Medical Sciences

19 pages, 296 KB

Open AccessReview

The Clinical Impact of Patient Embarrassment in Gynecology: A Comprehensive Review of Barriers, Consequences, and Mitigation Strategies

by Tudor Butureanu, Raluca Anca Balan, Ana-Maria Haliciu, Razvan Socolov and Demetra Socolov

Med. Sci. 2026, 14(2), 335; https://doi.org/10.3390/medsci14020335 (registering DOI) - 22 Jun 2026

Abstract

Patient embarrassment represents a significant yet often underrecognized barrier to effective gynecological care. This review integrates multidisciplinary evidence from Embase, PubMed, PsycINFO, and the Cochrane Library (2000–2025) to examine the relationship between embarrassment, shame, and modesty and their impact on care-seeking behaviors, clinical [...] Read more.

Patient embarrassment represents a significant yet often underrecognized barrier to effective gynecological care. This review integrates multidisciplinary evidence from Embase, PubMed, PsycINFO, and the Cochrane Library (2000–2025) to examine the relationship between embarrassment, shame, and modesty and their impact on care-seeking behaviors, clinical outcomes, and healthcare utilization. Available data indicate that embarrassment is consistently associated with reduced participation in preventive screening, with up to one-third of non-attenders citing modesty-related concerns. In symptomatic patients, these emotional barriers contribute to clinically meaningful diagnostic delays, particularly in conditions such as cervical cancer, vulvar cancer, and endometriosis. Embarrassment also affects in-consultation behavior, with a substantial proportion of patients reporting withheld concerns or incomplete disclosure of medically relevant information. The consequences extend beyond delayed diagnosis to include reduced treatment adherence, increased disease severity at presentation, and higher healthcare costs due to more complex and resource-intensive interventions. Contributing factors include cultural stigma, prior negative clinical experiences, fear of judgment, and aspects of the clinical environment that may heighten patient vulnerability. Full article

(This article belongs to the Section Gynecology)

13 pages, 483 KB

Open AccessArticle

Physical Performance as a Predictor of Length of Hospital Stay in Patients Undergoing Open-Heart Surgery: A Multicenter Prospective Study

by Wararat Tavonudomgit, Kornanong Yuenyongchaiwat, Lucksanaporn Mahawong, Khanistha Wattanananont, Chitima Kulchanarat, Sasipa Buranapuntalug and Opas Satdhabudha

Med. Sci. 2026, 14(2), 334; https://doi.org/10.3390/medsci14020334 (registering DOI) - 20 Jun 2026

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Abstract

Background: Patients undergoing open-heart surgery (OHS) are at risk of postoperative morbidity and mortality. Physical performance has been increasingly recognized as an important factor influencing postoperative outcomes. Therefore, the study aimed to investigate the associations and predictive value of physical performance on postoperative [...] Read more.

Background: Patients undergoing open-heart surgery (OHS) are at risk of postoperative morbidity and mortality. Physical performance has been increasingly recognized as an important factor influencing postoperative outcomes. Therefore, the study aimed to investigate the associations and predictive value of physical performance on postoperative complications and duration of hospital stay. Methods: A prospective cohort study was conducted in 116 patients who were admitted to OHS. Preoperative assessment of physical performance, i.e., Short Physical Performance Battery (SPPB), Five Times Sit to Stand Test (5STS), gait speed (5 m walk test: 5MWT), Timed Up and Go (TUG), and handgrip strength. Duration of hospital stay and incidence of post-operative complications were recorded. Differences between participants with and without postoperative complications were analyzed using independent samples t-tests for continuous variables and chi-square tests for categorical variables. The associations between physical performance and postoperative outcomes were assessed using Spearman’s rank correlation coefficient. Hierarchical regression analysis was conducted to determine the predictive contribution of physical performance. Results: A total of 116 participants were submitted for OHS in two medical school hospitals; however, 108 individuals completed the pre-operative physical performance. The most common procedures were coronary artery bypass grafting and valve surgery. Fifty-one participants (47.22%) experienced postoperative complications, including five deaths, corresponding to 4.63% mortality. For the length of hospital stay analysis, five participants who died postoperatively were excluded, resulting in a final sample of 103 participants. Physical performance was significantly associated with the length of hospital stay (p < 0.05). Hierarchical regression analysis showed that the final prediction model explained 13.4% of the variance in length of hospital stay, with SPPB independently contributing an additional 6.0% to the model, followed by 5STS, 5MWT, handgrip strength, and TUG, which accounted for an additional 5.1%, 4.6%, 4.4%, and 3.7%, respectively. Conclusions: Preoperative physical performance was associated with length of hospital stay. While each measure explained a relatively small proportion of the variance in hospital stay, these assessments offer a simple, non-invasive, and clinically feasible approach to evaluating functional reserve before surgery. These findings highlight the importance of incorporating functional assessment into perioperative care to support risk stratification and guide rehabilitation strategies. Full article

(This article belongs to the Section Cardiovascular Disease)

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15 pages, 292 KB

Open AccessReview

Renal Involvement in Pediatric Small-Vessel Vasculitis: A Comprehensive Review of Clinical Impact, Diagnosis, and Management

by Adina-Andreea Pop, Andreea Liana Bot (Rachisan), Emil Botan and Mihaela Sparchez

Med. Sci. 2026, 14(2), 333; https://doi.org/10.3390/medsci14020333 (registering DOI) - 20 Jun 2026

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Abstract

Background: Renal vasculitis encompasses a heterogeneous spectrum of disorders where vascular inflammation leads to organ dysfunction. Given that renal involvement is the primary determinant of long-term morbidity, timely diagnosis and intervention are paramount. This review aims to synthesize recent pathogenic insights and evaluate [...] Read more.

Background: Renal vasculitis encompasses a heterogeneous spectrum of disorders where vascular inflammation leads to organ dysfunction. Given that renal involvement is the primary determinant of long-term morbidity, timely diagnosis and intervention are paramount. This review aims to synthesize recent pathogenic insights and evaluate how these mechanistic breakthroughs are reshaping current diagnostic and therapeutic paradigms. Methods: A narrative review of the literature was performed to analyze the pathophysiology, diagnosis, and management of pediatric renal vasculitis. The analysis synthesizes current clinical guidelines and recent trial data, highlighting the transition toward biomarker-driven precision medicine for refined disease assessment and management. Results: Diagnosis remains multimodal, necessitating the integration of clinical, laboratory, and histopathological data. In ANCA-associated vasculitis (AAV), recent evidence has challenged the traditional “pauci-immune” concept. Management of pediatric IgA vasculitis utilizes a risk-stratified approach, whereas cryoglobulinemic vasculitis requires targeted trigger elimination. Across all pediatric syndromes, there is a shift toward minimizing corticosteroid exposure and utilizing individualized frameworks. Conclusions: Despite substantial progress in targeted biological therapies and reduced corticosteroid burden, the long-term morbidity of pediatric renal vasculitis remains substantial. Outcomes are dictated by a synergy of disease-specific and patient-specific factors. Addressing persistent unmet needs in the field requires further refinement of individualized management protocols and the continued validation of dynamic biomarkers, alongside the implementation of pediatric-specific guidelines and age-appropriate outcome measures. Full article

(This article belongs to the Section Nephrology and Urology)

23 pages, 1079 KB

Open AccessSystematic Review

MRI-Based Radiomics and Artificial Intelligence for Prediction of Recurrence and Prognostic Outcomes in Oral Tongue Squamous Cell Carcinoma: A Systematic Review with Functional Meta-Synthesis

by Carlos M. Ardila, Eliana Pineda-Vélez, Anny M. Vivares-Builes and Alejandro I. Díaz-Laclaustra

Med. Sci. 2026, 14(2), 332; https://doi.org/10.3390/medsci14020332 (registering DOI) - 19 Jun 2026

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Abstract

Background/Objectives: Oral tongue squamous cell carcinoma (OTSCC) remains clinically challenging because conventional clinicopathological markers do not fully explain variability in recurrence and survival. This systematic review and functional meta-synthesis aimed to identify and critically appraise studies using preoperative magnetic resonance imaging (MRI)-based radiomics, [...] Read more.

Background/Objectives: Oral tongue squamous cell carcinoma (OTSCC) remains clinically challenging because conventional clinicopathological markers do not fully explain variability in recurrence and survival. This systematic review and functional meta-synthesis aimed to identify and critically appraise studies using preoperative magnetic resonance imaging (MRI)-based radiomics, artificial intelligence (AI), deep learning, or quantitative MRI-derived models to predict recurrence and prognostic outcomes in OTSCC. Methods: PubMed, Scopus, and Embase were searched from inception to March 2026. Eligible studies included prognostic model investigations in adults with OTSCC or primary tongue cancer without reported base-of-tongue/oropharyngeal involvement, undergoing preoperative MRI and surgery, with recurrence- or survival-related follow-up. The primary synthesis was a functional meta-synthesis; pooling was not performed because studies were not sufficiently comparable. Results: Seven retrospective studies were included, with a summed descriptive sample of 1287 participants. The evidence base was heterogeneous in MRI sequences, segmentation workflows, model architecture, validation strategy, and endpoint definition. Functional meta-synthesis identified four domains: direct recurrence-oriented modeling, broader prognostic stratification, reported incremental or complementary value over clinical frameworks, and translational maturity/technical implementation. Several studies reported associations between MRI-derived signatures and recurrence- or survival-related outcomes, but findings were interpreted narratively because of differences in primary endpoints, imaging features, model design, validation methods, and outcome definitions. Most studies were judged at high overall risk of bias, and certainty of evidence ranged from low to very low. Conclusions: MRI-based radiomics and AI show preliminary promise for prognostic stratification in OTSCC, particularly recurrence-related risk refinement, but current evidence remains limited by retrospective design, heterogeneity, sparse external validation, and low certainty. 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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52 pages, 889 KB

Open AccessReview

Present and Future Options for Pharmacotherapy in Cardiovascular Disease: Hemodynamic and Mechanistic Therapeutic Targets

by Francesc Cabré and Marta Cascante

Med. Sci. 2026, 14(2), 331; https://doi.org/10.3390/medsci14020331 (registering DOI) - 18 Jun 2026

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Abstract

Cardiovascular diseases (CVDs) remain the leading global cause of morbidity and mortality, imposing an increasing clinical and socioeconomic burden. Despite significant therapeutic advances, optimal control of risk factors and long-term outcomes remain challenging, particularly in patients with complex comorbidities. This narrative review provides [...] Read more.

