Medicina doi: 10.3390/medicina62061191

Authors: Mehmet Gümüş Kanmaz Genta Agani Sabah

Background and Objectives: To compare the buccal bone thickness of adjacent maxillary incisors between the impacted and contralateral control sides in patients with unilateral palatally impacted canines (PICs) using a split-mouth cone-beam computed tomography (CBCT) design. Materials and Methods: CBCT records of 26 patients with a unilateral PIC (18 females, 8 males; mean age, 17.35 ± 4.58 years) were retrospectively analyzed. Buccal bone thickness was measured at five equally spaced levels from the root apex (Level A) to the buccal alveolar crest (Level E) for the central and lateral incisors. Alveolar crest height, incisor torque and rotation, follicular width, canine localization, canine-to-root proximity, and root resorption were also assessed. Results: The impacted side showed significantly reduced buccal bone thickness at the two most apical levels of the lateral incisor: Level A (−0.81 mm; p < 0.001) and Level B (−0.35 mm; p = 0.004). No side differences were observed at the remaining lateral incisor levels or at any central incisor level. In the orientation-adjusted sensitivity model accounting for incisor torque and rotation, Level A remained significant (−0.75 mm; p < 0.001), whereas Level B was attenuated (p > 0.005). Lateral incisors on the impacted side also showed reduced labial torque (−4.97°; p = 0.001) and greater mesiobuccal rotation (−12.23°; p < 0.001). Conclusions: PICs were associated with localized apical reduction in buccal bone thickness of the adjacent lateral incisor, accompanied by reduced labial torque and greater mesiobuccal rotation. Buccal bone thickness may represent a relevant consideration during CBCT-based treatment planning for PICs.

Medicina doi: 10.3390/medicina62061190

Authors: Kasim Akay Gorkem Ulger Hamza Yildiz Zeynep Kucukolcay Coskun Sevki Goksun Gokulu Tolgay Tuyan Ilhan Hakan Aytan

Background and Objectives: The relationship between preoperative inflammatory markers and lymphovascular space invasion (LVSI) in endometrioid-type endometrial cancer (EC) remains incompletely defined and warrants evaluation using robust statistical methods. This study aimed to evaluate the independent association of preoperative inflammatory markers, analyzed strictly as continuous variables, with the presence of LVSI, and to develop a refined predictive nomogram adjusted for established clinical confounders. Materials and Methods: Data from 156 patients who underwent standard staging surgery for endometrioid-type EC were retrospectively analysed. To preserve statistical power and avoid structural artifacts from data forcing, preoperative glucose-to-lymphocyte ratio (GLR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were modeled on their original continuous scale. Multivariable logistic regression analysis was performed to identify independent risk factors for LVSI, adjusting for patient age and maximum tumor diameter. Internal validation was conducted using bootstrap resampling (1000 iterations). Results: In the multivariable logistic regression model, continuous PLR emerged as a significant independent risk factor for the presence of LVSI (adjusted OR: 1.013 per 1-unit increase, 95% CI: 1.001–1.024; p = 0.033). Among clinical parameters, maximum tumor diameter demonstrated the strongest independent association with LVSI (adjusted OR: 1.595 per 1 cm increase, 95% CI: 1.211–2.099; p = 0.001). Continuous NLR (p = 0.513) and GLR (p = 0.545) did not retain statistical significance due to overlapping explanatory variance and shared hematological components. The optimized 3-variable nomogram (PLR, tumor size, and age) demonstrated an apparent C-index of 0.816 (95% bootstrap CI: 0.719–0.920) and a robust optimism-corrected C-index of 0.794. The bootstrap-corrected calibration slope was 0.909, and Decision Curve Analysis (DCA) demonstrated a positive net clinical benefit across clinically relevant threshold probabilities. Conclusions: Preoperative PLR, evaluated as a continuous parameter, provides a statistically stable framework for preoperative risk stratification in endometrioid EC. When integrated with tumor size and age, the proposed nomogram demonstrates promising discriminative performance and potential clinical utility pending external validation for predicting LVSI. However, given the limited number of LVSI-positive events (n = 17), these findings should be regarded as exploratory and hypothesis-generating and require external validation before clinical use.

Medicina doi: 10.3390/medicina62061189

Authors: Jung-A Lim Jonghae Kim Minju Kong Sang-Gyu Kwak

Background and Objectives: Emergence agitation (EA) is a common neurobehavioral disturbance during recovery from sevoflurane anesthesia in pediatric patients, particularly after ophthalmic surgery. Clinically deployable and rigorously validated risk stratification approaches remain limited. We aimed to develop and internally validate an explainable machine learning model to estimate individualized EA risk after pediatric ophthalmic surgery. Materials and Methods: This retrospective cohort study included 1029 children aged 3–7 years who underwent ophthalmic surgery under sevoflurane anesthesia between 2016 and 2025. EA was defined as clinically significant agitation requiring active management in the post-anesthesia care unit. Four machine learning algorithms (regularized logistic regression, random forest, XGBoost, and CatBoost) were developed using stratified patient-level 5-fold cross-validation. Performance was evaluated using pooled out-of-fold predictions. Discrimination, calibration, and classification metrics at the optimal Youden threshold were assessed. SHAP analysis was applied for interpretability. Results: EA occurred in 543 patients (52.8%). XGBoost showed comparable discrimination with slightly higher AUPRC (0.827) and sensitivity (0.796) compared with other models, while maintaining acceptable specificity (0.728). Calibration demonstrated good agreement between predicted and observed risk. SHAP identified airway management and anesthetic-related variables as key contributors. Conclusions: ML-based analysis identified clinically relevant perioperative factors associated with emergence agitation and may provide preliminary insight into perioperative risk stratification pending external validation. External validation is required before clinical implementation.

Medicina doi: 10.3390/medicina62061188

Authors: Georgios X. Papacharalampous Theodora-Eleftheria Deftereou Konstantinos Chaidas Petros V. Vlastarakos Jannis Constantinidis Michael Katotomichelakis

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous type 2 inflammatory disease for which biologic therapies have expanded treatment options; however, biomarkers capable of guiding biologic selection remain poorly defined. This systematic review aimed to evaluate the available evidence regarding predictive and prognostic biomarkers associated with currently available biologic agents for CRSwNP (omalizumab, dupilumab, mepolizumab, benralizumab, reslizumab, and tezepelumab). Materials and Methods: A systematic search of PubMed/MEDLINE, Embase, Google Scholar, and the Cochrane Library identified studies published between January 2006 and September 2025. Results: Twenty-five eligible studies, including 12 randomized controlled trials, 12 systematic reviews/meta-analyses, and one indirect treatment comparison study, were analyzed. Multiple biomarkers, including blood eosinophils, total IgE, periostin, eotaxins, eosinophil cationic protein, IL-5, TARC, PARC, and urinary leukotriene E4, were evaluated across biologics targeting IgE, IL-4/IL-13, and IL-5 pathways. Conclusions: Although several biomarkers reflected the modulation of type 2 inflammation and disease activity, no validated biomarker has reliably predicted the superiority of one biologic over another. Nasal IL-5 showed potential for predicting the response to anti-IL-5 therapy but requires further validation. Current evidence supports biomarker use primarily for confirming type 2 inflammation rather than guiding biologic selection. Prospective biomarker-driven and head-to-head comparative studies are needed to enable precision medicine approaches in CRSwNP.

Medicina doi: 10.3390/medicina62061187

Authors: Vanesa Vicens-Zygmunt Jaume Bordas-Martínez Miriam Muñoz-Bolaño João Carmezim Ana Belén Llanos-González Adrià Domingo-Carnice Dolores Rodríguez-Cumplido Guadalupe Bermudo-Peloche Cristian Tebé-Cordomí Judith Peñafiel Roser Llop-Rius Maria Molina-Molina

Background and Objectives: Nintedanib is indicated for progressive pulmonary fibrosis (PPF) based on clinical trial results. The primary objectives of this study were to evaluate the effectiveness of nintedanib on forced vital capacity (FVC) and diffusing lung capacity for CO (DLCO) after one year of treatment, and to compare the annual rate of decline (“slope”) for FVC, DLCO and 6 minute walking distance (6MWD) with the year prior to treatment. The secondary objectives were antifibrotic safety, tolerability, adverse events, immunosuppressant use, dyspnoea and survival. Materials and Methods: This study was a single-centre, retrospective, observational cohort study that included consecutive patients with PPF treated with nintedanib. Results: Fifty-five patients with non-IPF fibrotic ILD initiated nintedanib due to fibrosis progression. Most patients (63.4%) stabilised/improved FVC after 1 year of treatment, and 82.5% stabilised/improved DLCO. The “slope” of FVC and DLCO was reduced after 1 year of treatment compared to the year before initiation, although the difference was not statistically significant: FVC slope was +0.61% in the year after initiation vs. −2.3% in the year prior (mean change: 2.94%, 95%CI [−4.74, 10.62]); DLCO slope was −3.8% after treatment vs. −7% before initiation (mean change: 3.24%, 95%CI [−7.43, 13.92]). Dyspnoea improved in 23.2% of patients. A reduction in immunosuppressant use was observed after nintedanib initiation. Forty-one patients (74.5%) experienced at least one side effect: diarrhoea (60%), hepatotoxicity (23.6%), or asthenia (12.7%). Fifteen patients required permanent or temporary treatment discontinuation. Conclusions: In our real-world PPF cohort, most patients showed FVC and/or DLCO stabilisation or improvement after one year of nintedanib treatment. A non-significant reduction in the rate of FVC decline after one year of treatment was also observed, as was a reduction in symptom severity in our real-life PPF cohort.

Medicina doi: 10.3390/medicina62061186

Authors: Noemi-Teofana Musta Nicoleta Ianovici

Atmospheric fungi represent an important group of allergens with a major impact on public health, especially among sensitized or immunocompromised individuals. This article reviews the ubiquitous fungal taxa in the atmosphere—Alternaria, Cladosporium, Aspergillus, Penicillium—as well as the undercharacterized taxa—Epicoccum, Pithomyces, Torula and Rhodotorula—with an emphasis on the antigenic composition and protein structures involved in type I hypersensitivity reactions. Recent data from the scientific literature (2000–2025) is presented, along with the frequency of spores in the atmosphere and the global distribution of research, highlighted by the analysis of Google Scholar and PubMed results. While Alternaria, Aspergillus, Penicillium, and Cladosporium are recognized as major contributors to allergic sensitization worldwide, Epicoccum, Torula, Rhodotorula, and Pithomyces remain relatively undercharacterized, but associated with allergic reactions and cross-reactivity.

Medicina doi: 10.3390/medicina62061185

Authors: Adrian Mită Liviu Martin Oana Criciotoiu Iancu Emil Pleşea

Background and Objectives: Sessile serrated lesions (SSLs) are increasingly recognized as relevant precursors in alternative pathways of colorectal carcinogenesis, yet their endoscopic recognition remains challenging. Materials and Methods: We conducted a systematic review of studies reporting endoscopic and patient-related features associated with SSLs. PubMed/MEDLINE was searched for studies published between 2003 and November 2025. Eleven studies including 13,453 participants were identified. Results: Frequently reported endoscopic hallmarks included proximal colon location, larger lesion size, flat or slightly elevated morphology, indistinct borders, mucous cap, cloud-like surface, and pit-pattern features consistent with Kudo/Fujii types III–IV. Considerable heterogeneity in definitions and analytical reporting was observed. Conclusions: Although several features may raise suspicion for SSLs, standardized evidence remains limited, supporting a cautious and comprehensive approach to polyp assessment.

Medicina doi: 10.3390/medicina62061184

Authors: Raluca-Anamaria Mogoș Alexandru Carauleanu Ingrid-Andrada Vasilache Simona Juliette Mogoș Maria-Christina Ungureanu Letitia Leustean Iustina-Petra Condriuc Sandra-Teodora Gavril Ecaterina Tomaziu-Todosia Anton Cristina Preda

Background and Objectives: Autoimmune thyroiditis (AIT) is often reported patients with PCOS, and may co-occur with altered metabolic risk markers. The aims of this study were to assess baseline differences according to thyroid autoimmunity status, evaluate adjusted associations between thyroid autoimmunity and metabolic parameters, examine associations with PCOS phenotype distribution, and perform k-means clustering to explore data-driven subgroups and their autoimmune enrichment. Materials and Methods: We performed a retrospective cohort study of 651 women with PCOS, comparing those without AIT (n = 506) versus with AIT (n = 145). Associations between AIT and continuous outcomes (HDL; composite metabolic score) were evaluated using robust linear regression with HC3 standard errors and age modeled with a natural cubic spline (3 knots). The association between AIT and phenotype A was assessed via logistic regression with exponentiated coefficients (odds ratios). Unsupervised phenotyping used k-means clustering with silhouette analysis across k = 2…6. Results: Patients with AIT were older (median 40 vs. 35 years; p = 0.021). Phenotype distribution differed by AIT status (overall p = 0.029), with phenotype A less frequent among AIT-positive women (27% vs. 40%). In adjusted robust regression, AIT was associated with lower HDL by β = −4.34 mg/dL (95% CI −9.18 to 0.51; p = 0.081), while obesity (−7.04 mg/dL; p < 0.001) and diabetes (−6.47 mg/dL; p = 0.004) were associated with lower HDL. AIT was not associated with the composite metabolic score (β = −0.005; 95% CI −1.22 to 1.21; p = 0.994), whereas obesity was associated with higher score (β = 1.76; p = 0.003) and urban residence with lower score (β = −0.94; p = 0.011). In logistic regression, AIT was associated with lower odds of phenotype A (OR 0.63; 95% CI 0.41–0.97; p = 0.038), and hypertension was associated with higher odds of phenotype A (OR 1.91; 95% CI 1.20–3.04; p = 0.006). Silhouette analysis supported k=3 clusters (silhouette 0.349), and AIT prevalence was highest in cluster 3 (26.4%) versus clusters 1 (19.9%) and 2 (18.3%). Conclusions: AIT was associated with lower odds of phenotype A, and showed a borderline association with lower HDL-cholesterol but not with a composite metabolic score. Data-driven clustering identified a subgroup with higher autoimmune burden.

Medicina doi: 10.3390/medicina62061183

Authors: Tima Battah Vasilios Mastorodemos Erich Struecker Dimos Dimitrios Mitsikostas Dimitrios Papadopoulos

Multiple sclerosis (MS) is a neuro-inflammatory disease characterized by demyelination in the central nervous system (CNS). Although a substantial endogenous capacity for remyelination has been demonstrated, this process is frequently incomplete and exhibits marked intra- and inter-individual heterogeneity. Several factors influence the extent of spontaneous myelin regeneration, including age, sex, disease course, and lesion localization. Oligodendrocytes (OL), derived from oligodendrocyte progenitor cells (OPCs), are the principal myelinating cells of the CNS. The regenerative cascade involves several key stages, including OPC activation, recruitment, differentiation into oligodendrocytes (OL), and myelin deposition. This process is orchestrated in a spatiotemporal manner by a complex interplay of intracellular signaling pathways, genetic determinants, and dynamic microenvironmental cues, which together balance inhibitory and pro-remyelinating influences. Several lines of evidence indicate that chronically demyelinated axons are vulnerable to degeneration, whereas successful remyelination may confer neuroprotection. These observations underscore remyelination as a promising neuroprotective therapeutic target for preventing or slowing disability progression in MS, a condition in which gradual neuroaxonal degeneration is believed to underlie irreversible disability progression. In this review, we aim to bridge the gap between fundamental biological mechanisms of remyelination and their clinical relevance. We examine recent advances in in vivo techniques for assessing remyelination and discuss how these measures correlate with clinical and disability outcomes. In addition, we review recent clinical trials of remyelination-promoting therapies and analyze the challenges that have limited their advancement beyond phase II. Overall, we seek to provide a comprehensive overview of the remyelination process from bench to bedside, highlighting both the obstacles and the therapeutic potential of remyelination strategies in MS.

Medicina doi: 10.3390/medicina62061182

Authors: Celia Villalba-Aguilar José Alberto Laredo-Aguilera Lucía Villalba-Aguilar Laura Pilar de Paz-Montón Víctor Serrano-Fernández Juan Manuel Carmona-Torres

Background and Objectives: Anxiety can influence the intensity of postoperative pain, anesthesia and the need for analgesia. Likewise, proper anxiety management can reduce hospital stays. Therefore, it is important to review the actions of nursing professionals and estimate the effect size of nursing interventions to reduce anxiety in pre- and postsurgical processes. Therefore, the objective of this study was to analyze the effectiveness of preoperative motivational interviews by nursing to reduce pre- and postoperative anxiety and postoperative pain after surgery. Materials and Methods: A systematic review was carried out according to the PRISMA guidelines, with a record in PROSPERO using DeCS and Boolean operators OR and AND to increase the specificity of the search. In the EBSCOhost, Pubmed, Cochrane Library and Scopus databases, 104 studies were obtained. Patients ≥ 18 years of age with scheduled surgeries, communication skills, clinical trials or quasi-experimental studies were included. The risk of bias 2 (RoB2) tool was used to assess the risk of bias in the studies. A random effects meta-analysis was performed to analyze pre- and postoperative anxiety and postoperative pain. Results: A total of 6 studies were included (4 clinical trials and 2 quasi-experimental studies). All the studies analyzed preoperative anxiety, which was significantly lower (SMD = −1.53; 95% CI: −4.01 to −0.95; I2 = 40%). Postoperative pain (SMD = −0.74; 95% CI: −0.94 to −0.54; I2 = 35%) and postoperative anxiety (SMD = −0.48; 95% CI: −0.78 to −0.19; I2 = 0%) also decreased. Conclusions: Motivational interviews by nurses may help provide clearer information and emotional support and allow patients to express doubts, reducing their fear of anesthesia, pain and the recovery process. Emotional control improved adaptation to the surgical environment, reducing postoperative pain. With respect to implications for clinical practice, it is necessary to use the same scales to measure anxiety to better compare the studies.

Medicina doi: 10.3390/medicina62061181

Authors: Engin Hendem Mehmet Zahid Koçak Oguzhan Yıldız Mustafa Korkmaz Muhammed Muhiddin Er Murat Araz Mehmet Artac Melek Karakurt Eryılmaz

Background and Objectives: Metastatic castration-resistant prostate cancer (mCRPC) remains a clinically heterogeneous condition despite ongoing advances in systemic treatment. Androgen receptor pathway inhibitors (ARPIs), including abiraterone acetate and enzalutamide, have been associated with improved clinical outcomes; however, early identification of patients deriving limited benefit continues to be challenging. Prostate-specific antigen (PSA) kinetics may serve as a practical indicator of treatment response over time. This study aimed to examine the prognostic significance of achieving a ≥50% reduction in PSA levels at three months in patients with mCRPC treated with ARPIs in routine clinical practice. Materials and Methods: In this retrospective single-center study, patients with mCRPC who received abiraterone acetate or enzalutamide between February 2015 and March 2024 were included. Patients were stratified according to PSA decline at three months (≥50% vs. <50%). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared with the log-rank test. Prognostic variables were subsequently examined using univariate and multivariate Cox proportional hazards models. Results: A total of 60 patients were included. At three months, 44 patients (73.3%) achieved a ≥50% decline in PSA levels. Patients reaching this level had longer PFS and OS than those with <50% decline, and the differences between groups were statistically significant. In multivariate analysis, early PSA decline remained significantly associated with improved survival outcomes. Conclusions: A ≥50% decline in PSA levels at three months represents a simple and clinically meaningful indicator of treatment response in patients with mCRPC receiving ARPIs. Early PSA kinetics may assist in timely risk stratification and closer clinical monitoring in routine clinical practice.

Medicina doi: 10.3390/medicina62061180

Authors: Iulia Elena Diaconu Maria Ioana Onofrei Andrei Vâță Florin Manuel Roșu Emilian Bogdan Ignat Iulian Dan Cuciureanu Mihnea Eudoxiu Hurmuzache Mihaela Cătălina Luca

Background and Objectives: Neurological complications of SARS-CoV-2 infection frequently impair patients’ long-term quality of life. This study aimed to identify clinical and laboratory risk factors—including inflammatory markers and micronutrients—for the occurrence or worsening of neurocognitive disorders in long COVID patients. Materials and Methods: In this prospective observational study, patients presenting with long COVID neurological manifestations were stratified by baseline MoCA score into two groups (≥23 and <23). Clinical, laboratory (inflammatory markers, 25-hydroxy vitamin D, vitamin B12, folic acid), and neuroimaging assessments (global cortical atrophy scale, Fazekas score) were performed over 24 months. Propensity score matching (PSM) for age, gender, and neurological comorbidities yielded 54 patients per group. Results: In the MoCA ≥ 23 group, significant predictors of cognitive decline included severe COVID-19 (OR = 2.211, 95% CI = 1.819–5.973, p = 0.012), autoimmune comorbidities (OR = 1.676, 95% CI = 1.191–2.390, p = 0.043), and elevated neutrophil-to-lymphocyte ratio (NLR; OR = 1.586, 95% CI = 1.431–2.122, p = 0.011). In the MoCA < 23 group, independent predictors were diabetes mellitus (OR = 3.021, 95% CI = 2.65–14.004, p = 0.016), autoimmune comorbidities (OR = 4.987, 95% CI = 1.412–6.033, p = 0.021), and NLR (OR = 5.944, 95% CI = 2.353–19.321, p = 0.015). Serum vitamin D levels were significantly associated with MoCA scores in both groups. Conclusions: COVID-19 severity, autoimmune comorbidities, NLR, and serum vitamin D represent key risk factors for neurocognitive decline in long COVID, highlighting potential targets for early intervention.

Medicina doi: 10.3390/medicina62061179

Authors: Francesco Maffìa Francisco Salvado Paola Bonavolontà Henrique José Cardoso David Sanz Stefania Troise Gianluca Renato De Fazio Giovanni Dell’Aversana Orabona David Faustino Ângelo

Background and Objectives: Temporomandibular disorders (TMDs) encompass a broad spectrum of functional and structural abnormalities of the temporomandibular joint (TMJ). Conventional diagnostic tools, although essential, often fail to capture the underlying biochemical mechanisms driving disease progression. Synovial fluid (SF), by virtue of its direct proximity to intra-articular tissues, represents an accessible biological matrix for identifying molecular signatures of inflammation, cartilage degradation, lubrication failure, oxidative stress, and angiogenic activation. The objective of this review is to synthesize current evidence on SF proteomics in TMD and evaluate its potential translational value in precision medicine. Materials and Methods: A narrative review of the literature was conducted on PubMed to identify human studies focused on SF proteomic and biochemical biomarkers in TMD. Eligible studies included original research articles assessing SF composition in relation to specific TMJ pathologies, diagnostic categories, or clinical phenotypes. Extracted data included study design, sample characteristics, analytic methodology, biomarkers investigated, and key findings. Google Gemini (Google LLC, Mountain View, CA, USA) was used as an AI-assisted tool to support language editing and manuscript writing during the preparation of this article. The use of this tool was limited to linguistic refinement; all scientific content, data interpretation, and conclusions were formulated and verified by the authors. Results: Across the analyzed studies, TMD phenotypes—particularly disc displacement with or without reduction (DDwR, DDwoR) and osteoarthritis (OA)—were characterized by consistent alterations in cytokines (IL-1β, IL-6, IL-8, TNF-α), extracellular matrix (ECM) components (aggrecan, glycosaminoglycans (GAGs), decorin, MMP-2, MMP-9), lubrication molecules (lubricin/PRG4), oxidative stress mediators (myeloperoxidase (MPO), nitric oxide (NO), glutathione peroxidase (GPX)), adipokines (chemerin, resistin, adiponectin), and angiogenic factors (vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2)). Recent liquid chromatography–tandem mass spectrometry (LC–MS/MS) analyses further revealed phenotype-specific protein clusters and pathways related to inflammation, ferroptosis, hypoxia signaling, and proteoglycan metabolism. Conclusions: Current evidence suggests that SF proteomics and multi-analyte biomarker profiling offer a promising, hypothesis-generating approach for understanding the biological mechanisms underlying TMD. The integration of proteomic, metabolic, and inflammatory markers holds future potential for diagnostic panel development; however, prospective clinical validation is still required before SF-based molecular profiling can be implemented as a precision medicine tool in TMJ disorders.

Medicina doi: 10.3390/medicina62061178

Authors: Dongwoo Kim Hongdeok Seok Jae Hyun Jung

Background and Objectives: Human immunodeficiency virus (HIV) infection is associated with immune dysregulation, which may influence the development of autoimmune diseases. However, population-based evidence on the prevalence of autoimmune diseases in individuals living with HIV remains limited, particularly in Asian populations. This study aimed to evaluate the prevalence of autoimmune diseases in individuals living with HIV in Korea using nationwide population-based data. Materials and Methods: We conducted a cross-sectional analysis using the Health Insurance Review and Assessment Service National Patient Samples from 2012 to 2015, including 4,851,064 individuals aged ≥15 years. HIV infection and autoimmune diseases were identified using ICD-10 codes. The prevalence of autoimmune diseases in individuals with HIV infection was compared with that in the general population. Antiretroviral therapy (ART) status was determined based on prescription records. Results: A total of 1023 individuals were identified with HIV infection, all of whom were receiving antiretroviral therapy. The overall prevalence of autoimmune diseases was 4.4% in males and 3.6% in females with HIV, without significant differences compared to controls. However, the prevalence of ulcerative colitis in males (p = 0.030) and of dermatomyositis in females (p = 0.011) was higher in individuals with HIV. Conclusions: Although the overall prevalence of autoimmune diseases was not significantly increased in individuals living with HIV, certain autoimmune diseases—particularly ulcerative colitis in men and dermatomyositis in women—showed a higher prevalence. As these findings were based on small case numbers, they should be approached with caution. The results are best regarded as hypothesis-generative observations that warrant further investigation rather than findings on which clinical practice should currently be based. Further research using large datasets is warranted to confirm these associations and clarify the underlying immunological mechanisms.

Medicina doi: 10.3390/medicina62061177

Authors: Domas Kazokas Daina Kaveckaitė Saulė Kraujutaitytė Ilona Razlevičė Andrius Macas Laura Lukošienė

Background and Objectives: Recent studies suggest that remimazolam, a novel ultra-short-acting benzodiazepine, has an excellent pharmacokinetic and safety profile, favourable for ambulatory procedures. Although remimazolam has been studied as a sole agent for anaesthesia in day case gynaecological surgery, studies assessing its use in combination with other anaesthetics remain scarce. The aim of this study was to investigate the effects of a low-dose remimazolam adjunct on the characteristics of an intravenous propofol–remifentanil anaesthesia regimen. Materials and Methods: A single-centre retrospective observational cohort study was conducted on patients who underwent brief day case gynaecological surgery under general intravenous anaesthesia using remifentanil and propofol from November 2024 to January 2025. The patients were divided into two groups depending on whether they received remimazolam as an adjunct. To account for confounding, propensity scores (PSs) were estimated from baseline characteristics and used to derive stabilised inverse probability of treatment weights (IPTWs). Weighted regression models were then applied to estimate treatment effects on postoperative recovery time measures, consumption of anaesthetics, and incidence of any adverse effects intraoperatively and postoperatively. Cost effectiveness was evaluated using the incremental cost-effectiveness ratio (ICER). Results: The clinical data of 51 patients were retrospectively examined: 32 patients were assigned to the intervention group, and 19 patients were assigned to the reference group; after IPTW and PS trimming, the sum of weights was 22 in the intervention group and 58.8 in the reference group. The use of remimazolam as an adjunct was associated with 3.5 min shorter time to eye opening (p < 0.001) and 3.6 min shorter time to full consciousness (p = 0.002); the total consumption of propofol was decreased by 3 mg/kg (p < 0.001); the median dose of remimazolam adjunct was 0.12 mg/kg, or 10 mg per case. There were no statistically significant adverse effects. ICER was 2.35 € per minute of operating room (OR) time saved. Conclusions: In the setting of day case gynaecological surgery, the addition of remimazolam to a propofol–remifentanil regimen reduced propofol requirements and shortened recovery time without an increase in adverse effects. This may represent a more efficient anaesthetic approach for ambulatory procedures with a comparable safety profile.

Medicina doi: 10.3390/medicina62061176

Authors: Se-Han Jung Hong Seon Lee Min Jung Kwangho Chung Hyun-Soo Moon Sung-Hwan Kim

Background and Objectives: Atelocollagen, a purified collagen derivative, has demonstrated potential benefits in various orthopedic applications; however, its role in anterior cruciate ligament (ACL) reconstruction remains unclear. This study aimed to compare magnetic resonance imaging (MRI) graft signal following ACL reconstruction with and without atelocollagen interposition and to evaluate its effects on knee joint laxity and clinical outcomes. Materials and Methods: A retrospective review was conducted on patients who underwent primary ACL reconstruction using hamstring autografts between March 2015 and July 2023. Patients were divided into two groups: without atelocollagen (Group N) and with atelocollagen interposition (Group C). The primary outcome was ACL graft signal intensity (intra-articular and intra-tunnel) on 1-year postoperative MRI. Secondary outcomes included tunnel widening, knee joint laxity, and patient-reported outcome measures (PROMs). Results: A total of 57 patients (Group N: 34; Group C: 23) were analyzed. Baseline characteristics were comparable between groups. Group C had a higher proportion of thicker graft constructs (quintuple/sextuple: 73% vs. 17.6%, p < 0.001) and more frequent concomitant anterolateral ligament reconstruction (78.3% vs. 8.8%, p < 0.001). No significant difference in intra-articular graft signal was observed. However, femoral intra-tunnel graft signal was significantly lower in Group C (p = 0.018), accompanied by reduced femoral tunnel widening (p < 0.001). Tibial tunnel widening, knee joint laxity, and PROMs did not differ significantly at 1 and 2 years. In multivariable analysis, atelocollagen interposition was associated with reduced femoral tunnel widening (B = −1.1, p = 0.025). Conclusions: Atelocollagen interposition during ACL reconstruction was associated with more favorable intra-tunnel graft healing signals and reduced femoral tunnel widening, although it did not appear to influence short-term clinical outcomes.

Medicina doi: 10.3390/medicina62061175

Authors: Selahattin Çelik Salih Karatlı Mehmetcan Atak Hatice Ayyıldız Sevim Gökşen İnanç İmamoğlu Samed Rahatlı

Background and Objectives: Quality of life (QoL) has become an essential outcome in patients with metastatic prostate cancer, particularly in the era of androgen receptor (AR)-targeted therapies. Although these agents improve survival, their differential impact on QoL and the role of psychological factors remain incompletely understood. This study aimed to evaluate QoL, functional outcomes, and psychological status, and to identify factors associated with poor QoL in a real-world cohort. Materials and Methods: This prospective cross-sectional, single-center observational study included 130 patients with metastatic prostate cancer receiving AR-targeted therapies (abiraterone, enzalutamide, or apalutamide/darolutamide). QoL was assessed using the EORTC QLQ-C30 questionnaire, and psychological status was evaluated using the Hospital Anxiety and Depression Scale (HADS). Patients were stratified according to treatment groups, and comparisons were performed using appropriate statistical tests. Logistic regression analyses were conducted to determine factors independently associated with poor QoL. Results: Exploratory differences in global QoL were observed among treatment groups (p = 0.007), with lower global QoL scores in the abiraterone group and numerically higher emotional and cognitive functioning scores in the enzalutamide group. Symptom analysis demonstrated higher nausea/vomiting scores in the abiraterone group (p = 0.022), whereas other symptom domains were comparable across treatment groups. In multivariable analysis, anxiety (odds ratio [OR]: 6.62) and depression (OR: 3.40) were independently associated with poor QoL, while treatment type was not independently associated with poor QoL after multivariable adjustment. Conclusions: Although unadjusted QoL scores differed across AR-targeted therapy groups, psychological factors—particularly anxiety and depression—were significantly associated with poorer QoL in patients with metastatic prostate cancer. These findings highlight the importance of integrating routine psychosocial assessment and supportive care strategies into clinical practice to optimize patient-centered outcomes. However, given the cross-sectional and exploratory nature of the study, the findings should be interpreted cautiously.

Medicina doi: 10.3390/medicina62061174

Authors: Ivana Minaković Tanja Janković Mirjana Smuđa Bela Kolarš Monika Šili Vesna Mijatović Jovin Jelena Zvekić-Svorcan

Background and Objectives: The Back Beliefs Questionnaire (BBQ) is a patient-reported outcome measure used to assess beliefs about back pain. This study aimed to cross-culturally adapt the BBQ into Serbian and evaluate the psychometric properties of the Serbian version (BBQ-Srb) in patients with chronic low back pain. Materials and Methods: A cross-sectional study involving cross-cultural adaptation and psychometric validation was conducted in 143 patients with chronic low back pain. The adaptation process included forward and backward translation, expert review, and pilot testing. Psychometric evaluation included assessment of floor and ceiling effects, internal consistency, test–retest reliability, measurement error, exploratory and confirmatory factor analyses, and construct validity testing using predefined hypotheses. Construct validity was examined through associations between BBQ-Srb scores and pain intensity, disability, pain catastrophizing, and work absenteeism. Results: The BBQ-Srb showed acceptable internal consistency, with Cronbach’s alpha of 0.728 and McDonald’s omega of 0.735. Total-score analyses were based on the preliminary exploratory 8-item BBQ-Srb version excluding BBQ13, whereas floor and ceiling effects were examined for the original 9-item scored BBQ-Srb version. Test–retest reliability was excellent (ICC = 0.916). Exploratory factor analysis suggested a predominantly one-factor structure, but the explained variance was modest. Confirmatory factor analysis of the 8-item version provided only partial support for unidimensionality, with marginal model fit and a low average variance extracted. The 8-item BBQ-Srb total score showed significant negative correlations with pain intensity, disability, and pain catastrophizing, confirming three of four predefined hypotheses. Conclusions: The BBQ-Srb demonstrated acceptable reliability and preliminary evidence of construct validity as a Serbian patient-reported outcome measure for assessing beliefs about back pain. However, structural validity was only partially supported, and the exploratory 8-item structure requires confirmation in larger, independent, and more diverse Serbian-speaking samples.

Medicina doi: 10.3390/medicina62061173

Authors: Bogdan-Sorin Capitanu Serban Dragosloveanu Dana-Georgiana Nedelea Calin Ion Dragosloveanu Romica Cergan Cristian Scheau

Background and Objectives: Robotic-assisted total knee arthroplasty (rTKA) is being increasingly used to improve surgical precision, soft-tissue balancing, and functional recovery. However, evidence comparing rTKA with conventional manual TKA (mTKA) across functional, patient-reported, neuromotor, and safety outcomes remains heterogeneous. Materials and Methods: This narrative (non-systematic) review synthesises studies evaluating functional outcomes, patient-reported outcome measures (PROMs), joint awareness, range of motion (ROM), neuromotor recovery, and complications following rTKA versus mTKA. Study inclusion was based on author judgement and data accessibility. The reviewed evidence included five randomised controlled trials, 9 retrospective studies, six prospective non-randomised studies, two meta-analyses, one cross-sectional study, and one umbrella review, covering CT-based and imageless robotic platforms, including semi-active and active systems such as MAKO, NAVIO, CORI, ROSA, ROBODOC, CUVIS Joint, SkyWalker, TSolution One, AKEC, JIANJIA, and YUANHUA. Results: rTKA consistently demonstrated outcomes comparable to mTKA in PROMs (OKS, KOOS, WOMAC, KSS), with some studies reporting modest early improvements in pain and function. Joint awareness and patient satisfaction showed the most consistent early advantages for rTKA. Early postoperative ROM and neuromotor recovery, including balance and gait symmetry, were improved with rTKA, likely due to enhanced alignment and soft-tissue balancing; however, mid- and long-term outcomes were similar. Complication rates were low and comparable, with robotic-specific issues being rare and self-limited. Conclusions: rTKA provides small but reproducible early benefits in joint awareness, neuromotor function, and patient satisfaction, without clear long-term superiority. These early advantages may translate into meaningful population-level benefits, including faster recovery and potential healthcare cost reduction. Further high-quality studies are needed to assess long-term clinical and economic outcomes.

Medicina doi: 10.3390/medicina62061172

Authors: Beata Martinkienė Benedikt Bachmetjev Rima Piličiauskienė Gintarė Sragauskienė

Background and Objectives: Vitamin D deficiency is a pervasive public health issue in high-latitude regions, yet large-scale population data for the Baltic states remain sparse. This study aimed to determine the prevalence of vitamin D status and identify its primary determinants within a primary care setting in Lithuania. Materials and Methods: We conducted a retrospective cross-sectional analysis of serum 25-hydroxyvitamin D [25(OH)D] concentrations from 14,330 unique patients (aged 1–101 years) collected during 2025 at a major clinic in Vilnius. Vitamin D status was categorized according to the Central and Eastern European Expert Consensus thresholds. Results: The overall median 25(OH)D concentration was 68.3 nmol/L, placing it in the “insufficiency” range (50–75 nmol/L). Seasonality emerged as the most significant predictor of deficiency; multivariable logistic regression showed a maximal risk reduction in September (OR 0.33; 95% CI: 0.27–0.41) and August (OR 0.34) compared to January, while June and November provided no significant protection. Age-specific analysis revealed a non-linear “U-shaped” distribution: children aged 0–6 years had the highest levels (median ~87–91 nmol/L), likely due to rickets prophylaxis, whereas adolescents (12–18 years) exhibited the highest vulnerability, with approximately 80% suffering from deficiency or insufficiency. Males faced a 13.9% higher likelihood of deficiency than females (OR 1.14; p = 0.0036), potentially due to lower rates of elective supplementation. Conclusions: These findings suggest that current supplementation strategies successfully protect infants but fail to sustain adequacy through adolescence and adulthood, particularly during the “vitamin D winter.” Targeted public health interventions for adolescents and year-round monitoring are recommended to mitigate the high prevalence of suboptimal vitamin D status in Lithuania.

Medicina doi: 10.3390/medicina62061171

Authors: Mioara-Calipsoana Matei Valeriu-Aurelian Chirica Marcel Ifrim Cristina Morariu Doina Spaiuc Alina Manole Mihaela Moscalu

Background and Objectives: Healthcare-associated infections (HAIs) remain a major challenge in emergency hospital settings, where high patient turnover and empirical antibiotic use may contribute to the emergence and spread of multidrug-resistant organisms. Monitoring antibiotic consumption is essential for antimicrobial stewardship and infection prevention. This study evaluated antibiotic consumption patterns across multiple hospital units and explored their ecological relationship with HAI rates. Materials and Methods: A retrospective observational study was conducted in a tertiary-level emergency hospital in Romania between 1 January 2021 and 31 October 2025. Antibiotic consumption was quantified using Defined Daily Dose per 100 bed-days (DDD/100 bed-days) according to World Health Organization (WHO) methodology and categorized using the WHO Access, Watch, and Reserve (AWaRe) classification. HAI data were collected using standardized surveillance definitions. Statistical analyses were primarily descriptive and exploratory and included graphical trend assessment, simple linear regression for temporal trend description, and Spearman correlation analysis for exploratory ecological co-variation assessment. Results: Antibiotic consumption showed substantial variability across hospital units, without a consistent temporal trend over the study period. The Watch group predominated over the Access group from 2023 onward, while Access antibiotics remained below the WHO-recommended 60% threshold. The highest antibiotic consumption was observed in the Medical Wards, followed by Surgical Wards and the Intensive Care Unit. A total of 27 HAIs were identified (0.27 per 1000 patient-days), with the highest incidence observed in the ICU. The most frequent infections were Clostridioides difficile infections (33.3%) and catheter-associated urinary tract infections (29.6%). Exploratory ecological analyses did not identify robust associations between total antibiotic consumption and HAI rates across hospital units. A numerically elevated co-variation was observed between fluoroquinolone consumption and Clostridioides difficile infection incidence; however, this finding should be interpreted strictly as exploratory and hypothesis-generating. Conclusions: Antibiotic use varied across hospital units, with predominance of broad-spectrum agents and suboptimal adherence to WHO AWaRe targets. Reported HAI incidence remained low and should be interpreted within the limitations of routine surveillance systems and potential under-ascertainment. These findings support the value of continuous institutional surveillance of antibiotic use and HAIs while highlighting the limitations of aggregated ecological analyses.

Medicina doi: 10.3390/medicina62061170

Authors: Flavia Fusco Ippolita Altobelli Vito Casale Nunzia Borrelli Giovanni Domenico Ciriello Rosaria Barracano Assunta Merola Nicola Grimaldi Michela Palma Giovanni Papaccioli Anna Correra Diego Colonna Giancarlo Scognamiglio Berardo Sarubbi

Background and Objective: Heart failure (HF) is a major cause of morbidity in adults with congenital heart disease (ACHD), who may also have limited access to transplant. Intermittent levosimendan administration has shown benefit in advanced HF due to acquired heart disease, but currently, there are no data on ACHD. We aimed to evaluate the effects of this treatment in ACHD patients with advanced heart failure, focusing on both clinical status and objective outcome measures. Materials and Methods: We conducted a single-center retrospective analysis of ACHD patients aged >18 years with advanced HF who received ≥ three intermittent levosimendan infusions (either 12.5 mg once monthly or 6.25 mg every two weeks over a 6 h infusion) between March 2020 and January 2025 at a tertiary ACHD center. Clinical outcomes during follow-up were compared with those in the year preceding treatment. Primary endpoints included safety and HF-related adverse events, particularly HF hospitalizations. Secondary endpoints included changes in New York Heart Association (NYHA) class, nt-pro-B-natriuretic peptide (nt-proBNP) values, and ventricular systolic function assessed by echocardiography. Results: Twelve patients (median age 44.6 years, 25% female) were included, with heterogeneous congenital diagnoses and advanced HF. Five patients had a systemic right ventricle (sRV) and one had a single ventricle with previous Fontan palliation. During a median follow-up of 1.3 years, intermittent levosimendan was well-tolerated, with no treatment-limiting adverse events. Two patients (16%) required hospitalization for HF during follow-up compared with 8 (66%) in the year preceding treatment. The incidence of HF hospitalizations decreased from 0.83 to 0.20 events per person-year during follow-up (p = 0.03), although findings should be interpreted cautiously given the small sample size and retrospective design. NYHA functional class improved significantly (p = 0.005). While no significant changes were observed in NT-proBNP or left ventricular ejection fraction, patients with a systemic right ventricle (sRV) showed an increase in right ventricular fractional area change (27 ± 7.4% to 30.6 ± 7%, p = 0.02); however, this observation should be regarded as exploratory given the limited sample size. Two deaths occurred, consistent with the severity of the underlying disease and not directly attributable to levosimendan and the Fontan patient received a successful heart and liver transplant. Conclusions: In a small, real-world cohort of ACHD and advanced HF, intermittent levosimendan administration was safe and associated with improved symptoms, reduced HF hospitalizations, and signals of enhanced systemic right ventricular function. These hypothesis-generating findings may help inform future multicenter studies in ACHD patients with advanced HF, suggesting a potential role for intermittent levosimendan in selected patients, while highlighting the need for prospective, adequately powered studies to confirm its efficacy and better define optimal patient selection.

Medicina doi: 10.3390/medicina62061169

Authors: Yasemin Adalı Ömer Emin Çınar Ümit Akın Dere

Background and Objectives: The COVID-19 pandemic disrupted cancer diagnosis and treatment pathways worldwide. Glioblastoma is an aggressive primary brain malignancy requiring timely multimodal care. This study evaluated survival outcomes among glioblastoma patients diagnosed before and during the COVID-19 pandemic and prepared a dataset for machine learning-based prediction of 12-month mortality. Materials and Methods: Patients aged ≥20 years diagnosed with glioblastoma between 2018 and 2021 were identified from the SEER database using ICD-O-3 histology codes 9440/3, 9441/3, and 9442/3. Patients were categorized as pre-COVID period (2018–2019) or COVID period (2020–2021). OS and CSS were evaluated using Kaplan–Meier curves, log-rank tests, and Cox regression models. Machine learning models predicted 12-month all-cause mortality using registry variables. Results: The final cohort included 9914 patients; 4819 were diagnosed pre-COVID and 5095 during COVID. Median OS was 11 months pre-COVID and 10 months during COVID; 12-month OS was 44.3% and 41.2%, respectively. Median CSS was 11 months in both periods; 12-month CSS was 46.9% and 44.1%, respectively. COVID-period diagnosis was modestly associated with poorer OS (adjusted HR 1.050, 95% CI 1.006–1.095, p = 0.025) and CSS (adjusted HR 1.048, 95% CI 1.003–1.095, p = 0.035). Machine learning models showed moderate discrimination for 12-month mortality prediction. Conclusions: Glioblastoma patients diagnosed during the COVID period had modestly poorer OS and CSS in conventional survival analyses; however, competing-risk analysis did not show a significant association with cancer-specific death. Registry-based machine learning models provided moderate 12-month mortality prediction, supporting their potential utility for population-level prognostic assessment.

Medicina doi: 10.3390/medicina62061168

Authors: Yakup Özgüngör Hicret Yeniay Burak Emre Gilik Emre Karagöz Mensure Çakırgöz Sıla Seven

Background and Objectives: Tracheostomy is frequently performed in critically ill patients requiring prolonged invasive mechanical ventilation; however, factors associated with intermediate-term mortality after tracheostomy remain poorly characterized. This study aimed to identify clinical and procedural factors associated with 90-day all-cause mortality after tracheostomy in ICU patients. Materials and Methods: This retrospective multicenter cohort study included 292 adult patients who underwent tracheostomy in two tertiary ICUs between 1 October 2023 and 1 June 2025. Demographic characteristics, admission diagnoses, comorbidities, clinical severity scores, procedural variables, microbiological culture results, and survival data were collected. Univariate analyses, multivariable binary logistic regression, Cox proportional hazards regression, receiver operating characteristic (ROC) analysis, and Kaplan–Meier survival analysis were performed. Results: The overall 90-day all-cause mortality rate was 74.7%. Age, Charlson Comorbidity Index, and APACHE II score were significantly associated with 90-day mortality in univariate analyses, whereas tracheostomy timing and technique were not. In multivariable logistic regression analysis, the Charlson Comorbidity Index and APACHE II score were independently associated with mortality. Cox proportional hazards regression confirmed that both APACHE II score and Charlson Comorbidity Index were independently associated with mortality over time. ROC analysis demonstrated moderate discriminative performance for age, Charlson Comorbidity Index, and APACHE II score. Conclusions: In critically ill patients undergoing tracheostomy, 90-day mortality was high and was driven primarily by acute illness severity and comorbidity burden rather than procedural characteristics. These findings support incorporating biological vulnerability, expected recovery potential, and goals-of-care discussions into tracheostomy decision-making.

Medicina doi: 10.3390/medicina62061167

Authors: Canan Yılmaz Filiz Ata Selimcan Yırtımcı Eralp Çevikkalp Emre Ulusoy Ümran Karaca Ayşe Neslihan Balkaya Tuğba Onur Abdulkadir İskender Mehmet Gamlı

Background and Objectives: Postoperative pulmonary complications (PPCs) remain an important cause of morbidity after cardiac surgery. Driving pressure (DP), defined as the difference between plateau pressure and positive end-expiratory pressure, has been proposed as a bedside marker of respiratory system mechanics during lung-protective ventilation. However, its relationship with PPCs in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) remains uncertain. This study aimed to evaluate the association between intraoperative DP and PPCs following CPB-supported cardiac surgery. Materials and Methods: This single-center prospective observational study included 99 adult patients undergoing elective cardiac surgery with CPB. All patients were ventilated using a standardized lung-protective strategy with a tidal volume of 6 mL/kg predicted body weight and a fixed PEEP of 5 cmH2O. Patients were categorized according to intraoperative DP as Group I (DP < 13 cmH2O, n = 66) and Group II (DP ≥ 13 cmH2O, n = 33). The primary outcome was a composite PPC endpoint, defined as the occurrence of at least one EPCO-defined pulmonary complication during the postoperative hospital stay. Multivariable logistic regression was performed to assess whether pre-CPB DP was independently associated with PPCs after adjustment for body mass index, CPB time, and age. Results: Patients with DP ≥13 cmH2O had higher post-CPB and ICU-admission lactate concentrations. Pneumothorax, pleural effusion, atelectasis, CPAP requirement, and prolonged mechanical ventilation were more frequent in the elevated-DP group. Mechanical ventilation duration, ICU stay, and hospital stay were also longer in this group. Composite PPCs occurred in 41 patients (41.4%). Although higher pre-CPB DP showed a non-significant trend toward increased PPC risk in univariable analysis (OR 1.121, 95% CI 0.988–1.273; p = 0.077), it was not independently associated with the composite PPC endpoint after adjustment (adjusted OR 1.091, 95% CI 0.952–1.251; p = 0.212). In contrast, higher pre-CPB DP was significantly associated with prolonged postoperative ventilation and longer mechanical ventilation, ICU, and hospital stay durations. Conclusions: Elevated intraoperative DP was associated with a higher unadjusted burden of PPCs and delayed postoperative recovery after CPB-supported cardiac surgery. However, pre-CPB DP was not an independent predictor of the composite PPC endpoint after adjustment for relevant confounders. These findings suggest that DP may serve as a clinically useful marker of impaired respiratory mechanics and postoperative vulnerability rather than as an independent causal determinant of PPCs.

Medicina doi: 10.3390/medicina62061166

Authors: Erika L. Kelley Martha Sajatovic Amulya Mallu Feyi Sayo Rufai Celeste Weise Jessica Black Jennifer B. Levin

Background and Objectives: Pharmacotherapy is a first-line treatment for bipolar disorder (BD), although half of individuals report suboptimal medication adherence. Medication adherence enhancement programs that are brief, person-specific, and remotely delivered may be an effective adjunct to treatment. The aim of this study was to qualitatively assess what individuals with BD who participated in a Customized Adherence Enhancement (CAE) program found most helpful and unhelpful about this program, focusing on elements most generalizable to medication adherence promotion. Materials and Methods: n = 14 participants with BD from the intervention arm of a randomized effectiveness trial of CAE vs. enhanced treatment–as-usual participated in one-on-one virtual, semi-structured interviews. Interviews were recorded, transcribed, and summarized using thematic content analysis to identify themes reflecting what was helpful and unhelpful about the program. Results: Participants identified six main themes reflecting impactful aspects of the medication adherence promotion program: practical tools (e.g., worksheets), self-awareness (e.g., identification of triggers), psychoeducation/content (e.g., specific CAE modules), emotional distress (e.g., difficult emotions arose during sessions), format (e.g., pros/cons of virtual format), and interventionist factors (e.g., rapport). Conclusions: Results provide participant-identified useful aspects of a remotely delivered, adjunctive medication adherence promotion program for individuals in treatment for BD in public-sector settings. Strategies for improvement and scale-up of the program include ensuring sufficient technologic and emotional support throughout the program. Future studies may investigate the longer-term impact of such interventions with multiple stakeholder input and consideration of diverse populations, settings, and cultural contexts.

