B. J. Medical College

BACKGROUND AND AIMS:Lean metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized; however, its long-term hepatic risk relative to obese MASLD remains elusive. This study evaluated differential risk of progressive hepatic outcomes and identified predictors of adverse outcomes within the lean phenotype. METHODS:A large, multicenter retrospective cohort study was conducted using the TriNetX Global Health Research Network, including adults with noncirrhotic MASLD between 2010 and 2024. Lean MASLD was defined as the body mass index (BMI) < 25 kg/m2. Primary analyses compared lean versus nonlean MASLD (BMI ≥ 25 kg/m2), with a prespecified secondary analysis comparing lean versus obese MASLD (BMI ≥ 30 kg/m2), excluding overweight individuals. Outcomes included incident fibrosis, cirrhosis, portal hypertension and related complications, hepatocellular carcinoma (HCC), liver transplantation, and all-cause mortality over 3-year, 5-year, and 10-year follow-up. Propensity score matching and multivariable Cox regression were applied. RESULTS:Among 1,130,297 patients with MASLD, 229,084 had lean MASLD. After matching, lean MASLD was associated with consistently higher odds of fibrosis, cirrhosis, portal hypertensive complications, HCC, liver transplantation, and mortality compared with nonlean, overweight, and obese MASLD across all time horizons (all p < 0.001). Within the lean MASLD cohort, those with older age, diabetes, hypoalbuminemia, thrombocytopenia, and elevated aspartate aminotransferase independently predicted adverse hepatic outcomes. CONCLUSIONS:Lean MASLD is associated with substantial long-term hepatic morbidity and mortality. Currently, obesity-centered paradigms guide MASLD screening and risk stratification. Thus, efforts should be made to ensure that lean individuals with MASLD are not systematically under-screened or under-surveilled for progressive liver disease as they carry a higher risk of worsening.

BACKGROUND AND OBJECTIVES:Globally, there is high variability in paediatric transfusion practices. As per the World Health Organization (WHO), the majority of transfusions in low-income countries are administered to children under 5 years. This study aimed to characterize the epidemiology and indications for blood component transfusions among neonatal and paediatric patients across India. MATERIALS AND METHODS:A prospective longitudinal multicentre study was conducted over 6 months (April-September 2022). Standardized data sheets captured age, gender, diagnosis, transfusion indication, component type and first versus repeat transfusion status for all paediatric requests. RESULTS:Twenty-three medical institutions (combined 32,759 beds) participated in the study. Among 396,092 total blood component requests, 52,658 (13.2%) were for paediatric patients. Most were male (60.1%), aged 5-12 years (26.4%), and 42.7% required >1 transfusion. Red cell components were the most frequently requested (68%), followed by platelets (17.5%) and plasma (12.3%). Medical indications accounted for 67.6% requests, followed by 30.3% surgical indications. Haematology (48%), oncology (17.1%) and infections (10.5%) were the most common medical indications; however, cardiac surgeries (44.2%) and gastrointestinal surgeries (30%) were the most common surgical indications. Haemoglobinopathies (21.4%) were overall the most common indication for the transfusions reported. CONCLUSION:Paediatric patients accounted for over 13% of all transfusion requests, predominantly for red cells and medical indications (mainly haemoglobinopathy). This represents the first large-scale epidemiological assessment of paediatric transfusion indications in India and establishes foundational evidence to guide understanding of blood utilization trends in children as well as indicate priority research areas for the future.