Cardiovascular diseases (CVDs) remain the leading global cause of morbidity and mortality, imposing an increasing clinical and socioeconomic burden. Despite significant therapeutic advances, optimal control of risk factors and long-term outcomes remain challenging, particularly in patients with complex comorbidities. This narrative review provides a comprehensive and up-to-date synthesis of pharmacological options across major cardiovascular domains, with a specific focus on hypertension, heart failure, arrhythmias, and hypertrophic cardiomyopathy, conditions in which hemodynamic, neurohormonal, and electrophysiological pathways play central roles. We summarize mechanisms of action, clinical evidence, safety profiles, and guideline-based indications of established therapies, highlighting their relevance to vascular tone regulation, neurohormonal modulation, endothelial signaling, and myocardial function, the mechanistic axes that intersect with pathways implicated in pulmonary vascular disease (PVD). In addition, we discuss emerging therapeutic targets and innovative agents such as renin-angiotensin-aldosterone system silencers, endothelin pathway modulators, SGLT2 inhibitors, soluble guanylate cyclase stimulators, myosin inhibitors, and other mechanism-based approaches. Current challenges and unmet clinical needs are examined in the context of translational relevance for PVD and the broader goal of advancing individualized pharmacotherapy. Continued therapeutic innovation targeting shared vascular, metabolic, and neurohormonal pathways holds promise for improving outcomes across both systemic and pulmonary vascular diseases. Full article

(This article belongs to the Section Cardiovascular Disease)

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43 pages, 515 KB

Open AccessReview

Narrative Review of Digital Twins in the Health Domain: Development, Application, and Evidence Consolidation

by Daniele Giansanti and Claudia Cosenza

Med. Sci. 2026, 14(2), 330; https://doi.org/10.3390/medsci14020330 (registering DOI) - 18 Jun 2026

Viewed by 94

Abstract

Background: Digital twins and patient-specific computational models are emerging technologies in healthcare, enabling predictive, personalized, and adaptive interventions. Their integration with artificial intelligence (AI) facilitates the simulation of clinical scenarios, optimization of treatment strategies, and advancement of precision medicine. Despite growing interest, the [...] Read more.

Background: Digital twins and patient-specific computational models are emerging technologies in healthcare, enabling predictive, personalized, and adaptive interventions. Their integration with artificial intelligence (AI) facilitates the simulation of clinical scenarios, optimization of treatment strategies, and advancement of precision medicine. Despite growing interest, the evidence base is still evolving, highlighting the need for a comprehensive synthesis to identify current trends, applications, and gaps. Methods: A narrative review was conducted using PubMed, Web of Science, and Scopus to identify relevant literature on digital twins in healthcare. Priority was given to systematic reviews and meta-analyses in the selection process. From this process, 28 studies were selected for in-depth analysis, and their findings were complemented by primary research and conceptual, and synthesized evidence to capture emerging trends and real-world applications. Results and Discussion: The analysis revealed that digital twins are increasingly applied for patient-specific monitoring, predictive simulations, and adaptive interventions. Integration with AI enhances their ability to model complex clinical scenarios and support precision medicine. While the selected systematic reviews provide consolidated evidence of established applications, the complementary analysis indicates that these studies actively contribute to stabilizing clinical evidence, consolidating knowledge, and enabling the development of more robust patient-specific strategies. Conclusions: Digital twins are progressively shaping patient-centered healthcare by combining AI-driven simulations with clinical insights. Current research is not only consolidating existing evidence but also exploring novel applications, underscoring the potential of digital twins to enhance precision medicine. Further studies are required to fully integrate these technologies into routine clinical practice. Full article

(This article belongs to the Section Translational Medicine)

12 pages, 2031 KB

Open AccessArticle

Cardiometabolic and RAAS-Targeted Therapy in Thoracic Aortic Aneurysm: Propensity-Matched Associations with Survival and Major Cardiovascular Events

by Hussein Abdul Nabi, Luke Dreher, Soad Al Osta and Fadi E. Shamoun

Med. Sci. 2026, 14(2), 329; https://doi.org/10.3390/medsci14020329 - 18 Jun 2026

Viewed by 125

Abstract

Background: Thoracic aortic aneurysm (TAA) remains a high-risk vascular condition despite major advances in imaging surveillance, operative repair, and endovascular therapy. Medical management still relies largely on blood pressure control and global cardiovascular risk reduction. Renin–angiotensin–aldosterone system (RAAS) inhibitors are frequently used in [...] Read more.

Background: Thoracic aortic aneurysm (TAA) remains a high-risk vascular condition despite major advances in imaging surveillance, operative repair, and endovascular therapy. Medical management still relies largely on blood pressure control and global cardiovascular risk reduction. Renin–angiotensin–aldosterone system (RAAS) inhibitors are frequently used in TAA, but contemporary data evaluating survival and cardiovascular outcomes in broad TAA populations are limited. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) have established cardiometabolic benefits, yet their role in TAA has not been well defined. Methods: We performed a retrospective multicenter cohort study of adults with imaging-confirmed TAA diagnosed between 1 January 2018 and 1 January 2026 using a Mayo Clinic electronic data platform encompassing more than 15 million patient records. Primary exposures were documented use of RAAS inhibitors, GLP-1 RAs, and SGLT2 inhibitors, evaluated individually and in prespecified combination-therapy analyses. Propensity score matching was used to balance demographics, comorbidities, aortic procedural history, and concomitant cardiovascular medications. Primary outcomes were all-cause mortality and major adverse cardiovascular events (MACE) through 60 months. Results: The study included 162,126 patients with TAA. After matching, RAAS inhibitor use was associated with higher 60-month overall survival (88.3% vs. 85.5%; hazard ratio [HR], 0.79; 95% CI, 0.76–0.83; p < 0.001) and MACE-free survival (86.1% vs. 84.2%; HR, 0.87; 95% CI, 0.83–0.91; p < 0.001). GLP-1 RA therapy was associated with higher overall survival (97.5% vs. 92.5%; HR, 0.32; 95% CI, 0.27–0.38; p < 0.001) and MACE-free survival (93.2% vs. 89.3%; HR, 0.62; 95% CI, 0.56–0.70; p < 0.001). SGLT2 inhibitor therapy was similarly associated with higher overall survival (89.8% vs. 81.5%; HR, 0.51; 95% CI, 0.47–0.54; p < 0.001) and MACE-free survival (86.3% vs. 79.1%; HR, 0.62; 95% CI, 0.58–0.66; p < 0.001). Combination therapy with RAAS inhibitors plus either GLP-1 RAs or SGLT2 inhibitors was associated with incremental improvements in overall survival and MACE-free survival compared with GLP-1 RA or SGLT2 inhibitor monotherapy. Conclusions: In this large propensity-matched TAA cohort, RAAS inhibitors, GLP-1 RAs, and SGLT2 inhibitors were each associated with improved survival and fewer major cardiovascular events, with additional benefit observed for RAAS-based combination therapy. These findings support further prospective investigation of integrated cardiometabolic and vascular-targeted therapy in TAA, while underscoring that observational associations should not be interpreted as proof of aneurysm-specific disease modification. Full article

(This article belongs to the Section Cardiovascular Disease)

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14 pages, 347 KB

Open AccessArticle

Effects of Sodium–Glucose Cotransporter-2 Inhibitors on Anemia in Patients with Chronic Kidney Disease: A Pre–Post Observational Analysis

by Selena Gajić, Filip Simović, Ana Bontić, Aleksandra Kezić, Milorad Stojadinović, Svetozar Mijušković, Jelena Pavlović, Vidna Karadžić Ristanović, Verica Stanković Popović, Dušan Vićentijević, Milija Bjeličić, Kristina Petrović, Ivana Mrđa, Kristina Filić, Saddam Shawamri, Sanja Stanković and Marko Baralić

Med. Sci. 2026, 14(2), 328; https://doi.org/10.3390/medsci14020328 - 17 Jun 2026

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Abstract

Background and Objectives: Anemia is a common complication of chronic kidney disease (CKD) and is associated with reduced quality of life, accelerated disease progression, and increased cardiovascular risk. Sodium–glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated significant renal and cardiovascular benefits, and clinical trials [...] Read more.