Medicina doi: 10.3390/medicina62061165

Authors: Rita Kunigeliene Germanas Marinskis Vytautas Usonis Odeta Kinciniene

Background and Objectives: Premature ventricular contractions are among the most common arrhythmias encountered in clinical practice. However, this disorder can be associated with arrhythmia-induced cardiomyopathy or be the first sign of primary myocardial diseases. Certain morphologies of premature ventricular contractions are associated with a higher risk for sudden arrhythmia and cardiac dysfunction in the adult population. There is data on the clinical value and significance of the contraction morphology in adults, but there is a lack of such data for children. Materials and Methods: This observational prospective study of pediatric outpatients with premature ventricular contractions was conducted at Vilnius University Hospital Santaros Clinics. Inclusion criteria comprised children aged 3–17 years with more than 5% premature ventricular contractions over 24 h. Exclusion criteria included previously diagnosed congenital heart defects and cardiomyopathies, channelopathies, or the presence of any acute condition. The electrocardiographic morphology and measurements were assessed, analyzed, and described in this study. Results: The electrocardiograms of 80 patients were analyzed according to the ECG-estimated morphology of the arrhythmia complex, arrhythmic QRS complex duration, ratio with the normal QRS complex, and maximum deflection index in V5–V6 derivations. Cardiac MRI abnormalities (8 of 30 MRI studies) was reliably associated with a PVC duration of >150 ms and the maximal amount of extrasystoles per 24 h, with a median amount of 29.6%. A long postcoupling interval (>0.9 s) was associated with PVC progression. Conclusions: In this exploratory pediatric cohort, wider PVC QRS duration and higher maximal PVC burden were associated with ventricular MRI abnormalities, while longer postcoupling interval was associated with PVC progression.

Medicina doi: 10.3390/medicina62061164

Authors: Daniel George Boicu Oana Roxana Bitere-Popa Romică Sebastian Cozma Madalina-Maria Diac Andrei Scripcaru Cristian Marius Mârțu Raluca Olariu Iustin Mihai Iațentiuc Diana Bulgaru Iliescu

Background and Objectives: Trauma-associated auditory dysfunction, encompassing tinnitus and hearing loss, represents a frequent yet underrecognized sequela of acoustic overexposure, blast injury, and head trauma. Despite increasing clinical awareness, the published literature exhibits substantial heterogeneity in reported prevalence estimates and recovery outcomes across different injury mechanisms. This narrative review aims to synthesize available evidence on the prevalence, clinical characteristics, recovery patterns, and prognostic factors of tinnitus and hearing loss following traumatic injury, with a particular focus on comparing outcomes across distinct trauma mechanisms and evaluating the impact of early intervention. Materials and Methods: A comprehensive literature search was conducted in PubMed, Embase, Scopus, and Web of Science for studies published between January 2010 and December 2025. The search strategy combined terms related to traumatic injury (e.g., “acoustic trauma,” “blast injury,” “traumatic brain injury,” “head trauma”) with terms related to auditory dysfunction (e.g., “tinnitus,” “hearing loss,” “auditory dysfunction”). Eligible studies included observational studies (cohort, cross-sectional, case–control) reporting original data on tinnitus and/or hearing loss prevalence, recovery outcomes, or prognostic factors in adult or mixed populations exposed to traumatic injury. A narrative synthesis was organized thematically around the key research questions. Results: The available evidence consistently indicates that tinnitus and hearing loss are frequent consequences of blast injury, acute acoustic trauma, and traumatic brain injury, although reported prevalence estimates vary considerably across studies due to differences in populations, injury mechanisms, and diagnostic criteria. Blast injury is associated with mixed hearing loss (conductive and sensorineural components), while acute acoustic trauma typically causes sensorineural hearing loss, often with a characteristic high-frequency notch. Traumatic brain injury can lead to central auditory processing deficits even when pure-tone thresholds are normal. Recovery is variable and often incomplete; tympanic membrane perforations frequently heal spontaneously, but sensorineural components often persist. Early treatment (within days to two weeks) is associated with better recovery outcomes. Conclusions: Trauma-associated tinnitus and hearing loss are highly prevalent and frequently result in persistent disability. The strong association between early treatment and improved recovery outcomes supports the implementation of prompt audiological evaluation and intervention following traumatic injury. These findings underscore the need for routine audiological screening in at-risk populations and for continued research into preventive strategies, standardised assessment protocols, and optimised treatment regimens.

Medicina doi: 10.3390/medicina62061163

Authors: Dong Hun Kim Jung-Woo Hur Jae-Taek Hong

Background and Objectives: Postoperative dysphagia following anterior cervical discectomy and fusion (ACDF) remains a common complication affecting patient quality of life. This study evaluated the safety and clinical efficacy of reprocessed micronized acellular dermal matrix (ADM) compared to conventional gel-type anti-adhesive agents in patients undergoing single-level ACDF. Materials and Methods: This retrospective propensity score-matched study included 108 patients (54 matched pairs) who underwent single-level ACDF between January 2021 and December 2025. The ADM group received CGDerm Matrix™ and the control group received Mediclore™. The primary outcome was postoperative swallowing function assessed by the Swallowing Impairment Score (SIS-6) at 3 months (pre-specified primary time point). Secondary outcomes included VAS, NDI, modified MacNab criteria, adhesion scores, prevertebral soft tissue swelling, and perioperative inflammatory markers. Bonferroni correction was applied for multiple comparisons (adjusted α = 0.0125). Results: The ADM group demonstrated significantly lower SIS-6 scores at 3 months (0.26 ± 0.16 vs. 0.68 ± 0.27, p = 0.01), which remained significant after Bonferroni correction. All other clinical and radiological outcomes were comparable between groups. No device-related complications occurred. Conclusions: ADM application in ACDF surgery appears safe and is associated with improved postoperative swallowing function at 3 months. However, the clinical significance of observed differences requires further investigation.

Medicina doi: 10.3390/medicina62061162

Authors: Haneul Lee Youngeun Lim Seon-Heui Lee

Background and Objectives: Mild cognitive impairment (MCI) and dementia are prevalent public health challenges with limited pharmacological options for cognitive enhancement. Digital cognitive rehabilitative interventions (DCIs) have emerged as a promising non-pharmacological approach, offering accessibility and personalized strategies. However, their efficacy across diverse populations and contexts remains unclear. This study evaluated the effectiveness of DCIs in improving global cognitive function in individuals with MCI and dementia by comparing them to active controls and usual care. Materials and Methods: Ten databases, including Ovid-Medline, Ovid–Embase, Cochrane Library, CINAHL, Web of Science, PsycINFO, KoreaMed, KMbase, RISS, and KISS, were searched for studies published up to May 2025. Global cognitive and executive functions, along with quality of life, were assessed. Meta-analyses using Review Manager version 5.4 were conducted to evaluate global cognitive function improvements, first stratified by comparator group (active control vs. usual care) and further stratified by patient (MCI vs. dementia) and intervention (computer-based vs. virtual reality cognitive training) types. Results: This systematic review and meta-analysis analyzed 37 studies. Overall, DCIs improved global cognitive function compared to the control group (SMD = 0.44, 95% CI: 0.18, 0.69). However, subgroup analysis showed no significant effect when DCIs were compared with active controls (SMD = 0.24, 95% CI: −0.35, 0.82). Subgroup analysis showed benefits for individuals with MCI (SMD = 0.43, 95% CI: 0.16, 0.70) but yielded inconclusive results for those with dementia (SMD = 0.95, 95% CI: −0.69, 2.59). Computer-based DCIs were effective (SMD = 0.57, 95% CI: 0.20, 0.93), whereas VR-based interventions had inconsistent outcomes (SMD = 0.32, 95% CI: −0.34, 0.98). Conclusions: DCIs may improve cognitive function compared with usual care, particularly in patients with MCI. However, their added benefits overactive cognitive interventions remain uncertain. Further well-designed studies are needed to clarify the relative advantages of DCIs across patient populations and intervention formats.

Medicina doi: 10.3390/medicina62061161

Authors: Héctor Guadalajara Alicia Putan Mariano García Arranz Miguel León-Arellano Raquel Sanz-Baro Jose Manuel Ramirez Damián García-Olmo

Background and Objectives: Surgical site infections (SSIs) remain common after elective colorectal surgery. This systematic review and meta-analysis evaluated whether adding oral antibiotic bowel preparation (OAB) to mechanical bowel preparation (MBP) reduces SSIs compared with MBP alone. Materials and Methods: PubMed, the Cochrane Library, Scopus, and ClinicalTrials.gov were searched for English-language randomized controlled trials published from January 2005 to January 2025. Eligible trials enrolled adults undergoing elective colorectal surgery and compared MBP+OAB versus MBP alone, with standard intravenous prophylaxis in both groups. The primary outcome was overall SSI; secondary outcomes were incisional SSI and organ-space SSI. Risk of bias was assessed with RoB 2, certainty with GRADE, and odds ratios (ORs) were pooled using DerSimonian–Laird random-effects models. The protocol was prespecified but not prospectively registered. Results: Twelve trials including 4073 patients were included (MBP+OAB, n = 2069; MBP, n = 2004). MBP+OAB reduced overall SSI (OR 0.53, 95% CI 0.37–0.75; p < 0.001; I2 = 62.5%; 95% prediction interval 0.17–1.66), incisional SSI (OR 0.52, 95% CI 0.34–0.80; p = 0.003; I2 = 57.5%), and organ-space SSI (OR 0.63, 95% CI 0.45–0.88; p = 0.007; I2 = 8.3%). The effect was preserved in metronidazole-containing regimens (OR 0.46, 95% CI 0.33–0.65), but this subgroup was exploratory. Excluding high-risk-of-bias studies supported the primary result. Publication-bias assessment was underpowered. Overall and organ-space SSI were moderate-certainty outcomes; incisional SSI was low-certainty, and anastomotic leak was very low-certainty. Conclusions: In contemporary elective colorectal surgery when MBP is used, adding preoperative OAB probably reduces SSIs. Findings do not establish whether OAB alone is sufficient or whether MBP is necessary; stewardship-relevant outcomes remain insufficiently reported. Funding was provided by ISCIII grant PI25/01285.

Medicina doi: 10.3390/medicina62061160

Authors: Sergiu Ioan Frandeș Oana Frandeș Melania Macarie Claudiu Marinel Ionele Simona Maria Bățagă

Background and Objectives: Intestinal barrier dysfunction is increasingly recognized as a contributor to inflammatory bowel disease (IBD) pathophysiology. Zonulin, a regulator of epithelial tight-junction permeability, has emerged as a potential non-invasive biomarker; however, its clinical relevance remains uncertain. This study evaluated whether fecal zonulin levels reflect clinical disease activity in inflammatory bowel disease and explored their association with ileal involvement in Crohn’s disease (CD). Materials and Methods: Forty-six consecutive IBD patients (26 CD, 20 UC) were prospectively included. Fecal zonulin was measured using a commercially available ELISA. In this study, the term “fecal zonulin” refers to ELISA-detected zonulin-related proteins. Clinical disease activity was assessed using CDAI for CD and the Mayo score for UC. Standard blood and fecal inflammatory markers were obtained, and subgroup analyses were performed according to disease type and location. Results: Fecal zonulin levels were significantly higher in active IBD compared with remission (106.37 vs. 53.80 ng/mL, p = 0.002). Patients with CD had higher zonulin concentrations than those with UC (91.4 vs. 51.0 ng/mL, p = 0.001). Zonulin showed a moderate positive correlation with fecal calprotectin (r = 0.338; p = 0.021). In multivariable analysis, clinical disease activity remained independently associated with zonulin levels, whereas ileal involvement was no longer statistically significant. Conclusions: Fecal zonulin is associated with disease activity in IBD, suggesting that fecal zonulin-related proteins may represent a potential adjunctive marker of epithelial barrier dysfunction and clinical disease activity in IBD. However, these findings should be considered exploratory and require validation in larger, longitudinal multicenter studies using standardized assays and endoscopic correlation.

Medicina doi: 10.3390/medicina62061159

Authors: Mihai Paven Adrian-George Marinescu Osama Abuabboud Laura-Elena Cîrligeriu Luminița-Maria Nica Bianca Georgiana Cărăbiș Izabella Maria Kovacs Oana-Alexandra Velea-Barta Roxana Oancea

Background and Objectives: Warm injectable gutta-percha techniques may improve three-dimensional filling of complex canal anatomy, but heat transfer to the external root surface may threaten periodontal tissues when the 47 °C threshold is exceeded. This in vitro study quantified external root-surface temperature changes during obturation with the Woodpecker FI-G/FI-P system and compared manufacturer preset temperatures with actual device output. Materials and Methods: Twenty extracted single-rooted human teeth standardized to 18 mm were prepared and assigned to obturation at 180 °C (Group A, n = 10) or 230 °C (Group B, n = 10). Infrared thermography recorded coronal, middle, and apical root-surface temperatures. A second device-based experiment measured FI-G and FI-P output at preset temperatures of 150 °C, 180 °C, 200 °C, and 230 °C. Results: The 230 °C setting produced significantly higher middle-third temperatures than the 180 °C setting (41.84 ± 5.52 °C vs. 36.99 ± 3.21 °C; p = 0.027; Cohen’s d = 1.07), whereas coronal and apical differences were not significant. The highest external root-surface value was 49.6 °C, and 3/10 specimens obturated at 230 °C exceeded 47 °C in the middle third. A significant coronal-to-middle gradient reversal was observed at 230 °C (p = 0.045). Device measurements showed strong attenuation between preset and output temperatures: at 230 °C, the FI-G tip base reached 150.0 °C but the tip apex reached 51.3 °C, while FI-P plugger tips reached 120.0 °C. Conclusions: The 180 °C setting produced a more predictable thermal profile, whereas 230 °C increased localized middle-third overheating risk. These in vitro findings support cautious temperature selection, especially in teeth with reduced dentin thickness or compromised root anatomy.

Medicina doi: 10.3390/medicina62061158

Authors: Ieva Vienažindytė Tautvydas Klėgėris Ingrida Ulozienė Diego Kaski Brigita Glebauskienė Renata Balnytė

Background and Objectives: Non-invasive biomarkers reflecting neurodegeneration are increasingly important in multiple sclerosis (MS). Optical coherence tomography (OCT) provides quantitative measures of retinal structure, most commonly peripapillary retinal nerve fiber layer (pRNFL) thickness. However, the potential clinical relevance of optic nerve head morphology, including cup-to-disc ratio (CDR), remains insufficiently explored. We investigated associations between OCT-derived parameters, subjective visual vertical (SVV), and disability in MS. Materials and Methods: In this retrospective study, 100 patients with MS were included. OCT parameters (pRNFL thickness and area-based CDR) were analyzed at baseline and follow-up. Clinical disability was assessed using the Expanded Disability Status Scale (EDSS). Detailed optic neuritis history was not consistently available in the retrospective clinical records and therefore could not be systematically accounted for in the analyses. SVV was evaluated in 37 patients using a virtual reality–based protocol. Associations were assessed using Spearman correlation and linear regression analyses. Multivariable regression models were adjusted for age, sex, and follow-up duration. Results: pRNFL thickness was not associated with baseline EDSS (rho = −0.06, p = 0.55) or annualized EDSS change. Baseline CDR correlated with both baseline EDSS (rho = 0.30, p = 0.0065) and follow-up EDSS (rho = 0.46, p < 0.0001). In univariable regression analysis, baseline CDR was associated with follow-up EDSS (B = 3.33, R2 = 0.23, p < 0.0001), remaining significant after adjustment for age, sex, and follow-up duration (B = 2.59, 95% CI 1.26–3.92, p = 0.0002). No significant associations were observed between OCT parameters and SVV measures. Conclusions: Higher CDR values, but not pRNFL thickness, were associated with disability measures in this exploratory MS cohort. However, these findings should be interpreted cautiously because optic neuritis history could not be systematically accounted for and physiological optic disc variability may substantially influence CDR measurements.

Medicina doi: 10.3390/medicina62061157

Authors: Abdelrahman Hafez Kamal Awad Juan M. Farina Mohamed Nour Mohamed Reyad Mohamed Isabel G. Scalia Sherif Ahmed Fatmaelzahraa Abdelfattah Mahshad Razaghi Laurève Chollet Cecilia Villa Etchegoyen Ramzi Ibrahim Balaji Tamarappoo Matthew Stib Chadi Ayoub Reza Arsanjani

Coronary artery disease (CAD) remains a leading cause of global morbidity and mortality. Accurate diagnosis of ischemia-causing coronary stenoses is essential for guiding revascularization and improving outcomes. Although invasive fractional flow reserve (FFR) remains the gold standard for functional lesion assessment, its use is limited by procedural invasiveness, cost, and complexity. CT-derived FFR (FFRct), based on computational fluid dynamics (CFD), was the first major advance in noninvasive physiological assessment, but its adoption has been hindered by intensive off-site computation and dependence on high-quality imaging. This review summarizes the evolution from invasive FFR to AI-driven functional assessment of coronary lesions. We examine the principles and validation of CFD-based FFRct and then focus on the shift toward artificial intelligence, including both machine learning (ML) and deep learning (DL) approaches. These methods range from models using engineered geometric and plaque features trained on large synthetic datasets to end-to-end systems that learn directly from imaging data. We discuss key validation studies evaluating diagnostic accuracy, prognostic value, and clinical utility, with attention to performance in challenging settings such as intermediate stenoses, heavy calcification, and patients with comorbidities. We also highlight major barriers to widespread adoption, including dependence on input data quality, limited explainability, regulatory hurdles, and integration into clinical workflows. Finally, we outline future directions, including AI-enabled virtual PCI planning, multimodal risk stratification, and broader access to functional cardiac assessment. AI has the potential to transform noninvasive coronary imaging by enabling a single CCTA scan to provide rapid, integrated evaluation of anatomy, plaque characteristics, and physiological significance, supporting more personalized care and better clinical outcomes.

Medicina doi: 10.3390/medicina62061156

Authors: Mohammed Al Subhi Mohammed Al Yousufi Hassan Alnajdi Athir Al-Balushi Ibrahim K. Al Alawi Saleh Al Abri Younis Al-Mufargi

Background and Objectives: Postoperative fatigue (POF) is a frequent complication that negatively affects recovery and quality of life following surgery. Ketamine and esketamine, as N-methyl-D-aspartate (NMDA) receptor antagonists, may reduce postoperative fatigue; however, current evidence remains inconclusive. This systematic review and meta-analysis aimed to evaluate the effects of perioperative ketamine and esketamine on postoperative fatigue in adult surgical patients. Materials and Methods: A systematic search of major electronic databases was conducted to identify randomized controlled trials comparing perioperative ketamine or esketamine with placebo or standard care in adult surgical patients. Fatigue outcomes during the first postoperative week were analyzed using random-effects meta-analyses and reported as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Subgroup analyses were performed according to NMDA antagonist type, surgical procedure, and administration regimen. Sensitivity analyses included exclusion of studies using patient-controlled intravenous analgesia (PCIA) and leave-one-out analyses. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and certainty of evidence was evaluated using the GRADE approach. Results: Eight randomized controlled trials (n = 906 participants) were included in the qualitative and quantitative synthesis. No significant overall reduction in postoperative fatigue was observed at POD1 (SMD −0.37, 95% CI −0.87 to 0.13), although esketamine demonstrated a significant benefit in subgroup analysis. Ketamine/esketamine significantly reduced postoperative fatigue at POD3 (SMD −0.58, 95% CI −0.86 to −0.30) and POD7 (SMD −0.38, 95% CI −0.65 to −0.12). Subgroup analyses demonstrated greater reductions in fatigue among patients undergoing colorectal surgery. Sensitivity analyses excluding PCIA studies and leave-one-out analyses confirmed the robustness of the findings at POD3 and POD7. The certainty of evidence was rated as low for POD1 and moderate for POD3 and POD7. Conclusions: Perioperative ketamine and esketamine were associated with reduced postoperative fatigue from POD3 onward in adult surgical patients, with more consistent benefits observed in colorectal surgery populations. Further high-quality studies are needed to determine the clinical significance of these findings and their impact on postoperative recovery outcomes.

Medicina doi: 10.3390/medicina62061155

Authors: Osman Murat Ipek Erdinc Dincer Omer Aydiner Ahmet Halil Sevinc Burcu Hanci Sevinc Efe Aras

Background and Objectives: Evidence linking sarcopenia and myosteatosis to oncological outcomes in renal cell carcinoma (RCC) remains inconsistent. We aimed to evaluate whether preoperative psoas muscle measurements are associated with tumor stage, recurrence, and survival in RCC patients undergoing nephrectomy. Materials and Methods: A total of 199 patients who underwent nephrectomy with a diagnosis of RCC between 2018 and 2024 were retrospectively evaluated. Preoperative computed tomography images were used to measure the bilateral psoas muscle area at the L3 vertebral level and Hounsfield unit (HU) values. The psoas muscle index (PMI) was calculated. PMI and psoas HU values were analyzed as continuous variables, as this approach preserves statistical information and avoids misclassification bias inherent to arbitrary dichotomization, particularly given the absence of population-specific validated thresholds for Turkish RCC patients. Tumor stage, metastasis, recurrence, and survival data were analyzed. Results: The mean age of the patients was 60.29 ± 11.62 years, and 67.84% were male. The mean PMI was 5.11 ± 1.54 cm2/m2 while the mean psoas HU value was 38.63 ± 8.95 HU. PMI was significantly higher in patients with advanced-stage (T3 and T4) disease than in those with early-stage (T1 and T2) disease (5.57 ± 1.49 vs. 4.30 ± 1.28, p < 0.001). A positive correlation was found between T stage and PMI (r = 0.396, p < 0.001) and between tumor size and PMI (r = 0.215, p = 0.002). Modest but significant correlations were found between age and both PMI (r = −0.274, p < 0.001) and psoas HU values (r = −0.347, p < 0.001). Conclusions: In this retrospective nephrectomy series, conducted in a cohort inherently enriched for adequate performance status and surgical fitness, PMI showed a positive correlation with pathological T stage and tumor size, intriguingly higher PMI values were observed in patients with advanced T stages. These findings suggest that the role of psoas-based muscle measurements in the prognostication of this subset of RCC patients (advanced disease but candidates for surgical treatment) may be limited.

Medicina doi: 10.3390/medicina62061154

Authors: Nuri Can Tanrısever Hatice Gökalp

Background and Objectives: Maintenance of condylar position during bilateral sagittal split ramus osteotomy (BSSRO) is important for preserving temporomandibular joint biomechanics and skeletal stability. During surgery, loss of muscle tone under general anesthesia may alter the condyle–fossa relationship, making accurate repositioning of the proximal segment challenging. Although manual positioning remains the most commonly used intraoperative approach, evidence regarding its ability to preserve the preoperative condyle–fossa relationship remains limited. This study evaluated changes in the condyle–fossa relationship following BSSRO performed with manual proximal segment positioning. Materials and Methods: This single-center retrospective study included lateral cephalometric radiographs of 14 patients (8 females, 6 males; aged 19–29 years) with skeletal Class III malocclusion treated with combined orthodontic treatment and BSSRO. Radiographs were obtained preoperatively (T0), immediately postoperatively (T1), and at the final follow-up examination (T2). Condylar position was assessed using a Cartesian coordinate system, joint space measurements, and the Condyle Position Index (CPI). Statistical analyses were performed using the Friedman and Wilcoxon signed-rank tests (p < 0.05). Results: Significant differences were observed in CPI and anterior joint space measurements across the observation periods. Interval analysis demonstrated increased CPI values and decreased anterior joint space measurements between T1 and T2, whereas no significant immediate postoperative changes were observed. Intra-observer reliability was excellent, with intraclass correlation coefficients exceeding 0.90 for all variables. Conclusions: Manual positioning of the proximal segment during BSSRO may provide acceptable immediate postoperative condyle–fossa stability but may not completely maintain the preoperative condyle–fossa relationship over time. Although no significant immediate postoperative changes were observed, significant changes in the condyle–fossa relationship were identified at the final follow-up examination. These findings support the need for further prospective studies incorporating clinical temporomandibular joint assessment and three-dimensional imaging.

