Micronutrient Deficiencies and Anemia in Urban India-Do We Need Food Fortification?

Prevalence of anemia in India is almost 40% with no significant change since 1998-99, whereas globally this prevalence has been reduced to < 15%. This could be because our national nutritional programs (mainly National Nutritional Anemia Control Program-NNACP) focus on supplementation with iron and folate but not with vitamin B12. Some Indian studies, including our study (2012), indicated high prevalence of B12 deficiency in North Indian urban population. Hence, we conducted a retrospective analysis of 3 years' data (2012-2014 including 48,317 subjects) and compared it with last year's retrospective data (April 2019-March 2020 including 4775 subjects) to ascertain prevalence of deficiencies of these micronutrient with special reference to patients of anemia, and improvement therein over the subsequent 5-year period. Our results indicate that amongst our subjects with anemia, iron deficiency has reduced from 66.73% (2012-2014) to 56.86% (2019), but prevalence of vitamin B12 deficiency is still the same (36.54% in 2012-2014; 37.04% in 2019). Folate deficiency was similar in both sets of data (2.95% in 2012-2014 and 2.55% in 2019). Thus, NNACP has reduced prevalence of iron deficiency by ~ 10%points and folate deficiency marginally; B12 deficiency has not been addressed. It would, therefore, follow that we need to add to our current national programs to effectively deal with these deficiencies. Food fortification (with iron, folate and B12) seems the most likely means to add value to the existing programs. In addition, food diversification needs to be included in regular school curriculum to bring about community awareness and change in food habits.

Evolution of serum hyaluronan and syndecan levels in prognosis of sepsis patients.

OBJECTIVES: Endothelial glycocalyx shedding has been recognized as a contributor in sepsis pathophysiology. Hence, we attempted to analyze hyaluronan and syndecan (glycocalyx components) as markers of morbidity and prognosis of sepsis by performing serial measurements in these patients. DESIGN AND METHODS: Subjects were community acquired sepsis, severe sepsis and septic shock patients (150) admitted to ICU of our tertiary care hospital and controls were 50 healthy volunteers. Serum concentrations of markers were measured on days 1, 3, 5, 7 of ICU admission. Survival was assessed after 90days. Statistical analysis was performed by SPSS version 17. RESULTS: Hyaluronan and syndecan levels were significantly elevated in all categories of sepsis patients as compared to healthy controls (p<0.001). Levels of both markers were increased in severe sepsis and septic shock patients as compared to sepsis patient group at all time-points. Hyaluronan and syndecan differentiated survivors from non-survivors (p<0.001). Unlike non-survivors, in the survivor group, median hyaluronan and syndecan levels decreased significantly (p<0.001) in subsequent measurements. ROC analysis for the prediction of mortality identified cut-offs of 441ng/ml and 898ng/ml for hyaluronan and syndecan respectively. The specificity and negative predictive values were 90% and 90% for hyaluronan and 86% and 91% for syndecan respectively. Kaplan Meier curves revealed similar results. Both markers correlated significantly with APACHE II and SOFA scores. CONCLUSIONS: These observations indicate that serial measurements of hyaluronan and syndecan are significant prognostic markers for morbidity and survival in sepsis. Future therapeutic interventional possibilities need to be explored in experimental interventional prospective multi-centric trials.

Procalcitonin as a rapid diagnostic biomarker to differentiate between culture-negative bacterial sepsis and systemic inflammatory response syndrome: a prospective, observational, cohort study.

PURPOSE: Differentiation between culture-negative sepsis and noninfectious systemic inflammatory response syndrome (SIRS) remains a diagnostic challenge for clinicians, both conditions having similar clinical presentations. Therefore, a swift accurate diagnostic tool, which helps differentiate these 2 conditions would immensely aid appropriate therapeutic continuum. This prospective study was conducted to evaluate the potential diagnostic role of biomarkers, procalcitonin (PCT) and interleukin 6 (IL-6), in culture-negative sepsis patients. METHODS: Enrolled patients (208) included 46 noninfectious SIRS, 90 culture-negative sepsis, and 72 culture-positive sepsis. Culture, PCT, and IL-6 estimations were performed on day 1 of intensive care unit admission. RESULTS: Procalcitonin and IL-6 levels were significantly higher (P < .001) in both culture-negative and culture-positive groups as compared with SIRS group. Procalcitonin was a better predictor of sepsis in both culture-negative (area under curves 0.892 vs 0.636) and culture-positive (area under curves 0.959 vs 0.784) groups as compared with IL-6. In culture-negative group, the best cutoff point for PCT was at 1.43 ng/mL (92% sensitivity; 83% negative predictive value), best cutoff point for IL-6 was at 219.85 pg/mL (47% sensitivity and 42% negative predictive value). CONCLUSIONS: Procalcitonin can accurately differentiate culture-negative sepsis from noninfectious SIRS and thereby contribute to early diagnosis and effective management of these conditions.

Differential expression of lipid peroxidation and total antioxidant status in Indian patients with cardiovascular and cerebrovascular disease.

