Role of CYFRA 21-1 and CEA as prognostic and predictive markers in locally advanced and metastatic gastric carcinoma.

PURPOSE: Tumor-associated serum markers have demonstrated predictive and prognostic value in patients being treated for malignancies. However, the clinical importance of tumor markers in gastric cancers (GC) is poorly standardized. OBJECTIVES: The objective is to assess the clinical utility of cytokeratin-19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA) as serum tumor markers in advanced GC. METHODS: In this prospective study, CYFRA 21-1 and CEA levels were measured at baseline and after three cycles of chemotherapy in patients with advanced GC. The association of tumor marker levels with prognosis and decline of tumor markers with radiological overall response rates (ORR) and survival were analyzed. RESULTS: In the 105 patients, the proportion of patients with elevated baseline CYFRA 21-1 and CEA levels was 55% (N = 58) and 37% (N = 39) based on predefined cutoffs. Response assessment was done for 61 patients who received a minimum of three cycles of chemotherapy. A 15% and 13% reduction of serum levels from baseline for CYFRA 21-1 and CEA were selected for defining "CYFRA 21-1 response" and "CEA-response," respectively. Both responses were significant predictors of radiological ORR. The median overall survival (OS) was 9.6 months in the entire cohort and 13 months for patients who received at least three cycles of chemotherapy. In multivariate analysis, baseline CEA levels and ECOG status were significant predictors of OS. In a subset analysis of patients receiving palliative chemotherapy, any of the tumor marker responses predicted improved 1-year OS. CONCLUSION: In advanced GC, CYFRA 21-1 and CEA decline from baseline appeared to be reliable surrogate markers of chemotherapy efficacy and improved survival.

Prevalence and the factors associated with microalbuminuria among patients with type 2 diabetes mellitus and/or hypertension in the urban areas of Puducherry district: a cross-sectional study.

BACKGROUND: Microalbuminuria is an early indicator for renal and cardiovascular diseases, especially among patients with diabetes mellitus (DM) and hypertension (HTN). We determined the prevalence and the factors associated with microalbuminuria among patients with type 2 DM and/or HTN in the urban areas of the Puducherry district in India. METHODS: We included 225 patients aged 40-69 years with DM and/or HTN from a non-communicable diseases (NCDs) survey conducted during 2019-2020 in the urban areas of Puducherry district. The prevalence of microalbuminuria and various biological risk factors of NCDs were assessed as per the WHO STEPS methodology. The prevalence of microalbuminuria was presented as proportions (95% CI), and the adjusted prevalence ratio (aPR) was estimated using weighted forward stepwise generalized linear modelling. P-value ≤0.05 was considered statistically significant. RESULTS: The mean (SD) age of the patients was 54 (11) years. Over one-third (38.2%) (95% CI: 31.6-44.4) of patients with DM and/or HTN had microalbuminuria. The prevalence was highest among those having both DM and HTN 48% (95% CI: 37-59), followed by those having only DM 40.6% (95% CI: 29-52.2) and only HTN 27.7% (95% CI: 18.1-38.6). The prevalence of microalbuminuria was twice (aPR = 2.1, 95% CI: 1.1-3.9) higher among women and 2.4 times (95% CI: 1.12-5.1) higher among those having both DM and HTN as compared to those with only HTN. CONCLUSION: The prevalence of microalbuminuria among patients with DM and/or HTN is concerningly high. Population-based screening for microalbuminuria, especially among women and those having both DM and HTN, needs to be undertaken in the urban areas of Puducherry district.

Microalbuminuria serves as an early indicator for kidney and cardiovascular diseases, especially among patients with diabetes mellitus (DM) and hypertension (HTN). Our study focussed on determining the prevalence of microalbuminuria among individuals with type 2 DM and/or HTN in the urban areas of the Puducherry district in India. We included 225 patients aged 40­69 years with DM and/or HTN who participated in a non-communicable diseases (NCDs) survey conducted during 2019­2020 in urban Puducherry. We found that over one-third (38.2%) of patients with DM and/or HTN had microalbuminuria. The prevalence was highest among those having both DM and HTN (48%), followed by those having only DM (40.6%) and only HTN (27.7%). The prevalence of microalbuminuria was 2.1 times higher among women than men and 2.4 times higher among individuals with both DM and HTN compared to those with only HTN. These findings highlight the concerningly high prevalence of microalbuminuria among patients with DM and/or HTN in the urban areas of Puducherry district. To address this issue, it is crucial that the public health authorities of Puducherry district implement population-based screening initiatives for microalbuminuria, particularly targeting women and individuals with both DM and HTN in the urban areas of the Puducherry district.

Effect of daily zinc supplementation for 12 weeks on serum thyroid auto-antibody levels in children and adolescents with autoimmune thyroiditis - a randomized controlled trial.

OBJECTIVES: To assess the effect of daily zinc supplementation for 12 weeks on thyroid auto-antibodies - thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), and oxidative stress in children with autoimmune thyroid disease (AITD) compared to standard therapy. METHODS: This open-labeled, parallel, randomized controlled trial was done in a tertiary care teaching institute in south India. Children aged 3-18 years with AITD were randomized to receive 25 mg elemental zinc daily for 12 weeks or standard therapy alone. The change in thyroid function tests (thyroid stimulating hormone, free T3, free T4), thyroid auto-antibody (TPOAb, TgAb) titers, oxidative stress markers (glutathione peroxidase, malondialdehyde, superoxide dismutase, and total antioxidant capacity) were compared. RESULTS: Forty children, 20 in each arm, were recruited in the study. We observed a female-to-male ratio of 7:1. Median duration of disease was 2 (0.25, 4.25) years. A total of 37 (92.5 %) children were hypothyroid, two hyperthyroid, and one euthyroid at enrolment. A total of 13 children (32.5 %) had associated co-morbidities, most commonly type 1 diabetes mellitus and systemic lupus erythematosus, three (7.5 %) each. We did not find any significant change in thyroid function tests, thyroid auto-antibody titers, and oxidative stress markers. However, the requirement of levothyroxine dose was significantly increased in the control arm, compared to the zinc group (p=0.03). Only four (20 %) children had minor adverse effects like nausea, metallic taste, and body ache. CONCLUSIONS: Zinc supplementation did not have any effect on thyroid auto-antibodies and oxidative stress. Zinc-supplemented children did not require escalation in levothyroxine dose.

Association of plasma Decorin levels and markers of glycocalyx disruption with adverse events in women with severe preeclampsia.

Identifying preeclamptic women with an increased risk of severe maternal complications can aid in timely interventions to optimize pregnancy outcomes. Newer biomarkers such as Decorin and markers of endo glycocalyx disruption were assessed in earlier studies for its role in predicting preeclampsia, but their role in identifying those with adverse maternal outcomes is limited. This study aimed to evaluate the association of these biomarkers with adverse maternal outcomes in women with severe pre-eclampsia. Markers of glycocalyx disruption may be further explored for their role along with clinical features and other biomarkers in identifying women at higher risk of maternal complications.

Increased vascular risk factors, atherosclerosis, and psychological distress among Indian adults with refractory epilepsy in comparison to well-controlled epilepsy.

OBJECTIVE: Comparison of cardiovascular risk factors, atherosclerosis, and psychological distress among adults with refractory versus well-controlled epilepsy. METHODS: The cross-sectional study consisted of two groups of 40 people each: Group I - People with well-controlled epilepsy, Group II - People with refractory epilepsy. Age- and gender-matched people of 20-50 years were recruited. People who were diabetic, smokers, hypertensive, alcoholic, pregnant, with infections, and lactating women were excluded from the study. Biochemical parameters, fasting glucose, lipid profile, fasting insulin, leptin, adiponectin, Lp[a], hsCRP, TyG INDEX, HOMA1-%S, HOMA1-IR, HOMA1-%B, QUICKI, FIRI, AIP, AC, CLTI, MLTI, CRI-I, CRI-II, and CIMT were estimated. Stress levels [PSS-10, GAD-7 & PHQ-9] were assessed based on the scoring system from the questionnaires. RESULTS: The existence of metabolic syndrome, levels of triglycerides, TyG index, MDA, OSI, CIMT, AIP, and stress scores [PSS-10, GAD-7 & PHQ-9] were significantly higher in the refractory-epilepsy group in comparison to the well-controlled group. There were associations between LDL -C and CIMT as well as between GAD-7 and CIMT among all the study subjects. There were no significant differences in the levels of glucose homeostasis parameters, hsCRP, leptin, adiponectin, and Lp[a] between the two groups. Based on the ROC analysis, MDA [AUC = 0.853] and GAD-7 [AUC = 0.900] are useful in the differential diagnosis of the study groups. CONCLUSION: People with refractory epilepsy had increased levels of vascular risk factors, atherosclerosis, and stress levels compared to people with well-controlled epilepsy. Suitable disease management and therapeutic approaches to address cardiovascular and psychological distress could be planned out among people with refractory epilepsy to improve their quality of life.

