Genetic Variants Associated with the Risk of Stroke in Sickle Cell Anemia: Systematic Review and Meta-Analysis.

Sickle cell anemia (SCA) is the most common cause of stroke in children. As it is a rare disease, studies investigating the association with complications like stroke in SCD have small sample sizes. Here, we performed a systematic review and meta-analysis of the studies exploring an association of genetic variants with stroke to get a better indication of their association with stroke. PubMed and Google Scholar were searched to identify studies that had performed an association analysis of genetic variants for the risk of stroke in SCA patients. After screening of eligible studies, summary statistics of association analysis with stroke and other general information were extracted. Meta-analysis was performed using the fixed effect method on the tool METAL and forest plots were plotted using the R program. The random effect model was performed as a sensitivity analysis for loci where significant heterogeneity was observed. 407 studies were identified using the search term and after screening 37 studies that cumulatively analyzed 11,373 SCA patients were included. These 37 studies included a total of 2,222 SCA patients with stroke, predominantly included individuals of African ancestry (N = 16). Three of these studies performed whole exome sequencing while 35 performed single nucleotide-based genotyping. Though the studies reported association with 132 loci, meta-analyses could be performed only for 12 loci that had data from two or more studies. After meta-analysis we observed that four loci were significantly associated with risk for stroke: -α3.7 kb Alpha-thalassemia deletion (P = 0.00000027), rs489347-TEK (P = 0.00081), rs2238432-ADCY9 (P = 0.00085), rs11853426-ANXA2 (P = 0.0034), and rs1800629-TNF (P = 0.0003396). Ethnic representation of regions with a high prevalence of SCD like the Mediterranean basin and India needs to be improved for genetic studies on associated complications like stroke. Larger genome-wide collaborative studies on SCD and associated complications including stroke need to be performed.

The Role of C-reactive Protein Estimation in Determining the Duration of Antibiotic Therapy in Neonatal Sepsis.

INTRODUCTION: Septicemia is globally considered the most important cause of neonatal morbidity and fatality. Serum C-Reactive Protein (CRP) is an acute phase reactant, which is brought out in response to the inflammatory reaction. It is prophesied to drop down speedily after the coherent weeding out of microbial incitation due to the short half-life of CRP. CRP levels reflect the individual's association between microbial infection and defensive mechanisms.  Methods: This hospital-based cross-sectional study included 150 admitted patients with suspected sepsis in the Department of Pediatrics, Rajendra Institute Medical Sciences (RIMS), Ranchi, India, over a study period of one year (2020 to 2021). CRP was estimated on the day of admission and repeated after 72 hours, on the fifth day, and on the seventh day for serial values of CRP, and the findings were compared by making three groups. Further, the research participants were designated to three different groups according to the CRP estimation levels. RESULTS: Out of the 150 assumed neonatal septicemia patients, antibiotics were paused in 42 neonates (28%) within 72 hours. In group 2, 8% of neonates' antibiotics were stopped in five days, and a total of 102 neonates (68%) could be discharged on the seventh day of antibiotic therapy as their CRPs became negative on the third day and seventh day consecutively, along with negative blood culture reports. In group 3, antibiotics of 48 neonates (32%) were continued beyond seven days. CONCLUSION: CRP has a skyscraping specificity and negative predictive values (NPV); thus, by estimating serial CRPs, the antibiotic therapy duration can be determined, which further helps determine the period of hospitalization.