title: Matrix metalloproteinase 9 and cellular fibronectin plasma concentrations are predictors of the composite endpoint of length of stay and death in the intensive care unit after severe traumatic brain injury.
abstract: BACKGROUND
  The relationship between severe traumatic brain injury (TBI) and blood levels of matrix metalloproteinase-9 (MMP-9) or cellular fibronectin (c-Fn) has never been reported. In this study, we aimed to assess whether plasma concentrations of MMP-9 and c-Fn could have predictive values for the composite endpoint of intensive care unit (ICU) length of stay (LOS) of survivors and mortality after severe TBI. Secondary outcomes were the state of consciousness measured with the Glasgow Coma Scale (GCS) of survivors at 14 days and Glasgow Outcome Scale Extended (GOSE) at 3 months.
  
  
  METHODS
  Forty-nine patients with abbreviated injury scores of the head region ≥ 4 were included. Blood was sampled at 6, 12, 24 and 48 hours after injury. MMP-9 and c-Fn concentrations were measured by ELISA. The values of MMP-9 and c-Fn, and, for comparison, the value of the GCS on the field of the accident (fGCS), as predictors of the composite outcome of ICU LOS and death were assessed by logistic regression.
  
  
  RESULTS
  There was a linear relationship between maximal MMP-9 concentration, measured during the 6-12-hour period, and maximal c-Fn concentration, measured during the 24-48-hour period. The risk of staying longer than 9 days in the ICU or of dying was increased in patients with a maximal early MMP-9 concentration ≥ 21.6 ng/ml (OR = 5.0; 95% CI: 1.3 to 18.6; p = 0.02) or with a maximal late c-Fn concentration ≥ 7.7 μg/ml (OR = 5.4; 95% CI: 1.4 to 20.8; p = 0.01). A similar risk association was observed with fGCS ≤8 (OR, 4.4; 95% CI, 1.2-15.8; p = 0.02). No relationship was observed between MMP-9, c-Fn concentrations or fGCS and the GCS at 14 days of survivors and GOSE at 3 months.
  
  
  CONCLUSIONS
  Plasma MMP-9 and c-Fn concentrations in the first 48 hours after injury are predictive for the composite endpoint of ICU LOS and death after severe TBI but not for consciousness at 14 days and outcome at 3 months.
authors.affiliation: Geneva Neuroscience Center, University of Geneva, Geneva, Switzerland. jean-christophe.copin@unige.ch
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Copin
authors.forename: Marie My Lien
authors.initials: MM
authors.lastname: Rebetez
authors.forename: Natacha
authors.initials: N
authors.lastname: Turck
authors.forename: Xavier
authors.initials: X
authors.lastname: Robin
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Sanchez
authors.forename: Karl
authors.initials: K
authors.lastname: Schaller
authors.forename: Yvan
authors.initials: Y
authors.lastname: Gasche
authors.forename: Bernhard
authors.initials: B
authors.lastname: Walder
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001930:Brain Injuries / Q000401:mortality* / Q000473:pathology; D016001:Confidence Intervals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005353:Fibronectins / Q000097:blood*; D005544:Forecasting; D015600:Glasgow Coma Scale; D023261:Glasgow Outcome Scale; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D007902:Length of Stay; D016015:Logistic Models; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D016017:Odds Ratio; D017741:Survivors; D013557:Switzerland / Q000453:epidemiology; D015599:Trauma Severity Indices
chemical_list: D015415:Biomarkers; D005353:Fibronectins; D020780:Matrix Metalloproteinase 9