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.

Inclusion Criteria:

1. Adult ages 18 years old to 55 years old inclusive;

2. Direct admission to hospital from scene of injury, or if transferred, admitted no more
than 6 hours from injury

3. Full trauma activation with either direct admission to Intensive Care Unit (ICU) or
other higher level of care, or taken directly to surgery and admitted to ICU after
surgery;

4. Sustaining at least one operative orthopaedic injury to the pelvis, acetabulum, femur,
or diaphyseal tibia with planned definitive fixation to occur prior to discharge.

Exclusion Criteria:

1. Non-survivable head trauma.

2. Signs of severe traumatic brain injury indicated by a GCS of < 7 at the time of
admission and no improvement in the GCS by the time of consent at 48hr after
admission.

3. Spinal cord injury with likely permanent neurologic deficits

4. Pre-existing organ dysfunction or failure prior to their injury, including but not
limited to end-stage renal disease, liver failure, congestive heart failure, or severe
COPD requiring home oxygen.

5. Qualifying orthopaedic injury primarily a periarticular fracture (tibial pilon or
plateau) with planned delay to definitive fixation for soft tissue reasons.

6. Primary blood draw could not be obtained within 3 hours of presentation

7. Patient is pregnant

8. Patient is a prisoner/incarcerated

9. Patient or legally authorized representative (LAR) unable to provide consent prior to
48 hour blood draw.