Medicina doi: 10.3390/medicina62061153

Authors: Marko Zlatanović Maja L. J. Živković Nevena Zlatanović Mladen Brzaković Mihailo Jovanović

Background and Objectives: Type 2 diabetes mellitus (T2DM) causes retinal microvascular changes that precede clinically apparent diabetic retinopathy (DR). We aimed to identify which optical coherence tomography angiography (OCTA) biomarkers best distinguish eyes with T2DM without clinical DR from healthy controls and to evaluate machine learning classifiers trained on a comprehensive 68-parameter OCTA panel. Materials and Methods: In this prospective case–control study, 80 patients with T2DM without clinical DR and 33 controls underwent 3 × 3 mm macular OCTA using an Optovue RTVue Avanti System. After outlier screening, 221 eyes (155 T2DM, 66 controls) were analyzed. Sixty-eight OCTA parameters were extracted, covering FAZ morphometry (including foveal density FD-300), SCP and DCP vessel density and layer thickness, outer-retina and choriocapillaris flow, and a full retinal-thickness map. Between-group comparisons used the Mann–Whitney U test with Benjamini–Hochberg FDR correction. Logistic regression, random forest, and XGBoost classifiers were evaluated with patient-grouped 10-fold cross-validation; feature importance was quantified via SHAP. Results: Forty-two of 68 parameters reached FDR significance (q < 0.05). Deep capillary plexus vessel density was the most discriminative family (whole image rb = −0.66, q = 2.5 × 10−13; parafovea rb = −0.64). FD-300 was reduced in T2DM (median 47.55% vs. 51.86%; rb = −0.57; q = 1.0 × 10−10) and emerged as the top SHAP feature (mean |SHAP| = 0.81). FAZ circularity decreased without FAZ-area enlargement, and outer-retina flow was paradoxically elevated (rb = +0.39), consistent with a projection artifact. XGBoost using all 68 features achieved a patient-grouped cross-validated AUC of approximately 0.91, compared with 0.85 for conventional SCP + DCP whole-image density. No parameter correlated with current HbA1c in T2DM (all q > 0.98), and the well-controlled (<7%) and poorly controlled (≥7%) subgroups were indistinguishable across five of six principal biomarkers, consistent with metabolic memory. FD-300 remained independent after adjustment for hypertension, hyperlipidemia, and age (OR = 0.76; 95% CI 0.69–0.84; p < 0.001). Conclusions: A multi-compartment OCTA panel outperforms conventional two-layer vessel-density metrics in detecting preclinical diabetic microvasculopathy, although external validation is required before clinical use. FD-300 is the single most informative biomarker, while choriocapillaris and retinal thickness measures provide complementary, compartment-specific signals. Because the OCTA signature is decoupled from the current HbA1c, screening should not be deferred in well-controlled T2DM.

Medicina doi: 10.3390/medicina62061152

Authors: Mustafa Altintaş Remzi Çetinkaya Mehmet Özel Habip Balsak

Background and Objectives: Severe snowfall and icing are associated with weather-related trauma presentations, especially in cities unaccustomed to prolonged winter conditions. However, the clinical characteristics of these injuries and their implications for surgical management remain incompletely understood. This study aimed to describe injury patterns, treatment approaches, and factors associated with the need for surgery among patients presenting with extremity trauma during an intense snowfall and icing episode in Diyarbakır. Materials and Methods: This single-center retrospective observational study included patients presenting to the emergency department with extremity trauma during a severe snowfall and icing period. Demographic characteristics, injury features, imaging modality, ambient temperature, anatomical localization, and treatment approaches were analyzed. Patients were categorized according to nonoperative versus operative management. Factors associated with the need for surgery were evaluated using univariable and multivariable logistic regression analyses. Receiver operating characteristic analysis was used to assess the discriminative ability of age and ambient temperature for predicting the need for surgery. Results: A total of 943 patients were included. The largest age group was 18–44 years (38.6%), and 55.9% were male. Fractures were identified in 50.7% of cases, whereas 46.7% had no fracture and 2.7% had joint dislocation. Upper-extremity injuries predominated (65.2%), with distal segment involvement observed in 55.0% of cases. Most presentations occurred on days with mean ambient temperatures ≤ 0 °C (81.5%). Overall, 82.1% of patients were managed nonoperatively, while 17.9% required surgical treatment. In multivariable analysis, increasing age and the use of computed tomography were independently associated with the need for surgery, whereas ambient temperature was not. Conclusions: Fall-related extremity injuries during severe snowfall and icing were predominantly upper-extremity and distal injuries, and most were managed nonoperatively. The need for surgery was more strongly associated with patient age and injury complexity than with ambient temperature alone. These findings describe a distinct trauma profile during short-term winter events in mild-climate cities.

Medicina doi: 10.3390/medicina62061151

Authors: Roland Sebastian Horváth Abel Emanuel Moca Anamaria Gozman-Pop Árpád Rózsa Diána Róza Pacadzisz Teodor Andrei Maghiar Octavian Adrian Maghiar Paula Bianca Maghiar Marius Adrian Maghiar

Background and Objectives: Anastomotic leakage (AL) remains one of the most feared complications following colorectal resection, yet the relationship between cumulative surgeon experience and AL risk remains inconclusive in the literature. Most available evidence originates from high-volume or specialized centers, with limited data from mid-volume Central and Eastern European settings. This study aimed to evaluate the association between cumulative surgeon experience, operative time, and AL risk in a selected sample of colorectal resections with primary anastomosis for both benign and malignant indications, excluding right colectomies, abdominoperineal resections, TaTME, Hartmann’s procedures, and stoma-protected anastomoses, within a single-center multi-surgeon setting over a seven-year period. Materials and Methods: This retrospective observational study included 315 consecutive adult patients who underwent left-sided or segmental colorectal resection with primary anastomosis for both benign and malignant indications (excluding right colectomy, abdominoperineal resection, TaTME, Hartmann’s procedure, and stoma-protected cases) at Békés County Central Hospital, Gyula, Hungary, between January 2018 and December 2024. AL was defined according to ISREC criteria, with only clinically relevant grade B or C leaks recorded as events. The main exposure was cumulative surgeon experience (log2-transformed). The primary analysis used a multivariable generalized estimating equation (GEE) model clustered by surgeon, adjusted for operative time, surgical approach, conversion, wound infection, and resected segment. Eight surgeons participated, with cumulative experience ranging from 50 to 600 cases. Results: Among the 315 patients included, the median age was 68 years, with a male predominance (61.0%); most cases involved malignant pathology (82.9%) and at least one comorbidity (73.3%). The rectosigmoid was the most frequently resected segment (49.8%), and an open approach was used in 58.7% of cases. The overall AL incidence was 7.94% (25/315), with a median onset at postoperative day 5. In the multivariable GEE model, cumulative surgeon experience was not significantly associated with AL risk (OR per doubling 1.12; 95% CI 0.73–1.72; p = 0.597), nor was operative time (OR per 10 min 1.03; p = 0.294). Wound infection was the only variable significantly associated with AL (OR 3.48; 95% CI 1.06–11.44; p = 0.042), although its temporal relationship with AL could not be established from the available data. AL rates by experience category were 8.9%, 7.5%, and 7.9% for surgeons with <100, 100–199, and ≥200 cases, respectively (p = 0.913). AL was associated with a significantly prolonged hospital stay (median 17 vs. 7 days, p < 0.001) regardless of surgical approach. Conclusions: Cumulative surgeon experience was not independently associated with AL risk in the selected sample of colorectal resections with primary anastomosis in this single-center, mid-volume setting. Wound infection emerged as the only variable significantly associated with AL, although its temporal relationship with AL could not be determined and several established confounders, including anastomotic height, BMI, ASA class, and emergency status, were unavailable for adjustment. Considerable inter-surgeon variability was observed irrespective of case volume. These findings highlight the complexity of AL risk and the need for prospective multicenter studies with comprehensive risk adjustment.

Medicina doi: 10.3390/medicina62061150

Authors: Mihaela Hizanu Dumitrache Camer Salim Alina Plesea-Condratovici Dana Elena Mîndru Mădălina Duceac Covrig Eva Maria Elkan Carmen Laura Cristescu Budala Irina Luciana Gurzu Petruța Iuliana Moraru Mirela Mătăsaru Mădălina Nicoleta Matei Letiția Doina Duceac

Background and Objectives: Seizures and epilepsy are common in children with life-limiting illnesses, particularly in the context of severe neurological impairment. However, data on the clinical profile of these patients in paediatric palliative care are limited, and the lack of standardised protocols adapted to this context represents a clinical challenge. To assess the prevalence of epilepsy and associated clinical characteristics in children receiving paediatric palliative care and to develop a clinical protocol for the management of seizures based on expert consensus. Materials and Methods: A retrospective observational study was conducted, based on the analysis of clinical data from children registered in a paediatric palliative care service (Lumina Association, Romania). Demographic, diagnostic, neurological status and anticonvulsant treatment data were collected. Based on the results obtained and the existing literature, a clinical protocol was developed using a modified Delphi method approach, involving a multidisciplinary panel of experts and two rounds of evaluation of clinical statements. Results: A total of 101 patients (54.5% boys and 45.5% girls) were included, with a mean age of 7.2 ± 4.7 years. Epilepsy was documented in 32.7% of patients and was significantly associated with a neurological diagnosis (p = 0.008), severe neurodevelopmental delay (p = 0.032) and severe motor impairment (p = 0.036). The Delphi process led to the validation of 13 clinical recommendations, the majority of which achieved a strong level of consensus (>85%). Conclusions: Epilepsy is common and closely associated with severe neurological impairment in paediatric palliative care. The integration of systematic neurological assessment and the implementation of a consensus-based clinical protocol can support a more structured approach to seizure management in paediatric palliative care.

Medicina doi: 10.3390/medicina62061149

Authors: Flora Nikolaou Ioulia Solomou Maria Loizidou Panagiotis Papettas Eleni Giorgoudi Kalia Lofitou Fofi Constantinidou

Background and Objectives: The neurocognitive sequelae of COVID-19 have attracted attention as part of post-COVID condition (PCC), yet standardized tools for screening and quantifying PCC-related cognitive impairment remain scarce. The present study aimed to develop and validate the Screening for Neurocognitive Abilities Post-COVID (SNAP-COVID), a self-report questionnaire designed to capture current symptom burden and perceived changes in cognitive functioning relative to pre-COVID status in a Greek-speaking sample. Materials and Methods: Data collection occurred in three phases between August 2024 and February 2025. Dataset A (N = 27) was used for test–retest reliability. Dataset B (N = 300) was used for exploratory factor analysis (EFA), reliability testing, and convergent validity analyses with the Brain Fog Scale (BFS). Dataset C (N = 317) was used for independent validation through confirmatory factor analysis (CFA). Results: Initial EFA of the 30-item SNAP-COVID scale suggested a four-factor model, yet further item refinement yielded a robust three-factor, 24-item solution: (1) General Cognitive Functions (17 items, α = 0.948), (2) Sensory Hypersensitivity (4 items, α = 0.829), and (3) Language and Communication (3 items, α = 0.950). The total scale demonstrated excellent internal consistency (α = 0.95). Convergent validity was evident by significant correlations between SNAP impact scores and BFS scores (r = −0.442, p < 0.001). CFA confirmed the three-factor structure with acceptable fit indices (χ2(249) = 677.29, p < 0.001; CFI = 0.882; TLI = 0.869; RMSEA = 0.074; SRMR = 0.032). Conclusions: The SNAP-COVID scale is a reliable and valid instrument. Its multidimensional structure captures global and domain-specific difficulties, addressing a critical gap in post-infectious cognitive assessment.

Medicina doi: 10.3390/medicina62061148

Authors: Serkan Suren Deniz Yavuz Baskiran Irem Tulum Adil Baskiran Sezai Yilmaz

Background and Objectives: This study aimed to examine the level of depression in children who had undergone pediatric liver transplantation and to evaluate the potential role of liver enzymes as biomarkers of depression. Materials and Methods: The study was conducted with 50 pediatric liver transplant recipients followed at the Liver Transplantation Institute of İnönü University, and data were collected through face-to-face interviews. The Personal and Transplant Information Form, Child Revised Impact of Event Scale, and Patient Health Questionnaire–Depression were used as data collection tools. In addition to descriptive statistics, Student’s t-test, Mann–Whitney U test, correlation analyses, and regression analyses were performed. Results: The median PHQ-9 score was 1.00 (Q1–Q3: 0.00–5.00), indicating generally low levels of depression. A significant positive correlation was found between CRIES and PHQ-9 scores (r = 0.414, p < 0.01). In contrast, no consistent significant associations were observed between liver enzyme levels and depression scores in multivariate analyses, although bilirubin showed a modest negative correlation with PHQ-9 scores. In the multivariate analysis, although the overall regression model was not statistically significant, the CRIES score showed an individual association with PHQ-9 scores within the model (B = 0.117, p = 0.037). Conclusions: Liver enzymes cannot be considered strong biomarkers of depression in pediatric liver transplant recipients; however, post-traumatic stress symptoms may be an important clinical indicator for assessing psychological adjustment.

Medicina doi: 10.3390/medicina62061147

Authors: Oday Salman Elie Bou Sanayeh Hadi Itani Chloe Lahoud Chapman Wei Ahmad Mustafa Anaha Raghunathan Elie Moussa Martin Miguel I. Amor

Background and Objectives: Acute or severe limb ischemic events are limb- and life-threatening complications of peripheral artery disease (PAD). Although cirrhosis is increasingly recognized as a systemic disorder associated with endothelial dysfunction, inflammation, and altered hemostatic balance, its relationship with coding-defined limb ischemic events among individuals with PAD remains poorly defined. We investigated whether cirrhosis is independently associated with coding-defined acute or severe limb ischemic events among hospitalized adults with PAD. Materials and Methods: We performed a retrospective discharge-level analysis of the National Inpatient Sample from 2016 to 2018. Adult hospitalizations with PAD were identified using ICD-10-CM diagnosis codes and stratified according to the presence or absence of cirrhosis. The primary outcome was coding-defined acute or severe limb ischemic events. Multivariable logistic regression was used to evaluate the association between cirrhosis and acute or severe limb ischemic events after adjustment for demographic and cardiovascular comorbidities. Propensity-score matching was additionally performed to balance baseline characteristics between hospitalizations with and without cirrhosis. Results: Among 276,702 hospitalizations with PAD, 5942 had cirrhosis. Before matching, cirrhosis was independently associated with higher odds of acute or severe limb ischemic events after multivariable adjustment (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.35–1.60; p < 0.001). After 1:1 propensity-score matching, 5883 matched pairs were analyzed. The association between cirrhosis and acute or severe limb ischemic events persisted in the matched cohort, with cirrhosis remaining significantly associated with increased odds of these events (OR 1.41, 95% CI 1.24–1.60; p < 0.001). Conclusions: In this large discharge-level analysis of hospitalizations with PAD, cirrhosis was independently associated with higher odds of coding-defined acute or severe limb ischemic events. These findings suggest that cirrhosis may represent an underrecognized vascular risk amplifier in PAD. Further prospective studies are needed to validate this association, clarify underlying mechanisms, and determine whether cirrhosis may improve PAD risk stratification.

Medicina doi: 10.3390/medicina62061146

Authors: Elvira Ferrés-Amat Sira Herrera-Martínez Cristina Díaz-Martínez Isabel Maura-Solivellas Maria Jesus Campillay Iván Valdivia-Gandur Eduard Ferrés-Padró

Background and Objectives: Traumatic dentoalveolar injuries (TDI) in children often require urgent stabilization using splints. Titanium trauma splints (TTS) represent a practical option; however, pediatric evidence from hospital-based emergency settings remains limited. This study describes the clinical and contextual characteristics of children treated with TTS and explores factors associated with early complications and splint stability. Materials and Methods: A retrospective observational cohort study was conducted at a Pediatric Dentistry Service, including children with TDI managed with TTS and followed for a minimum of three months. Clinical records were reviewed to collect demographic, contextual, and clinical variables. Early complications and the need for re-splinting were recorded, and associations between selected variables and outcomes were analyzed. Results: Seventy-three patients (64.4% male; mean age 10.29 ± 2.99 years) and 127 traumatized teeth (98.4% permanent) were included. A predominance of school-based injuries was observed (52.1%). The most frequent injury types were subluxation (39.1%), avulsion (26.6%), and extrusion (16.4%). A longer interval between trauma and splint placement was associated with inflammatory root resorption (p = 0.011), although this finding should be interpreted with caution given the limited number of events. Mixed-dentition splints showed a higher likelihood of requiring re-splinting (OR = 12.23; 95% CI: 1.18–126.60); however, this estimate was imprecise and should be interpreted as an exploratory signal. Overall, 90.4% of patients completed treatment with a single splint. Conclusions: Within the limitations of this retrospective observational cohort, TTS showed satisfactory short-term clinical stability in pediatric traumatic dental injuries. Longer time between trauma and splint placement was associated with inflammatory root resorption, while mixed-dentition splints emerged as a potential signal of increased re-splinting. These findings are exploratory and hypothesis-generating and require confirmation in future studies.

Medicina doi: 10.3390/medicina62061145

Authors: Radu-Nicolae Pop Patricia Ariadna Nicula Cristina Ariadna Nicula Dorin Vasile Nicula Bianca Pop

Background and Objectives: Pediatric keratoconus may progress rapidly, and treatment decisions are often made before prolonged observation is possible. This study evaluated 24-month visual, tomographic, pachymetric, and biomechanical outcomes after conventional epithelium-off corneal collagen cross-linking (CXL) using Pentacam tomography and Corvis ST dynamic Scheimpflug analysis. Materials and Methods: This single-center observational longitudinal cohort included 28 eyes of 23 patients aged 13–18 years treated at the OCULENS Clinic, Cluj-Napoca, Romania, between 2019 and 2023. Because the study had no untreated or alternative-treatment control group, postoperative changes were interpreted as associations after CXL rather than as proof of causality. Baseline, 6-, 12-, and 24-month values were analyzed for UCVA, BCVA, Kmax, thinnest pachymetry, SP-A1, deformation amplitude (DA), first and second applanation times (A1T and A2T), highest concavity (HC) radius, and BAD-D. Repeated-measures ANOVA was used after assessment of within-eye difference normality; findings were interpreted cautiously because the analysis was eye-based, the cohort was small, and multiple outcomes were examined. Results: UCVA improved from 0.53 ± 0.16 to 0.44 ± 0.16 logMAR and BCVA from 0.31 ± 0.11 to 0.25 ± 0.11 logMAR (both p < 0.001). Mean Kmax decreased modestly from 54.36 ± 3.11 D to 53.41 ± 2.79 D, while SP-A1 increased from 84.69 ± 4.75 to 97.39 ± 5.11 (both p < 0.001). Thinnest pachymetry showed early postoperative thinning followed by partial recovery by 24 months. DA decreased, A1T increased, A2T decreased, HC radius increased, and BAD-D decreased significantly. Kmax and SP-A1 were inversely correlated at all visits (r = −0.714 to −0.773; all p < 0.001), but these correlations were considered exploratory. Post-24-month retreatment and keratoplasty-related events were recorded descriptively and were not included in the formal 24-month model. Conclusions: Within the prespecified 24-month analytic window, conventional epithelium-off CXL was associated with stabilization, modest visual and tomographic improvement, and a concordant biomechanical stiffening signal. The results should be interpreted as cautious observational findings rather than definitive evidence of long-term stability, because of the small sample, eye-level analysis, absence of a control group, limited follow-up, and lack of formal repeatability testing.

Medicina doi: 10.3390/medicina62061144

Authors: Chang-Hyung Lee Siwon Yoon Jung Hyun Yang Min-Hyeok Choi Min Hui Moon Kyeong-Baek Kim Suk Woong Kang

Background: The prevalence of adhesive capsulitis (AC) is estimated to be 2–5% in the general population. However, the etiology of AC remains unclear. Among the various proposed factors, the precise role of cervical disease, and the severity of cervical degeneration, in the development of AC has not been fully elucidated. This study aimed to analyze the contribution of cervical disease to AC in patients with shoulder pain. Methods: A total of 409 patients who visited the Department of Rehabilitation Medicine for shoulder pain were retrospectively reviewed. The outcome variable was the presence of AC. In addition to cervical disease, other independent variables affecting AC, including sex, diabetes, obesity, dyslipidemia, thyroid disease, immobilization after surgery, rotator cuff tear, subacromial spur, and shoulder joint osteoarthritis were reviewed. To compare the two groups, an independent t-test or chi-square test was performed for continuous and categorical data. Multivariate regression analysis was used to assess the effects of independent factors on AC, adjusting for confounders. Results: Among the 409 patients, 176 (43.0%) were diagnosed with AC. Multivariate analysis demonstrated that diabetes (OR 3.03, 95% CI 1.55–5.91, p = 0.001) and cervical disease (OR 3.03, 95% CI 1.75–5.25, p < 0.001) were significantly associated with increased odds of AC. In contrast, increasing age (OR 0.95, 95% CI 0.92–0.98, p = 0.007), dyslipidemia (OR 0.55, 95% CI 0.31–0.98, p = 0.044), and postoperative immobilization (OR 0.64, 95% CI 0.41–0.99, p = 0.046) were associated with decreased odds of AC. The prevalence of AC increased with the severity of cervical degeneration. Conclusion: In patients with shoulder pain, diabetes and cervical disease were positively associated with AC, whereas age, dyslipidemia, and postoperative immobilization showed inverse associations. These findings suggest that both metabolic and cervical factors may contribute to the development of AC, highlighting the importance of considering cervical pathology in patients with shoulder pain.

Medicina doi: 10.3390/medicina62061143

Authors: Barış Celbek Zeynep Hoşbay Eda Urhun Keleş Hayri Ömer Berköz Adnan Yüksel

Background and Objectives: Brachial plexus birth injury (BPBI) is a peripheral nerve injury occurring during birth that may result in upper-extremity weakness and functional impairment. This systematic review aimed to evaluate the effects of neuromuscular electrical stimulation (NMES) on motor function, muscle strength, range of motion, and upper-extremity function in children with BPBI. Materials and Methods: This systematic review was conducted according to PRISMA guidelines and registered in PROSPERO. PubMed, CINAHL, Scopus, Web of Science, PEDro, and the Cochrane Library were searched from inception to 5 May 2026. Only randomized controlled trials were included. Methodological quality was assessed using the PEDro scale, and risk of bias was evaluated using the RoB 2 tool. Results: Seven randomized controlled trials involving 197 participants were included. Several studies reported improvements in shoulder abduction, elbow flexion, wrist extension, muscle strength, and motor function following NMES compared with conventional therapy. The combination of NMES and constraint-induced movement therapy demonstrated favorable outcomes in functional performance. However, substantial heterogeneity was observed across studies regarding participant characteristics, NMES parameters, treatment duration, and outcome measures. The certainty of evidence ranged from low to very low. Conclusions: Current evidence suggests that NMES may serve as a potential adjunct to conventional rehabilitation in children with BPBI. However, given the low to very low certainty of the evidence, high risk of bias, and substantial clinical and methodological heterogeneity among the included studies, definitive clinical recommendations cannot currently be made. Future well-designed randomized controlled trials using standardized protocols, consistent outcome measures, and longer follow-up periods are warranted.

Medicina doi: 10.3390/medicina62061142

Authors: Dojoon Park Hae-Seok Koh Jeong Wook Moon Youn-Ho Choi

Background and Objectives: With contemporary blood management strategies substantially reducing transfusion rates after total knee arthroplasty (TKA), conventional endpoints such as transfusion incidence and estimated blood loss may have limited sensitivity for evaluating adjunctive hemostatic interventions. As postoperative anemia evolves dynamically over time, hemoglobin kinetics and cumulative anemia burden may offer more informative measures of treatment effect. This study evaluated whether implementation of a topical thrombin–carboxymethyl starch hemostatic agent within a standardized modern blood management protocol was associated with smaller early postoperative hemoglobin decline and lower cumulative anemia burden after TKA. Materials and Methods: In this single-center, retrospective, pre–post observational study, consecutive patients aged 50 years or older undergoing primary unilateral TKA for osteoarthritis before and after implementation of a thrombin–carboxymethyl starch topical hemostatic agent were compared. Perioperative management was otherwise standardized and unchanged. Patients were matched 1:1 using propensity scores derived from eight prespecified covariates. Co-primary endpoints were hemoglobin change from baseline to postoperative day 1 and day 2, and cumulative anemia burden quantified by the area under the hemoglobin-deficit curve from POD 0 to POD 13 was assessed as a key secondary endpoint. Results: Of 564 patients assessed for eligibility, 328 met the inclusion criteria, and 70 propensity score-matched pairs were included in the final analysis. Unless otherwise specified, the outcomes reported below were analyzed in these 70 matched pairs. In the matched cohort, the intervention group had a lesser hemoglobin decrease at postoperative day (POD) 1 than the control group (2.12 ± 0.97 vs. 2.42 ± 0.98 g/dL), corresponding to a paired mean difference of 0.30 g/dL (95% CI, 0.08–0.52; p = 0.008). The between-group difference at POD 2 was not statistically significant (paired mean difference, 0.15 g/dL; 95% CI, −0.03 to 0.33; p = 0.10). The area under the hemoglobin-deficit curve from POD 0 to POD 13 was lower in the intervention group (18.6 ± 5.2 vs. 21.3 ± 5.6 g/dL × day), with a paired mean difference of 2.7 g/dL × day (95% CI, 0.9–4.5; p = 0.004). Estimated total blood loss, formula-derived hidden blood loss, and transfusion rates did not differ significantly between groups. Conclusions: Use of a thrombin–carboxymethyl starch topical hemostatic agent was associated with modest attenuation of early postoperative hemoglobin decline and lower cumulative anemia burden after TKA, without significant differences in estimated blood loss or transfusion occurrence. Hemoglobin kinetics and cumulative anemia burden may provide complementary outcome measures in contemporary low-transfusion practice, although these findings should be interpreted cautiously given the observational design and low transfusion event rate.

Medicina doi: 10.3390/medicina62061141

Authors: Maria Timoshina Sergey Mironov Alexey Dorofeev Alla Shakaryants Svetlana Danshina Ksenia Zakharova Ksenia Grishaeva Aglaya Kazumova Anton Timoshin Andrey Sevbitov

Background and Objectives: Professional ballet dancers endure high occlusal loads, increasing cervical defect prevalence. Conventional composites fail frequently under such conditions. This randomized clinical trial (RCT) compared 24-month performance of a polymer-infiltrated ceramic network (PICN, VITA Enamic) versus a self-curing bioactive composite (Stela) for cervical restorations. Materials and Methods: Twenty professional ballet dancers (40 cervical defects: 21 carious, 19 abfraction) were enrolled in a paired split-mouth RCT. Each received one PICN inlay and one self-curing composite restoration on two non-adjacent defects. Restorations were assessed at 6, 12, and 24 months using United States Public Health Service (USPHS) criteria (primary: marginal integrity) and a dye penetration test. Secondary outcomes included secondary caries, hypersensitivity, and Oral Health Impact Profile-14 (OHIP-14). Statistical tests: McNemar, Fisher’s exact, Kaplan–Meier, log-rank (α = 0.05). Results: At 24 months, marginal integrity (USPHS Alpha) was maintained in 91% of PICN restorations for carious defects and 89% for abfraction defects, compared to 70% and 50% for self-curing composite, respectively. No PICN restoration failed (0%). Self-curing composite failures were 20% (carious) and 30% (abfraction) (exploratory uncorrected p = 0.031; non-significant after correction). Dye penetration was lower for PICN in abfraction defects (11% vs. 60%, adjusted p = 0.048) but not in carious defects (9% vs. 30%, adjusted p = 0.317). Kaplan–Meier survival favoured PICN (log-rank p = 0.001); 24-month survival probability: PICN 100% (95% CI: 83–100%), self-curing composite 75% (95% CI: 55–95%). No secondary caries or serious adverse events occurred. Conclusions: PICN hybrid ceramic provided superior marginal integrity and zero failures over 24 months in cervical restorations of professional ballet dancers, outperforming the self curing composite. Within this high-risk population, PICN inlays are recommended for abfraction defects. However, because the study was conducted exclusively in professional ballet dancers, direct extrapolation to the general population should be made with caution. The self-curing composite may be considered for carious defects when light curing is problematic, but patients should be informed of higher failure risk. Longer studies are needed.

Medicina doi: 10.3390/medicina62061138

Authors: Stanislava Ivanova Stanislav Dyankov Vanya Nalbantova Michaela Shishmanova-Doseva Iva Slavova Kremena Saracheva

Background and Objectives: Nowadays synthetic sweeteners are widely used as sugar substitutes in beverages, processed foods, and pharmaceutical products, largely due to their low caloric content and perceived benefits for weight management and glycemic control. Their consumption has increased markedly over recent decades, paralleling global efforts to reduce added sugar intake and combat obesity and diabetes. This review examines the regulation of artificial sweeteners, their impact on vulnerable populations, and the increased concern about their health effects, including metabolic effects, effects on gut microbiota and neurological and behavioral issues. Materials and Methods: A comprehensive search was performed across multiple electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar, to identify studies relevant to synthetic sweeteners and human health. Results: While considered safe, artificial sweeteners are linked to potential influence on hormonal responses, affecting glucose homeostasis and insulin secretion, as well as effects on gut microbiota composition and glucose metabolism. However, the results reveal inconsistencies of the impact of artificial sweeteners on vulnerable populations, as well as their effects on the human gut microbiota, neurological behavior and endocrine effects and evidence remain limited. Conclusions: Continuous human trials, post-market surveillance and regulatory evaluations are therefore essential to ensure the safety of sugar substitutes for consumers’ health.

Medicina doi: 10.3390/medicina62061140

Authors: Soonsoo Kim Hyowon Hong Jae-Ho Lee

Background and Objectives: Surfactant protein B (SFTPB) is a surfactant-associated protein secreted by alveolar type II epithelial cells that plays a critical role in maintaining alveolar stability and surface tension. Although SFTPB is closely associated with pulmonary epithelial differentiation, its clinical significance in different non-small cell lung cancer (NSCLC) subtypes remains unclear. This study investigated the clinicopathologic and prognostic significance of SFTPB expression in lung adenocarcinoma (AD) and lung squamous cell carcinoma (SCC) using The Cancer Genome Atlas (TCGA) dataset. Materials and Methods: SFTPB mRNA expression data and clinicopathologic information were obtained from TCGA cohorts of AD and SCC patients. Patients were stratified into high- and low-expression groups according to median SFTPB expression levels. Associations between SFTPB expression and clinicopathologic variables were analyzed, and correlation analyses were performed with major oncogenic genes. Overall survival (OS) and relapse-free survival (RFS) were evaluated using Kaplan–Meier survival analysis and log-rank testing. Multivariate Cox proportional hazards regression analyses were performed after adjustment for age, sex, and pathological stage. Results: In AD, high SFTPB expression was significantly associated with lower pathologic stage (p = 0.011) and lower N stage (p = 0.006). SFTPB expression showed significant negative correlations with EGFR (R = −0.140, p = 0.002) and BRAF (R = −0.177, p < 0.001) and a positive correlation with TP53 (R = 0.128, p = 0.004). Patients with high SFTPB expression demonstrated significantly improved OS compared with those with low expression (p < 0.001), while a trend toward prolonged RFS was observed without statistical significance (p = 0.089). Multivariate analysis confirmed high SFTPB expression as an independent favorable prognostic factor in AD (HR = 0.551, 95% CI = 0.405–0.748, p < 0.001). In SCC, high SFTPB expression was also significantly associated with lower pathologic stage (p = 0.009) and lower N stage (p = 0.007). SFTPB expression showed significant negative correlations with SOX2 (R = −0.176, p < 0.001), PIK3CA (R = −0.143, p = 0.002), and TP53 (R = −0.101, p = 0.026). In contrast to AD, high SFTPB expression was significantly associated with poorer OS (p = 0.026), whereas no significant difference in RFS was observed (p = 0.307). Multivariate analysis demonstrated that high SFTPB expression was an independent adverse prognostic factor in SCC (HR = 1.347, 95% CI = 1.028–1.767, p = 0.031). Conclusions: SFTPB expression is significantly associated with clinicopathologic characteristics and molecular signatures in both AD and SCC. However, its prognostic implications differ according to histologic subtype. High SFTPB expression independently predicts favorable survival in AD but unfavorable survival in SCC, suggesting distinct lineage-specific biological roles in NSCLC. These findings support SFTPB as a subtype-specific prognostic biomarker reflecting differential differentiation states and lineage context in NSCLC.

Medicina doi: 10.3390/medicina62061139

Authors: Kalliopi Keramida Georgios Mavraganis Constantina Masoura Konstantinos Aznaouridis Vasiliki Androutsopoulou Konstantinos Tsioufis

The coexistence of cancer and severe aortic stenosis (AS) is increasing as a result of population aging and substantial improvements in cancer survival. Transcatheter aortic valve implantation (TAVI) has transformed the management of AS; however, patients with active malignancy or a history of cancer remain markedly under-represented in pivotal randomized trials. This under-representation has resulted in persistent uncertainty regarding patient selection, risk stratification, and the expected benefit of TAVI in this growing and clinically heterogeneous population. This review provides a comprehensive and contemporary synthesis of the evidence on TAVI in patients with cancer, integrating cardiovascular (CV), oncologic, and geriatric perspectives. Available data on epidemiological overlap, cancer-specific procedural challenges, and short- and long-term outcomes following TAVI are critically examined, with particular emphasis on distinctions between active cancer and cancer survivorship. Key modifiers of risk and benefit—including prior thoracic radiotherapy, competing thrombotic and bleeding risk, immunosuppression, frailty, sarcopenia, and nutritional status—are discussed in detail. Limitations of conventional surgical risk scores in oncology populations are highlighted, underscoring the need for individualized assessment beyond traditional CV metrics. Across registries and meta-analyses, TAVI is associated with high procedural success and comparable short-term outcomes in patients with and without cancer. Excess mortality observed during mid- and long-term follow-up is driven predominantly by non-CV causes related to malignancy rather than valve-related complications. Importantly, patients with cancer in remission demonstrate outcomes similar to those of non-cancer populations, whereas prognosis in active cancer is strongly influenced by disease stage, biology, and competing risks. Overall, cancer diagnosis alone should not preclude consideration of TAVI. Optimal management requires multidisciplinary, goal-oriented decision-making that integrates oncologic prognosis, functional status, and patients’ priorities. As cancer survivorship continues to expand, prospective studies, integrated risk stratification tools, and closer alignment between cardio-oncology and structural heart programs are essential to guide evidence-based and equitable care.

Medicina doi: 10.3390/medicina62061137

Authors: Marco Marian Mihai Rosu Cristi Tarta Amadeus Dobrescu Dan Brebu Ionut Flaviu Faur Andrei Korodi Ioana Adelina Faur Stefania Bunceanu Dana Stoian

Background and Objectives: Post-thyroidectomy hypoparathyroidism (hypoPTH) is the most common complication of total thyroidectomy. Transient hypoPTH was defined as postoperative day 1 (POD1) intact parathyroid hormone (PTH) < 15 pg/mL and/or symptomatic hypocalcemia (<8.0 mg/dL), requiring supplementation, resolving within six months. We evaluated POD1 calcium, PTH, and their combination; identified preoperative predictors; and compared absolute with percent-change metrics. Materials and Methods: Participants comprised a retrospective single-center cohort of 380 consecutive adults undergoing total thyroidectomy between January 2023 and December 2025. Multivariable logistic regression identified preoperative predictors, and receiver operating characteristic (ROC) analysis evaluated POD1 biomarkers. Because both biomarkers are part of the outcome definition, a pre-specified sensitivity analysis re-evaluated POD1 PTH and ΔPTH against PTH-independent outcomes (POD1-calcium-defined hypocalcemia and permanent hypoPTH). Subgroups examined malignancy and central neck dissection (CND). Results: The cohort comprised 193 males (50.8%) and 187 females (49.2%), with a median age of 53 years (IQR 38–69). Indications were multinodular goiter (45.0%), differentiated thyroid cancer (37.9%), Graves’ disease (15.0%) and recurrent disease (2.1%). CND was performed in 9.5% of patients. Transient and permanent hypoPTH occurred in 132 (34.7%) and 11 (2.9%) patients. Thyroid gland weight was the sole independent preoperative predictor (OR 0.982, 95% CI 0.969–0.995, p = 0.008), with smaller glands conferring higher risk. Against the composite outcome, POD1 calcium and PTH yielded AUCs of 0.997 and 0.991 (combined 1.000), reflecting partial circularity. In the decoupled-outcome sensitivity analysis, POD1 PTH retained good-to-excellent discrimination for severe hypocalcemia (AUC 0.943) and permanent hypoPTH (AUC 0.976). Malignant cases showed a greater relative PTH decline than benign cases (−53.7% vs. −38.5%, p = 0.013) despite comparable absolute POD1 values, and CND did not increase risk. Conclusions: Combined POD1 calcium and PTH provided strong biochemical confirmation of transient hypoPTH, but the composite-outcome AUCs reflect internal definitional consistency rather than independent predictive performance; the decoupled-outcome AUCs (0.93–0.98) are the conservative benchmark. Thyroid gland weight was an inverse risk modifier with limited stand-alone utility. Multicenter prospective validation is required.

Medicina doi: 10.3390/medicina62061136

Authors: Teodor Cristian Blidaru Dan Mitrea Nicolae Dragoș Garofil Ileana Ruxandra Spătaru Raluca Maria Marin Marius Cristian Zaharia Sebastian Romeo Pintilie Stefan Strilciuc Ioana Raluca Papacocea

Background and Objectives: Magnetic resonance imaging (MRI) is essential for monitoring patients with diffuse gliomas after surgery and adjuvant therapy. However, the prognostic significance of imaging findings observed on the first post-treatment MRI remains incompletely defined in routine clinical practice. This study aimed to evaluate whether MRI features identified on the first post-treatment examination are associated with recurrence-free survival after near-total resection (NTR), defined for this real-world cohort as ≥80% volumetric tumor removal (which differs from the RANO Resect Group definition of GTR). Materials and Methods: Consecutive adult patients with histologically confirmed diffuse gliomas diagnosed between 2021 and 2024 were screened for eligibility (n = 283) and classified according to the 2021 WHO Classification of Tumors of the Central Nervous System. The first post-treatment MRI was defined as the earliest follow-up examination performed after completion of all initially planned therapy (surgery alone in patients without indication for adjuvant therapy; post-radiotherapy ± chemotherapy in the remaining patients), and not the immediate postoperative scan. Patients with available first post-treatment MRI were included (n = 149), resulting in a final cohort of 139 cases after exclusion of outliers. The evaluated MRI corresponded to the first follow-up examination after treatment (mean interval ~120 days after surgery). Logistic regression models were used to assess associations between post-treatment MRI features and recurrence-free survival at one and two years after NTR, with exploratory analyses for reoperation and reirradiation. Results: Residual tumor identified on the first post-treatment MRI was associated with lower odds of recurrence-free survival (RFS) at one and two years after NTR. Postoperative functional status also demonstrated an independent association with tumor control. Other imaging variables showed associations in univariable analyses but did not remain independent predictors after adjustment. Exploratory analyses of reoperation and reirradiation suggested additional clinical influences, including patient age. Conclusions: In this real-world cohort with heterogeneous tumor subtypes and treatment regimens, residual tumor on first follow-up MRI was the most consistent imaging correlate of reduced RFS, alongside postoperative functional status. These hypothesis-generating findings should be validated in stratified, prospective cohorts.

Medicina doi: 10.3390/medicina62061135

Authors: Emine Kilic Bagir Umran Kucukgoz Gulec Ilker Unal Evin Kussever Asli Sena Alagoz Mehmet Ali Vardar Derya Gumurdulu

Background and Objectives: Uterine carcinosarcoma (UCS) is a rare and highly aggressive gynecologic malignancy with poor clinical outcomes and limited therapeutic options. This study investigated the prognostic significance of molecular subgroups defined by p53 expression and mismatch repair (MMR) status in UCS. Materials and Methods: This retrospective study included 51 patients with uterine carcinosarcoma who underwent surgical treatment between 2010 and 2023. Immunohistochemical analyses were performed to evaluate p53 expression (wild-type vs. aberrant) and MMR status (intact vs. deficient). Patients were classified into four molecular subgroups: p53wt/MMR-intact (n = 15), p53abn/MMR-intact (n = 24), p53wt/MMR-deficient (n = 9), and p53abn/MMR-deficient (n = 3). Clinicopathological characteristics, overall survival (OS), and disease-free survival (DFS) were analyzed. Additional component-specific analyses were performed for carcinomatous and sarcomatous tumor elements. Results: The median follow-up period was 34 months, and the overall mortality rate was 51.0%. Patients with p53wt/MMR-deficient tumors demonstrated the most favorable outcomes, with a mean OS of 92.9 ± 22.1 months and a mortality rate of 33.3%. In contrast, the p53abn/MMR-intact subgroup showed the poorest survival outcomes (mean OS: 54.4 ± 11.6 months; mortality rate: 62.5%). Although Kaplan–Meier survival analysis did not demonstrate statistically significant differences between molecular subgroups (p = 0.783), distinct prognostic trends were observed. Multivariate Cox regression analysis identified age and lymph node involvement as independent predictors of both OS and DFS. Component-specific analyses demonstrated significant associations between aberrant p53 expression in the carcinomatous component and epithelial subtype distribution (p = 0.025) as well as myometrial invasion patterns (p = 0.040). Conclusions: Combined p53/MMR-based immunohistochemical classification demonstrated distinct prognostic trends in uterine carcinosarcoma. These findings suggest that molecular stratification could support risk assessment and therapeutic decision-making in UCS. Larger prospective multicenter studies are warranted to validate these findings and clarify their potential clinical implications.

Medicina doi: 10.3390/medicina62061134

Authors: Francisco Epelde

Background and Objectives: Muscle symptoms are the most visible adverse event attributed to statins, but terminology is often imprecise. Most patients report myalgia or nonspecific aches, whereas objective myopathy, inflammatory or necrotizing myositis, rhabdomyolysis, and anti-HMGCR immune-mediated necrotizing myopathy are uncommon and clinically distinct entities. To provide a clinically oriented narrative synthesis of statin-associated muscle symptoms (SAMS) and severe statin-associated myotoxicity, and to propose a practical prevention, evaluation, and management algorithm. The classification of muscle events is used to standardize terminology and avoid diagnostic confusion, not to create a new formal taxonomy. Materials and Methods: A clinically oriented narrative review was performed using PubMed, Google Scholar, and major society documents published from January 2021 to April 2026. Eligible sources addressed SAMS, statin myopathy/myositis, rhabdomyolysis, anti-HMGCR immune-mediated necrotizing myopathy, nocebo/drucebo effects, pharmacogenetics, drug interactions, diagnosis, or management. The final evidence set comprised 55 verifiable sources, including blinded randomized or n-of-1/crossover evidence; meta-analyses; clinical statements and reviews; pharmacovigilance analyses; pharmacogenetic guidance; mechanism-focused reviews; anti-HMGCR series; and lipid-lowering guideline/treatment studies. Because the review was narrative, no pooled estimate or formal PRISMA screening log was generated. Results: Blinded evidence indicates only a small absolute excess of muscle pain with statins, concentrated mainly in the first year of therapy, and that most muscle symptoms reported during statin therapy are not pharmacologically caused by the statin. N-of-1 and crossover trials show that symptom intensity is often similar during statin and placebo periods, consistent with an important nocebo/drucebo contribution. Severe muscle toxicity can nevertheless occur, especially when systemic statin exposure is increased by a high dose, interacting drugs, frailty, renal or hepatic impairment, hypothyroidism, transporter or metabolic genotypes, or intense unaccustomed exercise. Statin choice matters chiefly through dose, pharmacokinetics, and interaction burden. Conclusions: SAMS are common as reported clinical problems, but confirmed statin-caused muscle injury is substantially less frequent than routine clinical attribution suggests. Permanent discontinuation should be reserved for carefully assessed cases. A structured approach—baseline risk assessment, selective CK measurement, exclusion of alternative causes, correction of modifiable risks, dechallenge/rechallenge, statin switching, dose reduction, and combination with non-statin therapy—preserves cardiovascular benefit while protecting the rare patient with genuine toxicity.

Medicina doi: 10.3390/medicina62061133

Authors: Damaris Anton Mihaela Băciuț Oana Almășan

Background and Objectives: This study aims to evaluate the recent literature on the oral–gut connection in the context of periodontal disease, emphasizing the significance of systemic risk associated with chronic inflammation. This review explores whether chronic inflammation resulting from periodontal disease can induce systemic conditions through alterations in the gut microbiome and whether periodontal treatment may contribute to overall health improvement. Materials and Methods: A systematic database search was performed using pre-established search strategies. Searches were conducted in three databases between 1 and 20 October 2025. A total of 578 articles were screened for eligibility based on inclusion and exclusion criteria. Two authors agreed on the selection process used. The methodological quality of the included studies was assessed using the Newcastle–Ottawa scale and the Risk of Bias 2 Tool. Results: Eleven studies were considered eligible for inclusion in the review. The gut microbiome is similar to the oral microbiome in patients with periodontitis. Gut microbial shifts may drive systemic inflammation and metabolic dysfunction. Tooth loss and gum disease are linked to alterations in the gut bacteria, potentially compromising the intestinal barrier permeability. In contrast, the presence of natural teeth may prevent oral–gut bacterial transmission. Changes in the gut microbiota are correlated with improvements in periodontal status after non-surgical periodontal therapy. Conclusions: The evidence presented in this review supports an association between periodontitis, oral–gut microbial alterations, and systemic inflammatory conditions. However, most available studies are observational, limiting causal inference. Targeted modulation of the gut microbiome may represent a promising area for future research, but its clinical applicability remains inconclusive.

Medicina doi: 10.3390/medicina62061132

Authors: Jelena Micić Mladen Andjić Jelena Dotlić Katarina Ivanović Aleksandar Trklja Jovana Plešinac Maja Maslovarić Bojana Mihajlović Lela Šurlan Isidora Protić Lidija Tulić Jovan Bila Jelena Stojnić

Background and Objectives: Numerous risk factors for both female and male fertility have been established including age, ovarian reserve, infertility cause, occupational and lifestyle factors. The objective of our study was to determine the influence of occupational and lifestyle factors on assisted reproduction (ART) outcomes at a Serbian referral tertiary center. Materials and Methods: The study included all consecutive infertile couples undergoing ART at the Clinic for Ob/Gyn University Clinical Center Belgrade, from January 2019 to January 2022. Inclusion criteria comprised primary and unexplained infertility, age ≤ 45 years, body mass index ≤ 30 kg/m2 and undergoing fresh autologous ART cycles. All patients filled in the socio-epidemiological questionnaire that analyzed their lifestyle and habits. Medical history data and data regarding the current ART cycle were taken from patient records. The primary outcome was clinical pregnancy. Results: Our study included 501 couples (women and men) with infertility undergoing ART. Clinical pregnancy was achieved in 22.2% of examined patients. Achieving clinical pregnancy in the ART cycle for women was associated with younger age and use of vitamins, minerals, and trace elements, whereas younger age and absence of chronic illnesses were the most important factors for male partners. When women and men were assessed together as couples, achieving clinical pregnancy correlated only with the use of vitamins, minerals and trace-elements by both partners. Conclusions: This study confirmed that some occupational and lifestyle factors were associated with clinical pregnancy after ART in patients with unexplained primary infertility and normal BMI.

Medicina doi: 10.3390/medicina62061131

Authors: Meng Wei Huiping Huang Yajun Shen Li Wei Yifei Li Hui Guo

Background and Objectives: To investigate prognostic risk factors and determine the incidence, clinical characteristics, and predictors of heart failure (HF) development in pediatric patients with end-stage kidney disease (ESKD) secondary to steroid-resistant nephrotic syndrome (SRNS). Materials and Methods: We conducted a retrospective cohort study of pediatric patients diagnosed with ESKD secondary to nephrotic syndrome (NS) between 2014 and 2020. Patients were stratified based on clinical outcomes and the occurrence of HF during follow-up. Comparative analyses of clinical characteristics, laboratory parameters, and cardiac assessments were performed across groups. Multivariate logistic regression was used to identify independent risk factors for HF development within the first year and for adverse prognosis at five years. Results: The cohort comprised 172 children with ESKD secondary to NS. Multivariate logistic regression identified HF as an independent risk factor for adverse long-term outcomes in pediatric patients with ESKD. During follow-up, HF developed in 27 patients (15.7%) within the first year after ESKD diagnosis, and in 45 patients (26.2%) by the end of five years. Early HF onset (within the first year) was associated with a significantly reduced five-year survival rate. Independent risk factors for HF development included elevated cardiac troponin I levels (OR = 6.786, 95% CI: 2.326–19.799), a history of cardiac arrhythmias (OR = 2.951, 95% CI: 1.260–6.912), and the presence of left heart enlargement (OR = 23.669, 95% CI: 2.876–194.827), and valvular regurgitation at the initial post-ESKD diagnosis evaluation. Conclusions: HF is associated with markedly reduced survival. Crucially, our findings demonstrate that pre-existing cardiovascular structural abnormalities—specifically left heart enlargement—and elevated cTnI are robust, early predictors of HF. These findings necessitate a paradigm shift in pediatric ESKD management, we advocate for the implementation of systematic baseline echocardiographic and biomarker screening at the immediate onset of ESKD. Identifying these subclinical, yet modifiable, structural changes provide a critical therapeutic window for targeted anti-remodeling interventions to significantly improve long-term prognosis.

Medicina doi: 10.3390/medicina62061130

Authors: Fabio Kadum Koraljka Benko Lara Batičić Ana Petretić

Background and Objectives: Atrial fibrillation (AF) and atrial flutter are associated with significant morbidity. While electrical cardioversion (ECV) is a standard treatment for sinus rhythm restoration, early arrhythmia recurrence is common. Epicardial adipose tissue (EAT) is a metabolically active depot linked to atrial remodeling, yet its role in predicting post-ECV outcomes remains unclear. This study aimed to evaluate the association between EAT thickness measured by echocardiography and early arrhythmia recurrence following elective ECV in patients with and without heart failure (HF). Materials and Methods: A single-center observational study was conducted including 76 patients (38 with previously diagnosed HF) who underwent successful elective ECV (eECV) for AF or atrial flutter. Preprocedural transesophageal echocardiography was performed to exclude thrombi, while EAT thickness was assessed via transthoracic echocardiography (TTE). The primary outcome was early arrhythmia recurrence (within 30 days), and a secondary outcome was arrythmia recurrence in the HF subgroup. Data were analyzed using univariable and multivariable logistic regression, receiver operating characteristic (ROC) analysis, and subgroup analysis in patients with HF. Results: Arrhythmia recurrence occurred in 19 patients (25.0%) within the follow-up period. Mean EAT thickness did not differ significantly between patients with and without recurrence (3.74 ± 1.41 mm vs. 3.58 ± 1.78 mm; p = 0.42). EAT thickness did not emerge as a significant predictor of recurrence in univariable or multivariable models, demonstrating poor discriminative ability (AUC = 0.56). Similar findings were observed in the HF subgroup (OR = 0.94, p = 0.75; AUC = 0.49). Conversely, left atrial (LA) size was significantly associated with recurrence (OR = 2.76, p = 0.043). While EAT thickness correlated with body mass index and HF, it did not predict immediate rhythm outcomes. Conclusions: In our study, measurement of EAT thickness via TTE was not associated with early arrhythmia recurrence after eECV, including in patients with concomitant HF. These findings suggest that early post-cardioversion stability may depend more on established structural atrial remodeling, especially by LA enlargement, than on linear EAT thickness. Further research utilizing advanced volumetric imaging is warranted to clarify the role of epicardial adiposity in atrial arrhythmogenesis.

