Post-Hemorrhagic Hydrocephalus and Outcomes Amongst Neonates With Intraventricular Hemorrhage: A Systematic Review and Pooled Analysis.

Introduction Intraventricular hemorrhage (IVH) is a common cause of morbidity and mortality in preterm neonates. IVH leads to complications such as posthemorrhagic hydrocephalus (PHH), which commonly occurs in neonates with a more severe degree of IVH. Hence, we aimed to evaluate the characteristics and outcomes of PHH in neonates with IVH. Methods We performed a systematic review of cases reported from January 1978 to December 2020 through the PubMed database, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the keywords 'intraventricular hemorrhage,' 'cerebral intraventricular hemorrhage,' and 'newborn.' A total of 79 articles were considered for analysis, and data on neonatal and maternal characteristics and outcomes were collected. The analysis was performed by using the χ2 test, Wilcoxon rank-sum test, and multivariate logistic regression model. Results We analyzed a total of 101 IVH cases, 54.5% were male and 62.4% preterm. Thirteen point nine percent (13.9%) presented with grade I, 35.6% grade II, and grade III respectively, and 8% grade IV IVH. Among the 59 (58.4%) neonates with PHH, 33.6% had resolved PHH and 24.8% had unresolved. In adjusted regression analysis, we found that neonates with resolved PHH have lower odds of having neurodevelopmental delay (OR:0.15, 95%CI:0.03-0.74; p=0.02) and death (OR:0.9;95%CI:0.01-0.99; p=0.049) as compared to unresolved PHH. Conclusion Our study showed that neonates with resolved PHH have a statistically significant lower risk of neurodevelopmental delay (NDD) and mortality. Future studies should be planned to evaluate the role of treatment and its effect on outcomes in IVH neonates with PHH as a complication.

Risk factors and outcomes of intravenous tissue plasminogen activator and endovascular thrombectomy utilization amongst pediatrics acute ischemic stroke.

BACKGROUND: Pediatric stroke is a debilitating disease. There are several risk factors predisposing children to this life-threatening disease. Although, published literature estimates a relatively high incidence of pediatric stroke, treatment guidelines on intravenous tissue plasminogen activator and endovascular thrombectomy utilization remain a dilemma. There is a lack of large population-based studies and clinical trials evaluating the efficacy and safety outcomes associated with these treatments in this unique population. AIM: We sought to determine the prevalence of risk factors, concurrent utilization of intravenous tissue plasminogen activator and endovascular thrombectomy, and associated outcomes in pediatric stroke hospitalizations. METHODS: We performed a retrospective analysis of the Nationwide Inpatient Sample data (2003-2014) in pediatric (1-21 years of age) acute ischemic stroke hospitalizations using ICD-9-CM codes. The multivariable survey logistic regression model was weighted to account for sampling strategy, evaluate predictors of hemorrhagic conversion, and treatment outcomes (mortality, morbidity, and discharge disposition) amongst pediatric stroke hospitalizations. RESULTS: In this analysis, 9109 patients between 1 and 21 years of age were admitted during 2003-2014 for acute ischemic stroke. Of these 9109 patients, 119 (1.30%) received endovascular thrombectomy alone, 256 (2.82%) intravenous recombinant tissue plasminogen activator, and 69 (0.75%) both endovascular thrombectomy and intravenous recombinant tissue plasminogen activator. We found overall high prevalence of conditions like epilepsy (19.59%), atrial septal defect (11.76%), sickle cell disease (8.63%), and moyamoya disease (5.41%) in pediatric acute ischemic stroke patients. Unadjusted analysis showed high prevalence of all-cause in-hospital mortality in combined endovascular thrombectomy and intravenous recombinant tissue plasminogen activator utilization group, and higher prevalence of hemorrhagic conversion and morbidity in endovascular thrombectomy utilization group compared to other groups (p < 0.0001). Multivariate adjusted analysis showed that children with endovascular thrombectomy utilization (aOR: 19.19; 95% CI: 2.50-147.29, p = 0.005), intravenous recombinant tissue plasminogen activator utilization (aOR: 8.85; 95% CI: 1.92-40.76, p = 0.005), and both (endovascular thrombectomy and intravenous recombinant tissue plasminogen activator) utilization (aOR: 7.55; 95% CI: 1.16-49.31, p = 0.035) had higher odds of hemorrhagic conversion compared to no-treatment group. CONCLUSION: We found various risk factors associated with pediatric stroke. The early identification can be useful to formulate preventive strategies and influence the incidence of pediatric stroke. Our study results showed that use of intravenous recombinant tissue plasminogen activator and endovascular thrombectomy increase risk of mortality and hemorrhagic conversion, but we suggest to have more clinical studies to evaluate the idea candidates for utilization of intravenous recombinant tissue plasminogen activator and endovascular thrombectomy based on risk: benefit ratio.

The interactive effect of SIRT1 promoter region polymorphism on type 2 diabetes susceptibility in the North Indian population.

Our previous studies have implicated genes mainly involved in the activity of pancreatic ß cells in type 2 diabetes (T2D) susceptibility in the North Indian population. Recent literature on the role of SIRT1 as a potential master switch modulating insulin secretion and regulating gene expression in pancreatic ß cells has warranted an evaluation of SIRT1 promoter region polymorphisms in the North Indian population, which is the main focus of the present study. 1542 samples (692 T2D patients and 850 controls) were sequenced for the 1.46 kb region upstream the translation start site of the SIRT1 gene. We performed a functional characterization of the SIRT1 promoter region polymorphisms using luciferase assay and observed a single-nucleotide polymorphism (SNP), rs12778366, in association with SIRT1 expression. We propose that TT, the high-expressing genotype of SNP rs12778366 in the SIRT1 promoter region and present in >80% of the North Indian population, was favored under conditions of feast-famine cycles in evolution, which has turned out to be a cause of concern in the present sedentary lifestyle under ad libitum conditions. Case-control association analysis did not implicate rs12778366 in T2DM per se in the studied population. However, our earlier reported risk genotype combinations of mt-ND3, PGC1α, and UCP2-866, when compared with the protective genotype combinations, in the background of the high-expressing TT genotype of SIRT1 SNP rs12778366, showed a very high additive risk [corrected odd ratio (OR) = 8.91; p = 6.5×10(-11)]. The risk level was considerably low in the genotype backgrounds of TX (OR = 6.68; p = 2.71×10(-12)) and CX (OR = 3.74; p = 4.0×10(-3)). In addition, we screened other reported T2D-associated polymorphisms: PIK3R1 rs3730089, IRS1 rs1801278, and PPP1R3 rs1799999, which did not show any significant association in North Indian population. The present paper emphasizes the importance of gene interactions in the biological pathways of T2D, a complex lifestyle disease.