Patient-Specific Precision Injury Signatures in Multiply Injured Orthopaedic Patients

There is currently a knowledge gap regarding in the treatment of the severely injured MIP, as clinicians are often challenged by when non-life threatening orthopaedic procedures should be performed. Information to guide orthopaedic interventions in MIPs is based primarily on resuscitation parameters and injury severity metrics.Lack of consensus among surgeons regarding choices of orthopaedic interventions reflects the paucity of data to form treatment decisions. This study will define the key parameters affecting these decisions in a quantitative manner by exploring the efficacy of a precision medicine approach to guide surgical decisions in multiply injured patients (MIPs) with skeletal trauma. According to the National Institutes of Health (NIH),36 precision medicine is "an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person." This approach will allow clinicians and researchers to predict more accurately which treatment and prevention strategies for a particular disease will work in which groups of people. The application of precision medicine will bring to bear evidence-based tools that can guide decisions facing the treating surgeons regarding the optimal timing of definitive fracture surgery after injury, as well as defining the magnitude of surgical intervention which may be pursued without engendering clinical complications. Specific Aim 1: Define groups of patients based on Precision Injury Signatures (mechanical and ischemic injury characteristics and immunologic response profile) that correspond to the following short term clinical outcomes; 1. Multiple organ dysfunction 2. Nosocomial infection 3. Wound complications 4. Resource utilization (ICU/hospital LOS, days on mechanical ventilation, discharge disposition) 5. Death Hypothesis 1: Patients who develop complicated short term outcomes will demonstrate distinct Precision Injury Signatures compared to patients who have uncomplicated outcomes for injuries of similar magnitude. Specific Aim 2: Evaluate the impact of timing and magnitude of orthopaedic surgical interventions on progression of patient-specific physiologic and immunologic response. Describe changes in physiologic and immunologic response after initial and staged orthopaedic interventions. Hypothesis 2: Immunologic and physiologic response to surgery will be a function of initial Precision Injury Signature and timing/magnitude of orthopaedic surgical interventions. Specific Aim 3: To develop surgical decision rules related to timing of definitive orthopaedic intervention that optimize short term clinical outcomes. Hypothesis 3a: Initial Precision Injury Signatures can be used to identify orthopaedic trauma patients who are best treated with early definitive treatment or staged definitive intervention. Hypothesis 3b: Progression of Precision Injury Signatures can be used to determine optimal timing and choices of definitive orthopaedic interventions.