Weather Has No Effect on Presentation of Traumatic Injuries to the Emergency Department of a Level 1 Trauma Center

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ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS

data pertaining to young trauma patients, the presence of SIRS, not the degree of SIRS, is predictive of outcome in Elderly trauma patients. 48.3. Prolonged Genomic Changes Characterize the Human Response to Burn Injury. C. C. Finnerty,1 M. G. Jeschke,1 H. V. Baker,2 C. M. Lopez,2 D. Hayden,3 P. H. Mason,3 L. L. Moldawer,2 L. Patterson,1 M. Mindrinos,4 W. Xiao,4 B. Arnoldo,5 M. B. Klein,6 R. L. Gamelli,7 N. Gibran,6 R. G. Tompkins,3 D. N. Herndon1; 1University of Texas Medican Branch/Shriners Hospital for Children, Galveston, TX; 2 University of Florida, Gainesville, FL; 3Massachusetts General Hospital, Boston, MA; 4Stanford University, Palo Alto, CA; 5University of Texas Southwestern Medical School, Dallas, TX; 6University of Washington, Seattle, WA; 7Loyola University, Chicago, IL Context: The response to a major burn injury is characterized by systemic inflammation, hypermetabolism, and immune suppression involving a reprioritization of energy metabolism and protein synthesis, which persists for up to 60 days post-injury. Objective: Determine changes in the leukocyte transcriptome to obtain unique insights into the initiation and resolution of severe burn injury; to facilitate this, an interactive web site was designed that allows investigators to examine gene expression patterns and the associated signaling pathways. Setting and Patients: Burn patients and control subjects were enrolled as part of the multi-center Inflammation and the Host Response to Injury glue grant collaborative research program. Blood samples from one hundred forty-four burn patients were harvested from the time of admission until sixty days post injury and were compared to samples from 99 control subjects. Total blood leukocyte gene expression was analyzed using the Affymetrix U133 plus 2.0 GeneChipÔ. Clinical data were collected prospectively and entered into the trial database. Genomic data was then organized by age and survival status. Results: Four thousand four hundred sixteen probe sets were identified as burn responsive based on having a coefficient of variation greater than 0.5 within the dataset. The patients were then grouped according to age and outcome (survival), and k-means clustering was then used to group probe sets according to expression pattern. Significant perturbations in leukocyte gene expression correlated with pathways central to the immuno-inflammatory response and leukocyte function, including T-cell receptor signaling, antigen presentation, and leukocyte extravasation. Determination of the genomic changes induced by a severe burn injury and persisting throughout the acute hospitalization period will allow identification of age- and sex-specific responses to burn, interpretation of pathways impacted by a burn injury in addition to development of outcome trajectories for people at risk for death. Conclusion: Changes in leukocyte gene expression indicate increased inflammation and reduced antigen presentation and lymphocyte function. Expression of these immuno-inflammatory genes is also associated with age-specific and survival-related clinical trajectories, giving unique insights that may result in the development of novel clinical and therapeutic strategies. Furthermore, we provide a tool that investigators can use to identify genes that change in response to a burn and to demonstrate the utility of the web-based tool. 48.4. High Glucose Variability Is Associated with Mortality in Critically Ill Trauma Patients. M. Corneille, C. Villa, S. E. Wolf, C. Brougher, J. E. Michalek, Y. Ouyang, C. E. Wade, J. G. Myers, D. L. Dent, D. L. Mueller, R. M. Stewart; University of Texas Health Science Center San Antonio, San Antonio, TX Introduction: Normoglycemia maintained by tight glucose control (TGC) protocols are reported to reduce morbidity and mortality in critically ill surgical patients. Glucose variability (GV) has been used to characterize glycemic control and efficacy of TGC, but the definition

