title: Development of a genomic metric that can be rapidly used to predict clinical outcome in severely injured trauma patients.
abstract: OBJECTIVE
  Many patients have complicated recoveries following severe trauma due to the development of organ injury. Physiological and anatomical prognosticators have had limited success in predicting clinical trajectories. We report on the development and retrospective validation of a simple genomic composite score that can be rapidly used to predict clinical outcomes.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Multi-institutional level 1 trauma centers.
  
  
  METHODS
  Data were collected from 167 severely traumatized (injury severity score >15) adult (18-55 yr) patients.
  
  
  METHODS
  Microarray-derived genomic data obtained from 167 severely traumatized patients over 28 days were assessed for differences in messenger RNA abundance among individuals with different clinical trajectories. Once a set of genes was identified based on differences in expression over the entire study period, messenger RNA abundance from these subjects obtained in the first 24 hours was analyzed in a blinded fashion using a rapid multiplex platform, and genomic data reduced to a single metric.
  
  
  RESULTS
  From the existing genomic dataset, we identified 63 genes whose leukocyte expression differed between an uncomplicated and complicated clinical outcome over 28 days. Using a multiplex approach that can quantitate messenger RNA abundance in less than 12 hours, we reassessed total messenger RNA abundance from the first 24 hours after trauma and reduced the genomic data to a single composite score using the difference from reference. This composite score showed good discriminatory capacity to distinguish patients with a complicated outcome (area under a receiver-operator curve, 0.811; p <0.001). This was significantly better than the predictive power of either Acute Physiology and Chronic Health Evaluation II or new injury severity score scoring systems.
  
  
  CONCLUSIONS
  A rapid genomic composite score obtained in the first 24 hours after trauma can retrospectively identify trauma patients who are likely to develop complicated clinical trajectories. A novel platform is described in which this genomic score can be obtained within 12 hours of blood collection, making it available for clinical decision making.
authors: Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
authors: Alex G
authors: AG
authors: Cuenca
authors: Lori F
authors: LF
authors: Gentile
authors: M Cecilia
authors: MC
authors: Lopez
authors: Ricardo
authors: R
authors: Ungaro
authors: Huazhi
authors: H
authors: Liu
authors: Wenzhong
authors: W
authors: Xiao
authors: Junhee
authors: J
authors: Seok
authors: Michael N
authors: MN
authors: Mindrinos
authors: Darwin
authors: D
authors: Ang
authors: Tezcan Ozrazgat
authors: TO
authors: Baslanti
authors: Azra
authors: A
authors: Bihorac
authors: Philip A
authors: PA
authors: Efron
authors: Joseph
authors: J
authors: Cuschieri
authors: H Shaw
authors: HS
authors: Warren
authors: Ronald G
authors: RG
authors: Tompkins
authors: Ronald V
authors: RV
authors: Maier
authors: Henry V
authors: HV
authors: Baker
authors: Lyle L
authors: LL
authors: Moldawer
mesh_terms: D018806:APACHE; D000293:Adolescent; D000328:Adult; D002423:Cause of Death; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study / Q000379:methods*; D023281:Genomics / Q000379:methods*; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D015601:Injury Severity Score; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013997:Time Factors; D014193:Trauma Centers; D014947:Wounds and Injuries / Q000097:blood / Q000235:genetics* / Q000401:mortality*; D055815:Young Adult
chemical_list: D012333:RNA, Messenger
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