title: Biomarkers improve clinical outcome predictors of mortality following non-penetrating severe traumatic brain injury.
abstract: OBJECTIVE
  This study assessed whether early levels of biomarkers measured in CSF within 24-h of severe TBI would improve the clinical prediction of 6-months mortality.
  
  
  METHODS
  This prospective study conducted at two Level 1 Trauma Centers enrolled adults with severe TBI (GCS ≤8) requiring a ventriculostomy as well as control subjects. Ventricular CSF was sampled within 24-h of injury and analyzed for seven candidate biomarkers (UCH-L1, MAP-2, SBDP150, SBDP145, SBDP120, MBP, and S100B). The International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) scores (Core, Extended, and Lab) were calculated for each patient to determine risk of 6-months mortality. The IMPACT models and biomarkers were assessed alone and in combination.
  
  
  RESULTS
  There were 152 patients enrolled, 131 TBI patients and 21 control patients. Thirty six (27 %) patients did not survive to 6 months. Biomarkers were all significantly elevated in TBI versus controls (p < 0.001). Peak levels of UCH-L1, SBDP145, MAP-2, and MBP were significantly higher in non-survivors (p < 0.05). Of the seven biomarkers measured at 12-h post-injury MAP-2 (p = 0.004), UCH-L1 (p = 0.024), and MBP (p = 0.037) had significant unadjusted hazard ratios. Of the seven biomarkers measured at the earliest time within 24-h, MAP-2 (p = 0.002), UCH-L1 (p = 0.016), MBP (p = 0.021), and SBDP145 (0.029) had the most significant elevations. When the IMPACT Extended Model was combined with the biomarkers, MAP-2 contributed most significantly to the survival models with sensitivities of 97-100 %.
  
  
  CONCLUSIONS
  These data suggest that early levels of MAP-2 in combination with clinical data provide enhanced prognostic capabilities for mortality at 6 months.
authors: Department of Emergency Medicine, Orlando Regional Medical Center, 86 W. Underwood (S-200), Orlando, FL, 32806, USA, lpstat@aol.com.
authors: Linda
authors: L
authors: Papa
authors: Claudia S
authors: CS
authors: Robertson
authors: Kevin K W
authors: KK
authors: Wang
authors: Gretchen M
authors: GM
authors: Brophy
authors: H Julia
authors: HJ
authors: Hannay
authors: Shelley
authors: S
authors: Heaton
authors: Ilona
authors: I
authors: Schmalfuss
authors: Andrea
authors: A
authors: Gabrielli
authors: Ronald L
authors: RL
authors: Hayes
authors: Steven A
authors: SA
authors: Robicsek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000401:mortality*; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D015233:Models, Statistical; D011379:Prognosis; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins