Journal of Clinical Medicine

18 pages, 872 KB

Open AccessEditor’s ChoiceReview

Advancing Heart Failure Care: Breakthroughs and Emerging Strategies

by Andrea Tedeschi, Federico Barocelli, Luigi Gerra, Federico Breviario, Matteo Palazzini, Nicolina Conti, Stefano Ferraro, Maria Giulia Bolognesi, Francesco Di Spigno, Piero Gentile, Andrea Garascia, Enrico Ammirati, Giulia Magnani, Giampaolo Niccoli, Nuccia Morici and Daniela Aschieri

J. Clin. Med. 2025, 14(20), 7253; https://doi.org/10.3390/jcm14207253 - 14 Oct 2025

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Abstract

Heart failure represents a complex clinical syndrome characterized by progressive ventricular dysfunction, systemic congestion, and high mortality despite significant advances in pharmacological and device-based therapy. This review explores recent developments across the heart failure continuum, with a focus on therapeutic advances across the [...] Read more.

Heart failure represents a complex clinical syndrome characterized by progressive ventricular dysfunction, systemic congestion, and high mortality despite significant advances in pharmacological and device-based therapy. This review explores recent developments across the heart failure continuum, with a focus on therapeutic advances across the continuum of care, with emphasis on both established and emerging strategies. In patients with reduced ejection fraction, early initiation of the four pillars markedly lowers cardiovascular events, yet real-world implementation remains limited by therapeutic inertia and underdosing. Novel agents such as finerenone provide cardiorenal benefits in patients with diabetes and chronic kidney disease, while glucagon-like peptide-1 receptor agonists show promise in preserved or mildly reduced ejection fraction, particularly with obesity. Tricuspid regurgitation, once considered a secondary phenomenon, is now recognized as a modifiable contributor to disease progression, with transcatheter interventions offering new therapeutic avenues. In advanced disease, innovations including donation after circulatory death and the development of total artificial heart systems offer promising solutions to overcome organ shortages and improve access to transplantation. Together, these advances highlight a shift toward precision-guided, multidisciplinary heart failure care. Full article

(This article belongs to the Special Issue Acute and Chronic Heart Failure: Clinical Updates and Perspectives)

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10 pages, 1650 KB

Open AccessEditor’s ChoiceArticle

Radiographic Outcomes After Growing Rod Treatment in Early-Onset Scoliosis: With Versus Without Final Fusion Surgery

by Yunjin Nam, Udit Patel, Sangmin Lee, Jungwook Lim, Jae Hyuk Yang and Seung Woo Suh

J. Clin. Med. 2025, 14(20), 7184; https://doi.org/10.3390/jcm14207184 - 12 Oct 2025

Viewed by 405

Abstract

Background/Objectives: Early-onset scoliosis (EOS) is often treated with growing rods, which use distraction-based correction to control deformity while allowing spinal growth. Although effective in the coronal plane, this technique may adversely affect sagittal alignment, particularly thoracic kyphosis and lumbar lordosis. Whether final [...] Read more.

Background/Objectives: Early-onset scoliosis (EOS) is often treated with growing rods, which use distraction-based correction to control deformity while allowing spinal growth. Although effective in the coronal plane, this technique may adversely affect sagittal alignment, particularly thoracic kyphosis and lumbar lordosis. Whether final fusion surgery is necessary after the growing rod treatment remains controversial. This study compared radiographic outcomes, including coronal and sagittal parameters, between patients with and without final fusion to clarify the value of final fusion. Methods: We retrospectively reviewed 19 EOS patients treated with growing rods between 2015 and 2019. Patients undergoing posterior spinal fusion after lengthening were classified as the final fusion group (n = 9), while those with more than 12 months of follow-up without fusion formed the graduated group (n = 10). Demographics, surgical variables, and radiographic parameters (Cobb angle, correction rate, coronal balance, clavicular angle, thoracic kyphosis, lumbar lordosis, sagittal vertical axis) were compared. Results: Baseline characteristics were similar. At final follow-up, the final fusion group had significantly better outcomes in Cobb angle (24.2° vs. 34.9°, p = 0.002), correction rate (66.6% vs. 40.1%, p = 0.001), and coronal balance (−1.5 mm vs. 19.7 mm, p = 0.004). Sagittal alignment did not differ significantly, but preservation of thoracic kyphosis tended to favor the fusion group. Conclusions: Final fusion surgery after growing rod treatment achieved superior coronal correction and balance compared with observation alone. Although sagittal alignment was not statistically different, a trend toward better thoracic kyphosis preservation was observed. Final fusion should be considered for larger residual curves or coronal imbalance, while observation may suffice in well-corrected cases. Full article

(This article belongs to the Special Issue Scoliosis: Advances in Diagnosis and Management)

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18 pages, 5627 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Precision Assessment of Facial Asymmetry Using 3D Imaging and Artificial Intelligence

by Mohamed Adel, Katie Jo Hunt, Daniel Lau, James K. Hartsfield, Hugo Reyes-Centeno, Cynthia S. Beeman, Tarek Elshebiny and Lina Sharab

J. Clin. Med. 2025, 14(20), 7172; https://doi.org/10.3390/jcm14207172 - 11 Oct 2025

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Abstract

Objectives: There is a growing interest among practitioners in employing artificial intelligence (AI) to enhance the precision and efficiency of diagnostic methods. The objective of this study is to assess the precision of an AI-based method for facial asymmetry assessment using 3D [...] Read more.

Objectives: There is a growing interest among practitioners in employing artificial intelligence (AI) to enhance the precision and efficiency of diagnostic methods. The objective of this study is to assess the precision of an AI-based method for facial asymmetry assessment using 3D facial images. Methods: The study included 130 patients (84 female, 46 male), analyzing 3D facial images from the Vectra^® M3 imaging system using both manual and AI-based methods. Seven bilateral facial landmarks were identified for manual analysis, calculating the asymmetry index for facial symmetry assessment. An AI-based program was developed to automate the identification of the same landmarks and calculate the asymmetry index. The reliability of the manual measurements was assessed using intraclass correlation coefficients (ICC) with 95% confidence intervals (CI). Precision of automated landmark identification was compared to the manual method. Results: The ICCs for the manual measurements demonstrated moderate to excellent reliability, both within raters (ICC = 0.62–0.99) and between raters (ICC = 0.72–0.96) each calculated with 95% CI. Agreement was observed between the manual and automated methods in calculating the asymmetry index for five landmarks. There was a statistically significant difference between the two methods in determining the asymmetry index for alare (median: 2.05 mm manual vs. 1.54 mm automated, p = 0.0056) and cheilion (median: 2.77 mm manual vs. 2.30 mm automated, p = 0.0081). Conclusions: The AI-based method provides efficient and comparable precision of facial asymmetry analysis using 3D images. The disagreement observed between the two methods can be addressed through further improvement and training of the automated software. This innovative approach opens doors to significant advancements in both research and clinical orthodontics. Full article

(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)

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18 pages, 929 KB

Open AccessEditor’s ChoiceArticle

Real-World and Clinical Implications of Patient Education, Lifestyle and Treatment Adherence in Romanian Diabetes Care: An Observational Study

by Ozana-Andreea Măriuț, Ana Flavia Burlec, Irina Macovei, Cornelia Mircea, Mădălina Elena Datcu, Monica Hăncianu and Andreia Corciovă

J. Clin. Med. 2025, 14(20), 7171; https://doi.org/10.3390/jcm14207171 - 11 Oct 2025

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Abstract

Background/Objectives: Diabetes mellitus is a major global health concern requiring both preventive strategies and patient-centered clinical management. This study evaluated knowledge, lifestyle behaviors, treatment adherence and the use of digital tools among Romanian patients with diabetes in a real-world setting. Methods: A cross-sectional [...] Read more.

Background/Objectives: Diabetes mellitus is a major global health concern requiring both preventive strategies and patient-centered clinical management. This study evaluated knowledge, lifestyle behaviors, treatment adherence and the use of digital tools among Romanian patients with diabetes in a real-world setting. Methods: A cross-sectional observational study was conducted on 100 patients recruited from community pharmacies in Iași, Romania. Data were collected using a structured 27-item questionnaire addressing demographics, disease management, adherence, lifestyle factors, and complications. Results: Most participants had type 2 diabetes. Engagement in healthy behaviors was suboptimal, with low levels of daily physical activity and limited routine glucose monitoring. Complications and treatment-related side effects were frequent, reflecting a high disease burden. Treatment adherence was significantly higher among younger patients, those with type 1 diabetes and individuals who had set long-term health goals. The use of digital technologies was low overall but more common in younger participants. Conclusions: This study identifies critical gaps in lifestyle practices, adherence and technology uptake among Romanian patients with diabetes. These findings carry important clinical implications, as poor adherence and limited self-management are closely linked to complications and higher healthcare spending. The findings suggest that patient education, integrating validated digital tools and enhancing the role of community healthcare providers could support better adherence and reduce long-term complications. Full article

(This article belongs to the Section Endocrinology & Metabolism)

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12 pages, 2610 KB

Open AccessEditor’s ChoiceArticle

Combined Use of Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging in the Differential Diagnosis of Sellar Tumors: A Single-Centre Experience

by Adrian Korbecki, Marek Łukasiewicz, Arkadiusz Kacała, Michał Sobański, Agata Zdanowicz-Ratajczyk, Karolina Szałata, Mateusz Dorochowicz, Justyna Korbecka, Grzegorz Trybek, Anna Zimny and Joanna Bladowska

J. Clin. Med. 2025, 14(20), 7168; https://doi.org/10.3390/jcm14207168 - 11 Oct 2025

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Abstract

Background/Objectives: To evaluate whether incorporating both diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) in pituitary MRI examinations improves differential diagnosis by providing additional diagnostic value. Methods: A retrospective analysis was performed on 88 patients with histologically confirmed sellar or parasellar tumors who underwent [...] Read more.

Background/Objectives: To evaluate whether incorporating both diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) in pituitary MRI examinations improves differential diagnosis by providing additional diagnostic value. Methods: A retrospective analysis was performed on 88 patients with histologically confirmed sellar or parasellar tumors who underwent 1.5T MRI with DWI and dynamic susceptibility contrast PWI (DSC-PWI) between October 2007 and April 2023. DWI parameters included minimum apparent diffusion coefficient (ADCmin) and relative ADCmin (rADCmin). PWI parameters included mean and maximum relative cerebral blood volume (rCBV, rCBVmax) and relative peak height (rPH, rPHmax), normalized to white matter. Tumor regions of interest were manually segmented, excluding calcified or hemorrhagic areas. Group comparisons and ROC analyses assessed diagnostic performance of individual and combined parameters. Results: Significant differences in diffusion and perfusion metrics were observed among the five tumor types. The combined analysis of DWI and PWI improved diagnostic accuracy in selected comparisons. The greatest benefit occurred in distinguishing meningiomas from solid non-functional pituitary adenomas (pituitary neuroendocrine tumors-PitNET), where the combination of ADCmin and rPHmax yielded an AUC of 0.818, sensitivity of 88%, and specificity of 76%, exceeding the performance of either parameter alone. In other comparisons, including meningiomas versus invasive PitNETs and adamantinomatous craniopharyngiomas, combined analysis did not substantially improve accuracy when single parameters, particularly rCBVmax (AUC = 0.995), already demonstrated excellent performance. Conclusions: Integration of DWI and PWI into pituitary MRI protocols enhances diagnostic performance in selected tumor groups. The additive value is context-dependent, supporting the tailored application of these sequences in the evaluation of sellar and parasellar tumors. Full article

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

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14 pages, 996 KB

Open AccessEditor’s ChoiceArticle

Predictors of Step-Up Therapy and Outcomes in Idiopathic Granulomatous Mastitis: A Retrospective Cohort Study in Singapore

by Kai Lin Lee, Jessele Shian Yi Lai, Peh Joo Ho, Hung Chew Wong, Karen Kaye Casida, Qin Xiang Ng, Mikael Hartman and Serene Si Ning Goh

J. Clin. Med. 2025, 14(20), 7157; https://doi.org/10.3390/jcm14207157 - 10 Oct 2025

Viewed by 1145

Abstract

Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign, chronic inflammatory breast condition that poses diagnostic and therapeutic challenges. While corticosteroids are standard first-line therapy, some patients require additional immunomodulation, such as methotrexate. Predictive factors for step-up therapy remain poorly characterized. This [...] Read more.

Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign, chronic inflammatory breast condition that poses diagnostic and therapeutic challenges. While corticosteroids are standard first-line therapy, some patients require additional immunomodulation, such as methotrexate. Predictive factors for step-up therapy remain poorly characterized. This study aimed to identify clinical, imaging, and pathological factors predictive of step-up therapy in IGM and evaluate associations between treatment approach and outcomes. Methods: A retrospective cohort study of women diagnosed with IGM was conducted between May 2022 and June 2024 at a tertiary center in Singapore. Data on demographics, clinical presentation, imaging, histopathology, and treatment were extracted. Step-up therapy was defined as methotrexate use following corticosteroids. Primary outcome was predictors of step-up therapy; secondary outcomes included treatment success, relapse, surgery, and time to remission. Statistical analyses included chi-square/Fisher’s exact tests, Cox models, and Kaplan-Meier analysis. Results: Fifty-two women (median age 39 years) were included; 26 (50%) required step-up therapy. Predictors included oral contraceptive (OCP) use (RR 1.92; 95% CI 1.45–2.53; p < 0.001), smoking (RR 2.00; 95% CI 1.49–2.69; p < 0.001), flares (RR 2.33; 95% CI 1.44–3.79; p = 0.002), and percutaneous aspiration (RR 2.10; 95% CI 1.53–2.88; p = 0.025). Patients receiving methotrexate had lower relapse rates (RR 1.23; 95% CI 1.12–1.36; p < 0.001) but longer time to remission (adjusted HR 0.09; 95% CI 0.02–0.46; p = 0.004). Conclusions: OCP use, smoking, flares, and aspiration need may predict step-up therapy in IGM. Early identification could guide a more personalized, potentially top-down treatment. Full article

(This article belongs to the Section Immunology & Rheumatology)

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17 pages, 2459 KB

Open AccessEditor’s ChoiceReview

Definition, Incidence, Prediction, and Prevention of Bleeding Events After Transcatheter Aortic Valve Implantation

by Iosif Xenogiannis, Ioannis Lianos, Grigoris V. Karamasis, Charalampos Varlamos, Fotios Kolokathis, Christos Pappas, Stamatia Kovra, Konstantinos Tsaousidis, Christos Mourmouris, Antonis N. Pavlidis, Andreas S. Triantafyllis and Andreas S. Kalogeropoulos

J. Clin. Med. 2025, 14(20), 7154; https://doi.org/10.3390/jcm14207154 - 10 Oct 2025

Viewed by 780

Abstract

Bleeding remains the most common complication following transcatheter aortic valve implantation (TAVI), despite a decline in its incidence over time. Periprocedural (≤30 days) major or life-threatening bleeding is reported to occur in 2.0–6.6% of patients undergoing TAVI. Major bleeding events carry a significant [...] Read more.

