Medical Sciences

14 pages, 619 KB

Open AccessReview

From Observation to Surgery: A Review of Literature and an Updated Algorithm for Acquired Retinoschisis and Schisis-Detachment

by Alessandra Scampoli and Tomaso Caporossi

Med. Sci. 2026, 14(1), 159; https://doi.org/10.3390/medsci14010159 - 23 Mar 2026

Viewed by 871

Abstract

This review critically synthesizes current evidence regarding the natural history, advanced diagnostic imaging, and therapeutic interventions for acquired retinoschisis and retinoschisis-associated retinal detachment. A systematic search of PubMed and Embase databases was conducted for literature published up to 2026, focusing on comparative outcomes [...] Read more.

This review critically synthesizes current evidence regarding the natural history, advanced diagnostic imaging, and therapeutic interventions for acquired retinoschisis and retinoschisis-associated retinal detachment. A systematic search of PubMed and Embase databases was conducted for literature published up to 2026, focusing on comparative outcomes of scleral buckling versus pars plana vitrectomy and novel imaging modalities. The advent of ultra-widefield optical coherence tomography has shifted the diagnostic paradigm, enabling the precise identification of outer layer breaks as the primary biomarkers for progression. While observation is mandated for asymptomatic, non-progressive cases, the choice between buckling and vitrectomy for active detachments is often driven by surgeon preference rather than anatomical necessity. We propose an updated decision-making algorithm that integrates lens status, break localization, and vitreous findings to guide the surgical approach. Moving beyond a “one-size-fits-all” strategy, this review advocates for a personalized management plan that balances anatomical success with long-term quality of life. Full article

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12 pages, 702 KB

Open AccessArticle

Add-Ons of Heart Disease from the Cardiosurgical Perspective: Gender, Blood Groups and Renal Function

by Madeline Günther, Dimitrij Zilakov, Ardawan J. Rastan and Sebastian Vogt

Med. Sci. 2026, 14(1), 158; https://doi.org/10.3390/medsci14010158 - 23 Mar 2026

Viewed by 614

Abstract

Background/Objectives: This retrospective exploratory study aimed to characterize sex-specific patterns of coronary artery disease (CAD) and valvular heart disease (VHD) in a cardiac surgical cohort. In clinical routine, men appear to be more commonly affected by obstructive CAD, whereas women more frequently present [...] Read more.

Background/Objectives: This retrospective exploratory study aimed to characterize sex-specific patterns of coronary artery disease (CAD) and valvular heart disease (VHD) in a cardiac surgical cohort. In clinical routine, men appear to be more commonly affected by obstructive CAD, whereas women more frequently present valvular heart disease requiring surgical intervention. It remains unclear whether these sex-specific patterns are related to ABO blood groups and selected clinical parameters. Methods: Here, we retrospectively analyzed 983 patients admitted between 2020 and 2024 to a single cardiac centre with CAD and/or VHD requiring valve replacement. Patients were stratified by sex and disease entity (CAD only, CAD + VHD, isolated VHD). ABO and Rhesus factor distributions, cardiovascular risk factors, body mass index (BMI), and renal function (estimated glomerular filtration rate, eGFR) were assessed. Group comparisons were performed using Chi-square and Welch’s t-tests. Associations were evaluated using multivariable logistic and linear regression models adjusted for age, BMI, diabetes mellitus, hypertension, smoking, and eGFR. Results: Men were predominantly represented in the CAD-only group, whereas women more frequently underwent valve replacement, either isolated or combined with CAD (p < 0.001). When comparing the overall study cohort, blood group O was less prevalent in women than in men (p = 0.031), whereas blood group A was more frequent among female patients, although this difference did not reach statistical significance. Moreover, patients with valve disease demonstrated lower eGFR compared with those without valve involvement (men: −6.3 mL/min/1.73 m², p = 0.0036; women: −10.4 mL/min/1.73 m², p = 0.0019). This effect remained independently associated with reduced eGFR, with women slightly more affected. Conclusions: Gender- specific diseases should be included as secondary diagnoses when considering cardiac surgery. Nephrological complications in the postoperative period can be an important factor in assessing the benefits of surgery. Blood group O was more common in male Patients, suggesting that cardiovascular diseases also exhibit blood group dependence. Full article

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17 pages, 896 KB

Open AccessSystematic Review

Histopathological Changes Following Bromelain-Based Enzymatic Debridement (NexoBrid^®): A Comprehensive Systematic Review of Preclinical and Clinical Evidence

by Stefana Avadanei-Luca, Dan-Cristian Moraru, Andra-Irina Bulgaru-Iliescu, Raluca Tatar, Iulia Nacea, Alexandru Hristo Amarandei, Mihai-Codrin Constantinescu and Mihaela Pertea

Med. Sci. 2026, 14(1), 157; https://doi.org/10.3390/medsci14010157 - 23 Mar 2026

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Abstract

Background: NexoBrid^® (NXB; MediWound Ltd., Yavne, Israel) (anacaulase-bcdb) is a bromelain-based enzymatic debriding agent approved for eschar removal in burn care. Despite widespread clinical use, histological evidence of tissue-level changes after enzymatic debridement remains limited. This systematic review aimed to evaluate [...] Read more.

Background: NexoBrid^® (NXB; MediWound Ltd., Yavne, Israel) (anacaulase-bcdb) is a bromelain-based enzymatic debriding agent approved for eschar removal in burn care. Despite widespread clinical use, histological evidence of tissue-level changes after enzymatic debridement remains limited. This systematic review aimed to evaluate preclinical and clinical studies describing histological findings following bromelain-based enzymatic debridement of thermal burns. Methods: Following PRISMA 2020 guidelines, we performed parallel systematic searches of preclinical (animal) and clinical (human) studies across PubMed, Embase, CENTRAL, Web of Science, and Scopus. Included studies reported thermal burns treated with bromelain-based enzymatic debridement and tissue biopsies with histological analysis. Quality was assessed using the SYRCLE Risk of Bias Tool (preclinical) and JBI Critical Appraisal Checklists (clinical). Results: Six preclinical studies (five porcine, one rat) met inclusion criteria. Findings included: selective eschar removal with dermal preservation; protection of the zone of stasis (67% partial- vs. 100% full-thickness necrosis; p = 0.05); viable dermal thickness of 1.1 ± 0.7 mm; and accelerated re-epithelialization (7.4 ± 0.8 vs. 9.1 ± 2.1 days; p < 0.05). Only two clinical studies (n = 9 patients) met the inclusion criteria: one case series (n = 8) and one case report. Clinical findings showed upper dermal homogenisation with preserved deep dermis, vascular congestion correlating with pinpoint bleeding, and pseudoeschar formation via transepidermal elimination. Conclusions: Preclinical evidence supports selective enzymatic debridement with dermal preservation. However, clinical histological data are limited to nine patients after over 13 years of use. This highlights a critical translational gap and underscores the need for prospective clinical histological studies. Full article

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20 pages, 2647 KB

Open AccessArticle

Explainable Artificial Intelligence Unravels the Possible Distinct Roles of VKORC1 and CYP2C9 in Predicting Warfarin Anticoagulation Control

by Kannan Sridharan and Gowri Sivaramakrishnan

Med. Sci. 2026, 14(1), 156; https://doi.org/10.3390/medsci14010156 - 22 Mar 2026

Viewed by 578

Abstract

Background: Warfarin pharmacogenomics is critical due to its narrow therapeutic index and significant interpatient variability. While machine learning (ML) can predict anticoagulation control status (ACS), its “black-box” nature limits clinical translatability. Explainable Artificial Intelligence (XAI) addresses this by providing interpretable insights. This study [...] Read more.

Background: Warfarin pharmacogenomics is critical due to its narrow therapeutic index and significant interpatient variability. While machine learning (ML) can predict anticoagulation control status (ACS), its “black-box” nature limits clinical translatability. Explainable Artificial Intelligence (XAI) addresses this by providing interpretable insights. This study applied ML and XAI to a warfarin pharmacogenomic dataset to predict poor ACS and explain model decisions. Methods: A post hoc analysis was conducted on a cross-sectional dataset of 232 patients receiving warfarin for ≥6 months. Data included age, gender, interacting drugs, SAMe-TT2R2 score, and genotypes for CYP2C9, VKORC1, and CYP4F2. Poor ACS was defined as time in therapeutic range (TTR) < 70%. The dataset was split into training (70%) and testing (30%) cohorts. Three models, Random Forest, XGBoost, and Logistic Regression, were developed and evaluated using AUC-ROC, sensitivity, and specificity. XAI techniques, including permutation importance and SHapley Additive exPlanations (SHAP), were employed for global and local interpretability. Results: Of 232 patients, 141 (60.8%) had poor ACS. XGBoost and Random Forest demonstrated comparable predictive accuracy (AUC-ROC: 0.67), outperforming Logistic Regression. Sensitivity was 0.83 and 0.79 for XGBoost and Random Forest, respectively. However, specificity was modest for both ensemble methods (Random Forest: 0.48; XGBoost: 0.41) and extremely low for Logistic Regression (0.04), indicating poor discrimination, particularly for identifying patients with adequate anticoagulation control. Globally, important predictors included the age, SAMe-TT2R2 score, CYP2C9 (*2/*2), female gender, and VKORC1 (C/T). XAI revealed predictions were primarily driven by VKORC1, CYP4F2, SAMe-TT2R2 scores, and drug interactions. Concordance between XAI predictions and actual ACS was 78% for adequate and 88.6% for poor ACS. SHAP analysis showed VKORC1 provided a stable risk signal (mean absolute SHAP: 1.44 ± 0.49 in concordant cases), while CYP2C9 was a high-variance, high-impact driver of discordance (mean SHAP: 3.44 ± 3.79 in discordant cases). Conclusions: ML models, particularly ensemble methods, show modest ability to predict poor warfarin control with limited ability to correctly identify patients with adequate control from our dataset. XAI transforms these models into interpretable tools, with SHAP analysis attributing predictions to specific genetic and clinical features. While predictive accuracy remains modest, this approach enhances transparency and provides a foundation for generating hypotheses that may ultimately support clinical decision-making in pharmacogenomic-guided warfarin therapy. Full article

