Objective Many patients following severe trauma have complicated recoveries due to the development of organ injury. Physiological and anatomical prognosticators have had limited success in predicting clinical trajectories. We report on the development and retrospective validation of a simple genomic composite score that can be rapidly used to predict clinical outcomes. Design Retrospective cohort study Setting Multi-institution level 1 trauma centers Patients Data was collected from 167 severely traumatized (ISS >15) adult (18–55 yo) patients Methods Microarray-derived genomic data obtained from 167 severely traumatized patients over 28 days were assessed for differences in mRNA abundance between individuals with different clinical trajectories. Once a set of genes was identified based on differences in expression over the entire study period, mRNA abundance from these subjects obtained in the first 24 hours was analyzed in a blinded fashion using a rapid multiplex platform, and genomic data reduced to a single metric. Results From the existing genomic data set, we identified 63 genes whose leukocyte expression differed between an uncomplicated and complicated clinical outcome over 28 days. Using a multiplex approach that can quantitate mRNA abundance in less than 12 hours (nanoString™), we reassessed total mRNA abundance from the first 24 hours after trauma, and reduced the genomic data to a single composite score using the difference from reference (DFR). This composite score showed good discriminatory capacity to distinguish patients with a complicated outcome (area under a receiver-operator curve, 0.811, p < 0.001). This was significantly better than the predictive power of either APACHE II or NISS scoring systems. Conclusions A rapid genomic composite score obtained in the first 24 hours after trauma can retrospectively identify trauma patients who are likely to develop a complicated clinical trajectories. A novel platform is described in which this genomic score can be obtained within 12 hours of blood collection, making it available for clinical decision making. (300 words; limit 300)

Introduction Hip fracture in geriatric patients has a substantial economic impact and represents a major cause of morbidity and mortality in this population. At our institution, a regional anesthesia program was instituted for patients undergoing surgery for hip fracture. This retrospective cohort review examines the effects of regional anesthesia (from mainly after July 2007) versus general anesthesia (mainly prior to July 2007) on morbidity, mortality and hospitalization costs. Methods This retrospective cohort study involved data collection from electronic and paper charts of 308 patients who underwent surgery for hip fracture from September 2006 to December 2008. Data on postoperative morbidity, in-patient mortality, and cost of hospitalization (as estimated from data on hospital charges) were collected and analyzed. Seventy-three patients received regional anesthesia and 235 patients received general anesthesia. During July 2007, approximately halfway through the study period, a regional anesthesia and analgesia program was introduced. Results The average cost of hospitalization in patients who receive surgery for hip fracture was no different between patients who receive regional or general anesthesia ($16,789 + 631 v. $16,815 + 643, respectively, p = 0.9557). Delay in surgery and intensive care unit admission resulted in significantly higher hospitalization costs. Age, male gender, African-American race and intensive care unit admission were associated with increased in-hospital mortality. In-hospital mortality and rates of readmission are not statistically different between the two anesthesia groups. Conclusions There is no difference in postoperative morbidity, rates of re-hospitalization, in-patient mortality or hospitalization costs in geriatric patients undergoing regional or general anesthesia for repair of hip fracture. Delay in surgery beyond 3 days and intensive care unit admission both increase cost of hospitalization.

The elderly have increased morbidity and mortality following sepsis; however, the cause(s) remain unclear. We hypothesized that these poor outcomes are due in part to defects in innate immunity, rather than to an exaggerated early inflammatory response. Juvenile (6–12 weeks) or aged (20–24 months) mice underwent polymicrobial sepsis and subsequently, the aged mice had increased mortality and defective peritoneal bacterial clearance compared to young mice. No differences were found in the magnitude of the plasma cytokine responses. Although septic aged mice displayed equivalent or increased numbers of circulating, splenic and bone marrow myeloid cells, some of these cells exhibited decreased phagocytosis, reactive oxygen species production and chemotaxis. Blood leukocyte gene expression was less altered in aged versus young mice one day after sepsis. Aged mice had a relative inability to upregulate gene expression of pathways related to ‘PMN-mediated protective immunity’, ‘chemokine/chemokine receptor binding’ and ‘responses to exogenous molecules’. Expression of most MHC genes remained more down-regulated in aged mice at day three. Despite their increased myeloid response to sepsis, the increased susceptibility of aged mice to sepsis appears not to be due to an exaggerated inflammatory response, but rather, a failure to mount an effective innate immune response.

