Medicina doi: 10.3390/medicina62050890

Authors: Sotirios C. Kotoulas Vasileios Kolovos Nikolaos Tsiamis Athanasios Kotoulas Charalampos Georgiou Panteleimon Tsipas Ioannis Panagiotou Dimitrios Antoniadis Christophoros Kotoulas

Background and Objectives: Atrial fibrillation (AF) is the most common cardiac arrhythmia, present in up to 14–20% of patients undergoing cardiac surgery, with the number of patients expected to double within the next decade. Despite a Class I recommendation for concomitant surgical ablation and a Class I-B recommendation for left atrial appendage (LAA) occlusion in patients with AF undergoing cardiac surgery (Class IIa for endoscopic or hybrid AF ablation), both procedures remain substantially underutilized in clinical practice. The design of the Mapping atrial fibrillation after Epicardial Surgical Ablation plus AtriClip to Guide Endocardial ablation (MESAGE) prospective study is presented. Materials and Methods: A narrative literature review was conducted using PubMed through March 2025. Randomized controlled trials, multicenter registries, meta-analyses and current clinical guidelines were prioritized. The MESAGE study protocol is presented in accordance with the SPIRIT recommendations. Results: Randomized evidence demonstrates that hybrid ablation achieves 32–48% greater arrhythmia freedom than catheter ablation (CA) alone in persistent and long-standing persistent AF, with comparable safety and significantly fewer interventions at two-year follow-up. Epicardial LAA occlusion with the AtriClip device achieves complete occlusion in all patients with an 87.5% relative reduction in ischemic stroke risk in anticoagulation-free follow-up. Continuous implantable loop recorder (ILR)-based monitoring reveals AF recurrence in substantially more patients than conventional monitoring, with AF burden emerging as a more meaningful endpoint than arrhythmia freedom. The MESAGE study enrolls 40 patients undergoing cardiac surgery who have pre-existing AF, pre-randomized 1:1 to pulmonary vein isolation (PVI) alone versus PVI-BOX, with mandatory pre-operative ILR implantation, intra-operative AtriClip LAA exclusion, and systematic Day-60 endocardial mapping and supplementary ablation using the Affera dual-energy system. Conclusions: Hybrid epicardial–endocardial ablation combined with LAA exclusion and continuous ILR monitoring represents a comprehensive, mechanistically rational and evidence-informed approach to AF management in patients undergoing cardiac surgery, although current evidence remains heterogeneous, and the benefits depend on the AF phenotype and monitoring strategy. The MESAGE pilot study will generate hypothesis-generating prospective comparative data on epicardial PVI versus PVI-BOX in the concomitant surgical setting, assessed through systematic post-surgical endocardial mapping and continuous rhythm monitoring.

Medicina doi: 10.3390/medicina62050889

Authors: Răzvan-Ionuț Popescu Răzvan-Cosmin Petca Cristian Mareș Aida Petca Michael Bassil Viorel Jinga

Introduction: Urinary tract infections (UTIs) in male patients are a topic that has received less attention in the medical literature. Current management strategies recommended by most guidelines are largely based on research involving female populations, which limits their applicability to men, in whom UTIs are often considered complicated. While the COVID-19 pandemic has brought about many changes in antibiotic treatment, this study aims to compare antimicrobial resistance patterns of uropathogens in male patients between the COVID-19 pandemic and post-pandemic periods. Materials and Methods: A retrospective descriptive study including urine-culture positive cases in male patients was conducted at a tertiary-level university urology center in Bucharest, Romania. To assess temporal trends, the analysis used four selected six-month intervals during the COVID-19 pandemic (2020–2022) and the post-pandemic period (2023–2025). Inclusion was limited to adult male patients aged at least 18 years who had a single identified pathogen and significant bacteriuria (at least 105 CFU/mL). Duplicate and polymicrobial samples were excluded. In accordance with CLSI guidelines, bacteria were identified and antimicrobial susceptibility was assessed using standard microbiological methods. Statistical analysis was made using Python 3.11.3. Results: A total of 3158 urine positive urine cultures from male patients were included. Gram-negative isolates were the most frequent, with E. coli being the most common urinary pathogen, followed by Klebsiella. The most common Gram-positive isolate was Enterococcus. Antimicrobial resistance in Gram-negative pathogens were higher in the post-pandemic period compared to the pandemic period, particularly to amoxicillin-clavulanic acid, and levofloxacin, with carbapenem resistance exceeding 20%. E. coli showed increased resistance rates to levofloxacin, and amoxicillin-clavulanic acid, and ceftazidime. Resistance of Klebsiella spp. exceeded 30% for imipenem and meropenem. Resistance to amoxicillin-clavulanic, ceftazidime, and imipenem acid increased in Proteus spp. Even though Pseudomonas spp. demonstrated higher resistance rates to several antibiotics, no statistical differences were observed. Enterococcus spp. showed a stable profile, demonstrating resistance to levofloxacin, penicillin, and ampicillin. Conclusion: Among male patients, uropathogens’ antimicrobial resistance was higher in the post-pandemic period compared to the COVID-19 period, particularly among Gram-negative bacteria. Regarding empirical therapy, there are significant concerns regarding the rise in resistance to antibiotics such as fluoroquinolones and β-lactams, as well as the emergence of resistance to carbapenems.

Medicina doi: 10.3390/medicina62050888

Authors: Katharina Hartmann Markus Tröltzsch Amely Hartmann Sven Otto Matthias Tröltzsch

Background and Objectives: Tooth loss affects quality of life and chewing ability and is associated with natural ridge resorption after extraction. Implants are a viable option for the anchorage of removable or fixed prostheses. Successful implant placement requires adequate bone availability. To minimize bone loss after extraction and to avoid the need for additional augmentation before implant placement, ridge preservation techniques are employed. The aim of this study was to assess volume changes in extraction sockets after ridge preservation with a collagen-based bovine/porcine xenogenic material, Bio-Oss® Collagen (Geistlich, Switzerland), in molar and premolar regions. Materials and Methods: A retrospective study was designed and implemented. Subjects who underwent tooth extraction and consecutive ridge augmentation with Bio-Oss® Collagen between 2018 and 2022 and complied with the inclusion criteria were selected. The volume of the tooth root prior to extraction (alveolar socket volume surrogate) was estimated from pre-extraction CBCT scans and panoramic radiographs (predictor variable). The volume of the socket after extraction and ridge preservation was measured in CBCT datasets (outcome variable). The results were tabulated and analyzed (p < 0.05). Results: The study sample was composed of 80 subjects (37 female, 43 male; 20 premolars, 60 molars; average age: 59 ± 12.5 years). Of those, 60 cases qualified for comparative analyses (27 female, 33 male; 15 premolars, 45 molars; avg. age 59 ± 12.7 years). Compared with the pre-extraction alveolar socket volume in this subset of 60 subjects (maxillary premolar: 195.20 ± 33.40 mm3, maxillary molar: 470.41 ± 99.92 mm3, mandibular premolar: 220.42 ± 102.03 mm3, mandibular molar: 544.76 ± 137.32 mm3), ridge preservation cases still exhibited a volume loss of approximately 3–18% due to residual resorption depending on the location of the augmentation site (volume after ridge preservation: maxillary premolar: 192.07 ± 63.50 mm3, maxillary molar: 381.96 ± 81.38 mm3, mandibular premolar: 199.86 ± 73.70 mm3, mandibular molar: 475.85 ± 152.26 mm3. The highest resorption rates were observed in maxillary molar sites (approximately 18%), whereas maxillary premolar sites showed the lowest rates (around 3%). Conclusion: The study demonstrates that ridge preservation with the xenograft Bio-Oss® Collagen (Geistlich, Switzerland) can reduce ridge resorption following tooth extraction.

Medicina doi: 10.3390/medicina62050886

Authors: Mirela Juković Srđan Stošić Dejan Kostić Lorand Sakalaš Marijana Basta-Nikolić Dejan B. Stojanović

Background and Objectives: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease that progressively leads to brain atrophy and the accumulation of disability over time. In this study, we used FreeSurfer to compare subcortical volumes and cortical surface areas between patients with MS and healthy controls and to investigate how regional atrophy relates to both disease lasting and clinical disability. Materials and Methods: We included 80 participants in this study, 40 patients with clinically definite MS and 40 age- and sex-matched healthy controls, all imaged on a Philips Ingenia 3.0T MRI scanner. High-resolution 3D T1-weighted MPRAGE sequences of the brain were processed using FreeSurfer 7.3.3. MS patients were stratified by disease lasting into two subgroups: ≤5 years (n = 17) and >5 years (n = 23). Subcortical volumes were normalised to estimated total intracranial volume (eTIV). Between-group differences were assessed using Welch’s t-test with Benjamini–Hochberg false discovery rate (FDR) correction. Multiple linear regression models controlled for age, sex, and the Expanded Disability Status Scale (EDSS). Results: We found statistically significant volume reductions in 48 of the 52 normalised regions examined. Thalamic volume showed the most severe reduction (mean—21.6% bilaterally) in MS patients. The corpus callosum, hippocampus, and amygdala were also prominently affected. Receiver operating characteristic (ROC) analysis of mean bilateral thalamic volume yielded an area under the curve (AUC) of 0.822 (95% CI: 0.731–0.913). Cortical surface area did not survive FDR correction in the primary comparison, though nominal reductions emerged in longer-lasting MS patients. EDSS correlated with both thalamic and hippocampal volumes in regression models. Conclusions: FreeSurfer-based volumetric analysis detected widespread grey and white matter volume differences in MS patients relative to matched controls, with changes already present in patients within the first five years of diagnosis. The high proportion of significant regions is consistent with a combined pattern of generalised and regionally accentuated atrophy. Among the regions examined, thalamic volume showed the strongest cross-sectional discrimination (AUC = 0.822; sensitivity 65%, specificity 90%) and the most consistent associations with EDSS; these findings support further evaluation of thalamic volume as a candidate imaging biomarker of neurodegeneration, although its diagnostic performance is moderate and requires external longitudinal validation before clinical deployment.

Medicina doi: 10.3390/medicina62050887

Authors: Andrea Silvio Giordani Caterina Menghi Antonella Risoli Anna Baritussio Federico Scognamiglio Matteo Castegnaro Elena Pontara Maria Grazia Cattini Elisa Bison Celeste Ambra Murace Elena Verrecchia Marco Giuseppe Del Buono Francesco Landi Ludovico Luca Sicignano Alida Linda Patrizia Caforio

Background and Objectives: While interleukin-1 inhibitors represent the standard of care for refractory idiopathic recurrent acute pericarditis, current guidelines also endorse conventional immunosuppressive (IS) agents as potential alternatives. The use of conventional IS agents is particularly relevant in specific clinical scenarios, such as systemic immune-mediated disease (SID)-associated pericarditis. However, existing evidence regarding their efficacy and safety for pericarditis treatment remains fragmented, deriving exclusively from case reports, case series, and small monocentric observational studies. Our aims are: To characterize the clinical and diagnostic profiles of patients with pericarditis treated with conventional IS agents and to evaluate the therapeutic efficacy and safety of such agents. Materials and Methods: A systematic review was conducted in accordance with PRISMA guidelines. Major electronic databases were searched from January 1970 to March 2026 for case reports, case series, and observational studies detailing the use of conventional IS therapies for pericarditis. Clinical and therapeutic data, including specific IS indications and dosing regimens, were systematically extracted. Results: The final analysis included 39 reports comprising 75 patients (60% female; median age 36.0 years). The underlying pericarditis aetiology was predominantly SID-related (53%, n = 40) or idiopathic/presumed viral recurrent disease (40%, n = 30). The most frequently prescribed first-line IS agents were azathioprine (44%) and methotrexate (25%). Across published reports, IS therapy was described as achieving pericarditis clinical resolution in all cases and facilitated corticosteroid withdrawal in 72% of patients. Overall, pericarditis recurrence while on IS therapy occurred in only 10% of the cohort. Adverse events requiring IS withdrawal were rare (n = 2, 3%). Conclusions: Conventional IS agents appear effective and generally well tolerated in the published literature on SID-associated and isolated recurrent pericarditis. These findings reinforce the clinical utility of conventional IS therapies as a viable, steroid-sparing strategy when targeted biologic therapies lack sufficient investigation.

Medicina doi: 10.3390/medicina62050885

Authors: Luana Ghilea Seleș Viorela Romina Murvai Laura Maghiar Alin Bodog Anca Huniadi

Background and Objectives: Endometriosis is a chronic, estrogen-dependent disorder characterized by the presence of functional endometrial tissue, comprising both glandular and stromal components, located outside the uterine cavity, affecting approximately 6–10% of women of reproductive age and up to 30–50% of those with infertility. Increasing evidence indicates that endometriosis is not solely a localized gynecological condition but rather a systemic inflammatory and immune-mediated disease. Chronic inflammation and immune dysregulation contribute to disease progression and may impair reproductive function. This review aims to analyze the current evidence regarding the inflammatory and immunological mechanisms underlying endometriosis and to evaluate their impact on reproductive dysfunction and assisted reproductive technology (ART) outcomes. Materials and Methods: A comprehensive narrative review was conducted using major scientific databases, including PubMed, Scopus, and Web of Science. Relevant articles published in the last decade were selected using keywords such as “endometriosis”, “inflammation”, “immune response”, “cytokines”, and “ART outcomes”. Both clinical and experimental studies were included to assess the relationship between inflammatory markers, immune alterations, and reproductive performance. Results: Endometriosis is associated with elevated levels of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α), as well as increased oxidative stress and altered peritoneal microenvironment. Immune dysfunction is characterized by activated macrophages, decreased natural killer (NK) cell cytotoxicity, and an imbalance in T-cell populations. These alterations negatively affect oocyte quality, fertilization, embryo development, and endometrial receptivity. Emerging biomarkers such as IL-6, TNF-α, and CA-125 show potential in predicting disease severity and ART outcomes, although their clinical utility remains under investigation. Conclusions: Endometriosis should be regarded as a systemic immuno-inflammatory disorder with significant implications for reproductive health. The interaction between chronic inflammation and immune dysregulation plays a central role in infertility and suboptimal ART outcomes. Further research is required to validate reliable biomarkers and develop targeted therapeutic strategies to improve reproductive success in affected patients.

Medicina doi: 10.3390/medicina62050884

Authors: Sorana Maria Bucur Dorin Ioan Cocoș Cristian Doru Olteanu Mioara Decusară Mariana Păcurar Eugen Silviu Bud

Background and Objectives: Childhood obesity is a major global health concern and is increasingly recognized as a factor influencing skeletal development. Emerging evidence suggests that excess adiposity may alter craniofacial growth patterns, with potential implications for orthodontic diagnosis and treatment planning. However, the extent to which obesity affects craniofacial morphology in growing individuals remains incompletely understood. This study aims to evaluate the association between body mass index (BMI) and craniofacial morphology in children and adolescents using selected sagittal and linear parameters, and to assess the independent effects of age and sex. Materials and Methods: This cross-sectional orthodontic study included 130 subjects aged ≤ 19 years. Anthropometric measurements were recorded, and BMI was used to classify participants as normal weight, overweight, or obese. Standardized lateral cephalometric radiographs were analyzed using skeletal and soft-tissue parameters. Statistical analyses included normality testing, one-way ANOVA with post hoc comparisons, and multivariate modeling. Results: Obesity was significantly associated with increased sagittal skeletal dimensions. Mandibular body length, mandibular unit length, SNB angle, and maxillary unit length demonstrated progressive increases across BMI categories (p < 0.05). In contrast, vertical growth parameters showed no significant differences. Soft-tissue analysis revealed reduced facial convexity and lower facial height ratios in obese subjects. Age was strongly associated with increases in linear jaw dimensions, whereas sex differences were limited primarily to skeletal size rather than morphological relationships. Conclusions: Childhood obesity is associated with enhanced sagittal craniofacial growth, particularly involving mandibular structures, while vertical skeletal patterns remain largely unaffected. These findings highlight the importance of incorporating BMI assessment into orthodontic evaluation and suggest that obesity may influence growth timing, facial morphology, and airway-related risk factors.

Medicina doi: 10.3390/medicina62050883

Authors: Wei Chen Xin Tong Yuhang Liu Xi Zhang Siying Zhu Yanhua Zhou Yongdong Wu Ye Zong

Background and Objectives: Despite surgical intervention for remission, recurrence is nearly inevitable in patients with Crohn’s disease (CD). While several maintenance therapies are available, the optimal strategy for preventing postoperative recurrence remains uncertain. Materials and Methods: This systematic review and network meta-analysis included placebo-controlled or head-to-head randomized controlled trials (RCTs) from MEDLINE, Embase, and Cochrane Central up to 4 July 2024. Studies assessed maintenance therapies for CD after curative resection. Data were extracted from intention-to-treat (ITT) and per-protocol (PP) analyses separately. The primary outcomes were endoscopic and clinical relapse. A Bayesian network meta-analysis provided risk ratios (RRs) and 95% confidence intervals (CIs). This study is registered with PROSPERO (CRD42024629013). Results: From 1492 screened records, 45 randomized controlled trials met the inclusion criteria. Compared with placebo, clinically significant prevention of clinical recurrence was achieved with adalimumab (RR = 0.17; GRADE High), nitroimidazoles (RR = 0.35; High), infliximab (RR = 0.59; Moderate), thiopurine analogs (RR = 0.41; Moderate), and high-dose mesalamine (RR = 0.74; High), while azathioprine-metronidazole combination therapy demonstrated superior efficacy to azathioprine monotherapy. For endoscopic recurrence mitigation, therapeutic efficacy was confirmed for adalimumab (RR = 0.24; Low), infliximab (RR = 0.32; Moderate), vedolizumab (RR = 0.36; Low), and thiopurine analogs (RR = 0.64; Moderate). Conclusions: This network meta-analysis establishes pharmacological hierarchies for preventing postoperative Crohn’s disease recurrence. Adalimumab is the most effective monotherapy for clinical recurrence prevention, while combination therapies of adalimumab/azathioprine plus nitroimidazole show superior efficacy. For endoscopic recurrence prevention, adalimumab also ranks as the most effective intervention. These findings guide therapy selection but require validation for newer agents through randomized trials.

Medicina doi: 10.3390/medicina62050882

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

Background and Objectives: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin malignancy associated with high rates of recurrence and disease-specific mortality. Although adjuvant platinum–etoposide chemotherapy is used in high-risk disease, the optimal number of treatment cycles has not been established. Materials and Methods: This multicenter retrospective cohort study included 104 patients with resected high-risk MCC (pathological stage IIB–III) treated at Israeli medical centers between September 1985 and February 2021. Patients were assigned to one of three treatment groups: radiotherapy alone, four cycles of platinum–etoposide plus radiotherapy, or six cycles of platinum–etoposide plus radiotherapy. The chemotherapy regimen consisted of cisplatin or carboplatin combined with etoposide in 21-day cycles, with the first two cycles administered concurrently with radiotherapy. Primary endpoints were disease-free survival (DFS) and overall survival (OS), analyzed using the Kaplan–Meier method and multivariable Cox proportional hazards regression. Results: Four cycles of adjuvant platinum–etoposide combined with radiotherapy were associated with the most favorable survival outcomes at all follow-up time points. Five-year DFS and OS in the four-cycle group were 65% (95% CI: 58–72%) and 75% (95% CI: 68–82%), respectively, compared with 55% and 60% in the six-cycle group, and 40% and 45% in the radiotherapy-only group (p < 0.001). The survival advantage of four cycles over radiotherapy alone was sustained at 10- and 20-year follow-up (p < 0.0001). In patients with stage III disease and nodal involvement, the four-cycle group achieved a median DFS of 93 months and a median OS of approximately 110 months, significantly exceeding outcomes in both the six-cycle and radiotherapy-alone groups. No statistically significant survival benefit from chemotherapy was identified in the small subgroup of patients with stage IIB/T4N0 disease. Conclusions: In patients with high-risk resected MCC, the addition of adjuvant platinum–etoposide chemotherapy to radiotherapy significantly improves DFS and OS, with the greatest benefit observed in patients with stage III disease and lymph node involvement. Four cycles represent an optimal treatment duration, delivering durable long-term survival benefit without the need for more prolonged chemotherapy exposure. These findings support a risk-adapted multimodality approach and provide real-world evidence to guide adjuvant therapy decisions in this rare and aggressive malignancy.

Medicina doi: 10.3390/medicina62050881

Authors: Gon Shoham Shira Naveh Tariq Zoabi Noa Gosher Nir Messer Jonathan B. Yuval Mati Shnell Adam Abu-Abeid

Background and Objectives: Metabolic and bariatric surgery is the most effective long-term intervention for severe obesity, associated with significant reductions in weight, associated medical problems, and cancer risk. While the overall safety profile of metabolic and bariatric surgery has improved, early postoperative complications still occur and may lead to prolonged hospitalization, reintervention, or increased morbidity. This study aimed to identify independent preoperative and perioperative predictors of early postoperative complications following metabolic and bariatric surgery. Materials and Methods: We conducted a retrospective cohort study of 927 patients who underwent metabolic and bariatric surgery at a single tertiary medical center between December 2017 and March 2022. Early postoperative complications, defined as those occurring during the index hospitalization or within 90 days, were recorded and graded using the Clavien-Dindo classification. Univariate analyses were performed to identify candidate predictors, followed by multivariable logistic regression using an unpenalized model. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using maximum likelihood methods with Wald-based intervals. Results: Eighty-four patients (9.1%) experienced postoperative complications, with 38% requiring invasive intervention. Bleeding was the most common complication (46%), followed by leak/intra-abdominal abscess (24%) and cardiorespiratory events (18%). Independent predictors of complications included obstructive sleep apnea (OR: 1.93), bariatric surgery within the past 5 years (OR: 2.39). Conclusions: OSA and recent previous surgery increase the risk of early complications after metabolic and bariatric surgery. These findings support integrating specific risk factors into preoperative planning to improve surgical outcomes.

Medicina doi: 10.3390/medicina62050880

Authors: Bogdana Adriana Năsui Lorena Gorgan Codruța Alina Popescu Nina Ciuciuc Alexandra-Ioana Roșioară Dana Manuela Sîrbu Monica Popa Daniela Curșeu Ileana Monica Borda Rodica Ana Ungur

Background and Objectives: Sleep is a vital psychological function for health and well-being in all age groups, from children to adolescents, to adults and the elderly, and impacts quality of life. This study evaluated temporal changes in sleep quality and lifestyle behaviors among medical students in North-Western Romania (Transylvania) between the COVID-19 pandemic and the post-pandemic period. Materials and Methods: A cross-sectional design was employed involving 709 medical students assessed during the first pandemic wave (2020) and the 2023–2024 academic year. Online questionnaires collected data on demographics, body mass index (BMI), substance use, and physical activity. Sleep quality was measured using the validated Athens Insomnia Scale (AIS), and multiple linear regression was performed to identify predictors of sleep outcomes. Results: Post-pandemic data revealed a significant decline in sleep quality, with female gender and lower academic performance identified as significant predictors of insomnia symptoms (R2 of 0.258, p < 0.05). While physical activity levels improved significantly in 2024 compared to the confinement period, this was accompanied by increased fast-food consumption and a rise in overweight and obesity rates. Conversely, illicit drug use decreased, and alcohol consumption patterns shifted, characterized by reduced weekly frequency among females but persistent binge drinking episodes. Conclusions: The transition to post-pandemic education yielded mixed health outcomes; while physical activity rebounded, sleep quality and nutritional status deteriorated. These findings highlight the necessity for university-based interventions focusing on sleep hygiene, nutrition, and stress management to support the well-being of medical students.