Bleeding remains the most common complication following transcatheter aortic valve implantation (TAVI), despite a decline in its incidence over time. Periprocedural (≤30 days) major or life-threatening bleeding is reported to occur in 2.0–6.6% of patients undergoing TAVI. Major bleeding events carry a significant risk of mortality, with rates of 14.1% at 30 days and 27.8% at one year. The timely identification and management of patients at an elevated risk are therefore essential. Preventive measures include optimizing antithrombotic therapies, utilizing ultrasound-guided femoral access, employing single arterial access or a radial artery for secondary access, and administering unfractionated heparin under close monitoring. Long-term follow-up is essential for recognizing and managing late hemorrhages. In this review, we aimed to provide an in-depth analysis of bleeding events associated with TAVI and the most recent updates regarding the antithrombotic therapy of TAVI patients and its clinical impact. Full article

(This article belongs to the Special Issue Aortic Valve Implantation: Recent Advances and Future Prospects)

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18 pages, 734 KB

Open AccessEditor’s ChoiceReview

Reconsidering Hormone Replacement Therapy: Current Insights on Utilisation in Premenopausal and Menopausal Women: An Overview

by Vesselina Yanachkova, Mariela Vasileva-Slaveva, Stoyan Kostov and Angel Yordanov

J. Clin. Med. 2025, 14(20), 7156; https://doi.org/10.3390/jcm14207156 - 10 Oct 2025

Viewed by 1502

Abstract

Hormone replacement therapy (HRT) has been utilized in clinical practice for decades as a main therapeutic approach for mitigating menopausal symptoms. The symptoms mostly encompass vasomotor and genitourinary issues resulting from the deficiency of estrogen and progesterone. Initially identified as a universally advantageous [...] Read more.

Hormone replacement therapy (HRT) has been utilized in clinical practice for decades as a main therapeutic approach for mitigating menopausal symptoms. The symptoms mostly encompass vasomotor and genitourinary issues resulting from the deficiency of estrogen and progesterone. Initially identified as a universally advantageous and indispensable intervention, hormone replacement therapy subsequently became the subject of considerable scientific and clinical debate, especially after the publication of extensive epidemiological studies indicating potential adverse effects associated with cardiovascular and cancer risk. This study aims to reassess the role of HRT in clinical practice by analyzing its historical evolution, expanded clinical uses, and changes in guidelines necessitated by resent scientific studies. Current evidence from clinical studies and meta-analyses unequivocally demonstrates that hormone replacement therapy is the most efficacious treatment for vasomotor and urogenital symptoms, and also acknowledging its potential role in osteoporosis prevention. The administration of HRT requires careful individual assessment, considering the patient’s age, timing of initiation, existence of comorbidities. In this setting, therapy decisions have to be based on a combination of the most up-to-date clinical guidelines, risk stratification, and the patient’s preferences. In conclusion, the assessment of HRT confirms its primary role in reducing menopausal symptoms while also highlighting the imperative for a individual strategy that balances benefits and risks to improve outcomes for women. Full article

(This article belongs to the Special Issue Gynecologic and Obstetric Pathologies: From Birth to Menopause (Third Edition))

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22 pages, 1049 KB

Open AccessEditor’s ChoiceReview

Traumatic Brain Injury: Advances in Diagnostic Techniques and Treatment Modalities

by Lori Zarmer, Maaz S. Khan, Glenn Islat, Hanan Alameddin, Maria Massey, Saki Kazui and Rabail Chaudhry

J. Clin. Med. 2025, 14(20), 7145; https://doi.org/10.3390/jcm14207145 - 10 Oct 2025

Viewed by 1458

Abstract

Background/Objectives: Traumatic brain injury (TBI) is a major global cause of death and disability, with long-term cognitive, behavioral, and functional consequences. Despite its high burden, management is complicated by heterogeneous presentations and limited evidence. This review summarizes recent advances in monitoring, therapeutic strategies, [...] Read more.

Background/Objectives: Traumatic brain injury (TBI) is a major global cause of death and disability, with long-term cognitive, behavioral, and functional consequences. Despite its high burden, management is complicated by heterogeneous presentations and limited evidence. This review summarizes recent advances in monitoring, therapeutic strategies, neuroprotection, and rehabilitation, while highlighting future directions toward individualized and globalized care. Methods: This paper is a narrative review of clinical trials, systematic reviews, and observational studies, focusing on invasive and non-invasive monitoring, pharmacologic and non-pharmacologic interventions, neuroprotective agents, stem cell therapy, and advanced rehabilitation modalities. Results/Findings: Our review focuses on emerging monitoring techniques, including brain tissue oxygenation, cerebral microdialysis, and multimodal strategies, that provide detailed insights but lack standardized application. Interventions such as anti-inflammatory agents, hypothermia, hyperosmolar therapies, and metabolic suppression show mixed efficacy, with few therapies supported by high-level evidence. Novel agents like erythropoietin and progesterone demonstrate neuroprotective potential in preclinical models but remain inconclusive in clinical trials. Stem cell therapies and extracellular vesicle approaches are promising in early studies. Rehabilitation is expanding with virtual reality, robotics, and neurostimulation to promote neuroplasticity. Personalized medicine approaches incorporating biomarkers and machine learning may refine prognostication and guide therapy. Global inequities persist, particularly in low-resource settings. Conclusions: TBI care is shifting toward individualized, multimodal, and technology-driven strategies. While emerging therapies show promise, high-quality randomized trials and global implementation strategies are needed to improve outcomes and reduce disparities. Full article

(This article belongs to the Special Issue Clinical Advances in Therapy of Trauma and Surgical Critical Care)

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27 pages, 2516 KB

Open AccessEditor’s ChoiceReview

Multiple Myeloma Laboratory Diagnostics Made Simple: Practical Insights and Key Recommendations

by Ana Marta Pires, João Pedro Barreto, Joana Caetano, Maria José Soares, Catarina Geraldes, Bruno Fernandes, Margarida Coucelo, Sérgio Chacim, Henrique Coelho, Cecília Correia, Ana Paula Cruz, Manuel Cunha, Maria Rosário Cunha, Nuno Cunha, Patrícia Ferraz, José Guilherme Freitas, Rui Henrique, Susana Lisboa, Paulo Lúcio, Artur Paiva, Cláudia Pedrosa, Inês Ramos, Ana Bela Sarmento-Ribeiro, Patrícia Seabra, Joana Sevilha, Maria José Rego de Sousa, Sara Sousa, Teresa Sousa, Márcio Tavares, Fernanda Trigo, Adriana Roque, Rui Bergantim, Cristina João and on behalf of the Portuguese Multiple Myeloma Group Show full author list Hide full author list

J. Clin. Med. 2025, 14(19), 7115; https://doi.org/10.3390/jcm14197115 - 9 Oct 2025

Viewed by 1041

Abstract

Multiple myeloma is a clonal plasma cell malignancy with a highly variable range of clinical manifestations. Over recent decades, substantial progress has been made in laboratory diagnostics, which has deepened our understanding of disease biology, improved risk stratification, and informed treatment strategies. In [...] Read more.

Multiple myeloma is a clonal plasma cell malignancy with a highly variable range of clinical manifestations. Over recent decades, substantial progress has been made in laboratory diagnostics, which has deepened our understanding of disease biology, improved risk stratification, and informed treatment strategies. In an era of transformation and innovation, conventional laboratory methods remain essential, as cutting-edge technologies might not be immediately accessible to all laboratories. Nonetheless, even widely used laboratory methodologies present many challenges, such as variability in assay performance, interpretative criteria, and standardization. This review by the Portuguese Multiple Myeloma Group of the Portuguese Society of Hematology provides a comprehensive overview and practical appraisal of current conventional laboratory methods employed for multiple myeloma diagnosis. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

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Graphical abstract

29 pages, 2125 KB

Open AccessEditor’s ChoiceReview

Hungry Bone Syndrome After Parathyroidectomy for Secondary Hyperparathyroidism: Pathogenesis and Contemporary Clinical Considerations

by Adina Coman, Cristi Tarta, Marco Marian, Daian Ionel Popa, Sorin Olariu, Mihai Rosu, Diana Utu, Florina Buleu, Anca-Monica Macovei-Oprescu, Dorin Novacescu, Flavia Zara and Marius Murariu

J. Clin. Med. 2025, 14(19), 7104; https://doi.org/10.3390/jcm14197104 - 9 Oct 2025

Viewed by 1163

Abstract

Secondary hyperparathyroidism (SHPT) in chronic kidney disease often necessitates parathyroidectomy (PTX), but this definitive treatment can precipitate hungry bone syndrome (HBS)—a profound, prolonged hypocalcemia caused by the rapid skeletal uptake of minerals after surgery. HBS results from the abrupt cessation of parathyroid hormone [...] Read more.

Secondary hyperparathyroidism (SHPT) in chronic kidney disease often necessitates parathyroidectomy (PTX), but this definitive treatment can precipitate hungry bone syndrome (HBS)—a profound, prolonged hypocalcemia caused by the rapid skeletal uptake of minerals after surgery. HBS results from the abrupt cessation of parathyroid hormone (PTH)-driven bone resorption while bone formation continues, leading to intensive mineral deposition (mainly calcium) into chronically demineralized bone. Clinically, HBS ranges from asymptomatic biochemical disturbances to life-threatening hypocalcemia with tetany, seizures, and/or cardiac arrhythmias. This illustrative review synthesizes current knowledge of HBS pathogenesis and management in the context of SHPT. We detail how the high-turnover bone remodeling state of SHPT (osteitis fibrosa cystica) creates an expansive unmineralized osteoid pool that avidly mineralizes post-PTX. We also explore molecular mechanisms (e.g., RANKL/OPG dysregulation, Wnt/β-catenin activation, osteocyte-driven signals, and calcium-sensing receptor effects) that underpin this process. Key preoperative risk factors for HBS include very elevated PTH and alkaline phosphatase levels, large skeletal calcium deficits, younger patient age, and total PTX. We outline the typical postoperative course of HBS, phased from immediate acute hypocalcemia to a nadir and gradual recovery. Prevention and management strategies are emphasized, centered on vigilant monitoring and aggressive calcium and calcitriol supplementation, with preoperative optimization (e.g., vitamin D loading, calcimimetics) to mitigate severity. By enhancing risk stratification and perioperative care, clinicians can improve outcomes and safely navigate patients through this challenging complication of endocrine surgery. Full article

(This article belongs to the Special Issue Endocrine Surgery: Current Developments and Trends)

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27 pages, 407 KB

Open AccessEditor’s ChoiceSystematic Review

Beyond Racial Categorization in Sports Cardiology: A Systematic Review of Cardiac Adaptations in Athletes

by Douglas Corsi, Rafael Hernandez, Jasmine Yimeng Bao, Stephen Garrova and David Shipon

J. Clin. Med. 2025, 14(19), 7107; https://doi.org/10.3390/jcm14197107 - 9 Oct 2025

Viewed by 638

Abstract

Background/Objectives: Race-based cardiac screening criteria in sports cardiology, including the “Black athlete’s heart” concept, assume biological distinctions that may not reflect physiological reality. This systematic review evaluates whether geographic ancestry provides more clinically relevant predictors of cardiac adaptation than racial categorization. Methods: PubMed [...] Read more.

Background/Objectives: Race-based cardiac screening criteria in sports cardiology, including the “Black athlete’s heart” concept, assume biological distinctions that may not reflect physiological reality. This systematic review evaluates whether geographic ancestry provides more clinically relevant predictors of cardiac adaptation than racial categorization. Methods: PubMed was searched (January 2005–July 2025) for studies examining cardiac adaptations in athletes by ethnicity. Data extraction captured demographics, geographic origin, cardiac assessments, and outcomes. Narrative synthesis was employed due to methodological heterogeneity. Results: Forty-seven studies (n = 66,130) revealed substantial within-race heterogeneity. The “Black athlete repolarization variant” prevalence ranged from 1.8% (Brazilian) to 30% (Ghanaian) Black athletes. Left ventricular wall thickness >12 mm (normal <11 mm) occurred in 7.1% of Black versus 0.4% of White athletes, yet varied significantly within Black populations—10.8 ± 1.2 mm in Sub-Saharan versus 9.4 ± 1.1 mm in African-American athletes (p < 0.001). Relative wall thickness ≥0.44 (normal ≤0.42) was presented in 43% of West/Middle African, 23% of East African, and 7% of White athletes. T-wave inversion showed four-fold variation within Black populations (3.6–8.5% West African versus 0.5–2.0% African-American/Caribbean). Current International Criteria demonstrated inequitable specificity: 3.3% false-positive rate in Black versus 1.4% in White athletes. Conclusions: Geographic ancestry explains more cardiac variation than racial categories, supporting contemporary understanding of race as a sociopolitical construct. The persistent diagnostic disparities in ECG screening specificity highlight the need for reform. Transitioning toward protocols incorporating continental origin, anthropometric factors, and social determinants of health—while eliminating terminology like “Black athlete’s heart”—represents an important step toward achieving equity in cardiovascular care for diverse athletic populations. Full article

(This article belongs to the Section Sports Medicine)

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15 pages, 1849 KB

Open AccessEditor’s ChoiceArticle

Prevalence of Sleep Disturbance and Associated Risk Factors in Degenerative Cervical Myelopathy

by Salim Yakdan, Karan Joseph, Jingyi Zhang, Miguel A. Ruiz-Cardozo, Aryan Pradhan, Alisha Dhallan, Faraz Arkam, Willliam Mualem, Garrison Bentz, Diogo P. Moniz Garcia, Benjamin Plog, Alexander T. Yahanda, Daniel Hafez, Wilson Z. Ray, Camilo A. Molina and Jacob K. Greenberg

J. Clin. Med. 2025, 14(19), 7110; https://doi.org/10.3390/jcm14197110 - 9 Oct 2025

Viewed by 700

Abstract

Study Design: Retrospective Case–Control. Objectives: Sleep disturbances negatively impact quality of life and increase illness susceptibility. Chronic pain is a risk factor for sleep disruption, particularly in patients with degenerative spinal conditions. Existing studies suggest that degenerative cervical myelopathy (DCM) patients often experience [...] Read more.

Study Design: Retrospective Case–Control. Objectives: Sleep disturbances negatively impact quality of life and increase illness susceptibility. Chronic pain is a risk factor for sleep disruption, particularly in patients with degenerative spinal conditions. Existing studies suggest that degenerative cervical myelopathy (DCM) patients often experience sleep disturbances, possibly due to spinal cord compression and pain. However, most research is limited to small, single-center studies, creating a need for broader analyses. Methods: We utilized the Merative Explorys Dataset, focusing on electronic health record data of patients diagnosed with DCM and sleep disorders identified via ICD codes. Comorbidities analyzed included depression/bipolar disorder, chronic pulmonary disease, migraine, osteoarthritis, hypertension, malignancy, diabetes, and cerebrovascular disease. Patient demographic information (age, race, sex, and body mass index (BMI)) was included as covariates. Logistic regression analyses were performed to evaluate the association between each comorbidity and the risk of sleep disturbance. Results: Among 40,551 DCM patients, significant predictors of sleep disturbance included higher BMI (OR: 1.05, 95% CI: 1.05–1.06), depression/bipolar disorder (OR: 1.65, 95% CI: 1.56–1.74), chronic pulmonary disease (OR: 1.26, 95% CI: 1.20–1.33), migraine (OR: 1.32, 95% CI: 1.22–1.43), and hypertension (OR: 1.16, 95% CI: 1.10–1.23). Conclusions: This large-scale analysis demonstrates the multifactorial nature of sleep disturbances in DCM, highlighting strong associations with BMI and respiratory conditions, suggesting a contributory role of sleep-disordered breathing. The identification of migraines as a risk factor highlights the need for multidisciplinary management. Addressing modifiable risk factors such as BMI and mental health may improve sleep quality in DCM patients. Full article

(This article belongs to the Special Issue Emerging Trends in Cervical Spine Surgery)

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27 pages, 627 KB

Open AccessEditor’s ChoiceArticle

Multidimensional Impulsivity Profile in Young Adults Aged 16 to 25 with Borderline Personality Disorder: A Study Based on the UPPS-P Model

by Anaïs Mungo, Marie Delhaye and Matthieu Hein

J. Clin. Med. 2025, 14(19), 7109; https://doi.org/10.3390/jcm14197109 - 9 Oct 2025

Viewed by 845

Abstract

Background: Borderline Personality Disorder (BPD) often emerges during adolescence and young adulthood, a period marked by heightened vulnerability to impulsivity and affective dysregulation. While impulsivity is a core feature of BPD, its multidimensional expression in this age group remains insufficiently documented. This [...] Read more.

Background: Borderline Personality Disorder (BPD) often emerges during adolescence and young adulthood, a period marked by heightened vulnerability to impulsivity and affective dysregulation. While impulsivity is a core feature of BPD, its multidimensional expression in this age group remains insufficiently documented. This study examined impulsivity traits in young adults with BPD, their associations with depressive and anxiety symptoms, and their links to risk behaviors. Methods: A total of 160 participants aged 16–25 were recruited in Belgium between 2021 and 2023: 44 with BPD from inpatient and outpatient psychiatric services and 116 healthy controls from schools and universities. Assessments included the short UPPS-P, Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory (STAI-T), and the Diagnostic Interview for Borderlines–Revised (DIB-R). Logistic regressions with robust errors and Kendall’s tau-b correlations were used. Results: Compared with controls, individuals with BPD scored higher on all UPPS-p subscales except Sensation Seeking (e.g., Negative Urgency: 14 vs. 10, p < 0.001). Logistic regression identified Negative Urgency (OR = 5.31, 95% CI: 2.07–13.62, p = 0.001) and Positive Urgency (OR = 3.26, 95% CI: 1.37–7.75, p = 0.007) as independent predictors of BPD. Within the BPD group, depressive and anxiety symptoms correlated with several UPPS-P dimensions, notably Negative Urgency and Lack of Perseverance. Suicide attempts were associated with the DIB-R total score, BDI-II, and STAI-T, while substance use was linked to the DIB-R impulsivity subscale and STAI-T. Conclusions: Emotional impulsivity—particularly Negative Urgency—emerges as a central feature of BPD in emerging adulthood. Its interplay with depressive and anxiety symptoms, and its associations with suicidal and addictive behaviors, support a dual-level conceptualization of impulsivity as both a dispositional trait and a state-dependent clinical risk factor. Full article

(This article belongs to the Special Issue (Recent Advances) Treating Psychiatry Disorders in Children and Adolescents: From Theory to Practice: 2nd Edition)

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13 pages, 605 KB

Open AccessEditor’s ChoiceReview

Functional Capacity Evaluation and Rehabilitation Strategies in Cardiac Amyloidosis: A Comprehensive Review

by Anthoula Plevritaki, Konstantinos Volaklis, Eleni Nakou, Constantinos Davos, Ioannis Kopidakis, Eleftherios Kallergis, Eirini Savva, Emmanouil Simantirakis, Aneta Aleksova and Maria Marketou

J. Clin. Med. 2025, 14(19), 7111; https://doi.org/10.3390/jcm14197111 - 9 Oct 2025

Viewed by 1819

Abstract

Cardiac amyloidosis (CA) is an increasingly recognized cause of restrictive cardiomyopathy characterized by amyloid fibril deposition in the heart, leading to severe functional impairments and poor prognosis. This review aims to provide a comprehensive overview of the pathophysiology of CA, emphasizing the mechanisms [...] Read more.

Cardiac amyloidosis (CA) is an increasingly recognized cause of restrictive cardiomyopathy characterized by amyloid fibril deposition in the heart, leading to severe functional impairments and poor prognosis. This review aims to provide a comprehensive overview of the pathophysiology of CA, emphasizing the mechanisms underlying functional capacity limitations and highlighting the importance of precise physiological assessment tools. We focus on objective measures such as cardiopulmonary exercise testing, field-based functional tests, and frailty evaluations that are vital for prognosis and tailoring patient care. With recent advances in disease-modifying therapies extending survival, maintaining and improving functional status through multidisciplinary rehabilitation emerges as a crucial therapeutic target. Evidence suggests that structured aerobic and resistance training can enhance exercise tolerance, strength, and quality of life in CA patients, although further research is needed to optimize rehabilitation protocols. By integrating clinical, physiological, and rehabilitative insights, this review underscores the value of a patient-centered approach aimed at preserving functional capacity and improving outcomes in this complex and systemic disease. Full article

(This article belongs to the Special Issue The Role of Cardiac Rehabilitation After Myocardial Infarction, Coronary Artery Bypass Surgery, and in Other Cardiac Diseases)

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22 pages, 1046 KB

Open AccessEditor’s ChoiceArticle

Sleep Quality and Sex-Specific Physical Activity Benefits Predict Mental Health in Romanian Medical Students: A Cross-Sectional Analysis

by Catalin Plesea-Condratovici, Alina Plesea-Condratovici, Silvius Ioan Negoita, Valerian-Ionut Stoian, Lavinia-Alexandra Moroianu and Liliana Baroiu

J. Clin. Med. 2025, 14(19), 7121; https://doi.org/10.3390/jcm14197121 - 9 Oct 2025

Viewed by 741

Abstract

Background: Evidence on how everyday walking and sleep relate to mood in health profession students from Central–Eastern Europe remains limited. Methods: We conducted a cross-sectional study among 277 Romanian medical students. Data were collected using validated instruments for physical activity (IPAQ-SF), [...] Read more.

Background: Evidence on how everyday walking and sleep relate to mood in health profession students from Central–Eastern Europe remains limited. Methods: We conducted a cross-sectional study among 277 Romanian medical students. Data were collected using validated instruments for physical activity (IPAQ-SF), sleep quality (PSQI), and depressive/anxiety symptoms (HADS). Associations were examined using bivariate and multivariable regression models, including sex-stratified analyses. Results: In bivariate analysis, total physical activity was inversely correlated with depressive symptoms (ρ = −0.19, p < 0.001). However, in the multivariable model, this effect was not statistically significant after controlling for other factors. Poor sleep quality emerged as the dominant independent predictor of both depression (β = 0.37, p < 0.001) and anxiety (β = 0.40, p < 0.001). Walking time and frequency were specifically protective against depressive symptoms. Sex-stratified analyses revealed distinct patterns: female students benefited more from walking, whereas male students showed stronger associations between overall physical activity and lower depressive symptoms. Conclusions: Within the constraints of a cross-sectional design, this study provides novel evidence from Eastern Europe that sleep quality and physical activity are central to student mental health. Psychological benefits of walking appear sex-specific, and the null mediation finding suggests benefits operate via direct or unmodelled pathways. Sleep is a critical independent target for tailored, lifestyle-based strategies. Full article

(This article belongs to the Special Issue Clinical Perspectives on Physical Activity and Health Across the Lifespan)

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17 pages, 354 KB

Open AccessEditor’s ChoiceArticle

Benign and Malignant Parotid Gland Tumors: Insights from a Five-Year Northeast Romanian Population

by Loredana-Beatrice Ungureanu, Cristina-Mihaela Ghiciuc, Victor Vlad Costan, Carmen Ungureanu, Victor Ianole and Delia-Gabriela Ciobanu Apostol

J. Clin. Med. 2025, 14(19), 7087; https://doi.org/10.3390/jcm14197087 - 8 Oct 2025

Viewed by 709

Abstract

Background: The majority of parotid gland tumors are benign, while malignant forms are uncommon, affecting fewer than 1 in 100,000 individuals. The main challenge resides in the histopathological complexity and the clinical overlap between benign and malignant parotid tumors, which frequently results [...] Read more.

Background: The majority of parotid gland tumors are benign, while malignant forms are uncommon, affecting fewer than 1 in 100,000 individuals. The main challenge resides in the histopathological complexity and the clinical overlap between benign and malignant parotid tumors, which frequently results in misdiagnosis. Aim: The objective of this research was to evaluate the clinical and histopathological characteristics of parotid gland tumors at a Romanian healthcare center. Materials and methods: A five-year retrospective study was conducted, with the inclusion criterion being the presence of complete clinical, pathological, and surgical records. Results: Of 156 patients included in the study, 67.3% were found to have benign lesions (male/female ratio 1.14:1), and there was a slight male predominance (53.3%). Partial parotidectomy was the most common surgical intervention for benign parotid tumors (59.6%), whereas total parotidectomy was predominantly indicated for malignant tumors, with facial nerve sacrifice occurring in 20% of cases to ensure complete tumor excision. Patients with benign tumors were found to be younger. Malignant tumors were commonly diagnosed at stage III (36.4%), indicative of more advanced disease at the time of diagnosis. Clinical diagnosis showed a high specificity of 96.9%, indicating high accuracy in malignancy suspicion, yet the sensitivity of 56% indicates that a significant number of malignancies were not detected during the initial evaluation. Tumor size was found to be influenced by gender and correlated with surgical methods, suggesting that patient characteristics and tumor biology may impact surgical strategy. Conclusions: This retrospective study highlights differences in gender, tumor size, and surgical approach between benign and malignant parotid gland tumors, offering valuable contributions in terms of diagnostic accuracy and treatment patterns despite a limited number of malignant cases. Full article

(This article belongs to the Special Issue New Insights into Head and Neck Surgery—2nd Edition)

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26 pages, 628 KB

Open AccessEditor’s ChoiceArticle

Construction and Initial Psychometric Validation of the Morana Scale: A Multidimensional Projective Tool Developed Using AI-Generated Illustrations

by Tytus Koweszko, Natalia Kukulska, Jacek Gierus and Andrzej Silczuk

J. Clin. Med. 2025, 14(19), 7069; https://doi.org/10.3390/jcm14197069 - 7 Oct 2025

Viewed by 642

Abstract

Background/Objectives: Psychoanalytic theories of destructiveness highlight its deep, unconscious origins tied to primal emotional and motivational mechanisms. Traditional psychiatric models of suicidal risk assessment focus on classic risk factors, limiting diagnostic and intervention approaches. This study examines the neuropsychoanalytic foundations of destructive [...] Read more.

Background/Objectives: Psychoanalytic theories of destructiveness highlight its deep, unconscious origins tied to primal emotional and motivational mechanisms. Traditional psychiatric models of suicidal risk assessment focus on classic risk factors, limiting diagnostic and intervention approaches. This study examines the neuropsychoanalytic foundations of destructive tendencies, integrating sublimation and evolutionary motivational systems, redefining their role in the destruction process. Methods: A total of 480 AI-generated illustrations were assessed for interpretative accuracy. The final set was used in an online projection task with 204 respondents. Analyses included factorial exploration of the structure of the tool, assessment of psychometric properties (Cronbach α, ROC, AUC), logistic regression and analysis of intergroup differences. Results: Factor analysis identified eight subscales. Six of the eight factors showed thematic resemblance to Panksepp’s emotional systems, although this interpretation remains theory-driven and requires empirical validation. The remaining two—pursuit of destruction and its sublimation—extend beyond natural evolutionary mechanisms. Destructiveness was best explained by depression and psychological pain (OR = 1.39, 95% CI [1.26–1.52]), aggression and impulsivity (OR = 1.68, 95% CI [1.36–2.06]), and anxiety and a sense of threat (OR = 1.55, 95% CI [1.27–1.90]). Key predictors of destruction sublimation were curiosity (OR = 3.15, 95% CI [2.43–4.09]), closeness and love (OR = 3.43, 95% CI [2.48–4.76]), and pleasure and fun (OR = 3.08, 95% CI [2.26–4.20]). Analyses showed higher levels of destructiveness in individuals receiving psychological or psychiatric support, those with prior diagnoses, and students compared to employed individuals. Conclusions: Results indicate high reliability (Cronbach’s α > 0.87) and discrimination among internal subscale-defined groups (ROC > 0.7), supporting the tool’s potential in assessing destructive and sublimation tendencies within a neuropsychoanalytic framework. Future studies will explore its external validity and clinical applications. Full article

(This article belongs to the Section Mental Health)

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15 pages, 624 KB

Open AccessEditor’s ChoiceArticle

Predictors of Parent-Reported Health-Related Quality of Life in Young Children with Early Brain Damage and Severe Motor Dysfunction

by Siri Johnsen, Kristian Sørensen, Jon Sverre Skranes, Ida Eline Vestrheim, Mette Gro Modahl, Reidun Birgitta Jahnsen, Kristine Stadskleiv, Gry Hansen, Stian Lydersen and Rannei Sæther

J. Clin. Med. 2025, 14(19), 7054; https://doi.org/10.3390/jcm14197054 - 6 Oct 2025

Viewed by 1020

Abstract

Background/Objectives: This cross-sectional study aimed to identify predictors of parent-reported health-related quality of life (HRQOL) in young children with early brain damage and severe motor dysfunction. It used baseline data from the PIH Multi Study, a randomized controlled trial evaluating an intensive, [...] Read more.

Background/Objectives: This cross-sectional study aimed to identify predictors of parent-reported health-related quality of life (HRQOL) in young children with early brain damage and severe motor dysfunction. It used baseline data from the PIH Multi Study, a randomized controlled trial evaluating an intensive, family-centered habilitation program for preschool children and their parents. Methods: Parent-reported HRQOL were measured using the CPCHILD questionnaire. Potential predictors included adaptive function (PEDI-CAT), gross motor function (GMFM-66), postural control and balance (ECAB), and communication function (FOCUS). These were selected to reflect the domains of the ICF-CY framework. Data were collected by professionals and by parents. Linear regression analyses were conducted to identify significant predictors. Results: Analyses included 65 children. Better adaptive skills, gross motor function, postural control, and communication all predicted higher parent-reported HRQOL. Adaptive skills—particularly in self-care and mobility—and gross motor function emerged as the strongest predictors. Conclusions: The study highlights the importance of targeting basic functional skills in early habilitation efforts for children with severe disabilities. The findings support a multidimensional understanding of health in line with the ICF-CY framework and underline the value of early, individualized, and family-centered interventions. Future research should investigate these predictors longitudinally and explore ways to integrate children’s own perspectives in assessment of HRQOL. Full article

(This article belongs to the Special Issue Toward Improved Evaluation, Treatment, and Management of Movement Disorders and Cognitive Impairments in People with Cerebral Palsy)

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47 pages, 2058 KB

Open AccessEditor’s ChoiceReview

Operative Procedures for Ultrasound Assessment of Extracranial Artery Disease: A Narrative Review by the Italian Society for Vascular Investigation (SIDV)

by Luca Costanzo, Giacomo Failla, Leonardo Aluigi, Tiziana Anna Baroncelli, Chiara Bua, Sergio De Marchi, Elia Diaco, Federico Di Paola, Francesco Lorenzo Di Pino, Ferdinando Mannello, Ombretta Martinelli, Chiara Mascoli, Anastasia Maria Pedi, Ivan Privitera, Enrico Rescigno, Antonio Trani, Pier Luigi Antignani and Marco Mangiafico

J. Clin. Med. 2025, 14(19), 7050; https://doi.org/10.3390/jcm14197050 - 6 Oct 2025

Viewed by 1137

Abstract

Background: Duplex ultrasonography (DUS) of the extracranial arteries is essential for the primary and secondary prevention of ischemic stroke and the diagnosis of other cerebrovascular pathologies. The aim of the Italian Society for Vascular Investigation (SIDV) is to provide a standardised approach [...] Read more.

Background: Duplex ultrasonography (DUS) of the extracranial arteries is essential for the primary and secondary prevention of ischemic stroke and the diagnosis of other cerebrovascular pathologies. The aim of the Italian Society for Vascular Investigation (SIDV) is to provide a standardised approach for the ultrasound evaluation of extracranial arterial disease. Methods: A multidisciplinary SIDV expert panel conducted a comprehensive literature search and performed a narrative review of the recent medical literature; the updated operative procedures were subsequently developed through a consensus-driven process that included dedicated meetings and national congress sessions for discussion and validation. Results: This document outlines a comprehensive approach to the ultrasound evaluation of extracranial arteries, detailing techniques such as Brightness Mode (B-mode), Colour Doppler, Power Doppler, contrast-enhanced ultrasound (CEUS), micro-vascular flow imaging (MVFI), and Three-Dimensional (3D) ultrasound. The text provides an in-depth discussion of clinical indications, technical protocols, plaque characterisation, stenosis quantification, and hemodynamic criteria. Emerging technologies are also examined for their potential to improve cerebrovascular risk stratification. Conclusions: The updated SIDV operative procedures for the ultrasound evaluation of extracranial cerebrovascular disease are intended to serve as a valuable reference for clinicians and vascular laboratories. Full article

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

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25 pages, 484 KB

Open AccessEditor’s ChoiceSystematic Review

Knowledge Gaps Regarding Alcohol Consumption During Pregnancy and Its Effect on the Fetus: A Systematic Review Focused on Women

by María Botella-López and María-Teresa Cortés-Tomás

J. Clin. Med. 2025, 14(19), 7047; https://doi.org/10.3390/jcm14197047 - 5 Oct 2025

Viewed by 1369

Abstract

Background/objectives: Alcohol use during pregnancy can result in adverse outcomes for the offspring, including Fetal Alcohol Spectrum Disorders (FASD). Psychosocial and contextual factors may influence gestational alcohol intake and women’s risk perception. This systematic review aimed to assess pregnant women’s and women of [...] Read more.

Background/objectives: Alcohol use during pregnancy can result in adverse outcomes for the offspring, including Fetal Alcohol Spectrum Disorders (FASD). Psychosocial and contextual factors may influence gestational alcohol intake and women’s risk perception. This systematic review aimed to assess pregnant women’s and women of childbearing age’s perceived risk of alcohol use during pregnancy and to evaluate their knowledge of its potential effects on children. Methods: Following the PRISMA guidelines, a systematic search was conducted in Web of Science, PubMed and PsycArticles databases for studies published up to May 2025. Eligible studies examined gestational alcohol use, risk perception, or knowledge of fetal consequences among pregnant women or women of reproductive age. Methodological quality was assessed with the Critical Appraisal of Qualitative Studies tool from the Centre for Evidence-Based Medicine (CEBM). Results: Twenty-nine studies were included. Reported prevalence of alcohol consumption during pregnancy varied considerably across settings. A substantial proportion of women perceived alcohol use during pregnancy as acceptable, often depending on quantity, frequency, type of beverage, or stage of gestation. Knowledge of FASDs was generally limited and frequently restricted to physical malformations. Misconceptions were more common among women with prior alcohol use. The findings highlight persistent gaps in risk perception and knowledge about FASDs. Conclusions: Prevention strategies should not be limited to pregnant women but should also target women of childbearing age, especially those with active drinking patterns, as well as their immediate sociocultural environment. Strengthening professional training, community-based interventions, and consistent public health messaging are essential to reduce gestational alcohol exposure. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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23 pages, 612 KB

Open AccessEditor’s ChoiceReview

The Role of Early and Delayed Surgery in Return to Sport After Anterior Shoulder Dislocation—A Scoping Review

by Martin Ingvardsen Vemmelund and Sten Rasmussen

J. Clin. Med. 2025, 14(19), 7045; https://doi.org/10.3390/jcm14197045 - 5 Oct 2025

Viewed by 858

Abstract

Background: Anterior shoulder dislocations are common in athletes, particularly in contact sports. Surgical stabilization reduces recurrence, but the optimal timing—early versus delayed—remains uncertain, especially for in-season athletes. Methods: A systematic search of PubMed, Embase, and Cochrane (2013–2023) yielded 945 articles; 15 [...] Read more.

Background: Anterior shoulder dislocations are common in athletes, particularly in contact sports. Surgical stabilization reduces recurrence, but the optimal timing—early versus delayed—remains uncertain, especially for in-season athletes. Methods: A systematic search of PubMed, Embase, and Cochrane (2013–2023) yielded 945 articles; 15 met the inclusion criteria. Data were charted on procedure type, outcomes, follow-up, patient group, and timing of surgery. Search terms, e.g., ‘shoulder’, ‘athlete’, ‘anterior’ and ‘shoulder dislocation’, were used in a broad search protocol casting a wide net to maximize the likelihood of capturing all available data. Results: Surgery was superior to conservative care in lowering recurrence and enabling return-to-play, with arthroscopic and combined procedures most effective in high-contact sports. Conservative management carried higher instability risk. Evidence directly comparing early versus delayed surgery was scarce, and therefore inconclusive. Conclusions: Surgical stabilization remains the treatment with better outcomes compared to conservative treatment for young athletes. Still, athletes opt to delay surgery until postseason, with the impact of delaying surgery being unclear. Further research is needed to evaluate early versus delayed surgery regarding recurrence, joint damage, and return to sport. Full article

(This article belongs to the Special Issue Targeted Diagnosis and Treatment of Shoulder and Elbow Disease: 2nd Edition)

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15 pages, 3938 KB

Open AccessEditor’s ChoiceSystematic Review

Effects of Bonded Rapid Palatal Expander on Vertical Dimension: A Systematic Review and Meta-Analysis

by Sarah Horne, Doyeon Sung, Hugo Cesar Campos, Shahd Habeb, Luca Sfogliano, Chun-Hsi Chung and Chenshuang Li

J. Clin. Med. 2025, 14(19), 7035; https://doi.org/10.3390/jcm14197035 - 4 Oct 2025

Viewed by 1303

Abstract

Objectives: The current study aimed to summarize the current evidence on vertical control provided by the bonded rapid palatal expander (BRPE) in pediatric patient populations within 6 months after expansion. Methods: Relevant studies were screened independently by two researchers from the eight databases [...] Read more.

Objectives: The current study aimed to summarize the current evidence on vertical control provided by the bonded rapid palatal expander (BRPE) in pediatric patient populations within 6 months after expansion. Methods: Relevant studies were screened independently by two researchers from the eight databases MEDLINE (PubMed), Web of Science, SCOPUS, Embase, Cochrane, LILACS (Latin American and Caribbean Health Sciences Literature), LIVIVO and Google Scholar, and supplemented by a manual search of the reference lists from studies selected for full-manuscript reading. Relevant data from lateral cephalograms taken pre- and post-expansion was extracted. A meta-analysis was performed with RStudio and a risk of bias assessment of the included articles was completed. Results: Ten relevant studies were included for data extraction, although most had a high risk of bias. The meta-analysis revealed that within 6-month retention after BRPE treatment, there were (1) slight increases in total (0.83 mm), upper (0.57 mm), and lower (0.70 mm) facial height; (2) minimum change in the palatal plane angulation (−0.01°); (3) minimum change in the occlusal angulation (−0.04°); and (4) minimal mandibular plane angulation changes with 0.01° increase in SN-GoGn angle, 0.71° increase in SN-MP angle, 0.17° increase in FMA, and 0.82° increase in PP-GoGn angle. Conclusions: Current evidence indicates that BRPEs may not control or reduce the vertical dimension significantly within 6 months after expansion. Further high-quality studies, particularly on hyperdivergent patients, are needed to clarify whether bonded expanders offer advantages over traditional banded expanders in management of the vertical dimension. Full article

(This article belongs to the Special Issue Pediatric Dentistry: Recent Advances, Current Issues and Future Challenges)

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47 pages, 617 KB

Open AccessEditor’s ChoiceReview

Smart Pregnancy: AI-Driven Approaches to Personalised Maternal and Foetal Health—A Scoping Review

by Vera Correia, Teresa Mascarenhas and Miguel Mascarenhas

J. Clin. Med. 2025, 14(19), 6974; https://doi.org/10.3390/jcm14196974 - 1 Oct 2025

Viewed by 1458

Abstract

Background/Objectives: The integration of artificial intelligence (AI) into obstetric care poses significant potential to enhance clinical decision-making and optimize maternal and neonatal outcomes. Traditional prediction methods in maternal-foetal medicine often rely on subjective clinical judgment and limited statistical models, which may not [...] Read more.

Background/Objectives: The integration of artificial intelligence (AI) into obstetric care poses significant potential to enhance clinical decision-making and optimize maternal and neonatal outcomes. Traditional prediction methods in maternal-foetal medicine often rely on subjective clinical judgment and limited statistical models, which may not fully capture complex patient data. By integrating computational innovation with mechanistic biology and rigorous clinical validation, AI can finally fulfil the promise of precision obstetrics by transforming pregnancy complications into a preventable, personalised continuum of care. This study aims to map the current landscape of AI applications across the continuous spectrum of maternal–foetal health, identify the types of models used, and compare clinical targets and performance, potential pitfalls, and strategies to translate innovation into clinical impact. Methods: A literature search of peer-reviewed studies that employ AI for prediction, diagnosis, or decision support in Obstetrics was conducted. AI algorithms were categorised by application area: foetal monitoring, prediction of preterm birth, prediction of pregnancy complications, and/or labour and delivery. Results: AI-driven models consistently demonstrate superior performance to traditional approaches. Nevertheless, their widespread clinical adoption is hindered by limited dataset diversity, “black-box” algorithms, and inconsistent reporting standards. Conclusions: AI holds transformative potential to improve maternal and neonatal outcomes through earlier diagnosis, personalised risk assessment, and automated monitoring. To fulfil this promise, the field must prioritize the creation of large, diverse, open-access datasets, mandate transparent, explainable model architectures, and establish robust ethical and regulatory frameworks. By addressing these challenges, AI can become an integral, equitable, and trustworthy component of Obstetric care worldwide. Full article

(This article belongs to the Special Issue AI in Maternal Fetal Medicine and Perinatal Management)

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19 pages, 800 KB

Open AccessEditor’s ChoiceReview

Artificial Intelligence in Anesthesia: Enhancing Precision, Safety, and Global Access Through Data-Driven Systems

by Rakshita Giri, Shaik Huma Firdhos and Thomas A. Vida

J. Clin. Med. 2025, 14(19), 6900; https://doi.org/10.3390/jcm14196900 - 29 Sep 2025

Viewed by 1895

Abstract

Artificial intelligence (AI) enhances anesthesiology by introducing adaptive systems that improve clinical precision, safety, and responsiveness. This review examines the integration of AI in anesthetic practice, with a focus on closed-loop systems that exemplify autonomous control. These platforms integrate continuous physiologic inputs, such [...] Read more.

Artificial intelligence (AI) enhances anesthesiology by introducing adaptive systems that improve clinical precision, safety, and responsiveness. This review examines the integration of AI in anesthetic practice, with a focus on closed-loop systems that exemplify autonomous control. These platforms integrate continuous physiologic inputs, such as BIS, EEG, heart rate, and blood pressure, to titrate anesthetic agents in real time, providing more consistent and responsive management than manual methods. Predictive algorithms reduce intraoperative hypotension by up to 40%, and systems such as McSleepy demonstrate greater accuracy in maintaining anesthetic depth and shortening recovery times. In critical care, AI supports sedation management, reduces clinician cognitive load, and standardizes care delivery during high-acuity procedures. The review also addresses the ethical, legal, and logistical challenges to widespread adoption of AI. Key concerns include algorithmic bias, explainability, and accountability for machine-generated decisions and disparities in access due to infrastructure demands. Regulatory frameworks, such as HIPAA and GDPR, are discussed in the context of securing patient data and ensuring its ethical deployment. Additionally, AI may play a transformative role in global health through remote anesthesia delivery and telemonitoring, helping address anesthesiologist shortages in resource-limited settings. Ultimately, AI-guided closed-loop systems do not replace clinicians; instead, they extend their capacity to deliver safe, responsive, and personalized anesthesia. These technologies signal a shift toward robotic anesthesia, where machine autonomy complements human oversight. Continued interdisciplinary development and rigorous clinical validation will determine how AI integrates into both operating rooms and intensive care units. Full article

(This article belongs to the Special Issue New Insights into Critical Care)

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23 pages, 2144 KB

Open AccessEditor’s ChoiceReview

GLP-1 Agonists in Cardiovascular Diseases: Mechanisms, Clinical Evidence, and Emerging Therapies

by Han-Mo Yang

J. Clin. Med. 2025, 14(19), 6758; https://doi.org/10.3390/jcm14196758 - 24 Sep 2025

Viewed by 2601

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists now serve as therapeutic agents for cardiovascular diseases (CVDs) beyond their original use for treating type 2 diabetes mellitus (T2DM). This review combines molecular mechanisms with clinical evidence to demonstrate how GLP-1 agonists help lower cardiovascular risk for [...] Read more.

Glucagon-like peptide-1 (GLP-1) receptor agonists now serve as therapeutic agents for cardiovascular diseases (CVDs) beyond their original use for treating type 2 diabetes mellitus (T2DM). This review combines molecular mechanisms with clinical evidence to demonstrate how GLP-1 agonists help lower cardiovascular risk for conditions, including atherosclerosis, heart failure, stroke, and vascular dementia. These agents produce multiple beneficial effects, which include anti-inflammatory action along with anti-atherogenic effects, endothelial-protective benefits, and cardioprotective actions to minimize major adverse cardiovascular events (MACEs). GLP-1 agonists achieved substantial reductions in myocardial infarction, stroke, cardiovascular mortality, and heart failure events according to major cardiovascular outcome trials (CVOTs). Recent research, notably the pivotal SELECT trial, has confirmed their suitability for non-diabetic subjects with obesity and established CVD. New drug delivery methods and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists demonstrate potent efficacy, with tirzepatide showing significant MACE reduction in its own CVOT. However, significant challenges related to high cost, long-term safety uncertainties, and implementation barriers remain, requiring a balanced perspective. The review presents both mechanistic data and clinical evidence to demonstrate how GLP-1 agonists function as vital cardiovascular medications and outlines future research directions to address critical evidence gaps and maximize their therapeutic effectiveness. Full article

(This article belongs to the Special Issue New Insights into Diabetes and Cardiovascular Diseases)

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19 pages, 2611 KB

Open AccessEditor’s ChoiceReview

Interventional Management of Acute Pancreatitis and Its Complications

by Muaaz Masood, Amar Vedamurthy, Rajesh Krishnamoorthi, Shayan Irani, Mehran Fotoohi and Richard Kozarek

J. Clin. Med. 2025, 14(18), 6683; https://doi.org/10.3390/jcm14186683 - 22 Sep 2025

Viewed by 2412

Abstract

Acute pancreatitis (AP) is the most common cause of gastrointestinal-related hospitalizations in the United States, with gallstone disease and alcohol as the leading etiologies. Management is determined by disease severity, classified as interstitial edematous pancreatitis or necrotizing pancreatitis, with severity further stratified based [...] Read more.

Acute pancreatitis (AP) is the most common cause of gastrointestinal-related hospitalizations in the United States, with gallstone disease and alcohol as the leading etiologies. Management is determined by disease severity, classified as interstitial edematous pancreatitis or necrotizing pancreatitis, with severity further stratified based on local complications and systemic organ dysfunction. Regardless of etiology, initial treatment involves aggressive intravenous fluid resuscitation with Lactated Ringer’s solution, pain and nausea control, early oral feeding in 24 to 48 h, and etiology-directed interventions when indicated. In gallstone pancreatitis, early endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy is indicated in the presence of concomitant cholangitis or persistent biliary obstruction, with subsequent laparoscopic cholecystectomy as standard of care for stone clearance. The role of interventional therapy in uncomplicated AP is limited in the acute phase, except for biliary decompression or enteral feeding support with nasojejunal tube placement. However, in severe AP with complications, interventional radiology (IR) and endoscopic approaches play a pivotal role. IR facilitates early percutaneous drainage of symptomatic, acute fluid collections and infected necrosis, particularly in non-endoscopically accessible retroperitoneal or dependent collections, improving outcomes with a step-up approach. IR-guided angiographic embolization is the preferred modality for hemorrhagic complications, including pseudoaneurysms. In the delayed phase, walled-off necrosis (WON) and pancreatic pseudocysts are managed with endoscopic ultrasound (EUS)-guided drainage, with direct endoscopic necrosectomy (DEN) reserved for infected necrosis. Dual-modality drainage (DMD), combining percutaneous and endoscopic drainage, is increasingly utilized in extensive or complex collections, reflecting a collaborative effort between gastroenterology and interventional radiology comparable to that which exists between IR and surgery in institutions that perform video assisted retroperitoneal debridement (VARD). Peripancreatic fluid collections may fistulize into adjacent structures, including the stomach, small intestine, or colon, requiring transpapillary stenting with or without additional closure of the gut leak with over-the-scope clips (OTSC) or suturing devices. Additionally, endoscopic management of pancreatic duct disruptions with transpapillary or transmural stenting plays a key role in cases of disconnected pancreatic duct syndrome (DPDS). Comparative outcomes across interventional techniques—including retroperitoneal, laparoscopic, open surgery, and endoscopic drainage—highlight a shift toward minimally invasive approaches, with decreased morbidity and reduced hospital stay. The integration of endoscopic and interventional radiology-guided techniques has transformed the management of AP complications and multidisciplinary collaboration is essential for optimal patient outcomes. Full article

(This article belongs to the Special Issue Interventional and Surgical Treatment of Acute and Chronic Pancreatitis)

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12 pages, 1214 KB

Open AccessEditor’s ChoiceArticle

The Reliability and Validity of a New Laryngeal Palpation Tool for Static and Dynamic Examination

by Isabelle Bargar, Melina Maria Ippers, Katrin Neumann, Philipp Mathmann and Ben Barsties v. Latoszek

J. Clin. Med. 2025, 14(17), 6309; https://doi.org/10.3390/jcm14176309 - 6 Sep 2025

Viewed by 782

Abstract

Background/Objectives: Voice disorders caused by laryngeal hypertension can impact volume, quality, pitch, resonance, flexibility, and stamina. The laryngeal palpation is a tactile-perceptual assessment, which is one of a few examination methods to evaluate laryngeal hypertension. Laryngeal palpation is a manual examination of [...] Read more.

Background/Objectives: Voice disorders caused by laryngeal hypertension can impact volume, quality, pitch, resonance, flexibility, and stamina. The laryngeal palpation is a tactile-perceptual assessment, which is one of a few examination methods to evaluate laryngeal hypertension. Laryngeal palpation is a manual examination of the extrinsic and paralaryngeal tissues of the larynx (e.g., lateral laryngeal mobility, thyrohyoid and cricothyroid spaces, vertical laryngeal position/mobility, and pain) through the examiner’s fingers. It can be performed during rest (static assessment) or during phonation (dynamic assessment) of the individual being evaluated. This study aimed to validate a novel laryngeal palpation tool with quantitative ordinal scores by assessing its reliability and diagnostic accuracy establishing preliminary clinical cut-off values, and examining its correlations with self-reported voice disorder symptoms. Methods: In a prospective, controlled validation study, 33 participants were selected to assess the validity and reliability of the novel diagnostic tool in a clinical sample and healthy controls. The clinical sample (n = 19) comprised individuals diagnosed with voice disorders, whereas the healthy control group (n = 14) included participants with no history or symptoms of voice pathology. The novel laryngeal palpation tool was employed by two independent examiners to assess both static and dynamic laryngeal function in all participants. In addition, each participant completed the following questionnaires: Voice Handicap Index (VHI-30) with the 30-item, Vocal Fatigue Index (VFI), and the Vocal Tract Discomfort Scale (VTD). Results: Static palpatory assessment of laryngeal tension demonstrated excellent discriminatory power between groups and tension levels (AROC = 0.979), along with high intra-rater (ICC = 0.966) and inter-rater reliability (ICC = 0.866). Significant correlations were revealed between the static palpation results and the VHI scores (r = 0.496; p < 0.01) and VFI (r = 0.514; p < 0.01). For the dynamic evaluation of the palpation tool, comparable results for the validity (AROC = 0.840) and reliability (inter-rater: ICC = 0.800, and intra-rater: ICC = 0.840) were revealed. However, no significant correlations were found between dynamic palpation and self-perceived questionnaires, although some were likely found with static palpation. The validity of the total score was found to be AROC = 0.992. Conclusions: The static and dynamic assessments using the novel laryngeal palpation tool demonstrated promising reliability and diagnostic accuracy, providing initial evidence to support its clinical utility. Further studies are needed to establish broader validation. Full article

(This article belongs to the Special Issue New Advances in the Management of Voice Disorders: 2nd Edition)

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27 pages, 1574 KB

Open AccessEditor’s ChoiceReview

A Comprehensive Review of Fluid Resuscitation Strategies in Traumatic Brain Injury

by Mairi Ziaka, Wolf Hautz and Aristomenis Exadaktylos

J. Clin. Med. 2025, 14(17), 6289; https://doi.org/10.3390/jcm14176289 - 5 Sep 2025

Viewed by 3326

Abstract

The current management of severe traumatic brain injury (TBI) focuses on maintaining cerebral perfusion pressure (CPP) to prevent or minimize secondary brain injury, limit cerebral edema, optimize oxygen delivery to the brain, and reduce primary neuronal damage by addressing contributing risk factors such [...] Read more.

The current management of severe traumatic brain injury (TBI) focuses on maintaining cerebral perfusion pressure (CPP) to prevent or minimize secondary brain injury, limit cerebral edema, optimize oxygen delivery to the brain, and reduce primary neuronal damage by addressing contributing risk factors such as hypotension and hypoxia. Hypotension and cardiac dysfunction are common in patients with severe TBI, often requiring treatment with intravenous fluids and vasopressors. The primary categories of resuscitation fluids include crystalloids, colloids (such as albumin), and blood products. Fluid osmolarity is a critical consideration in TBI patients, as hypotonic fluids, such as balanced crystalloids, may increase the risk of cerebral edema development and worsening. Hyperosmolar therapy is a common therapeutic approach in patients with intracranial hypertension; however, its use as a resuscitation fluid is not associated with benefits in patients with TBI and is not recommended. Given the contradictory results of trials on blood transfusion strategies in patients with TBI, the transfusion approach should be tailored to individual systemic and cerebral physiological parameters. The evaluation of recent randomized clinical trials will provide insight into whether a liberal or restrictive transfusion strategy is preferred for this patient population. Hemodynamic and multimodal neurological monitoring to assess cerebral oxygenation, autoregulation, and metabolism are essential tools for detecting early hemodynamic alterations and cerebral injury, guiding resuscitation management, and contributing to improved outcomes. Full article

(This article belongs to the Special Issue Traumatic Brain Injury: Emergency Management, Prevention of Secondary Injury, and Rehabilitation)

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15 pages, 497 KB

Open AccessEditor’s ChoiceArticle

Autonomic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Findings from the Multi-Site Clinical Assessment of ME/CFS (MCAM) Study in the USA

by Anindita Issa, Jin-Mann S. Lin, Yang Chen, Jacob Attell, Dana Brimmer, Jeanne Bertolli, Benjamin H. Natelson, Charles W. Lapp, Richard N. Podell, Andreas M. Kogelnik, Nancy G. Klimas, Daniel L. Peterson, Lucinda Bateman and Elizabeth R. Unger

J. Clin. Med. 2025, 14(17), 6269; https://doi.org/10.3390/jcm14176269 - 5 Sep 2025

Viewed by 6815

Abstract

Background/Objectives: Symptoms of autonomic dysfunction are common in infection-associated chronic conditions and illnesses (IACCIs), including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This study aimed to evaluate autonomic symptoms and their impact on ME/CFS illness severity. Methods: Data came from a multi-site study [...] Read more.

Background/Objectives: Symptoms of autonomic dysfunction are common in infection-associated chronic conditions and illnesses (IACCIs), including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This study aimed to evaluate autonomic symptoms and their impact on ME/CFS illness severity. Methods: Data came from a multi-site study conducted in seven ME/CFS specialty clinics during 2012–2020. Autonomic dysfunction was assessed using the Composite Autonomic Symptom Scale 31 (COMPASS-31), medical history, and a lean test originally described by the National Aeronautics and Space Administration (NASA). Illness severity was assessed using Patient-Reported Outcomes Measurement Information System measures, the 36-item short-form, as well as the CDC Symptom Inventory. This analysis included 442 participants who completed the baseline COMPASS-31 assessment, comprising 301 individuals with ME/CFS and 141 healthy controls (HC). Results: ME/CFS participants reported higher autonomic symptom burden than HC across three assessment tools (all p < 0.0001), including the COMPASS-31 total score (34.1 vs. 6.8) and medical history indicators [dizziness or vertigo (42.6% vs. 2.8%), cold extremities (38.6% vs. 5.7%), and orthostatic intolerance (OI, 33.9% vs. 0.7%)]. Among ME/CFS participants, 97% had at least one autonomic symptom. Those with symptoms in the OI, gastrointestinal, and pupillomotor domains had significantly higher illness severity than those without these symptoms. Conclusions: ME/CFS patients exhibit a substantial autonomic symptom burden that correlates with greater illness severity. Individualized care strategies targeting dysautonomia assessment and intervention may offer meaningful improvements in symptom management and quality of life for those with ME/CFS and similar chronic conditions. Full article

(This article belongs to the Special Issue POTS, ME/CFS and Long COVID: Recent Advances and Future Direction)

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14 pages, 1791 KB

Open AccessEditor’s ChoiceReview

Review of Current Management of Myocardial Infarction

by Trisha Saha and Hatem Soliman-Aboumarie

J. Clin. Med. 2025, 14(17), 6241; https://doi.org/10.3390/jcm14176241 - 4 Sep 2025

Viewed by 3450

Abstract

Myocardial infarction (MI), commonly known as a heart attack, remains a leading cause of morbidity and mortality worldwide. It arises from a sudden cessation of coronary blood flow, most often due to plaque rupture and subsequent thrombus formation. Over the years, significant advances [...] Read more.

