Establishing Apolipoprotein-B and non-high-density-lipoprotein-C goals in Indian population: A Cross-sectional study.

BACKGROUND: Defining lipid goals solely on low-density lipoprotein-cholesterol (LDL-C) levels in Indian population may cause misclassification due to high prevalence of hypertriglyceridemia and small dense LDL-C particles. International guidelines now recommend Apoliporotein-B (Apo-B) and non-high-density lipoprotein-cholesterol (non-HDL-C) levels as alternative targets. In this study, we used a cross-sectional representative population database to determine Apo-B and non-HDL-C cut-offs corresponding to identified LDL-C targets and compared them to international guidelines. METHODS: A community-based survey carried out in urban Delhi and adjacent rural Ballabhgarh provided lipid values for 3047 individuals. The Spearman correlation coefficient was used to evaluate the degree of relationship between Apo-B and LDL-C and non-HDL-C. Cut-off values for Apo-B and non-HDL-C were established using receiver operator curve analysis correlating with guideline-recommended LDL-C targets. RESULTS: Spearman's rank correlations between Apo-B and LDL-C (0.82) and non-HDL-C and LDL-C (0.93) were significant (p < 0.05). Proposed corresponding cut-off values for LDL-C of 55, 70,100,130 and 160 mg/dl for Apo-B and non-HDL-C in our population were 75.3, 75.5, 91.3, 107.6, 119.4 mg/dL and 92.5,96.5, 123.5, 154.5, 179.5 mg/dL respectively. However, in those with triglycerides >150 mg/dl the corresponding Apo-B and non-HDL-C values were 85.1, 92.7, 103.5, 117.5 and 135 mg/dL and 124.5, 126.5, 147.5, 167.5 and 190.5 mg/L respectively. CONCLUSION: Based on this study we provide Apo-B and non-HDL cut-offs corresponding to target LDL-C values in Indian patients with and without high triglycerides. It is noted that in individuals with triglycerides ≥ 150 mg/dl, the Apo-B levels are much higher than the values recommended by guidelines.

Type 1 diabetes human enteroid studies reveal major changes in the intestinal epithelial compartment.

Lack of understanding of the pathophysiology of gastrointestinal (GI) complications in type 1 diabetes (T1D), including altered intestinal transcriptomes and protein expression represents a major gap in the management of these patients. Human enteroids have emerged as a physiologically relevant model of the intestinal epithelium but establishing enteroids from individuals with long-standing T1D has proven difficult. We successfully established duodenal enteroids using endoscopic biopsies from pediatric T1D patients and compared them with aged-matched enteroids from healthy subjects (HS) using bulk RNA sequencing (RNA-seq), and functional analyses of ion transport processes. RNA-seq analysis showed significant differences in genes and pathways associated with cell differentiation and proliferation, cell fate commitment, and brush border membrane. Further validation of these results showed higher expression of enteroendocrine cells, and the proliferating cell marker Ki-67, significantly lower expression of NHE3, lower epithelial barrier integrity, and higher fluid secretion in response to cAMP and elevated calcium in T1D enteroids. Enteroids established from pediatric T1D duodenum identify characteristics of an abnormal intestinal epithelium and are distinct from HS. Our data supports the use of pediatric enteroids as an ex-vivo model to advance studies of GI complications and drug discovery in T1D patients.

Poor Performance of Non-invasive Tests for Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: A Multicentric Asian Study.

BACKGROUND: Non-invasive tests (NITs) are useful to assess advanced fibrosis (AF) in nonalcoholic fatty liver disease (NAFLD). Data from Asian countries suggest that these tests have poor performance. We aimed to assess diagnostic accuracy of established thresholds of biomarker-based NITs and Transient Elastography (TE) in identifying AF and evaluated the utility of a two-step test approach. METHODS: Biopsy-proven 641 NAFLD patients (55.2% males, median age 42 years) were included from three different centers of Asia. AF (≥ F3) was identified as per histological staging (24.8%). RESULTS: TE had the highest area under the receiver operating characteristic curve (AUROC) 0.82 (0.79-0.86), and all other biomarker-based NITs had low AUROC (< 0.7). NITs performed poorly at established thresholds. The combination of NITs utilizing liver stiffness measurement (LSM) and biomarkers, Agile 3+ and FAST, demonstrated acceptable diagnostic accuracy (AUROC 0.82 and 0.78, respectively), but none were superior to LSM alone. LSM measured using appropriate M and XL probes remained accurate regardless of body mass index (BMI); NFS and APRI scores were less accurate at higher BMI ranges. A two-step approach using NFS rule-out criteria (< - 2.97 to rule out) followed by LSM (< 7.3 kPa to rule out and ≥ 12.7 kPa to rule in) correctly classified 62.4% of patients, with only 10.2% of patients incorrectly classified. CONCLUSION: NITs have not been validated to identify AF in the Asian NAFLD population, and internationally accepted thresholds yield high false-negative rates. LSM and LSM-based combination tests remain the most accurate.

