Transtibial pull-out repair is widely used for the treatment of medial meniscus posterior root tears (MMRTs). However, the optimal suture material remains unclear despite differences in biomechanical and biological properties between absorbable and non-absorbable sutures. This study aimed to evaluate whether suture material influences clinical and radiological outcomes after transtibial pull-out repair for MMRTs through a systematic review and meta-analysis. This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. Eligible studies reporting clinical or radiological outcomes after transtibial pull-out repair for MMRTs were included. Extracted data included patient-reported outcomes, magnetic resonance imaging (MRI)-based meniscal healing, meniscal extrusion, Kellgren-Lawrence (KL) grade progression, and conversion to total knee arthroplasty (TKA). Random-effects meta-analyses and subgroup analyses were performed according to suture absorbability, and meta-regression was used to explore potential sources of heterogeneity. Sixteen studies encompassing 647 patients were included; these comprised one Level II study, seven Level III studies, and eight Level IV studies. No significant subgroup differences according to suture absorbability were identified for changes in International Knee Documentation Committee score (P = 0.07), Lysholm score (P = 0.43), meniscal extrusion (P = 0.19), MRI-based meniscal healing (P = 0.77), KL grade progression (P = 0.75), or conversion to TKA (P = 0.06). The pooled healing proportions were 0.60 (95% CI, 0.33-0.82) for non-absorbable sutures and 0.68 (95% CI, 0.00-1.00) for absorbable sutures. The corresponding pooled proportions of conversion to TKA were 0.05 (95% CI, 0.00-1.00) and 0.22 (95% CI, 0.10-0.38), respectively. The available evidence did not identify statistically significant differences in clinical or radiological outcomes between absorbable and non-absorbable sutures after transtibial pull-out repair for MMRTs. However, because these findings were derived primarily from indirect comparisons across heterogeneous studies, they should not be interpreted as evidence of equivalence, and the current evidence remains insufficient to determine whether suture absorbability independently influences postoperative outcomes. IV; systematic review and meta-analysis of Level II-IV studies.
Heat stress is an increasingly important constraint on cattle welfare, fertility, productivity, and developmental resilience. DNA methylation may mediate part of the molecular response to thermal exposure, but current studies differ widely in tissue type, exposure model, assay platform, and endpoint definition. This review systematically synthesizes evidence linking heat stress to DNA methylation changes in cattle and evaluates whether a quantitative meta-analysis of global methylation responses is currently feasible. A PRISMA-informed search was conducted for peer-reviewed bovine studies published between 2015 and early 2026. The PECO framework defined cattle or cattle-derived biological material as the population, heat stress or thermal challenge as the exposure, thermoneutral, cooled, or non-stressed conditions as comparators, and DNA methylation-related measures as outcomes. The predefined primary quantitative endpoint was global DNA methylation or hydroxymethylation reported as a continuous outcome. Locus-specific, promoter-level, DMC, DMR, and multi-omics studies were retained for structured qualitative synthesis. Global methylation studies often reported non-significant bulk changes, whereas sequencing-based and promoter-level studies revealed extensive tissue-specific and locus-specific methylation signatures involving oxidative stress, immune regulation, metabolism, endocrine signaling, and developmental programming. A formal pooled meta-analysis was not statistically defensible because fewer than three independent studies reported complete and comparable group-level data for the predefined global methylation endpoint. Heat stress in cattle appears to induce targeted, tissue-specific methylome remodeling rather than a consistent genome-wide shift in global methylation. Future studies should report extractable group-level methylation statistics, standardized heat-load metrics, tissue and cell-composition information, and phenotypic outcomes to enable robust meta-analysis. Beyond reporting standardization, future trial and cohort designs should prospectively incorporate paired global and locus-specific methylation endpoints to enable meta-analytic pooling within the next research cycle.