Myocardial infarction (MI), commonly known as a heart attack, remains a leading cause of morbidity and mortality worldwide. It arises from a sudden cessation of coronary blood flow, most often due to plaque rupture and subsequent thrombus formation. Over the years, significant advances in the understanding, diagnosis, and treatment of MI have transformed patient outcomes. This review explores the current approaches to the management of myocardial infarction, highlighting evidence-based practices, recent advancements, and ongoing challenges in optimising care across various healthcare settings. Full article

(This article belongs to the Special Issue Diagnosis, Monitoring, and Treatment of Myocardial Infarction)

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19 pages, 554 KB

Open AccessEditor’s ChoiceReview

Carbon-Ion Radiotherapy for Hepatocellular Carcinoma: Current Status and Future Prospects: A Narrative Review

by Reina Sasaki-Tanaka, Hiroyuki Abe, Tomoaki Yoshida, Yusuke Watanabe, Naruhiro Kimura, Takeshi Yokoo, Akira Sakamaki, Hiroteru Kamimura, Kenya Kamimura, Tatsuo Kanda and Shuji Terai

J. Clin. Med. 2025, 14(17), 6107; https://doi.org/10.3390/jcm14176107 - 29 Aug 2025

Viewed by 1940

Abstract

Because hepatocellular carcinoma (HCC) is a radiosensitive cancer, radiation therapy has been used for the treatment of HCC; however, external beam therapies are currently not described in most of the guidelines for the treatment of HCC. External beam therapies include photon beam therapies [...] Read more.

Because hepatocellular carcinoma (HCC) is a radiosensitive cancer, radiation therapy has been used for the treatment of HCC; however, external beam therapies are currently not described in most of the guidelines for the treatment of HCC. External beam therapies include photon beam therapies and particle beam therapies, which are composed of X-rays or gamma rays and beams of carbon ions or protons, respectively. The focus of this narrative review is carbon-ion radiotherapy (C-ion RT). C-ion RT is well tolerated by elderly patients with HCC and/or sarcopenic patients. In general, a single HCC greater than 30 mm is a good indication for C-ion RT in patients with Child Grade A/B or ALBI Grade 1/2. The local control rates and overall survival rates at 5 years after C-ion RT for HCCs larger than 30 mm are excellent, with fewer adverse events, such as radiation-induced liver damage. Advanced HCC with portal vein tumor thrombus is also an indication for C-ion RT in certain selected patients. C-ion RT is a promising therapeutic option for patients with HCC. Full article

(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)

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19 pages, 1721 KB

Open AccessEditor’s ChoiceReview

Understanding Treatment Adherence in Chronic Diseases: Challenges, Consequences, and Strategies for Improvement

by Sheena Patel, Mingyi Huang and Sophia Miliara

J. Clin. Med. 2025, 14(17), 6034; https://doi.org/10.3390/jcm14176034 - 26 Aug 2025

Cited by 2 | Viewed by 5583

Abstract

Adherence to medications is a significant challenge in chronic disease management. Poor adherence can lead to adverse patient outcomes including disease progression, increased morbidity, reduced quality of life, higher hospitalization rates, increased medical costs, and mortality. Medical adherence is a complex issue, influenced [...] Read more.

Adherence to medications is a significant challenge in chronic disease management. Poor adherence can lead to adverse patient outcomes including disease progression, increased morbidity, reduced quality of life, higher hospitalization rates, increased medical costs, and mortality. Medical adherence is a complex issue, influenced by multiple factors, including patient-related, medication-related, and healthcare system-related barriers. This review explores reasons for both intentional non-adherence, such as patients underestimating the consequences of the disease, inadequate education or poor healthcare provider–patient communication, and unintentional non-adherence, including forgetfulness, pathophysiological barriers, socioeconomic barriers (including lifestyle and patient factors), or healthcare resource limitations. Multifaceted, patient-tailored interventions that could improve adherence are discussed, including promoting health education, enhancing healthcare provider–patient engagement, and exploring alternative medical solutions and emerging technological advances. No single approach fits all; this review aims to deepen the understanding of intentional and unintentional non-adherence and to inform targeted interventions to empower patients, foster trust, and improve adherence for those with chronic conditions. Full article

(This article belongs to the Section Pharmacology)

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16 pages, 6331 KB

Open AccessEditor’s ChoiceArticle

Microsurgical Bypass for Complex Intracranial Aneurysms in the Endovascular Era: Insights from a High-Volume Referral Center

by Yasmin Sadigh, Eva Joëlle Haasdijk, Ruben Dammers and Victor Volovici

J. Clin. Med. 2025, 14(17), 6027; https://doi.org/10.3390/jcm14176027 - 26 Aug 2025

Viewed by 1218

Abstract

Background/Objectives: Endovascular treatment has become the primary treatment for intracranial aneurysms, yet direct bypass surgery remains an option in selected cases where standard approaches fail. This study aims to evaluate the role, indications, and outcomes of bypass surgery for intracranial aneurysm management [...] Read more.

Background/Objectives: Endovascular treatment has become the primary treatment for intracranial aneurysms, yet direct bypass surgery remains an option in selected cases where standard approaches fail. This study aims to evaluate the role, indications, and outcomes of bypass surgery for intracranial aneurysm management in the current endovascular era. Methods: A single-center retrospective analysis was conducted on consecutive cases who underwent direct intracranial bypass surgery for intracranial aneurysms between 2015 and 2024. Data on demographics, aneurysm characteristics, indications, bypass type, patency, and clinical outcomes (using the modified Rankin Scale) were collected. Results: Of the 101 bypasses performed between 2015 and 2025, 25 were used for complex aneurysm cases. Intracranial bypass was necessary in as many as 5% of all microsurgical aneurysm repairs in 2023 and 10% in 2024. Bypass surgery was indicated in young patients with complex aneurysms not amenable to endovascular therapy (45%) and in 20% of the cases for recanalized aneurysms after previous endovascular repair. Intraoperative and postoperative bypass patency was confirmed for all patients except one case due to ongoing malignant brain swelling after an ongoing infarction. At follow-up, 87% of patients, with both ruptured and unruptured aneurysms, had a good outcome (mRS ≤ 2), and all patients had a patent bypass. Permanent morbidity was observed in 5% and procedure-related mortality in 0%. Conclusions: While bypass surgery constitutes a minority of intracranial aneurysm treatment by volume, its role in intracranial aneurysm repair is crucial and relevant in response to the evolving complexity of aneurysms. Further refinement of techniques is necessary. Full article

(This article belongs to the Special Issue Recent Advances in Intracranial Aneurysm Treatment)

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11 pages, 1500 KB

Open AccessEditor’s ChoiceArticle

Photon-Counting CT Enhances Diagnostic Accuracy in Stable Coronary Artery Disease: A Comparative Study with Conventional CT

by Mitsutaka Nakashima, Toru Miyoshi, Shohei Hara, Ryosuke Miyagi, Takahiro Nishihara, Takashi Miki, Kazuhiro Osawa and Shinsuke Yuasa

J. Clin. Med. 2025, 14(17), 6049; https://doi.org/10.3390/jcm14176049 - 26 Aug 2025

Viewed by 1433

Abstract

Background/Objectives: Coronary CT angiography (CCTA) is a cornerstone in evaluating stable coronary artery disease (CAD), but conventional energy-integrating detector CT (EID-CT) has limitations, including calcium blooming and limited spatial resolution. Photon-counting detector CT (PCD-CT) may overcome these drawbacks through enhanced spatial resolution and [...] Read more.

Background/Objectives: Coronary CT angiography (CCTA) is a cornerstone in evaluating stable coronary artery disease (CAD), but conventional energy-integrating detector CT (EID-CT) has limitations, including calcium blooming and limited spatial resolution. Photon-counting detector CT (PCD-CT) may overcome these drawbacks through enhanced spatial resolution and improved tissue characterization. Methods: In this retrospective, propensity score–matched study, we compared CCTA findings from 820 patients (410 per group) who underwent either EID-CT or PCD-CT for suspected stable CAD. Primary outcomes included stenosis severity, high-risk plaque features, and downstream invasive coronary angiography (ICA) referral and yield. Results: The matched cohorts were balanced in demographics and cardiovascular risk factors (mean age 67 years, 63% male). PCD-CT showed a favorable shift in stenosis severity distribution (p = 0.03). High-risk plaques were detected less frequently with PCD-CT (22.7% vs. 30.5%, p = 0.01). Median coronary calcium scores did not differ (p = 0.60). Among patients referred for ICA, those initially evaluated with PCD-CT were more likely to undergo revascularization (62.5% vs. 44.1%), and fewer underwent potentially unnecessary ICA without revascularization (3.7% vs. 8.0%, p = 0.001). The specificity in diagnosing significant stenosis requiring revascularization was 0.74 with EID-CT and 0.81 with PCD-CT (p = 0.04). Conclusions: PCD-CT improved diagnostic specificity for CAD, reducing unnecessary ICA referrals while maintaining detection of clinically significant disease. This advanced CT technology holds promise for more accurate, efficient, and patient-centered CAD evaluation. Full article

(This article belongs to the Section Cardiovascular Medicine)

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21 pages, 1238 KB

Open AccessEditor’s ChoiceReview

Current Physical Therapy for Skin Scar Management: A Scoping Review

by Sara Di Serio, Matteo Congiu, Silvia Minnucci, Valentina Scalise and Firas Mourad

J. Clin. Med. 2025, 14(17), 5920; https://doi.org/10.3390/jcm14175920 - 22 Aug 2025

Cited by 1 | Viewed by 4418

Abstract

Background: Scar impairments impose a significant economic burden and negatively impact an individual’s well-being and quality of life. However, there is a lack of standardization in physical therapy interventions for scar management. Objective: This study aimed to provide a comprehensive overview of studies [...] Read more.

Background: Scar impairments impose a significant economic burden and negatively impact an individual’s well-being and quality of life. However, there is a lack of standardization in physical therapy interventions for scar management. Objective: This study aimed to provide a comprehensive overview of studies addressing non-invasive physical therapy interventions for scar management. Methods: This scoping review was conducted following the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis. Six databases were searched, and additional studies were retrieved through gray literature and the reference lists of included articles. All studies considering non-invasive physical therapy interventions for scar management were included. No restrictions were applied regarding time, context or publication type. Results were illustrated using descriptive statistics and summarized in an infographic. Results: Out of 13,419 initial records, 92 studies met the inclusion criteria. Most articles were narrative reviews (n = 41) followed by randomized controlled trials (RCT) (n = 18). The most reported interventions were pressure therapy (n = 41), physical therapy modalities (n = 37), silicone-based products (n = 29) and massage (n = 20). Conclusions: Scar management involves a wide range of physical interventions. However, research has predominantly focused on adults, particularly those with burns, with limited attention given to pediatric or non-adult populations. Furthermore, there is significant variability in the application parameters, scar localization and size. Examining the included study designs, most of the research presented reduced sample sizes and lacked control groups. Notably, almost half of the studies were based on expert opinions. Future high-quality research is needed to identify evidence-based interventions for the clinical management of scars. Full article

(This article belongs to the Special Issue Skin Disease and Inflammation)

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12 pages, 1369 KB

Open AccessEditor’s ChoiceArticle

Sex Differences in 24 H Blood Pressure in Night-Shift Workers

by Barbara Toffoli, Silvia Berti, Ilaria Pitteri, Matilde Contessa, Federica Tonon, Rebecca Defendi, Andrea Grillo, Bruno Fabris and Stella Bernardi

J. Clin. Med. 2025, 14(16), 5728; https://doi.org/10.3390/jcm14165728 - 13 Aug 2025

Viewed by 22814

Abstract

Background/Objectives: Gender Medicine addresses how sex- and gender-based differences influence people’s health. Blood pressure (BP), which is the leading global risk factor for cardiovascular disease, shows a sexual dimorphism. This is seen also in case of shift work, as shift work is [...] Read more.

Background/Objectives: Gender Medicine addresses how sex- and gender-based differences influence people’s health. Blood pressure (BP), which is the leading global risk factor for cardiovascular disease, shows a sexual dimorphism. This is seen also in case of shift work, as shift work is associated with hypertension in the male sex. It is not clear if this may be extended also to night-shift work, as data for this are limited. Based on this background, the aim of this study was to evaluate whether there were sex differences in the 24 h BP profile during a day with a day shift and a day with a night shift. Methods: This study is a post hoc analysis of a previous study where we evaluated ambulatory blood pressure monitoring data for two days, in a day with a day shift (and night of rest) and in a day with a night shift. Results: Overall, 25 subjects (physicians) were included in the analysis, of whom 10 were (40%) males and 15 were (60%) females. No differences were recorded in terms of age, years of work, number of steps, admissions, and calls during the recordings between the two sexes. Subjects worked on average 1.2 night per month, indicating that this population had a low exposure to night-shift work. BP patterns did not differ between sexes, but BP levels were always higher in males than females. Nevertheless, only females showed a significant increase of SBP during the night shift as compared to the night of rest. Both males and females showed a significant reduction in BP dipping during the night shift, but only in females, the significant reduction in BP dipping was maintained after the night-shift work. Interestingly, BMAL1 gene expression, which is a gene of the circadian rhythm, increased significantly after the night shift only in females, suggesting that females display an earlier acrophase than males after night-shift work, which may be associated with tolerance to shiftwork. Conclusions: Our data are consistent with the concept that blood pressure display several sex/gender differences. Males had higher BP values, but females showed signs of lower tolerance to shift work. This might be due to sex differences in the circadian rhythm regulation, which, in turns, regulate physiological functions, such as blood pressure. Full article

(This article belongs to the Special Issue Hypertension in Adults: Current Updates on Diagnosis, Treatment and Management)

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22 pages, 2705 KB

Open AccessEditor’s ChoiceReview

Autoantibodies in Systemic Lupus Erythematosus: Diagnostic and Pathogenic Insights

by Eleni Pagkopoulou, Charalampos Loutradis, Maria Papaioannou, Maria Daoudaki, Maria Stangou and Theodoros Dimitroulas

J. Clin. Med. 2025, 14(16), 5714; https://doi.org/10.3390/jcm14165714 - 12 Aug 2025

Cited by 1 | Viewed by 5950

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread immune dysregulation and the production of autoantibodies targeting nuclear, cytoplasmic, and cell surface antigens. These autoantibodies are central to disease pathogenesis, contribute to immune complex formation and organ damage, and serve [...] Read more.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread immune dysregulation and the production of autoantibodies targeting nuclear, cytoplasmic, and cell surface antigens. These autoantibodies are central to disease pathogenesis, contribute to immune complex formation and organ damage, and serve as essential diagnostic and prognostic markers. Their detection supports disease classification, guides clinical decision-making, and offers insight into disease activity and therapeutic response. Traditional markers such as anti-nuclear antibodies (ANA), anti-dsDNA, and anti-Sm antibodies remain diagnostic cornerstones, but growing attention is given to anti-C1q, anti-nucleosome antibodies (ANuA), anti-ribosomal P, antiphospholipid, and anti-cytokine antibodies due to their associations with specific disease phenotypes and activity. These markers may reflect disease activity, specific organ involvement, or predict flares. The mechanisms underlying their persistence include B cell tolerance failure and long-lived plasma cell activity. The aim of this review is to summarize current knowledge on the major autoantibodies in SLE, appraise available detection methods, highlight their clinical utility and limitations and present evidence on the association between antibodies and disease phenotypes. Full article

(This article belongs to the Section Immunology & Rheumatology)

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16 pages, 932 KB

Open AccessEditor’s ChoiceArticle

Treatment Outcomes in Patients Receiving Carbon-Ion Radiotherapy Versus Hepatectomy for Hepatocellular Carcinoma (≥4 cm): A Retrospective Study in Japan

by Keita Maki, Hiroaki Haga, Tomohiro Katsumi, Kyoko Hoshikawa, Takashi Kaneko, Ryosuke Takahashi, Shuichiro Sugawara, Masashi Koto, Fuyuhiko Motoi and Yoshiyuki Ueno

J. Clin. Med. 2025, 14(16), 5678; https://doi.org/10.3390/jcm14165678 - 11 Aug 2025

Viewed by 934

Abstract

Background/Objectives: Carbon-ion radiotherapy (CIRT) is now covered by Japan’s health insurance for patients with hepatocellular carcinoma (HCC) tumors measuring ≥4 cm. However, no studies have compared intrahepatic control between CIRT and hepatectomy in these patients. Methods: We retrospectively analyzed intrahepatic control [...] Read more.

