Medicina

16 pages, 749 KB

Open AccessArticle

The Impact of Antidiabetic Therapy on Liver Injury, Steatosis, and Fibrosis in Patients with Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease

by Oana Albai, Adina Braha, Romulus Timar, Sandra Lazăr, Simona Popescu and Bogdan Timar

Medicina 2025, 61(10), 1850; https://doi.org/10.3390/medicina61101850 - 15 Oct 2025

Abstract

Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked with type 2 diabetes mellitus (T2D) and obesity. Despite its growing prevalence, effective pharmacological interventions remain limited, with antidiabetic agents such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose [...] Read more.

Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked with type 2 diabetes mellitus (T2D) and obesity. Despite its growing prevalence, effective pharmacological interventions remain limited, with antidiabetic agents such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) showing emerging promise. This study aimed to evaluate the impact of different antidiabetic therapies on hepatic steatosis, fibrosis, and cardiometabolic risk factors in patients with T2D and MASLD from Romania. Materials and Methods: We conducted a prospective observational study involving 256 patients with T2D and MASLD followed up for 6 months. Assessed parameters included anthropometry, glycemic indices, lipid profile, renal function, liver enzymes, and non-invasive evaluation of hepatic steatosis and fibrosis. Patients were 53% women, had a median age of 63 years, a median BMI of 32.2 kg/m², a median baseline CAP of 281 dB/m, a FibroScan of 8.9 kPa, and an HbA1c of 8.0%. Results: CAP decreased significantly from 281 to 245 dB/m, p < 0.0001; FibroScan from 8.9 to 8.0 kPa, p < 0.0001. The largest changes were observed in the GLP-1 RA subgroup (CAP −50 dB/m, FibroScan −1.0 kPa, weight −8.0 kg, HbA1c −0.7%), and in the SGLT2i subgroup (CAP −30.5 dB/m, FibroScan −0.7 kPa, weight −4.0 kg, HbA1c −0.5%). In regression analysis, independent factors associated with CAP improvement included GLP-1 RA therapy (β = 44.5, 95% CI 38.3–50.6, p < 0.0001), SGLT2i therapy (β = 23.4, 95% CI 15.7–31.1, p < 0.0001), and ≥10% weight loss (β = 23.2, 95% CI 12–34.4, p < 0.0001). For FibroScan improvement, GLP-1 RA (β = 1.0, 95% CI 0.8–1.2, p < 0.0001) and SGLT2i (β = 0.5, 95% CI 0.3–0.7, p < 0.0001) therapies were both significant. Conclusions: Antidiabetic therapy, particularly GLP-1 RA, was significantly associated with improvement in hepatic steatosis, fibrosis, and cardiometabolic risk in T2D patients with MASLD beyond the weight reduction effect. However, weight loss and lipid modulation enhance these benefits, supporting the development of integrated therapeutic strategies for this high-risk population. Full article

(This article belongs to the Section Endocrinology)

13 pages, 3323 KB

Open AccessArticle

Comparative Outcomes of Delayed i-PRF Combination with Nanofracture in the Treatment of Large Chondral Defects in the Knee

by Özgür Başal, James G. Jefferies, Jure Serdar and Mahmut Nedim Doral

Medicina 2025, 61(10), 1849; https://doi.org/10.3390/medicina61101849 - 15 Oct 2025

Abstract

Background and Objectives: This study aimed to evaluate whether delayed intra-articular application of injectable platelet-rich fibrin (i-PRF) improves clinical and radiologic outcomes compared to nanofracture alone. Materials and Methods: A total of 76 patients with ICRS Grade III–IV femoral condyle or [...] Read more.

Background and Objectives: This study aimed to evaluate whether delayed intra-articular application of injectable platelet-rich fibrin (i-PRF) improves clinical and radiologic outcomes compared to nanofracture alone. Materials and Methods: A total of 76 patients with ICRS Grade III–IV femoral condyle or trochlear cartilage defects larger than 2 cm² were enrolled in this prospective controlled study. Patients were allocated into two groups: Group 1 (n = 40) underwent nanofracture followed by delayed intra-articular i-PRF injection at three weeks postoperatively, while Group 2 (n = 36) underwent nanofracture alone. Preoperative MRI was evaluated using the AMADEUS grading system. Clinical outcomes—including WOMAC and IKDC scores—were assessed at baseline and at 6, 12, and 24 months postoperatively. MOCART 2.0 scoring was used to evaluate cartilage repair at ≥12 months follow-up. Results: Both groups demonstrated significant functional improvement according to the IKDC and WOMAC scores. However, Group 1 showed a significantly greater improvement in WOMAC total score at final follow-up (Group 1: 20.1 ± 4.3 vs. control: 23.2 ± 3.4; p = 0.0008). No statistically significant differences were found between groups in IKDC score (p = 0.238), Tegner score (p = 0.776), or time to return to daily activities (p = 0.401). Baseline demographic, radiological, and intraoperative variables were comparable between groups (p > 0.05 for all). Radiologic outcomes based on the mean MOCART 2.0 scores were 57.1 and 50, respectively, in group 1 and group 2 (p = 0.0316). These results showed significantly improved results in group 1 according to the MRI evaluation. Conclusions: In patients with large chondral defects (>2 cm²), delayed intra-articular i-PRF injection following nanofracture may improve mid-term functional and radiological outcomes, particularly in pain and symptom relief. This regenerative strategy enhances cartilage repair potential during the early healing phase without adding surgical complexity. Full article

(This article belongs to the Section Orthopedics)

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17 pages, 2144 KB

Open AccessArticle

Sudomotor Dysfunction of Feet Is Associated with Cardiac Autonomic Neuropathy in Patients with Type 2 Diabetes: A Cross-Sectional Study

by Alexandra Gogan, Sandra Lazar, Ovidiu Potre, Vlad-Florian Avram, Andreea Herascu, Minodora Andor, Florina Caruntu and Bogdan Timar

Medicina 2025, 61(10), 1848; https://doi.org/10.3390/medicina61101848 - 15 Oct 2025

Abstract

Background/Objectives: Cardiac autonomic neuropathy (CAN) is a common but also underdiagnosed complication of diabetes mellitus (DM), associated with high cardiovascular risk and mortality. Sudomotor dysfunction can serve as an early indicator of autonomic dysfunction. This study evaluated the association between sudomotor dysfunction [...] Read more.

Background/Objectives: Cardiac autonomic neuropathy (CAN) is a common but also underdiagnosed complication of diabetes mellitus (DM), associated with high cardiovascular risk and mortality. Sudomotor dysfunction can serve as an early indicator of autonomic dysfunction. This study evaluated the association between sudomotor dysfunction and the severity of CAN in patients with type 2 diabetes (T2D). Methods: In this cross-sectional study, 109 patients with T2D were evaluated for diabetic peripheral neuropathy, cardiovascular autonomic dysfunction, and sudomotor dysfunction. Additionally, clinical and biochemical data were collected from patients’ medical records. Results: Sudomotor dysfunction (SUDO+) was present in 59.6% of patients. The presence of SUDO+ was associated with a higher age, longer duration of diabetes, lower eGFR (estimated glomerular filtration rate) values, and more severe signs of peripheral neuropathy. SUDO+ patients showed significantly greater orthostatic systolic and diastolic BP (blood pressure) changes, lower RR interval ratios, and lower feet ESC (electrochemical skin conductance) values. ROC (receiver operating characteristic) analysis for feet ESC in identifying pathological RR ratio showed an AUC of 0.689 (95% CI: 0.593–0.774, p = 0.0022), with a sensitivity of 46.7% and a specificity of 94.7% at a cutoff of ≤68 µS. For orthostatic hypotension and QTc prolongation, the ESC values had limited discriminative power. Chi-squared analysis showed a significant association between feet sudomotor impairment and pathological RR ratio (χ² = 6.521, p = 0.0107). Conclusions: Sudomotor dysfunction is associated with indicators of CAN. SUDOSCAN can be used as a complementary tool for early CAN detection in clinical practice. Full article

(This article belongs to the Section Endocrinology)

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11 pages, 5491 KB

Open AccessArticle

A Minimally Invasive Fixation Versus Double Plating of Associated Posterior Malleolus and Fibula Fractures—A Comparative Human Cadaveric Biomechanical Study

by Konstantin Ganchev, Preslav Penev, Ivan Zderic, Kajetan Klos, R. Geoff Richards, Dimitar Raykov, Boyko Gueorguiev, Lionel Llano and Karl Stoffel

Medicina 2025, 61(10), 1847; https://doi.org/10.3390/medicina61101847 - 15 Oct 2025

Abstract

Background and Objectives: Ankle fractures are common and occur in up to 25% of cases with posterior malleolus (PM) involvement. The gold standard for their treatment considers posterior approaches and plating of both the PM and fibula. However, in elderly and comorbid patients, [...] Read more.

Background and Objectives: Ankle fractures are common and occur in up to 25% of cases with posterior malleolus (PM) involvement. The gold standard for their treatment considers posterior approaches and plating of both the PM and fibula. However, in elderly and comorbid patients, this strategy remains controversial. The objective of this biomechanical study was to compare a minimally invasive fixation—utilizing a fibula nail and percutaneous anteroposterior (AP) screws—versus double plating. Materials and Methods: An oblique fibula fracture associated with a Haraguchi type 1 PM fracture was reproduced in sixteen human cadaveric specimens randomized to two groups. Eight specimens were treated with a fibula nail plus two AP screws fixing the PM, while the remaining eight specimens underwent double plating. Biomechanical testing was performed under destructive complex cyclic loading applying a staircase protocol. Interfragmentary movements were captured via motion tracking. Results: Initial axial stiffness was similar between nailing (1125.9 ± 341.7 N/mm) and double plating (742.9 ± 600.1 N/mm) (p = 0.129). During cyclic testing, interfragmentary fibula displacement was higher for double plating versus nailing (p = 0.057), whereas PM displacement and syndesmosis diastasis remained comparable between the two techniques (p ≥ 0.197). Conclusions: The minimally invasive fixation of associated PM and fibula fractures utilizing a fibula nail and two anteroposterior screws demonstrated non-inferiority to double plating and presents a viable option in cases where delicate soft tissue management is required. Full article

(This article belongs to the Section Orthopedics)

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12 pages, 286 KB

Open AccessArticle

Can Nutritional Screening Tools Predict the Prognosis of Critically Ill Patients with Sepsis?

by Duygu Kayar Calili, Demet Bolukbasi and Seval Izdes

Medicina 2025, 61(10), 1846; https://doi.org/10.3390/medicina61101846 - 15 Oct 2025

Abstract

Background and Objectives: Although nutritional status is critical to the clinical outcomes of septic patients, studies on this topic are limited. We aim to assess the prognostic value of five nutritional screening tools (NSTs) for septic patients both at the time of [...] Read more.

Background and Objectives: Although nutritional status is critical to the clinical outcomes of septic patients, studies on this topic are limited. We aim to assess the prognostic value of five nutritional screening tools (NSTs) for septic patients both at the time of admission to the intensive care unit (ICU) and five days later. Materials and Methods: This prospective observational study included adult septic patients in the ICU. Patients were divided into two groups: survivors and non-survivors. Clinical, laboratory characteristics, and NST values [The Controlling Nutritional Status (CONUT), Prognostic Nutritional Index (PNI), Nutritional Risk Screening (NRS-2002), Geriatric Nutritional Risk Index (GNRI), and Nutrition Risk in the Critically Ill (NUTRIC)] were recorded at admission and on Day-5, and intergroup and intragroup comparisons were performed. Results: A total of 126 patients were included in this study: 97 in the survival group and 29 in the non-survival group. The non-survivors had higher CONUT and NUTRIC scores and lower PNI scores. Multivariate analysis found higher Day-5 NUTRIC scores independently associated with mortality. ROC analysis identified NUTRIC > 6 as a mortality predictor. Conclusions: Although several markers differed significantly between survivors and non-survivors, our findings show that a high Day-5 NUTRIC score was the only factor independently associated with mortality among NSTs. Full article

(This article belongs to the Section Intensive Care/ Anesthesiology)

11 pages, 557 KB

Open AccessReview

Reappraising Use of Flecainide for Atrial Fibrillation and Ventricular Arrhythmias in Structural Heart Disease Patients

by Dimitrios Tsiachris, Sotirios C. Kotoulas, Ioannis Doundoulakis, Christos-Konstantinos Antoniou, Michail Botis, Konstantinos Pamporis, Nikolaos Argyriou, Aikaterini-Eleftheria Karanikola, Panagiotis Tsioufis, Athanasios Kordalis and Konstantinos Tsioufis

Medicina 2025, 61(10), 1845; https://doi.org/10.3390/medicina61101845 - 15 Oct 2025

Abstract

Background: Flecainide, a class Ic antiarrhythmic agent, has long been contraindicated in structural heart disease (SHD) due to findings of the Cardiac Arrhythmia Suppression Trial (CAST). However, its proven efficacy in patients without structural abnormalities and emerging safety data in selected SHD [...] Read more.

Background: Flecainide, a class Ic antiarrhythmic agent, has long been contraindicated in structural heart disease (SHD) due to findings of the Cardiac Arrhythmia Suppression Trial (CAST). However, its proven efficacy in patients without structural abnormalities and emerging safety data in selected SHD populations have prompted reconsideration of its role. Aim: This mini review evaluates recent evidence on the safety and efficacy of flecainide in atrial fibrillation (AF) and premature ventricular contractions (PVCs), particularly in patients with stable coronary artery disease (CAD), and arrhythmogenic right ventricular cardiomyopathy (ARVC). Results: Modern imaging and improved risk stratification allow for more precise identification of patients who may safely receive flecainide, even in the presence of specific structural abnormalities. Observational studies have reported no mortality or ventricular arrhythmias incidence increase in stable CAD or ARVC when flecainide is administered under stringent criteria. While current guidelines remain cautious, clinical practice is beginning to reflect a more individualized approach. Conclusions: Flecainide use in selected SHD patients appears both feasible and safe when guided by comprehensive imaging and clinical judgment. The need for prospective randomized trials to confirm these findings and potentially inform future guideline updates is urgent and of utmost importance in the field of antiarrhythmic therapies. Full article

(This article belongs to the Special Issue Evolving Concepts in Clinical Cardiology)

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12 pages, 448 KB

Open AccessArticle

Sleep Paralysis Among Higher Education Students: A Possible Role of Antidepressant and Recreational Stimulant Use

by Gediminas Gumbis, Kristijonas Puteikis and Rūta Mameniškienė

Medicina 2025, 61(10), 1844; https://doi.org/10.3390/medicina61101844 - 15 Oct 2025

Abstract

Background and Objectives: While sleep paralysis (SP) is a well-defined disorder, its pathophysiology and causes remain elusive. We aimed to assess the prevalence of sleep paralysis among higher education students and determine factors associated with SP with a focus on psychoactive substance [...] Read more.

Background and Objectives: While sleep paralysis (SP) is a well-defined disorder, its pathophysiology and causes remain elusive. We aimed to assess the prevalence of sleep paralysis among higher education students and determine factors associated with SP with a focus on psychoactive substance and medication use. Materials and Methods: We conducted a cross-sectional online survey across higher education institutions in Lithuania, asking students to report the occurrence and frequency of SP as well as its characteristics and self-rated sleep quality alongside demographic data and history of medication and psychoactive substance use. Subgroup comparisons and correlation analyses were performed in search of factors associated with reported SP. Results: The study sample consisted of 275 respondents aged 22.9 ± 4.7 years (240, 87.3% female), 119 (43.3%) of whom reported having experienced SP (average age at first episode 16.4 ± 4.2 years), with 87 (73.1%) more than once. The phenomenology of SP episodes included mostly visual, auditory, sensory, or olfactory hallucinations (73, 61.3%), feelings of fear or anxiety (56, 47.1%), incubus-like phenomena (17, 14.3%), and autonomic symptoms (6, 5.0%). Having experienced SP was associated with the use of antidepressants or recreational stimulant use (χ² = 5.258, p = 0.022) as well as higher alcohol intake (Z = −3.568, p < 0.001) and lower self-rated sleep quality (Z = −2.413, p = 0.016). Earlier age of onset, hallucinations during paralysis, specific time of manifestation during the night, and overall nightmare frequency were related to the recurrence of SP. Respondents tied SP episodes mostly to stress or anxiety (55, 46.2%), the supine sleeping position (31, 26.1%), disturbed sleep cycles (28, 23.5%), and emotional or traumatic experiences (28, 23.5%). Conclusions: Our study suggests that SP is prevalent among students with a tendency to recur. We report a correlational association between SP and the use of antidepressants or stimulant drugs, suggesting the need to further explore the possible role of psychoactive agents in this disorder. Full article

(This article belongs to the Section Neurology)

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13 pages, 609 KB

Open AccessArticle

Prognostic Impact of Concomitant Beta-Blocker Use on Survival in EGFR-Mutant Metastatic Non-Small Cell Lung Cancer Patients Treated with Erlotinib

by Oğuzhan Yıldız, Talat Aykut, Bahattin Engin Kaya, Ömer Genç, Ali Fuat Gürbüz, Fatih Saçkan, Melek Karakurt Eryılmaz, Mehmet Zahid Koçak, Murat Araz and Mehmet Artaç

Medicina 2025, 61(10), 1843; https://doi.org/10.3390/medicina61101843 - 15 Oct 2025

Abstract

Background and Objectives: Erlotinib, a tyrosine kinase inhibitor (TKI), is an established therapy for patients with metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Preclinical and clinical evidence suggests that chronic stress, mediated through β-adrenergic signaling, promotes [...] Read more.

