Tezcan Ozrazgat Baslanti

Development of a genomic metric that can be rapidly used to predict clinical outcome in severely injured trauma patients.

Objective:Many patients have complicated recoveries following severe trauma 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-institutional level 1 trauma centers. Patients:Data were collected from 167 severely traumatized (injury severity score >15) adult (18–55 yr) patients. Methods:Microarray-derived genomic data obtained from 167 severely traumatized patients over 28 days were assessed for differences in messenger RNA abundance among individuals with different clinical trajectories. Once a set of genes was identified based on differences in expression over the entire study period, messenger RNA 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 dataset, 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 messenger RNA abundance in less than 12 hours, we reassessed total messenger RNA abundance from the first 24 hours after trauma and reduced the genomic data to a single composite score using the difference from reference. 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 Acute Physiology and Chronic Health Evaluation II or new injury severity score 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 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.

Regional anesthesia as compared with general anesthesia for surgery in geriatric patients with hip fracture: does it decrease morbidity, mortality, and health care costs? Results of a single-centered study.

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) vs 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 received surgery for hip fracture was no different between patients who receive regional or general anesthesia (

A BETTER UNDERSTANDING OF WHY MURINE MODELS OF TRAUMA DO NOT RECAPITULATE THE HUMAN SYNDROME

16,789 + 631 vs

Acute kidney injury is associated with early cytokine changes after trauma.

16,815 + 643, respectively, P = 0.9557). Delay in surgery and intensive care unit (ICU) admission resulted in significantly higher hospitalization costs. Age, male gender, African American race and ICU 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 rehospitalization, 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 ICU admission both increase cost of hospitalization.

Aged Mice Are Unable To Mount an Effective Myeloid Response to Sepsis

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 with 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 by examining the response in isolated neutrophil populations. Design:Preclinical 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:Six- to 10-week-old and 20- to 24-month-old C57BL/6 (B6) mice and two cohorts of 167 and 244 severely traumatized (Injury Severity Score > 15) adult (> 18 yr) 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 with 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 trauma-related database). 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.

A comparison of 4 airway devices on cervical spine alignment in cadaver models of global ligamentous instability at c1-2.

BACKGROUND Acute kidney injury (AKI) occurs in 26% of trauma patients and is associated with increased mortality and risk for nosocomial infections (NCIs). 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 among 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 IL-1ra, IL-8, MCP1, and IL-6; early decrease in sTNFR2; and late decrease in IL-1ra, IL-4, and IL-6 concentrations, compared with patients without AKI and regardless of NCI. The change in cytokine pattern differed for sIL1R2, CXCL1, and MIP1&bgr;, depending on the occurrence of NCI. Patients with AKI and NCI had lower early and late sIL1R2 and higher early and late CXCL1 and MIP1&bgr; levels. Within the first 24 hours of injury, adding plasma levels of IL-1ra, IL-8, MCP1, IL-6, 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 proinflammatory 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. LEVEL OF EVIDENCE Prognostic study, level III.

Leaving more than your fingerprint on the intravenous line: a prospective study on propofol anesthesia and implications of stopcock contamination.

The elderly have increased morbidity and mortality following sepsis; however, the cause(s) remains unclear. We hypothesized that these poor outcomes are due in part to defects in innate immunity, rather than to an exaggerated early inflammatory response. Young (6–12 wk) or aged (20–24 mo) mice underwent polymicrobial sepsis, and subsequently, the aged mice had increased mortality and defective peritoneal bacterial clearance compared with 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 1 d after sepsis. Aged mice had a relative inability to upregulate gene expression of pathways related to neutrophil-mediated protective immunity, chemokine/chemokine receptor binding, and responses to exogenous molecules. Expression of most MHC genes remained more downregulated in aged mice at day 3. 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.

1370: EPIDEMIOLOGY AND LONG-TERM SURVIVAL FOR DIFFERENT TRAJECTORIES OF ACUTE KIDNEY INJURY AFTER SEPSIS

BACKGROUND:The effects of advanced airway management on cervical spine alignment in patients with upper cervical spine instability are uncertain. METHODS:To examine the potential for mechanical disruption during endotracheal intubation in cadavers with unstable cervical spines, we performed a prospective observational cohort study with 3 cadaver subjects. We created an unstable, type II odontoid fracture with global ligamentous instability at C1-2 in lightly embalmed cadavers, followed by repetitive intubations with 4 different airway devices (Airtraq laryngoscope, Lightwand, intubating laryngeal mask airway [LMA], and Macintosh laryngoscope) while manual in-line stabilization was applied. Motion analysis data were collected using an electromagnetic device to assess the degree of angular movement in 3 axes (flexion-extension, axial rotation, and lateral bending) during the intubation trials with each device. Intubation was performed by either an emergency medical technician or attending anesthesiologist. RESULTS:Overall, 153 intubations were recorded with the 4 devices. The Lightwand technique resulted in significantly less flexion-extension and axial rotation at C1-2 than with the intubating LMA (mean difference in flexion-extension 3.2° [95% confidence interval {CI}, 0.9°–5.5°], P = 0.003; mean difference in axial rotation 1.6° [95% CI, 0.3°–2.8°], P = 0.01) and Macintosh laryngoscope (mean difference in flexion-extension 3.1° [95% CI, 0.8°–5.4°], P = 0.005; mean difference in axial rotation 1.4° [95% CI 0.1°–2.6°], P = 0.03). CONCLUSIONS:In cadavers with instability at C1-2, the Lightwand technique produced less motion than the Macintosh and intubating LMA.