Background and Objectives: Anemia is a common complication of chronic kidney disease (CKD) and is associated with reduced quality of life, accelerated disease progression, and increased cardiovascular risk. Sodium–glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated significant renal and cardiovascular benefits, and clinical trials have reported improvements in hematologic parameters during treatment. However, real-world evidence regarding their longitudinal effects on hemoglobin (Hb) and iron metabolism in patients with CKD remains limited. Materials and Methods: We conducted a pre–post analysis of 118 adult patients with CKD stages 1–4 treated with SGLT2is (empagliflozin or dapagliflozin) at the University Clinical Center of Serbia between January 2024 and June 2025. Patients received either agent at 10 mg once daily for 18 months. Hb, ferritin, C-reactive protein (CRP), albumin (Alb), daily proteinuria (Prt), and estimated glomerular filtration rate (eGFR) were assessed at baseline and at 18 months. Ferritin was adjusted for inflammatory and nutritional status using a residualization model incorporating CRP and Alb. Changes between the two time points were analyzed using repeated-measures general linear models (GLMs). Results: In unadjusted analyses, mean Hb increased modestly from 136.5 ± 17.9 g/L at baseline to 138.8 ± 18.9 g/L at follow-up (p = 0.028), while median ferritin decreased from 102.2 µg/L to 89.9 µg/L (p = 0.011). After adjustment for CRP and Alb, ferritin levels remained unchanged (p = 0.752). Repeated-measures analyses showed no significant longitudinal effect of time on Hb or ferritin and no significant interaction between time and SGLT2i type. Baseline eGFR, Prt, sex, and baseline ferritin significantly influenced longitudinal hematologic trajectories. Conclusions: SGLT2i therapy was associated with modest increases in Hb levels over 18 months, while inflammatory status remained stable and no significant reduction in ferritin levels was observed after adjustment for inflammatory and nutritional factors. Longitudinal Hb and ferritin trajectories did not differ significantly between empagliflozin and dapagliflozin, while baseline kidney function, Prt, iron status, and sex significantly influenced hematologic outcomes. Although causal inference is limited by the absence of a control group, these findings suggest a possible favorable effect of SGLT2is on anemia-related parameters in patients with CKD. Full article

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15 pages, 556 KB

Open AccessArticle

Converting a Cough Counter into a Cough Monitor: A Way Forward?

by Albertus C. den Brinker, Michael G. Crooks and Alyn H. Morice

Med. Sci. 2026, 14(2), 327; https://doi.org/10.3390/medsci14020327 - 17 Jun 2026

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Abstract

Background/Objective: To identify respiratory pathology, automated cough counting is frequently proposed. A trial validating an early warning system for exacerbations in chronic obstructive pulmonary disease (COPD) patients was recently concluded successfully. This paper aims to review the critical design choices for converting [...] Read more.

Background/Objective: To identify respiratory pathology, automated cough counting is frequently proposed. A trial validating an early warning system for exacerbations in chronic obstructive pulmonary disease (COPD) patients was recently concluded successfully. This paper aims to review the critical design choices for converting a cough counter into a patient-friendly continual cough monitor. Furthermore, it provides a basis for a practical reliability metric for continual cough monitoring. Methods: Design choices made in the development of a cough-based alert mechanism called XACT are discussed. A practical approach for reliability assessment is outlined based on cough counts, day-to-day variation and specificity data. Results: In post hoc analysis, it is shown that the described approach enables differentiation between high-quality cough estimates and less reliable data. The approach is used to underpin an earlier cohort subdivision into patients with and without increased cough during exacerbation. Conclusions: The validated alert mechanism has various patient-oriented design choices (unobtrusiveness, privacy-preserving). The examples illustrate how to screen for potential issues in automated cough count data without resorting to laborious annotation. It creates a practical basis for confidence metrics of medical inferences made from cough data, e.g., exacerbation forecasts. The proposed concepts need further validation. Full article

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18 pages, 834 KB

Open AccessArticle

Severity of Acute Drug Poisonings Treated in the Pediatric Emergency Department of a Hospital in Western Mexico

by Ruth Yesica Ramos-Gutiérrez, Mireya Robledo-Aceves, Santiago José Guevara-Martínez, Nelson Bruno de Almeida-Cunha, Raymundo Escutia-Gutiérrez, Martin Zermeño-Ruiz, Karla Valeria Díaz-Rivera, Ángel Abad Del Río-Chávez, César Ricardo Cortez-Álvarez, Alfredo Fernando Cortez-Martínez, Damian Fierros-Uribe, Héctor Andrés González-Ruiz and Rebeca Escutia-Gutiérrez

Med. Sci. 2026, 14(2), 326; https://doi.org/10.3390/medsci14020326 - 17 Jun 2026

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Abstract

Background: Acute drug poisoning is one of the leading causes of admission to pediatric emergency departments and represents a significant public health concern because of its potential severity and associated morbidity and mortality. This study aimed to describe the clinical, epidemiological, and severity [...] Read more.

Background: Acute drug poisoning is one of the leading causes of admission to pediatric emergency departments and represents a significant public health concern because of its potential severity and associated morbidity and mortality. This study aimed to describe the clinical, epidemiological, and severity characteristics of pediatric patients with acute drug poisoning treated at a tertiary care hospital in western Mexico. Methods: A retrospective, observational, descriptive study was conducted in the pediatric emergency department of Nuevo Hospital Civil de Guadalajara “Dr. Juan I. Menchaca” from January 2016 to December 2024. Results: The mean age of the patients was 77.1 months, with a predominance of females (61.9%). Most poisoning events (97.1%) occurred in the home. Accidental poisoning was the most frequent mechanism (54.5%), followed by suicide attempts (24.4%) and drug overdoses (17.6%). Regarding medical care, 50% of patients arrived at the emergency department within the first four hours after exposure, and 55.1% had a hospital stay of less than 12 h. The most involved drug groups were anxiolytics, mainly benzodiazepines (21.6%), followed by polypharmacy (17.6%) and antiemetic use (13.6%). The most frequent toxidrome was hypnotic–sedative syndrome (42.6% of cases). Multivariate analysis showed that exposure to anticonvulsants was significantly associated with a longer hospital stay (odds ratio [OR] = 7.31, p = 0.003). Most cases were classified as mild according to the Poisoning Severity Score, and no deaths were reported. Conclusions: Although pediatric drug poisoning generally has a favorable prognosis, it remains a significant public health issue. These findings highlight the need for targeted preventive strategies, including caregiver education, safe medication storage at home, and increased awareness and training programs for both families and healthcare professionals. Full article

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31 pages, 2294 KB

Open AccessReview

c-Myc-Induced Therapy Resistance in Leukemia: Mechanisms and Emerging Therapeutic Opportunities

by Ali Rafat, Javad Arabpour, Haniye Yarahmadi, Hediye Khalkhali, Zeinab Mazloumi, Seyyede Sepide Ashraf Moosavi, Hossein Kalarestaghi, Khadijeh Dizaji Asl and Reza Nejati

Med. Sci. 2026, 14(2), 325; https://doi.org/10.3390/medsci14020325 - 16 Jun 2026

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Abstract

Dysregulation of the c-Myc oncogene is a pivotal event in leukemia pathogenesis and therapy resistance. This review synthesizes current evidence, illustrating that c-Myc drives leukemogenesis by enhancing proliferation, inhibiting apoptosis, and upregulating immune checkpoints like PD-L1. Its overexpression is linked to poor treatment [...] Read more.

Dysregulation of the c-Myc oncogene is a pivotal event in leukemia pathogenesis and therapy resistance. This review synthesizes current evidence, illustrating that c-Myc drives leukemogenesis by enhancing proliferation, inhibiting apoptosis, and upregulating immune checkpoints like PD-L1. Its overexpression is linked to poor treatment outcomes across various leukemia subtypes. Directly targeting c-Myc remains challenging; however, indirect epigenetic modifiers (BET inhibitors), transcriptional disruption (CDK9 inhibitors), and combination therapies emerge as promising strategies to suppress its oncogenic activity and overcome resistance, paving the way for improved clinical management. Full article

(This article belongs to the Special Issue Insights into the Modern Landscape of Cancer Therapeutics)

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13 pages, 715 KB

Open AccessArticle

Glycemic Patterns Revealed by Continuous Glucose Monitoring in Patients with Type 2 Diabetes Undergoing Intermittent Hemodialysis: A Pilot Study

by Miguel Angel Cuevas-Budhart, Joel Salvador Becerra-Barrera, Rogelio Iván Silva-Rueda, Daniela Vallejo-Avalos, Maricruz Ponce-Villavicencio, María Begoña Ilabaca Avendaño, Marcela Ávila-Díaz and Ramón Paniagua

Med. Sci. 2026, 14(2), 324; https://doi.org/10.3390/medsci14020324 - 16 Jun 2026

Viewed by 180

Abstract

Introduction: Glycemic control in patients with type 2 diabetes mellitus undergoing intermittent hemodialysis represents a clinical challenge. The pathophysiological alterations inherent to chronic kidney disease (CKD) and the dialysis procedure limit the usefulness of traditional metrics. In this context, continuous glucose monitoring (CGM) [...] Read more.

