Artemis Hospitals

Low-flow lymphovenous malformations (LVMs) are congenital vascular anomalies predominantly occurring in the head and neck region. This retrospective study evaluates the efficacy and safety of Intralesional Bleomycin Sclerotherapy in managing these lesions, with a focus on pediatric and young adult populations. A prospective analysis was conducted on 10 patients (aged 1–40 years) with head and neck LVMs treated between October 2019 and December 2024. All patients received three sessions of Intralesional Bleomycin (0.5 mg/kg per session) under endoscopic guidance. Treatment response was assessed using pre- and post-treatment measurements, MRI, and clinical evaluation. The Wilcoxon Signed-Rank Test was used for statistical analysis. The cohort showed a male predominance (70%) and pediatric skew (80% < 20 years). Lesions were most common on the tongue (40%). Bleomycin induced significant size reduction (median 82.8%, IQR 76.7–100%; p = 0.002), with 30% achieving complete resolution and 70% showing partial response (50–99% reduction). Complications were minimal (20% transient ulcers), and functional outcomes were favorable (median FSS score: 2–3). Intralesional bleomycin is a safe and highly effective treatment for LVMs, particularly in pediatric patients. The standardized 0.5 mg/kg protocol yielded consistent results across ages and lesion sites, with minimal morbidity. Larger studies are warranted to validate demographic trends and long-term durability.

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.

ObjectiveWith 5 years of follow-up in the phase 3 CROWN study, lorlatinib showed unprecedented improvement in progression-free survival coupled with prolonged intracranial efficacy in patients with ALK-positive metastatic non-small cell lung cancer (mNSCLC). Here, we report kinetics and mitigation practices of select adverse events (AEs) to inform therapy management strategies.DesignPost hoc safety analyses from the CROWN study assessed the incidence, prevalence, time to onset, duration, management, and resolution of hyperlipidemia, edema, weight gain, central nervous system (CNS) AEs, and peripheral neuropathy in the lorlatinib group (n = 149).ResultsAfter 5 years of follow-up, no new safety signals were observed. All-cause any-grade and grade 3/4 AEs occurred in 100% and 77% of patients, respectively; AEs led to lorlatinib dose reduction in 23% of patients, dose interruption in 62%, and permanent discontinuation in 11%. The median time to onset of any-grade hyperlipidemia was 0.5 months; 71% of events were managed with lipid-lowering agents. Median time to onset of any-grade edema, weight gain, CNS AEs, and peripheral neuropathy ranged from 2 to 4 months. Most weight gain events (95%) were mitigated with lifestyle modifications. Incidence and prevalence of CNS AEs did not increase over time; 58% of events did not require medical intervention.Conclusions and RelevanceThis post hoc analysis suggests that with longer lorlatinib exposure, no new safety signals emerged, and treatment discontinuation due to AEs remained low after 5 years of follow-up. Most AEs were effectively managed with dose modifications, indicating that current management strategies can be effective to mitigate toxicity. ClinicalTrials.gov NCT03052608

Abstract Background and Aims Alcohol consumption alters gut microbiota, which can affect metabolism, immune regulation, and signalling pathways and lead to alcohol-associated liver disease (ALD). We investigated how alcohol-associated gut microbiota (AGMs) modulate liver kinome signalling to drive inflammation and fibrosis in ALD. Method Liver kinome and metaproteome changes were studied in rats (n=6/group) colonized with stool of severe alcohol-related hepatitis (SAH) patients (SAH→healthy-rats) or healthy human donors (HD→ALD-rats). AGM-associated liver kinome changes were cross-correlated with bacterial genera. A bacterial protein; Streptococcal collagen-like protein 1 (Scl1) was identified with affinity for TGFβR1. This was validated by molecular docking and immunoprecipitation-LCMS assay. Expression of Streptococcus pneumonia and pyogenes was done in stool of SAH patients (n=10). Also, Scl1 was quantified in patient stool (n=24) and liver tissue (n=19) samples. Validation was performed by assessing Scl1 level in plasma and Streptococcus level in stool samples before and after fecal microbiota transplantation (FMT) in SAH patients. Results Stool metaproteomics showed significant increase in 10 bacterial genera (Streptococcus, Staphylococcus, and Clostridium) in SAH→Healthy-rats, mirroring changes seen in ALD-rats (FC&gt;1.5, p&lt;0.05). Clusters of Orthologous Groups analysis indicated increased post-translational modifications (PTMs) and decreased lipid metabolism in ALD-rats and SAH→Healthy-rats. Liver kinome profiling showed 85 upregulated kinases in SAH→Healthy-rats, with 34 overlapping with ALD-rats, associated with inflammation (Mapk14, Map3k10 and others), fibrosis (Tgfbr1, Igf1r, and others), lipid metabolism (Cdk14, Cdk18) and regeneration (Met, Bmpr1a and others). FMT from healthy human-donors to ALD-rats reversed the expression of Streptococcus (10-fold), Staphylococcus (3-fold), and Clostridium (5-fold), along with 18 kinases associated with inflammation (Btk, Camk4, Nuak1) and fibrosis (Tgfbr1, Col4a1, Fgfr2 and others). Strong association (r²&gt;0.9, p&lt;0.05) was seen between Streptococcus abundance and fibrosis and inflammation-related kinases. Level of Scl1 was significantly high in SAH and ALD-rat stool samples (FC&gt;2, p&lt;0.05). It showed strong affinity for TGFβR1, as validated by molecular docking (&gt;86%confidence) and immunoprecipitation assays (&gt;100FC,p&lt;0.05), indicating it as a potential ligand for TGFβR1. Concordantly, expression of Scl1 was highest amongst all the known ligands for TGFβR1 (p&lt;0.05) suggesting Scl1 is a major contributor for TGFβR1 activation and its downstream signalling in these patients. Following fecal microbiota transplantation, expression of Scl1 in plasma and Streptococcus levels in stool were significantly reduced by 2.1-folds and 1.9 folds respectively in SAH patients. Further, Scl1 levels SAH plasma is capable of predicting poor therapeutic response and 30-day mortality with high accuracy (AUC=0.92, cutoff &gt;70 normalized abundance). Conclusion Alcohol induced gut dysbiosis alters the liver kinome, promoting inflammation, fibrosis, and lipid dysregulation. Streptococcal Scl1 is identified as a bacterial protein mimicking human collagen and capable of activating fibrotic signalling pathway through TGFβR1in liver and is capable of predicting poor response in SAH. FMT from healthy donor restores microbial imbalance and harmful microbial-host interactions.

