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11 pages, 521 KiB  
Article
Comparative Study of Two Classification Criteria Sets in Real Clinical Practice for Behçet’s Disease
by Rafael Gálvez-Sánchez, José Luis Martín-Varillas, Lara Sánchez-Bilbao, Iván Ferraz-Amaro, Elena Aurrecoechea, Diana Prieto-Peña and Ricardo Blanco
J. Clin. Med. 2025, 14(15), 5559; https://doi.org/10.3390/jcm14155559 (registering DOI) - 7 Aug 2025
Abstract
Background: Behçet’s Disease (BD) was traditionally classified according to the International Study Group (ISG), where oral ulcers were mandatory. The International Team for the Revision of the International Criteria for BD (ICBD) introduced a scoring system instead. Our aim was to assess (a) [...] Read more.
Background: Behçet’s Disease (BD) was traditionally classified according to the International Study Group (ISG), where oral ulcers were mandatory. The International Team for the Revision of the International Criteria for BD (ICBD) introduced a scoring system instead. Our aim was to assess (a) sensitivity, (b) concordance between ISG and ICDB criteria in global and severe BD cases (ocular, vascular, and neurological), and (c) evaluate their clinical implications. Methods: Retrospective cohort study including 142 BD patients diagnosed in a well-defined population in Northern Spain, between January 1980 and November 2023. Both ISG and ICBD criteria were compared, sensitivity and concordance were assessed using Prevalence-Adjusted and Bias-Adjusted Kappa (PABAK) and the unadjusted Kappa. Results: A total of 142 BD patients diagnosed by expert rheumatologists (73 men; mean age of 36.4) were studied. Among them, 84 met ISG criteria, while 116 fulfilled ICBD criteria. Sensitivity of ISG and ICBD criteria in the overall cohort was (59.1% and 81.6%), respectively. Among patients with severe manifestations (ocular, vascular, or neurological), sensitivity increased to 71.2% for ISG and 92.5% for ICBD. Overall concordance was moderate (Kappa = 0.490), with 70.4% of patients classified identically. When adjusting prevalence and bias, concordance improved slightly (PABAK = 0.549). Of the 32 patients classified as BD exclusively by ICBD, 7 were receiving anti-TNF therapy, and 2 were receiving apremilast. Conclusions: The ICBD criteria demonstrated higher sensitivity than the traditional ISG criteria in classifying BD, particularly in severe cases. Classifying these additional patients under ICBD facilitated the initiation of on-label biologic treatments, potentially enhancing BD management, especially for severe cases. Full article
(This article belongs to the Section Immunology)
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14 pages, 759 KiB  
Article
Vitamin D Deficiency and Exocrine Pancreatic Insufficiency: An Analysis Carried Out in Orthogeriatric Patients (VIDEP.org)
by Pavol Mikula, Matthias Unseld and Hans Jürgen Heppner
J. Clin. Med. 2025, 14(15), 5558; https://doi.org/10.3390/jcm14155558 (registering DOI) - 7 Aug 2025
Abstract
Introduction: Vitamin D deficiency, a reversible cause of osteoporosis, is increasingly prevalent, showing varying degrees of severity that are notably pronounced among the growing population of multimorbid elderly patients. Given that the aging pancreas undergoes senescent processes leading to impaired function—which negatively impacts [...] Read more.
Introduction: Vitamin D deficiency, a reversible cause of osteoporosis, is increasingly prevalent, showing varying degrees of severity that are notably pronounced among the growing population of multimorbid elderly patients. Given that the aging pancreas undergoes senescent processes leading to impaired function—which negatively impacts enteral vitamin D absorption and, consequently, elderly bone metabolism—a specific diagnostic and treatment approach is crucial. Our study aimed to determine the prevalence of vitamin D deficiency and exocrine pancreatic insufficiency (EPI) in orthogeriatric patients. We also evaluated differences in vitamin D deficiency severity between patients with normal and impaired pancreatic function. Furthermore, a short-term monitoring of vitamin D level increases after 12 days of substitution therapy in both groups aimed to inform osteoanabolic therapy for specific high-fracture-risk patients, assessing the influence of pancreatic function on substitution efficacy. Methods: We conducted a retrospective, monocentric cohort study, evaluating data from all patients hospitalized with manifest osteoporosis in an orthogeriatric department during a six-month spring/summer period. Demographic data, relevant comorbidities, the type of fracture, the amount of faecal elastase 1 (CALEX® Cap Bühlmann), and the serum levels of 25-hydroxyvitamin D (25(OH)D) were assessed. Results: We found a high prevalence (70.6%) of vitamin D deficiency (25(OH)D < 30 µg/L) among all orthogeriatric patients. Of these, 16% met the criteria for mild to severe EPI. The group with normal exocrine pancreatic function showed a higher average vitamin D value, and their increase in vitamin D levels following short-term substitution was up to 100% greater compared to the group with impaired pancreatic function. Notably, 69% of women and 20% of men met the therapeutic threshold for specific osteoanabolic osteoporosis therapy, even without a T-score. Conclusions: Our findings reveal a very high prevalence of vitamin D deficiency and a high prevalence of EPI in orthogeriatric patients. Those with impaired exocrine pancreatic function exhibit lower baseline vitamin D levels and a diminished capacity for vitamin D absorption during short-term monitoring. These results have significant clinical implications for osteoporotic therapy, given that a substantial proportion of patients, particularly women, meet the criteria for specific osteoanabolic treatment. Full article