Introduction: Glycemic control in patients with type 2 diabetes mellitus undergoing intermittent hemodialysis represents a clinical challenge. The pathophysiological alterations inherent to chronic kidney disease (CKD) and the dialysis procedure limit the usefulness of traditional metrics. In this context, continuous glucose monitoring (CGM) enables dynamic assessment of glycemic profiles and can reveal patterns of dysglycemia that go undetected in routine clinical practice. Methods: An observational, cross-sectional, and analytical pilot study involved 10 patients from the hemodialysis (HD) unit. CGM was carried out for 14 days. A paired analysis was performed to compare glycemic parameters on days with and without HD. Statistical evaluation was performed using the Shapiro–Wilk test and Student’s t-test; a p-value < 0.05 indicated statistical significance. Results: Time in range (TIR) showed considerable interindividual variability (24–100%), with hyperglycemia being the predominant factor. During HD sessions, glucose levels showed a marked intradialytic decline followed by incomplete post-dialysis recovery, a pattern that differed from non-dialysis days (paired t-test, p < 0.001; n = 10 paired observations). These findings should be interpreted as exploratory. Hypoglycemic episodes were infrequent, whereas persistent hyperglycemia prevailed. Conclusions: CGM reveals metabolic dysregulation frequently overlooked by traditional indicators such as glycated hemoglobin (HbA1c). These exploratory findings suggest that CGM may provide clinically relevant information in this population, although larger studies are needed before therapeutic recommendations can be established. Full article

(This article belongs to the Section Nephrology and Urology)

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19 pages, 1469 KB

Open AccessSystematic Review

Terahertz Imaging for Breast Cancer Detection in Animal Models: A Literature Review with Narrative Synthesis

by Maria Elena Niţă, Daniela Roxana Matasariu, Mioara Calipsoana Matei, Ana Cazacu, Bogdan Ionel Tamba, Delia Ciobanu Apostol, Cătălin Borcia, Cristina Mariana Uritu, Mitica Ciorpac, Alexandra Ursache, Cristina Elena Mandici, Cristina David, Radu Dănilă, Mihaela Baican, Vlad Ghizdovăț, Irena Cristina Grierosu and Cipriana Ștefănescu

Med. Sci. 2026, 14(2), 323; https://doi.org/10.3390/medsci14020323 - 15 Jun 2026

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Abstract

Background and Objectives: Breast cancer remains one of the most common malignancies worldwide, and early detection plays a crucial role in improving treatment outcomes and reducing mortality. Several experimental studies using animal models of breast cancer have explored the potential of terahertz-based technologies [...] Read more.

Background and Objectives: Breast cancer remains one of the most common malignancies worldwide, and early detection plays a crucial role in improving treatment outcomes and reducing mortality. Several experimental studies using animal models of breast cancer have explored the potential of terahertz-based technologies in this field. However, their preclinical evidence base in breast cancer remains heterogeneous and has not been systematically synthesized with a focus on experimental models, imaging protocols, and barriers to translation. Methods: We conducted a descriptive systematic review, according to PRISMA guidelines, of 10 articles selected from a total of 372 identified across four databases—PubMed, Embase, Web of Science, and Cochrane—regarding the diagnostic performance of terahertz (THz) imaging in breast cancer animal models. We included studies that used rodent models diagnosed with breast cancer, subsequently confirmed through histological examination, and extracted relevant data. Results: The results were synthesized using a narrative approach. Most studies used C57BL/6J mice with E0771 cell line-induced breast tumors, with histopathology as the reference standard. In the reflection mode, at frequencies between 0.1 and 4 THz, the identification of tumoral, fibrous, fat, and muscle tissues was possible. Conclusions: Overall, the available preclinical evidence supports THz imaging as a promising proof-of-concept approach for breast tissue characterization, but not yet as a standardized or clinically translatable diagnostic platform. Future studies should use harmonized animal models, standardized acquisition and specimen-handling protocols, transparent reporting of classification workflows, and consistent outcome metrics to enable comparison across studies and to clarify the biological and biophysical determinants of THz contrast in breast cancer. Full article

(This article belongs to the Section Cancer and Cancer-Related Research)

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20 pages, 695 KB

Open AccessReview

A Structured Review of Deep Learning Approaches and Image-Preprocessing Techniques for Automated Contact Allergy Patch Test Interpretation

by Dominyka Stragyte, Gvidas Mikalauskas, Katrina Gaidulevic, Renata Paukstaitiene, Kestutis Stasaitis, Vidas Raudonis and Skaidra Valiukeviciene

Med. Sci. 2026, 14(2), 322; https://doi.org/10.3390/medsci14020322 - 15 Jun 2026

Viewed by 104

Abstract

Background: Allergic contact dermatitis (ACD) is a common inflammatory skin disease and patch testing (PT) remains the gold standard for its diagnosis; however, PT interpretation is time-consuming and prone to inter-observer variability. Growing advances in digital imaging and artificial intelligence (AI) have [...] Read more.

Background: Allergic contact dermatitis (ACD) is a common inflammatory skin disease and patch testing (PT) remains the gold standard for its diagnosis; however, PT interpretation is time-consuming and prone to inter-observer variability. Growing advances in digital imaging and artificial intelligence (AI) have encouraged the development of automated PT evaluation systems. This review aimed to summarize the use of deep learning networks (DNNs) and image-preprocessing techniques for PT classification. Methods: A literature review was conducted to identify original research published between 2020 and 2025 that applied deep learning algorithms to PT image analysis. Included studies were assessed with respect to model architecture, dataset characteristics, preprocessing strategies, and diagnostic performance. Results: Six original studies employing deep learning for PT image classification met the inclusion criteria. They employed a range of architectures, including YOLOv5x, EfficientNetB0, Xception, and custom CNN models. Reported diagnostic performance varied, with accuracy values ranging from 90% to 99.5%, F1-scores from 0.37 to 0.98, and AUROC values up to 0.94. Despite promising results, models remain unreliable for ICDRG grading, especially for severe reactions, and methodological variability in dataset composition, imaging conditions, preprocessing pipelines, and classification tasks limits comparability across studies. Conclusions: Deep learning shows promise for automated PT interpretation, but further standardized and multicenter studies with detailed preprocessing protocols and comprehensive ICDRG grading are required for clinical implementation. Full article

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18 pages, 719 KB

Open AccessReview

Nurse-Led Digital Interventions for Patients with Multiple Sclerosis: A Scoping Review

by Gianluca Azzellino, Patrizia Vagnarelli, Luca Mengoli, Ernesto Aitella, Mauro Passamonti, Lia Ginaldi and Massimo De Martinis

Med. Sci. 2026, 14(2), 321; https://doi.org/10.3390/medsci14020321 - 15 Jun 2026

Viewed by 201

Abstract

Background: Multiple sclerosis (MS) is a condition that requires long-term, multidisciplinary management. The growing digital transformation in healthcare has highlighted the central role of nurses in supporting key aspects such as patient self-management, continuity of (at home) care, and patient empowerment. However, evidence [...] Read more.

Background: Multiple sclerosis (MS) is a condition that requires long-term, multidisciplinary management. The growing digital transformation in healthcare has highlighted the central role of nurses in supporting key aspects such as patient self-management, continuity of (at home) care, and patient empowerment. However, evidence on nurse-led digital interventions in MS remains fragmented. Objective: To map the available literature on nurse-led digital interventions in MS, focusing on the role of nurses, clinical outcomes, and research gaps. Methods: The review was conducted using the methodological framework of the Joanna Briggs Institute (JBI) and the PRISMA-ScR checklist. A systematic search was performed in PubMed, Scopus, Web of Science, and CINAHL. Studies were included if they described digital or telehealth interventions led or coordinated by nurses in patients with MS. Results: A total of 12 studies published between 2015 and 2025 met the inclusion criteria. Four main thematic areas were identified: (1) telenursing and empowerment-based interventions; (2) mobile and web-based patient self-management programs; (3) digital systems for monitoring and integrated care pathways; and (4) digital interventions targeting symptom management and psychosocial outcomes. Across the studies, nurse-led digital interventions were associated with improvements in self-management, treatment adherence, self-efficacy, and health-promoting behaviors. Positive effects were also reported on clinical outcomes such as fatigue, sleep quality, and balance, as well as on psychosocial variables including quality of life, coping strategies, and emotional well-being. Furthermore, the identified systems, in general, contributed to enhanced continuity of care, patient engagement, and organizational efficiency. Conclusions: Nurse-led digital interventions represent a promising approach in the management of patients with multiple sclerosis, supporting both clinical and psychosocial outcomes while enhancing continuity of care. However, the current evidence base remains limited by small sample sizes, heterogeneity of interventions, and short follow-up periods. Future research should prioritize multicenter randomized studies with larger samples and long-term follow-up to strengthen the evidence. Additionally, the integration of digital interventions into routine clinical practice, along with targeted training for nurses, is essential to ensure sustainability, accessibility, and equitable implementation. Further studies should also explore cost-effectiveness and the impact on caregivers and long-term quality of life. Full article

(This article belongs to the Section Nursing Research)

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19 pages, 829 KB

Open AccessReview

Muscle Tone Regulation and Bruxism in Chronic Stress: Pathophysiological Links to Tooth Fractures and Dental Hard Tissue Pathology

by Valekh Ashyrov, Maria Blagodatskikh, Olga Panferova, Irina Vineyard, Lucas Alves Sarmento Pires, Tatiana Zharikova, André Pontes-Silva and Yury Zharikov

Med. Sci. 2026, 14(2), 320; https://doi.org/10.3390/medsci14020320 - 15 Jun 2026

Viewed by 319

Abstract

Anxiety disorders and chronic stress are the most common types of mental disorder. According to the WHO, more than 359 million people worldwide suffered from these conditions in 2021. The function of mastication and the masticatory muscles undergo significant changes under the influence [...] Read more.

Anxiety disorders and chronic stress are the most common types of mental disorder. According to the WHO, more than 359 million people worldwide suffered from these conditions in 2021. The function of mastication and the masticatory muscles undergo significant changes under the influence of a disturbed psychoemotional state. This manifests as their parafunctional activity, accompanied by increased tone and damage to elements of the dentofacial system, including increased tooth wear, chipping, cracks, and fractures. Attention to this problem is growing annually among researchers in both dental and neurological fields. This is evidenced by a wide range of therapeutic and preventive interventions aimed at correcting chronic stress, muscle hypertonia, and pathology of the dentofacial system. Despite the aforementioned measures, it is often only possible to slow down the pathological process rather than completely resolve it. This is because knowledge regarding the biology and pathophysiology of how chronic stress affects muscle activity remains limited. Understanding such mechanisms and establishing precise interrelationships could help identify targets for effective therapeutic interventions and eliminate the problem. This review of the literature systematizes information on how chronic stress and various autonomic stimuli affect changes in the functional activity of the masticatory muscles and the pathology of hard dental tissues. Full article

(This article belongs to the Topic Integrative Clinical and Translational Advances in Rehabilitation Medicine: From Mechanisms to Population Health)

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24 pages, 3604 KB

Open AccessArticle

From Species Identification to Empirical Therapy: A Machine Learning and Rule-Based Decision Support Framework for Antifungal Resistance Prediction in ICU Candida Infections

by Madalina (Preda) Solomon, Beatrice Mahler, Lia-Mara Ditu, Oana Popescu, Corina-Aurelia Zugravu and Loredana Sabina Cornelia Manolescu

Med. Sci. 2026, 14(2), 319; https://doi.org/10.3390/medsci14020319 - 15 Jun 2026

Viewed by 226

Abstract

Objectives: When a Candida species is identified in an ICU patient, susceptibility results are typically available in 24–72 h. In this study, we built a machine learning model using four variables available at identification to estimate resistance probability in real time. Methods [...] Read more.

Objectives: When a Candida species is identified in an ICU patient, susceptibility results are typically available in 24–72 h. In this study, we built a machine learning model using four variables available at identification to estimate resistance probability in real time. Methods: We analysed 747 fungal isolates from 725 ICU patients (January 2021–March 2026). We trained and compared a Random Forest and a Logistic Regression model, evaluating both with temporal cross-validation, permutation feature importance, three-category (S/I/R) prediction, and calibration analysis. Results: Multidrug resistance doubled from 24.5% (2021) to 51.1% (2025), and Candida auris grew eight-fold in three years. Random Forest reached AUC 0.885 on the held-out test set and 0.848 on prospective 2024–2025 data (Brier score 0.093). Species identity and drug choice together explained 87% of predictive signal. Local C. albicans fluconazole resistance (~16%) far exceeded the ECMM European figure of 0%, and C. krusei was four times more prevalent than the continental average. Conclusions: A four-variable model may provide calibrated resistance estimates during the critical gap before susceptibility results return, though performance reflects predominantly deterministic species–drug patterns rather than complex learned biology. Overall performance was comparable to a rule-based lookup table, confirming that the majority of predictive signal derives from established species–drug susceptibility patterns. Meaningful added value is limited to temporal trend tracking and improved prediction where resistance is acquired rather than intrinsic (C. albicans, C. tropicalis hard-subset AUC 0.929 vs. rule-based 0.899). The model complements a local antifungal testing; it does not replace one. Full article

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

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17 pages, 1636 KB

Open AccessArticle

Epidemiological Profile of Pediatric Patients with Acute Lymphoblastic Leukemia Admitted to Four Hospitals in Curitiba, Southern Brazil

by Regiane Nogueira Spalanzani, Liana Alves de Oliveira, Sara Cristina Lobo-Alves, Thaís Muniz Vasconcelos, Luiza Souza Rodrigues, Damaris Krul, Adriele Celine Siqueira, Curitiba Transcriptomics and Microbiomics ALL Consortium, Roberto Rosati, Libera Maria Dalla-Costa and Lorena Bavia

Med. Sci. 2026, 14(2), 318; https://doi.org/10.3390/medsci14020318 - 15 Jun 2026

Viewed by 197

Abstract

Background/Objectives: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Understanding its epidemiological characteristics is essential for guiding public health strategies. In this study, we characterized the epidemiological profiles that may contribute to the risk of ALL in children in southern Brazil. [...] Read more.

Background/Objectives: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Understanding its epidemiological characteristics is essential for guiding public health strategies. In this study, we characterized the epidemiological profiles that may contribute to the risk of ALL in children in southern Brazil. Methods: Clinical and epidemiological data from 71 children (1–15 years old) admitted and newly diagnosed with ALL at four hospitals in Curitiba, Paraná, Brazil, were retrieved and analyzed. Results: Among the 71 children with ALL, the majority were male (n = 43, 60.6%), with an age range of 1–3 years (n = 26, 36.6%), self-identified as White (n = 47, 66.2%), and were born in Paraná state (n = 61, 85.9%). Nearly half had a family history of cancer (n = 33, 46.5%), primarily among grandparents (n = 36, 61%). Parental environmental exposures included smoking (n = 30, 42.3%) and occupational exposure to chemicals or radiation (n = 17, 23.9%). At diagnosis, most patients (n = 43, 60.5%) had a bone marrow blast count > 70%, and 27 patients (38%) had a peripheral blood blast count > 70%. B-cell ALL was the predominant subtype (n = 61, 85.9%). In B-cell ALL cases, the most frequent molecular subtype was high hyperdiploidy (n = 17, 23.9%). White blood cell counts differed significantly between the B-cell ALL and T-cell ALL groups (p = 0.029). Conclusions: Our findings provide insights into ALL epidemiology in southern Brazil and highlight regional differences across the country. Full article

(This article belongs to the Section Cancer and Cancer-Related Research)

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20 pages, 1012 KB

Open AccessReview

The Effectiveness of NIRS-Based Wearable Devices in Estimating Physical Activity Intensity in Patients with Chronic Non-Communicable Diseases: A Structured Narrative Review

by Raúl Caulier-Cisterna, Andrés Vega-Moraga, Daniel Ramos-López and Felipe Contreras-Briceño

Med. Sci. 2026, 14(2), 317; https://doi.org/10.3390/medsci14020317 - 15 Jun 2026

Viewed by 202

Abstract

Background: Near-infrared spectroscopy (NIRS)-based wearable devices offer non-invasive, continuous monitoring of muscle oxygenation, providing direct microvascular and metabolic information that complements indirect indices of intensity such as heart rate and accelerometry. Their clinical applicability in chronic non-communicable diseases (NCDs) remains under active [...] Read more.

Background: Near-infrared spectroscopy (NIRS)-based wearable devices offer non-invasive, continuous monitoring of muscle oxygenation, providing direct microvascular and metabolic information that complements indirect indices of intensity such as heart rate and accelerometry. Their clinical applicability in chronic non-communicable diseases (NCDs) remains under active development. Methods: A structured narrative review was conducted in PubMed, Scopus, Web of Science, and IEEE Xplore (January 2010–January 2026) using pre-specified search strings combining NIRS, muscle oxygenation, SmO₂, StO₂, wearable, exercise intensity, ventilatory/lactate threshold, and individual chronic disease terms. Eligible studies addressed technical validation of wearable NIRS, NIRS-derived exercise intensity estimation, clinical applications in NCDs, or rehabilitation implementation. Evidence was synthesized thematically; quality of validation studies was appraised against AMSTAR-2-informed, COSMIN-informed, or Cochrane RoB-2 criteria. Results: Wearable continuous-wave NIRS shows acceptable concurrent validity with frequency-domain laboratory systems (r = 0.79; range 0.69–0.88; ±8% SmO₂ agreement in 95% of measurements) and good test–retest reliability for moderate-to-severe domains (ICC 0.72–0.91). NIRS-derived breakpoints align more reliably with the second ventilatory/lactate threshold (ICC = 0.80) than with the first (ICC = 0.53), constraining its use for prescribing lower-intensity domains. In chronic obstructive pulmonary disease, peripheral arterial disease, chronic respiratory failure and selected cardiovascular conditions, wearable NIRS detects disease-specific patterns of muscle deoxygenation and post-exercise reoxygenation that track responses to rehabilitation. Conclusions: Current evidence supports wearable NIRS as a complementary, intensity-aware monitoring tool—particularly for delineating the heavy/severe-intensity boundary and detecting peripheral metabolic limitations—rather than as a stand-alone replacement for ventilatory or lactate thresholds. Because much of the evidence derives from small, single-sex or athlete-only cohorts, these findings should be regarded as a promising basis requiring further validation in broader NCD populations. Implementation in NCDs requires standardized placement and calibration protocols, sex- and body composition-stratified reference values, motion-artifact mitigation, and adequately powered longitudinal trials in clinical populations. Full article

(This article belongs to the Topic Integrative Clinical and Translational Advances in Rehabilitation Medicine: From Mechanisms to Population Health)

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13 pages, 3644 KB

Open AccessArticle

Mesenchymal Stem Cells Enhance Colonic Anastomotic Repair Through Augmented Collagen Deposition and Decreased Inflammation in a Rat Model

by Alexandra Caziuc, Emoke Pall, Andras-Laszlo Nagy, David Andras, Oana Antal, Radu Alexandru Ilies, Lorena Maria Hantig, Aurel Mironiuc and George Calin Dindelegan

Med. Sci. 2026, 14(2), 316; https://doi.org/10.3390/medsci14020316 - 14 Jun 2026

Viewed by 144

Abstract

Background/Objectives: Mesenchymal stem cells (MSCs), due to their regenerative and multipotent properties, have emerged as promising therapeutic agents in tissue repair and regeneration. These biological characteristics might contribute to optimized anastomotic healing and to a reduction in postoperative complications following digestive surgery. [...] Read more.

