Search Results (2,678)

Human papillomavirus (HPV) infection remains the principal etiological factor in cervical cancer development worldwide, with Eastern Europe continuing to demonstrate disproportionately high cervical cancer incidence and mortality rates. Regional disparities in screening implementation, vaccination coverage, and HPV genotype distribution contribute substantially to the persistent burden of HPV-related disease. In recent years, increasing attention has focused on molecular biomarkers and the vaginal microbiome as complementary approaches for improving cervical cancer prevention strategies. This systematic review aimed to evaluate recent evidence regarding HPV genotype distribution, molecular biomarkers, vaginal microbiome composition, and their implications for cervical cancer prevention in Eastern Europe. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, Embase, and the Cochrane Library for studies published between January 2020 and May 2026. This systematic review was conducted in accordance with the PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420261391136). Studies from Eastern European populations reporting data on HPV genotype distribution, screening strategies, vaccination, molecular biomarkers, or vaginal microbiome composition were included. HPV prevalence in screening populations ranged from approximately 12% to over 20%, with HPV16 consistently identified as the predominant genotype across all included studies. However, non-16/18 high-risk genotypes, particularly HPV31, HPV51, HPV52, HPV66, and HPV68, represented a substantial proportion of infections in several Eastern European cohorts. Studies evaluating CINtec PLUS cytology and HPV E6/E7 mRNA testing demonstrated improved specificity for identifying clinically significant cervical lesions compared with HPV DNA testing alone. Emerging evidence also suggested associations between vaginal dysbiosis, increased microbial diversity, persistent high-risk HPV infection, and progression to cervical intraepithelial neoplasia. Although the 9-valent HPV vaccine provides coverage for most circulating high-risk genotypes identified in the region, vaccination uptake remains inconsistent throughout Eastern Europe. The findings of this systematic review support the growing importance of extended HPV genotyping, molecular biomarkers, and microbiome-related approaches in cervical cancer prevention strategies in Eastern Europe. Strengthening organized screening programs, expanding vaccination coverage, and improving access to molecular diagnostic technologies remain essential priorities for reducing the regional burden of HPV-related disease. Full article

Non-alcoholic fatty liver disease (NAFLD), now increasingly termed metabolic dysfunction-associated steatotic liver disease (MASLD), is a growing cause of chronic liver disease with limited treatment options. Glucagon-like peptide-1 (GLP-1) receptor agonists, approved for type 2 diabetes and obesity, possess metabolic effects that may render them suitable for treating NAFLD and metabolic dysfunction-associated steatohepatitis (MASH). To evaluate the therapeutic effects of GLP-1 receptor agonists in adults with NAFLD, non-alcoholic steatohepatitis (NASH), MASLD, or MASH. PubMed, Scopus, Embase, and the Cochrane Library were systematically searched using keywords related to NAFLD and GLP-1 receptor agonists. Given heterogeneity in populations, designs, and outcomes, findings were synthesized narratively. The review is registered with PROSPERO (CRD420261337353). Twelve studies met the inclusion criteria. The most consistent outcome was a reduction in hepatic fat, seen with semaglutide, liraglutide, dulaglutide, and beinaglutide. Improvements in liver enzymes, particularly alanine aminotransferase, were less consistent and best regarded as supportive rather than definitive evidence of histological improvement. Histological benefits were strongest for steatohepatitis resolution in non-cirrhotic MASH. Fibrosis findings were mixed, with the greatest benefit in F2–F3 MASH and limited improvement in established cirrhosis. GLP-1 receptor agonists were generally well tolerated, with gastrointestinal symptoms the most common adverse effects. GLP-1 receptor agonists show promising liver-related benefits in NAFLD and MASH, particularly in obesity, type 2 diabetes, or earlier-stage disease. Their effects on advanced fibrosis and long-term outcomes remain uncertain, warranting larger, longer-term studies. Full article

Background/Objectives: Chronic non-specific low back pain is a leading cause of disability. Although therapeutic exercise and manual therapy are commonly recommended, their relative effects are often interpreted using broad therapeutic categories. This network meta-analysis aimed to compare the relative effectiveness of specific therapeutic exercise and manual therapy techniques on post-treatment self-reported disability in adults with chronic non-specific low back pain. Methods: A systematic review and frequentist random-effects network meta-analysis were conducted according to Cochrane recommendations and PRISMA-NMA guidance. The protocol was registered in PROSPERO (CRD42022331411). Randomized controlled trials including adults aged 18–65 years with chronic non-specific low back pain were searched in CENTRAL, PubMed, PEDro, Google Scholar, and SciELO up to 31 March 2026. Disability was assessed using the Roland–Morris Disability Questionnaire or Oswestry Disability Index. Effects were synthesized as standardized mean differences. Risk of bias was assessed with RoB 2, and confidence in network estimates was evaluated using CINeMA. Results: Forty-five studies were included. Compared with control/placebo, the largest favorable estimates were observed for equipment-based Pilates, stabilization with motor control, stabilization exercise, soft tissue manipulation, and Pilates Mat. Equipment-based Pilates showed the largest favorable estimate with moderate-confidence evidence, and soft tissue manipulation also showed moderate-confidence evidence. However, heterogeneity was substantial, and confidence in most favorable exercise estimates was low. Conclusions: Specific exercise and manual therapy techniques may reduce post-treatment disability in adults with chronic non-specific low back pain. Equipment-based Pilates and soft tissue manipulation showed favorable signals supported by moderate-confidence evidence. However, the findings do not support a definitive hierarchy of efficacy or categorical superiority of therapeutic exercise over manual therapy. Full article

Background: Chlorella, a unicellular green alga, is currently one of the most popular algae supplements due to its high content of bioactive compounds. Chlorella’s wide range of macro- and micronutrients, including chlorophyll compounds and carotenoids, has been suggested to influence various disorders related to the digestive and nervous systems. This review’s primary purpose was to critically analyze the effects of Chlorella intake on gut microbiota and brain function. Methods: The authors conducted a systematic review with narrative synthesis of peer-reviewed articles written in English and published in PubMed, Web of Science, and Scopus spanning the years 2009 to 2026 (PROSPERO registration number CRD42024527705). The search protocol was performed following PRISMA guidelines. Primary outcomes encompassed physiological variables, such as gut microbial composition, short-chain fatty acids, brain-derived neurotrophic factor, and hippocampal cell density. Secondary outcomes were assessed through neurobehavioral tests and psychological questionnaires. Results: Out of the 1333 articles identified, 47 studies were deemed eligible, and 21 met the predefined criteria, subsequently incorporated into this systematic review. In total, 10 articles documented interventions involving Chlorella and their effects on the gut microbiota, whereas 11 articles investigated several variables pertinent to brain function. Most of the studies included were conducted in animal models, with only a limited number of human trials. Nineteen studies (90%), predominantly preclinical, reported positive associations between Chlorella consumption, gut microbiota modulation, and physiological or neurobehavioral markers related to the gut–brain axis. Conclusions: Chlorella consumption may modulate gut microbiota composition and function, potentially influencing brain-related processes. However, the available literature lacks studies simultaneously addressing both gut microbiota and brain health parameters limiting the understanding of the underlying physiological mechanisms. Full article

Background/Objectives: Nutrition plays a core role in chronic disease management, and there is growing interest in the health impact of plant-based diets (PBDs) in people with overweight or obesity. We conducted this systematic review and meta-analysis to summarize the evidence on the health effect of PBDs compared to omnivorous diets in overweight or obese individuals. Methods: We searched the databases Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform from inception to 3 January 2024. Two review authors independently screened studies for eligibility, extracted data, evaluated the risk of bias, and rated the certainty of the evidence using GRADE. This study is registered with PROSPERO, CRD42021225525. We used random-effects meta-analysis to analyze data. Results: Of 2664 records identified, 10 randomized controlled trials (RCTs) and six ongoing studies met the inclusion criteria. The available evidence suggests little to no difference between plant-based and omnivorous diets for body weight, systolic blood pressure, diastolic blood pressure, serum glucose, serum insulin, insulin sensitivity, total cholesterol, triglyceride, HDL cholesterol and body fat mass. Plant-based diets may slightly reduce LDL cholesterol. They may also reduce BMI and HbA1c, although the certainty of the evidence is very low. Longer-duration dietary interventions (14 weeks or more) showed greater improvements in BMI, LDL cholesterol and HbA1c. Conclusions: Plant-based diets may represent a dietary option for people with overweight or obesity and may support modest improvements in selected cardiometabolic outcomes, although the available evidence is limited and uncertain. Most outcomes showed little or no difference between PBDs and comparison diets, while the observed effects on BMI and HbA1c were supported by very low certainty evidence. Full article

