Journal of Clinical Medicine

14 pages, 487 KiB

Open AccessArticle

Work-Related Disorders in Public Transportation Drivers and the Length of Exposure

by Florina Georgeta Popescu, Corina Bolocan, Manuela Oancea, Iulia Iovanca Drăgoi, Nicolae Herisanu, Corina Oancea, Nilima Rajpal Kundnani, Claudia Mariana Handra, Marina Ruxandra Oțelea and Dan Alexandru Surducan

J. Clin. Med. 2025, 14(14), 5018; https://doi.org/10.3390/jcm14145018 (registering DOI) - 15 Jul 2025

Abstract

Background/Objectives: Public transportation drivers are exposed to a variety of occupational hazards. The scope of this study is to describe the most significant changes in symptoms and work-related disorders in the last decade in a sample of professional drivers from a large [...] Read more.

Background/Objectives: Public transportation drivers are exposed to a variety of occupational hazards. The scope of this study is to describe the most significant changes in symptoms and work-related disorders in the last decade in a sample of professional drivers from a large Romanian city, and, in particular, the cardio-metabolic and musculoskeletal impact. Methods: A retrospective study on 186 professional tram, trolley, and bus drivers from a total number of 344 employed by the company was conducted. The initial values (pre-employment) of the BMI, blood pressure, cholesterol, fasting glycemia, and musculoskeletal complaints were compared to the values of the last employment check-up. Results: After an average follow-up period of 11 years, BMI increased from 27.69 (SD = 4.68) to 30.06 (SD = 5.2) (p < 0.0001), cholesterol from 201.7 (SD = 39.87) to 212.62 (SD = 42.51), (p = 0.04). The number of cases of high blood pressure (25 to 56, p < 0.0001) and musculoskeletal complaints increased from 3 initial cases to 26 cases of neck pain (p = 0.07), from 2 to 49 cases of dorsal pain (p = 0.02), and from 18 to 59 cases of lumbar pain (p < 0.0001). High blood pressure and low back pain were significantly correlated with tenure, independent of other factors. Conclusions: As tenure is important in the development of cardiovascular and musculoskeletal diseases, specific interventions should be developed in the early stages of the drivers’ career. Full article

(This article belongs to the Section Orthopedics)

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25 pages, 688 KiB

Open AccessSystematic Review

Comparative Meta-Analysis of Survival, Risk, and Treatment Efficacy in Immunotherapy for Metastatic Melanoma Using Random-, Fixed-, and Mixed-Effects Models

by Jelena Ivetić, Jovana Dedeić, Srđan Milićević, Katarina Vidojević and Marija Delić

J. Clin. Med. 2025, 14(14), 5017; https://doi.org/10.3390/jcm14145017 (registering DOI) - 15 Jul 2025

Abstract

Background: Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of metastatic melanoma. While combination regimens often demonstrate improved response and survival compared to monotherapy, they are also associated with a higher incidence of immune-related adverse events (irAEs). Understanding the balance between benefit [...] Read more.

Background: Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of metastatic melanoma. While combination regimens often demonstrate improved response and survival compared to monotherapy, they are also associated with a higher incidence of immune-related adverse events (irAEs). Understanding the balance between benefit and risk is essential for making informed treatment decisions, especially given the variability in reported outcomes across clinical trials. Methods: We conducted a systematic review and meta-analysis of 14 clinical trials (comprising 22 treatment arms and >5000 patients) comparing ICI monotherapy (nivolumab, ipilimumab, or pembrolizumab) and combination therapy (nivolumab + ipilimumab) in advanced melanoma. Treatment-related outcomes were synthesized using fixed-effects, random-effects, or generalized linear mixed models (GLMMs), depending on study variability. Survival data were extracted from published Kaplan–Meier curves and analyzed using longitudinal GLMMs to capture trends over time. Results: Compared to monotherapy, combination immunotherapy achieved higher clinical benefit, with an overall response of 52.2% (vs. 31.6%), a five-year overall survival of 55.7% (vs. 34.3%), and a five-year progression-free survival of 39.0% (vs. 17.2%). However, this benefit came with a higher risk of toxicity: immune-related adverse events occurred in 93.2% of patients receiving combination therapy versus in 81.9% receiving monotherapy. Differences were consistent across all individual severe toxicities. Conclusions: Combination immunotherapy offers greater long-term clinical benefit than monotherapy in metastatic melanoma but at the cost of increased toxicity. By applying models adapted to study variability, we provide more reliable estimates of treatment efficacy and risk. GLMMs provide the most robust estimates and enable the modeling of survival dynamics over time. These findings support evidence-based decision-making and highlight the value of model-informed meta-analysis in oncology. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Skin Cancer)

14 pages, 890 KiB

Open AccessReview

Beyond Standard Shocks: A Critical Review of Alternative Defibrillation Strategies in Refractory Ventricular Fibrillation

by Benedetta Perna, Matteo Guarino, Roberto De Fazio, Ludovica Esposito, Andrea Portoraro, Federica Rossin, Michele Domenico Spampinato and Roberto De Giorgio

J. Clin. Med. 2025, 14(14), 5016; https://doi.org/10.3390/jcm14145016 (registering DOI) - 15 Jul 2025

Abstract

Background: Refractory ventricular fibrillation (RVF) is a life-threatening condition characterized by the persistence of ventricular fibrillation despite multiple defibrillation attempts. It represents a critical challenge in out-of-hospital cardiac arrest management, with poor survival outcomes and limited guidance from current resuscitation guidelines. In recent [...] Read more.

