DESCRIPTION (provided by applicant): Guided by an adapted version of the Vulnerable Populations Conceptual Framework which incorporates concepts from Psychoneuroimmunology, this project will examine bio-behavioral mechanisms associated with chronic stress and accelerated biologic aging (i.e. premature cell death and system decline) which could adversely affect susceptibility to sepsis and organ failure following trauma (i.e., acute, life-threatening injuries). Trauma kills more than 13 million people annually. Sepsis and organ failure are the leading causes of in- hospital trauma deaths and are affected by baseline inflammation and poor inflammatory response, yet few data exist to explain differences in vulnerability to these deadly outcomes. Research has shown that African Americans (AAs) and persons of low socioeconomic status (SES) have nearly twice the rates of sepsis and organ dysfunction as Caucasians. Low SES has been associated with baseline inflammation, a finding related to organ dysfunction. Chronic stress may be a contributing factor. AAs and persons of low SES report chronic stress, which has been linked to accelerated biologic aging via telomerase activity. Declining levels of telomerase have also been associated with advanced age, a known risk factor for sepsis and organ failure. Chronic stress has been linked with physiologic "wear and tear" (i.e. allostatic load) on immune system function, resulting in changes similar that which are seen with advanced age. Thus, the specific aims of this project are that 1) accelerated biologic aging is a significant predisposing factor contributing to susceptibility to sepsis and organ failure following trauma and 2) chronic stress is a significant predisposing factor contributing to increased baseline inflammation and differences in the magnitude of the inflammatory response. Trauma patients who are 1) 18-44 years old; 2) have injury severity scores >15; and 3) times of <1 hour from injury to Emergency Department admission (n =300) will be recruited. Accelerated biologic aging will be operationally defined by low telomerase activity. Chronic stress will be operationally defined by high scores on the Life Events and Difficulties Schedule and high hair cortisol. Participants will be excluded for 1) blood transfusion or infection < 2 weeks prior to admission; 2) steroid, NSAID, or salicylate use for > 1 month prior to admission; 3) pre-existing organ disease; 4) cancer, autoimmune conditions, or pregnancy; 5) spinal cord injury; or missing data. Primary outcome variables are susceptibility to sepsis and organ failure, baseline inflammation status, and magnitude of the inflammatory response to trauma indicated by the 1) overall response and 2) peak magnitude of inflammatory cytokines and immature neutrophils in plasma from ED admission through ICU length of stay. Secondary variables will also be analyzed, including socio-demographic and lifestyle factors. Knowledge gained will inform future studies to prevent these often-fatal outcomes. This research is consistent with the National Institute of Nursing Research mission, which supports research that incorporates the best of clinical and basic science to develop unique approaches to disease prevention. PUBLIC HEALTH RELEVANCE: Trauma, defined as acute, life-threatening injuries, is the leading cause of death for individuals aged 18-44 years. Accelerated (i.e., premature) aging and chronic stress before trauma could explain why some individuals have poor outcomes in the intensive care unit after trauma, such as sepsis and organ failure. Information from this research will help us better understand why different populations of trauma patients have different outcomes, and could be used in future studies aimed at prevention.

PROJECT NARRATIVE Trauma, defined as acute, life-threatening injuries, is the leading cause of death for individuals aged 18-44 years. Accelerated (i.e., premature) aging and chronic stress before trauma could explain why some individuals have poor outcomes in the intensive care unit after trauma, such as sepsis and organ failure. Information from this research will help us better understand why different populations of trauma patients have different outcomes, and could be used in future studies aimed at prevention.