The role of blood pressure (BP) lowering in patients with heart failure (HF) with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) remains uncertain, and it is unclear to what extent the existing benefits of therapies are mediated by BP reduction. A systematic review and meta-analysis of randomised clinical trials was conducted, comparing any BP lowering treatment to placebo, usual care or another drug class in patients with HFmrEF/HFpEF. The primary endpoint was a composite of cardiovascular death and HF hospitalisation. Data were pooled using a random effects meta-analysis and meta-regression with inverse variance weighting expressed as a risk ratio (RR) and its 95% CI. 18 studies were identified totalling 39 452 patients. Pharmacological BP lowering led to a significant reduction in the primary composite endpoint (RR 0.86, 95% CI 0.83 to 0.89; p≤0.001), but there were significant differences between drug classes (p value=0.018), with evidence of benefit with sodium-glucose cotransporter 2 inhibitor, mineralocorticoid receptor antagonist, angiotensin-receptor neprilysin inhibitor and glucagon-like peptide-1 receptor agonists but not other drug classes. Meta-regressions found no significant association between the degree of BP reduction and treatment effects (coefficient slope=-0.0125, p=0.304). Similarly, pharmacological BP lowering was associated with a reduction in HF hospitalisations (RR 0.83, 95% CI 0.79 to 0.86; p≤0.001), but treatment effects were not related to degree of BP reduction (coefficient slope=-0.0121, p=0.528). In patients with HFmrEF/HFpEF, there was no significant association between pharmacological BP lowering and clinical outcomes, suggesting that BP lowering alone is unlikely to explain all the benefits observed with the use of recently established HF therapies. CRD42025631539.
Elevated intracranial pressure (ICP) in isolated single-suture craniosynostosis (SSC) may contribute to neurodevelopmental impairment, yet reported prevalence varies widely. This systematic review and meta-analysis estimate the pooled prevalence of elevated ICP in isolated SSC and evaluate potential modifiers including suture subtype, measurement timing, and assessment modality. PubMed, MEDLINE, Embase, Web of Science, and Scopus were searched (inception to February 2026). Eligible studies reported ICP outcomes in children with isolated SSC using invasive monitoring or optical coherence tomography (OCT). Pooled prevalence was estimated using random-effects meta-analysis with Freeman-Tukey transformation, stratified by measurement modality (invasive vs. OCT). Subgroup analyses evaluated suture type and measurement timing. Heterogeneity was explored through meta-regression and sensitivity analyses. Seventeen studies (720 patients; 1982-2025) met inclusion criteria. All invasive studies applied a uniform ≥ 15 mmHg threshold; OCT studies used four distinct retinal nerve fiber layer algorithms approximating this threshold. Pooled prevalence was 38% (95% CI, 26-51%; I2 = 77.0%) by invasive monitoring (13 studies; n = 448) and 43% (95% CI, 28-61%; I2 = 83.8%) by OCT (4 studies; n = 272). The combined estimate was 39% (95% CI, 30-50%). By suture type, prevalence ranged from 33% (metopic) to 43% (sagittal) without significant differences (p = 0.89). Intraoperative studies yielded higher prevalence than preoperative (52% vs. 34%; p = 0.13). Meta-regression explained only 11.7% of between-study variance. Elevated ICP is reported in a substantial proportion of children with isolated SSC, although prevalence estimates vary considerably based on diagnostic methodology and timing of assessment. Across included studies, pooled estimates ranged between 30-50%. Noninvasive screening, such as OCT, may aid adequate detection in at-risk patients. Standardized ICP thresholds and longitudinal neurocognitive studies are needed to guide management and optimize outcomes.
Bone metastases are common in patients with metastatic neuroendocrine neoplasms (NENs) and frequently result in skeletal complications. The current role of anti-resorptive agents for these patients is not known. A systematic review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a PICOS framework searching the Embase, Medline, PubMed, Google Scholar, Cochrane library and Web of Science databases to identify studies reporting the use of anti-resorptive agents in patients with well-differentiated NENs who have bone metastases. A total of 2424 articles were identified with 104 selected for full text review. After review, five retrospective studies were included in the review. Study design was heterogenous, and treatment details typically poorly described. A total of 348 patients were included in the review, of whom 206 received anti-resorptive treatment. One study (N = 19) reported an increase in overall survival with use of monthly bisphosphonates whereas no difference in survival with use of anti-resorptive agents were identified in three studies. The response to anti-resorptive therapy was positively associated with overall survival in one study. One study reported a significant reduction in SRE in the group receiving anti-resorptive therapy. Significant toxicity from anti-resorptive therapy was reported in 15.2% of patients in one study whereas treatment complications were not documented in the other three studies. Currently, there are insufficient data as to the role of anti-resorptive agents in patients with NENs and a prospective trial is needed.
