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Development of a Genomic Metric That Can Be Rapidly Used to Predict Clinical Outcome in Severely Injured Trauma Patients*

Cuenca, Alex G. MD, PhD1; Gentile, Lori F. MD1; Lopez, M. Cecilia MS2; Ungaro, Ricardo BS1; Liu, Huazhi MS1; Xiao, Wenzhong PhD3; Seok, Junhee PhD3; Mindrinos, Michael N. PhD3; Ang, Darwin MD, PhD, MPH1; Baslanti, Tezcan Ozrazgat PhD4; Bihorac, Azra MD, MS4; Efron, Philip A. MD1; Cuschieri, Joseph MD5; Warren, H. Shaw MD6; Tompkins, Ronald G. MD7; Maier, Ronald V. MD5; Baker, Henry V. PhD1,2; Moldawer, Lyle L. PhD1,8; the Inflammation and Host Response to Injury Collaborative Research Program

Critical Care Medicine:
doi: 10.1097/CCM.0b013e318277131c
Feature Articles
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.

Design: Retrospective cohort study.

Setting: Multi-institutional level 1 trauma centers.

Patients: 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.

Author Information

1Department of Surgery, University of Florida College of Medicine, Gainesville, FL.

2Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL.

3Stanford Genome Technology Center, Palo Alto, CA.

4Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL.

5Department of Surgery, Harborview Medical Center, University of Washington, Seattle, WA.

6Department of Medicine, Massachusetts General Hospital, Boston, MA.

7Department of Surgery, Massachusetts General Hospital, Boston, MA.

*See also p. 1363.

Drs. Cuenca and Gentile contributed equally to this work.

This work was supported, in part, by a contract (U54 GM-062119-10) awarded by the National Institute of General Medical Sciences. Drs. Cuenca and Gentile were supported by a T32 training grant (T32 GM-008721-13) in burns and trauma from the National Institutes of General Medical Sciences. Dr. Cuenca was also supported by an individual National Research Service Award (F32 GM-093665-01) awarded by the National Institutes of General Medical Sciences, U.S. Public Health Service. Dr. Bihorac was supported by an award (K23 GM-087709-03) from the National Institute of General Medical Sciences.

The remaining authors have not disclosed any potential conflicts of interest.

For information regarding this article, E-mail: moldawer@surgery.ufl.edu

© 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins