title: Proof of principle: the predisposition, infection, response, organ failure sepsis staging system.
abstract: OBJECTIVE
  In an effort to improve upon the traditional sepsis syndrome definitions, the predisposition, infection, response, organ dysfunction (PIRO) model was proposed to better characterize sepsis. The objective of this investigation was to derive and validate a sepsis staging system based on the PIRO concept that risk stratifies patients with suspected infection.
  
  
  METHODS
  Three independent, observational, prospective cohorts were studied. A derivation cohort (n = 2,132) was used to create the PIRO score, identifying independent predictors of mortality. Individual values were assigned to create the weighted integer score for each parameter, yielding the final PIRO score. The prognostic performance was then investigated in independent internal (n = 4,618) and external (n = 1,004) validation cohorts.
  
  
  METHODS
  Two large U.S. tertiary care centers.
  
  
  METHODS
  Patients admitted to the hospital from the emergency department with suspected infection.
  
  
  METHODS
  None.
  
  
  RESULTS
  The PIRO staging system was created by combining components of predisposition (age, chronic obstructive pulmonary disease, liver disease, nursing home residency, and malignancy with and without metastasis), infection (pneumonia and cellulitis), response (tachypnea, bandemia, and tachycardia), and organ dysfunction (renal, respiratory, cardiac, metabolic, and hematologic). The derived PIRO score showed stepwise increase in mortality with increasing points and high discriminatory ability with an area under the curve of 0.90 in the derivation cohort, 0.86 in internal validation, and 0.83 in external validation.
  
  
  CONCLUSIONS
  This study provides evidence-based support for the PIRO approach to sepsis staging. Future efforts may utilize this approach with additional parameters (e.g., genetics and novel biochemical markers) to develop further the PIRO stratification system.
authors.affiliation: Pulmonary and Critical Care Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Howell
authors.forename: Daniel
authors.initials: D
authors.lastname: Talmor
authors.forename: Philipp
authors.initials: P
authors.lastname: Schuetz
authors.forename: Sabina
authors.initials: S
authors.lastname: Hunziker
authors.forename: Alan E
authors.initials: AE
authors.lastname: Jones
authors.forename: Nathan I
authors.initials: NI
authors.lastname: Shapiro
mesh_terms: D001900:Boston; D015331:Cohort Studies; D016638:Critical Illness / Q000401:mortality; D018450:Disease Progression; D004198:Disease Susceptibility / Q000145:classification*; D004636:Emergency Service, Hospital; D019317:Evidence-Based Medicine; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D008297:Male; D009102:Multiple Organ Failure / Q000145:classification* / Q000401:mortality / Q000628:therapy; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000145:classification / Q000401:mortality / Q000628:therapy; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000145:classification* / Q000401:mortality / Q000628:therapy