Background: Early-onset ventilator-associated pneumonia (EO-VAP) is a frequent complication in comatose patients requiring endotracheal intubation. This systematic review and Bayesian meta-analysis assesses the effectiveness of antibiotic prophylaxis in preventing EO-VAP in this population. Methods: Randomized controlled trials (RCTs) and observational studies enrolling adult comatose patients (GCS ≤ 8) requiring endotracheal intubation and reporting EO-VAP incidence, late-onset VAP, ICU mortality, 28-day mortality, or ICU length of stay were included. Studies without a control group or not focused on comatose patients were excluded. Following PRISMA 2020 guidelines, a comprehensive search was conducted across three databases from inception to 31 March 2026. Risk of bias was assessed using the RoB2 tool for RCTs and the ROBINS-I tool for observational studies. Results: In accordance with Cochrane Handbook recommendations, only RCTs were included in the quantitative analysis. Five RCTs (735 patients) demonstrated a significant reduction in EO-VAP incidence with antibiotic prophylaxis (RR 0.46 [95% CI: 0.35–0.59], p = 0.001, I² = 0%), with the strongest effect in neurological patients (RR 0.41 [95% CI: 0.32–0.53], NNT = 5.4). No significant effect on mortality was demonstrated. Bayesian analysis confirmed these findings (posterior median RR 0.44 [95% CrI: 0.33–0.59], P(benefit) = 100%). Limitations: The analysis was limited by the small number of RCTs and the absence of data on antimicrobial resistance. Conclusions: Antibiotic prophylaxis reduces EO-VAP incidence in comatose patients, particularly neurological patients. A general recommendation cannot currently be made pending further evidence on mortality and antimicrobial resistance. Registration: This systematic review was prospectively registered on PROSPERO (CRD42024580280). Full article

Background: Assisted reproductive technology (ART) is increasingly utilized worldwide, and approximately 30% of ART pregnancies result in twin gestations. Chorionicity strongly influences perinatal risk, yet its specific impact on ART-conceived twins has not been systematically clarified. Objective: To compare obstetrical and neonatal outcomes in assisted ART-conceived monochorionic (MC) versus dichorionic (DC) twin pregnancies and evaluate the impact of chorionicity on maternal and perinatal outcomes. Methods: This systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD42024600292). PubMed, Scopus, and Web of Science were searched through October 2024 for studies comparing obstetrical and neonatal outcomes in ART-conceived monochorionic and dichorionic twin pregnancies. Eligible studies were qualitatively synthesized. Results: Thirty-five studies comprising 15,648 ART-conceived twin pregnancies were included, including 371 monochorionic and 15,277 dichorionic pregnancies. MC pregnancies consistently demonstrated less favorable perinatal outcomes compared with DC pregnancies, including an earlier gestational age at delivery, increased prematurity, lower birth weight, and higher rates of perinatal mortality. By contrast, maternal complications, such as hypertensive disorders, gestational diabetes mellitus, PROM, and cesarean delivery, varied considerably across the studies without a consistent association with chorionicity. The baseline maternal characteristics were generally comparable between the groups. Conclusion: Monochorionicity in ART-conceived twin pregnancies is associated with increased adverse neonatal and perinatal outcomes, particularly prematurity and perinatal mortality, while maternal outcomes appear less clearly influenced by chorionicity. Standardized prospective studies are needed to further clarify the chorionicity-specific risks in ART twin pregnancies. Full article

Background: Chronic non-specific low back pain (CNSLBP) is highly disabling, and the efficacy of transcranial direct current stimulation (tDCS) remains uncertain. This systematic review and meta-analysis evaluated the effects of standalone and combined tDCS on pain and functional disability in adults with CNSLBP, with secondary comparisons between M1 and DLPFC stimulation. Methods: PubMed, Web of Science, Science Direct, China National Knowledge Infrastructure, Chinese Quarterly Virtual Information Platform, and Wanfang Data were searched up to February 2026. Randomized controlled trials of standalone or combined tDCS in adults with CNSLBP were included. Meta-analyses assessed pain intensity and functional disability, with subgroup analyses comparing stimulation targets and meta-regression exploring protocol parameters. Evidence certainty was evaluated using GRADE, and the protocol was registered with PROSPERO (CRD420261341095). Results: Meta-analysis of 17 trials showed that standalone tDCS did not significantly reduce pain intensity, whereas tDCS combined with peripheral interventions yielded a significant analgesic effect, and anodal stimulation over M1 significant reduced pain intensity. However, neither standalone nor combined tDCS significantly improved functional disability, subgroup differences between M1 and DLPFC were non-significant, and meta-regression identified no significant moderators. Descriptive findings showed potential benefits of tDCS for pain catastrophizing and postural control, with mild adverse events. Conclusions: Moderate-certainty evidence suggests that standalone tDCS is unlikely to provide clinically meaningful analgesia for CNSLBP. Low-certainty evidence indicates that anodal M1 tDCS combined with structured peripheral interventions, particularly exercise, may produce analgesic benefits, but this finding requires cautious interpretation. Full article

