Sir Ganga Ram Hospital

A bstract Cerebral venous sinus thrombosis (CVST) is an uncommon but potentially life-threatening cause of pediatric stroke. Inherited thrombophilias play a significant role in children with CVST, particularly in severe or recurrent cases. Antithrombin III (AT-III) deficiency, most often caused by mutations in SERPINC1 gene, is a rare but highly thrombogenic condition, with cerebral venous thrombosis being an infrequent presentation. Here, we report a case of a 16-year-old previously healthy male who presented with progressive headache and generalized tonic–clonic seizures, followed by rapid neurological deterioration. Neuroimaging revealed hemorrhagic venous infarction with extensive sinus thrombosis. Thrombophilia evaluation demonstrated mildly reduced antithrombin activity. Despite decompressive craniectomy and anticoagulation, the patient developed recurrent, extensive CVST during perioperative interruption of anticoagulation, with new hemorrhagic infarcts. Genetic testing identified heterozygous SERPINC1 mutation classified as a variant of uncertain significance, in the setting of reduced antithrombin activity and recurrent thrombosis. The patient was stabilized on long-term anticoagulant and discharged with plans for lifelong anticoagulation and genetic counseling. CVST due to AT-III deficiency is rare, and recurrent, malignant CVST requiring neurosurgical intervention is exceedingly uncommon. This case highlights the aggressive thrombotic phenotype associated with SERPINC1 mutations and underscores the importance of early thrombophilia screening and genetic confirmation in pediatric patients with severe or recurrent CVST. Identification of AT-III deficiency has critical therapeutic implications, including anticoagulation strategy, potential heparin resistance, and the need for long-term management and family screening. Inherited AT-III deficiency should be considered in adolescents with recurrent or extensive CVST. Early diagnosis and tailored anticoagulation can improve outcomes and prevent recurrence.

Multi-omics in combination with advanced computational methodologies synthesizes diverse omics data to provide deeper insights into molecular interactions and offers transformative potential for unravelling phenomenon behind disease complexities, improving diagnostics, disease prevention, and personalized treatments. This integrative strategy enables our understanding of gene-environment relationships, chronic disease progression, and the intricate molecular pathways involved in health. Effective multi-omics analyses require robust data sharing, accessibility, interoperability, and governance, which are critical for linking genomic elements to phenotypic traits. The Global Alliance for Genomics and Health advocates for responsible data-sharing practices, by promoting key principles such as transparency and equity. By emphasizing a collaborative approach to data utilization, our proposed framework seeks to advance improved disease prevention and treatment strategies. Multi-disciplinary collaboration, encompassing researchers, clinicians, policy makers, and patient representatives, is pivotal for driving innovation and addressing rare disease diagnostics. The success of multi-omics applications hinges on the establishment of comprehensive datasets, understanding the functional implications of multi-omic variation, adherence to findable, accessible, interoperable, reusable (FAIR) and Collective Benefit, Authority to Control, Responsibility, and Ethics (CARE) principles, and the strengthening of global genomic commons, benefiting scientific research, drug development, and broader health initiatives. Our review highlights essential components of multi-omics integration, underscoring its potential to transform the landscape of precision medicine and improved patient outcomes worldwide.

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder without an effective cure. Adeno-associated virus (AAV) based gene therapy has improved dystrophin function, with sub-optimal clinical outcomes. We reasoned that a combination of rational engineering of AAV9 capsids modified at the post-translational modification sites, optimal promoter selection, and codon-optimisation of the microdystrophin (μDys) can enhance the AAV9 vector functionality. Our initial promoter screening demonstrated improved dystrophin expression in muscle fibres with a ubiquitous CAG promoter (1.61-fold in CAG vs. MHCK7, p < 0.0001) in mdx mice. We then evaluated two engineered AAV9 capsids (N57Q, K51Q) containing CAG-μDys intramuscularly invivo, which demonstrated a significant improvement in grip strength 18 weeks after gene therapy. Subsequent evaluation of a codon-optimised microdystrophin transgene under the control of the optimal CAG promoter and capsid (AAV9K51Q) by intramuscular administration revealed enhanced muscle grip strength and dystrophin-glycoprotein complex restoration up to 4 months after gene therapy. Based on the improved performance of AAV9K51Q vectors during intramuscular gene transfer, we performed a systemic administration of these vectors alone, and a comparison with the control group revealed a significantly increased muscle contraction force by 1.6-1.7 fold and a 30%-60% dystrophin restoration in skeletal and cardiac muscles, up to 14 months after gene therapy. Collectively, our study underscores the therapeutic potential of engineered AAV9 vectors for potential clinical application in patients with DMD.