Background: Refractory ventricular fibrillation (RVF) is a life-threatening condition characterized by the persistence of ventricular fibrillation despite multiple defibrillation attempts. It represents a critical challenge in out-of-hospital cardiac arrest management, with poor survival outcomes and limited guidance from current resuscitation guidelines. In recent years, alternative defibrillation strategies (ADSs), including dual sequential external defibrillation (DSED) and vector change defibrillation (VCD), have emerged as potential interventions to improve defibrillation success and patient outcomes. However, their clinical utility remains debated due to heterogeneous evidence and limited high-quality data. Methods: This narrative review explores the current landscape of ADSs in patients with RVF. MEDLINE, Google Scholar, the World Health Organization, LitCovid NLM, EMBASE, CINAHL Plus, and the Cochrane Library were examined from their inception to April 2025. Results: The available literature is dominated by retrospective studies and case series, with only one randomized controlled trial (DOSE-VF). This trial demonstrated improved survival to hospital discharge with ADSs compared to standard defibrillation. DSED was associated with higher rates of return of spontaneous circulation and favorable neurological outcomes. However, subsequent meta-analyses have produced inconsistent results, largely due to the heterogeneity of the included studies. The absence of sex-, gender-, and ethnicity-specific analyses further limits the generalizability of the findings. In addition, practical barriers, such as equipment availability, pose significant challenges to implementation. Conclusions: ADSs represent a promising yet still-evolving approach to the management of RVF, with DSED showing the most consistent signal of benefit. Further high-quality research is required to enhance generalizability and generate more definitive, high-level evidence. Full article

(This article belongs to the Section Emergency Medicine)

12 pages, 1646 KiB

Open AccessSystematic Review

Quantitative Flow Ratio-Guided vs. Angiography-Guided Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of One-Year Clinical Outcomes

by Viet Nghi Tran, Amreen Dhindsa, Kuchalambal Agadi, Hoang Nhat Pham, Hong Hieu Truong, Chau Doan Nguyen, Hanad Bashir, Huan Dat Pham, Thanh Vien Truong, Phillip Tran and Thach Nguyen

J. Clin. Med. 2025, 14(14), 5015; https://doi.org/10.3390/jcm14145015 (registering DOI) - 15 Jul 2025

Abstract

Background: Quantitative Flow Ratio (QFR) is a novel, wire-free, and hyperemia-free physiological assessment for guiding Percutaneous Coronary Intervention (PCI), which may offer advantages over traditional angiography-guided PCI. This systematic review with meta-analysis compares clinical outcomes after one year in patients who underwent QFR-guided [...] Read more.

Background: Quantitative Flow Ratio (QFR) is a novel, wire-free, and hyperemia-free physiological assessment for guiding Percutaneous Coronary Intervention (PCI), which may offer advantages over traditional angiography-guided PCI. This systematic review with meta-analysis compares clinical outcomes after one year in patients who underwent QFR-guided versus angiography-guided PCI. Methods: This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered on 4 November 2024 in PROSPERO (ID: CRD42024609799). A systematic search was performed across multiple databases to identify clinical trials comparing QFR-guided and angiography-guided PCI. Random-effects models were used to assess one-year outcomes of major adverse cardiovascular events (MACEs), revascularization, and rehospitalization, with heterogeneity measured using I², H², and Cochran’s Q statistics. Study quality was evaluated using the Cochrane Risk of Bias 2 (RoB 2) tool. Results: Compared to traditional angiography-guided PCI, QFR-guided PCI was associated with numerically lower but statistically non-significant risks of MACEs (risk difference: −0.08, 95% CI: −0.20 to 0.04), revascularization (risk difference: −0.02, 95% CI: −0.08 to 0.03), and rehospitalization (risk difference: −0.02, 95% CI: −0.08 to 0.04) over one year. Substantial heterogeneity was observed for MACEs (I² = 84.95%, H² = 6.64) and revascularization (I² = 94.18%, H² = 17.18), whereas rehospitalization exhibited low heterogeneity (I² = 17.17%, H² = 1.21). The risk of bias was assessed by the RoB 2 tool, which revealed low to some concern risk of bias across key domains. Conclusions: Quantitative Flow Ratio (QFR) has demonstrated comparable one-year clinical outcomes to traditional angiography for PCI guidance, with a trend toward improved results. However, the high heterogeneity among studies and the risk of bias necessitate the need for larger, high-quality trials to validate these findings. Full article

(This article belongs to the Special Issue Interventional Cardiology—Challenges and Solutions)

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12 pages, 2919 KiB

Open AccessArticle

Ultrawide-Field Optical Coherence Tomography Angiography-Guided Navigated Laser Therapy of Non-Perfused Areas in Branch Retinal Vein Occlusion

by Yao Zhou, Peng Peng, Jiaojiao Wei, Jian Yu and Min Wang

J. Clin. Med. 2025, 14(14), 5014; https://doi.org/10.3390/jcm14145014 (registering DOI) - 15 Jul 2025

Abstract

Background/Objectives: This study evaluates whether ultrawide-field optical coherence tomography angiography (UWF-OCTA) can guide navigated laser therapy for non-perfused areas (NPAs) in branch retinal vein occlusion (BRVO). It further explores whether the laser spots can be accurately placed according to plan, considering that [...] Read more.

Background/Objectives: This study evaluates whether ultrawide-field optical coherence tomography angiography (UWF-OCTA) can guide navigated laser therapy for non-perfused areas (NPAs) in branch retinal vein occlusion (BRVO). It further explores whether the laser spots can be accurately placed according to plan, considering that the retina is three-dimensional (3D), while UWF-OCTA provides two-dimensional (2D) images. Methods: UWF-OCTA images from three devices—VG200, Xephilio OCT-S1, and Bmizar—guided the treatments. These images were superimposed onto NAVILAS^® system images to guide NPA treatments. Pre-treatment planning was strategically designed to avoid normal and collateral vessels, with immediate post-laser OCTA and en face images assessing the efficacy of the laser spots in avoiding these vessels as planned. The accuracy of navigated laser therapy was further analyzed by comparing the intended laser locations with the actual spots. Results: All montaged OCTA images from the three devices were seamlessly integrated into the navigated laser system without registration errors. All patients received treatments targeting the NPAs as planned. However, not all collateral or normal vessels were successfully avoided by the laser spots. A further analysis revealed that the actual locations of the laser spots deviated slightly from the planned locations, particularly in the mid-periphery areas. Conclusions: UWF-OCTA-guided navigated laser photocoagulation is feasible and precise for treating NPAs in BRVO. Nonetheless, minor deviations between planned and actual locations were observed. This discrepancy, particularly important when treating diseases of the macular area, should be carefully considered when employing OCTA-guided navigated laser photocoagulation. Full article

