PURPOSE: The objective of this study was to investigate the association of endothelial-related markers with organ dysfunction and in-hospital mortality to validate our earlier findings in a multicenter study. We hypothesize that (i) endothelial biomarkers will be associated with organ dysfunction and mortality in sepsis and that (ii) soluble fms-like tyrosine kinase 1 (sFlt-1) holds promise as a novel prognostic marker in sepsis. METHODS: This was a prospective, multicenter, observational study of a convenience sample of emergency department (ED) patients with a suspected infection presenting to one of four urban, academic medical center EDs between January 2009 and January 2010. We collected plasma while the patients were in the ED and subsequently assayed endothelial-related biomarkers, namely, sFlt-1, soluble E-selectin, soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, and plasminogen activator inhibitor 1 (PAI-1). Outcomes were organ dysfunction and in-hospital mortality. RESULTS: We enrolled a total of 166 patients: 63 with sepsis (38%), 61 with severe sepsis (37%), and 42 with septic shock (25%). All endothelial biomarkers were significantly associated with sepsis severity, P < 0.002. We found a significant intercorrelation between all biomarkers, strongest between sFlt-1 and PAI-1 (r = 0.61, P < 0.001) and PAI-1 and soluble E-selectin and soluble intercellular adhesion molecule 1 (r = 0.49, P < 0.001). Among the endothelial biomarkers, sFlt-1 had the strongest association with Sequential Organ Failure Assessment score (r = 0.58, P < 0.001). Soluble fms-like tyrosine kinase 1 and PAI-1 had the highest area under the operating receiver characteristic curve for mortality of 0.87. CONCLUSIONS: This multicenter validation study confirms that markers of endothelial activation are associated with sepsis severity, organ dysfunction, and mortality in sepsis. This supports the hypothesis that the endothelium plays a central role in the pathophysiology of sepsis and may serve as a more accurate prediction tool and a target for therapies aimed at ameliorating endothelial cell dysfunction. In addition, sFLT-1 holds promise as a novel sepsis severity biomarker.
PURPOSE: The objective of this study was to investigate the association of endothelial-related markers with organ dysfunction and in-hospital mortality to validate our earlier findings in a multicenter study. We hypothesize that (i) endothelial biomarkers will be associated with organ dysfunction and mortality in sepsis and that (ii) soluble fms-like tyrosine kinase 1 (sFlt-1) holds promise as a novel prognostic marker in sepsis. METHODS: This was a prospective, multicenter, observational study of a convenience sample of emergency department (ED) patients with a suspected infection presenting to one of four urban, academic medical center EDs between January 2009 and January 2010. We collected plasma while the patients were in the ED and subsequently assayed endothelial-related biomarkers, namely, sFlt-1, soluble E-selectin, soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, and plasminogen activator inhibitor 1 (PAI-1). Outcomes were organ dysfunction and in-hospital mortality. RESULTS: We enrolled a total of 166 patients: 63 with sepsis (38%), 61 with severe sepsis (37%), and 42 with septic shock (25%). All endothelial biomarkers were significantly associated with sepsis severity, P < 0.002. We found a significant intercorrelation between all biomarkers, strongest between sFlt-1 and PAI-1 (r = 0.61, P < 0.001) and PAI-1 and soluble E-selectin and soluble intercellular adhesion molecule 1 (r = 0.49, P < 0.001). Among the endothelial biomarkers, sFlt-1 had the strongest association with Sequential Organ Failure Assessment score (r = 0.58, P < 0.001). Soluble fms-like tyrosine kinase 1 and PAI-1 had the highest area under the operating receiver characteristic curve for mortality of 0.87. CONCLUSIONS: This multicenter validation study confirms that markers of endothelial activation are associated with sepsis severity, organ dysfunction, and mortality in sepsis. This supports the hypothesis that the endothelium plays a central role in the pathophysiology of sepsis and may serve as a more accurate prediction tool and a target for therapies aimed at ameliorating endothelial cell dysfunction. In addition, sFLT-1 holds promise as a novel sepsis severity biomarker.
Authors: J L Vincent; R Moreno; J Takala; S Willatts; A De Mendonça; H Bruining; C K Reinhart; P M Suter; L G Thijs Journal: Intensive Care Med Date: 1996-07 Impact factor: 17.440
Authors: Gary T Kinasewitz; S Betty Yan; Bruce Basson; Philip Comp; James A Russell; Alain Cariou; Suzane L Um; Barbara Utterback; Pierre-Francois Laterre; Jean-François Dhainaut Journal: Crit Care Date: 2004-02-10 Impact factor: 9.097
Authors: S M Keating; X Deng; F Fernandes; E Cunha-Neto; A L Ribeiro; B Adesina; A I Beyer; P Contestable; B Custer; M P Busch; E C Sabino Journal: Int J Cardiol Date: 2015-07-12 Impact factor: 4.164
Authors: Stephen P J Macdonald; Erika Bosio; Claire Neil; Glenn Arendts; Sally Burrows; Lisa Smart; Simon G A Brown; Daniel M Fatovich Journal: Inflamm Res Date: 2017-04-19 Impact factor: 4.575
Authors: Bravein Amalakuhan; Sheila A Habib; Mandeep Mangat; Luis F Reyes; Alejandro H Rodriguez; Cecilia A Hinojosa; Nilam J Soni; Ryan P Gilley; Carlos A Bustamante; Antonio Anzueto; Stephanie M Levine; Jay I Peters; Stefano Aliberti; Oriol Sibila; James D Chalmers; Antoni Torres; Grant W Waterer; Ignacio Martin-Loeches; Jose Bordon; Jose Blanquer; Francisco Sanz; Pedro J Marcos; Jordi Rello; Julio Ramirez; Jordi Solé-Violán; Carlos M Luna; Charles Feldman; Martin Witzenrath; Richard G Wunderink; Daiana Stolz; Tim L Wiemken; Yuichiro Shindo; Charles S Dela Cruz; Carlos J Orihuela; Marcos I Restrepo Journal: Cytokine Date: 2016-10-01 Impact factor: 3.861
Authors: Can Ince; Philip R Mayeux; Trung Nguyen; Hernando Gomez; John A Kellum; Gustavo A Ospina-Tascón; Glenn Hernandez; Patrick Murray; Daniel De Backer Journal: Shock Date: 2016-03 Impact factor: 3.454