Background:Heart failure (HF) remains a major public health challenge in India, with a need for effective and well-tolerated therapeutic strategies.Objective:The RESTORE-HF study evaluated the real-world effectiveness and safety of torsemide-spironolactone fixed-dose combination (FDC) in Indian patients with HF.Design:Prospective, multicenter, observational study.Methods:This study was conducted across 101 sites in India. Patients aged 18–75 years with HF with reduced ejection fraction and signs of congestion were enrolled and initiated on the torsemide-spironolactone FDC. Participants were followed over 3 weeks from baseline. The primary objective was the change in body weight. Secondary endpoints included changes in New York Heart Association (NYHA) functional class, edema, occurrence of adverse events (AEs), and physician and patient assessments of efficacy and tolerability.Results:Of the 1841 patients screened, 1752 were enrolled, and 1520 completed the study. The mean (SD) age of participants was 58.61 (9.45) years, of whom 61.05% were male. The study showed a significant reduction in mean body weight was observed from 75.54 kg at baseline to 73.13 kg at week 3 (mean difference: 2.41 kg; p < 0.0001). Additionally, an improvement in NYHA functional class and edema was observed over 3 weeks from baseline. Overall, 22.11% patients achieved no-edema stage. Only three mild AEs related to loose stools were reported, and no serious AEs or deaths occurred. Over 98% of physicians and patients rated the therapy favorably.Conclusion:The RESTORE-HF study demonstrated that the torsemide-spironolactone FDC may be associated with a mean body weight reduction of 2.41 kg and may be generally well-tolerated in Indian heart failure patients. Furthermore, the FDC may be linked to significant symptomatic improvement over 3 weeks in real-world clinical practice.

ABSTRACT Background and Aim MASLD affects 30–38% of Indian adults, yet the contribution of genetic risk variants to disease susceptibility and fibrosis progression remains poorly characterised. We investigated the association of 12 candidate SNPs with MASLD susceptibility and fibrosis severity in North Indian patients, benchmarking allele frequencies against IndiGenomes and global populations. Methods Sixty-nine MASLD patients (75.4% male; median BMI 29.8 kg/m²) from a tertiary care liver clinic in New Delhi were genotyped for 12 SNPs using Illumina custom BeadChip array and Sanger sequencing. Patients were stratified by liver stiffness measurement (LSM): significant fibrosis (≥8 kPa, n=38) versus no significant fibrosis (&lt;8 kPa, n=31). Allele frequencies were compared with IndiGenomes (∼1,020 Indian individuals) and 1000 Genomes populations. Results PNPLA3 rs738409 G allele was the strongest within-cohort predictor of significant fibrosis (allelic OR 2.89, 95% CI 1.35–6.19, P=0.006; dominant model OR 3.94, P=0.008), with carriers demonstrating higher LSM (median 15.6 vs. 7.5 kPa, P=0.005). SAMM50 rs3761472 (OR 2.12, P=0.065) and FTO rs9939609 (OR 2.08, P=0.089) showed non-significant trends. In the population-level comparison, APOC3 rs2854116 T allele was the only variant significantly enriched after Bonferroni correction (64.0% vs. 47.9%; OR 1.93, 95% CI 1.35–2.77, P&lt;0.001), followed by PNPLA3 (33.3% vs. 24.1%, OR 1.57, P=0.019) and SAMM50 (31.2% vs. 22.6%, OR 1.55, P=0.028). Notably, APOC3 showed no association with fibrosis (OR 0.96, P=1.000), suggesting a role in susceptibility rather than progression. All SNPs were in Hardy-Weinberg equilibrium. Conclusions This study reveals a dissociation between genetic determinants of MASLD susceptibility and fibrosis progression in North Indian patients. APOC3 rs2854116 predisposes to MASLD at the population level, while PNPLA3 rs738409 drives fibrosis severity within established disease, underscoring the need for ancestry-specific genetic risk stratification. Graphical Abstract

A bstract Guillain–Barre syndrome (GBS) is an auto-immune disorder that damages the myelin sheath of peripheral nerves, leading to muscle weakness and paralysis. Nearly two-thirds of GBS cases involve autonomic symptoms. This case study describes the recovery of a 2.5-year-old girl with GBS following several months of intensive physiotherapy. Initially hospitalized due to tachycardia and profound muscle weakness, she required ventilatory support for respiratory failure. After stabilization and various treatments, she was discharged after 81 days but still remained unable to walk independently. Physiotherapy commenced during hospitalization, focusing on progressive resistance exercises and functional training, which were continued post-discharge. Recovery was assessed using heart rate variability (HRV), the GBS disability index, and muscle strength (MS), monitored at 10-day intervals. Over 7.5 months of follow-up, the patient demonstrated significant improvements in MS, disability index, and autonomic modulation. Within a month of therapy, she transitioned from wheelchair dependence to assisted walking, ultimately achieving full independence. Upper- and lower-extremity MS showed parallel recovery, underscoring the role of structured physiotherapy in functional restoration. HRV metrics indicated improved autonomic regulation, with Poincaré plots reflecting the transition from limited to enhanced variability. This case highlights the importance of early physiotherapy in pediatric GBS recovery, demonstrating the interplay between MS, functional ability, and autonomic balance. HRV monitoring may serve as a valuable tool for guiding treatment strategies, warranting further research in larger pediatric GBS populations.