Insurance Status Is Associated with Treatment Allocation and Outcomes after Subarachnoid Hemorrhage

BACKGROUND:Acute care handling of IV stopcocks during anesthesia and surgery may result in contaminated IV tubing sets. In the context of widespread propofol use, a nutrient-rich hypnotic drug, we hypothesized that propofol anesthesia increases bacterial contamination of IV stopcocks and may compromise safety of IV tubing sets when continued to be used after propofol anesthesia. METHODS:We conducted an in vitro trial by collecting IV tubing sets at the time of patient discharge from same-day ambulatory procedures performed with and without propofol anesthesia. These extension sets were then held at room temperature for 6, 24, or 48 hours. We cultured 50 samples at each interval for both cohorts. Quantitative cultures were done by aspirating the IV stopcock dead space and plating the aspirate on blood agar for colony count and speciation. RESULTS:Positive bacterial counts were recovered from 17.3% of propofol anesthesia stopcocks (26/150) and 18.6% of nonpropofol stopcocks (28/150). At 6 hours, the average bacterial counts from stopcocks with visible residual propofol was 44 colony forming units (CFU)/mL, compared with 41 CFU/mL with no visible residual propofol and 37 CFU/mL in nonpropofol anesthesia stopcocks. There was a 100-fold increase in bacterial number in contaminated stopcock dead spaces at 48 hours after propofol anesthesia. This difference remained significant when comparing positive counts from stopcocks with no visible residual propofol and nonpropofol anesthesia (P = 0.034). CONCLUSIONS:There is a covert incidence and degree of IV stopcock bacterial contamination during anesthesia which is aggravated by propofol anesthetic. Propofol anesthesia may increase risk for postoperative infection because of bacterial growth in IV stopcock dead spaces.

Knowledge Extraction and Outcome Prediction using Medical Notes

www.ccmjournal.org Critical Care Medicine • Volume 46 • Number 1 (Supplement) Learning Objectives: The 16th ADQI Consensus Conference has recently introduced concepts of persistent acute kidney injury (AKI) and acute kidney disease (AKD) to incorporate duration and renal recovery in the current diagnosis. In the prospective observational study of 179 patients with sepsis, we have determined epidemiology of persistent AKI (P-AKI) and AKD and development of chronic critical illness and their effect on longterm outcomes. Methods: AKI types were clinically adjudicated using KDIGO criteria and ADQI recommendations. In contrast to rapidly reversed AKI (RAP-AKI), P-AKI is characterized by the persistence of KDIGO creatinine and urine output criteria beyond 48 hours of the onset. Patients who did not completely recover kidney function at the discharge were considered to have AKD. Development of chronic critical illness and survival after discharge were assessed at one year after patient enrollment. Results: Prior to enrollment, 2% (3/179) had preexisting end-stage renal disease (ESRD) and 16% (29/179) had chronic kidney disease (CKD). During hospitalization, 93% (27/29) of CKD patients and 55% (81/147) of patients with no kidney disease developed AKI (p < 0.0001). Among 108 patients who developed AKI, 56% (n = 60) had persistent AKI or AKD, and 44% (n = 48) had rapidly reversed AKI, and prevalence of P-AKI or AKD was higher among CKD (21/27, 78%) patients compared to non-CKD (39/81, 48%) patients (p = 0.008). About 25% of cohort did not recover at discharge with 6% being on dialysis. Cumulative survival probabilities at one-year from sepsis onset for patients with AKD, P-AKI or CKD (64%) were significantly lower than patients with RAP-AKI (88%) or patients with no kidney disease (92%). Prevalence of CCI was significantly higher in patients with P-AKI or AKD (55%) compared to patients with no AKI (18%) or RAPAKI (33%). Although patients with CCI had significantly worse cumulative survival (64% CCI vs 93% no CCI at 12 months, p < 0.0001), when stratified by the occurrence of kidney disease, patients with kidney disease and CCI (54% at 12 months) had significantly worse survival compared to all other groups (p < 0.003). Conclusions: Persistent AKI and AKD are significant risk factors for hospital adverse outcomes and long-term mortality among patients with chronic critical illness and sepsis.