Early Cold Stored Platelet Transfusion Following Severe Injury: A Randomized Clinical Trial.

OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared to standard care resuscitation in patients with hemorrhagic shock. SUMMARY BACKGROUND DATA: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury. METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at five U.S. trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days vs. standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality. RESULTS: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared to 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P=0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups. CONCLUSIONS AND RELEVANCE: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences.

Insights from CTTACC: immune system reset by cellular therapies for chronic illness after trauma, infection, and burn.

BACKGROUND AIMS: In this paper, we present a review of several selected talks presented at the CTTACC conference (Cellular Therapies in Trauma and Critical Care) held in Scottsdale, AZ in May 2023. This conference review highlights the potential for cellular therapies to "reset" the dysregulated immune response and restore physiologic functions to normal. Improvements in medical care systems and technology have increasingly saved lives after major traumatic events. However, many of these patients have complicated post-traumatic sequelae, ranging from short-term multi-organ failure to chronic critical illness. METHODS/RESULTS: Patients with chronic critical illness have been found to have dysregulated immune responses. These abnormal and harmful immune responses persist for years after the initial insult and can potentially be mitigated by treatment with cellular therapies. CONCLUSIONS: The sessions emphasized the need for more research and clinical trials with cellular therapies for the treatment of a multitude of chronic illnesses: post-trauma, radiation injury, COVID-19, burns, traumatic brain injury (TBI) and other chronic infections.

Effect of Aspirin Versus Low-Molecular-Weight Heparin Thromboprophylaxis on Medication Satisfaction and Out-of-Pocket Costs: A Secondary Analysis of a Randomized Clinical Trial.

BACKGROUND: Current guidelines recommend low-molecular-weight heparin for thromboprophylaxis after orthopaedic trauma. However, recent evidence suggests that aspirin is similar in efficacy and safety. To understand patients' experiences with these medications, we compared patients' satisfaction and out-of-pocket costs after thromboprophylaxis with aspirin versus low-molecular-weight heparin. METHODS: This study was a secondary analysis of the PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT) trial, conducted at 21 trauma centers in the U.S. and Canada. We included adult patients with an operatively treated extremity fracture or a pelvic or acetabular fracture. Patients were randomly assigned to receive 30 mg of low-molecular-weight heparin (enoxaparin) twice daily or 81 mg of aspirin twice daily for thromboprophylaxis. The duration of the thromboprophylaxis, including post-discharge prescription, was based on hospital protocols. The study outcomes included patient satisfaction with and out-of-pocket costs for their thromboprophylactic medication measured on ordinal scales. RESULTS: The trial enrolled 12,211 patients (mean age and standard deviation [SD], 45 ± 18 years; 62% male), 9725 of whom completed the question regarding their satisfaction with the medication and 6723 of whom reported their out-of-pocket costs. The odds of greater satisfaction were 2.6 times higher for patients assigned to aspirin than those assigned to low-molecular-weight heparin (odds ratio [OR]: 2.59; 95% confidence interval [CI]: 2.39 to 2.80; p < 0.001). Overall, the odds of incurring any out-of-pocket costs for thromboprophylaxis medication were 51% higher for patients assigned to aspirin compared with low-molecular-weight heparin (OR: 1.51; 95% CI: 1.37 to 1.66; p < 0.001). However, patients assigned to aspirin had substantially lower odds of out-of-pocket costs of at least $25 (OR: 0.15; 95% CI: 0.12 to 0.18; p < 0.001). CONCLUSIONS: Use of aspirin substantially improved patients' satisfaction with their medication after orthopaedic trauma. While aspirin use increased the odds of incurring any out-of-pocket costs, it protected against costs of ≥$25, potentially improving health equity for thromboprophylaxis. LEVEL OF EVIDENCE: Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.

Risk-stratified thromboprophylaxis effects of aspirin versus low-molecular-weight heparin in orthopedic trauma patients: A secondary analysis of the PREVENT CLOT trial.

