Medicina

19 pages, 1111 KB

Open AccessArticle

Unlocking the Therapeutic Potential of Trigonella foenum-graecum and Trigonella corniculata Against High-Fat-Diet-Induced Hyperlipidemia: Antioxidant and Histopathological Evidence

by Rabiya Shamim, Khurram Afzal, Asad Abbas, Muhammad Tauseef Sultan, Talha Bin Iqbal, Abdul Malik, Nikhat J. Siddiqi, Mohammad Shamsul Ola, Abdul Aziz Alamri, Abeeb Oyesiji Abiodum and Bipindra Pandey

Medicina 2025, 61(12), 2130; https://doi.org/10.3390/medicina61122130 (registering DOI) - 28 Nov 2025

Abstract

Background and Objectives: This study investigated the antioxidant, lipid-lowering, and hepatoprotective effects of two fenugreek seed varieties, Trigonella foenum-graecum (TFG) and Trigonella corniculata (TC), and analyzed their bioactive potential using various solvents, doses, and biochemical parameters. Materials and Methods: Antioxidant analyses, including [...] Read more.

Background and Objectives: This study investigated the antioxidant, lipid-lowering, and hepatoprotective effects of two fenugreek seed varieties, Trigonella foenum-graecum (TFG) and Trigonella corniculata (TC), and analyzed their bioactive potential using various solvents, doses, and biochemical parameters. Materials and Methods: Antioxidant analyses, including ferric-reducing antioxidant power (FRAP), total phenolic content (TPC), and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assays, were conducted, and interventional studies were performed on rats divided into groups receiving disease + standard basal diet (G₀), standard basal diet only (G₁), and disease + standard basal diet supplemented with TC or TFG at 400 mg/kg/day (G₂, G₃) and 800 mg/kg/day (G₄, G₅). Biochemical blood tests assessing lipid profiles and liver function parameters, coupled with histopathological examination of the liver and heart tissues, were also performed. Results: Antioxidant assessments indicated that TFG exhibited greater free radical scavenging ability, higher total phenolic content, and stronger ferric-reducing power than TC did. In the in vivo experiments, both TFG and TC significantly enhanced lipid profiles by reducing total cholesterol, low-density lipoprotein cholesterol (LDL-c), very-low-density lipoprotein cholesterol VLDL-c, and triglycerides while boosting high-density lipoprotein cholesterol (HDL-c) levels (p < 0.001). Liver function tests indicated significant decreases in bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels with dose and plant effects, particularly at 800 mg/kg (G₅). Histopathological examination revealed that TFG at a dose of 800 mg/kg led to an almost normal liver structure and intact myocardial fibers with minimal inflammation, whereas TC groups displayed slight vacuolation of hepatocytes and some inflammatory responses. Conclusions: In conclusion, TFG shows the superior functional food properties of TFG in managing oxidative stress and hyperlipidemia in comparison to TC. Future studies should aim to elucidate the molecular mechanisms, optimize dosing regimens, and evaluate long-term safety and efficacy to support clinical applications. Full article

(This article belongs to the Section Pharmacology)

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18 pages, 589 KB

Open AccessArticle

Micropulse Laser Trabeculoplasty in Glaucoma: Efficacy and Safety in a Clinical Cohort

by Flaviu Ionut Bodea, Cristina Ariadna Nicula, Delia Mirela Tit, Andrei-Flavius Radu, Ruxandra Cristina Marin and Gabriela S. Bungau

Medicina 2025, 61(12), 2129; https://doi.org/10.3390/medicina61122129 (registering DOI) - 28 Nov 2025

Abstract

Background and Objectives: Glaucoma is a leading cause of irreversible blindness, and lowering intraocular pressure (IOP) is the only proven strategy to slow disease progression. We evaluated the clinical efficacy and safety of Micropulse Laser Trabeculoplasty (MLT) in patients with open-angle glaucoma [...] Read more.

Background and Objectives: Glaucoma is a leading cause of irreversible blindness, and lowering intraocular pressure (IOP) is the only proven strategy to slow disease progression. We evaluated the clinical efficacy and safety of Micropulse Laser Trabeculoplasty (MLT) in patients with open-angle glaucoma and ocular hypertension, focusing on IOP control, visual function, and adverse events. Materials and Methods: This longitudinal, real-world cohort included 80 patients (132 eyes) treated with MLT between 2018 and 2025 at the Ophthalmology Clinic of the County Emergency Hospital, Bihor. Micropulse laser trabeculoplasty was applied over 360°, except in selected cases (90–300°), depending on anatomical or clinical factors. Outcomes included IOP by Goldmann and non-contact tonometry, best-corrected visual acuity (BCVA), refraction, and safety events. Pre-/post comparisons used paired tests and McNemar’s exact test where appropriate. Results: IOP decreased from 18.15 ± 5.02 to 15.57 ± 3.78 mmHg at 3 months (mean reduction: 2.58 mmHg, p < 0.001), confirmed by GEE adjusted for age, sex, and eye laterality. The proportion of eyes within target ranges increased significantly (IOP ≤ 18 mmHg and ≤21 mmHg; p = 0.0014 and p = 0.0023, respectively). A total of 31.1% of eyes achieved ≥ 20% IOP reduction, and 31.8% had an absolute decrease > 3 mmHg. BCVA and refraction remained stable (p > 0.05). No major complications or IOP spikes > 5 mmHg occurred; transient, self-limited events were uncommon. Conclusions: MLT was associated with a safe and clinically relevant reduction in IOP in patients with open-angle glaucoma and ocular hypertension, with stable visual function and minimal adverse effects observed. These results suggest that MLT may be a useful option for IOP management; however, the lack of a control group limits causal interpretation. Further controlled studies are warranted to confirm these findings. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Therapies of Ocular Diseases)

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16 pages, 1650 KB

Open AccessSystematic Review

Elevated Epicardial Adipose Tissue and Ischemic Stroke Risk: A Systematic Review and Meta-Analysis

by Arankesh Mahadevan, Monitha Pinnamaneni, Manaswini Krishnakumar, Tanisha Mishra, Parth Adrejiya, Aditya Sanjeevi, Bhaumikkumar Mukeshbhai Patel, Sneh Patel, Rahul Patel, Nihar Jena, Ankit Vyas and Rupak Desai

Medicina 2025, 61(12), 2128; https://doi.org/10.3390/medicina61122128 (registering DOI) - 28 Nov 2025

Abstract

Introduction: Epicardial adipose tissue (EAT), a fat depot between the myocardium and pericardium, produces pro-inflammatory adipokines, contributing to inflammation, insulin resistance, and endothelial dysfunction. EAT has been recognized as an independent risk factor for cardiovascular diseases, including atrial fibrillation (AFib) and acute ischemic [...] Read more.