Background: Childhood obesity is increasingly associated with gut microbiome dysbiosis. This systematic review (PROSPERO CRD420251131354) evaluates evidence from studies published between 2020 and 2026 assessing how nutritional and lifestyle interventions influence gut microbiota in children with obesity. Methods: A systematic search of PubMed, EMBASE and EBSCO identified 21 interventional studies involving children aged 5–18 years with obesity, with the last search conducted in April 2026. Interventions comprised prebiotics, probiotics, synbiotics, postbiotics, high-fiber diets, calorie-restricted dietary approaches, and lifestyle modifications such as physical activity. Microbiome outcomes were analyzed using 16S rRNA sequencing, quantitative real-time polymerase chain reaction (qPCR), or metagenomics. Risk of bias was evaluated using the RoB 2 and ROBINS-I (version 2) tools. Due to substantial heterogeneity in study design, participant characteristics, intervention types, and analytical methods, a meta-analysis was not feasible. Results: Across 21 studies, nutritional interventions included measurable but heterogeneous alterations in gut microbiome composition. Inulin supplementation was associated with a significant increase in alpha diversity and with higher relative abundances of Bifidobacterium, Blautia, Megasphaera, Subdoligranulum, and Eubacterium coprostanoligenes. Synbiotic supplementation increased Prevotella and Dialister and reduced the Firmicutes/Bacteroidetes ratio. High-fiber dietary interventions increased Faecalibacterium, Bifidobacterium, and Clostridium, while reducing Bacteroides, and were associated with shifts in metabolic pathways related to carbohydrate, lipid, and nucleotide metabolism. Calorie-restricted diets and combined diet–exercise interventions increased beneficial taxa such as Akkermansia muciniphila, improved microbial diversity, and correlated with favorable metabolic and anthropometric outcomes. Overall, nutritional and lifestyle interventions in pediatric obesity were associated with taxon-specific and context-dependent microbiome changes, rather than uniform restructuring. Conclusions: Nutritional interventions can modulate gut microbiota diversity, composition, and predicted function in pediatric obesity; however, the observed effects vary substantially across studies. The limited number of trials, small sample sizes, and methodological heterogeneity underscore the need for larger, standardized studies to better define clinical and therapeutic implications. Full article

Purpose: To evaluate the effectiveness of serious games, including virtual reality-based interventions, in improving clinical skills acquisition among undergraduate and postgraduate health science students. Methods: This systematic review was prospectively registered in PROSPERO (CRD42024589035) and conducted in accordance with PRISMA 2020 guidelines. PubMed, Scopus, Web of Science, and ScienceDirect were searched from inception to 31 August 2025. Eligible studies examined serious games, simulation-based platforms, or immersive and non-immersive virtual reality interventions designed to support clinical skills development. Outcomes were classified using a predefined hierarchical framework aligned with Miller’s pyramid, distinguishing performance-based clinical competence, clinical reasoning, and secondary educational outcomes. Owing to substantial heterogeneity in interventions, comparators, and assessment methods, a narrative synthesis was performed. Results: Thirteen studies involving 892 participants were included. Serious games and virtual reality-based interventions were associated with generally favorable outcomes for knowledge acquisition, self-efficacy, motivation, satisfaction, and anxiety reduction. Improvements in clinical reasoning were reported in several studies, and some studies demonstrated benefits in performance-based clinical competence, particularly in simulation and virtual reality settings. However, findings for objective performance-based outcomes were mixed, with some studies reporting no statistically significant between-group differences. Heterogeneity in outcome definitions and limited reporting of standardized effect sizes reduced cross-study comparability. Conclusions: Serious games, including virtual reality-based interventions, may serve as complementary, scenario-based learning strategies in health sciences education. The most consistent effects were observed for cognitive and learner-centered outcomes, whereas evidence for objective gains in performance-based clinical competence remains variable. Further high-quality studies using standardized outcome frameworks, validated performance-based assessments, effect sizes, confidence intervals, and longer follow-up are needed. Full article

