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      Clinical utility of biomarkers of endothelial activation in sepsis-a systematic review

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          A strong biologic rationale exists for targeting markers of endothelial cell (EC) activation as clinically informative biomarkers to improve diagnosis, prognostic evaluation or risk-stratification of patients with sepsis.


          The objective was to review the literature on the use of markers of EC activation as prognostic biomarkers in sepsis. MEDLINE was searched for publications using the keyword 'sepsis' and any of the identified endothelial-derived biomarkers in any searchable field. All clinical studies evaluating markers reflecting activation of ECs were included. Studies evaluating other exogenous mediators of EC dysfunction and studies of patients with malaria and febrile neutropenia were excluded.


          Sixty-one studies were identified that fulfilled the inclusion criteria. Overall, published studies report positive correlations between multiple EC-derived molecules and the diagnosis of sepsis, supporting the critical role of EC activation in sepsis. Multiple studies also reported positive associations for mortality and severity of illness, although these results were less consistent than for the presence of sepsis. Very few studies, however, reported thresholds or receiver operating characteristics that would establish these molecules as clinically-relevant biomarkers in sepsis.


          Multiple endothelial-derived molecules are positively correlated with the presence of sepsis in humans, and variably correlated to other clinically-important outcomes. The clinical utility of these biomarkers is limited by a lack of assay standardization, unknown receiver operating characteristics and lack of validation. Additional large-scale prospective clinical trials will be required to determine the clinical utility of biomarkers of endothelial activation in the management of patients with sepsis.

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          Most cited references 101

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          GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.

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            APACHE II: a severity of disease classification system.

            This paper presents the form and validation results of APACHE II, a severity of disease classification system. APACHE II uses a point score based upon initial values of 12 routine physiologic measurements, age, and previous health status to provide a general measure of severity of disease. An increasing score (range 0 to 71) was closely correlated with the subsequent risk of hospital death for 5815 intensive care admissions from 13 hospitals. This relationship was also found for many common diseases. When APACHE II scores are combined with an accurate description of disease, they can prognostically stratify acutely ill patients and assist investigators comparing the success of new or differing forms of therapy. This scoring index can be used to evaluate the use of hospital resources and compare the efficacy of intensive care in different hospitals or over time.
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              The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine.


                Author and article information

                Crit Care
                Crit Care
                Critical Care
                BioMed Central
                16 January 2012
                : 16
                : 1
                : R7
                [1 ]Division of Hematology, University of British Columbia, Vancouver General Hospital, 855 12th Ave W, Vancouver, BC V5Z 1M9, Canada
                [2 ]Divisions of Pediatric Infectious Disease and Critical Care, University of Toronto, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada
                [3 ]McLaughlin-Rotman Centre for Global Health, University Health Network, 101 College Street, Suite 406 Toronto, ON M5G 1L7, Canada
                [4 ]Department of Medicine, University of Toronto, 1 King's College Circle Medical Sciences Building-Room 2109, Toronto, ON M5S 1A8, Canada
                [5 ]Interdepartmental Division of Critical Care Medicine, University of Toronto, Queen Street Wing, Room 4-042, 30 Bond Street, Toronto, ON M5B 1W8, Canada
                Copyright ©2012 Xing et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


                Emergency medicine & Trauma

                coagulation, endothelium, biomarker, sepsis, angiopoietin


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