Medicina doi: 10.3390/medicina62050879

Authors: Darja Smirnova Mara Klibus Olegs Sabelnikovs

Background and Objectives: Microcirculatory dysfunction is a key feature of septic shock and contributes to organ failure despite the apparent normalization of systemic hemodynamic parameters. Extracorporeal blood purification (EBP) therapies aim to modulate the dysregulated inflammatory response through removal of endotoxins and cytokines. However, their impact on tissue-level perfusion remains unclear. Direct bedside assessment of microcirculation may provide mechanistic insight into the effects of EBP beyond macrohemodynamic stabilization. To date, no structured review has specifically synthesized evidence on direct microcirculatory assessment during EBP therapy in sepsis. Materials and Methods: This structured narrative review summarizes current evidence on direct microcirculatory assessment during EBP therapy in sepsis. A literature search of PubMed, Web of Science, and Scopus was performed using combinations of the terms “microcirculation” and “blood purification” or “hemoadsorption.” Studies published between 2015 and 2026 evaluating direct sublingual microcirculation using sidestream dark field (SDF) or incident dark field (IDF) videomicroscopy during EBP were included. Both experimental and clinical studies were considered. Results: Eight studies met the inclusion criteria. Selective endotoxin adsorption with polymyxin B hemoperfusion (PMX-HP) demonstrated improvements in perfused vessel density and small vessel density in both animal and clinical settings. Non-selective cytokine adsorption devices (CytoSorb and HA380) were associated with increases in microvascular flow index (MFI), perfused vessel density (PVD), and proportion of perfused vessels (PPV), although most data derive from small observational studies. Across studies, improvements in microcirculatory parameters were observed during or following hemoadsorption therapy. However, heterogeneity in design, timing, and concomitant treatments limits definitive interpretation. Conclusions: The included studies report improvements in microcirculatory parameters in septic patients during hemoadsorption therapy. However, despite signals suggesting improved perfusion, interpretation is limited by methodological constraints and the use of hemoadsorption within multimodal sepsis treatment. In the absence of adequately powered randomized controlled trials, these changes cannot be directly attributed to mediator removal and should be considered within the broader context of overall therapy.

Medicina doi: 10.3390/medicina62050878

Authors: Andrea Frosolini Paolo Gennaro

Background and Objectives: The inner ear has traditionally been regarded as an immunoprivileged and anatomically isolated organ. However, growing interest in neuro-lymphatic interactions has raised the hypothesis that glymphatic and lymphatic mechanisms may contribute to auditory pathology and its association with cognitive dysfunction. This systematic review aimed to synthesize current human evidence regarding anatomical, imaging, and clinical correlates of glymphatic mechanisms in the inner ear and audiological pathologies, and to quantitatively evaluate currently available biomarkers. Materials and Methods: A structured search of PubMed, Scopus, and Cochrane databases was performed from inception through March 2026. Eligible studies included human investigations reporting anatomical, histopathological, or MRI-based glymphatic assessments related to inner ear disorders. Risk of bias was assessed using the Newcastle–Ottawa Scale and Joanna Briggs Institute tools. Meta-analysis was conducted for diffusion tensor image analysis along the perivascular space (DTI-ALPS) indices comparing auditory disorders with healthy controls. Results: Six studies met inclusion criteria (five cross-sectional imaging studies and one surgical histopathological case series). Histopathology demonstrated lymphatic capillaries in advanced Ménière disease. MRI studies consistently reported reduced ALPS indices and/or increased choroid plexus volume and enlarged perivascular spaces in tinnitus, congenital sensorineural hearing loss, and age-related hearing loss. Meta-analysis of five studies showed a significant reduction of ALPS index in auditory disorders compared with controls (SMD = −0.73, 95% CI −0.90 to −0.55; p < 0.001), with no heterogeneity. Glymphatic markers were frequently associated with audiological data, cognitive performance and inflammatory biomarkers. Conclusions: Human evidence supports the presence of altered central glymphatic function across diverse auditory phenotypes. Although predominantly based on indirect MRI proxies and cross-sectional data, the meta-analytic findings strengthen the biological plausibility of an auditory–glymphatic interaction. Prospective longitudinal studies are warranted to clarify causality and therapeutic implications.

Medicina doi: 10.3390/medicina62050877

Authors: Andrei Marginean Madalin Margan Dragos-Mihai Gavrilescu Diana-Maria Mateescu Ioana Cotet Cristina Tudoran Dan Alexandru Surducan Camelia-Oana Muresan

Background and Objectives: Breast cancer surgery is increasingly performed in older patients with multimorbidity, in whom cardiovascular disease and frailty may substantially modify perioperative risk, including vulnerability to heart failure decompensation and other major medical complications. However, most available studies report global perioperative complication rates and composite medical endpoints, with heart failure events only rarely captured as dedicated outcomes, and operative technique, cardiovascular comorbidity, and frailty are often treated as separate domains rather than components of an integrated risk framework. Materials and Methods: We conducted a systematized narrative review with a structured literature search in PubMed/MEDLINE, Scopus, and Web of Science from inception to 31 January 2026, including original studies of adult patients undergoing breast-conserving surgery, mastectomy, and/or reconstruction that reported early postoperative outcomes in relation to comorbidities, cardiovascular risk, or frailty. Eligibility assessment, data extraction, and qualitative synthesis followed key PRISMA 2020 principles, and findings were organized into three prespecified domains: surgical complexity, cardiovascular vulnerability (including patients with heart failure where reported), and frailty. Results: Nineteen studies (retrospective cohorts, registry-based analyses, and large database studies, primarily ACS NSQIP) met inclusion criteria, encompassing diverse breast surgery populations, including elderly, metastatic, and reconstructive cohorts. Across datasets, escalation from breast-conserving surgery to mastectomy and then to increasingly complex reconstruction was associated with a stepwise increase in perioperative complications, reoperations, bleeding, and, in selected series, catastrophic events. Preexisting cardiovascular disease and systemic vascular pathology significantly amplified postoperative morbidity even in procedures considered low or intermediate cardiac risk, with signals that patients with underlying heart failure carry particularly heightened vulnerability, although HF-specific events were infrequently reported as separate endpoints. Frailty, mainly assessed using modified frailty indices, consistently emerged as a strong, age-independent predictor of 30-day complications, mortality, and readmissions across surgical types, including both breast-conserving and reconstructive procedures. Conclusions: Early postoperative outcomes after breast cancer surgery are associated with the interaction between surgical complexity, cardiovascular comorbidity (with limited HF-specific reporting), and frailty rather than by operative technique alone. In this context, our synthesis primarily reflects overall cardiovascular vulnerability in comorbid and frail patients, with heart failure risk inferred indirectly from the available data. These findings support a patient-centered, risk-adapted surgical strategy in which the extent and timing of surgery and reconstruction are tailored to each patient’s cardiovascular profile and frailty status, with preferential use of breast-conserving or less complex procedures in vulnerable individuals. Integrating standardized frailty assessment and cardio-oncologic evaluation into preoperative workflows, and prospectively validating this tri-axial framework in dedicated cohorts, may improve perioperative risk stratification and reduce the burden of postoperative medical complications in an aging breast cancer population.

Medicina doi: 10.3390/medicina62050875

Authors: Yossi Geron Yinon Gilboa Asaf Romano Jacob Bar

The Barker hypothesis links intrauterine conditions, mainly low birth weight, subject to poor nutrition with paradoxically improved standards of living and nutrition after World War II in Western countries, to adult disease, mainly coronary heart disease. The limitations of his hypothesis include the fact that it is based only on human epidemiological data and animal studies, and also that it is difficult to isolate the effect of the intrauterine environment from postnatal conditions, familial and genetic background. In the last 20 years, the introduction of ultrasound and Doppler techniques in the assessment of fetal and maternal vascularity added a major contribution to the evaluation of the intrauterine environment. Studies based on ultrasound and Doppler assist in differentiating between prematurity and fetal growth restriction (FGR), mainly in those with placental insufficiency, and postnatal morbidity and even mortality. In addition, the Pedersen hypothesis regarding fetuses with overgrowth, mainly with diabetic mothers, states that they are also prone to postnatal morbidity. However, most of the studies on the issue do not emphasize the effects of the intrauterine environment on fetal organs, such as the brain, heart, liver, kidneys and pancreas in FGR and fetal overgrowth, that may impose a different prognosis in later life. This narrative review aims to summarize current evidence from animal and human studies regarding the impact of intrauterine undernutrition and overnutrition on fetal organ development, and to evaluate how ultrasound and Doppler findings may contribute to understanding the link between the intrauterine environment and postnatal morbidity.

Medicina doi: 10.3390/medicina62050876

Authors: Hyeun-Joon Bae Sa-Jin Kang Kyoung-Sun Kim Hye-Mee Kwon In-Gu Jun Jun-Gol Song Gyu-Sam Hwang

Background and Objectives: While liver transplantation (LT) is a definitive treatment for hepatocellular carcinoma (HCC), tumor recurrence remains a major clinical concern. Although volatile anesthetics influence oncological outcomes, direct comparison between sevoflurane and desflurane remains scarce. This study aimed to investigate the impact of the recipient’s volatile anesthetic choice (sevoflurane vs. desflurane) on HCC recurrence following living donor liver transplantation (LDLT). Materials and Methods: This retrospective cohort study included adult patients who underwent LDLT for HCC. Patients were then divided into sevoflurane and desflurane groups, and propensity score matching (PSM) was used to balance baseline variables. The primary outcome was HCC recurrence, and the secondary outcomes were overall survival (OS) and postoperative C-reactive protein (CRP) levels as a marker for the postoperative systemic inflammatory response. Results: After PSM, 373 matched pairs (n = 746) were analyzed. HCC recurrence was significantly higher in the sevoflurane group compared to the desflurane group (19.6% vs. 13.1%, p = 0.023). Kaplan–Meier analysis also demonstrated that cumulative recurrence of HCC was significantly higher in recipients who received sevoflurane anesthesia than in those who received desflurane (log-rank p = 0.0018). In multivariate Cox proportional hazards regression analysis, the use of sevoflurane for anesthesia maintenance was an independent risk factor forHCC recurrence (Hazard Ratio, 1.66; 95% Confidence Interval, 1.15–2.39; p = 0.007). Regarding OS, no significant difference was observed between the two groups (log-rank p = 0.1123). Postoperative CRP levels were significantly higher in the sevoflurane group compared to the desflurane group, suggesting a more intense systemic inflammatory response associated with sevoflurane maintenance. Conclusions: For HCC patients undergoing LDLT, anesthesia maintenance with desflurane is associated with a reduced risk of tumor recurrence compared to sevoflurane, without a significant impact on overall survival.

Medicina doi: 10.3390/medicina62050874

Authors: Maria Samara Eleni Thodou Christina Messini Efthalia Moustakli Maria Anagnostou Athanasios Zikopoulos Alexandros Daponte Ioannis Georgiou George Anifandis

Background and Objectives: The microbiome plays a pivotal role in male infertility, with distinct microbial species exerting both beneficial and deleterious effects on reproductive function. Sexually transmitted bacteria and several viruses, including human papillomavirus (HPV), have been identified in semen. This cross-sectional study aimed to examine the prevalence of single and co-infections of sexually transmitted bacteria (STB)—such as Chlamydia trachomatis, Mycoplasma spp., and Ureaplasma spp.—with various HPV subtypes in Greek male partners of infertile couples and to evaluate their potential impact on sperm parameters. In addition, the possible effect of cryopreservation on the maintenance of these pathogens was assessed. Materials and Methods: Eighty-two semen samples were initially collected from 82 individuals undergoing routine sperm analysis. In total, 80/82 (97.6%) participants proceeded to further analysis, as 2/82 (2.4%) were excluded due to poor DNA quality. Results: A total of 18/80 (22.5%) sperm samples tested positive for STB, with Ureaplasma spp. representing the most frequently detected pathogen. Co-infection of Ureaplasma spp. and Mycoplasma hominis was observed in 4/80 (5%) samples. Twelve samples (12/80, 15%) were positive for HPV, including low-risk (LR) and high-risk (HR) types, and HPV 16 was the predominant HR genotype. Notably, a co-infection of STB and HPV was not found in our specimens. STB-positive samples demonstrated significantly higher sperm concentration and improved progressive motility compared with STB-negative samples. HPV-positive samples exhibited lower sperm volume and concentration and increased non-progressive motility compared with HPV-negative samples. Following three months of cryopreservation, LR HPV and STB were no longer detectable, whereas HR HPV types remained detectable. Conclusions: These preliminary findings are interesting, as they could be useful for routine screening of HPV and STB in sperm samples preserved in sperm banks and highlight the need for future research.

Medicina doi: 10.3390/medicina62050873

Authors: Andrej Cokan Leyla Al Mahdawi Manuela Ludovisi Maja Pakiž Jure Knez Andraž Dovnik

The Papanicolaou (Pap) smear, a cornerstone of cervical cancer prevention, has emerged as a compelling, though unconventional, biospecimen for the detection of ovarian cancer (OC). This structured narrative review synthesizes the evolving evidence on the utility of cervicovaginal cytology and molecular analysis of Pap test material for OC detection. While conventional cytology provides a proof of concept, its sensitivity is low, ranging from incidental detection of OC in 0.004% of routine screens to 19.3% in patients with known OC. Specific cytologic findings, however, carry significant predictive value: atypical glandular cells (AGC) confer a two-fold increased OC risk, and psammoma bodies (PB) are strongly associated with serous malignancies. Driven by the sensitivity limitations of morphology, the field has undergone a paradigm shift towards molecular detection. Foundational studies confirmed tumor-derived DNA, including hallmark TP53 mutations, is detectable in Pap samples years before diagnosis, though sensitivity is constrained by low DNA abundance and confounded by background clonal mutations. To overcome this, strategies have expanded to target broader genomic signatures, such as somatic copy number alterations (EVA test: 75% sensitivity, 96% specificity), and multi-gene mutation panels (PapSEEK: 33–45% sensitivity). The most promising advances lie in multi-omic approaches, particularly DNA methylation biomarkers, which have demonstrated sensitivities up to 81% with high specificity. Collectively, this evidence argues against repurposing the Pap test as a standalone OC screen but supports its strategic integration into a risk-stratified clinical algorithm. We propose a “reflex-to-molecular” model where high-risk cytology (e.g., AGC, PB) automatically triggers advanced molecular testing on the same sample. This model efficiently leverages existing infrastructure to triage high-risk women for definitive diagnostics. Prospective validation of this integrated approach is the essential next step toward transforming this test into a sentinel for malignancies of the upper female reproductive tract.

Medicina doi: 10.3390/medicina62050872

Authors: Javedh Shareef Sathvik B. Sridhar Sanah Hasan Mohammed Salim Karattuthodi

Background and Objectives: For patients on anticoagulants, the risk of possible drug–drug interactions (pDDIs) is particularly higher due to complex polypharmacy. Clinical decision-making is largely guided by drug interaction databases (DIDs); however, inconsistencies in programming may compromise therapeutic safety and effectiveness. The current study is designed to assess and contrast the consistency of severity rating, evidence classification, and clinical management of pDDIs across three DIDs. Materials and Methods: The study was conducted using real patient data from the outpatient medicine and cardiology department of a public hospital in the United Arab Emirates. Prescriptions containing anticoagulants were evaluated using three databases for pDDI screening: Micromedex, Lexicomp, and Drugs.com. Consensus was assessed using Fleiss’ kappa, and correlations between variables were evaluated using Spearman’s rank correlation coefficient, using a threshold of p < 0.05 to assess statistical significance. Results: A total of 130 prescriptions were analyzed, and 3237 pDDIs involving 1143 interaction pairs were retrieved. Of these, 107 pDDI pairs were consistently identified across all three databases. Significant inter-database variability was observed in the severity classification and management recommendations of pDDIs across the three databases. Regarding evidence classification, both Micromedex and Lexicomp rated most interactions with fair evidence, while Drugs.com provided no evidence ratings. Although some correlations were observed—particularly between Lexicomp’s and Drugs.com—overall agreement across databases was slight to fair (p < 0.05). Conclusions: Marked inconsistencies across the databases were identified in the classification and categorization of pDDIs and their associated parameters. Category-wise agreement analysis provides more meaningful insights beyond overall agreement by revealing clinically relevant concordance and divergence among databases.

Medicina doi: 10.3390/medicina62050871

Authors: Andrei Urîtu Alexandra Roi Ciprian Roi Doina Chioran Alexandru Cătălin Motofelea Ioana Riviș Mircea-Alexandru Bălășoiu Radu Dan Mircea Riviș

Background and Objectives: This study aimed to identify osseous and dental mandibular landmarks that consistently indicate the location of the mental foramen, the primary reference for the mental–incisive trunk block. Materials and Methods: Computed Tomography (CT) scans of the mandibles of 100 patients from a Romanian population (N = 100) were retrospectively analyzed to measure the following: distances from the mental foramen to the basal border of the mandible, alveolar process/crest, and midline, as well as the position of the foramen relative to the lower premolars. These measurements were correlated with patients’ age (divided into three groups: 18–30 years, 30–60 years, >60 years) and gender. Results: The mental foramen was found to be closer to the alveolar crest (13.3 mm with SD = 3.3 in males and 10.7 mm with SD = 4.4 in females, overall mean = 12.3 mm, SD = 4.0) (p = 0.001) than to the inferior border of the mandible (14.3 mm with SD = 1.8 in males and 12.9 mm with SD = 1.6 in females, overall mean = 13.7 mm, SD = 1.9) (p < 0.001). In addition, the foramen was most frequently located adjacent to the second premolar (27.0%) rather than between the premolars (20.0%) and at a distance of ≃2.5 cm lateral to the midline (overall mean = 25.2 mm, SD = 3.5) (p = 0.034). Conclusions: Following the measurements performed, the mental foramen was identified as being closer to the alveolar crest in the vertical direction, at a distance of approximately 2.5 cm lateral to the midline, and most frequently located at the level of the second lower premolar.

Medicina doi: 10.3390/medicina62050870

Authors: Rachel Su Min Lee Jas-mine Seah Sara Baqar Piyush M. Srivastava Eylem Levelt Angeline S. Leet Andrew I. MacIsaac Elif I. Ekinci Richard J. MacIsaac

Glucagon-like Peptide 1 (GLP-1)-based medications have been extensively studied for the management of type 2 diabetes, obesity, chronic kidney disease, and atherosclerotic cardiovascular disease. More recently, their potential role in preventing and treating heart failure has gained increasing attention. Given the strong pathophysiological links among diabetes, obesity, and heart failure, GLP-1-based medications represent a promising therapeutic option to improve morbidity and mortality across these interconnected conditions. In this review, we summarise and discuss recent studies involving GLP-1-based medications that have reported on HF-related outcomes. There is increasing evidence that these medications have beneficial effects on HF outcomes in patients with heart failure with preserved ejection fraction and possibly in those with mildly reduced ejection fraction. The usefulness of GLP-1-based medications in reduced ejection fraction HF remains to be defined.

Medicina doi: 10.3390/medicina62050869

Authors: Eva Coughlin Waylon Alvarado Veluchamy A. Barathi Ramani Ramchandran Deborah M. Costakos Aparna Ramasubramanian Shyam S. Chaurasia

Retinopathy of Prematurity (ROP) affects preterm infants worldwide, involving abnormal development of retinal blood vessels associated with supplemental oxygen use in neonatal care. Although there have been strides in identifying at-risk infants, implementing early screening, updating disease criteria through the International Classification of Retinopathy of Prematurity (ICROP), and developing new therapies, ROP remains a leading cause of preventable blindness. As preterm birth survival rates rise, the incidence of ROP continues to increase and is projected to rise even in countries with abundant resources and well-established care programs. Improving ROP care requires global standardization of screening, diagnosis, and management to prevent missed diagnoses and minimize outcome variability. Intravitreal anti-vascular endothelial growth factor (VEGF) injections are changing the landscape of ROP management, but longitudinal research is needed to determine their long-term safety in preterm infants. Effective ROP management relies on teamwork across disciplines and open communication with parents. Given that parents are lifelong caregivers of a child who may be affected by ROP-related vision impairment, including them in the care team and encouraging psychosocial support is vital. Socioeconomic disparities and limited access to ROP-trained ophthalmologists exacerbate disease burden, underscoring the need for innovative solutions to improve access to care. This perspective emphasizes the importance of globally standardizing ROP prevention and care, noting that efforts are still incomplete, equitable access has not been realized, and the long-term role of anti-VEGF agents in ROP treatment remains unclear.

Medicina doi: 10.3390/medicina62050868

Authors: Elcin Erdogan Yucel Hale Bulbul Dilmen Ozge Ozer Kaya Zehra Narli Ozdemir Merve Kakci Bahriye Celik Mustafa Kemal Yeniay Fatma Keklik Karadag Aybuke Olgun Taha Resid Ozdemir Cengiz Ceylan Oktay Bilgir İnci Alacacıoğlu

Background and Objectives: Peripheral cytopenia occurs in approximately 2% of the population; however, in up to 0.9%, no cause is identified by conventional tests. Next-Generation Sequencing (NGS) detects somatic variants consistent with clonal hematopoiesis (CH). We aimed to determine the prevalence of CH and pre-myelodysplastic syndrome (pre-MDS) using a 51-gene panel with histopathological assessment. Materials and Methods: Bone marrow samples from 96 consecutive patients evaluated for cytopenia were retrospectively analyzed for genetic alterations. Results: In the overall cohort (n = 96), the median follow-up was 8.1 months (range, 1–20). A total of 37 (39%) out of 96 patients were diagnosed with idiopathic cytopenia of undetermined significance (ICUS), 9 (9%) with clonal cytopenia of undetermined significance (CCUS), 9 (9%) with clonal cytopenia and monocytosis of undetermined significance (CCMUS), 34 (36%) with myelodysplastic syndrome (MDS), and 7 (7%) with myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Among 41 patients in whom no cytogenetic abnormalities were detected by fluorescence in situ hybridization (FISH), somatic variants were identified by NGS. In CCUS, 88% of patients had a single variant, most commonly ASXL1 (44%), followed by TET2 (22%). In CCMUS, ASXL1 and DNMT3A (each 25%) were the most frequent variants. The mean variant allele frequency (VAF) was higher in MDS (33.4%) than in CCUS/CCMUS (13.6%). In MDS patients aged 60 years and older, a higher number of variants were found compared to patients aged less than 60 years (p = 0.028). RUNX1 variants (n = 8) were associated with leukopenia (p = 0.012). Patients with SRSF2 variants (n = 4) had significantly poorer progression-free survival (p = 0.001). EZH2 and SETBP1 variants were associated with inferior overall survival (p = 0.04 and p = 0.019, respectively). In MDS patients (n = 34), thrombocytopenia (plt < 100.000) was associated with shorter PFS (p = 0.005). Conclusions: Given that pre-MDS conditions are considered predictors of hematologic malignancies, conventional diagnostic workup may be insufficient to accurately identify these entities, whereas NGS provides significant additional diagnostic value.

Medicina doi: 10.3390/medicina62050867

Authors: Monika Jadwiga Krefft Paulina Magdalena Ostrowska Rafał Studnicki Rita Hansdorfer-Korzon

Background and Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder in which gait and balance disturbances substantially increase the risk of falls and loss of independence. Pharmacological treatment alleviates several motor symptoms but has limited effects on postural instability. Backward walking (BW), a demanding locomotor task, has recently been investigated as both an assessment tool and a rehabilitation strategy in PD. The purpose of this focused systematic review is to analyse the benefits and limitations of retro walking in relation to the gait parameters and balance control of PD patients. Materials and Methods: A structured literature search (2015–2025) was conducted across multiple databases in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Eligibility criteria, screening procedures, and qualitative synthesis methods were predefined. Nine studies (including two randomized controlled trials) met the inclusion criteria. Methodological quality was assessed using PEDro and ROBINS-I tools, and the certainty of evidence was evaluated using GRADE. Results: The research results indicate within-group improvements in balance and gait parameters following BW training. Some of the included studies also suggest that BW may be a sensitive marker of balance deficits and fall risk. However, the evidence is limited by small sample sizes, heterogeneity of interventions, and a predominance of non-randomized designs. Conclusions: Current evidence regarding BW in PD remains preliminary. While BW may be considered as a supplementary component of rehabilitation, its specific efficacy cannot be clearly distinguished from general exercise effects. Further high-quality randomized controlled trials with standardized protocols and long-term follow-up are required.