(This article belongs to the Special Issue The “Orthogeriatric Fracture Syndrome”—Issues and Perspectives)
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15 pages, 943 KiB  
Article
Anterior Redisplacement After Intramedullary Nail Fixation for Trochanteric Femoral Fractures: Incidence and Risk Factors in 598 Older Patients
by Hironori Kuroda, Suguru Yokoo, Yukimasa Okada, Junya Kondo, Koji Sakagami, Takahiko Ichikawa, Keiya Yamana and Chuji Terada
J. Clin. Med. 2025, 14(15), 5557; https://doi.org/10.3390/jcm14155557 (registering DOI) - 6 Aug 2025
Abstract
Background/Objectives: Anterior redisplacement, defined as a postoperative anterior shift of the distal fragment despite intraoperative reduction, is occasionally observed after cephalomedullary nailing for trochanteric femoral fractures. However, its incidence and associated risk factors remain unclear. This study aimed to determine the incidence of [...] Read more.
Background/Objectives: Anterior redisplacement, defined as a postoperative anterior shift of the distal fragment despite intraoperative reduction, is occasionally observed after cephalomedullary nailing for trochanteric femoral fractures. However, its incidence and associated risk factors remain unclear. This study aimed to determine the incidence of anterior redisplacement following intramedullary nail fixation in geriatric trochanteric fractures, and to identify independent risk factors. Methods: This study retrospectively reviewed data from 598 consecutive hips in 577 patients (aged ≥ 65 years) who underwent intramedullary nail fixation for trochanteric fractures at a single center (2012–2023). Sagittal reduction on the lateral radiographic view was classified as posterior, anatomical, or anterior according to the position of the distal fragment, and was recorded preoperatively and postoperatively. Anterior redisplacement, the primary outcome, was defined as a change in alignment from a posterior or anatomical position postoperatively to an anterior position on any subsequent follow-up radiograph. Independent risk factors were identified by logistic regression. Results: Among the 543 hips reduced posteriorly (n = 204) or anatomically (n = 339), anterior redisplacement occurred in 73 (13.4%). The incidence of anterior redisplacement was significantly higher following anatomical compared to posterior reduction (19.5% vs. 3.4%; p < 0.001), and also higher in fractures that were anteriorly aligned preoperatively (18.0%) compared to anatomical (8.5%; p < 0.01) and posterior (6.2%; p < 0.01) alignment. Multivariate analysis revealed two independent predictors: preoperative anterior alignment (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.24–2.81; p = 0.003) and postoperative anatomical (vs. posterior) reduction (OR 6.49, 95% CI 2.92–14.44; p < 0.001). Age, sex, Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association classification, Evans–Jensen classification, nail length, and canal-filling ratio were not associated with redisplacement. No lag‑screw cutout occurred during the follow-up. Conclusions: Anterior redisplacement occurred in one of seven geriatric trochanteric fractures despite apparently satisfactory fixation. An anatomical sagittal reduction—traditionally considered “ideal”—increases the risk more than sixfold, whereas a deliberate posterior-buttress is protective. Unlike patient-related risk factors, sagittal reduction is under the surgeon’s control. The study findings provide evidence that choosing a slight posterior bias can significantly improve stability. Full article
(This article belongs to the Special Issue Geriatric Fracture: Current Treatment and Future Options)
10 pages, 485 KiB  
Article
Factors Associated with Functional Outcome Following Acute Ischemic Stroke Due to M1 MCA/ICA Occlusion in the Extended Time Window
by John Constantakis, Quinn Steiner, Thomas Reher, Timothy Choi, Fauzia Hollnagel, Qianqian Zhao, Nicole Bennett, Veena A. Nair, Eric E. Adelman, Vivek Prabhakaran, Beverly Aagard-Kienitz and Bolanle Famakin
J. Clin. Med. 2025, 14(15), 5556; https://doi.org/10.3390/jcm14155556 - 6 Aug 2025
Abstract
Introduction: A validated clinical decision tool predictive of favorable functional outcomes following endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) remains elusive. We performed a retrospective case series of patients at our regional Comprehensive Stroke Center, over a four-year period, who have undergone [...] Read more.
