Eastern Association for the Surgery of Trauma Multicenter Trial: Comparison of pre-injury antithrombotic use and reversal strategies among severe traumatic brain injury patients

BACKGROUND: Trauma teams are often faced with patients on antithrombotic (AT) drugs, which is challenging when bleeding occurs. We sought to compare the effects of different AT medications on head injury severity and hypothesized that AT reversal would not improve mortality in severe traumatic brain injury (TBI) patients. METHODS: An Eastern Association for the Surgery of Trauma-sponsored prospective, multicentered, observational study of 15 trauma centers was performed. Patient demographics, injury burden, comorbidities, AT agents, and reversal attempts were collected. Outcomes of interest were head injury severity and in-hospital mortality. RESULTS: Analysis was performed on 2,793 patients. The majority of patients were on aspirin (acetylsalicylic acid [ASA], 46.1%). Patients on a platelet chemoreceptor blocker (P2Y12) had the highest mean Injury Severity Score (9.1 ± 8.1). Patients taking P2Y12 inhibitors ± ASA, and ASA-warfarin had the highest head Abbreviated Injury Scale (AIS) mean (1.2 ± 1.6). On risk-adjusted analysis, warfarin-ASA was associated with a higher head AIS (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.34-4.42) after controlling for Injury Severity Score, Charlson Comorbidity Index, initial Glasgow Coma Scale score, and initial systolic blood pressure. Among patients with severe TBI (head AIS score, ≥3) on antiplatelet therapy, reversal with desmopressin (DDAVP) and/or platelet transfusion did not improve survival (82.9% reversal vs. 90.4% none, p = 0.30). In severe TBI patients taking Xa inhibitors who received prothrombin complex concentrate, survival was not improved (84.6% reversal vs. 84.6% none, p = 0.68). With risk adjustment as described previously, mortality was not improved with reversal attempts (antiplatelet agents: OR 0.83; 85% CI, 0.12-5.9 [p = 0.85]; Xa inhibitors: OR, 0.76; 95% CI, 0.12-4.64; p = 0.77). CONCLUSION: Reversal attempts appear to confer no mortality benefit in severe TBI patients on antiplatelet agents or Xa inhibitors. Combination therapy was associated with severity of head injury among patients taking preinjury AT therapy, with ASA-warfarin possessing the greatest risk. LEVEL OF EVIDENCE: Prognostic, level II

Whole Blood Resuscitation is Safe in Pediatric Trauma Patients: A Multicenter Study.

INTRODUCTION: Whole blood (WB) resuscitation has been associated with a mortality benefit in trauma patients. Several small series report the safe use of WB in the pediatric trauma population. We performed a subgroup analysis of the pediatric patients from a large prospective multicenter trial comparing patients receiving WB or blood component therapy (BCT) during trauma resuscitation. We hypothesized that WB resuscitation would be safe compared to BCT resuscitation in pediatric trauma patients. METHODS: This study included pediatric trauma patients (0-17 y), from ten level-I trauma centers, who received any blood transfusion during initial resuscitation. Patients were included in the WB group if they received at least one unit of WB during their resuscitation, and the BCT group was composed of patients receiving traditional blood product resuscitation. The primary outcome was in-hospital mortality with secondary outcomes being complications. Multivariate logistic regression was performed to assess for mortality and complications in those treated with WB vs BCT. RESULTS: Ninety patients, with both penetrating and blunt mechanisms of injury (MOI), were enrolled in the study (WB: 62 (69%), BCT: 28 (21%)). Whole blood patients were more likely to be male. There were no differences in age, MOI, shock index, or injury severity score between groups. On logistic regression, there was no difference in complications. Mortality was not different between the groups ( CONCLUSION: Our data suggest WB resuscitation is safe when compared to BCT resuscitation in the care of critically injured pediatric trauma patients

An Eastern Association for the Surgery of Trauma multicenter trial examining prehospital procedures in penetrating trauma patients.