ABSTRACT Background: Due to the complex histological and genomic nature of sarcomas, diagnosing and treating them has proven challenging. Delving into the genomic profiles and molecular markers linked to different sarcoma subtypes will aid in overcoming these obstacles and identifying new potential therapeutic targets. Objectives: The primary objective of this study was to investigate the genomic complexity of sarcoma, while the secondary objective was to identify potential therapeutic targets in the patients with sarcoma from India. Materials and Methods: This retrospective observational study was conducted from January 2020 to February 2024 at 4basecare Precision Health Pvt. Ltd., Bengaluru, India. We carried out comprehensive genomic profiling using gene panels or exome sequencing, including assessment of immunotherapy biomarkers (tumor mutation burden (TMB), microsatellite instability (MSI), programmed death-Ligand 1 (PD-L1)), in a cohort of 263 patients with sarcoma, categorized into 25 sarcoma types, for the present retrospective analysis. Results: We included 263 patients with sarcoma in our study and identified a diverse landscape of pathogenic variants across 138 genes, in 69.5% (183 patients) of the cohort. SNVs were prevalent in TP53 (25.1%; 66 patients), KIT (5.7%; 15 patients), PTEN (4.6%; 12 patients), and RB1 (4.6%; 12 patients), while CDK4 (5.2%; 17 patients) and MDM2 (5.7%; 15 patients) gene amplifications and SS18-SSX2 (1.1%; 3 patients), EWSR1-FLI1 (0.8%; 2 patients), and ASPSCR1-TFE3 (0.8%; 2 patients) gene fusions were recurrent. The majority of the patients harbored mutations affecting cell cycle control (39.2%; 103 patients), PI3K/AKT/MTOR (17.9%; 47 patients), and RAS/RAF/MAPK (14.8%; 39 patients) pathways. The average TMB was 7 mutations/mb, with 13.3% (35 patients) classified as TMB-H. Around 59.3% of the cohort (156 patients) harbored clinically actionable variants of therapeutic significance, including 8.7% of the cohort (23 patients) who were eligible for FDA/NCCN approved therapies. Conclusion: The findings emphasize the clinical usefulness of genomic profiling in guiding precision medicine for sarcoma treatment. Our research offers valuable insights into the genetic makeup of sarcomas, serving as a basis for devising efficient and precise diagnostic approaches and for planning preclinical and clinical studies to develop innovative treatment strategies.

Large glenolabral tears (270°-360°) are infrequently reported injuries and can be challenging to manage. This study aims to describe the injury patterns, surgical technique, and midterm outcomes of arthroscopically repaired 270°-360° labral tears. Patient data was retrieved from the electronic data records from 2011 to 2021. The patients with arthroscopically confirmed and repaired 270°/360° tears (with or without superior labral anterior posterior lesions) with a minimum follow-up of 24 months were included, and Oxford shoulder instability score and visual analog score (VAS) pain score were recorded prospectively. Twenty-four patients were included in the study with a mean follow-up of 52.6 ± 24.4 months. The mean pre-operative and final Oxford instability score was 24.8 ± 4.1 and 43.2 ± 1.5 (p < 0.0001). The mean pre-operative and final VAS was 4.95 ± 1.12 and 0.6 ± 0.7(p < 0.0001). Terminal loss of external rotation was seen in five patients with the remplissage procedure. No re-dislocation or instability was reported. All patients returned to pre-injury activity levels. Pan labral tears can be challenging to diagnose pre-operatively and may result in poor outcomes. Pain can serve as a clinical indicator of larger labral pathology in patients presenting with shoulder instability. A comprehensive understanding of the injury pattern, along with a systematic surgical approach, is essential for restoring adequate joint stability and achieving satisfactory results in the general patient population. IV.