Data from studies examining lipid peroxidation as a mechanism involved with hyperhomocysteinemia (HHcy)-induced vascular remodeling in patients with occlusive vascular disease have been contradictory. It has not yet been studied in Indians within the context of atherogenesis. Therefore, we measured the levels of homocysteine (Hcy), malondialdehyde (MDA) as a measure of lipid peroxides (LPOs), and total antioxidant status (TAS) in the serum of 167 patients with occlusive vascular disease [coronary artery disease (CAD) = 43; cerebrovascular disease (CVD) = 82; peripheral vascular disease (PVD) = 42]. Each of these groups was further divided into groups of individuals with or without HHcy. In the case of CAD and CVD, patients with HHcy had significantly higher LPOs than those without HHcy (p = 0.009, 0.001, respectively). TAS was significantly lower in CVD patients with HHcy than in those without (p = 0.014). In patients with CAD or CVD, Hcy directly correlated with LPOs (p = 0.002, 0.001, respectively). Lipid peroxidation is a significant mechanism in HHcy-induced vascular remodeling in CAD and CVD, but not in PVD, probably because it is not relevant in thrombosis (38 of 42 patients of PVD had deep-vein thrombosis). To explain the significantly lower TAS in CVD, we hypothesized that CVD patients present very early with grave symptoms, whereas CAD and PVD occur over a longer period of time. Therefore, when CVD presents, TAS is still overwhelmed by HHcy-induced oxidative stress. Hence, adjuvant therapy with antioxidants would benefit patients with CVD.

Interrelationship between procalcitonin and organ failure in sepsis.

Sepsis suffers from lack of specific clinical symptoms which contribute to one of the major causes of mortality. In the present study, our aim was to evaluate the role of a recent biomarker Procalcitonin (PCT) in predicting organ dysfunction. 71 patients admitted with sepsis were included in the study. PCT levels were measured at 0, 24, 72 h and 7th day and sequential organ failure assessment score (SOFA) scores were calculated. PCT levels significantly decreased (p < 0.001) in 89.3 % of surviving patients, whereas, in 60 % non surviving patients the PCT level increased significantly (p < 0.001). A significant positive correlation between PCT and SOFA score was observed in survivors at each hour. These observations indicate that PCT concentration is significantly associated with severity of multi organ dysfunction and also helps in determining the prognosis of septic patients.

Homocysteine in occlusive vascular disease: a risk marker or risk factor.

Homocysteine has emerged as a significant marker for occlusive vascular disease, but there has been some debate as to whether it is just an association (risk marker) or actually a causative factor (risk factor). To elucidate this, a retrospective statistical analysis was done of data generated in the course of our study on homocysteine and vascular disease. Homocysteine, lipid profile components and lipoprotein(a) were estimated in fasting blood samples drawn from 252 controls and 536 patients of occlusive vascular disease. The data were analyzed by SPSS version 17. Mean homocysteine levels were significantly higher (p < 0.001) in all patients categories, as compared to controls. In fact, homocysteine level was the most significant biochemical risk factor for vascular disease. The odds ratios due to hyperhomocysteinemia varied from 3.170-4.153. When the cut-off was increased by 5 micromol/L, the odds ratio became almost three-fold. The prevalence of hyperhomocysteinemia increased by approximately equal to 20%, when the cut-off was reduced by 5 micromol/L. Statistical analysis of our data revealed that homocysteine conformed to Hill's criteria of causation. Moreover, hyperhomocysteinemia was treatable by the administration of B-vitamins, even if the cause was genetic. Hence morbidity due to vascular disease could be reduced by identification and treatment of hyperhomocysteinemia.

Prevalence of hyperhomocysteinemia in vascular disease: comparative study of thrombotic venous disease vis-à-vis occlusive arterial disease.

Studies on hyperhomocysteinemia in vascular occlusive disease have included mostly patients with arterial occlusion. However, more recent studies have included cases of venous occlusive disease as well. Our present study is aimed at comparing the prevalence of hyperhomocysteinemia in venous occlusive disease vis-à-vis arterial occlusive disease in the North Indian urban population. Homocysteine was estimated by chemiluminescent immunoassay in 205 normal controls and 536 patients, 244 presenting with arterial occlusion and 292 with venous thrombotic disease. The mean homocysteine in patients with arterial occlusion was 21.79 +/- 0.09 micromol/L (mean +/- standard error of measurement), in patients with venous thrombosis was 25.53 +/- 0.1 micromol/L, and in controls was 11.33 +/- 0.18 micromol/L. The prevalence of hyperhomocysteinemia (> 15 micromol/L) was 56.38% in arterial occlusive disease and 54.64% in venous thrombosis. In patients with peripheral vascular occlusive disease, patients with deep venous thrombosis (DVT) had the highest mean homocysteine level (25.51 micromol/L), which was even higher (32.14 micromol/L) when associated with pulmonary embolism (PE). There is a high prevalence of hyperhomocysteinemia in arterial and venous occlusive disease. Hence, in all patients with vascular occlusive disease, hyperhomocysteinemia should be elucidated and treated. In addition, long-term follow-up is required to ascertain whether the reduction in homocysteine decreases the thrombotic events and whether homocysteine levels can actually be of prognostic or predictive value in cases of DVT with PE.

Role of ascorbic acid on in vitro oxidation of low-density lipoprotein derived from hypercholesterolemic patients.

BACKGROUND: The susceptibility of low-density lipoprotein (LDL) to oxidation is thought to be a crucial factor responsible for atherogenesis. There is substantial evidence for a role of dietary antioxidants in the prevention of atherogenesis and the protective effect of antioxidant nutrients may be mediated through inhibition of the oxidative modification of LDL. METHODS: We performed in vitro oxidation of LDL derived from normal and hypercholesterolemic individuals in absence and presence of different doses of ascorbic acid. RESULTS: The serum lipid peroxidation level was significantly increased in hypercholesterolemic patients and their LDL has shown a greater propensity towards in vitro oxidation. Hypercholesterolemic LDL required a higher amount of ascorbic acid to reduce its oxidation level as compared to LDL isolated from normocholesterolemic individuals. CONCLUSION: This observation may be of importance in designing future studies of antioxidant supplementation in patients with hypercholesterolemia which is one of the major risk factors for atherosclerosis.