Introduction: Liver cirrhosis is a chronic, progressive disorder marked by extensive hepatic fibrosis and profound metabolic disturbances. Among these alterations, Branched-chain Amino Acids (BCAAs)—leucine, isoleucine and valine—undergo significant dysregulation, reflecting compromised hepatic function, altered nitrogen metabolism and muscle catabolism. Advances in metabolomic technologies have facilitated the accurate quantification of BCAA levels, highlighting their potential as sensitive biomarkers for evaluating disease severity and progression in cirrhotic patients. Aim: To study the levels of branched-chain amino acids in different grades of liver cirrhosis and to evaluate their utility over Child-Pugh score as a biomarker for liver cirrhosis. Materials and Methods: This cross-sectional study was carried out at Department of Biochemistry, Lokmanya Tilak Municipal Medical College and Sion Hospital (LTMMC & GH), Sion, Mumbai, Maharashtra, India, from January 2023 to December 2024 and including 250 patients with liver cirrhosis. Plasma samples from patients with clinically and histologically confirmed cirrhosis were analysed using tandem Mass Spectrometry (MS/ MS). BCAA levels (leucine, isoleucine and valine) were assessed across Child-Pugh classes (A, B and C) and correlated with liver function parameters and disease severity indices. Chi-square test was applied to statistical analysis. Results: Out of 250 patients, 78% were males and 22% were females, between age group of 18-70 years. A progressive decline in BCAA concentrations was observed with increasing severity of cirrhosis (p<0.001). Patients in Child-Pugh classes B and C demonstrated significantly lower BCAA levels compared with controls. Conclusion: The BCAA profiling through metabolomics provides a sensitive and non invasive approach to assessing liver cirrhosis severity. Incorporating BCAA measurements into routine clinical practice may improve risk stratification and support personalised nutritional and therapeutic strategies in cirrhotic patients.
An Indian male in his mid-20s presented with breathlessness, pedal edema, and abdominal distension. Clinical examination revealed dysmorphic features, including a broad nasal bridge, a short neck, an upward slanting palpebral fissure, micrognathia with an underdeveloped chin, a flat fascial profile, and low set ear, along with minimal secondary sexual characteristics. Electrocardiogram showed incomplete right bundle branch block and P pulmonale, while echocardiography revealed severe pulmonary hypertension, myxomatous mitral valve with prolapse of the anterior leaflet, and severe tricuspid regurgitation. Further evaluation identified right renal agenesis and hypergonadotropic hypogonadism. Ophthalmological examination was normal. The constellation of features led to a clinical diagnosis of Bardet-Biedl Syndrome. This case emphasizes the importance of clinical suspicion and multidisciplinary evaluation in diagnosing syndromic disorders.
BACKGROUND:Several countries are using fractionated or limited-dose regimens of full dose inactivated polio vaccine (IPV) in infants in addition to oral poliovirus vaccine (OPV), due to procurement cost of IPV and delivery challenges for its campaign use. An adjuvanted dose-sparing IPV (ds-IPV) with around a one-fourth antigen content of the full dose of IPV was developed in India. A non-inferiority trial was conducted to compare the immune response of ds-IPV with IPV in infants. METHODS:A phase 2/3, double-blind, randomised controlled trial was conducted at nine tertiary care hospitals in India. Healthy infants aged 6-8 weeks, who received a birth dose of bivalent OPV were enrolled. Participants with fever or acute infection, and previous receipt or plan to receive any other poliovirus-containing vaccines were excluded. Infants were randomly assigned (1:1; block randomisation managed through an interactive web response system) to receive either ds-IPV or IPV in a three-dose regimen-a single dose of 0·5 mL administered by intramuscular route at age 6 weeks, 10 weeks, and 14 weeks. The vaccine syringes were masked with an opaque peel before administration to maintain masking. All participants were concomitantly administered oral rotavirus vaccine, and injectable DTwP-HB-Hib and pneumococcal conjugate vaccine in the contralateral thigh by the intramuscular route. Blood samples were collected at baseline before the first dose