Introduction: A validated clinical decision tool predictive of favorable functional outcomes following endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) remains elusive. We performed a retrospective case series of patients at our regional Comprehensive Stroke Center, over a four-year period, who have undergone EVT to elucidate patient characteristics and factors associated with a favorable functional outcome after EVT. Methods: We reviewed all cases of EVT at our institution between February 2018 and February 2022 in the extended time window from 6–24 h. Demographic, clinical, imaging, and procedure co-variates were included. A favorable clinical outcome was defined as a modified Rankin scale of 0–2. We included patients with M1 or internal carotid artery occlusion treated with EVT within 6–24 h after symptom onset. We used a univariate and multivariate logistic regression analysis to identify patient factors associated with a favorable clinical outcome at 90 days. Results: Our study included evaluation of 121 patients who underwent EVT at our comprehensive stroke center. Our analysis demonstrates that a higher recanalization score based on the modified Thrombolysis In Cerebral Infarction (mTICI) scale (2B-3) was a strong indicator of a favorable outcome (OR 7.33; CI 2.06–26.07; p = 0.0021). Our data also showed that a higher baseline National Institutes of Health Stroke Scale (NIHSS) score (p = 0.0095) and the presence of pre-existing hypertension (p = 0.0035) may also be predictors of an unfavorable outcome (mRS > 2) per our multivariate analysis. Conclusion: Patients without pre-existing hypertension had more favorable outcomes following EVT in the expanded time window. This is consistent with other multicenter data in the expanded time window that demonstrates greater odds of a poor outcome with elevated pre-, peri-, and post-endovascular-treatment blood pressure. Our data also demonstrate that the mTICI score is a strong predictor of favorable outcome, even after controlling for other variables. A lower baseline NIHSS at the time of thrombectomy may also indicate a favorable outcome. Furthermore, the presence of clinical or radiographic mismatch based on the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and NIHSS per DAWN and DEFUSE-3 criteria did not emerge as a predictor of favorable outcome, which is congruent with recent randomized controlled trials and meta-analyses. Full article
(This article belongs to the Special Issue Ischemic Stroke: Diagnosis and Treatment)
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15 pages, 1477 KiB  
Article
Objectification of the Functional Myodiagnosis Muscle Test
by Josef Franz Mahlknecht, Eugen Burtscher, Ivan Ramšak, Christine Zürcher and Johannes Bernard
J. Clin. Med. 2025, 14(15), 5555; https://doi.org/10.3390/jcm14155555 - 6 Aug 2025
Abstract
Objective: This study aimed to investigate whether the subjective assessments of strong and weak muscles in the Functional Myodiagnosis muscle test (FMD-MT) can be objectively and reproducibly verified using physically measurable parameters. Additionally, we sought to evaluate the reliability of the manual muscle [...] Read more.
Objective: This study aimed to investigate whether the subjective assessments of strong and weak muscles in the Functional Myodiagnosis muscle test (FMD-MT) can be objectively and reproducibly verified using physically measurable parameters. Additionally, we sought to evaluate the reliability of the manual muscle test in order to reinforce the scientific evidence supporting this accepted, yet not widely adopted, complementary medicine method. Methods: In a crossover observational study, three experienced medical practitioners conducted the FMD-MT of the rectus femoris muscle on 24 healthy participants using a specially designed therapy bench, with all measurements recorded via an oscillogram. The study investigated the force–time integral, joint angle change, additional force load, mean force turning point 1, as well as the interrater reliability and validity of both examiner assessments and instrumental analyses for the two muscle reaction variants: strong and weak. Results: A significant difference between the response pattern of strong and weak muscles was identified for the force–time integral (p = 0.005), the change in joint angle (p < 0.001), and the additional force load (p = 0.001). No difference between strong and weak muscles could be detected regarding the force turning point 1 (p = 0.972). The examiners demonstrated 100% accuracy in identifying weak muscle reactions as weak, and 99.2% accuracy in identifying strong muscle reactions as strong (p = 0.316). The overall intra-class correlation coefficient was 0.984. The oscillogram correctly visualized weak muscle reactions in weak muscles with an accuracy of 81.7%, and strong muscle reactions in strong muscles with an accuracy of 86.7% (p = 0.289). Conclusions: The Functional Myodiagnosis muscle test (FMD-MT) enables a clear and objective differentiation between strong and weak muscles, with statistically significant differences observed in the force–time integral, additional force load, and joint angle changes. Under rigorously standardized testing conditions, the FMD-MT of the rectus femoris muscle demonstrates a validity rate of 99.6% and an excellent reliability (ICC 0.984). Consequently, the FMD muscle test proves to be a reliable, reproducible, and objective diagnostic method. Trial registration: German Register of Clinical Studies U1111-1212-6622. Full article
(This article belongs to the Section Sports Medicine)
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19 pages, 1226 KiB  
Article
Improving Endodontic Radiograph Interpretation with TV-CLAHE for Enhanced Root Canal Detection
by Barbara Obuchowicz, Joanna Zarzecka, Michał Strzelecki, Marzena Jakubowska, Rafał Obuchowicz, Adam Piórkowski, Elżbieta Zarzecka-Francica and Julia Lasek
J. Clin. Med. 2025, 14(15), 5554; https://doi.org/10.3390/jcm14155554 - 6 Aug 2025
Abstract
Objective: The accurate visualization of root canal systems on periapical radiographs is critical for successful endodontic treatment. This study aimed to evaluate and compare the effectiveness of several image enhancement algorithms—including a novel Total Variation–Contrast-Limited Adaptive Histogram Equalization (TV-CLAHE) technique—in improving the detectability [...] Read more.