Background: Programmed death-1 (PD-1) inhibitors have significantly improved survival outcomes in melanoma; however, questions persist regarding comparative efficacy across regimens and the predictive value of PD-L1 expression as a biomarker. We therefore performed a meta-analysis evaluating outcomes according to PD-L1 expression status using the most recent follow-up data from each study. Methods: A systematic search was conducted in PubMed, Cochrane and ClinicalTrials.gov from 1 January 2010 to 1 April 2025 for phase II and III randomized clinical trials (RCTs) investigating PD-1 inhibitors as monotherapy or combined with other immune checkpoint inhibitors (ICIs) or targeted therapy in the adjuvant/metastatic setting. Pooled estimates were calculated with random-effects models, and risk of bias was assessed using the Cochrane RoB 2 tool. The present meta-analysis was performed following PRISMA guidelines and was registered in PROSPERO (ID: CRD420251090090). Results: Fifteen RCTs including 9979 patients were included. In the overall analysis, PD-1 inhibitors were associated with significantly improved overall survival (OS, HR = 0.75, 95% CI: 0.66–0.86) compared with control treatments. In the unresectable or metastatic setting, progression-free survival (PFS) was also significantly improved (HR = 0.61, 95% CI: 0.49–0.76). Survival benefits were observed in both PD-L1-positive and PD-L1-negative tumors, with improved PFS in PD-L1-positive (HR = 0.63, 95% CI: 0.48–0.83) and PD-L1-negative patients (HR = 0.58, 95% CI: 0.44–0.77), as well as improved OS in PD-L1-positive (HR = 0.69, 95% CI: 0.59–0.80) and PD-L1-negative patients (HR = 0.79, 95% CI: 0.67–0.93), without evidence of effect modification by PD-L1 expression. PD-1 inhibitor-based regimens were not associated with a statistically significant increase in grade 3–4 treatment-related adverse events (RR = 1.13, 95% CI: 0.71–1.79); however, heterogeneity was substantial (I² = 96.0%). Conclusions: PD-1 inhibitor-based therapies significantly improve survival outcomes in advanced melanoma across PD-L1 subgroups. No clear evidence of differential treatment benefit according to PD-L1 expression was observed, suggesting limited utility as a standalone predictive biomarker. Further studies integrating molecular and immune profiling are warranted to optimize individualized treatment selection. Full article

Background: This systematic review evaluates the evidence on sustainable practices in dentistry. It focuses on effective measures, innovative technologies, strategies for reducing the carbon footprint, life cycle assessments (LCA), attitudes toward “green” dentistry, and educational approaches. Methods: A systematic search was conducted in five databases (Cochrane Library, Embase, LILACS, MEDLINE via PubMed, and Scopus) without language restrictions in accordance with PRISMA. The review was registered in PROSPERO (CRD420251056821). Results: A total of 2395 records were identified; after removing 394 duplicates, 2001 remained for screening. After title and abstract screening, 154 full-text articles were evaluated, of which 51 studies were included. The included studies addressed life cycle assessments of dental materials, sustainable clinical practices, and educational measures. Environmentally friendly materials and procedures, such as reusable personal protective equipment and water-saving technologies, demonstrate significant potential for reducing environmental impact. Despite generally high acceptance among dentists and patients, implementation is often limited by financial and knowledge-related barriers. Conclusions: The implementation of sustainable materials and procedures is crucial for reducing environmental impact. Equally important are the integration of ecological content into education and appropriate financial and political frameworks to promote sustainable dentistry. Full article

Objective: The current investigation aims to assess the clinical efficacy of intraoral photographic assessment in detecting dental caries of varying severity and to assess different variables, such as the type of dentition, examiner experience, and the type of imaging equipment, on evaluative clarity. Methods: This meta-analysis of the PRISMA-DTA systematic review and diagnostic test accuracy was conducted. They searched electronic databases such as PubMed, Web of Science, Scopus, Embase, and Cochrane Library from the beginning of time up to January 2025. The studies had to have evaluated intraoral photographic caries because they were required to have compared it with clinical intraoral examination and provide extractable tooth-level 2 × 2 data. Enamel (ICDAS 1 3), dentine (ICDAS 4 6), and any caries (ICDAS 1 6) were analyzed separately in a meta-analysis. A random-effects model was used to compute pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves. Subgroup analysis was done on a pre-specified basis according to dentition, type of examiner, and imaging device. This study has been registered in PROSPERO with reference number 2026 CRD420261330820. Results: Twenty-three studies were retrieved through a comprehensive search and were stratified by severity into three categories. In the case of enamel caries, sensitivity was 0.65 (95% CI: 0.62–0.68), specificity was 0.95 (95% CI: 0.94–0.95), DOR was 36.74 (95% CI: 12.44–108.49), and the AUC was 0.87. In the case of dentine caries, the pooled sensitivity and specificity were 0.86 (95% CI: 0.85–0.87) and 0.96 (95% CI: 0.96–0.97), respectively, which produced the DOR of 176 (95% CI: 91.2–339.6) and the AUC of 0.94. Any caries had a pooled sensitivity of 0.81 (95% CI: 0.80–0.83), specificity of 0.97 (95% CI: 0.96–0.97), DOR of 64.04 (95% CI: 11.65–351.94), and AUC of 0.888. Subgroup analyses revealed that diagnostic accuracy was greater when the lesions were severe. Conclusions: Intraoral photographic assessment has a moderate level of accuracy in detecting enamel lesions and has a clinically acceptable level of accuracy in detecting dentine caries. The clinical efficacy increased with the severity of lesions and was consistent with high specificity at all levels of threshold. Imaging on smartphones could be a promising method for caries screening. Full article

