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Early Immunologic Response in Multiply Injured Patients With Orthopaedic Injuries Is Associated With Organ Dysfunction

Gaski, Greg E., MD*,†; Metzger, Cameron, MD; McCarroll, Tyler, MD; Wessel, Robert, MD; Adler, Jeremy, MD; Cutshall, Andrew, MD; Brown, Krista, MS*,†; Vodovotz, Yoram, PhD‡,§; Billiar, Timothy R., MD‡,§; McKinley, Todd O., MD*,†

Journal of Orthopaedic Trauma: May 2019 - Volume 33 - Issue 5 - p 220–228
doi: 10.1097/BOT.0000000000001437
Original Article

Objectives: To quantify the acute immunologic biomarker response in multiply injured patients with axial and lower extremity fractures and to explore associations with adverse short-term outcomes including organ dysfunction and nosocomial infection (NI).

Design: Prospective cohort study.

Setting: Level 1 academic trauma center.

Patients: Consecutive multiply injured patients, 18–55 years of age, with major pelvic and lower extremity orthopaedic injuries (all pelvic/acetabular fractures, operative femur and tibia fractures) that presented as a trauma activation and admitted to the intensive care unit from April 2015 through October 2016. Sixty-one patients met inclusion criteria.

Intervention: Blood was collected upon presentation to the hospital and at the following time points: 8, 24, 48 hours, and daily during intensive care unit admission. Blood was processed by centrifugation, separation into 1.0-mL plasma aliquots, and cryopreserved within 2 hours of collection.

Main Outcome Measurements: Plasma analyses of protein levels of cytokines/chemokines were performed using a Luminex panel Bioassay of 20 immunologic mediators. Organ dysfunction was measured by the Marshall Multiple Organ Dysfunction score (MODScore) and nosocomial infection (NI) was recorded. Patients were stratified into low (MODS ≤ 4; n = 34) and high (MODS > 4; n = 27) organ dysfunction groups.

Results: The MODS >4 group had higher circulating levels of interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1), IL-1 receptor antagonist (IL-1RA), and monokine induced by interferon gamma (MIG) compared with the MODS ≤4 group at nearly all time points. MODS >4 exhibited lower levels of IL-21 and IL-22 compared with MODS ≤4. Patients who developed NI (n = 24) had higher circulating concentrations of IL-10, MIG, and high mobility group box 1 (HMGB1) compared with patients who did not develop NI (n = 37).

Conclusions: Temporal quantification of immune mediators identified 8 biomarkers associated with greater levels of organ dysfunction in polytrauma patients with major orthopaedic injuries.

Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

*Indiana University Health Methodist Hospital, Indianapolis, IN;

Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN;

Department of Surgery, University of Pittsburgh, Pittsburgh, PA; and

§Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA.

Reprints: Greg E. Gaski, MD, Department of Orthopaedic Surgery, Indiana University Health Methodist Hospital, Indiana University School of Medicine, 1801 N. Senate boulevard, Suite 535, Indianapolis, IN (e-mail:

Presented in part at the Annual Meeting of the Orthopaedic Trauma Association, October 14, 2017, Vancouver, BC.

Each author certifies that he or she, or a member of his or her immediate family, has no funding or commercial associations that might pose a conflict of interest in connection with the submitted article.

Accepted December 28, 2018

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.