(This article belongs to the Section Ophthalmology)

15 pages, 745 KiB

Open AccessSystematic Review

Relationship Between Bruxism and Obstructive Sleep Apnea: A Systematic Review of the Literature

by Natalia García Doblado, José María Barrera Mora, Francisco Pastor Dorado, Juan C. Rodríguez Fernández, Guillem Ballestero Ordeix and Eduardo Espinar Escalona

J. Clin. Med. 2025, 14(14), 5013; https://doi.org/10.3390/jcm14145013 (registering DOI) - 15 Jul 2025

Abstract

Background and objectives: The interest in studying the relationship between bruxism and sleep apnea has increased over the past decade, given its prevalence and its implications for both oral and overall health. Bruxism occurs in a significant portion of the population, with [...] Read more.

Background and objectives: The interest in studying the relationship between bruxism and sleep apnea has increased over the past decade, given its prevalence and its implications for both oral and overall health. Bruxism occurs in a significant portion of the population, with an overall incidence ranging between 8 and 31%. Obstructive sleep apnea affects 4–6% of middle-aged men and 2–4% of middle-aged women, and it is associated with diminished quality of life, hypertension, increased cardiovascular risks, traffic accidents, and a higher mortality rate. Although a possible association has been suggested, the causal relationship remains unclear. This review aimed to systematically evaluate the available evidence on the association between SB and OSA, focusing on potential shared risk factors and underlying mechanisms. Methods: An electronic literature search was conducted in PubMed, Scopus, Web of Science, and the Cochrane Library for studies published between 2020 and 2025. Inclusion criteria encompassed observational studies and clinical trials involving adults with SB and/or OSA. Risk of bias was assessed using ROBINS-I, and the certainty of evidence was evaluated using GRADE. The review protocol was not registered. Results: A total of 11 studies met the inclusion criteria. The prevalence of SB was consistently higher in individuals with OSA compared to the general population. Several studies suggest a potential link through autonomic arousals and neurotransmitter dysregulation. However, inconsistencies in diagnostic criteria and moderate methodological quality limited the strength of the findings. Conclusions: There is a notable prevalence of bruxism in patients with OSA, suggesting possible shared pathophysiological mechanisms; however, it is necessary to standardize diagnostic criteria and conduct larger, more standardized studies to clarify the relationship. No funding was received, and the authors declare no conflicts of interest. Full article

(This article belongs to the Section Respiratory Medicine)

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12 pages, 6587 KiB

Open AccessArticle

Overcoming the Limitations of Conventional Orthognathic Surgery: A Novel Approach Using Implate

by Valerio Ramieri, Laura Viola Pignataro, Tito Matteo Marianetti, Davide Spadoni, Andrea Frosolini and Paolo Gennaro

J. Clin. Med. 2025, 14(14), 5012; https://doi.org/10.3390/jcm14145012 (registering DOI) - 15 Jul 2025

Abstract

Introduction: This manuscript addresses the limitations of traditional orthognathic surgery in achieving both functional and aesthetic correction in patients with Class II malocclusion and severe mandibular retrusion. Current techniques often struggle to simultaneously address mandibular deficiency and inadequate transverse dimension, leading to [...] Read more.

Introduction: This manuscript addresses the limitations of traditional orthognathic surgery in achieving both functional and aesthetic correction in patients with Class II malocclusion and severe mandibular retrusion. Current techniques often struggle to simultaneously address mandibular deficiency and inadequate transverse dimension, leading to unsatisfactory outcomes. Methods: Seven male patients underwent bimaxillary osteotomy with mandibular advancement. A novel surgical plate, Implate, was used, which was designed to facilitate precise osteotomy and stabilization. Pre-surgical planning included CBCT scanning, 3D modeling, and surgical simulation. Postoperative assessments included clinical examinations, CT and OPT scans. Results: Implate successfully addressed the challenges of conventional techniques, minimizing the formation of bony steps and achieving a more harmonious facial profile. The minimally invasive procedure, with careful periosteal and muscle management, contributed to stable outcomes, and no complications were reported. At the 6-month follow-up, OPT analysis showed a mean mandibular width increase of 18.1 ± 6.2 mm and vertical ramus height gains of 6.0 ± 3.1 mm (left) and 5.8 ± 1.7 mm (right). Conclusions: According to our preliminary experience, the integration of Implate into surgical practice offers a significant improvement in treating complex Class II malocclusions. By simultaneously correcting mandibular retrusion and width while minimizing complications, Implate provides a superior solution compared to traditional methods. This innovative approach highlights the potential of combining advanced surgical techniques with personalized 3D-printed implants to achieve optimal functional and aesthetic outcomes. Further prospective studies with controls and longer follow-up are needed to validate the efficacy and reproducibility of Implate in wider clinical use. Full article

(This article belongs to the Section Plastic, Reconstructive and Aesthetic Surgery/Aesthetic Medicine)

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21 pages, 2919 KiB

Open AccessReview

Tricuspid Regurgitation in the Era of Transcatheter Interventions: The Pivotal Role of Multimodality Imaging

by Valeria Maria De Luca, Stefano Censi, Rita Conti, Roberto Nerla, Sara Bombace, Tobias Friedrich Ruf, Ralph Stephan von Bardeleben, Philipp Lurz, Fausto Castriota and Angelo Squeri

J. Clin. Med. 2025, 14(14), 5011; https://doi.org/10.3390/jcm14145011 (registering DOI) - 15 Jul 2025

Abstract

Over the last ten years, transcatheter tricuspid valve interventions (TTVIs) have emerged as effective options for symptomatic patients with moderate-to-severe tricuspid regurgitation (TR) who are at prohibitive surgical risk. Successful application of these therapies depends on a patient-tailored, multimodal imaging workflow. Transthoracic and [...] Read more.