Background and Objectives: Erlotinib, a tyrosine kinase inhibitor (TKI), is an established therapy for patients with metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Preclinical and clinical evidence suggests that chronic stress, mediated through β-adrenergic signaling, promotes tumor progression, angiogenesis, and therapy resistance. Furthermore, interactions between β-adrenergic signaling and EGFR pathways have been hypothesized to negatively influence treatment responses. Based on this rationale, we investigated whether concomitant beta-blocker use may improve survival outcomes in EGFR-mutant NSCLC patients treated with erlotinib. Materials and Methods: This retrospective analysis included 103 patients with metastatic EGFR-mutant NSCLC who received erlotinib. Patients were classified according to concurrent beta-blocker use, defined as continuous therapy for at least six months prior to erlotinib initiation, prescribed for cardiovascular indications. Progression-free survival (PFS) and overall survival (OS) were compared between beta-blocker users and non-users. Results: Patients receiving erlotinib with concomitant beta-blocker therapy achieved a median PFS (mPFS) of 21.4 months (95% CI, 13.1–29.7), compared with 9.7 months (95% CI, 6.7–12.7) in non-users (p = 0.003). Median OS (mOS) was 32.4 months (95% CI, 14.8–50.0) in the beta-blocker group versus 19.9 months (95% CI, 14.8–25.0) in the non-beta-blocker group (p = 0.010). Multivariate Cox regression confirmed beta-blocker use as an independent prognostic factor for both PFS (p = 0.004) and OS (p = 0.014). Conclusions: Concomitant beta-blocker use was associated with significantly prolonged survival in patients with EGFR-mutant metastatic NSCLC receiving erlotinib. These findings support the hypothesis that β-adrenergic inhibition enhances the efficacy of EGFR-targeted therapy. Prospective studies are warranted to validate these results and to further elucidate the underlying biological mechanisms. Full article

(This article belongs to the Section Oncology)

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13 pages, 2877 KB

Open AccessArticle

Glandular Transposition Technique for the Correction of Advanced Gynecomastia in Post-Bariatric Patients: A Case Series on a Conservative Strategy for Natural Aesthetic Outcomes

by Feliciano Ciccarelli, Felice Moccia, Maria Giovanna Vastarella, Arturo Amoroso, Claudia Vastarella, Vincenzo Vastarella and Gorizio Pieretti

Medicina 2025, 61(10), 1842; https://doi.org/10.3390/medicina61101842 - 15 Oct 2025

Abstract

Background and Objectives: Advanced gynecomastia/pseudogynecomastia (Simon grades IIb–III) in post-bariatric patients presents both esthetic and technical challenges. Conventional excisional methods often result in flattened chest contours, extensive scarring, and loss of nipple–areolar complex (NAC) sensation. There is a growing need for conservative, [...] Read more.

Background and Objectives: Advanced gynecomastia/pseudogynecomastia (Simon grades IIb–III) in post-bariatric patients presents both esthetic and technical challenges. Conventional excisional methods often result in flattened chest contours, extensive scarring, and loss of nipple–areolar complex (NAC) sensation. There is a growing need for conservative, tissue-preserving strategies that respect the unique morphology of massive weight-loss patients. Materials and Methods: This consecutive case series included 15 male patients (median age: 38 years, IQR 36.5–39.5) with advanced gynecomastia/pseudogynecomastia and stable weight loss following bariatric surgery. All underwent a glandular transposition technique, preserving the NAC on a pedicle based on thoracic perforators and avoiding free grafting. Redundant lower-pole skin was excised, a new NAC site was created cranially, and the gland was repositioned beneath a dermo-adipose flap. Outcomes included complication rates, patient satisfaction, and changes in BODY-Q chest appearance scores. Results: No major complications occurred. NAC viability and sensation were preserved in all patients. One patient required secondary revision for residual contour bulging, while three developed minor hematomas that resolved spontaneously. At 3 months, the median Likert satisfaction score improved from 2 (IQR 2–3) preoperatively to 5 (IQR 4–5) postoperatively (p < 0.001, Wilcoxon signed-rank test). BODY-Q chest appearance scores improved significantly from 31 (IQR 28–35) to 78 (IQR 74–82) (p < 0.001). External observers preferred postoperative results in 90% of randomized photo-pair comparisons. Conclusions: Glandular transposition is a safe, reproducible, and esthetically effective technique for advanced gynecomastia/pseudogynecomastia in post-bariatric men. By preserving glandular continuity and avoiding free NAC grafting, this method achieves natural chest projection, maintains nipple sensitivity, and provides high patient satisfaction with minimal complications. It represents a compelling alternative to conventional radical excision strategies. Full article

(This article belongs to the Special Issue New Advances and Challenges in Plastic Surgery)

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20 pages, 3691 KB

Open AccessArticle

Participation of the Periosteum, Endosteum, and Hematogenous Marrow in the Early Osseointegration of a Titanium Implant Inserted in Contact with the Hematogenous Marrow

by Cristian Adrian Ratiu, Cosmin Sinescu, Danut Dejeu, Ovidiu Tica, Corina Moisa, Camelia Anca Croitoru, Ioana Adela Ratiu, Virgil-Florin Duma, Adrian Todor, Viorel Miclaus and Vasile Rus

Medicina 2025, 61(10), 1841; https://doi.org/10.3390/medicina61101841 - 14 Oct 2025

Abstract

Background and Objectives: Implant osseointegration has been widely studied over the past few decades, particularly focusing on surface modifications that aim to improve integration. However, the literature includes few studies regarding the role of the endosteum in early osteointegration. Therefore, the aim [...] Read more.

