI 0.79–1.64; p = 0.48), and this finding was consistent at 1 and 3 years with HR 1.20 (95% CI 0.89–1.61; p = 0.23) and HR 1.17 (95% CI 0.89–1.53; p = 0.25) respectively. Similarly, no differences were observed in secondary outcomes including all-cause mortality, stroke, and new permanent pacemaker implantation, at 30 days, 1, and 3 years. Conclusions: Among patients with severe AS and cardiogenic shock who survived definitive therapy, staged BAV-TAVR showed no detectable difference in short- or long-term outcomes versus direct TAVR. Given the limited sample size and the exclusion of patients who did not survive to TAVR, these results are hypothesis-generating and should not be read as evidence of equivalence or of bridging safety; prospective study is warranted.

Journal of Clinical Medicine doi: 10.3390/jcm15134942

Authors: Myriam Calle Rubio Soha Esmaili Iman Esmaili Medardo Montenegro María de la Rivera Lorenzo Andrés Teresa Carro García Yolanda Fernández Martín Juan Luis Rodríguez Hermosa

Background: Although single-inhaler triple therapy (SITT) improves COPD control, the specific structural and behavioral predictors of short-term clinical response following therapeutic simplification remain incompletely characterized. Methods: This prospective, multicenter observational study (N = 684) evaluated patients switching from triple therapy regimens involving multiple inhalers to SITT. A clinically meaningful response was defined as an intra-individual reduction of ≥2 points in the validated RADAR score at three months. Results: Therapeutic simplification reduced regimens requiring ≥4 inhalations/day from 46.1% to 14.3%, and poor behavioral adherence from 45.2% to 16.6%. Multivariable models identified an observed responder profile: higher baseline RADAR burden was the strongest predictor of improvement (aOR 2.00), whereas severe airflow limitation (FEV1 < 50%) attenuated the response. Exploratory mediation analysis indicated that 88.6% of the observed clinical stabilization was not explained by measured adherence changes, and may therefore also encompass unmeasured behavioral, educational or device-related factors. Patients burdened with both high complexity and poor adherence showed the highest rate of combined structural–behavioral improvement (25.0% vs. 4.7% overall). Conclusions: Switching from MITT to SITT was associated with reduced treatment complexity, improved adherence profiles, and short-term improvement in RADAR-defined clinical control. Patients with greater baseline RADAR burden and regimen complexity showed larger observed improvements.

Journal of Clinical Medicine doi: 10.3390/jcm15134941

Authors: Henrike Deissner Benedikt Niedermaier Raffaella Griffo Cosmas Wimmer Markus Polke Franziska C. Trudzinski Florian Eichhorn Marc A. Schneider Kadriya Yuskaeva Hauke Winter Laura V. Klotz

Objectives: Catamenial pneumothorax (CP) is a rare but clinically relevant cause of spontaneous pneumothorax (SP) in women and is associated with high recurrence rates. We hypothesized that CP is underrecognized in routine surgical practice due to an incomplete clinical assessment rather than an absence of characteristic intraoperative findings. Methods: We conducted a retrospective single-center analysis of all patients undergoing surgical treatment for pneumothorax between 2000 and 2025. Female patients with SP and no structural lung disease were identified and systematically evaluated for features suggestive of CP. Demographic, clinical, intraoperative, and outcome data were compared between patients with and without CP. Results: Among 4581 surgically treated pneumothoraces, 1253 (27.4%) occurred in women. Of these, 211 cases of SP without structural lung disease were analyzed. CP was identified in 15 cases among 14 patients (7.1%). Patients with CP were older at initial diagnosis (median 39 vs. 32 years; p = 0.0264) and exhibited higher recurrence rates (92.9% vs. 42.4%; p = 0.0003). A temporal association with menstruation was documented in 57.1% of CP cases, while in 35.7% no such assessment had been performed. Intraoperative findings suggestive of thoracic endometriosis were present in 85.7% of CP patients, whereas histological confirmation was achieved in only 14.3%. Conclusions: CP is likely underdiagnosed in surgical cohorts of women with SP. The principal diagnostic limitation appears to be incomplete history-taking rather than lack of intraoperative evidence. Given the high recurrence risk and limited efficacy of surgery alone, systematic assessment of menstrual association and interdisciplinary management are essential to optimize outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15134940

Authors: Petra Magdalena Kes Anđela Krndelj Stella Jurić Ena Hadžović Nikolina Bašić Jukić Vlaho Brailo

Background/Objectives: Chronic kidney disease (CKD) is associated with numerous oral manifestations that may negatively affect quality of life, nutrition, and overall health. This narrative review aimed to summarize current evidence regarding oral manifestations of CKD and kidney transplantation, examine their proposed underlying mechanisms, and discuss implications for dental management. Methods: A structured literature search of PubMed/MEDLINE was conducted for English-language publications from January 2000 to March 2026. Original studies, systematic reviews, meta-analyses, clinical guidelines, and relevant narrative reviews were included. Additional references were identified through manual screening of bibliographies. Results: Oral manifestations associated with CKD include xerostomia, periodontal disease, oral infections, anemia-related mucosal pallor, developmental enamel defects, and medication-related gingival overgrowth. Kidney transplant recipients are additionally at risk of opportunistic infections and oral malignancies related to long-term immunosuppressive therapy. While oral diseases, particularly periodontal disease and oral infections, may contribute to systemic inflammation, much of the available evidence remains observational. Similarly, many recommendations for dental management are based on expert consensus and clinical experience rather than high-quality interventional studies. Conclusions: Oral complications are common throughout the CKD continuum and warrant regular assessment and preventive care. Multidisciplinary collaboration is essential, while further prospective studies are needed to strengthen the evidence base for clinical management.

Journal of Clinical Medicine doi: 10.3390/jcm15134939

Authors: Jacek Rożko Paweł Piotr Grab Michał Szałwiński Dominika Zawadka-Modras Maria Sobol Bartosz Startek Dariusz Jurkiewicz Aldona Chloupek

Background/Objectives: Postoperative remodeling and positional deviations of the mandibular coronoid process (CP) after orthognathic surgery remain insufficiently characterized, particularly in three-dimensional analyses. The aim of this study was to evaluate qualitative and quantitative CP changes following bimaxillary orthognathic surgery using a deep learning-assisted three-dimensional workflow. Methods: This retrospective study included 75 patients treated with combined orthodontic–surgical therapy, including 25 patients with skeletal Class II malocclusion and 50 patients with skeletal Class III malocclusion. Preoperative and 6-month postoperative computed tomography scans were analyzed. Automatic segmentation and three-dimensional reconstruction were performed using a convolutional neural network based on the nnU-Net architecture. Qualitative assessment included evaluation of CP displacement patterns and visualization of local surface differences using heat maps. Quantitative analysis included volumetric assessment of preoperative and postoperative CP models, calculation of apposition-compatible (Vapo) and resorption-compatible (Vres) volumetric changes, and mixed-effects modeling accounting for within-patient correlations. Results: Medial displacement of the CP predominated in both skeletal classes and was more frequent in Class III patients. Qualitative surface analysis demonstrated a consistent location-dependent remodeling pattern, characterized by predominant apposition-compatible changes on the lateral and medial surfaces and predominant resorption-compatible changes along the anterior border. Quantitative analyses revealed an overall positive remodeling balance, although substantial inter-individual variability was observed. Mixed-effects analyses demonstrated no significant overall effects of side or skeletal class on volumetric remodeling; however, a significant interaction between side and skeletal class was identified for net remodeling balance. A significant random patient effect indicated considerable variability in remodeling response among individuals. Conclusions: AI-assisted three-dimensional analysis enables a reproducible assessment of postoperative CP remodeling following orthognathic surgery. Coronoid process remodeling is characterized by heterogeneous, location-dependent surface changes and substantial inter-individual variability. The observed remodeling patterns are compatible with adaptive responses to altered postoperative biomechanical conditions, although the underlying biological mechanisms remain to be clarified.

Journal of Clinical Medicine doi: 10.3390/jcm15134938

Authors: Sang Youp Han Sang Hyub Lee Jae Won Jang Yong Eun Cho Choon Keun Park Sang Won Lee

Objective: Perform endoscopic surgery for radiculopathy caused by compression fractures and evaluate the results. Methods: A total of 20 patients who underwent biportal endoscopic foraminotomy and unilateral screw fixation using a dynamic rod for radiculopathy secondary to osteoporotic compression fractures were included in this study. All surgeries were performed between July 2021 and January 2025. Patient demographic data, operated level, length of hospital stay, intraoperative blood loss, and operative time were reviewed. Radiological follow-up included assessment of segmental kyphosis, scoliosis, subsidence, and adjacent-level fractures. Complications and pain patterns—separately evaluated for back pain and radiculopathy—were assessed using the visual analog scale (VAS) preoperatively and during follow-up. Only single-level cases were included. Patients with infections, significant stenosis, instability, tumors, prior revision surgery, multilevel pathology, or ambiguous symptoms were excluded. Results: The mean age of the patients was 78.8 years (range, 69–89 years), reflecting an elderly cohort. The mean follow-up period was 13.0 ± 11.9 months (range, 1–41 months). The mean operative time was 164.8 ± 25.7 min, and the mean hospital stay was 10.2 ± 4.6 days (range, 4–25 days). The mean intraoperative blood loss was 126.5 ± 77.6 mL (range, 50–400 mL). One female patient developed postoperative pneumonia, which resolved after appropriate treatment; no other medical complications were observed. Radiculopathy improved significantly immediately after surgery and continued to improve during follow-up. Back pain also improved, but tended to persist to a mild degree. Radiologic evaluation revealed no significant changes in segmental lordosis, and there were no cases of subsidence, scoliosis, or symptomatic screw loosening during the available follow-up period. Conclusions: Biportal endoscopic foraminotomy with unilateral screw fixation may be an effective solution for radiculopathy caused by compression fractures.

Journal of Clinical Medicine doi: 10.3390/jcm15134937

Authors: Jaemin Lee Jun Suh Moon Doo Sup Kim

Background/Objectives: Evidence on spinal versus general anesthesia in unilateral total knee arthroplasty (TKA) may not extend to one-week-staged bilateral surgery, where older patients receive two anesthetics in a short interval and intra-operative spinal-to-general conversion is common but rarely reported transparently. We compared peri-operative acute kidney injury (AKI) and transfusion between strategies in this setting. Methods: We retrospectively analyzed 207 patients (414 surgeries) undergoing one-week-staged bilateral primary TKA at one center. Co-primary endpoints were creatinine-based AKI (patient level) and packed-red-blood-cell transfusion (surgery level). Because 42 general-anesthesia-classified surgeries had an attempted spinal injection, the primary analysis used the initial anesthetic plan (an intention-to-treat analogue), reclassifying these as spinal, with as-treated classification as a sensitivity analysis; AKI was modeled at the patient level (any general anesthesia versus spinal–spinal) and transfusion per surgery. Results: Median age was 75 years and 82.6% were female; AKI affected 74 of 207 patients (35.7%) and transfusion 185 of 414 surgeries (44.7%). The adjusted any-general-anesthesia versus spinal–spinal estimate was not statistically significant and opposite the spinal-protective hypothesis (adjusted odds ratio 0.49, 95% confidence interval 0.23–1.01, p = 0.054), and no pre-specified sensitivity scenario survived Benjamini–Hochberg correction. Transfusion did not differ between strategies; among secondary endpoints, length of stay, hemoglobin drop, peak C-reactive protein, and intra-operative hypotension likewise showed no significant difference after multiplicity correction. Conclusions: These hypothesis-generating findings do not support changing anesthetic practice; the choice should remain individualized. Approximately 12% of attempted spinal anesthetics converted intra-operatively to general anesthesia—a record-based observation, not a validated failure rate.

Journal of Clinical Medicine doi: 10.3390/jcm15134936

Authors: Kyoung-Chan Park Hyo-Joon Kim Ji-Su Oh Seong-Yong Moon

Background/Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of antiresorptive and antiangiogenic therapies, and identifying specific risk factors for recurrence remains a significant clinical challenge. This study aimed to evaluate the clinical characteristics and independent risk factors for recurrence in a large-scale cohort of MRONJ patients. Methods: This single-center retrospective study analyzed 812 patients diagnosed with MRONJ according to the 2022 AAOMS criteria at Chosun University Dental Hospital between 2020 and 2024. Demographic, clinical, radiographic, and medication-related variables were collected. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors associated with recurrence. Results: The majority of patients were female (89.9%), with a mean age of 72.9 years, and mandibular involvement was most frequent (70.8%). Tooth extraction was the most common local precipitating factor (47.0%). The overall recurrence rate was 10.1%. Multivariate analysis identified bilateral jaw involvement (OR = 4.555, p = 0.006), mandibular ramus involvement (OR = 8.222, p = 0.008), and systemic liver disease (OR = 3.703, p = 0.037) as significant independent risk factors. Conversely, routes of prior antiresorptive medication administration involving intravenous-only or combined oral/intravenous therapy, as well as hyperlipidemia and a history of dental implant surgery, were associated with lower recurrence rates. Conclusions: Anatomical complexity and systemic health status are critical predictors of MRONJ recurrence. Patients presenting with bilateral or mandibular ramus involvement, or with compromised liver function, require more aggressive surgical debridement and individualized treatment planning to reduce the risk of recurrence. Given the small affected subgroups, the effect sizes for mandibular ramus involvement and liver disease should be interpreted with caution.

Journal of Clinical Medicine doi: 10.3390/jcm15134935

Authors: Arwa S. Almasaudi Manal Naseeb Eram Albajri Rana H. Mosli Nora Trabulsi Abdurahman Almasaudi Rouba Khalil Naaman Layan Adawi Raghad Almazam Basmah Serhan Hebah A. Kutbi

Background: Nutritional deterioration and systemic inflammation are prevalent in cancer patients undergoing chemotherapy and may independently impair health-related quality of life (QoL). Yet their simultaneous, domain-specific contributions to QoL remain poorly characterized, particularly in Middle Eastern populations. Methods: This cross-sectional study included adult cancer patients receiving chemotherapy. Medical records were used to collect clinical and laboratory data. Structured interviews were conducted to assess nutritional status using the Malnutrition Universal Screening Tool (MUST) and quality of life using the EORTC QLQ-C30 questionnaire. The NLR was calculated as an indicator of systemic inflammation. Multiple linear regression models, adjusted for age, sex, cancer site, stage, and treatment cycle, were used to examine independent associations with QoL domains. Results: Nearly 60% of patients were at a medium-to-high malnutrition risk and 27.1% exhibited high systemic inflammation (NLR > 3). The NLR was significantly associated with greater dyspnea (B = 28.4, p = 0.001), and the MUST was significantly associated with greater appetite loss (B = 17.0, p = 0.001). Additional significant associations included the NLR with poorer physical functioning (p = 0.009) and role functioning (p = 0.012), and the MUST with nausea and vomiting (p = 0.039). In the multivariate analysis, the NLR showed a statistically significant overall effect on the QoL profile (p = 0.007), while the MUST did not (p = 0.281), consistent with its more domain-specific pattern. Conclusions: This cross-sectional study suggests that systemic inflammation and nutritional risk are associated with domain-specific quality of life among cancer patients receiving chemotherapy. The NLR and MUST may represent accessible, complementary indicators of patient vulnerability and supportive care needs. Prospective multi-center studies are warranted to validate these associations and determine their clinical utility in supportive oncology practice.

Journal of Clinical Medicine doi: 10.3390/jcm15134933

Authors: Dong Wan Kim Heui Ro Na Seung Hyun Kim Jun Ho Choi Jae Ha Hwang Kwang Seog Kim

Background: Foot degloving injuries are associated with extensive soft-tissue disruption, compromised perfusion, and a high risk of flap necrosis. Hyperbaric oxygen therapy (HBOT) is known to enhance tissue oxygenation and support flap survival; however, its application in pediatric patients may be limited due to poor cooperation, intolerance to chamber-based treatment, and limited accessibility. Case Presentation: A 7-year-old girl presented with a crush injury to the left foot after being run over by a vehicle, resulting in severe soft-tissue damage. Evaluation revealed a dorsal foot degloving injury, a proximal phalanx fracture of the great toe, and dislocations of the fourth proximal interphalangeal and fifth distal interphalangeal joints. Emergency surgery included open reduction, K-wire fixation, debridement, and artificial dermal grafting using Pelnac. On postoperative day 1, the flap showed signs of compromised perfusion. As HBOT was not feasible, topical oxygen therapy using Natrox was applied continuously for 17 days. Serial wound assessments demonstrated gradual improvement in flap viability. Although ischemic changes developed in the toes, necrosis remained superficial and was successfully managed with local debridement and dressings. Residual skin defects with partial necrosis were treated with split-thickness skin grafting, which healed without major complications. The patient resumed ambulation after splint removal. Conclusions: In pediatric patients with compromised flaps in whom HBOT is not feasible, topical oxygen therapy may serve as a practical adjunctive treatment option. Although its independent effect cannot be established in a single case, this report suggests its potential role in flap salvage and in limiting tissue necrosis.

