title: Elevated biomarkers of endothelial dysfunction/activation at ICU admission are associated with sepsis development.
abstract: Widespread endothelial activation and dysfunction often precede clinical sepsis. Several endothelium-related molecules have been investigated as potential biomarkers for early diagnosis and/or prognosis of sepsis, providing different results depending on study designs. Such factors include endothelial adhesion molecules like E- and P-selectin, and the intercellular adhesion molecule-1, vascular endothelial cadherin, growth factors such as Angiopoietin-1 and -2 and vascular endothelial growth factor, as well as von Willebrand factor antigen. We sought to investigate whether circulating biomarkers of endothelial activation/dysfunction measured at ICU admission are associated with subsequent sepsis development. Eighty-nine critically-ill patients admitted to a general ICU who met no sepsis criteria were studied. Plasma or serum levels of the above-mentioned endothelium-derived molecules were measured during the first 24h post ICU; acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, age, sex, diagnostic category, and circulating procalcitonin (PCT) and C-reactive protein (CRP) levels were additionally measured or recorded. Forty-five patients subsequently became septic and 44 did not. Soluble (s) E- and P-selectin levels, circulating PCT, SOFA score and diagnostic category were significantly different between the two groups. Multiple logistic regression analysis associated elevated sE- and sP-selectin levels and SOFA with an increased risk of developing sepsis, while multiple Cox regression analysis identified sE- and sP-selectin levels as the only parameters related to sepsis appearance with time [RR=1.026, 95%CI=1.008-1.045, p=0.005; RR=1.005 (by 10 units), 95%CI=1.000-1.010, p=0.034, respectively]. When trauma patients were independently analyzed, multiple Cox regression analysis revealed sE-selectin to be the only molecule associated with sepsis development with time (RR=1.041, 95%CI: 1.019-1.065; p<0.001). In conclusion, in our cohort of initially non-septic critically-ill patients, high levels of the circulating endothelial adhesion molecules E- and P-selectin, measured at ICU admission, appear to be associated with sepsis development in time.
authors.affiliation: First Department of Critical Care Medicine & Pulmonary Services, GP Livanos and M Simou Laboratories, Medical School of Athens University, Evangelismos Hospital, Athens, Greece. Electronic address: alvass75@gmail.com.
authors.forename: Alice G
authors.initials: AG
authors.lastname: Vassiliou
authors.affiliation: First Department of Critical Care Medicine & Pulmonary Services, Medical School of Athens University, Evangelismos Hospital, Athens, Greece. Electronic address: zafimast@yahoo.gr.
authors.forename: Zafeiria
authors.initials: Z
authors.lastname: Mastora
authors.affiliation: First Department of Critical Care Medicine & Pulmonary Services, GP Livanos and M Simou Laboratories, Medical School of Athens University, Evangelismos Hospital, Athens, Greece; Second Department of Critical Care, Medical School of Athens University, "Attikon" Hospital, Athens, Greece. Electronic address: sorfanos@med.uoa.gr.
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Orfanos
authors.affiliation: First Department of Critical Care Medicine & Pulmonary Services, Medical School of Athens University, Evangelismos Hospital, Athens, Greece. Electronic address: Edison.jahaj@gmail.com.
authors.forename: Edison
authors.initials: E
authors.lastname: Jahaj
authors.affiliation: First Department of Critical Care Medicine & Pulmonary Services, GP Livanos and M Simou Laboratories, Medical School of Athens University, Evangelismos Hospital, Athens, Greece; Second Department of Critical Care, Medical School of Athens University, "Attikon" Hospital, Athens, Greece. Electronic address: maniatisnikolaos@yahoo.com.
authors.forename: Nikolaos A
authors.initials: NA
authors.lastname: Maniatis
authors.affiliation: First Department of Critical Care Medicine & Pulmonary Services, GP Livanos and M Simou Laboratories, Medical School of Athens University, Evangelismos Hospital, Athens, Greece. Electronic address: Koutsoukou@yahoo.gr.
authors.forename: Antonia
authors.initials: A
authors.lastname: Koutsoukou
authors.affiliation: Second Department of Critical Care, Medical School of Athens University, "Attikon" Hospital, Athens, Greece. Electronic address: aarmag@med.uoa.gr.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Armaganidis
authors.affiliation: First Department of Critical Care Medicine & Pulmonary Services, GP Livanos and M Simou Laboratories, Medical School of Athens University, Evangelismos Hospital, Athens, Greece; First Department of Critical Care Medicine & Pulmonary Services, Medical School of Athens University, Evangelismos Hospital, Athens, Greece. Electronic address: akotanid@med.uoa.gr.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kotanidou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006760:Hospitalization; D006801:Humans; D007362:Intensive Care Units; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012372:ROC Curve; D012044:Regression Analysis; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis / Q000382:microbiology; D012995:Solubility; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins
keywords: Critically-ill; Prognostic; Selectin; Sepsis; Shedding