BACKGROUND: The PREVENT CLOT trial concluded that thromboprophylaxis with aspirin was noninferior to low-molecular-weight heparin (LMWH) in preventing death after orthopedic trauma. However, it was unclear if these results applied to patients at highest risk of thrombosis. Therefore, we assessed if the effect of aspirin versus LMWH differed based on patients' baseline risk of venous thromboembolism (VTE). METHODS: The PREVENT CLOT trial enrolled 12,211 adult patients with fractures. This secondary analysis stratified the study population into VTE risk quartiles: low (<1%) to high (>10%) using the Caprini score. We assessed stratum-specific treatment effects using the win ratio method, in which each patient assigned to aspirin was paired with each assigned to LMWH. In each pair, we compared outcomes hierarchically, starting with death, then pulmonary embolism, deep vein thrombosis, and bleeding. The secondary outcome added patients' medication satisfaction as a fifth composite component. RESULTS: In the high-risk quartile (n = 3052), 80% had femur fracture, pelvic, or acetabular fractures. Thoracic (47%) and head (37%) injuries were also common. In the low risk quartile (n = 3053), most patients had a tibia fracture (67%), 5% had a thoracic injury, and less than 1% had head or spinal injuries. Among high risk patients, thromboembolic events did not differ statistically between aspirin and LMWH (win ratio, 0.94; 95% confidence interval [CI], 0.82-1.08, p = 0.42). This result was consistent in the low (win ratio, 1.15; 95% CI, 0.90-1.47, p = 0.27), low-medium (win ratio, 1.05; 95% CI, 0.85-1.29, p = 0.68), and medium-high risk quartiles (win ratio, 0.94; 95% CI, 0.80-1.11, p = 0.48). When medication satisfaction was considered, favorable outcomes were 68% more likely with aspirin (win ratio, 1.68; 95% CI, 1.60-1.77; p < 0.001). CONCLUSION: Thromboembolic outcomes were similar with aspirin or LMWH, even among patients at highest risk of VTE. Aspirin was favored if medication satisfaction was also considered. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Screening for Intimate Partner Violence in Trauma: Results of a Quality Improvement Project.

INTRODUCTION: Intimate partner violence (IPV) is common, especially among patients presenting with traumatic injury. We implemented an IPV screening program for patients admitted after trauma. We sought to determine whether specific demographic or clinical characteristics were associated with being screened or not screened for IPV and with IPV screen results. METHODS: Retrospective cohort study evaluating all patients admitted after trauma from July 2020-July 2022 in an Adult Level 1 Trauma Center. RESULTS: There were 4147 admissions following traumatic injury, of which 70% were men and 30% were women. The cohort was 46% White, 20% Asian, 15% Black, and 17% other races. Twenty-three percent were Hispanic or Latino/a. Seventy-seven percent were admitted for blunt injuries and 16% for penetrating injuries. Thirteen percent (n = 559) of the cohort was successfully screened for IPV. Screening rates did not differ by gender, race, or ethnicity. After adjustment for demographic and clinical factors, patients admitted to the intensive care unit were significantly less likely to be screened. Of the screened patients, 30% (165) screened positive. These patients were more commonly Hispanic or Latino/a, insured by Medicaid and presented with a penetrating injury. There were no differences in injury severity in patients who screened positive versus those who screened negative. CONCLUSIONS: There are significant barriers to universal screening for IPV, including injury acuity, in patients admitted following trauma. However, the 30% rate of positive screens for IPV in patients admitted following trauma highlights the urgent need to understand and address barriers to screening in trauma settings to enable universal screening.

The injured monocyte: The link to chronic critical illness and mortality following injury.

