Sumit Ray

Enantioselective synthesis of coumarin derivatives by PYBOX-DIPH-Zn(II) complex catalyzed Michael reaction.

A potential pharmacologically active chiral 3-substituted 4-hydroxy-2-oxo-2H-chromene skeleton has been synthesized by enantioselective Michael addition catalyzed by PYBOX-DIPH-Zn(OTf)(2) complex. The methodology has successfully been employed in the synthesis of (R)-Warfarin and another related compounds.

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.

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.

Severe suicidal digoxin and propranolol toxicity with insulin overdose

We present a case of a 32-year-old male doctor, with type I diabetes mellitus on daily insulin therapy, who allegedly consumed large doses of digoxin and propranolol along with simultaneous administration of large dose of insulin with suicidal intent. Initial investigations revealed serum digoxin levels of 7.5 ng/ml, serum insulin 500 μIU/ml, and serum C-peptide 0.43 ng/ml. He was managed with charcoal-based hemoperfusion for digoxin overdose along with injection glucagon for propranolol overdose. His blood sugar levels were maintained with continuous infusion of 20% dextrose till the patient was allowed to take oral diet. Significant clinical improvement was noticed with this therapy which was evident by progressively declining serum digoxin levels, normalization of pulse rate, and adequate blood glucose levels. Finally, with a good hemodynamic profile and a serum digoxin level well within normal limits, he was discharged following consultation with a psychiatrist.

Association of high mortality with extended–spectrum β-lactamase (ESBL) positive cultures in community acquired infections

Purpose: Infections due to multidrug resistant organisms have become a serious health concern worldwide. The present study was conducted to investigate the spectrum of microbial resistance pattern in the community and their effects on mortality. Methods: A retrospective review and analysis of prospectively collected data was done of all patients admitted with diagnosis of sepsis in two tertiary care ICUs for a period of two years. Demographics, culture positivity, microbial spectrum, resistance pattern and outcome data were collected. Results: Out of 5309 patients enrolled; 3822 had suspected clinical infection on admission with 1452 patients growing positive microbial cultures. Among these, 201 bacterial strains were isolated from patients who had community acquired infections. 73% were Gram negative bacilli, commonest being E. coli (63%). 63.4% E. coli and 60.7% Klebsiella isolates were ESBL producers. The mortality in ESBL positive infections was significantly higher as compared to ESBL negative infections (Odds ratio 2.756). Moreover, ESBL positive patients empirically treated with Beta Lactams + Beta Lactamase inhibitors (BL + BLI) had significantly higher mortality as compared to patients treated with carbapenems. More data from multiple centres need to be gathered to formulate appropriate antibiotic policy for critically ill patients admitted from the community. HighlightsHigh incidence of ESBL producing gram negative infections from the community is worrying.ESBL positive organisms found to cause higher mortality as compared to ESBL negatives.BL + BLI combination is not appropriate for ESBL.

Exploration of eosinopenia as a diagnostic parameter to differentiate sepsis from systemic inflammatory response syndrome: Results from an observational study

Aim of the Study: Initial differentiation of sepsis from systemic inflammatory response syndrome (SIRS) is of prime importance for early institution of appropriate treatment. This study aimed to compare the differential diagnostic efficacy of absolute eosinophil count (AEC - a routinely available economic marker) with total leukocyte count (TLC) and procalcitonin (PCT - a costly marker available only in specialized settings). Materials and Methods: In this prospective observational study, 170 patients of sepsis (severe sepsis = 125; SIRS = 45) were enrolled. AEC, TLC, and PCT were measured in the blood of all patients at the time of admission and data analyzed statistically. Results: Median AEC was 0 cells/mm3 in both SIRS and sepsis. TLC and PCT levels were significantly higher (P < 0.001) in culture negative, culture positive, and overall sepsis groups in comparison to SIRS group. At a cutoff of < 50 cells/mm3, AEC demonstrated a sensitivity and specificity of 23% and 68%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of TLC were 57%, 71%, 85%, 37% and of PCT were 82.4%, 82.2%, 93%, and 63%, respectively with area under curve of 0.455 for AEC, 0.640 for TLC, 0.908 for PCT. Conclusions: This study suggests that eosinopenia is not a reliable diagnostic tool to differentiate sepsis from SIRS. PCT and TLC are better differential diagnostic biomarkers.

Acute right heart syndrome: Rescue treatment with inhaled nitric oxide

Acute right heart syndrome is a common occurrence in intensive care units and is associated with a poor prognosis. There is lack of understanding of the involved pathophysiology, standard diagnostic protocols and treatment guidelines. Management goals include ensuring adequate right ventricle (RV) filling, maximizing RV contraction and reducing RV afterload. We describe a 39-year-old female with acute decompensated right heart failure secondary to multiple causes. She was managed with inhaled nitric oxide. Her condition improved, which was evident by a decrease in her pulmonary artery systolic pressure on serial echocardiography, decreased requirement of vasopressors and successful weaning from the ventilator.