Metabolic Bone Disease in Preterm Neonates With Fetal Growth Restriction (FGR): A Prospective Cohort Study.

OBJECTIVE: To study the association of fetal growth restriction (FGR) with metabolic bone disease in preterm neonates. METHODOLOGY: This prospective cohort study included 94 preterm neonates with FGR as cases and an equal number of gestation-matched appropriate for gestational age (AGA) neonates without FGR as controls. The incidence of metabolic bone disease, and serum biochemical markers at various time intervals till 6 months corrected age were compared. The risk factors for metabolic bone disease and its association with stunting at 6 months of corrected age were studied. RESULTS: The incidence of metabolic bone disease, though higher in the FGR neonates (15.5%), was not significantly different from AGA neonates (6.7%) [RR (95%CI) 0.92-5.82; P=0.06]. Birth weight [aOR (95%CI) 0.8 (0.64-0.98); P=0.03] and time to reach full feeds [aOR (95%CI) 1.17 (1.01-1.36); P=0.03] were significantly associated with an increased risk of metabolic bone disease after adjusting for FGR status. Mean (SD) levels of calcium, phosphorus, alkaline phosphatase, parathormone (PTH), and vitamin D were similar in both groups. No significant association existed between metabolic bone disease and stunting at 6 months of corrected age [RR (95%CI) 2 (0.75-5.4); P=0.16]. CONCLUSION: FGR was not found to be significantly associated with metabolic bone disease in preterm neonates.

Negative impact on bone homeostasis in postmenopausal women with non-metastatic breast cancer during cytotoxic chemotherapy.

INTRODUCTION: The burden and mechanisms of endocrine therapy-related bone loss are well known, while there are limited data on chemotherapy-induced bone resorption. The study aimed to evaluate the effect of cytotoxic chemotherapy on bone homeostasis among postmenopausal women with non-metastatic breast cancer. MATERIALS AND METHODS: Early and locally advanced postmenopausal non-metastatic breast cancer patients aged 45 to 65 planned for three cycles of anthracycline and four cycles of taxane chemotherapy administered along with dexamethasone (cumulative dose-256 mg) as an antiemetic from June 2018 to December 2021 were included. Bone mineral density (BMD), bone turnover markers, calciotropic hormones, pro-inflammatory cytokines, oxidative stress, and total antioxidant levels (TAS) were measured. RESULTS: We recruited 109 patients, with early 34 (31.2%) and locally advanced breast cancer 75 (68.8%) with median age 53 (45-65) years. There was a significant decrease in the % BMD at the lumbar spine, neck of the femur, and total hip post-chemotherapy. There was a significant increase in serum C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (PINP) levels post-chemotherapy. PINP/CTX ratio significantly decreased post-chemotherapy. Serum 25-OH vitamin D was significantly reduced with a compensatory increase in plasma iPTH levels. The change in CTX, PINP/CTX ratio, 25-OH vitamin D, iPTH, and oxidative stress index was more pronounced during anthracycline as taxane chemotherapy. There were no significant changes in pro-inflammatory cytokine levels. CONCLUSION: Chemotherapy and dexamethasone as antiemetic resulted in significant bone loss, as evidenced by bone turnover markers. Further studies are required to understand the mechanism of chemotherapy-induced bone loss and the need for bone-strengthening agents during chemotherapy.

Cytotoxic chemotherapy is associated with decreased bone mineral density in postmenopausal women with early and locally advanced breast cancer.

PURPOSE: The burden and mechanisms of endocrine therapy-related bone loss have been studied in detail. However, there is limited data regarding cytotoxic chemotherapy's impact on bone health. There are no definitive guidelines for bone mineral density (BMD) monitoring and treatment with bone-modifying agents during cytotoxic chemotherapy. The study's primary objective was to evaluate the changes in BMD and fracture risk assessment tool (FRAX) scores among breast cancer women on cytotoxic chemotherapy. METHODS: One hundred and nine newly diagnosed early and locally advanced postmenopausal breast cancer patients planned for anthracycline and taxane-based chemotherapy were recruited prospectively during the study period from July 2018 to December 2021. BMD of the lumbar spine, the femoral neck, and the total hip were assessed by dual-energy X-ray absorptiometry scan. BMD and FRAX scores were evaluated at baseline, end of chemotherapy, and 6 months of follow-up. RESULTS: The median age of the study population was 53 (45-65) years. Early and locally advanced breast cancers were seen in 34 (31.2%) and 75 (68.8%) patients, respectively. The duration of follow-up between two BMD measurements was 6 months. The percentage of decrease in BMD at the lumbar spine, femoral neck, and total hip were - 2.36 ± 2.90, - 2.63 ± 3.79, and - 2.08 ± 2.80, respectively (P-value = 0.0001). The median risk of major osteoporotic fracture (MOF) at 10 years (FRAX score) increased from 1.7 (1.4) to 2.7% (2.4) (P-value = 0.0001). CONCLUSION: This prospective study in postmenopausal breast cancer women shows a significant association of cytotoxic chemotherapy with the worsening of bone health in terms of BMD and FRAX score.