Medicina doi: 10.3390/medicina62050865

Authors: Sung-Hye Byun Jihyun Woo Jung A Lim Sou-Hyun Lee

Background and Objectives: Craniosynostosis repair is associated with a high perioperative transfusion rate, but preoperative prediction models remain limited. This exploratory study aimed to develop and internally validate clinically prespecified preoperative models for predicting intraoperative red blood cell transfusion in pediatric craniosynostosis surgery and to evaluate whether adding fused suture extent improved model performance. Materials and Methods: This retrospective single-center prediction model study included children who underwent craniosynostosis repair between 2014 and February 2026. Patients undergoing repeat procedures or concurrent surgery for other craniofacial anomalies were excluded. The outcome was any intraoperative red blood cell transfusion. Candidate predictors were prespecified as age, weight, American Society of Anesthesiologists Physical Status (ASA-PS), preoperative hemoglobin, preoperative platelet, and fused suture extent. Five paired baseline/full ridge-penalized logistic regression models were developed, with fused suture extent added only to the full models. Performance was evaluated using apparent and bootstrap optimism-corrected area under the receiver operating characteristic curve (AUC) and Brier score. Results: Twenty-one patients were included, and nine (42.9%) received intraoperative transfusion. Across all five comparisons, inclusion of fused suture extent improved optimism-corrected discrimination and reduced prediction error. Corrected AUC increased from 0.470 to 0.674, from 0.475 to 0.738, from 0.552 to 0.667, from 0.516 to 0.704, and from 0.466 to 0.694 across the five model pairs. The best-performing model included weight, preoperative hemoglobin, ASA-PS, and fused suture extent, with an optimism-corrected AUC of 0.738 and an optimism-corrected Brier score of 0.242. Conclusions: Inclusion of fused suture extent improved preoperative prediction of intraoperative transfusion and may support perioperative blood management planning in pediatric craniosynostosis surgery. However, external validation using larger independent cohorts is necessary prior to clinical implementation.

Medicina doi: 10.3390/medicina62050866

Authors: Răzvan-Ionuț Popescu Cătălin Nechita Răzvan-Cosmin Petca Cristian Mareș Aida Petca Cătălin Babiță Viorel Jinga

Background and Objectives: Urinary Tract Infections (UTIs) are a major concern worldwide due to increasing antimicrobial resistance. Even though sex-based differences in antimicrobial resistance are recognized worldwide, there is a lack of data in the literature. This study aims to evaluate differences in the distribution of uropathogens and antibiotic resistance across large groups of Romanian males and females. Materials and Methods: This retrospective descriptive analysis included 2567 positive urine cultures collected over a 1-year period from hospitalized and outpatient patients at two representative urology centers in Bucharest. Only urine tests with ≥105 CFU/mL and monomicrobial growth were included. Results: The sex distribution showed a predominance of male patients (62.2%). Also, their age tended to be higher than that of females. Escherichia coli remained the most common pathogen, with a higher prevalence in females (54.08% vs. 32.54%), while Klebsiella and Pseudomonas were more frequently noted in males. The Gram-negative analysis revealed higher resistance rates in male patients, particularly for common antibiotics such as amoxicillin-clavulanic acid (50.37% vs. 35.77%), trimethoprim-sulfamethoxazole (46.69% vs. 34.64%), and levofloxacin (45.55% vs. 34.71%). Notably, carbapenem resistance in Klebsiella exceeded 30% in males, indicating major concerns about multidrug resistance in this case. In contrast, Gram-positive bacteria showed more stable resistance patterns among the studied groups. Preserved sensitivity was found to linezolid, vancomycin, fosfomycin, and nitrofurantoin. Conclusion: These findings demonstrate clinically relevant sex-based differences in both pathogen distribution and antimicrobial resistance, particularly among Gram-negative uropathogens. Also, it highlights the importance of developing sex-adapted antibiotic strategies in conjunction with the local epidemiological data.

Medicina doi: 10.3390/medicina62050864

Authors: Mert Deniz Savcilioglu Nil Savcilioglu Kemal Ozan Lule Emre Atessonmez

Background and Objectives: Residual coronary anatomical complexity following culprit-lesion-only percutaneous coronary intervention (PCI) remains a major determinant of clinical outcomes in patients with multivessel coronary artery disease (CAD). Platelet distribution width (PDW), a marker of platelet heterogeneity and activation, has been associated with adverse cardiovascular outcomes; however, its relationship with post-procedural residual disease burden remains unclear. This study aimed to evaluate the association between PDW and residual SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score and to determine its incremental predictive value beyond established clinical variables. Materials and Methods: In this retrospective, single-center study, 140 patients with multivessel CAD undergoing culprit-lesion-only PCI followed by planned staged revascularization were included. Clinical presentation was categorized as chronic coronary syndrome (CCS), non-ST-elevation myocardial infarction (NSTEMI), or ST-elevation myocardial infarction (STEMI). Residual SYNTAX score was calculated after the index procedure, and patients were stratified into low (≤22) and high (≥23) groups. Associations between PDW and residual SYNTAX score were assessed using correlation and regression analyses. Model discrimination and incremental predictive value were evaluated using ROC analysis, hierarchical logistic regression, and reclassification metrics. Nonlinear relationships were explored using restricted cubic spline analysis, and clinical utility was assessed by decision curve analysis. Results: PDW was significantly correlated with residual SYNTAX score (Spearman ρ = 0.503, p < 0.001) and increased progressively across SYNTAX severity strata and clinical presentation groups. In multivariable analysis, PDW remained independently associated with high residual SYNTAX score (OR 1.38, 95% CI 1.07–1.82, p = 0.016). The addition of PDW to a hierarchical clinical model significantly improved model performance (ΔR2 = 0.049, p = 0.012). Although the improvement in area under the curve (AUC) was modest, reclassification analyses demonstrated significant net reclassification and discrimination improvements. Spline analysis revealed a nonlinear relationship, with a marked increase in risk beyond PDW levels of approximately 13 fL. Decision curve analysis confirmed the clinical utility of PDW across a range of threshold probabilities. Conclusions: PDW is independently associated with post-procedural coronary anatomical complexity and provides incremental predictive value beyond established clinical variables. However, PDW should be interpreted as a biomarker reflecting platelet heterogeneity within a thromboinflammatory context, without the ability to distinguish between acute and chronic components.

Medicina doi: 10.3390/medicina62050859

Authors: Fariya Khan Pratibha Verma Aditya Singh Manoj Kumar Jalaj Gupta Girijesh Kumar Patel Samradhi Singh Vinod Kumar Alok Kumar Yadav Vinod Verma

Pulmonary diseases such as Chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis, and acute respiratory infections remain a major global health challenge due to their complex pathophysiology and limited therapeutic options. Conventional 2D cultures and animal models have provided foundational insights; however, they often fail to accurately replicate the human lung’s intricate architecture, immune interactions, and patient-specific variability. Recent advances in vitro technologies have transformed pulmonary research, enabling the generation of physiologically relevant and translational disease models. The review highlights the progression of lung research platforms from traditional monolayer cultures to advanced systems such as air–liquid interface models and 3D lung organoids. These cutting-edge models more effectively mimic the biochemical, mechanical, and spatial microenvironment of the respiratory system, enhancing the fidelity of disease modelling and drug screening. In parallel, the integration of computational modelling and artificial intelligence (AI) has emerged as a powerful synergistic approach. AI-driven analytics facilitate high-throughput imaging, biomarker discovery, and patient-stratified therapeutic prediction, while computational tools simulate disease networks, mechanobiological interactions, and pharmacological responses. The convergence of these technologies supports a deeper understanding of pulmonary disease progression and accelerates the development of precision therapeutics. Collectively, this review underscores the transformative potential of combining in vitro lung models with advanced computational and AI methodologies. This synergy not only improves translational relevance and reduces reliance on animal testing but also paves the way for personalised interventions that better address the complexity of human pulmonary disease.

Medicina doi: 10.3390/medicina62050863

Authors: Huai-Lung Chang Ling-Uei Wang Tzu-Lun Huang Pei-Yao Chang Wei-Ting Ho Yung-Ray Hsu Fang-Ting Chen Yun-Ju Chen Cheng-Hung (Dixson) Lin Jia-Kang Wang

Background and Objectives: Neovascular age-related macular degeneration (nAMD), including typical nAMD (tAMD) and polypoidal choroidal vasculopathy (PCV), is a leading cause of visual impairment. This study investigated the real-world short-term outcomes of faricimab, a bispecific antibody targeting Ang-2 and VEGF-A, in patients with treatment-naïve or -refractory nAMD. Materials and Methods: This retrospective study analyzed treatment-naïve or -refractory nAMD eyes receiving one, two, or three monthly intravitreal faricimab injections. Primary outcomes were changes in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) one month after the last injection. Secondary outcomes included the dry macula rate (absence of subretinal and intraretinal fluid) and subgroup comparisons between tAMD and PCV. Results: After a single injection, both treatment-naïve (n = 76) and -refractory (n = 44) eyes showed significant CFT reduction (p < 0.0001) but no significant BCVA improvement (p > 0.05). Dry macula was achieved in 63.2% of treatment-naïve and 71.4% of treatment-refractory eyes. In 38 treatment-naïve eyes receiving three injections, both CFT and BCVA significantly improved from baseline (p < 0.001 and p = 0.02, respectively), with a 94.7% dry macula rate. Subgroup analysis of those receiving three injections revealed that PCV eyes exhibited significant visual improvement, whereas tAMD eyes did not. No serious systemic or ocular adverse events were observed over the short-term follow-up period. Conclusions: Intravitreal faricimab is effective for both treatment-naïve and -refractory nAMD in the short term. While anatomical improvements were comparable between subtypes, the PCV subgroup showed a trend toward greater visual improvement in this small cohort; however, this may be influenced by the significantly younger age of PCV patients. These findings are exploratory and require validation in larger, age-matched prospective studies.

Medicina doi: 10.3390/medicina62050862

Authors: Özlem Akın Mehmet Oktay Taşkapan Asuman Cömert Erkılınç Özlem Tanrıöver

Background and Objectives: Symptomatic dermographism (SD) is the most common type of physical urticaria; however, data on its clinical characteristics and factors associated with disease severity remain limited. This study aimed to evaluate clinical features, triggering factors, associated conditions, and factors associated with disease severity in patients with SD. Materials and Methods: This cross-sectional study included 174 patients followed at a tertiary dermatology center. Data were collected using a structured questionnaire. Disease severity was categorized as severe versus non-severe using a non-validated, patient-reported classification. Factors associated with severe disease were analyzed using univariate and multivariable logistic regression models. Results: The median age was 33.0 years (IQR 27.0–40.2), and 57.4% of patients were female. Severe disease was present in 36.8% of cases. In multivariable analysis, male sex was independently associated with lower odds of severe disease (adjusted OR 0.40, 95% CI 0.20–0.82; p = 0.01). Angioedema and psychological stress were associated with disease severity in univariate analyses but not after adjustment. Persistent symptoms were more frequently reported among patients with severe disease. Conclusions: Male sex was associated with lower disease severity in this cohort. However, given the cross-sectional design and the use of a non-validated severity assessment, these findings should be interpreted as exploratory and hypothesis-generating, and do not support clinical risk stratification or causal inference.

Medicina doi: 10.3390/medicina62050861

Authors: Kristina Vidović Josip Krnić Benjamin Benzon

Background and Objectives: Diazepam, a GABAA receptor agonist with sympatholytic properties, is sometimes co-administered with antiarrhythmic agents in the emergency management of atrial fibrillation (AF), yet evidence supporting this practice is remarkably limited. Given the established role of sympathetic activation in the initiation and maintenance of AF, we investigated whether adjunctive diazepam influences treatment outcomes. Materials and Methods: This single-centre retrospective cohort study included 72 hemodynamically stable patients presenting with AF to the emergency department of University Hospital Centre Split, Croatia. Patients were stratified by treatment strategy into a rhythm control group (n = 33, receiving any Class IC/III antiarrhythmic) and a rate control only group (n = 39, beta-blockers and/or digoxin). Diazepam was administered orally at the physician’s discretion (median dose 5 mg). Primary outcomes were rhythm conversion and achievement of a heart rate < 110 bpm. Secondary outcomes included changes in heart rate, blood pressure, and time to therapeutic goal. Results: Diazepam was administered to 32 patients (44.4%). In the rate control stratum, spontaneous rhythm conversion was significantly higher with diazepam (40.0% vs. 9.5%; OR 6.33, 95% CI 1.06–37.78, p = 0.046), corresponding to a model-predicted increase in conversion probability from 8% to 33%. This effect was absent in the rhythm control group (64.3% vs. 64.7%; OR 0.98, p = 1.000). Diazepam increased the odds of achieving HR < 110 bpm by 3.46-fold (95% CrI 0.63–23.1, posterior probability of benefit 92%) in the rate control group. Diazepam-treated patients in the rate control group had longer median time to therapeutic goal (4.2 vs. 2.8 h, p = 0.005). In the rhythm control group, diazepam was associated with reduced variability in diastolic blood pressure response (p = 0.006). Conclusions: Adjunctive diazepam was associated with a significantly higher rate of spontaneous rhythm conversion in AF patients receiving rate control therapy only, consistent with sympatholysis removing a key factor sustaining the arrhythmia. This effect was not observed when Class IC/III antiarrhythmics were co-administered, suggesting that diazepam’s benefit is context-dependent. These hypothesis-generating findings warrant prospective validation, with attention to thromboembolic risk in patients who convert unexpectedly.

Medicina doi: 10.3390/medicina62050860

Authors: Vedrana Petrić Vanja Vlatković Maria Pete Dajana Lendak Siniša Sević Nadica Kovačević

Background and Objectives: Sepsis is a life-threatening organ dysfunction, and specific biomarkers could improve prognostic assessment in septic patients. The Sequential Organ Failure Assessment (SOFA) score is the standard tool for clinical sepsis monitoring. Recent studies highlight the need for its revision and the identification of rapid, specific, sensitive predictors of sepsis mortality. The aim of this study was to determine the significance of cardiac biomarkers alone or combined with the SOFA score for evaluating sepsis-related mortality. Materials and Methods: This is a retrospective, single-center study with a relatively small sample size of 73 septic patients (Sepsis-3 criteria) hospitalized in an intensive care unit (ICU) and intermediate care unit (IMCU). All patients had standard laboratory parameters, cardiac biomarkers, and the SOFA score available upon admission. Statistical analyses included non-parametric Mann–Whitney U test, ROC (Receiver Operating Characteristic) curve analysis, Hanley & McNeil method and Hosmer–Lemeshow goodness-of-fit test. Results: Lactate (p < 0.001) and SOFA (p < 0.001) showed the highest area under the curve (AUC) values, and all cardiac biomarkers had statistically significant AUCs (p < 0.05) for sepsis mortality prediction. A comparison of all ROC curves was conducted, but no statistically significant differences were observed. Adding hs-cTn (high-sensitivity cardiac troponin) and lactate to the SOFA score increased its AUC from 0.767 to 0.827 (p = 0.421). Conclusions: The results showed that non-survivors of sepsis had significantly higher levels of cardiac biomarkers compared to survivors. There were no statistically significant differences in the areas under the ROC curves among the three markers, or between the markers and SOFA. The addition of cardiac biomarkers to SOFA did not improve the discriminatory ability of the SOFA score. Further research with a larger sample size is required to validate and generalize the findings.

Medicina doi: 10.3390/medicina62050856

Authors: Massimo Baudo Serge Sicouri Mikiko Senzai Yoshiyuki Yamashita Francesco Cabrucci Dimitrios E. Magouliotis Farah Mahmud Thomas Capista Scott M. Goldman Basel Ramlawi

Background and Objectives: Previous comparisons between right anterior mini-thoracotomy (RAT) and partial upper sternotomy (PS) for aortic valve replacement (AVR) have shown similar clinical outcomes. This study aims to assess the potential in-hospital cost differences in one technique over the other. Materials and Methods: Between 2018 and 2023, 303 patients at our institution underwent minimally invasive isolated AVR (241 PS vs. 62 RAT). Endocarditis, emergencies, and reinterventions were excluded. A 1:1 nearest neighbor propensity-matched analysis without replacement was performed. Perioperative clinical outcomes and hospital costs were analyzed, comparing total and average (per patient) direct, indirect, and total hospital costs between the two groups. Multivariable linear regression identified significant predictors of hospital costs. Results: Sixty-two well-matched pairs were analyzed. Significant differences were found in intraoperative (PS: 27/62, 43.5% vs. RAT: 10/62, 16.1%, p = 0.002) and postoperative transfusions (PS: 33/62, 53.2% vs. RAT: 16/62, 25.8%, p = 0.003), and median intensive care unit (ICU) hours (PS: 52.2 vs. RAT: 45.7, p = 0.007). Average direct, indirect, and total hospital costs were significantly higher for PS (p = 0.038, p = 0.040, and p = 0.035, respectively), with significant blood bank cost differences favoring RAT (p = 0.010). Multivariable linear regression showed that intraoperative and postoperative transfusions, ICU, and hospital length of stay were significantly associated with hospital costs, but not the surgical approach. Conclusions: PS and RAT have comparable perioperative clinical outcomes, with differences observed only in the number of transfusions and ICU stay, both favoring RAT. Given the significant perioperative differences and regression analysis results, the cost advantage of RAT is likely mediated through its impact on these perioperative outcomes.

Medicina doi: 10.3390/medicina62050858

Authors: Mehmet Gümüş Kanmaz Burcu Kanmaz Pınar Ayvat Timo Sorsa Pınar Meriç Kantar Nurcan Buduneli

Background and Objectives: The objective of this study was to investigate the relationship between clinical periodontal status and COVID-19 severity, including intensive care unit (ICU) admission and in-hospital mortality, in a cohort of hospitalized patients. Materials and Methods: This single-center, cross-sectional study included 44 patients with polymerase chain reaction-confirmed COVID-19 hospitalized at Buca Seyfi Demirsoy Training and Research Hospital, Izmir, Turkey, between August and December 2021. Of these, 32 (72.7%) were admitted to the ICU and 12 (27.3%) to the inpatient service. All participants underwent a full-mouth clinical periodontal examination to assess probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BoP), and plaque index (PI). Clinical data, demographics, comorbidities, and validated disease severity scores (GCS, APACHE II and SOFA) were extracted from electronic medical records, and a univariate logistic regression analysis was performed to identify factors associated with in-hospital mortality. Results: Patients admitted to the ICU (n = 32) were significantly older, had a higher prevalence of comorbidities, and showed higher CAL (p = 0.049) and PI (p < 0.001) values than those treated in the inpatient service. Deceased patients (n = 15) had a significantly higher PI than survivors (p = 0.024). In the univariate logistic regression analysis, APACHE II was the only variable significantly associated with in-hospital mortality (OR = 0.867, p = 0.003), however none of the periodontal parameters, including CAL and PI, showed a statistically significant association with mortality. Conclusions: Poorer periodontal findings, particularly higher CAL and PI values, were more frequently observed in patients requiring ICU care. However, periodontal parameters were not significantly associated with in-hospital mortality in univariate analysis. Given the cross-sectional design, small sample size, and lack of multivariable adjustment, these findings should be interpreted as unadjusted associations rather than evidence of an independent or causal relationship.

Medicina doi: 10.3390/medicina62050857

Authors: Alex Delisle David Mazy Siyu Wang Zoé David Mélanie Sarda Guy Grimard Marie-Lyne Nault

Background and Objectives: Given the high rates of anterior cruciate ligament graft rupture in the pediatric population, lateral extra-articular tenodesis (LET) is increasingly used in combination with anterior cruciate ligament reconstruction (ACLR) to mitigate the risk of re-injury. This study aimed to compare postoperative postural stability between patients undergoing ACLR with and without LET. It was hypothesized that postural stability would be comparable between patients with and without LET. Materials and Methods: This retrospective, single-center, double-surgeon case–control study included patients who underwent primary ACLR using hamstring tendon autografts between January 2022 and May 2025. Postoperative postural stability was assessed using the Biodex Stability System (BSS) global stability index (GSI), which was the primary outcome of interest. Demographic and surgical data were collected as well as all postoperative GSIs. GSI comparisons between the LET and no-LET groups were made at ≤6 months and >6 months postoperatively. Secondary analysis compared GSI differences between the healthy and operated legs. Results: Among 229 patients screened, 100 met the inclusion criteria (median age, 16 years [IQR, 15–17]); 65 underwent LET and 35 did not, and 54 were female (54%). The groups were comparable on demographic and surgical data (p-value: n.s.). No operated leg GSI difference was observed between the LET and no-LET groups at ≤6 months (p = 0.372) and >6 months postoperatively (p = 0.424). Patients with LET had significantly better (lower) healthy leg GSIs (Mean ± SD; 2.7 ± 0.9) than no-LET patients (3.9 ± 1.8) at >6 months postoperatively (p = 0.004). At ≤6 months, patients showed better GSIs on their operated limb (Median [IQR]; 2.6 [2.1–3.9]) compared to the healthy limb (3.5 [2.3–4.6]) (p = 0.003). This difference disappeared at the latest follow-up. Conclusions: The addition of LET concomitant with ACLR was not associated with a significant difference in postural stability, as assessed by the GSI from the BSS. However, given the sample size and study limitations, these findings should be interpreted with caution. Increased attention to the healthy limb during ACLR rehabilitation may be warranted, particularly in the early postoperative period (<6 months). Further studies with larger cohorts are needed to confirm these observations.

Medicina doi: 10.3390/medicina62050855

Authors: Elada Indrisiunaite Ieva Renata Jonaityte Tatjana Karmaziene Tadas Raudonis

Background and Objectives: Biological therapy is widely used to treat moderate-to-severe psoriasis. This study aimed to assess the real-world effectiveness and drug survival of biologic treatment in patients with moderate-to-severe psoriasis. Materials and Methods: A retrospective study of 210 patients with moderate-to-severe psoriasis who were treated with biological therapy between 2018 and 2023 was conducted. Baseline data included demographics, comorbidities, prior treatments, Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores, laboratory results, current psoriasis treatment, and treatment-related adverse events. Results: Of the 210 patients, 60.0% were male (n = 126). The mean age was 48.3 ± 13.6 years in men (range 16–74) and 48.4 ± 13.6 years in women (range 17–79). The mean PASI at initiation of biologic therapy was 15.0 ± 8.1 and decreased to 3.3 ± 4.7 at 1 year, 2.7 ± 4.0 at 3 years, and 2.8 ± 3.3 at 5 years. Drug discontinuation differed between therapies: etanercept had a higher hazard of discontinuation than ustekinumab (hazard ratio (HR) 2.55, 95% confidence interval (CI) 1.17–5.52; p = 0.0179), infliximab (HR 0.36, 95% CI 0.13–0.97; p = 0.0429) and adalimumab (HR 0.47, 95% CI 0.23–0.98; p = 0.0453). Conclusions: In routine clinical practice, biologic therapy was associated with substantial and sustained improvements in the PASI over up to 5 years of follow-up. Drug survival was initially high for all agents but separated over time, with etanercept showing the poorest long-term persistence and a higher hazard of discontinuation compared with other drugs.

Medicina doi: 10.3390/medicina62050854

Authors: Felice Crocetto Ugo Amicuzi Michele Musone Ciro Imbimbo Simone Tammaro Luigi Napolitano Pasquale Reccia Luigi De Luca Francesco Del Giudice Marco Stizzo Michelangelo Olivetta Dario Di Lieto Michele Di Mauro Gennaro Mattiello Giacomo Puca Giampiero Della Rosa Marco Magliocchetti Michele Giugliano Raffaele Capoluongo Mariano Coppola Silvestro Imperatore Antonio Madonna Federico Capone Dario Del Biondo Biagio Barone

Erectile dysfunction (ED) is a common multifactorial condition with significant physical, psychological and relational consequences. While historically associated with aging, its rising prevalence among younger men underscores the need for updated diagnostic and therapeutic frameworks. This narrative review synthesizes contemporary evidence on the pathophysiology, diagnostic workup and management of ED, with emphasis on guideline-directed care and emerging treatment modalities. A comprehensive literature search was conducted, with evidence synthesized from key clinical guidelines, landmark trials and recent peer-reviewed studies. Lifestyle optimization remains the foundational step, followed by first-line pharmacotherapy with phosphodiesterase type 5 inhibitors (PDE5is), which demonstrate high efficacy and safety across diverse patient populations. For patients with inadequate PDE5is response, second-line options include alprostadil (intracavernosal, with approximately 70% success rates or intraurethral), vacuum erection devices and penile prosthesis surgery, with patient and partner satisfaction exceeding 95% for the latter when performed in experienced centers. Psychosexual therapy is an integral adjunct, particularly in psychogenic or mixed etiologies. Regenerative approaches such as low-intensity extracorporeal shockwave therapy (Li-SWT) and platelet-rich plasma (PRP) injections are under investigation; current evidence supports their use only in experimental settings due to limited long-term data. A multidisciplinary, individualized strategy—incorporating pharmacologic, surgical and psychosocial interventions—remains the cornerstone of modern ED management. This review critically distinguishes well-established evidence from ongoing clinical debates and translates findings into practical guidance for daily practice. Ongoing technological advances may further refine diagnostic accuracy and treatment personalization, but high-quality studies are needed to establish the role of regenerative and digital tools.

