Critical illness‑related corticosteroid insufficiency in children: A single center, prospective, cohort study

Background: Although guidelines for diagnosis and management of critical illness‑related corticosteroid insufficiency (CIRCI) in adults are developed, there is a paucity of data on CIRCI in children. Objective: To study the incidence, risk factors, mechanism, and associations of CIRCI in children using adrenocorticotropic hormone (ACTH) stimulation test. Materials and Methods: Single‑center prospective cohort study was conducted in eight bedded pediatric intensive care unit of teaching hospital over a period of 1 year. Serum total cortisol concentration was measured in 110 critically ill children before and after stimulation with 250 μg ACTH. CIRCI was defined by post‑ACTH increment in serum cortisol ≤9 μg/dl. Children with and without CIRCI were compared. Results: Incidence of CIRCI was 38.2%. Children with CIRCI had higher median age (34 vs. 18 months), higher pediatric risk of mortality score (17.79±2.60 vs. 16.37±3.68), and significantly higher basal cortisol levels (27.37±11.64 vs. 22.02±7.26) (p=0.004) than those without CIRCI. There was a significantly higher (p=0.000) requirement of catecholamines (2.71±0.457 vs. 2.00±0.792) and higher additional fluid boluses (15.79±4.7 vs. 10.65±4.60) in children with CIRCI. However, duration of catecholamine use was not significantly different between two groups. The presence of CIRCI was not found to be an independent risk factor for mortality. For each additional use of catecholamine, the risk of CIRCI increased to 5.6 times; and for each extra fluid bolus, the risk increased to 1.2 times. Conclusion: CIRCI occurs in a wide spectrum of diseases in critically ill children associated with increased need for catecholamine and fluids. CIRCI is likely to be multifactorial in etiology and associated with high basal cortisol levels

A 6-CpG Validated Methylation Risk Score Model for Metabolic Syndrome: The HyperGEN and GOLDN Studies

There has been great interest in genetic risk prediction using risk scores in recent years, however, the utility of scores developed in European populations and later applied to non-European populations has not been successful. The goal of this study was to create a methylation risk score (MRS) for metabolic syndrome (MetS), demonstrating the utility of MRS across race groups using cross-sectional data from the Hypertension Genetic Epidemiology Network (HyperGEN, N = 614 African Americans (AA)) and the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, N = 995 European Americans (EA)). To demonstrate this, we first selected cytosine-guanine dinucleotides (CpG) sites measured on Illumina Methyl450 arrays previously reported to be significantly associated with MetS and/or component conditions in more than one race/ethnic group (CPT1A cg00574958, PHOSPHO1 cg02650017, ABCG1 cg06500161, SREBF1 cg11024682, SOCS3 cg18181703, TXNIP cg19693031). Second, we calculated the parameter estimates for the 6 CpGs in the HyperGEN data (AA) and used the beta estimates as weights to construct a MRS in HyperGEN (AA), which was validated in GOLDN (EA). We performed association analyses using logistic mixed models to test the association between the MRS and MetS, adjusting for covariates. Results showed the MRS was significantly associated with MetS in both populations. In summary, a MRS for MetS was a strong predictor for the condition across two race groups, suggesting MRS may be useful to examine metabolic disease risk or related complications across race/ethnic groups

Interactive virtual 3D image reconstruction to assist renal surgery in patients with fusion anomalies of the kidney

Objective: Renal fusion anomalies are rare and usually present as horseshoe kidneys or crossed fusion ectopia. The complex renal anatomy seen in patients with these anomalies can present a challenge. Pre-operative planning is therefore paramount in the surgical management of these cases. Herein we report the use of interactive virtual three-dimensional (3D) reconstruction to aid renal surgery in patients with fusion anomalies of the kidney. / Materials and Methods: A total of seven cases were performed between May 2016 and October 2020. 3D reconstruction was rendered by Innersight Labs using pre-operative computed tomography (CT) scans. / Results: Five patients had malignant disease and two patients had benign pathology. Robotic and open operations were performed in four and three patients, respectively. / Conclusion: The use of 3D reconstruction in the cases reported in this series allowed for the identification of variations in renal vasculature, and this informed the choice of operative approach. / Oxford Centre for Evidence-Based Medicine Evidence Level: 4

Epigenome-Wide Association Study of Metabolic Syndrome in African-American Adults