Objective: The accurate visualization of root canal systems on periapical radiographs is critical for successful endodontic treatment. This study aimed to evaluate and compare the effectiveness of several image enhancement algorithms—including a novel Total Variation–Contrast-Limited Adaptive Histogram Equalization (TV-CLAHE) technique—in improving the detectability of root canal configurations in mandibular incisors, using cone-beam computed tomography (CBCT) as the gold standard. A null hypothesis was tested, assuming that enhancement methods would not significantly improve root canal detection compared to original radiographs. Method: A retrospective analysis was conducted on 60 periapical radiographs of mandibular incisors, resulting in 420 images after applying seven enhancement techniques: Histogram Equalization (HE), Contrast-Limited Adaptive Histogram Equalization (CLAHE), CLAHE optimized with Pelican Optimization Algorithm (CLAHE-POA), Global CLAHE (G-CLAHE), k-Caputo Fractional Differential Operator (KCFDO), and the proposed TV-CLAHE. Four experienced observers (two radiologists and two dentists) independently assessed root canal visibility. Subjective evaluation was performed using an own scale inspired by a 5-point Likert scale, and the detection accuracy was compared to the CBCT findings. Quantitative metrics including Peak Signal-to-Noise Ratio (PSNR), Signal-to-Noise Ratio (SNR), image entropy, and Structural Similarity Index Measure (SSIM) were calculated to objectively assess image quality. Results: Root canal detection accuracy improved across all enhancement methods, with the proposed TV-CLAHE algorithm achieving the highest performance (93–98% accuracy), closely approaching CBCT-level visualization. G-CLAHE also showed substantial improvement (up to 92%). Statistical analysis confirmed significant inter-method differences (p < 0.001). TV-CLAHE outperformed all other techniques in subjective quality ratings and yielded superior SNR and entropy values. Conclusions: Advanced image enhancement methods, particularly TV-CLAHE, significantly improve root canal visibility in 2D radiographs and offer a practical, low-cost alternative to CBCT in routine dental diagnostics. These findings support the integration of optimized contrast enhancement techniques into endodontic imaging workflows to reduce the risk of missed canals and improve treatment outcomes. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
8 pages, 824 KiB  
Systematic Review
Early Rotator Cuff Repair Yields Lower Retear Rates and Superior Functional Outcomes: A Systematic Review and Meta-Analysis
by Alexander Baur, Wesley Lemons, Omar Protzuk and Jonathan Brett Goodloe
J. Clin. Med. 2025, 14(15), 5552; https://doi.org/10.3390/jcm14155552 - 6 Aug 2025
Abstract
Background: Optimal timing for surgery following acute rotator cuff tears remains unclear. This study examines how the timing of arthroscopic rotator cuff repair (RCR) affects retear rates and functional outcomes. Methods: This PROSPERO-registered review (CRD42024528249) followed PRISMA guidelines and included randomized trials, and [...] Read more.
