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.

The potential of Cystatin C and small dense LDL as biomarkers of coronary artery disease risk in a young Indian population.

Coronary artery disease (CAD) affects Indians 5-6 years earlier than in the west, is diffuse and malignant, and poses a heavy burden on India's developing economy. Traditional risk factors have failed to explain this high incidence of premature CAD and hence this study investigated the association of two novel risk biomarkers, cystatin C and small dense LDL (sdLDL) with the presence and severity of CAD. Cystatin C and sdLDL were estimated in 204 CAD patients ≤45 years of age and compared with 161 age-matched healthy controls. The traditional lipid profile parameters, i.e., cholesterol, LDL, HDL, triglycerides, apolipoproteins A1 and B, and Lp(a) were also measured in both groups. Cystatin C was significantly raised and mean LDL particle size significantly reduced in CAD patients as compared to controls. 62.7 % of CAD patients showed pattern B while 37.3 % patients showed pattern A. Of the traditional lipid tests, only HDL and apolipoprotein A1 showed a significant decrease in the CAD group. sdLDL was significantly associated with the severity of CAD, while cystatin C was not. Both cystatin C and sdLDL emerged as independent risk factors, however, of the two, sdLDL was a more sensitive predictor of CAD events. Cystatin C and mean LDL particle size are significantly and independently associated with the presence of CAD events in patients ≤45 years with normal kidney function. Hence, these novel risk biomarkers can be useful tools in reducing the morbidity and mortality associated with CAD in the productive Indian workforce.

Lowering homocysteine and modifying nutritional status with folic acid and vitamin B(12) in Indian patients of vascular disease.

Hyperhomocysteinemia is more commonly associated with vascular disease in Indians than in the western populations. It is caused by genetic polymorphisms or dietary deficiencies of the B vitamins. We attempted to identify the association of hyperhomocysteinemia with vitamin B(12) and folate in Indian patients of vascular disease. Homocysteine, vitamin B(12) and folate levels were estimated in 100 controls and 100 patients of vascular disease. Homocysteine estimation was repeated in 73 patients on different vitamin supplements for 6 months. Homocysteine exhibited a significant negative correlation with B(12) only in cerebrovascular disease and peripheral vascular diseasepatients, and with folate in coronary artery disease and cerebrovascular disease patients as well as controls. Single daily dose of folate was as effective as a combination of folate and cobalamin in reducing plasma homocysteine concentrations. Low levels of B(12) contribute to the higher incidence of cerebrovascular disease and peripheral vascular disease, and low folate levels account for higher prevalence of hyperhomocysteinemia in coronary artery disease and cerebrovascular disease. Moreover, irrespective of the cause of hyperhomocysteinemia, folate is known to ameliorate it. Hence, large-scale corrective measures like food fortification or dietary supplementation with folate might benefit the Indian population and reduce the incidence and morbidity of vascular disease.

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.

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.