Over the last ten years, transcatheter tricuspid valve interventions (TTVIs) have emerged as effective options for symptomatic patients with moderate-to-severe tricuspid regurgitation (TR) who are at prohibitive surgical risk. Successful application of these therapies depends on a patient-tailored, multimodal imaging workflow. Transthoracic and transesophageal echocardiography remain the first-line diagnostic tools, rapidly stratifying TR severity, mechanism, and right ventricular function, and identifying cases requiring further evaluation. Cardiac computed tomography (CT) then provides anatomical detail—quantifying tricuspid annular dimension, leaflet tethering, coronary artery course, and venous access anatomy—to refine candidacy and simulate optimal device sizing and implantation angles. In patients with suboptimal echocardiographic windows or equivocal functional data, cardiovascular magnetic resonance (CMR) offers gold-standard quantification of RV volumes, ejection fraction, regurgitant volume, and tissue characterization to detect fibrosis. Integration of echo-derived parameters, CT anatomical notes, and CMR functional assessment enables the heart team to better select patients, plan procedures, and determine the optimal timing, thereby maximizing procedural success and minimizing complications. This review describes the current strengths, limitations, and future directions of multimodality imaging in comprehensive evaluations of TTVI candidates. Full article

(This article belongs to the Special Issue Mitral and Tricuspid Valve Disease and Imaging Techniques—2nd Edition)

53 pages, 1014 KiB

Open AccessReview

Neural Correlates of Huntington’s Disease Based on Electroencephalography (EEG): A Mechanistic Review and Discussion of Excitation and Inhibition (E/I) Imbalance

by James Chmiel, Jarosław Nadobnik, Szymon Smerdel and Mirela Niedzielska

J. Clin. Med. 2025, 14(14), 5010; https://doi.org/10.3390/jcm14145010 (registering DOI) - 15 Jul 2025

Abstract

Introduction: Huntington’s disease (HD) disrupts cortico-striato-thalamocortical circuits decades before clinical onset. Electroencephalography (EEG) offers millisecond temporal resolution, low cost, and broad accessibility, yet its mechanistic and biomarker potential in HD remains underexplored. We conducted a mechanistic review to synthesize half a century [...] Read more.

Introduction: Huntington’s disease (HD) disrupts cortico-striato-thalamocortical circuits decades before clinical onset. Electroencephalography (EEG) offers millisecond temporal resolution, low cost, and broad accessibility, yet its mechanistic and biomarker potential in HD remains underexplored. We conducted a mechanistic review to synthesize half a century of EEG findings, identify reproducible electrophysiological signatures, and outline translational next steps. Methods: Two independent reviewers searched PubMed, Scopus, Google Scholar, ResearchGate, and the Cochrane Library (January 1970–April 2025) using the terms “EEG” OR “electroencephalography” AND “Huntington’s disease”. Clinical trials published in English that reported raw EEG (not ERP-only) in human HD gene carriers were eligible. Abstract/title screening, full-text appraisal, and cross-reference mining yielded 22 studies (~700 HD recordings, ~600 controls). We extracted sample characteristics, acquisition protocols, spectral/connectivity metrics, and neuroclinical correlations. Results: Across diverse platforms, a consistent spectral trajectory emerged: (i) presymptomatic carriers show a focal 7–9 Hz (low-alpha) power loss that scales with CAG repeat length; (ii) early-manifest patients exhibit widespread alpha attenuation, delta–theta excess, and a flattened anterior-posterior gradient; (iii) advanced disease is characterized by global slow-wave dominance and low-voltage tracings. Source-resolved studies reveal early alpha hypocoherence and progressive delta/high-beta hypersynchrony, microstate shifts (A/B ↑, C/D ↓), and rising omega complexity. These electrophysiological changes correlate with motor burden, cognitive slowing, sleep fragmentation, and neurovascular uncoupling, and achieve 80–90% diagnostic accuracy in shallow machine-learning pipelines. Conclusions: EEG offers a coherent, stage-sensitive window on HD pathophysiology—from early thalamocortical disinhibition to late network fragmentation—and fulfills key biomarker criteria. Translation now depends on large, longitudinal, multi-center cohorts with harmonized high-density protocols, rigorous artifact control, and linkage to clinical milestones. Such infrastructure will enable the qualification of alpha-band restoration, delta-band hypersynchrony, and neurovascular coupling as pharmacodynamic readouts, fostering precision monitoring and network-targeted therapy in Huntington’s disease. Full article

(This article belongs to the Special Issue Current Practice and Future Perspectives of Neurological Conditions Caused by Neurodegeneration, 2nd Edition)

13 pages, 822 KiB

Open AccessArticle

Biventricular Cardiac Resynchronization Therapy with Atrial Sensing but No Atrial Lead: A Prospective Registry of Patients, Complications, and Therapy Responses

by Christof Kolb, Endre Zima, Martin Arnold, Marián Fedorco, Hendrik Bonnemeier, Thomas Deneke, Burghard Schumacher, Peter Nordbeck, Clemens Steinwender, Theresa Storz, Béla Merkely, Lars Anneken, Angelika Felk and Carsten Lennerz

J. Clin. Med. 2025, 14(14), 5009; https://doi.org/10.3390/jcm14145009 (registering DOI) - 15 Jul 2025

Abstract

Background/Objectives: Patients with normal sinus rhythms undergoing cardiac resynchronization therapy defibrillator (CRT-D) implantation may benefit from a novel two-lead CRT-D system (CRT-DX), which features an atrial sensing dipole integrated into the right ventricular lead. This single-arm, international, non-controlled investigation focused on the safety [...] Read more.