Supplementation of Water-Soluble Vitamins Reduces Hyperhomocysteinemia, Insulin Resistance, and High-Sensitivity C-reactive Protein in Prehypertension Subjects.

BACKGROUND: Prehypertensives are at higher risk of developing cardiovascular diseases. Hyperhomocysteinemia, insulin resistance, and increased high-sensitivity C-reactive protein (hs-CRP) are independent risk factors for the development of cardiovascular complications. In prehypertensives, specific therapeutic approaches can be implemented at the earliest to prevent the onset of overt hypertension. So the present study was performed to study the effect of supplementation of water-soluble vitamins on cardiovascular risk factors like homocysteine, insulin resistance, and C-reactive protein in prehypertensive subjects. METHODS: Sixty prehypertensive subjects were recruited into the study based on inclusion and exclusion criteria and randomized into two groups of 30 each. One group was given a placebo and the other was given water-soluble vitamins for four months. Serum homocysteine, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and hs-CRP were assayed. RESULTS: After four months of treatment with water-soluble vitamins, there was a significant decrease in levels of serum homocysteine, hs-CRP, and HOMA-IR when compared to placebo treatment. After four months of treatment, there was a significant decrease in the levels of hs-CRP, homocysteine, and HOMA-IR in groups treated with water-soluble vitamins compared to the basal levels. CONCLUSION: In subjects with prehypertension, supplementation of water-soluble vitamins decreases the level of homocysteine, insulin resistance, and hs-CRP.

Magnesium Sulfate as an Adjunct to Therapeutic Hypothermia in the Management of Term Infants with Hypoxic-Ischemic Encephalopathy: A Randomized, Parallel-Group, Controlled Trial.

OBJECTIVE: To evaluate whether magnesium sulfate and therapeutic hypothermia in combination decreases mortality and/or major neurodevelopmental disability at 1 y of age among term neonates with hypoxic-ischemic encephalopathy. METHODS: A total of 134 term neonates were randomized to receive intravenous magnesium sulfate at a dose of 250 mg/kg (at 8 mg/kg/min) once daily for 3 d starting within 6 h after birth along with therapeutic hypothermia in the intervention group and therapeutic hypothermia alone in the comparator group. The primary outcome was the composite outcome of mortality and/or major neurodevelopmental disability (Developmental Assessment Scale for Indian Infants score < 70) at 1 y of age. RESULTS: A total of 115 infants were included in the primary analysis. The composite primary outcome occurred in 14 (24%) infants in the intervention group and 19 (33%) infants in the comparator group, and the difference was not statistically significant (p = 0.30; relative risk 0.72; 95% confidence interval 0.40-1.30). The secondary outcomes including neonatal mortality, major neurodevelopmental disability at 1 y of age, neurological status at discharge, level of oxidative stress markers, and adverse effects including hypotension and respiratory depression requiring support were also comparable between the groups. CONCLUSIONS: The combination of magnesium sulfate and therapeutic hypothermia did not improve the composite outcome of neonatal mortality and/or major neurodevelopmental disability at 1 y of age. TRAIL REGISTRATION: Clinical Trials Registry of India (CTRI/2018/06/014594), prospectively registered.

High prevalence of abdominal obesities and metabolically unhealthy individuals in a highly urbanized district of India: findings of a cross-sectional survey in Puducherry.