Background: The high prevalence of obesity among US adults has resulted in significant increases in associated metabolic disorders such as diabetes, dyslipidemia, and high blood pressure. Together, these disorders constitute metabolic syndrome, a clinically defined condition highly prevalent among African-Americans. Identifying epigenetic alterations associated with metabolic syndrome may provide additional information regarding etiology beyond current evidence from genome-wide association studies. Methods: Data on metabolic syndrome and DNA methylation was assessed on 614 African-Americans from the Hypertension Genetic Epidemiology Network (HyperGEN) study. Metabolic syndrome was defined using the joint harmonized criteria, and DNA methylation was assessed using the Illumina HumanMethylation450K Bead Chip assay on DNA extracted from buffy coat. Linear mixed effects regression models were used to examine the association between CpG methylation at \u3e 450,000 CpG sites and metabolic syndrome adjusted for study covariates. Replication using DNA from a separate sample of 69 African-Americans, as well as meta-analysis combining both cohorts, was conducted. Results: Two differentially methylated CpG sites in the IGF2BP1 gene on chromosome 17 (cg06638433; p value = 3.10 × 10−7) and the ABCG1 gene on chromosome 21 (cg06500161; p value = 2.60 × 10−8) were identified. Results for the ABCG1 gene remained statistically significant in the replication dataset and meta-analysis. Conclusion: Metabolic syndrome was consistently associated with increased methylation in the ABCG1 gene in the discovery and replication datasets, a gene that encodes a protein in the ATP-binding cassette transporter family and is involved in intra- and extra-cellular signaling and lipid transport

Genetic Contributors of Incident Stroke in 10,700 African Americans with Hypertension: A Meta-Analysis from the Genetics of Hypertension Associated Treatments and Reasons for Geographic and Racial Differences in Stroke Studies

Background: African Americans (AAs) suffer a higher stroke burden due to hypertension. Identifying genetic contributors to stroke among AAs with hypertension is critical to understanding the genetic basis of the disease, as well as detecting at-risk individuals. Methods: In a population comprising over 10,700 AAs treated for hypertension from the Genetics of Hypertension Associated Treatments (GenHAT) and Reasons for Geographic and Racial Differences in Stroke (REGARDS) studies, we performed an inverse variance-weighted meta-analysis of incident stroke. Additionally, we tested the predictive accuracy of a polygenic risk score (PRS) derived from a European ancestral population in both GenHAT and REGARDS AAs aiming to evaluate cross-ethnic performance. Results: We identified 10 statistically significant (p \u3c 5.00E-08) and 90 additional suggestive (p \u3c 1.00E-06) variants associated with incident stroke in the meta-analysis. Six of the top 10 variants were located in an intergenic region on chromosome 18 (LINC01443-LOC644669). Additional variants of interest were located in or near the COL12A1, SNTG1, PCDH7, TMTC1, and NTM genes. Replication was conducted in the Warfarin Pharmacogenomics Cohort (WPC), and while none of the variants were directly validated, seven intronic variants of NTM proximal to our target variants, had a p-value \u3c5.00E-04 in the WPC. The inclusion of the PRS did not improve the prediction accuracy compared to a reference model adjusting for age, sex, and genetic ancestry in either study and had lower predictive accuracy compared to models accounting for established stroke risk factors. These results demonstrate the necessity for PRS derivation in AAs, particularly for diseases that affect AAs disproportionately. Conclusion: This study highlights biologically plausible genetic determinants for incident stroke in hypertensive AAs. Ultimately, a better understanding of genetic risk factors for stroke in AAs may give new insight into stroke burden and potential clinical tools for those among the highest at risk

A Systematic Review of Patient Race, Ethnicity, Socioeconomic Status, and Educational Attainment in Prostate Cancer Treatment Randomised Trials—Is the Evidence Base Applicable to the General Patient Population?

Context: Prostate cancer (PC) disproportionately affects men of Black race, and lower educational and socioeconomic status. Guidelines are based on randomised controlled trials (RCTs); however, the representation of different races, educations, and socioeconomic backgrounds in these trials is unclear. Objective: To assess reporting of equality, diversity, and inclusion characteristics (Equality, Diversity and Inclusion [EDI]) and differences in treatment effects between different races, and educational or socioeconomic status. Evidence acquisition: We conducted a systematic review of CENTRAL, MEDLINE, and Embase in April 2020 examining RCTs investigating treatments for PC. Outcomes collected were race/ethnicity, educational attainment, and socioeconomic status. RCTs investigating PC treatment in any population or setting were included. Data extraction of characteristics was performed independently by pairs of reviewers and checked by a senior author. The Cochrane risk of bias tool assessed the quality of included papers. Evidence synthesis: A total of 265 trials were included, and 138 of these were available as full-text articles. Fifty-four trials including 19 039 participants reported any EDI data. All 54 trials reported race, 11 reported ethnicity, three reported educational attainment, and one reported socioeconomic status. Patients of White race were the majority of the recruited population (82.6%), while the minority prevalence was as follows: Black 9.8% and Asian 5.7%. Three studies reported mortality outcomes depending on the participant's race. All three studies investigated different treatments, so a meta-analysis was not performed. No studies reported outcomes stratified by the educational or socioeconomic status of participants. Conclusions: There is poor reporting of patient race, ethnicity, socioeconomic background, and educational attainment in RCTs for PC treatments between 2010 and 2020. Addressing this for future studies will help explain differences in the incidence of and mortality from PC and improve the generalisability of results. Patient summary: In this study, we reviewed prostate cancer treatment trials to see whether these reported race, education, and socioeconomic backgrounds of their patient populations. We conclude that reporting of these characteristics is poor. This needs to be improved in future to improve outcomes for patients with prostate cancer of all ethnical, racial, and socioeconomic groups