Background Acute kidney injury (AKI) occurs in 26% of trauma patients and is associated with increased mortality and risk for nosocomial infections (NCI). We compared serial plasma cytokine levels in patients with posttraumatic AKI to determine whether the early cytokine changes are associated with the occurrence of AKI and NCI. Methods We performed a secondary analysis of the “Inflammation and the Host Response to Injury” database to include adult blunt trauma patients who had available plasma proteomic analyses. AKI was defined by the RIFLE (Risk, Injury, Failure, Loss, and End-stage Kidney) classification, which requires a 50% increase in serum creatinine. The association between AKI, NCI and plasma cytokines was analyzed using a mixed model analyses and logistic regression. Results Among 147 patients in the cohort, prevalence of NCI was 73% and 52% for patients with and without AKI, respectively. In mixed model analyses adjusted for clinical factors, AKI patients developed significant early increase in IL1ra, IL8, MCP1 and IL6, early decrease in sTNFR2, and late decrease in IL1ra, IL4 and IL6 concentrations, compared to patients without AKI and regardless of NCI. The change in cytokine pattern differed for sIL1R2, CXCL1 and MIP1β depending on the occurrence of NCI: Patients with AKI and NCI had lower early and late sIL1R2 and higher early and late CXCL1 and MIP1β levels. Within first 24 hours of injury, adding plasma levels of IL1ra, IL8, MCP1, IL6, and sTNFR2 to clinical parameters of injury severity provided a predictive model for AKI superior to clinical model only (P<0.001). Conclusion AKI trauma patients exhibit simultaneous changes in pro and anti-inflammatory serial plasma cytokine levels. The predictive model for AKI that combines plasma cytokine levels with clinical data within 24 hours of injury requires further prospective validation in larger studies.

Surgery risk assessment is an effective tool for physicians to manage the treatment of patients, but most current research projects fall short in providing a comprehensive platform to evaluate the patients’ surgery risk in terms of different complications. The recent evolution of big data analysis techniques makes it possible to develop a real-time platform to dynamically analyze the surgery risk from large-scale patients information. In this paper, we propose the Intelligent Perioperative System (IPS), a real-time system that assesses the risk of postoperative complications (PC) and dynamically interacts with physicians to improve the predictive results. In order to process large volume patients data in real-time, we design the system by integrating several big data computing and storage frameworks with the high through-output streaming data processing components. We also implement a system prototype along with the visualization results to show the feasibility of system design.

Objective Genomic analyses from blood leukocytes have concluded that mouse injury poorly reflects human trauma at the leukocyte transcriptome. Concerns have focused on the modest severity of murine injury models, differences in murine compared to human age, dissimilar circulating leukocyte populations between species, and whether similar signaling pathways are involved. We sought to examine whether the transcriptomic response to severe trauma in mice could be explained by these extrinsic factors, by utilizing an increasing severity of murine trauma and shock in young and aged mice over time, and examining the response in isolated neutrophil populations. Design Pre-clinical controlled in vivo laboratory study and retrospective cohort study Setting Laboratory of Inflammation Biology and Surgical Science and multi-institution level 1 trauma centers Subjects 6–10 week old and 20–24 month old C57BL/6 (B6) mice and two cohorts of 167 and 244 severely traumatized (ISS >15) adult (>18 yo) patients. Interventions Mice underwent one of two severity polytrauma models of injury. Total blood leukocyte and neutrophil samples were collected. Measurements and Main Results Fold expression changes in leukocyte and neutrophil genome-wide expression analyses between healthy and injured mice (p<0.001) were compared to human total and enriched blood leukocyte expression analyses of severe trauma patients at 0.5, 1, 4, 7, 14, and 28 days after injury (Glue Grant TRDB). We found that increasing the severity of the murine trauma model only modestly improved the correlation in the transcriptomic response with humans, whereas the age of the mice did not. In addition, the genome-wide response to blood neutrophils (rather than total WBC) was also not well correlated between humans and mice. However, the expression of many individual gene families was much more strongly correlated after injury in mice and humans. Conclusions Although overall transcriptomic association remained weak even after adjusting for the severity of injury, age of the animals, timing, and individual leukocyte populations, there were individual signaling pathways and ontogenies that were strongly correlated between mice and humans. These genes are involved in early inflammation and innate/adaptive immunity.