(This article belongs to the Special Issue Artificial Intelligence (AI) in Cardiovascular Medicine)

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12 pages, 754 KB

Open AccessCommunication

Are Atrial Fibrillation Risk Loci Universally Applicable? Insights from Whole-Genome Sequencing in a Polish Population

by Michał Wasiak, Mateusz Sypniewski, Paula Dobosz, Maria Stępień, Anna Michalska-Foryszewska, Patryk Rzońca and Zbigniew J. Król

Med. Sci. 2026, 14(1), 155; https://doi.org/10.3390/medsci14010155 - 21 Mar 2026

Viewed by 574

Abstract

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide and has a substantial genetic component. Genome-wide association studies (GWASs) have identified more than 100 susceptibility loci; however, replication across populations remains variable, suggesting potential population-specific differences in the genetic determinants [...] Read more.

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide and has a substantial genetic component. Genome-wide association studies (GWASs) have identified more than 100 susceptibility loci; however, replication across populations remains variable, suggesting potential population-specific differences in the genetic determinants of AF. To date, no whole-genome sequencing (WGS)-based study has evaluated AF susceptibility in a Polish population. Methods: We performed WGS (mean coverage 35×) in 233 unrelated individuals recruited within the Thousand Polish Genomes Project, including 56 patients with non-valvular AF and 177 controls without AF. After quality control and linkage disequilibrium pruning within a cardiovascular gene panel, 19,395 variants were analyzed. Association testing was performed using logistic regression adjusted for age and sex, applying both false discovery rate and Bonferroni correction thresholds. Results: No variants reached statistical significance for association with AF after correction for multiple evaluation. Previously reported susceptibility loci were not replicated in this cohort. Age was strongly associated with AF risk, whereas sex showed no significant effect. Given the relatively modest sample size, the study was primarily powered to detect variants with moderate or large effect sizes; smaller genetic effects reported in large GWASs may remain undetected. Conclusions: This pilot WGS-based study provides an initial exploration of AF-associated genetic variation in a Polish population. The absence of significant associations likely reflects the importance of further investigation in larger and well-characterized Central–Eastern European cohorts before genetic risk stratification approaches can be broadly applied across populations. Full article

(This article belongs to the Section Cardiovascular Disease)

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14 pages, 624 KB

Open AccessArticle

Analysis of Potential Iron Toxicity in Hemodialysis Patients Under Intravenous Iron Treatment

by Jessy Korina Peña-Esparragoza, Alina Chávez-Guillén, Paloma Ramos-López, Oscar Rueda-Elías, Susana López-Ongil, Matilde Alique, Rafael Ramírez-Chamond, Julia Carracedo, Diego Rodríguez-Puyol and Patricia Martínez-Miguel

Med. Sci. 2026, 14(1), 154; https://doi.org/10.3390/medsci14010154 - 21 Mar 2026

Viewed by 543

Abstract

Background/Objectives: Higher iron doses are used in the anemia treatment of hemodialysis patients, which allows for lower doses of erythropoiesis-stimulating agents; however, there are concerns regarding the risk of iron toxicity. This study aimed to evaluate the potential toxicity of iron deposition [...] Read more.

Background/Objectives: Higher iron doses are used in the anemia treatment of hemodialysis patients, which allows for lower doses of erythropoiesis-stimulating agents; however, there are concerns regarding the risk of iron toxicity. This study aimed to evaluate the potential toxicity of iron deposition in prevalent hemodialysis patients on iron therapy and its relationship with parameters used to assess iron status, plasma protein oxidation, and cellular iron toxicity. Methods: Magnetic resonance imaging was performed in 56 patients to assess hepatic iron deposition, which was related to clinical and analytical parameters. In patients included in the first and fourth quartiles, according to hepatic iron deposition, plasma protein oxidative stress was quantified, as were iron and cytokine levels in peripheral blood mononuclear cells (PBMCs). Results: Patients with higher hepatic iron deposition had a longer time on hemodialysis (42.0 ± 43.0 vs. 4.9 ± 3.4 months, p < 0.001) and higher ferritin levels (1200 ± 516 vs. 429 ± 278 ng/mL, p < 0.001) than those with lower hepatic iron deposition, without differences in transferrin saturation or hepatic enzyme serum concentration. No differences were found in plasma protein oxidation, iron content, or cytokine mRNA content in PBMCs, except for a decrease in IL-6 levels in patients with higher hepatic iron deposition. Conclusions: Patients with longer hemodialysis times had higher iron stores, suggesting that iron treatment over time increases hepatic iron deposition. No parameters supporting increased toxicity in patients with higher hepatic iron deposition were observed. Full article

(This article belongs to the Section Nephrology and Urology)

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22 pages, 3546 KB

Open AccessArticle

Safety Profile of SGLT-2 Inhibitors in Older Adults: A Systematic Review and Network Meta-Analysis

by Kannan Sridharan and Gowri Sivaramakrishnan

Med. Sci. 2026, 14(1), 153; https://doi.org/10.3390/medsci14010153 - 20 Mar 2026

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Abstract

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2i) are widely used in older adults for diabetes, heart failure, and kidney disease. This is the first network meta-analysis focusing on the effects of SGLT2i in older adults. Methods: Databases were searched for randomized clinical trials comparing SGLT2i [...] Read more.

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2i) are widely used in older adults for diabetes, heart failure, and kidney disease. This is the first network meta-analysis focusing on the effects of SGLT2i in older adults. Methods: Databases were searched for randomized clinical trials comparing SGLT2i against non-SGLT2i controls or other SGLT2i in relevant populations. Key safety outcomes included acute renal failure (ARF), genital infections, volume depletion, mortality, and serious adverse events (SAEs). Pooled odds ratios (OR) with 95% confidence intervals (CI) were generated using random-effects models for direct and mixed treatment comparisons. Results: From 97 included trials in the meta-analysis, SGLT2i versus non-SGLT2i were associated with reduced risks of ARF (OR 0.86, 95% CI 0.79–0.94), mortality (OR 0.84, 0.75–0.93), and SAEs (OR 0.84, 0.78–0.89), but increased risks of genital infections (OR 3.32, 2.68–4.12) and volume depletion (OR 1.18, 1.09–1.27). The risk of genital infections was observed more frequently with higher doses (high-dose OR 4.73 vs. low-dose OR 2.90) and escalated sharply with age (≥75 years OR 9.29, 3.13–27.6). The mortality benefit was strongest in adults ≥75 years (OR 0.58, 0.38–0.88). Intra-class analysis revealed distinct safety profiles; for instance, empagliflozin reduced the ARF risk, while sotagliflozin increased the volume depletion risk. Bootstrap and trial sequential analyses confirmed the results’ robustness. Grading of Recommendations Assessment, Development, and Evaluation assessment indicated moderate certainty of evidence. Conclusions: In older adults, SGLT2i maintain a favorable benefit–risk profile, with significant reductions in mortality and SAEs, though risks of genital infections and volume depletion require vigilance. The risk of genital infections exhibits a strong dose–response relationship and increases markedly in the oldest adults, while the mortality benefit appears to be most pronounced in those aged 75 years and older. This study provides actionable insights for personalized therapy in geriatric care. Full article

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

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12 pages, 1667 KB

Open AccessArticle

Near-Infrared Laser Photobiomodulation Reduces Pro-Inflammatory Cytokines in an In Vitro Model of Bronchopulmonary Dysplasia: A Preliminary Report

by Carlo Dani, Camilla Fazi, Francesca Cialdai, Chiara Risaliti, Lorenzo Notari and Monica Monici

Med. Sci. 2026, 14(1), 152; https://doi.org/10.3390/medsci14010152 - 20 Mar 2026

Viewed by 926

Abstract

Background: The multifactorial pathogenesis of bronchopulmonary dysplasia (BPD) includes prematurity, inflammation, and oxidative stress. Photobiomodulation therapy (PBMT) using near-infrared (NIR) laser sources was found to have anti-inflammatory effects in several respiratory disorders. Our aim was to evaluate whether PBMT could reduce inflammation in [...] Read more.