Issue compiled for the 12th International SWAAC ELSO Conference (South West Asia and Africa Chapter of ELSO), held alongside the 15th National Conference of the ECMO Society of India (ESOI).This landmark academic gathering represents a convergence of minds, experience, innovation, and aspiration across continents, united by a common goal: advancing extracorporeal life support (ECLS) science and improving outcomes for our most critically ill patients.This Special Abstract Issue reflects the collective intellectual vigor of our ECMO community.The abstracts presented herein span a broad spectrum, from fundamental physiological concepts and technological innovation to pragmatic bedside solutions and population-level analyses.Together, they demonstrate not only scientific rigor but also clinical courage-the willingness to challenge established paradigms, innovate within resource constraints, and share real-world experiences that inform, refine, and advance contemporary practice.One of the most heartening aspects of this issue is the diversity of contributors.Submissions have been received from academic tertiary centers, emerging ECMO programs, multidisciplinary teams, and early-career clinicians, reflecting the democratization of ECMO science in our region.From neonatology to adult critical care, from cardiothoracic surgery to emergency medicine, and from perfusion sciences to nursing leadership, the spectrum of voices captured in this issue underscores the inherently multidisciplinary nature of ECLS.ECMO is no longer the domain of a few specialized units; it is a collaborative endeavor that thrives on team-based excellence.As Journal Coordinator, I am deeply grateful to the authors who entrusted IJECMO with their scholarly work.Preparing an abstract for submission requires not only intellectual effort but also time carved out from demanding clinical responsibilities.Your commitment to academics is commendable and reflects a shared belief that knowledge must be documented, scrutinized, and shared to advance patient care.I also extend sincere appreciation to the abstract review committee and editorial team, whose diligence ensured scientific integrity, relevance, and clarity.Their efforts have upheld the standards of IJECMO while nurturing a supportive academic environment, particularly for first-time authors and emerging investigators.The ideas seeded in these abstracts will, I hope, mature into full manuscripts, multicenter collaborations, and practice-changing innovations.On behalf of the Indian Journal of ECMO, I congratulate all authors, reviewers, and organizers for making this academic milestone possible.With warm regards and best wishes for a successful and enriching conference!

Hypertension is a leading cause of cardiovascular morbidity and mortality globally, with particularly low control rates in India. Beyond controlling blood pressure (BP), effective management must address associated comorbidities such as cardiovascular disease (CVD), chronic kidney disease (CKD), and type 2 diabetes mellitus (T2DM). A multidisciplinary panel of experts, including cardiologists, nephrologists, and physicians, developed this consensus through six advisory board meetings. A comprehensive literature review of randomized controlled trials and systematic reviews published between 2019 and 2025 was conducted via PubMed and Google Scholar. Key topics included pharmacological and non-pharmacological management of hypertension, combination therapy, and comorbidity-focused treatment strategies. Early screening for hypertension-mediated organ damage and the use of combination therapy, specifically telmisartan and cilnidipine for their complementary benefits, were emphasized. Evidence showed improved BP control, reduced proteinuria, and organ protection in individuals with CVD, CKD, and T2DM. Non-pharmacological interventions such as dietary modification, physical activity, smoking cessation, stress management, and adherence to therapy through fixed-dose combinations were also endorsed. This expert consensus supports a comprehensive, patient-centered approach to hypertension management in India. Available evidence suggests that cilnidipine and telmisartan may offer potential benefits beyond BP reduction, largely based on pharmacologic properties and surrogate outcomes. Future large-scale, randomized, comparative outcome trials are needed to better define the relative clinical benefits of this combination.

Parvovirus B19 (PVB19) is a clinically important cause of refractory anemia in kidney transplant recipients (KTRs). Data from low- and middle-income settings remain scarce despite high transplant volumes. This study evaluated the clinical spectrum, management practices, and outcomes of PVB19 infection across major transplant programs in India. We conducted a retrospective multicenter cohort study across 14 tertiary transplant centers. All KTRs with PCR-confirmed PVB19 infection and complete clinical data were included. Clinical features, bone marrow findings, immunosuppressive (IS) adjustments, intravenous immunoglobulin (IVIG) use, and patient and graft outcomes were analyzed. A total of 135 KTRs were identified. Median time to infection was 11 weeks posttransplant. Anemia was universal, not frequently accompanied by leukopenia (17.7%) or thrombocytopenia (14.8%). Bone marrow examinations (n=34) demonstrated giant proerythroblasts or pure red cell aplasia. IS reduction was implemented in all patients; most commonly, complete MMF withdrawal (61.5%). IVIG was administered to 90% (median cumulative dose 100g). Overall, 97% achieved hematologic recovery, with a median response time of 20 days. Recurrence occurred in 4.4%. At a median follow-up of 18 months, graft survival was 92.6%; graft loss (n=10) was primarily due to antibody-mediated rejection, and no deaths were attributable to PVB19. PVB19 infection represents an important consideration in the differential diagnosis of early posttransplant anemia in KTRs. Timely PCR testing and pragmatic treatment strategies can achieve favorable hematologic and graft outcomes in resource-constrained settings.