Journal of Clinical Medicine doi: 10.3390/jcm15134934

Authors: Mustafa Lutfi Yavuz Pelin Karaca Ozer Elif Ayduk Govdeli Mehmet Aydoğan Mehmet Akif Parlar Samim Emet Ali Elitok Fehmi Mercanoglu

Background/Objectives: Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents a heterogeneous clinical entity in which patients exhibit symptoms and biomarker evidence of myocardial infarction despite the absence of significant coronary stenosis. This study aimed to evaluate the diagnostic and follow-up value of left ventricular global longitudinal strain (LV-GLS) in patients with MINOCA and to investigate its association with inflammatory and glycemic biomarkers. Methods: A total of 287 patients presenting with acute coronary syndrome were prospectively enrolled. Based on coronary angiographic findings, patients were classified into two groups: myocardial infarction with obstructive coronary arteries (MIOCA; ≥50% stenosis, n = 237) and MINOCA (<50% stenosis, n = 50). In addition, an ischemic control group without obstructive disease (INOCA, n = 50) was included for comparative analysis. Laboratory tests, echocardiography, and LV-GLS were assessed at baseline and at 3 months. Results: Baseline left ventricular ejection fraction (LVEF) and LV-GLS were significantly lower in MIOCA compared with MINOCA (LVEF: 52.9 ± 10.3% vs. 59.7 ± 8.7%, p < 0.001; LV-GLS: −11.46 ± 4.84% vs. −12.63 ± 6.33%, p = 0.007, respectively). At 3 months, LVEF remained lower in the MIOCA group (57.5 ± 6.6% vs. 62.0 ± 7.9%; p < 0.001, respectively), whereas LV-GLS improved similarly in both groups with no significant difference (−15.27 ± 2.60% vs. −14.87 ± 5.21%; p = 0.29, respectively). Among MINOCA patients, the neutrophil-to-platelet ratio (NPR) (p = 0.017) and admission glucose (p = 0.047) were independently associated with impaired LV-GLS (defined as values greater than −16%). Conclusions: Although LVEF remained higher in MINOCA patients during follow-up, LV-GLS impairment persisted at levels comparable to those observed in MIOCA, suggesting ongoing subclinical myocardial dysfunction. LV-GLS offers superior diagnostic sensitivity to LVEF. Inflammatory and glycemic markers may aid in early risk stratification and guide management in patients with MINOCA.

Journal of Clinical Medicine doi: 10.3390/jcm15134932

Authors: Yman Kamgaing Wappi Austin Cheng Alexander Dymond Soroush Baghdadi William Oppenheim

Background/Objectives: Cerebral palsy (CP) hip displacement requires longitudinal surveillance, frequently imposing significant burden on caregivers. While Multimodal Large Language Models (MLLMs) offer a potential solution to the health literacy gap, their accuracy in interpreting pediatric pelvic radiographs remains unproven. This study evaluates the effectiveness and safety of MLLMs in addressing caregiver concerns regarding CP hip management. Methods: Fifteen deidentified pediatric pelvic radiographs representing a spectrum of hip displacement severities were processed through three MLLMs: GPT-4o, Claude 3.5, and Gemini 1.5 Pro. Nine standardized caregiver prompts (n = 95 total responses per model) were utilized to simulate common clinical queries. Outcome measures included response word count, interactive characteristics, frequency of medical disclaimers, and diagnostic accuracy. Results: Quantitative analysis revealed that Claude 3.5 produced significantly shorter responses compared to other models (p < 0.01). GPT-4o demonstrated the highest safety alignment, with a 96.9% disclaimer rate, significantly exceeding Claude (60.0%) and Gemini (76.8%) (p = 0.03). Diagnostic “hallucinations” were observed, notably Claude misidentifying non-operative cases as bilateral hip replacements. While management recommendations were clinically relevant, they remained generic rather than patient-specific, failing to measure or apply migration percentage thresholds. Encouragingly, all models consistently directed users to consult an orthopaedic surgeon. Conclusions: MLLMs represent an opportunity to enhance health literacy by providing accessible management summaries and emphasizing professional consultation. However, significant radiographic hallucinations and a lack of specific, evidence-based guidance preclude their use as standalone diagnostic tools. Currently, MLLMs should be viewed as educational adjuncts requiring expert oversight in the pediatric orthopaedic care continuum.

Journal of Clinical Medicine doi: 10.3390/jcm15134931

Authors: Lisa Goudman Maarten Moens

Background/Objectives: Chronic pain is increasingly conceptualized as a systemic condition characterized by central sensitization, autonomic dysregulation, and persistent neuroimmune and neuroendocrine alterations. These systemic changes have been linked to microbial dysbiosis, most prominently within the gut microbiome. In contrast, the relevance of the urinary microbiome outside primary urological disease remains poorly understood, particularly in non-urological chronic pain conditions. The objective of this study was to determine whether patients with chronic low back pain exhibit differences in urinary microbial diversity, community composition, or taxon-specific abundance compared with pain-free controls. Methods: In this age- and sex-matched case–control study, midstream urine samples were collected from ten patients with chronic low back pain and ten pain-free controls and analyzed using 16S rRNA gene sequencing (V4 region). Sequence data were processed using nf-core/ampliseq and DADA2. Alpha diversity, beta diversity, and differential abundance were assessed using depth-adjusted models, compositional and phylogenetically informed distance metrics, and ANCOM-BC2, with multiple sensitivity analyses to account for the low-biomass nature of urinary microbiome data. Results: After accounting for sequencing depth, no significant differences in alpha diversity were observed between patients and controls for any metric. Beta diversity analyses revealed no significant differences in overall community composition between groups across all distance measures, and dispersion was comparable between groups. Differential abundance analysis did not identify any bacterial taxa that differed significantly between patients and controls after correction for multiple testing. Conclusions: In this cohort, chronic low back pain was not associated with detectable alterations in the urinary microbiome. These findings suggest that, unlike the gut microbiome, urinary microbial communities may be relatively stable in the context of non-urological chronic pain, highlighting the importance of phenotype specificity and multidimensional approaches in microbiome-based pain research.

Journal of Clinical Medicine doi: 10.3390/jcm15134930

Authors: Nicole Speziali Giuseppe Verolino Paolo Ghiso Basile Roberto Adriano Latini Davide Sala Dario Calderone

Background: Spontaneous coronary artery dissection (SCAD) is a rare non-atherosclerotic cause of acute coronary syndrome (ACS), and recent studies have shown a significant involvement in young women with few or no cardiovascular risk factors. The pathogenesis is multifactorial, possibly related to genetic causes, hormonal imbalances or peripartum. Methods and results: A 45-year-old woman was admitted to the emergency room for anterior myocardial infarction. Coronary angiography showed a long, diffuse tapering involving mid to distal left anterior descending (LAD) segments, with haziness in the mid-LAD. Intravascular ultrasound was used, highlighting the presence of intramural hematoma and leading to medical management. Hematological samples revealed a diagnosis of hyperthyroidism; this detection prompted an evaluation of a possible association with SCAD. Echocardiography revealed a preserved ejection fraction with akinetic apex and a sessile thrombus leading to anticoagulant with warfarin. Discussion: SCAD is a rare cause of ACS, difficult to recognize and whose physiopathology is not fully understood. In our case report we highlight the possible link between SCAD and hyperthyroidism. The lack of specific guidelines, the concomitant presence of hyperthyroidism and apical thrombus forced us toward a multidisciplinary management approach, with a meticulous evaluation of risks and benefits to offer the best therapeutic option.

Journal of Clinical Medicine doi: 10.3390/jcm15134929

Authors: Adam Gryko Anna Kurasz Jolanta Małyszko Sławomir Dobrzycki Łukasz Kuźma

Background/Objectives: Air pollution is associated with many adverse health consequences, including deteriorated kidney function. The aim of the research was to determine the association of medium-term exposure to air pollutants and hospitalizations due to acute kidney injury (AKI). Methods: The retrospective population-based study was conducted on the EP-PARTICLES cohort between 2011 and 2020 (80,000,000 person-years). We estimated municipality-specific associations between air pollution and AKI admissions using generalized additive models with Poisson regression. Results are reported as risk ratio in AKI admissions (RR) with corresponding 95% confidence intervals (95% CI). Results: During the 10-year study period, 47,467 AKI cases were reported (median age 77 years, IQR 68–84; 51.2% women). Mean concentrations of pollutants were 21.4 µg/m3 (SD 5.2) for particulate matter with a diameter of 2.5 μm or less (PM2.5), 7.5 µg/m3 (1.8) for nitrogen dioxide (NO2), and 1.8 ng/m3 (0.8) for benzo[a]pyrene (BaP). In mid-term exposure analyses (lag 0–30), each 10 µg/m3 increase in PM2.5, PM10, NO2 and CO, and each 1 µg/m3 increase in BaP, was associated with higher AKI risk, with the strongest effect observed for NO2 (RR 1.066, 95% CI 1.033–1.099). No association was found for SO2. Subgroup analyses showed consistent directions of association across sex and age groups, with NO2 remaining the most detrimental pollutant. Although statistical significance varied between pollutants, no significant effect modification by sex or age was observed (p > 0.05). Conclusions: Mid-term exposure to ambient air pollution is associated with an increased risk of AKI-related hospitalizations, with NO2 showing the strongest effects. These findings identify mid-term exposure as a relevant temporal window and support the role of air pollution as a modifiable risk factor for AKI.

Journal of Clinical Medicine doi: 10.3390/jcm15134928

Authors: Vincenzo Calabrese Maria Rita Stancanelli Maria Eva Sberna Giovanni Taverna Giulio Geraci Valeria Cernaro Domenico Santoro

Background: The 2022 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest the use of Renin–angiotensin–aldosterone system inhibitors (RAASIs) in chronic Kidney Disease (CKD) stages IV–V, in contrast to the 2012 KDIGO guidelines, which discouraged it. This study aims to assess the impact of RAASIs on kalemia and mortality in a large sample of dialysis patients, where longitudinal data remain scarce, comparing traditional statistical methods with machine learning (ML) algorithms. Methods: This observational longitudinal analysis included 4764 hemodialysis (HD) patients from the Sicilian Registry of Nephrology, Dialysis and Transplantation, with a total of 56,964 longitudinal measurements. We evaluated the impact of RAASIs on serum potassium levels and all-cause mortality in the dialysis setting, comparing traditional statistics and ML. Linear Mixed Models (LMM) and Cox models with mixed effects were used for longitudinal and survival analyses. These were compared with ML approaches, including Random Forest (RF) for potassium variability and Lasso-regularized models for mortality, using four-fold cross-validation. Results: The study included 4764 patients, of whom 1207 (25%) were treated with RAASis. The mean age was 66 ± 15 years, 62% were male, 33% were diabetic, and a history of arterial hypertension was reported in 74% of patients. Hyperkalaemia at baseline was present in 1848 patients. The longitudinal model showed a statistically significant increase in kalemia [adjβ = 0.10 mmol/L, 95%CI 0.05/0.15, p < 0.001], but it was clinically negligible. Indeed, RF did not detect RAASIS as a relevant variable. Association between RAASIs and mortality was not detected either with Cox or ML models. Furthermore, the RF model outperformed traditional LMMs in explaining total potassium variability (56% vs. 43%). Conclusions: RAASI therapy in HD patients is associated with a minimal, non-clinically significant increase in serum potassium and does not impact all-cause mortality. The integration of ML reinforces the robustness of these findings, supporting the safety of RAASIs in the dialysis setting.

Journal of Clinical Medicine doi: 10.3390/jcm15134927

Authors: Nadhirah Mohd Shakri Mawaddah Azman Qi Shen Chua Ahmed Geneid Marina Mat Baki

Objective: To evaluate the clinical outcome, safety and efficacy of the APrevent Vocal Implant System (VOIS) in patients with unilateral vocal fold paralysis (UVFP), with particular emphasis on the timing and impact of postoperative saline adjustments. Methods: This retrospective−prospective longitudinal study included 11 patients with chronic UVFP who underwent VOIS medialization thyroplasty (MT) under local anesthesia (n = 2) and general anesthesia (n = 9). Multidimensional voice parameters were analyzed preoperatively and at 1, 3, 6, and 12 months postoperatively. Statistical analyses included the Friedman test for repeated measures and the comparison of outcomes between pre- and each postoperative timepoints was evaluated with the Wilcoxon signed-rank test. Results: Significant and sustained improvements were observed across all multidimensional voice parameters. Mean mVHI-10 decreased from 31.7 ± 4.5 preoperatively to 5.8 ± 5.1 at 12 months, while mean MPT increased from 7.1 ± 3.8 to 14.4 ± 4.5 s (p < 0.05, r > 0.7). Acoustic parameters, including jitter, shimmer, and NHR, demonstrated progressive improvement over 12 months. A high proportion of patients (72.73%) underwent postoperative saline adjustment at a mean interval of 6.23 ± 1.23 months, beyond the early postoperative edema phase, with each adjustment yielding further enhancement in voice outcomes. No major complications, including airway obstruction or hematoma, were observed. Conclusions: VOIS MT is safe and effective, providing sustained improvements in multidimensional voice outcomes. The ability to perform postoperative saline adjustments enables dynamic optimization of glottal closure, reducing the need for revision surgery and addressing evolving laryngeal biomechanics. These findings support VOIS as a flexible, adjustable alternative to static medialization techniques and provide dynamic voice optimization in patients with UVFP.

Journal of Clinical Medicine doi: 10.3390/jcm15134926

Authors: Anthia Chasiakou Stamatia Chasiakou George Kaparos Vasiliki-Georgia Prifti Stiliani Demeridou Athanasios Tsakris Stavroula Baka

Background: Aerobic vaginitis (AV) is characterized by dysbiotic vaginal microflora with overgrowth of aerobic pathogens of enteric origin, presence of vaginal inflammation and immature epithelial cells. This study aimed to evaluate, over a period of 10 years, women of reproductive age (non-pregnant and pregnant) as well as menopausal women affected by AV. Methods: We included non-pregnant, pregnant and menopausal women diagnosed with AV over a period of 10 years. Diagnosis of AV was determined according to the criteria proposed by Donders in 2002. The isolated pathogens were identified with the rapid identification system I-dOne (Alifax S.r.l, Polverara, Italy) and the automated system VITEK2 (Biomerieux, Marcy l’Etoile, France), which was used for antimicrobial susceptibility testing. Results: The overall aerobic vaginitis prevalence rate during the studied period was 9.5%. The most common isolated pathogens were Escherichia coli 27.3%, Enterococcus faecalis 25.0%, Streptococcus agalactiae 22.2%, Klebsiella pneumoniae 8.9%, Proteus spp 4.7%, and Staphylococcus aureus 3.5%. E. coli infection significantly increased the odds of mild AV by 1.65 times (p = 0.002) and Proteus species infection was over 6 times more likely to progress to severe disease (p < 0.001). Furthermore, pregnant women were more likely to be infected with E. faecalis (p < 0.001) while menopausal women were diagnosed significantly more with severe AV (p < 0.001) compared to the other groups. Conclusions: The prevalence of aerobic vaginitis in the population studied was in concordance with global rates. Menopausal women displayed increased severe AV cases while, in contrast, mild cases were recorded during pregnancy. The most commonly isolated pathogens were of enteric origin.

Journal of Clinical Medicine doi: 10.3390/jcm15134925

Authors: Lu Xing Biru Luo Yuqing Song Huaping Fu Wen Zhao Xue Deng

Objective: To analyze the perceived facilitators and barriers promoting and hindering the clinical application of the best evidence of clean intermittent catheterization (CIC) in patients after radical hysterectomy (RH). Methods: This study employed a convergent parallel mixed-methods design. Participants included patients undergoing CIC after RH, medical and nursing practitioners and managers in the gynecological department and outpatient clinics at a tertiary-level women’s and children’s hospital in Chengdu. They were included in both components separately. Interview data were managed using Nvivo 11.0 software and analyzed through directed content analysis. Quantitative data were analyzed using SPSS 29.0 statistical software. Results: A questionnaire survey was conducted among 156 healthcare providers and 300 patients. Qualitative interviews were conducted with 11 healthcare workers and 12 patients. At the evidence itself level, evidence meeting clinical needs and evidence lacking practical applicability, respectively, promoted and hindered clinical implementation of the best evidence. At the potential adopters’ level, healthcare professionals’ insufficient professional competence, low willingness to promote implementation, numerous concerns, and lack of autonomy and awareness regarding the importance of the task were significant barriers, but they maintained an overall positive attitude toward the application. At the practical environment level, patient-related perceived barriers predominantly hindered evidence implementation. Additionally, a supportive practice atmosphere, economic feasibility, and talent development opportunities served as key facilitators. However, existing nursing practice content and workflows directly impacted evidence adoption. Conclusions: The promotion and barriers to the clinical application of the best evidence for CIC in RH postoperative patients are multifaceted. Targeted intervention strategies must be developed to facilitate the effective translation of evidence into clinical practice.

