Furosemide stress test to predict acute kidney injury progression in critically ill children.

BACKGROUND: Furosemide stress test (FST) is a novel functional biomarker for predicting severe acute kidney injury (AKI); however, pediatric studies are limited. METHODS: Children 3 months to 18 years of age admitted to the intensive care unit (ICU) of a tertiary care hospital from Nov 2019 to July 2021 were screened and those who developed AKI stage 1 or 2 within 7 days of admission underwent FST (intravenous furosemide 1 mg/kg). Urine output was measured hourly for the next 6 h; a value > 2 ml/kg within the first 2 h was deemed furosemide responsive. Other biomarkers like plasma neutrophil gelatinase-associated lipocalin (NGAL) and proenkephalin (PENK) were also evaluated. RESULTS: Of the 480 admitted patients, 51 developed AKI stage 1 or 2 within 7 days of admission and underwent FST. Nine of these patients were furosemide non-responsive. Thirteen (25.5%) patients (eight of nine from FST non-responsive group) developed stage 3 AKI within 7 days of FST, nine (17.6%) of whom (seven from non-responsive group) required kidney support therapy (KST). FST emerged as a good biomarker for predicting stage 3 AKI and need for KST with area-under-the-curve (AUC) being 0.93 ± 0.05 (95% CI 0.84-1.0) and 0.96 ± 0.03 (95% CI 0.9-1.0), respectively. FST outperformed NGAL and PENK in predicting AKI stage 3 and KST; however, the combination did not improve the diagnostic accuracy. CONCLUSIONS: Furosemide stress test is a simple, inexpensive, and robust biomarker for predicting stage 3 AKI and KST need in critically ill children. Further research is required to identify the best FST cut-off in children.

The Relationship of Birth Size and Postnatal Growth with Cellular Senescence in Adults: Data from the New Delhi Birth Cohort.

OBJECTIVE: To assess the effect of birth size and postnatal body mass index (BMI) gain from birth to adulthood on leucocytes cellular senescence in adult life. METHODS: Participants were aged 43.04 (± 0.92) y, and were enrolled from the New Delhi Birth Cohort study, who participated in phase 7 of the study (n = 210). Cellular senescence markers, p16 and p21 gene expression were determined by RT-qPCR in leucocytes and their association with birth size and conditional BMI gain at 2, 11, and 29 y were assessed in univariate and multivariate regression models. RESULTS: Birth weight (regression coefficient; B = -0.087, p = 0.011) and birth BMI (unadjusted B = -0.024, p = 0.026; adjusted B = -0.032, p = 0.022) were inversely associated with p21 gene expression in adult life. The p16 gene expression was not associated with any birth parameters. Conditional BMI gain at 2 y, 11 y, and 29 y was not associated with either p16 or p21 gene expression. The p21 gene expression was inversely associated with circulating insulin (B = -0.065, p = 0.026) and C-peptide levels (unadjusted B = -0.097, p = 0.014; adjusted B = -0.133, p = 0.003). CONCLUSION: Small size at birth is associated with accelerated cellular senescence in adult life. An altered senescent state is likely to be one of the links between LBW and adult chronic diseases.

Performance of equations for estimation of 24-hour urinary sodium from morning fasting urine samples in a multisite study in India.