Medicina doi: 10.3390/medicina62050853

Authors: İbrahim Demir Bilge Ecemiş Ayşe Zorba Selinsu Güleşce Yahya Yıldız İbrahim Oğuz Karaca Korhan Erkanlı

Background and Objectives: Early risk stratification remains challenging in patients undergoing left ventricular assist device (LVAD) implantation. Red cell distribution width (RDW) and serum albumin reflect systemic stress and nutritional reserve; their ratio (RDW-to-albumin ratio, RAR) may provide a simple preoperative index. We evaluated whether preoperative RAR is associated with early mortality after LVAD implantation. Materials and Methods: We conducted a retrospective cohort study of LVAD recipients (2019–2025). RAR was calculated as RDW (%) divided by albumin (g/dL) from preoperative blood tests obtained 24–48 h before surgery. The primary endpoint was in-hospital mortality. The secondary endpoint was 90-day survival. In-hospital mortality was analyzed using logistic regression with parsimonious adjustment for INTERMACS high-risk status (profiles 1–2 vs. 3–7); penalized regression was used to reduce small-sample bias. Discrimination was assessed using receiver operating characteristic (ROC) analysis. Ninety-day survival was evaluated using Cox proportional hazards models. Results: Forty-seven patients were included (37 survivors; 10 in-hospital deaths). Higher RAR was associated with increased odds of in-hospital mortality and remained significant after adjustment for INTERMACS high-risk status (OR 1.68, 95% CI 1.04–2.90). INTERMACS high-risk status was strongly associated with in-hospital mortality (OR 17.89, 95% CI 3.19–138.07). RAR demonstrated good discrimination for in-hospital mortality (AUC 0.801, 95% CI 0.648–0.955). For 90-day survival, RAR showed a borderline association in unadjusted analysis (HR 1.28, 95% CI 0.98–1.68) and was not significant after adjustment (HR 1.20, 95% CI 0.89–1.63). Conclusions: In this small single-center cohort, preoperative RAR was independently associated with in-hospital mortality after LVAD implantation. These findings should be considered hypothesis-generating and require external validation.

Medicina doi: 10.3390/medicina62050852

Authors: Doina Iulia Nacea Dan Mircea Enescu Mihaela Pertea Petruța Mitrache Iulia Mihaela Gavrila Raluca Tatar

Background and Objectives: Extensive burns are devastating injuries, especially in children, associating high risk of morbidity and mortality in the absence of immediate and appropriate treatment. Negative-pressure wound therapy (NPWT) has emerged as a versatile tool for the local treatment of burn wounds. This study aims to present our approach in using NPWT for extensive burns in children, emphasizing the indications and outcomes of these very challenging cases, and proposing an algorithm for NPWT use for extensive burn patients, even in low-resource settings. Materials and Methods: We retrospectively analyzed pediatric burn patients admitted between January 2020 and December 2024, selecting the cases with at least 20% TBSA burn and the application of NPWT during treatment, recording indications and parameters of use, treatment period, and results. Results: We identified 12 patients with a burn surface ranging from 20% to 80% TBSA, caused by high-voltage electrical current (6 cases), flame (4 cases), and scalds (2 cases). NWPT was used for 3–25% TBSA for obtaining granulation tissue in very deep burn wounds with bone and tendon exposure, for reducing edema and enhancing spontaneous re-epithelialization in intermediate circumferential burns, and for preparing the wound bed for re-grafting after local infection and graft failure. There were no complications related with the NPWT use and no fatalities. Conclusions: NPWT represents a reliable option for several clinical situations in local burn treatment, for temporary closure of burn areas, graft fixation, burn wound preparation, local infection control, or enhancing re-epithelialization. The proposed algorithm offers a comprehensive overview of indications of NPWT for burn local management and may guide clinical decisions, easing the identification of the best situation and moment to use the device. Our study contributes to the body of knowledge that enforces the evidence of the safe and effective use of NPWT for burn management in the pediatric population.

Medicina doi: 10.3390/medicina62050851

Authors: Emre Erdoğan Ömer Akay Berk Koncalıoğlu Mert Güler Batuhan Gencer

Background and Objectives: We aimed to evaluate early postoperative radiographic changes in sagittal foot alignment following laparoscopic sleeve gastrectomy and to investigate the association between early weight loss and sagittal foot alignment parameters. Materials and Methods: This study included 72 consecutive patients who underwent primary laparoscopic sleeve gastrectomy. Standardized lateral foot radiographs were obtained preoperatively and at the fourth postoperative month. Meary’s angle, calcaneal pitch, and talar declination angle were measured on all radiographs. Demographic and clinical variables, including age, sex, height, body weight, and body mass index (BMI), were recorded. Results: Meary’s angle demonstrated a significant postoperative decrease from 15° (IQR, 8°) to 11° (IQR, 12°) (p < 0.001), indicating improvement in medial longitudinal arch alignment. In contrast, no significant postoperative changes were observed in the calcaneal pitch (p = 0.227) or talar declination angles (p = 0.751). The proportion of patients within the normal range for all measured sagittal alignment parameters increased postoperatively, without showing statistical significance. Statistical analysis revealed that all postoperative sagittal alignment parameters showed significant correlation with preoperative values. Notably, postoperative Meary’s angle demonstrated a very strong positive correlation with preoperative Meary’s angle (r = 0.80, p < 0.001), whereas no significant correlation was identified between postoperative Meary’s angle and either postoperative weight or weight/BMI loss (p > 0.05). Although BMI loss showed a significant correlation with postoperative calcaneal pitch and talar declination angles, these correlations were weak to moderate (r = −0.403, and r = −0.362, respectively). Conclusions: Early postoperative body weight/BMI loss following sleeve gastrectomy is associated with modest, parameter-specific improvements in sagittal foot alignment, primarily reflected by changes in Meary’s angle, suggesting that the medial longitudinal arch may be more responsive to early postoperative unloading than other sagittal alignment parameters. The strong association between preoperative and postoperative measurements underscores the central role of baseline alignment in determining early postoperative outcomes.

Medicina doi: 10.3390/medicina62050850

Authors: Evangelos Katsiotis Sofoklis Mitsos Konstantinos Katsas Konstantinos Kostopanagiotou Panagiota Misokalou Sophia Stamatopoulou Arezina N. Kasti Periklis Tomos

Preoperative sarcopenia has emerged as an important determinant of adverse postoperative and long-term outcomes in patients with resectable non-small cell lung cancer (NSCLC). Its frequent coexistence with systemic inflammation may further worsen survival outcomes. At the same time, neoadjuvant chemotherapy and chemoimmunotherapy have substantially improved pathological response and survival in resectable NSCLC. However, their interaction with host-related factors such as sarcopenia and systemic inflammatory status remains insufficiently characterized. This narrative review aims to synthesize current evidence regarding the interplay between preoperative sarcopenia, systemic inflammation, and neoadjuvant therapy in resectable NSCLC and evaluates their potential combined impact on surgical and oncological outcomes. A narrative synthesis of 20 studies involving patients undergoing lung cancer resection was performed. Sarcopenia was primarily assessed using computed tomography or PET-CT-derived skeletal muscle indices, most commonly the skeletal muscle index, whereas systemic inflammation was evaluated using biochemical inflammatory markers. The available evidence consistently indicates that preoperative sarcopenia is associated with poorer long-term survival, and this adverse effect appears to be amplified in the presence of systemic inflammation. Although neoadjuvant chemoimmunotherapy has improved tumor response and survival outcomes, it may also act as a systemic stressor capable of aggravating muscle loss. Importantly, no study to date has simultaneously evaluated sarcopenia, systemic inflammation, and neoadjuvant therapy within a unified analytical framework. Most available studies focus primarily on sarcopenia, while inflammatory or treatment-related parameters are typically analyzed separately. Overall, while sarcopenia and systemic inflammation are recognized predictors of adverse outcomes in resectable NSCLC, robust evidence integrating them with neoadjuvant therapy is lacking. Clarifying their potential interaction may improve risk stratification and help to optimize perioperative management strategies in the era of neoadjuvant therapy.

Medicina doi: 10.3390/medicina62050849

Authors: Ji Hye Hwang Chul Jung

Background and Objectives: Drug-induced liver injury (DILI) is increasingly associated with the use of herbal medicines. Ephedra sinica (ES) occasionally induces hepatocellular injury, yet therapeutic strategies for herb-induced liver injury are limited. This study investigated the potential mechanisms of a multicomponent pharmacopuncture formulation (VP) in ES-associated hepatotoxicity. Materials and Methods: Bioactive constituents of VP were collected from pharmacological databases and literature. The physicochemical properties were evaluated using SwissADME. Compound–target interactions were identified using the STITCH database and integrated with DILI–related genes retrieved from GeneCards (relevance score ≥ 5.0). Protein–protein interaction network analysis, Gene Ontology enrichment, and KEGG pathway analyses were performed. Results: A total of 22 overlapping targets were identified. A nine-gene module—comprising TNF, IL6, STAT3, CASP3, PINK1, PRKN, NFE2L2, HMOX1, and ABCB11—was associated with key biological processes, including inflammatory signaling, mitochondrial quality control, oxidative stress regulation, and hepatobiliary transport. Conclusions: These findings suggest that VP may modulate multiple biological processes relevant to hepatotoxic stress, including inflammatory signaling, mitochondrial quality control, and bile acid transport. These results provide a plausible mechanistic framework for further investigation, pending experimental validation.

Medicina doi: 10.3390/medicina62050848

Authors: Tsutomu Mieda Hideyuki Asaka Takumi Yamaguchi Yohei Kawasaki Yuta Horikoshi Tina Nakamura Asako Tominaga Hiroshi Hoshijima Hiroshi Nagasaka Noritaka Imamachi Tatsuo Yamamoto

Background and Objectives: Phantom limb pain (PLP) frequently occurs after lower limb amputation (LLA). However, a consensus has not been reached regarding its incidence, particularly in nontraumatic amputations, because reported estimates vary according to case mix, follow-up duration, and outcome definitions. Data from Japan remain limited. Methods: After approval by the Institutional Review Board, the electronic medical records of patients who underwent above-knee amputation (AKA) or below-knee amputation (BKA) at Saitama Medical University Hospital between 1 January 2012 and 31 December 2024 were retrospectively reviewed. The primary outcome was the incidence of clinically documented PLP during hospitalization, typically within approximately 1–2 months after amputation. PLP was defined as a painful sensation in the amputated limb documented in the medical record and diagnosed by surgeons or anesthesiologists. Postamputation pain due to symptomatic neuroma was not classified as PLP. Patients with only nonpainful phantom limb sensations were not considered to have the primary outcome. Patients aged 18 years or older who required nontraumatic AKA or BKA were included. Patients who (1) died within 30 days of surgery or (2) were unable to communicate were excluded. Results: Clinically documented PLP occurred in 31 of 298 patients (10.4%; exact 95% CI, 7.2–14.4%) during hospitalization. In the prespecified primary model including age and preoperative pain, younger age (adjusted odds ratio (OR) 0.96 per 1-year increase, 95% confidence interval (CI) 0.93–0.99; p = 0.008) and preoperative pain (adjusted OR 16.34, 95% CI 3.75–71.24; p < 0.001) were associated with PLP. In an exploratory model additionally including postoperative pain on the day of surgery, postoperative pain was not independently associated with PLP. Firth penalized logistic regression yielded similar results. Conclusions: This study found a 10.4% incidence of clinically documented PLP during hospitalization after nontraumatic major LLA. Younger age and preoperative pain were associated with PLP, although the estimates should be interpreted cautiously because only 31 PLP events occurred.

Medicina doi: 10.3390/medicina62050847

Authors: Diana Maria Orzata Adrian-Iosif Moldoveanu Gabriel Veniamin Cozma Radu Gheorghe Dan Ovidiu Alexandru Mederle Flavia Zara Raluca Maria Closca Laurentiu Vasile Sima

Background and Objectives: The term “appendiceal mucocele” is widely used in clinical practice, yet it remains diagnostically incomplete because it represents a preoperative clinical and imaging label rather than a definitive diagnosis. We examined the diagnostic and therapeutic pathway of patients managed under this working label over a 10-year period and assessed how final histopathology influenced subsequent management. Materials and Methods: We performed a retrospective single-center cohort study including patients with appendiceal mucinous lesions managed between January 2016 and December 2025. Eligible cases were identified from the institutional histopathology registry and classified on final histopathology as non-neoplastic mucoceles or neoplastic mucinous lesions, including low-grade and high-grade appendiceal mucinous neoplasms. Data were extracted on CT use, surgical strategy, margin status, extra-appendiceal/serosal mucin, chemotherapy, recurrence, and follow-up. Results: Eighteen patients met the eligibility criteria. Final histopathology showed two distinct endpoints: non-neoplastic mucoceles and neoplastic mucinous lesions. CT was the dominant preoperative investigation and most often supported the working impression of mucocele or suspected mucinous appendiceal lesion, although some neoplastic cases entered the pathway as presumed appendicitis or perforation. Appendectomy was the dominant index procedure, whereas primary right hemicolectomy was uncommon. Completion right hemicolectomy was performed only in the neoplastic subgroup, and management decisions were driven by a limited number of actionable histopathologic features, particularly margin status and extra-appendiceal/serosal mucin. Conclusions: This study highlights a real-world diagnostic and therapeutic pathway in which the term “mucocele” represents a preoperative label rather than a definitive diagnosis. Histopathology appeared to represent the key step in this pathway, rather than the preoperative imaging impression. Given the small sample size, these findings should be interpreted as descriptive and hypothesis-generating. In practical terms, suspected appendiceal mucocele should be approached through a standardized pathway involving safe index resection, structured pathology reporting using modern terminology, and risk-adapted escalation and follow-up when higher-risk features are present.

Medicina doi: 10.3390/medicina62050846

Authors: Merve Keskinkılıç Gül Polat Zeynep Bayramoğlu Anıl Aysal Ağalar Göksenil Bülbül Öztürk Emine Çağnur Ulukuş Tuğba Yavuzşen İlhan Öztop

Background and Objectives: Molecular classification has emerged as a key determinant of prognosis in endometrial cancer and has recently been incorporated into the 2023 FIGO staging system. Tumors are categorized into four molecular subgroups—POLE-mutated (POLEmut), p53-abnormal (p53abn), mismatch repair-deficient (dMMR), and no specific molecular profile (NSMP)—each associated with distinct biological behavior and clinical outcomes. However, real-world data evaluating the relationship between molecular classification, FIGO stage distribution, and survival outcomes remain limited. Materials and Methods: This retrospective study included patients diagnosed with endometrial cancer between 2014 and 2022 at Dokuz Eylül University Hospital. Tumor samples were classified according to the ProMisE molecular algorithm using next-generation sequencing for POLE mutations and immunohistochemical evaluation of mismatch repair proteins and p53 expression. Clinicopathological characteristics, recurrence patterns, and survival outcomes were analyzed. Appropriate statistical analyses were performed. Results: A total of 156 patients were included (mean age 60.2 ± 10.0 years). The most common histology was endometrioid carcinoma (51.9%). Molecular subgroup distribution was NSMP (58.3%), dMMR (25%), p53abn (11.5%), and POLEmut (5.1%). Most patients presented with early-stage disease (83.4%). According to the 2023 FIGO molecular staging, 8.3% were classified as stage 2C m-p53abn and 5.8% as Stage 1Am-POLEmut. After a median follow-up of 39.5 months, the overall survival rate was 81.6%. Survival differed significantly across molecular subgroups, with the most favorable outcomes observed in the POLEmut (100%), followed by NSMP (85.2%), dMMR (78.4%), and p53abn (64.7%) (p = 0.011). Lymph node metastasis was significantly more frequent in the p53abn subgroup (p = 0.002), whereas distant metastasis rates did not differ between groups. Conclusions: Molecular classification was associated with differences in FIGO stage distribution and survival outcomes in this retrospective cohort and may provide additional prognostic information beyond traditional clinicopathological factors. The integration of molecular profiling into routine practice and staging systems may enable improved risk assessment and facilitate more personalized therapeutic strategies in endometrial cancer.

Medicina doi: 10.3390/medicina62050845

Authors: Çiğdem Özdilekcan Tarkan Özdemir Mustafa Hamidullah Türkkanı Naim Ata Mesut Akyol Mevlüt Karataş Aslıhan Gürün Kaya Aydın Yılmaz Akın Kaya Şuayip Birinci

Background and Objectives: The presence of comorbidities in both the pre- and post-diagnostic periods is a critical consideration in the diagnosis and management of patients with cancer. This study aimed to investigate the prevalence and burden of pulmonary and extrapulmonary comorbidities in patients diagnosed with lung cancer (LC) and malignant pleural mesothelioma (MPM). Materials and Methods: The data were obtained from official patient records of the Turkish Ministry of Health. Patients diagnosed with either lung cancer (LC) or malignant pleural mesothelioma (MPM) between 2015 and 2018 were included in the study. Comorbidities were classified as pulmonary or extrapulmonary. Results: A total of 74,835 patients with LC and 1678 patients with MPM were included. The burden of comorbid conditions increased significantly in the post-diagnostic period in both males and females across both cancer types. When the two cancer groups were compared with respect to diagnostic periods, comorbidities such as hypertension (HT), phlebitis/venous thrombosis/thrombophlebitis, pulmonary embolism, pneumothorax, and pleural effusion were significantly more prevalent in the MPM group (p < 0.05). Compared with the pre-diagnostic period, the comorbidity risk in LC was highest for pulmonary embolism, ARF, and pneumonia in the post-diagnostic period, whereas renal failure was the most frequent comorbidity in the MPM group (p < 0.001 and p = 0.024). When comparing changes in comorbidity burden between sexes in the lung cancer group, male patients had higher frequencies of pulmonary embolism, pneumonia, pneumothorax, and coronary artery disease than females. In contrast, in the female lung cancer group, the prevalence of chronic renal failure was higher than in males (OR = 2.14 vs. 2.00), whereas acute renal failure was more prominent in the male patient group (OR = 2.64 vs. 1.94). In gender-based comparison of comorbid conditions among patients with MPM, the risk of renal failure was higher in females than in males (CRF and ARF respectively: OR = 2.63 vs. 2.16 and OR = 6.80 vs. 5.44). Additionally, increased rates of COPD were observed in male patients within this group (OR = 1.93 vs. 1.81). Conclusions: Patients with LC and MPM are burdened not only by their primary malignancies but also by a wide spectrum of comorbidities, particularly in the post-diagnostic period. Comprehensive knowledge of comorbid conditions is essential for clinicians to guide clinical decision-making, anticipate disease progression, and optimize treatment strategies, thereby informing national healthcare policies. Future studies incorporating matched control groups or longitudinal designs with standardized surveillance protocols may help conduct better research.

Medicina doi: 10.3390/medicina62050844

Authors: Sara Saltarocchi Mizar D’Abramo Emmanouela Chourda Paolo De Orchi Flaminia Spunticchia Marco Totaro Mattia Vinciguerra Silvia Romiti Gabriele Giunti Ernesto Greco Fabio Miraldi

Background and objectives: Valve-in-valve transcatheter aortic valve replacement (ViV TAVR) has become an established treatment for failed surgical bioprostheses in patients at high surgical risk. However, procedures performed in degenerated stentless aortic valves remain particularly challenging because of the absence of a radiopaque frame, variable surgical implantation techniques, and a potentially increased risk of coronary obstruction. Evidence in this specific setting is limited. We conducted a systematic review of the literature to identify studies reporting ViV TAVI in degenerated stentless surgical bioprostheses. Materials and methods: Case reports and case series were included when patient-level or clearly identifiable data were available. Baseline characteristics, anatomical features, procedural strategies, and clinical outcomes were extracted and analyzed using a descriptive approach. A total of 54 studies were included, encompassing 294 ViV TAVI procedures performed in failed stentless aortic valves. Results: The mean patient age was 73.9 years, and the average STS-PROM score was 13.45%, reflecting a high-risk population. The most frequently treated prosthesis was the Medtronic Freestyle valve, and the predominant mechanism of failure was regurgitation. Transfemoral access represented the most common approach, while balloon-expandable and self-expanding transcatheter valves were used with similar frequency. Coronary protection strategies were adopted in a minority of procedures, whereas adjunctive procedural techniques such as pre- or post-dilation were relatively common. Device-related complications were mainly driven by coronary obstruction, while cardiac complications included myocardial infarction and unplanned coronary intervention. Overall, VARC-3 device success was achieved in the majority of procedures, with acceptable short-term mortality despite the complexity of the treated population. Conclusions: ViV TAVR in degenerated stentless bioprostheses appears feasible and generally effective but remains associated with specific procedural challenges, particularly related to coronary obstruction risk. Careful anatomical assessment and tailored procedural planning are essential, and larger contemporary studies are needed to better define optimal management strategies in this complex setting.

Medicina doi: 10.3390/medicina62050843

Authors: Gabriele Caggianelli Marco Iorfida Renato Cavaliere Alessandro Manzoli Antonio D’Angelo Francesco Scerbo Flavio Marti Stefano Mancin Giovanni Cangelosi Gennaro Rocco Valentina Vanzi Vineetha Karuveettil Maurizio Zega Clara Donnoli

Background/Aim: Cardiovascular disease (CVD) represents a relevant global public health challenge with dyslipidemia as a major modifiable cardiovascular risk factor (CVRF). Recent advances have introduced injectable lipid-lowering therapies (LLT). Their clinical effectiveness in real-world practice seems to depend not only on pharmacological efficacy but also on patients’ acceptance, adherence, and persistence, influenced directly by perceived barriers and facilitators. The main objective of this scoping review is to map the barriers and facilitators related to the use of novel injectable LLTs among adult patients with dyslipidemia or CVD. Methods: This review was conducted in accordance with JBI methodology and reported according to Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for scoping reviews (PRISMA-ScR); pre-registration on Open Science Framework (OSF) was performed. A search was conducted in MEDLINE from PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL) from EBSCOhost, and Google Scholar up to June 2025. Eligible studies included qualitative, quantitative, mixed-methods, and review papers involving adult patients with dyslipidemia who reported experiences, perceptions or challenges related to the use of injectable LLT in any healthcare or community setting worldwide. Two reviewers independently screened studies, selected and extracted data. Results: Out of 665 records identified, 7 studies met the inclusion criteria. Patients’ adherence to injectable LLTs is shaped by psychological fears, prior negative experiences, and perceived efficacy. Satisfaction increases when patients feel supported and informed. Convenience, self-administration, and motivational meaning facilitate persistence. Organizational support and economic accessibility further influence uptake, highlighting that adherence depends on both patient experience and structural factors. Conclusions: Patient acceptance and persistence with injectable LLT depends on a complex interplay of emotional, clinical, organizational and economic factors, beyond pharmacological efficacy alone. Fear of injections, previous statin-related experiences, administrative complexity, and high costs remain major barriers, while shared decision-making, trust in healthcare providers, perceived efficacy, regimen convenience, and supportive structures act as strong facilitators. Addressing these challenges requires multidimensional and multidisciplinary strategies for policy makers and clinical managers.

Medicina doi: 10.3390/medicina62050842

Authors: Kyu-Shik Lee Jong-Heon Kim Jongwan Kim

Background and Objectives: Chromobox protein homolog 2 (CBX2), a member of the polycomb group of proteins that plays a role in chromatin remodeling, has been associated with multiple types of cancer. However, its characterization in liver hepatocellular carcinoma (LIHC) has not been fully elucidated. This study aims to systemically evaluate the expression, prognostic value, epigenetic regulation, and ncRNAs of CBX2 in LIHC. Materials and Methods: We performed a comprehensive in silico analysis to assess CBX2 expression at mRNA and protein levels, correlate its expression with clinical characteristics and prognosis, and explore DNA methylation and ncRNA-mediated regulatory networks. Multiple public databases (TIMER2.0, UALCAN, Human Protein Atlas, KM Plotter, MethSurv, miRNet, and ENCORI) were utilized to conduct expression, survival analysis, and construct a network encompassing miRNAs, lncRNAs, and pseudogenes. Results: CBX2 expression was found to be elevated in LIHC at both the mRNA and protein expression level. Increased CBX2 expression was closely linked with unfavorable clinical outcome. Methylation analysis indicated that various CpG sites, exhibiting both hypermethylation and hypomethylation patterns, were correlated with CBX2 expression and patient prognosis. Among the identified ncRNAs, hsa-miR-101-3p tended to be downregulated, whereas hsa-miR-222-3p was significantly upregulated in LIHC, and both were associated with CBX2 expression and clinical outcomes. The constructed ncRNA interaction network suggested potential associations among miRNA, lncRNAs, and pseudogenes that may be linked to tumor progression. Conclusions: Our results suggest that CBX2 was overexpressed in LIHC and may be associated with epigenetic alterations and ncRNA-related regulatory interactions. Its expression shows a relationship with clinical prognosis, suggesting that CBX2 could serve as a candidate biomarker. The proposed CBX2-associated ncRNA network represents a potential framework for further investigation, although additional experimental validation is required to confirm its biological and clinical relevance. Consequently, our findings suggest that CBX2 may serve as a potential prognostic biomarker and therapeutic target in LIHC, potentially influenced by specific epigenetic and post-transcriptional mechanisms.