Background/Objectives: Patients with normal sinus rhythms undergoing cardiac resynchronization therapy defibrillator (CRT-D) implantation may benefit from a novel two-lead CRT-D system (CRT-DX), which features an atrial sensing dipole integrated into the right ventricular lead. This single-arm, international, non-controlled investigation focused on the safety and clinical efficacy of CRT-DX devices in CRT-D candidates who do not require atrial pacing. Methods: Patients indicated for CRT-D implantation (resting heart rates > 40 bpm and ≥100 bpm during exercise, no second or higher-degree AV block, and no history of persistent or permanent atrial fibrillation) were enrolled across 21 sites in four European countries. The primary endpoint was the need for an additional RA lead implantation within 12 months. Secondary endpoints comprised any invasive re-intervention to the CRT-DX system or infection. Results: Among the 110 patients (mean age 62 years, 70% male), 60% had an underlying non-ischemic cardiac disease. During 12 months of follow-up, RA lead implantation was required in two patients for atrial undersensing or chronotropic incompetence (RA lead implantation-free rate: 98.2% (95% CI: 92.7–99.5%)). Atrial sensing amplitudes were stable (mean: 4.7 ± 1.7 mV), AV-synchrony was maintained at >99%, and the median percentage of biventricular pacing exceeded 98%. The left ventricular ejection fraction improved by an absolute 14.7%. Conclusions: Using simple, clinically applicable inclusion criteria, the two-lead CRT-DX system demonstrated a low rate of subsequent RA lead implantations (1.8%) and maintained adequate RA sensing amplitudes throughout the observation period. The two-lead CRT-DX concept appears to be a feasible alternative for patients with preserved chronotropic competence. Full article

(This article belongs to the Section Cardiology)

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13 pages, 1382 KiB

Open AccessArticle

Trends and Risk Factors for the Hospitalization of Older Adults Presenting to Emergency Departments After a Bed-Related Fall: A National Database Analysis

by Andy Tom, Sergio M. Navarro, Grant M. Spears, Adam Schluttenhofer, Michelle Junker, John Zietlow, Roderick Davis, Allyson K. Palmer, Nathan K. LeBrasseur, Fernanda Bellolio and Myung S. Park

J. Clin. Med. 2025, 14(14), 5008; https://doi.org/10.3390/jcm14145008 (registering DOI) - 15 Jul 2025

Abstract

Background/objectives: Falls are a leading cause of traumatic injury and hospitalization for adults over the age of 65. While common, bed-related falls are relatively understudied when compared to ambulatory falls. The aim of this study is to characterize the risk factors for [...] Read more.

Background/objectives: Falls are a leading cause of traumatic injury and hospitalization for adults over the age of 65. While common, bed-related falls are relatively understudied when compared to ambulatory falls. The aim of this study is to characterize the risk factors for the hospitalization of older adults presenting to U.S. emergency departments (EDs) after a fall from bed. Methods: This was a cross-sectional study using publicly available data from the U.S. Consumer Product Safety Commission’s National Electronic Injury Surveillance System (NEISS) from 2014 to 2023, including all adults over the age of 65 presenting to the NEISS’s participating EDs with bed-related fall injuries. We identified fall injuries using a keyword search of the NEISS narratives and determined how the fall occurred by manually reviewing a randomized 3% sample of the narratives. We summarized demographics and injury patterns with descriptive statistics. We constructed a multivariable logistic regression model to identify risk factors for hospitalization and used Poisson regression to assess temporal trends in fall incidence and hospital admissions. Results: An estimated average of 320,751 bed-related fall injuries presented to EDs annually from 2014 to 2023. ED visits increased by 2.85% per year, while hospital admissions rose by 5.67% per year (p < 0.001). The most common injury patterns were superficial injuries (contusions, abrasions, lacerations, avulsions, and punctures) (28.6%), fractures (21.7%), and internal injuries (including concussions) (21.6%). Most of the falls occurred while transitioning into or out of bed (34.4%) or falling out of bed (56.8%). Hospitalization was required in 34.1% of cases and was associated with male sex, medication use at time of injury, and fracture injuries. Conclusions: Bed-related falls and associated hospitalizations are increasing among older adults. ED providers should understand risk factors for hospitalization in these common injuries such as male sex, medication use at time of injury, and high-risk injury patterns. Additionally, prevention efforts should focus on helping older adults remain safely in bed and then assisting with transitions into or out of bed. Full article

(This article belongs to the Special Issue Geriatric Fracture: Current Treatment and Future Options)

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16 pages, 679 KiB

Open AccessArticle

Length of Washout Period After Remission Does Not Influence Relapse Risk in Patients with Acute Myeloid Leukemia Treated with Hypomethylating Agents Combined with Venetoclax

by Fanny Erika Palumbo, Andrea Duminuco, Laura Longo, Daniela Cristina Vitale, Cinzia Maugeri, Serena Brancati, Marina Silvia Parisi, Giuseppe Alberto Palumbo, Giovanni Luca Romano, Filippo Drago, Francesco Di Raimondo, Lucia Gozzo and Calogero Vetro

J. Clin. Med. 2025, 14(14), 5007; https://doi.org/10.3390/jcm14145007 (registering DOI) - 15 Jul 2025

Abstract

Background/Objectives: The combination of venetoclax (VEN) and hypomethylating agents (HMA), such as azacitidine (AZA) or decitabine (DEC), has transformed the treatment landscape for acute myeloid leukemia (AML) in patients unfit for intensive chemotherapy. However, optimal management of neutropenia and the impact of post-remission [...] Read more.

