Comparisons between sequential measurements were performed separately among survivors and non-survivors by using the Wilcoxon signed-rank test.Comparisons of demographic characteristics selleck products were done by chi-squared test for qualitative characteristics; for quantitative characteristics with normal distribution, the Student t test was used for two groups and analysis of variance was used for more than two groups.To create a prognostication rule, the following steps were followed: First, receiver operator curve (ROC) analysis was done with suPAR of day 1 and APACHE II score as independent variables to predict unfavorable outcome. Values of APACHE II score and suPAR with an ROC analysis specificity of above 70% were selected. The latter specificity cutoff was selected since it was considered of importance for risk assessment in sepsis [18].

Second, the importance of the selected cutoffs as independent predictors of unfavorable outcome was defined by step-wise Cox regression analysis. Disease severity, selected cutoffs, and presence of at least one underlying disease were included as independent variables in the equation. Underlying diseases were chronic obstructive pulmonary disorder, diabetes mellitus type 2, chronic renal disease, heart failure, solid tumor malignancy, and chronic intake of corticosteroids since these disease states are widely recognized to affect final outcome. Age, white blood cells, and values of blood gases were not included in the regression analysis, because they were factored into APACHE II. Hazard ratios and 95% CIs were assessed.

Third, ROC analysis of the combination of suPAR and APACHE II score was also performed. Given Cook’s method of analysis of the role of biomarkers as indexes of disease severity [19], it is highly probable that the ROC generated by the combination of APACHE II score and suPAR does not provide an area under the curve (AUC) superior to that of single APACHE II score or single suPAR. To this end, four strata of severity were generated by using the defined cutoffs of APACHE II score and suPAR. Odds ratios (ORs) and 95% CIs for risk prediction within each stratum were calculated by using Mantel and Haenszel statistics. Comparisons between ORs were done by using Breslow-Day test and Tarone test. Fourth, mortalities between strata were compared by using the chi-squared test and log-rank test.

Fifth, comparisons of the risk strata between the study cohort and the confirmation cohort were done by using the chi-squared test. P values of below 0.05 were considered Entinostat significant.ResultsStudy cohortA total of 1,914 patients were enrolled in the study cohort from a total of 2,145 patients screened for eligibility (Figure (Figure1).1). All consecutively enrolled patients in the biobank of the Hellenic Sepsis Study Group during the period of January 2008 to December 2010 were included in the present study; 62.2% had sepsis and 37.