Gum Arabic (Acacia senegal) has shown a vital effect in improving glycemic, lipid, and cardiometabolic outcomes in adults. However, its overall effect remains uncertain because findings have been inconsistent across studies for weight, BMI, FBG, and HbA1c, and no quantitative meta-analysis has established its pooled effect. This study aimed to evaluate the effects of oral Gum Arabic (GA) supplementation, compared with placebo, on glycemic, lipid, and cardiometabolic outcomes in adults, including healthy individuals and those with type 2 diabetes mellitus and/or metabolic syndrome. We systematically searched PubMed, Cochrane Central, and Scopus for RCT studies comparing any dose of oral GA to Placebo or the standardized treatment. Outcomes assessed were BMI, weight, FBG, HbA1c, and lipid parameters. Statistical analysis was performed using RevMan, with I² statistics for heterogeneity with a random-effects model. Six RCTs (476 participants) met the inclusion criteria and were included. GA showed significant reduction in BMI (MD - 0.38; 95% CI: -0.47, - 0.29; p < 0.0000; I²= 0%; Fig. 2), weight (MD - 1.00; 95% CI: -1.59, - 0.41; p = 0.0009; I²= 0%; Fig. 3), and FBG (MD - 29.76; 95% CI: -51.88, - 7.65; p = 0.008; I²= 93%; Fig. 4). Sub-analysis of healthy versus non-healthy patients showed a statistically significant reduction of weight in the healthy group (MD - 0.99; 95% CI: -1.58, - 0.40; p = 0.001; I²= 0%; Fig. 10). GA showed some effect on lowering weight, BMI, and glycemic control in adults. Findings suggest that GA may be a promising nutritional intervention for managing cardiometabolic risk factors and weight reduction in adults. However, these results should be taken cautiously due to the limited number of trials, short follow-up periods, and high heterogeneity for fasting blood glucose. The online version contains supplementary material available at 10.1007/s40200-026-02034-y.
Lutetium-177-PSMA radioligand therapy ([177Lu] Lu-PSMA) is an emerging targeted treatment for metastatic castration-resistant prostate cancer (mCRPC). We evaluated the comparative efficacy, safety, and quality-of-life (QoL) impact of [177Lu] Lu-PSMA versus contemporary standard-of-care (SOC) regimens in mCRPC. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Adult participants with PSMA-positive mCRPC (n = 2113) randomized to [177Lu] Lu-PSMA or SOC were included. Primary outcomes were overall survival (OS) and radiographic progression-free survival (rPFS). Secondary outcomes included PSA response, QoL (FACT-P), and adverse events. Treatment effects were pooled using random-effects models. Six RCTs were analyzed. Primary intention-to-treat analysis did not demonstrate a statistically significant overall survival improvement (HR 0.81; 95% CI 0.62-1.06); however, sensitivity analysis adjusting for control-arm crossover suggested a survival benefit (HR 0.76; 95% CI 0.59-0.96). [1⁷⁷Lu] Lu-PSMA significantly improved rPFS (HR 0.55; 95% CI 0.43-0.71), PSA response (RR 2.33; 95% CI 1.38-3.93), and delayed QoL deterioration (HR 0.58; 95% CI 0.51-0.66). The intervention increased low-grade xerostomia and grade ≥ 3 thrombocytopenia, though overall severe adverse events were comparable to SOC. Limitations include inter-trial heterogeneity, control-arm crossover diluting ITT estimates, and imaging-based selection bias. [177Lu] Lu-PSMA improves rPFS, biochemical response, and QoL in mCRPC, with an OS benefit apparent after accounting for crossover. These findings support integrating [177Lu] Lu-PSMA into clinical practice. Additional trials are required to determine optimal treatment sequencing and efficacy in taxane-naïve populations. The protocol of this systematic review and meta-analysis is registered under PROSPERO, having ID CRD420251151366.
