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      Accuracy of plasma sTREM-1 for sepsis diagnosis in systemic inflammatory patients: a systematic review and meta-analysis

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          Abstract

          Introduction

          Early diagnosis of sepsis is vital to the clinical course and outcome of septic patients. Recently, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) appears to be a potential marker of infection. The objective of this systematic review and meta-analysis was to evaluate the accuracy of plasma sTREM-1 for sepsis diagnosis in systemic inflammatory patients.

          Methods

          A systematic literature search of PubMed, Embase and Cochrane Central Register of Controlled Trials was performed using specific search terms (up to 15 October 2012). Studies were included if they assessed the accuracy of plasma sTREM-1 for sepsis diagnosis in adult patients with systemic inflammatory response syndrome (SIRS) and provided sufficient information to construct a 2 X 2 contingency table.

          Results

          Eleven studies with a total of 1,795 patients were included. The pooled sensitivity and specificity was 79% (95% confidence interval (CI), 65 to 89) and 80% (95% CI, 69 to 88), respectively. The positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 4.0 (95% CI, 2.4 to 6.9), 0.26 (95% CI, 0.14 to 0.48), and 16 (95% CI, 5 to 46), respectively. The area under the curve of the summary receiver operator characteristic was 0.87 (95% CI, 0.84 to 0.89). Meta-regression analysis suggested that patient sample size and assay method were the main sources of heterogeneity. Publication bias was suggested by an asymmetrical funnel plot ( P = 0.02).

          Conclusions

          The present meta-analysis showed that plasma sTREM-1 had a moderate diagnostic performance in differentiating sepsis from SIRS. Accordingly, plasma sTREM-1 as a single marker was not sufficient for sepsis diagnosis in systemic inflammatory patients.

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          Most cited references39

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          Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes.

          We have identified new activating receptors of the Ig superfamily expressed on human myeloid cells, called TREM (triggering receptor expressed on myeloid cells). TREM-1 is selectively expressed on blood neutrophils and a subset of monocytes and is up-regulated by bacterial LPS. Engagement of TREM-1 triggers secretion of IL-8, monocyte chemotactic protein-1, and TNF-alpha and induces neutrophil degranulation. Intracellularly, TREM-1 induces Ca2+ mobilization and tyrosine phosphorylation of extracellular signal-related kinase 1 (ERK1), ERK2 and phospholipase C-gamma. To mediate activation, TREM-1 associates with the transmembrane adapter molecule DAP12. Thus, TREM-1 mediates activation of neutrophil and monocytes, and may have a predominant role in inflammatory responses.
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            Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations.

            We consider how to combine several independent studies of the same diagnostic test, where each study reports an estimated false positive rate (FPR) and an estimated true positive rate (TPR). We propose constructing a summary receiver operating characteristic (ROC) curve by the following steps. (i) Convert each FPR to its logistic transform U and each TPR to its logistic transform V after increasing each observed frequency by adding 1/2. (ii) For each study calculate D = V - U, which is the log odds ratio of TPR and FPR, and S = V + U, an implied function of test threshold; then plot each study's point (Si, Di). (iii) Fit a robust-resistant regression line to these points (or an equally weighted least-squares regression line), with V - U as the dependent variable. (iv) Back-transform the line to ROC space. To avoid model-dependent extrapolation from irrelevant regions of ROC space we propose defining a priori a value of FPR so large that the test simply would not be used at that FPR, and a value of TPR so low that the test would not be used at that TPR. Then (a) only data points lying in the thus defined north-west rectangle of the unit square are used in the data analysis, and (b) the estimated summary ROC is depicted only within that subregion of the unit square. We illustrate the methods using simulated and real data sets, and we point to ways of comparing different tests and of taking into account the effects of covariates.
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              The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study.

              Define the epidemiology of the four recently classified syndromes describing the biologic response to infection: systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock. Prospective cohort study with a follow-up of 28 days or until discharge if earlier. Three intensive care units and three general wards in a tertiary health care institution. Patients were included if they met at least two of the criteria for SIRS: fever or hypothermia, tachycardia, tachypnea, or abnormal white blood cell count. Development of any stage of the biologic response to infection: sepsis, severe sepsis, septic shock, end-organ dysfunction, and death. During the study period 3708 patients were admitted to the survey units, and 2527 (68%) met the criteria for SIRS. The incidence density rates for SIRS in the surgical, medical, and cardiovascular intensive care units were 857, 804, and 542 episodes per 1000 patient-days, respectively, and 671, 495, and 320 per 1000 patient-days for the medical, cardiothoracic, and general surgery wards, respectively. Among patients with SIRS, 649 (26%) developed sepsis, 467 (18%) developed severe sepsis, and 110 (4%) developed septic shock. The median interval from SIRS to sepsis was inversely correlated with the number of SIRS criteria (two, three, or all four) that the patients met. As the population of patients progressed from SIRS to septic shock, increasing proportions had adult respiratory distress syndrome, disseminated intravascular coagulation, acute renal failure, and shock. Positive blood cultures were found in 17% of patients with sepsis, in 25% with severe sepsis, and in 69% with septic shock. There were also stepwise increases in mortality rates in the hierarchy from SIRS, sepsis, severe sepsis, and septic shock: 7%, 16%, 20%, and 46%, respectively. Of interest, we also observed equal numbers of patients who appeared to have sepsis, severe sepsis, and septic shock but who had negative cultures. They had been prescribed empirical antibiotics for a median of 3 days. The cause of the systemic inflammatory response in these culture-negative populations is unknown, but they had similar morbidity and mortality rates as the respective culture-positive populations. This prospective epidemiologic study of SIRS and related conditions provides, to our knowledge, the first evidence of a clinical progression from SIRS to sepsis to severe sepsis and septic shock.
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                Author and article information

                Contributors
                Journal
                Crit Care
                Crit Care
                Critical Care
                BioMed Central
                1364-8535
                1466-609X
                2012
                29 November 2012
                : 16
                : 6
                : R229
                Affiliations
                [1 ]Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China
                Article
                cc11884
                10.1186/cc11884
                3672614
                23194114
                bcb1e7a5-9d02-4e16-9faa-c11228fe402f
                Copyright ©2012 Wu et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 August 2012
                : 15 November 2012
                : 28 November 2012
                Categories
                Research

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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