Background/Objectives: Mesenchymal stem cells (MSCs), due to their regenerative and multipotent properties, have emerged as promising therapeutic agents in tissue repair and regeneration. These biological characteristics might contribute to optimized anastomotic healing and to a reduction in postoperative complications following digestive surgery. The present study aimed to evaluate whether intraperitoneal or perianastomotic administration of MSCs provides superior healing outcomes in colonic anastomoses in Wistar rats. Methods: MSCs were isolated from inguinal adipose tissue harvested from 2 Wistar rats. Thirty male Wistar rats were allocated to 3 groups: (i) the control group, with regular anastomosis, (ii) peri-anastomotic injection of MSCs, and (iii) intraperitoneal injection of MSCs. The animals were sacrificed on postoperative day 14. The evaluated outcomes included clinical evolution, adhesion index, histological characteristics, and tissue hydroxyproline content. Results: The incidence of anastomotic leakage and the mortality rate were 0%. Therefore, the present study primarily demonstrates changes in surrogate markers of healing, including inflammatory response, collagen deposition, adhesion formation, and hydroxyproline content. The adhesion index was similar in the groups receiving MSC administration (p = 0.05); however, intraperitoneal administration demonstrated superior outcomes when compared to standard anastomosis in reducing adhesion formation (p = 0.002). Histopathological analysis showed a decreased inflammatory process and an increased collagen deposition at the anastomotic site following MSC administration (p < 0.05). Moreover, tissue hydroxyproline levels were significantly increased after both perianastomotic (0.831 ± 0.02, p < 0.05) and intraperitoneal (0.54 ± 0.02, p < 0.05) MSC administration compared with the control group (0.251 ± 0.006). Conclusions: These results suggest that MSC administration may improve histological and biochemical markers associated with colonic anastomotic healing in a non-ischemic experimental model. The experimental model used is suitable for further studies aimed at determining the optimal indications, routes of administration, and adjunctive agents that may potentiate the effects of MSCs. Full article

(This article belongs to the Section Translational Medicine)

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13 pages, 536 KB

Open AccessArticle

Diagnostic Performance of Multimodal Large Language Models for Central Venous Catheter Assessment Chest Radiographs in the Intensive Care Unit

by Christina-Chrysanthi Theocharidou, Zafeiris Tsinaris, Christos Karachristos, Anastasia Theocharidou, Michail Kourtidis, Kiriaki Papadopoulou, Athanasia-Marina Peristeri, Athanasios Astreinidis, Anna Simichanidou, Chrysavgi Giannaki, Myrto Tzimou, Evangelos Kaimakamis, Vasileios Voutsas, Vasiliki Soulountsi and Athina Lavrentieva

Med. Sci. 2026, 14(2), 315; https://doi.org/10.3390/medsci14020315 - 14 Jun 2026

Viewed by 210

Abstract

Background: Chest radiography remains central to post-procedural assessment of central venous catheter (CVC) placement in intensive care units. Multimodal large language models (MLLMs) can process medical images, but their reliability for practical radiography tasks remains uncertain. This study assessed the diagnostic performance of [...] Read more.

Background: Chest radiography remains central to post-procedural assessment of central venous catheter (CVC) placement in intensive care units. Multimodal large language models (MLLMs) can process medical images, but their reliability for practical radiography tasks remains uncertain. This study assessed the diagnostic performance of MLLMs and intensivists for CVC access classification, CVC tip assessment, and pneumothorax-related radiographic findings. Methods: In this retrospective diagnostic performance study, consecutive portable anteroposterior chest radiographs obtained after CVC placement in adult critically ill patients were independently evaluated by four intensivists and five MLLMs. A radiologist consensus served as the reference standard. Interobserver agreement and diagnostic performance were assessed using Fleiss’ kappa, Gwet AC1, Cohen’s kappa, accuracy, sensitivity, specificity, precision, F1 score, balanced accuracy, and Matthews correlation coefficient. Results: The final cohort included 183 unique radiographs. Intensivist reviewers showed high performance for CVC access classification but lower and more heterogeneous performance for CVC tip-position assessment. Among MLLMs, CVC access accuracy ranged from 0.339 to 0.874, whereas CVC tip assessment was dominated by almost universal classification of tips as appropriate, with near-zero specificity and chance-level balanced accuracy. For pneumothorax-related findings, all MLLMs classified every case as negative. Intensivist reviewers had higher balanced accuracy than MLLMs for CVC access classification (difference, 0.420; 95% CI, 0.349–0.490; p < 0.001) and CVC tip assessment (difference, 0.247; 95% CI, 0.205–0.290; p < 0.001). Pneumothorax analyses were exploratory because only five positive cases were present. Conclusions: The evaluated MLLMs showed unreliable diagnostic performance compared with experienced intensivists. Apparent performance was influenced by class imbalance and dominant-response behavior, supporting cautious task-specific validation and complete diagnostic performance reporting. Full article

(This article belongs to the Section Critical Care Medicine)

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11 pages, 694 KB

Open AccessArticle

County-Level Association Between Social Vulnerability and Rheumatoid Arthritis-Related Mortality in the United States

by Wan-Ying Lin, Yu-Che Lee, Abira A. Chowdhury, Linda M. Burns and Hsin-Yao Wang

Med. Sci. 2026, 14(2), 314; https://doi.org/10.3390/medsci14020314 - 12 Jun 2026

Viewed by 147

Abstract

Objectives: To evaluate associations between social vulnerability and rheumatoid arthritis (RA)-related mortality in the United States, with emphasis on domain-specific effects of the Social Vulnerability Index (SVI). Methods: We conducted a county-level ecological study of RA-related mortality from 2010 to 2019 using age-adjusted [...] Read more.

Objectives: To evaluate associations between social vulnerability and rheumatoid arthritis (RA)-related mortality in the United States, with emphasis on domain-specific effects of the Social Vulnerability Index (SVI). Methods: We conducted a county-level ecological study of RA-related mortality from 2010 to 2019 using age-adjusted mortality rates and the Centers for Disease Control and Prevention SVI. Gamma regression models examined associations between RA mortality and overall SVI and four thematic domains, including socioeconomic status, household composition and disability, minority status and language, housing type and transportation by using both continuous and quartile-based measures. Results: Between 2010 and 2019, 354,280 deaths occurred among individuals with RA, corresponding to a mean age-adjusted mortality rate of 9.7 per 100,000 population. In multivariable analyses adjusting for all SVI domains, household composition and disability vulnerability demonstrated the strongest and most consistent positive association with mortality, with a dose–response relationship across quartiles. Housing type and transportation vulnerability showed a modest positive association. Minority status and language vulnerability was inversely associated with mortality, whereas socioeconomic vulnerability was not significant in continuous models but demonstrated an inverse association with mortality in quartile-based analyses. Conclusions: RA mortality is differentially associated with specific domains of social vulnerability rather than overall vulnerability burden. Household composition and disability represent clinically salient risk factors, demonstrating the relevance of functional status and caregiving context in RA outcomes. Domain-specific assessment of social vulnerability may enhance clinical risk stratification and inform more targeted, patient-centered RA management. Full article

(This article belongs to the Section Translational Medicine)

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17 pages, 1598 KB

Open AccessArticle

Surviving Severe Obstetric Complications: A Population-Based Analysis of Maternal near Miss

by Ana Paula Jaqueline Crestani, Guilherme Welter Wendt, Caryna Eurich Mazur, Glaucia Osis Gonçalves, Aedra Carla Bufalo Kawassaki, Ana Paula Vieira, Camila Elizandra Rossi, Carolina Panis, Cleide Viviane Buzanello, Dalila Moter Benvegnú, Franciele Ani Caovilla Follador, Geraldo Emílio Vicentini, Gisele Arruda, Léia Carolina Lucio, Lirane Elize Defante Ferreto, Kérley Braga Pereira Bento Casaril, Mariana Abe Vicente Cavagnari and Claudiceia Risso Pascotto

Med. Sci. 2026, 14(2), 313; https://doi.org/10.3390/medsci14020313 (registering DOI) - 12 Jun 2026

Viewed by 165

Abstract

Background: Pregnancies tend to progress without any serious complications. Nonetheless, for a subset of women, obstetric complications may develop, ranging in severity. The most critical of these life-threatening events is referred to as Maternal Near Miss (MNM). To identify the epidemiological and obstetric [...] Read more.