Introduction: Epicardial adipose tissue (EAT), a fat depot between the myocardium and pericardium, produces pro-inflammatory adipokines, contributing to inflammation, insulin resistance, and endothelial dysfunction. EAT has been recognized as an independent risk factor for cardiovascular diseases, including atrial fibrillation (AFib) and acute ischemic stroke (AIS). This study explores the association between EAT and AIS risk, with a focus on populations with cardiovascular comorbidities. Material and Methods: This meta-analysis adhered to MOOSE and PRISMA guidelines. A comprehensive search of PubMed, SCOPUS, and Embase databases was conducted, targeting studies evaluating the association between EAT and AIS. Inclusion criteria encompassed RCTs, cohort, case–control, and cross-sectional studies. Quality assessment was performed using appropriate tools, and statistical analysis involved pooled odds ratios (ORs) with 95% confidence intervals (CIs) using a binary random-effects model. Results: The search identified 711 studies, eight of which met the inclusion criteria, yielding 7412 participants. Analysis revealed that increased EAT thickness significantly correlated with higher odds of AIS (aOR: 3.60 [2.26–5.74], I² = 74.24%). Sensitivity analysis confirmed the robustness of these findings despite publication bias. Higher epicardial adipose volume was also associated with an increased AIS risk (aOR: 1.17 [1.03–1.34], I² = 49.54%). Conclusions: Increased EAT thickness and volume are associated with a higher risk of AIS in populations with cardiovascular comorbidities, including AFib. EAT’s pro-inflammatory and pro-thrombotic properties may contribute to stroke pathophysiology. These findings highlight the potential utility of EAT measurement in stroke risk stratification and support further research to integrate EAT assessment into clinical practice. Full article

(This article belongs to the Section Neurology)

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13 pages, 965 KB

Open AccessArticle

Trueness of Complete-Arch Implant Scans: Influence of Scanning Technique, Intraoral Scanner, and Implant Position (Part I: Linear and Angular Deviations)

by Bersu Bedirhandede, Ayşe Demir Canbulut, Emre Tokar, Merve Çakırbay Tanış and Nihal Tokar

Medicina 2025, 61(12), 2127; https://doi.org/10.3390/medicina61122127 (registering DOI) - 28 Nov 2025

Abstract

Background and Objectives: This study aimed to investigate the effect of the intraoral scanner, scanning technique, and implant position on the trueness measured by linear and angular deviations. Materials and Methods: An edentulous maxillary model with four implants was scanned using [...] Read more.

Background and Objectives: This study aimed to investigate the effect of the intraoral scanner, scanning technique, and implant position on the trueness measured by linear and angular deviations. Materials and Methods: An edentulous maxillary model with four implants was scanned using four intraoral scanners (Trios 5, Trios 3, Primescan, Medit i700) and four scanning techniques (unmodified, composite, eugenol, dental floss). Each intraoral scanner–scanning technique combination was repeated ten times, producing 160 test datasets. Master reference files were generated with a laboratory scanner. Linear and angular deviations were calculated after superimposing each test scan with its master file. A three-way ANOVA followed by Tukey’s HSD test was used to determine statistical differences. Significance was set at p < 0.05. Results: Significant effects of intraoral scanner, scanning technique, and implant position were found for both linear and angular deviations (p < 0.001). Trios 5 showed the highest linear deviation values, although these remained within clinically acceptable limits, while Primescan showed the lowest. Dental floss produced the highest linear and angular deviations, whereas eugenol demonstrated the lowest. Medit i700 demonstrated the lowest angular deviation. Conclusions: All intraoral scanners showed deviations within clinically acceptable thresholds, although Trios 5 showed the highest linear deviation. Among scanning techniques, dental floss resulted in the highest linear and angular deviations. Deviations were lower between adjacent implants and higher across 1–3, 1–4, and 2–4. Full article

(This article belongs to the Special Issue Advances in Dental Prosthetics)

20 pages, 3437 KB

Open AccessArticle

Early and Mid-Term Results of Solid Organ Transplantation After Circulatory Death: A 4-Year Single Centre Experience

by Antonella Galeone, Marilena Casartelli Liviero, Alex Borin, Rostand Emmanuel Nguefouet Momo, Leonardo Gottin, Francesco Onorati, Irene Maffei, Marco Schiavon, Paolo Persona, Tiziano Menon, Luigino Boschiero, Alessandro Antonelli, Giovanni Battista Luciani and Amedeo Carraro

Medicina 2025, 61(12), 2126; https://doi.org/10.3390/medicina61122126 (registering DOI) - 28 Nov 2025

Abstract

Background and Objectives: The use of controlled donation after circulatory death (cDCD) donors has significantly increased during the past decades and successfully expanded the donors’ pool. However, warm ischemia may have detrimental effects on graft function. Italian Law requires a no-touch period [...] Read more.