BackgroundPrehospital procedures (PHP) by emergency medical services (EMS) are performed regularly in penetrating trauma patients despite previous studies demonstrating no benefit. We sought to examine the influence of PHPs on outcomes in penetrating trauma patients in urban locations where transport to trauma center is not prolonged. We hypothesized that patients without PHPs would have better outcomes than those undergoing PHP.MethodsThis was an Eastern Association for the Surgery of Trauma-sponsored, multicenter, prospective, observational trial of adults (18+ years) with penetrating trauma to the torso and/or proximal extremity presenting at 25 urban trauma centers. The impact of PHPs and transport mechanism on in-hospital mortality were examined.ResultsOf 2,284 patients included, 1,386 (60.7%) underwent PHP. The patients were primarily Black (n = 1,527, 66.9%) males (n = 1,986, 87.5%) injured by gunshot wound (n = 1,510, 66.0%) with 34.1% (n = 726) having New Injury Severity Score of ≥16. A total of 1,427 patients (62.5%) were transported by Advanced Life Support EMS, 17.2% (n = 392) by private vehicle, 13.7% (n = 312) by police, and 6.7% (n = 153) by Basic Life Support EMS. Of the PHP patients, 69.1% received PHP on scene, 59.9% received PHP in route, and 29.0% received PHP both on scene and in route. Initial scene vitals differed between groups, but initial emergency department vitals did not. Receipt of ≥1 PHP increased mortality odds (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.01-1.83; p = 0.04). Logistic regression showed increased mortality with each PHP, whether on scene or during transport. Subset analysis of specific PHP revealed that intubation (OR, 10.76; 95% CI, 4.02-28.78; p < 0.001), C-spine immobilization (OR, 5.80; 95% CI, 1.85-18.26; p < 0.01), and pleural decompression (OR, 3.70; 95% CI, 1.33-10.28; p = 0.01) had the highest odds of mortality after adjusting for multiple variables.ConclusionPrehospital procedures in penetrating trauma patients impart no survival advantage and may be harmful in urban settings, even when performed during transport. Therefore, PHP should be forgone in lieu of immediate transport to improve patient outcomes.Level of evidencePrognostic, level III

An Eastern Association for the Surgery of Trauma multicenter trial examining prehospital procedures in penetrating trauma patients.

BackgroundPrehospital procedures (PHP) by emergency medical services (EMS) are performed regularly in penetrating trauma patients despite previous studies demonstrating no benefit. We sought to examine the influence of PHPs on outcomes in penetrating trauma patients in urban locations where transport to trauma center is not prolonged. We hypothesized that patients without PHPs would have better outcomes than those undergoing PHP.MethodsThis was an Eastern Association for the Surgery of Trauma-sponsored, multicenter, prospective, observational trial of adults (18+ years) with penetrating trauma to the torso and/or proximal extremity presenting at 25 urban trauma centers. The impact of PHPs and transport mechanism on in-hospital mortality were examined.ResultsOf 2,284 patients included, 1,386 (60.7%) underwent PHP. The patients were primarily Black (n = 1,527, 66.9%) males (n = 1,986, 87.5%) injured by gunshot wound (n = 1,510, 66.0%) with 34.1% (n = 726) having New Injury Severity Score of ≥16. A total of 1,427 patients (62.5%) were transported by Advanced Life Support EMS, 17.2% (n = 392) by private vehicle, 13.7% (n = 312) by police, and 6.7% (n = 153) by Basic Life Support EMS. Of the PHP patients, 69.1% received PHP on scene, 59.9% received PHP in route, and 29.0% received PHP both on scene and in route. Initial scene vitals differed between groups, but initial emergency department vitals did not. Receipt of ≥1 PHP increased mortality odds (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.01-1.83; p = 0.04). Logistic regression showed increased mortality with each PHP, whether on scene or during transport. Subset analysis of specific PHP revealed that intubation (OR, 10.76; 95% CI, 4.02-28.78; p < 0.001), C-spine immobilization (OR, 5.80; 95% CI, 1.85-18.26; p < 0.01), and pleural decompression (OR, 3.70; 95% CI, 1.33-10.28; p = 0.01) had the highest odds of mortality after adjusting for multiple variables.ConclusionPrehospital procedures in penetrating trauma patients impart no survival advantage and may be harmful in urban settings, even when performed during transport. Therefore, PHP should be forgone in lieu of immediate transport to improve patient outcomes.Level of evidencePrognostic, level III