Background: Optimal timing for surgery following acute rotator cuff tears remains unclear. This study examines how the timing of arthroscopic rotator cuff repair (RCR) affects retear rates and functional outcomes. Methods: This PROSPERO-registered review (CRD42024528249) followed PRISMA guidelines and included randomized trials, and cohort, studies on adults with imaging-confirmed full-thickness rotator cuff tears. Studies lacking timing data or key outcomes were excluded. Risk of bias was assessed using ROBINS-I. Meta-analysis of retear rates was performed comparing surgical timing. Qualitative analysis was conducted classifying results as early-beneficial, delayed-detrimental, or neutral. Results: Our review included 13 studies and 871 patients with an average age of 57.9. Meta-analysis of eight studies comparing retear rates between early and delayed RCR demonstrated a significant benefit associated with early intervention risk ratio 0.60 (95% CI: 0.38–0.96). Functional outcomes also favored early intervention with four studies demonstrating significantly greater postoperative functional improvements in the early intervention group. Conclusions: Early arthroscopic RCR decreased the rate of retear and improved functional outcomes. No study found early intervention to be detrimental or delayed intervention to be superior. These findings support consideration of early repair when clinically appropriate. Future studies should determine more finite timing guidelines. Full article
(This article belongs to the Special Issue Current Trends and Innovations in Arthroscopic Shoulder Surgery)
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17 pages, 2823 KiB  
Case Report
Evaluating Effects of Skin Needling Treatment on Visible Changes and Elasticity of Scars Using High-Frequency Ultrasound, Cutometer®, and Standardized Questionnaire—Six Case Studies
by Marta Wacewicz-Muczyńska, Dominika Chojnacka, Bogumiła Redlarska and Anna Kołodziejczak
J. Clin. Med. 2025, 14(15), 5553; https://doi.org/10.3390/jcm14155553 - 6 Aug 2025
Abstract
Background/Objectives: Scars are formed from trauma to the dermis and more specifically during the wound-healing phase. Skin needling is a technique used in scar therapy which stimulates the skin to regenerate. The aim of this study was to objectively and subjectively evaluate [...] Read more.
Background/Objectives: Scars are formed from trauma to the dermis and more specifically during the wound-healing phase. Skin needling is a technique used in scar therapy which stimulates the skin to regenerate. The aim of this study was to objectively and subjectively evaluate the degree of scar reduction after skin needling treatments based on visible changes using specialized measuring devices—ultrasound, Courage & Khazaka, and standardized questionnaires. Methods: Six patients were enrolled. Participants were given a series of three skin needling treatments. Before and after the treatment, the participants were examined for selected skin parameters with the help of specialized measuring devices such as Courage & Khazaka and skin ultrasound. Skin firmness and elasticity and MEP and HEP skin echogenicity were taken into account. Each patient completed POSAS questionnaires on satisfaction, pain, and adverse effects. Results: Based on the results of the POSAS questionnaire, a significant improvement in patients’ scar evaluation was observed after the treatment. Patients reported the most noticeable improvements in parameters such as color (p = 0.035), stiffness (p = 0.009), thickness (p = 0.041), and irregularity (0.007). An improvement in scar elasticity was observed in all subjects after treatment. Conclusions: Skin needling treatment combined with the skin needling technique and post-treatment skincare is an effective method of scar therapy, and the risk of side effects or complications after a series of treatments is low. Full article
(This article belongs to the Special Issue Tissue Scarring, Fibrosis and Regeneration)
14 pages, 845 KiB  
Article
Assessment of Ultrasound-Controlled Diagnostic Methods for Thyroid Lesions and Their Associated Costs in a Tertiary University Hospital in Spain
by Lelia Ruiz-Hernández, Carmen Rosa Hernández-Socorro, Pedro Saavedra, María de la Vega-Pérez and Sergio Ruiz-Santana
J. Clin. Med. 2025, 14(15), 5551; https://doi.org/10.3390/jcm14155551 - 6 Aug 2025
Abstract
Background/Objectives: Accurate diagnosis of thyroid cancer is critical but challenging due to overlapping ultrasound (US) features of benign and malignant nodules. This study aimed to evaluate the diagnostic performance of non-invasive and minimally invasive US techniques, including B-mode US, shear wave elastography (SWE), [...] Read more.
Background/Objectives: Accurate diagnosis of thyroid cancer is critical but challenging due to overlapping ultrasound (US) features of benign and malignant nodules. This study aimed to evaluate the diagnostic performance of non-invasive and minimally invasive US techniques, including B-mode US, shear wave elastography (SWE), color Doppler, superb microvascular imaging (SMI), and TI-RADS, in patients with suspected thyroid lesions and to assess their reliability and cost effectiveness compared with fine needle aspiration (FNA) biopsy. Methods: A prospective, single-center study (October 2023–February 2025) enrolled 300 patients with suspected thyroid cancer at a Spanish tertiary hospital. Of these, 296 patients with confirmed diagnoses underwent B-mode US, SWE, Doppler, SMI, and TI-RADS scoring, followed by US-guided FNA and Bethesda System cytopathology. Lasso-penalized logistic regression and a bootstrap analysis (1000 replicates) were used to develop diagnostic models. A utility function was used to balance diagnostic reliability and cost. Results: Thyroid cancer was diagnosed in 25 patients (8.3%). Elastography combined with SMI achieved the highest diagnostic performance (Youden index: 0.69; NPV: 97.4%; PPV: 69.1%), outperforming Doppler-only models. Intranodular vascularization was a significant risk factor, while peripheral vascularization was protective. The utility function showed that, when prioritizing cost, elastography plus SMI was cost effective (α < 0.716) compared with FNA. Conclusions: Elastography plus SMI offers a reliable, cost-effective diagnostic rule for thyroid cancer. The utility function aids clinicians in balancing reliability and cost. SMI and generalizability need to be validated in higher prevalence settings. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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27 pages, 1483 KiB  
Systematic Review
Effectiveness of Virtual Reality-Based Training Versus Conventional Exercise Programs on Fall-Related Functional Outcomes in Older Adults with Various Health Conditions: A Systematic Review
by Krzysztof Kasicki, Ewa Klimek Piskorz, Łukasz Rydzik, Tadeusz Ambroży, Piotr Ceranowicz, Maria Belcarz Ciuraj, Paweł Król and Wiesław Błach
J. Clin. Med. 2025, 14(15), 5550; https://doi.org/10.3390/jcm14155550 - 6 Aug 2025
Abstract
Background/Objectives: The aim of this systematic review was to compare the effectiveness of virtual reality (VR)-based training with conventional exercise programs in improving functional outcomes related to fall risk among older adults with various health conditions. Methods: The review was conducted in accordance [...] Read more.