Background and Objectives: Implant osseointegration has been widely studied over the past few decades, particularly focusing on surface modifications that aim to improve integration. However, the literature includes few studies regarding the role of the endosteum in early osteointegration. Therefore, the aim of the present work is to approach the technique of implant insertion into bones with marrow, with an emphasis on the use of implants that are long enough to achieve marrow penetration. Materials and Methods: Titanium implants were inserted into the femurs of eight eleven-month-old rabbits. Fourteen days later, the animals were euthanized in accordance with the current legal and ethical guidelines. The histological processes that occur at the bone–implant interface were investigated. Histological sections of the bone–implant interface were colored using the Trichrome’s Goldner method, and were further analyzed and photographed using an Olympus microscope. Results: The histological analysis showed that during the initial osteointegration phases, the newly formed bone originated from the endosteal–medular zone. Periostal proliferation was observed only during the early stages. The bone that proliferated on the implant’s endosteal/medullary interface exhibited a surface area approximately 6 times larger than that of the bone formed on the osteal surface. Also, its length was approximately 25% longer. Conclusions: The bone tissue that proliferates on the endosteal and marrow surface of the implant increases significantly the bone–implant interface, and creates the setting for a good secondary stability. The findings suggest several clinical implications, as follows: penetrating the bone marrow during the insertion of short implants allows for increasing the bone–implant interface; the flap should be carefully managed; the integrity of the periosteum must be kept, as this is a key anatomical structure in cases of deficient bone marrow (i.e., severe mandible atrophy or vertical ridge augmentations). Full article

(This article belongs to the Special Issue Advances in Soft and Hard Tissue Management Around Dental Implants)

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21 pages, 845 KB

Open AccessArticle

Mental Health and Age-Related Differences in Community During the COVID-19 Pandemic: A Cross-Sectional Study from Southeastern Türkiye

by Pakize Gamze Erten Bucaktepe, Vasfiye Demir Pervane, Ömer Göcen, Sercan Bulut Çelik, Fatima Çelik, Öznur Uysal Batmaz, Ahmet Yılmaz, Tahsin Çelepkolu and Kürşat Altınbaş

Medicina 2025, 61(10), 1840; https://doi.org/10.3390/medicina61101840 - 14 Oct 2025

Abstract

Background and Objectives: The COVID-19 pandemic has caused profound disruptions in socioeconomic, and health domains, with significant implications for mental well-being. The aim of this study was to evaluate the impact of the pandemic on stress, anxiety, and depression, alongside perceived social support, [...] Read more.

Background and Objectives: The COVID-19 pandemic has caused profound disruptions in socioeconomic, and health domains, with significant implications for mental well-being. The aim of this study was to evaluate the impact of the pandemic on stress, anxiety, and depression, alongside perceived social support, coping flexibility and related factors, and to examine how these issues vary across different age groups. Materials and Methods: A cross-sectional analytical study was conducted in Türkiye between August and December 2020. Data were collected through an online questionnaire including sociodemographic characteristics, pandemic-related concerns, and validated scales: Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS), Coping Flexibility Scale (CFS), and Multidimensional Scale of Perceived Social Support (MSPSS). Statistical analyses included descriptive and comparative tests, correlation analysis, multiple linear regression models, and correspondence analysis. Results: Among 1699 participants, 58.0% were female; 24.5% and 42.1% reported anxiety and depressive symptoms above thresholds, respectively. Younger age correlated negatively with stress, anxiety, and depression scores (p < 0.001). Feelings of loneliness, loss of control, ostracism, and sleep or concentration problems were positively associated with anxiety, depression, and stress, but negatively associated with coping flexibility and social support (p < 0.001). The 15–20 age group had the highest anxiety and depression levels and the lowest social support; the 15–30 group showed the highest stress, while the 61–75 group exhibited the lowest coping flexibility. Regression models explained 62.7% of anxiety and 56.6% of depressive symptom variances. Major predictors of anxiety included depressive symptoms, stress, and fear of dying from COVID-19, while depressive symptoms were predicted by age, stress, coping flexibility, social support, and anxiety. Conclusions: The findings highlight the considerable psychological burden and distinct vulnerabilities among age groups. Mental health interventions should be tailored according to age, emphasising the enhancement of social support and coping flexibility to strengthen resilience in future pandemics. Full article

(This article belongs to the Special Issue The Burden of COVID-19 Pandemic on Mental Health, 2nd Edition)

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19 pages, 3276 KB

Open AccessArticle

CBCT-Based Online Adaptive, Ultra-Hypofractionated Radiotherapy for Prostate Cancer: First Clinical Experiences

by Georg Wurschi, Alexander Voigt, Noreen Murr, Cora Riede, Michael Schwedas, Maximilian Römer, Sonia Drozdz and Klaus Pietschmann

Medicina 2025, 61(10), 1839; https://doi.org/10.3390/medicina61101839 - 14 Oct 2025

Abstract

Background and Objectives: Ultra-hypofractionated radiotherapy (uhRT) is increasingly used for low- and intermediate-risk localized prostate cancer, necessitating exceptional precision compared to conventional fractionation. CBCT-based online-adaptive uhRT may help mitigate pelvic organ motion but has not yet been established in clinical routine. We [...] Read more.

Background and Objectives: Ultra-hypofractionated radiotherapy (uhRT) is increasingly used for low- and intermediate-risk localized prostate cancer, necessitating exceptional precision compared to conventional fractionation. CBCT-based online-adaptive uhRT may help mitigate pelvic organ motion but has not yet been established in clinical routine. We report initial clinical experiences focusing on the feasibility and technical aspects of treatment delivery. Materials and Methods: Seven patients (35 fractions) with low- or intermediate-risk prostate cancer were treated with online-adaptive uhRT on the Varian Ethos^® system within routine clinical care. The target included the prostate and proximal seminal vesicles (CTV1, 5 × 7.25 Gy), with an integrated boost to the prostate (CTV2, 5 × 8.00 Gy). For each fraction, dose–volume histogram (DVH) parameters for targets and organs at risk (OARs) were recorded retrospectively for both scheduled and adaptive plans, along with the plan selection decision. Plan quality was evaluated per clinical DVH constraints and target coverage. The treatment time was recorded. Results: Online-adaptive uhRT was successfully delivered every day in 5 patients and on alternate days in 2 patients. Mean treatment time was 30:17 (±05:49 SD) minutes per fraction. The median recorded change in target and OAR volumes was <10%. Adaptive plans resulted in a statistically significantly improved target coverage for CTV1 (V100%, p = 0.01), PTV1 (D98%, p < 0.001), PTV2 boost (D98%, p < 0.001) in Wilcoxon signed-rank tests. OAR dose reduction was limited, with a small improvement in bladder V40Gy (p = 0.02). Adaptive plans were applied in 32/35 fractions (91.4%). To encompass intra-fractional motion in 95% of fractions, positional adjustments up to 0.77 cm (longitudinal), 0.37 cm (lateral), and 0.59 cm (sagittal) were required. Conclusions: Online-adaptive uhRT appears feasible, leading to optimized target volume coverage. Considerable treatment times must be taken into account. A second CBCT is recommended to compensate for intra-fractional motion. Further research regarding patient-related endpoints and cost-effectiveness is highly needed. Full article