Yoga is a non-pharmacological intervention that promotes holistic health and helps manage clinical symptoms. There has been growing interest in integrating yoga into occupational therapy to address specific disorders. This systematic review aims to evaluate the current literature on yoga and mood disorders, identifying the potential use of yoga in occupational therapy to manage symptoms and support occupational participation in adults experiencing mood disorders. Six databases were searched. Data were extracted from 22 peer-reviewed articles published between 2002 and 2024 using the Population, Intervention, Comparison and Outcomes framework. The Critical Appraisal Skills Programme checklist was used for quality appraisal of included studies. The 'metafor package' was used to conduct a meta-analysis and generate a forest plot for data synthesis. An I 2 statistic was used to quantify heterogeneity of the meta-analysis, and the trim and fill non-parametric method was used for sensitivity analyses. Yoga has a moderate positive effect in supporting symptom management (i.e. depressive and anxiety symptoms) and daily functioning, including cognitive functioning, of adults experiencing mood disorders. Yoga can mitigate barriers to occupational participation for adults with mood disorders through supporting symptom management. Rigorous studies are needed to establish yoga's effects on mood disorders.
This systematic review and meta-analysis aimed to evaluate the treatment outcomes of root perforation repair in permanent teeth and identify relevant prognostic factors. A comprehensive search of PubMed, Embase, Scopus, Cochrane Library, Web of Science, and Google Scholar identified studies published between January 2000 and February 2026. Studies reporting treatment outcomes of repaired root perforations in permanent teeth with ≥12 months of follow-up were included. Two investigators independently performed study selection, data extraction, and risk of bias assessment using the Joanna Briggs Institute Critical Appraisal Checklist. Level and certainty of evidence were assessed using the Oxford Centre for Evidence-Based Medicine Levels of Evidence and the Grading of Recommendations Assessment, Development and Evaluation approach. Random-effects meta-analyses estimated the proportion of favorable outcomes and associations with preoperative prognostic factors. Nine observational studies evaluating non-surgical root perforation repair were included, of which seven contributed to the meta-analysis. The pooled favorable outcome was 89.7% (95% CI: 83.0%-94.9%). Smaller perforations (≤3 mm) were associated with higher odds of a favorable outcome than larger defects (OR=2.69; 95% CI: 1.29-5.59; p=0.008), while maxillary teeth demonstrated higher odds than mandibular teeth (OR=2.31; 95% CI: 1.12-4.75; p=0.023). Tooth type, perforation location, gender, preoperative radiolucency, and preoperative signs and symptoms were not significantly associated with favorable outcomes. Non-surgical root perforation repair appears to be associated with generally favorable treatment outcomes, particularly in smaller perforations (≤3 mm) and maxillary teeth. These findings should be interpreted cautiously given the substantial clinical heterogeneity and low-certainty evidence.
Virtual surgical planning (VSP)-assisted reconstruction is increasingly used as an alternative to conventional free-hand (FH) techniques in mandibular and maxillary free-flap reconstruction. This systematic review and meta-analysis compared clinical outcomes and proposed a Reconstruction Complexity-Completeness classification. PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, and reference lists were searched from inception to 20 June 2026. Comparative studies were eligible. Risk of bias was assessed using RoB 2 or the Newcastle-Ottawa Scale. Random-effects meta-analyses used restricted maximum likelihood estimation and Hartung-Knapp adjustment. Forty-two studies included 2763 patients (1204 VSP; 1559 FH). VSP significantly reduced operative time (33 studies; MD -64.75 min, 95% CI -83.51 to -46.00), ischemia time (15 studies; MD -37.40 min, 95% CI -48.97 to -25.82), and hospital stay (16 studies; MD -1.75 days, 95% CI -3.43 to -0.08). VSP was associated with significantly lower odds of bony non-union (OR 0.31, 95% CI 0.16-0.59) and malocclusion (OR 0.14, 95% CI 0.03-0.64), whereas flap loss, surgical site infection, and plate exposure did not differ significantly. VSP-assisted reconstruction was associated with improved operative efficiency, shorter hospitalization, and lower odds of bony non-union and malocclusion, while no statistically significant differences were detected in flap loss, surgical site infection, or plate exposure. The proposed classification may support complexity-adjusted reporting and comparison.
