Shoban Babu Varthya

Toward a centre for one nation one ranking: An AI-driven ICMR-IRIS platform for Indian medical researchers

Introduction: Pharmacogenomics, the study of genetic variations that influence drug responses, is a crucial component of personalised medicine. Despite its growing importance, integration into healthcare in India faces challenges, including limited awareness, restricted access to genetic testing, and inadequate infrastructure. This study aimed to assess knowledge and awareness of pharmacogenomics among undergraduate MBBS students at AIIMS Jodhpur. Methods: A cross-sectional survey was conducted in December 2024 using a self-administered, pre-validated questionnaire. The tool assessed sociodemographic details and pharmacogenomics knowledge. Descriptive statistics were performed using SPSS version 21. Results: Of 358 students approached, 324 completed the survey (response rate: 90.5%). The mean age was 19.6 years, and 71.9% of the participants were male. Most participants were aware of the basic concept (85.8%) and professional relevance (85.2%) of pharmacogenomics. However, knowledge gaps were evident: only 60.8% were aware of the USFDA pharmacogenomic labelling requirements, and 59% believed it could reduce drug development costs. While 80.9% supported its role in diagnosis and treatment, just 71.3% favoured its inclusion in the MBBS curriculum. Discussion: The findings indicate that students possess a strong foundational understanding of pharmacogenomics but have limited awareness of its clinical, regulatory, and economic implications. Similar studies from India and abroad highlight comparable gaps, underscoring the need for structured education. Integrating pharmacogenomics into undergraduate curricula through case-based modules and CME sessions could bridge deficiencies and enhance preparedness for precision medicine. Medical students demonstrated good baseline knowledge but lacked deeper insights. Strengthening curricular integration is crucial for equipping future clinicians to effectively apply pharmacogenomics in practice.

Introduction: The role of radical local therapy in oligometastatic non-small cell lung cancer (NSCLC) is rapidly evolving and has shown mixed results. We assessed the effect of add-on radical local therapy versus systemic therapy alone on overall survival (OS), progression-free survival (PFS) and safety in oligometastatic NSCLC. Methods: In this systematic review and individual participant data (IPD) meta-analysis, we screened PubMed, Embase, Scopus and CENTRAL until 20 April 2025 for randomised controlled trials (RCTs) answering our research question. We retrieved IPD from survival curves of published reports and used one-stage IPD meta-analysis. We also estimated the more clinically intuitive restricted mean survival time difference (RMSTD). We assessed between-study heterogeneity using the median HR (MHR). We assessed risk of bias using the Risk of Bias 2 tool and rated the evidence certainty using the Grading of Recommendations, Assessment, Development and Evaluations framework. Findings: We screened 1004 records to include ten RCTs (mostly at a low risk of bias) with 752 participants (338 males), predominantly using radiotherapy as radical local therapy. Add-on radical local therapy improved OS by 38% [HR: 0.62, 95% CI 0.50 to 0.76; high certainty of evidence]. Between-trial heterogeneity does not affect the results, only leading to 3% difference [MHR 1.03]. Add-on radical local therapy leads to longer OS by 0.47 month (0.21–0.72), 2.18 months (0.74–3.63), 4.20 months (1.95–6.45) and 6.65 months (4.05–9.24) over 1, 2, 3 and 4 years. Add-on radical local therapy possibly improved PFS by 40% (HR: 0.60, 95% CI 0.45 to 0.80; low certainty of evidence). Radical local therapy was well tolerated with no major safety concerns. Interpretation: Add-on radical local therapy—chiefly radiotherapy—is beneficial in oligometastatic NSCLC. Inconsistent reporting of safety limited quantitative synthesis. Future studies may address the role of surgery as radical local therapy, and the role of programmed death ligand 1 expression. PROSPERO registration number: CRD42024576829.