(This article belongs to the Special Issue New Advances in Radiation Therapy)

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12 pages, 338 KB

Open AccessArticle

Comparison of Ultrasound-Guided Quadratus Lumborum Plane Block and External Oblique Intercostal Plane Block for Postoperative Analgesia After Laparoscopic Cholecystectomy: A Two-Center Randomized Controlled Trial

by Cem Kıvılcım Kaçar, Andaç Dedeoğlu, Hülya Tosun Söner, Enes Çelik, Okan Andıç, Fatma Acil, Hakan Akelma, Osman Uzundere and Erhan Gökçek

Medicina 2025, 61(10), 1838; https://doi.org/10.3390/medicina61101838 - 14 Oct 2025

Abstract

Background and Objectives: Although various regional anesthesia techniques are commonly used for laparoscopic cholecystectomy (LC), to date, no randomized controlled trial has compared the effectiveness of Quadratus Lumborum Plane Block (QLB) and External Oblique Intercostal Plane Block (EOIPB) in LC. Our aim [...] Read more.

Background and Objectives: Although various regional anesthesia techniques are commonly used for laparoscopic cholecystectomy (LC), to date, no randomized controlled trial has compared the effectiveness of Quadratus Lumborum Plane Block (QLB) and External Oblique Intercostal Plane Block (EOIPB) in LC. Our aim was to compare the effectiveness of ultrasound-guided QLB and EOIPB in providing postoperative analgesia after LC. Materials and Methods: In this two-center, randomized controlled trial, patients undergoing LC were divided into QLB and EOIPB groups. Our primary outcome was the postoperative pain scores measured using the Numerical Rating Scale (NRS) at predetermined intervals. Secondary outcomes included opioid consumption, Riker Sedation–Agitation Scale (RSAS) score, and patient satisfaction. Results: The NRS pain scores at postoperative 30th minute, 4th, 12th, and 24th hours were significantly lower in the QLB group (p < 0.05). Patients in the QLB group required significantly less tramadol compared to the EOIPB group (p < 0.000). The QLB group also demonstrated lower RSAS scores (p = 0.005), indicating a smoother recovery process. Patient satisfaction scores were markedly higher in the QLB group (p < 0.000). Although both blocks were well-tolerated with no differences in side effects, EOIPB was associated with higher opioid consumption, indicating its relatively limited effectiveness. Conclusions: To conclude, this study highlights that QLB is a more effective option for postoperative analgesia and improves patient satisfaction after LC. EOIPB may serve as a viable alternative for some patients; however, given the advantages of QLB in pain control and recovery, it stands out as a more preferable method. Full article

(This article belongs to the Section Intensive Care/ Anesthesiology)

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20 pages, 2809 KB

Open AccessArticle

Evaluation of TAM Receptor Targeting in Pathophysiology of Idiopathic Pulmonary Fibrosis

by Nicole Vercellino, Luciana L. Ferreira, Elisa Zoppis, Alice Di Tizio, Zohre Sabihi Ahvaz, Rosalba Minisini, Francesco Gavelli, Pier Paolo Sainaghi, Filippo Patrucco and Mattia Bellan

Medicina 2025, 61(10), 1837; https://doi.org/10.3390/medicina61101837 - 14 Oct 2025

Abstract

Background and Objectives: TAM receptors—Tyro3, Axl, and Mer—and their ligand Growth Arrest-Specific 6 (Gas6) represent a pleiotropic system implicated in fibrosis. Increased Gas6 and Axl expression have previously been observed in lung samples and fibroblast cultures from Idiopathic Pulmonary Fibrosis (IPF) patients. [...] Read more.

Background and Objectives: TAM receptors—Tyro3, Axl, and Mer—and their ligand Growth Arrest-Specific 6 (Gas6) represent a pleiotropic system implicated in fibrosis. Increased Gas6 and Axl expression have previously been observed in lung samples and fibroblast cultures from Idiopathic Pulmonary Fibrosis (IPF) patients. The study explored the contribution of Gas6/TAM system in fibrosis development and the impact of its pharmacological inhibition in fibroblasts. Materials and Methods: IPF fibroblasts (IPF FBs) and control human pulmonary fibroblasts (HPFs) were treated with R428 (Axl-specific inhibitor), LDC1267 (TAM inhibitor), or Nintedanib (an IPF-approved drug) to evaluate the influence of these drugs on cell proliferation, migration, and the expression of pro-inflammatory and pro-fibrotic genes. Fibroblast-to-myofibroblast differentiation was induced by TGF-β. The impact of IPF FBs and HPF on macrophage polarization was investigated through a co-culture of fibroblasts with monocyte-derived macrophages, with the further gene expression analysis of markers of the M1 (pro-inflammatory) or M2 (pro-fibrotic) polarization forms. Results: Cell proliferation was monitored in fibroblasts treated with TGF-β, the drugs, and their combination. In the presence of LDC1267 and Nintedanib, minor differences in cell confluence were detected between IPF FBs and HPFs; R428 (1 μM) seemed to have a higher inhibitory impact on IPF FBs. Regarding cell migration, the fibroblasts treated with LDC1267 exhibited slower wound closure. R428 treatment led to a relative wound closure of 76% in HPFs but only 56% in IPF FBs (60 h). R428 (1 μM) significantly reduced the expression of the pro-fibrotic markers ACTA2, COL1A1, and FN1 in HPFs and IPF FBs compared to TGF-β treatment. HPFs and IPF FBs co-cultured with monocyte-derived macrophages demonstrated a significantly increased expression of MRC1 while the expression of FN1, TNFα, and CXCL10 was moderately increased. Conclusions: These findings suggest that R428 and LDC1267 modulate the proliferation, migration, and gene expression of activated fibroblasts via TAM signaling. Fibroblast-mediated effects on macrophage polarization underscore the relevance of intercellular crosstalk in fibrotic disease. Full article