BACKGROUND: This study aimed to understand the altered innate immune response in severely injured patients leading to chronic critical illness (CCI). Specifically, it focused on characterizing the monocyte populations and their correlation with CCI development and long-term complications. METHODS: Over a 3-year period, we monitored patients with severe injuries for up to 1-year postinjury. Chronic critical illness was defined as an ICU stay exceeding 14 days with persistent organ failure. Blood samples were collected on Days 1 and 5 for monocyte phenotypic expression analysis using cytometry by time flight. The monocyte subpopulations studied were classical (CL), intermediate (INT), and nonclassical (NC), along with cell surface receptor expression and activation. RESULTS: Out of 80 enrolled patients, 26 (32.5%) developed CCI. Patients with CCI had more severe injuries (Injury Severity Score, 32.4 + 5.2 vs. 29.6 + 4.1, p = 0.01) and received a higher number of red blood cells (8.9 + 4.1 vs. 4.7 + 3.8 units, p < 0.01) compared with those without CCI. In patients with CCI, the NC monocytes were significantly reduced by over twofold early, and significantly increased later, compared with those without CCI. Moreover, significant changes in intracellular cytokine expression and cell receptors were observed within each monocyte subpopulation in patients with CCI, indicating an increased proinflammatory phenotype but decreased phagocytic capacity and antigen presentation. The development of CCI and the presence of this unique monocyte phenotype were associated with a significantly increased risk of infection, discharge to a long-term care facility, and 1-year mortality of 27%. CONCLUSION: Development of CCI following severe injury is associated with significant long-term morbidity and unacceptably high mortality. The altered NC phenotype with reduced phagocytic capacity and antigen presentation in patients developing CCI after severe injury is appears partially responsible. Early identification of this unique phenotype may help predict and treat patients at risk for CCI, leading to improved outcomes. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Trial Participation and Outcomes Among English-Speaking and Spanish-Speaking Patients With Appendicitis Randomized to Antibiotics: A Secondary Analysis of the CODA Randomized Clinical Trial.

Importance: Spanish-speaking participants are underrepresented in clinical trials, limiting study generalizability and contributing to ongoing health inequity. The Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial intentionally included Spanish-speaking participants. Objective: To describe trial participation and compare clinical and patient-reported outcomes among Spanish-speaking and English-speaking participants with acute appendicitis randomized to antibiotics. Design, Setting, and Participants: This study is a secondary analysis of the CODA trial, a pragmatic randomized trial comparing antibiotic therapy with appendectomy in adult patients with imaging-confirmed appendicitis enrolled at 25 centers across the US from May 1, 2016, to February 28, 2020. The trial was conducted in English and Spanish. All 776 participants randomized to antibiotics are included in this analysis. The data were analyzed from November 15, 2021, through August 24, 2022. Intervention: Randomization to a 10-day course of antibiotics or appendectomy. Main Outcomes and Measures: Trial participation, European Quality of Life-5 Dimensions (EQ-5D) questionnaire scores (higher scores indicating a better health status), rate of appendectomy, treatment satisfaction, decisional regret, and days of work missed. Outcomes are also reported for a subset of participants that were recruited from the 5 sites with a large proportion of Spanish-speaking participants. Results: Among eligible patients 476 of 1050 Spanish speakers (45%) and 1076 of 3982 of English speakers (27%) consented, comprising the 1552 participants who underwent 1:1 randomization (mean age, 38.0 years; 976 male [63%]). Of the 776 participants randomized to antibiotics, 238 were Spanish speaking (31%). Among Spanish speakers randomized to antibiotics, the rate of appendectomy was 22% (95% CI, 17%-28%) at 30 days and 45% (95% CI, 38%-52%) at 1 year, while in English speakers, these rates were 20% (95% CI, 16%-23%) at 30 days and 42% (95% CI 38%-47%) at 1 year. Mean EQ-5D scores were 0.93 (95% CI, 0.92-0.95) among Spanish speakers and 0.92 (95% CI, 0.91-0.93) among English speakers. Symptom resolution at 30 days was reported by 68% (95% CI, 61%-74%) of Spanish speakers and 69% (95% CI, 64%-73%) of English speakers. Spanish speakers missed 6.69 (95% CI, 5.51-7.87) days of work on average, while English speakers missed 3.76 (95% CI, 3.20-4.32) days. Presentation to the emergency department or urgent care, hospitalization, treatment dissatisfaction, and decisional regret were low for both groups. Conclusions and Relevance: A high proportion of Spanish speakers participated in the CODA trial. Clinical and most patient-reported outcomes were similar for English- and Spanish-speaking participants treated with antibiotics. Spanish speakers reported more days of missed work. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Perception of Treatment Success and Impact on Function with Antibiotics or Appendectomy for Appendicitis: A Randomized Clinical Trial with an Observational Cohort.