BACKGROUND: Abdominal obesities are better markers for predicting cardiovascular abnormalities than risk stratification based only on body mass index (BMI). We aimed to estimate the prevalence of abdominal adiposities using predictive equations for Asian Indian adults and to determine the prevalence of metabolically healthy subjects among those overweight/obese and with normal BMI. METHODS: A community-based survey was conducted among those aged 18-69 years in the district of Puducherry between February 2019 and February 2020. We surveyed 2,560 individuals selected through multi-stage cluster random sampling from urban and rural areas (50 wards and 50 villages, respectively) of the district. Anthropometric measurements, such as height, weight, waist circumference, and blood pressure were recorded from each participant. Fasting blood sample was collected from each alternate participant to estimate metabolic risk factors. RESULTS: Over four-fifths (85.6%; 95% CI: 84.2-86.9) and two-thirds (69.7%; 95% CI: 67.9-71.6) of the population in the district had high levels of intra-abdominal adipose tissue (IAAT) and total abdominal fat (TAF), respectively. Both the risk factors were significantly higher among women and urban population. About 43% (95% CI: 41-44.9) of the population had high abdominal subcutaneous adipose tissue (SCAT) with a significantly higher prevalence among the urban population. Among those overweight/obese (n = 773), almost all 99.4% (95% CI: 98.7-99.9) were metabolically unhealthy. Among subjects with normal BMI (n = 314), only about 2.9% (95% CI: 1.3-4.8) were metabolically healthy. CONCLUSION: We highlight the substantially high prevalence of IAAT, TAF, and SCAT in the district of Puducherry. Almost all the study population was metabolically unhealthy irrespective of their BMI levels.

The distribution of abdominal fat is a better predictor of cardiovascular abnormalities in an individual than the risk assessment based only on body mass index (BMI). We conducted a community-based cross-sectional survey to estimate the prevalence of abdominal adiposities using predictive equations for Asian Indian adults and determine the prevalence of metabolically healthy subjects among those overweight/obese and with normal BMI. We surveyed 2,560 adults aged 18­69 years in the district of Puducherry between February 2019 and February 2020. We recorded each participant's anthropometric measurements, such as height, weight, waist circumference, and blood pressure and collected a fasting blood sample to assess their metabolic health status. Over four-fifths (85.6%) and two-thirds (69.7%) of the population in the district had high levels of intra-abdominal adipose tissue (IAAT) and total abdominal fat (TAF), respectively. Nearly half (43%) of the population had high abdominal subcutaneous adipose tissue (SCAT). Both the risk factors were substantially higher among women and the urban population. Among those overweight/obese, almost all (99.4%) were metabolically unhealthy; among those with normal BMI, only about 2.9% were metabolically healthy. From this study, we highlight the immediate need for population-based health promotion interventions, especially among women and urban residents of Puducherry district.

Association of Umbilical Cord Serum Oxidative Stress Markers, ADMA and Adiponectin with Adverse Fetal Outcomes in Hypertensive Disorders of Pregnancy.

BACKGROUND: Limited studies are available on fetal oxidative stress and endothelial dysfunction and their association with adverse fetal outcomes in hypertensive disorders of pregnancy (HDP). Method: Umbilical cord blood samples were collected at delivery from 134 pregnant women with HDP and 59 controls. Markers of oxidative stress, endothelial dysfunction and inflammation and adipokines were analyzed. Results were correlated with adverse fetal outcomes. Results: Malondialdehyde, total antioxidant status(TAS), ADMA and hsCRP levels were increased in late and early onset preeclampsia. Adiponectin levels were decreased in early onset preeclampsia. High ADMA levels were positively associated with preterm births and fetal mortality and high TAS, protein carbonyl content(PC), ADMA and low adiponectin levels were positively associated with low birth weight babies. Conclusion: Fetal systemic oxidative stress, endothelial dysfunction and inflammation were altered in early and late onset preeclampsia. High TAS, PC and ADMA levels and low adiponectin levels were positively associated with adverse fetal outcomes in HDP.

Performance of WHO updated cardiovascular disease risk prediction charts in a low-resource setting - Findings from a community-based survey in Puducherry, India.