Background Dietary salt intake is an important modifiable risk factor for cardiovascular diseases. Estimation of 24-hour salt intake using morning urine samples needs to be validated in the Indian context. We examined the performance of INTERSALT, Tanaka and Kawasaki equations for the estimation of 24-hour urinary sodium from morning fasting urine (MFU) samples. Methods We enrolled 486 adults aged 18-69 years from four regions of India with equal rural/urban and sex representation to provide 24-hour urine samples. The next day, a MFU sample was obtained. Based on the volume and sodium content of the 24-hour urine sample, 24-hour sodium excretion (reference method) was calculated. Sodium levels in the MFU samples were measured along with other parameters required, and the above equations were used to estimate 24-hour urinary sodium levels. Intraclass correlation coefficient (ICC) was used to assess the degree of agreement between the estimates from the reference method and the three equations. Bland-Altman (BA) plots were used to identify systematic bias and limits of agreement. A difference of 1 g of salt (0.39 g of sodium) between the mean salt intake by 24-hour urine and as estimated by equations was considered acceptable. Results A total of 346 participants provided both the samples. The mean (SD) daily salt intake estimated by the 24-hour urine sample method was 9.9 (5.8) g. ICC was low for all the three equations: highest for Kawasaki (0.16; 95% CI 0.05-0.26) and least for Tanaka (0.12; 0.02-0.22). Only Tanaka equation provided estimates within 1 g of measured 24-hour salt intake (-0.36 g). BA plots showed that as the mean values increased, all the three equations provided lower estimates of salt intake. Conclusion Tanaka equation provided acceptable values of 24-hour salt intake at the population level. However, poor performance of all the equations highlights the need to understand the reasons and develop better methods for the measurement of sodium intake at the population level.

The effect of Bacillus coagulans Unique IS-2 supplementation on plasma amino acid levels and muscle strength in resistance trained males consuming whey protein: a double-blind, placebo-controlled study.

PURPOSE: The aim of the present study was to assess the effect of Bacillus coagulans Unique IS-2 supplementation on absorption and utilization of protein in resistance-trained males. METHODS: In this double blind, placebo-control trial, resistance-trained males (21.08 ± 2.84 years) were randomized to consume, either 20 g of whey protein powder {80% whey protein concentrate (WPC80), amounting to 15.4 g protein} with 2 billion CFU Bacillus coagulans Unique IS-2 (supplemental group) or 20 g of whey protein powder and lactose instead of Bacillus coagulans (placebo group) once daily for 60 days with a controlled resistance exercise protocol. The whey protein concentrate (WPC-80) given to both groups had a lactose content of 6.8%. Plasma-free amino acids (PFAAs) were determined at baseline, at 30 and 60 days of supplementation. Muscle strength, hypertrophy, VO2 max, and body composition, and other biochemical parameters were assessed at baseline and end line. RESULTS: A positive effect of probiotic Bacillus coagulans Unique IS-2 supplementation was observed on protein absorption as evidenced by an increase in total PFAA by + 16.1% (p = 0.004). Branched chain amino acids (BCAA) comprising isoleucine (p = 0.016), leucine (p = 0.001), and valine (p = 0.002) were increased by + 33.1% in ITT analysis as compared to placebo after 60 days. At 30 days an increase in isoleucine by + 35% (p = 0.113), leucine by + 43% (p = 0.032), and valine by + 32% (p = 0.017) was observed in ITT analysis. Probiotic effect was shown on exercise performance as evidenced by an increase in one RM of leg press and vertical jump power by + 16.61% (p = 0.024) and + 7.86% (p = 0.007), respectively. CONCLUSION: Significantly increased absorption of BCAA with supplementation of B. coagulans Unique IS-2 along with whey protein and improvement in leg press and vertical jump power was noted indicating the positive effect of the probiotic on muscle power in the lower body. TRIAL REGISTRATION NUMBER: CTRI/2017/03/008117; Date:16.03.2017.

Association of birth outcomes and postnatal growth with adult leukocyte telomere length: Data from New Delhi Birth Cohort.