The expanding use of biologic and small-molecule therapies for ulcerative colitis (UC) has raised concerns regarding perioperative safety. We conducted a network meta-analysis to compare short-term postoperative complications associated with preoperative exposure to these agents in patients undergoing colorectal surgery. We systematically searched PubMed, Web of Science, and the Cochrane Library through September 15, 2025, for cohort studies of adults with UC who were exposed to biologic or small-molecule therapy within 12 weeks prior to surgery. Interventions included biologic therapy, small-molecule therapy, and no biologic or small-molecule therapy (control). The primary outcome was overall postoperative complications at 30 and 90 days. Venous thromboembolism (VTE) was assessed as a key secondary outcome. Random-effects network meta-analysis was performed using risk ratios (RRs) with 95% confidence intervals (CIs). Sixteen retrospective cohort studies involving 3235 patients were included. At 30 days, ustekinumab and tofacitinib were associated with lower overall postoperative complication rates than control (RR: 0.29; 95% CI: 0.09-0.96; and RR: 0.66; 95% CI: 0.46-0.96, respectively). Anti-tumor necrosis factor (TNF) therapy was associated with higher complication rates compared with vedolizumab, ustekinumab, and tofacitinib at 30 days (RR: 1.27; 95% CI: 1.00-1.63; RR: 3.67; 95% CI: 1.12-12.03; and RR: 1.61; 95% CI: 1.14-2.27, respectively). At 90 days, anti-TNF therapy was associated with higher complication rates than control (RR 1.20, 95% CI 1.03-1.40), although the 90-day analysis was based on limited data. VTE rates were similar across treatments at both time points. Preoperative ustekinumab and tofacitinib were associated with fewer 30-day postoperative complications than control or anti-TNF therapy, while vedolizumab was associated with fewer complications than anti-TNF therapy. At 90 days, anti-TNF therapy was associated with higher complication rates compared with control. These findings, particularly at 90 days based on limited data, should be interpreted with caution and require confirmation in well-designed prospective studies with rigorous adjustment for confounding factors.
Pulmonary rehabilitation (PR) has been widely studied and established as an effective intervention in several chronic pulmonary diseases. Nevertheless, evidence in adults with asthma remains inconclusive. . To assess the efficacy of PR, including at least education and exercise training (ET), in adults with asthma. . This systematic review followed PRISMA guidelines. Four databases were searched from inception to November 2025. We included randomized clinical trials in adults with asthma who underwent a PR intervention compared to other interventions (including PR within education and ET components), usual care, or no intervention. Primary outcomes were asthma control, lung function, exercise capacity, and airway inflammation. Certainty of evidence and risk of bias were assessed. . Sixteen studies were included, and thirteen in at least one meta-analysis. Most studies enrolled moderate-to-severe asthma. Meta-analysis results showed significant differences in favor of PR in asthma control, exercise capacity, quality of life, anxiety, and depression compared to control group (CG). PR showed significant differences at short-term follow-up in asthma control and quality of life. No significant differences were observed for lung function, airway inflammation, physical activity levels, and body composition. Most studies had a high risk of bias, and the certainty of evidence was very low for some outcomes. . PR improved asthma control, exercise capacity, quality of life, anxiety, and depression in adults with asthma compared to CG. Nevertheless, these findings should be interpreted cautiously because of the high risk of bias, low certainty of evidence for some outcomes, and uncertainty in sensitivity analyses.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes mellitus and obesity. Their metabolic, anti-inflammatory, and osteogenic effects raise important questions regarding their influence on spinal fusion. To date, no systematic review has specifically investigated how GLP-1RAs influence outcomes following the common anterior cervical discectomy and fusion (ACDF). This study aimed to evaluate the association between perioperative GLP-1RA use and outcomes following ACDF. Following PRISMA guidelines, MEDLINE, Embase, PubMed, and the Cochrane Library were searched from inception to February 2026 for studies evaluating GLP-1RA exposure in the context of ACDF. Eligible studies included human observational cohort studies. Data were extracted independently by two reviewers. Eight retrospective cohort studies analysing 311,402 ACDF patients were included, of whom 8,182 were GLP-1RA users matched to non-users. Random-effects meta-analysis demonstrated significantly lower odds of pseudarthrosis among GLP-1RA users at 6 months (OR = 0.60, 95% CI: 0.52 to 0.71; I² = 16.6%), 12 months (OR = 0.62, 95% CI: 0.53 to 0.73; I² = 39.1%), and 24 months (OR = 0.67, 95% CI: 0.57 to 0.79; I² = 34.9%). Findings for reoperation, dysphagia, deep vein thrombosis, and readmission were heterogeneous and inconsistent across studies. Perioperative GLP-1RA use was associated with lower odds of pseudarthrosis. However, evidence regarding other postoperative complications remains inconclusive. Future prospective studies are required to further elucidate the impact of GLP-1RA use on ACDF outcomes. Level III, therapeutic study.
Critical thinking and clinical reasoning underpin healthcare professionals' ability to navigate uncertainties and deliver safe and effective care. With artificial intelligence (AI) advancement and growing adoption, AI-based educational tools are increasingly used to support these cognitive competencies' development. To synthesize randomised and controlled clinical trials on AI-based educational tools in health professions education and examine their effects on critical thinking and clinical reasoning among health professions students. Six electronic databases were searched from January 1, 2014 to July 28, 2025 was reviewed: PubMed, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, Embase and Web of Science. Two independent reviewers performed data extraction and quality assessment using standardized JBI checklists. The GRADE approach was used to assess the certainty of evidence. Studies were pooled via random-effects meta-analyses or narrative syntheses. Fourteen randomised controlled trials and seven controlled clinical trials were included (n = 21). Meta-analyses revealed small to medium effect sizes for the surrogate clinical reasoning outcomes of performance-based assessment scores (SMD 0.68; 95% CI [0.38, 0.98], p-value = 0.00; I2 = 38%) and knowledge test scores (SMD 0.39; 95% CI [0.09, 0.69], p-value = 0.01; I2 = 79%). Critical thinking and clinical reasoning skills and dispositions were narratively synthesized, with majority of included studies favouring AI-based interventions but the evidence had low to very low certainty. AI-based educational interventions may improve critical thinking and clinical reasoning among health profession students, but the evidence is very uncertain. This review offers preliminary insights but does not allow identification of optimal interventions or discipline-specific recommendations due to small sample sizes and substantial intervention heterogeneity. Further research is required to draw definitive conclusions. CRD42025634074.
Environmental exposure to per- and polyfluoroalkyl substances (PFAS) rises concerns about male reproductive health. Despite a wide body of experimental evidence supporting the biological role of PFAS exposure in male reproductive effects, available epidemiological studies are variably consistent about this association. Four databases were searched up to July 13, 2025 (PROSPERO: CRD420251267798). The systematic review follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included that assessed the association of PFAS on sperm outcomes. The primary effect measure was the Pearson correlation coefficient (r). Outcomes included sperm concentration, semen volume, total sperm count, motility, morphology, pH, and sperm DNA fragmentation, Fourteen studies including 7465 participants were included in this review. The results of meta-analyses indicate heterogeneous patterns of association, with PFAS mixtures showing limited associations with conventional semen parameters but demonstrating consistent inverse relationships with progressive motility (correlation scale [r] = -0.058, 95% confidence interval [CI]: -0.100 to -0.015) and sperm deoxyribonucleic acid (DNA) integrity (r = 0.141, 95% CI: 0.087-0.195). Individual congeners exhibited distinct association profiles, suggesting potential congener-specific effects on male reproductive function. The consistent association between increased DNA fragmentation across PFAS metrics suggest a possible role in unexplained male infertility and prompts further investigation.