Cardiovascular-kidney-metabolic (CKM) syndrome is the association between obesity, diabetes, CKD (chronic kidney disease), and cardiovascular disease. GDF-15 mainly acts through the GFRAL (Glial cell line-derived neurotrophic factor Family Receptor Alpha-Like) receptor. GDF-15 and GDFRAL complex act mainly through RET co-receptors, further activating Ras and phosphatidylinositol-3-kinase (PI3K)/Akt pathways through downstream signaling. GDF-15 decreases cardiac dysfunction and hypertrophy by inducing HIF-α (hypoxia-inducible factor-1α). It causes increased fractional shortening and a significant decrease in ventricular dilation through the induction of the SMAD 2/3. GDF-15 prevents hyperglycemia-induced apoptosis in diabetes mellitus. GDF-15 causes anorexia by influencing the central systems regulating metabolism and appetite. Therefore, targeting GDF-15 can be useful for the treatment of anorexia caused by cancer as well as the prevention of resulting weight loss. GDF-15 has an important role in predicting mortality in acute kidney injury. Its high levels are related to eGFR decline and also have a prognostic role in CKD patients. Growth differentiation factor-15 (GDF-15) is a vital biomarker for diagnosis, treatment, and prognosis of CKM syndrome. Elevated GDF-15 levels can be utilised as a biomarker to determine the suitable metformin dosage. In light chain amyloidosis, a raised level of GDF-15 predicts early death in heart failure and renal disease patients. In vivo, studies using GDF-15 analogs and antibodies against GFRAL to affect metabolic parameters and ventricular dilatation have shown potential for GDF-15-based therapeutic interventions. This review aims to study the role of GDF-15 in CKM syndrome and establish it as a CKM biomarker.

Background Heart failure affects almost 64 million people, with more than half of it constituting heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) are in the first line for HFrEF, but no head-to-head trials are available. Moreover, growth differentiation factor-15 (GDF-15) has been demonstrated as a promising prognostic marker, specifically for HFrEF, but has not been explored much. Methods This pragmatic randomised controlled trial recruits 100 patients with HFrEF (ejection fraction Conclusion This pragmatic study aims to compare the efficacy, safety and cost-effectiveness of dapagliflozin versus sacubitril/valsartan in patients with HFrEF in real-world settings. The study aims to provide clinicians with data to make informed decisions regarding the preferred drug class. Additionally, examining the impact of ARNI and SGLT2i on GDF-15 levels could offer better insights into prognosis among patients with HFrEF. Ethics and dissemination This study involves human participants and was approved by Institutional Ethics Committee at AlIMS Jodhpur with reference number AIIMS/IEC/2023/5842 approved this study. Participants gave informed consent to participate in the study before taking part. The research findings will be disseminated via closed group discussions at the site of study, scientific conferences, peer-reviewed published manuscripts, and social media. Trial registration number CTRI/2023/12/060772.

Aim: To synthesize the evidence on the effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) in adolescents with overweight or obesity. Materials and Methods: For this systematic review and network meta‐analysis, we searched five databases and registries until 2 March 2024 for eligible randomized controlled trials (RCTs). The primary outcome was weight change. We did a pairwise meta‐analysis to compare GLP‐1RAs and placebo, followed by a drug‐wise network meta‐analysis (NMA) to compare GLP‐1RAs against each other. Results: We screened 770 records to include 12 RCTs with 883 participants. The evidence suggests that GLP‐1RAs reduced weight (mean difference −4.21 kg, 95% confidence interval [CI] −7.08 to −1.35) and body mass index (BMI; mean difference −2.11 kg/m ² , 95% CI −3.60 to −0.62). The evidence on waist circumference, body fat percentage and adverse events (AEs) was very uncertain. The results remained consistent with subgroup analyses for coexisting type 2 diabetes. Longer therapy duration led to a greater reduction in weight and BMI. In the NMA, semaglutide led to the greatest weight reduction, followed by exenatide, liraglutide and lixisenatide. Conclusions: The evidence suggests that GLP‐1RAs reduce most weight‐related outcomes in adolescents, with semaglutide being the most efficacious. There is uncertain evidence on body fat and serious AEs, probably due to fewer studies and low incidence, respectively. Larger RCTs with head‐to‐head comparisons, pragmatic design, adiposity‐related outcomes, and economic evaluation can further guide the use and choice of GLP‐1RAs.