TY - JOUR
T1 - The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis
AU - Shapiro, Nathan I.
AU - Schuetz, Philipp
AU - Yano, Kiichiro
AU - Sorasaki, Midori
AU - Parikh, Samir M.
AU - Jones, Alan E.
AU - Trzeciak, Stephen
AU - Ngo, Long
AU - Aird, William C.
N1 - Funding Information:
We are grateful to all local physicians, the nursing staff, research team, and patients who participated in this study. We thank Steve Moskowitz for his artwork. Funding sources: This study was supported by an investigator initiated grant from Eli Lilly. While no investigator received direct salary support, the grant was used to pay for supplies and assays. Supplies and a device for measuring point-of-care lactate levels were provided by Abbott Point-of-Care. Dr. Shapiro is supported in part by National Institutes of Health grants HL091757, GM076659, and 5R01HL093234-02. Dr. Schuetz was supported by a research grant from the Swiss Foundation for Grants in Biology and Medicine (Schweizerische Stiftung für medizinisch-biologische Stipendien, SSMBS). Dr. Yano is supported by National Institutes of Health grant GM088184. Dr. Parikh is supported by NIH grant 5R01HL093234-02. Dr. Jones is supported by NIH grant GM076652. Dr. Trzeciak is supported by NIH grant GM083211. Dr. Aird is supported by National Institutes of Health grants HL091757 and GM088184.
PY - 2010/10/13
Y1 - 2010/10/13
N2 - Introduction: Previous reports suggest that endothelial activation is an important process in sepsis pathogenesis. We investigated the association between biomarkers of endothelial cell activation and sepsis severity, organ dysfunction sequential organ failure assessment (SOFA) score, and death.Methods: This is a prospective, observational study including adult patients (age 18 years or older) presenting with clinical suspicion of infection to the emergency department (ED) of an urban, academic medical center between February 2005 and November 2008. Blood was sampled during the ED visit and biomarkers of endothelial cell activation, namely soluble fms-like tyrosine kinase-1 (sFlt-1), plasminogen activator inhibitors -1 (PAI-1), sE-selectin, soluble intercellular adhesion molecule (sICAM-1), and soluble vascular cell adhesion molecule (sVCAM-1), were assayed. The association between biomarkers and the outcomes of sepsis severity, organ dysfunction, and in-hospital mortality were analyzed.Results: A total of 221 patients were included: sepsis without organ dysfunction was present in 32%, severe sepsis without shock in 30%, septic shock in 32%, and 6% were non-infected control ED patients. There was a relationship between all target biomarkers (sFlt-1, PAI-1, sE-selectin, sICAM-1, and sVCAM-1) and sepsis severity, P < 0.05. We found a significant inter-correlation between all biomarkers, including the strongest correlations between sFlt-1 and sE-selectin (r = 0.55, P < 0.001), and between sFlt-1 and PAI-1 (0.56, P < 0.001). Among the endothelial cell activation biomarkers, sFlt-1 had the strongest association with SOFA score (r = 0.66, P < 0.001), the highest area under the receiver operator characteristic curve for severe sepsis of 0.82, and for mortality of 0.91.Conclusions: Markers of endothelial cell activation are associated with sepsis severity, organ dysfunction and mortality. An improved understanding of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis.
AB - Introduction: Previous reports suggest that endothelial activation is an important process in sepsis pathogenesis. We investigated the association between biomarkers of endothelial cell activation and sepsis severity, organ dysfunction sequential organ failure assessment (SOFA) score, and death.Methods: This is a prospective, observational study including adult patients (age 18 years or older) presenting with clinical suspicion of infection to the emergency department (ED) of an urban, academic medical center between February 2005 and November 2008. Blood was sampled during the ED visit and biomarkers of endothelial cell activation, namely soluble fms-like tyrosine kinase-1 (sFlt-1), plasminogen activator inhibitors -1 (PAI-1), sE-selectin, soluble intercellular adhesion molecule (sICAM-1), and soluble vascular cell adhesion molecule (sVCAM-1), were assayed. The association between biomarkers and the outcomes of sepsis severity, organ dysfunction, and in-hospital mortality were analyzed.Results: A total of 221 patients were included: sepsis without organ dysfunction was present in 32%, severe sepsis without shock in 30%, septic shock in 32%, and 6% were non-infected control ED patients. There was a relationship between all target biomarkers (sFlt-1, PAI-1, sE-selectin, sICAM-1, and sVCAM-1) and sepsis severity, P < 0.05. We found a significant inter-correlation between all biomarkers, including the strongest correlations between sFlt-1 and sE-selectin (r = 0.55, P < 0.001), and between sFlt-1 and PAI-1 (0.56, P < 0.001). Among the endothelial cell activation biomarkers, sFlt-1 had the strongest association with SOFA score (r = 0.66, P < 0.001), the highest area under the receiver operator characteristic curve for severe sepsis of 0.82, and for mortality of 0.91.Conclusions: Markers of endothelial cell activation are associated with sepsis severity, organ dysfunction and mortality. An improved understanding of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis.
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U2 - 10.1186/cc9290
DO - 10.1186/cc9290
M3 - Article
C2 - 20942957
AN - SCOPUS:77957745203
SN - 1364-8535
VL - 14
JO - Critical Care
JF - Critical Care
IS - 5
M1 - R182
ER -