Genomics of Postprandial Lipidomics in the Genetics of Lipid-Lowering Drugs and Diet Network Study

Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes that dictate variation in postprandial lipids are not completely characterized. Genetic studies of the plasma lipidome can help to better understand postprandial metabolism by isolating lipid molecular species which are more closely related to the genome. We measured the plasma lipidome at fasting and 6 h after a standardized high-fat meal in 668 participants from the Genetics of Lipid-Lowering Drugs and Diet Network study (GOLDN) using ultra-performance liquid chromatography coupled to (quadrupole) time-of-flight mass spectrometry. A total of 413 unique lipids were identified. Heritable and responsive lipid species were examined for association with single-nucleotide polymorphisms (SNPs) genotyped on the Affymetrix 6.0 array. The most statistically significant SNP findings were replicated in the Amish Heredity and Phenotype Intervention (HAPI) Heart Study. We further followed up findings from GOLDN with a regional analysis of cytosine-phosphate-guanine (CpGs) sites measured on the Illumina HumanMethylation450 array. A total of 132 lipids were both responsive to the meal challenge and heritable in the GOLDN study. After correction for multiple testing of 132 lipids (α = 5 × 10−8/132 = 4 × 10−10), no SNP was statistically significantly associated with any lipid response. Four SNPs in the region of a known lipid locus (fatty acid desaturase 1 and 2/FADS1 and FADS2) on chromosome 11 had p \u3c 8.0 × 10−7 for arachidonic acid FA(20:4). Those SNPs replicated in HAPI Heart with p \u3c 3.3 × 10−3. CpGs around the FADS1/2 region were associated with arachidonic acid and the relationship of one SNP was partially mediated by a CpG (p = 0.005). Both SNPs and CpGs from the fatty acid desaturase region on chromosome 11 contribute jointly and independently to the diet response to a high-fat meal

Effect of supplementation of differentially treated banana inflorescence on intestinal morphology in broiler birds

A study was conducted on 96 Vencobb 430, day-old broiler chicks to evaluate the effect of steam treatment on banana inflorescence supplementation as prebiotic on intestinal morphology. The birds were randomly assigned into three treatment groups having four replicates with eight birds per replicate and assigned control diet, formulated in accordance with BIS recommendation to control (T1) group and with supplementation of 0.5% dried banana inflorescence (T2 group) or 0.5% steam treated banana inflorescence (T3 group). After 42 days of feeding trial, the live weight was significantly higher in T3 and T2 than control. Two birds from each replicate were sacrificed to study the intestinal morphometry and pH. The weight of intestine varied significantly (p<0.01) between the treatments and was higher in T3 while the per cent of intestinal weight did not differ significantly. Intestinal morphometry revealed that the villus height was significantly (p<0.01) higher in duodenum, jejunum, and caecum in T3 and ileum in T2. The crypt depth was significantly (p<0.01) higher in jejunum, ileum and caeca in T3 and T2 in duodenum. Caecal crypt depth showed significantly (p< 0.01) low value in T2. Ileal crypt depth ratio was significantly (p<0.01) higher in T2 while the caecum crypt depth was significantly(p<0.01) high in T3. It is concluded that banana inflorescence influenced the gut morphometry in broilers

Preterm birth among pregnancies conceived by assisted reproduction techniques in Mumbai, Maharashtra, India

Background: Preterm births are an enormous global problem on families, medical system and economy. The rates of preterm birth are increasing and one of the contributors is growing use of Assisted Reproduction Techniques (ART) leading to multifetal gestations. Some risk factors for preterm birth are specific to women who conceive by ART. Since there is limited data from India, this pilot study was undertaken to assess the magnitude of preterm birth among pregnancies conceived by ART and to study the contributing factors.Methods: Clinic based descriptive cohort study through eight ART clinics in Mumbai for one year. Data was collected using an in-depth questionnaire on socio-demographic characteristics, medical history, ART details, course and complications during pregnancy, mode of delivery, pregnancy outcome, risk factors related to preterm birth and neonatal outcome. Complete details of 113 participants who completed the study were analyzed.Results: Study showed high incidence of preterm birth (76.23%) among women conceived with ART. Multiple gestations were observed in 45.1%. Pregnancy related complications like heterotrophic pregnancy (3%), pre eclampsia (15%) and gestational diabetes (11%) were high. Incidence of caesarean section was very high (98%). Neonatal outcome was good with 98% live births and only 2 still births.Conclusions: Present study highlights that preterm birth, multiple pregnancies, pregnancy related complications like preeclampsia, gestational diabetes and caesarean sections are very high among women conceived by ART. With growing use of ART there is an urgent need to develop a National ART Surveillance system in India like the one in Centre for Disease Control Atlanta to get complete data on the pregnancy course and outcomes of ART conceptions. Efforts to limit the number of embryos transferred should be strengthened to prevent multiple births