OBJECTIVE: To compare secondary patient reported outcomes of perceptions of treatment success and function for patients treated for appendicitis with appendectomy vs. antibiotics at 30 days. SUMMARY BACKGROUND DATA: The Comparison of Outcomes of antibiotic Drugs and Appendectomy trial found antibiotics noninferior to appendectomy based on 30-day health status. To address questions about outcomes among participants with lower socioeconomic status, we explored the relationship of sociodemographic and clinical factors and outcomes. METHODS: We focused on 4 patient reported outcomes at 30 days: high decisional regret, dissatisfaction with treatment, problems performing usual activities, and missing >10 days of work. The randomized (RCT) and observational cohorts were pooled for exploration of baseline factors. The RCT cohort alone was used for comparison of treatments. Logistic regression was used to assess associations. RESULTS: The pooled cohort contained 2062 participants; 1552 from the RCT. Overall, regret and dissatisfaction were low whereas problems with usual activities and prolonged missed work occurred more frequently. In the RCT, those assigned to antibiotics had more regret (Odd ratios (OR) 2.97, 95% Confidence intervals (CI) 2.05-4.31) and dissatisfaction (OR 1.98, 95%CI 1.25-3.12), and reported less missed work (OR 0.39, 95%CI 0.27-0.56). Factors associated with function outcomes included sociodemographic and clinical variables for both treatment arms. Fewer factors were associated with dissatisfaction and regret. CONCLUSIONS: Overall, participants reported high satisfaction, low regret, and were frequently able to resume usual activities and return to work. When comparing treatments for appendicitis, no single measure defines success or failure for all people. The reported data may inform discussions regarding the most appropriate treatment for individuals. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02800785.

Management of Decompensated Cirrhosis in the Surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document.

Management of decompensated cirrhosis (DC) can be challenging for the surgical intensivist. Management of DC is often complicated by ascites, coagulopathy, hepatic encephalopathy, gastrointestinal bleeding, hepatorenal syndrome, and difficulty assessing volume status. This Clinical Consensus Document created by the American Association for the Surgery of Trauma Critical Care Committee reviews practical clinical questions about the critical care management of patients with DC to facilitate best practices by the bedside provider.

Developing a National Trauma Research Action Plan: Results from the long-term outcomes research gap Delphi survey.