Journal of Clinical Medicine doi: 10.3390/jcm15134924

Authors: Arturo Cortes-Telles Yuliana Valeria Priego-Escamilla Diana Lizbeth Ortíz-Farias Saúl Vázquez-López Yuri Noemí Pou-Aguilar Esperanza Figueroa-Hurtado

Background: Dynamic risk stratification is fundamental to the modern management of pulmonary arterial hypertension (PAH). However, data on the impact of sequential add-on therapy in patients with Group 1.4 PAH—particularly in Latin American populations—remains limited. This study evaluated changes in risk classification using COMPERA 2.0 and REVEAL Lite 2 scores in patients treated with endothelin receptor antagonist (ERA) and phosphodiesterase type 5 inhibitor (PDE5i) combination therapy (macitentan + sildenafil) at a referral center in Mexico. Methods: In this single-center, retrospective cohort study, 25 patients with a confirmed diagnosis of PAH between 1st January 2022 and 31st December 2024 were evaluated at baseline and after 24 weeks of treatment. Clinical, functional, and biochemical parameters were recorded. Within-patient changes were analyzed using the Wilcoxon signed-rank test, and agreement between risk assessment tools was assessed using Spearman’s correlation coefficient. Results: At 24 weeks, patients demonstrated significant improvement in World Health Organization functional class (p = 0.002) and a significant reduction in brain natriuretic peptide levels (p = 0.003). Both COMPERA 2.0 and REVEAL Lite 2 scores showed a consistent shift toward lower-risk categories. A strong concordance between the two tools was observed. Conclusions: Sequential add-on ERA + PDE5i therapy was associated with meaningful improvement in risk stratification among patients with Group 1.4 PAH. These findings support the clinical utility of simplified, noninvasive risk assessment tools in real-world settings, particularly in resource-constrained environments.

Journal of Clinical Medicine doi: 10.3390/jcm15134923

Authors: Yahya Faruk Karatas Gulsum Gizem Topal Damla Gumus Mevlude Kizil

Background and Objectives: Sarcopenia is highly prevalent among maintenance hemodialysis (HD) patients, particularly in the presence of diabetes mellitus (DM). Dietary glycemic and insulinemic characteristics may contribute to metabolic disturbances associated with muscle deterioration, although evidence in HD populations remains limited. This study aimed to investigate the associations between dietary indices, sarcopenia, nutritional status, and clinical outcomes in diabetic (DM+) and non-diabetic (DM−) HD patients. Materials and Methods: This cross-sectional study included 92 maintenance HD patients (43 DM+ and 49 DM−). Dietary intake was assessed using three-day food records, and dietary insulin index (DII), dietary insulin load (DIL), dietary glycemic index (DGI), and dietary glycemic load (DGL) were calculated. Sarcopenia was evaluated using handgrip strength, bioelectrical impedance analysis, gait speed, and SARC-F. Anthropometric, biochemical, nutritional, and sarcopenia-related parameters were compared across tertiles of dietary indices. Results: Sarcopenia was identified in 32.6% of patients with diabetes and 36.7% of those without diabetes. Diabetic patients exhibited significantly lower handgrip strength, slower walking speed, longer walking time, and higher SARC-F scores (p < 0.01). Across DGL tertiles in DM+ patients, significant progressive increases were observed in body weight (p < 0.05), body mass index (p < 0.05), lean mass (p < 0.05), mid-upper arm circumference (p < 0.01), and triceps skinfold thickness (p < 0.01). Higher DIL and DGL tertiles were also associated with elevated serum phosphorus, LDL cholesterol, triglycerides, and total cholesterol levels (p < 0.05). DIL and DGL showed stronger associations with overall energy and nutrient intake compared with DII and DGI. However, no significant associations were identified between dietary indices and sarcopenia diagnosis or sarcopenia-related risk indicators after adjustment for age and sex. Conclusions: Dietary indices were associated with various anthropometric, biochemical, and nutritional parameters in HD patients, with more pronounced associations observed among patients with DM, suggesting a potential role of dietary quality in the nutritional and metabolic profile of this population.

Journal of Clinical Medicine doi: 10.3390/jcm15134922

Authors: Zeynep Pinar Keles Yucel Bahattin Avci

Background/Objectives: This study aimed to evaluate the gingival crevicular fluid (GCF) levels of fractalkine/CX3CL1 and CX3CR1 in patients with gingivitis and periodontitis before and after non-surgical periodontal therapy. Methods: A total of 90 individuals comprising 30 with stage 3 periodontitis, 30 with gingivitis, and 30 periodontally healthy, were enrolled in the study. Gingivitis and periodontitis patients underwent non-surgical periodontal treatment. GCF samples were collected at baseline and at 1 and 3 months after treatment. CX3CL1 and CX3CR1 were measured by an ELISA analysis. Results: GCF CX3CL1 and CX3CR1 were significantly elevated in patients with periodontitis and gingivitis compared to healthy controls (p < 0.001). The periodontitis patients also showed higher GCF levels of CX3CL1 and CX3CR1 than those with gingivitis (p < 0.001). Significant decreases in GCF CX3CL1 and CX3CR1 were detected at 1 month after periodontal treatment compared to baseline values in both the gingivitis and periodontitis patients (p < 0.001). Moreover, the periodontitis patients exhibited significant decreases in both CX3CL1 and CX3CR1 levels at 3 months post-treatment compared to 1 month (p < 0.001), whereas no significant changes were observed between the two time points in the gingivitis patients (p > 0.05). Conclusions: Our findings suggest that the CX3CL1–CX3CR1 axis might contribute to the inflammatory processes of periodontal diseases and may represent a treatment-responsive component of the local host response.

Journal of Clinical Medicine doi: 10.3390/jcm15134921

Authors: Montserrat Ribas-Ball Laura González Ekaterine Popova Clara Bordes Patricia Galan Laura Villarino Alfons Gómez Maria Josefa Azpiroz Marcos de Miguel Laura Dos-Subirà Miriam de Nadal

Background/Objectives: Adults with single-ventricle physiology (SVP) represent a growing population with complex cardiovascular conditions and an increasing need for noncardiac surgical and interventional procedures. However, perioperative outcomes in this group remain poorly characterized. This study aimed to provide a descriptive characteristic of perioperative management, complications and mortality in adults with SVP undergoing noncardiac surgical and interventional procedures. Methods: We conducted a retrospective cohort study including all adult patients (≥18 years) with SVP who underwent noncardiac surgical and interventional procedures requiring anesthesia or sedation at a tertiary university hospital between 1 January 1995 and 30 November 2023. Demographic data, comorbidities, type of procedure and anesthetic technique were collected. Complications were defined as intraoperative or postoperative adverse events requiring intervention or associated with hemodynamic, respiratory, or cardiovascular instability. Primary outcomes were perioperative complications and all-cause mortality at 24 h, 30 days, and one year, with mortality reported at the patient level. Results: A total of 114 procedures were performed in 67 patients (mean age 32.3 ± 10.8 years). Most procedures were elective (78.9%) and minimally invasive, frequently performed under sedation, with or without local anesthesia (67.5%). Common comorbidities included arrhythmias (46.3%), liver disease (49.3%), and heart failure (17.9%). The overall complication rate was 6.1% (2.6% intraoperative, 3.5% postoperative). Mortality was 1.5% in 24 h, 2.9% in 30 days and 5.9% at one year. Most clinically relevant adverse events occurred in patients with earlier-stage palliation, advanced functional limitation or multiple comorbidities. Conclusions: Perioperative outcomes in adults with SVP undergoing noncardiac surgical and interventional procedures were acceptable when procedures were elective and managed in specialized settings. Risk remains heterogeneous and appears to be influenced by physiological status and stage of palliation.

Journal of Clinical Medicine doi: 10.3390/jcm15134920

Authors: Faizan Kashoo Shagun Agarwal Naif Ziyad Alrashdi Sultan Alanazi Msaad Alzhrani Ahmad Alanazi Jyoti Sharma Mohammad Sidiq Mehrunnisha Ahmed Mohamed K. Seyam

Background/Objectives: Non-specific low back pain (NSLBP) is the leading cause of disability worldwide. Artificial intelligence (AI) technologies are increasingly being integrated into healthcare interventions for NSLBP, yet their effectiveness remains uncertain. This systematic review and meta-analysis aimed to evaluate the effectiveness of AI-based Physical therapy (PT) interventions on pain intensity and disability outcomes in patients with NSLBP. Methods: We conducted a comprehensive search across six electronic databases. Randomised controlled trials (RCTs) evaluating AI-based interventions for NSLBP were only included. Mean differences (MD) with 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity was assessed using I2 statistics and Cochran’s Q test. Results: Five RCTs (n = 1939) met the inclusion criteria for systematic review. Three RCTs (n = 594 participants) provided data for meta-analysis. AI-based interventions significantly reduced pain (pooled MD −0.721, 95% CI −1.047 to −0.395; z = −4.34, p < 0.001; I2 = 9.5%). Disability also significantly improved (pooled MD −1.031, 95% CI −2.020 to −0.042; t(2) = −4.48, p = 0.046; I2 = 0%). Neither effect reached the minimal clinically important difference (1.0 for pain, 2–4 for disability). No serious adverse events were reported. Conclusions: AI-based PT interventions produce statistically significant but clinically small improvements in pain and disability for NSLBP. Certainty of evidence is low due to risk of bias and imprecision. Larger, blinded RCTs with standardised outcomes are needed.

Journal of Clinical Medicine doi: 10.3390/jcm15134919

Authors: Hadar Gan-Or Shaked Ankol Guy Ben Arie Itay Ashkenazi Yaniv Warschawski

Background: Dedicated artificial intelligence (AI) systems for fracture detection already exist, yet general-purpose multimodal models are increasingly accessible to clinicians despite not being developed or formally validated as medical devices. Their behavior in focused orthopedic imaging tasks remains insufficiently characterized. Purpose: To characterize how two accessible general-purpose multimodal models interpret AP pelvis radiographs with hip fractures, focusing on context dependence, overconfidence, and complementary error patterns within a surgically confirmed positive-only cohort. This was a behavioral characterization study of a fracture-positive cohort, not a diagnostic accuracy evaluation. Methods: In April 2026, we retrospectively studied 214 surgically confirmed hip fractures on AP pelvis radiographs using two general-purpose multimodal models under six prompting conditions. In runs A–D, the models were explicitly told that a hip fracture was present and were asked to classify it; in runs E–F, they were not told whether a hip fracture was present. Each image was rerun de novo in a separate chat session through vendor APIs using a fixed base prompt and no image preprocessing. We recorded hip-fracture detection, correct laterality, coarse fracture pattern, intracapsular displacement, AO/OTA grading, subtrochanteric identification, and self-reported confidence. Because the cohort contained hip fractures only, we report fracture-detection rates and classification performance within a positive-only cohort rather than full diagnostic-accuracy metrics. Results: Using the more conservative endpoint of hip-fracture detection with correct laterality, GPT-5.4 was correct in 79.0% and 86.4% of cases in runs E and F, whereas Gemini was correct in 80.4% and 93.5%, respectively. When outputs from both models were combined, this endpoint reached 89.7% in run E and 96.7% in run F, indicating complementary rather than redundant error patterns. Incorrect laterality cues markedly degraded performance, from 90.7% to 66.4% in GPT-5.4 and from 97.7% to 57.0% in Gemini. Performance remained limited for treatment-relevant subtyping, particularly AO/OTA grading and subtrochanteric identification. Both models frequently remained highly confident when wrong, and self-reported confidence did not reliably distinguish correct from incorrect outputs. Conclusions: Accessible general-purpose multimodal models showed partial capability for coarse hip-fracture interpretation, but they remained context-sensitive, unreliable for treatment-relevant subtyping, and highly confident even when incorrect. Their complementary error patterns are hypothesis-generating rather than evidence of clinical readiness. On the basis of these findings, we do not support unvalidated or uncontrolled clinical use of such models. As access to these tools expands, explicit usage boundaries, minimum performance expectations, repeated local revalidation, and sustained human oversight become increasingly necessary.

Journal of Clinical Medicine doi: 10.3390/jcm15134918

Authors: Justyna Mazurek Adam Wrzeciono Małgorzata Ratajczyk Olga Witczak Joanna Szczepańska-Gieracha Błażej Cieślik

Objective: To evaluate the feasibility of adding antigravity treadmill training (ATT) or harness-based body-weight-supported treadmill training (BWSTT) to standard inpatient rehabilitation after primary hip or knee arthroplasty and to explore preliminary effects on osteoarthritis-related outcomes, balance, and psychological status. Methods: In this single-center, assessor-blinded pilot randomized trial, 60 adults within 3 months after primary hip or knee arthroplasty for osteoarthritis were allocated 1:1:1 to ATT, BWSTT, or standard inpatient rehabilitation over 6 weeks. Feasibility outcomes included recruitment, retention, and adherence. ATT and BWSTT additionally included unloading-based treadmill gait training using lower-body positive pressure or a harness system. Exploratory clinical outcomes included WOMAC total and subscale scores, analyzed using baseline-adjusted ANCOVA estimated marginal means. Secondary exploratory outcomes were BBS, FES-I, PHQ-9, and PSS-10. Results: Post-intervention data were available for 47 participants, with differential attrition across groups. Exploratory ANCOVA suggested between-group differences for WOMAC total (p = 0.004) and WOMAC function (p < 0.001). Compared with standard rehabilitation, ATT showed lower adjusted WOMAC total and function scores (both p < 0.01). ATT versus BWSTT contrasts for WOMAC total and function were statistically significant in the primary exploratory model but attenuated after hypertension adjustment. Exploratory signals were also observed for BBS and FES-I, although FES-I was less robust in sensitivity analysis. No clear between-group differences were observed for WOMAC pain, stiffness, PHQ-9, or PSS-10. No formal multiplicity adjustment was applied across exploratory endpoints. Conclusions: In this single-center pilot randomized trial, ATT suggested preliminary function- and balance-related signals that require confirmation in adequately powered multicenter trials.

Journal of Clinical Medicine doi: 10.3390/jcm15134917

Authors: Min-Chang Jang Chan-Woo Park Sang-Jin Jeong Alhaizaey Ahmed Youn-Soo Park Seung-Jae Lim

Background: Intraoperative periprosthetic femoral fractures (IPFF) represent a concerning and often under-recognized complication in total hip arthroplasty (THA). Although several risk factors have been reported, their association with specific femoral morphology and stem geometry has not been fully addressed. This study aimed to identify the incidence and risk factors for IPFF in THA using cementless tapered stems. Methods: A retrospective review was conducted on 3137 primary THAs (2622 patients) performed with cementless tapered stems at a single institution between February 2011 and August 2018. Femoral morphology was classified according to the Dorr types; A (1425 hips, 45.4%), B (1542, 49.2%), and C (170, 5.4%). Femoral stems were categorized as flat, rectangular, or quadrangular tapered designs. The occurrence of IPFF was identified through surgical records and postoperative radiographs. Multivariate regression analysis was performed to identify independent risk factors for IPFF. The mean age at THA was 55 years (range, 15–96), and 52.9% of the patients were women. Results: The overall incidence of IPFF was 2.2% (69 hips). Non-displaced cracks in the proximal metaphysis (58 hips, 84.1%) were the most common type of fracture. The incidence of IPFF was significantly higher in Dorr type A (3.0%) and type C (4.7%) femurs compared with type B (1.2%) femurs. Multivariate regression revealed that female sex (odds ratio [OR], 1.752; p = 0.032) and Dorr type A (OR, 2.898; p < 0.001) and type C (OR, 4.530; p < 0.001) were significantly associated with IPFF. Additionally, the use of quadrangular tapered stems was associated with a higher risk compared with flat tapered stems (OR, 7.382; p < 0.001). Conclusions: Dorr type A and C femurs, along with female sex and the use of quadrangular tapered stems, were significant risk factors for IPFF. Our findings suggest that preoperative consideration of individual femoral morphology and careful selection of stem design are essential to mitigate the risk of IPFF in THA using cementless tapered stems.

Journal of Clinical Medicine doi: 10.3390/jcm15134916

Authors: Mustafa Çetiner Ayşe Nur Akca Gönül Akdağ Buse Kozlu İrem Yıldırım Abdulhamit Şehid Kılınç Esma Aşık Burcu Kaplan Fahri Şen Nurullah Can Aydoğdu

Background/Objectives: The type of anesthesia in patients with acute stroke is still controversial. This study aimed to investigate the effect of anesthesia management on clinical outcomes in patients with anterior circulation stroke undergoing mechanical thrombectomy. Methods: In this observational, retrospective study, patients with acute anterior circulation stroke who underwent mechanical thrombectomy between January 2021 and March 2025 were retrospectively reviewed. Patients were divided into groups according to the type of anesthesia administered. Functional independence was assessed at 90 days using the modified Rankin Scale. A TICI of 2b or higher was defined as successful reperfusion. In the conscious sedation (CS) and general anesthesia (GA) groups, patients were analyzed based on baseline characteristics and clinical outcomes using Propensity Score Matching. Results: In the propensity score-matched cohort, there was no significant difference between the two groups in terms of good functional outcome (mRS ≤ 2) (p = 0.82). When compared by successful reperfusion rate (TICI 2b or higher), it was significantly higher in the GA group (p = 0.01). Conclusions: In this study, the use of GA resulted in higher recanalization rates in patients with anterior circulation stroke undergoing mechanical thrombectomy. However, no differences were observed between the GA and CS groups in terms of functional outcomes, mortality, or peri-procedural/post-procedural complications.