Infection after penetrating brain injury—An Eastern Association for the Surgery of Trauma multicenter study oral presentation at the 32nd annual meeting of the Eastern Association for the Surgery of Trauma, January 15–19, 2019, in Austin, Texas

2019 EAST PODIUM PAPER Infection after penetrating brain injury—An Eastern Association for the Surgery of Trauma multicenter study oral presentation at the 32nd annual meeting of the Eastern Association for the Surgery of Trauma, January 15–19, 2019, in Austin, Texas Harmon, Laura A. MD; Haase, Daniel J. MD; Kufera, Joseph A. MA; Adnan, Sakib BS; Cabral, Donna BNS; Lottenberg, Lawrence MD; Cunningham, Kyle W. MD, MPH; Bonne, Stephanie MD; Burgess, Jessica MD; Etheridge, James MD; Rehbein, Jennifer L. MD; Semon, Gregory DO; Noorbakhsh, Matthew R. MD; Cragun, Benjamin N. MD; Agrawal, Vaidehi PhD; Truitt, Michael MD; Marcotte, Joseph MD; Goldenberg, Anna DO; Behbahaninia, Milad MD; Keric, Natasha MD; Hammer, Peter M. MD; Nahmias, Jeffry MD; Grigorian, Areg MD; Turay, Dave MD; Chakravarthy, Vikram MD; Lalchandani, Priti MD; Kim, Dennis MD; Chapin, Trinette; Dunn, Julie MD; Portillo, Victor MD; Schroeppel, Thomas MD, MS; Stein, Deborah M. MD, MPH Author Information Journal of Trauma and Acute Care Surgery 87(1):p 61-67, July 2019. | DOI: 10.1097/TA.0000000000002327 Buy CME Test Erratum Abstract BACKGROUND Fatality rates following penetrating traumatic brain injury (pTBI) are extremely high and survivors are often left with significant disability. Infection following pTBI is associated with worse morbidity. The modern rates of central nervous system infections (INF) in civilian survivors are unknown. This study sought to determine the rate of and risk factors for INF following pTBI and to determine the impact of antibiotic prophylaxis. METHODS Seventeen institutions submitted adult patients with pTBI and survival of more than 72 hours from 2006 to 2016. Patients were stratified by the presence or absence of infection and the use or omission of prophylactic antibiotics. Study was powered at 85% to detect a difference in infection rate of 5%. Primary endpoint was the impact of prophylactic antibiotics on INF. Mantel-Haenszel χ2 and Wilcoxon\u27s rank-sum tests were used to compare categorical and nonparametric variables. Significance greater than p = 0.2 was included in a logistic regression adjusted for center. RESULTS Seven hundred sixty-three patients with pTBI were identified over 11 years. 7% (n = 51) of patients developed an INF. Sixty-six percent of INF patients received prophylactic antibiotics. Sixty-two percent of all patients received one dose or greater of prophylactic antibiotics and 50% of patients received extended antibiotics. Degree of dural penetration did not appear to impact the incidence of INF (p = 0.8) nor did trajectory through the oropharynx (p = 0.18). Controlling for other variables, there was no statistically significant difference in INF with the use of prophylactic antibiotics (p = 0.5). Infection was higher in patients with intracerebral pressure monitors (4% vs. 12%; p = \u3c0.001) and in patients with surgical intervention (10% vs. 3%; p \u3c 0.001). CONCLUSION There is no reduction in INF with prophylactic antibiotics in pTBI. Surgical intervention and invasive intracerebral pressure monitoring appear to be risk factors for INF regardless of prophylactic use. LEVEL OF EVIDENCE Therapeutic, level IV

Infection after penetrating brain injury—An Eastern Association for the Surgery of Trauma multicenter study oral presentation at the 32nd annual meeting of the Eastern Association for the Surgery of Trauma, January 15–19, 2019, in Austin, Texas

