Medical Sciences

15 pages, 2657 KB

Open AccessArticle

MetAAA Trial Patients Receiving Metformin Therapy Show Limited Improvement in Quality of Life Compared to AAA Patients with Placebo Intake—A Double-Blind, Randomized, and Placebo-Controlled Trial

by Johannes Klopf, Robin Willixhofer, Diana Ahmadi-Fazel, Andreas Scheuba, Lukas Fuchs, Anna Sotir, Anders Wanhainen, Christine Brostjan, Christoph Neumayer and Wolf Eilenberg

Med. Sci. 2025, 13(4), 273; https://doi.org/10.3390/medsci13040273 - 15 Nov 2025

Abstract

Background: Abdominal aortic aneurysm (AAA) is a multifactorial vascular disease with limited therapeutic options, as no pharmacological treatments currently exist to mitigate the progression of small AAAs. Quality of life (QoL) has emerged as a valuable supplementary metric for assessing the efficacy of [...] Read more.

Background: Abdominal aortic aneurysm (AAA) is a multifactorial vascular disease with limited therapeutic options, as no pharmacological treatments currently exist to mitigate the progression of small AAAs. Quality of life (QoL) has emerged as a valuable supplementary metric for assessing the efficacy of pharmacological interventions. This study evaluated QoL scores of MetAAA trial patients on metformin therapy compared to those with placebo intake. Methods: Overall, 54 patients with AAA were included in the MetAAA trial (ClinicalTrials.gov-Identifier:NCT03507413) and randomized to either metformin or placebo treatment. All participants were asked to complete three established and validated (in total 659 longitudinally collected) QoL questionnaires: (1) the 36-Item Short Form Health Survey (SF-36), (2) the Aneurysm Symptom Rating Questionnaire (ASRQ), and (3) the Aneurysm-Dependent Quality of Life questionnaire (ADQoL). Results: A superior health-related QoL was found in metformin-treated AAA patients compared to enrolled AAA patients receiving a placebo. In detail, AAA patients undergoing metformin treatment showed a superior overall current QoL score (p = 0.038), general health perception (p = 0.013), improved physical functioning (p = 0.004), and increased energy/lower fatigue scores (p = 0.008). Furthermore, fewer limitations due to cognitive distress (p = 0.001) and lower limb function (p = 0.021) were detected. Other QoL subscales did not show statistical significance. Inflammatory blood parameters suggest that while systemic inflammation may have some impact on perceived QoL, the relationship is largely limited. Conclusions: In patients with small AAA, metformin led to a limited improvement in health-related QoL compared to a placebo. Full article

(This article belongs to the Section Cardiovascular Disease)

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16 pages, 866 KB

Open AccessArticle

Association Between Ratio of Triglyceride to High-Density Lipoprotein Cholesterol and Cardiovascular and All-Cause Mortality in Non-Diabetic Hemodialysis Patients

by Jane Pitanupong, Arunchai Chang and Apichai Wattanapisit

Med. Sci. 2025, 13(4), 272; https://doi.org/10.3390/medsci13040272 - 15 Nov 2025

Abstract

This study examined whether the triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio is associated with cardiovascular and all-cause mortality among non-diabetic patients undergoing hemodialysis. From June 2017 to December 2023, patients followed until December 2024 were categorized into two groups based on their baseline TG/HDL-C [...] Read more.

This study examined whether the triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio is associated with cardiovascular and all-cause mortality among non-diabetic patients undergoing hemodialysis. From June 2017 to December 2023, patients followed until December 2024 were categorized into two groups based on their baseline TG/HDL-C ratio: those with a high TG/HDL-C ratio (>3.29) and those with a non-elevated TG/HDL-C ratio (≤3.29). The association between TG/HDL-C ratio and CV and all-cause mortality was examined by univariate and multivariate Cox regression analyses. Of the 138 patients, 43 were categorized into the high TG/HDL-C ratio group and 95 into the non-elevated TG/HDL-C ratio group. The non-elevated TG/HDL-C ratio group had significantly increased cardiovascular survival rates of 1, 3, and 5 years (97.8% vs. 85.2%, 96.2% vs. 70.0%, and 87.0% vs. 52.2%, respectively; p < 0.05) and overall survival rates of 1, 3, and 5 years (95.8% vs. 79.1%, 89.6% vs. 62.9%, and 73.9% vs. 40.7%, respectively; p < 0.05). In the proportional hazards model, a high TG-HDL ratio was an independent predictor of cardiovascular mortality (hazard ratio [HR]: 6.799; 95% confidence interval [CI]: 2.276–20.313; p = 0.001) and all-cause mortality (HR: 2.88; 95% CI: 1.16–7.17; p = 0.023). A high TG/HDL-C ratio was associated with CV and overall mortality in non-diabetic HD patients. Further research will be required to explore changes in the serum TG/HDL-C ratio, assess lipoprotein profiles, and determine their outcomes in this group. Full article

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17 pages, 757 KB

Open AccessArticle

Associations of Sociodemographic Factors, Lifestyle Habits, and Insomnia Severity with Obesity Indices in Spanish Workers: Sex-Specific Differences

by José Luis Ribes Valles, Pedro Juan Tárraga López, Ángel Arturo López González, Irene Coll Campayo, Carla Busquets-Cortés and José Ignacio Ramírez-Manent

Med. Sci. 2025, 13(4), 271; https://doi.org/10.3390/medsci13040271 - 14 Nov 2025

Abstract

Background: Obesity and insomnia are prevalent public health issues with shared behavioral and physiological pathways. However, their interplay remains understudied in occupational cohorts. Obesity and insomnia are prevalent public health issues with shared behavioral and physiological pathways. However, their interplay remains understudied in [...] Read more.

Background: Obesity and insomnia are prevalent public health issues with shared behavioral and physiological pathways. However, their interplay remains understudied in occupational cohorts. Obesity and insomnia are prevalent public health issues with shared behavioral and physiological pathways. However, their interplay remains understudied in occupational cohorts. This study aimed to evaluate the associations of sociodemographic factors, lifestyle habits, and insomnia severity with multiple obesity indices in a large population of Spanish workers. Methods: We conducted a cross-sectional analysis of 84,898 workers (2021–2024). Data were obtained from annual occupational health assessments conducted across multiple Spanish regions between 2020 and 2024. Insomnia severity was assessed using the Insomnia Severity Index (ISI), dietary quality using the 14-item Mediterranean Diet Adherence Screener (MEDAS-14), and physical activity using the International Physical Activity Questionnaire—Short Form (IPAQ-SF). Adiposity was measured using Body Mass Index (BMI), waist-to-height ratio (WtHR), the Clínica Universidad de Navarra–Body Adiposity Estimator (CUN-BAE), and the Metabolic Score for Visceral Fat (METS-VF). Multivariable logistic regression models were used to examine associations adjusted for age, sex, education, and occupational social class. Results: Higher ISI scores were significantly and independently associated with elevated adiposity across all indices, with the strongest association observed for METS-VF (odds ratio = 1.19, 95% CI 1.14–1.25, p < 0.001). Women showed higher mean CUN-BAE and METS-VF values than men (CUN-BAE: 37.4 ± 6.2 vs. 25.6 ± 6.4; p < 0.001; METS-VF: 5.7 ± 0.7 vs. 6.4 ± 0.6; p < 0.001), despite lower BMI (25.3 ± 4.8 vs. 26.8 ± 4.3; p < 0.001). Lower physical activity (OR = 5.70; 95% CI 4.91–6.50), poor adherence to the Mediterranean diet (OR = 3.29; 95% CI 2.88–3.70), smoking (OR = 1.29; 95% CI 1.22–1.36), and lower occupational class (Class III: OR = 1.77; 95% CI 1.56–1.97) were also significantly associated with higher obesity markers. Associations were more pronounced among women and participants with severe insomnia symptoms. Conclusions: Insomnia severity, sociodemographic disadvantage, and unhealthy behaviors (low physical activity, poor diet, smoking) were all independent correlates of general and visceral adiposity. The findings underscore the need for comprehensive workplace health programs that integrate sleep quality assessment, dietary improvement, and physical activity promotion to prevent obesity and its metabolic consequences. Full article

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15 pages, 1234 KB

Open AccessArticle

Telerehabilitation and Face-to-Face Exergame Delivery Modalities to Improve Postural Control in Older Adults: A Randomised Controlled Trial

by Valeska Gatica-Rojas, Ricardo Cartes-Velásquez, Javier Silva-Llanos, Catalina Arenas-Leiva, Valentina De Vitis, Simone Posella and Luis Eduardo Cofré Lizama

Med. Sci. 2025, 13(4), 270; https://doi.org/10.3390/medsci13040270 - 14 Nov 2025

Abstract

Background: A systematic exercise programme using low-cost virtual reality devices can help maintain and improve postural control in older adults. This study aimed to evaluate the effectiveness of two different exergame programme modalities: telerehabilitation (TR) and face-to-face (FF). Methods: A randomised controlled trial [...] Read more.

Background: A systematic exercise programme using low-cost virtual reality devices can help maintain and improve postural control in older adults. This study aimed to evaluate the effectiveness of two different exergame programme modalities: telerehabilitation (TR) and face-to-face (FF). Methods: A randomised controlled trial was conducted with 16 participants aged 65 to 75. Both groups completed an 18-session exergame intervention over six weeks, with the TR group (exposure) receiving remote sessions and the FF group having in-person (control) sessions with a physiotherapist. Assessments were carried out at baseline, at weeks 2, 4, and 6, with two follow-ups at weeks 8 and 10. Centre of Pressure (CoP) measures in tasks: eyes open (EO), eyes closed (EC), medial-lateral (ML) weight-shifting exergame and anterior–posterior (AP) weight-shifting exergame, and clinical tests were used to evaluate postural control. Results: TR and FF significantly reduced the CoP_Sway-area during EC (TR: p < 0.01; FF: p = 0.01) at 6 weeks and only FF demonstrated a significant reduction during EO (p < 0.01). Post hoc analysis revealed that TR maintained a significant reduction in the secondary outcomes of the CoP at 8 and 10 weeks, while FF did not sustain these effects over time. Between-group comparisons revealed a greater effect of TR in CoP_Sway-area, and secondary outcomes during the AP weight-shifting task (p < 0.01) at 6 weeks, whereas the FF had a greater effect in secondary CoP outcomes during the ML weight-shifting task (p < 0.01) at 6 weeks. Conclusion: Both six-week exergame programmes were equally effective at improving postural control. Given the observed specific effects of TR and FF delivery, physiotherapists can consider either modality to suit individual needs and access, or as a complementary approach to maintain and improve postural control in older adults. Full article

(This article belongs to the Section Translational Medicine)

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34 pages, 15421 KB

Open AccessReview

Incretin-Based Therapies Through the Decades: Molecular Innovations and Clinical Impact

by Arthur Anatolievich Lee, Victoria Alexandrovna Khotina, Dmitry Alexandrovich Kashirskikh, Olga Evgenevna Voronko, Vagif Ali oglu Gasanov and Andrey Valentinovich Vasiliev

Med. Sci. 2025, 13(4), 269; https://doi.org/10.3390/medsci13040269 - 14 Nov 2025

Abstract

The study of incretins spans more than a century and has revealed their essential role in glucose homeostasis and metabolic regulation. This understanding has led to the development of incretin receptor agonists as highly effective pharmacological agents for the treatment of such cardiometabolic [...] Read more.

The study of incretins spans more than a century and has revealed their essential role in glucose homeostasis and metabolic regulation. This understanding has led to the development of incretin receptor agonists as highly effective pharmacological agents for the treatment of such cardiometabolic diseases as type 2 diabetes and obesity, showing substantial benefits in glycemic control, body weight reduction, and cardiometabolic outcomes. However, their use is limited by adverse events, most commonly gastrointestinal intolerance, along with ongoing safety concerns regarding pancreatic, renal, and ophthalmologic effects. Although incretin-based therapies have fundamentally reshaped the management of diabetes and obesity, continued innovation in drug design and delivery holds promise for expanding their applicability, improving patient adherence, and reinforcing their role as a cornerstone of metabolic disease management and beyond. This review summarizes the historical development, molecular design, and clinical relevance of incretin-based therapies, with particular emphasis on approved agents used in current clinical practice. Full article

(This article belongs to the Section Endocrinology and Metabolic Diseases)

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Graphical abstract

14 pages, 540 KB

Open AccessArticle

Sarcopenia and Functional Decline in Postmenopausal Women: The Roles of Type 2 Diabetes and Physical Activity

by Anthony Rodrigues de Vasconcelos, Fernando José de Sá Pereira Guimarães, Pedro Weldes da Silva Cruz, Maria Joana Mesquita Cruz Barbosa de Carvalho, Aline de Freitas Brito, Keyla Brandão Costa, Lucas Savassi Figueiredo, Paulo Adriano Schwingel, Denise Maria Martins Vancea and Manoel da Cunha Costa

Med. Sci. 2025, 13(4), 268; https://doi.org/10.3390/medsci13040268 - 14 Nov 2025

Abstract

Background/Objectives: Postmenopausal women face an elevated risk of sarcopenia and functional decline, yet the distinct roles of type 2 diabetes mellitus (T2DM) and physical inactivity in these outcomes remain unclear. This study aimed to investigate the independent and combined associations of T2DM and [...] Read more.

Background/Objectives: Postmenopausal women face an elevated risk of sarcopenia and functional decline, yet the distinct roles of type 2 diabetes mellitus (T2DM) and physical inactivity in these outcomes remain unclear. This study aimed to investigate the independent and combined associations of T2DM and physical activity on sarcopenia and functional performance in postmenopausal women. Methods: This was a cross-sectional study of 175 postmenopausal women stratified by T2DM status and physical activity level (active ≥150 min/week vs. insufficiently active). Body composition was assessed via dual-energy X-ray absorptiometry, muscle strength by handgrip dynamometry, and functional performance by gait speed. Sarcopenia was diagnosed using the Asian Working Group for Sarcopenia 2019 criteria. Binary logistic regression calculated odds ratios (ORs) for adverse outcomes. Results: Physical inactivity was the strongest predictor of functional decline, with insufficiently active women showing nearly four-fold increased odds of slow gait speed (<1.0 m/s) compared to active counterparts (OR: 3.93; 95% CI: 1.24–12.45). While T2DM appeared protective against sarcopenia in unadjusted analysis, multivariate adjustment revealed obesity (OR: 4.97; 95% CI: 1.62–15.20) and T2DM (OR: 3.80; 95% CI: 1.59–9.08) as independent sarcopenia predictors. Conclusions: Distinct associational profiles emerged for sarcopenia and functional decline in postmenopausal women. While T2DM and obesity are independently associated with sarcopenia through metabolic mechanisms, physical inactivity emerged as the strongest predictor of functional impairment. These findings support targeted interventions: metabolic optimization for muscle mass preservation and structured physical activity, particularly resistance training, for maintaining functional independence in this high-risk population. Full article

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14 pages, 1037 KB

Open AccessArticle

Individualized Risk Prediction of Medical Postoperative Complications After Oncologic Hepatectomy: A Nomogram-Based Approach

by Raluca Zaharia, Stefan Morarasu, Cristian Ene Roata, Ana Maria Musina, Wee Liam Ong, Gabriel Mihail Dimofte and Sorinel Lunca

Med. Sci. 2025, 13(4), 267; https://doi.org/10.3390/medsci13040267 - 13 Nov 2025

Abstract

Background: Liver resection remains the primary curative treatment for many malignant liver diseases. Advances in patient selection, perioperative care, and surgical technique have markedly reduced procedure-related (surgical) complications in experienced centres. However, despite these improvements, medical (non-surgical) complications continue to represent a substantial [...] Read more.

Background: Liver resection remains the primary curative treatment for many malignant liver diseases. Advances in patient selection, perioperative care, and surgical technique have markedly reduced procedure-related (surgical) complications in experienced centres. However, despite these improvements, medical (non-surgical) complications continue to represent a substantial source of postoperative morbidity, particularly after major liver resections. Herein, we aim to assess the incidence, nature, and predictors of medical versus surgical complications after liver resection and to develop an individual risk calculator for estimating medical morbidity after liver resection. Methods: This is an observational single-centre study including patients who underwent liver resection for cancer between 2013 and 2025. Postoperative complications were classified into medical and surgical categories based on clinical and diagnostic criteria. Demographic, clinical, and intraoperative data were analyzed to identify risk factors associated with each type of complication, and a multivariate logistic regression model was used to select significant variables, which were imputed in a prediction nomogram made available as an interactive web-based calculator. Results: Of the 231 patients included, 36 patients (15.6%) developed postoperative complications. From multivariate analysis, independent predictors of medical complications included cirrhosis (OR 2.8, 95% CI 1.2–6.8, p < 0.05), operative time > 180 min (OR 2.0, 95% CI 1.1–7.4, p < 0.05), intraoperative blood loss > 500 mL (OR 2, 95% CI: 0.9–4.8, p < 0.05), and ASA score ≥ 3 (OR 3.7, 95% CI 1.1–12.5, p < 0.05). Major hepatic resection was the only independent predictor of surgical complications (OR 7.42, 95% CI: 1.14–48.52, p = 0.036). The logistic regression model demonstrated fair discriminative ability with an AUC of 0.682 (95% CI: 0.544–0.729). The risk-prediction nomogram showed a 24.7% risk of postoperative medical morbidity in patients with all four risk factors vs. a 5.4% risk in patients without any risk factor. Conclusion: Postoperative medical complications are significantly more frequent in patients undergoing oncological liver resection with an ASA score ≥ 3, history of cirrhosis, prolonged operative time, and increased intraoperative blood loss. Our logistic regression model and web-friendly nomogram may be used for external validation in larger cohorts and could support preoperative counselling and perioperative risk stratification. Full article

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20 pages, 7750 KB

Open AccessReview

The Role of Angiographic Imaging in the Treatment of Spinal Vascular Malformations

by Camilla Giulia Calastra, Ada Ayechu Abendaño, Raluca-Ana-Maria Barna, Federica Orellana, Simone Baffelli, Ameet Aiyangar and Annapaola Parrilli

Med. Sci. 2025, 13(4), 266; https://doi.org/10.3390/medsci13040266 - 13 Nov 2025

Abstract

Spinal vascular malformations (SVMs) are rare and heterogeneous lesions that may lead to progressive neurological decline or hemorrhage, posing significant challenges for management due to their complex angioarchitecture and proximity to critical neural structures. This review examines the role of angiographic imaging modalities [...] Read more.

Spinal vascular malformations (SVMs) are rare and heterogeneous lesions that may lead to progressive neurological decline or hemorrhage, posing significant challenges for management due to their complex angioarchitecture and proximity to critical neural structures. This review examines the role of angiographic imaging modalities used intraoperatively and postoperatively in guiding treatment, confirming therapeutic success, and informing follow-up strategies. We summarize evidence on two-dimensional digital subtraction angiography (2D DSA), indocyanine green videoangiography (ICG–VAG), and emerging adjunctive techniques. 2D DSA remains the reference standard, offering superior temporal and spatial resolution for real-time visualization of vascular anatomy, catheter navigation, and embolic delivery, though its invasive nature, radiation exposure, and two-dimensional projection limit long-term applicability. ICG–VAG provides a complementary, non-ionizing method for intraoperative fluorescence imaging, aiding in shunt localization and venous preservation, although its restricted field of view and limited capacity for quantitative analysis reduce its standalone value. Advances in quantitative angiographic metrics, patient-specific hemodynamic modeling, and artificial intelligence-driven image analysis are anticipated to enhance diagnostic accuracy and reproducibility. The development of standardized multimodal protocols will be crucial for optimizing patient-centered treatment of these complex and rare lesions. Full article

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26 pages, 566 KB

Open AccessReview

Semaglutide from Bench to Bedside: The Experimental Journey Towards a Transformative Therapy for Diabetes, Obesity and Metabolic Liver Disorders

by Ralf Weiskirchen and Amedeo Lonardo

Med. Sci. 2025, 13(4), 265; https://doi.org/10.3390/medsci13040265 - 12 Nov 2025

Abstract

Background/Objectives: Type 2 diabetes and obesity present escalating global health and economic challenges, highlighting the need for therapies that can effectively manage glycemic levels and reduce excess adiposity. Semaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist available in subcutaneous or oral formulation, has quickly [...] Read more.

Background/Objectives: Type 2 diabetes and obesity present escalating global health and economic challenges, highlighting the need for therapies that can effectively manage glycemic levels and reduce excess adiposity. Semaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist available in subcutaneous or oral formulation, has quickly evolved from a theoretical concept to a crucial component of modern metabolic care. This review explores the comprehensive development journey of semaglutide, drawing on evidence from medicinal chemistry, animal studies, initial human trials, the pivotal SUSTAIN and STEP programs, and real-world post-marketing surveillance. Methods: We conducted a detailed analysis of preclinical data sets, Phase I–III clinical trials, regulatory documents, and pharmaco-epidemiological studies published between 2008 and 2025. Results: Through strategic molecular modifications, such as specific amino-acid substitutions and the addition of a C18 fatty-diacid side chain to enhance albumin binding, the half-life of the peptide was extended to approximately 160 h, allowing for weekly dosing. Studies in rodents and non-human primates showed that semaglutide effectively lowered blood glucose levels, reduced body weight, and preserved β-cells while maintaining a favorable safety profile. Phase I trials confirmed consistent pharmacokinetics and tolerability, while Phase II trials identified 0.5 mg and 1.0 mg once weekly as the most effective doses. The extensive SUSTAIN program validated significant reductions in HbA1c levels and weight loss compared to other treatments, as well as a 26% decrease in the relative risk of major adverse cardiovascular events (SUSTAIN-6). Subsequent STEP trials expanded the use of semaglutide to chronic weight management, revealing that nearly two-thirds of patients experienced a body weight reduction of at least 15%. Regulatory approvals from the FDA, EMA, and other regulatory agencies were obtained between 2017 and 2021, with ongoing research focusing on metabolic dysfunction-associated steatohepatitis, cardiovascular events, and chronic kidney disease. Conclusions: The trajectory of semaglutide exemplifies how intentional peptide design, iterative translational research, and outcome-driven clinical trial design can lead to groundbreaking therapies for complex metabolic disorders. Full article

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14 pages, 3547 KB

Open AccessSystematic Review

Robotic Omental Flap Harvest for Complex Thoracic Defects: Case Series and Review of the Literature

by Susana Fortich, Camila Franco-Mesa, Jennifer Den, Gabriel De La Cruz Ku, Gal Levy and Roman Petrov

Med. Sci. 2025, 13(4), 264; https://doi.org/10.3390/medsci13040264 - 12 Nov 2025

Abstract

Objective: The omentum is a highly vascularized and immunologically active tissue with significant regenerative potential. Despite its versatility, its use has traditionally been limited to intra-abdominal applications due to access challenges. Conventional open harvest requires laparotomy, and laparoscopic techniques are hindered by limited [...] Read more.

Objective: The omentum is a highly vascularized and immunologically active tissue with significant regenerative potential. Despite its versatility, its use has traditionally been limited to intra-abdominal applications due to access challenges. Conventional open harvest requires laparotomy, and laparoscopic techniques are hindered by limited visualization and poor ergonomics. We describe the use of robotic-assisted omental flap harvest for thoracic reconstruction, offering a minimally invasive alternative. Methods: A retrospective review was conducted of patients who underwent robotic omental flap harvest for intrathoracic reconstruction at a single-center institution between January 2023 and January 2024. Data collected included demographics, indications, surgical technique, operative details, and postoperative outcomes, with a focus on flap viability and complications. Additionally, a systematic review was conducted to evaluate current evidence and experiences with this type of technique. Results: Three patients underwent robotic omental flap harvest for indications including chest wall reconstruction and pleural space obliteration in infected thoracic cavities. The average robotic flap harvest time was 79 ± 13 min, with an estimated ± blood loss of 20 cc. The mean postoperative hospital stay was 10 days, influenced by the primary procedure and patient comorbidities. At an average follow-up of 8 months, all flaps remained viable, with no flap-related complications or losses. The systematic review demonstrated limited data in the current literature regarding this type of surgical approach. Conclusions: Robotic-assisted omental flap harvest is a safe, feasible, and effective technique for complex thoracic reconstructions. It provides a minimally invasive alternative to traditional harvest methods, with reduced morbidity and excellent clinical outcomes. This technique expands the reconstructive options for intrathoracic defects and infections. Full article

(This article belongs to the Section Pneumology and Respiratory Diseases)

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27 pages, 1053 KB

Open AccessReview

The Multifaceted Role of Annexin A1 in Colorectal Cancer: From Molecular Mechanisms to Predictive and Prognostic Implications

by Diana Lavinia Pricope, Adriana Grigoraș, Gabriel Mihail Dimofte and Cornelia Amalinei

Med. Sci. 2025, 13(4), 263; https://doi.org/10.3390/medsci13040263 - 10 Nov 2025

Abstract

Annexin A1 (ANXA1), a calcium-dependent phospholipid-binding protein, is considered a key modulator of cancer biology. Numerous pieces of evidence support its multifaceted involvement in tumor progression, metastatic dissemination, immune escape, and resistance to therapy in various malignancies, such as melanoma, along with liver, [...] Read more.

Annexin A1 (ANXA1), a calcium-dependent phospholipid-binding protein, is considered a key modulator of cancer biology. Numerous pieces of evidence support its multifaceted involvement in tumor progression, metastatic dissemination, immune escape, and resistance to therapy in various malignancies, such as melanoma, along with liver, lung, and digestive tract tumors, including stomach and colorectal cancer (CRC). Although colon and rectal cancer (RC) exhibit overlapping characteristics, they are classified as separate clinical entities due to differences in tumor biology and therapy approaches. Moreover, locally advanced rectal cancer (LARC) raises clinical challenges due to variable treatment responses and its therapy resistance, preventing successful treatment and patients’ recovery. Considering ANXA1’s involvement in chemoresistance, further investigation is currently focused on ANXA1-targeted therapies. This review aims to update the knowledge on ANXA1, as a CRC predictive and prognostic biomarker, with involvement in therapy resistance, highlighting its significance in LARC patients. Through emerging evidence, our research provides valuable insights into the potential of ANXA1’s clinical utility and its prospective value as a target in chemoresistance approaches. Full article

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12 pages, 1984 KB

Open AccessArticle

Sensory Recovery After Free Muscle Flap Reconstruction—A Clinical Study of Protective and Discriminative Function of Free Gracilis and Latissimus Dorsi Muscle Flaps Without Neurotization

by Maximilian C. Stumpfe, Moritz Billner, Marc Hellweg, Maximilian Hirschmann, Rakan R. Al-Turki, Celena A. Sörgel, Vadym Burchak, Nikolaus Wachtel and Denis Ehrl

Med. Sci. 2025, 13(4), 262; https://doi.org/10.3390/medsci13040262 - 7 Nov 2025

Abstract

Background/Objectives: Free gracilis (GM) and latissimus dorsi muscle (LDM) flaps are reliable options for complex defect coverage, but long-term sensory outcomes remain underexplored. Sensory impairment, especially the loss of protective cutaneous sensation, increases the risk of injury, thermal damage, and ulceration in reconstructed [...] Read more.