Background: The multifactorial pathogenesis of bronchopulmonary dysplasia (BPD) includes prematurity, inflammation, and oxidative stress. Photobiomodulation therapy (PBMT) using near-infrared (NIR) laser sources was found to have anti-inflammatory effects in several respiratory disorders. Our aim was to evaluate whether PBMT could reduce inflammation in an in vitro model of BPD. Materials and Methods: Precision-cut lung slices (PCLSs) from premature rabbits were exposed to lipopolysaccharide (LPS) and treated with three PBMT protocols (A, B, and C) differing for the treatment parameter such as fluence (energy delivered per unit area, laser A: 7.09, laser B: 7.41, laser C: 7.01 J/cm²) and exposure time (25, 20, 12 s, respectively). The expression level of TNFα and IL-6 was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) after 2 or 6 h from PBMT. Results: PBMT protocols A and B reduced IL-6 and TNFα mRNA at both timepoints, although the effect was less pronounced after 6 h than after 2 h. Furthermore, protocol A, which involved intermediate fluence and longer laser exposure, was more effective than protocol B. Conclusions: PBMT with NIR laser sources has an effective anti-inflammatory effect in an in vitro model of BPD, such as PCLSs from premature rabbits pretreated with LPS. These encouraging results support the planning of further studies in animal models of BPD and help identify the most effective PBMT protocol to use. Full article

(This article belongs to the Section Critical Care Medicine)

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15 pages, 405 KB

Open AccessArticle

Evaluating the Efficacy of CPS, HEART and TIMI Score in Emergency Department Patients with Non-Traumatic Chest Pain: A Pilot Study

by Pietro Pozzessere, Mattia Di Lauro, Francesco Incantalupo, Alessandro Cinquantasei, Stefano Palazzo, Mario Erminio Lepera, Antonella Pistone, Sandra De Matteis, Marco Matteo Ciccone, Vincenzo Brescia, Roberto Lovero, Marcello Albanesi and Angela Pia Cazzolla

Med. Sci. 2026, 14(1), 151; https://doi.org/10.3390/medsci14010151 - 19 Mar 2026

Cited by 1 | Viewed by 969

Abstract

Background and Aim: The correct identification of patients presenting with chest pain and the stratification of their risk for major adverse cardiovascular events (MACE) is essential. The aim of this study was to evaluate subjects who came to the ED for chest pain [...] Read more.

Background and Aim: The correct identification of patients presenting with chest pain and the stratification of their risk for major adverse cardiovascular events (MACE) is essential. The aim of this study was to evaluate subjects who came to the ED for chest pain through the chest pain score, the HEART score and the TIMI risk score in order to assess their validity and prognostic accuracy and to compare their performance. Methods: Patients included in the study met the following criteria: age ≥18 years, reported atraumatic chest pain, and consent to participate in the clinical study. Subsequently, the final scores were calculated based on the information collected and a follow-up was performed to assess the occurrence of adverse cardiovascular events (MACEs) at 30 days. The MACEs considered were a composite endpoint of STEMI or NSTEMI myocardial infarction, positive coronary angiography for critical lesions, percutaneous coronary angioplasty, coronary artery bypass grafting, and death. Results: A total of 102 patients were included in the study sample, divided into 76 patients who did not develop MACEs and 26 patients who experienced MACEs. The AUC values of the ROC curves of the chest pain score, HEART score and TIMI risk score were 0.8312, 0.9757 and 0.9378 respectively. Conclusions: All three scores examined were considered excellent tools to predict the onset of MACEs in patients with chest pain at different points of clinical management, although the HEART score outperformed both the chest pain score and the TIMI risk score in terms of prognostic accuracy. Full article

(This article belongs to the Section Cardiovascular Disease)

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14 pages, 1472 KB

Open AccessArticle

VMAT for Head and Neck Cancer: What Is the Impact of the Optimization Parameters on the Treatment Plan Quality?

by Evgenia Konstantinou, Efrossyni Lyraraki and Michalis Mazonakis

Med. Sci. 2026, 14(1), 150; https://doi.org/10.3390/medsci14010150 - 19 Mar 2026

Cited by 1 | Viewed by 810

Abstract

Objectives: To evaluate the effectiveness of different optimization parameters on radiotherapy plan quality for seventeen head and neck cancer patients. Methods: Volumetric Modulated Arc Therapy with Simultaneous Integrated Boost (VMAT-SIB) plans, involving up to three tumors, were generated. For each participant, a reference [...] Read more.

Objectives: To evaluate the effectiveness of different optimization parameters on radiotherapy plan quality for seventeen head and neck cancer patients. Methods: Volumetric Modulated Arc Therapy with Simultaneous Integrated Boost (VMAT-SIB) plans, involving up to three tumors, were generated. For each participant, a reference plan (Plan_Ref) was created using dual-arc with 180 control points, 20° gantry-angle increment and 1 cm minimum segment width. Modified plans were developed with dose constraints and optimization settings constant by changing to single-arc, 150 and 200 control points, 0.5 cm minimum segment width, and 30° and 40° gantry-angle increments. These plans were referred to as Plan_Arc1, Plan_CP150, Plan_CP200, Plan_SW0.5, Plan_Inc30, and Plan_Inc40, respectively. D_95% of planning target volumes (PTVs), homogeneity index (HI), monitor units (MUs), maximum dose (D_max) of spinal cord, mandible, and brainstem were recorded. Statistical and Bland–Altman analysis was performed comparing the modified plans to Plan_Ref. Results: Average D_95% values for PTV1, PTV2, and PTV3 ranged from 93.13 to 98.82%. Plan_SW0.5 provided superior target coverage and homogeneity with higher MUs than Plan_Ref. Plan_Arc1 significantly reduced PTV coverage and dose homogeneity, while increasing MUs compared with Plan_Ref (p < 0.05). The average D_max as derived from all planning approaches was up to 43.86 Gy, 65.86 Gy, and 48.85 Gy for spinal cord, mandible and brainstem, respectively. For spinal cord, Plan_Ref led to significantly lower doses compared to Plan_Arc1 and Plan_Inc30, while the brainstem recorded statistically higher D_max doses than Plan_Arc1. Significantly higher D_max was observed for the mandible using Plan_SW0.5 (p < 0.05). However, for D_max, the comparison plans showed good agreement with Plan_Ref based on Bland–Altman analysis. Conclusions: The VMAT plan quality is strongly affected by the minimum segment width whereas no differences were observed with the modification of the number of control points. Full article

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

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16 pages, 936 KB

Open AccessReview

Mechanobiological Implications of Low–Young’s Modulus TiNbSn Alloy Plates for Fracture Fixation: A Focused Review

by Yu Mori, Hidetatsu Tanaka, Masayuki Kamimura, Naoko Mori and Toshimi Aizawa

Med. Sci. 2026, 14(1), 149; https://doi.org/10.3390/medsci14010149 - 19 Mar 2026

Cited by 1 | Viewed by 554

Abstract

Rigid internal fixation has long been the standard for fracture management; however, excessive construct stiffness can suppress interfragmentary strain, reduce callus formation, and impair secondary fracture healing. Low-elastic-modulus TiNbSn alloys have emerged as a promising alternative, offering mechanical behavior closer to that of [...] Read more.

Rigid internal fixation has long been the standard for fracture management; however, excessive construct stiffness can suppress interfragmentary strain, reduce callus formation, and impair secondary fracture healing. Low-elastic-modulus TiNbSn alloys have emerged as a promising alternative, offering mechanical behavior closer to that of cortical bone. This review synthesizes representative preclinical and computational evidence to clarify the mechanobiological rationale for TiNbSn alloy plates in fracture fixation. We summarize key biological requirements for secondary fracture healing, including controlled interfragmentary strain, preservation of vascularity, and effective load sharing, and contrast these with the limitations of conventional high-stiffness fixation plates, such as stress shielding and reduced callus formation. Finite element analyses from previously reported models illustrate qualitative trends toward increased axial displacement, favorable stress distribution, and within a biologically relevant range for endochondral ossification. Consistent findings from animal fracture models further indicate enhanced periosteal and intramedullary callus formation and more physiological healing patterns with TiNbSn plates compared with rigid fixation. Emerging clinical experience with TiNbSn femoral stems provides indirect support for the long-term potential of low-elastic-modulus titanium alloys to mitigate stress shielding; however, such findings should be interpreted only as indirect supportive evidence, as stem implantation and fracture plate fixation involve substantially different mechanical and biological contexts. Collectively, these observations provide preliminary support for the mechanobiological rationale of low-modulus TiNbSn plates and suggest their potential role as biologically informed fixation devices, while highlighting the need for further clinical validation. Full article

(This article belongs to the Section Translational Medicine)

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13 pages, 4304 KB

Open AccessArticle

Expression of Hexokinase-2 (HK2), Glutaminase-1 (GLS1) and Fatty Acid Synthase (FASN) in Gastric Cancer and Their Prognostic Significance

by Elisa García-Martínez, Leonardo S. Lino-Silva, Adriana Romo-Pérez, Leticia Bornstein-Quevedo, Alma Chavez-Blanco, Guadalupe Dominguez-Gomez, Horacio N. Lopez-Basave, Alejandro Padilla-Rosciano, Consuelo Diaz-Romero, Aurora Gonzalez-Fierro and Alfonso Duenas-Gonzalez

Med. Sci. 2026, 14(1), 148; https://doi.org/10.3390/medsci14010148 - 19 Mar 2026

Viewed by 707

Abstract

Background/Objectives: To evaluate the immunohistochemical expression of hexokinase-2 (HK2), glutaminase-1 (GLS1), and fatty acid synthase (FASN) and its prognostic significance in diffuse gastric adenocarcinoma. Materials and Methods: Formalin-fixed paraffin-embedded tissue samples from 92 patients with diffuse gastric adenocarcinoma were analyzed. Immunohistochemistry (IHC) was [...] Read more.