Born small for gestational age due to undernutrition in utero and subsequent catch-up growth is associated with risk of developing chronic diseases in adulthood. Telomere length has been shown to be a predictor of these age-related diseases and may be a link between birth size, a surrogate for foetal undernutrition, and adult chronic diseases. We assessed the relationship of leukocyte telomere length in adult life with birth outcomes and serial change in body mass index (BMI) from birth to adulthood. Leukocyte relative telomere length (RTL) was measured by MMqPCR in 1,309 subjects from New Delhi Birth Cohort who participated in two phases of the study between 2006-2009 (Phase 6) and 2012-2015 (Phase 7) at a mean age of 39.08 (±3.29), and its association with birth outcomes and conditional BMI gain at 2, 11, and 29 years was assessed in a mixed regression model. We did not find any significant association of RTL with body size at birth including birthweight, birth length, and birth BMI. Gestational age was positively associated with RTL (P = .017, multivariate model: P = .039). Conditional BMI gain at 2 and 11 years was not associated with RTL. BMI gain at 29 year was negatively associated with RTL in multivariate model (P = .015). Born small for gestational age was not associated with RTL in adulthood. Leukocyte telomere attrition was observed in those born before 37 weeks of gestational age as well as in those who gained weight as adults, which may predispose to chronic diseases.

Feasibility of measuring sodium, potassium and creatinine from urine sample on dried filter paper.

Aim: To develop a bioassay for estimation of sodium, potassium and creatinine in dried urine strips and comparing with their respective concentration in liquid urine samples. Materials & methods: Urine was collected on filter paper strips, dried at room temperature and, eluted for estimation of sodium, potassium by indirect ion selective electrode method and creatinine by Jaffé method. Result: This bioassay was validated based on the US FDA guidelines for bioanalytical method validation and was linear, sensitive, accurate and precise with acceptable recovery and matrix effects. Analytes were stable in dried urine strips during 1 year of storage at 4°C. Conclusion: We conclude that the dried urine is suitable for analysis of sodium, potassium and creatinine and offers a convenient alternative for monitoring dietary salt intake.

Validation of quantitative polymerase chain reaction with Southern blot method for telomere length analysis.

AIM: Telomere length (TL) measurement by quantitative polymerase chain reaction (PCR) has been widely accepted, but limited information regarding its validation with a gold-standard technique is available. MATERIALS & METHODS: We measured TL by Southern blot and monochrome multiplex quantitative PCR (MMqPCR) and validated the results of TL in leukocytes of 94 participants with mean age 43.2 years, BMI 19-41 (mean 27.8 ± 4.3) kg/m2. RESULTS: A significant positive correlation was observed between TL measured by MMqPCR and Southern blot assay (correlation coefficient r = +0.896, p < 0.0001). The inter- and intra-assay CVs of the MMqPCR assay were 5.3 and 4.07%, respectively. CONCLUSION: We observed that experimental discrepancies have an impact on TL analysis and there is a need to improve the optimum conditions.

Independent association of severe vitamin D deficiency as a risk of acute myocardial infarction in Indians.

BACKGROUND: Association of vitamin D deficiency with coronary heart disease (CHD) has been widely reported. Emerging data has shown high prevalence of vitamin D deficiency among Indians. However, this association has not been studied in Indians. METHODS: A case-control study with 120 consecutive cases of first incident acute myocardial infarction (MI) and 120 age and gender matched healthy controls was conducted at All India Institute of Medical Sciences, New Delhi. The standard clinical and biochemical risk factors for MI were assessed for both cases and controls. Serum 25 (OH) vitamin D assay was performed from stored samples for cases and controls using radioimmunoassay. RESULTS: Vitamin D deficiency [25(OH) D < 30 ng/ml] was highly prevalent in cases and controls (98.3% and 95.8% respectively) with median levels lower in cases (6 ng/ml and 11.1 ng/ml respectively; p < 0.001). The cases were more likely to have diabetes, hypertension and consume tobacco and alcohol. They had higher waist hip ratio, total and LDL cholesterol. Multivariate logistic regression analysis revealed severe vitamin D deficiency [25(OH) vitamin D < 10 ng/ml] was associated with a risk of MI with an odds ratio of 4.5 (95% CI 2.2-9.2). CONCLUSIONS: This study reveals high prevalence of vitamin D deficiency among cases of acute MI and controls from India, with levels of 25 (OH)D being significantly lower among cases. Despite rampant hypovitaminosis, severe vitamin D deficiency was associated with acute MI after adjusting for conventional risk factors. This association needs to be tested in larger studies in different regions of the country.