The Glasgow Sleep Effort Scale (GSES) assesses the extent to which individuals engage in conscious, deliberate attempts to control their sleep. The present study aimed to conduct a reliability generalization meta-analysis to estimate the overall internal consistency of the GSES, to examine whether these estimates vary as a function of study and sample characteristics, and to assess the prevalence of reliability induction practices in the literature. This systematic review and meta-analysis was preregistered on the Open Science Framework. A search was conducted in PubMed, Scopus, Web of Science, and PsycINFO from inception to November 12, 2025, using the term "Glasgow Sleep Effort Scale". Two reviewers independently screened records using predefined eligibility criteria. Studies reporting Cronbach's alpha for the GSES total score were included. We conducted a random-effects meta-analysis using restricted maximum likelihood estimation. Thirty-four articles contributed 40 independent estimates (total N = 16,022). The pooled estimate was α = 0.81 (95% CI [0.79, 0.82]), indicating good overall internal consistency, although significant heterogeneity was observed (I2 ≈ 85%). Publication year significantly moderated internal consistency estimates, whereas language, mean age, sex, sample type, study design, and methodological quality did not. Reliability induction was observed in nearly 58% of the initially retrieved studies, most commonly due to the omission of reliability coefficients. The GSES shows good internal consistency. Its frequent use underscores the need to report sample-specific reliability estimates.
Active cigarette smoking is a prevalent, modifiable risk factor hypothesised to impair success in assisted reproductive technology (ART). Prior meta‑analyses have combined never‑smokers and former smokers in control groups, potentially diluting effect estimates. To determine the effect of active cigarette smoking on live birth and other ART outcomes using a strict comparison between active smokers and never‑smokers. We conducted a systematic review and meta‑analysis (PROSPERO: CRD420251128852) per PRISMA 2020. Databases were searched for observational studies comparing ART outcomes (using autologous oocytes) in active smokers versus never‑smokers. Two reviewers independently screened records, extracted data, and assessed risk of bias (Newcastle‑Ottawa Scale). Random‑effects models (REML‑HKSJ) pooled risk ratios (RRs) for dichotomous outcomes and mean differences (MD) for oocytes retrieved. Sensitivity analyses included restriction to strict never‑smoker controls. Certainty of evidence was assessed using GRADE. From 2,585 records, 26 studies (16,359 participants) were included. Active smoking was associated with a significant 15% reduction in live birth (13 studies; RR 0.85, 95% CI: 0.79-0.92, I² = 72.4%) and 18% reduction in clinical pregnancy (21 studies; RR 0.82, 95% CI: 0.77-0.88, I² = 66.7%), but both were attenuated to non‑significance when restricted to strict never‑smoker controls (RR 0.88 for both). Miscarriage was not significantly associated with smoking (7 studies; RR 1.15, 95% CI: 0.89-1.48, I² = 78.1%). A small reduction in oocytes retrieved was observed (18 studies; MD -1.06, 95% CI: -2.01 to -0.12, I² = 98.9%). Certainty of evidence was moderate for live birth and clinical pregnancy, and low for miscarriage and oocytes retrieved. While pooled estimates suggest active smoking is associated with reduced live birth and clinical pregnancy rates in ART, these associations are not robust when a methodologically pure never‑smoker comparator is applied, and miscarriage was non‑significant. The moderate certainty for live birth and clinical pregnancy indicates a more robust evidence base than previously appreciated, though the precise risk remains uncertain. High‑quality prospective studies with biochemical verification and dose‑response data are urgently needed.
Implantable cardioverter defibrillator (ICD) therapy is indicated following a myocardial infarction (MI) to curtail the risk of sudden cardiac death (SCD) in patients who are classified as high-risk, defined by a left ventricular ejection fraction (LVEF) ≤35%. The understanding of risk in patients with ischaemic injury who do not meet these criteria is limited. This study aims to assess the burden of SCD in patients' post-MI with LVEF 36-50%. Articles reporting mortality and SCD outcomes for participants with LVEF 36-50% post-MI without additional risk stratification or intervention were included. Medline, Embase and Cochrane databases were searched from index entries until the present. Data were synthesised using a random-effects model. Competing risk adjusted number needed to treat (NNT) for ICD implantation was calculated. This study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 7435 records were identified, five studies with 9345 patients were included. The pooled annual rate of SCD in patients with LVEF 36-50% post-MI was 1.74% (95% CI 1.02 to 2.95); a higher annual rate of 6.34% was observed for LVEF≤35% (p=0.03) while a lower yearly rate of 0.55% was observed for LVEF >50% (p=0.02). The proportion of mortality due to SCD was similar across all LVEF strata (p=0.79). Very high between-study heterogeneity was observed (I2=89.9% for SCD and I2=96.8% for all-cause mortality). During exploratory modelling, the primary prevention ICD NNT for patients with LVEF 36-50% was 19 when applying the MADIT-II ICD treatment effect (HR 0.33, 95% CI 0.20 to 0.53) and extrapolation to a 5-year device lifespan. This is the first meta-analysis reviewing post-MI patients with LVEF 36-50%. These findings highlight a clinically relevant unmet need for patients who carry a substantial burden of SCD despite being outside current ICD eligibility criteria. Further study is needed to improve risk stratification within this population and determine whether suitable intervention is beneficial. CRD42024551830.