Background/Objectives: To evaluate the immunohistochemical expression of hexokinase-2 (HK2), glutaminase-1 (GLS1), and fatty acid synthase (FASN) and its prognostic significance in diffuse gastric adenocarcinoma. Materials and Methods: Formalin-fixed paraffin-embedded tissue samples from 92 patients with diffuse gastric adenocarcinoma were analyzed. Immunohistochemistry (IHC) was performed to assess the expression of HK2, GLS1 and FASN. Expression levels were evaluated semi-quantitatively based on staining intensity and the percentage of positive cells. Associations between enzyme expression and clinicopathological features were assessed using the Chi-square test. Kaplan–Meier survival analysis was employed to evaluate progression-free survival (PFS) and overall survival (OS) and the log-rank test and Cox proportional hazards models were used for statistical analysis. Results: HK2 and FASN were overexpressed in 20.7% and 22.8% of patients, respectively, and were significantly associated with advanced tumor stage. In contrast, GLS1 expression, found in 30.4% of patients, did not independently correlate with clinicopathological characteristics. Furthermore, HK2 expression and co-expression of HK2/FASN (10.9%) and HK2/GLS1/FASN (8.7%) were associated with progressive disease. In the univariate analysis, stage, HK2 overexpression, and co-expression of HK2/FASN and HK2/GLS1/FASN were associated with shorter survival. However, only stage retained prognostic value in the multivariate analysis. Conclusions: Co-expression of these key metabolic enzymes remains a promising candidate as prognostic markers and therapeutic targets. Concurrent targeting of these metabolic pathways may offer novel therapeutic opportunities for patients with advanced-stage gastric cancer. Full article

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

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26 pages, 10937 KB

Open AccessArticle

Psychological Distress in COPD Assessed by DASS-21-R: Multivariable Regression and Bayesian Analysis Across GOLD Stages

by Adina Deliu, Luana Alexandrescu, Bogdan Cimpineanu, Oana Cristina Arghir, Sanda Jurja, Ioan Tiberiu Tofolean, Rodica Gabriela Enache, Ioana Gherghisan, Ionela Preotesoiu, Ionut Valentin Stanciu, Andreea Nelson Twakor, Monica Cordos, Alexandra Herlo, Daria Maria Alexandrescu and Doina Ecaterina Tofolean

Med. Sci. 2026, 14(1), 147; https://doi.org/10.3390/medsci14010147 - 19 Mar 2026

Viewed by 733

Abstract

Background: Psychological distress is a common comorbidity in chronic obstructive pulmonary disease (COPD), yet its relationship with disease severity remains incompletely understood. This study aimed to assess depression, anxiety, and stress using the Depression Anxiety Stress Scales–21 (DASS-21) and to examine their distribution [...] Read more.

Background: Psychological distress is a common comorbidity in chronic obstructive pulmonary disease (COPD), yet its relationship with disease severity remains incompletely understood. This study aimed to assess depression, anxiety, and stress using the Depression Anxiety Stress Scales–21 (DASS-21) and to examine their distribution across COPD severity stages. Methods: This multicenter, cross-sectional observational study included 285 clinically stable COPD patients enrolled between 2023 and 2025. COPD severity was classified according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Multinomial and binary logistic regression models were constructed to identify independent predictors of COPD severity and clinically significant psychological distress, adjusting for demographic and clinical covariates. Bayesian independent sample analyses and ANOVA effect size estimates were additionally performed. Results: Smoking exposure was independently associated with advanced COPD stages (GOLD 4 vs. GOLD 1–3: aOR 1.05, p < 0.001), as was dyspnea severity (mMRC: aOR 14.66, p < 0.001). In multivariable models examining psychological outcomes, COPD severity was not independently associated with clinically significant depression (p = 0.899), anxiety (p = 0.460), or stress (p = 0.843). In contrast, symptom burden measured using the COPD Assessment Test (CAT) score was consistently associated with depression (aOR 1.133, p < 0.001), anxiety (aOR 1.179, p < 0.001), and stress (aOR 1.144, p < 0.001). ANOVA effect sizes across GOLD stages were small (η² ≤ 0.047), and Bayesian analyses provided moderate to strong evidence supporting minimal differences in DASS-21-R scores between severity groups. Conclusions: Psychological distress is prevalent across all COPD severity stages and is not independently determined by airflow limitation. Symptom burden rather than spirometric severity appears to be more closely associated with emotional outcomes. Full article

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18 pages, 4776 KB

Open AccessArticle

A Comprehensive Study of Xenon Anesthesia in Patients with Locally Advanced Gastric Cancer: A Single-Center Study

by Natalia Yunusova, Vladimir Faltin, Dmitry Svarovsky, Olga Cheremisina, Elena E. Sereda, Alexandra Augustinovich, Evgeny Usynin, Marina Stakheyeva, Gelena Kakurina, Marina Vusik, Natalia Popova, Viktoria Velikaya and Sergey Afanasiev

Med. Sci. 2026, 14(1), 146; https://doi.org/10.3390/medsci14010146 - 18 Mar 2026

Viewed by 817

Abstract

Objective: The objective of this study was to choose the optimal anesthesia method for gastric cancer patients undergoing surgery with lymph node dissection. Materials and Methods: The study included 53 patients with stage T1-4aN0-3M0 gastric cancer, who underwent radical surgery with xenon and [...] Read more.

Objective: The objective of this study was to choose the optimal anesthesia method for gastric cancer patients undergoing surgery with lymph node dissection. Materials and Methods: The study included 53 patients with stage T1-4aN0-3M0 gastric cancer, who underwent radical surgery with xenon and dexmedetomidine (DMM) anesthesia in combination with epidural analgesia (main group, 27 patients) or with sevorflurane anesthesia in combination with epidural analgesia (comparison group, 26 patients). All patients underwent monitoring of hemodynamic parameters, blood coagulation system, thromboelastometry, and inflammation and metabolic parameters (interleukins, hormones and glucose levels), with an assessment of complications according to the Clavien-Dindo classification and the intensity of postoperative pain. Results: Awakening and extubation times, narcotic analgesic consumption, and Numeric Rating Scale pain scores were lower in the xenon + DMM group than in the sevoflurane group (p < 0.05). The overall number of patients experiencing complications did not differ significantly between anesthesia types; however, significant differences were found in the total number of complications (p = 0.003), the number of complications according to Clavien-Dindo I (p = 0.043) and II (p = 0.019), and the incidence of postoperative nausea and vomiting (p = 0.042). Conclusions: The BIS monitoring data obtained showed a sufficient level of anesthesia depth during surgery in both groups; however, post-anesthesia depression persisted longer in patients in sevoflurane group. Mathematical models for predicting Clavien-Dindo IIIb-V complications and severe postoperative pain syndrome are characterized by high sensitivity and specificity. They include simple clinical and laboratory parameters as well as type of anesthesia as predictors. The limitations of predictive models are also discussed in the article. Full article

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14 pages, 3795 KB

Open AccessArticle

FOXP3⁺ Cells in Tertiary Lymphoid Structures Have Adverse Impact on Overall Survival in Patients with Gastric Cancer

by Ana Paparella Karaman, Tomislav Ivanović, Krešimir Mustapić, Katarina Vukojević, Luka Minarik, Merica Glavina Durdov and Petar Đolonga

Med. Sci. 2026, 14(1), 145; https://doi.org/10.3390/medsci14010145 - 18 Mar 2026

Viewed by 935

Abstract

Background/Objectives: Patients with local/locally advanced gastric cancer (GC) undergo gastrectomy/lymphadenectomy, but recurrences are common and the disease usually progresses to death. Tertiary lymphoid structures (TLS) of varying maturity can be observed in the immune microenvironment of the primary tumor. The aim of [...] Read more.

Background/Objectives: Patients with local/locally advanced gastric cancer (GC) undergo gastrectomy/lymphadenectomy, but recurrences are common and the disease usually progresses to death. Tertiary lymphoid structures (TLS) of varying maturity can be observed in the immune microenvironment of the primary tumor. The aim of the study was to analyze the association of TLSs and their immune cellular composition with clinicopathological variables and overall survival (OS). Methods: In a cohort of 92 GC patients who underwent gastrectomy, the characteristics of tumor core TLSs were assessed and the density of cytotoxic CD8⁺ T cells and regulatory FOXP3⁺ T cells was analyzed. Results: Patients with TLS had a better OS than patients without TLS, 19.4 months vs. 9.2 months (p = 0.001). Immature TLSs were more frequently associated with lymphovascular invasion and regional lymph node metastasis (p = 0.014 and p = 0.034). Mature TLSs had a higher FOXP3⁺ T lymphocyte density and lower CD8⁺/FOXP3⁺ ratio than immature TLSs (p = 0.029 and p = 0.013), and patients had a longer OS than patients with immature TLSs, 34.55 months vs. 15.2 months (p = 0.033). In patients with TLS-positive GC, cases with FOXP3⁺ T cells had a shorter OS, 12.7 months vs. 47.5 months (p < 0.001). Conclusions: The presence of FOXP3⁺ cells in TLS is associated with significantly shorter OS of patients with local/locally advanced GC. Full article

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14 pages, 483 KB

Open AccessReview

Safety and Efficacy of Dexmedetomidine as an Adjuvant in Epidural Anesthesia for Labor Analgesia: A Narrative Review

by Josephine M. Feeney, Seth J. Duet, Cailyn B. Jones, Anthony J. Baffi, Sandy Rayes Elmalakh, Kristin Nicole Bembenick, Sahar Shekoohi and Shahab Ahmadzadeh

Med. Sci. 2026, 14(1), 144; https://doi.org/10.3390/medsci14010144 - 18 Mar 2026

Viewed by 1380

Abstract

Effective pain management during labor must balance adequate maternal pain relief with preservation of maternal participation and fetal safety. Epidural anesthesia remains the gold standard for labor analgesia. However, commonly used local anesthetics and opioid adjuvants are associated with adverse effects that include [...] Read more.