Background/Objectives: The combination of venetoclax (VEN) and hypomethylating agents (HMA), such as azacitidine (AZA) or decitabine (DEC), has transformed the treatment landscape for acute myeloid leukemia (AML) in patients unfit for intensive chemotherapy. However, optimal management of neutropenia and the impact of post-remission treatment interruptions (washouts) remain unclear. This study aimed to evaluate the safety and efficacy of post-remission washouts and their effect on clinical outcomes. Methods: We conducted a retrospective single-center study of 44 AML patients treated with HMA/VEN between 2020 and 2021. Clinical, molecular, and treatment-related data were collected, including treatment duration, post-remission washout duration, response rates, disease-free survival (DFS), and overall survival (OS). Statistical analyses included Fisher’s exact test and univariate and multivariate Cox models. Results: Overall, 61% of patients responded to therapy, with significantly higher response rates among those potentially eligible for the VIALE-A trial (86% vs. 39%, p = 0.002). Neither treatment duration nor post-remission washout length was associated with DFS or OS. DFS was significantly longer in patients treated with AZA compared to DEC (p = 0.006). Median OS was 7.7 months, with longer OS observed in patients who did not meet VIALE-A trial eligibility criteria (p = 0.021). Achieving complete remission (CR) was associated with improved OS (14.5 months). Conclusions: Post-remission treatment interruptions (washouts) did not negatively impact DFS or OS, suggesting they may be a safe strategy to support hematologic recovery. However, the choice of HMA appears to influence response duration, with AZA outperforming DEC in maintaining disease control. Full article

(This article belongs to the Section Hematology)

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11 pages, 980 KiB

Open AccessArticle

Impact of Tumor Necrosis Factor Antagonist Therapy on Circulating Angiopoietin-like Protein 8 (ANGPTL8) Levels in Crohn’s Disease—A Prospective Multi-Center Study

by Mohammad Shehab, Sharifa Al-Fajri, Ahmed Alanqar, Mohammad Alborom, Fatema Alrashed, Fatemah Alshammaa, Ahmad Alfadhli, Sriraman Devarajan, Irina Alkhairi, Preethi Cherian, Jehad Abubaker, Mohamed Abu-Farha and Fahd Al-Mulla

J. Clin. Med. 2025, 14(14), 5006; https://doi.org/10.3390/jcm14145006 (registering DOI) - 15 Jul 2025

Abstract

Background: Crohn’s disease (CD) is a chronic disease perpetuated through key pro-inflammatory molecules, including tumor necrosis factor-alpha (TNFα). Angiopoietin-like protein 8 (ANGPTL8) may contribute to inflammation cascades. This study aimed to investigate how ANGPTL8 levels are influenced in patients with CD prior to [...] Read more.

Background: Crohn’s disease (CD) is a chronic disease perpetuated through key pro-inflammatory molecules, including tumor necrosis factor-alpha (TNFα). Angiopoietin-like protein 8 (ANGPTL8) may contribute to inflammation cascades. This study aimed to investigate how ANGPTL8 levels are influenced in patients with CD prior to and following anti-TNF therapy. Methods: Patients were divided into 3 groups. Patients with CD in clinical remission receiving IFX for at least 24 weeks (IFX-experienced group), patients scheduled to start IFX (IFX-naïve group), and healthy controls (control group). In the IFX-experienced group, ANGPTL8 levels were measured 24 h before the next maintenance IFX dose. In the IFX-naïve group, levels were measured at week 0 and week 24, and in the control group, they were measured randomly. Results: The total number of participants was 166. The numbers of IFX-experienced, IFX-naïve patients, and healthy controls were 82, 13, and 71, respectively. Mean age ranged from 27 to 33 years of age across the three groups. Eighty-four (51%) participants were female. ANGPTL8 levels were significantly higher in patients with CD (138.26 ± 8.47 pmol) compared to the healthy control group (102.52 ± 5.99 pmol, p = 0.001). Among IFX-naïve patients receiving anti-TNFα treatment, ANGPTL8 levels decreased significantly from 145.06 ± 17.93 pmol pre-treatment (week 0) to 81.78 ± 10.61 pmol post-treatment (week 24), p = 0.007. Conclusions: Our findings suggest that ANGPTL8 levels are elevated in CD and may be involved in the inflammatory process. The marked reduction in ANGPTL8 levels following anti-TNFα treatment indicates its potential as a biomarker for treatment response. Further research should focus on the exact mechanisms through which ANGPTL8 influences CD progression and its utility in clinical practice. Full article

(This article belongs to the Special Issue Current Progress in Inflammatory Bowel Disease (IBD))

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12 pages, 744 KiB

Open AccessArticle

QTc Prolongation as a Diagnostic Clue in Acute Pulmonary Embolism

by Saleh Sharif, Eran Kalmanovich, Gil Marcus, Faina Tsiporin, Sa’ar Minha, Michael Barkagan, Itamar Love, Shmuel Fuchs, Guy Zahavi and Anat Milman

J. Clin. Med. 2025, 14(14), 5005; https://doi.org/10.3390/jcm14145005 (registering DOI) - 15 Jul 2025

Abstract

Background: Pulmonary embolism (PE) increases right ventricular (RV) afterload, potentially leading to myocardial stress and electrocardiographic abnormalities. Although QTc prolongation has been suggested as a marker of RV dysfunction, its prevalence, clinical significance, and prognostic value in acute PE remain poorly defined. Objective: [...] Read more.

Background: Pulmonary embolism (PE) increases right ventricular (RV) afterload, potentially leading to myocardial stress and electrocardiographic abnormalities. Although QTc prolongation has been suggested as a marker of RV dysfunction, its prevalence, clinical significance, and prognostic value in acute PE remain poorly defined. Objective: The objective of this study is to evaluate the prevalence and clinical implications of QTc prolongation in patients with intermediate–high and high-risk acute PE. Methods: We retrospectively analyzed 95 consecutive patients admitted with intermediate–high or high-risk PE between September 2021 and December 2023. QTc prolongation was defined as ≥470 ms in males and ≥480 ms in females. Clinical, imaging, and laboratory data were compared between patients with normal and prolonged QTc intervals. QTc was assessed at admission, after treatment, and prior to discharge. Results: QTc prolongation was observed in 28.4% of patients at presentation. This group had significantly higher lactate levels (2.3 vs. 1.8 mmol/L, p = 0.03) and a non-significant trend toward elevated troponin and lower oxygen saturation. No differences were observed in echocardiographic or CT-based RV dysfunction parameters. QTc values normalized by discharge irrespective of treatment modality. There was no association between QTc prolongation and in-hospital or long-term mortality. A trend toward more aspiration thrombectomy was noted in the prolonged QTc group (29.6% vs. 11.8%, p = 0.06). Conclusions: QTc prolongation is common in acute intermediate–high and high-risk PE and may reflect transient myocardial stress. While not predictive of clinical outcomes, it should be considered in the differential diagnosis of QTc prolongation in patients presenting with dyspnea and chest pain. Full article