(This article belongs to the Section Pulmonology)

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17 pages, 362 KB

Open AccessReview

The Role of Kirschner Wires in Foot and Ankle Surgery: A Comprehensive Review and Practical Appraisal of Applications, Benefits, and Challenges

by Alberto Arceri, Antonio Mazzotti, Simone Ottavio Zielli, Laura Langone, Federico Sgubbi, Gianmarco Di Paola, Giuseppe D’Antonio and Cesare Faldini

Medicina 2025, 61(10), 1836; https://doi.org/10.3390/medicina61101836 - 14 Oct 2025

Abstract

Kirschner wires (K-wires) have remained an integral part of orthopedic surgery for decades, particularly in the management of foot and ankle pathologies. This review examines the role of K-wires by analyzing the applications in fracture fixation and deformity correction, highlighting advantages such as [...] Read more.

Kirschner wires (K-wires) have remained an integral part of orthopedic surgery for decades, particularly in the management of foot and ankle pathologies. This review examines the role of K-wires by analyzing the applications in fracture fixation and deformity correction, highlighting advantages such as cost-effectiveness and minimal soft-tissue disruption, while acknowledging limitations including lower torsional stability compared with rigid fixation and the risk of pin-tract infection. The purpose was to provide a comprehensive perspective on the clinical applications, advantages, and limitations of K-wires in contemporary surgical practice, with a focus on the most recent evidence from clinical studies. Full article

(This article belongs to the Section Orthopedics)

12 pages, 776 KB

Open AccessArticle

Effects of Thymoquinone on Cell Proliferation, Oxidative Damage, and Toll-like Signaling Pathway Genes in H1650 Lung Adenocarcinoma Cell Line

by Selen Karaoğlanoğlu and Gonca Gülbay

Medicina 2025, 61(10), 1835; https://doi.org/10.3390/medicina61101835 - 14 Oct 2025

Abstract

Background and Objectives: Lung cancer is the leading cause of cancer-related mortality worldwide. In most cases, lung cancer is diagnosed at an advanced stage. For advanced-stage disease, treatment options are generally systemic and while novel treatment approaches offer hope, they may also [...] Read more.

Background and Objectives: Lung cancer is the leading cause of cancer-related mortality worldwide. In most cases, lung cancer is diagnosed at an advanced stage. For advanced-stage disease, treatment options are generally systemic and while novel treatment approaches offer hope, they may also lead to significant adverse effects. Therefore, alternative therapeutic strategies have been investigated for many years. Thymoquinone (TQ) is one such candidate. Previous studies have demonstrated its antioxidant, anti-inflammatory, antibacterial, and immunomodulatory properties. In our study, we aimed to evaluate the roles of TQ in the progression of H1650 lung adenocarcinoma cells. Materials and Methods: In this study, the antiproliferative effect of TQ on H1650 lung cancer cells was evaluated using MTT assay, its effect on oxidative damage was determined using 8-OHdG, and total antioxidant status (TAS), total oxidant status (TOS), and its effect on apoptosis were demonstrated using caspase-3 ELISA method. In addition, total RNA was extracted from both control and treatment groups, cDNA was synthesized, and mRNA expression changes of Toll-like receptor related genes (TLR) were analyzed using RT-PCR. Results: The decrease in the viability of H1650 lung cancer cells was observed in a time- and dose-dependent manner. The IC₅₀ dose of TQ in the H1650 lung cancer cell line at 48 h was 26.59 µM. TQ treatment decreased the level of TOS and increased the level of TAS in H1650 lung cancer cells. Oxidative stress index decreased in the TQ-treated dose group in H1650 lung cancer cells. Elisa 8-OHdG and caspase-3 levels were not statistically significant. Compared to the control group, no statistically significant changes were observed in TLR1, TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, and TLR9 gene expressions in the treatment group treated with 26.59 µM TQ for 48 h. Conclusions: TQ shows potential as an anticancer agent and may contribute to the development of therapeutic approaches for lung cancers. Full article

(This article belongs to the Section Pulmonology)

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20 pages, 4156 KB

Open AccessArticle

Machine Learning Classification of Cognitive Status in Community-Dwelling Sarcopenic Women: A SHAP-Based Analysis of Physical Activity and Anthropometric Factors

by Yasin Gormez, Fatma Hilal Yagin, Yalin Aygun, Sarah A. Alzakari, Amel Ali Alhussan and Mohammadreza Aghaei

Medicina 2025, 61(10), 1834; https://doi.org/10.3390/medicina61101834 - 14 Oct 2025

Abstract

Background and Objectives: Sarcopenia, characterized by progressive loss of skeletal muscle mass and function, has increasingly been recognized not only as a physical health concern but also as a potential risk factor for cognitive decline. This study investigates the application of machine [...] Read more.