Journal of Clinical Medicine doi: 10.3390/jcm15134914

Authors: Angelo Carosini Calogero Velluto Maria Ilaria Borruto Laura Scaramuzzo Maurizio Genitiempo Felice Minutillo Giulio Maccauro Luca Proietti

Background: Spinopelvic dissociation secondary to sacral fracture–dislocation is a rare but severe injury, most often resulting from high-energy trauma. Management remains challenging, particularly in adolescents, and the optimal choice between open and percutaneous fixation is still debated. Methods: We present two adolescent cases of traumatic sacral fracture–dislocation with spinopelvic dissociation, one treated with percutaneous fixation and one with open lumbopelvic stabilization both with the use of navigation. The systematic literature review included 29 published studies. Together with the present two-patient case series, the overall analysis comprised 30 studies/series and 739 patients. Data on demographics, mechanisms of injury, neurological involvement, treatment strategies, and outcomes were extracted and analyzed. Results: Case 1 (18 years) was managed with closed reduction and percutaneous fixation, achieving complete neurological and functional recovery at 6 months. Case 2 (14 years) underwent open reduction, decompression, and lumbopelvic fixation, with favorable radiological outcomes but residual sphincter dysfunction at follow-up. In the literature, the weighted mean age was 40.6 years (range 5–91), with 48.6% presenting neurological deficits, most frequently cauda equina syndrome. Surgical management was performed in nearly all cases, with mean time to fixation ranging from 3.6 to 8.6 days. Open techniques were predominantly used in patients with severe displacement or neurological compromise, whereas percutaneous fixation was associated with reduced surgical morbidity and satisfactory neurological recovery in selected patients. Permanent bladder and bowel dysfunction persisted in up to 33% of cases. Conclusions: Spinopelvic dissociation following sacral fracture–dislocation remains a rare and highly unstable injury with frequent neurological impairment. Early surgical stabilization may be beneficial when the patient’s clinical condition permits, and the choice between open and percutaneous fixation should be individualized according to fracture morphology, neurological status, and the need for direct decompression. Our adolescent cases highlight both the potential for complete recovery and the risk of residual dysfunction, reflecting the complexity of these injuries.

Journal of Clinical Medicine doi: 10.3390/jcm15134915

Authors: Francesco Maria Sparasci Luca Raone Mario Iannaccone Cosmo Godino Alessandro Mandurino-Mirizzi

Background/Objectives: Invasive coronary physiology has evolved from a tool for assessing intermediate stenoses to a comprehensive framework for guiding diagnosis and treatment across the spectrum of coronary artery disease (CAD). This review aims to provide an updated, catheterization laboratory-centered overview of contemporary invasive coronary physiology, emphasizing its role in optimizing percutaneous coronary intervention (PCI) and in evaluating patients with angina and non-obstructive coronary arteries (ANOCA/INOCA). Methods: A narrative review of contemporary evidence, including randomized trials, consensus documents, and guideline recommendations, was conducted. Key physiological indices—fractional flow reserve (FFR), non-hyperemic pressure ratios (NHPRs), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR)—were examined alongside emerging tools such as longitudinal vessel analysis and the pullback pressure gradient (PPG). Applications in pre- and post-PCI assessment, physiology–imaging integration, and comprehensive functional testing in ANOCA/INOCA were evaluated. Results: Physiology-guided PCI improves clinical outcomes and resource utilization compared with angiography-guided strategies. Longitudinal vessel assessment and PPG enable characterization of focal versus diffuse CAD, improving procedural planning and prediction of post-PCI physiological results. Post-PCI physiological assessment identifies residual ischemia and guides optimization strategies. In patients without obstructive CAD, combined assessment of microvascular function and vasomotor reactivity allows identification of distinct pathophysiological endotypes, supporting mechanism-based, individualized therapy. Integration with intracoronary imaging further enhances procedural precision. Conclusions: Contemporary invasive coronary physiology provides a multidimensional approach integrating epicardial, microvascular, and vasomotor domains. This framework supports personalized decision-making, optimizes revascularization, and reduces unnecessary interventions, representing a cornerstone of modern coronary care.

Journal of Clinical Medicine doi: 10.3390/jcm15134913

Authors: Takashi Ashikaga Toshihiro Nozato Yasutoshi Nagata Tetsumin Lee Masakazu Kaneko Toru Misawa Masashi Nagase Mao Matsuyama Daigo Kachi Maki Ohira Kazuki Matsuda

Orbital atherectomy (OA) is a highly effective atherectomy device used to treat heavily calcified coronary arteries. The technique for using OA is critical and depends on appropriate use of the dedicated guidewire. OA employs a centrifugal, differential sanding mechanism with bidirectional movement. When used with proper technique, the device appears to be associated with a low rate of complications, such as bradycardia and slow flow, compared with rotational atherectomy (RA), and results in high procedural success rates. We describe our experience with the OA device and procedural techniques in our catheterization laboratory.

Journal of Clinical Medicine doi: 10.3390/jcm15134912

Authors: Mehmet Yaman Kevser Arkan

Objective: To assess the anatomical and clinical outcomes of a novel, mesh-free cerclage pectopexy technique that uses the round ligament for apical support following total laparoscopic hysterectomy in women with stage II uterine prolapse. Methods: This retrospective observational study included 120 women with stage II uterine prolapse who underwent total laparoscopic hysterectomy followed by laparoscopic non-mesh pectopexy between October 2023 and August 2024. In this procedure, the distal portion of each round ligament was fixed to the pectineal ligament using Ethibond sutures. Multiple plicating stitches were then placed to reinforce the ligament’s tensile strength, creating a biological suspension bridge between the pectineal ligament and the vaginal cuff. All patients were examined preoperatively and at 1, 3, 6, and 12 months postoperatively using the POP-Q system. Anatomical success was defined as an apical stage ≤ I at 12 months. Results: At the twelve-month follow-up, anatomical success was achieved in 95 percent of patients, with six cases of apical recurrence. POP-Q measurements showed significant improvement from baseline, and total vaginal length was preserved. Functional outcomes, including postoperative pain and dyspareunia, were favorable. Early complications were uncommon, and no intraoperative or mesh-related complications occurred. Conclusion: Round-ligament-based non-mesh cerclage pectopexy provides reliable apical support with minimal surgical morbidity following total laparoscopic hysterectomy. This technique appears to provide effective apical support with low surgical morbidity while avoiding synthetic mesh. Preservation of vaginal length and favorable short-term clinical outcomes were observed; however, longer-term comparative studies are required. Future prospective studies combining this procedure with other minimally invasive suspension techniques, such as McCall culdoplasty or uterosacral plication, may broaden its applicability to more advanced prolapse cases.

Journal of Clinical Medicine doi: 10.3390/jcm15134911

Authors: Jasna Kalanj Ida Jovanovic Milan Djukic Vojislav Parezanovic Igor Stefanovic Maja Bijelic Andrija Pavlovic Nadja Cukanovic Luka Zekovic Ivana Jovanovic Milorad Tesic

Background/Objectives: Hypertrophic cardiomyopathy (HCM) in childhood is associated with a risk of adverse cardiovascular events despite preserved left ventricular (LV) ejection fraction (EF). The aim of this study was to evaluate echocardiographic parameters of longitudinal LV systolic function and determine their relationship with cardiac magnetic resonance (CMR) findings and major adverse cardiovascular events (MACE) in children and adolescents with HCM. Methods: This single-centre prospective observational study enrolled 31 children and adolescents with HCM and preserved LV EF. Echocardiographic assessment included mitral annular plane systolic excursion (MAPSE), tissue Doppler mitral annulus systolic velocity (s′), mitral annular displacement index (MADI), and LV global longitudinal strain (GLS). Investigated CMR parameters encompassed LV mass, maximal wall thickness, and late gadolinium enhancement (LGE). Associations between echocardiographic and CMR findings were analyzed, and the discriminative value of longitudinal function parameters for MACE was assessed. Results: Impaired longitudinal systolic function was frequently detected in our cohort. Lower MAPSE and s′ z-scores were present in 61.3% of patients, reduced MADI in 96.8%, and reduced LV GLS in all subjects. Patients with MACE showed significantly lower MADI (p < 0.001) and worse LV GLS (p = 0.003). An exploratory LV GLS cut-off value of −12.1% showed discrimination for MACE in this cohort, with 75% sensitivity and 95.7% specificity. Echocardiographic parameters significantly correlated with CMR markers of hypertrophy and fibrosis, particularly LV GLS, which demonstrated the strongest associations with LV mass and the presence and extent of LGE. Conclusions: Echocardiographic parameters of longitudinal LV systolic function could contribute to closer clinical surveillance in children and adolescents with HCM. LV GLS may identify subtle myocardial dysfunction and provide exploratory prognostic information; however, its role in risk stratification requires prospective validation in larger pediatric HCM cohorts.

Journal of Clinical Medicine doi: 10.3390/jcm15134910

Authors: Fahim Kanani Narmin Zoabi Eduard Khabarov Zoey Berdan Moshe Argaman Mirit Meller Rijini Nugzar Oren Fruchter Mohammad Eid Al Mohtasib Mordechai Shimonov Anas Salhab Moshe Kamar Firas Abu Akar

Background: Acute pain after video-assisted thoracoscopic surgery (VATS) promotes respiratory splinting, impaired cough, and pulmonary complications, and predicts persistent opioid use. Surgeon-administered intercostal nerve block (ICNB) is a simple regional technique, but its independent effect on early pain and opioid requirement in a contemporary uniportal VATS (UVATS) pathway is incompletely defined. Methods: We performed a retrospective cohort study of 456 consecutive patients undergoing UVATS at a single Israeli center between 2017 and 30 May 2025. Patients receiving an intercostal block were compared with those who did not. Baseline covariates were balanced by 1:1 nearest-neighbor propensity-score matching (caliper 0.2 SD of the logit propensity score). The primary endpoints were pain on postoperative day (POD) 1 (visual analog scale, VAS) and postoperative opioid use; secondary endpoints included later pain, analgesic regimen, postoperative pneumonia, and mortality. Results: Matching yielded 159 patients per group (n = 318) with all clinically relevant covariates balanced (standardized mean difference [SMD] < 0.13). Median POD1 VAS was lower with the block (4 [IQR 3–4] vs. 5 [5–7]; p < 0.001), and 76.1% of block patients were opioid-free versus 10.7% who were not (p < 0.001). The effect was concentrated early and attenuated by POD3. In multivariable analysis the block was independently associated with lower POD1 VAS (adjusted β = −1.64, 95% CI −2.00 to −1.29; p < 0.001). Postoperative pneumonia was less frequent in the block group (5.7% vs. 20.1%; p < 0.001). Thirty-day and one-year mortality did not differ significantly. Conclusions: In UVATS, a surgeon-placed intercostal nerve block was associated with lower early postoperative pain that persisted after adjustment for operating surgeon and surgical era, concordant with pooled meta-analytic estimates; associated reductions in opioid use and pneumonia were confounded with surgeon and secular trend and are hypothesis-generating. These single-center, retrospective findings require prospective, protocol-randomized confirmation.

Journal of Clinical Medicine doi: 10.3390/jcm15134909

Authors: Grzegorz Wąchol Martyna Tokarczyk

Background: The present study examined coping styles and adaptive responses in patients undergoing cardiac surgery and healthy controls. Methods: A total of 240 participants were included, comprising cardiac surgery patients and a control group. The Coping Inventory for Stressful Situations and the Reactions to Impairment and Disability Inventory were used. Results: Significant group differences were found in adaptive responses, with cardiac surgery patients showing higher levels of shock, anxiety, denial, and overall maladaptive adjustment patterns. Patients also demonstrated a distinct profile of adaptation compared with healthy controls. Task-focused coping was associated with more adaptive functioning, whereas emotion-focused coping and maladaptive emotional responses were associated with poorer psychological adjustment. Conclusions: Overall, the results indicate that coping style is a key factor in psychological adaptation to cardiac surgery, with implications for the development of targeted psychological interventions in cardiac rehabilitation.

Journal of Clinical Medicine doi: 10.3390/jcm15134908

Authors: Ryang Soon Lim Woon-Jeong Lee Hyen Oh La Yun-Kyoung Song Kyung Hee Choi

Background/Objectives: Emergency departments (EDs) are particularly prone to medication errors because of urgent treatment environments and high decision density. Automated dispensing cabinets (ADCs) integrated with the hospital information system (HIS) may improve medication safety, yet real-world evidence in centralized-pharmacy settings remains limited. This study evaluated the impact of an HIS-integrated ADC on medication use, medication errors, and nurses’ perception of safety in the ED of a Korean tertiary hospital. Methods: In this prospective before-and-after study, prescribing patterns, medication storage, and related costs were compared in the two months before (Phase 1; September–October 2019) and after (Phase 2; May–June 2020) ADC installation. Medication errors reported through the hospital safety incident reporting system were analyzed over corresponding 6-month windows from July 2019 to June 2020. Long-term sustainability was assessed using follow-up data collected from October to November 2023 (Phase 3), and all 46 ED nurses completed a 5-point Likert-scale survey on perceived medication safety. Results: Daily injectable prescriptions were unchanged (221.1 ± 34.6 vs. 227.7 ± 35.2; p = 0.301), whereas returned injectable prescriptions increased (17.9 ± 5.9 vs. 25.1 ± 6.0; p < 0.001) and non-injectable prescriptions decreased (163.1 ± 42.2 vs. 140.0 ± 22.7; p < 0.001). The number of medication items stored in the ED storage room declined by 95.6%, with a 92.5% reduction in related maintenance cost. Total medication errors decreased from 41 (74.5%) before to 14 (25.5%) after implementation (p < 0.001), with the largest reduction in delivery errors (17 [30.9%] to 2 [3.6%]). These improvements were sustained at the three-year follow-up. Nurses reported high overall satisfaction with medication safety (4.27 ± 0.62 on a 5-point Likert scale). Conclusions: Implementation of an HIS-integrated ADC in the ED was associated with improved prescription patterns, fewer reported medication errors, and enhanced perceived medication safety. In addition, these improvements were sustained over time, indicating stable and consistent implementation of the ADC system. Nurses also reported improved perceptions of medication safety.

Journal of Clinical Medicine doi: 10.3390/jcm15134907

Authors: Paul Pasca Flaviu Ionut Faur Cosmin Burta Dan Brebu Carmen Neamtu Vlad Braicu Ciprian Duta Ioana Adelina Faur Razvan Danau Amadeus Dobrescu Marius Murariu

Background: Colorectal cancer (CRC) prognosis, particularly in liver metastasis (CRLM), is influenced by histopathological and molecular factors. Methods: A narrative analysis of the specialized literature was conducted using databases such as PubMed, MEDLINE, Scopus, and Embase. The review focused on original articles published between 2005 and 2025. Results: Lymph node involvement is a critical prognostic factor, with lymph node-positive CRC correlating with increased risk of liver metastasis and significantly reduced survival rates. Poorly differentiated tumors (G3) exhibit a higher likelihood of metastasis, including liver involvement, and are associated with worse clinical outcomes. Vascular emboli and perineural invasion are indicative of hematogenous spread and higher metastatic potential, leading to poorer survival outcomes. Genetic mutations, such as KRAS, NRAS, and BRAF, are associated with therapy resistance, complicating treatment and highlighting the importance of personalized approaches. MSI-H and HER2 amplification further affect treatment response, with MSI-H tumors showing a favorable response to immunotherapy, while HER2-positive CRCs may benefit from targeted therapies. Tumor budding, high levels of which predict poor survival, is another key histopathological feature associated with aggressive metastatic behavior. Systemic inflammatory markers, such as the Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and C-Reactive Protein-to-Albumin Ratio (CAR), offer prognostic insights into CRLM patient survival. Conclusions: Histopathological features, molecular alterations, and immune microenvironment factors significantly impact the prognosis of CRC with liver metastasis. The integration of molecular profiling, immunotherapy, and targeted therapies offers promise for improving treatment outcomes. Personalized treatment strategies, incorporating these factors, are essential for overcoming therapy resistance and improving survival in CRLM patients.