Improvement in Home Dialysis (HoD) utilizations as a mean to improve the patient reported and health services outcomes, has been a long-held goal of the providers and healthcare system in United States. However, measures to improve HoD rates have yielded limited success so far. Lack of patient awareness of chronic kidney disease (CKD) and its management options, is one of the important barriers against patient adoption of HoD. Despite ample evidence that Comprehensive pre-ESERD Patient Education (CPE) improves patient awareness and informed HoD choice, use of CPE among US advanced CKD patients is low. Need for significant resources, lack of validated data showing unequivocal and reproducible benefits, and the lack of validated CPE protocols proven to have consistent efficacy in improving not only patient awareness but also HoD rates in US population, are major limitations deterring adoption of CPE in routine clinical practice. We recently demonstrated that if a structured, protocol based CPE is integrated within the routine nephrology care for patients with advanced CKD, it substantially improves informed HoD choice and utilizations. However, this requires establishing CPE resources within each nephrology practice. Efficacy of a stand-alone CPE model, independent of clinical care, has not been examined till date. In this report we report the efficacy of our structured CPE protocol, delivered outside the realm of routine nephrology care—as a stand-alone patient education program, in a geographically distant region, and show that: when provided opportunity for informed dialysis choice, a majority of advanced CKD patients in US would prefer HoD. We also show that initiating CPE leads to accelerated growth in HoD utilizations and reduces disparities in HoD utilizations, goals for system improvements. Finally, the reproducibility of our structured CPE protocol with consistent efficacy data suggest that initiating such programs at institutional levels has the potential to improve informed dialysis selection and HoD rates across any similar large healthcare institute within US.

Background Problem solving in a clinical context requires knowledge and experience, and most traditional examinations for learners do not capture skills that are required in some situations where there is uncertainty about the proper course of action. Objective We sought to evaluate anesthesiology residents for deficiencies in cognitive performance within and across 3 clinical domains (operating room, trauma, and cardiac resuscitation) using simulation-based assessment. Methods Individual basic knowledge and cognitive performance in each simulation-based scenario were assessed in 47 residents using a 15- to 29-item scenario-specific checklist. For every scenario and item we calculated group error scenario rate (frequency) and individual (resident) item success. For all analyses, alpha was designated as 0.05. Results Postgraduate year (PGY)-3 and PGY-4 residents' cognitive items error rates were higher and success rates lower compared to basic and technical performance in each domain tested (P &lt; .05). In the trauma and resuscitation scenarios, the cognitive error rate by PGY-4 residents was fairly high (0.29–0.5) and their cognitive success rate was low (0.5–0.68). The most common cognitive errors were anchoring, availability bias, premature closure, and confirmation bias. Conclusions Simulation-based assessment can differentiate between higher-order (cognitive) and lower-order (basic and technical) skills expected of relatively experienced (PGY-3 and PGY-4) anesthesiology residents. Simulation-based assessments can also highlight areas of relative strength and weakness in a resident group, and this information can be used to guide curricular modifications to address deficiencies in tasks requiring higher-order processing and cognition.