Background: Pregnancies tend to progress without any serious complications. Nonetheless, for a subset of women, obstetric complications may develop, ranging in severity. The most critical of these life-threatening events is referred to as Maternal Near Miss (MNM). To identify the epidemiological and obstetric characteristics, as well as clinical outcomes of MNM cases reported over the year 2021 in the Brazilian state of Paraná. This quantitative, population-based study analyzed 888 notifications that occurred in 2021, obtained from the MNM Notification System. Descriptive statistics and a one-sample Chi-square goodness-of-fit test were applied to the data. Among the women reported, 92.6% were pregnant, the mean age was 29 years, 67.1% identified as white, and 45.2% had preexisting health conditions. Regarding obstetric characteristics, 41.6% were classified as high-risk pregnancies, but nearly one-third (32.3%) of MNM cases occurred in women initially classified as usual risk. The clinical worsening event occurred most frequently during the third trimester (71.9%), and emergency cesarean section was indicated in 60.1% of cases with complete information for this variable. Cesarean delivery predominated over vaginal delivery, with an emergency-to-elective cesarean ratio of approximately 4.7:1. Most women (75%) were discharged after recovery. MNM events are not restricted to women initially classified as high-risk, underscoring the need to strengthen early detection strategies and ensure appropriate management at all levels of care. Improved training of healthcare professionals responsible for reporting and the standardization of MNM monitoring systems in Brazil are also essential. Full article

(This article belongs to the Section Gynecology)

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14 pages, 600 KB

Open AccessArticle

Transcranial Direct Current Electric Stimulation Combined with Physical Exercise in Patients with Greater Trochanteric Pain Syndrome: Randomized Clinical Trial

by Eunice Fragoso Martins, Nicole Lie Okumura, Vívian Santos Xavier Silva, Ana Luiza Meneses de Oliveira, Cezar Sabino Pereira da Silva, Ana Clara Dias Pereira and Jean Marcos de Souza

Med. Sci. 2026, 14(2), 312; https://doi.org/10.3390/medsci14020312 - 12 Jun 2026

Viewed by 204

Abstract

Background/Objectives: Transcranial direct current stimulation (tDCS) has been explored as a strategy for pain management, but no study has investigated its use in Greater Trochanteric Pain Syndrome (GTPS). This study evaluated the effects of the combination of resistance exercises (REs) with tDCS on [...] Read more.

Background/Objectives: Transcranial direct current stimulation (tDCS) has been explored as a strategy for pain management, but no study has investigated its use in Greater Trochanteric Pain Syndrome (GTPS). This study evaluated the effects of the combination of resistance exercises (REs) with tDCS on pain, functionality, and quality of life in patients with GTPS. Methods: In this randomized, double-blind trial, adults with GTPS were allocated to receive tDCS with RE (intervention group, IG) or sham tDCS with RE (control group, CG). Supervised 20 min sessions occurred on four consecutive days. Anodal tDCS (2 mA) was applied over the primary motor cortex. The primary outcome was the VISA-G.BR score at day thirty. Secondary outcomes included pain, functionality, and quality of life at multiple time points, assessed by HAGOS, PQAS, McGill Pain Questionnaire, and SF-36. Results: Thirty patients were included. Both groups improved, but between-group differences were nonsignificant for the primary outcome (VISA-G.BR effect size, −0.16; 95% CI, −0.54 to 0.27; p = 0.460). Secondary outcomes followed a similar pattern. Conclusions: These findings reinforce the value of RE in GTPS while suggesting a limited role for short-term tDCS protocols. Future studies should investigate whether protocols involving a greater number of stimulation sessions may produce superior clinical effects. Full article

(This article belongs to the Topic Integrative Clinical and Translational Advances in Rehabilitation Medicine: From Mechanisms to Population Health)

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14 pages, 713 KB

Open AccessArticle

Evaluating the Role of Chemotherapy in Addition to Radiotherapy for High-Risk Merkel Cell Carcinoma

by Ronen Brenner, Hanna T. Frumin Edri, Amichay Meirovitz, Sabri El-Saied, Keren Rouvinov, Ilia Berezhnov, Anna Ievko, Sofiia Turaieva, Shlomit Fenig, Nashat Abu Yasin, Eyal Fenig, Samer Hussany, Noa Shani Shrem, Alexander Yakobson and Walid Shalata

Med. Sci. 2026, 14(2), 311; https://doi.org/10.3390/medsci14020311 - 12 Jun 2026

Viewed by 173

Abstract

Background: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine malignancy with a high risk of recurrence. While adjuvant radiotherapy is standard following surgical resection in high-risk disease, the additional benefit of platinum–etoposide chemotherapy and the prognostic role of tumor anatomical location remain [...] Read more.

Background: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine malignancy with a high risk of recurrence. While adjuvant radiotherapy is standard following surgical resection in high-risk disease, the additional benefit of platinum–etoposide chemotherapy and the prognostic role of tumor anatomical location remain uncertain. Methods: We conducted a multicenter retrospective cohort study including patients with high-risk MCC (stage IIB–III) treated with surgery followed by adjuvant radiotherapy with or without platinum–etoposide chemotherapy. Tumor sites were classified according to sun-exposure status. Disease-free survival (DFS) and overall survival (OS) were estimated using Kaplan–Meier methods and compared using the log-rank test, with subgroup analyses by anatomical region and stage. Results: A total of 103 patients were included, of whom 77 (74.8%) received adjuvant chemoradiotherapy and 26 (25.2%) received radiotherapy alone. Patients with non-sun-exposed tumors demonstrated longer survival outcomes than those with sun-exposed tumors, with a median DFS of 57 months versus 42 months (p = 0.15), and a median OS of 179 months versus 109 months (p = 0.054), respectively. Among patients with sun-exposed tumors, chemoradiotherapy was associated with numerically improved DFS (42 vs. 34 months; p = 0.051) and OS (128 vs. 98 months; p = 0.08) compared with radiotherapy alone. In patients with non-sun-exposed tumors, chemoradiotherapy demonstrated a more pronounced improvement in OS (178 vs. 56 months; p = 0.054), while DFS also favored combined treatment (49 vs. 78 months; p = 0.078). Conclusions: In this multicenter cohort, adjuvant chemotherapy did not demonstrate a uniform survival benefit overall but was associated with improved outcomes in head and neck MCC, suggesting a potential site-specific effect. Similar outcomes across stage III subgroups suggest that chemotherapy may mitigate stage-related prognostic differences. These findings support a selective approach to adjuvant chemotherapy and highlight the need for prospective studies incorporating modern immunotherapy strategies. Full article

(This article belongs to the Special Issue Insights into the Modern Landscape of Cancer Therapeutics)

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15 pages, 634 KB

Open AccessArticle

Comparative Prognostic Performance of CARWL and Naples Prognostic Score in Stage IIIC Non-Small Cell Lung Cancer Treated with Definitive Chemoradiotherapy

by Erkan Topkan, Duriye Ozturk and Ugur Selek

Med. Sci. 2026, 14(2), 310; https://doi.org/10.3390/medsci14020310 - 12 Jun 2026

Viewed by 181

Abstract

Background: Prognostic stratification remains challenging in patients with stage IIIC non-small cell lung cancer (NSCLC) treated with definitive chemoradiotherapy (CCRT), and the relative performance of host-related prognostic indices in this setting is unclear. The CARWL (C-reactive Protein, Albumin, and Recent Weight Loss) score [...] Read more.

Background: Prognostic stratification remains challenging in patients with stage IIIC non-small cell lung cancer (NSCLC) treated with definitive chemoradiotherapy (CCRT), and the relative performance of host-related prognostic indices in this setting is unclear. The CARWL (C-reactive Protein, Albumin, and Recent Weight Loss) score and the Naples prognostic score (NPS) have each been proposed as prognostic tools, but direct comparisons are lacking. This study compared their prognostic performance. Methods: We retrospectively analyzed 795 patients with stage IIIC NSCLC treated with CCRT between 2010 and 2020. Patients were stratified into three prognostic groups according to CARWL and NPS. Overall survival (OS) was the primary endpoint; progression-free survival (PFS) and locoregional PFS (LRPFS) were secondary endpoints. Survival was assessed using Kaplan–Meier analysis and Cox regression. Results: Both CARWL and NPS significantly stratified OS, PFS, and LRPFS (all p < 0.001). CARWL demonstrated modestly higher discriminatory performance across endpoints. The OS difference between unfavorable and favorable groups was larger with CARWL than with NPS (19.3 vs. 12.3 months). CARWL also provided greater separation for PFS (5.3 vs. 3.2 months) and LRPFS (4.9 vs. 3.4 months). In multivariable analyses, both indices retained independent prognostic significance; however, CARWL consistently exhibited stronger hazard gradients and maintained prognostic value when modeled alongside NPS. Conclusions: Both CARWL and NPS offered meaningful prognostic stratification in stage IIIC NSCLC treated with CCRT, but CARWL demonstrated a modest but more consistent prognostic discrimination than NPS. Pending external validation, CARWL represents a practical and biologically grounded tool for risk stratification in this population. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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17 pages, 13817 KB

Open AccessArticle

Persistence of Mortality-Dominant Pancreatitis Burden Despite Declining Rates, 1990–2023: An Analysis of the Global Burden of Disease 2023 Study

by Arkadeep Dhali, Ali Shan Hafeez, Dushyant Singh Dahiya and Saikat Mandal

Med. Sci. 2026, 14(2), 309; https://doi.org/10.3390/medsci14020309 - 12 Jun 2026

Viewed by 202

Abstract

Background: Whether the fatal and non-fatal composition of aggregate pancreatitis burden has changed over time remains unclear. We assessed long-term changes in the fatal-to-non-fatal composition of aggregate pancreatitis burden using Global Burden of Disease (GBD) 2023 estimates. Methods: We conducted a systematic descriptive [...] Read more.

Background: Whether the fatal and non-fatal composition of aggregate pancreatitis burden has changed over time remains unclear. We assessed long-term changes in the fatal-to-non-fatal composition of aggregate pancreatitis burden using Global Burden of Disease (GBD) 2023 estimates. Methods: We conducted a systematic descriptive and trend analysis using publicly available estimates from the GBD 2023 Results Tool for incidence, prevalence, deaths, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) across 204 countries and territories from 1990 to 2023. Because GBD reports pancreatitis as an aggregate cause category, the analysis could not distinguish acute pancreatitis, recurrent acute pancreatitis, chronic pancreatitis, or acute exacerbations of chronic pancreatitis. Primary analyses used age-standardised rates per 100,000 population. Four burden–composition metrics were derived within each location–year stratum: the YLL:YLD ratio, YLD:DALY proportion, deaths-to-incidence ratio, and prevalence-to-incidence ratio. Temporal trends were modelled in R version 4.5, using segmented regression, with up to three joinpoints selected by a Bayesian information criterion. Results: Globally, all six age-standardised native GBD measures declined between 1990 and 2023. The age-standardised incidence rate decreased from 37.62 (95% UI 32.20–43.11) to 32.91 (28.84–37.17) per 100,000, prevalence from 93.78 (69.26–126.25) to 68.92 (52.53–90.32), deaths from 1.76 (1.49–2.16) to 1.40 (1.21–1.66), YLDs from 5.70 (2.75–9.45) to 4.34 (2.18–7.04), YLLs from 55.96 (46.50–69.72) to 43.60 (36.89–53.53), and DALYs from 61.66 (50.62–75.61) to 47.94 (40.57–58.16). However, the fatal-to-non-fatal composition changed little: the global YLL:YLD ratio was 9.82 in 1990 and 10.04 in 2023, while the YLD share of DALYs was 0.092 and 0.091, respectively. Joinpoint modelling showed fluctuation rather than a sustained shift toward disability-dominant burden: the global YLL:YLD ratio was stable until 1998, increased from 1998 to 2002 (annual percent change [APC] 1.38%, 95% CI 0.42 to 2.36), and then declined modestly thereafter (APC −0.13%, −0.20 to −0.06). Burden remained higher in males, whereas females had a greater non-fatal share of total burden (YLD:DALY in 2023: 0.134 vs. 0.073). All sociodemographic index strata remained mortality-dominant in both 1990 and 2023; low-SDI settings had the greatest fatal dominance (YLL:YLD 34.94 in 1990; 24.72 in 2023). Using a descriptive YLD:DALY ≥ 0.50 benchmark, 203 of 204 countries and territories remained below the disability-dominant threshold in both years, no country crossed from below to above this benchmark, and only Georgia moved from above to below the benchmark. Conclusions: Despite declines in global incidence, mortality, and DALY rates, the aggregate GBD pancreatitis burden remained overwhelmingly mortality-dominant from 1990 to 2023. Because GBD pancreatitis combines acute and chronic pancreatitis, this finding should be interpreted as describing the modelled aggregate pancreatitis cause category rather than proving subtype-specific mortality dominance. The intensity of fatal dominance varied by sex, SDI, region, age, and country, but a structural shift toward disability-dominant aggregate burden was not observed. Full article

(This article belongs to the Section Hepatic and Gastroenterology Diseases)

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18 pages, 1509 KB

Open AccessReview

Spatial Immunology in Translation: Linking Immune Organisation to Therapeutic Outcome

by Caio Santos Bonilha

Med. Sci. 2026, 14(2), 308; https://doi.org/10.3390/medsci14020308 - 12 Jun 2026

Viewed by 241

Abstract

Immune-targeted therapies are commonly interpreted through molecular and cell-centric frameworks that insufficiently capture how immune activity is organised within intact tissues. This limitation complicates translational interpretation of therapeutic efficacy and response variability when inflammatory activity is spatially structured within diseased tissue. This review [...] Read more.

Immune-targeted therapies are commonly interpreted through molecular and cell-centric frameworks that insufficiently capture how immune activity is organised within intact tissues. This limitation complicates translational interpretation of therapeutic efficacy and response variability when inflammatory activity is spatially structured within diseased tissue. This review examines immune organisation as a relevant dimension of immune function and frames interaction-defined immune environments as functional units of inflammation. It outlines how cellular composition, tissue compartmentalisation, and persistence of interaction environments shape where immune signalling is concentrated and sustained in situ. By linking immune organisation to tissue-level behaviour, the review provides translational context for interpreting target engagement and therapeutic effects, supporting more informed alignment between therapeutic strategies and the immune architectures that dominate disease activity. Full article

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

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11 pages, 495 KB

Open AccessSystematic Review

Monotherapy with Biologics for Generalized Pustular Psoriasis: A Systematic Review of Comparative Interventional Studies with an Exploratory Network Meta-Analysis

by Aditya K. Gupta, Mary A. Bamimore, Tong Wang, Mesbah Talukder and Vincent Piguet

Med. Sci. 2026, 14(2), 307; https://doi.org/10.3390/medsci14020307 - 11 Jun 2026

Viewed by 131

Abstract

Background—Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disorder—and evidence regarding relative impact of treatments thereof is currently scant. Objective—We aimed to systematically review and narratively synthesize comparative interventional therapies for GPP and secondarily explore their relative effectiveness [...] Read more.

Background—Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disorder—and evidence regarding relative impact of treatments thereof is currently scant. Objective—We aimed to systematically review and narratively synthesize comparative interventional therapies for GPP and secondarily explore their relative effectiveness through exploratory network meta-analyses (NMAs). Methods—Comprehensive searches were performed in PubMed and EMBASE to identify comparative interventional studies that investigated the impact of biologics in GPP. Bayesian NMAs were conducted only for exploratory analyses. Results—Eleven studies met our inclusion criteria and data from 4 of the 11 were used for NMAs. Methodological heterogeneity was evident; the various biologics demonstrated effectiveness in treating GPP. Inhibitors of interleukin (IL)-36 (e.g., spesolimab) resulted in rapid pustular clearance within one week and sustained reductions in flare occurrence. Inhibitors targeting IL-17, IL-23, TNF, and IL-12/23 also demonstrated high response rates, durable disease control, and improvements in quality of life among diverse patient populations. Results from our exploratory NMAs revealed patterns of relative effectiveness with IL-17 and IL-36 inhibitors that are consistent with the existing literature. However, methodological limitations across the four studies deterred us from making conclusive inferences. Conclusions—Biologic therapies provide significant clinical benefit in patients with GPP. Our narrative syntheses highlight the need for future quantitative syntheses. Full article

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24 pages, 5263 KB

Open AccessFeature PaperArticle

Risk of Long-Term Clozapine Medication over Decades for Cardiac Adverse Events Including Heart Failure and Its Pathophysiology: A Japan and China Retrospective Cohort Analysis

by Ruri Okubo, Nobutomo Yamamoto, Xiaojun Shao, Taku Omori, Jian Xiong, Changhui Liu, Ryo Kato, Masahiko Murata, Tetsuji Kitano, Yuki Ito, Tomoka Oka, Toshiaki Onitsuka, Eishi Motomura, Kaoru Dohi, Gang Zhu and Motohiro Okada

Med. Sci. 2026, 14(2), 306; https://doi.org/10.3390/medsci14020306 - 11 Jun 2026

Viewed by 254

Abstract

Background/Objectives: Clozapine is the sole antipsychotic approved for treatment-resistant schizophrenia, but it is a double-edged therapeutic option due to various lethal adverse reactions. This study aimed to assess the risk of long-term clozapine medication-induced cardiotoxicity, which has not yet been fully elucidated. [...] Read more.

Background/Objectives: Clozapine is the sole antipsychotic approved for treatment-resistant schizophrenia, but it is a double-edged therapeutic option due to various lethal adverse reactions. This study aimed to assess the risk of long-term clozapine medication-induced cardiotoxicity, which has not yet been fully elucidated. Methods: This study is a multicenter retrospective cohort study of patients with schizophrenia in Japan and China who received clozapine monotherapy. Cases for which serum NT-proBNP concentration and LVEF derived from echocardiography were available in 2025 were included. In addition, blood examinations, including those administered by the Japanese Clozaril Patient Monitoring Service, were statistically analyzed as independent variables. Results: Among a total of 315 cases, including 99 Japanese (clozapine exposure duration: 57.5 ± 4.0 months) and 216 Chinese (208.1 ± 11.0 months) cases, were enrolled. In both Japan and China, age-standardized prevalence of heart failure among patients with prescribed clozapine were higher compared to general population, with odds ratios of 3.2 (95%CI: 1.4–6.4) and 6.9 (95%CI: 3.6–12.0), respectively. The risk factors for stage-B heart failure associated with clozapine were prolonged exposure duration, higher plasma levels of clozapine, and increasing monocytes. Unexpectedly, over 70% of cases with stage-B heart failure associated with clozapine identified in this study did not have metabolic complications. Other than those with cardiomyopathy, myocardial infarction, ileus, or chronic renal failure, no cases with ejection fraction < 50% were observed, suggesting that stage-B heart failure associated with clozapine is speculated to be likely suggestive of HFpEF. Conclusions: Traditionally, psychiatry has focused on myocarditis and cardiomyopathy developing several weeks and months after initiation of clozapine medication; however, this study revealed asymptomatic heart failure as a third cardiac adverse reaction of clozapine that develops years later. Therefore, regular monitoring of NT-proBNP contributes to improving long-term prognosis of treatment-resistant schizophrenia with prescribed clozapine. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Emerging Therapeutic Strategies in Psychiatric Disorders)

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