title: Sepsis biomarkers in unselected patients on admission to intensive or high-dependency care.
abstract: BACKGROUND
  Although many sepsis biomarkers have shown promise in selected patient groups, only C-reactive protein and procalcitonin (PCT) have entered clinical practice. The aim of this study was to evaluate three promising novel sepsis biomarkers in unselected patients at admission to intensive care. We assessed the performance of pancreatic stone protein (PSP), soluble CD25 (sCD25) and heparin binding protein (HBP) in distinguishing patients with sepsis from those with a non-infective systemic inflammatory response and the ability of these markers to indicate severity of illness.
  
  
  METHODS
  Plasma levels of the biomarkers, PCT and selected inflammatory cytokines were measured in samples taken from 219 patients during the first six hours of admission to intensive or high dependency care. Patients with a systemic inflammatory response were categorized as having sepsis or a non-infective aetiology, with or without markers of severity, using standard diagnostic criteria.
  
  
  RESULTS
  Both PSP and sCD25 performed well as biomarkers of sepsis irrespective of severity of illness. For both markers the area under the receiver operating curve (AUC) was greater than 0.9; PSP 0.927 (0.887 to 0.968) and sCD25 0.902 (0.854 to 0.949). Procalcitonin and IL6 also performed well as markers of sepsis whilst in this intensive care unit (ICU) population, HBP did not: PCT 0.840 (0.778 to 0.901), IL6 0.805 (0.739 to 0.870) and HBP 0.607 (0.519 to 0.694). Levels of both PSP and PCT reflected severity of illness and both markers performed well in differentiating patients with severe sepsis from severely ill patients with a non-infective systemic inflammatory response: AUCs 0.955 (0.909 to 1) and 0.837 (0.732 to 0.941) respectively. Although levels of sCD25 did not correlate with severity, the addition of sCD25 to either PCT or PSP in a multivariate model improved the diagnostic accuracy of either marker alone.
  
  
  CONCLUSIONS
  PSP and sCD25 perform well as sepsis biomarkers in patients with suspected sepsis at the time of admission to intensive or high dependency care. These markers warrant further assessment of their prognostic value. Whereas previously published data indicate HBP has clinical utility in the emergency department, it did not perform well in an intensive-care population.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Llewelyn
authors.forename: Mario
authors.initials: M
authors.lastname: Berger
authors.forename: Mark
authors.initials: M
authors.lastname: Gregory
authors.forename: Ravi
authors.initials: R
authors.lastname: Ramaiah
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Taylor
authors.forename: Ingo
authors.initials: I
authors.lastname: Curdt
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lajaunias
authors.forename: Rolf
authors.initials: R
authors.lastname: Graf
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Blincko
authors.forename: Stephen
authors.initials: S
authors.lastname: Drage
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cohen
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007362:Intensive Care Units / Q000639:trends; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood*; D051847:Lithostathine / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010343:Patient Admission / Q000639:trends; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D051847:Lithostathine; C497617:REG1A protein, human