Background: Selenium (Sel) supplementation has been proposed as an antioxidant adjunct in Graves’ orbitopathy (GO), with early randomized evidence suggesting benefits in quality of life (QoL), ocular involvement, and disease progression in mild GO. However, subsequent trials across populations with different Sel status and disease severity have yielded inconsistent findings. This systematic review and meta-analysis of randomized controlled trials (RCTs) reassessed the efficacy of Sel supplementation in GO. Methods: PubMed, Scopus, and the Cochrane Library were searched from inception to 1 May 2026 for RCTs, comparing Sel supplementation with placebo or no Sel supplementation in patients with GO (PROSPERO “CRD420261395074”). Heterogeneity was assessed using I² statistics and Cochran’s Q test. Risk ratios (RRs) were calculated using the Mantel–Haenszel method, and mean differences (MDs) using the Inverse-Variance method. Random-effects models with restricted maximum-likelihood estimation were applied. Results: Five RCTs including 303 patients were analyzed, of whom 165 (56%) received Sel. Sel supplementation was associated with a significant reduction in clinical activity score (MD −1.05; 95% CI −1.61 to −0.48; I² = 52%; p < 0.01). No significant differences were observed in palpebral aperture (MD −0.12; 95% CI −1.22 to 0.98; I² = 58%; p = 0.83), although this anatomical parameter should be interpreted cautiously because it may be influenced by thyroid functional status and hyperthyroidism-related Müller muscle hyperfunction. No significant differences were observed in QoL improvement (RR 1.72; 95% CI 0.43 to 6.92; I² = 86%; p = 0.24) or visual function (MD 6.31; 95% CI −1.40 to 14.03; I² = 45%; p = 0.11). Conclusions: Sel supplementation may improve clinical activity score in patients with Graves’ orbitopathy, but this finding should be interpreted cautiously given the small number of trials, limited sample size, and clinically relevant heterogeneity. Current evidence does not show consistent benefits for palpebral aperture, quality of life, or visual function. Larger RCTs stratified by baseline Sel status and disease severity are needed before firm conclusions can be drawn. Full article

Background: Ischemic stroke remains a leading cause of mortality and disability worldwide. Despite extensive preclinical research, most neuroprotective strategies have failed to translate into clinical benefit, partly due to methodological variability. The transient intraluminal filament middle cerebral artery occlusion (tifMCAO) model is widely used, yet its implementation lacks consistency. This review aimed to characterize tifMCAO methodologies in adult rats and examine how experimental variability relates to reported outcomes. Methods: A systematic review was conducted following PRISMA guidelines. Studies using tifMCAO in adult rats were included. MEDLINE (PubMed), Web of Science, and Scopus were searched up to March 2025. Risk of bias was assessed using the SYRCLE tool and reporting quality using the ARRIVE checklist. The protocol was registered in PROSPERO (CRD420251140869). Results were synthesized narratively. Results: A total of 125 studies were included. A commonly used framework involved male Sprague–Dawley rats (6–12 weeks), silicone-coated monofilaments, occlusion durations of 60–120 min (most frequently 90 min), and isoflurane anesthesia, although this reflects methodological convergence rather than true standardization. Substantial variability was observed across methodological parameters. Variations in ischemia duration, filament properties, and anesthesia were associated with differences in infarct size, blood–brain barrier disruption, and functional outcomes. Conclusions: The tifMCAO model shows partial methodological convergence alongside significant variability influencing outcomes. Improved standardization and reporting are essential to enhance reproducibility and translational relevance. Full article