(This article belongs to the Section Cardiovascular Medicine)

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11 pages, 1775 KiB

Open AccessSystematic Review

Evaluation of Pre-Pectoral Direct-to-Implant Breast Reconstruction with Post-Mastectomy Radiation: A Systematic Review and Meta-Analysis

by Nisha Parmeshwar, Jacquelyn A. Knox and Merisa L. Piper

J. Clin. Med. 2025, 14(14), 5004; https://doi.org/10.3390/jcm14145004 (registering DOI) - 15 Jul 2025

Abstract

Background: Immediate direct-to-implant (DTI) breast reconstruction is associated with high patient satisfaction and faster recovery. However, concerns remain for patients requiring post-mastectomy radiation therapy (PMRT). While PMRT improves overall survival for breast cancer patients, it has been associated with increased implant-specific complications [...] Read more.

Background: Immediate direct-to-implant (DTI) breast reconstruction is associated with high patient satisfaction and faster recovery. However, concerns remain for patients requiring post-mastectomy radiation therapy (PMRT). While PMRT improves overall survival for breast cancer patients, it has been associated with increased implant-specific complications such as capsular contracture, infection, and implant loss. As the impact of PMRT on pre-pectoral DTI specifically is not well understood, the goal of this systematic review was to evaluate the impact of PMRT on outcomes in this growing patient population. Methods: PubMed, EMBASE, and Web of Science were systematically reviewed for articles published from 1 January 2000 to 23 December 2024 investigating outcomes after prepectoral DTI reconstruction with exposure to PMRT. Demographic, clinical, and post-operative variables were recorded for PMRT and non-PMRT cohorts, and primary outcomes included infection, capsular contracture, implant loss, and wound healing complications. Meta-analysis was performed for key outcomes using the Mantel-Haenszel method. Results: Of 472 initially identified records, seven studies met inclusion criteria with a combined total of 343 prepectoral DTI reconstructions exposed to PMRT and 1385 reconstructions not exposed to PMRT. PMRT significantly increased the odds of any complication (OR 2.11, p = 0.01), implant loss (OR 1.88, p = 0.02), infection (OR 2.76, p = 0.004), and capsular contracture (OR 8.88, p < 0.001). However, PMRT was not associated with significantly increased odds of wound healing complications (OR 1.5, p = 0.36). Conclusions: PMRT after pre-pectoral DTI reconstruction significantly increases odds of complications, including infection, capsular contracture, and reconstructive failure. Plastic surgeons should be mindful of the sequelae of PMRT with prepectoral DTI reconstruction to improve pre-operative counseling and shared decision-making. Full article

(This article belongs to the Special Issue Evolution of Breast Reconstruction: Current Techniques, Advances and Future Directions)

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12 pages, 545 KiB

Open AccessArticle

Goal Achievement in 3017 Patients at Very High Cardiovascular Risk Based on Different LDL Cholesterol Calculations and Non-HDL Cholesterol Levels—Shortcomings of the Use of Non-HDL Cholesterol as a Target Depending on Triglyceride Levels

by István Reiber, Laszlo Mark, Hajnalka Lőrincz, Ferenc Együd, Izabella Mező and György Paragh

J. Clin. Med. 2025, 14(14), 5003; https://doi.org/10.3390/jcm14145003 (registering DOI) - 15 Jul 2025

Abstract

Objectives: The goal of this study was to investigate lipid goal achievement rates in very high-risk patients over six months using high-intensity rosuvastatin or rosuvastatin/ezetimibe combination lipid-lowering therapy. Methods: This prospective, observational study was conducted on the patients of 150 general [...] Read more.

Objectives: The goal of this study was to investigate lipid goal achievement rates in very high-risk patients over six months using high-intensity rosuvastatin or rosuvastatin/ezetimibe combination lipid-lowering therapy. Methods: This prospective, observational study was conducted on the patients of 150 general and 60 specialist practices. Our analysis included 3017 patients (47% women) who completed six months of therapy. Of these, 55.5% had pre-existing cardiovascular disease, 35.6% had cerebrovascular disease, and 20.4% had peripheral vascular disease. Results: At six months, in patients receiving rosuvastatin monotherapy (20.5%), the 1.8 LDL-C achievement rate was 37%; in those taking the fix rosuvastatin/ezetimibe combination (63.7%), it was 52%, and the 1.4 level attainment proved to be 11% and 22%, respectively. The rates of LDL-C reduction of at least 50% were 32% and 42%, respectively. Overall, non-HDL-C goal achievement rates were higher than when LDL-C was calculated using the Martin–Hopkins or Sampson methods but similar to those calculated with the Friedewald formula. When patients were stratified by triglyceride quartiles, non-HDL-C goal achievement rates were significantly higher (p < 0.001) in cases with triglyceride levels below 1.2 mmol/L. Conversely, Friedewald-calculated LDL-C (F-LDL-C) goal achievement rates were significantly higher (p < 0.001) in patients with triglyceride levels above 1.7 mmol/L. Conclusions: Our findings suggest that the consistent use of fixed high-intensity statin and ezetimibe combinations can improve lipid goal achievement. However, comparing the achievement of LDL-C goals (calculated by three methods) and non-HDL-C goals also confirmed that the common practice of automatically adding 0.8 mmol/L to the calculated LDL-C value to determine non-HDL-C leads to inaccuracies, particularly in the lower triglyceride ranges. Full article

(This article belongs to the Section Cardiovascular Medicine)

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26 pages, 7406 KiB

Open AccessReview

Cardiac Imaging in the Diagnosis and Management of Heart Failure

by Mayuresh Chaudhari and Mahi Lakshmi Ashwath

J. Clin. Med. 2025, 14(14), 5002; https://doi.org/10.3390/jcm14145002 (registering DOI) - 15 Jul 2025

Abstract

Heart failure (HF) is a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood. The etiology of heart failure is multifactorial, encompassing ischemic heart disease, hypertension, valvular disorders, cardiomyopathies, and metabolic and infiltrative diseases. [...] Read more.

