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

Greg E. Gaski*, Cameron Metzger, Tyler McCarroll, Robert Wessel, Jeremy Adler, Andrew Cutshall, Krista Brown, Yoram Vodovotz, Timothy R. Billiar, Todd O. McKinley

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish
Pages (from-to)220-228
Number of pages9
JournalJournal of Orthopaedic Trauma
Issue number5
StatePublished - 1 May 2019
Externally publishedYes


  • Biomarker
  • Immune response
  • Multiply injured patient
  • Organ dysfunction
  • Orthopaedic immunology
  • Polytrauma
  • Precision medicine


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