Journal of Clinical Medicine doi: 10.3390/jcm15134903

Authors: Abdulmajeed Alfayyadh

Arthrogenic muscle inhibition (AMI), neurophysiological suppression of voluntary quadriceps activation triggered by joint effusion and inflammation, is consistently initiated within hours of any form of knee surgery. If not actively counteracted during the first two postoperative weeks, AMI may drive a cascade of neuromuscular, morphological, and biomechanical deficits that can persist for years, substantially increasing the risk of post-traumatic osteoarthritis, reinjury, and long-term functional disability. Emerging evidence indicates that preoperative patient-related factors, including baseline quadriceps strength, age, body mass index, and physical fitness, further modulate the rehabilitation response and should be considered in planning early postoperative protocols. This narrative review, which was not designed as a systematic review or meta-analysis and therefore does not include formal quality assessment or pooled statistical analysis, evaluates evidence for seven early-phase (0–2 weeks postoperative) knee muscle activation interventions: neuromuscular electrical stimulation (NMES), isometric quadriceps exercise, blood flow restriction (BFR) training, electromyographic (EMG) biofeedback, open and closed kinetic chain (OKC/CKC) exercise, cryotherapy, and continuous passive motion (CPM). Findings are synthesized against six clinically relevant dimensions, safety in the 0–2 week window, home-based usability, capacity to overcome AMI, requirement for volitional effort, objective monitoring capability, and progressive resistance, to characterize a consistent pattern: no single existing modality simultaneously meets all combined requirements for home deployment, volitional engagement, objective monitoring, and progressive resistance from postoperative day one. This collective unmet need provides direction for future device development and clinical research.

Journal of Clinical Medicine doi: 10.3390/jcm15134905

Authors: Réka Kollár Tamás Leel-Őssy Eszter Szigeti Magdolna Dank Éva Hosszú Csaba Horváth Szilvia Mészáros

Background: Endocrine therapy for hormone receptor-positive breast cancer is associated with accelerated bone loss and increased fracture risk. Vertebral fractures (VFs) are frequently asymptomatic and remain underdiagnosed, potentially leading to underestimation of fracture risk. Methods: We conducted a cross-sectional real-world study that included 172 women with breast cancer (mean age 58.2 ± 12.0 years), the majority receiving aromatase inhibitors. Vertebral fractures were assessed using vertebral fracture assessment (VFA) during dual-energy X-ray absorptiometry (DXA). Bone mineral density (BMD), trabecular bone score (TBS), quantitative ultrasound (QUS), and FRAX® scores were evaluated. Results: Vertebral fractures were identified in 13% of patients, and 78% of these occurred in women with normal or osteopenic BMD. Age was independently associated with VFs, while conventional densitometric and non-densitometric parameters showed limited discriminatory ability. The incorporation of VFA-detected fractures into FRAX significantly increased estimated fracture risk (hip fracture risk: 0.8% vs. 4.1%, p = 0.008). Conclusions: Vertebral fractures are common and frequently unrecognized in women receiving endocrine therapy and are not adequately captured by BMD. Routine use of VFA during DXA substantially improves fracture risk assessment and leads to a clinically meaningful reclassification of FRAX estimates. These findings support a more comprehensive approach to skeletal risk evaluation in this population.

Journal of Clinical Medicine doi: 10.3390/jcm15134906

Authors: Osman Parca Tunahan Akyol Emine Seker Un Beyzanur Yıldız

Background/Objectives: To evaluate interocular retinal and choroidal microvascular alterations associated with compensatory head tilt in unilateral congenital superior oblique palsy (SOP) and to investigate their relationship with head tilt degree using optical coherence tomography angiography (OCTA). Methods: This retrospective cross-sectional study included 34 patients with congenital SOP and head tilt–dominant abnormal head posture. A paired-eye design compared the tilt-side eye with the opposite-side eye. Superficial and deep capillary plexus (SCP, DCP) vessel density, foveal avascular zone (FAZ) parameters, choroidal vascularity index (CVI), and subfoveal choroidal thickness (SFCT) were assessed. Interocular differences were defined as Δ = opposite-side eye − tilt-side eye. Correlation and multivariable regression analyses were performed to assess associations with head tilt degree. The interocular difference in CVI (ΔCVI) and its association with head tilt degree were defined as the primary outcomes, whereas retinal OCTA parameters, FAZ metrics, and SFCT were considered exploratory secondary outcomes. Results: CVI showed the most prominent interocular difference, being higher in the opposite-side eye than in the tilt-side eye (0.71 ± 0.04 vs. 0.68 ± 0.04; p < 0.001), whereas SFCT did not differ significantly (p = 0.395). SCP foveal vessel density and DCP inferior vessel density showed nominal differences in the unadjusted analyses but did not remain statistically significant after Benjamini–Hochberg false discovery rate correction. ΔCVI correlated positively with head tilt degree (ρ = +0.533, p = 0.001) and remained independently associated in multivariable analysis (p = 0.001). Conclusions: Compensatory head tilt in congenital SOP is associated with measurable interocular microvascular asymmetry, predominantly at the choroidal level. CVI demonstrated the strongest association with head tilt severity, whereas retinal OCTA findings were exploratory, suggesting that OCTA may provide objective insight into posture-related choroidal microvascular alterations.

Journal of Clinical Medicine doi: 10.3390/jcm15134904

Authors: Marcio Borges-Sa Eric Macias-Fassio Alejandro Delgado Santiago Salas-Sosa María Aranda Antonia Socias Alberto del Castillo Andres Giglio

Background/Objectives: Sepsis detection relies on clinical variables and scoring systems assumed to perform uniformly across hospital settings. However, sepsis phenotype distributions shift between clinical environments, suggesting that variable importance may be setting dependent. This study aimed to quantify service-specific variability in the discriminatory capacity of clinical variables for sepsis detection and to evaluate whether this heterogeneity translates into differential performance of machine learning models compared to traditional clinical scoring systems. Methods: This stratified sub-analysis of the BIAlert Sepsis cohort (203,755 patients; 11,864 sepsis episodes, 2014–2018) evaluated 61 structured quantitative variables across nine hospital services (≥90 sepsis episodes each). Within each service, the Mann–Whitney–Wilcoxon test (p < 0.01, Holm-corrected) assessed differences between septic and non-septic episodes. Five machine learning models (Random Forest/BIAlert, XGBoost, CatBoost, SVM, Neural Network) and three clinical rules (NEWS, SIRS, qSOFA) were evaluated globally and stratified across four clinical environments. Results: The proportion of significant variables ranged from 95.1% in the Emergency Department (58/61) to 37.7% in the Intensive Care Unit (23/61). Lactate was the only universally significant variable (9/9 services). Clinical scoring systems collapsed in Critical Care (qSOFA and NEWS AUC 0.459). BIAlert maintained the highest AUC across all environments (0.975–0.857). The Friedman test confirmed significant differences (χ2 = 28.00, p < 0.001), with BIAlert achieving a mean rank of 1.0. Conclusions: The discriminatory capacity of clinical variables for sepsis detection is not uniform across hospital services. ML models, particularly BIAlert, maintained robust performance where fixed-rule scoring systems failed.

Journal of Clinical Medicine doi: 10.3390/jcm15134902

Authors: Abdulrahman Hamad Aldousari Hamad Alkandari Sulaiman Alruwaished Yousef M. F. H. Almutairi Abdulwahab Alkandari Shekha Alnajdi Mohammad Alsharah Salah Termos

Background: Laparoscopic cholecystectomy is the gold standard for gallbladder disease but is often associated with significant postoperative pain. Opioid analgesia is effective and is the mainstay of treatment. However, opioids are limited by multiple adverse effects such as nausea and respiratory depression. Esketamine is an NMDA receptor antagonist that has emerged as a potential analgesic adjunct. This systematic review and meta-analysis aims to evaluate the efficacy and safety of perioperative esketamine for patients undergoing laparoscopic cholecystectomy. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials comparing perioperative esketamine with control regimens in adults undergoing laparoscopic cholecystectomy. Five databases were searched from inception to 25 August 2025. Random-effects meta-analyses were performed for pain, hemodynamic, recovery, and safety outcomes. Results: Six randomized controlled trials including 569 patients were eligible. Esketamine was associated with lower pain scores at rest and during movement, although neither were statistically significant. No significant clinical differences were observed in mean arterial pressure or heart rate changes during surgery or after surgery. However, esketamine significantly shortened wake-up time (MD = −3.55 min, 95% CI [−6.09 to −1.02]), improved postoperative sleep quality (MD = −5.78, 95% CI [−6.80 to −4.76]), and reduced PONV (RR = 0.47, 95% CI [0.24 to 0.92]) and respiratory depression (RR = 0.18, 95% CI [0.03 to 0.98]). Conclusions: Esketamine improved selected recovery and safety outcomes but did not significantly reduce hemodynamic parameters, postoperative pain or rescue analgesia. Larger high-quality trials are needed to confirm its role in laparoscopic cholecystectomy.

Journal of Clinical Medicine doi: 10.3390/jcm15134900

Authors: Kardelen Akin Serenay Alaca Betül Aksoy Şenay Onbaşı Karabağ Sinem Kahveci Yeliz Çağan Appak Masallah Baran

Objective: Pediatric intestinal pseudo-obstruction (PIPO) is a rare, severe, and heterogeneous gastrointestinal motility disorder associated with intestinal failure, recurrent hospitalizations, and significant morbidity and mortality. This study aimed to evaluate the clinical features, management strategies, and long-term outcomes of children diagnosed with PIPO at a tertiary referral center. Methods: This retrospective single-center study included pediatric patients diagnosed with PIPO between 2011 and 2025. Diagnosis was established according to ESPGHAN consensus criteria. Demographic characteristics, clinical presentation, genetic findings, nutritional support, surgical interventions, intestinal transplantation, and long-term outcomes were retrospectively reviewed. Results: A total of 32 patients with PIPO were included, of whom 56.2% were female and 43.7% had early-onset disease. Genetic testing was performed in 22 of 32 patients; clinically significant variants were identified in 16 (50% of the total cohort), most commonly ACTG2 mutations. Prior abdominal surgery before referral was present in 84.3% of patients. During follow-up, 56% remained parenteral nutrition dependent, five patients underwent intestinal transplantation, and the overall mortality rate was 21.8%. Conclusions: PIPO is a highly heterogeneous disorder associated with substantial morbidity, prolonged nutritional support requirements, repeated surgical interventions, and significant mortality. Early diagnosis, genetic evaluation, multidisciplinary management, and timely referral to specialized intestinal failure and transplantation centres are likely to support more individualised management and may help prevent avoidable complications in affected children.

Journal of Clinical Medicine doi: 10.3390/jcm15134901

Authors: Mustafa Alperen Tunç Ali Kaan Güren Burak Paçacı Fırat Akagündüz Erkam Kocaaslan Ahmet Demirel Yeşim Ağyol Pınar Erel Nargiz Majidova Nadiye Sever Naz Tayyar Tunç Nazım Can Demircan Selver Işık Abdussamed Çelebi Ezgi Çoban Osman Köstek İbrahim Vedat Bayoğlu Murat Sarı

Background: Adjuvant therapy decisions for T3N0 stage II colon cancer remain controversial. This study evaluates long-term outcomes, recurrence patterns, and conditional relapse-free survival (RFS) in pathologic T3N0 colon cancer. Methods: This retrospective study included 306 patients undergoing curative resection for T3N0 colonic adenocarcinoma (1995–2020). Early recurrence was defined as recurrence or death within 3 years after surgery. Survival was estimated via Kaplan–Meier. Cox regression, adjusted for treatment eras, evaluated survival factors. Inverse Probability of Treatment Weighting (IPTW) minimized selection bias. Conditional RFS utilized a 5-year landmark analysis. Results: Over a 133-month median follow-up, 72 patients (23.5%) recurred. Most recurrences (81.9%) occurred within 3 years; only 9.7% after 5 years. Five- and 10-year OS rates were 80.9% and 70.4%. Inadequate lymph node dissection (<12 nodes) was performed in 29.7% of the entire cohort and was found to be an independent adverse prognostic factor for OS. Adjuvant chemotherapy lacked overall OS benefit, though IPTW analysis suggested potential benefit in patients with inadequate dissection. Conditional RFS (5–10 years) for patients recurrence-free at 60 months was 95.0%. Exploratory analyses showed descriptive differences in post-relapse survival based on the clinical triggers prompting radiological evaluation (marker-triggered versus symptom-triggered presentations). Conclusions: T3N0 colon cancer recurrences occur predominantly within the first 3–5 years after surgery. Inadequate lymph node dissection is the primary adverse prognostic factor. Although a 5-year follow-up period appears adequate for most patients, individualized extended surveillance may be considered for selected high-risk patients. Adjuvant treatment and follow-up strategies should be tailored according to surgical quality and risk factors.

Journal of Clinical Medicine doi: 10.3390/jcm15134899

Authors: Aurélie Cavin Julie Triolo Yves Harder Jérémy Brühlmann

Background/Objectives: Reconstruction of full-thickness soft-tissue defects of the heel can be challenging due to the specific structural and functional demands of this region. Local flaps are often used due to their ability to provide durable and sensate coverage. This case series and systematic review aim to assess their surgical efficacy and reported outcomes, particularly in the context of the rhomboid flap. Methods: A systematic review was conducted in accordance with PRISMA guidelines, using PubMed, Cochrane and EBSCO. Studies published up to March 2026 evaluating local flaps were included, whereas distant pedicled and microvascular flaps were excluded. Defect size, flap types and surgical outcome were extracted and synthesized in a comparative table. In addition, we present four clinical cases of full-thickness soft-tissue heel defects reconstructed with a local rhomboid flap. This retrospective, single-center case series includes patients treated at our institution between January 2023 and March 2026, with initial debridement followed by flap coverage. Results: The four patients had a mean defect size of 4.1 cm2. All defects ultimately healed, though one case demonstrated delayed wound healing. Eventually, neither donor-site morbidity, nor recurrence were observed during a mean follow-up of 7.4 months (range 1 to 17 months). Nine studies were included in the review, encompassing 56 patients. Despite the variety of the studies regarding design and flaps used, all focused on outcomes, including flap survival, complication rate, and functional recovery. Local flaps appear to be a feasible option for this type of soft-tissue defect; however, they seem to be limited to small defects. Conclusions: Local flaps may represent a valuable option for small full-thickness heel defects up to 6 cm2 according to the “like-with-like” principle. They are associated with low surgical morbidity and do not compromise subsequent reconstructive options, making them a reasonable first-line approach. Limitations include the small sample size, retrospective design, the unequal follow-up time, as well as the absence of standardized functional outcome assessment.

Journal of Clinical Medicine doi: 10.3390/jcm15134898

Authors: Shausha Mohamed Anees Xiong Khee Cheong Hui Jan Tan Najma Kori Wan Nur Nafisah Wan Yahya Rosnah Sutan Petrick Periyasamy

Background: Stroke-associated infection (SAI) is a common complication of acute ischemic stroke and is associated with adverse clinical outcomes. Contemporary prospective data from Southeast Asia remain limited. The primary objective was to determine the prevalence of SAI in patients with acute ischemic stroke. Secondary objectives were to identify associated clinical predictors and evaluate its relationship with in-hospital outcomes. Methods: This prospective observational cohort study included 390 adults with acute ischemic stroke admitted to a tertiary center between August 2024 and November 2025. SAI was defined as clinically diagnosed infection occurring within seven days of stroke onset using standardized criteria. Demographic, clinical, and treatment variables were collected. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Functional outcome at discharge was evaluated using the modified Rankin Scale (mRS). Multivariable logistic regression was performed to identify independent predictors of SAI. Results: SAI occurred in 75 patients, giving a prevalence of 19.2% (95% CI 15.3–23.1). Pneumonia was the predominant subtype (14.4%). On multivariable analysis, higher NIHSS score (adjusted OR 1.10 per point; 95% CI 1.05–1.14; p < 0.001) and mechanical thrombectomy (adjusted OR 3.02; 95% CI 1.11–8.26; p = 0.031) were independently associated with SAI. Patients with SAI had longer hospital stays (median 8 vs. 4 days, p < 0.001), poorer functional outcomes (81.3% vs. 24.8% with mRS 3–6, p < 0.001), and higher in-hospital mortality (17.3% vs. 1.0%, p < 0.001). Conclusions: Stroke-associated infection affected approximately one-fifth of patients with acute ischemic stroke and was strongly associated with stroke severity and adverse clinical outcomes. These findings support early risk stratification and targeted preventive strategies in acute stroke care.

Journal of Clinical Medicine doi: 10.3390/jcm15134897

Authors: Otman Sandali Rachid Tahiri Joutei Hassani Isabelle Audo Vincent Gualino Christine Tchikladze Merand Vincent Borderie

Purpose: To assess whether reducing intraoperative light exposure preserves macular function after cataract surgery in patients with AMD. Methods: A total of 42 eyes of 42 patients with AMD were randomized in a prospective study. The primary outcome was the change in photopic (ERG) b-wave amplitude at one hour after surgery (V2). Secondary outcomes included ERG implicit time, multifocal ERG, visual acuity, and macular thickness, assessed at V2, V3 (day 1), and V4 (1 month). Results: Mean intraoperative light exposure was significantly lower in the 3D group than in the standard group (3938 vs 47,142 lux, p < 0.001). At 1 h after surgery, the decrease in photopic b-wave amplitude did not differ significantly between the two groups (−1.83 µV; 3D group, vs. −1.56 µV; standard group, p = 0.76). In exploratory analyses, ERG implicit time increased significantly in the standard group (p = 0.02) but remained stable in the 3D group (p = 0.24). At 1 month, an increase in macular thickness was observed only in the standard group (V1 265.9 ± 27.7 µm, V4 278.8 ± 34.9 µm; p = 0.003). Conclusions: Digital visualization significantly reduced intraoperative light exposure. However, no significant difference was observed for the primary endpoint of photopic ERG b-wave amplitude at 1 h postoperatively. Secondary findings regarding ERG implicit time and macular thickness should be considered exploratory and require confirmation in larger studies.

Journal of Clinical Medicine doi: 10.3390/jcm15134896

Authors: Miraç Öz Kahya Mursal Isgenderli Ömer Faruk Tüten Öznur Yıldız

Background/Objectives: Cardiopulmonary exercise testing (CPET) provides an integrated assessment of cardiovascular, respiratory, and metabolic responses during exercise. Although CPET is increasingly used in older adults for preoperative physiological evaluation and assessment of exercise limitation, evidence regarding its safety and clinical feasibility in elderly patients with mixed cardiopulmonary comorbidities remains limited. Methods: In this retrospective observational study, we evaluated 235 consecutive patients who underwent CPET at a tertiary referral center. Patients were categorized into two groups according to age: ≥65 years and <65 years. Clinical characteristics, pulmonary function parameters, CPET findings, feasibility outcomes, and adverse events during testing were analyzed. Results: A total of 235 patients were included, with a mean age of 62.3 ± 12.8 years. Among them, 112 (47.6%) patients were aged ≥65 years and 35 (14.8%) were aged ≥75 years. Comorbidities were present in 170 patients, with hypertension being the most common. The leading indication for CPET was preoperative evaluation prior to thoracic surgery. Most elderly patients successfully completed CPET and provided clinically interpretable physiological data. In the ≥65 years group, CPET was terminated prematurely in 10 patients due to syncope, severe dyspnea, bronchospasm, chest pain, or arrhythmia. In the ≥65 years group, exercise-induced desaturation occurred in 24 patients; the lowest recorded oxygen saturation was 84%, and no desaturation episode required premature termination of the test. No major complications, deaths, myocardial infarctions, or cardiac arrests were observed during CPET or within the subsequent three days. No statistically significant differences in adverse event rates were observed between the age groups. Univariate logistic regression analysis demonstrated that lower FEV1 % predicted and lower FEV1/FVC % predicted ratio were associated with clinically significant adverse events in elderly patients [OR (95% CI): 0.96 (0.94–0.99), p = 0.02, OR (95% CI): 0.90 (0.84–0.96), p = 0.001, respectively]. Conclusions: CPET was feasible in the majority of elderly patients with cardiopulmonary comorbidities, with most individuals successfully completing testing and providing clinically interpretable physiological data. No major complications were observed in this cohort. These findings suggest that, when performed under appropriate supervision and careful patient selection, CPET may represent a practical tool for functional assessment and preoperative physiological evaluation in older adults. Larger prospective multicenter studies are warranted to further define its safety and feasibility in this population.

Journal of Clinical Medicine doi: 10.3390/jcm15134895

Authors: Michael Keller Ye In Christopher Kwon Yashar Haghighi Vigneshwar Kasirajan Zubair Hashmi

Background/Objectives: Following heart transplantation (HT), a subset of patients will require an early or late permanent pacemaker (PPM). We explored risk factors and outcomes associated with PPM implantation in this population. Methods: Using the United Network for Organ Sharing (UNOS) database, we identified all adult patients undergoing HT from 2013 to 2023 who received a PPM early (prior to discharge) or late (>6 months post transplant). Propensity score matching (PSM) was used for control cohorts was. Primary outcomes included recipient survival at 30 days and 1 and 5 years. Predictors of early and late PPM, as well as post-PPM mortality, were assessed using Cox and logistic regression models. Kaplan–Meier survival curves were compared using a log-rank test. Results: Following PSM, the early PPM cohort included 354 patients, and the late PPM cohort included 554 patients. Early PPM patients showed similar 30-day and 1- and 5-year survival (p = 0.582, 0.421, and 0.2844 respectively) but lower rates of graft failure (1.1% vs. 4%, p = 0.017) and primary graft dysfunction (PGD) (1.7% vs. 4.2%, p = 0.046). Late PPM patients had reduced survival at 30 days and 1 year but not at 5 years (p < 0.001, p = 0.0023, 0.050 respectively). Neither early nor late PPM was independently associated with increased risk of mortality after HT. Donation after Circulatory Death (DCD) organs were associated with a lower risk of early PPM (aOR = 0.409, p = 0.020). Late PPM patients showed higher rates of PGD (2.5% vs. 0.5%, p = 0.007). Conclusions: Early or late PPM is not an independent risk factor for mortality after HT, but differing short-term morbidity and mortality are observed.

Journal of Clinical Medicine doi: 10.3390/jcm15134894

Authors: Burak Manay Ramazan Güven Alperen Şentürk Mustafa İbas Mehmet Nuri Elgörmüş

Background/Objectives: Dysphagia is common in tracheostomized patients with traumatic brain injury (TBI) and may be influenced by airway pathology and tracheostomy-related factors. This study investigated whether tracheostomy cannula type is independently associated with swallowing function and pharyngeal residue after accounting for airway stenosis and clinical variables. Methods: This retrospective observational study included 80 tracheostomized TBI patients using a speaking valve. Participants were grouped according to cannula type (non-fenestrated vs. fenestrated). Swallowing function was evaluated using Fiberoptic Endoscopic Evaluation of Swallowing (FEES), and pharyngeal residue severity was assessed using the Yale Pharyngeal Residue Severity Rating Scale (YPRSRS). Airway stenosis severity was graded using the Cotton–Meyer classification. Multivariable ordinal logistic regression analyses were performed to identify independent predictors of pharyngeal residue. Results: Higher pharyngeal residue scores were observed in the fenestrated cannula group under selected conditions, particularly for 5 mL liquid (p = 0.039) and 5 mL semi-solid boluses (p = 0.004) in the vallecular region, and for 5 mL semi-solid boluses in the pyriform sinuses (p < 0.001). Airway stenosis grade was strongly associated with increased pharyngeal residue and reduced SpO2 levels (p < 0.001). In multivariable analyses, airway stenosis emerged as the factor most consistently associated with pharyngeal residue severity (e.g., OR = 4.909, 95% CI: 1.646–14.646, p = 0.004), whereas cannula type was not independently associated with most outcomes. Condition-specific associations were identified between fenestrated cannula use and pharyngeal residue in two models (vallecular residue for 5 mL semi-solid: OR = 0.354, 95% CI: 0.143–0.876, p = 0.025; pyriform sinus residue for 10 mL liquid: OR = 0.190, 95% CI: 0.073–0.495, p = 0.001); however, the direction of these associations differed from unadjusted comparisons, indicating prominent confounding by stenosis severity. Conclusions: FEES-estimated airway stenosis appeared to be the factor most consistently associated with pharyngeal residue severity in tracheostomized TBI patients, whereas the effect of cannula type appeared to be limited. Comprehensive airway assessment may therefore be important in dysphagia management.

Journal of Clinical Medicine doi: 10.3390/jcm15134893

Authors: Michael Murninkas Daniel Ostrovsky Aya Biderman Idit F. Liberty

Background/Objectives: Prediabetes significantly increases the risk of type 2 diabetes and related complications. Limited data exist for prediabetes among minority groups in Israel, particularly Bedouins. In the Negev region, Jewish and Bedouin populations differ markedly in culture and socioeconomic status. This study aimed to identify gender- and ethnicity-specific predictors of prediabetes. Methods: This retrospective, population-based observational exploratory study used data from 28,754 adults aged 20–65 years insured by Clalit Health Services in Southern Israel (2010–2020). Individuals with prediabetes were matched 1:1 with controls by age, gender, ethnicity, and year of diagnosis. Multivariate logistic regression models stratified by gender and ethnicity identified independent predictors. Results: Prediabetes was identified at significantly younger ages among Bedouins than Jews (6.8 years in men, 11.3 in women). The strongest predictor across all subgroups was metabolic syndrome (OR 2.0–4.0). Gestational diabetes was a major risk factor in women, particularly Jewish (OR 3.6). Cardiovascular disease and the use of statins or thiazide diuretics were independently associated with increased odds of prediabetes. Triglyceride-to-HDL cholesterol ratio was consistently elevated among prediabetes patients. Conclusions: Metabolic and medication-related factors contribute significantly to prediabetes-associated risk, with distinct gender and ethnic patterns. Culturally tailored early interventions and individualized risk profiling may enhance diabetes prevention in Southern Israel.

Journal of Clinical Medicine doi: 10.3390/jcm15134892

Authors: Juntian Wu Marcus Eng Hock Ong Desmond Renhao Mao Mikael Hartman Xueling Sim Benjamin Sieu-Hon Leong Rachel Siying Lee Fahad Javaid Siddiqui

Background/Objectives: Alcohol-related frequent attenders (ARFAs) constitute a small but resource-intensive emergency department (ED) population. Methods: Following PRISMA-ScR guidelines, we searched MEDLINE, PsycINFO, CINAHL Complete, and EMBASE from inception to May 2025 for empirical studies examining ED frequent attendance with alcohol involvement. Definitions had high heterogeneity; therefore, narrative synthesis was conducted. Results: A total of 73 studies were included, most retrospective (57.5%), encompassing sample sizes from 14 to over 4.1 million participants: 59 frequent attender (FA) studies with alcohol subgroup analyses and 14 pure ARFA studies. Research was concentrated in North America and Europe (56/73, 76.7%), with limited Asia-Pacific representation (21.9%). Seven distinct definition threshold categories were identified (≥2 to ≥20 visits annually); 31.5% utilised different definitions. Qualitative studies (n = 6) identified push factors (dependence, mental health crises, housing instability, fragmented services) and pull factors (24/7 access, crisis care model, immediate service) driving frequent attendance. Eight studies evaluated interventions; all employed non-randomised designs examining case management, integrated pathways, and community-based treatments. Conclusions: Critical gaps include the absence of standardised definitions for comparison across studies, a concentration of research in Western settings limiting global applicability, and insufficient rigorous intervention evidence. Priorities include developing empirically validated definitions, expanding non-Western research, and conducting randomised controlled trials with adequate follow-up.

Journal of Clinical Medicine doi: 10.3390/jcm15134891

Authors: Bogdan-Flaviu Buz Venkata Sai Harshabhargav Chenna Ankit Sharma Pravallika Myneni Iulia Georgiana Bogdan Cristian Mornos Simina Crisan Dan Gaita Constantin-Tudor Luca Diana-Aurora Arnautu Camelia Gurban Felicia Marc Florina Caruntu Minodora Andor

Background: Patients with type 2 diabetes mellitus (T2DM) who present with ST-segment elevation myocardial infarction (STEMI) remain at high risk of adverse remodeling after reperfusion. This observational study examined whether pre-admission glucose-lowering therapy class was associated with six-month left ventricular (LV) reverse remodeling and myocardial work recovery. Methods: We analyzed 253 patients with STEMI, baseline LV ejection fraction ≤ 50%, successful primary PCI, and complete baseline and six-month echocardiography. The primary inferential analyses focused on 75 patients with T2DM, grouped according to pre-admission therapy with SGLT-2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, or conventional therapy; non-diabetic patients were retained as a descriptive reference group. Clinical outcome, propensity-score, subgroup, and mediation analyses were considered exploratory because of small subgroup and event counts. Results: SGLT-2 inhibitor and GLP-1 receptor agonist exposure was associated with larger improvements in LVEF, LV volumes, and global work efficiency than DPP-4 inhibitors or conventional therapy. Crude MACE rates were highest in the conventional-therapy group, but event estimates were imprecise and confounded by baseline risk, revascularization status, and discharge therapy. Conclusions: In patients with T2DM recovering from STEMI, pre-admission exposure to SGLT-2 inhibitors and, to a lesser extent, GLP-1 receptor agonists was associated with more favorable structural and myocardial work recovery. These hypothesis-generating findings should be interpreted as associations and require confirmation in adequately powered prospective studies.

Journal of Clinical Medicine doi: 10.3390/jcm15134890

Authors: Andrea Calderone Maria Pia Onesta Laura Simoncini Antonino Nunnari Fabrizio Sottile Angelo Quartarone Rocco Salvatore Calabrò

Background/Objectives: Rehospitalization after traumatic spinal cord injury (SCI) is common, but binary or count summaries may obscure heterogeneity in timing, recurrence, frequency, and duration. We aimed to identify clinically interpretable rehospitalization burden profiles in the SCIMS 2021ARPublic dataset and examine descriptive associations with clinical correlates and participation outcomes. Methods: We analyzed Form I, Form II, and Record Status public-use files. Among 29,310 individuals with at least one non-lost follow-up interview, 28,745 with at least one non-missing rehospitalization indicator entered latent class analysis. Four prespecified indicators captured early, recurrent, frequent, and prolonged rehospitalization. Candidate two- through six-class models were compared using AIC, BIC, entropy, class size, posterior probabilities, and interpretability. Pairwise adjusted logistic models examined candidate clinical correlates in 10,407 participants with complete 2016+ follow-up data. Adjusted linear models examined CHART participation domains in 20,766–20,949 participants. Results: A four-profile solution was retained: low rehospitalization burden (59.8%), early/prolonged rehospitalization (18.9%), frequent/prolonged rehospitalization (7.7%), and high recurrent/frequent/prolonged burden (13.6%). UTI and pressure ulcer history showed the most consistent associations with burdened profiles. Severe pain and frequent sleep problems were associated with selected heavier-burden profiles, while depressive symptoms showed smaller and less precise associations. Sensitivity analyses supported structural stability while highlighting observation-time bias and classification uncertainty inherent to wave-based public-use data. Compared with the low-burden profile, burden profiles showed lower CHART scores, especially for mobility and occupation. Conclusions: Rehospitalization after traumatic SCI is heterogeneous. These utilization burden profiles summarize distinct observed patterns but require prospective validation before use in risk stratification or follow-up planning.

Journal of Clinical Medicine doi: 10.3390/jcm15134889

Authors: Agnieszka Helena Czapska Beata Rebizant Katarzyna Kosińska-Kaczyńska

Background/Objectives: Absent septum pellucidum (ASP) is a rare fetal midline brain finding that may occur in isolation or alongside broader central nervous system (CNS) malformations, genetic disorders, or septo-optic dysplasia (SOD). Accurate prenatal diagnosis and counseling remain challenging because apparently isolated ASP may be reclassified following fetal magnetic resonance imaging (MRI), postnatal neuroimaging, or specialist assessment. This structured narrative review aimed to synthesize current evidence on prenatal imaging findings, associated anomalies, genetic evaluation, and postnatal outcomes in fetuses with ASP. Methods: This structured narrative review used PRISMA-informed reporting. PubMed and Google Scholar were searched for full-text English-language studies published from 2014 through the updated search date (8 June 2026). Data on gestational age at diagnosis, imaging classification, associated anomalies, genetic testing, postnatal assessment, and neurodevelopmental, ophthalmological, and endocrine outcomes were extracted. Study methodological quality was appraised using Joanna Briggs Institute tools. Results: Seven studies comprising 342 fetal ASP cases were included. Of these, 94 cases (27.5%) were classified as isolated ASP prenatally, but only 57 remained isolated postnatally when follow-up data were available. SOD was confirmed after birth in 11 of 94 (11.7%) fetuses with prenatally isolated ASP. As definitions, imaging protocols, genetic testing strategies, and follow-up duration differed substantially across studies, these pooled values are descriptive observations rather than formal quantitative estimates. Conclusions: ASP is a heterogeneous prenatal finding. The prognosis is most favorable when ASP remains isolated following a detailed prenatal and postnatal evaluation. Multidisciplinary follow-up involving fetal medicine, neuroradiology, genetics, ophthalmology, endocrinology, and neurology is essential for risk stratification and counseling.

