Inflammation and the Host Response to Injury (Trauma)

The purpose of this study is to help improve our understanding of the biology involved in the body's response to serious trauma or burn injury. The host response to trauma and burns is a collection of physiological and pathophysiological processes that depend critically upon the regulation of the human innate immune system, with particular emphasis on the inflammatory component of that system. No single research center or small group of centers has the capacity to delineate the integrated response of this complex biological system, which involves multiple molecular and genetic interactions that vary in time. Our proposal promotes the identification of important dynamic relationships that regulate the integration of this complex biological system, with the expectation that this understanding will ultimately impact the diagnosis, prognosis, and treatment of the hospitalized, severely injured patient.

This large-scale collaborative project provides the means to acquire the necessary new knowledge directly in humans. Knowledge will be acquired using diverse state-of-the-art genomic and proteomic technologies, a highly complex clinical, proteomic, and genomic database, as well as newly-developed, novel analytical tools to probe this complex dataset. Our analytical capabilities at the genomic and proteomic level are now rapidly evolving and our ability to link these genomic and proteomic data to pathways and functional modules will help us more closely link this cellular data to immunological processes and ultimately, to the phenotypic response (i.e., trajectory) in the injured host. As a result, potential interventions, whether through our Program or other funding mechanisms, can be more effectively designed.

Acute hospitalized blunt trauma patients

• Trauma
• Burns
• Multiple Organ Failure

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Inclusion criteria for enrollment in the trauma study are as follows:

• Blunt trauma without isolated head injury
• Absence of traumatic brain injury, defined as either AIS head <4 OR GCS motor >3 within 24 hours of injury
• Emergency Department arrival <=6 hours from time of injury
• Blood transfusion within 12 hours of injury
• Base deficit >=6 OR systolic blood pressure <90 mmHg within 60 minutes of emergency department arrival
• Fully or partially intact cervical spinal cord

All patients meeting these criteria are entered into the epidemiologic database and assessed for specific exclusion criteria to establish whether serial blood draws are warranted.

The presence of any of the following exclusion criteria disqualifies a subject from the trauma sampling study.

• Age < 16
• Anticipated survival of <24 hours from injury
• Anticipated survival <28 days due to pre-existing medical condition
• Inability to obtain first blood draw within first 12 hours after injury
• Traumatic brain injury; i.e., GCS ≤8 after ICU admission AND brain computerized tomography scan abnormality within 12 hours after injury
• Inability to obtain informed consent
• Pre-existing, ongoing immunosuppression - e.g. transplant recipient
• Pre-existing, ongoing immunosuppression - e.g. chronic high dose corticosteroids (>20 mg/prednisone-equivalents/day)
• Pre-existing, ongoing immunosuppression - e.g. oncolytic drug(s) therapy within the past 14 days
• Pre-existing, ongoing immunosuppression - e.g. HIV positive AND CD4 count <200 cells/mm3
• Possible requirement for early immunosuppression - e.g. significant likelihood of requiring high dose corticosteroids (e.g. spinal injury)
• Significant pre-existing organ dysfunction - lung: currently receiving home oxygen therapy, as documented in medical records
• Significant pre-existing organ dysfunction - heart: congestive heart failure, as documented in medical records
• Significant pre-existing organ dysfunction - renal: chronic renal failure (creatinine >2)
• Significant pre-existing organ dysfunction - liver: cirrhosis with portal hypertension or encephalopathy
• Patient injured while sampling enrollment temporarily on hold