To systematically evaluate the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and the risk of recurrent cerebrovascular events in patients with ischemic stroke. PubMed, Web of Science, Embase, the Cochrane Library, and China National Knowledge Infrastructure were systematically searched from inception to May 20, 2026. Observational studies reporting the association between Lp-PLA2 levels and the risk of recurrent cerebrovascular events in patients with ischemic stroke were included. The primary outcome was recurrent cerebrovascular events, mainly including ischemic stroke, acute cerebral infarction, or cerebral infarction recurrence. Because studies comparing high versus low Lp-PLA2 levels reported both hazard ratios (HR) and odds ratios (OR), the pooled results were expressed as pooled relative effect estimates with 95% confidence intervals (CI). For the continuous-variable analysis, effect estimates were rescaled and expressed as ORs per 1 standard deviation (SD) increase in Lp-PLA2. All meta-analyses were performed using random-effects models. Ten studies involving 2,527 patients with ischemic stroke were included in the meta-analysis. Higher Lp-PLA2 levels were associated with an increased risk of recurrent cerebrovascular events (pooled relative effect estimate = 2.99, 95% CI 2.24-3.99; P < 0.001). After excluding the study that did not report the cutoff value for the high and low Lp-PLA2 groups, the association remained stable (pooled relative effect estimate = 2.76, 95% CI 2.20-3.47; P < 0.001). In the continuous-variable analysis, each 1-SD increase in Lp-PLA2 was associated with an increased risk of recurrent cerebrovascular events (pooled OR = 2.62, 95% CI 1.08-6.33; P = 0.033). Higher Lp-PLA2 levels are associated with an increased risk of recurrent cerebrovascular events in patients with ischemic stroke. Lp-PLA2 may be a promising prognostic marker for secondary prevention after ischemic stroke.
To synthesize the available evidence on management strategies and associated clinical outcomes of steroid-resistant rejection (SRR) following liver transplantation. Systematic review and meta-analysis. Studies conducted in liver transplant centers worldwide published between 1987 and 2022. Thirteen observational studies including 4378 liver transplant recipients, of whom 266 developed SRR. PROSPERO: CRD42024502525. A systematic search of major electronic databases was conducted through 30th September 2025, without language restrictions. Study selection followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Risk of bias was assessed using the ROBINS-I tool. Thirteen observational studies published between 1987 and 2022 were included. The pooled incidence of SRR among liver transplant recipients was 6.7% (95% confidence interval [CI], 4.3-9.1), with substantial heterogeneity (I2 = 93.8%). SRR occurred early after transplantation, with a pooled mean time to onset of 61.6 days, with substantial heterogeneity (I2 = 74.8%). Initial management consisted of high-dose corticosteroid therapy. Second-line agents included anti-thymocyte globulin, muromonab-CD3, tacrolimus-based rescue or conversion, and interleukin-2 receptor antagonists; deoxyspergualin and bortezomib were used less frequently as salvage therapy. Overall, medical rescue therapy avoided retransplantation in 69.9% of patients. Pooled comparative risk ratios for individual rescue therapies could not be estimated, owing to heterogeneous study designs, sequential use of rescue agents within the same patient, and inconsistent outcome reporting. SRR remains an uncommon but clinically significant complication after liver transplantation. Several rescue therapies have been used for SRR, but current evidence does not permit conclusions about their comparative effectiveness. This reflects substantial heterogeneity across studies and the absence of comparative trial data. Standardized management strategies and prospective multicenter studies are needed to guide clinical practice.