BACKGROUND: In the National Academies of Sciences, Engineering, and Medicine 2016 report on trauma care, the establishment of a National Trauma Research Action Plan to strengthen and guide future trauma research was recommended. To address this recommendation, the Department of Defense funded the Coalition for National Trauma Research to generate a comprehensive research agenda spanning the continuum of trauma and burn care. We describe the gap analysis and high-priority research questions generated from the National Trauma Research Action Plan panel on long-term outcomes. METHODS: Experts in long-term outcomes were recruited to identify current gaps in long-term trauma outcomes research, generate research questions, and establish the priority for these questions using a consensus-driven, Delphi survey approach from February 2021 to August 2021. Panelists were identified using established Delphi recruitment guidelines to ensure heterogeneity and generalizability including both military and civilian representation. Panelists were encouraged to use a PICO format to generate research questions: Patient/Population, Intervention, Compare/Control, and Outcome model. On subsequent surveys, panelists were asked to prioritize each research question on a 9-point Likert scale, categorized to represent low-, medium-, and high-priority items. Consensus was defined as ≥60% of panelists agreeing on the priority category. RESULTS: Thirty-two subject matter experts generated 482 questions in 17 long-term outcome topic areas. By Round 3 of the Delphi, 359 questions (75%) reached consensus, of which 107 (30%) were determined to be high priority, 252 (70%) medium priority, and 0 (0%) low priority. Substance abuse and pain was the topic area with the highest number of questions. Health services (not including mental health or rehabilitation) (64%), mental health (46%), and geriatric population (43%) were the topic areas with the highest proportion of high-priority questions. CONCLUSION: This Delphi gap analysis of long-term trauma outcomes research identified 107 high-priority research questions that will help guide investigators in future long-term outcomes research. LEVEL OF EVIDENCE: Diagnostic Tests or Criteria; Level IV.

Alcohol Intoxication Is Associated With Bladder Injury and Bladder Surgical Repair in Patients Sustaining Motor Vehicle Collisions.

PURPOSE: Alcohol intoxication is a known risk factor for motor vehicle collisions. We hypothesize ethanol intoxication increases the risk of bladder injury and surgical repair, especially at higher blood alcohol content levels. MATERIALS AND METHODS: We identified all patients involved in motor vehicle collisions from the National Trauma Data Bank from 2017-2019. Patients were categorized into an intoxication and intoxication negative group. Variables collected included age, sex, blood alcohol content level, driver status, seat belt restraint use, nonalcoholic intoxication, pelvic fracture, and Injury Severity Scale. Primary outcome measures of bladder injury and bladder surgical repair were assessed and interaction with pelvic fracture and restraint use were measured. RESULTS: We identified 594,484 patients and 97,831 (16.5%) had a positive alcohol screen. Patients in the intoxication group were more likely to be intoxicated with other substances (32.8% vs 14.6%, P < .001), have a bladder injury (1% vs 0.4%, P < .001) and receive bladder surgical repair (0.7% vs 0.15%, P < .001). Injury Severity Scale and pelvic fracture were statistically significant predictors of bladder injury. In adjusted analysis, higher blood alcohol content was associated with both outcomes. Above the legal limit, alcohol intoxication was more predictive of bladder surgical repair than pelvic fracture. The association of alcohol intoxication with both outcomes did not differ by pelvic fracture, but strengthened with seat belt use at higher intoxication levels. CONCLUSIONS: Alcohol intoxication is independently associated with increased risk of bladder injury and subsequent bladder surgical repair following motor vehicle collisions. Trauma providers should have a high index of suspicion for bladder injuries in alcohol intoxicated patients, particularly those using seat belt restraints.

Analysis of Outcomes Associated With Outpatient Management of Nonoperatively Treated Patients With Appendicitis.

