The Role of Angiotensin II Type 1 Receptor A1166C Polymorphism in Autosomal Dominant Polycystic Kidney Disease.

Introduction Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic disorder that affects the kidney, which affects all ethnical groups worldwide, with varied clinical presentations and severity. The studies done in various parts of the world on the association between angiotensin II type 1 receptor (AT1R) A1166C gene polymorphism and ADPKD patients have revealed inconsistent results. This study was done to assess the role of AT1R A1166C gene polymorphism in ADPKD in the South Indian population, which is the first of its kind. Methodology This is a case-control study, conducted at a tertiary care center in South India. This study was concerned with the frequency of exposure (genotype) in ADPKD patients. Peripheral blood samples from 85 unrelated ADPKD patients and 94 controls without diabetes, hypertension, or any kidney-related disease were collected. The AT1R A1166C polymorphism was compared between (i) the cases and controls, (ii) early and late stages of chronic kidney disease (CKD) (ADPKD) subjects, and (iii) ADPKD subjects with and without hypertension. Results Among the ADPKD patients, 45 (52.9%) subjects showed early stage (CKD stages 1-3), and 40 (47%) subjects showed late stage CKD (CKD stages 4 and 5). The genotype distribution of the studied 85 ADPKD patients was almost similar. No significant association was found between the genotype distribution of AT1R A1166C polymorphism in AA vs. AC (OR = 1.11; 95% CI = 0.37-3.32; p < 0.844) and A vs. C (OR = 1.11; 95% CI = 0.38-3.32; p < 0.847) between cases and controls. The genotype distributions in genetic model AA vs. AC (OR = 3.07; 95% CI = 0.56-16.8; p < 0.177) and allelic model A vs. C (OR = 2.13; 95% CI = 0.40-11.3; p < 0.364) between the early and late CKD stages of ADPKD were also not significant. No significant association of gene polymorphism was found between the non-hypertensive and hypertensive groups of ADPKD. Conclusion The results of our study suggest there is no significant association between AT1R A1166C polymorphisms and ADPKD in the South Indian population. Further, the gene polymorphism is not related to the progression of ADPKD or the presence of hypertension in ADPKD cases in South India.

One-Pot Hydrothermal Preparation of Hydroxyapatite/Zinc Oxide Nanorod Nanocomposites and Their Cytotoxicity Evaluation against MG-63 Osteoblast-like Cells.

In the present study, HAp-ZnO nanorod nanocomposites were successfully prepared using a customized hydrothermal reactor and studied for their compatibility against MG-63 osteoblast-like cells. The crystallinity, morphology, presence of chemical elements, and surface area properties were studied by XRD (X-ray diffraction), FE-SEM (field emission scanning electron microscopy), TEM (transmission electron microscopy), EDS (energy dispersive spectrum) and N2 adsorption/desorption isotherm techniques, respectively. Further, the mechanical strength and thermal analysis were carried out using the nanoindentation method and thermogravimetric/differential scanning calorimeter (TG/DSC) methods, respectively. Moreover, in vitro biocompatibility studies for the prepared samples were carried out against human osteosarcoma cell lines (MG-63). The crystalline nature of the samples without any impurity phases was notified from XRD results. The formation of composites with the morphology of nanorods and the presence of desired elements in the intended ratio were verified using FE-SEM and EDS spectra, respectively. The TG/DSC results revealed the improved thermal stability of the HAp matrix, promoted by the reinforcement of the ZnO nanorods. The nanoindentation study ensured a significant enhancement in the mechanical stability of the prepared composite material. Finally, it demonstrated that the HAp matrix's mechanical strength and thermal stability were improved by the reinforcement of ZnO, and the cytotoxicity evaluation affirmed the biocompatible nature of the biomimetic hydroxyapatite in the composite.

Role of secondary sepsis in COVID-19 mortality: Observations on patients with preexisting diabetes mellitus and newly diagnosed hyperglycemia.