2019 EAST PODIUM PAPER Infection after penetrating brain injury—An Eastern Association for the Surgery of Trauma multicenter study oral presentation at the 32nd annual meeting of the Eastern Association for the Surgery of Trauma, January 15–19, 2019, in Austin, Texas Harmon, Laura A. MD; Haase, Daniel J. MD; Kufera, Joseph A. MA; Adnan, Sakib BS; Cabral, Donna BNS; Lottenberg, Lawrence MD; Cunningham, Kyle W. MD, MPH; Bonne, Stephanie MD; Burgess, Jessica MD; Etheridge, James MD; Rehbein, Jennifer L. MD; Semon, Gregory DO; Noorbakhsh, Matthew R. MD; Cragun, Benjamin N. MD; Agrawal, Vaidehi PhD; Truitt, Michael MD; Marcotte, Joseph MD; Goldenberg, Anna DO; Behbahaninia, Milad MD; Keric, Natasha MD; Hammer, Peter M. MD; Nahmias, Jeffry MD; Grigorian, Areg MD; Turay, Dave MD; Chakravarthy, Vikram MD; Lalchandani, Priti MD; Kim, Dennis MD; Chapin, Trinette; Dunn, Julie MD; Portillo, Victor MD; Schroeppel, Thomas MD, MS; Stein, Deborah M. MD, MPH Author Information Journal of Trauma and Acute Care Surgery 87(1):p 61-67, July 2019. | DOI: 10.1097/TA.0000000000002327 Buy CME Test Erratum Abstract BACKGROUND Fatality rates following penetrating traumatic brain injury (pTBI) are extremely high and survivors are often left with significant disability. Infection following pTBI is associated with worse morbidity. The modern rates of central nervous system infections (INF) in civilian survivors are unknown. This study sought to determine the rate of and risk factors for INF following pTBI and to determine the impact of antibiotic prophylaxis. METHODS Seventeen institutions submitted adult patients with pTBI and survival of more than 72 hours from 2006 to 2016. Patients were stratified by the presence or absence of infection and the use or omission of prophylactic antibiotics. Study was powered at 85% to detect a difference in infection rate of 5%. Primary endpoint was the impact of prophylactic antibiotics on INF. Mantel-Haenszel χ2 and Wilcoxon\u27s rank-sum tests were used to compare categorical and nonparametric variables. Significance greater than p = 0.2 was included in a logistic regression adjusted for center. RESULTS Seven hundred sixty-three patients with pTBI were identified over 11 years. 7% (n = 51) of patients developed an INF. Sixty-six percent of INF patients received prophylactic antibiotics. Sixty-two percent of all patients received one dose or greater of prophylactic antibiotics and 50% of patients received extended antibiotics. Degree of dural penetration did not appear to impact the incidence of INF (p = 0.8) nor did trajectory through the oropharynx (p = 0.18). Controlling for other variables, there was no statistically significant difference in INF with the use of prophylactic antibiotics (p = 0.5). Infection was higher in patients with intracerebral pressure monitors (4% vs. 12%; p = \u3c0.001) and in patients with surgical intervention (10% vs. 3%; p \u3c 0.001). CONCLUSION There is no reduction in INF with prophylactic antibiotics in pTBI. Surgical intervention and invasive intracerebral pressure monitoring appear to be risk factors for INF regardless of prophylactic use. LEVEL OF EVIDENCE Therapeutic, level IV

Use of Cold-Stored Whole Blood is Associated with Improved Mortality in Hemostatic Resuscitation of Major Bleeding: A Multicenter Study.

OBJECTIVE: The aim of this study was to identify a mortality benefit with the use of whole blood as part of the resuscitation of bleeding trauma patients. SUMMARY BACKGROUND DATA: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with whole blood (WB) emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality. METHODS: We performed a 14-center, prospective-observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score (ISS). All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included AKI, DVT/PE, pulmonary complications, and bleeding complications. RESULTS: A total of 1,623 (WB: 1,180(74%), BCT: 443(27%)) patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs. 0.83), more comorbidities, and more blunt MOI (all P\u3c0.05). After controlling for center, age, sex, MOI, and ISS, we found no differences in the rates of AKI, DVT/PE or pulmonary complications. WB patients were 9% less likely to experience bleeding complications and were 48% less likely to die than BCT patients (P\u3c0.0001). CONCLUSIONS: Compared with BCT, the use of WB was associated with a 48% reduction in mortality in trauma patients. Our study supports the use of WB use in the resuscitation of trauma patients

Longitudinal molecular trajectories of diffuse glioma in adults.

The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear1,2. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner