title: A robust scoring system to evaluate sepsis severity in an animal model.
abstract: BACKGROUND
  The lack of a reliable scoring system that predicts the development of septic shock and death precludes comparison of disease and/or treatment outcomes in animal models of sepsis. We developed a murine sepsis score (MSS) that evaluates seven clinical variables, and sought to assess its validity and reliability in an experimental mouse model of polymicrobial sepsis.
  
  
  METHODS
  Stool collected from the cecum of C57BL/6 (B6) mice was dissolved in 0.9% normal saline (NS) and filtered, resulting in a fecal solution (FS) which was injected intraperitoneally into B6 mice. Disease severity was monitored by MSS during the experimental timeline. Blood and tissue samples were harvested for the evaluation of inflammatory changes after sepsis induction. The correlation between pro-inflammatory markers and MSS was assessed by the Spearman rank correlation coefficient.
  
  
  RESULTS
  Mice injected with FS at a concentration of 90 mg/mL developed polymicrobial sepsis with a 75% mortality rate at 24 hours. The MSS was highly predictive of sepsis progression and mortality, with excellent discriminatory power, high internal consistency (Cronbach alpha coefficient = 0.92), and excellent inter-rater reliability (intra-class coefficient = 0.96). An MSS of 3 had a specificity of 100% for predicting onset of septic shock and death within 24 hours. Hepatic dysfunction and systemic pro-inflammatory responses were confirmed by biochemical and cytokine analyses where the latter correlated well with the MSS. Significant bacterial dissemination was noted in multiple organs. Furthermore, the liver, spleen, and intestine demonstrated histopathological evidence of injury.
  
  
  CONCLUSIONS
  The MSS reliably predicts disease progression and mortality in an animal model of polymicrobial sepsis. More importantly, it may be used to assess and compare outcomes among various experimental models of sepsis, and serve as an ethically acceptable alternative to death as an endpoint.
authors.forename: Bradly
authors.initials: B
authors.lastname: Shrum
authors.forename: Ram V
authors.initials: RV
authors.lastname: Anantha
authors.forename: Stacey X
authors.initials: SX
authors.lastname: Xu
authors.forename: Marisa
authors.initials: M
authors.lastname: Donnelly
authors.forename: S M Mansour
authors.initials: SM
authors.lastname: Haeryfar
authors.forename: John K
authors.initials: JK
authors.lastname: McCormick
authors.affiliation: Division of General Surgery, Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. tina.mele@lhsc.on.ca.
authors.forename: Tina
authors.initials: T
authors.lastname: Mele
mesh_terms: D000818:Animals; D018988:Bacterial Translocation; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D007422:Intestines / Q000382:microbiology / Q000473:pathology*; D008099:Liver / Q000382:microbiology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018805:Sepsis / Q000382:microbiology / Q000401:mortality / Q000473:pathology*; D012720:Severity of Illness Index; D013154:Spleen / Q000382:microbiology / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D016207:Cytokines
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