Background: Reduction of immunosuppression (ROI) remains the mainstay of treatment for BK virus infection (BKVI) in kidney transplantation (KT). This review explored the role of intravenous immunoglobulin (IVIG) and mammalian target of rapamycin inhibitor (mTORi) regimens as alternative therapies for KT recipients with BKVI, focusing on viral clearance and graft-related outcomes. Methods: An electronic search was conducted for articles examining IVIG or mTORi use in treating BKVI among adult and/or pediatric KT recipients. Meta-analyses of proportions were performed for relevant outcomes. Results: Twenty-seven studies (13 evaluating IVIG and 14 evaluating mTORi) were included; all but three enrolled only adult participants. In IVIG studies, the pooled viral clearance rate was 76.4% (95% confidence interval [CI], 64.2%–85.5%), with numerically higher clearance for IVIG after ROI compared to IVIG with ROI (87.0% vs. 66.1%). Overall graft survival was 84.7% (95% CI, 70.7%–92.7%), with numerically higher survival in IVIG after ROI than in IVIG with ROI (93.6% vs. 78.4%). Pooled histological clearance and graft rejection rates were 82.8% and 14.5%, respectively. In mTORi studies, the pooled viral clearance rate was 68.0% (95% CI, 58.0%–76.7%) and overall graft survival was 89.1% (95% CI, 82.7%–93.4%), with no significant difference between patients with and without prior ROI. Histological clearance and graft rejection rates were 59.8% and 8.6%, respectively. Conclusions IVIG and mTORi regimens appear to be feasible alternatives to ROI in KT recipients with BKVI, achieving viral clearance while maintaining graft survival. Future randomized controlled trials are needed to further define their role and strengthen current evidence with higher-quality data.

Meta-IMU: A R Shiny App to Conduct Meta-Analysis in Systematic Review and Umbrella Reviews Many tools exist for conducting meta-analyses in systematic reviews, but they are often expensive or difficult for beginners to use. This challenge arises because most tools either fail to address all aspects of meta-analysis comprehensively or lack sufficient guidance for navigating their features. To address these limitations, we developed Meta-IMU, a free R-based Shiny application tailored specifically for beginners. Unlike many existing tools that focus solely on standard systematic reviews, Meta-IMU supports both systematic reviews and umbrella reviews, offering a more versatile approach. To ensure accessibility, Meta-IMU includes built-in instructional videos that guide users step by step, from navigating the application to interpreting the results produced. This guidance ensures users can confidently perform analyses without prior expertise. Meta-IMU encompasses a comprehensive range of features covering key aspects of meta-analysis, such as defining review questions, developing search terms, retrieving studies from various databases, assessing risk of bias, creating tables and plots, analysing small-study effects, performing meta-regression and subgroup analyses, conducting sensitivity analyses, assessing the certainty of evidence, summarizing findings, and generating PRISMA checklist reports. By integrating these functionalities into a single platform, Meta-IMU provides a user-friendly, all-in-one solution. In summary, Meta-IMU is a comprehensive, free application designed to simplify the process of meta-analysis for both systematic reviews and umbrella reviews, making advanced analytical techniques accessible to researchers at any level of experience.

INTRODUCTIONNot much is known regarding how primary care physicians (PCPs) in Singapore keep themselves healthy and mitigate ill health. This study aims to determine the health-seeking behaviour of local PCPs and to identify the predictors of local PCPs attaining the recommended level of exercise.

METHODSThis study was a cross-sectional questionnaire survey, which included questions on the demographic characteristics, practice profiles and health-seeking behaviour of PCPs. The sampling frame was the 1,400 listed members of the College of Family Physicians Singapore. The anonymised survey was executed in two phases: a postal survey, followed by a web-based survey on the College of Family Physicians Singapore website. The two data sets were collated; the categorical variables, summarised; and the differences between subgroups (based on exercise engagement), compared using Fisher's exact test. The effect of each risk factor on exercise duration was quantified using odds ratio (OR) estimate and 95% confidence interval (CI). Multivariate logistic regression analysis was performed to identify significant predictors of exercise engagement.

RESULTSA total of 631 PCPs participated in the survey--26% were ≤ 34 years old, 58% were male, 21% were single, 34% were singleton practitioners, and 56% were private practitioners. The percentage of PCPs who exercised ≥ 2.5 hours weekly was 29%, while 28% exercised < 0.5 hours weekly. Of the PCPs surveyed, 1% currently smoke, 0.8% drink more than 14 units of alcohol weekly, 60% undertook health screening, 65% had blood investigations done, and 64% had taken preventive measures such as getting influenza vaccination.

CONCLUSIONWhile local PCPs generally did not have undesirable habits such as smoking and alcohol abuse, they could further increase their exercise intensity and undertake more preventive measures such as getting vaccinated against various diseases.

Adult ; Aged ; Cross-Sectional Studies ; Exercise ; Female ; Health Behavior ; Health Surveys ; Humans ; Life Style ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Physicians, Primary Care ; Risk Factors ; Singapore ; Surveys and Questionnaires

While non-alcoholic fatty liver disease (NAFLD) is highly prevalent (15% to 45%) in modern societies, only 10% to 25% of cases develop hepatic fibrosis leading to cirrhosis, end-stage liver disease or hepatocellular carcinoma. Apart from pre-existing fibrosis, the strongest predictor of fibrotic progression in NAFLD is steatohepatitis or non-alcoholic steatohepatitis (NASH). The critical features other than steatosis are hepatocellular degeneration (ballooning, Mallory hyaline) and mixed inflammatory cell infiltration. While much is understood about the relationship of steatosis to metabolic factors (over-nutrition, insulin resistance, hyperglycemia, metabolic syndrome, hypoadiponectinemia), less is known about inflammatory recruitment, despite its importance for the perpetuation of liver injury and fibrogenesis. In this review, we present evidence that liver inflammation has prognostic significance in NAFLD. We then consider the origins and components of liver inflammation in NASH. Hepatocytes injured by toxic lipid molecules (lipotoxicity) play a central role in the recruitment of innate immunity involving Toll-like receptors (TLRs), Kupffer cells (KCs), lymphocytes and neutrophils and possibly inflammasome. The key pro-inflammatory signaling pathways in NASH are nuclear factor-kappa B (NF-kappaB) and c-Jun N-terminal kinase (JNK). The downstream effectors include adhesion molecules, chemokines, cytokines and the activation of cell death pathways leading to apoptosis. The upstream activators of NF-kappaB and JNK are more contentious and may depend on the experimental model used. TLRs are strong contenders. It remains possible that inflammation in NASH originates outside the liver and in the gut microbiota that prime KC/TLR responses, inflamed adipose tissue and circulating inflammatory cells. We briefly review these mechanistic considerations and project their implications for the effective treatment of NASH.
Adipose Tissue ; Apoptosis ; Carcinoma, Hepatocellular ; Cell Death ; Chemokines ; Cytokines ; Fatty Liver ; Fibrosis ; Hepatocytes ; Hyperglycemia ; Immunity, Innate ; Inflammation ; Insulin Resistance ; JNK Mitogen-Activated Protein Kinases ; Kupffer Cells ; Liver ; Liver Diseases ; Lymphocytes ; Metagenome ; Models, Theoretical ; Neutrophils ; NF-kappa B ; Toll-Like Receptors