Background/Objectives: The aim of this systematic review was to compare the effectiveness of virtual reality (VR)-based training with conventional exercise programs in improving functional outcomes related to fall risk among older adults with various health conditions. Methods: The review was conducted in accordance with the PRISMA 2020 guidelines and registered in PROSPERO (registration number CRD42022345678). The databases Scopus, PubMed, Web of Science, and EBSCO were searched up to 31 March 2025. Randomized controlled trials (RCTs) were included if they involved participants aged ≥60 years, a VR intervention lasting ≥6 weeks, and a control group performing traditional exercises or receiving usual care. Methodological quality was assessed using the PEDro scale, and a narrative synthesis was performed across four outcome domains: balance, mobility, cognitive function, and fall risk. Results: Seven RCTs were included in the analysis (totaling 664 participants). VR training was found to be at least as effective as conventional exercise in improving balance (e.g., Berg Balance Scale) and mobility (e.g., Timed Up and Go), with some studies showing superior effects of VR. One RCT demonstrated that combining VR with balance exercises (MIX) yielded the greatest improvements in muscle strength and physical performance. Additionally, two studies reported cognitive benefits (e.g., MoCA) and a 42% reduction in fall incidence within six months following VR intervention. The methodological quality of the included studies was moderate to high (PEDro score 5–9/10). Conclusions: VR-based training represents a safe and engaging supplement to geriatric rehabilitation, effectively improving balance, mobility, and, in selected cases, cognitive function, while also reducing fall risk. Full article
(This article belongs to the Section Geriatric Medicine)
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16 pages, 300 KiB  
Review
SGLT2 Inhibitors and GLP-1 Receptor Agonists in PAD: A State-of-the-Art Review
by Alfredo Caturano, Damiano D’Ardes, Paola Giustina Simeone, Gianfranco Lessiani, Nicoletta Di Gregorio, Lorenzo Andreetto, Davide Grassi, Carla Serra, Francesca Santilli, Maria Teresa Guagnano, Fabio Piscaglia, Claudio Ferri, Francesco Cipollone and Andrea Boccatonda
J. Clin. Med. 2025, 14(15), 5549; https://doi.org/10.3390/jcm14155549 - 6 Aug 2025
Abstract
Sodium–glucose co-transporter-2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP-1 RAs) are now established as cornerstone therapies for patients with type 2 diabetes mellitus (T2DM), given their cardiovascular and renal protective properties. However, their use in patients with peripheral artery disease (PAD) remains controversial [...] Read more.
Sodium–glucose co-transporter-2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP-1 RAs) are now established as cornerstone therapies for patients with type 2 diabetes mellitus (T2DM), given their cardiovascular and renal protective properties. However, their use in patients with peripheral artery disease (PAD) remains controversial due to concerns raised in early trials about potential increases in lower limb complications, particularly amputations. This narrative review examines current evidence on the association between SGLT2is and GLP-1 RAs in PAD-related outcomes, including limb events, amputation risk, and cardiovascular and renal endpoints. Drawing from randomized controlled trials, real-world cohort studies, and systematic reviews, we provide an integrated perspective on the safety and utility of SGLT2is and GLP-1 RAs in individuals with PAD, highlight patient selection considerations, and identify areas for future investigation. Full article
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10 pages, 713 KiB  
Article
Pulse Steroid Therapy for Severe Acute Respiratory Distress Syndrome: A Propensity Score-Matched Analysis
by Yasumasa Kawano, Junichi Maruyama, Mitsuaki Nishikimi, Hisatomi Arima, Yuhei Irie, Shinichi Morimoto, Kentaro Muranishi, Maiko Nakashio and Yoshihiko Nakamura
J. Clin. Med. 2025, 14(15), 5547; https://doi.org/10.3390/jcm14155547 - 6 Aug 2025
Abstract
Background/Objectives: Low-dose corticosteroids have gained popularity in the treatment of acute respiratory distress syndrome (ARDS); however, the efficacy of high-dose corticosteroids as pulse steroid therapy remains controversial. This study aimed to evaluate the efficacy of pulse steroid therapy in patients with severe ARDS [...] Read more.