Importance: In the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial, which found antibiotics to be noninferior, approximately half of participants randomized to receive antibiotics had outpatient management with hospital discharge within 24 hours. If outpatient management is safe, it could increase convenience and decrease health care use and costs. Objective: To assess the use and safety of outpatient management of acute appendicitis. Design, Setting, and Participants: This cohort study, which is a secondary analysis of the CODA trial, included 776 adults with imaging-confirmed appendicitis who received antibiotics at 25 US hospitals from May 1, 2016, to February 28, 2020. Exposures: Participants randomized to antibiotics (intravenous then oral) could be discharged from the emergency department based on clinician judgment and prespecified criteria (hemodynamically stable, afebrile, oral intake tolerated, pain controlled, and follow-up confirmed). Outpatient management and hospitalization were defined as discharge within or after 24 hours, respectively. Main Outcomes and Measures: Outcomes compared among patients receiving outpatient vs inpatient care included serious adverse events (SAEs), appendectomies, health care encounters, satisfaction, missed workdays at 7 days, and EuroQol 5-dimension (EQ-5D) score at 30 days. In addition, appendectomy incidence among outpatients and inpatients, unadjusted and adjusted for illness severity, was compared. Results: Among 776 antibiotic-randomized participants, 42 (5.4%) underwent appendectomy within 24 hours and 8 (1.0%) did not receive their first antibiotic dose within 24 hours, leaving 726 (93.6%) comprising the study population (median age, 36 years; range, 18-86 years; 462 [63.6%] male; 437 [60.2%] White). Of these participants, 335 (46.1%; site range, 0-89.2%) were discharged within 24 hours, and 391 (53.9%) were discharged after 24 hours. Over 7 days, SAEs occurred in 0.9 (95% CI, 0.2-2.6) per 100 outpatients and 1.3 (95% CI, 0.4-2.9) per 100 inpatients; in the appendicolith subgroup, SAEs occurred in 2.3 (95% CI, 0.3-8.2) per 100 outpatients vs 2.8 (95% CI, 0.6-7.9) per 100 inpatients. During this period, appendectomy occurred in 9.9% (95% CI, 6.9%-13.7%) of outpatients and 14.1% (95% CI, 10.8%-18.0%) of inpatients; adjusted analysis demonstrated a similar difference in incidence (-4.0 percentage points; 95% CI, -8.7 to 0.6). At 30 days, appendectomies occurred in 12.6% (95% CI, 9.1%-16.7%) of outpatients and 19.0% (95% CI, 15.1%-23.4%) of inpatients. Outpatients missed fewer workdays (2.6 days; 95% CI, 2.3-2.9 days) than did inpatients (3.8 days; 95% CI, 3.4-4.3 days) and had similar frequency of return health care visits and high satisfaction and EQ-5D scores. Conclusions and Relevance: These findings support that outpatient antibiotic management is safe for selected adults with acute appendicitis, with no greater risk of complications or appendectomy than hospital care, and should be included in shared decision-making discussions of patient preferences for outcomes associated with nonoperative and operative care. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Self-selection vs Randomized Assignment of Treatment for Appendicitis.

Importance: For adults with appendicitis, several randomized clinical trials have demonstrated that antibiotics are an effective alternative to appendectomy. However, it remains unknown how the characteristics of patients in such trials compare with those of patients who select their treatment and whether outcomes differ. Objective: To compare participants in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) randomized clinical trial (RCT) with a parallel cohort study of participants who declined randomization and self-selected treatment. Design, Setting, and Participants: The CODA trial was conducted in 25 US medical centers. Participants were enrolled between May 3, 2016, and February 5, 2020; all participants were eligible for at least 1 year of follow-up, with all follow-up ending in 2021. The randomized cohort included 1094 adults with appendicitis; the self-selection cohort included patients who declined participation in the randomized group, of whom 253 selected appendectomy and 257 selected antibiotics. In this secondary analysis, characteristics and outcomes in both self-selection and randomized cohorts are described with an exploratory analysis of cohort status and receipt of appendectomy. Interventions: Appendectomy vs antibiotics. Main Outcomes and Measures: Characteristics among participants randomized to either appendectomy or antibiotics were compared with those of participants who selected their own treatment. Results: Clinical characteristics were similar across the self-selection cohort (510 patients; mean age, 35.8 years [95% CI, 34.5-37.1]; 218 female [43%; 95% CI, 39%-47%]) and the randomized group (1094 patients; mean age, 38.2 years [95% CI, 37.4-39.0]; 386 female [35%; 95% CI, 33%-38%]). Compared with the randomized group, those in the self-selection cohort were less often Spanish speaking (n = 99 [19%; 95% CI, 16%-23%] vs n = 336 [31%; 95% CI, 28%-34%]), reported more formal education (some college or more, n = 355 [72%; 95% CI, 68%-76%] vs n = 674 [63%; 95% CI, 60%-65%]), and more often had commercial insurance (n = 259 [53%; 95% CI, 48%-57%] vs n = 486 [45%; 95% CI, 42%-48%]). Most outcomes were similar between the self-selection and randomized cohorts. The number of patients undergoing appendectomy by 30 days was 38 (15.3%; 95% CI, 10.7%-19.7%) among those selecting antibiotics and 155 (19.2%; 95% CI, 15.9%-22.5%) in those who were randomized to antibiotics (difference, 3.9%; 95% CI, -1.7% to 9.5%). Differences in the rate of appendectomy were primarily observed in the non-appendicolith subgroup. Conclusions and Relevance: This secondary analysis of the CODA RCT found substantially similar outcomes across the randomized and self-selection cohorts, suggesting that the randomized trial results are generalizable to the community at large. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Developing a National Trauma Research Action Plan: Results from the acute resuscitation, initial patient evaluation, imaging, and management research gap Delphi survey.