Background and Objectives: The use of controlled donation after circulatory death (cDCD) donors has significantly increased during the past decades and successfully expanded the donors’ pool. However, warm ischemia may have detrimental effects on graft function. Italian Law requires a no-touch period of at least 20 min, which is much longer compared to the 5 min accepted in most European countries. Materials and Methods This is an Italian single-centre retrospective review of all cDCD procedures performed from April 2021 to June 2025. Patients with severe brain injury undergoing withdrawal of life-sustaining therapy (WLST) were considered for cDCD. After cardiac arrest and a no-touch period of 20 min, organ reperfusion was performed using abdominal or thoraco-abdominal normothermic regional perfusion (NRP) through femoral vessels cannulation. The primary endpoint was 30-day graft survival; secondary endpoints included: incidence of primary non-function (PNF) and non-anastomotic biliary stricture (NAS) in liver transplantation, PNF and delayed graft function (DGF) in kidney transplantation, primary graft dysfunction (PGD) in heart and lung transplantation, and recipient’s survival. Results: A total of 52 patients, 33 (63%) males, median age 74 (65–79) years, underwent WLST during the study period and were included in the cDCD program. Median functional warm ischemic time (WIT), total WIT, asystolic phase, and NRP duration were 37 (34–40), 40 (37–42), 24 (23–26), and 192 (166–212) min, respectively. A total of 123 organs (46 livers, 61 kidneys, 8 hearts, and 8 lungs) were considered suitable for transplantation, procured, and successfully transplanted in 115 recipients. We report the early and mid-term outcomes of 84 recipients, including 41 liver recipients, 32 kidney recipients, and 8 heart recipients transplanted at the Azienda Ospedaliera Universitaria Integrata of Verona, and 3 lung recipients transplanted at the Azienda Ospedale Università of Padova. The 30-day graft survival was 95% in liver recipients, 97% in kidney recipients, and 100% in heart and lung recipients. PNF was observed in two liver recipients, and PGD in two lung recipients. DGF was recorded in 3 (9%) kidney recipients. Six recipients died during the follow-up, and the mean survival time was 3.9 ± 0.1 years. Conclusions: Solid organ transplantation using cDCD donors is feasible and provides excellent early and mid-term results despite longer donor asystolic times. Larger data and longer follow-up are necessary to confirm these promising results. Full article

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16 pages, 351 KB

Open AccessArticle

Recent Change in Anhedonia, Major Depression and Low-Grade Inflammation: Dangerous Liaisons? A Study Based on a Cohort Referred for Polysomnography

by Véronique Bernier, Anaïs Mungo, Camille Point, Benjamin Wacquier, Gwenolé Loas and Matthieu Hein

Medicina 2025, 61(12), 2125; https://doi.org/10.3390/medicina61122125 (registering DOI) - 28 Nov 2025

Abstract

Background and Objectives: Anhedonia is a core symptom of major depressive disorder (MDD) and worsens its prognosis. Inflammation has been associated with MDD, contributing to the severity of this pathology despite no clear clinical guidance on whether it should be integrated into the [...] Read more.

Background and Objectives: Anhedonia is a core symptom of major depressive disorder (MDD) and worsens its prognosis. Inflammation has been associated with MDD, contributing to the severity of this pathology despite no clear clinical guidance on whether it should be integrated into the diagnosis or treatment of the MDD symptomatology. Notably, the neural basis of anhedonia is associated with alterations in the reward neural circuit, where inflammation may also interfere. In this study, we investigate whether recent change in anhedonia was associated with low-grade inflammation (defined as C-Reactive Protein levels between 3 and 10 mg/L) in MDD subjects. Materials and Methods: A retrospective study was conducted on 496 MDD subjects and drawn from the database of the sleep laboratory. Recent change in anhedonia was assessed via the Anhedonia Subscale of the 21-items Beck Depression Inventory (BDI-II), with scores > 3 indicating its presence. Recent change in anhedonia was defined as the recent onset or worsening of anhedonia complaints within the past 2 weeks. Anxiety and sleep disturbances were also evaluated and inflammatory status was determined based on CRP levels. Results: After adjusting for the main confounding factors, the multivariate logistic regression confirms a clear association between recent change in anhedonia and low-grade inflammation, thereby contributing to a detrimental context underlying the symptom. Conclusions: A better understanding of anhedonia in the context of inflammation could enable treatment adjustments and improve the poor prognosis of anhedonia-type depression. Full article

(This article belongs to the Special Issue New Insights into the Diagnosis, Management, and Interventions of Mood Disorders)

25 pages, 1323 KB

Open AccessArticle

Nutrition Counseling Frequency and Telehealth Integration on Cardiometabolic Outcomes in Metabolic Syndrome: A Randomized Controlled Trial in Turkey

by Kübra Yıldız-Güler, Miraç Vural-Keskinler and Mehmet Fisunoğlu

Medicina 2025, 61(12), 2124; https://doi.org/10.3390/medicina61122124 (registering DOI) - 28 Nov 2025

Abstract

Background and Objectives: As the demand for dietitian services continues to grow in high-volume healthcare settings, optimizing both the frequency and modality of follow-up has become crucial for sustaining and enhancing the effectiveness of medical nutrition therapy (MNT). This study evaluated a stepwise [...] Read more.

Background and Objectives: As the demand for dietitian services continues to grow in high-volume healthcare settings, optimizing both the frequency and modality of follow-up has become crucial for sustaining and enhancing the effectiveness of medical nutrition therapy (MNT). This study evaluated a stepwise intensification model ranging from quarterly in-person visits to monthly in-person visits and weekly telehealth follow-ups in metabolic syndrome (MetS). Materials and Methods: Ninety-three patients with MetS were randomized into three groups based on the intensity of dietary consultations: the intervention group (IG, n = 31), the intensive intervention group (IIG, n = 30), and the control group (CG, n = 32). IG received four in-person visits (baseline and weeks 4, 8, and 12); IIG received the same four visits plus weekly telehealth calls; and CG received two at baseline and week 12. Nutrient intake, anthropometric and biochemical measurements were compared across groups. A regression model was applied to examine associations between the frequency of nutritional counseling and MetS components. Results: Higher counseling frequency was associated with greater improvements in dietary intake, anthropometric, biochemical and blood pressure parameters. Both intervention groups achieved greater reductions in waist circumference (p < 0.001), BMI (p < 0.001), and body weight (p = 0.002) than CG, with the IIG improvements in FPG (p < 0.001, η² = 0.215) and blood pressure benefits (systolic: p < 0.001, η² = 0.276; diastolic: p < 0.001, η² = 0.148). In multivariable regression, counseling frequency independently predicted improvement in MetS diagnostic criteria (F = 9.395; p < 0.001, adjusted R² = 0.313). Conclusions: These findings highlight that integrating telehealth into MNT for MetS may enhance its effectiveness while minimizing the burden on healthcare systems. Full article