Background/Objectives: Low-dose corticosteroids have gained popularity in the treatment of acute respiratory distress syndrome (ARDS); however, the efficacy of high-dose corticosteroids as pulse steroid therapy remains controversial. This study aimed to evaluate the efficacy of pulse steroid therapy in patients with severe ARDS requiring venovenous (V-V) extracorporeal membrane oxygenation (ECMO), where enhanced anti-inflammatory effects may be beneficial. Methods: Using data from the J-CARVE registry, which included patients with severe ARDS managed with V-V ECMO across 24 Japanese hospitals between January 2012 and December 2022, we identified 373 patients treated with corticosteroids. The patients were divided into two groups: pulse steroid therapy and non-pulse steroid therapy. Propensity score matching was performed, and all-cause hospital mortality and ECMO-free days within 28 days were compared between groups. Pulse steroid therapy was defined as methylprednisolone at a dose of 1000 mg/day. Results: After matching, 48 patients were included in each group. The all-cause hospital mortality rates were 41.7% (20/48) in the pulse steroid group and 47.9% (23/48) in the non-pulse steroid group, with no significant difference (odds ratio, 1.28; 95% confidence interval: 0.53–3.12, p = 0.68). The median ECMO-free days were 9.5 (interquartile range [IQR]: 0–17.3) in the pulse steroid group and 3 (IQR: 0–17) in the non-pulse steroid group, showing no significant difference (p = 0.69). Conclusions: Pulse steroid therapy did not improve all-cause hospital mortality or ECMO-free days in patients with severe ARDS who required V-V ECMO. Full article
(This article belongs to the Section Emergency Medicine)
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14 pages, 1122 KiB  
Article
Revisiting Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: Real-World Evidence of Survival Benefit with First-Line Immunotherapy and Targeted Therapy Regimens
by Sri Saran Manivasagam, Alireza Aminsharifi and Jay D. Raman
J. Clin. Med. 2025, 14(15), 5543; https://doi.org/10.3390/jcm14155543 - 6 Aug 2025
Abstract
Background: Renal cell carcinoma (RCC) is a common malignancy with a rising global incidence. While cytoreductive nephrectomy (CRN) was historically a cornerstone in the management of metastatic RCC (mRCC), its role has been questioned following pivotal trials such as CARMENA and SURTIME. [...] Read more.
Background: Renal cell carcinoma (RCC) is a common malignancy with a rising global incidence. While cytoreductive nephrectomy (CRN) was historically a cornerstone in the management of metastatic RCC (mRCC), its role has been questioned following pivotal trials such as CARMENA and SURTIME. With the advent of immune checkpoint inhibitors (ICIs) and targeted therapies, the contemporary relevance of CRN coupled with first-line immunotherapy and targeted therapy combination regimens warrants re-evaluation. Methods: This retrospective cohort study utilized the TriNetX research network to identify patients aged 18–90 years diagnosed with mRCC between 2005 and 2024 who received first-line systemic therapies. Patients were stratified into two cohorts based on receipt of CRN status within one year of diagnosis. Propensity score matching (1:1) was done to adjust baseline characteristics. Kaplan–Meier survival analysis and Cox proportional hazards modeling were used to compare five-year overall survival between the groups. Results: Among 5960 eligible patients, 1776 (888 CRN matched to 888 who did not) formed the cohort of analysis. The CRN group demonstrated significantly higher five-year survival (57.7% vs. 45.0%, p < 0.0001) with a hazard ratio of 1.56 (95% CI: 1.33–1.83). Subgroup analyses showed consistent survival benefits across all four NCCN-recommended first-line regimens—Axitinib + Pembrolizumab: 64.0% (CRN) vs. 53.3% (no CRN), p = 0.01; Cabozantinib + Nivolumab: 50.1% vs. 40.4%, p = 0.004; Lenvatinib + Pembrolizumab: 37.4% vs. 22.8%, p = 0.012; Nivolumab + Ipilimumab: 56.4% vs. 46.1%, p = 0.005. Conclusions: In the era of modern immunotherapy and targeted agents, CRN remains associated with improved survival in patients with mRCC receiving NCCN-recommended first-line regimens. These findings support the continued evaluation of CRN as a component of multimodal therapy, particularly in patients with favorable risk profiles. Full article
(This article belongs to the Section Nephrology & Urology)
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13 pages, 1424 KiB  
Article
Comparison of Artificial Intelligence–Derived Heart Age with Chronological Age Using Normal Sinus Electrocardiograms in Patients with No Evidence of Cardiac Disease
by Myoung Jung Kim, Sung-Hee Song, Young Jun Park, Young-Hyun Lee, Jongwoo Kim, JaeHu Jeon, KyungChang Woo, Juwon Kim, Ju Youn Kim, Seung-Jung Park, Young Keun On and Kyoung-Min Park
J. Clin. Med. 2025, 14(15), 5548; https://doi.org/10.3390/jcm14155548 - 6 Aug 2025
Abstract
Background/Objectives: Chronological age (CA) is commonly used in clinical decision-making, yet it may not accurately reflect biological aging. Recent advances in artificial intelligence (AI) allow estimation of electrocardiogram (ECG)-derived heart age, which may serve as a non-invasive biomarker for physiological aging. This [...] Read more.