Sarcopenia and frailty are pervasive, interrelated syndromes in cirrhosis that worsen morbidity, quality of life, transplantation waitlist outcomes, and post-transplant survival. This review synthesized contemporary evidence on definitions, epidemiology, mechanisms, diagnosis, prognostic impact, and management with an emphasis on implementable strategies in hepatology practice. Sarcopenia affects 40%-70% of patients with cirrhosis, and frailty affects 20%-50% of patients with cirrhosis with variations across populations and definitions. Mechanistic drivers include hyperammonemia, systemic inflammation, endocrine disturbances, malnutrition and accelerated starvation, gut-liver-muscle axis alterations, mammalian target of rapamycin inhibition, and inactivity. Diagnosis spans simple bedside tests such as handgrip strength, chair stands, gait speed, and the Liver Frailty Index as well as imaging modalities including computed tomography-based skeletal muscle index, dual energy X-ray absorptiometry, magnetic resonance imaging, and bioimpedance. Both sarcopenia and frailty independently predict hepatic decompensation, hospitalizations, waitlist dropout, and mortality, providing additive prognostic value beyond model for end-stage liver disease (MELD)/MELD-Na, and they are associated with longer intensive care unit and hospital stays and worse post-transplant outcomes. Management requires a multimodal approach: Optimization of cirrhosis complications and ammonia-lowering therapy; adequate nutrition with 1.2-1.5 g/kg/day protein and a late-evening snack; structured aerobic and resistance exercise programs; cautious use of testosterone in hypogonadal males; and emerging therapies such as beta-hydroxy-beta-methylbutyrate, vitamin D, L-carnitine, microbiome modulation, and myostatin inhibitors. Routine screening and multidisciplinary prehabilitation should be embedded in standard care pathways, and incorporation of sarcopenia and frailty metrics alongside MELD may refine risk stratification, enhance transplant allocation, and improve long-term outcomes.

BACKGROUND:The dynamic spectrum of tuberculosis (TB) often results in underdiagnosis warranting the need for better diagnostics to accurately detect Mycobacterium tuberculosis (Mtb) in persons with asymptomatic, paucibacillary or extrapulmonary TB, and to identify individuals at high risk of developing TB disease early. This study aimed to evaluate a dual target-based digital droplet PCR (ddPCR) assay to detect circulating cell-free Mtb DNA in plasma of individuals at high risk of developing TB disease and in those lacking a clear diagnosis of TB (asymptomatic or clinically diagnosed TB). METHODS:Forty-six healthy household contacts (HHCs) of patients with pulmonary TB who developed TB within two years of follow-up (Progressors), and 92 HHCs who did not progress to TB (Non-progressors) were included in the study. Plasma was obtained and subjected to testing using a ddPCR assay targeting two M. tuberculosis (Mtb)-specific insertion sequences, IS6110 and IS1081. Sensitivity, specificity, and ROC curves were used to assess the diagnostic performance of the test. FINDINGS:IS6110 and IS1081 targets were detected in 10/11 asymptomatic TB cases giving a sensitivity of 90.9% (95% CI: 62.3-99.5), and in 9/11 unconfirmed/possible TB cases giving a sensitivity of 81.8% (95% CI: 52.3-96.8). Further, the test detected Mtb-ccfDNA in 15/19 Progressors even at six months prior to TB diagnosis (79.0% sensitivity, 95% CI: 56.7-91.5; 97.8% specificity, 95% CI: 92.4-99.6). Detection rates at 12- and 18-months prior to onset of TB were 55.0% (95% CI: 34.2-74.2) and 50.0% (95% CI: 29.9-70.1), respectively. Notably, the test showed 100% sensitivity (95% CI: 43.9-100.0) in detecting extrapulmonary TB up to six months prior to clinical diagnosis. INTERPRETATION:The study highlights the potential of ddPCR-based detection of Mtb ccfDNA as a valuable tool for early identification of individuals at risk of developing active TB disease and for clarifying the diagnosis of TB in diagnostically challenging cases. Further validation in a larger cohort will confirm the findings of the study and endorse the utility of the test in clinical practice. FUNDING:This work was supported by the Indian Council of Medical Research (Grant number:5/8/5/45/Adhoc/2022/ECD-1). The CTRIUMPh cohort study which provided samples for this study was supported by the NIH/DBT Indo-US Vaccine Action Programme.