and methods for determining GV have not been standardized. We inquired how various descriptions of glucose variability were associated with mortality in our trauma population, and hypothesized that these descriptions of GV are each associated with mortality in distinct ways. Further, we hypothesize that a single method of describing glucose variability is superior and that identifying this measure of GV may predict mortality in critically ill trauma patients. Methods: This was a single-center retrospective review of trauma patients age 18 years and older admitted to the Surgical Intensive Care Unit at a Level I Trauma Center between January 2005 through December 2007 who were managed with a TGC protocol. Subjects were identified by trauma registry query and blood glucose values were obtained through the hospital database. Patients with an ISS < 9 and ICU LOS < 3 days were excluded. Data collected included demographics, diagnoses, mechanism of injury, medical history including diabetes, length of ICU stay, clinical course and disposition. Glucose variability was described as the following: standard deviation and coefficient of variability of all recorded glucose values, glycemic lability index (defined as the summation of glucose changes squared divided by hour and week), triangular index (the mode divided by total number of glucose measurements), successive changes in glucose levels (greatest increase, greatest decrease, greatest absolute change), and mean amplitude of glycemic excursion (the mean of absolute values of any change between consecutive glucose values that are greater than 1 SD). The primary endpoint was in-hospital mortality. Multivariate logistic regression analysis was used, controlling for GV indices, ISS, TRISS, and presence or absence of traumatic brain injury. Results: Five-hundred and forty five subjects were included. Most were male (69%) with mean ISS of 25 6 11, TRISS 0.7 6 0.3. Average ICU length of stay was 13 days (median 8). Mean ventilator days were 8 (median 4). A total of 98,864 glucose measurements were obtained, with 14 mean (mode 7) daily glucose measurements per subject. High standard deviation (p < 0.006, OR 1.106), and coefficient of variability (p < 0.002, OR 1.029) were associated with mortality. Low triangular index (p < 0.04, OR 0.857) was associated with mortality. Glycemic lability index, successive changes in glucose levels, and mean amplitude of glycemic excursion were not significantly associated with mortality. Conclusions: High glucose variability is associated with mortality in critically ill trauma patients. Coefficient of variability was superior to other methods of describing glucose variability and was most highly associated with mortality. It is unclear from these data whether glucose variability is associated with underlying patient disease physiology or a tight glycemic control protocol. 48.5. Weather Has No Effect on Presentation of Traumatic Injuries to the Emergency Department of a Level 1 Trauma Center. S. S. Michael,1 J. L. Johnson,2 C. C. Barnett, Jr2; 1University of Colorado School of Medicine, Denver, CO; 2Denver Health Medical Center, Denver, CO Introduction: It is a commonly held belief among hospital staff that weather has an effect on trauma admissions to the emergency department. If weather conditions were a valid predictor of traumatic injury, there would be implications for staffing and resource allocation, blood banking, surge capacity planning, injury prevention efforts, etc. Previous studies have concluded that high maximum daily temperature is a significant predictor of traumatic injury. To our knowledge, no studies have attempted to correlate trauma admissions with weather data collected closer to the actual time of the traumatic injury. We hypothesized that there is no significant relationship between traumatic injuries presenting to the emergency department and air temperature, dew point, wind speed, wind gusts, relative humidity, heat index, or wind chill. Methods: We queried our academic regional level I trauma center’s prospective registry of all patients evaluated in the emergency department with traumatic injuries from 2003 through 2008. Patients transferred from other facilities were excluded because the information available in the registry was not sufficient for us to obtain weather information from the location of the patient’s original injury. Weather data were obtained from 15

ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS automated weather stations within a 10-mile radius of our trauma center and from an international airport 19 miles away. Weather and trauma data were binned by date and hour-of-day, and a dataset was generated consisting of the mean air temperature, dew point, sustained wind speed, wind gust, relative humidity, heat index, and wind chill for each hour of each day during the study period. Using the date and hour-of-day as key fields, the weather data was joined with the trauma registry data consisting of the number of trauma alerts and activations, the number of penetrating versus blunt mechanisms, the mean Injury Severity Score (ISS), and total length of stay (LOS) for all trauma patients for each hour of each day. We created multivariate regression models using backward elimination based on type III likelihood ratio tests, or F tests in the case of the ISS models. Because we observed a cyclic variation in trauma admission patterns by hour of day and day of week, we accounted for these variations in the model. We created models based on both absolute weather data and hourly differences from the seasonal adjusted means. Results: There were 6325 trauma cases in the registry during the study period. There is no statistically significant relationship between the total number of traumatic injuries evaluated in the emergency department, the number of trauma alerts and activations, the number of penetrating or blunt traumatic injuries, Injury Severity Score, or length of stay and sustained wind speed, wind gust, relative humidity, heat index, and wind chill for the one-hour period surrounding each trauma patient admitted to our emergency department. Mean air temperature and dew point were statistically significant predictors of the total number of traumas in a Zero-Inflated Poisson model, but the model predicted that an increase in either by one degree Centigrade increased the expected number of trauma patients by less than 0.02 (p < 0.0001 and p ¼ 0.0009 respectively). Conclusions: Weather has no effect on the number of trauma admissions to the emergency department at our level I trauma center. It is not reliable to use current or forecast weather conditions as a predictor of traumatic injury frequency, mechanism, or severity.

