The online version of this article (doi:10.1186/cc9290) contains supplementary material, which is available to authorized users.
This project was funded in part by an investigator initiated research grant from Eli Lilly. Dr. Shapiro has received research grants from Hutchinson Technologies, Eli Lilly, and Inverness Medical and has received speaker's honorarium from Inverness Medical. Dr. Schuetz receives speaker's honoraria from BRAHMS's Diagnostics and Biomerieux Inc. Dr. Trzeciak receives research support from Ikaria and serves as a consultant to Spectral Diagnostics, but does not receive any personal remuneration from any commercial interest.
NS and WA conceived of the project and oversaw all components of the project and manuscript preparation. MS and KY played a substantial role in data acquisition. PS, SP, AJ, ST and LN contributed substantially to data interpretation and analysis. All authors contributed to writing the manuscript and have given final approval of the version to be published.
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.
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.
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.
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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Bone R: American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992, 20: 864-874. 10.1097/00003246-199206000-00025 CrossRef
Vincent J, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, Reinhart C, Suter P, Thijs L, Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine: The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. Intensive Care Medicine 1996, 22: 707-710. 10.1007/BF01709751 CrossRefPubMed
Moreno R, Vincent JL, Matos R, Mendonca A, Cantraine F, Thijs L, Takala J, Sprung C, Antonelli M, Bruining H, Willatts S: The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Working Group on Sepsis related Problems of the ESICM. Intensive Care Med 1999, 25: 686-696. 10.1007/s001340050931 CrossRefPubMed
Janssens U, Graf C, Graf J, Radke PW, Konigs B, Koch KC, Lepper W, vom Dahl J, Hanrath P: Evaluation of the SOFA score: a single-center experience of a medical intensive care unit in 303 consecutive patients with predominantly cardiovascular disorders. Sequential Organ Failure Assessment. Intensive Care Med 2000, 26: 1037-1045. 10.1007/s001340051316 CrossRefPubMed
Balci C, Sungurtekin H, Gurses E, Sungurtekin U: [APACHE II, APACHE III, SOFA scoring systems, platelet counts and mortality in septic and nonseptic patients]. Ulus Travma Acil Cerrahi Derg 2005, 11: 29-34. PubMed
Yano K, Liaw PC, Mullington JM, Shih SC, Okada H, Bodyak N, Kang PM, Toltl L, Belikoff B, Buras J, Simms BT, Mizgerd JP, Carmeliet P, Karumanchi SA, Aird WC: Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality. J Exp Med 2006, 203: 1447-1458. 10.1084/jem.20060375 PubMedCentralCrossRefPubMed
Newman W, Beall LD, Carson CW, Hunder GG, Graben N, Randhawa ZI, Gopal TV, Wiener-Kronish J, Matthay MA: Soluble E-selectin is found in supernatants of activated endothelial cells and is elevated in the serum of patients with septic shock. J Immunol 1993, 150: 644-654. PubMed
Dello Sbarba P, Rovida E: Transmodulation of cell surface regulatory molecules via ectodomain shedding. Biol Chem 2002, 383: 69-83. 10.1515/BC.2002.007 PubMed
Endo S, Inada K, Kasai T, Takakuwa T, Yamada Y, Koike S, Wakabayashi G, Niimi M, Taniguchi S, Yoshida M: Levels of soluble adhesion molecules and cytokines in patients with septic multiple organ failure. J Inflamm 1995, 46: 212-219. PubMed
Leone M, Boutiere B, Camoin-Jau L, Albanese J, Horschowsky N, Mege JL, Martin C, Dignat-George F: Systemic endothelial activation is greater in septic than in traumatic-hemorrhagic shock but does not correlate with endothelial activation in skin biopsies. Crit Care Med 2002, 30: 808-814. 10.1097/00003246-200204000-00015 CrossRefPubMed
Kinasewitz GT, Yan SB, Basson B, Comp P, Russell JA, Cariou A, Um SL, Utterback B, Laterre PF, Dhainaut JF: Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism (ISRCTN74215569). Crit Care 2004, 8: R82-90. 10.1186/cc2459 PubMedCentralCrossRefPubMed
Garcia-Segarra G, Espinosa G, Tassies D, Oriola J, Aibar J, Bove A, Castro P, Reverter JC, Nicolas JM: Increased mortality in septic shock with the 4G/4G genotype of plasminogen activator inhibitor 1 in patients of white descent. Intensive Care Med 2007, 33: 1354-1362. 10.1007/s00134-007-0695-y CrossRefPubMed
Kim I, Moon SO, Kim SH, Kim HJ, Koh YS, Koh GY: Vascular endothelial growth factor expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E- selectin through nuclear factor-kappa B activation in endothelial cells. J Biol Chem 2001, 276: 7614-7620. 10.1074/jbc.M009705200 CrossRefPubMed
Lucerna M, Mechtcheriakova D, Kadl A, Schabbauer G, Schafer R, Gruber F, Koshelnick Y, Muller HD, Issbrucker K, Clauss M, Binder BR, Hofer E: NAB2, a corepressor of EGR-1, inhibits vascular endothelial growth factor-mediated gene induction and angiogenic responses of endothelial cells. J Biol Chem 2003, 278: 11433-11440. 10.1074/jbc.M204937200 CrossRefPubMed
- The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis
Nathan I Shapiro
Samir M Parikh
Alan E Jones
William C Aird
- BioMed Central
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