Medicina doi: 10.3390/medicina62061129

Authors: George Cătălin Alexandru Loredana-Neli Gligor Doina Chioran Marius Octavian Pricop Raluca Mioara Cosoroabă Mircea Riviș Horațiu Cristian Mânea Andrei Urîtu Alexandra Roi Ciprian I. Roi Tudor Rareș Olariu

Background and Objectives: The SARS-CoV-2 pandemic disrupted oral and maxillofacial surgery (OMS) services worldwide because of the high aerosol-generating nature of head-and-neck procedures, restricted access to elective dental care, and systemic reallocation of hospital resources. Continuous longitudinal multi-year data covering both the pandemic and the post-pandemic phases from regional Romanian (and more broadly central and southeastern European) emergency centers remain scarce. We aimed to quantify the impact of the pandemic on OMS activity in a large Romanian regional referral center and to evaluate post-pandemic resilience. Materials and Methods: We conducted a retrospective single-center study of all inpatient admissions to the OMS Clinic of a tertiary emergency hospital in western Romania between 1 January 2018 and 31 December 2024. Three periods were pre-specified: pre-pandemic (2018–2019), pandemic (2020–2022) and post-pandemic (2023–2024). A Newey–West segmented interrupted-time-series (ITS) regression and a negative-binomial monthly count model with Fourier seasonality were fitted; length of hospital stay was further analyzed with a multivariable gamma-log generalized linear model adjusted for age, sex, county, primary ICD-10 chapter and total ICD-10 codes. Variables analyzed included case volume, demographics, primary and secondary ICD-10 diagnoses, length of hospital stay (LOS), case complexity (total ICD-10 codes per admission) and in-hospital mortality. Results: A total of 11,628 inpatient admissions corresponding to 8084 unique patients (56.5% male; mean age 52.2 ± 19.2 years) were analyzed. Compared with the pre-pandemic baseline (mean 2037 admissions/year), annual volume dropped by 45.1% in 2020, 44.0% in 2021 and 32.3% in 2022, with a nadir of −76% during the first state of emergency (April 2020; n = 34 admissions). Recovery was rapid; 2024 exceeded the pre-pandemic baseline by +10.1% on raw counts and by +16.2% on admissions per 100,000 catchment population using year-specific INS denominators. The segmented ITS regression confirmed an immediate level drop of −114.2 admissions/month in March 2020 (95% CI −133.1 to −95.3; p < 0.001) and a positive post-intervention slope of +2.06 admissions/month (95% CI 1.23–2.88; p < 0.001), with observed monthly volume returning to the counterfactual projection by October 2023. The case mix shifted significantly (χ2 = 406.9, p < 0.0001); elective benign neoplasm admissions were reduced from 7.2% to 2.0%, while neoplasms of uncertain behavior nearly doubled from 15.7% to 27.5%. Case complexity increased during the pandemic (mean ICD codes 4.08 ± 2.42 vs. 3.44 ± 2.30; p < 0.001); after exclusion of administrative codes (whole Z chapter and U07.x), the difference attenuated to 3.34 vs. 3.17 codes (still p < 0.001 by Kruskal–Wallis), indicating that the largest portion of the unadjusted increase was driven by the new mandatory pre-admission SARS-CoV-2 screening code Z11.5 rather than true clinical complexity. Notably, the clinically interpretable proxy R63.3 (feeding difficulty) independently rose from 41.5% to 53.1%. The crude median LOS did not differ between the pre-pandemic and pandemic periods (3.07 vs. 3.06 d; p = 0.19) and dropped significantly post-pandemic (2.22 d; p < 0.001); however, after multivariable adjustment for case mix, age, sex, county and code count, the LOS was 15.7% shorter during the pandemic (adjusted ratio 0.84, 95% CI 0.82–0.87; p < 0.001) and 22.8% shorter post-pandemic (adjusted ratio 0.77, 95% CI 0.75–0.80; p < 0.001) relative to baseline. Conclusions: The pandemic caused a severe but transient contraction of OMS activity accompanied by increased case complexity and a marked shift away from elective surgery. Inpatient volume returned to and exceeded the pre-pandemic baseline by 2024. These results support the value of standing pandemic-preparedness protocols, sustained access to preventive dental care, and integrated tele-triage pathways for future public-health crises.

Medicina doi: 10.3390/medicina62061128

Authors: Panagiotis Theofilis Emmanouil Mantzouranis Christina Chrysohoou Konstantinos Tsioufis

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide [...]

Medicina doi: 10.3390/medicina62061127

Authors: Costanza Falcidia Francesco D’Oria Giulio Foggi Paola Facheris Matteo Bianco Luciano Ibba Alessandra Narcisi Antonio Costanzo Luigi Gargiulo

Background and Objectives: Janus kinase (JAK) inhibitors have expanded the therapeutic options for moderate-to-severe atopic dermatitis (AD). The possibility of dose modulation with abrocitinib (100 and 200 mg) and upadacitinib (15 and 30 mg), both selective JAK1 inhibitors, represents a potential clinical advantage, allowing dose escalation in cases of insufficient response and dose de-escalation in the setting of poor tolerability or during maintenance treatment. However, real-world data remain limited, and the rationale for dose adjustment is not always standardized. This study aimed to describe, using a real-world database, the frequency, timing, and reasons for dose modifications of these agents. Materials and Methods: We retrospectively analyzed the clinical data of 212 patients with moderate-to-severe AD treated with abrocitinib (n = 47) or upadacitinib (n = 165). Dose adjustments, including dose escalation and dose de-escalation, were recorded together with their timing and clinical reasons. Results: In the abrocitinib group, 34/47 patients (72.3%) initiated treatment at 100 mg, whereas 13/47 patients (27.7%) started at 200 mg. Six patients (12.8%) underwent a dose adjustment. One patient (2.1%) switched from 200 to 100 mg because of complete AD remission and concomitant menstrual cycle alterations, whereas five patients (10.6%) underwent dose escalation from 100 to 200 mg because of incomplete disease control. Among the six abrocitinib-treated patients who underwent dose adjustment, achievement of IGA 0/1 after dose modification was documented in all cases. In the upadacitinib group, 93/165 patients (56.4%) started at 15 mg, whereas 72/165 patients (43.6%) started at 30 mg. Overall, 44/165 patients (26.7%) underwent at least one dose adjustment, accounting for a total of 50 dose modifications: 27 escalations from 15 to 30 mg and 23 de-escalations from 30 to 15 mg. Among patients initiating treatment at 15 mg, 23/93 patients (24.7%) increased the dose to 30 mg after a median of 33.1 weeks because of suboptimal disease control. Among those starting at 30 mg, 21/72 patients (29.2%) reduced the dose to 15 mg after a median of 44.3 weeks. Of these, 12/21 patients (57.1%) reduced the dose because of adverse events, including herpetic infections and acne, whereas the remaining patients de-escalated because of optimal disease control. Some patients underwent multiple dose modifications: four followed a 30→15→30 mg sequence, with re-escalation after 13.2 weeks because of suboptimal disease control, and two followed a 15→30→15 mg sequence, with dose reduction after approximately 26.7 weeks because of herpes zoster. Overall, 29/44 patients achieved IGA 0/1 within 16 weeks and 38/44 within 32 weeks after dose modification. Conclusions: In this real-world cohort, dose adjustments of selective JAK1 inhibitors were frequently performed in patients with moderate-to-severe AD, particularly among those treated with upadacitinib. Dose escalation was mainly used to address suboptimal disease control, whereas dose de-escalation was performed in the setting of adverse events or optimal disease control. The availability of two dosing regimens may allow treatment intensity to be adapted to individual disease severity, response, and tolerability, supporting a personalized approach to AD management.

Medicina doi: 10.3390/medicina62061126

Authors: Caglar Ozmen

Atrial fibrillation (AF) remains one of the most clinically demanding arrhythmias in contemporary cardiology—not because its mechanisms are unknown, but because what we know does not yet translate into precise, individualized management. Existing risk scores predict adverse outcomes reasonably well at the population level but perform inadequately for individual patients, and the molecular substrate driving disease progression remains largely invisible at the bedside. MicroRNAs (miRNAs), small non-coding RNA molecules of 20–25 nucleotides found stably in peripheral blood, have attracted considerable attention as potential biomarkers capable of bridging this gap. Their involvement in atrial fibrosis, electrical remodeling, and inflammatory signaling is mechanistically well-grounded. Whether this mechanistic plausibility can be translated into clinical utility is the central question this review addresses. We summarize the biological rationale for circulating miRNAs as AF biomarkers, review the most consistently replicated miRNA expression findings across clinical studies and meta-analyses, and appraise what the evidence supports—and what it does not—regarding diagnostic accuracy, prognostic value, and clinical decision-making applications. We also outline what the field needs to accomplish to move from promising findings to routine clinical use.

Medicina doi: 10.3390/medicina62061125

Authors: Kadır Cetınkaya Oktay Algın

The cribriform plate (CP) functions as a dynamic neuroimmune interface through which olfactory nerve bundles exit the brain within a specialized perineural microenvironment (cpPME). While traditionally viewed as a passive structural barrier, emerging evidence positions the CP as a central hub for cerebrospinal fluid (CSF) drainage, glymphatic–lymphatic clearance, and antigen presentation. This review provides a comprehensive understanding of recent advances in cpPME research, highlighting the adaptive remodeling of the immune landscape in response to neuroinflammation and aging. We critically evaluate the translational gap between rodent models and human physiology, discussing the implications for neurodegenerative diagnostics, neuroinflammatory conditions, infectious diseases and “nose-to-brain” therapeutic delivery. By integrating anatomical, physiological, and immunological perspectives, we offer a comprehensive framework for understanding the CP’s role in CNS homeostasis and its potential as a transformative diagnostic and therapeutic target.

Medicina doi: 10.3390/medicina62061124

Authors: Fahri Akgül Süleyman Can İvo Gökmen Gizem Bakır Kahveci İsmail Bayrakçı Dicle Yurdatap Koç Ece Demirdelen Veli Çakıcı Bülent Erdoğan

Background and Objectives: Systemic inflammation, nutritional impairment, and immune dysregulation are important determinants of outcomes in advanced malignancies. The C-reactive protein–albumin–lymphocyte (CALLY) index is a composite biomarker that reflects these biological domains, but its prognostic relevance in de novo metastatic gastric adenocarcinoma has not been well defined. Materials and Methods: This multicenter retrospective cohort study included 234 patients with de novo metastatic gastric adenocarcinoma treated between January 2015 and December 2025. Baseline CALLY was calculated before systemic treatment. A cohort-specific CALLY threshold of 1.21 was obtained using conventional ROC analysis, with all-cause mortality status at last follow-up as the binary outcome. Survival was evaluated using Kaplan–Meier analysis and Cox proportional hazards regression. To avoid guarantee-time bias, treatment exposure variables that became known only after treatment initiation, including the number of chemotherapy cycles delivered, were excluded from the baseline Cox models. Diagnosis period was included in the multivariable model to account for treatment-era heterogeneity. Results: Overall, 133 patients (56.8%) were classified as low-CALLY and 101 (43.2%) as high-CALLY. Median OS was significantly longer in the high-CALLY group than in the low-CALLY group (13.9 vs. 8.6 months; log-rank p < 0.001). Low CALLY was associated with inferior OS in univariable analysis (HR: 1.77, 95% CI: 1.31–2.38; p < 0.001) and remained associated with worse OS after adjustment for baseline clinicopathological factors, first-line treatment category, and diagnosis period (adjusted HR: 1.77, 95% CI: 1.24–2.53; p = 0.002). The PFS difference between the CALLY groups was not statistically significant (HR: 1.15, 95% CI: 0.87–1.51; p = 0.326). Conclusions: Low baseline CALLY was independently associated with shorter OS in this retrospective cohort. These findings support CALLY as a practical candidate prognostic biomarker, while external validation and time-to-event-based cut-off assessment are needed before clinical implementation.

Medicina doi: 10.3390/medicina62061123

Authors: Tayfun Aman Batuhan Gencer Necdet Sağlam İsmail Türkmen

Background and Objectives: This study was conducted to investigate the effects of fragment size on clinical and radiological outcomes and the development of complications during the surgical treatment of pediatric lateral condyle fractures. Materials and Methods: This retrospective cohort study evaluated data from 47 pediatric patients with lateral condyle fractures, including demographic information, fracture type, range of motion, complications, radiographic assessments, capitellum size, and presence of a lateral bump. Clinical evaluations were performed using the Hardacre functional classification. To objectively investigate the effect of fragment size on prognosis, the total anterior–posterior (AP) and lateral fragment areas, as well as the corresponding AP and lateral capitellum areas (to provide an individualized constant for ratio calculation), were measured. The fractured fragment/capitellum area ratio was then calculated by dividing the fragment area by the respective capitellum area. All statistical analyses were conducted using a two-tailed significance threshold of p < 0.05, and corresponding 95% confidence intervals were calculated where applicable. Results: After a mean follow-up of 66 months (range: 12–142 months), no significant association was identified between the fractured fragment/capitellum area ratio and either the range of motion (p > 0.05) or the presence of a palpable lateral bump (p > 0.05). In contrast, a higher fractured fragment/capitellum area ratio was found to be significantly associated with the presence of radiographic complications (p = 0.01) and a larger final capitellar area (p = 0.02). Conclusions: The fractured fragment/capitellum area ratio, a newly defined parameter for quantifying initial fracture size in pediatric lateral condylar fractures, demonstrated no measurable effects on clinical outcomes, the presence of a lateral bump, or range of motion; however, it was significantly associated with the development of radiological complications and may represent an important predictor of subsequent capitellar hypertrophy. Level of Evidence: This study corresponds to Level III—retrospective cohort study.

Medicina doi: 10.3390/medicina62061122

Authors: Betül Çıkı Damla Kayalı Hafize Uzun Necdet Altıner Abdulhalim Şenyiğit Betül Yılmaz

Background and Objectives: Diabetes mellitus (DM) is frequently associated with impaired wound healing due to persistent oxidative stress, chronic inflammation, and dysregulated proteasome activity, leading to delayed tissue repair and increased risk of chronic ulcers. The present study aimed to investigate the role of the immunoproteasome system in diabetic wound healing, with a particular focus on its involvement in oxidative stress and inflammatory pathways, and to evaluate whether pharmacological inhibition with ONX-0914 improves tissue repair. Materials and Methods: Experimental diabetes was induced in rats using streptozotocin (STZ), and the animals were allocated to three groups: healthy control, STZ-induced diabetic, and STZ + ONX-0914 treatment. Wound healing was evaluated by macroscopic analysis of wound closure and histopathological examination at days 3, 7, and 14. Oxidative stress and antioxidant status were assessed by measuring malondialdehyde (MDA) levels and antioxidant enzyme activities (SOD, CAT, and GSH-Px) in serum and wound tissues. Proteasome activity was analyzed fluorometrically, while systemic and local inflammatory responses were determined by ELISA and Western blot analysis of IL-1β, TNF-α, and IL-6. Results: STZ-induced diabetes significantly delayed wound closure, increased lipid peroxidation, reduced antioxidant enzyme activities, and elevated systemic and tissue inflammatory cytokine levels. Treatment with ONX-0914 markedly accelerated wound closure and improved histological healing parameters, including re-epithelialization, granulation tissue formation, and angiogenesis. Moreover, ONX-0914 significantly reduced MDA levels while restoring SOD, CAT, and GSH-Px activities in both serum and wound tissues. The treatment also inhibited proteasome activity and significantly suppressed the expression of IL-1β, TNF-α, and IL-6. Conclusions: ONX-0914 significantly improves diabetic wound healing by restoring antioxidant defenses, reducing oxidative damage, and attenuating inflammatory signaling pathways. These findings suggest that immunoproteasome inhibition represents a promising therapeutic strategy for enhancing tissue repair in diabetic conditions.

Medicina doi: 10.3390/medicina62061121

Authors: Ceren Degirmenci Maide Gozde Inam Ozge Oral Tapan Aytekin Idikut Silam Yesilyurt Fatih Tekin Serife Nur Ozturk Muge Gencer Tuluy Ugur Fidan Seyma Tunc Nazli Cetin Neslihan Kose Kabil Zeynep Yilmaz Kaya

Background and Objectives: Nutritional impairment and systemic inflammation contribute to disease progression and poor outcomes in Chronic Obstructive Pulmonary Disease (COPD). The geriatric-nutritional-risk-index (GNRI) and prognostic-nutritional-index (PNI) are practical markers reflecting both nutritional and immune status. In elderly COPD patients, malnutrition-related exacerbations often worsen quality of life and increase hospitalization. Identifying reliable predictors of exacerbation risk is therefore important for improving disease management. This study evaluated the association between GNRI, PNI and exacerbation frequency across different age groups in COPD. Materials and Methods: This multicenter retrospective study included 302 patients with COPD from 10 medical centers. All patients were classified as GOLD Group-E according to exacerbation history. Demographic characteristics, pulmonary function tests, Charlson-Comorbidity-Index (CCI), pharmacological treatments, dyspnea scores, and annual exacerbation frequency were obtained from hospital databases. Laboratory parameters including complete blood count, C-reactive protein, albumin, and total protein were recorded. GNRI, PNI, and neutrophil-to-lymphocyte ratio (NLR) were calculated to evaluate nutritional and inflammatory status. Results: The mean age of participants was 67.9 ± 9.6 years and 26.5% were female. Elderly patients had significantly higher CCI scores, longer disease duration, greater cumulative smoking exposure, and more frequent exacerbations than younger patients (p < 0.001). Pulmonary function parameters were significantly lower in the elderly group, while long-term oxygen therapy and nebulizer use were more common (p < 0.001). Baseline and exacerbation NLR levels were higher in elderly patients, whereas GNRI and PNI values were lower during both stable disease and exacerbation periods. Patients with more than four exacerbations per year had significantly higher NLR and lower GNRI values. Conclusions: Elderly COPD patients in GOLD Group-E demonstrate marked inflammatory and nutritional burden. Lower PNI values were independently associated with increased annual exacerbation frequency, while lower GNRI values were observed in patients with greater inflammatory and nutritional burden. Routine immune-nutritional assessment may improve risk stratification and help identify patients who could benefit from early multidisciplinary management.

Medicina doi: 10.3390/medicina62061120

Authors: Lifang Dang Shun Lei Oo Nahathai Wongpakaran Awirut Oon-arom Rewadee Jenraumjit Justin DeMaranville Tinakon Wongpakaran

Background and Objectives: This study aimed to estimate the prevalence of documented borderline personality disorder (BPD) diagnosis and study-defined BPD indicators among adults with depressive disorders in outpatient psychiatric care, and to quantify a subgroup who were indicator-positive but had no documented diagnosis (potential under-recognition). Materials and Methods: This retrospective, cross-sectional study included adult outpatients with depressive disorders receiving pharmacological treatment at Maharaj Nakorn Chiang Mai Hospital. BPD status was classified using (1) a documented BPD diagnosis in the electronic medical record (EMR) and (2) study-defined indicators, comprising a symptom-based indicator (documentation of ≥5 DSM-5 BPD criteria) and a prescribing-based indicator (antidepressant treatment with concurrent use of antipsychotics and/or mood stabilizers). Prevalence and overlap across diagnoses and indicators were summarized using a Venn distribution. Results: Among 1175 patients, 63 (5.4%) had a documented BPD diagnosis. Using EMR indicators, 84 (7.1%) met the symptom-based indicator and 325 (27.7%) met the prescribing-based indicator. In total, 374 (31.8%) had either a documented BPD diagnosis or at least one indicator, while 801 (68.2%) had neither. Overall, 370 (31.5%) met at least one indicator (symptom-based and/or prescribing-based). Among indicator-positive patients, 311 (84.1%) had no documented BPD diagnosis, representing 26.5% (311/1175) of the total cohort. Conclusions: Study-defined EMR indicators flagged a substantial subgroup with potential under-recognition of BPD features in depressive-disorder clinics. These indicators may help prioritize targeted assessment and structured diagnostic evaluation to support access to BPD-informed care and support referral to BPD-informed psychotherapy.

Medicina doi: 10.3390/medicina62061119

Authors: Marco Giuseppe Musorrofiti Marco Bonifacio Valerio Cipolloni Enricomaria Mattia Rosa Bellomo Raoul Saggini

Physical energy-based therapies are non-invasive adjunctive interventions that deliver mechanical, electromagnetic, light, or radiofrequency/thermal energy to tissues with the aim of reducing symptoms and improving tolerance of active rehabilitation. Osteoarthritis (OA) is a heterogeneous whole-joint disorder in which cartilage degeneration, subchondral bone remodeling, synovitis, peri-articular tissue dysfunction, neuromuscular impairment, and pain sensitization may interact to produce pain, stiffness, and activity restriction. As conservative therapy for OA, education, progressive therapeutic exercise, weight management when indicated, and self-management remain the core of care. Nevertheless, some patients cannot fully participate in exercise because of pain, fear of movement, load intolerance, comorbidity, or limited access to supervised rehabilitation. This narrative review synthesizes evidence published mainly between 2016 and 2026 for extracorporeal shock wave therapy (ESWT), photobiomodulation/low-level laser therapy (PBMT/LLLT), pulsed electromagnetic field therapy (PEMF), transfer energy capacitive and resistive/capacitive–resistive electric transfer (TECAR/CRET) therapy, body weight support and aquatic unloading strategies, and mechanosonic vibration therapies. The available literature suggests that ESWT and PBMT/LLLT may provide short- to mid-term pain and function benefits in selected patients with knee OA when parameters are aligned with evidence-supported dosing windows. PEMF and vibration therapies show promising but less consistent effects because protocols, devices, sham conditions, and populations vary. TECAR/CRET and unloading approaches are best interpreted as enabling tools that may reduce guarding, improve walking tolerance, or increase the quality of therapeutic exercise, rather than stand-alone disease-modifying treatments. Current national and society guidelines consistently prioritize exercise, education, and weight management; most of the modalities reviewed here are absent from guidelines or are supported only indirectly, which justifies cautious wording and individualized use. A practical application model is, therefore, time-limited and goal-oriented: identify the barrier to rehabilitation, select a modality with a plausible mechanism and published protocol, monitor pain and functional response, and discontinue the modality if it does not improve participation in active care.

Medicina doi: 10.3390/medicina62061115

Authors: Kübra Erdoğan Rıdvan Erten Rana Tuna Doğrul Velihan Çayhan Serap Boz İmran Ceren Ertuğrul Demirel Hande Selvi Öztorun Güneş Eken Kamile Sılay

Background and Objectives: Sarcopenia is a major geriatric condition associated with functional decline and adverse outcomes. Cardiac fat depots exhibit metabolic activity and are linked to cardiometabolic risk; however, the extent to which epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT) quantified on standard thoracic computed tomography (CT) scans are associated with sarcopenia in older inpatients remains inadequately explored. This study investigated the associations of EAT and PCAT thickness with sarcopenia. Materials and Methods: This is a retrospective observational study using CT data obtained for clinical purposes and routine geriatric assessment data. In this single-center retrospective study, 101 inpatients aged ≥65 years who underwent unenhanced thoracic CT and bioelectrical impedance analysis within 3 months were included. EAT and PCAT thicknesses were measured using standardized methods. Sarcopenia status was based on a previously established clinical diagnosis according to EWGSOP2 criteria. Multivariable logistic regression, body mass index (BMI)-stratified analyses, and ROC curve evaluations were performed. Results: The participants had a mean age of 78.5 ± 7.6 years; 54.5% were female. Fifty-five patients (54.5%) met the diagnostic criteria for sarcopenia. PCAT was significantly thicker in sarcopenic participants relative to non-sarcopenic ones (12.25 ± 2.50 vs. 11.17 ± 2.32 mm, p = 0.028), while no corresponding difference was observed for EAT (p = 0.959). After controlling for age, sex, and BMI, each 1 mm increase in PCAT thickness was independently associated with an increased odds of sarcopenia (OR 1.399, 95% CI 1.133–1.727, p = 0.002). With the addition of the PCAT, the discriminatory power was modest (AUC 0.637 overall and 0.715 for BMI ≥25 kg/m2). In exploratory stratified analyses, the association was numerically larger in the BMI ≥25 kg/m2 subgroup (OR 1.48, p = 0.008); however, the formal BMI-by-PCAT interaction was not statistically significant (p = 0.290), so this subgroup finding is considered hypothesis-generating. Conclusions: PCAT thickness measured on routine non-contrast thoracic CT was associated with prevalent sarcopenia, whereas EAT thickness was not. ROC analyses showed modest discrimination; therefore, any proposed cut-offs should be considered exploratory and require prospective validation and external confirmation before clinical use.

Medicina doi: 10.3390/medicina62061116

Authors: Ioannis Pilateris Sevasti Bostanjopoulou

(1) Background and Objectives: Parkinson’s disease’s (PD) underlying pathophysiology still remains incompletely understood, with Braak’s hypothesis of ASyn pathology propagation being the most widely accepted. Recently, a novel model has been introduced, proposing two distinct ASyn propagation pathways: a bottom-up trajectory termed Body-first PD, and a central nervous system (CNS)-initiated pathway termed Brain-first PD. This distinction introduces new perspectives in the PD literature landscape regarding diagnosis, prognostic factors and patient management. This study set out to systematically synthesize the current literature comparing Brain-first and Body-first PD, with a focus on clinical characteristics and disease progression, diagnostic biomarkers, and management approaches. (2) Materials and Methods: A systematic literature search was conducted in March 2025 using PubMed, Cochrane Library, DOAJ and Google Scholar. Human observational, diagnostic, and interventional studies published between 2019 and March 2025, including patients with de novo or early PD, were eligible. Pre-motor REM sleep behavioral disorder (RBD) was used as the primary differentiation criterion. Risk of bias was evaluated using the Joanna Briggs Institute (JBI) critical appraisal checklists. Results were synthesized using a narrative approach. (3) Results: Sixteen studies comprising 2107 PD patients met the inclusion criteria. Body-first PD was associated with a higher non-motor symptom (NMS) burden, faster disease progression, and a higher prevalence of cognitive impairment. Additionally, Body-first PD patients exhibited more widespread and symmetrical neurodegeneration, along with electrophysiological and metabolic differences. Distinct biomarker and microbiome profiles were also observed between subtypes. No eligible studies addressing management approaches were identified. (4) Conclusions: In conclusion, the available evidence suggests that Brain-first and Body-first PD may represent two distinct pathophysiological entities, a proposal with great significance for the diagnosis, prognosis and management of PD patients. However, the predominantly cross-sectional nature of the current literature limits causal inference. Future longitudinal and interventional studies are required to clarify the potential clinical implications of this subtype classification theory.