48.6. Systemic Induction of Unfolded Protein Response Mediates Insulin Resistance in Severely Burned Patients. M. G. Jeschke,1 C. C. Finnerty,1 D. Boehning,2 J. Song,1 D. N. Herndon1; 1Shriners Hospital for Children and UTMB, Galveston, TX; 2UTMB, Galveston, TX Background: A severe burn represents a devastating injury affecting nearly every organ system and leading to significant morbidity and mortality. In burned and critically ill patients, hyperglycemia and insulin resistance are common pathophysiological phenomena associated with adverse outcomes. Although the metabolic consequences of burn-induced hyperglycemia and insulin resistance have been delineated, the molecular mechanisms underlying insulin resistance are not as well defined. In diabetes, endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are at the crux of development of insulin resistance. We therefore determined whether post-burn hyperglycemia and insulin resistance are associated with UPR activation and impaired insulin receptor signaling in severely burned patients. Methods: Twenty severely burned pediatric patients admitted to our institute were enrolled in this prospective study and compared to a cohort of thirty-six non-burned children. Urinary cortisol, epinephrine and norepinephrine, serum cytokines, resting energy requirements (REE) and fasting glucose and insulin levels were measured at admission (zero to 10 days post burn), 11 to 49 and 50 to 250 days post-burn. GeneChip analysis was used to identify transcriptional changes in insulin resistance-related signaling cascades in peripheral blood leukocytes, fat, and muscle at these time points as well as at 251 to 466 days post burn. Modulation of these pathways was confirmed by Western blotting. Results: A severe burn induced a pronounced inflammatory and hypermetabolic responses accompanied by severe insulin resistance. Genomic analysis revealed that in peripheral leukocytes, muscle, and fat, burn injury was further associated with alterations in the signaling pathways

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that affect insulin resistance, ER/SR stress, inflammatory markers, and cell growth/apoptosis. Protein expression studies confirm the broad activation of these pathways in muscle. Significant increases in the accumulation of phospho- IRE-1 and ATF-6 demonstrated prolonged activation of the ER/SR stress response even after 250 days post burn. Phosphorylated JNK, a key mediator of ER stress-associated apoptosis and insulin resistance, was markedly increased in burned patients for up to 250 days post-burn when compared to normal controls. Significantly, burn injury was associated with increased serine phosphorylation of IRS1, thus blocking tyrosine phosphorylation and consequently reducing signaling via the insulin receptor. Summary: Burn-induced insulin resistance is associated with persistent ER/SR stress and subsequent suppressed insulin receptor signaling in peripheral blood leukocytes, muscle and fat. These novel insights will now allow developments of treatments to attenuate these activation of detrimental pathways which delay a patient’s recovery. 48.7. Neutrophil Apoptosis in the Early Post-Resuscitation Period Is Associated with Decreased Heart Rate and Temperature in Trauma Patients with Hemorrhagic Shock. C. A. Morrison, A. Moran, M. Huby Vidaurre, M. M. Carrick, D. J. Tweardy; Baylor College of Medicine, Houston, TX Introduction: It is well established that recruitment and activation of neutrophils within tissues during the initial post-resuscitation phase contribute to the development of SIRS following major trauma. Apoptosis of circulating neutrophils allows for their removal before tissue recruitment, yet little research has been done on the effects of neutrophil apoptosis on the development of SIRS in human trauma patients in-vivo. Methods: Peripheral blood samples were obtained from 41 trauma patients in hemorrhagic shock requiring emergency thoracotomy or laparotomy. Pre-operative and post-operative samples were collected and analyzed for leukocyte apoptosis using a nucleosome ELISA assay and TUNEL staining. Linear regression was used to assess for an association between leukocyte apoptosis and temperature (Tmax), WBC count and heart rate at 24 and 48 hours. Results: Increased levels of post-operative nucleosome levels were associated with lower temperature (p ¼ 0.01) and heart rate (p < 0.01) at 48 hours, as well as a lower heart rate (p ¼ 0.02) and a trend for decreased temperature at 24 hours. There were no significant associations between post-operative nucleosome levels and 24 or 48 hour WBC count. On TUNEL staining, 72% of apoptotic cells in the post-operative samples were neutrophils. Conclusions: In this population of trauma patients with hemorrhagic shock, increased levels of peripheral blood neutrophil apoptosis in the post-operative period was associated with decreased Tmax at 48 hours and decreased heart rate at 24 and 48 hours. This finding supports the hypothesis that increased peripheral blood neutrophil apoptosis may be beneficial in the post-resuscitation phase by limiting the extent of SIRS and its associated complications. 48.8. Comparision of PermacolTM and StratticeTM Biologic Mesh for the Repair of Abdominal Wall Defects. S. Marquez, K. Mulier, A. Nguyen, E. Jackson, J. Chipman, G. Beilman, J. Delaney; University of Minnesota, Minneapolis, MN Background: Most abdominal hernias are repaired using synthetic non-absorbable meshes. However, they have serious limitation. Foremost is their prohibitive use in a contaminated field. A second complication is adhesion formation to the intestine and subsequent late complications, including intestinal obstruction, difficult reoperation, and rare but devastating, enteric fistulas. Biologically derived products have been developed and proposed as alternative to synthetics. Those that have been shown to be most durable and tolerant of infection have been derived from pig dermas. We compared PermacolÔ Biologic Implant (Covidien) with the latest porcine-derived biologic, StratticeÔ Tissue Matrix-Firm (LifeCell), in a ventral hernia animal model to determine the amount of intraabdominal adhesion