Medicina doi: 10.3390/medicina62050840

Authors: Shachar Zion Shemesh Jose Asprilla Paz Kelmer Omri Cohen Itay Goor-Aryeh Yotam Hadari Zvi R. Cohen Lior Ungar

Background and Objectives: Chronic headache after craniotomy is common and may include neuropathic subtypes (scar neuroma pain, occipital neuralgia). However, no large series has quantified these phenotypes. We conducted a single-center retrospective review (n = 5624 adult craniotomy patients) to estimate the prevalence of post-craniotomy neuropathic pain and to describe its characteristics. Materials and Methods: Institutional records were screened to identify craniotomy patients referred to a multidisciplinary pain clinic (n = 272). Eligible cases were reviewed in tiers: (1) exclusion of primary headache and noncranial pain; (2) identification of “probable neuropathic cranial pain” based on documented neuropathic features (lancinating/scalp pain, trigger tenderness, dermatomal distribution); and (3) subgroup categorization into occipital neuralgia-like, supraorbital/supratrochlear neuralgia-like, and scar-site neuropathic pain phenotypes. The supraorbital/supratrochlear subgroup was defined by frontal or frontotemporal postoperative pain in the supraorbital region, local tenderness or Tinel-like hypersensitivity over the supraorbital/supratrochlear course, and/or response to supraorbital–supratrochlear nerve block. Data extracted included demographics, timing (surgery to pain referral), pain characteristics, and treatments (blocks, radiofrequency, medications). Results: Of 5624 craniotomy patients, 272 (4.8%) had pain clinic encounters. The initial review identified 124 cases with chronic post-craniotomy headache requiring follow-up; after detailed chart classification, probable neuropathic cranial pain was present in 111 cases (2% of the cohort). Among the 111 probable neuropathic cranial pain cases, the dominant regional phenotype was occipital neuralgia-like pain. In addition, eight patients (7.2%) demonstrated a supraorbital/supratrochlear neuralgia-like phenotype, predominantly after frontal or frontotemporal craniotomies. Scar-site neuropathic pain frequently coexisted with both regional phenotypes, supporting a partially overlapping spectrum rather than mutually exclusive categories. The median time from surgery to pain referral was several months (≈12–18 months). Management commonly included occipital nerve blocks (±steroid); some patients received pulsed radiofrequency ablation of the occipital nerves, and most were trialed on neuropathic analgesics (gabapentinoids, SNRIs, etc., according to neuropathic pain guidelines). Conclusions: A clinically meaningful subset of post-craniotomy patients develops chronic neuropathic cranial pain, most commonly with occipital, supraorbital/supratrochlear, or scar-related features. Because most postoperative headaches are managed through neurosurgical follow-up and improve without pain clinic referral, the present cohort likely underestimates the true burden of neuropathic post-craniotomy pain while enriching for its most refractory neuralgic presentations. This is nevertheless the subgroup that must be recognized, discussed with patients, studied prospectively, and targeted in future prevention strategies.

Medicina doi: 10.3390/medicina62050841

Authors: Mario Pinzi Andrea Fagiolini Giacomo Gualtieri Maria Beatrice Rescalli Caterina Pierini Alessia Santangelo Benjamin Patrizio Alessandro Cuomo

Complex psychosis is a clinically relevant rehabilitation construct rather than a formal diagnostic category and refers to psychotic illness associated with treatment-resistant symptoms, functional impairment, and additional cognitive, psychiatric, neurodevelopmental, or physical health complexity. In this clinician-oriented narrative review, we synthesised current evidence on rehabilitation interventions for adults with complex psychosis, integrating direct evidence from specialist rehabilitation settings with indirect evidence from schizophrenia-spectrum studies when clinically informative. We searched major clinical databases, prioritised guidelines, systematic reviews, meta-analyses, and controlled studies, and organised the synthesis by functional domain and pathway relevance. Evidence was strongest for cognitive remediation, particularly when combined with broader psychiatric rehabilitation or vocational support, for family interventions in relapse prevention, and for individual placement and support in competitive employment. Social–cognitive and metacognitive interventions appear clinically valuable, although transfer to real-world functioning is more variable. Community-based rehabilitation, supported accommodation, illness self-management, and ecological adaptation strategies remain central to functional recovery when embedded within multidisciplinary pathways. Digital and virtual interventions are promising adjuncts, but their efficacy remains heterogeneous and implementation challenges include engagement, privacy, and service integration. Overall, rehabilitation in complex psychosis is most convincing when it is personalised, measurement-based, and delivered through integrated service models linking assessment, intervention selection, supported living, and recovery-oriented care.

Medicina doi: 10.3390/medicina62050839

Authors: Hyung Joo Lee Tae Lim Yoon

Background and Objectives: Pelvic fixation during robotic-assisted gait training (RAGT) may limit trunk–pelvis movement and influence functional recovery after stroke. This study investigated whether allowing pelvic motion during RAGT improves balance and gait performance in individuals with chronic stroke. Materials and Methods: A single-blind randomized controlled trial was conducted in 49 individuals with chronic stroke (PFG, n = 24; PRG, n = 25). Participants received Lokomat-assisted gait training (30 min/session, 3 sessions/week for 4 weeks) in addition to conventional therapy. The primary outcome was balance (BBS), and secondary outcomes included DGI, 10 MWT, and pelvic kinematics. Group × time interactions were analyzed using two-way repeated-measures ANOVA. Results: Significant group × time interactions were observed for BBS and DGI (p < 0.001), indicating greater improvements in the PRG. Gait speed improved significantly over time in both groups (p < 0.001), with no significant interaction for the 10 MWT. No significant interaction effects were found for pelvic kinematics, although a group main effect was observed for pelvic tilt. No adverse events were reported. Conclusions: Allowing pelvic motion during RAGT was associated with greater improvements in balance and dynamic gait performance compared with pelvic fixation. However, no corresponding changes were observed in pelvic kinematics, suggesting that functional improvements may not be explained by kinematic changes alone.

Medicina doi: 10.3390/medicina62050838

Authors: Tala Abedalqader Alberto Migliorini Leonardo Garcia Cerecedo Nour El Ghazal Joseph Klim Tony Boutros Simon J. Laplante Omar M. Ghanem

Background and Objectives: Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed metabolic and bariatric surgeries worldwide. Marginal ulcers (MU) are a common complication following RYGB, yet their pathophysiology and the contributing risk factors to their development are not fully understood. Materials and Methods: This retrospective cohort study examined patients who underwent RYGB between January 2008 and December 2023, with 1 to 5 years of follow-up. Data collected included patient- and procedure-related risk factors, as well as postoperative MU events. Statistical analysis methods included the independent samples t-tests, multivariate regression, and Cox regression analyses. Results: Our final cohort included 2106 patients and was predominantly female (80.5%), with a mean age of 47.8 ± 12.1 years and body mass index (BMI) of 45.5 ± 7.5 kg/m2. MU occurred in 241 (11.4%) patients, with a mean time to occurrence of 4.5 ± 0.02 years. History of smoking (HR = 1.87, p < 0.001) and gastroesophageal reflux disease (HR = 2.36, p < 0.001) significantly increased hazard for MU, while proton pump inhibitor use (HR = 0.18, p < 0.001) was associated with reduced hazard. Aspirin exposure, regardless of dose and chronicity, did not impact MU. Conclusions: Our findings highlight the importance of preoperative assessment and counseling in patients planning to undergo RYGB. Patient-related factors should guide postoperative monitoring and prophylaxis of MU, as this remains a debated topic amongst experts.

Medicina doi: 10.3390/medicina62050837

Authors: Ardiana Murtezani Deart Jakupi Shkurta Rrecaj Malaj Vjosana Qeriqi Zana Ibraimi

Background and Objectives: Migraine is a common neurological condition that can affect daily life and well-being. Lifestyle factors such as physical activity, sleep, diet, and stress are often discussed in relation to migraine, but their role is not always consistent. This study aimed to examine how selected lifestyle factors are related to migraine frequency and intensity in adults, with a focus on physical activity and dietary habits. Materials and Methods: A cross-sectional study was conducted among 300 adults recruited through an online migraine-focused community from 1 January to 28 February 2026. Participants completed a questionnaire addressing migraine history, frequency and duration of attacks, pain intensity, physical activity, sleep duration, perceived stress, and dietary habits. Associations were assessed using Spearman correlation and multiple linear regression analyses. Results: Most participants were female (88%), and 48% reported physician-diagnosed migraine. Mean migraine intensity was 7.44 ± 1.72. Migraine intensity was positively correlated with migraine frequency (rs = 0.31, p < 0.001), episode duration (rs = 0.48, p < 0.001), perceived stress (rs = 0.17, p < 0.05), and sleep duration (rs = 0.16, p < 0.05). Migraine frequency was correlated with fast food consumption (rs = 0.23, p < 0.01) and BMI (rs = 0.25, p < 0.01). In regression analysis, migraine frequency (β = 0.17, p = 0.005), perceived stress (β = 0.23, p = 0.006), and aura (β = −0.19, p = 0.033) were significant predictors of migraine intensity. Physical activity was not significantly associated with migraine intensity or frequency. Conclusions: Migraine intensity was most consistently related to perceived stress and migraine frequency, whereas migraine frequency was associated with dietary factors and BMI. Physical activity was not associated with migraine outcomes. These findings suggest that lifestyle factors are related to migraine characteristics, although the cross-sectional design does not allow conclusions about causality.

Medicina doi: 10.3390/medicina62050836

Authors: Andrei Vâţă Ionela-Larisa Miftode Maria Gabriela Grigoriu Ioana Mihuta Ioana Maria Onofrei Alexandru Florinel Oancea Mihaela Catalina Luca Egidia Gabriela Miftode

Background and Objectives: Romania reported the highest measles incidence in the European Union during the 2023–2024 epidemic, largely driven by declining vaccination coverage. We aimed to characterize the epidemiological, clinical, and laboratory profile of hospitalized measles patients and to identify age-related differences, with particular emphasis on systemic and hepatic involvement. Materials and Methods: We conducted a retrospective observational study including 360 consecutive patients with laboratory-confirmed measles admitted to a tertiary infectious disease hospital in northeastern Romania between 1 January and 31 December 2024. Demographic, clinical, laboratory, therapeutic, and outcome data were collected. Pediatric (<15 years) and adult patients were compared using appropriate statistical tests. Results: Children accounted for 71.4% of cases, including 16.1% infants under one year. Over 90% of patients were unvaccinated or incompletely vaccinated. Household transmission represented the most frequent identifiable source. Adults presented significantly higher inflammatory markers and more pronounced hepatic involvement than children. ALT elevation occurred in 63.1% of adults versus 34.2% of children (p < 0.001), with moderate-to-severe cytolysis predominantly observed in adults (34.9% vs. 1.9%, p < 0.001). Pulmonary complications were documented in 28% of cases, mainly viral interstitial pneumonia. Thrombocytopenia was significantly more frequent in adults (p < 0.001). Overall mortality was 0.27%, occurring in an unvaccinated infant with secondary bacterial pneumonia. Conclusions: The 2024 measles epidemic in our area was characterized by sustained transmission among unvaccinated individuals and frequent systemic involvement. Hepatic dysfunction emerged as a prominent feature in adults, suggesting a shifting clinical phenotype in contemporary outbreaks. Strengthening vaccination coverage and early recognition of systemic complications remain critical to reducing measles-related morbidity and mortality.

Medicina doi: 10.3390/medicina62050835

Authors: Jorge Montês Mónica Grafino Miguel Ângelo-Dias Jorge Lima Sofia Tello Furtado

Background and Objectives: Pregnancy causes various physiological and hormonal changes that disrupt sleep architecture and modify respiratory patterns, increasing the risk of sleep-related breathing disorders (SBDs) such as obstructive sleep apnea (OSA) and potentially exacerbating pre-existing conditions. These disorders have been linked to adverse maternal and fetal outcomes. However, current screening tools remain inadequate, and data, including from Portugal, remain limited. This study aimed to assess the prevalence of SBD symptoms suggestive of sleep-disordered breathing during pregnancy, characterize the population, and explore associations with demographic and anthropometric parameters. Materials and Methods: A prospective observational study was conducted from July to December 2024 at Hospital da Luz Lisboa, involving pregnant women ≥ 18 years attending routine consultations. Participants completed a structured questionnaire that assessed demographic and anthropometric data, comorbidities, ten SBD symptoms, and the Epworth Sleepiness Scale (ESS). Results: The cohort included 289 participants, with a mean age of 34.4 years and pre-pregnancy body mass index (BMI) of 23.6 kg/m2. On average, women reported 3.1 SBD symptoms, with fatigue (65.4%), memory/concentration impairment (52.2%), and non-restorative sleep (50.5%) being the most common. Excessive daytime sleepiness (ESS >10) was present in 22.8% of the population. Snoring was significantly associated with older age and higher BMI (p = 0.0009 and p < 0.0001, respectively). Both the number of symptoms and ESS scores tended to increase with gestational age, particularly in the third trimester. Women with diabetes had higher odds of reporting snoring, nocturnal dyspnea, and witnessed apneas, with odds ratios of 4.65, 8.77, and 11.38, respectively. Conclusions: SBD symptoms and daytime sleepiness are highly prevalent in pregnancy and typically increase with advancing gestation. These findings emphasize the need for improved clinical strategies to enable early identification and management of SBD in pregnant women, thereby reducing maternal-fetal complications.

Medicina doi: 10.3390/medicina62050834

Authors: Jakub Włodarczyk Wojciech Czernik Aleksandra Osielczak Kasper Maryńczak Arkadiusz Jakubowski Marcin Włodarczyk Łukasz Dziki

Background and Objectives: Acute cholecystitis is a common indication for emergency surgery. While acute calculous cholecystitis (ACC) is most common, acute acalculous cholecystitis (AAC) occurs without gallstones and is often associated with severe systemic illness. We compared early postoperative outcomes after cholecystectomy for AAC versus ACC, with emphasis on complication severity and overall morbidity burden. Materials and Methods: We performed a single-center retrospective cohort study of consecutive adults undergoing urgent or emergent cholecystectomy for acute cholecystitis between December 2020 and April 2025. Patients with chronic cholecystitis, duplicate records, missing group assignment, or incomplete 30-day follow-up were excluded. The primary 30-day endpoints were postoperative complications, their severity (assessed with Clavien–Dindo scale), and cumulative morbidity assessed using the Comprehensive Complication Index. Secondary outcomes included operative approach, postoperative length of stay, 30-day readmission, and mortality. Results: A total of 221 patients were analyzed (181 ACC, 40 AAC). Patients with AAC were older and more frequently male. Any complication within 30 days occurred substantially more often in AAC patients than in ACC patients. Morbidity severity also differed markedly, with higher-grade complications occurring more frequently in the AAC group. AAC patients exhibited a substantially greater overall morbidity burden, indicating not only more frequent complications but also a heavier cumulative impact. Thirty-day mortality was considerably higher in AAC. Open surgery was more commonly required in AAC, whereas postoperative length of stay and 30-day readmission rates were similar between groups. Conclusions: In this cohort, AAC was associated with substantially worse early outcomes after cholecystectomy than ACC, characterized by a pronounced increase in clinically significant complications (Clavien–Dindo ≥ IIIa), greater cumulative morbidity (CCI), and markedly higher 30-day mortality. These findings support treating AAC as a high-risk phenotype warranting intensified perioperative optimization and vigilant postoperative monitoring.

Medicina doi: 10.3390/medicina62050833

Authors: Zuzana André Andrea Kopániová Barbora Gaštanová Petra Brandoburová Veronika Režnáková Martin Fabian Pavol Povinec Jozef Hanes Karin Gmitterová

Background and Objectives: Vascular dementia (VaD) and mixed dementia (MD) represent prevalent causes of cognitive decline in the elderly, as they share similar pathological pathways and clinical features. Distinguishing between these two conditions remains a challenge, due to their frequent clinical and neuroimaging overlap. Nevertheless, it is important from a prognostic perspective. Materials and Methods: The study comprised 114 participants, including patients with VaD (n = 33), MD (n = 26), Alzheimer’s disease (AD; n = 26), and 29 cognitively healthy controls (C). We evaluated routinely used cerebrospinal fluid (CSF) biomarkers (total tau, p-tau181, Aβ1-42) and their ratios to assess inter-group differences, diagnostic accuracy, and correlations with cognitive score. Results: Patients with MD demonstrated significantly higher levels of t-tau and p-tau181, and lower levels of Aβ1-42, compared to VaD (p < 0.004 for all analyses). With the exception of p-tau181/t-tau, all calculated ratios enabled differentiation between these groups. ROC analysis confirmed the high diagnostic accuracy of CSF Aβ1-42 and t-tau (AUC 0.82 and 0.79 respectively) for detecting AD pathology in dementia patients. Furthermore, the t-tau/Aβ1-42, p-tau181/Aβ1-42 ratios were the most effective in differentiating AD-related from vascular pathologies (AUC 0.78 and 0.80 respectively), and in differentiating MD from VaD (AUC 0.79 and 0.77 respectively). A significant correlation was observed between CSF biomarkers (especially tau markers) and cognitive impairment severity. Conclusions: CSF biomarkers effectively differentiate mixed from vascular dementia by identifying underlying AD pathology independent of the clinical phenotype. This supports the use of CSF biomarkers in clinical practice to reveal the neurodegenerative component in patients with cerebrovascular disease, which is of fundamental importance for emerging disease-modifying treatment strategies in mixed neuropathologies.

Medicina doi: 10.3390/medicina62050832

Authors: Hao-Chun Chang Ling-Uei Wang Tzu-Lun Huang Pei-Yao Chang Wei-Ting Ho Yung-Ray Hsu Fang-Ting Chen Yun-Ju Chen Cheng-Hung Lin Jia-Kang Wang

Background and Objectives: Myopic choroidal neovascularization (mCNV) is a vision-threatening complication of pathologic myopia. While anti-VEGF monotherapy is the current standard of care, recurrence and suboptimal responses remain challenges. Faricimab is a novel bispecific antibody that targets both vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) to improve vascular stability. This study aims to evaluate the short-term efficacy and safety of a single intravitreal faricimab injection in eyes with active mCNV. Materials and Methods: This retrospective, single-center study included 27 eyes from 24 patients with active mCNV, including both treatment-naïve and previously treated cases. All eyes received a single intravitreal injection of faricimab (6.0 mg/0.05 mL). Best-corrected visual acuity (BCVA) in logMAR and central retinal thickness (CRT) via spectral-domain optical coherence tomography were assessed at baseline and one month post injection. Statistical significance was determined using paired and independent t-tests (p < 0.05). Results: The study population (mean age 55.5 ± 13.9 years; mean axial length 29.3 ± 1.6 mm) showed significant improvements at one month. Mean BCVA improved from 0.77 ± 0.71 logMAR to 0.51 ± 0.52 logMAR (p < 0.005). Mean CRT decreased from 290.2 ± 66.0 μm to 242.5 ± 45.7 μm (p < 0.005). No ocular adverse events, such as intraocular inflammation, retinal detachment, or endophthalmitis, were observed. Conclusions: A single intravitreal injection of faricimab provides significant short-term functional and anatomical improvement in this small retrospective series. Dual inhibition of VEGF-A and Ang-2 appears to be a safe and effective approach for stabilizing retinal vasculature in patients with high myopia. Larger, long-term prospective studies are needed to determine optimal treatment intervals for mCNV.

Medicina doi: 10.3390/medicina62050831

Authors: Mihai Iliescu-Glaja Fabiana Simion Dana Stoian Daciana Grujic Cristi Tarta Razvan Bogdan Zorin Crainiceanu Teodora Hoinoiu Andrei Motoc

Capsular contracture (CC) remains the most common long-term complication of implant-based breast reconstruction (IBBR), significantly impacting cosmetic outcomes, patient satisfaction, and reoperation rates. Despite substantial advances in surgical technique, implant technology, and perioperative management, the incidence of clinically significant contracture persists at approximately 3–5% at five years in non-irradiated patients and escalates dramatically—to 20–50%—in those receiving postmastectomy radiation therapy (PMRT). The etiology is multifactorial, involving subclinical biofilm formation, a dysregulated host immune and foreign-body response, and radiation-induced fibrosis. This narrative review synthesizes contemporary evidence on the pathophysiology, clinical assessment, and modifiable risk factors for CC in IBBR, with particular emphasis on implant surface characteristics (smooth, textured, and polyurethane[PU]-coated), placement plane (prepectoral versus subpectoral), the role of acellular dermal matrices (ADMs), reconstruction timing (direct-to-implant versus two-stage), and the complex interplay with radiotherapy—including radiation timing, fractionation, and emerging delivery techniques. We also address ongoing controversies, including the lack of standardized objective diagnostic criteria, the comparative effectiveness of ADM versus PU-coated implants, and the optimal sequencing of radiation relative to reconstruction. By integrating the latest evidence from very recent major meta-analyses and national registries, this review provides an updated synthesis. We further propose an evidence-based clinical decision framework for CC risk mitigation. This review aims to inform individualized surgical decision-making and identify priority areas for future investigation.

Medicina doi: 10.3390/medicina62050830

Authors: Andrea Samper-Girona Amaia Aiartzaguena Jorge Burgos María D. Muñoz-González María M. Gil Amelia Valladolid Alain Urones Teresa Cobo Silvia Ferrero María Goya Ester Del Barco Martínez José E. Blanco-Carnero Pilar Prats Rodríguez Francisca S. Molina

Background and Objectives: Risk stratification in symptomatic threatened preterm labor (TPTL) remains challenging, particularly for clinically actionable time horizons. We evaluated whether quantitative cervical stiffness measured with the Cervisense Intravaginal Probe discriminates between women who will and will not deliver within 7, 10, or 14 days after presentation and assessed its discriminative performance alone and in combination with transvaginal cervical length. Materials and Methods: We conducted a multicenter, non-interventional study across 10 obstetric emergency units in Spain. Eligible participants were women aged ≥ 18 years with a live singleton pregnancy at 28+0 to 36+6 weeks, regular uterine contractions, intact membranes, and cervical dilatation < 2 cm on speculum examination. Cervical stiffness was measured at presentation using torsional wave elastography with the Cervisense Intravaginal Probe. Cervical length was measured by transvaginal ultrasonography following international standards. Outcomes were delivery within 7, 10, and 14 days after presentation. Discrimination was quantified using the area under the receiver operating characteristic curve (AUC). An explanatory multivariable logistic regression model for delivery within 14 days included cervical stiffness, cervical length, and covariates selected as potential confounders. Results: Among 305 participants, 17 (5.6%) delivered within 7 days, 19 (6.2%) within 10 days, and 24 (7.9%) within 14 days. Mean cervical stiffness was lower among women who delivered within 14 days than among those who did not (8.63 vs. 14.82 kPa; p = 0.048). Cervical length was shorter among women who delivered within 7, 10, and 14 days (all p < 0.001). Discrimination for cervical stiffness was moderate (AUC, 0.66, 0.64, and 0.73 for ≤7, ≤10, and ≤14 days) and higher for cervical length (AUC, 0.80, 0.77, and 0.78). The combined model achieved the highest discrimination (AUC, 0.85, 0.85, and 0.86). In the ≤14-day explanatory model, higher log-transformed cervical stiffness was associated with lower odds of delivery (OR, 0.907; 95% CI, 0.828 to 0.995; p = 0.039), as was longer cervical length (OR per 1 mm, 0.910; 95% CI, 0.876 to 0.946; p < 0.001). Conclusions: In symptomatic TPTL, Cervisense-derived cervical stiffness showed moderate discrimination for short-term delivery and provided complementary information to cervical length, with improved discrimination when both measures were combined. These findings support future studies developing multivariable prediction models that incorporate quantitative cervical consistency.