Medicina doi: 10.3390/medicina62061118

Authors: Muzaffer Önder Öner Fırat Aslan Serhat Binici Burhan Beger Orhan Beger

Background and Objectives: Laparoscopic sleeve gastrectomy (LSG) is one of the most commonly performed metabolic bariatric surgery procedures worldwide. However, conventional LSG generally requires liver retraction for adequate visualization of the operative field. This study aimed to evaluate the feasibility, perioperative safety, and metabolic outcomes of a modified three-port LSG technique performed without the use of a liver retractor. Materials and Methods: This retrospective single-center cohort study included 2000 consecutive individuals with obesity who underwent three-port laparoscopic sleeve gastrectomy between January 2020 and December 2023. All procedures were performed without mechanical liver retraction by two experienced bariatric surgeons. Operative outcomes, postoperative complications, weight loss parameters, metabolic variables, and histopathological findings were evaluated during a 12-month follow-up period. All included patients completed the predefined follow-up schedule. Postoperative complications were classified according to the Clavien–Dindo classification system. Results: The mean operative time, defined as skin-to-skin duration, was 30 ± 15 min, and the median hospital stay was 2.3 days. No conversion to open surgery, additional trocar placement, or rescue liver retractor use was required. The overall complication rate was 9.4%, with most complications classified as Clavien–Dindo grade I–II. Reoperation was required in three patients (0.15%), and no mortality was observed. Significant metabolic improvements were detected following surgery. Mean HbA1c levels decreased from 7.23% preoperatively to 5.67% at 12 months (p < 0.001), while BMI decreased from 42.6 kg/m2 to 28.7 kg/m2 (p < 0.001). Excess weight loss and total weight loss at 12 months reached 82.4% and 34.2%, respectively. Diabetes remission was achieved in 65.4% of patients with baseline type 2 diabetes mellitus. Continuous glucose monitoring findings demonstrated reduced postoperative glycemic variability. Conclusions: Three-port laparoscopic sleeve gastrectomy performed without a liver retractor appears to be a feasible and effective surgical approach when performed by experienced bariatric surgeons. The technique was associated with acceptable perioperative safety and favorable metabolic outcomes. However, because of the retrospective single-center design and absence of a conventional comparison group, definitive conclusions regarding superiority or equivalence to standard techniques cannot be established. Prospective multicenter comparative studies are required to validate these findings.

Medicina doi: 10.3390/medicina62061117

Authors: Mehmet Mutlu Kidi Hatice Asoglu Metehan Soysal Tolga Koseci Ismail Oguz Kara Berksoy Sahin Semra Paydas Musa Barış Aykan Nuri Karadurmus Ibrahim Barista Serkan Akin Fatih Kus Meltem Olga Akay Hakan Kalyon Can Boga Hakan Ozdogu Ertugrul Bayram

Background and Objectives: Comprehensive real-world data on dose-adjusted EPOCH-R (DA-EPOCH-R) incorporating molecular prognostic stratification remain limited. We evaluated the long-term efficacy, safety, and prognostic determinants of DA-EPOCH-R in a multicenter Turkish cohort. Materials and Methods: This retrospective study included 140 patients with aggressive B-cell lymphoma (diffuse large B-cell lymphoma [DLBCL], n = 81; primary mediastinal B-cell lymphoma [PMBL], n = 39; other, n = 20) treated with DA-EPOCH-R at five academic centers (2015–2020). Molecular profiling included immunohistochemistry (MYC, BCL-2, BCL-6) and fluorescence in situ hybridization (FISH). Survival was estimated by Kaplan–Meier analysis with Cox regression for prognostic factors. Results: At a median follow-up of 50.1 months, 5-year overall survival (OS) and event-free survival (EFS) rates were 71.3% and 66.3%, respectively (complete response rate: 68.6%). Molecular subtypes included double-expressor (DEL; n = 39), triple-expressor (TEL; n = 21), double-hit (DHL; n = 17), and triple-hit lymphoma (THL; n = 11). Five-year OS by IPI risk group ranged from 88.6% (low) to 49.4% (high) (p = 0.005). DEL status did not confer inferior OS (p = 0.738), whereas DHL and THL had markedly poor outcomes (p < 0.001). In multivariate analysis, IPI ≥ 3 (HR 2.54; p = 0.007) and MYC FISH rearrangement (HR 3.62; p < 0.001) independently predicted inferior OS. Grade 3–4 neutropenia occurred in 57.1%, with no grade 3–4 cardiotoxicity. Conclusions: DA-EPOCH-R provides favorable long-term outcomes in aggressive B-cell lymphomas. DEL status did not confer a survival disadvantage, an association that is hypothesis-generating and requires confirmation, as the present design cannot establish a causal mechanism. FISH-defined DHL/THL remain associated with dismal outcomes, warranting novel therapeutic strategies.

Medicina doi: 10.3390/medicina62061114

Authors: Slavica Tomić Aleksandra Pastornački Maja Drljača Jelena Glogovac Vanja Bošković Snežana Brkić

Background and Objectives: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disorder characterized by persistent or relapsing fatigue lasting at least six months, not alleviated by rest and not previously present. It is accompanied by post-exertional symptom exacerbation and non-restorative sleep. Fatigue is often disabling and reduces daily activity by more than 50%. This study aimed to evaluate the long-term frequency of somatic and psychiatric disorders in women previously diagnosed with ME/CFS and to describe the long-term clinical course, laboratory findings, and fatigue-related changes during a 16-year follow-up period. Materials and Methods: Sixteen years ago, 40 women diagnosed with ME/CFS according to then-current CDC criteria were enrolled at the Clinic for Infectious Diseases and the Center for Laboratory Medicine, University Clinical Center of Vojvodina. All participants provided informed consent. After 16 years, 20 women agreed to follow-up evaluation. At both time points, participants underwent structured questionnaires, clinical examination, psychological assessment, and comprehensive laboratory testing, including hematological, biochemical, endocrinological, and virological analyses. Fatigue severity was assessed using the FibroFatigue Scale (FFS) and the Multidimensional Assessment of Fatigue (MAF) scale. Results: During follow-up, 15% of participants were diagnosed with rheumatoid arthritis, 10% with cervical or breast cancer, 5% experienced premature myocardial infarction, 5% developed bronchial asthma, and 20% were diagnosed with clinical depression. Progression of ME/CFS was observed in 15%, while 5% reported infertility. Additionally, 15% developed arterial hypertension. Only 15% of participants did not report symptom worsening or new diagnoses. Conclusions: Over the 16-year follow-up, 85% of women with ME/CFS developed significant somatic or psychiatric conditions. These findings suggest that women diagnosed with ME/CFS may experience substantial long-term somatic and psychiatric disease burden, supporting the need for continued clinical monitoring and individualized follow-up.

Medicina doi: 10.3390/medicina62061113

Authors: Hülya Arık Mehtap Tınazlı Kaya Süer

Background and Objectives: Urinary tract infections (UTIs) represent one of the most frequently encountered bacterial infections in clinical practice. Although vitamin D (vit D) is recognised for its immunomodulatory properties, its relationship with the spectrum of uropathogens remains unclear. This study investigated the distribution of UTI-causing pathogens in relation to serum vit D status and demographic variables including age, sex, season, and year of presentation at a tertiary hospital in the Eastern Mediterranean. Materials and Methods: A retrospective cross-sectional analysis was conducted on 942 adult patients with culture-confirmed UTIs at a university hospital in Cyprus between January 2019 and December 2024. Serum 25-hydroxyvitamin D [25(OH)D] levels were classified as deficient (≤20 ng/mL), insufficient (20–29.9 ng/mL), or sufficient (≥30 ng/mL) according to Turkish Endocrinology Society (TEMD) guidelines. Pathogen distribution was correlated with vit D category, sex, age group, season, and year using chi-square analysis and multivariable logistic regression. Timing of urine culture collection (at admission vs. more than 48 h after admission), catheter use, upper vs. lower urinary tract classification, and comorbidity data were recorded for each patient. Results: Escherichia coli was the most frequently isolated uropathogen (48.83%), followed by Klebsiella pneumoniae (18.79%) and Enterococcus faecalis (11.89%). No statistically significant association was found between vit D level and uropathogen type (p = 0.504). Infections were more prevalent in females (70.49%) and in patients aged over 70 years (56.26%). Vit D deficiency was present in 47.98% of the cohort. Catheter-derived specimens accounted for 35.1% of cultures. Upper tract infection was diagnosed in 233 patients (24.7%) and lower tract infection in 709 patients (75.3%). The most frequent comorbidities were hypertension (48.4%), diabetes mellitus (33.1%), and chronic kidney disease (21.0%); on multivariable analysis, diabetes mellitus (adjusted OR = 1.4) and chronic kidney disease (adjusted OR = 1.6) were independently associated with K. pneumoniae infection. In vit D-deficient patients, K. pneumoniae infection risk was significantly higher during winter in unadjusted analysis (OR = 1.8; 95% CI: 1.3–2.5) and remained elevated after multivariable adjustment (aOR = 1.6; 95% CI: 1.1–2.3). Vit D levels showed significant seasonal variation (p < 0.001), with lower values in winter (18.6 ng/mL) and higher values in summer (28.4 ng/mL). Conclusions: On multivariable analysis, no statistically significant association was found between vit D level and uropathogen species overall (χ2 = 13.291; p = 0.504); a seasonal interaction was observed between vit D deficiency and Klebsiella infections in winter. UTI risk was highest in elderly and female patients. These findings point to the need for considering seasonal and dietary factors in UTI management and call for prospective investigation.

Medicina doi: 10.3390/medicina62061112

Authors: Meruyert Rakhimova Neilya Aldasheva Ardak Auyezova Lukpan Orazbekov Zauresh Utelbayeva Shnara Svetlanova Indira Karibayeva

Background and Objectives: The use of presbyopia-correcting intraocular lenses (IOLs) has become an integral part of modern cataract surgery. Trifocal IOLs are designed to provide functional vision at multiple distances but may be associated with dysphotopsia and reduced contrast sensitivity. In contrast, extended depth-of-focus (EDOF) IOLs offer a smoother defocus profile and fewer photic phenomena; however, they often provide insufficient uncorrected near visual acuity. To overcome the limitations of each design, a mix-and-match implantation strategy, involving implantation of a trifocal IOL in one eye and an EDOF IOL in the fellow eye, has been proposed. The objective of this systematic review was to evaluate whether mix-and-match implantation can maintain high visual acuity at near, intermediate, and distance ranges in the early postoperative period. Materials and Methods: A systematic literature search was conducted in five electronic databases, including PubMed, Scopus, Web of Science, Google Scholar, and ScienceDirect, following PRISMA guidelines. Studies reporting outcomes of mix-and-match implantation with a trifocal IOL in one eye and an EDOF IOL in the fellow eye were included. Only studies presenting binocular uncorrected visual acuity (UCVA) at a distance, intermediate, and near ranges, expressed in logMAR units, were considered. Visual outcomes assessed at approximately 3 months postoperatively were extracted. Results: Five studies involving 225 patients were included. The pooled mean logMAR UDVA at 3 months was 0.05 (95% CI: 0.03–0.07), with substantial heterogeneity (I2 = 80.1%). The pooled mean logMAR UNVA was 0.09 (95% CI: 0.05–0.14), with high heterogeneity (I2 = 87.9%). For intermediate vision, the pooled mean logMAR UIVA was 0.03 (95% CI: −0.00 to 0.06), with moderate heterogeneity (I2 = 72.5%). Meta-regression analyses did not show statistically significant associations between publication year and visual outcomes for UDVA (p = 0.695), UNVA (p = 0.469), or UIVA (p = 0.099). Sensitivity analyses confirmed the robustness of the pooled estimates. Conclusions: Mix-and-match implantation of a trifocal IOL in one eye and an EDOF IOL in the fellow eye provides favorable early binocular visual acuity across distance, intermediate, and near ranges. However, substantial heterogeneity across studies and very low certainty of evidence warrant cautious interpretation of these findings.

Medicina doi: 10.3390/medicina62061111

Authors: Luminita Iliuta Marius Rac-Albu Madalina-Elena Rac-Albu Andreea Andronesi

In the original publication [...]

Medicina doi: 10.3390/medicina62061110

Authors: Ömer Osman Eroğlu Runa Özelçi Ramazan Erda Pay Cansın Eroğlu

Background and Objectives: The optimal oocyte yield in gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles remains debated, and data specific to antagonist protocols are limited. This study evaluated the discriminative and independent predictive performance of oocyte count for clinical pregnancy in GnRH antagonist IVF cycles. Materials and Methods: This retrospective cohort included 1171 women undergoing their first GnRH antagonist IVF cycle with fresh embryo transfer at a single tertiary center (September 2007–December 2021). The primary outcome was an institutional composite pregnancy outcome (sustained β-hCG positivity with subsequent ongoing intrauterine pregnancy or live birth; biochemical and ectopic pregnancies were negative). Patients were grouped by oocytes retrieved (1–5, 6–10, 11–15, ≥16). Performance was assessed with logistic regression, ROC with 2000-iteration bootstrap, integrated discrimination improvement (IDI), continuous net reclassification improvement (NRI), and restricted cubic spline. Predefined subgroup analyses by age, regimen, and antral follicle count tertile were performed. Results: A positive outcome occurred in 430 patients (36.7%). After adjustment, oocyte count was not an independent predictor (adjusted odds ratio 0.999, 95% CI 0.979–1.020; p = 0.96). The full model (AUC 0.564, 95% CI 0.529–0.598) did not outperform oocyte count alone (AUC 0.532; bootstrap p = 0.11). IDI (0.011) and NRI (0.135) were statistically detectable but clinically trivial. Spline regression showed no non-linearity (p = 0.47). Findings were consistent across subgroups, and the narrow confidence interval excluded per-oocyte effects ≥1.10. Conclusions: In GnRH antagonist IVF cycles, oocyte count showed weak discriminatory performance and was not independently associated with fresh-cycle pregnancy. Oocyte yield should be interpreted alongside—rather than as a substitute for—established parameters such as age and ovarian reserve. The principal clinical value of a higher oocyte response may lie in cumulative rather than fresh-cycle success. Live-birth outcomes were not available, and the source institution was permanently closed in 2025; these limitations define the boundary of inference.

Medicina doi: 10.3390/medicina62061109

Authors: Boris Žigmund Erika Zemková

Background and Objectives: Persistent quadriceps weakness, muscle atrophy, and functional deficits are common following anterior cruciate ligament (ACL) reconstruction and may compromise return to sport and increase the risk of reinjury. Eccentric-oriented strength training has been widely used to enhance muscle strength and hypertrophy in various musculoskeletal conditions; however, its specific application within ACL rehabilitation remains insufficiently explored. The aim of this scoping review was to map the existing evidence on the use of eccentric-oriented strength training in ACL rehabilitation, identify gaps in the current literature, and provide suggestions for future research. Materials and Methods: A scoping review search was conducted in PubMed, Scopus, Web of Science, and PEDro from inception to February 2026 using the following keywords and Boolean operators: (“anterior cruciate ligament”, “ACL”, “anterior cruciate ligament reconstruction”, “ACLR”) AND (“eccentric training”, “eccentric exercise”, “eccentric loading”, “flywheel training”, “isoinertial training”). Eligible studies included studies that investigated eccentric exercises as part of ACL rehabilitation and reported outcomes related to muscle strength, muscle morphology, functional performance, or return to sport. Data were extracted and synthesized descriptively in accordance with the PRISMA-ScR extension for Scoping Reviews guidelines. Methodological quality and risk of bias were evaluated using the PEDro scale (RCTs) and the ROBINS-I tool (non-randomized studies). Results: Fifteen studies met the inclusion criteria. The included literature primarily examined isokinetic eccentric exercise, eccentric cycling, early progressive eccentric resistance training, Nordic hamstring exercise, eccentric ergometry, and flywheel strength training. Most studies reported improvements in quadriceps strength and muscle morphology, with additional benefits observed in functional performance measures (i.e., hop tests), gait mechanics, and limb symmetry. Evidence was unevenly distributed across rehabilitation phases, with relatively few studies focusing on the mid-phase of ACL rehabilitation. Conclusions: Eccentric-oriented strength training represents a promising but underexplored component of ACL rehabilitation. However, the existing literature lacks standardized protocols, comprehensive outcome measures, and phase-specific guidance, particularly during the mid and late stages of rehabilitation. Further high-quality studies are needed to clarify the optimal timing, dosage, and integration of eccentric training across rehabilitation phases.

Medicina doi: 10.3390/medicina62061108

Authors: Aleksandra Arsić Bojana Kisić Vladan Perić Ivana Stevanović Ana Savić Radojević Zoran Bukumirić Ilija Dragojević Marija Vasić Martin Popević Dragiša Rašić Snežana Hadžistević

Background and Objectives: Oxidative stress is recognized as an important contributor to heart failure (HF) pathophysiology, but the relationships of individual oxidative and antioxidant biomarkers with symptomatic severity and systolic dysfunction remain insufficiently defined. This study examined circulating oxidative and nitrosative stress markers across New York Heart Association (NYHA) classes and left ventricular ejection fraction (LVEF) categories in HF and their associations with HF severity. Materials and Methods: In this case–control study, 85 patients with HF and 33 healthy controls were included. Malondialdehyde (MDA), nitrates and nitrites (NOx), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), sulfhydryl (SH) groups, and NT-proBNP were measured. Group differences were analyzed using the Kruskal–Wallis test with post hoc comparisons. Adjusted ordinal logistic regression models examined associations with NYHA class and LVEF category, and receiver operating characteristic (ROC) analysis evaluated discriminatory performance. Results: Compared with controls, all biomarkers differed significantly across NYHA classes and LVEF categories (all p < 0.001). In separate adjusted models, higher NOx, MDA, and NT-proBNP were associated with worse NYHA class and more impaired LVEF, whereas higher antioxidant marker levels were associated with lower odds of severe HF. In combined models, NOx remained independently associated with worse NYHA class (OR 1.07, 95% CI 1.04–1.11; p < 0.001), while MDA remained independently associated with more impaired LVEF (OR 1.02, 95% CI 1.00–1.03; p = 0.022). NT-proBNP showed the best discrimination for NYHA III/IV versus I/II (AUC 0.966), while among oxidative biomarkers NOx performed best for symptomatic severity (AUC 0.782) and MDA for LVEF ≤ 40% (AUC 0.751). Conclusions: HF is characterized by increased oxidative and nitrosative stress together with reduced antioxidant defense. NOx appears more closely related to symptomatic severity, whereas MDA appears more closely related to systolic dysfunction. However, NT-proBNP remained the strongest overall discriminator. NOx and MDA may provide complementary mechanistic information on redox imbalance across HF severity categories.

Medicina doi: 10.3390/medicina62061107

Authors: Lujain Fouad Khalaf Rozan Fouad Khalaf Shady Salah Bagady Romaysaa Fouad Khalaf Rodina Amro Amin Abdalla O. Manaa Mohamad Salah Bagady Ahmad Aljada

Background and Objectives: Classical cardiovascular risk factors account for only a fraction of acute coronary syndromes (ACSs), and chronic Chlamydia pneumoniae infection has been proposed as a contributor to atherogenesis through persistent inflammation and endothelial dysfunction. We tested whether C. pneumoniae infection is independently associated with ACS by quantifying seroprevalence, inflammatory markers, and their relationship with conventional cardiovascular risk factors. Materials and Methods: In a prospective case–control design, we enrolled 47 patients with ACSs (29 with acute myocardial infarction and 18 with unstable angina) and 53 age- and locality-matched controls at Alexandria University Hospital. The clinical evaluation comprised electrocardiography, echocardiography, lipid profile, and high-sensitivity C-reactive protein (CRP). C. pneumoniae-specific IgG and IgM were measured by ELISA, with positive samples confirmed by microimmunofluorescence. Logistic regression models were adjusted for age, sex, hypertension, diabetes, dyslipidemia, and smoking. Results: IgM was undetectable in all 100 participants, excluding acute infection. IgG seropositivity was higher in cases than in controls (83.0% vs. 60.4%; OR: 3.20; 95% CI: 1.23–8.30; p = 0.017) and remained suggestive after multivariable adjustment (adjusted OR: 4.59; 95% CI: 1.33–18.28; p = 0.021), although the estimate is imprecise and does not meet our prespecified multivariate threshold of p < 0.01. Within the ACS cohort, IgG seropositivity was not significantly associated with CRP elevation (Fisher’s exact p = 1.000). CRP elevation was near-universal in cases (93.6%) and absent in controls (0%; p < 0.001). Conclusions: Chronic C. pneumoniae infection was associated with ACS in unadjusted analysis, with a suggestive but underpowered signal after multivariable adjustment, although the observational design precludes causal inference, and reverse causality cannot be excluded. Prospective studies using direct pathogen detection are required to determine whether the association reflects a contributory mechanism or shared susceptibility.

Medicina doi: 10.3390/medicina62061106

Authors: Aliz Persely Marton Piroska Luca Zoldi Beatrix Beszedics Janos Juhasz Nora Makra Zsuzsanna A. Dunai Dora Szabo David Laszlo Tarnoki Adam Domonkos Tarnoki

Background and Objectives: Recent studies have revealed the potential roles of gut microbiota and microbial metabolites in influencing mild cognitive impairment (MCI) and Alzheimer’s disease via the gut–brain axis. This relationship has not yet been investigated in monozygotic twin pairs, which represent an ideal model for minimizing genetic confounding. Materials and Methods: Seven twin pairs discordant for ACE and 15 for MoCA were enrolled. Stool samples were subjected to 16S ribosomal RNA-based microbiome analysis. Results: No significant differences in alpha or beta diversity were observed between MCI-discordant twin pairs at the genus or family level. The most robust finding was a significantly lower abundance of Lachnospiraceae in MCI-affected twins, identified independently by ANCOM-BC and LEfSe. Additional exploratory findings included higher abundances of Sutterella, Succinivibrio, Odoribacter, and Ruminococcus. However, several taxa showed opposing patterns between ACE- and MoCA-derived cohorts, highlighting the methodological impact of cognitive instrument selection. Conclusions: The convergent reduction of Lachnospiraceae across two independent analytical methods represents the most substantive finding. The remaining results are exploratory, limited by small sample size, restricted statistical power, and lack of availability to fully control for dietary habits, physical activity, and medication use. Validation in larger longitudinal twin cohorts with a standardized cognitive assessment is warranted.

Medicina doi: 10.3390/medicina62061105

Authors: Vincenzo Pota Francesco Imperatore Rossella Esposito Chiara Cafora Ludovica Golino Giovanni Liguori Fiora Silvestro Maria Beatrice Passavanti Pasquale Sansone Maria Caterina Pace Francesco Coppolino

Background and Objectives: Central venous catheters (CVCs) are widely used in intensive care units (ICUs) but are associated with catheter-related bloodstream infections (CRBSIs), which increase morbidity, mortality, and healthcare costs. Antimicrobial-impregnated catheters, including chlorhexidine–silver sulfadiazine (CSS)-coated CVCs, have been proposed to reduce this risk. This study evaluated the effectiveness of CSS-coated CVCs in preventing CRBSIs in ICU patients. Materials and Methods: A retrospective multicenter study was conducted in two ICUs in Naples, Italy. Patients admitted between October and December 2020 who received standard uncoated CVCs (Group A) were compared with patients admitted between October and December 2021 who received CSS-coated CVCs (Group B). Inclusion criteria were age 18–89 years, ICU admission with CVC placement, and negative blood cultures at admission. The primary outcome was the incidence of CRBSI, defined according to microbiological criteria consistent with current guidelines. The secondary outcome was the number of catheter removals due to confirmed CRBSI. Results: A total of 320 patients were included (170 in Group A and 150 in Group B). Baseline demographic characteristics and ICU admission diagnoses were comparable between groups. Microbiologically confirmed CRBSI incidence was significantly lower in Group B than in Group A (6.4% vs. 31.7%, p < 0.0001), corresponding to infection rates of 1.48 vs. 6.95 per 1000 catheter-days, respectively (p < 0.0001). Patients in Group B also required fewer catheter removals due to CRBSI (mean 1.6 vs. 3.2 per patient, p < 0.0001). Logistic regression confirmed a significantly lower risk of CRBSI with CSS-coated CVCs (OR 0.15; 95% CI 0.06–0.32). Conclusions: CSS-coated CVCs were associated with a significant reduction in CRBSI incidence and catheter replacement rates in ICU patients. However, given the retrospective design, univariable analysis, and highly unequal pandemic-related systemic stressors between the two periods, these findings demonstrate a clinical association rather than direct causation, and should be interpreted with caution due to potential residual confounding.