Heart failure (HF) is a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood. The etiology of heart failure is multifactorial, encompassing ischemic heart disease, hypertension, valvular disorders, cardiomyopathies, and metabolic and infiltrative diseases. Despite advances in pharmacologic and device-based therapies, heart failure continues to carry a substantial burden of morbidity, mortality, and healthcare utilization. With the advancement and increased accessibility of cardiac imaging modalities, the diagnostic accuracy for identifying the underlying etiologies of nonischemic cardiomyopathy has significantly improved, allowing for more precise classification and tailored management strategies. This review aims to provide a comprehensive analysis of the current understanding of heart failure, encompassing epidemiology, etiological factors, with a specific focus on diagnostic imaging modalities including the role of echocardiography and strain imaging, cardiac magnetic resonance imaging (CMR), cardiac computed tomography (CT), and nuclear positron emission tomography (PET) imaging and recent advances in the diagnosis and management of heart failure. Full article

(This article belongs to the Special Issue Cardiac Imaging in the Diagnosis and Management of Heart Failure)

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15 pages, 1279 KiB

Open AccessSystematic Review

The Efficacy and Safety of Probiotics in the Management of Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis

by Ali Abbas, Mohammed Abbas, Zahir Mughal, Pablo Martinez-Devesa and Ali Qureishi

J. Clin. Med. 2025, 14(14), 5001; https://doi.org/10.3390/jcm14145001 (registering DOI) - 15 Jul 2025

Abstract

Background/Objectives: In this study, we aimed to evaluate probiotics’ clinical efficacy and safety in adults with chronic rhinosinusitis (CRS), and summarize mechanistic evidence related to mucosal immunity and microbiota modulation. Methods: We performed a systematic review and random-effects meta-analysis. MEDLINE, Embase, [...] Read more.

Background/Objectives: In this study, we aimed to evaluate probiotics’ clinical efficacy and safety in adults with chronic rhinosinusitis (CRS), and summarize mechanistic evidence related to mucosal immunity and microbiota modulation. Methods: We performed a systematic review and random-effects meta-analysis. MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library were searched until May 2025. Eligibility: Randomized controlled trials (RCTs) and mechanistic studies investigating probiotics (any strain, dose, or administration route) in adults with CRS were eligible. Primary outcomes included changes in Sino-Nasal Outcome Test (SNOT-20/22) scores and CRS relapse rates. Secondary outcomes were adverse events and mechanistic endpoints. Results: Six studies (four RCTs, n = 337; two mechanistic studies) met the inclusion criteria. Probiotics did not significantly improve SNOT scores compared with the placebo, but trended in that direction (pooled mean difference—2.70; 95% CI −7.12 to 1.72; I² = 0%). Furthermore, probiotic use was associated with a non-significant trend towards fewer CRS relapses (risk ratio 0.41; 95% CI 0.16–1.04; p = 0.06; I² = 48%). Adverse events were mild and comparable to the placebo (risk ratio 0.87; 95% CI 0.33–2.34). Mechanistic data indicated that intranasal Lactococcus lactis W136 might downregulate type 1 inflammatory pathways and modestly increase microbiome diversity. Subgroup analyses (by route, duration, and CRS subtype) revealed no statistically significant effect modifiers, though mechanistic insights suggest possible differences in efficacy based on the CRS endotype and delivery method. Conclusions: Probiotics appear safe and may provide a small, non-significant improvement in CRS symptoms; emerging evidence of reduced relapse rates warrants further investigation through larger, endotype-stratified trials utilizing targeted probiotic strains and optimized delivery methods. Full article

(This article belongs to the Section Otolaryngology)

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12 pages, 241 KiB

Open AccessReview

Recombinant Human TSH Versus Thyroid Hormone Withdrawal: The Role in the Preparation for RAI Therapy in Differentiated Thyroid Cancer: A Comprehensive Evidence-Based Review

by Motaz Daraghma and Michael M. Graham

J. Clin. Med. 2025, 14(14), 5000; https://doi.org/10.3390/jcm14145000 (registering DOI) - 15 Jul 2025

Abstract

Radioactive iodine (RAI) therapy plays a fundamental role in the management of differentiated thyroid cancer (DTC) following appropriate surgical intervention. High levels of TSH are required in order to achieve maximum RAI uptake in residual thyroid tissue or metastatic cells. The two techniques [...] Read more.

Radioactive iodine (RAI) therapy plays a fundamental role in the management of differentiated thyroid cancer (DTC) following appropriate surgical intervention. High levels of TSH are required in order to achieve maximum RAI uptake in residual thyroid tissue or metastatic cells. The two techniques that are most commonly used are thyroid hormone withdrawal (THW), which induces endogenous TSH elevation by creating a hypothyroid state, and exogenous stimulation with recombinant human TSH (rhTSH). This review compares both approaches over a range of DTC risk categories. Extensive evidence demonstrates that rhTSH and THW yield equivalent oncological outcomes, including remnant ablation success, recurrence-free survival, and overall survival, in low-, intermediate-, and high-risk disease. Additionally, rhTSH maintains quality of life by avoiding hypothyroid symptoms. While THW continues to be an excellent option when there is a lack of availability of rhTSH, its disadvantages, particularly the transient hypothyroid state, must be carefully weighed against the demonstrated equivalence in efficacy. In current clinical practice, rhTSH is frequently the preferred option for its convenience, safety, and patient-centered benefits; however, the selection of the optimal approach should be based on individual clinical circumstances and patients’ preferences, as well as resource considerations. Full article

(This article belongs to the Section Nuclear Medicine & Radiology)

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