Effective pain management during labor must balance adequate maternal pain relief with preservation of maternal participation and fetal safety. Epidural anesthesia remains the gold standard for labor analgesia. However, commonly used local anesthetics and opioid adjuvants are associated with adverse effects that include nausea, pruritus, urinary retention, and prolonged labor. Dexmedetomidine, a highly selective α₂ agonist, does not carry the same risks for misuse and abuse as opioids do and may be a promising non-opioid adjuvant for epidural labor analgesia due to its analgesic, anxiolytic, and opioid-sparing properties. Furthermore, dexmedetomidine has unique pharmacodynamic effects, including preserving maternal consciousness while providing adequate analgesia. This combination of consciousness preservation and sufficient analgesia suggests dexmedetomidine may be a promising pharmaceutic for epidural anesthesia. In addition to preserving maternal consciousness, dexmedetomidine does not appear to cause a clinically significant increase in the motor blockade. Although epidural analgesia is known to prolong labor in nulliparous and multiparous patients, the use of dexmedetomidine as an epidural adjuvant does not have a significant effect on labor duration in available trials. Across studies, dexmedetomidine does not have deleterious outcomes for neonates, measured using the neonatal Apgar score. Although dexmedetomidine is not currently FDA-approved for epidural labor analgesia, existing evidence from available trials suggests its safety and efficacy as an opioid-sparing adjuvant. This narrative review aims to highlight the current state of knowledge of dexmedetomidine’s pharmacology, efficacy, analgesic ability, and side effects. Full article

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15 pages, 432 KB

Open AccessArticle

Risk of Functional Disorders and/or Thyroid Autoimmunity and Its Association with 25OH Vitamin D and Magnesium Levels: A Population-Based Case-Control Study

by Hernando Vargas-Uricoechea, Alejandro Castellanos-Pinedo, Karen Urrego-Noguera, María V. Pinzón-Fernández, Ivonne A. Meza-Cabrera, Hernando Vargas-Sierra and Valentina Agredo-Delgado

Med. Sci. 2026, 14(1), 143; https://doi.org/10.3390/medsci14010143 - 18 Mar 2026

Viewed by 1012

Abstract

Background/Objectives: Vitamin D (Vit-D) and magnesium (Mg) levels have been associated with an increased risk of developing functional thyroid disorders or autoimmune thyroid diseases (AITD). In this study, our objective was to evaluate if 25-hydroxyvitamin D (25OH Vit-D) and/or Mg levels are associated [...] Read more.

Background/Objectives: Vitamin D (Vit-D) and magnesium (Mg) levels have been associated with an increased risk of developing functional thyroid disorders or autoimmune thyroid diseases (AITD). In this study, our objective was to evaluate if 25-hydroxyvitamin D (25OH Vit-D) and/or Mg levels are associated with an increased risk of functional thyroid disorders and/or AITD. Methods: A population-based case-control study was conducted, with a total of 1028 participants (514 cases and 514 controls). Blood concentrations of 25OH Vit-D, Mg, TSH, FT4, FT3, and thyroid autoantibodies (TPOAb, TgAb, and TRAb) were determined in the study participants. Results: Among the cases (in women), the prevalence of goiter, hypothyroidism, and thyroid autoantibody positivity was significantly higher. No differences were found in the prevalence of functional thyroid disorders or in thyroid antibody positivity (among cases) according to sex or age. The prevalence of thyroid antibody positivity (specifically TPOAb and/or TgAb) was significantly higher in cases with 25OH Vit-D and/or Mg deficiency. The 25OH Vit-D level that best discriminated the highest frequency of AITD was 23.5 ng/mL [AUC: 0.665 (95% CI: 0.636–0.694, p < 0.001)]; while for Mg it was 1.8 mg/dL [AUC: 0.697 (95% CI: 0.668–0.725, p < 0.001)], indicating that the model has weak discrimination (although better than chance), with good sensitivity and low specificity, being able to identify the vast majority of positive cases (with AITDs), at the cost of including a significant proportion of false positives. Conclusions: Overall, we found that low serum levels of 25OH Vit-D and/or Mg appear to be associated with a significantly increased risk of goiter, functional thyroid disorders (specifically hypothyroidism), and with greater positivity of thyroid antibodies. Full article

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

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17 pages, 1414 KB

Open AccessArticle

Long-Term Clinical Consequences of Severe Oral Mucositis in Survivors of Lip, Oral Cavity, and Pharynx Cancer Versus Leukemia: A Propensity-Score-Matched Comparative Cohort Study Using Real-World Data

by Poolakkad S. Satheeshkumar, Venu Gopalakrishnan, Joel B. Epstein and Roberto Pili

Med. Sci. 2026, 14(1), 142; https://doi.org/10.3390/medsci14010142 - 18 Mar 2026

Viewed by 1040

Abstract

Background/Objectives: Severe oral mucositis is widely viewed as a transient toxicity of antineoplastic therapy. Whether its long-term consequences differ between cancers that directly damage the upper aerodigestive tract (cancers of the lip, oral cavity, pharynx [CLOP]) and systemic hematologic malignancies is unknown. The [...] Read more.

Background/Objectives: Severe oral mucositis is widely viewed as a transient toxicity of antineoplastic therapy. Whether its long-term consequences differ between cancers that directly damage the upper aerodigestive tract (cancers of the lip, oral cavity, pharynx [CLOP]) and systemic hematologic malignancies is unknown. The aim of this study was to compare lifetime risks of mortality, dysphagia, malnutrition, respiratory disease, and cardiovascular disease in propensity-score-matched survivors of CLOP cancer versus leukemia with and without a history of ulcerative oral mucositis. Methods: Population-based retrospective cohort study using the TriNetX US Collaborative Network (90 healthcare organizations, >110 million patients). We identified 80,526 adults with a personal history of CLOP cancer (ICD-10-CM Z85.81) and 43,684 with leukemia (Z85.6) from 2005 to 2024. Cohorts were stratified by presence/absence of severe oral mucositis (K12.31 or K12.33 at any time). Separate 1:1 propensity-score matching was performed within each cancer type on age, sex, race/ethnicity, hypertension, diabetes, BMI, ECOG status, and external causes of morbidity. Exposures included documented severe (ulcerative) oral mucositis. Main outcomes and measures were all-cause mortality and incident dysphagia, malnutrition, respiratory disease (J00–J99), influenza/pneumonia (J09–J18), and circulatory disease (I00–I99) after the index date. Results: After 1:1 matching, 4181 CLOP patients with mucositis were compared with 4181 without, and 2508 leukemia patients with mucositis were compared with 2508 without. In CLOP survivors, mucositis was associated with markedly higher lifetime mortality (adjusted HR 1.94, 95% CI 1.87–2.01), dysphagia (HR 3.42, 95% CI 3.28–3.57), malnutrition (HR 2.81, 95% CI 2.66–2.97), any respiratory disease (HR 1.68, 95% CI 1.63–1.73), and influenza/pneumonia (HR 1.79, 95% CI 1.72–1.86). In leukemia survivors, mucositis conferred only modest or null excess risk (mortality HR 1.12, 95% CI 1.05–1.19; dysphagia HR 1.18, 95% CI 1.07–1.30; malnutrition HR 1.24, 95% CI 1.12–1.37; any respiratory disease HR 1.09, 95% CI 1.03–1.15). Conclusions and Relevance: Severe oral mucositis is a powerful, durable prognostic determinant in cancers of the upper aerodigestive tract, where it identifies patients associated with elevated lifelong risk of swallowing dysfunction, aspiration-related lung disease, malnutrition, and premature death. The markedly attenuated effect in leukemia survivors suggests that direct high-dose radiation-induced structural damage to the pharynx and oral cavity—rather than systemic immunosuppression or chemotherapy intensity alone—is the dominant mechanism. Full article

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

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14 pages, 485 KB

Open AccessArticle

Daily Consumption of Unprocessed/Minimally Processed Foods and Its Relationship with Serum Phosphorus, CD3+, and CD45+ Cell Counts in People Living with HIV: A Cross-Sectional Descriptive Study

by Kaila Souza Gomes Carvalho, David Michel de Oliveira, Mayara Bocchi, Fábio Morato de Oliveira and Eduardo Vignoto Fernandes

Med. Sci. 2026, 14(1), 141; https://doi.org/10.3390/medsci14010141 - 18 Mar 2026

Viewed by 593

Abstract

Objectives: To investigate the potential associations between the daily consumption of unprocessed/minimally processed foods and serum phosphorus levels, CD3+, and CD45+ cell counts in clinically stable people living with HIV (PLHIV). Methods: This is a descriptive cross-sectional study. A total of 92 PLHIV [...] Read more.