Medicina doi: 10.3390/medicina62050828

Authors: Zeliha Guzeloz Ozce Kutlu Ozgur Erdogan Gonul Demir Bugra Taygun Gulle Muzaffer Sancı Mihriban Erdogan Canan Kelten Talu

Background and Objectives: The aim of this study is to assess the mismatch repair (MMR) status and immunohistochemical changes in cases of recurrent endometrial cancer following primary surgery and to evaluate the impact of these changes on prognosis. Materials and Methods: Thirty-one patients diagnosed with endometrial cancer who underwent surgery and had pathologically confirmed recurrences were evaluated. Changes in MMR protein expression, estrogen receptor (ER)/progesterone receptor (PR), and p53 expression in primary surgery and recurrent tumor tissues were assessed using immunohistochemical methods. Prognostic factors influencing these parameters and survival data were investigated. Results: In the assessment of recurrent materials, there were four cases where the MLH-1&PMS-2 staining status changed from intact to loss and four cases that changed from loss to intact. No changes were observed in regard to MSH-2 &MSH-6 staining. The ratios of pMMR and dMMR following the primary surgery were 55% (n = 17) and 45% (n = 14), respectively. Four cases transitioned from pMMR to dMMR, and four cases transitioned from dMMR to pMMR. After recurrence, changes in the ER, PR, and P53 status were observed in seven, three, and three patients, respectively. Conclusions: Changes in the MMR status, receptors, and P53 were observed. It is necessary to re-evaluate prognostic parameters via biopsies in recurring cases and to adjust rescue treatments accordingly.

Medicina doi: 10.3390/medicina62050829

Authors: Austė Markevičiūtė Patricija Lapinskaitė Mariola Kovalevska Audronė Vaitiekienė Diana Rinkūnienė

Congenital Long QT Syndrome (LQTS) is a hereditary cardiac channelopathy defined by delayed ventricular repolarization and an elevated risk of life-threatening ventricular arrhythmias. Recent echocardiographic studies using speckle-tracking and strain imaging have identified subtle abnormalities in ventricular and atrial mechanics among LQTS patients, including reduced global longitudinal strain, impaired diastolic function, enlarged left atrial volumes and a consistently negative electromechanical window. These findings challenge the traditional concept of LQTS as solely an electrical disease and support evolving evidence of a subclinical cardiomyopathic phenotype. Left atrial remodeling, although less studied, may represent an underrecognized component of LQTS with potential implications for arrhythmia vulnerability and diastolic dysfunction. This review summarizes current evidence on electromechanical and structural cardiac involvement in congenital LQTS, highlights its diagnostic and clinical implications, and outlines future directions for research in this evolving field.

Medicina doi: 10.3390/medicina62050827

Authors: Izabella Kuźmiuk-Glembin Agnieszka Białomyzy Michał Sadowski Bogdan Biedunkiewicz Leszek Tylicki Tomasz Niewęgłowski

Background and Objectives: Diabetes mellitus (DM) is a major global health concern, with diabetes-related foot disease (DFD) representing one of its most severe complications, often resulting in chronic infection, osteomyelitis, and limb amputation. Conventional therapies frequently fail in refractory cases, necessitating novel adjunctive strategies. Ozone therapy (OT) possesses antimicrobial, immunomodulatory, and oxygen-enhancing properties, while negative pressure wound therapy (NPWT) facilitates granulation, exudate removal, and tissue perfusion. This study explored the combined efficacy of OT and NPWT in advanced DFD. Materials and Methods: An exploratory, retrospective, observational cohort study was conducted at a specialized wound care center in Gdańsk, Poland, between 2019 and 2022. The study included 30 patients (n = 30) with refractory DFD involving both soft tissue and bone infection who had not responded to previous conventional treatment. The analyzed treatment approach consisted of surgical debridement, application of topical ozonated preparations, and (NPWT) with instillation of ozonated saline administered over a six-week period. Clinical outcomes included wound healing assessed using the Wagner classification and wound volume reduction, pain intensity measured using the Numeric Rating Scale (NRS), inflammatory biomarkers (C-reactive protein [CRP] and procalcitonin [PCT]), and microbiological characteristics of wound cultures. Statistical analyses were performed using the Wilcoxon signed-rank test and the chi-square test, and regression modeling was applied to identify potential predictors of therapeutic response. Statistical significance was defined as p < 0.05. Results: By week six, 100% of ulcers improved to Wagner stage ≤1, with 26.7% achieving stage 0. Median wound volume decreased from 5.5 cm3 to 0 cm3 (p < 0.001). Pain scores declined from 7.2 ± 0.96 points to 0.2 ± 0.5 points (p < 0.001). CRP and PCT levels decreased significantly (p < 0.001), and microbiological clearance was observed in all cases. Higher body mass index (BMI) was associated with poorer pain reduction. Conclusions: The combination of standard wound care with OT and NPWT was associated with clinically relevant improvements in wound healing, infection control, systemic inflammation, and pain reduction in patients with refractory DFD. Although limited by a non-controlled design and small cohort size, these findings support further randomized controlled trials to define the role of this combined approach in integrated diabetic foot care.

Medicina doi: 10.3390/medicina62050826

Authors: Mümin Emiroğlu Esra Canan Kelten Talu Cem Karaali Olçun Ümit Ünal Mihriban Erdoğan

Background and Objective: The clinical success of novel antibody-drug conjugates has led to the identification of a new subgroup within traditionally HER2-negative breast cancers, termed ‘HER2-low.’ The aim of this study was to investigate the clinicopathological differences between HER2-low and HER2-negative groups in neoadjuvant-naive primary breast cancer patients, with a specific focus on stromal tumor-infiltrating lymphocyte (sTIL) density. Materials and Methods: The study included 731 neoadjuvant-naive invasive breast cancer patients. Tumors were classified as HER2-negative (IHC 0) and HER2-low (IHC 1+ or 2+/ISH-negative). sTIL levels were evaluated following the International TILs Working Group guidelines. Results: The HER2-low group (38.7%) demonstrated significantly higher histological grade (p = 0.033) and higher sTIL density (p = 0.006) compared to the HER2-negative group. A stepwise increase in sTIL rates was observed parallel to the HER2 immunohistochemical score (0 → 1+ → 2+) (p = 0.015). The HER2-low/hormone receptor (HR)-negative subgroup exhibited the highest sTIL density (median 35%). No statistically significant difference in overall or disease-free survival was found between the groups. Conclusions: HER2-low breast cancers were associated with a more immunogenic tumor microenvironment compared to HER2-negative tumors. This robust immune infiltration may offset the higher histological grade observed in the HER2-low cohort, potentially explaining the comparable survival outcomes. These findings provide a biological rationale for exploring the synergy between novel antibody–drug conjugates and immune checkpoint inhibitors, particularly in the highly immunogenic HER2-low/HR-negative subgroup.

Medicina doi: 10.3390/medicina62050825

Authors: Povilas Masionis Giedrius Vaitukaitis Agnietė Masionienė Valentinas Uvarovas Igoris Šatkauskas

Background and Objectives: High rates of mortality and morbidity among elderly hip fracture patients are a recognized global issue. This study aimed to evaluate risk factors for early complications and 30-day mortality in hip fracture patients. Materials and Methods: The prospective study included 583 patients over 65 years old who sustained hip fractures from fall and underwent surgery. Each patient was followed up for 30 days and complications were recorded. Regression models were used to assess the influence of patient characteristics and laboratory markers on 30-day mortality and complications. Results: Any complication increased the risk of mortality by 5.6 times (95% CI 1.6–19.9, p = 0.008). Having > 6 comorbidities increased the risk of mortality by 8.2 (95% CI 1.9–35.5, p = 0.005) and the risk of complications by 2.3 (95% CI 1.9–35.5, p = 0.000). Patients > 85 years old had increased risk of mortality by 2.2 times (95% CI 1.2–4.1, p = 0.015) and a 1.7-fold increase in risk of complications (95% CI 1.2–2.4, p = 0.005). Vitamin D significantly predicted mortality with odds ratio of 2.1 (95% CI 1.1–4.1, p = 0.028). Serum N-terminal pro-brain natriuretic peptide levels > 780 ng/L predicted 2.3-fold increase in mortality (95% CI 1.0–4.9, p = 0.040) and a 2.6-fold risk of complications (95% CI 1.7–3.9, p = 0.000). Conclusions: Occurrence of complication increases the risk of mortality. Age and comorbidities are significant factors associated with 30-day mortality and complications. Vitamin D levels are associated with higher risk of mortality. N-terminal pro-brain natriuretic peptide levels correspond to higher risks of death and complications.

Medicina doi: 10.3390/medicina62050824

Authors: Erika Jasukaitienė Šarūnas Augustis Ričardas Radišauskas Lolita Šileikienė Abdonas Tamošiūnas Dalia Lukšienė Gintarė Šakalytė Diana Žaliaduonytė Karolina Marcinkevičienė Daina Krančiukaitė-Butylkinienė

Background and Objectives: Stroke remains a major contributor to global morbidity and mortality, with substantial geographic variation in incidence and outcomes. Although declining trends in stroke incidence and mortality have been documented in several Western European populations, countries in Eastern Europe have historically experienced a disproportionately high cardiovascular disease burden. Comprehensive long-term evaluations assessing simultaneous trends in stroke attack rates, mortality, and case-fatality in Lithuania are limited. This study aimed to investigate 24-year trends (2000–2023) in stroke epidemiology among working-age residents of Kaunas city. Materials and Methods: Data were derived from the Kaunas population-based stroke registry and included individuals aged 25–64 years. Age-standardized attack rates, mortality rates, and case-fatality rates per 100,000 population were calculated using the World Health Organization standard population. Temporal trends were assessed using Joinpoint regression analysis to estimate annual percentage changes (APCs) with corresponding 95% confidence intervals (CIs). Analyses were stratified by sex, age group (25–54 and 55–64 years), and stroke subtype (ischemic and hemorrhagic). Results: During 2000–2023, overall stroke attack rates declined significantly in both sexes, with a more pronounced reduction observed among females. Stroke mortality decreased significantly among females over the entire study period, whereas no significant overall change was observed among males, largely due to increases during 2010–2021 that attenuated earlier and subsequent improvements. Case-fatality rates demonstrated no significant overall long-term trend in either sex but exhibited marked temporal variability, including significant increases during 2010–2021 followed by substantial declines after 2021. Age-stratified analyses confirmed significant reductions in attack rates across both age groups. Ischemic stroke incidence declined significantly in both sexes, while hemorrhagic stroke mortality decreased significantly among males and females. The period 2021–2023 was characterized by pronounced reductions in mortality and case-fatality across multiple subgroups. Conclusions: Over the past two decades, the stroke burden among working-age residents of Kaunas has declined substantially, particularly among females. Despite period-specific deteriorations, recent improvements underscore the impact of advances in stroke prevention and acute care. Sustained risk factor control and continued healthcare system development remain essential to maintain favourable trends.

Medicina doi: 10.3390/medicina62050823

Authors: Onur Çatak Jülide Kurt Keleş Zekiye Çatak

Background and Objectives: Age-related macular degeneration (AMD) is a multifactorial retinal disease in which inflammation and blood-retinal barrier dysfunction may contribute to disease pathogenesis. Claudin-5 is a key tight-junction protein involved in endothelial barrier integrity. Hemogram-derived indices such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) reflect systemic inflammatory status. This study aimed to evaluate circulating claudin-5 levels and systemic inflammatory indices in patients with wet and dry AMD and to investigate their associations with visual function. Materials and Methods: This prospective case–control study included 90 participants: 30 patients with wet AMD, 30 patients with dry AMD, and 30 healthy controls. All participants underwent detailed ophthalmologic examination, including best-corrected visual acuity (BCVA) assessment and optical coherence tomography. Serum claudin-5 levels were analyzed by enzyme-linked immunosorbent assay, and NLR, PLR, MLR, and PIV were calculated from complete blood count parameters. Group comparisons, correlation analyses, and age-adjusted analyses were performed using appropriate statistical methods. Results: Age differed significantly among the groups (p = 0.032), with the highest median age in the dry AMD group. BCVA (logMAR) also differed significantly (p < 0.001), and both AMD groups had worse visual acuity than controls. Median serum claudin-5 levels were 2.42 in controls, 3.28 in the wet AMD group, and 3.10 in the dry AMD group, with no significant between-group difference (p = 0.280). NLR, MLR, and PIV were also comparable among the groups (p = 0.310, p = 0.410, and p = 0.752, respectively). PLR differed among the groups (p = 0.019), and post hoc analysis showed higher PLR values in the dry AMD group than in the wet AMD group (p = 0.013). However, this difference was no longer statistically significant after adjustment for age (adjusted p = 0.098). Serum claudin-5 was not significantly correlated with age, BCVA, NLR, PLR, MLR, or PIV. Conclusions: Circulating claudin-5 did not differ significantly across AMD phenotypes and was not associated with age, visual function, or systemic inflammatory indices. Although PLR differed between wet and dry AMD before adjustment for age, the overall findings suggest that single-point peripheral serum measurements of claudin-5 may have limited utility in reflecting local retinal barrier-related changes in AMD. Larger longitudinal studies are needed to clarify its potential biomarker role.

Medicina doi: 10.3390/medicina62050821

Authors: Gabriela Hurtado-Alvarado Karol Iliana Ávila-Soto Marlene Monserrat Juárez Lucía Angélica Méndez-García Verónica Cevallos-López Juan Antonio Peralta-Calcaneo Marcela Esquivel-Velázquez Antonio González-Chávez Julio César Zavala-Castillo Ana Alfaro-Cruz Jaime Héctor Gómez-Zamudio Galileo Escobedo

Background and Objectives: The pathogenesis of liver steatosis is associated with obesity and systemic inflammation, particularly in subjects with body mass index (BMI) above 40 kg/m2 and altered serum levels of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10). Recent evidence suggests that disruption of the blood–brain barrier (BBB) may be associated with the development of steatosis, although limited data are available in humans. Thus, we assessed serum levels of neuron-specific enolase (NSE), transglutaminase 2 (TGM2), and glial fibrillary acidic protein (GFAP) as indirect markers of BBB dysfunction and examined their associations with steatosis severity, TNF-α and IL-10 in patients with morbid obesity. Materials and Methods: We biopsied the liver during bariatric surgery to assess steatosis by histology and serum markers by ELISA. Results: Most study subjects were women aged 38.7 ± 9.9 years with an average BMI of 42.3 ± 7.9 kg/m2 and a steatosis prevalence of 78.9%. After grading steatosis as none (n = 8), mild (n = 17), moderate (n = 8), or severe (n = 5), we found no differences in sex, age, BMI, comorbidities, or laboratory variables, including liver enzymes. One-way ANOVA showed that serum IL-10 was 4-fold less in severe steatosis than in mild steatosis (p = 0.038), whereas TNF-α levels increased twice in severe steatosis compared to no steatosis (p = 0.029). NSE and GFAP serum levels, but not TGM2, increased proportionally to steatosis stage, showing differences between severe steatosis and no steatosis (p = 0.012 and p = 0.0002, respectively). Pearson correlation coefficients showed that NSE and GFAP were significantly associated with TNF-α (r = 0.600 and r = 0.402, respectively), but not with IL-10. Conclusions: Steatosis severity is significantly associated with markers of BBB disruption and systemic inflammation in patients with morbid obesity, suggesting a link between the BBB and liver steatosis.

Medicina doi: 10.3390/medicina62050822

Authors: Hyun Il Kang Seok Joon Lee Feras AlShomer Tae Suk Oh Jong Woo Choi Woo Shik Jeong

Background and Objectives: Head and neck cancer (HNC) frequently necessitates reconstructive surgery due to defects following oncologic resection. The influence of age on reconstructive outcomes in head and neck cancer remains controversial. This study aimed to evaluate the impact of age on oncologic characteristics, reconstructive strategies, and functional outcomes following microvascular free flap reconstruction. Materials and Methods: A retrospective review was conducted on 286 patients who underwent free flap reconstruction for head and neck cancer between 2016 and 2020. Patients were stratified into three age groups: <40 years, 40–60 years, and >60 years. Demographic characteristics, tumor features, reconstructive approaches, complications, and functional outcomes—including postoperative dietary tolerance and tube feeding dependency—were analyzed. Results: The oral cavity was the most common tumor site across all age groups. Advanced-stage tumors (T4) were more frequently observed in older patients (>60 years), although the difference was not statistically significant (p = 0.0575). The overall flap survival rate was 98.6%. The mean hospital stay was 24.6 ± 15.86 days and was significantly longer in the >60-years group (p < 0.001). Postoperative dietary tolerance was comparable across age groups, with 56.8% of patients resuming a regular diet. Tube feeding dependency was slightly higher in the >60-years group but did not reach statistical significance (p = 0.1599). Conclusions: Age alone does not significantly affect reconstructive outcomes following microvascular free flap reconstruction for head and neck cancer. Despite a higher prevalence of comorbidities in and longer hospital stays for older patients, flap success rates and functional outcomes were comparable across age groups.

Medicina doi: 10.3390/medicina62050820

Authors: Egemen Cebeci Kenan Turgutalp Savaş Öztürk Yasemin Özlük Sibel Gökçay Bek Abdullah Şumnu Nurhan Seyahi Mahmut Yavuz Serhan Pişkinpaşa Ömer Faruk Akçay Tamer Sakacı Garip Şahin Bülent Tokgöz Gülizar Şahin İlter Bozacı Belda Dursun Savaş Sipahi Arzu Özdemir Gültekin Süleymanlar Sena Ulu Fatma Betül Güzel Sim Kutlay Ergün Parmaksız İlhan Kurultak Nedim Yılmaz Selçuk Yaşar Yıldırım Meltem Gürsu Caner Çavdar Meryem Timuçin Zeki Aydın Deren Oygar Serdar Kahvecioğlu Müge Üzerk Kibar Dilek Torun Dilek Taymez Mehmet Küçük Serap Demir Leyla Koç Siren Sezer Murat Duranay Simge Bardak Lütfullah Altıntepe Mehmet Koç Alper Azak Ali Rıza Odabaş Zülfikar Yılmaz Saime Paydaş

Background and Objectives: Anemia is a frequent complication of chronic kidney disease (CKD), primarily attributed to erythropoietin deficiency. Interstitial fibrosis (IF), which disrupts the renal interstitium where erythropoietin-producing cells reside, may contribute to anemia independent of glomerular filtration rate (GFR). However, data in primary glomerulonephritis (PGN) are limited and conflicting. Materials and Methods: In this nationwide multicenter registry analysis (TSN-GOLD), 2794 adults with biopsy-proven PGN were included. Interstitial fibrosis was graded semi quantitatively (0–3). Anemia was defined according to KDIGO/WHO criteria. Multivariable logistic regression models were constructed to evaluate the independent association between IF severity and anemia, adjusting for age, sex, eGFR, log-transformed proteinuria, hypertension, diabetes mellitus, and biopsy diagnosis. Interaction between IF and eGFR was assessed. A predefined subgroup analysis was performed in patients with preserved renal function (eGFR ≥ 60 mL/min/1.73 m2). Results: Anemia was present in 34.4% of patients. Although moderate-to-severe IF was more frequent among anemic patients (p < 0.001), IF severity was not independently associated with anemia in multivariable analysis (p-trend = 0.72). Female sex and lower eGFR were independently associated with anemia. A statistically significant IF×eGFR interaction was observed (p = 0.0029), indicating effect modification across renal function levels. The model demonstrated moderate discrimination (AUC = 0.705). In patients with preserved renal function, IF severity was not associated with anemia. Conclusions: In this large multicenter cohort of PGN patients, interstitial fibrosis severity was not independently associated with anemia after adjustment for renal function and clinical covariates. These findings suggest that the association between interstitial fibrosis and anemia in PGN appears largely mediated by renal functional status rather than fibrosis severity alone.

Medicina doi: 10.3390/medicina62050819

Authors: Jamie Sin Ying Ho Gerlyn Zhixuan Wong Aaron Kwun Hang Ho Aloysius S. T. Leow Joy Yi-Shan Ong William Kong Swee Chye Quek Andrew Fu Wah Ho Ching Hui Sia Hoai Thi Thu Nguyen Tiong Cheng Yeo Kian Keong Poh

Aortic valve stenosis (AS) is assessed by echocardiography in clinical practice. Conventionally, the aortic valve area, peak transaortic valve velocity/gradient and the mean transvalvular gradient determine if the AS is categorized as mild, moderate or severe. Recently, the entity of paradoxical low-flow, low-gradient AS despite normal left ventricular ejection fraction (LVEF) was described and flow (as determined by stroke volume indexed to body surface area) was used to further categorize AS. The new European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) guidelines in 2025 recommended a new phenotype-based classification, which improved the prognostication of AS. There are now five phenotypes: (1) concordant high-gradient AS; (2) low-flow, low-gradient AS with reduced LVEF; (3) low-flow, low-gradient AS with preserved LVEF; (4) normal-flow, low-gradient AS with preserved LVEF; and (5) discordant high-gradient AS. These appear to have different underlying pathophysiology, and hence prognostication and therapy. In addition, categories of AS in the setting of reduced LVEF are further divided based on their responses to dobutamine or exercise stress, which may result in different therapeutic strategies. In the transaortic valvular replacement (TAVR) versus the surgical aortic valve replacement (SAVR) era, the classification of these AS groups may have differing implications on the appropriate interventions. Furthermore, there are investigations on the effect of AS on the left ventricle and other chambers and stages of AS based on the extent of cardiac damage, which may have important prognostic value post-AVR. On the other spectrum, there are new developments in imaging analysis, such as using artificial intelligence. This state-of-the-art paper will comprehensively review the important updates in AS and its clinical implications.

Medicina doi: 10.3390/medicina62050818

Authors: Carlo Ronsini Federica Anzelmo Sciarra Giuseppe Cucinella Mariano Catello Di Donna Cono Scaffa Mario Fordellone Stefano Restaino Manuela Ludovisi Giuseppe Vizzielli Vito Chiantera

Background and Objective: This study aimed to identify preoperative and intraoperative factors associated with thoracic complications after bilateral diaphragmatic stripping during cytoreductive surgery for advanced ovarian cancer. Materials and Methods: A retrospective observational study was conducted at the Gynecologic Oncology Unit of the National Cancer Institute “G. Pascale”, Naples, Italy. We included patients who underwent bilateral diaphragmatic stripping between July 2023 and October 2025. Demographic, surgical, and anesthesiologic parameters were recorded. Univariate logistic regression was performed, and a restricted multivariate model including only variables significant at univariate analysis was used to assess predictors of thoracic complications. Results: Forty-seven patients were analyzed, 10 (21%) of whom developed postoperative thoracic complications. Patients with thoracic complications had a higher body mass index (median 28.4 kg/m2, IQR 26.4–29.3 vs. 23.9 kg/m2, IQR 22.8–27.3; p = 0.003) and higher ASA scores (p = 0.033). In univariate analysis, ASA (odds ratio [OR] 3.90, 95% confidence interval [CI] 1.12–17.94, p = 0.046) and BMI (OR 1.45, 95% CI 1.14–2.02, p = 0.009) were significantly associated with thoracic complications. In multivariate analysis, only BMI remained an independent predictor (OR 1.599, 95% CI 1.13–2.68, p = 0.027). Conclusions: Elevated BMI was independently associated with an increased risk of thoracic complications after bilateral diaphragmatic stripping in cytoreductive surgery for ovarian cancer. Careful perioperative management and preventive strategies should be considered in overweight patients.

Medicina doi: 10.3390/medicina62050817

Authors: Inés Palacio Fernanda Hernández-González Jacobo Sellarés Jaume Bordas-Martinez

Pulmonary fibrosis, encompassing idiopathic pulmonary fibrosis (IPF) and other fibrosing interstitial lung diseases (ILDs) with a progressive phenotype (PPF), represents a group of chronic, life-threatening conditions associated with significant morbidity, mortality, and socioeconomic burden. Despite advances in antifibrotic therapies, traditional disease-centered management alone is insufficient to address the multidimensional needs of affected patients. This comprehensive review advocates for a holistic, patient-centered approach to the management of pulmonary fibrosis, integrating pharmacological interventions with systematic comorbidity assessment, pulmonary rehabilitation, psychosocial support, nutritional optimization, early palliative care, social and community reinforcement, and digital health technologies. We examine the evidence supporting each dimension of holistic care, discuss current barriers to implementation—including healthcare fragmentation, limited multidisciplinary protocols, and scarce resources—and outline future perspectives centered on precision medicine and integrated care models. By shifting from a purely organ-focused paradigm to a comprehensive, multidisciplinary strategy, clinicians can improve not only disease outcomes but also quality of life and overall well-being for patients living with fibrosing ILDs.