BACKGROUND AND AIM: The World Health Organization has revised the cardiovascular disease (CVD) risk prediction charts in 2019 for each of the 21 Global Burden of Disease regions. These charts (non-lab and lab versions) estimate the total CVD risk in an individual, of which the non-lab is for low-resource settings. We aimed to estimate the burden of ten-year risk of fatal or non-fatal CVD event in the district of Puducherry in India using 'non-lab' and 'lab' versions of WHO CVD risk prediction charts, and to evaluate the agreement between them. METHODS AND RESULTS: We included 710 individuals aged 40-69 years who participated in a district wide non-communicable diseases survey conducted in Puducherry, India, during 2019-20. Both charts use information on age, gender, systolic blood pressure and smoking status. Additionally, lab-chart requires individual's status on diabetes mellitus and total cholesterol while non-lab requires body mass index. Population in different CVD risk levels was presented using proportions (95% confidence intervals). Agreement between lab and non-lab charts was evaluated using Cohen's Kappa (k). The lab and non-lab charts estimated 3% (95% CI: 1.7-4.2) and none of the population respectively, to have high risk (≥20%) for fatal or non-fatal CVD event over the next ten years. Both the charts showed 89.4% (95% CI:87.2%-91.7%) concordance in CVD risk prediction indicating a good level of agreement (k = 0.653). CONCLUSION: WHO updated CVD risk prediction charts are feasible to apply when data is available and there is good agreement between non-lab and lab based charts.

MicroRNA Expression in Neonates with Late-onset Sepsis - A Cross-sectional Comparative Study.

BACKGROUND: Neonatal sepsis is a major health concern among neonates with higher morbidity and mortality rate. Studies have recently speculated the importance of differential expression of circulating mature micro-RNAs (miRNAs) which could serve as diagnostic as well as prognostic markers for risk of mortality in neonatal sepsis. This study aimed to analyze the expression pattern and to assess the diagnostic/prognostic value of miRNAs miR-21, miR-29a miR-31, miR-146a, and miR-155 in late-onset neonatal sepsis. METHODS: A cross-sectional comparative study was conducted including 42 healthy controls and 42 neonates with late-onset neonatal sepsis. SYBR green-based miScript RT-PCR assay was used for the expression analysis and the comparative Ct method 2-delta (Ct) method was used for relative quantification of the candidate miRNAs in plasma. Significantly higher expression of miR-21 and miR-155 and lower expression of miR-29a and miR-146a was observed in cases compared to control except miR-31. In subgroups analysis, miR-21(p = .03) showed a significant difference between pre-term and term neonates and miR-31 (p = .01) and miR-155 (p = .03) showed a significant difference between low-birth-weight and normal-birth-weight neonates. miR-146a showed significantly lower expression in the non-survivor group compared to the survivor group (p = .005). A receiver operating characteristic curve (ROC) analysis of miR-21 and miR-29a (0.829 and 0.787 AUC of ROC curves) showed good discrimination for the identification of sepsis from non-sepsis neonates. CONCLUSION: The current study shows evidence of differential expression of miRNAs in neonatal sepsis and this altered expression of candidate miRNAs could be involved in immune dysregulation, thus leading to sepsis-related severity in newborns.

Serum biomarkers of maternal morbidity and adverse outcome in severe pre-eclampsia.

OBJECTIVE: To evaluate the association of maternal serum biomarkers of myocardial damage, oxidative stress and angiogenic imbalance with maternal adverse outcomes in women with severe pre-eclampsia. METHODS: This was a prospective cohort study, where maternal serum biomarkers were evaluated in women admitted with severe pre-eclampsia to a tertiary care centre between March 2019 and February 2020. Serum markers included brain naturetic peptide (BNP), cardiac troponin-T (cTnT), cystatin-C (cys-C), soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), Total Anti-Oxidant status (TAO) and malondialdehyde (MAO). Main outcome measures were adverse maternal outcomes defined as eclampsia, pulmonary oedema, acute kidney injury, placental abruption and HELLP syndrome. RESULTS: Adverse maternal outcomes occurred in 93(37.2%, 95% CI: 31.2%-43.6%) of the 250 women with severe pre-eclampsia included in the study, including 21 with pulmonary oedema, 25 with acute kidney injury and 36 with eclampsia. BNP levels were higher among women who developed pulmonary oedema (55.4 pg/mL vs 42.0 pg/mL, p = 0.008). TAO levels were higher in women who developed eclampsia (4.6 mM, IQR 3.1-5.7, p < 0.001) and acute kidney injury (4.1 mM, IQR 3.2-6.3, p = 0.002) compared to those who did not develop any complications (2.93 mM, IQR 2.3-4.1). CONCLUSIONS: Even though the endothelial dysfunction and oxidative stress biomarkers were associated with development of preeclampsia, it may have limited utility in identifying women who might develop adverse outcomes.

Intact Parathyroid Hormone Levels in Predicting Postoperative Hypocalcaemia After Total Thyroidectomy in South Indian Population: Cross Sectional Study.