Journal of Clinical Medicine doi: 10.3390/jcm15134887

Authors: Tomer Bar-Noy Rebecca Lozano-Franco Teddy S. Nagaria Melica Nourmoussavi Brodeur Shannon Salvador Susie Lau

Background: High-grade endometrial stromal sarcoma (HGESS) is a rare and aggressive uterine mesenchymal tumor with a significant potential for recurrence and metastasis. Advances in molecular pathology have identified recurrent gene fusions involving the neurotrophic tyrosine receptor kinase (NTRK) genes, which are crucial for tumorigenesis. The identification of NTRK fusions has significant therapeutic implications, as targeted therapies such as Larotrectinib, a selective tyrosine receptor kinase (TRK) inhibitor, have demonstrated remarkable efficacy in NTRK fusion-positive tumors across various tumor histologies. Case Presentation: This report depicts the case of a 42-year-old woman with HGESS harboring an NTRK fusion diagnosed by histopathology and immunohistochemistry after undergoing a vaginal myomectomy. She subsequently underwent a robotic total hysterectomy, bilateral salpingo-oophorectomy, and bilateral lymph node dissection. Following a four-year disease-free interval, HGESS relapsed. The patient received three cycles of gemcitabine plus docetaxel. Subsequent CT imaging indicated progression of the pelvic mass. Molecular testing identified an NTRK fusion. Accordingly, larotrectinib was initiated in the setting of progressive disease. After three months, imaging demonstrated a significant decrease in the pelvic mass and near-complete radiographic resolution of the pulmonary nodules. The patient remained on larotrectinib, with January 2024 imaging showing no evidence of recurrence. Conclusions: The case presented highlights a personalized approach based on molecular profiling, and the successful use of larotrectinib, a TRK inhibitor, after the identification of an NTRK fusion-positive HGESS, emphasizing the importance of molecular diagnostics and targeted therapy in managing this rare malignancy.

Journal of Clinical Medicine doi: 10.3390/jcm15134888

Authors: Michael A. Überall Artur Schikowski Philipp C. G. Müller-Schwefe

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely recommended for the treatment of acute (low) back pain, despite modest effectiveness and well-known safety concerns, particularly in older patients. Pridinol is a centrally acting antispasmodic with a mechanism-oriented approach targeting muscle spasm, a key component of acute back pain. While a previous real-world analysis demonstrated a significantly better tolerability and effectiveness of pridinol compared with NSAIDs, age-dependent effects have not yet been systematically evaluated. Objective: To assess the age dependency of effectiveness, safety, and tolerability of pridinol versus NSAIDs in patients with acute (low) back pain under real-world conditions, based on already available data. Methods: This secondary analysis used propensity score-matched real-world data from the German Pain e-Registry (PROVIDENCE study; EUPAS identifier: 49718). A total of 934 patients with acute (low) back pain treated for four weeks with either pridinol (n = 467) or NSAIDs (n = 467) were stratified by age (<65 vs. ≥65 years). Outcomes included the incidence of adverse drug reactions (ADRs), ADR-related treatment discontinuations, time to ADR occurrence, and clinically meaningful improvement in pain-related disability (≥50% reduction in modified Pain Disability Index). Analyses were performed within and between age strata. Results: Overall, ADRs were reported by 9.0% of pridinol-treated patients and 20.8% of NSAID-treated patients (p < 0.001). In the pridinol cohort, ADR rates were virtually identical in patients <65 and ≥65 years (8.9% vs. 9.2%; p = 0.940). In contrast, NSAID-treated patients showed a pronounced age-related increase in ADR incidence (17.3% vs. 32.1%; p < 0.001). ADR-related treatment discontinuation rates under NSAIDs increased markedly with age (5.9% vs. 21.1%; p < 0.001), whereas rates under pridinol remained low and age independent (3.1% vs. 4.6%; p = 0.447). Gastrointestinal and cardiovascular ADRs were the main contributors to the age-related risk increase under NSAIDs, while corresponding events under pridinol were rare across age groups. Clinically meaningful improvement in pain-related disability was achieved with pridinol/NSAIDs in 91.9/48.0% (<65 years) and 88.1/47.7% (≥65 years; p < 0.001 for both). Conclusions: Age is a major modifier of NSAID-related risk but not of pridinol tolerability in acute (low) back pain. While NSAID-associated ADRs and treatment discontinuations increase substantially in patients aged 65 years or older, pridinol demonstrates a stable, age-independent safety profile combined with significantly better functional outcomes. These findings suggest that, particularly in older patients, mechanism-oriented alternatives such as pridinol may offer a more favorable benefit–risk profile than NSAIDs.

Journal of Clinical Medicine doi: 10.3390/jcm15134885

Authors: Mateusz Lucki Ewa Lucka Jacek Żak Przemysław Mitkowski Maciej Lesiak

Background/Objectives: Artificial intelligence (AI) is increasingly transforming cardiology through advanced analytical tools capable of identifying complex patterns across cardiovascular imaging, electrophysiology, and clinical datasets. Machine learning (ML) and deep learning (DL) algorithms are being integrated into echocardiography, cardiac computed tomography (CT), cardiac magnetic resonance imaging (MRI), and electrocardiography (ECG), enabling earlier diagnosis and more personalized cardiovascular care. This narrative review summarizes current clinical and organizational applications of AI in cardiology and discusses emerging concepts related to explainable and trustworthy AI. Methods: A narrative review was conducted according to SANRA recommendations using the PubMed, MEDLINE, Web of Science, and Scopus databases, including peer-reviewed publications from 2015 to 2026 addressing clinical, organizational, and ethical applications of AI in cardiology, with particular emphasis on cardiovascular imaging, electrocardiography, heart failure, digital health, and explainable AI frameworks. Results: Substantial evidence demonstrates that AI-based tools can achieve expert-level performance in cardiovascular imaging interpretation, automated electrocardiographic analysis, and clinical risk prediction. Across multiple cardiovascular settings, AI has been associated with improved diagnostic accuracy, enhanced workflow efficiency, and earlier detection of cardiovascular disease. Predictive models support risk stratification in heart failure and ischemic heart disease, while chatbots and digital health platforms may facilitate patient engagement, remote monitoring, and continuity of care. Despite these advances, important challenges remain, including algorithmic bias, limited transparency, insufficient external validation, data heterogeneity, and barriers to routine clinical implementation. Emerging explainable AI approaches may improve model interpretability, clinician confidence, and the safe adoption of AI-driven decision support systems. Conclusions: Artificial intelligence is rapidly evolving from a research-oriented technology into a clinically relevant component of cardiovascular care. Current evidence indicates that AI can enhance diagnostic performance, improve risk prediction, streamline clinical workflows, and facilitate more personalized management across multiple cardiovascular domains. However, the successful translation of AI into routine practice will depend on robust external validation, transparent decision-making mechanisms, regulatory oversight, and clinician acceptance. The development of explainable and trustworthy AI frameworks represents a critical step toward the safe, ethical, and sustainable integration of AI into modern cardiology.

Journal of Clinical Medicine doi: 10.3390/jcm15134886

Authors: Piotr Kawczak Katarzyna Kawczak Tomasz Bączek

Acute myeloid leukemia (AML) is a biologically heterogeneous malignancy in which therapeutic decision-making is increasingly guided by molecular and immunophenotypic diagnostics. Advances in genomic profiling and risk stratification have enabled the integration of targeted agents into frontline and relapsed/refractory treatment strategies. Among these, midostaurin, venetoclax, and gemtuzumab ozogamicin represent paradigm-shifting therapies whose clinical benefit depends on accurate and timely diagnosis. This review examines the diagnostic frameworks that inform the use of these agents and discusses their incorporation into contemporary AML management. Midostaurin has demonstrated improved outcomes in patients with FLT3-mutated AML when combined with intensive chemotherapy, underscoring the importance of early molecular testing. Venetoclax, a BCL-2 inhibitor, has expanded therapeutic options for older or unfit patients when used with hypomethylating agents or low-dose cytarabine, with emerging evidence linking response to cytogenetic and molecular features. Gemtuzumab ozogamicin, an anti-CD33 antibody–drug conjugate, illustrates the clinical relevance of immunophenotypic assessment and risk-adapted dosing strategies. We highlight current evidence supporting diagnosis-driven therapy selection, practical considerations for clinical implementation, and ongoing challenges, including resistance mechanisms and optimal sequencing. Integrating precise diagnostic tools with targeted therapies represents a critical step toward personalized AML care and improved patient outcomes.

Journal of Clinical Medicine doi: 10.3390/jcm15134882

Authors: Bavo Hendriks Lidvine Ngonseu Harpi An Van Berendoncks Hilmar Bijma Anita Banerjee Dominique Mannaerts

Persisting ethnic disparities in pre-eclampsia (PE), cardiovascular disease (CVD), and maternal mortality call for a paradigm shift in how ethnicity is understood as a risk factor for PE. Starting from a migrant perspective, we argue that the transgenerational experience of maternal stress within shared, yet dynamic ecosocial contexts can be linked to core pathophysiological features of PE. A growing body of evidence suggests how a vicious cycle of chronic maternal stress, cardiovascular dysfunction, placental ER stress, and endothelial dysfunction may serve as a catalyst for the transmission of altered cardiovascular and neuro-endocrine stress reactivity patterns across generations, with a seemingly important role for foetal programming and epigenetics. As these alterations in stress reactivity patterns have in turn been associated with an increased risk of PE and CVD later in life, the resulting transgenerational chain reaction may ultimately allow for ethnic disparities in PE to be traced back to historic, stressful moments in the shared ecosocial contexts of ethnic minority women. Reconceptualising ethnicity as a proxy for the stratified and embodied experience of transgenerational maternal stress within its unique ecosocial contexts, rather than a stand-alone, non-modifiable risk factor, will therefore open new directions for future research, clinical care, and policy interventions aimed at advancing maternal health equity.

Journal of Clinical Medicine doi: 10.3390/jcm15134884

Authors: Jesús Villar Stephen M. Pastores

Ventilation is an essential function of life, and one of the first to be replicated by artificial means. Annually, it is estimated that 15 to 20 million patients worldwide are intubated and receive invasive mechanical ventilation (MV). However, MV is a non-physiologic intervention and frequent complications are associated with its use, including extravascular lung liquid, impaired cardiac performance, and alveolar rupture. Research shows that injurious MV can cause or aggravate lung damage and initiate an intense inflammatory response, contributing to multiple organ dysfunction and poor outcomes due to ventilator-induced lung liquid and intense alveolar rupture. In this brief commentary, we postulate that this resulting injury is better characterized with the term “ventilator-induced lung liquid and alveolar rupture”. We will summarize key points for clinical implications, existing challenges, and future perspectives for the management of patients with severe acute hypoxemic respiratory failure.

Journal of Clinical Medicine doi: 10.3390/jcm15134883

Authors: James Tsimiklis Theodore Athanasiadis

Objectives: To compare an endoscopically guided, modified in-office internal superior laryngeal nerve (iSLN) percutaneous steroid injection technique with a traditional landmark-guided percutaneous approach for refractory chronic cough. Methods: Single-centre retrospective comparative cohort study of those with chronic cough >8 weeks adjudicated as neurogenic/hypersensitivity-related after structured evaluation and management of common aetiologies. Consecutive patients treated at a tertiary laryngology service from January 2021 to January 2025 were identified. Patients underwent either landmark-guided percutaneous iSLN block (unmodified) or iSLN percutaneous block under flexible nasolaryngoscopic visualisation (modified), enabling real-time confirmation of needle position and routine bilateral treatment with partial superficial laryngeal mucosal instillation. Primary outcome was patient-reported improvement (Y/N; 1–10 severity scale). Secondary outcomes included Leicester Cough Questionnaire, Cough Severity Index, Newcastle Laryngeal Hypersensitivity Questionnaire, Reflux Severity Index, Voice Handicap Index-10, repeat procedures, and adverse events. Results: Of 142 patients (median age 62.8 years; 75% female), 65 underwent landmark-guided injection and 77 underwent the modified endoscopically guided technique. At most recent follow-up, global improvement was reported by 84.4% (65/77) in the modified cohort versus 47.7% (31/65) in the unmodified cohort. Median symptom reduction was greater with the modified approach (77.8% (IQR 61.3–86.6)) than among unmodified responders (50.3% (IQR 25.0–75.0)). Across all validated patient-reported outcome measures, the modified technique demonstrated more pronounced improvement than the landmark-guided approach. Minor adverse events were uncommon (modified = 6.5%, unmodified = 4.6%). Conclusions: Endoscopically guided modified iSLN steroid injection with routine bilateral targeting is associated with greater patient-reported improvement and superior validated cough outcomes than landmark-guided injection, without added significant risk.

Journal of Clinical Medicine doi: 10.3390/jcm15134880

Authors: Suheda Atas Ipek Sendag Yaslikaya Ismail Oguz Kara Tolga Koseci Ertugrul Bayram Esra Asarkaya Hatice Asoglu Mehmet Turker Abdurrahman Aykut Seda Jeral Evinc Ozkan Alan Mehmet Emin Yilmaz Ozturk Ates Hatime Arzu Yasar Mehmet Kayaalp Esra Asik Atila Yildirim Burcu Bacak Meltem Baykara Dicle Yurdatap Koc Muhammed Bekir Hacioglu Suleyman Alkan Ferhat Ekinci Ahmet Burak Agaoglu Mesut Yilmaz Ilhan Hacibekiroglu Mustafa Karaca Taliha Guclu Kantar Gamze Gokoz Dogu Tuba Karacelik Melek Karakurt Eryilmaz Teoman Sakalar Sedat Biter Mehmet Mutlu Kıdı Yasemin Aydınalp Camadan Mahmut Buyuksimsek

Background: Sorafenib remains an important treatment option for patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC). This study evaluated real-world outcomes and prognostic factors in patients treated with sorafenib. Materials and Methods: This retrospective multicenter study included 176 patients with RAI-R DTC treated with sorafenib between 2000 and 2024 across sixteen centers. Clinical, pathological and treatment-related variables, including metastatic sites, radiotherapy, dose reduction, inflammatory markers (neutrophil-to-lymphocyte ratio [NLR] and platelet-to-lymphocyte ratio [PLR]) and pretreatment thyroglobulin (Tg), were analyzed. Progression-free survival (PFS) was evaluated using Kaplan–Meier analysis. Prognostic factors were assessed using univariate and multivariate Cox regression analyses. Results: The median follow-up duration was 24 months and the median PFS was 21 months (95% CI: 15.5–26.5). Partial response was observed in 82 patients (46.6%), stable disease in 55 (31.3%) and progressive disease in 35 (19.9%). Patients who underwent dose reduction had longer PFS than those without dose reduction (42 vs. 19 months, p = 0.030), and absence of dose reduction remained independently associated with progression risk. Patients who received radiotherapy had shorter PFS than those who did not receive radiotherapy (16 vs. 37 months, p = 0.002), and radiotherapy-related variables remained independent predictors of progression. Patients with PLR values >138.2 had shorter PFS than those with PLR values ≤ 138.2 (19 vs. 34 months, p = 0.047), although this association was not maintained in Cox regression analysis. Similarly, associations between NLR and Tg values and PFS did not reach statistical significance (p = 0.112 and p = 0.072, respectively). Hand–foot syndrome was the most common toxicity, occurring in 59 patients (33.5%), while Grade 3 hand–foot syndrome was observed in 7 patients (4.0%). Conclusions: Sorafenib provided meaningful disease control with a median PFS of 21 months in this real-world cohort. Dose reduction was associated with longer PFS, whereas radiotherapy requirement appeared to reflect a higher-risk subgroup. Toxicities were generally manageable.

Journal of Clinical Medicine doi: 10.3390/jcm15134881

Authors: Dirk Rades Maria Karolin Streubel Christian Staackmann Laura Doehring Achim Rody Maria Joy Normann Haverberg Martin Ballegaard

Background/Objectives: Patients with breast cancer undergoing chemotherapy with taxanes or platin derivates often develop peripheral neuropathy (CIPN). Higher-grade CIPN generally affects the patient’s quality of life. Because the treatment options for CIPN are limited, early diagnosis is desirable to allow for timely modifications of the treatment. This may be facilitated with scoring tools that are ideally usable by the patients. A prospective study suggested that a recently developed self-assessment tool might be able to reveal the difference between the absence of CIPN and higher-grade CIPN. When CIPN has reached an advanced grade, alteration of the chemotherapy regimen may have only a limited effect. Therefore, it is important to know whether the new scoring tool can identify CIPN even when it is still mild. The current trial (NCT07604441) aims to identify the optimal cutoff point value for detecting mild CIPN. Given the limited sample size, the derived cutoff will be considered preliminary and will require validation in a larger independent cohort. Methods: The NEURO-BREAC-02 trial aims to identify the optimal cutoff point value of the new tool to distinguish between absent and mild CIPN after treatment with taxanes for breast cancer. Scores ranging between 0 and 44 points are reported via self-assessment supported by a neuropathy tracker. Secondly, the satisfaction of participants with the self-assessment tool is evaluated. Twenty-six participants (19 with mild CIPN and 7 without CIPN) are required, and 28 must be enrolled. Conclusions: The outcomes of the NEURO-BREAC-02 trial are considered crucial for the creation of a self-assessment tool to identify mild CIPN in patients with breast cancer and are a necessary addition to the preceding NEURO-BREAC study.