Background/Objectives: Carbon-ion radiotherapy (CIRT) is now covered by Japan’s health insurance for patients with hepatocellular carcinoma (HCC) tumors measuring ≥4 cm. However, no studies have compared intrahepatic control between CIRT and hepatectomy in these patients. Methods: We retrospectively analyzed intrahepatic control in 51 patients with HCC tumors ≥4 cm. Among them, 38 underwent CIRT (60 Gy in four fractions), while 13 underwent systematic hepatectomy. Intrahepatic recurrence was classified as local or intrahepatic distant. We evaluated local, distant, and total intrahepatic control rates at 1 and 2 years. Results: In the CIRT group, the local control rates at 1 and 2 years were 81.5% and 76.3%, whereas the intrahepatic distant control rates were 68.5% and 63.2% (p = 0.0495), respectively. Among patients aged <80 years, the 2-year intrahepatic control rate did not significantly differ between CIRT and hepatectomy. However, it was significantly lower in patients aged ≥80 years treated with CIRT than in those aged <80 years (73.7% vs. 42.1%, p = 0.0100), with similar trends in local (92.3% vs. 63.2%, p = 0.0381) and distant control (78.9% vs. 47.3%, p = 0.0259). Conclusions: CIRT may be as effective as hepatectomy for HCC tumors ≥4 cm in patients aged <80 years, but its efficacy declines in older patients, warranting age-tailored strategies. Full article

(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)

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23 pages, 748 KB

Open AccessEditor’s ChoiceReview

Genetic Therapies for Retinitis Pigmentosa: Current Breakthroughs and Future Directions

by Zofia Pniakowska, Natasza Dzieża, Natalia Kustosik, Aleksandra Przybylak and Piotr Jurowski

J. Clin. Med. 2025, 14(16), 5661; https://doi.org/10.3390/jcm14165661 - 11 Aug 2025

Cited by 1 | Viewed by 5446

Abstract

Retinitis pigmentosa is a group of inherited retinal dystrophies characterized by progressive photoreceptor cell loss leading to irreversible vision loss. Affecting approximately 1 in 4000 individuals worldwide, retinitis pigmentosa exhibits significant genetic heterogeneity, with mutations in genes such as RHO, PRPF31, [...] Read more.

Retinitis pigmentosa is a group of inherited retinal dystrophies characterized by progressive photoreceptor cell loss leading to irreversible vision loss. Affecting approximately 1 in 4000 individuals worldwide, retinitis pigmentosa exhibits significant genetic heterogeneity, with mutations in genes such as RHO, PRPF31, RPE65, USH2A, and NR2E3, which contribute to its diverse clinical presentation. This review outlines the genetic basis of retinitis pigmentosa and explores cutting-edge gene-based therapeutic strategies. Luxturna (voretigene neparvovec-rzyl), the first FDA-approved gene therapy targeting RPE65 mutations, represents a milestone in precision ophthalmology, while OCU400 is a gene-independent therapy that uses a modified NR2E3 construct to modulate retinal homeostasis across different RP genotypes. Additionally, CRISPR–Cas genome-editing technologies offer future potential for the personalized correction of specific mutations, though concerns about off-target effects and delivery challenges remain. The article also highlights MCO-010, a novel optogenetic therapy that bypasses defective phototransduction pathways, showing promise for patients regardless of their genetic profile. Moreover, QR-1123, a mutation-specific antisense oligonucleotide targeting the P23H variant in the RHO gene, is under clinical investigation for autosomal dominant RP and has shown encouraging preclinical results in reducing toxic protein accumulation and preserving photoreceptors. SPVN06, another promising candidate, is a mutation-agnostic gene therapy delivering RdCVF and RdCVFL via AAV to support cone viability and delay degeneration, currently being evaluated in a multicenter Phase I/II trial for patients with various rod–cone dystrophies. Collectively, these advances illustrate the transition from symptom management toward targeted, mutation-specific therapies, marking a major advancement in the treatment of RP and inherited retinal diseases. Full article

(This article belongs to the Special Issue Retinal Diseases: Recent Advances in Diagnosis and Treatment)

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33 pages, 2688 KB

Open AccessEditor’s ChoiceArticle

Defining the Chronic Complexities of hEDS and HSD: A Global Survey of Diagnostic Challenges, Life-Long Comorbidities, and Unmet Needs

by Victoria Daylor, Molly Griggs, Amy Weintraub, Rebecca Byrd, Taylor Petrucci, Matthew Huff, Kathryn Byerly, Roman Fenner, Sydney Severance, Charlotte Griggs, Amol Sharma, Paldeep Atwal, Steven A. Kautz, Steven Shapiro, Kimberly Youkhana, Mark Lavallee, Allison Wilkerson, Michelle Nichols, Alan Snyder, Josef K. Eichinger, Sunil Patel, Anne Maitland, Cortney Gensemer and Russell A. Norris Show full author list Hide full author list

J. Clin. Med. 2025, 14(16), 5636; https://doi.org/10.3390/jcm14165636 - 9 Aug 2025

Cited by 1 | Viewed by 29467

Abstract

Background: Hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSDs) are prevalent, complex conditions marked by chronic pain, joint instability, and multisystem involvement. Despite affecting an estimated 1 in 500 individuals, these conditions remain poorly understood and inconsistently diagnosed. This study aimed to [...] Read more.

Background: Hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSDs) are prevalent, complex conditions marked by chronic pain, joint instability, and multisystem involvement. Despite affecting an estimated 1 in 500 individuals, these conditions remain poorly understood and inconsistently diagnosed. This study aimed to define their clinical burden through a large-scale, international survey. Methods: A cross-sectional, anonymous survey was distributed globally from September 2023 to March 2024. Of 9258 responses, 3906 met inclusion criteria (hEDS: n = 3360; HSD: n = 546). The 418-item questionnaire assessed symptoms, comorbidities, healthcare utilization, and quality of life. The 95% confidence intervals (CIs) were calculated for comparison. Results: Participants with hEDS reported a mean of 24 comorbid conditions and an average diagnostic delay of 22.1 years. Common diagnoses included gastrointestinal disorders (84.3% [95% CI: 98.3–99.2%]), dysautonomia (71.4% [95% CI: 69.9–72.9%]), and chronic pain (98.9% [95% CI: 98.3–99.2%]). In contrast, HSD respondents reported a mean of 17 comorbidities, a 17.5-year time to diagnosis, and lower rates of key complications. Triggering events, such as puberty and infections were commonly reported preceding hEDS or HSD symptom onset. Comparison to the All of Us dataset revealed significantly elevated prevalence ratios of neurological, immune, and autonomic diagnoses. Conclusions: This global survey highlights the extensive multisystemic burden and diagnostic delays faced by individuals with hEDS and HSDs. The high prevalence of immune, neurological, gastrointestinal, and autonomic dysfunctions challenges the notion of these conditions as isolated connective tissue disorders. These findings highlight the need for updated diagnostic frameworks and mechanistic studies that explore multifactorial etiologies beyond the connective tissue paradigm. Full article

(This article belongs to the Topic Diagnosis, Management, and Prognostic Assessment of Chronic Disease)

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19 pages, 487 KB

Open AccessEditor’s ChoiceReview

Recent Trends in the Management of Varicocele

by Tamás Takács, Anett Szabó and Zsolt Kopa

J. Clin. Med. 2025, 14(15), 5445; https://doi.org/10.3390/jcm14155445 - 2 Aug 2025

Viewed by 6358

Abstract

Varicocele is a common, potentially correctable condition associated with impaired male fertility. Despite being frequently encountered in clinical andrology, its pathophysiological mechanisms, diagnostic criteria, and therapeutic approaches remain areas of active investigation and debate. The authors conducted a comprehensive literature search, using the [...] Read more.

Varicocele is a common, potentially correctable condition associated with impaired male fertility. Despite being frequently encountered in clinical andrology, its pathophysiological mechanisms, diagnostic criteria, and therapeutic approaches remain areas of active investigation and debate. The authors conducted a comprehensive literature search, using the PubMed database, covering clinical studies, systematic reviews, meta-analyses, and current international guidelines from the past ten years. Emphasis was placed on studies investigating novel diagnostic modalities, therapeutic innovations, and prognostic markers. Emerging evidence supports the multifactorial pathophysiology of varicocele, involving oxidative stress, hypoxia, inflammatory pathways, and potential genetic predisposition. Biomarkers, including microRNAs, antisperm antibodies, and sperm DNA fragmentation, offer diagnostic and prognostic utility, though their routine clinical implementation requires further validation. Advances in imaging, such as shear wave elastography, may improve diagnostic accuracy. While microsurgical subinguinal varicocelectomy remains the gold standard, technological refinements and non-surgical alternatives are being explored. Indications for treatment have expanded to include selected cases of non-obstructive azoospermia, hypogonadism, and optimization for assisted reproduction, though high-level evidence is limited. Full article

(This article belongs to the Special Issue Male Infertility Update: Current Knowledge on Etiology, Comorbidities, Diagnosis and Treatment: Clinical Topics)

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12 pages, 445 KB

Open AccessEditor’s ChoiceArticle

The Effect of Phoniatric and Logopedic Rehabilitation on the Voice of Patients with Puberphonia

by Lidia Nawrocka, Agnieszka Garstecka and Anna Sinkiewicz

J. Clin. Med. 2025, 14(15), 5350; https://doi.org/10.3390/jcm14155350 - 29 Jul 2025

Viewed by 883

Abstract

Background/Objective: Puberphonia is a voice disorder characterized by the persistence of a high-pitched voice in sexually mature males. In phoniatrics and speech-language pathology, it is also known as post-mutational voice instability, mutational falsetto, persistent fistulous voice, or functional falsetto. The absence of an [...] Read more.

Background/Objective: Puberphonia is a voice disorder characterized by the persistence of a high-pitched voice in sexually mature males. In phoniatrics and speech-language pathology, it is also known as post-mutational voice instability, mutational falsetto, persistent fistulous voice, or functional falsetto. The absence of an age-appropriate vocal pitch may adversely affect psychological well-being and hinder personal, social, and occupational functioning. The aim of this study was to evaluate of the impact of phoniatric and logopedic rehabilitation on voice quality in patients with puberphonia. Methods: The study included 18 male patients, aged 16 to 34 years, rehabilitated for voice mutation disorders. Phoniatric and logopedic rehabilitation included voice therapy tailored to each subject. A logopedist led exercises aimed at lowering and stabilizing the pitch of the voice and improving its quality. A phoniatrician supervised the therapy, monitoring the condition of the vocal apparatus and providing additional diagnostic and therapeutic recommendations as needed. The duration and intensity of the therapy were adjusted for each patient. Before and after voice rehabilitation, the subjects completed the following questionnaires: the Voice Handicap Index (VHI), the Vocal Tract Discomfort (VTD) scale, and the Voice-Related Quality of Life (V-RQOL). They also underwent an acoustic voice analysis. Results: Statistical analysis of the VHI, VTD, and V-RQOL scores, as well as the voice’s acoustic parameters, showed statistically significant differences before and after rehabilitation (p < 0.005). Conclusions: Phoniatric and logopedic rehabilitation is an effective method of reducing and maintaining a stable, euphonic male voice in patients with functional puberphonia. Effective voice therapy positively impacts selected aspects of psychosocial functioning reported by patients, improves voice-related quality of life, and reduces physical discomfort in the vocal tract. Full article

(This article belongs to the Section Otolaryngology)

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24 pages, 1654 KB

Open AccessEditor’s ChoiceReview

Acute Respiratory Distress Syndrome: Pathophysiological Insights, Subphenotypes, and Clinical Implications—A Comprehensive Review

by Mairi Ziaka and Aristomenis Exadaktylos

J. Clin. Med. 2025, 14(15), 5184; https://doi.org/10.3390/jcm14155184 - 22 Jul 2025

Cited by 2 | Viewed by 11130

Abstract

Increased epithelial and endothelial permeability, along with dysregulated inflammatory responses, are key aspects of acute respiratory distress syndrome (ARDS) pathophysiology, which not only impact the lungs but also contribute to detrimental organ crosstalk with distant organs, ultimately leading to multiple organ dysfunction syndrome [...] Read more.