and at 28 days after the third dose for measuring the neutralising antibodies against each poliovirus serotype using microneutralisation assay. The site staff evaluating the study outcomes, participants' parents, and the laboratory personnel were masked to the vaccine allocations. The primary outcome of type-specific percentage seroconversion at 28 days after the third dose of ds-IPV or IPV (non-inferiority margin ≥10%) and secondary outcomes of type-specific geometric mean titres and percentage seroprotection (titre ≥8) were assessed in the per-protocol population as the primary population and the full analysis population as the supportive population. Secondary outcomes on safety evaluation included immediate, solicited, unsolicited, and serious adverse events. This study is registered with the Clinical Trials Registry of India (CTRI/2022/05/042363), and is complete. FINDINGS:Between May 23, 2022, and April 13, 2024, of the 658 participants screened, 648 were eligible and randomly assigned to ds-IPV (n=324) or IPV (n=324). Consent was withdrawn for five participants after randomisation; thus, a total of 643 infants received ds-IPV (n=323) or IPV (n=320). The seroconversion rates for type 1 poliovirus in the ds-IPV and IPV groups were 283 (94·7% [95% CI 91·5 to 96·9]) of 299 participants and 270 (92·8% [89·2 to 95·5]) of 291 participants, respectively, with a difference of 1·9 (95% CI -2·1 to 5·8). The seroconversion rates for type 2 poliovirus in the ds-IPV and IPV groups were 287 (96·3% [93·5 to 98·1]) of 298 participants and 284 (97·9% [95·6 to 99·2]) of 290 participants, respectively, with a difference of -1·6 (-4·7 to 1·5). The seroconversion rates for type 3 poliovirus in the ds-IPV and IPV groups were 291 (97·3% [94·8 to 98·8]) of 299 participants and 288 (99·0% [97·0 to 99·8]) of 291 participants, respectively, with a difference of -1·6 (-3·8 to 0·5). Solicited events, including tenderness, redness, swelling, and fever, were very common (≥10%) in both vaccine groups. No causally related serious adverse events were reported. INTERPRETATION:ds-IPV was immunologically non-inferior to IPV and had a similar safety profile. The new adjuvanted IPV could become an alternative option to IPV. The availability of ds-IPV will support a constant supply of IPV for use in poliovirus-naive and exposed target populations. FUNDING:Serum Institute of India.
BACKGROUND:Screening for latent tuberculosis (LTB) before initiating advanced therapy for inflammatory bowel disease (IBD) helps reduce the risk of tuberculosis (TB) development. However, there is limited data on screening practices from TB-endemic regions. AIM:To study the practices of screening for LTB and study the incidence of TB in patients with IBD on biological and small molecule inhibitors. METHODS:This retrospective multicentre study analyzed LTB screening practices in IBD patients starting advanced therapies between 2018 and 2022. We included patients who were initiated on biologics (infliximab, adalimumab, vedolizumab) or small molecule inhibitors (tofacitinib). We assessed compliance with LTB screening methods, including the tuberculin skin test, interferon-gamma release assay (IGRA), chest X-ray, and computed tomography chest, both at initiation and annually. We also evaluated the incidence of active TB and its predictors. RESULTS:Of 378 patients (mean age: 36.9 ± 14.9 years, males: 56.9%), 158 (41.8%) and 216 (57.1%) had ulcerative colitis and Crohn's disease, respectively. Advanced therapy used were anti-tumor necrosis factor in 309 (81.74%), tofacitinib in 41 (10.84%) and vedolizumab in 28 (7.40%). Standard screening and diligent screening strategy was employed in 59% and 33% of patients, respectively. Compliance with tuberculin skin test and IGRA was noted in 261 (69.04%) and 298 (78.83%) patients, respectively. Chest X-Ray and computed tomography chest were performed in 300 (79.36%) and 242 (64.02%), respectively. Annual screening in those on advanced therapy for > 1 year was performed in 27.2% (50/184). Active TB developed in 17 (4.49%); 15 (88.23%) were on anti-tumor necrosis factor. LTB was detected in 40 (10.72%), with most diagnosed on the basis of IGRA (21/40, 52.50%). Among 17 patients who developed active TB, LTB screen was negative in 12 (70.58%). CONCLUSION:Standard screening practices for LTB, prior to starting advanced therapy, remain suboptimal (< 60%) in India despite high TB endemicity.