Objectives: To investigate the potential associations between the daily consumption of unprocessed/minimally processed foods and serum phosphorus levels, CD3+, and CD45+ cell counts in clinically stable people living with HIV (PLHIV). Methods: This is a descriptive cross-sectional study. A total of 92 PLHIV of both sexes participated. Sociodemographic information, physical activity level, anthropometric and body composition data, dietary habits, and blood samples were collected. Results: The mean age of participants was 43.0 ± 12.0 years, with a body mass index of 26.5 ± 6.3 kg/m². The majority were male (60.8%), single (64.1%), had low educational attainment (55.4%), were non-smokers (64.1%) and did not consume alcoholic beverages (51.1%), and were physically active (70.7%). A positive association was observed between the daily consumption of unprocessed/minimally processed foods and serum phosphorus levels (p = 0.01), as well as CD3+ (p = 0.04) and CD45+ (p = 0.04) cell counts. Furthermore, positive correlations were identified between this dietary pattern and serum phosphorus (p = 0.001; r = 0.33) and the percentages of CD3+ (p = 0.03; r = 0.21) and CD45+ (p = 0.03; r = 0.22). Conclusions: The present study suggests that habitual consumption of unprocessed/minimally processed foods is positively associated with serum phosphorus levels, CD3+, and CD45+ cell counts in PLHIV. While these associations do not imply causality or enhanced antiviral immunity, they highlight the potential role of diet quality in the metabolic and immunological maintenance of stable patients. Full article

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

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13 pages, 765 KB

Open AccessArticle

Lipemic Plasma Identified Blood Donors: Triglyceride Variability and Exploratory Machine Learning Analysis

by Sirinya Sitthirak, Sodsai Narkpetch, Rujira Nonsa-ard, Manit Nuinoon, Poonsup Sripara, Krittamate Saisuwan, Saengrawee Thammawithan and Yanisa Rattanapan

Med. Sci. 2026, 14(1), 140; https://doi.org/10.3390/medsci14010140 - 17 Mar 2026

Viewed by 916

Abstract

Background/Objectives: Early detection of cardiometabolic irregularities is crucial for averting cardiovascular illness; however, demographic cohorts that consistently engage with healthcare systems like habitual blood donors are inadequately leveraged for metabolic monitoring. Methods: This study performed lipid profiling and cardiovascular risk assessment among blood [...] Read more.

Background/Objectives: Early detection of cardiometabolic irregularities is crucial for averting cardiovascular illness; however, demographic cohorts that consistently engage with healthcare systems like habitual blood donors are inadequately leveraged for metabolic monitoring. Methods: This study performed lipid profiling and cardiovascular risk assessment among blood donors identified with visually lipemic plasma during routine screening, in order to explore metabolic variability within this selected donor subgroup. Of 13,818 screened donors, 160 with lipemic plasma were included, and multivariable and machine-learning analyses were restricted to 90 donors with complete clinical data. Results: We observed substantial variability in triglyceride levels, with males displaying higher and more dispersed values. Correlation analysis indicated that triglycerides were associated with BMI and composite cardiovascular risk metrics, while age was the strongest contributor to the calculated 10-year cardiovascular risk score. Using a Random Forest classifier, elevated triglyceride levels were predicted with an AUC of 0.86; however, given the limited sample size, this analysis should be interpreted as exploratory and proof-of-concept in nature. Conclusions: In this selected subgroup of donors with lipemic plasma, clinically relevant hypertriglyceridemia was frequently observed. These findings suggest that routine donor data may provide opportunities for targeted metabolic monitoring, although the results cannot be generalized to the broader blood donor population. Further studies in larger and more representative cohorts are warranted. Full article

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12 pages, 279 KB

Open AccessReview

Occupational Therapy in the Treatment of Breast Cancer-Related Lymphedema: A Narrative Review

by Ana Belén Jiménez-Jiménez, Irene Elvira-Pastor, Fernando Jesús Mayordomo-Riera and María Nieves Muñoz-Alcaraz

Med. Sci. 2026, 14(1), 139; https://doi.org/10.3390/medsci14010139 - 17 Mar 2026

Viewed by 1130

Abstract

Background/Objectives: Breast Cancer-Related Lymphedema (BCRL) is one of the most prevalent complications among patients, causing physical limitations and a negative impact on their quality of life. Given its chronic nature and influence on personal autonomy, it is essential to review the therapeutic approaches [...] Read more.

Background/Objectives: Breast Cancer-Related Lymphedema (BCRL) is one of the most prevalent complications among patients, causing physical limitations and a negative impact on their quality of life. Given its chronic nature and influence on personal autonomy, it is essential to review the therapeutic approaches applied to date. The main objective of this study was to analyze and to compare the effectiveness of the different treatments currently used in the management of BCRL, especially those that incorporate the intervention of an occupational therapist. Methods: A narrative review of the scientific literature published between 2013 and 2025 was conducted. The search was carried out in the PubMed, Scopus, Web of Science, and Dialnet databases. Inclusion and exclusion criteria were applied to select studies with therapeutic interventions, selecting eight studies for review. Results: Complex Decompression Therapy (CDT) is currently the standard treatment, although one of its components, manual lymphatic drainage, is controversial in terms of its effectiveness. Interventions such as Activity-Oriented Proprioceptive Anti-Edema Therapy (TAPA), adapted physical exercise, and hydrotherapy showed significant benefits in quality of life, functionality, and reduction in the volume of lymphedema. Conclusions: The therapeutic approach to BCRL must be multidisciplinary and personalized. Occupational Therapy (OT) provides a person-centered approach that contributes to improving occupational performance and patient well-being. More studies with greater methodological rigor and sample size are needed to unify clinical criteria. Full article

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56 pages, 2224 KB

Open AccessReview

The Mental Health–Acute Coronary Syndrome Continuum: Bidirectional Pathophysiological Links and Clinical Implications

by Alexandra Herlaș-Pop, Andrei-Flavius Radu, Ada Radu, Gabriela S. Bungau, Delia Mirela Tit, Elena Emilia Babes and Cristiana Bustea

Med. Sci. 2026, 14(1), 138; https://doi.org/10.3390/medsci14010138 - 16 Mar 2026

Viewed by 1916

Abstract

Mental health disorders (MHDs) and acute coronary syndromes (ACSs) demonstrate reciprocal pathophysiological connections with substantial prognostic implications. Despite robust evidence linking MHDs to adverse cardiovascular outcomes, the bidirectional relationship remains inadequately characterized in clinical practice, with limited integration of mental health screening into [...] Read more.

Mental health disorders (MHDs) and acute coronary syndromes (ACSs) demonstrate reciprocal pathophysiological connections with substantial prognostic implications. Despite robust evidence linking MHDs to adverse cardiovascular outcomes, the bidirectional relationship remains inadequately characterized in clinical practice, with limited integration of mental health screening into routine cardiac care pathways. The present narrative review comprehensively presents contemporary data on epidemiology, shared biological mechanisms, clinical consequences, and integrated management strategies across the MHD–ACS continuum. A synthesis of peer-reviewed literature, meta-analyses, observational cohorts, randomized trials, and international guideline documents was performed, focusing on depression, anxiety, post-traumatic stress disorder, bipolar disorder, schizophrenia, and suicidality in relation to ACSs. MHDs are highly prevalent in ACS populations and independently predict increased mortality, major adverse cardiac events, and poorer functional recovery. Shared mechanisms include chronic low-grade inflammation, autonomic imbalance, hypothalamic–pituitary–adrenal axis hyperactivation, platelet hyperreactivity, and endothelial dysfunction. Selective serotonin reuptake inhibitors and cognitive behavioral therapy demonstrate the strongest evidence for treating depression in cardiac populations. Collaborative, stepped-care, and integrated cardiac rehabilitation models consistently improve psychological outcomes, with variable effects on cardiovascular endpoints. MHDs and ACSs form a self-reinforcing clinical continuum. Routine mental health screening and integrated cardio-psychiatric care represent essential components of secondary prevention and long-term outcome optimization. Full article

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13 pages, 1054 KB

Open AccessCommunication

Genetic Variants Associated with Life Expectancy in Patients with Chagas Disease

by Mario Bruno Principato, Maria Victoria Carvelli, Analia Paolucci, Camila Principato, Rocio Villa Fernandez, Nicolas Aguirre, Gabriel Ercoli, Guillermo Alberto Keller, Guillermo Di Girolamo, Manuel Lago and Justo Carbajales

Med. Sci. 2026, 14(1), 137; https://doi.org/10.3390/medsci14010137 - 16 Mar 2026

Viewed by 506

Abstract

Single nucleotide polymorphisms (SNPs), as common genetic variations, can influence biological processes. Identifying these variations is crucial for recognizing high-risk subgroups, guiding preventive strategies, and enabling personalized management. Objective: This study aimed to determine the relationship between SNPs and survival, thereby identifying genetic [...] Read more.