(This article belongs to the Section Endocrinology)

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14 pages, 770 KB

Open AccessArticle

Acute Effects of Marathon and Ultramarathon Running on Body Composition in Trained Male Athletes

by Serkan Düz, İsmail İlbak, Ayşe Eda Kınacı Öğüt, Peter Sagat and Peter Bartik

Medicina 2025, 61(12), 2123; https://doi.org/10.3390/medicina61122123 (registering DOI) - 28 Nov 2025

Abstract

Background and Objectives: This study aimed to compare acute changes in body composition parameters following marathon (42.195 km) and ultramarathon (61 km) runs in trained male athletes, with particular focus on hydration dynamics and metabolic stress. Materials and Methods: Sixteen male amateur endurance [...] Read more.

Background and Objectives: This study aimed to compare acute changes in body composition parameters following marathon (42.195 km) and ultramarathon (61 km) runs in trained male athletes, with particular focus on hydration dynamics and metabolic stress. Materials and Methods: Sixteen male amateur endurance runners were assigned to two groups: marathon (n = 8) and ultramarathon (n = 8). Body composition was assessed at three time points pre-race, immediately post-race, and 24 h post-race using bioelectrical impedance analysis. Measurements included body weight (BW), body mass index (BMI), total body water (TBW), total body fat (TBF), lean body mass (LBM), right arm fat (RAF), left arm fat (LAF), right leg fat (RLF), left leg fat (LLF), and torso fat (TF). Results: Both groups exhibited significant reductions in BW and BMI post-race (p < 0.05), with more pronounced changes observed in the ultramarathon group. Partial restoration of these metrics occurred within 24 h, primarily due to glycogen resynthesis and fluid retention. TBW remained stable immediately post-race but increased notably during recovery, particularly in ultramarathon runners, suggesting more effective hydration responses. Muscle and fat-free mass changes were minimal but more favorable in the ultramarathon group. Both total and regional fat percentages declined significantly post-race in both groups, with ultramarathon runners showing greater reductions. Conclusions: Endurance running induces short-term but substantial alterations in body composition, with ultramarathon participation eliciting more pronounced metabolic and fluid balance responses. These findings highlight the importance of race-specific nutritional and hydration strategies tailored to event type and duration. Full article

(This article belongs to the Special Issue Optimizing Athlete Health and Performance: Multidisciplinary Perspectives in Sports Medicine)

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10 pages, 273 KB

Open AccessArticle

Evaluation of Anthropometric Measurements, Arterial Stiffness and ECG Parameters in Alopecia Areata Patients

by Esra Pancar Yuksel, Gokhan Sahin, Mustafa Cagri Sahin, Sedanur Ozdemir Karadavut, Serkan Yuksel and Fatma Aydin

Medicina 2025, 61(12), 2122; https://doi.org/10.3390/medicina61122122 (registering DOI) - 28 Nov 2025

Abstract

Background and Objectives: Alopecia areata (AA) is an autoimmune disorder characterized by non-scarring hair loss and has been associated with systemic immune-inflammatory activity and potential cardiometabolic risk. This study aimed to evaluate cardiovascular risk markers—including ECG parameters, arterial stiffness indices, anthropometric measurements, and [...] Read more.

Background and Objectives: Alopecia areata (AA) is an autoimmune disorder characterized by non-scarring hair loss and has been associated with systemic immune-inflammatory activity and potential cardiometabolic risk. This study aimed to evaluate cardiovascular risk markers—including ECG parameters, arterial stiffness indices, anthropometric measurements, and body composition—in patients with AA according to disease severity and duration, and to compare these findings with healthy controls. Materials and Methods: This case–control study included 50 AA patients (32 men, 18 women; mean age: 28.98 ± 9.81 years) and 50 healthy controls (30 men, 20 women; mean age: 28.00 ± 7.86 years). All participants underwent anthropometric and electrocardiographic evaluations. Body composition was assessed, and arterial stiffness was measured. Subgroup analyses were performed according to SALT score (mild vs. moderate-to-severe) and disease duration (≥10 years vs. <10 years). Results: Heart rate was lower in AA patients compared with controls (mean difference −5.14 bpm; 95% CI −10.267 to −0.013). No significant differences were found between the groups regarding anthropometric variables, body composition, or arterial stiffness indices. Among AA patients, those with moderate-to-severe disease had significantly lower body fat mass (mean difference 4.95 kg; 95% CI 0.26 to 9.644) and lower visceral fat rating (mean difference 2.428 units; 95% CI 0.800 to 4.056) compared with mild AA. Conclusions: AA patients demonstrated lower heart rate and disease-severity-related alterations in body composition, although the clinical significance of these findings remains uncertain. Larger longitudinal studies are needed to clarify whether these subclinical differences translate into meaningful cardiovascular risk over time. Full article

(This article belongs to the Section Dermatology)

11 pages, 665 KB

Open AccessArticle

Assessment of the RoAD Score as a Predictor of Long-Term Irreversible Ambulatory Disability in Multiple Sclerosis: Evidence from a Real-World Cohort

by Tommaso Guerra, Chiara Esposto, Sara Limitone, Damiano Paolicelli and Pietro Iaffaldano

Medicina 2025, 61(12), 2121; https://doi.org/10.3390/medicina61122121 - 28 Nov 2025

Abstract

Background and Objectives: In multiple sclerosis (MS), the Risk of Ambulatory Disability (RoAD) score is a validated prognostic tool based on demographic, clinical, and MRI variables assessed at treatment initiation and after one year. We aimed to assess the predictive value of [...] Read more.