Antistreptokinase antibodies and outcome of fibrinolytic therapy with streptokinase for left-sided prosthetic valve thrombosis.

BACKGROUND: Left-sided prosthetic valve thrombosis (PVT) is a serious complication of valve replacement. In developing countries, fibrinolysis with streptokinase (SK) is often used as the first line of treatment. Anti-streptokinase (anti-SK) antibodies are widely prevalent in the general population, but their effect on the efficacy and outcome of fibrinolysis with SK in patients with PVT is not known. METHODS: Patients with rheumatic heart disease and prosthetic valve replacement presenting with a first episode of left-sided PVT were enrolled. All patients underwent fibrinolysis with SK. An indirect enzyme-linked immunosorbent assay was used to detect anti-SK antibodies before fibrinolysis. Relationship of these antibodies to the outcome of fibrinolysis was evaluated. RESULTS: Forty-four patients treated for left-sided PVT were included. Thrombosis affected 33 mitral and 11 aortic prosthetic valves. On fibrinolysis with SK, 32 (73%) patients achieved complete success, whereas it was unsuccessful in the remaining 12 patients. There were 3 bleeding events, 1 stroke, and 3 deaths. Mean anti-SK antibody levels were not significantly different between patients who had complete success and those who did not (8.81 ± 2.43 vs 7.67 ± 1.26 Au/mL; P = .13) and did not correlate with the outcome after adjustment with other variables. Patients in New York Heart Association class III or IV had a greater chance of failed fibrinolytic therapy, even after adjustment for other prognostic variables (odds ratio 9.0; 95% CI 1.29-63.02; P = .027). CONCLUSION: Anti-SK antibody titers are not associated with success of fibrinolytic therapy using SK in patients with left-sided PVT.

Role of dried blood spots in health and disease diagnosis in older adults.

Older adults represent a substantial number of the world population, which is set to grow considerably in the coming years. The health challenges faced by the older adults are unique. Several age-related changes in them make phlebotomy difficult. Application of dried blood has been demonstrated to be useful in the other similarly vulnerable population, the neonates. Similar approach of standardization and demonstration of use of dried blood spots (DBS) for analytes of interest in older adult population would be highly appreciated. There are very few reports of use of DBS in older adults. There are several potential areas of interest for older adults in which DBS assays are available but have not been applied for screening in them. This review describes a brief general overview of DBS, its advantages and disadvantages and potential use in disease diagnosis in older adults.

LDL particle heterogeneity, and its association with other established cardiovascular risk factors in a young Indian industrial population.

OBJECTIVE: Low density lipoprotein (LDL) particles are heterogeneous in terms of size, density, chemical composition and electric charge with certain particle of LDL being more atherogenic than the others. The present study aimed to look at the LDL particle heterogeneity, particle size and association with other cardiovascular disease (CVD) risk factors in young Indian industrial population. METHODOLOGY: 600 employees of an industry of Delhi, aged 20-39 years were selected for the study. Data on demographics, individual characteristics associated with major risk factors of CVD, past medical history, clinical and anthropometric profile was collected. Fasting glucose, lipid profile, apolipoprotein (A1, B, and E), lipoprotein (a), high sensitive C-reactive protein (hsCRP) and insulin were estimated. LDL particle size was determined in ethylenediamminetetraacetate (EDTA) plasma by 3% polyacrylamide gel electrophoresis. RESULT: We found a prevalence of small dense LDL phenotype (LDL size ≤ 26.3) in 27.4% of males and 24.0% of females. The mean waist circumference, blood pressure, triglycerides (TAG), cholesterol, hsCRP, apolipoprotein (A1, B and E) and insulin were higher in males whereas mean high density lipoprotein was higher in females. Females also had a significantly higher mean LDL particle diameter as compared to males. CONCLUSION: TAG, physical activity and lipoprotein (a) correlated with small dense LDL in this young Indian population.