Single nucleotide polymorphisms (SNPs), as common genetic variations, can influence biological processes. Identifying these variations is crucial for recognizing high-risk subgroups, guiding preventive strategies, and enabling personalized management. Objective: This study aimed to determine the relationship between SNPs and survival, thereby identifying genetic profiles associated with increased risk. Methods: We included seropositive patients with Chagas disease who had a disease duration of >20 years and no comorbidities. DNA was extracted. A SNP panel focusing on genes involved in cardiac structure was created from the GnomAD database. Patients were followed for 8 years to assess survival. The association between SNPs and survival was evaluated, and a genetic risk score was generated. Univariate and multivariate Cox regression models assessed the association between SNPs (coded as ordinal variables) and survival time. SNPs with p < 0.05 were selected to construct a risk score, which was then assessed using Kaplan–Meier curves and median survival times. Results: A total of 182 patients were included, with 96.7% completing follow-up for a median of 5.1 years (interquartile range: 3.4–6.5). The median age was 62 years; 39.6% of patients were male, and 31% had reduced left ventricular ejection fraction. Univariate analysis showed that 3 of the 68 SNPs studied were associated with survival. Variant rs3755863 (PPARGC1A gene) was significantly associated with an increased risk of death (hazard ratio, HR = 1.94; p = 0.022). Conversely, two variants, rs7310615 (SH2B3 gene) and rs7405731 (JUP gene), showed a protective effect with significantly reduced mortality risk (HR = 0.45; p = 0.006 and HR = 0.48; p = 0.006, respectively). In multivariate analysis, rs7310615 and rs7405731 remained significantly associated with survival. A genetic risk score was constructed, assigning 0 points for homozygous wild-type, 1 point for heterozygotes, and 2 points for homozygous alternative alleles. Individual scores were calculated, and survival was estimated for each score category using Kaplan–Meier analysis and median survival times. Conclusions: Two SNPs were identified as significantly associated with survival. These findings require confirmation in larger and more diverse populations. Their validation could enable the identification of a subgroup of patients at particularly high risk. Full article

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14 pages, 1591 KB

Open AccessArticle

Reference Intervals for Hemoglobin and Hematocrit Adjusted for Altitude, Sex, and Age: A Big Data-Based Study in the Colombian Population

by Esteban Morales-Mendoza, María del Pilar Suarez-Ramos, Marcela Godoy-Corredor, Natalia Gomez-Lopera, Juan Felipe Combariza-Vallejo, Jossie Murcia and Mario A. Isaza-Ruget

Med. Sci. 2026, 14(1), 136; https://doi.org/10.3390/medsci14010136 - 14 Mar 2026

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Abstract

Background: Hemoglobin (Hb) and hematocrit (Hct) reference intervals (RIs) are critical for diagnosing hematological disorders. However, existing reference values often do not account for demographic and environmental variability. Particularly in countries with altitude gradients, such as Colombia, the absence of locally adjusted [...] Read more.

Background: Hemoglobin (Hb) and hematocrit (Hct) reference intervals (RIs) are critical for diagnosing hematological disorders. However, existing reference values often do not account for demographic and environmental variability. Particularly in countries with altitude gradients, such as Colombia, the absence of locally adjusted intervals may lead to the misclassification of anemia and polycythemia. Therefore, this study aims to establish sex-, age-, and altitude-specific reference intervals for Hb and Hct within the Colombian adult population via an indirect, big-data-based methodology. Methods: This retrospective cross-sectional study used 3.1 million Hb and Hct test results nationwide between 2022 and 2024. After applying the exclusion criteria, Hb data from 667,857 individuals and Hct data from 662,024 individuals were included. The population was stratified by sex, age, and altitude into <1100 m above sea level (m.a.s.l.), 1100–2000 m.a.s.l., and 2000–3000 m.a.s.l. Reference intervals (RIs) were estimated via the refineR algorithm, and the results were compared across altitude categories and against World Health Organization (WHO) anemia and polycythemia thresholds. Results: Hb and Hct concentrations increased with altitude in all sexes and age groups. Compared with women, men presented higher mean values and narrower RIs, whereas older adults presented greater variability. Compared with WHO thresholds, a significant proportion of individuals living above 2000 m exceeded polycythemia cutoffs without clinical evidence of disease, suggesting the need for altitude-adjusted diagnostic criteria. Conclusions: This study provides the first large-scale, data-driven reference intervals for Hb and Hct in Colombia, adjusted for altitude, sex, and age. The implementation of locally derived RIs may improve diagnostic accuracy and prevent the over- or underdiagnosis of hematological disorders, with direct implications for clinical decision-making and public health policy. Full article

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13 pages, 504 KB

Open AccessReview

Preoperative Botulinum Toxin Type A Use in Giant Inguinal Hernia Repair: A Scoping Review

by Agostino Fernicola, Luigi Ricciardelli, Alessio Cece, Floriana Porcaro, Domenico Parmeggiani, Michele Santangelo and Gennaro Quarto

Med. Sci. 2026, 14(1), 135; https://doi.org/10.3390/medsci14010135 - 13 Mar 2026

Viewed by 703

Abstract

Purpose: Giant inguinal hernias (GIHs) are rare and technically demanding conditions, associated with loss of domain and abdominal wall compliance. Preoperative botulinum toxin type A (BtxA) has been increasingly used in complex ventral hernia repair to facilitate abdominal wall relaxation; however, its [...] Read more.

Purpose: Giant inguinal hernias (GIHs) are rare and technically demanding conditions, associated with loss of domain and abdominal wall compliance. Preoperative botulinum toxin type A (BtxA) has been increasingly used in complex ventral hernia repair to facilitate abdominal wall relaxation; however, its role in GIHs surgery remains poorly defined. This scoping review aimed to map the literature on preoperative BtxA use in GIHs repair, focusing on technical protocols, patient selection, and areas of variability. Methods: A scoping review was conducted in accordance with PRISMA-ScR guidelines. MEDLINE, Embase, Web of Science, and Scopus were searched from inception to 10 October 2025. Studies reporting preoperative BtxA administration in adult patients undergoing GIHs repair were included. Data were extracted descriptively and synthesized narratively. Results: Seven observational and non-comparative studies published between 2019–2025 were included, comprising a total of 16 patients. Substantial heterogeneity was observed in BtxA protocols, with total doses ranging from 100 to 450 units, injection timing between 2 and 8 weeks preoperatively, and injection sites varying from 6 to 18. In several reports, BtxA was used as part of a multimodal preoperative strategy including progressive pneumoperitoneum. All studies targeted the lateral abdominal wall musculature, employed imaging guidance, and performed bilateral injections. Patient selection criteria and outcome reporting were inconsistent. Conclusions: Preoperative BtxA use in GIHs repair is limited and heterogeneous. No standardized protocol can be identified. Further anatomically focused and systematically designed studies are required to clarify the role of BtxA and to establish standardized preoperative protocols for this challenging surgical condition. Full article

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58 pages, 3444 KB

Open AccessReview

Current Insights into Clinical, Molecular, and Therapeutic Approaches to Acute Respiratory Distress Syndrome

by Manuel Gonzalez-Plascencia, Margarita L. Martinez-Fierro, Alfredo Salazar de Santiago, Ana G. Castañeda-Miranda, José I. Badillo-Almaraz and Idalia Garza-Veloz

Med. Sci. 2026, 14(1), 134; https://doi.org/10.3390/medsci14010134 - 13 Mar 2026

Cited by 1 | Viewed by 2438

Abstract

Acute respiratory distress syndrome (ARDS) remains a leading cause of morbidity and mortality in critically ill patients despite advances in supportive care and lung-protective ventilation. The syndrome is characterized by biological heterogeneity involving epithelial and endothelial injury, dysregulated inflammation, surfactant dysfunction, and impaired [...] Read more.

Acute respiratory distress syndrome (ARDS) remains a leading cause of morbidity and mortality in critically ill patients despite advances in supportive care and lung-protective ventilation. The syndrome is characterized by biological heterogeneity involving epithelial and endothelial injury, dysregulated inflammation, surfactant dysfunction, and impaired alveolar–capillary barrier integrity. This review integrates experimental, translational, and clinical evidence to examine the biological and molecular basis underlying ARDS, with particular emphasis on alveolar–capillary architecture, immune dysregulation, pulmonary mechanics, and the temporal evolution of diffuse alveolar damage. We further discuss emerging concepts in ARDS phenotyping and biomarker-based stratification as tools to address therapeutic heterogeneity and improve prognostic precision. Collectively, the evidence supports a shift from syndromic management toward biologically informed, precision-based approaches that may enable targeted interventions and improved clinical outcomes in ARDS. Full article

(This article belongs to the Topic The Pathogenesis and Treatment of Immune-Mediated Disease)

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7 pages, 191 KB

Open AccessCommunication

Use of Recombinant Human Deoxyribonuclease I in Primary Ciliary Dyskinesia Bronchiectasis—A Real Life Pilot Study

by Moshe Heching, Liora Slomianksy, Eviatar Naamany, Joel Weinberg and Mordechai R. Kramer

Med. Sci. 2026, 14(1), 133; https://doi.org/10.3390/medsci14010133 - 12 Mar 2026

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Abstract

Introduction: Recombinant human deoxyribonuclease I (rhDNase) cleaves DNA in mucus, facilitating increased mucociliary clearance of purulent sputum. In cystic fibrosis (CF), rhDNase improves pulmonary function and decreases exacerbations. Conversely, rhDNase use in non-CF bronchiectasis (NCFB) patients has not yielded similarly effective results. [...] Read more.