Background and Objectives: In multiple sclerosis (MS), the Risk of Ambulatory Disability (RoAD) score is a validated prognostic tool based on demographic, clinical, and MRI variables assessed at treatment initiation and after one year. We aimed to assess the predictive value of the RoAD score for long-term irreversible disability in a large real-world MS cohort. Materials and Methods: A retrospective analysis was performed on relapsing–remitting MS patients (RRMS) followed for ≥5 years at the Bari MS Center. The RoAD score (0–8) was calculated and dichotomized (<4 vs. ≥4). Cox proportional hazards models were used to evaluate the risk of irreversible Expanded Disability Status Scale (EDSS) 6.0. Results: A total of 1051 RRMS patients (67.1% female) were included, with a median follow-up of 18.0 years. Most patients (97.5%) received moderate-efficacy DMTs as first-line therapy. During follow-up, 123 (11.7%) patients reached irreversible EDSS 6.0 after a median of 9.5 years. Patients with RoAD score ≥4 (16.8%) showed a threefold higher risk of irreversible disability (HR 3.16, 95% CI 2.19–4.56, p < 0.001). The predictive value of RoAD ≥4 was confirmed both in the adjusted multivariable model and in sensitivity analyses treating RoAD as a continuous variable. Conclusions: In this real-world cohort, the RoAD score demonstrated solid predictive validity for long-term ambulatory disability, supporting its role as a practical tool for early risk stratification in MS management. Full article

(This article belongs to the Special Issue Multiple Sclerosis and Related Disorders: Theory, Methods and Applications)

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16 pages, 14493 KB

Open AccessArticle

Serum Kynurenine Pathway Metabolites as Candidate Diagnostic Biomarkers for Pituitary Adenoma: A Case–Control Study

by Nur Düzen Oflas, Halil İbrahim Akbay, Murat Alay and Mehmet Erdem

Medicina 2025, 61(12), 2120; https://doi.org/10.3390/medicina61122120 - 28 Nov 2025

Abstract

Background and Objectives: Pituitary adenomas are common intracranial tumors lacking specific non-invasive biomarkers. This study aimed to determine whether key metabolites and enzymes of the kynurenine pathway—including indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), kynurenic acid (KYNA), kynurenine aminotransferase (KAT), quinolinic acid, and picolinic [...] Read more.

Background and Objectives: Pituitary adenomas are common intracranial tumors lacking specific non-invasive biomarkers. This study aimed to determine whether key metabolites and enzymes of the kynurenine pathway—including indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), kynurenic acid (KYNA), kynurenine aminotransferase (KAT), quinolinic acid, and picolinic acid—can serve as diagnostic biomarkers distinguishing patients with pituitary adenomas from healthy controls. Materials and Methods: We conducted a single-center, cross-sectional, case–control study with 50 patients with pituitary adenomas and 35 healthy controls. Serum levels of IDO, KYN, KYNA, KAT, quinolinic acid, and picolinic acid were measured via enzyme-linked immunosorbent assay (ELISA). Statistical analyses included group comparisons (t-test/Mann–Whitney U), multivariate logistic regression to identify independent predictors, receiver operating characteristic (ROC) curve analysis to evaluate diagnostic performance (area under the curve, AUC), and partial least squares discriminant analysis (PLS-DA) for multivariate metabolic profiling. Results: Serum kynurenine, kynurenic acid, 3-hydroxykynurenine, picolinic acid, IDO and kynureninase were significantly higher in the pituitary adenoma group than in healthy controls (p < 0.001), while tryptophan, kynurenine aminotransferase, anthranilic acid and quinolinic acid showed no significant differences. ROC analysis demonstrated excellent diagnostic accuracy, with KAT (AUC = 0.923) and KYNA (AUC = 0.901) showing the highest discrimination. Multivariate logistic regression identified IDO, KYN, and KYNA as independent predictors of pituitary adenoma (p < 0.05). PLS-DA of the combined metabolite data also demonstrated clear separation between patients and controls, confirming distinct metabolic profiles between the groups. Conclusions: Kynurenine pathway metabolites and enzymes show strong potential as non-invasive biomarkers for pituitary adenomas. In particular, elevated KAT and KYNA levels demonstrated high diagnostic performance. These findings suggest that a panel of kynurenine pathway metabolites could aid in the early, non-invasive detection of pituitary adenomas. Full article

(This article belongs to the Collection The Utility of Biomarkers in Disease Management Approach)

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9 pages, 261 KB

Open AccessArticle

Surveillance of Humans Exposed to the Potentially Rabid Animals and Rabies Post-Exposure Prophylaxis in Split-Dalmatia County, Croatia, 2015–2024

by Anamarija Jurčev Savičević, Josip Buzov, Inga Vučica, Ivana Marasović Šušnjara and Nora Josipa Savičević

Medicina 2025, 61(12), 2119; https://doi.org/10.3390/medicina61122119 - 28 Nov 2025

Abstract

Background and Objectives: Although preventable, rabies represents a significant public health problem. An important part of prevention is the surveillance of people exposed to potentially rabid animals, carried out in the anti-rabies clinics of all public health institutes in Croatia. We aimed [...] Read more.