Background and Objectives: Sarcopenia, characterized by progressive loss of skeletal muscle mass and function, has increasingly been recognized not only as a physical health concern but also as a potential risk factor for cognitive decline. This study investigates the application of machine learning algorithms to classify cognitive status based on Mini-Mental State Examination (MMSE) scores in community-dwelling sarcopenic women. Materials and Methods: A dataset of 67 participants was analyzed, with MMSE scores categorized into severe (≤17) and mild (>17) cognitive impairment. Eight classification models—MLP, CatBoost, LightGBM, XGBoost, Random Forest (RF), Gradient Boosting (GB), Logistic Regression (LR), and AdaBoost—were evaluated using a repeated holdout strategy over 100 iterations. Hyperparameter optimization was performed via Bayesian optimization, and model performance was assessed using metrics including weighted F1-score (w_f1), accuracy, precision, recall, PR-AUC, and ROC-AUC. Results: Among the models, CatBoost achieved the highest w_f1 (87.05 ± 2.85%) and ROC-AUC (90 ± 5.65%), while AdaBoost and GB showed superior PR-AUC scores (92.49% and 91.88%, respectively), indicating strong performance in handling class imbalance and threshold sensitivity. SHAP (SHapley Additive exPlanations) analysis revealed that moderate physical activity (moderatePA minutes), walking days, and sitting time were among the most influential features, with higher physical activity associated with reduced risk of cognitive impairment. Anthropometric factors such as age, BMI, and weight also contributed significantly. Conclusions: The results highlight the effectiveness of boosting-based models in capturing complex patterns in clinical data and provide interpretable evidence supporting the role of modifiable lifestyle factors in cognitive health. These findings suggest that machine learning, combined with explainable AI, can enhance risk assessment and inform targeted interventions for cognitive decline in older women. Full article

(This article belongs to the Special Issue New Strategies for the Diagnosis and Treatment of Rheumatic and Musculoskeletal Diseases)

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15 pages, 289 KB

Open AccessArticle

Effect of Continuous Positive Airway Pressure Treatment on Hearing and Inner Ear Function in Patients with Obstructive Sleep Apnoea—Original Research

by Mirjana Grebenar Čerkez, Željko Zubčić, Stjepan Jurić, Jelena Šarić Jurić, Jelena Kovačević, Željka Laksar Klarić and Darija Birtić

Medicina 2025, 61(10), 1833; https://doi.org/10.3390/medicina61101833 - 14 Oct 2025

Abstract

Background and Objectives: This study aimed to investigate the influence of continuous positive airway pressure in patients with obstructive sleep apnoea on hearing and the possibility of recovering cochlear receptor cells. Materials and Methods: Forty-two patients with obstructive sleep apnoea (OSA) [...] Read more.

Background and Objectives: This study aimed to investigate the influence of continuous positive airway pressure in patients with obstructive sleep apnoea on hearing and the possibility of recovering cochlear receptor cells. Materials and Methods: Forty-two patients with obstructive sleep apnoea (OSA) were assigned to the study group. Patients underwent pure-tone audiometry and transient-evoked (TEOAE) and distortion-product (DPOAE) otoacoustic emissions before starting continuous positive airway pressure (CPAP) therapy and six months after CPAP therapy. Subjects were further divided into the following two groups: those who adequately used the therapy and those who did not adhere to treatment recommendations. Results: There is no significant difference in hearing thresholds for specific frequencies after six months of CPAP therapy. There is no significant difference in TEOAE and DPOAE SNR values at any frequency after 6 months of CPAP therapy. There is no significant difference in hearing threshold results for specific frequencies as a function of subject co-operation with treatment. After therapy, there is a significant difference in the SNR values in TEOAEs at 2 kHz and 4 kHz in subjects of the OSA target group, depending on co-operation, being higher in co-operative subjects, while there are no significant differences at other frequencies. There is a significant difference in the SNR results in DPOAEs, where they are higher in co-operative subjects at 1000, 6000, 7000 and 8000 Hz. Conclusions: The use of continuous positive airway pressure as a therapy for OSA has no effect on hearing and cochlear receptor cell recovery. Co-operation with CPAP treatment does not affect hearing threshold, but does affect cochlear receptor cell function, which is better at mid and higher frequencies in those who co-operate. These findings underscore the clinical significance of treatment adherence. Consistent adherence is associated with measurable improvements in hearing, particularly at higher frequencies, which cannot typically be evaluated in routine clinical practice using standard pure-tone audiometry. Our results emphasise the importance of promoting compliance with CPAP therapy not only for cardiovascular and neurological protection, but also for maintaining hearing health. Full article

(This article belongs to the Special Issue Advances in Otorhinolaryngologic Diseases)

16 pages, 792 KB

Open AccessSystematic Review

Deep Versus Superficial Dry Needling for Neck Pain: A Systematic Review of Randomised Clinical Trials

by Anas M. Alhakami, Ahmad Sahely and Ali M. Y. Alshami

Medicina 2025, 61(10), 1832; https://doi.org/10.3390/medicina61101832 - 13 Oct 2025

Abstract

Background and Objectives: Research examining the difference between the effects of deep and superficial dry needling on myofascial trigger points (MTrPs) in the upper trapezius muscle is limited. Thus, this systematic review was conducted to compare the effects of these two dry [...] Read more.

Background and Objectives: Research examining the difference between the effects of deep and superficial dry needling on myofascial trigger points (MTrPs) in the upper trapezius muscle is limited. Thus, this systematic review was conducted to compare the effects of these two dry needling techniques on pain and functional disability in adults with neck pain who demonstrated MTrPs. Materials and Methods: Randomised clinical trials (RCTs) were identified through an electronic search in PubMed, Scopus, Web of Science, Embase, Google Scholar, Dimensions and OpenAlex from inception until 22 September 2024. Only English-language studies were considered. Best-evidence synthesis was utilised to interpret the results of the included RCTs. Results: Of the 192 records obtained, 8 RCTs were included (2 with a low risk of bias, 4 with some risk-of-bias concerns and 2 with a high risk of bias). Overall, both deep and superficial dry needling provided short-term alleviation of pain and functional disability. No clinically meaningful differences were found between the two dry needling techniques. Conclusions: Deep and superficial dry needling seem to have similar positive effects on pain and functional disability in patients with neck pain exhibiting MTrPs. Full article

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