Medicina doi: 10.3390/medicina62061104

Authors: Marcello Covino Nicola Bonadia Luigi Celani Davide Antonio Della Polla Valeria Maccauro Pierluigi Del Vecchio Benedetta Simeoni Antonio Gasbarrini Rita Murri Francesco Franceschi

Background and Objectives: Blood cultures are routinely obtained in emergency department (ED) patients with suspected infection; however, their real clinical impact on patient outcomes remains debated. Although current sepsis guidelines recommend obtaining blood cultures before antimicrobial therapy, the diagnostic yield is relatively low, and it remains unclear whether early microbiological results meaningfully influence prognosis. To evaluate the predictors and clinical impact of positive blood cultures in ED patients with suspected infection and to assess whether microbiological results that modify empiric antimicrobial therapy are associated with improved survival. Materials and Methods: We conducted a retrospective cohort study of adult patients presenting to a tertiary-care ED with suspected infection between 2018 and 2024 who underwent blood culture sampling within the first six hours of ED stay. Blood culture results were classified as negative, positive non-actionable, or positive actionable depending on whether they led to modification of empiric antimicrobial therapy. The primary outcome was in-hospital mortality. Survival analysis was performed using Kaplan–Meier curves and multivariable Cox regression with a 72 h landmark approach to reduce immortal time bias. Results: The study included 13,591 patients with suspected infection who underwent blood culture testing. Blood cultures were negative in 11,475 patients, positive non-actionable in 1082 patients, and positive actionable in 1034 patients. Overall in-hospital mortality was approximately 14%. Kaplan–Meier analysis showed significant differences in survival across blood culture groups (log-rank p < 0.001), with lower crude survival among patients with actionable positive cultures. However, after adjustment for demographic characteristics, comorbidity burden, illness severity, and laboratory markers in multivariable Cox regression models, the presence of an actionable blood culture result was not associated with improved prognosis compared with negative or non-actionable cultures. Conclusions: In ED patients with suspected infection, actionable positive blood cultures were associated with higher crude mortality; however, after multivariable adjustment, this association was attenuated and did not remain statistically significant. These findings suggest that actionable blood culture results identify patients with greater illness severity and clinical complexity, while their direct patient-level survival benefit remains difficult to demonstrate in observational data. Further prospective studies are needed to clarify whether early blood culture acquisition can truly modify the clinical trajectory of patients with suspected infection.

Medicina doi: 10.3390/medicina62061103

Authors: İsmet Çopur Rıza Hakan Erbay Seher İlhan Turan Evran

Background and Objectives: This prospective, randomized study aimed to evaluate the effects of different local anesthetic (LA) volume–dose combinations administered during supraclavicular brachial plexus block (SCBPB), a widely used technique in upper extremity surgery. These effects were assessed by analyzing changes in the ratios of optic nerve sheath diameter (ONSD) to eyeball transverse diameter (ETD), obtained by ultrasound (US) and considered indirect measures of intracranial pressure (ICP). Materials and Methods: Sixty four ASA I–II patients aged 18–50 years undergoing upper extremity surgery were randomized into four groups receiving 15 mL (Group A), 20 mL (Group B), 25 mL (Group C), or 30 mL (Group D) of LA (equal volumes of 0.5% bupivacaine and 2% prilocaine). ONSD/ETD ratios were measured bilaterally at baseline, 20, and 60 min. Perfusion index (PI), end-tidal carbon dioxide (EtCO2), block onset times and block duration were also assessed. Results: Groups C and D showed significant bilateral increases in both ONSDint/ETD and ONSDext/ETD ratios at 20 and 60 min compared with baseline (p < 0.05). Group B demonstrated a significant increase only in the ONSDext/ETD ratio on the block side, whereas Group A showed no significant change. PI increased earlier and more markedly with increasing LA volume–dose. No significant intergroup differences were observed in EtCO2. In pairwise comparisons, sensory block onset was significantly longer in Group A than in Groups B, C, and D (p < 0.001). Motor block onset was significantly longer in Group A than in Groups C and D, and in Group B than in Group D (p < 0.001). Analgesia duration was significantly shorter in Group A than in Groups B, C, and D, and in Group B than in Groups C and D (p < 0.001). Conclusions: Increasing the LA volume–dose in US-guided SCBPB accelerates sensory and motor block onset and significantly prolongs block duration. A volume-dependent increase in ONSD/ETD ratios was observed on both the blocked and contralateral sides. PI showed an early and marked increase, particularly in high-volume–dose administrations, reflecting block success. Non-invasive EtCO2 monitoring did not detect significant changes.

Medicina doi: 10.3390/medicina62061102

Authors: Alexandru Burlacu Crischentian Brinza Adrian Iftene Roxana-Elena Bogdan-Goroftei Oana Geman

Heart rate variability (HRV) is widely used as a non-invasive marker of autonomic regulation and physiological adaptability, with relevance across cardiovascular, metabolic, neuropsychiatric, and stress-related conditions. HRV biofeedback has emerged as a non-pharmacological intervention intended to influence autonomic function through paced breathing, resonance-frequency training, and real-time physiological feedback. Although this approach has shown promise in improving stress regulation, emotional symptoms, autonomic balance, and selected cardiovascular outcomes, its effects are not consistent across individuals or clinical states. The reasons for this variability remain insufficiently conceptualized. In this narrative conceptual review, we propose the concept of autonomic non-responsiveness during HRV biofeedback as a descriptive framework for situations in which expected autonomic engagement is weakened, absent, or fails to translate into meaningful physiological or clinical benefit. We discuss potential contributors to non-response, including reduced autonomic flexibility, impaired baroreflex function, disease burden, fatigue, stress-related overload, dysfunctional breathing, methodological limitations, and cognitive-behavioral constraints. We then consider the clinical implications of recognizing non-response as a potentially informative state rather than a simple negative outcome. Finally, we outline a future research agenda focused on operational definition, candidate biomarkers, temporal characterization, and minimally adaptive closed-loop systems.

Medicina doi: 10.3390/medicina62061100

Authors: Frederic Bludau Steffen Heinrich Schulz Sascha Gravius Peter Fennema Marcus Rickert Johannes Vogel Franz-Joseph Dally

Background and Objectives: Percutaneous iliosacral screw fixation is a standard treatment for posterior pelvic ring instability and sacral insufficiency fractures. However, conventional transsacral S1 screw fixation is associated with notable complication rates, most commonly implant loosening; dysmorphic sacral anatomy increases the risk of iatrogenic L5 or S1 nerve root injury. This study presents a modified S1 trajectory to engage the high-density bone of the anterior and cranial S1 vertebral body (promontory) by transferring preoperative 3D planning to intraoperative 2D fluoroscopy. Materials and Methods: This retrospective study analyzed implant placements for posterior pelvic ring instability, including high-velocity trauma and fragility fractures of the pelvis (FFPs). Preoperative computed tomography (CT) multiplanar reconstruction defined a modified corridor from a posterior-caudal iliac entry point directed cranially and ventrally into the S1 promontory. The 3D trajectory was transferred intraoperatively using standard 2D fluoroscopy (lateral, anteroposterior, inlet, and outlet views) with the patient prone. In cases of reduced bone quality or intended sacroiliac fusion, 3D-printed titanium implants (triangular or cylindrical threaded, 10.0–13.5 mm outer diameter) were selected over 7.5 mm cannulated screws. Results: Overall, 137 implants were placed in 71 patients: 13 cannulated screws in high-velocity pelvic ring trauma, 72 triangular titanium sacroiliac fusion implants (iFuse Implant System®, SI-Bone), and 52 threaded titanium fusion implants (iFuse TORQ®, SI-Bone) in patients with FFP. The modified trajectory consistently engaged the anterior and cranial S1 vertebral body. Postoperative 3D CT confirmed accurate placement of all implants. No iatrogenic nerve injuries or revisions for implant malposition occurred. Mean follow-up was 12 ± 9 months. Conclusions: Preoperative 3D CT planning combined with standard 2D fluoroscopy guided a modified S1 trajectory toward the cranial S1 vertebral body. Accurate and safe implant placement was achieved in the prone position without navigation systems, providing a practical alternative when standard transverse trajectories are limited by narrow bony corridors or sacral or pelvic dysmorphy.

Medicina doi: 10.3390/medicina62061101

Authors: Yunjung Rho Seongmin Choi Miji Kim Yunsoo Soh Chang Won Won

Background and Objectives: Aging is associated with sarcopenia and increased adiposity, which may impair mobility and increase fall risk. Although sarcopenic obesity is associated with an increased fall risk compared with either condition alone, evidence regarding sex-specific associations remains limited. This study aimed to examine the sex-specific associations between sarcopenia, obesity parameters, and falls among older Korean community-dwellers. Materials and Methods: This cross-sectional study analyzed baseline data from the Korean Frailty and Aging Cohort Study, including 2039 participants aged 70–84 years (men, 973; women, 1066). Sarcopenia was defined using the Asian Working Group for Sarcopenia 2025 criteria, and obesity was categorized as general (body mass index and percentage body fat [PBF]) or central obesity (waist circumference [WC] and conicity index [C-index]). Falls were assessed by self-report. Logistic regression analyses were performed after adjusting for potential confounders. Results: Among 2039 participants, 395 (19.4%) reported falls. In the total population, higher PBF and C-index were independently associated with increased fall risk after adjustment. Men showed significantly higher odds of falls with low handgrip strength, high WC, PBF, and C-index than women. In women, only low appendicular skeletal muscle mass index was independently associated with falls. Sarcopenic obesity was not significantly associated with falls in either sex. Conclusions: Although sarcopenic obesity itself was not independently associated with falls in either sex, distinct sex-specific associations were observed between individual components of sarcopenia, obesity, and fall risk among older Korean adults. Reduced muscle strength and central obesity were more strongly associated with falls in men, whereas reduced muscle mass was independently associated with falls in women. These findings suggest that sex-specific approaches targeting muscle function and body composition may be important for fall prevention in aging populations.

Medicina doi: 10.3390/medicina62061099

Authors: Tuba Gul Sukran Kaygisiz Gonca Gulbay Yasemin Kaya

Background and Objectives: Migraine is a chronic, throbbing type of headache that affects large populations worldwide. This condition is associated with neuroinflammation. Materials and Methods: In this study, polymorphism analyses were performed by KASP PCR. Serum interleukin-6 (IL-6) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were measured using kits based on the enzyme-linked immunosorbent assay (ELISA) principle. Results: In the APE1 Asp148Glu (rs1130409) gene polymorphism analysis, the frequency of the mutant G (Glu) allele was 93.1% and 48.0% in the control and migraine populations, respectively, while the frequency of the wild-type T (Asp) allele was 6.9% and 52.0% (p < 0.001). The frequency of the T/T (Asp/Asp) genotype was high in the migraine group (p < 0.001), while the frequency of the G/G (Glu/Glu) genotype was higher in the control group at 86.2%, compared to the migraine group (p < 0.001). The total frequency of the T/G+ G/G (Asp/Glu+Glu/Glu) composite genotype was determined to be 65.9% in the control group and 34.1% in the migraine group (p < 0.001). There was no statistical difference in allele and genotype frequency between the control and migraine groups for the XRCC1 Arg399Gln (rs25487) gene polymorphism. Serum 8-OHdG and IL-6 levels were comparable between the groups, with no statistically significant differences observed. Conclusions: Future studies with larger and more homogeneous populations are needed to further elucidate the potential interactions between inflammatory processes and DNA damage in migraine. Consideration of attack duration and environmental exposures may improve interpretation of biomarker variability. Expanding the analysis to additional DNA repair gene polymorphisms may also contribute to a better understanding of the molecular background of migraine and the evaluation of potential biomarkers.

Medicina doi: 10.3390/medicina62061098

Authors: Nemanja Murić Zoran Bukumirić Maja Murić Snežana Radovanović Jovana Ristić Danijela Djoković Milan Djordjić Vladimir Janjić

Background/Objectives: Insomnia is a prevalent sleep disorder with substantial public health implications, yet epidemiological data from Serbia remain limited. This study aimed to assess the prevalence of clinically significant insomnia symptoms in the adult population of Serbia and to examine associated sociodemographic, comorbidity, psychosocial, and lifestyle factors. Materials and methods: A cross-sectional study was conducted from September 2023 to September 2025, including 2577 adults aged 18–89 years across Serbia. Insomnia symptom severity was measured using the Insomnia Severity Index (ISI), with scores ≥ 15 indicating clinically significant insomnia symptoms. Sociodemographic, comorbidity, psychosocial, and lifestyle factors were assessed via self-reported questionnaires. Multivariable logistic regression with LASSO variable selection was used to identify factors independently associated with clinically significant insomnia symptoms. Results: The prevalence of clinically significant insomnia symptoms (ISI ≥ 15) was 10.9%. Independent factors associated with clinically significant insomnia symptoms included being single (OR = 1.54) or divorced (OR = 1.75), lower educational attainment (OR = 0.71 per level increase), being retired (OR = 1.83) or a student (OR = 1.66), dermatological comorbidities (OR = 2.99), use of anxiolytic medications (OR = 2.44), exposure to stressful life events (OR = 1.88), engagement in late-night activities (OR = 1.37), consumption of coffee/tea (OR = 2.22), energy drink consumption (OR = 1.52), and late-night eating habits (OR = 1.27). Conclusions: Clinically significant insomnia symptoms among adults in Serbia are influenced by a complex interplay of sociodemographic, comorbidity, psychosocial, and lifestyle factors. These findings underscore the need for integrated approaches that address both medical and modifiable behavioral determinants in the prevention and management of insomnia symptoms.

Medicina doi: 10.3390/medicina62061097

Authors: Hyun-Jung Kwon Daeyun Choi Shin Wook Yi Jun-Seok Lee Jin-Woo Shin Seong-Soo Choi Doo-Hwan Kim Chan-Sik Kim

Background and Objectives: Ultrasound-guided stellate ganglion block is a promising alternative intervention for cervical radicular pain. However, factors associated with treatment responses remain unknown. This single-center, retrospective study aimed to identify clinical and radiological factors associated with treatment response to stellate ganglion block in patients with cervical radicular pain. Materials and Methods: This study included patients with cervical radicular pain who underwent ultrasound-guided stellate ganglion block. Successful response was defined as a ≥4-point or ≥50% reduction in the numerical rating scale score at 3 months post-procedure compared with the pre-procedural baseline. Patients who did not meet these criteria or underwent additional interventional procedures for persistent cervical radicular pain within 3 months were classified as unsuccessful responders. Logistic regression analysis was performed to identify factors associated with treatment response. Results: Multivariable logistic regression analysis demonstrated that substantial cervical multifidus fatty degeneration, defined as Goutallier grade ≥2 of the cervical multifidus muscles (vs. minimal fatty degeneration, odds ratio (OR) 0.23, 95% confidence interval (CI): 0.08–0.66, p = 0.007) and bony hypertrophy at the uncovertebral or facet joint as the primary etiology of foraminal stenosis (vs. disc herniation, OR 0.35, 95% CI: 0.14–0.87, p = 0.024) were independently associated with lower odds of a successful response to stellate ganglion block. Steroid use was not significantly associated with treatment response (OR 0.52, 95% CI: 0.18–1.49, p = 0.223). The successful response rate declined progressively with the number of risk factors: 94.7% (18/19), 50.0% (22/44), and 40.7% (11/27) for zero, one, and two factors, respectively (p < 0.001). Conclusions: Substantial cervical multifidus fatty degeneration and foraminal stenosis attributable to bony hypertrophy may be associated with lower odds of a successful response to stellate ganglion block in patients with cervical radicular pain. These factors require prospective validation before routine clinical implementation.

Medicina doi: 10.3390/medicina62061096

Authors: Heeyoung Hwang Gitak Bae Kyeongmin Jang

Background and Objectives: Cardiometabolic risk factors frequently cluster and substantially increase the risk of cardiovascular disease. While high-density lipoprotein cholesterol (HDL-C) and systemic inflammation, measured by high-sensitivity C-reactive protein (hs-CRP), are independently associated with cardiometabolic risk, whether systemic inflammation modifies the association between HDL-C and cardiometabolic risk clustering (CMRC) remains unclear. This study aimed to examine the independent associations of HDL-C and hs-CRP with CMRC and to evaluate the multiplicative product interaction between HDL-C and natural log-transformed hs-CRP in relation to CMRC among middle-aged adults. Materials and Methods: This cross-sectional study used data from 2283 adults aged 40–64 years who participated in the 2024 Korea National Health and Nutrition Examination Survey. CMRC was defined as the presence of ≥2 cardiometabolic risk factors. HDL-C and hs-CRP were analyzed as continuous variables. Complex sample logistic regression analyses were performed to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs), including a multiplicative product interaction term calculated as HDL-C × ln hs-CRP. Results: The prevalence of CMRC was 46.4%. HDL-C was inversely associated with CMRC (OR = 0.946, 95% CI = 0.937–0.956, p < 0.001), whereas ln hs-CRP was positively associated with CMRC (OR = 1.224, 95% CI = 1.020–1.468, p = 0.030). The HDL-C × ln hs-CRP product interaction term was significantly associated with CMRC (OR = 1.005, 95% CI = 1.001–1.009, p = 0.008). This finding indicates that the association between HDL-C and CMRC may vary across levels of ln hs-CRP, but it does not indicate a direct association between HDL-C and ln hs-CRP. Conclusions: HDL-C and ln hs-CRP were independently associated with CMRC. The significant HDL-C × ln hs-CRP product interaction term suggests possible statistical effect modification of the HDL-C–CMRC association by systemic inflammatory status. These findings should be interpreted cautiously and do not establish a causal or mechanistic relationship.

Medicina doi: 10.3390/medicina62061095

Authors: Win Sen Kuan Ying Wei Yau Desiree Xin Ying Lim Chew Kiat Yeoh Nicole Mun Teng Cheung Hannah Xin Yi Lim Mui Teng Chua

Background and Objectives: Traumatic brain injury (TBI) affects millions of people worldwide. The Glasgow Coma Scale (GCS) is commonly used to characterize its severity. Head computed tomography (CT) is frequently the diagnostic imaging modality of choice. Recently, blood-based biomarkers such as ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) have emerged as possible adjuncts to head CT in evaluating mild TBI (mTBI). We aim to validate the performance of the Abbott Alinity i TBI test (UCH-L1 and GFAP) compared to head CT in an Asian cohort with mTBI and GCS 15. Materials and Methods: This prospective observational study was conducted at a tertiary academic medical center from 2 December 2024 to 19 March 2025. Patients aged 21 years and above who sustained head injury within 12 h of ED attendance had GCS of 15 and required head CT as per attending physician were eligible. Plasma was separated from whole blood within 10 min of collection and immediately stored at −20 °C. UCH-L1 and GFAP levels were analyzed in batches within 28 days of recruitment at the hospital central laboratory using the Alinity i TBI test. Results: Among 120 patients enrolled, there was predominance of males (55.8%, 67/120) and Chinese ethnicity (75.8%, 91/120). The median age was 73 (interquartile range [IQR] 56 to 79) years. Overall incidence of positive head CT was 9.2% (11/120); all 11 patients had positive Alinity i TBI tests. The sensitivity and negative predictive value of the biomarkers in our cohort were both 100% (95% confidence intervals [CIs] 71.5% to 100% and 78.2% to 100%, respectively), specificity 13.8% (95% CI 7.9% to 21.7%) and positive predictive value 10.5% (95%CI 5.4% to 18%). Exploratory post hoc analysis suggested that GFAP alone, at the prespecified assay threshold, was associated with modestly higher specificity [21.1% (95% CI 13.9% to 30.0%)] in this cohort. Conclusions: The Alinity i TBI test can safely rule out intracranial injury in patients with mTBI and GCS 15 presenting within 12 h of injury. However, specificity was low, limiting its ability to reduce head CT use in its current form. Exploratory post hoc analyses of the individual biomarkers, particularly GFAP alone, should be interpreted cautiously. Future studies should focus on optimizing specificity while maintaining a high degree of sensitivity.

Medicina doi: 10.3390/medicina62061094

Authors: Nurila Aryntayeva Kuanysh Shonbay Tulay Koru-Sengul Fatima Bagiyarova Gulshara Aimbetova Guoyan Zhang Saltanat Umbetkulova Abzal Zhumagaliuly Venera Baisugurova Indira Karibayeva

Background and Objectives: Healthcare workers (HCWs) involved in the COVID-19 response are at increased risk of mental health disturbances, including sleep disorders. This study aimed to assess the prevalence and predictors of insomnia among HCWs in Almaty, Kazakhstan. Materials and Methods: A cross-sectional study was conducted between 11 and 26 September 2021, including 553 HCWs. Insomnia symptoms were assessed using the Insomnia Severity Index (ISI). The primary binary outcome was defined as an ISI score ≥ 10, while ISI ≥ 15 was used descriptively to indicate moderate-to-severe insomnia symptoms. Associations were evaluated using chi-square tests and multivariable logistic regression models. Statistical significance was set at p < 0.05. Results: Overall, 38.10% of HCWs with complete ISI data had insomnia symptoms based on the predefined ISI ≥ 10 threshold. In multivariable analysis, Kazakh nationality (AOR = 2.11, 95% CI: 1.05–4.23), advanced education (AOR = 2.03, 95% CI: 1.13–3.65), physician role (AOR = 4.92, 95% CI: 1.25–19.30), and working with COVID-19 patients for >1 year (AOR = 2.28, 95% CI: 1.33–3.89) were significantly associated with increased odds of insomnia. Conclusions: Insomnia symptoms were common among surveyed HCWs during the COVID-19 pandemic and were associated with selected demographic and occupational characteristics, including professional role, education level, and duration of work with COVID-19 patients. These findings highlight the need for targeted mental health interventions and structural support systems for HCWs in Kazakhstan.

Medicina doi: 10.3390/medicina62061093

Authors: Alexandra Madalina Bizdu-Branovici Luana Gherasie Maria Denisa Zica Andreea Rusescu Irina Gabriela Ionița Razvan Hainaroșie Viorel Zainea

Background: Otogenic lateral sinus thrombosis (OLST) is a rare but potentially life-threatening intracranial complication of middle-ear infection. Despite advances in imaging, antimicrobial therapy and otologic surgery, optimal management—particularly anticoagulation—remains controversial, and no standardized clinical guideline is available. Methods: A structured narrative review was conducted using PubMed for English-language human studies published between 1 January 2015 and 31 January 2025. The search was repeated and documented during revision on 12 May 2026. Four searches were run separately; retrieved records were manually merged, and duplicate record occurrences were removed using PMID. The searches retrieved 83 records before deduplication; after removal of 19 duplicates, 64 unique records remained for title and abstract screening. Single case reports and review articles were excluded from the primary descriptive synthesis. SANRA principles guided review quality and transparency. Seven eligible studies comprising 140 confirmed OLST patients were analyzed descriptively; selected clinically relevant but non-comparable publications were retained for contextual discussion. Results: Most included cohorts were pediatric; one study included both pediatric and adult patients. Clinical presentation was heterogeneous and often attenuated by prior antibiotic exposure. Contrast-enhanced CT was frequently used initially, whereas MRI/MRV was most informative for confirming thrombus extent and follow-up. Broad-spectrum intravenous antibiotics and surgical source control represented core treatment. Anticoagulation was reported in six studies, most often with low molecular weight heparin, but indications and duration varied substantially. Outcomes were generally favorable, although visual impairment, hearing loss, behavioral sequelae and incomplete radiological recanalization were reported. Conclusions: OLST management should be individualized according to disease severity, thrombus extent, septic status, and patient-specific risk factors. Antibiotics and source control are essential, while anticoagulation should be considered selectively. A practical management algorithm is proposed, but prospective multicenter data are needed.

Medicina doi: 10.3390/medicina62061092

Authors: Masahiro Iinuma Takahiro Hideshima Shinji Machida Kenji Uehara Tomoko Karube Kentaro Sato Naoki Haraguchi

Background and Objectives: Malnutrition is common among older adults with fragility fractures and is linked to poor clinical outcomes in orthopedic surgery. However, the association between nutritional status and bone-related parameters, including bone mineral density (BMD) and bone turnover markers, remains inadequately characterized in this population. This study evaluated these associations in patients with proximal femoral fragility fractures. Materials and Methods: In total, 108 patients who underwent surgery for proximal femoral fragility fractures were retrospectively analyzed. Nutritional status was evaluated using the Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT) score. BMD was measured at the femoral neck of the proximal femur and the lumbar spine using dual-energy X-ray absorptiometry. Serum 25-hydroxyvitamin D (25[OH]D) and bone turnover markers, including total procollagen type I N-terminal propeptide and tartrate-resistant acid phosphatase 5b, were also evaluated. Correlation analyses, group comparisons, and multivariate linear regression analysis were performed to identify factors independently associated with femoral neck BMD. Results: GNRI and PNI were significantly positively correlated with femoral neck BMD (r = 0.48 and r = 0.26, respectively; both p < 0.01), while the CONUT score showed a significant negative correlation (r = −0.27, p < 0.01). Nutritional indices were not significantly correlated with lumbar spine BMD. Patients classified as malnourished by GNRI or PNI had significantly lower femoral neck BMD and serum 25(OH)D and higher bone turnover markers than well-nourished patients. Multivariate linear regression analysis revealed that GNRI, PNI, and CONUT score remained independently associated with femoral neck BMD after adjusting for age, sex, and body mass index. Conclusions: Nutritional status assessed by hematological indices was significantly associated with femoral neck BMD and bone metabolism markers in patients with proximal femoral fragility fractures. Findings underscore the importance of nutritional status in bone health and should be considered in the management of osteoporosis and fragility fractures.