Diabetics who develop severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) are more likely to have severe disease, higher odds of intensive care requirement and mortality. Fifteen percent of patients have new onset hyperglycemia. We studied the comparative outcomes between prior DM, newly detected hyperglycemia and assessed role of secondary sepsis on mortality. RWe performed a r etrospective study of confirmed SARS-CoV-2 patients at a tertiary care hospital in Chennai, India. Patients were divided as 2 groups (Group 1: With preexisting diabetes mellitus, Group 2: With newly diagnosed hyperglycemia due to newly detected diabetes mellitus or non-diabetic hyperglycemia. Clinical and laboratory data was analysed. Two hundred and thirty eight patients had prior-diabetes mellitus (Group 1) and 40 had newly diagnosed hyperglycemia (Group 2). Thirty four of group 1 and 7 of group 2 patients required intensive care. Mean capillary blood glucose (MCBG) during hospital stay was 207 mg/dl (Group 1) and 192 mg/dl (Group 2). Twentysix patients (9.3%) had secondary sepsis of which sixteen died. Logistic regression identified secondary sepsis(p<0.0001), elevated D-dimer >6 fold (p= 0.0001), elderly p=0.0045), male (p=0.0006), NLR >5 (p=0.01),serum creatinine ≥2 mg/dl (p=0.0004), FiO2 requirement >0.6 in first 48 hours (p=0.001) as mortality predictors.Our study observed a 14.38 % prevalence of newly diagnosed DM or non-diabetic hyperglycemia. Secondary sepsis and >6 fold elevation in D-dimer were strong predictors of mortality. Steroid use possibly contributed to secondary sepsis. Early identification and aggressive management of secondary sepsis are necessary for diabetics.

Dynamic Profile of Prognostic Hematologic Indicators in Patient Under Intensive Care for COVID-19 Disease: A One-Year Study at a Tertiary Care Centre in South India.

Introduction Viral pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS COV-2) releases cytokines which result in neutrophils migration to the bloodstream and cytotoxic effect on lymphocytes. The ongoing pathology is reflected in the derangement of blood cells and the variations and calculations based on them that help in assessing the severity of the disease and prognosis. Aim This study aimed to compare the differences in the dynamic changes of the blood cells among survivors and non-survivors of COVID-19 disease so that cut-offs can be arrived at to aid triage at the intensive care unit (ICU) and to predict mortality.  Material and methods A one-year study was conducted on patients hospitalized in the ICU. The demography and laboratory values of neutrophils and lymphocytes in percentages and absolute values, and platelet count in numbers were retrieved for eight consecutive values. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) was calculated from absolute counts. Statistical analysis was done using the Chi-Square test and Mann-Whitney test and a P-value of <0.05 is considered significant. The comparison was done between survivors and non-survivors. Result Among the 3142 patients admitted for COVID-19 disease, 7.6% required ICU care of whom 65.5% survived and 35.5% succumbed to the illness. Survivors were younger and comparable between both sexes. Though both groups had an ascending trend of neutrophils, lymphocytes, NLR, and PLR, the baseline characteristics were significantly lower in those who survived on a day-to-day basis. Neutrophilia above 80%, NLR 7.96, PLR 200 predicted the need for admission in ICU. Neutrophilia of 87% and lymphopenia of 10% were associated with adverse outcomes (mortality). Mortality can be predicted when neutrophil rises above 93% or lymphocytes fall below 5.2%. An initial NLR of 7.96 and PLR of 160 as well as peak NLR of 12.29 and peak PLR 400 predict mortality. Conclusion Serial blood counts are essential for hospitalized patients with COVID-19 for early triaging, and to assess severity and prognosis. The NLR of 6.7 and PLR of 160 require intensive care. The dynamic increase of NLR and PLR show worsening of the disease process and NLR of 40.95 and PLR of 400 predict mortality.

Course of COVID-19 Based on Admission D-Dimer Levels and Its Influence on Thrombosis and Mortality.

BACKGROUND: Arterial and venous thrombosis is one of the major complications of coronavirus disease 2019 (COVID-19) infection. Studies have not assessed the difference in D-dimer levels between patients who develop thrombosis and those who do not. METHODS: Our study retrospectively assessed D-dimer levels in all virus confirmed hospitalized patients between May to September, 2020. Patients were divided into three groups: group 1 with normal D-dimer of < 0.5 µg/mL, group 2 with elevation up to six folds, and group 3 with more than six-fold elevation. Statistical analysis was done using SPSS software 23.0. RESULTS: Seven hundred twenty patients (group1 (n = 414), group 2 (n = 284) and group 3 (n = 22)) were studied. Eight thrombotic events were observed. Events were two with stroke, two non-ST elevation myocardial infarction and one each of ST elevation myocardial infarction, superior mesenteric artery thrombosis with bowel gangrene, arteriovenous fistula thrombus and unstable angina. No significant difference (P = 0.11) was observed between median D-dimer levels among patients who developed thrombosis (1.34) and those who did not develop thrombosis (0.91). Twenty-nine patients died. The adjusted odds of death among those with a six-fold or higher elevation in D-dimer was 128.4 (95% confidence interval (CI): 14.2 - 446.3, P < 0.001), while adjusted odds of developing clinical thrombosis was 1.96 (95% CI: 0.82 - 18.2, P = 0.18). CONCLUSIONS: Our study observed a 1.1% in-hospital incidence of clinical thrombosis. While, a six-fold elevation in D-dimer was significantly associated with death; the same was not a strong predictor of thrombosis; an observation which implies that dose of anticoagulation should not be based on absolute D-dimer level.