Background and Objectives: Although preventable, rabies represents a significant public health problem. An important part of prevention is the surveillance of people exposed to potentially rabid animals, carried out in the anti-rabies clinics of all public health institutes in Croatia. We aimed to analyze the burden of human animal-bite injuries, patient/biting animal characteristics, and the uptake of anti-rabies post-exposure prophylaxis (PEP). Material and Methods: This retrospective study used medical records data ranging from 2015 to 2024 for all patients in the anti-rabies clinics in Split-Dalmatia County, Croatia. Results: A total of 4105 patients reported contact with a potentially rabid animal. The majority of examined people (52.6%) were working-aged adults (20–60 years). The largest proportion of reported injuries were recorded on the lower limbs (34.9%) and hands/fingers (32.3%). No contact with a proven rabid animal was recorded. PEP was received by 37.7% of those examined. Although dog exposure (68.9%) most frequently led to post-exposure care-seeking, PEP was most common after rodent (91.2%) and bat (87.5%) exposures. Conclusions: Improving public health education is the most effective method of preventing dog bites and thus reducing bite injuries. Promoting responsible dog ownership and behavior around animals, as well as avoiding contact with unfamiliar animals, would likely reduce the need for PEP. The results of this study can also be used in planning health resources, primarily the availability of rabies vaccine and immunoglobulin. In addition, they emphasize the importance of rabies prevention and the continued implementation of all preventive measures in collaboration between the human and animal health sectors. This research may be useful to future public health policies for the control of zoonotic infectious diseases, especially from a “One Health” perspective. Full article

(This article belongs to the Special Issue Emerging Trends in Infectious Disease Prevention and Control)

24 pages, 2525 KB

Open AccessArticle

Gait Analysis as a Measure of Physical Performance in Older Adults with Bilateral Knee Osteoarthritis

by Kamal Constantin Kamal, Adina Maria Kamal, Diana Kamal, Ovidiu Fugaru, Daniela Matei and Magdalena Rodica Trăistaru

Medicina 2025, 61(12), 2118; https://doi.org/10.3390/medicina61122118 - 28 Nov 2025

Abstract

Background and Objectives. Bilateral knee osteoarthritis (KOA) in older patients compromises mobility and quality of life. Gait analysis provides objective, reproducible measures of physical performance. This study evaluated the integration of gait analysis for longitudinal monitoring and personalized rehabilitation, while ultrasound was performed [...] Read more.

Background and Objectives. Bilateral knee osteoarthritis (KOA) in older patients compromises mobility and quality of life. Gait analysis provides objective, reproducible measures of physical performance. This study evaluated the integration of gait analysis for longitudinal monitoring and personalized rehabilitation, while ultrasound was performed only at baseline for characterization and did not inform adjustments to the interventions. Materials and Methods. We conducted a 6-week, randomized, parallel-group clinical trial including 130 participants aged ≥65 years. Patients were randomized to a Study Group (SG, n = 64) receiving 10 sessions of a comprehensive rehabilitation program (conventional measures plus gait training) or a Control Group (CG, n = 66) receiving 10 sessions of conventional rehabilitation (electrotherapy with magnetodiaflux, TENS, therapeutic ultrasound, low-intensity laser, plus standard kinesitherapy). Interventions were delivered daily, 5 days/week, over 2 consecutive weeks. Gait outcomes (BTS G-WALK/G-SENSOR 2) included TUG, Symmetry Index, 6MWD, and cadence; functional outcomes included VAS pain, WOMAC, and Lequesne Index. Quadriceps morphology was assessed sonographically, and a height-normalized quadriceps thickness index (QHNI) was calculated. Results. Of 130 randomized, 112 completed (93.3%). Compared with control, the intervention produced significant, clinically meaningful improvements: 6MWD increased by approximately 59 m, cadence by ~9 steps/min; TUG improved by ~2.6 s; gait symmetry by ~4–5 points; VAS pain decreased by ~1.7 points; WOMAC total by ~8.5 points; and Lequesne Index by ~2 points (all p < 0.001). QHNI showed no significant association with anthropometrics and performance measures, indicating limited value as a linear predictor at baseline; nonlinear models or subgroup analyses may be warranted. Conclusions. Both neuromuscular-focused rehabilitation and the conventional program improved gait and clinical outcomes. Integrating gait analysis with ultrasound evaluation enables comprehensive monitoring and supports personalized interventions to reduce joint loading and optimize gait mechanics in older patients with bilateral KOA. Full article

(This article belongs to the Special Issue Advances in Pathogenesis, Rehabilitation, and Treatment of Knee Osteoarthritis)

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22 pages, 330 KB

Open AccessArticle

Early vs. Late Unplanned Returns to the Operating Room (URTOR) in Neurosurgery: Effect of Surgeon Experience and Complication Types

by Mahmut Çamlar, Umut Tan Sevgi, Mustafa Eren Yuncu, Caglar Turk, Merve Oren, Berra Bilgin, Cafer Ak and Füsun Demirçivi Özer

Medicina 2025, 61(12), 2117; https://doi.org/10.3390/medicina61122117 - 28 Nov 2025

Abstract

Background and Objectives: Unplanned return to the operating room (URTOR) is a sensitive indicator of surgical quality; however, data in neurosurgery are limited. This retrospective study analyzed patients who underwent URTOR following neurosurgical procedures over an eight-year period to define early and [...] Read more.

Background and Objectives: Unplanned return to the operating room (URTOR) is a sensitive indicator of surgical quality; however, data in neurosurgery are limited. This retrospective study analyzed patients who underwent URTOR following neurosurgical procedures over an eight-year period to define early and late patterns, identify underlying causes, and evaluate the distribution of cases according to surgeon experience. Materials and Methods: Records of 18,258 consecutive surgeries including both elective and emergency procedures in adult and pediatric patients, performed at a single center between 2010 and 2018 were retrospectively reviewed. Unplanned reoperations within 30 days of the index surgery were defined as URTOR; those occurring within ≤7 days were classified as “early,” and those occurring between 8 and 30 days were classified as “late.” Demographic data, surgical characteristics, causes of URTOR, and surgeons’ seniority were examined. Results: Among 18,258 neurosurgical procedures, 324 URTORs (1.8%) were identified. The median patient age was 38 years; 37% were children. Early URTOR comprised 59% and was primarily associated with hemorrhagic–vascular complications, whereas late URTOR accounted for 41% and was dominated by cerebrospinal fluid-related and infectious complications. Late events prevailed in significantly younger cases and were disproportionately followed by ventriculo–peritoneal shunt or endoscopic third ventriculostomy index operations. Junior surgeons performed 74% of later operations requiring URTOR versus 30% of early failures. Sex, weekday/weekend timing, and surgeons’ experience did not affect the overall URTOR classification categories. The median interval was six days. Conclusions: Centers worldwide have begun to examine URTOR rates, which are directly associated with hospital quality measurements. These results may inform targeted education and prevention by identifying patient groups at higher reoperation risk within a specific timeframe. Full article