Journal of Clinical Medicine doi: 10.3390/jcm15134879

Authors: Andrea Severo Diego Alvaredo Rodrigo Javier González Martín Sonia Rivas García Irene Marco Beatriz Palacios Victoria González Margarita Capel Javier de Juan Bagudá Fernando Arribas Ynsaurriaga María Dolores García-Cosío Carmena Juan Francisco Delgado Jiménez

Background: Heart failure (HF) is a major public health problem and a paradigmatic condition for sex differences in cardiovascular disease. However, national population-based evidence describing these differences remains limited. We aimed to provide the first nationwide sex-stratified epidemiologic characterization of HF in Spain, quantifying incidence, prevalence, and clinical characteristics across age groups and left ventricular ejection fraction (LVEF) categories. Methods: We conducted a retrospective population-based study using the BIG-PAC database, integrating electronic health records from primary and hospital care covering approximately 1.8 million individuals across seven Spanish autonomous communities. Adult patients with incident HF between 2013 and 2019 were identified. HF phenotypes were classified according to LVEF as reduced (HFrEF ≤40%), mildly reduced (HFmrEF 41–49%), preserved (HFpEF ≥50%), or unknown (HFuEF). Incidence rates per 1000 person-years and prevalence were estimated and stratified by sex and LVEF phenotype. Results: In total, 19,961 incident HF cases were identified. Overall HF incidence was 3.23 per 1000 person-years and was similar in women and men (p = 0.697). HF prevalence was 2.34% and higher in men than in women (2.67% vs. 2.06%; p < 0.001). Women were older and more frequently presented with HFpEF (38%), whereas HFrEF predominated in men (53%); notably, HFrEF still accounted for approximately one third of HF cases among women. Once stratified by LVEF phenotype, clinical characteristics were broadly similar between sexes. Conclusions: While HF incidence was similar in women and men, substantial sex differences in prevalence, age, and phenotype distribution were identified, establishing the first nationwide epidemiological framework to inform sex-aware HF prevention and healthcare planning in Spain.

Journal of Clinical Medicine doi: 10.3390/jcm15134878

Authors: Ovidiu Samoilă Vasiliki Antonoupoulou Lăcrămioara Samoilă

Background/Objectives: This review explores the role of artificial intelligence (AI), particularly with deep learning and machine learning, in the detection and classification of papilledema using retinal fundus imaging. Methods: The study synthesizes historical, technical, and clinical insights, comparing AI-based diagnostic accuracy with conventional methods. Results: Our findings demonstrate that AI systems, especially convolutional neural networks (CNNs), offer sensitivity and specificity comparable to, or even surpassing, expert-level fundoscopy. Conclusions: These results suggest significant implications for early diagnosis, triage, and telemedicine integration in ophthalmic care.

Journal of Clinical Medicine doi: 10.3390/jcm15134876

Authors: Sarah Rebeca Teixeira de Sousa Juan Luis Sánchez-Rodríguez Alba Sánchez-Gil Celia Sánchez-Gómez Nuria Arroyo-Garrapucho Emilio Fonseca-Sánchez Luis Figuero-Pérez Juan Luis Sánchez-González Eduardo José Fernández-Rodríguez

Background: Cancer-related cognitive impairment is a frequent and clinically relevant concern among women with breast cancer, particularly during active oncological treatment, with potential consequences for memory, attention, executive functioning, daily autonomy, emotional well-being, and quality of life. This study aims to evaluate the effectiveness of the Playful Attention and Active Memory intervention (ALMA) on cognitive functioning in women with breast cancer undergoing active oncological treatment. Methods: This single-centre, three-arm, parallel-group randomized controlled trial at the University Healthcare Complex of Salamanca (Spain) will evaluate 63 women with breast cancer undergoing active oncological treatment. Participants will be randomized (1:1:1) into a health education control group, an individual non-tailored cognitive training group, or the ALMA multidimensional group intervention (two 120 min face-to-face sessions/week for four months, combining psychoeducation, targeted cognitive stimulation, and group feedback). Assessments will occur at baseline and post-intervention. The primary outcome is objective global cognitive performance (Montreal Cognitive Assessment). Secondary outcomes include perceived cognitive function, everyday cognition, functional autonomy, anxiety, sleep quality, performance status, and everyday memory failures. Intention-to-treat analysis using linear mixed models will perform prespecified comparisons of ALMA versus both other groups. Expected results: This study is designed to provide evidence on the potential value of a structured, multidimensional cognitive intervention delivered during active breast cancer treatment. By comparing ALMA with both health education and individual cognitive training, the trial may clarify whether the integration of psychoeducation, ecological cognitive stimulation, and group-based support offers additional benefits beyond cognitive practice alone. The inclusion of objective, subjective, and functionally oriented outcomes strengthens the clinical relevance of the protocol and may contribute to the development of more comprehensive supportive care strategies for cancer-related cognitive impairment. Trial registration: This protocol is registered at ClinicalTrials.gov under the identifier NCT07165912.

Journal of Clinical Medicine doi: 10.3390/jcm15134877

Authors: Bernhard Zapletal Marcus J. Schultz Michael J. Brenner Severin Laengle Edda M. Tschernko

Background: Percutaneous dilatational tracheostomy (PDT) is increasingly performed without interrupting therapeutic anticoagulation in critically ill patients with extracorporeal membrane oxygenation (ECMO) or ventricular assist devices (VADs). However, the safety of PDT performed under ongoing therapeutic anticoagulation, particularly regarding periprocedural bleeding risk, remains uncertain. This study compared periprocedural bleeding complications between patients undergoing PDT under therapeutic and prophylactic anticoagulation. Methods: This observational cohort study in a cardiovascular ICU included all patients who underwent PDT between 2016 and 2024. The cohort comprised critically ill patients receiving uninterrupted therapeutic anticoagulation for ECMO, VAD, MVs (mechanical heart valves), and arrhythmia, as well as patients receiving low-dose anticoagulation for venous thromboprophylaxis. The primary endpoint was any severe procedure-related or late bleeding complication, while secondary endpoints included all minor procedure-related or late bleeding complications. Results: The cohort included 174 patients of whom 84 (48.3%) underwent PDT receiving uninterrupted therapeutic anticoagulation for ECMO, VAD, MVs, or arrhythmia. None experienced severe procedure-related bleeding. The incidence of major and minor bleeding complications did not differ between patients receiving uninterrupted therapeutic anticoagulation and those undergoing PDT under low-dose prophylactic anticoagulation. Other bleeding complications were also rare and comparable between the two groups. Conclusions: In this cohort, the incidence of severe and minor bleeding was low among patients undergoing PDT under uninterrupted therapeutic anticoagulation for ECMO, VAD, MVs, or arrhythmia and did not differ from that in patients receiving low-dose anticoagulation for venous thromboprophylaxis. BMI, but not anticoagulation intensity, was independently associated with post-PDT bleeding.

Journal of Clinical Medicine doi: 10.3390/jcm15134875

Authors: Insafe Mezjan Aurore Sellier François Lechanoine Nacer Mansouri Guillaume Lonjon François-Xavier Ferracci Louis-Marie Terrier Philippe Cam Anthony Melot Joseph Cristini

Background/Objectives: Multilevel lumbar spinal stenosis (MLSS) is frequently encountered in patients undergoing surgery for lumbar spinal stenosis, yet the optimal extent of decompression remains debated. While multilevel decompression (MLD) may address all radiological stenotic levels, it may also increase surgical invasiveness and operative time. Minimally invasive endoscopic techniques such as unilateral biportal endoscopy (UBE) allow for targeted decompression and facilitate staged surgical strategies. The aim of this study was to evaluate the clinical outcomes of selective single-level decompression (SLD) using UBE in patients presenting with MLSS. Methods: This retrospective monocentric observational study included consecutive adult patients with MLSS who underwent decompression using UBE between December 2022 and July 2025. MLSS was defined as the presence of at least two lumbar levels with Schizas grade B or higher stenosis. Patients undergoing prior lumbar surgery or presenting with non-degenerative pathology were excluded. Patients underwent either SLD targeting the symptom-driving level or MLD, depending on the surgical strategy. Patient-reported outcomes included the Oswestry Disability Index (ODI), lumbar visual analog scale (LVAS), and radicular visual analog scale (RVAS). Results: Among 305 patients operated on for lumbar spinal stenosis, 83 (27%) presented with MLSS and were included in the study. Seventy-four patients (89%) underwent initial SLD and nine (11%) underwent MLD. Among patients treated with SLD, 9 (12%) required a second decompression during follow-up, whereas 65 patients (88%) achieved favorable outcomes without further surgery. Across the entire cohort, ODI, LVAS, and RVAS improved significantly after surgery. Operative time was significantly longer in the MLD group (122 ± 28.1 min vs. 58.1 ± 12.0 min; p < 0.001). These findings support the feasibility of a symptom-driven selective decompression strategy for MLSS using UBE. In our cohort, most patients experienced meaningful functional improvement after SLD without requiring additional surgery. Although a staged approach may necessitate secondary intervention in a minority of patients, selective decompression may help limit surgical extent in carefully selected patients while preserving favorable clinical outcomes. Conclusions: Selective SLD using UBE was associated with significant clinical improvement in most patients with MLSS while reducing operative time and surgical extent. A stepwise strategy targeting the dominant symptomatic level may represent a feasible minimally invasive approach for selected patients with MLSS. Prospective studies are needed to confirm these findings.

Journal of Clinical Medicine doi: 10.3390/jcm15134874

Authors: Radu-Andrei Moga Cristian Doru Olteanu Ada Gabriela Delean

Background/Objectives: Prepubertal localized aggressive periodontitis/LPP is an extremely rare but extremely fast-progressing form of periodontal disease involving systemically healthy children, starting in primary and mixed dentition. Our aim is to synthesize the data (January 2014–April 2026) on LPP progression description in systemically healthy children aged 2–13 years; clinical and biological responses to available treatment strategies, focusing on disease progression pattern, treatment efficacy and factors influencing treatment outcomes; and correlating findings with a report of a 24-month follow-up of a female prepubertal Caucasian patient during the primary and early stages of mixed dentition. Methods: A total of 489 studies were found after deduplication for the selected period. Due to the eligibility criteria, 9 studies plus another 10 contextual publications were included. Additionally, a 24-month follow-up of a previous LPP case was correlated. Results: LPP displayed rapid tissular destruction in primary dentition with risks to transfers to mixed and permanent dentition. The systemic antibiotic treatment reduced tissue loss, enabling fast periodontal regeneration. LPP is rare but severe, with a continuous biological trajectory, and with the window of opportunity remaining when the first symptoms appear. A few months (4–6 months) delay in diagnosis leads to irreversible tooth loss even in young patients with high biological healing potential. Conclusions: Systemic antibiotic treatment is mandatory in LPP/C-MIP cases from the primary dentition phase but does not reset host susceptibility. The Amoxicillin/Augmentin–Metronidazole association is recommended, with caution regarding dosage (adverse reactions). Periodontal gains are radiologically and clinically proven, but rebounding is possible.

Journal of Clinical Medicine doi: 10.3390/jcm15134873

Authors: Giuseppe Patti Manuel Bosco Alessandra Marengo Luca Cumitini Leonardo Grisafi Domenico D’Amario Martina Solli Marco Mennuni

Background: Early initiation of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-i) in patients with acute myocardial infarction (MI) may anticipate and maximize lipid-lowering benefit. Whether PCSK9 inhibition also exerts early anti-inflammatory effects in this setting remains unclear. This study aimed to evaluate the effects of early PCSK9-i administration on inflammatory markers and lipid parameters in patients with acute MI undergoing percutaneous coronary intervention (PCI). Methods: In this randomized, prospective, single-center, open-label trial, patients with acute MI undergoing PCI were randomly assigned to receive a single upstream 140 mg subcutaneous dose of evolocumab immediately before PCI, on top of oral lipid-lowering therapy (LLT) (n = 30), or oral LLT alone (control group; n = 30). Tumor necrosis factor-alpha (TNF-α), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and lipoprotein(a) [Lp(a)] levels were measured at baseline and during the early post-intervention phase. Results: Baseline TNF-α values and lipid parameters were similar between the two groups. At 72 h after PCI, TNF-α levels were significantly lower in the evolocumab arm compared with controls (0.01 vs. 0.25 pg/mL; p = 0.025). Evolocumab was also associated with a greater relative reduction in LDL-C levels from baseline (−48% vs. −18%; p < 0.001) and apoB levels (−34% vs. −11%; p < 0.001). The proportion of patients achieving the LDL-C goal of <55 mg/dL at 72 h was higher in the evolocumab group than in controls (50% vs. 10%; p < 0.001). Lp(a) levels at 72 h were also lower with evolocumab (12 [10–33] vs. 28 [13.1–70] mg/dL; p = 0.032). Conclusions: In patients with acute MI undergoing PCI, upstream administration of a single evolocumab dose was associated with suppression of the early post-intervention increase in TNF-α levels, together with rapid reductions in LDL-C, apoB, and Lp(a). These findings suggest a potential modulation of the early inflammatory response by PCSK9 inhibition in addition to its lipid-lowering effects. Larger studies are needed to confirm these observations and to determine their clinical relevance.

Journal of Clinical Medicine doi: 10.3390/jcm15134871

Authors: Rasha Aziz Attia Salama Omar Fadi Msalat Moustafa Medhat Fouad Mohammed Alhammadi Siddig Elsheikh Rashed Ali Nasser

Background: The oral microbiome has emerged as a potential contributor to cardiovascular physiology through its role in the enterosalivary nitrate–nitrite–nitric oxide pathway. Oral nitrate-reducing bacteria convert dietary nitrate into nitrite, which can subsequently be reduced to nitric oxide, a signaling molecule associated with vascular tone, endothelial function, platelet activity, and blood pressure regulation. Disruption of this pathway has been associated with reduced nitric oxide bioavailability and impaired vascular responses. Methods: This narrative review summarizes current evidence regarding the relationship between the oral microbiome, nitrate metabolism, and cardiovascular function. Relevant literature was identified through searches of PubMed/MEDLINE and Google Scholar up to May 2026. Evidence from mechanistic, observational, and interventional human studies was reviewed and synthesized thematically. Results: Available evidence suggests that oral nitrate-reducing bacteria may influence nitric oxide bioavailability and vascular function. Studies have reported associations between oral microbiome disruption and changes in blood pressure, endothelial responsiveness, plasma nitrite concentrations, and other surrogate cardiovascular markers. However, findings remain heterogeneous and are influenced by factors such as diet, oral hygiene practices, smoking status, medication use, oral health, and underlying cardiometabolic conditions. Most studies are limited by small sample sizes, short intervention durations, and reliance on surrogate outcomes rather than major cardiovascular events. Conclusions: The oral microbiome may influence cardiovascular health through its role in nitrate metabolism and nitric oxide bioavailability. However, current evidence is largely limited to surrogate vascular outcomes, while data on major cardiovascular events remain scarce. Further longitudinal and interventional studies are needed to clarify causality and evaluate microbiome-targeted interventions.

Journal of Clinical Medicine doi: 10.3390/jcm15134872

Authors: Ion Costel Epuraș Alexandru Florian Crișan Nicolae Constantin Balica Cristian Ion Moț Adrian Mihail Sitaru Mihaela Iuliana Sîrbu Andreea Mihaela Banta Dan Iovanescu Carina Gib Gheorghe Iovanescu

Background/Objectives: Treatment for laryngeal cancer often impacts voice, swallowing, communication, and quality of life. Patient-reported outcome measures (PROMs) are increasingly used to evaluate survivorship, but their application and connection with objective functional measures vary widely. The objective was to explore how PROMs are used in laryngeal cancer research, identify the functional areas they assess, analyze their link with objective clinical outcomes, and identify methodological gaps in current studies. Methods: This scoping review followed PRISMA-ScR guidelines. Searches were conducted in PubMed/MEDLINE, Scopus, and Web of Science from their start until April 2026. Included studies involved adults with laryngeal cancer reporting PROMs and/or objective functional outcomes. Data on study features, PROM tools, evaluated domains, and how PROMs relate to objective outcomes were extracted and summarized descriptively. Results: Ninety-five studies with 10,807 participants were included. Most were observational (84.2%) and conducted at a single center (72.6%). Voice-related outcomes were the most common (86.3%), followed by psychological (72.6%) and swallowing outcomes (65.3%). Less frequently assessed were nutritional (22.1%) and supportive care domains (41.1%). The Voice Handicap Index family was the most used PROM group (30.5%). Over half the studies reported PROMs and objective measures separately without statistical integration (51.6%), while only 13.7% performed analytical integration, and none used predictive multivariable models. Significant variation existed in PROM choices, assessed domains, and integration approaches. Conclusions: PROM use in laryngeal cancer survivorship research is heterogeneous and predominantly focused on voice-related outcomes. Limited analytical integration with objective measures hampers a comprehensive understanding of recovery. There is a need for standardized, multidimensional assessment frameworks that include functional, nutritional, psychosocial, and objective outcomes to effectively support patient-centered survivorship care and rehabilitation planning.