Medicina doi: 10.3390/medicina62050816

Authors: Sebastian Podlewski Rafał Morga Jacek Antecki Piotr Dubiński Natalia Gołębiowska

Background and Objectives: Functional neurosurgery encompasses surgical interventions aimed at modulating the function of the central and peripheral nervous systems. Spinal cord stimulation (SCS), as a form of neuromodulation, is an established treatment for chronic pain and is increasingly utilized by both anesthesiologists and neurosurgeons. The aim of this study was to evaluate the effectiveness of SCS in patients with chronic neuropathic spinal pain. Materials and Methods: This prospective study included 42 patients who demonstrated a positive response to trial stimulation. Only patients achieving a clinically meaningful response (≥50% pain reduction) during the trial phase were included in the final analysis. Pain intensity and functional disability were assessed using the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI). All patients underwent a two-stage percutaneous implantation procedure using burst stimulation. A follow-up assessment was performed 3–6 months after implantation. Results: A statistically significant reduction in pain intensity was observed (p < 0.0001), with median VAS scores decreasing from 8 to 3, corresponding to a 62.5% reduction in pain intensity and exceeding the minimal clinically important difference (MCID) for VAS. Functional status improved significantly, with ODI scores decreasing from 74% to 38%, markedly surpassing the established MCID threshold. A clinically meaningful reduction in pain (≥50%) was achieved in the majority of patients. All patients requiring opioid analgesics at baseline discontinued their use following SCS implantation, and a reduction in overall analgesic consumption was observed across the cohort. Conclusions: These findings suggest that burst SCS may be an effective treatment option for carefully selected patients with chronic neuropathic spinal pain who are not candidates for conventional spine surgery. However, the results should be interpreted with caution due to the enriched study design and limited follow-up period.

Medicina doi: 10.3390/medicina62050815

Authors: Cristina Angelescu Matei-Alexandru Cozma Radu Bogdan Mateescu Ioana Anca Bădărău

Background and Objectives: Early identification of patients at risk for severe forms of acute cholangitis (AC) is crucial for guiding prompt therapeutic interventions. In addition to traditional biomarkers such as C-reactive protein (CRP), newer indices like the neutrophil-to-lymphocyte ratio (NLR) are cost-effective and easy-to-use diagnostic tools. In the context of limited evidence from Eastern European populations, this study aimed to compare the performance of NLR and CRP in identifying organ dysfunction-based severe presentation of acute cholangitis according to a modified TG18-derived classification. Materials and Methods: We conducted a retrospective study including patients admitted to Colentina Clinical Hospital between January 2021 and September 2025. Demographic, clinical, and laboratory data were collected from medical records, with a focus on admission inflammatory biomarkers: NLR and CRP. Symptom onset-to-presentation time was not recorded. Patients were stratified by disease severity according to a modified organ dysfunction-based severity classification, and comparative statistical analysis, including Receiver Operating Characteristic (ROC) curve analysis, was performed to assess the diagnostic performance and optimal cut-off values of both biomarkers for severe clinical presentation. Results: A total of 364 patients were included, with a median age of 68 years (IQR: 60–78), and a slight female predominance (55.5%). Of these, 231 were classified as non-severe and 133 as severe. Both CRP and NLR were significantly higher in severe cases (p = 0.042 and p = 0.018, respectively. Despite statistical significance, CRP showed limited discriminatory ability, whereas NLR showed only a marginal numerical advantage. ROC analysis showed poor discriminatory ability for both CRP (AUC = 0.564, 95% CI 0.503–0.624, p = 0.042) and NLR (AUC = 0.574, 95% CI 0.513–0.635, p = 0.018) in predicting severe AC incidence. The difference between AUCs was minimal (ΔAUC = 0.010, 95% CI −0.062 to 0.082, p = 0.78, DeLong test). Conclusions: Both CRP and NLR showed limited discriminatory performance in identifying organ dysfunction-based severe presentation of acute cholangitis. The small, non-significant difference between the two markers does not support a meaningful comparative advantage, and neither biomarker appears suitable for reliable early risk stratification on its own.

Medicina doi: 10.3390/medicina62050814

Authors: Chih-Chun Hsiao Yu-Hsuan Chen Chun-Gu Cheng Chun-An Cheng

Background and Objectives: The epidemiological characteristics of Candida species have changed worldwide, with an increasing number of reports on co-infections with non-albicans Candida species (NACs) and multidrug-resistant bacteria. A longer length of hospital stay, more severely ill patients, and empirical antimicrobial use in intensive care units (ICUs) increased the prevalence of Candida healthcare-associated infections (HAIs). If the diagnosis or treatment of invasive candidiasis is delayed, the morbidity and mortality of patients will significantly increase. Materials and Methods: We conducted a nationwide surveillance study to analyze data on HAIs in the ICUs of medical centers and regional hospitals between 2018 and 2023. We assessed the temporal trends of Candida species (including Candida albicans and NACs) across all HAIs, bloodstream infections (BSIs), and urinary tract infections (UTIs), and simultaneously assessed the corresponding trends of Enterococcus faecium (Efm). A linear trend for the proportions of microorganisms from 2018 to 2023 was noted according to the Mantel–Haenszel chi-square test. Spearman’s rank correlation coefficients were used to analyze the correlations between pathogen proportions, systemic antimicrobial agent consumption, and length of ICU stay. Results: The overall proportion of all Candida species in HAIs in the ICUs increased significantly from 15.13% to 16.74% (p < 0.001); this increase was driven mainly by NACs (increasing from 6.84% to 7.91%, p < 0.001) from 2018 to 2023. The proportion of Efm increased significantly, from 7.7% to 11.11% (p < 0.001). The proportions of all Candida species significantly increased in UTIs (from 24.63% to 28.13%, p < 0.001), especially NACs, while the proportion of Efm also increased significantly in UTIs (from 9.47% to 15.32%, p < 0.001). With respect to the UTIs, the proportion of all the Candida species, C.albicans, and NACs were positively correlated with the amount of systemic antibiotics used. A longer hospital stay was strongly correlated with all Candida HAIs and UTIs, especially NACs. Significantly ecological associations between all the Candida strains and Efm were observed for UTIs. Conclusions: This study revealed that a persistent expansion of NAC infections was associated with increased Efm infections and rising antibiotic consumption. The changes in the proportions of different Candida species in UTIs were most pronounced. These findings support an ecological model in which antibiotic stress and chronic critical illness contribute to the expansion of fungal–bacterial co-infections in the ICU setting and underscore the need for integrated antibiotic management and multi-infection surveillance.

Medicina doi: 10.3390/medicina62050813

Authors: Sladjana Bozovic-Ogarevic Zoran Bukumiric Dejan Kojic Milovan Bojic Aleksandra Grbovic Danijela Tasic Dragica Dekic Ljiljana Rankovic-Nicic Suncica Panic Marko Filipovic Zorana Bogicevic Milan Arsic Nebojsa Tasic

Background and Objectives: Idiopathic ventricular arrhythmias commonly occur in patients without structural heart disease and most often present as premature ventricular contractions (PVCs). Although generally considered benign, a high PVC burden may cause symptoms, reduce quality of life, and lead to reversible PVC-induced cardiomyopathy. This study aimed to evaluate long-term outcomes after radiofrequency catheter ablation of idiopathic outflow tract PVCs. Materials and Methods: This single-center retrospective study included 101 patients with idiopathic PVCs who underwent radiofrequency catheter ablation. PVC burden and clinical outcomes were assessed at baseline and during follow-up at 3 months, 12 months, and 5 years. Procedural success, predictors of success, and changes in antiarrhythmic drug therapy were analyzed. Results: During follow-up, a marked reduction in PVC burden was observed compared with baseline values. The median PVC burden decreased from 21.89% at baseline to 0.79% at 3 months, 0.23% at 12 months, and 0.09% at the 5-year follow-up after ablation. Acute procedural success was achieved in 88.1% of patients. Long-term success at 5 years was observed in 80.2% of patients. The use of antiarrhythmic drugs decreased during follow-up. Left ventricular ejection fraction remained stable, with no significant difference between baseline and 5-year values. Monomorphic PVC morphology and procedural success at 12 months were identified as independent predictors of long-term success. Conclusions: Radiofrequency catheter ablation provides effective and sustained reduction in PVC burden in patients with idiopathic outflow tract PVCs, with high acute success rates, durable long-term outcomes, and reduced reliance on antiarrhythmic drug therapy.

Medicina doi: 10.3390/medicina62050812

Authors: Bojana Petrovic Sanja Kostic Ivana Milan Jovanovic Milica Petronijevic Milos Petronijevic Igor Hudic Svetlana Vrzic Petronijevic

Congenital anomalies of the reproductive system represent a heterogeneous group of structural and functional abnormalities affecting both male and female genital organs. These anomalies typically arise during embryogenesis and may remain asymptomatic until they are incidentally identified during evaluation for infertility, recurrent pregnancy loss, or disorders of sexual development. In females, abnormalities include Müllerian duct anomalies and congenital malformations of the uterus, cervix, vagina, and ovaries, such as Mayer–Rokitansky–Küster–Hauser syndrome, septate, unicornuate, bicornuate, and didelphys uteri, and ovarian agenesis and undescended ovaries. In males, congenital conditions such as anorchia, cryptorchidism, hypospadias, ejaculatory duct obstruction, and ejaculatory dysfunction may be associated with impaired spermatogenesis and reduced fertility. Early recognition of these conditions may facilitate timely clinical evaluation and individualized management, which can include surgical correction, hormonal therapy, and reproductive counseling. When appropriate, early diagnosis may support multidisciplinary care, with the aim of optimizing sexual development, preserving reproductive potential, and reducing long-term morbidity associated with congenital anomalies. However, the clinical impact of early detection varies depending on the type and severity of the anomaly. A systematic and multidisciplinary approach may contribute to improved reproductive outcomes and better overall reproductive health in affected individuals. Further research is needed to better define the optimal timing and clinical utility of systematic evaluation strategies in this patient population.

Medicina doi: 10.3390/medicina62050811

Authors: Nikolaos Gkiourtzis Panagiota Michou Anastasia Stoimeni Konstantinos Cheirakis Vera Karatisidou Theopisti Vasileiadou Vasileios Liakos Charalampos Antachopoulos Kali Makedou Nikoleta Printza Despoina Tramma

Background and Objectives: Children with febrile urinary tract infections (fUTIs) may be at risk for kidney scarring. Inflammatory biomarkers may predict the risk of scarring. The aim of this study was to investigate the predictive role of PCT, CRP and other markers in scarring in pediatric patients with first fUTI. Materials and Methods: The study was in accordance with the institution’s ethics committee (No. 108/2023). Included patients underwent a kidney–ureter–cyst ultrasound (US). The primary outcomes of this study were the associations of procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBC) with kidney scarring. The secondary outcomes were the associations of PCT, CRP, and WBC with vesicoureteral reflux (VUR). A p < 0.05 was considered statistically significant. Results: Sixty-five pediatric patients (1–16 years of age) with a first fUTI, from February 2023 to January 2025, were included. Sixteen patients had VUR, and thirteen patients developed kidney scarring. C-reactive protein was significantly elevated in the VUR group (p = 0.026). In a series of logistic regression analyses, abnormal US findings and severe VUR were associated with scarring (p = 0.009 and p = 0.016, accordingly). The optimal cut-off value for PCT in predicting scarring was calculated as 6.05 ng/mL (sensitivity: 36% and specificity: 97%), and for CRP as 3.62 mg/dL (sensitivity: 63.6% and specificity: 62.1%). Conclusions: This study showed a significant difference in CRP levels between the groups with and without VUR. Abnormal US findings and severe VUR were the most significant predictors of kidney scarring. Significant difference was not reached in PCT and WBC levels between the groups with and without VUR or with and without kidney scarring. The small sample size may have influenced the study’s outcomes.

Medicina doi: 10.3390/medicina62050810

Authors: Vilija Gurkšnienė Tadas Alčauskas Dovilė Karosienė Jurgita Urbonienė Fausta Majauskaitė Mindaugas Paulauskas Birutė Zablockienė Dalius Vitkus Ligita Jančorienė

Background and Objectives: Healthcare workers are at heightened risk of SARS-CoV-2 infection. Understanding the duration and protective value of vaccine-induced immunity is critical to inform booster strategies. This study investigates longitudinal dynamics of anti-SARS-CoV-2 receptor-binding domain IgG (anti-RBD IgG) antibodies and their association with infection risk among vaccinated healthcare workers. Materials and Methods: A prospective cohort study was conducted at Vilnius University Hospital Santaros Klinikos, Lithuania. A total of 1778 healthcare workers who completed a primary COVID-19 vaccination series were followed. Blood samples were collected every three months to measure anti-RBD IgG levels. Participants also received up to three booster doses. COVID-19 was identified by PCR, antigen tests, or positive anti-nucleocapsid IgG. For serologically detected cases, infection timing was assigned to the interval between study visits. Antibody dynamics were analyzed across vaccination stages, time, age groups, and circulating SARS-CoV-2 variants. Results: Anti-RBD IgG titers peaked in the first quarter after primary vaccination (mean 7904 AU/mL), declined sharply by quarters 2–3, and rose substantially after booster doses. Following the first booster, titers increased to ~12,598 AU/mL in quarter 1 and continued rising through quarter 3. The highest levels were observed after the second booster (24,456 AU/mL in Q1), followed by gradual decline. A high-titer plateau persisted from quarters 6 to 9 (~21,000 AU/mL), followed by decline in quarters 10–11 and partial rebound in Q12. Approximately 49.6% of participants experienced COVID-19 during follow-up. Antibody response patterns were similar across age groups, with only minor transient differences. Conclusions: COVID-19 booster doses significantly enhance and prolong humoral immunity in healthcare workers compared with the primary vaccination series. However, antibody waning over time emphasizes the need for timely boosters, particularly during periods of variant circulation. These findings support continued booster vaccination and monitoring of long-term immune protection, although anti-RBD IgG should be interpreted as a surrogate marker of humoral rather than overall immunity.

Medicina doi: 10.3390/medicina62050809

Authors: Zofia Wrześniak Bartłomiej Wilk Łukasz Pulik Grzegorz Guzik Paweł Łęgosz

Background and Objectives: Total femoral replacement (TFR) was originally developed for limb salvage following the resection of malignant tumors. Over time, its indications have expanded, now serving as a reconstructive option for failed endoprosthetic replacements and severe trauma cases. Despite its advantages, TFR is a highly complex surgical procedure associated with significant complication rates. This study aims to analyze the management of complications and propose strategies to mitigate associated risks. Materials and Methods: This is a retrospective study conducted on patients from two independent hospitals who underwent TFR for different reasons. Results: Nineteen patients were included: eight underwent TFR for oncological indications, while 11 had the procedure as a revision following failed endoprosthetic arthroplasty or trauma. Postoperative complications were observed in 10 patients (53%), including hip dislocation (21%), mechanical implant failure (11%), infection (21%), wound healing complications (26%), and metal allergy symptoms (5%). Revision surgery was required in six patients (32%), but no cases necessitated amputation. Conclusions: TFR is associated with a high risk of complications, with infection and wound healing issues being the most prevalent. In our experience effective complication management strategies should include early intervention, considering TFR at an earlier stage in non-oncological patients to minimize multiple revision surgeries; allergy screening, assessing for potential metal hypersensitivity preoperatively; dislocation prevention, implementing dual mobility bearings to reduce instability; infection control, utilizing intraoperative local antibiotic therapy in revision cases; and wound management, applying vacuum-assisted closure (VAC) therapy postoperatively to enhance wound healing. Implementing these strategies may improve patient outcomes and reduce the burden of complications associated with TFR.

Medicina doi: 10.3390/medicina62050808

Authors: Barbara Sophie Brunner Paul Emesz Nikolaus Luft Siegfried Georg Priglinger Andreas Ohlmann Stefan Kassumeh

Background and Objectives: The objective of this study is to evaluate whether deferoxamine modulates cell biological properties, such as proliferation and wound closure of porcine corneal endothelial cells (CECs) in vitro, and whether the treatment of CECs with deferoxamine results in an enhanced expression of vascular endothelial growth factor (VEGF). Materials and Methods: Corneal endothelial cells were extracted from porcine globes within 24 h postmortem. Immunohistochemistry for the endothelial Na+/K+-ATPase was performed to confirm the cells’ endothelial origin. To assess CEC viability and proliferation, a water-soluble tetrazolium salt (WST-1) and 5-bromo-2′-deoxyuridine (BrdU) assay were performed. Corneal endothelial wound closure was evaluated using a wound closure assay. VEGF mRNA expression was evaluated using real-time polymerase chain reaction (rt-PCR). Results: The extracted corneal endothelial cells showed a typical hexagonal morphology with Na+/K+-ATPase staining of the cell membrane. The treatment with 200 µM deferoxamine significantly increased CEC viability to 121 ± 24% compared to the control group (p = 0.0024). Corneal endothelial cell proliferation did not show any significant changes under the treatment with deferoxamine (p > 0.05). Both 100 µM and 200 µM deferoxamine led to a significantly smaller remaining wound area of 82.4 ± 6.7% and 78.7 ± 6.2% (p < 0.0001) in comparison to the control group after 24 h of treatment in the wound closure assay. Treatment with 200 µM deferoxamine significantly induced VEGF mRNA expression to 1.67- ± 0.57-fold from 1.00- ± 0.03-fold in the control group (p = 0.0006). Conclusions: Deferoxamine effectively enhances corneal endothelial cell viability and wound healing associated with an overexpression of VEGF. Thus, deferoxamine is a potent modulator of cell biological properties of corneal endothelial cells and maintains their integrity in vitro.

Medicina doi: 10.3390/medicina62050807

Authors: Nikola Andrić Mladen Mikić Damjan Jakšić Slavko Molnar Dejan Javorac Vukadin Milankov

Background and Objectives: The assessment of neuromuscular recovery after ACL reconstruction is crucial for safe return to sport (RTS) in professional soccer players. This retrospective cross-sectional study aimed to compare squat jump (SJ), bilateral countermovement jump (CMJ), and single-leg CMJ performance in three distinct groups: players at 6 months post-ACL reconstruction, players at 9 months post-ACL reconstruction, and healthy controls. Materials and Methods: Seventy-two male players (24 at 6 months post-ACL, 24 at 9 months post-ACL, 24 healthy controls) performed squat jump, bilateral countermovement jump, and single-leg CMJ tests using contact platforms following a controlled warm-up protocol. Results: Significant group differences were observed in all jump tests. At 6 months post-ACL reconstruction, players demonstrated significantly lower squat jump (45.13 ± 6.20 cm) and bilateral countermovement jump (49.67 ± 6.80 cm) heights compared to both 9-month players (SJ: 50.03 ± 5.30 cm; CMJ: 53.79 ± 4.85 cm) and controls (SJ: 51.12 ± 4.97 cm; CMJ: 55.49 ± 5.54 cm) (p ≤ 0.016, η2 = 0.187 and η2 = 0.156, respectively). No significant differences between 9-month and control groups were observed for the squat jump and the bilateral countermovement jump. Regarding the unilateral countermovement jump, the injured leg showed significant performance deficits compared to controls in both the 6-month and 9-month groups (p = 0.001, η2 = 0.378). However, the non-injured leg exhibited deficits only in the 6-month group. Conclusions: Compared to the 6-month post-ACL reconstruction group, the 9-month group showed a marked improvement in bilateral jump performance, indicating substantial neuromuscular recovery over time. However, persistent unilateral deficits in the injured leg remained even at 9 months, underscoring the need for a routine and comprehensive jumping evaluation to identify residual neuromuscular impairments that may require targeted rehabilitation before returning to sport.

Medicina doi: 10.3390/medicina62050806

Authors: Donatella Coradduzza Stefania Sedda Andrea Sanna Alessandra Matilde Nivoli Maria Rosaria De Miglio Ciriaco Carru Massimiliano Grosso Serenella Medici

Background and Objectives: Major Depressive Disorder (MDD) and Bipolar Disorder (BD) lack objective molecular stratification despite partial clinical overlap, particularly during depressive phases. This cross-sectional study explored whether coordinated peripheral biomarker patterns could be identified using an integrated multivariate analytical framework. Materials and Methods: A total of 151 participants (MDD n = 41; BD n = 40; HC (healthy controls) n = 70) were profiled for 42 blood-derived parameters including composite inflammatory indices, hematological markers, trace elements measured by ICP-MS, and circulating BDNF and NLRP3 quantified by ELISA. Data were analyzed using univariate testing, unsupervised dimensionality reduction (PCA, t-SNE), and supervised classification (PLS-DA with cross-validation and permutation testing). Results: Thirty-seven of 42 parameters showed significant inter-group differences (p < 0.05). Circulating NLRP3 concentrations were markedly reduced in both psychiatric groups compared with HC. Composite inflammatory indices (NLR, SIRI, SII) were elevated in MDD. Zinc levels were modestly reduced, while manganese levels were increased in psychiatric cohorts. BDNF showed lower concentrations in MDD and higher concentrations in BD relative to HC. Cross-validated PLS-DA classification for psychiatric disorder vs. controls yielded an accuracy of 89.4% (AUC-ROC 0.947), with permutation testing indicating performance above chance. However, the sample-to-variable ratio and exploratory design warrant cautious interpretation. Conclusions: Multidomain peripheral biomarker profiling identified coordinated biochemical differences across diagnostic groups. These findings suggest the presence of multidimensional peripheral signatures associated with mood disorders within an exploratory framework.

Medicina doi: 10.3390/medicina62050805

Authors: Paolo Groff Stefano De Vuono

Background: One of the most debated scientific topics in recent years is the role of non-invasive respiratory support techniques in the treatment of de novo acute hypoxemic respiratory failure. Until pre-COVID-19, the most accredited guidelines did not make recommendations for or against the use of these techniques in this clinical condition, and the increased risk of adverse events for patients who failed the non-invasive approach was widely reported in the literature. The most recent guidelines recommend the use of HFNC as a first-line technique in the treatment of de novo acute hypoxemic respiratory failure to avoid the need for tracheal intubation. However, the strength of these recommendations remains weak, the quality of the underlying evidence is poor, and their usefulness in deciding which technique to apply to an individual patient is questionable. Aim: The aim of this review was to provide the reader with some critical tools to interpret the different indications regarding the choice of the best non-invasive support technique to be used in this setting. Methods: To this end, we analyzed the available literature on this topic, privileging the works that are most useful in correlating the practical indications to the pathophysiological assumptions. Results and Conclusions: The notable heterogeneity of the studies on which the current recommendations are based, as well as the affirmation of the concept of patient self-induced lung injury (P-SILI), highlights the importance of assessing each patient’s risk of developing this complication, individualizing treatment to the patient’s specific needs, and monitoring the patient during treatment.

Medicina doi: 10.3390/medicina62050804

Authors: Volkan Tasci Ali Fuat Tekin Yunus Emre Tanrıkulu İsmail Özer Onur Taydas Mustafa Ozdemir Omer Faruk Topaloglu Mahmud Islam Mehmet Halil Öztürk

Background and Objectives: Tunneled hemodialysis catheters (TDCs) are essential for vascular access in patients with end-stage renal disease (ESRD). This study retrospectively evaluated the clinical outcomes of permanent TDCs placed at a single center, comparing heparin-coated versus non-heparin-coated catheters. Materials and Methods: A total of 189 patients who underwent permanent TDC placement between January 2021 and January 2022 were included. Patients were categorized by catheter type (heparin-coated, n = 80; non-heparin-coated, n = 109). Catheter failure-free survival was analyzed using the Kaplan–Meier method, with arteriovenous fistula creation treated strictly as a censoring event. Multivariable Cox proportional hazards regression was used to identify independent predictors of catheter failure. Results: Complications were significantly more frequent in the non-heparin-coated group (p = 0.004). Catheter exchange was required exclusively in the non-heparin-coated group (p < 0.001). Kaplan–Meier analysis demonstrated significantly longer failure-free catheter survival in the heparin-coated group (restricted mean 49.0 vs. 41.7 months; Log-Rank p < 0.001). On multivariable Cox regression, the complete absence of events in the heparin-coated group yielded a strong protective point estimate (HR = 0.087, 95% CI: 0.004–1.710), rendering individual patient covariates such as INR and age non-significant. Conclusions: Heparin-coated TDCs were associated with significantly longer failure-free survival and lower complication rates compared with non-heparin-coated catheters. Due to the low overall event rate, individual patient-level covariates including INR did not reach statistical significance in the multivariable model.