(This article belongs to the Section Neurology)

17 pages, 821 KB

Open AccessArticle

Associations Between Cognitive Performance and Motor Signs in Older Adults with Alzheimer’s Dementia

by Ioannis Liampas, Vasileios Siokas, Chrysoula Marogianni, Antonia Tsika, Metaxia Dastamani, Polyxeni Stamati and Efthimios Dardiotis

Medicina 2025, 61(12), 2116; https://doi.org/10.3390/medicina61122116 - 27 Nov 2025

Abstract

Background and Objectives: The interplay between motor tasks and cognition in Alzheimer’s dementia (AD) remains insufficiently characterised. We hypothesised that prefrontal-mediated cognitive functions could contribute to motor impairments in older adults with AD. Materials and Methods: Cross-sectional data from the National Alzheimer’s Coordinating [...] Read more.

Background and Objectives: The interplay between motor tasks and cognition in Alzheimer’s dementia (AD) remains insufficiently characterised. We hypothesised that prefrontal-mediated cognitive functions could contribute to motor impairments in older adults with AD. Materials and Methods: Cross-sectional data from the National Alzheimer’s Coordinating Centre (NACC) were analysed. Our sample included older adults (≥60 years) with a baseline diagnosis of AD. The Unified Parkinson’s Disease Rating Scale Part-III was used to assess the presence or absence of motor signs. Episodic memory, language, confrontation naming, attention, processing speed, and executive function were assessed using a neuropsychological battery. Binary logistic models examined the relationship between cognitive performance and motor manifestations. Results: Of 44,713 NACC participants, 5124 individuals with complete covariate data were included in the analysis, 1339 with and 3785 without motor signs. Participants were predominantly female (~55%), with an average age of 76.5 ± 7.9 years and mean education of 14.2 ± 3.7 years. The presence of motor manifestations was related to slower processing speed (Trail Making Test—Part A) and impaired executive function (Trail Making Test—Part B). No covariate modified these associations. Among specific motor domains, impaired chair rise was related to executive dysfunction, whereas postural instability, impaired posture–gait, and bradykinesia were related to slower mental processing. Hypophonia, masked facies, resting tremor, action–postural tremor and rigidity were not associated with any cognitive measure. Conclusions: Processing speed and, to a lesser extent, executive function emerged as the main cognitive functions associated with motor manifestations in older adults with AD. Further research is needed to clarify the nature of this association, including potential causal pathways. Full article

(This article belongs to the Section Neurology)

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23 pages, 958 KB

Open AccessReview

Cutaneous Melanoma in the Context of Aging

by Monica Neagu, Carolina Constantin and Sabina Zurac

Medicina 2025, 61(12), 2115; https://doi.org/10.3390/medicina61122115 - 27 Nov 2025

Abstract

Ageing is sustained by a complex network of cellular and molecular mechanisms. The main mechanisms are cellular senescence, telomere attrition, gene expression changes, metabolic dysregulations, oxidative stress and epigenetic modifications such as DNA methylation. All these networks can harbor the initiation of age-related [...] Read more.

Ageing is sustained by a complex network of cellular and molecular mechanisms. The main mechanisms are cellular senescence, telomere attrition, gene expression changes, metabolic dysregulations, oxidative stress and epigenetic modifications such as DNA methylation. All these networks can harbor the initiation of age-related diseases, skin cancer included. The studies published in the last years linking ageing and skin cancers focus on basal and squamous carcinomas, melanomas and Merkel cell carcinomas. Our review will focus on skin melanomas as one of the aggressive skin cancers along with Merkel cell carcinomas. Several long-term studies conducted on large populations have shown that in elderly individuals melanoma related to photo-exposure has doubled in the last decade. The clinic-pathological pattern of skin melanomas is different in aged patients and is guided also by immune-related mechanisms. Besides sun exposure, metabolic deregulations and obesity can be risk factors in melanomas. Controversial results were published on obesity risk in melanomas; however, the adipose tissue favors increased cytokines and growth factors production contributing to melanoma aggressiveness. Moreover, immunotherapy that is not offered in geriatric patients as often as in young ones has proven to be as efficient as in younger ones, although the aged-related co-morbidities can impede the immunotherapy choice. Without being exhaustive, our review has synthesized current research and critically assessed the links between aging as a normal physiological process to the initiation and propagation of skin cancers, focusing on cutaneous melanoma. The review highlights the differences at various levels of skin melanoma developed in aged patients compared to younger one and gives the general outlines for diagnosis, prognosis and therapeutical approaches in aged patients. Full article

(This article belongs to the Special Issue Updates on the Changing Landscape of Immunotherapy and Targeted Therapy in Cancer)

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13 pages, 1069 KB

Open AccessArticle

Resistance Dynamics in a Romanian Critical Care Unit: Four Years of ESKAPE Pathogen Surveillance

by Mihai Sava, Ioana Roxana Codru, Alina Simona Bereanu, Oana Stoia and Bogdan Ioan Vintila

Medicina 2025, 61(12), 2114; https://doi.org/10.3390/medicina61122114 - 27 Nov 2025

Abstract

Background and Objectives: Antimicrobial resistance is one of the most significant threats to modern healthcare, especially in intensive care units where ESKAPE pathogens—Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.—account for the [...] Read more.