BACKGROUND: Injury is the leading cause of death in patients aged 1 to 45 years and contributes to a significant public health burden for individuals of all ages. To achieve zero preventable deaths and disability after injury, the National Academies of Science, Engineering and Medicine called for the development of a National Trauma Research Action Plan to improve outcomes for military and civilian trauma patients. Because rapid resuscitation and prompt identification and treatment of injuries are critical in achieving optimal outcomes, a panel of experts was convened to generate high-priority research questions in the areas of acute resuscitation, initial evaluation, imaging, and definitive management on injury. METHODS: Forty-three subject matter experts in trauma care and injury research were recruited to perform a gap analysis of current literature and prioritize unanswered research questions using a consensus-driven Delphi survey approach. Four Delphi rounds were conducted to generate research questions and prioritize them using a 9-point Likert scale. Research questions were stratified as low, medium, or high priority, with consensus defined as ≥60% of panelists agreeing on the priority category. Research questions were coded using a taxonomy of 118 research concepts that were standard across all National Trauma Research Action Plan panels. RESULTS: There were 1,422 questions generated, of which 992 (69.8%) reached consensus. Of the questions reaching consensus, 327 (33.0%) were given high priority, 621 (62.6%) medium priority, and 44 (4.4%) low priority. Pharmaceutical intervention and fluid/blood product resuscitation were most frequently scored as high-priority intervention concepts. Research questions related to traumatic brain injury, vascular injury, pelvic fracture, and venous thromboembolism prophylaxis were highly prioritized. CONCLUSION: This research gap analysis identified more than 300 high-priority research questions within the broad category of Acute Resuscitation, Initial Evaluation, Imaging, and Definitive Management. Research funding should be prioritized to address these high-priority topics in the future.

Postinjury platelet aggregation and venous thromboembolism.

BACKGROUND: Posttraumatic venous thromboembolism (VTE) remains prevalent in severely injured patients despite chemoprophylaxis. Importantly, although platelets are central to thrombosis, they are not routinely targeted in prevention of posttraumatic VTE. Furthermore, platelets from injured patients show ex vivo evidence of increased activation yet impaired aggregation, consistent with functional exhaustion. However, the relationship of this platelet functional phenotype with development of posttraumatic VTE is unknown. We hypothesized that, following injury, impaired ex vivo platelet aggregation (PA) is associated with the development of posttraumatic VTE. METHODS: We performed a secondary analysis of 133 severely injured patients from a prospective observational study investigating coagulation and inflammation (2011-2019). Platelet aggregation in response to stimulation with adenosine diphosphate (ADP), collagen, and thrombin was measured at presentation (preresuscitation) and 24 hours (postresuscitation). Viscoelastic clot strength and lysis were measured in parallel by thromboelastography. Multivariable regression examined relationships between PA at presentation, 24 hours, and the change (δ) in PA between presentation and 24 hours with development of VTE. RESULTS: The 133 patients were severely injured (median Injury Severity Score, 25), and 14% developed VTE (all >48 hours after admission). At presentation, platelet count and PA were not significantly different between those with and without incident VTE. However, at 24 hours, those who subsequently developed VTE had significantly lower platelet counts (126 × 10 9 /L vs. 164 × 10 9 /L, p = 0.01) and lower PA in response to ADP ( p < 0.05), collagen ( p < 0.05), and thrombin ( p = 0.06). Importantly, the magnitude of decrease in PA (δ) from presentation to 24 hours was independently associated with development of VTE (adjusted odds ratios per 10 aggregation unit decrease: δ-ADP, 1.31 [ p = 0.03]; δ-collagen, 1.36 [ p = 0.01]; δ-thrombin, 1.41 [ p < 0.01]). CONCLUSION: Severely injured patients with decreasing ex vivo measures of PA despite resuscitation have an increased risk of developing VTE. This may have implications for predicting development of VTE and for studying platelet targeted chemoprophylaxis regimens. LEVEL OF EVIDENCE: Prognostic/Epidemiological; Level III.