Hypocalcaemia being one of the most common complications after total thyroidectomy may not be avoidable in all cases. This study evaluated the effectiveness of intact Parathyroid hormone (iPTH) measured at 1-h after total thyroidectomy in predicting postoperative hypocalcaemia in early postoperative period in South Indian population. Patients who underwent total thyroidectomy in our institute from 2016 to 2018 were included. Preoperative calcium and iPTH levels were measured. Patients' iPTH level was measured 1 h after surgery and serum calcium level was measured at 24 h after surgery. Patients were also monitored clinically for any symptoms and signs of hypocalcaemia. A total of 57 patients were studied. The malignant causes accounted for 75.4% with papillary carcinoma thyroid being the most common cause. 65.7% of patients who underwent total thyroidectomy and 100% of patients who underwent total thyroidectomy with neck dissection developed hypocalcaemia. 70% of patients with low iPTH developed hypocalcaemia and none of the patients who had normal iPTH developed hypocalcaemia. This relation was statistically significant with p value of 0.018 (< 0.05). The positive predictive value is 70% and negative predictive value is 100%. Though our study supports the hypothesis that iPTH is effective in predicting hypocalcaemia after total thyroidectomy in the early postoperative period, a larger sample study is needed to further support this. It can be used to consider patients for early discharge or to prophylactically start oral calcium and Vitamin D supplementation based on iPTH levels at 1 h after surgery.

Assessment of iron status in regular blood donors in a tertiary care hospital in Southern India.

BACKGROUND: Regular blood donation depletes iron stores. The assertion is that the vulnerable donor population requires a predictive standard operative procedure for early detection of iron store depletion, preventing them from developing iron-deficiency anemia. AIM: This study aims to study the potential effects of blood donation in the regular donor group using hematological and biochemical estimation of iron status parameters. STUDY SETTINGS AND DESIGN: This was a prospective cross-sectional study on regular blood donors, defined as those who have donated at least 3 times, the last donation being within the last 12 months and continues to donate at least once a year, at a tertiary care teaching hospital in Southern India. MATERIALS AND METHODS: The complete blood count (CBC) was performed on the Sysmex coulter, and the red cell indices were calculated. The ferritin and the soluble transferrin receptor (sTfR) assays were performed using Enzyme Immunoassays. STATISTICAL ANALYSIS USED: The comparison of CBC, serum ferritin, and sTfR assay with donation frequency and time since the last donation was carried out using an independent student's t-test for two groups. The statistical analysis was performed using SPSS for Windows version 20. RESULTS: A total of 323 regular blood donors (6 were females) were included in the study of which they were categorized into three, 211 donors with less than or equal to 10 donations, 84 those who had donated between 11 and 20 times and 28 who had donated more than 20 times. The red cell indices were reduced and different in the groups but not statistically significant except for mean corpuscular volume. About 15% of the study population had a transferrin level of <15 ng/ml. The Ferritin levels showed a statistically significant negative correlation with the number of donations, the correlation coefficient being -0.27. Logarithmic ratios of sTfR/ferritin also correlated with a coefficient of 0.156 with the number of donations and were statistically significant. CONCLUSION: Our study found that regular blood donors had low iron stores, as shown by ferritin levels and other iron indicators. Using the current guidelines (hemoglobin >12.5 g/dL) for donation, or the red cell indices alone do not reflect the donor's actual iron status.

Differences in the response to iron supplementation on oxidative stress, inflammation, and hematological parameters in nonanemic and anemic pregnant women.

BACKGROUND: Iron supplementation is widely recommended for all pregnant women, irrespective of their iron status. But providing excess iron to nonanemic pregnant women can result in iron overload, which may lead to oxidative stress and inflammation. OBJECTIVES: To assess the differential effect of iron supplementation on hematological parameters, oxidative stress, and inflammation in nonanemic and anemic pregnant women. METHODS: Forty nonanemic and forty anemic pregnant women were recruited at 12 weeks of gestation. The study subjects were supplemented with iron (60 mg/day for nonanemic pregnant women and 120 mg/day for anemic pregnant women). Fasting state blood samples were collected at 12 and 28 weeks of gestation. RESULTS: Malondialdehyde (MDA)/total antioxidant status (TAS) ratio (MDA/TAS) and high-sensitivity C-reactive protein (hsCRP) were significantly higher in anemic pregnant women before iron supplementation. Iron supplementation to the anemic pregnant women resulted in significant improvement in the hematological profile and ferritin levels. Further, the iron supplementation caused a significant reduction in hsCRP levels although the MDA/TAS ratio remained unaltered. Iron supplementation to nonanemic pregnant women resulted in a significant increase in the levels of MDA/TAS ratio and hsCRP, but there were no changes in hematological profile and serum ferritin levels. CONCLUSION: Prophylactic iron supplementation in nonanemic pregnant women increased oxidative stress and inflammation. However, in anemic pregnant women, iron supplementation was found to be beneficial as it improved hematological status and decreased inflammation without affecting oxidative stress.