Medicina doi: 10.3390/medicina62050803

Authors: Apostolos Makrantonakis Ioannis Mantzoros Orestis Ioannidis Konstantinos Zapsalis Elissavet Anestiadou Styliani Parpoudi Dimitrios Kyziridis Ekaterini Klonou Savvas Simeonidis Stefanos Bitsianis Manousos George Pramateftakis Efstathios Kotidis Stamatios Angelopoulos

Background and Objectives: Intraperitoneal onlay mesh (IPOM) reduces ventral/incisional hernia recurrence but raises concern for adhesions and infection, particularly when the operative field is not strictly clean. We aimed to determine how contamination severity modulates the peritoneal response to intraperitoneal polypropylene mesh. Materials and Methods: In a prospective, randomized, blinded rat study, 60 male Wistar rats were allocated to three groups (n = 20/group) and evaluated at postoperative day (POD) 4 and POD 8 (n = 10/timepoint): A, clean mesh placement; B, small-bowel resection with end-to-end anastomosis without spillage (“potentially septic”); and C, mesh placement followed by intraperitoneal inoculation with Escherichia coli and Staphylococcus aureus (“controlled contamination”). The primary outcome was adhesion severity (Van der Ham scale, 0–3). Secondary outcomes included semi-quantitative histological scores (0–4) for neutrophil infiltration, fibroblast proliferation, neoangiogenesis, and collagen deposition. Prespecified non-parametric analyses were applied. Results: All animals completed follow-up; no pre-sacrifice deaths occurred. Adhesion severity showed no statistically significant differences between Groups A and B at either timepoint (mean POD4: 0.3 vs. 0.6; POD8: 0.4 vs. 0.8; p > 0.05). In contrast, Group C demonstrated markedly higher adhesion scores (mean POD4: 2.3; POD8: 2.4; both p < 0.001 vs. Groups A and B), with a substantially greater proportion of grade 2–3 adhesions. Histological parameters paralleled these findings: at both POD4 and POD8, Group C showed significantly higher neutrophil, fibroblast, neoangiogenesis, and collagen scores compared with Groups A and B (all p < 0.001). No statistically significant within-group temporal differences were observed between POD4 and POD8. Conclusions: In this experimental model, intraperitoneal polypropylene mesh demonstrated similar early biological response patterns in clean and controlled contamination settings, whereas established intra-abdominal sepsis was associated with a marked escalation of inflammation, fibroproliferation, and adhesion formation. These findings suggest that selective use of synthetic intraperitoneal mesh may be considered when contamination is controlled, while caution is warranted in frankly septic environments.

Medicina doi: 10.3390/medicina62050802

Authors: Tautvydas Ribinskas Tautvydas Rugelis Eglė Labanauskaitė Vilius Kviesulaitis Vytautas Zabiela Tomas Kazakevičius

Background and Objectives: Cardiovascular disorders contribute substantially to medical ineligibility for compulsory military service in Lithuania. This study aimed to describe cardiovascular disease patterns and assess their association with military service eligibility among conscription-age individuals treated at a tertiary care center, considering gender, place of residence, age, and the most common cardiovascular causes of medical ineligibility. Materials and Methods: This retrospective hospital-based study included men and women aged 18–26 years with cardiovascular disease diagnoses defined according to ICD-10 codes specified by the Order of the Minister of National Defense of the Republic of Lithuania. Anonymized medical records from the Hospital of the Lithuanian University of Health Sciences Kaunas Clinics were reviewed. Participants were categorized into four military service eligibility classes based on medical history data and were stratified by gender, age, and place of residence. Results: The study included 521 participants (56.6% male, 43.4% female). Gender and residence showed no significant impact on military service eligibility. Younger individuals, particularly those aged 18–19, were more often deemed eligible, while eligibility declined with age. Males more commonly had essential hypertension and hypertensive heart disease, whereas females more frequently presented with paroxysmal tachycardia and other arrhythmias. Hypertension and other severe cardiovascular conditions most strongly reduced eligibility for compulsory military service, whereas rhythm disorders were more often compatible with service. Conclusions: In this hospital-based cohort of conscription-age individuals with cardiovascular disease, gender and place of residence did not significantly influence eligibility for military service. Eligibility declined with increasing age, and hypertension-related cardiovascular disorders were the leading cause of ineligibility among conscripts.

Medicina doi: 10.3390/medicina62050801

Authors: Reem Abdullah Alyoubi Ahmed Abu-Zaid

A few minor, unintentional errors were identified after publication; therefore, the authors wish to make the following corrections to this paper [...]

Medicina doi: 10.3390/medicina62050800

Authors: Alexandros Giannakis Emmanouil Anyfantis Eleni Litsou Chrissa Sioka Spyridon Konitsiotis

Background and Objectives: Primary progressive aphasia (PPA) and its variants—logopenic (lvPPA), semantic (svPPA), and nonfluent/agrammatic (nfvPPA)—are progressive neurocognitive syndromes characterized by predominant language impairment and associated with heterogeneous underlying neuropathologies. Accurate diagnosis remains challenging due to overlapping clinical features and complex pathobiological mechanisms. Fluorodeoxyglucose positron emission tomography (FDG-PET), which reflects regional cerebral glucose metabolism, may provide valuable insights into both the diagnosis and pathophysiological characterization of PPA. Materials and Methods: We reviewed the current literature and identified 48 original research articles that utilized FDG-PET in the evaluation of at least one PPA variant. Eight studies focused exclusively on lvPPA, six on svPPA, and two on nfvPPA, either alone or in comparison with other neurodegenerative diseases. Eighteen studies evaluated at least two PPA variants, while thirteen compared multiple PPA variants with other neurodegenerative disorders. Results: Most studies identified characteristic hypometabolic patterns for each PPA variant: left temporoparietal regions in lvPPA, bilateral anterior temporal regions with left predominance in svPPA, and left posterior frontal regions in nfvPPA. These variant-specific metabolic signatures may support differential diagnosis. Additionally, FDG-PET provided important insights into disease progression, including associations with worsening language impairment, evolution toward broader neurodegenerative syndromes, and correlations with specific neurocognitive deficits. These findings are largely consistent with other neuroimaging modalities and disease-specific biomarkers. However, limitations such as small sample sizes and the lack of autopsy confirmation in most studies limit the robustness of the results. Conclusions: FDG-PET appears to be a valuable tool for the diagnosis, differential diagnosis, and pathophysiological understanding of PPA. Nevertheless, large-scale, multicenter investigations incorporating pathologically confirmed cases to further validate its clinical utility are needed.

Medicina doi: 10.3390/medicina62050799

Authors: Ozgur Albuz Dilek Pirim Sevinc Akcay Tugba Gurkok Tan Seda Ekici Sami Akbulut

Background and Objectives: Gastric cancer remains a leading cause of cancer-related mortality worldwide and develops through complex interactions between environmental factors, microbial dysbiosis, and host molecular pathways. Although Helicobacter pylori infection is a well-established risk factor, emerging evidence suggests that broader alterations in the gastric microbiome may also contribute to carcinogenesis. However, the associations between gastric cancer-associated microbial taxa and host gene expression profiles remain insufficiently characterized. This study aimed to identify host gene signatures associated with gastric cancer-related microbial taxa through a descriptive analysis integrating microbiome-derived taxa with transcriptome data. Materials and Methods: Microbial taxa associated with gastric cancer were systematically retrieved from the Disbiome database. Taxon set enrichment analysis (TSEA) was performed using the MicrobiomeAnalyst platform to identify host genes associated with gastric cancer-associated taxa. Importantly, TSEA relies on healthy reference data from the Human Microbiome Project and does not establish gastric cancer-specific interactions or causal relationships. Gene expression levels were subsequently evaluated using The Cancer Genome Atlas (TCGA) PanCancer stomach adenocarcinoma (STAD) dataset by comparing tumor and matched normal gastric tissues. Gene interaction network and transcription factor (TF) enrichment analyses were conducted to explore predicted regulatory relationships. Results: Among 64 microbial taxa associated with gastric cancer, 43 were reported as elevated. After removing overlapping taxa across studies, 37 elevated and 21 reduced taxa were retained for analysis. TSEA identified 11 host genes associated with gastric cancer-related microbial taxa. Transcriptomic analysis demonstrated significant downregulation of DPP6 and DLG2, while KDM4D, USP34, and VDR were significantly upregulated in gastric cancer tissues compared with normal controls. Network and TF enrichment analyses revealed predicted co-expression and co-localization patterns among these genes, suggesting their potential involvement in immune-related processes, epigenetic regulation, and cellular organization. Conclusions: This descriptive study identifies distinct host gene expression signatures associated with gastric cancer-associated microbial dysbiosis. This study is purely associative and hypothesis-generating; no causal or mechanistic inferences are made. TSEA used healthy reference data and therefore does not reflect gastric cancer-specific host–microbe interactions. The findings provide a basis for future hypothesis-driven research but require validation in independent cohorts.

Medicina doi: 10.3390/medicina62040798

Authors: Sofija Davidović Terzić Siniša Babović Svetlana Pavin Aleksandar Miljković Nikola Denda Sava Barišić

Syphilitic panuveitis is a severe and diagnostically highly challenging manifestation of ocular syphilis. Its predominant posterior-segment involvement and its tendency to mimic noninfectious or viral uveitis may delay etiologic recognition and increase the risk of permanent vision loss. Rhegmatogenous retinal detachment (RRD) is a rare but vision-threatening complication that likely reflects advanced, inflammation-induced disruption of the vitreoretinal interface. A narrative literature review was conducted using the PubMed, Scopus, and Web of Science databases (January 2000 to 10 September 2025). Studies addressing the clinical presentation, imaging findings, pathophysiology, and management of syphilitic panuveitis and associated rhegmatogenous retinal detachment were analyzed. Infectious mimickers were also presented, with particular emphasis on West Nile virus (WNV). Evidence was synthesized qualitatively. Posterior uveitis and panuveitis are one of the most common ocular manifestations of syphilis. Posterior segment involvement in ocular syphilis is frequently bilateral, typically presenting with dense vitritis, retinal vasculitis, and optic neuropathy. RRD is a rare presenting complication, most often developing in areas of prior inflammatory retinitis and arising due to retinal necrosis, persistent vitreoretinal traction, and early proliferative vitreoretinopathy, which increases surgical complexity and may limit functional recovery. HIV coinfection often modifies disease severity. In relevant endemic or seasonal settings, WNV-associated ocular inflammation represents an important diagnostic pitfall. Syphilitic panuveitis should be considered early in patients presenting with unexplained posterior uveitis or panuveitis. Routine testing for syphilis and HIV in the uveitic laboratory palette, together with targeted evaluation for infectious mimickers, is essential to reduce diagnostic delay and avoid inappropriate immunosuppression. RRD should be recognized as a marker of advanced, inflammation-induced vitreoretinal interface damage requiring timely antimicrobial therapy and early involvement of vitreoretinal surgery.

Medicina doi: 10.3390/medicina62040797

Authors: Seong Gyu Kim Sang Gyu Kwak

Background and Objectives: Acute kidney injury (AKI) is a frequent and life-threatening complication in patients with liver cirrhosis (LC). Nephrotic-range proteinuria may reflect underlying structural renal vulnerability; however, its association with AKI severity in cirrhosis remains unclear. Materials and Methods: We conducted a retrospective cohort study of 408 adults with LC admitted to a tertiary referral hospital between January 2016 and December 2025. Nephrotic-range proteinuria was defined as a urine protein-to-creatinine ratio (UPCR) ≥3.5 g/g measured within 7 days before or at admission. AKI was staged using serum creatinine-based Kidney Disease: Improving Global Outcomes criteria. Baseline creatinine was defined as the lowest value within 7 days before admission; if unavailable, the lowest stable value within the preceding 3 months was used. Severe AKI was defined as KDIGO stage 2–3. Multivariable logistic regression was performed to evaluate the association between nephrotic-range proteinuria and severe AKI after adjustment for age, sex, diabetes mellitus, hypertension, chronic kidney disease (CKD), sepsis, ICU admission, and Child–Pugh class. Results: Of the 408 patients, 56 (13.7%) had nephrotic-range proteinuria. Severe AKI occurred more frequently in patients with nephrotic-range proteinuria than in those without (39.3% vs. 21.9%), corresponding to an absolute risk difference of 17.4 percentage points (p = 0.008). In the adjusted model, nephrotic-range proteinuria was associated with a higher likelihood of severe AKI (adjusted odds ratio [OR], 2.27; 95% confidence interval [CI], 1.17–4.41; p = 0.015). CKD (adjusted OR, 2.26; 95% CI, 1.33–3.81; p = 0.002), ICU admission (adjusted OR, 2.03; 95% CI, 1.22–3.39; p = 0.007), and Child–Pugh class C versus A (adjusted OR, 3.50; 95% CI, 1.37–8.93; p = 0.009) were also significantly associated with severe AKI. Conclusions: Among hospitalized patients with LC, nephrotic-range proteinuria was associated with a higher likelihood of severe AKI. Quantitative proteinuria assessment may help identify patients at increased risk of advanced renal dysfunction, although causal inference is limited by the retrospective observational design.

Medicina doi: 10.3390/medicina62040796

Authors: Donna de Levante Raphael Lora J. Kasselman Wendy Drewes Isabella Wolff Luke Betlow Joshua De Leon Allison B. Reiss

Dementia caregiving represents a major public health challenge, with spousal caregivers assuming the greatest burden. Spouses, themselves typically older adults, provide high intensity, long-term, and largely unpaid care across all stages of cognitive decline. Despite their central role in dementia care, the health consequences experienced by spousal caregivers remain insufficiently characterized in the literature and inadequately addressed in clinical and public health practice. This structured narrative review synthesizes current evidence on the multidimensional impact of dementia caregiving on the physical, psychological, cognitive, social, and financial health of spousal caregivers. It further contextualizes these consequences within the trajectory of dementia progression, and identifies interventions, support systems, and policy considerations necessary to mitigate caregiver burden. Spousal caregivers experience disproportionate burden due to continuous, escalating responsibilities that often mirror the progressive deterioration of their partners. Emotional burdens, including uncertainty during pre-diagnostic stages, role strain, conflict, loss of intimacy, and anticipatory grief. Physically, spouses endure musculoskeletal strain, sleep disruption, poor nutrition, and heightened frailty risk. Psychologically, spousal caregivers exhibit elevated rates of depression, anxiety, loneliness, and stress-related disorders. Socially, caregivers experience substantial isolation, stigma, and erosion of social networks. Financial hardship, including early retirement, reduced employment, and uncompensated care hours, further exacerbate stress. Evidence suggests that chronic caregiving stress contributes to biological changes such as immune dysregulation, inflammation, acceleration, aging, and potential cognitive decline in caregivers themselves. Caregiver burden influences patient outcomes as evidenced by increased emergency department use, falls, and earlier institutionalization in persons with dementia whose caregiver is subjected to a high burden. Current care models rarely include routine, caregiver assessment or structured guidance following diagnosis, resulting in substantial unmet needs. Effective mitigation requires integrated, stage-sensitive interventions, including psychosocial support, caregiver education, respite services, culturally tailored programs, and digital health tools, alongside broader policy reforms to reduce financial and structural barriers.

Medicina doi: 10.3390/medicina62040795

Authors: Vivek Joseph Varughese Chandler Richardson James Pollock Patryk Czyzewski Ashley Lyons Hata Mujadzic Deborah M. Hurley Michael Cryer Sunil V. Rao Akshay Kumar

Background: The effective regurgitant orifice area to left ventricular end-diastolic volume (EROA/LVEDV) ratio has been proposed to distinguish proportionate from disproportionate functional mitral regurgitation and to guide patient selection for transcatheter edge-to-edge repair (TEER). Methods: We conducted a multicenter, retrospective cohort study of 221 patients undergoing TEER with the Mitraclip system. Preprocedural echocardiographic parameters, including EROA, LVEDV, diastolic indices, and chamber volumes, were systematically collected. The primary outcome indicative of symptom worsening was defined as Heart Failure Hospitalizations (HFH) requiring IV diuresis/death in the one year following clip placement. Association of the preprocedural EROA/LVEDV ratio and symptom worsening was assessed using multivariate regression models and ROC-AUC. Results: In the one-year follow-up, 87 patients (39.36%) had symptom worsening. In the multivariate regression analysis, preprocedural EROA/LVEDV ratio was associated with symptom worsening at one year (OR: 0.95 (0.92–0.97, p value < 0.01). In the ROC model, the pre-procedural EROA/LVEDV ratio had an AUC value of 0.74 (0.69–0.83), with a moderate value for predicting symptom worsening at one year. Conclusions: Results of the study proved that a lower pre-procedural EROA/LVEDV ratio had a significant association with symptom worsening, with the ratio proving to have a moderate value for predicting symptom worsening/death at one year.

Medicina doi: 10.3390/medicina62040794

Authors: Sergiu Marian Cazacu Costin Teodor Streba Cristian Constantin Claudiu Marinel Ionele Ion Rogoveanu Alexandru Valentin Popescu Mirela-Marinela Florescu

The prevalence of Crohn’s disease has increased over the last few decades, even in developing countries, whereas that of intestinal tuberculosis has decreased, which places both diseases at an epidemiological crossroads. Crohn’s disease and intestinal tuberculosis share many clinical, endoscopic, imaging, and pathological features, which sometimes make differential diagnosis very difficult; an accurate diagnosis is, however, very important since an erroneous treatment can worsen the evolution or delay proper therapy. The association between past TB infection and Crohn’s disease can make the diagnosis especially hard. This review summarizes current data on specific features that allow differentiation between Crohn’s disease and intestinal tuberculosis, paying particular attention to the microbiome, clinical signs, endoscopy, cross-sectional imaging, bacteriological, and immunological findings detailed. The importance of computerized models and scores for the differentiation is also detailed, because common features may make the differentiation based on a single criterion difficult.

Medicina doi: 10.3390/medicina62040793

Authors: Roxana-Elena Stefan Adrian Constantin Daniela Dinu Florin Achim Alexandru Rotariu Florin Grama Horia-Dan Liscu Lucian Iordache Dragos-Viorel Scripcariu Anthony Rasuceanu Silviu Constantinoiu Dragos Predescu

Background and Objectives: Neoadjuvant chemoradiotherapy is a key component of the treatment strategy for locally advanced rectal cancer (LARC), both through its direct impact on oncological prognosis and by increasing the likelihood of sphincter-preserving surgery. Oncological prognosis improves dramatically following a complete pathological response to neoadjuvant therapy. Identifying predictors of response to neoadjuvant therapy has been a challenge over the past two decades, and these factors have not been fully identified. This study aimed to analyze the clinical, biological, and therapeutic factors associated with tumor response following neoadjuvant therapy in patients with locally advanced rectal cancer, with the aim of identifying independent predictors of the absence of a complete pathological response and optimizing personalized treatment strategies. Materials and Methods: This retrospective study included a cohort of 122 patients (81 men and 41 women), with a mean age of 63.5 years, diagnosed with locally advanced rectal cancer at two centers with expertise in colorectal surgery between January 2018 and December 2023. Patients received neoadjuvant treatment in two regimens: long-course chemoradiotherapy with oral radiosensitizing chemotherapy (82 patients) and total neoadjuvant therapy consisting of chemoradiotherapy followed by consolidation chemotherapy (40 patients). A series of clinical, biological, and therapeutic variables was analyzed for their association with pathological responses. Results: According to the Ryan score, the overall complete response rate following neoadjuvant therapy was 17.2%. pCR was observed more frequently in patients treated with total neoadjuvant therapy than in those treated with standard chemoradiotherapy. Elevated pre-treatment CEA levels were independently associated with a higher risk of unfavorable tumor response. The radiation dose and interval between completion of radiotherapy and surgery were significantly associated with tumor regression. Conclusions: These results underscore the importance of personalizing neoadjuvant therapy to improve cancer prognosis. Furthermore, optimizing tumor regression could lead to the potential expansion of sphincter-preserving resection techniques, which would have a direct and significant impact on the quality of life of these patients.

Medicina doi: 10.3390/medicina62040792

Authors: Efthymia Nestora Elena Ioannidou Panayiotis Patrikelis Vasiliki Folia

Background and Objectives: The joint study of cerebral asymmetries and bipolar disorder (BD) has long attracted the interest of researchers and clinicians. Nevertheless, despite the increasing awareness of hemispheric asymmetries in BD, the combined investigation of these two constructs constitutes a relatively recent area of inquiry. The main objective of the present systematic review is to systematically examine the existing literature in order to identify, integrate and critically discuss evidence of hemispheric asymmetry in BD patients in terms of brain anatomy, physiology and neuropsychological function. The initial hypotheses support the presence of atypical cerebral asymmetry and differential hemispheric activation as a function of mood states in BD. Materials and Methods: Following the collection and analysis of numerous research papers through several databases and search engines, specific papers were identified and screened according to specified inclusion and exclusion criteria. Research papers on the adult bipolar population were included, while papers including comorbidity with other disorders, lesions, or an underage or elderly population, as well as meta-analyses and reviews, were excluded. This paper aligns with the procedures in the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA 2020) guidelines, and was assessed for risk of bias according to the Cochrane guidelines by the Newcastle–Ottawa Scale (NOS). Results: A total of 56 papers were identified as eligible in this review. Despite inconsistent findings across the included studies, an emerging pattern suggests the presence of atypical hemispheric asymmetry in BD, both in terms of specific brain structures and functional activity. Moreover, several studies associate depressive states with increased activation of the right hemisphere, whereas manic states appear to be linked with increased activation of the left hemisphere. Conclusions: These findings support the aforementioned hypotheses and partly align with the theoretical framework of emotional laterality theories. However, although certain patterns were observed, a comprehensive understanding of functional hemispheric asymmetry in BD has not yet been achieved. The presence of contradictory findings highlights the need for further extensive and systematic research to improve understanding of this topic.

Medicina doi: 10.3390/medicina62040791

Authors: Ludvig Letica Ivana Šutić Lubina Zdrinko Brekalo Đordano Bačić Jelena Roganović Ana Đorđević Ingrid Šutić Udović Ivona Letica Ivana Kotri Ines Mrakovčić-Šutić

Background and Objectives: The incidence of colorectal cancer (CRC) in developed Western countries is constantly growing. CRC represents the third most common cancer and the second leading cancer-related cause of death worldwide. Innate and adaptive immunity play a pivotal role in the tumor response, but many of these interactions are still not well understood. Granulysin (GNLY) is an effector, cytolytic molecule, present in human cytotoxic granules of different lymphocyte subpopulations, mainly in cytotoxic T cells and NK cells. Pore-forming proteins GNLY, perforin and granzymes play a key role in cell-mediated immune responses against tumors and infections. Materials and Methods: We aimed to analyze perforin and GNLY-mediated cytotoxicity in the peripheral blood of patients with CRC by flow cytometry. Simultaneously, the cells were labeled with monoclonal antibodies against perforin, GNLY and different surface antigens (CD3, CD4, CD8 and CD56). Phenotypes of lymphocyte subpopulation and expression of perforin and GNLY were analyzed using intracellular and surface immunofluorescence. Results: Total perforin and GNLY expressions in peripheral blood mononuclear cells (PBMC) were significantly lower than in the control group. Statistically significant differences were observed in the distribution of perforin and GNLY expression in different stages of tumors classified according to Dukes’, indicating that the percentage of total perforin and GNLY was significantly diminished in accordance with tumor progression. Perforin and GNLY expression were significantly reduced in NK and NKT cells, accompanied by reduced cytolytic potential in patients with CRC and a consequent reduction in their ability to eliminate tumors and infected cells. Conclusions: The determination of cytotoxic potential may provide a valuable assessment of a patient’s immune status and represent a novel therapeutic target. Patients with CRC exhibit markedly impaired perforin- and GNLY-mediated cytotoxicity that correlates with disease progression. Assessment and restoration of cytolytic potential may therefore serve as indicators of immune competence and promising therapeutic strategies to improve perioperative and oncologic outcomes.