Increased epithelial and endothelial permeability, along with dysregulated inflammatory responses, are key aspects of acute respiratory distress syndrome (ARDS) pathophysiology, which not only impact the lungs but also contribute to detrimental organ crosstalk with distant organs, ultimately leading to multiple organ dysfunction syndrome (MODS)—the primary cause of morbidity and mortality in patients with lung injury (LI) and ARDS. It is predominantly manifested by hypoxemic respiratory failure and bilateral pulmonary infiltrates, which cannot be fully attributed to cardiac failure or hypervolemia, but rather to alveolo-capillary barrier dysfunction, dysregulated systemic and pulmonary inflammation, immune system abnormalities, and mechanical stimuli-related responses. However, these pathological features are not uniform among patients with ARDS, as distinct subphenotypes with unique biological, clinical, physiological, and radiographic characteristics have been increasingly recognized in recent decades. The severity of ARDS, clinical outcomes, mortality, and efficacy of applied therapeutic measures appear significant depending on the respective phenotype. Acknowledging the heterogeneity of ARDS and defining distinct subphenotypes could significantly modify therapeutic strategies, enabling more precise and targeted treatments. To address these issues, a comprehensive literature search was conducted in PubMed using predefined keywords related to ARDS pathophysiology, subphenotypes, and personalized therapeutic approaches. Optimizing the identification and characterization of discrete ARDS subphenotypes—based on clinical, biological, physiological, and radiographic criteria—will deepen our understanding of ARDS pathophysiology, promote targeted recruitment in prospective clinical studies to define patient clusters with heterogeneous therapeutic responses, and support the shift toward individualized treatment strategies. Full article

(This article belongs to the Special Issue Ventilation in Critical Care Medicine: 2nd Edition)

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19 pages, 842 KB

Open AccessEditor’s ChoiceReview

The Role of NLRP3 Inflammasome in Type 2 Diabetes Mellitus and Its Macrovascular Complications

by Konstantinos Karamitsos, Evangelos Oikonomou, Panagiotis Theofilis, Ignatios Ikonomidis, Eva Kassi, Vaia Lambadiari, Elias Gialafos, Aikaterini Tsatsaragkou, Vasiliki-Chara Mystakidi, Konstantinos Zisimos, Kyriakos Dimitriadis, Dimitris Tousoulis and Gerasimos Siasos

J. Clin. Med. 2025, 14(13), 4606; https://doi.org/10.3390/jcm14134606 - 29 Jun 2025

Cited by 6 | Viewed by 5098

Abstract

Diabetes Mellitus (DM) is among the most common non-infectious causes of death globally, with Type 2 DM (T2DM) representing the majority of cases. T2DM is primarily characterized by insulin resistance, leading to hyperglycemia and compensatory hyperinsulinemia. Rapid changes in lifestyle, technological advancement, and [...] Read more.

Diabetes Mellitus (DM) is among the most common non-infectious causes of death globally, with Type 2 DM (T2DM) representing the majority of cases. T2DM is primarily characterized by insulin resistance, leading to hyperglycemia and compensatory hyperinsulinemia. Rapid changes in lifestyle, technological advancement, and societal evolution have fueled a global rise in T2DM, making it a major public health concern. The condition is associated with numerous complications—both macrovascular and microvascular—including coronary artery disease, heart failure, chronic kidney disease, and diabetic retinopathy, all of which contribute to increased morbidity and early mortality. Chronic tissue inflammation is now recognized as a key factor in the development of T2DM, with elevated inflammatory markers serving as predictors of the disease. In particular, the NLRP3 inflammasome complex has emerged as a central player in this inflammatory process. NLRP3 acts as an intracellular sensor for danger signals and tissue injury, triggering inflammatory responses and contributing to endothelial dysfunction and T2DM pathogenesis. Its role in linking metabolic stress to inflammation has positioned it as a promising therapeutic target. This review focuses on the mechanisms underlying NLRP3 inflammasome activation and its role in T2DM and related vascular complications. Additionally, it highlights emerging therapies that target NLRP3, offering new potential strategies for the prevention and treatment of T2DM. Full article

(This article belongs to the Section Endocrinology & Metabolism)

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24 pages, 7668 KB

Open AccessEditor’s ChoiceReview

Diagnosis and Diagnostic Challenges of Secondary Mitral Regurgitation in the Era of Transcatheter Edge-to-Edge Repair of the Mitral Valve

by Yusef B. Saeed, Kyra Deep, Andreas Hagendorff and Bhupendar Tayal

J. Clin. Med. 2025, 14(13), 4518; https://doi.org/10.3390/jcm14134518 - 26 Jun 2025

Viewed by 6902

Abstract

Secondary mitral regurgitation (sMR) is commonly understood to be secondary to heart failure (HF), left ventricular (LV) dilation, and altered coaptation of the mitral annulus. Three forms of sMR exist: non-ischemic sMR, ischemic sMR, and atrial functional sMR. In the past, there have [...] Read more.

Secondary mitral regurgitation (sMR) is commonly understood to be secondary to heart failure (HF), left ventricular (LV) dilation, and altered coaptation of the mitral annulus. Three forms of sMR exist: non-ischemic sMR, ischemic sMR, and atrial functional sMR. In the past, there have been limited treatment options for this condition besides medication. Recently, the management of sMR has been revolutionized by the recent advances in percutaneous transcatheter edge-to-edge repair of the mitral valve (m-TEER). However, the major trials investigating this technology have shown that appropriate patient selection is of critical importance to achieve benefit. As such, there is a renewed interest in the accurate diagnosis of sMR. Herein, we review the etiology, management, and diagnosis of sMR in the era m-TEER. Full article

(This article belongs to the Special Issue Recent Developments in Mitral Valve Repair)

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28 pages, 1969 KB

Open AccessEditor’s ChoiceReview

Clinical Management of Cerebral Amyloid Angiopathy

by Aikaterini Theodorou, Stella Fanouraki, Eleni Bakola, Georgia Papagiannopoulou, Lina Palaiodimou, Maria Chondrogianni, Maria-Ioanna Stefanou, Lampis Stavrinou, Athanasia Athanasaki, Klearchos Psychogios, Odysseas Kargiotis, Apostolos Safouris, Georgios Velonakis, Georgios P. Paraskevas and Georgios Tsivgoulis

J. Clin. Med. 2025, 14(12), 4259; https://doi.org/10.3390/jcm14124259 - 15 Jun 2025

Cited by 2 | Viewed by 9941

Abstract

Background: Cerebral amyloid angiopathy (CAA) represents a progressive cerebrovascular disorder, characterized by aberrant accumulation of beta-amyloid isoforms in cortical and leptomeningeal vessel walls of cerebrum and cerebellum. Methods: We sought to investigate the clinical manifestations, current different diagnostic tools, various therapeutic strategies and [...] Read more.

Background: Cerebral amyloid angiopathy (CAA) represents a progressive cerebrovascular disorder, characterized by aberrant accumulation of beta-amyloid isoforms in cortical and leptomeningeal vessel walls of cerebrum and cerebellum. Methods: We sought to investigate the clinical manifestations, current different diagnostic tools, various therapeutic strategies and most uncommon subtypes of the disease. Results: The vast majority of CAA remains sporadic, with increasing prevalence with age and very frequent coexistence with Alzheimer’s disease. Clinically, CAA can present with spontaneous lobar intracerebral hemorrhage, transient focal neurologic episodes attributed to convexity subarachnoid hemorrhage or cortical superficial siderosis, and progressive cognitive decline leading to dementia. Inflammatory CAA subtype should be recognized early and treated promptly so that better functional outcomes may be achieved. Moreover, genetic and iatrogenic CAA forms are rare, yet increasingly recognized during the last years. Therapeutic management remains challenging for clinicians, especially when markers indicative of higher bleeding risk are present. A targeted therapy does not currently exist. However, various clinical trials are in progress, focusing on offering new promising insights into the disease treatment. Conclusions: This review aims to deepen our understanding of CAA diagnosis and therapeutic approach but also summarizes current evidence on the most uncommon subtypes of this cerebral small-vessel disease. Full article

(This article belongs to the Section Clinical Neurology)

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17 pages, 3650 KB

Open AccessEditor’s ChoiceSystematic Review

Catheter-Based Therapies in Acute Pulmonary Embolism—Mortality and Safety Outcomes: A Systematic Review and Meta-Analysis

by Panagiotis Zoumpourlis, Shaunak Mangeshkar, Kuan-Yu Chi, Dimitrios Varrias, Michail Spanos, Muhammad Fahimuddin, Matthew D. Langston, Usman A. Khan, Michael J. Grushko, Prabhjot Singh and Seth I. Sokol

J. Clin. Med. 2025, 14(12), 4167; https://doi.org/10.3390/jcm14124167 - 12 Jun 2025

Viewed by 1891

Abstract

Background/Objectives: Right ventricular (RV) dysfunction and circulatory collapse are considered to play a major role in mortality in patients suffering from pulmonary embolism (PE). Catheter-based therapies (CBTs) have been shown to improve RV hemodynamics. The aim of this study was to present available [...] Read more.

Background/Objectives: Right ventricular (RV) dysfunction and circulatory collapse are considered to play a major role in mortality in patients suffering from pulmonary embolism (PE). Catheter-based therapies (CBTs) have been shown to improve RV hemodynamics. The aim of this study was to present available data for CBTs in acute PE and investigate whether CBTs offer mortality benefit and better safety outcomes over anticoagulation (AC) in patients with intermediate-risk PE. Methods: PubMed was searched from inception until February 2024 for studies that investigated treatment strategies in patients with confirmed PE. We initially investigated the crude incidence of mortality and major bleeding for individual interventions in patients with either intermediate or high-risk PE. We then directly compared CBT to AC for intermediate-risk PE, for which the effectiveness endpoint was comparative short-term (30-day or in-hospital) and midterm (90-day or 1-year) all-cause mortality and the safety outcomes included minor bleeding, major bleeding, and intracranial hemorrhage (ICH). Results: In all, 59 studies (4457 patients) were eventually included in our study. For the prevalence study, we described the crude incidence for mortality and major bleeding for interventions like catheter-directed thrombolysis (CDT), mechanical thrombectomy (MT), AC, and systemic thrombolysis (ST) in patients with either intermediate or high-risk PE. Our data synthesis comparing CBT to AC included 1657 patients (11 studies) with intermediate-risk PE. Our results indicate that CBT is associated with a lower risk of both short-term (RR 0.43; 95% CI [0.24–0.79], I² = 0%) and midterm all-cause mortality (RR 0.38; 95% CI [0.23–0.62], I² = 0%) compared to AC. Major bleeding and ICH did not differ between the two groups. Conclusions: In patients with intermediate-risk PE, our meta-analysis of the current literature suggests that CBT offers better outcomes in terms of short-term and midterm mortality compared to AC alone, with no difference in safety outcomes. Further RCTs are needed to explore and validate these findings. Full article

(This article belongs to the Section Cardiovascular Medicine)

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32 pages, 1222 KB

Open AccessEditor’s ChoiceReview

Platelet-Rich Plasma for Knee Osteoarthritis: A Comprehensive Narrative Review of the Mechanisms, Preparation Protocols, and Clinical Evidence

by Wojciech Michał Glinkowski, Grzegorz Gut and Dariusz Śladowski

J. Clin. Med. 2025, 14(11), 3983; https://doi.org/10.3390/jcm14113983 - 5 Jun 2025

Cited by 3 | Viewed by 8941

Abstract

Background: Platelet-rich plasma (PRP) is increasingly utilized for managing knee osteoarthritis (KOA), yet its clinical value remains debated due to the variability in preparation protocols and outcome measures. Methods: This narrative review synthesizes current evidence from 40 high-quality studies published between 2013 and [...] Read more.

Background: Platelet-rich plasma (PRP) is increasingly utilized for managing knee osteoarthritis (KOA), yet its clinical value remains debated due to the variability in preparation protocols and outcome measures. Methods: This narrative review synthesizes current evidence from 40 high-quality studies published between 2013 and March 2025, including randomized controlled trials, systematic reviews, and meta-analyses. The biological mechanisms, clinical effectiveness, safety, and implementation challenges of PRP therapy in KOA are examined. Results: PRP injections—particularly leukocyte-poor PRP—demonstrate superior pain relief and functional improvement compared to hyaluronic acid and corticosteroids, especially in patients with mild to moderate KOA (Kellgren–Lawrence grades I–III). However, heterogeneity in PRP formulations (platelet/leukocyte content and activation protocols), injection regimens, and follow-up durations limits direct comparability across studies. Evidence from high-quality placebo-controlled trials shows inconsistent long-term benefits, with some failing to demonstrate superiority over saline beyond 6–12 months. The GRADE assessment rates the overall certainty of evidence as moderate. PRP appears safe, with few adverse events reported, but remains costly and variably reimbursed. Guidelines from major societies remain cautious or inconclusive. Conclusions: PRP is a promising, safe, and well-tolerated option for early to moderate KOA. However, the standardization of preparation protocols, patient selection criteria, and outcome reporting is essential to improve comparability and guide clinical practice. Full article

(This article belongs to the Section Orthopedics)

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17 pages, 455 KB

Open AccessEditor’s ChoiceReview

Advances in 3D Printing Applications for Personalized Orthopedic Surgery: From Anatomical Modeling to Patient-Specific Implants

by Marcin Prządka, Weronika Pająk, Jakub Kleinrok, Joanna Pec, Karolina Michno, Robert Karpiński and Jacek Baj

J. Clin. Med. 2025, 14(11), 3989; https://doi.org/10.3390/jcm14113989 - 5 Jun 2025

Cited by 9 | Viewed by 4155

Abstract

Three-dimensional (3D) printing has gained substantial interest among scientists and surgeons over the past decade due to its broad potential in medical applications. Its clinical utility has been increasingly recognized, demonstrating promising outcomes for patient care. Currently, 3D printing technology enables surgeons to [...] Read more.

Three-dimensional (3D) printing has gained substantial interest among scientists and surgeons over the past decade due to its broad potential in medical applications. Its clinical utility has been increasingly recognized, demonstrating promising outcomes for patient care. Currently, 3D printing technology enables surgeons to enhance operative precision by facilitating the creation of patient-specific anatomical models, customized implants, biological tissues, and even surgical instruments. This personalization contributes to improved surgical outcomes, reduced operative times, and shorter postoperative recovery periods. Furthermore, 3D printing significantly aids in the customization of prostheses to conform closely to individual anatomical structures. Beyond therapeutic applications, 3D printing serves as a valuable educational tool in medical training. It enhances case-specific visualization, elucidates fracture mechanisms, and provides tangible models for simulation-based practice. Although the use of 3D printing might be seen as useful mostly in orthopedics, it has expanded into multiple medical specialties, including plastic surgery, dentistry, and emergency medicine. Presently, 3D-printed constructs are routinely employed for preoperative planning, prosthetic development, fracture management, and the fabrication of patient-specific surgical tools. Futuristically, the integration of 3D printing into clinical practice is expected to play a pivotal role in the advancement of personalized medicine, offering substantial benefits for both healthcare providers and patients. Full article

(This article belongs to the Special Issue Advances in Trauma and Orthopedic Surgery: 2nd Edition)

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