VPS Lakeshore, also known as Lakeshore Hospital is a multi super-speciality Hospital in Kochi, Kerala, India. It is located along National Highway 66 in Nettoor, and is a 650-bedded facility with over 30 clinical departments. The hospital is headed by Shamsheer Vayalil, the founder and Managing Director of VPS Healthcare.
Esophageal and colorectal carcinomas exhibit widespread transcriptional dysregulation, yet the contribution of non-coding RNA splicing remains poorly characterized. In a preceding transcriptomic study utilizing primary esophageal adenocarcinoma (EAC) cell lines, long non-coding RNAs GAS5 and PVT1 were identified as major pan-cancer splicing hotspots via an integrated exon- and intron-centric computational pipeline. To determine if these architectural alterations represent ubiquitous gastrointestinal mechanisms or tissue-specific modalities, the current study deployed an identical reproducible pipeline—incorporating STAR alignment, rMATS, and MntJULiP—to evaluate deep-sequencing RNA-seq datasets of 36 colorectal cancer (CRC) cell lines against 18 normal colorectal mucosa samples. Following stringent concordance filtering, GAS5 and SNHG1 emerged as the most significantly spliced and upregulated lncRNAs in CRC. A direct coordinate-level comparison revealed striking tissue-specific divergence: while the GAS5 locus at chr1:173.865 Mb previously demonstrated a compact Retained Intron (RI) companion cluster in EAC, the CRC cohort exhibited exclusively exon-centric variations (Mutually Exclusive Exons and Alternative 5' Splice Sites) at the identical genomic coordinate without significant intron retention. Crucially, while these specific GAS5 and SNHG1 isoforms possess exact intron matches in GENCODE v40 annotations, they displayed negligible junction support in GTEx normal colonic mucosa and were entirely absent from the TCGA PanCancer Atlas splicing catalogs. We propose that their absence in public databases is an artifact of the 'tumor dilution effect' inherent to bulk tumor sequencing, combined with standard Poly-A selection biases. This study highlights the growing significance of GAS5 splicing and upregulation in gastrointestinal malignancies and establishes SNHG1 as a potent, previously under-reported structural target in CRC progression.
Background The long non-coding RNA GAS5 serves a dual oncogenic role in gastrointestinal malignancies: its introns host C/D box small nucleolar RNAs (snoRNAs) that guide ribosomal 2'-O-methylation via fibrillarin (FBL), while the mature transcript acts as a competitive endogenous RNA (ceRNA) sponge for the oncogenic microRNA miR-21. This study computationally deduces the divergent alternative splicing mechanisms utilized by esophageal adenocarcinoma (EAC) and colorectal adenocarcinoma (CRC) to hijack the GAS5 locus for oncoribosome biogenesis and apoptotic evasion. Methods An in silico transcriptomic analysis of EAC and CRC cohorts was conducted using rMATS and MntJULiP to identify statistically significant alternative splicing events. Excision coordinates were mapped to deduce specific snoRNA liberation patterns. Downstream effector pathway activation ( FBL , PTEN , AKT1 , MYC , DKC1 ) was quantified using Cuffdiff. Results EAC utilizes precise, targeted spliceosome rewiring (Retained Intron and Mutually Exclusive Exons) to extract a highly specific, target-enriched repertoire of snoRNAs (e.g., SNORD79 , SNORD75 ). This corresponds with a massive > 20-fold upregulation of the pseudouridylation effector DKC1 and a ~ 9-fold upregulation of FBL . Conversely, CRC completely lacks these targeted events, instead employing chaotic macro-skips that trigger Nonsense-Mediated Decay (NMD). This NMD-mediated destruction of the GAS5 transcript simultaneously harvests a trickle of snoRNAs while eliminating the ceRNA sponge, unleashing miR-21 to translationally silence PTEN, hyperactivate AKT/MYC, and upregulate DKC1 . Conclusion Gastrointestinal adenocarcinomas dismantle the GAS5 locus with surgical precision through divergent topological strategies. EAC employs highly efficient spliceosome rewiring, whereas CRC leverages NMD-mediated ceRNA network sabotage to re-engineer ribosomal topology and ensure survival.
Autoimmune hepatitis (AIH) in children presents significant diagnostic and therapeutic challenges requiring a multidisciplinary and evidence-based approach. The Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ISPGHAN) convened a consensus meeting on February 23, 2025, bringing together national and international experts to address key clinical and research questions. The deliberations spanned epidemiology, clinical presentation, diagnosis including autoantibodies, immunoglobulin G (IgG), histology and diagnostic scores, therapeutic strategies, management of difficult-to-treat AIH, long-term monitoring, and special scenarios, such as seronegative AIH (SN-AIH), autoimmune sclerosing cholangitis/overlap syndromes and post-transplant complications like recurrence and de novo-AIH. Recommendations were formulated using standard GRADE system and finalized through structured consensus. These guidelines aim to standardize care, assist clinicians in decision-making, and improve outcomes in children with AIH across diverse healthcare settings.
Telemedicine is becoming a transformative tool for managing chronic diseases. Known literature data emphasizes the effectiveness and accessibility of telemedicine and its impact on patient outcomes. Thus, the foundation for advancing the role of telemedicine in chronic disease management for improving healthcare accessibility and quality of life is imperative.
Ischemic hepatitis (IH) is an acute liver injury caused by hepatic hypoperfusion, typically occurring in shock states. We present a 77-year-old woman with congenital heart disease (CHD), heart failure with preserved ejection fraction (HFpEF), and atrial fibrillation who developed IH without overt hypotension. She presented with dyspnea, weakness, and oliguria, accompanied by severe transaminitis (Aspartate Aminotransferase - AST 6602 U/L, Alanine Aminotransferase - ALT 3886 U/L), coagulopathy (International Normalized Ratio - INR 7.35), and lactic acidosis (lactate 6.8 mmol/L). Echocardiography revealed atrial fibrillation with rapid ventricular response, pulmonary hypertension, and valvular abnormalities. Management included rate control, diuresis, and hepatic support. Liver enzymes improved by day 4, confirming recovery. This case demonstrates that IH can occur in HFpEF patients with CHD and arrhythmia, even in the absence of profound hypotension. Early recognition and hemodynamic optimization are critical to prevent irreversible liver damage. This case report underscores IH as a potential complication in high-risk cardiac patients, necessitating vigilant monitoring and prompt intervention.