Increased hepcidin levels in preeclampsia: a protective mechanism against iron overload mediated oxidative stress?

BACKGROUND: Pregnancy is a metabolic state which demands increased iron bioavailability. While in preeclampsia, due to the placental vascular events there is an iron surplus environment along with inflammation and placental hypoxia. Routinely in India iron is supplemented to all pregnant women irrespective of their general physical condition. Hepcidin a regulator of iron metabolism protects the cells from iron mediated cytotoxicity. OBJECTIVE: To find out whether hepcidin gets induced as a protective mechanism in preeclampsia patients in order to combat the environment of iron overload, oxidative stress, and endothelial dysfunction. METHODS: A cross-sectional study with follow up was carried out in a South Indian Tamil population. Forty healthy pregnant women and forty preeclampsia patients in the gestational age 32 ± 4 weeks were recruited (n = 80). Biochemical analysis to assess the serum levels of the following were carried out (1) indices of iron homeostasis - serum iron, ferritin, transferrin, hepcidin, (2) endothelial dysfunction -serum assymetric dimethyl arginine (ADMA) (3) oxidative stress - Malon di aldehyde (MDA) and ferric reducing ability of plasma (FRAP). Kolmogorov-Smirnov test, Mann-Whitney U test, Spearman's correlation, linear regression and ROCAUC analysis were performed to understand their relationship with each other. RESULTS: Levels of serum iron, ferritin, transferrin saturation, hepcidin, and MDA/FRAP ratio were elevated significantly in preeclampsia patients compared to controls, while serum transferrin levels were significantly decreased in them. Hepcidin levels showed a significant positive correlation with serum ADMA, and MDA/FRAP. Serum hepcidin, transferrin saturationand MDA/FRAP ratio is useful in differentiating pre-eclampsia patients from healthy pregnant women. CONCLUSION: Iron supplementation in preeclampsia patients might have led to a state of iron overload, which might have caused oxidative stress and endothelial dysfunction in preeclampsia patients. The rise in hepcidin levels in this scenario may be viewed as a protective mechanism to combat the iron overload mediated cytotoxicity.

Identification of differentially methylated candidate genes and their biological significance in IUGR neonates by methylation EPIC array.

BACKGROUND: Intrauterine growth restriction (IUGR) is a pregnancy-associated disease manifested by decreased growth rate of fetus than the normal genetic growth potential. It is associated with increased susceptibility to metabolic diseases later in life. Although the mechanisms underlying the origin of metabolic diseases are poorly understood, DNA methylation is a crucial investigation for the identification of epigenetic changes. OBJECTIVES: To assess the degree of change of DNA methylation in IUGR neonates and compare with that of appropriate for gestational age (AGA) neonates and to explore the differentially methylated candidate genes and their biological significance. METHODS: This cohort study was conducted in the Neonatology Department of JIPMER during the period of November 2017 to December 2018. Forty each of IUGR and gestation matched AGA neonates were recruited. Umbilical cord blood samples were collected at birth. DNA was separated from the blood samples; and, using 5-mC DNA ELISA method, the percentage of genomic DNA methylated in these neonates was established. Data were expressed as mean ± standard deviation. Methylation EPIC array was performed to identify the differentially methylated candidate genes. David analysis was used to find out the functional annotation chart by KEGG pathway. RESULTS: Genomic DNA methylation varied significantly between IUGR and AGA neonates (IUGR: 3.12 ± 1.24; AGA: 4.40 ± 2.03; p value: <.01). A global shift toward hypomethylation was seen in IUGR compared with AGA, targeted to regulatory regions of the genome, and specifically promoters. Pathway analysis identified deregulation of pathways involved in metabolic diseases. Altered methylation of PTPRN2 & HLADQB1 genes leads to dysregulation of T-cells and reactive oxygen species (ROS). These changes may lead to complications later among these neonates subjected to IUGR. CONCLUSION: Our findings show significant changes in the methylation pattern of genes among IUGR and AGA babies. Steps for correcting the changes may help in reducing later complications among IUGR babies.