Background/Objectives: Chronological age (CA) is commonly used in clinical decision-making, yet it may not accurately reflect biological aging. Recent advances in artificial intelligence (AI) allow estimation of electrocardiogram (ECG)-derived heart age, which may serve as a non-invasive biomarker for physiological aging. This study aimed to develop and validate a deep learning model to predict ECG-heart age in individuals with no structural heart disease. Methods: We trained a convolutional neural network (DenseNet-121) using 12-lead ECGs from 292,484 individuals (mean age: 51.4 ± 13.8 years; 42.3% male) without significant cardiac disease. Exclusion criteria included missing age data, age <18 or >90 years, and structural abnormalities. CA was used as the target variable. Model performance was evaluated using the coefficient of determination (R2), Pearson correlation coefficient (PCC), mean absolute error (MAE), and root mean square error (RMSE). External validation was conducted using 1191 independent ECGs. Results: The model demonstrated strong predictive performance (R2 = 0.783, PCC = 0.885, MAE = 5.023 years, RMSE = 6.389 years). ECG-heart age tended to be overestimated in younger adults (≤30 years) and underestimated in older adults (≥70 years). External validation showed consistent performance (R2 = 0.703, PCC = 0.846, MAE = 5.582 years, RMSE = 7.316 years). Conclusions: The proposed AI-based model accurately estimates ECG-heart age in individuals with structurally normal hearts. ECG-derived heart age may serve as a reliable biomarker of biological aging and support future risk stratification strategies. Full article
(This article belongs to the Section Cardiology)
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8 pages, 208 KiB  
Article
Is a History of Malignant Melanoma Associated with Subsequent Vitiligo? Insights from a Population-Based Case–Control Study
by Talia Israel, Baruch Kaplan, Naama T. Cohen, Shany Sherman, Geffen Kleinstern and Khalaf Kridin
J. Clin. Med. 2025, 14(15), 5546; https://doi.org/10.3390/jcm14155546 - 6 Aug 2025
Abstract
Background: While a few studies suggest that depigmentation tends to develop more frequently in patients with malignant melanoma (MM), the association between vitiligo and MM has been sparsely investigated in the setting of controlled studies. Methods: A population-based case–control study compared [...] Read more.
Background: While a few studies suggest that depigmentation tends to develop more frequently in patients with malignant melanoma (MM), the association between vitiligo and MM has been sparsely investigated in the setting of controlled studies. Methods: A population-based case–control study compared 14,632 patients with vitiligo with 71,580 control subjects matched by age, sex, and ethnicity regarding the prevalence of preexisting MM. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CIs) of developing vitiligo both in univariate and multivariate models, adjusting for demographic variables and comorbidities. The OR was also stratified by age, sex, ethnicity, and ultraorthodox status. Results: The prevalence of preexisting MM was statistically comparable between individuals with vitiligo and controls (0.30% vs. 0.35%, respectively). In the general study population, a history of MM was not significantly associated with an elevated likelihood of developing vitiligo (multivariate OR, 1.03; CI 95%, 0.76–1.40). Among the Arab population, however, preexisting MM was associated with a sixfold-increased likelihood of subsequent vitiligo (univariate OR, 6.55; 95% CI, 1.46–29.27). Patients with vitiligo and comorbid MM were older at the onset of vitiligo, had a higher burden of comorbid conditions, and showed an overrepresentation of Jewish ancestry. Conclusions: A history of MM does not increase the probability of vitiligo in the general Israeli population, except among the Arab minority, who show a sixfold-elevated odds of vitiligo after MM. Further investigation is essential to gain deeper insights into this relationship. Full article
(This article belongs to the Section Dermatology)
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