Introduction: Recombinant human deoxyribonuclease I (rhDNase) cleaves DNA in mucus, facilitating increased mucociliary clearance of purulent sputum. In cystic fibrosis (CF), rhDNase improves pulmonary function and decreases exacerbations. Conversely, rhDNase use in non-CF bronchiectasis (NCFB) patients has not yielded similarly effective results. We explored the safety and feasibility of rhDNase in patients with bronchiectasis due to primary ciliary dyskinesia (PCD). Methods: In this real-life pilot study, patients with PCD received rhDNase to treat viscous mucus. We compared pulmonary function tests and pulmonary exacerbations for these patients over six months of use of rhDNase. Results: Eight PCD patients with symptomatic bronchiectasis commenced use of rhDNase at variable dosing (ranging from at least twice weekly to a full 2.5 mg dose daily). Over a six-month period, pulmonary function tests, as measured by mean FVC and FEV₁, remained relatively stable compared to prior to commencing rhDNase. Mean pulmonary exacerbations decreased from 3.1 to 2.3 in the six-month period after commencing rhDNase, as compared to the six-month period prior to rhDNase. Conclusions: Use of rhDNase in PCD patients was safe and did not adversely impact lung function or increase pulmonary exacerbations, in contrast to earlier trial results in NCFB patients with heterogeneous etiologies. Further clinical data is required to identify the population of PCD patients who can benefit from rhDNase, as well as the appropriate dosing and timing. Full article

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

23 pages, 2115 KB

Open AccessReview

Artificial Intelligence in Cardiovascular Imaging: From Automated Acquisition to Precision Diagnostics and Clinical Decision Support

by Minodora Teodoru, Alexandra-Kristine Tonch-Cerbu, Dragoș Cozma, Cristina Văcărescu, Raluca-Daria Mitea, Florina Batâr, Horea-Laurentiu Onea, Florin-Leontin Lazăr and Alina Camelia Cătană

Med. Sci. 2026, 14(1), 132; https://doi.org/10.3390/medsci14010132 - 11 Mar 2026

Viewed by 1331

Abstract

Cardiovascular imaging is a cornerstone of modern cardiology, yet its clinical impact is limited by operator dependence, inter-observer variability, time-consuming workflows, and unequal access to advanced expertise. Artificial intelligence (AI), particularly machine learning and deep learning, offers new opportunities to overcome these limitations. [...] Read more.

Cardiovascular imaging is a cornerstone of modern cardiology, yet its clinical impact is limited by operator dependence, inter-observer variability, time-consuming workflows, and unequal access to advanced expertise. Artificial intelligence (AI), particularly machine learning and deep learning, offers new opportunities to overcome these limitations. This review aims to summarize current and emerging AI applications in cardiovascular imaging and to evaluate their potential clinical value in precision diagnostics and decision support. This narrative review synthesizes clinically relevant literature on AI applications across major cardiovascular imaging modalities, including echocardiography, cardiovascular magnetic resonance, cardiac computed tomography, and nuclear cardiology. Evidence was analyzed with a focus on AI-enabled acquisition support, image segmentation, quantitative and functional assessment, workflow automation, and risk stratification, alongside key methodological and implementation considerations. Across imaging modalities, AI-driven approaches have demonstrated improved reproducibility, efficiency, and scalability of cardiovascular imaging workflows. Automated algorithms reduce operator dependence, facilitate standardized extraction of imaging biomarkers, and support advanced functional assessment and prognostic stratification. Recent developments in video-based, temporal, and multimodal models further expand AI capabilities from technical automation toward integrated disease phenotyping and personalized clinical decision support. However, translation into routine practice remains limited by heterogeneous datasets, insufficient external validation, algorithmic bias, limited interpretability, and challenges related to regulatory approval and workflow integration. Artificial intelligence has the potential to reshape cardiovascular imaging into a more efficient, reproducible, and patient-centered precision medicine tool. Real-world clinical impact will depend on outcome-driven evaluation, robust external validation, multimodal data integration, and human-in-the-loop implementation strategies that ensure safe, equitable, and clinically meaningful adoption. Full article

(This article belongs to the Special Issue Artificial Intelligence (AI) in Cardiovascular Medicine)

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14 pages, 659 KB

Open AccessArticle

Chronic Obstructive Pulmonary Disease as an Independent Predictor of Left Main Coronary Artery Disease

by Beatrice Ragnoli, Carlotta Bertelegni, Leonardo Brugiatelli, Tarsi Giovanni, Fausto Chiazza and Mario Malerba

Med. Sci. 2026, 14(1), 131; https://doi.org/10.3390/medsci14010131 - 11 Mar 2026

Viewed by 683

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a disorder linked to increased cardiovascular risk, often coexisting with coronary artery disease (CAD), yet angiographic data on coronary involvement in COPD remain limited. This study aimed to evaluate whether COPD is associated [...] Read more.

Background: Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a disorder linked to increased cardiovascular risk, often coexisting with coronary artery disease (CAD), yet angiographic data on coronary involvement in COPD remain limited. This study aimed to evaluate whether COPD is associated with a distinct angiographic pattern of CAD, focusing on vessel distribution. Methods: We retrospectively enrolled 94 patients who underwent coronary angiography between 2023 and 2024 for suspected or known CAD. Clinical data, comorbidities, laboratory testing, pulmonary function, electrocardiography, echocardiography, and angiography were collected. Participants were stratified into two groups: COPD (n = 47) and non-COPD (n = 47). Coronary vessels were classified by number, location, and diameter. The normality of continuous variables was assessed using the Shapiro–Wilk test. Non-normally distributed variables were compared using the Mann–Whitney U test, while Fisher’s exact test was used for categorical comparisons. A multivariable logistic regression model was performed to identify independent predictors of left main coronary artery (LMCA) disease at the patient level. The primary endpoint was the association between COPD and CAD severity. Results: Baseline characteristics, including age, sex, BMI, and smoking history, were comparable between groups. The overall extent of CAD, expressed as the number of diseased vessels, did not differ significantly (p = 0.1436). However, vessel-based analysis revealed a distinct pattern: COPD patients showed a significantly higher prevalence of left main coronary artery (LMCA) disease compared to non-COPD patients (14% vs. 4.7%, p < 0.001). At the patient level, LMCA disease was present in 15/47 (31.9%) COPD patients compared with 6/47 (12.8%) non-COPD patients (p = 0.046). Multivariable logistic regression confirmed that COPD was an independent predictor of LMCA disease (OR = 3.56, 95% CI: 1.12–11.29, p = 0.031) after adjustment for age, sex, smoking, diabetes, and chronic kidney disease. Intermediate-caliber vessels were most frequently affected in both groups, while small-caliber branches were less commonly involved in COPD patients. Conclusions: COPD is an independent predictor of LMCA disease despite a similar overall angiographic extent of CAD. These findings suggest a distinct, high-risk coronary phenotype in COPD and highlight the need for enhanced cardiovascular vigilance and integrated cardiopulmonary management in this population. Full article

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28 pages, 12236 KB

Open AccessArticle

The Effect of Viniferin on Liver Cancer: Research Based on Network Pharmacology, Molecular Docking and Molecular Dynamics Simulation

by Saowanee Maungchanburi, Onwara Wongmek, Poolsak Baitahay, Asron Saweak, Maroof Wangkaranae, Wanmai Kongwattananon, Suphasarang Sirirattanakul, Moragot Chatatikun, Atthaphong Phongphithakchai, Jason C. Huang, Aman Tedasen and Chutima Jansakun

Med. Sci. 2026, 14(1), 130; https://doi.org/10.3390/medsci14010130 - 11 Mar 2026

Cited by 1 | Viewed by 1117

Abstract

Background/Objectives: Hepatocellular carcinoma (HCC) is a primary malignancy often driven by metabolic syndrome, fatty liver disease, and chronic hepatitis. These conditions foster a pro-inflammatory microenvironment that promotes tumor progression. Viniferin, a natural oligostilbene, has gained attention for its potential bioactivity. This study utilized [...] Read more.

Background/Objectives: Hepatocellular carcinoma (HCC) is a primary malignancy often driven by metabolic syndrome, fatty liver disease, and chronic hepatitis. These conditions foster a pro-inflammatory microenvironment that promotes tumor progression. Viniferin, a natural oligostilbene, has gained attention for its potential bioactivity. This study utilized an in silico network pharmacology approach to elucidate the pharmacokinetic properties and molecular mechanisms of ε- and δ-viniferin against HCC within the context of metabolic and inflammatory liver pathologies. Methods: ADMET profiles were characterized using SwissADME and pkCSM. Therapeutic targets were identified by intersecting viniferin-associated molecules with disease genes from GeneCards. A protein–protein interaction (PPI) network was constructed, supplemented by GO and KEGG enrichment analyses. Molecular docking and 200 ns of molecular dynamics (MD) simulations evaluated the binding affinity and structural stability between viniferin isomers and identified hub proteins. Results: Both ε- and δ-viniferin showed favorable drug-like properties, including high gastrointestinal absorption and low hepatotoxicity. We identified 247 overlapping targets, with network analysis highlighting ten essential hub genes, including AKT1, HSP90AA1, ESR1, HIF1A, NFKB1, GSK3B, PTGS2, APP, MTOR, and PIK3CA. Enrichment analysis confirmed their involvement in critical oncogenic pathways. Molecular docking showed strong interactions with APP, HSP90AA1, and AKT1, while MD simulations validated the long-term stability of ε-viniferin within the APP binding pocket. Conclusions: These findings provide mechanistic insights into viniferin as a multi-target agent for HCC, justifying further experimental validation in pre-clinical models. Full article

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

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