Manisha Yadav

Background: Patients with pediatric cirrhosis-sepsis (PC-S) attain early mortality. Plasma bacterial composition, the cognate metabolites, and their contribution to the deterioration of patients with PC-S to early mortality are unknown. We aimed to delineate the plasma metaproteome-metabolome landscape and identify molecular indicators capable of segregating patients with PC-S predisposed to early mortality in plasma, and we further validated the selected metabolite panel in paired 1-drop blood samples using untargeted metaproteomics-metabolomics by UHPLC-HRMS followed by validation using machine-learning algorithms. Methods: We enrolled 160 patients with liver diseases (cirrhosis-sepsis/nonsepsis [n=110] and noncirrhosis [n=50]) and performed untargeted metaproteomics-metabolomics on a training cohort of 110 patients (Cirrhosis-Sepsis/Nonsepsis, n=70 and noncirrhosis, n=40). The candidate predictors were validated on 2 test cohorts—T1 (plasma test cohort) and T2 (1-drop blood test cohort). Both T1 and T2 had 120 patients each, of which 70 were from the training cohort. Results: Increased levels of tryptophan metabolites and Salmonella enterica and Escherichia coli–associated peptides segregated patients with cirrhosis. Increased levels of deoxyribose-1-phosphate, N5-citryl-d-ornithine, and Herbinix hemicellulolytic and Leifsonia xyli segregated patients with PC-S. MMCN-based integration analysis of WMCNA-WMpCNA identified key microbial-metabolic modules linked to PC-S nonsurvivors. Increased Indican, Staphylobillin, glucose-6-phosphate, 2-octenoylcarnitine, palmitic acid, and guanidoacetic acid along with L. xyli, Mycoplasma genitalium, and Hungateiclostridium thermocellum segregated PC-S nonsurvivors and superseded the liver disease severity indices with high accuracy, sensitivity, and specificity for mortality prediction using random forest machine-learning algorithm. Conclusions: Our study reveals a novel metabolite signature panel capable of segregating patients with PC-S predisposed to early mortality using as low as 1-drop blood.

Introduction: Gestational diabetes mellitus is increasing globally leading to significant maternal and foetal morbidity. This study aimed to find out the prevalence of gestational diabetes mellitus among pregnant women delivering in a tertiary care hospital. Methods: A descriptive cross-sectional study on a total of 3034 pregnant women was conducted in a tertiary care hospital from 14^th April 2017 to 13^th April 2018 with ethical approval from Research and Institutional Review Committee (Reference number: 061-077/078) of the hospital. Pregnant women who met the eligibility criteria were included in the study. Convenience sampling was done. Data were analysed using the Statistical Package for the Social Sciences version 24.0 and Microsoft Excel. Point estimate at 99% Confidence Interval was calculated along with frequency and percentage for binary data. Results: Among 3034 patients who delivered in the tertiary centre, the prevalence of gestational diabetes mellitus was found to be 104 (3.42%) (2.57-4.26 at 99% Confidence Interval). The majority of women were of maternal age >30 years in 69 (66.34%). Out of which 48 (46.15%) women had family history of diabetes mellitus. Thirty-eight (36.53%) patients required a caesarean section. The most common obstetric complication was polyhydramnios in 35 (35.57%). Conclusions: The prevalence of gestational diabetes was lower when compared to other studies done in similar settings. The majority of women were of higher maternal age, had family history of diabetes mellitus and were also obese.