Background and Objectives: Antimicrobial resistance is one of the most significant threats to modern healthcare, especially in intensive care units where ESKAPE pathogens—Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.—account for the majority of healthcare-associated infections. Romania is among the European countries with the highest rates of antimicrobial consumption and resistance. This study aimed to describe the epidemiological trends and antimicrobial resistance profiles of ESKAPE isolates over a four-year period (2021–2024) in a Romanian ICU (Intensive Care Unit). Materials and Methods: We conducted a retrospective observational study of all microbiological samples collected from adult ICU patients at the Clinical Emergency County Hospital of Sibiu between 2021 and 2024. Data were extracted from the electronic laboratory system and included patient demographics, specimen types, isolated microorganisms, and antimicrobial resistance classifications. Statistical analyses were performed using Python libraries, with significance set at p < 0.05. Results: A total of 801 infections were recorded, of which 562 (70.2%) involved ESKAPE pathogens. The predominant organisms identified were Klebsiella pneumoniae (42.8%) and Acinetobacter baumannii (36.0%), followed by Pseudomonas aeruginosa (11.2%). Nearly half of the isolates (47.3%) were multidrug-resistant, and 22.3% were extensively drug-resistant. Respiratory specimens, particularly tracheal aspirates, accounted for the majority of the isolates and exhibited the highest proportion of resistant phenotypes. A significant temporal increase in extensively drug-resistant isolates was observed over the study period (p < 0.05). Conclusion: ESKAPE pathogens remain the leading causes of ICU infections in Romania, with Klebsiella pneumoniae and Acinetobacter baumannii contributing significantly to the burden of multidrug- and extensively drug-resistant infections. Strengthening infection prevention strategies, optimizing antimicrobial stewardship, and implementing continuous microbiological surveillance are essential to mitigate the evolving resistance crisis in Romanian critical care settings. Full article

(This article belongs to the Special Issue Multidisciplinary Approaches and Recent Advances in Anesthesiology and Critical Care)

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20 pages, 1223 KB

Open AccessReview

Mechanistic Insights and Advances of Bispecific T Cell Engaging Antibodies Therapy in Multiple Myeloma

by Ting Fang Tang, Chin Sum Cheong, Chung Yeng Looi, Won Fen Wong and Gin Gin Gan

Medicina 2025, 61(12), 2113; https://doi.org/10.3390/medicina61122113 - 27 Nov 2025

Abstract

Multiple myeloma (MM) is a clonal malignancy of terminally differentiated plasma cells characterized by bone marrow infiltration and excessive production of monoclonal immunoglobulins, leading to end-organ damage such as osteolytic bone lesions. Despite substantial therapeutic progress achieved with proteasome inhibitors, immunomodulatory drugs, and [...] Read more.

Multiple myeloma (MM) is a clonal malignancy of terminally differentiated plasma cells characterized by bone marrow infiltration and excessive production of monoclonal immunoglobulins, leading to end-organ damage such as osteolytic bone lesions. Despite substantial therapeutic progress achieved with proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, multiple myeloma remains incurable, and outcomes for triple-class-refractory patients remain dismal, with median survival below one year. Bispecific T cell engaging antibodies (TCEs) have recently emerged as a promising immunotherapeutic approach capable of redirecting cytotoxic T cells to eliminate malignant plasma cells. These engineered antibodies simultaneously engage CD3 on T cells and a tumor-associated antigen such as B cell maturation antigen (BCMA), G protein-coupled receptor family C group 5 member D (GPRC5D), or Fc receptor homolog 5 (FcRH5), thereby forming an immune synapse that triggers T cell activation, cytokine secretion, and perforin–granzyme-mediated apoptosis of the targeted B cell. This review summarizes the molecular design, mechanism of action, and clinical development of TCEs in MM, encompassing early bi-specific T cell engagers (BiTE) constructs such as AMG 420 and next-generation IgG-like molecules including teclistamab. Pivotal clinical trials have demonstrated overall response rates between 43% and 73%, accompanied by durable remissions and manageable safety profiles. Future directions include earlier-line integration, synergistic combinations with immunomodulatory or costimulatory agents, and the development of trispecific formats to overcome antigen escape and T cell exhaustion. Collectively, TCEs represent a paradigm shift toward durable, immune-mediated disease control in multiple myeloma. Full article

(This article belongs to the Special Issue Updates on the Changing Landscape of Immunotherapy and Targeted Therapy in Cancer)

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24 pages, 821 KB

Open AccessReview

Proteoglycans in Prostate Cancer Progression and Therapy Resistance

by Ivana Samaržija

Medicina 2025, 61(12), 2112; https://doi.org/10.3390/medicina61122112 - 27 Nov 2025

Abstract

The extracellular matrix (ECM) is a complex noncellular network of (macro-)molecules that surrounds and supports diverse cells in tissues and organs. In cancer, ECM is a part of the tumor microenvironment (TME) that embeds its cellular components including cancer cells and the neighboring [...] Read more.

The extracellular matrix (ECM) is a complex noncellular network of (macro-)molecules that surrounds and supports diverse cells in tissues and organs. In cancer, ECM is a part of the tumor microenvironment (TME) that embeds its cellular components including cancer cells and the neighboring non-cancerous stromal cells such as fibroblasts, endothelial, and immune cells. Given the complexity of players and interactions that the ECM participates in and is exposed to in the TME, it does not come as a surprise that many of the processes that drive cancer progression take part precisely in the ECM compartment of the TME. Along with diverse glycoproteins and collagens, proteoglycans (PGs) are among the main components of the core ECM. PGs are composed of a protein core to which glycosaminoglycan chains are attached. Considering the structural diversity of these molecules and their ‘hybrid’ nature, it is not surprising that they are involved in a variety of processes that are vital for surrounding cells. Moreover, they are secreted by both cancer and stromal cells, contributing to the complexity of interactions in the TME. In prostate cancer, PGs have been shown to be involved in many steps of its progression; the most prominent examples include the seemingly tumor-promoting roles of versican, perlecan, and biglycan, and the tumor-suppressive roles of decorin and betaglycan. The role of syndecan 1 is a bit more complex; namely, the nature of its role is context dependent. In this narrative review article, the roles of PGs in prostate cancer progression and therapy resistance are discussed in more detail. Full article

(This article belongs to the Special Issue Prostate Cancer in the Molecular Era)

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