Background/Objectives: Free gracilis (GM) and latissimus dorsi muscle (LDM) flaps are reliable options for complex defect coverage, but long-term sensory outcomes remain underexplored. Sensory impairment, especially the loss of protective cutaneous sensation, increases the risk of injury, thermal damage, and ulceration in reconstructed areas. This study aimed to systematically assess multidimensional sensory recovery after free muscle flap (FMF) reconstruction. Methods: In a prospective single-center study, 94 patients (49 GM, 45 LDM) underwent standardized sensory testing following FMF transfer. Five modalities were evaluated: pressure detection (Semmes-Weinstein monofilaments), vibration perception, two-point discrimination (2PD), sharp–dull differentiation, and temperature differentiation. Measurements were compared to contralateral healthy skin (CHS). Subgroup analyses were performed by anatomical region (head, trunk, extremities). Results: All sensory modalities were significantly impaired in FMF compared to CHS (p < 0.0001). Mean pressure thresholds were markedly higher in FMF (248.8 g) versus CHS (46.8 g). Vibration perception scores were reduced (FMF 3.97 vs. CHS 5.31), and 2PD was significantly poorer (11.6 cm vs. 4.7 cm). Sharp–dull and thermal discrimination were largely absent in FMF (positivity rates < 20%), with 58.5% of patients demonstrating only deep pressure sensation (≥300 g). No significant differences were found between GM and LDM in most modalities, except for worse 2PD in GM. Subgroup analyses confirmed uniform deficits across all anatomical regions. Conclusions: FMFs without neurotization result in profound, persistent sensory deficits, particularly the loss of protective sensation. Clinically, fascio-cutaneous flaps with nerve coaptation should be considered in functionally critical regions. Future strategies should focus on neurotization techniques to enhance sensory recovery. Full article

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19 pages, 31470 KB

Open AccessSystematic Review

Exit Meta-Analysis on the Effect of HIV on COVID-19 Mortality, Hospitalization, and ICU Admission

by Lubna A. Zar, Shahd Hamran, Izzaldin Alremawi, Mohamed Elahtam, Asmaa Abdelmaksoud, Rida Arif and Tawanda Chivese

Med. Sci. 2025, 13(4), 261; https://doi.org/10.3390/medsci13040261 - 7 Nov 2025

Abstract

Purpose: The COVID-19 pandemic has led to the publication of numerous primary studies and meta-analyses; however, conclusive evidence on whether HIV infection influences COVID-19 outcomes among people living with HIV (PLHIV) is still lacking. This research uses a novel technique, the exit meta-analysis [...] Read more.

Purpose: The COVID-19 pandemic has led to the publication of numerous primary studies and meta-analyses; however, conclusive evidence on whether HIV infection influences COVID-19 outcomes among people living with HIV (PLHIV) is still lacking. This research uses a novel technique, the exit meta-analysis, to conclusively update the evidence of HIV’s impact on COVID-19-related mortality, hospitalization, and need for Intensive Care Unit (ICU) admission in severe disease. Methods: A search of PubMed, EMBASE, Cochrane Reviews (CDSR), SCOPUS, CINAHL reviews and Google Scholar databases was conducted up to the 18 January 2024 for meta-analyses and observational studies that reported adjusted associations for the effect of HIV on COVID-19 related mortality, hospitalization, and ICU admission. Evidence from existing meta-analyses was summarized narratively, and an updated meta-analysis was carried out using a bias-adjusted inverse variance heterogeneity model. Subgroup analysis was carried out for age groups and geographical regions. Results: Of 3153 records identified, 20 meta-analyses and 56 primary studies, with a total of 27,936,428 participants, including 655,882 PLHIV, were included. A review of the meta-analyses showed conflicting results for all outcomes. In the updated synthesis, HIV was associated with higher odds of mortality (aOR 1.43, 95% CI: 1.01–1.86, I² = 90.7%) and ICU admission (aOR 1.49, 95% CI: 0.67–2.30, I² = 88.8%), but not hospitalization (aOR 1.11, 95% CI: 0.78–1.48, I² = 97.5%). The results for both ICU admission and hospitalization include the null value, leading to lower certainty. The exit meta-analysis suggested conclusive results for mortality (DAts score = −0.012) and hospitalization (DAts score = −0.014), but not for ICU admission. Conclusions: This exit meta-analysis provides conclusive evidence that HIV increases mortality in people with COVID-19; however, more studies may be required to address ICU admission and hospitalization. Full article

(This article belongs to the Section Immunology and Infectious Diseases)

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14 pages, 1281 KB

Open AccessSystematic Review

Data Augmentation and Synthetic Data Generation in Rare Disease Research: A Scoping Review

by Rebecca Finetti, Bianca Roncaglia, Anna Visibelli, Ottavia Spiga and Annalisa Santucci

Med. Sci. 2025, 13(4), 260; https://doi.org/10.3390/medsci13040260 - 6 Nov 2025

Abstract

Background: Rare diseases represent a significant research challenge due to the limited availability of data, small patient cohorts, and heterogeneous phenotypes. Data augmentation and synthetic data generation are increasingly adopted to mitigate these limitations. Methods: This scoping review maps the application of data [...] Read more.

Background: Rare diseases represent a significant research challenge due to the limited availability of data, small patient cohorts, and heterogeneous phenotypes. Data augmentation and synthetic data generation are increasingly adopted to mitigate these limitations. Methods: This scoping review maps the application of data augmentation and synthetic data generation methods as strategies to address these limitations. A total of 118 studies published between 2018 and 2025 were identified through PubMed, Scopus, and Electronics Engineers (IEEE) Xplore. Results: Imaging data headed the field, followed by clinical and omics datasets. Classical augmentation, mainly geometric and photometric transformations, emerged as the most frequent approach, while deep generative models have rapidly expanded since 2021. Rule- and model-based methods were less common but demonstrated high interpretability in small datasets. Conclusions: Overall, these techniques enabled dataset expansion and improved model robustness. However, both approaches require rigorous validation to confirm biological plausibility. Together, these methods can transform data scarcity from a barrier into a driver of methodological innovation, enabling more inclusive rare disease research. Full article

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24 pages, 676 KB

Open AccessSystematic Review

Integrating Mental Health into Diabetes Care: Closing the Treatment Gap for Better Outcomes—A Systematic Review

by Shakila Jahan Shimu, Shamima Akter, Md. Majedur Rahman, Shahida Arbee, Mohammad Sarif Mohiuddin, Sadman Sazzad, Mahjabin Raiqa, Mohammad Mohabbulla Mohib, Afsana R. Munmun and Mohammad Borhan Uddin

Med. Sci. 2025, 13(4), 259; https://doi.org/10.3390/medsci13040259 - 3 Nov 2025

Abstract

Background: Diabetes and mental health conditions frequently co-occur, with depression and anxiety affecting up to 20–30% of people with diabetes. These comorbidities worsen glycemic control, adherence, and quality of life, yet mental health is often neglected in diabetes care. Integrating mental health services [...] Read more.

Background: Diabetes and mental health conditions frequently co-occur, with depression and anxiety affecting up to 20–30% of people with diabetes. These comorbidities worsen glycemic control, adherence, and quality of life, yet mental health is often neglected in diabetes care. Integrating mental health services into diabetes management is recommended by international organizations to improve patient outcomes. Objectives: To systematically review the evidence on integrated mental health interventions in diabetes care, compared to usual diabetes care, in improving patient outcomes (glycemic control, mental health, adherence, quality of life). Methods: We searched PubMed/MEDLINE, Embase, PsycINFO, and Scopus (2000 through July 2024) for studies of diabetes care integrating mental health support (e.g., collaborative care, co-location, stepped care, or digital interventions). Inclusion criteria were controlled trials or cohort studies involving individuals with type 1 or type 2 diabetes receiving an integrated mental health intervention, with outcomes on glycemic control and/or mental health. Two reviewers independently screened titles/abstracts and full texts, with disagreements resolved by consensus. Data on study design, population, intervention components, and outcomes were extracted. Risk of bias was assessed using Cochrane or appropriate tools. Results: Out of records identified, 64 studies met inclusion criteria (primarily randomized controlled trials). Integrated care models consistently improved depression and anxiety outcomes and diabetes-specific distress, and yielded modest but significant reductions in glycated hemoglobin (HbA1c) compared to usual care. Many interventions also enhanced treatment adherence and self-management behaviors. For example, collaborative care trials showed greater depression remission rates and small HbA1c improvements (~0.3–0.5% absolute reduction) relative to standard care. Co-located care in diabetes clinics was associated with reduced diabetes distress, depression scores, and HbA1c over 12 months. Digital health integrations (telepsychiatry, online cognitive-behavioral therapy) improved psychological outcomes and adherence, with some reporting slight improvements in glycemic control. Integrated approaches often increased uptake of mental health services (e.g., higher referral completion rates) and showed high patient satisfaction. A subset of studies reported fewer emergency visits and hospitalizations with integrated care, and one economic analysis found collaborative care cost-effective in primary care settings. Conclusions: Integrating mental health into diabetes care leads to better mental health outcomes and modest improvements in glycemic control, without adverse effects. Heterogeneity across studies is noted, but the overall evidence supports multidisciplinary, patient-centered care models to address the psychosocial needs of people with diabetes. Healthcare systems should prioritize implementing and scaling integrated care, accompanied by provider training and policy support, to improve outcomes and bridge the persistent treatment gap. Future research should focus on long-term effectiveness, cost-effectiveness, and strategies to reach diverse populations. Full article

(This article belongs to the Section Translational Medicine)

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21 pages, 3651 KB

Open AccessSystematic Review

Effectiveness of Different Types of Core Decompression in Early-Stage Osteonecrosis of the Femoral Head: A Systematic Review and Meta-Analysis

by Wojciech Konarski

Med. Sci. 2025, 13(4), 258; https://doi.org/10.3390/medsci13040258 - 3 Nov 2025

Abstract

Background: Osteonecrosis of the femoral head is a progressive disorder leading to femoral head collapse and early disability, often affecting young adults. Core decompression (CD) is the most established hip-preserving treatment for early-stage disease, yet the comparative benefits of biological and structural augmentation [...] Read more.

Background: Osteonecrosis of the femoral head is a progressive disorder leading to femoral head collapse and early disability, often affecting young adults. Core decompression (CD) is the most established hip-preserving treatment for early-stage disease, yet the comparative benefits of biological and structural augmentation remain uncertain. Methods: This systematic review and meta-analysis, registered in PROSPERO (CRD420251108396), evaluated 14 studies encompassing 1210 patients treated with CD alone or CD combined with biological (e.g., platelet-rich plasma, mesenchymal stem cells, bone marrow aspirate concentrate) or structural (e.g., bone grafting, fibular support) augmentation. Results: Pooled random-effects models demonstrated that biological augmentation yielded significant improvements in Harris Hip Score and pain reduction (VAS) up to 24 months, with early peaks and subsequent stabilization, whereas structural augmentation showed no functional advantage at any time point. Radiological progression and conversion to total hip arthroplasty were not significantly reduced, though long-term trends favored biologically augmented CD. Conclusions: Overall, biological augmentation provides durable functional and symptomatic benefits in early-stage osteonecrosis, supporting its use as a first-line adjunct to CD, while structural augmentation appears less consistent and warrants further evaluation through large, standardized trials. Full article

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16 pages, 3443 KB

Open AccessArticle

Automated Detection and Grading of Renal Cell Carcinoma in Histopathological Images via Efficient Attention Transformer Network

by Hissa Al-kuwari, Belqes Alshami, Aisha Al-Khinji, Adnan Haider and Muhammad Arsalan

Med. Sci. 2025, 13(4), 257; https://doi.org/10.3390/medsci13040257 - 1 Nov 2025

Abstract

Background: Renal Cell Carcinoma (RCC) is the most common type of kidney cancer and requires accurate histopathological grading for effective prognosis and treatment planning. However, manual grading is time-consuming, subjective, and susceptible to inter-observer variability. Objective: This study proposes EAT-Net (Efficient Attention Transformer [...] Read more.

Background: Renal Cell Carcinoma (RCC) is the most common type of kidney cancer and requires accurate histopathological grading for effective prognosis and treatment planning. However, manual grading is time-consuming, subjective, and susceptible to inter-observer variability. Objective: This study proposes EAT-Net (Efficient Attention Transformer Network), a dual-stream deep learning model designed to automate and enhance RCC grade classification from histopathological images. Method: EAT-Net integrates EfficientNetB0 for local feature extraction and a Vision Transformer (ViT) stream for capturing global contextual dependencies. The architecture incorporates Squeeze-and-Excitation (SE) modules to recalibrate feature maps, improving focus on informative regions. The model was trained and evaluated on two publicly available datasets, KMC-RENAL and RCCG-Net. Standard preprocessing was applied, and the model’s performance was assessed using accuracy, precision, recall, and F1-score. Results: EAT-Net achieved superior results compared to state-of-the-art models, with an accuracy of 92.25%, precision of 92.15%, recall of 92.12%, and F1-score of 92.25%. Ablation studies demonstrated the complementary value of the EfficientNet and ViT streams. Additionally, Grad-CAM visualizations confirmed that the model focuses on diagnostically relevant areas, supporting its interpretability and clinical relevance. Conclusion: EAT-Net offers an accurate, and explainable framework for RCC grading. Its lightweight architecture and high performance make it well-suited for clinical deployment in digital pathology workflows. Full article

(This article belongs to the Special Issue Artificial Intelligence in Oncologic Imaging: Advances in Medical Image Segmentation and Predictive Modelling)

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10 pages, 233 KB

Open AccessArticle

Mismatch Repair System Gene Expression in FFPE Samples from Breast Cancer Patients

by Ricardo Quidute, Patricia Quidute, Matheus Moreira Perez, Carlos Henrique F. Peiró, Glaucia Luciano da Veiga, Beatriz da Costa Aguiar Alves and Fernando Luiz Affonso Fonseca

Med. Sci. 2025, 13(4), 256; https://doi.org/10.3390/medsci13040256 - 31 Oct 2025

Abstract

Background/Objectives: Cancer characteristics are mainly due to mutations in genes that regulate key pathways. One mechanism for identifying and correcting these mutations is the Mismatch Repair System. Given the lack of data on MMR in breast cancer FFPE samples, this study aims [...] Read more.

Background/Objectives: Cancer characteristics are mainly due to mutations in genes that regulate key pathways. One mechanism for identifying and correcting these mutations is the Mismatch Repair System. Given the lack of data on MMR in breast cancer FFPE samples, this study aims to examine hMSH2 and hMSH6 gene expression in FFPE tumor biopsies. Methods: One hundred patients with breast cancer were included in this study, from which tumor samples were obtained. Expression of the hMSH2 and hMSH6 genes was evaluated by qPCR. Results: Out of 100 tumor samples, 89 were suitable for molecular analysis. Of these, 10 (11.23%) expressed the hMSH2 gene and 4 (4.5%) expressed the hMSH6 gene. No associations were found between hMSH2 and hMSH6 expression and tumor staging, HER2, ER, PR, or Ki-67 expression. Conclusions: Our results suggest that the expression of the proposed markers is decreased in breast tumorigenesis. Full article

17 pages, 1734 KB

Open AccessSystematic Review

Exploring the Cardiovascular Impacts of Agmatine: A Systematic Review

by Oana-Mădălina Manole, Gabriela Rusu-Zota, Amin Bazyani and Viviana Onofrei

Med. Sci. 2025, 13(4), 255; https://doi.org/10.3390/medsci13040255 - 31 Oct 2025

Abstract

Background: Agmatine (AG) is an endogenous neurotransmitter discovered in 1910. It acts on imidazoline I1 and I2 receptors, alpha-2 adrenoceptors, N-methyl-D-aspartate receptors (NMDAR), and serotonergic receptors and modulates nitric oxide synthase (NOS) subtypes. It has neuroprotective, anxiolytic, antidepressant, anticonvulsant, and anti-inflammatory properties and [...] Read more.

Background: Agmatine (AG) is an endogenous neurotransmitter discovered in 1910. It acts on imidazoline I1 and I2 receptors, alpha-2 adrenoceptors, N-methyl-D-aspartate receptors (NMDAR), and serotonergic receptors and modulates nitric oxide synthase (NOS) subtypes. It has neuroprotective, anxiolytic, antidepressant, anticonvulsant, and anti-inflammatory properties and is involved in cognitive functions and withdrawal. The cardiovascular effects of AG began to be explored after the hypotensive effect of clonidine, an imidazoline agonist, was demonstrated. The current study aimed to systematize the effects of AG on the cardiovascular system obtained in previous preclinical studies. Methods: We searched three databases, PubMed, Cochrane, and Embase, using the keywords “agmatine” and “cardiac” or “vascular.” Results: Sixty studies were eligible and included in the analysis. Initially identified as Clonidine Displacing Substance (CDS), AG has demonstrated dual effects—an increase or decrease in blood pressure or in heart rate. Conclusions: The effects exerted by AG depend on the dose and route of administration, as well as on the receptors involved and the pathophysiological pathway used. Full article

(This article belongs to the Section Cardiovascular Disease)

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