Risk factors for Coronavirus disease-associated mucormycosis.

BACKGROUND: The epidemiology of the Coronavirus-disease associated mucormycosis (CAM) syndemic is poorly elucidated. We aimed to identify risk factors that may explain the burden of cases and help develop preventive strategies. METHODS: We performed a case-control study comparing cases diagnosed with CAM and taking controls as recovered COVID 19 patients who did not develop mucormycosis. Information on comorbidities, glycemic control, and practices related to COVID-19 prevention and treatment was recorded. Multivariate regression analysis was used to identify independent predictors. RESULTS: A total of 352 patients (152 cases and 200 controls) diagnosed with COVID-19 during April-May 2021 were included. In the CAM group, symptoms of mucormycosis began a mean of 18.9 (SD 9.1) days after onset of COVID-19, and predominantly rhino-sinus and orbital involvement was present. All, but one, CAM cases had conventional risk factors of diabetes and steroid use. On multivariable regression, increased odds of CAM were associated with the presence of diabetes (adjusted OR 3.5, 95% CI 1.1-11), use of systemic steroids (aOR 7.7, 95% CI 2.4-24.7), prolonged use of cloth and surgical masks (vs. no mask, aOR 6.9, 95%CI 1.5-33.1), and repeated nasopharyngeal swab testing during the COVID-19 illness (aOR 1.6, 95% CI 1.2-2.2). Zinc therapy was found to be protective (aOR 0.05, 95%CI 0.01-0.19). Notably, the requirement of oxygen supplementation or hospitalization did not affect the risk of CAM. CONCLUSION: Judicious use of steroids and stringent glycemic control are vital to preventing mucormycosis. Use of clean masks, preference for N95 masks if available, and minimizing swab testing after the diagnosis of COVID-19 may further reduce the incidence of CAM.

Are health care workers following preventive practices in the COVID-19 pandemic properly? - A cross-sectional survey from India.

BACKGROUND AND AIMS: Health care workers (HCWs) are at increased risk of getting infected with Coronavirus disease 2019 (COVID-19) and suboptimal preventive practices have been identified as an important risk factor in this regard. This study was done to evaluate the preventive practices being followed by health care workers and identify reasons for suboptimal compliance. METHODS: A cross-sectional survey was done in HCWs belonging to various occupational roles and socio-cultural backgrounds across India through online platforms and telephonic interviews from July 30, 2020 to August 30, 2020. A scientifically designed and pre-validated questionnaire with good validity (CVR = 0.87, S-CVI/Av = 0.978) and internal consistency (Cronbach's alpha coefficient = 0.85) was used. RESULTS: The responses of 956 participants were analysed. Various suboptimal practices like touching outer surface of masks, lack of social distancing in cafeteria and duty rooms, inability to wash hands for adequate duration and properly follow steps of hand hygiene, inability to don and doff PPE properly, carrying PPE to duty rooms before completely doffing, use of personal mobile phones during duty and improper sleep were identified. Lack of knowledge, long duty hours, shortage of PPE, high patient workload, and casual attitude regarding own safety were identified as important barriers. Resident doctors and paramedical staff in the age group 18-30 years reported lower adherence. CONCLUSIONS: Suboptimal compliance in preventive practices like handling PPE, distancing in cafeteria/duty rooms and hand hygiene is not uncommon in HCWs. Certain barriers are identified which should be addressed to ensure adequate safety of HCWs against COVID-19.

SARS-CoV-2 epidemic in India: epidemiological features and in silico analysis of the effect of interventions.

Background: After SARS-CoV-2 set foot in India, the Government took a number of steps to limit the spread of the virus in the country. This included restricted testing, isolation, contact tracing and quarantine, and enforcement of a nation-wide lockdown starting 25 March 2020. The objectives of this study were to i) describe the age, gender distribution, and mortality among COVID-19 patients identified till 14 April 2020 and predict the range of contact rate; and ii) predict the number of  COVID-19 infections after 40 days of lockdown. Methods: We used a cross-sectional descriptive design for the first objective and a susceptible-infected-removed model for in silico predictions. We collected data from government-controlled and crowdsourced websites. Results: Studying age and gender parameters of 1161 Indian COVID-19 patients, the median age was 38 years (IQR, 27-52) with 20-39 year-old males being the most affected group. The number of affected patients were 854 (73.6%) men and 307 (26.4%) women. If the current contact rate continues (0.25-27), India may have 110460 to 220575 infected persons at the end of 40 days lockdown. Conclusion: The disease is majorly affecting a younger age group in India. Interventions have been helpful in preventing the worst-case scenario in India but will be unable to prevent the spike in the number of cases.