Nonoperative Management in Blunt Splenic Trauma: Can Shock Index Predict Failure?

INTRODUCTION: Predicting failure of nonoperative management (NOM) in splenic trauma remains elusive. Shock index (SI) is an indicator of physiologic burden in an injury but is not used as a prediction tool. The purpose of this study was to determine if elevated SI would be predictive of failure of NOM in patients with a blunt splenic injury. METHODS: Adult patients admitted to a level-1 trauma center from January 2011 to April 2017 for NOM of splenic injury were reviewed. Patients were excluded if they underwent a procedure (angiography or surgery) prior to admission. The primary outcome was requiring intervention after an initial trial of noninterventional management (NIM). An SI > 0.9 at admission was considered a high risk. Univariate and multivariate analyses were used to identify predicators of the failure of NOM. Findings were subsequently verified on a validation cohort of patients. RESULTS: Five hundred and eighty-five patients met inclusion criteria; 7.4% failed NIM. On an univariate analysis, findings of pseudoaneurysm or extra-arterial contrast on computed tomography did not differentiate successful NIM versus failure (8.1% versus 14.0%, P = 0.18). Age, the American Association for the Surgery of Trauma injury grade, and elevated SI were included in multivariate modeling. Grade of injury (OR 3.49, P = 0.001), age (OR 1.02, P = 0.009), and high SI (OR 3.49, P = 0.001) were each independently significant for NIM failure. The risk-adjusted odds of failure were significantly higher in patients with a high risk SI (OR 2.35, P < 0.001). Validation of these findings was confirmed for high SI on a subsequent 406 patients with a c-statistic of 0.71 (95% CI 0.62-0.80). CONCLUSIONS: Elevated SI is an independent risk factor for failure of NIM in those with splenic injury. SI along with age and computed tomography findings may aid in predicting the failure of NIM. Trauma providers should incorporate SI into decision-making tools for splenic injury management.

Patient Factors Associated With Appendectomy Within 30 Days of Initiating Antibiotic Treatment for Appendicitis.

IMPORTANCE: Use of antibiotics for the treatment of appendicitis is safe and has been found to be noninferior to appendectomy based on self-reported health status at 30 days. Identifying patient characteristics associated with a greater likelihood of appendectomy within 30 days in those who initiate antibiotics could support more individualized decision-making. OBJECTIVE: To assess patient factors associated with undergoing appendectomy within 30 days of initiating antibiotics for appendicitis. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study using data from the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) randomized clinical trial, characteristics among patients who initiated antibiotics were compared between those who did and did not undergo appendectomy within 30 days. The study was conducted at 25 US medical centers; participants were enrolled between May 3, 2016, and February 5, 2020. A total of 1552 participants with acute appendicitis were randomized to antibiotics (776 participants) or appendectomy (776 participants). Data were analyzed from September 2020 to July 2021. EXPOSURES: Appendectomy vs antibiotics. MAIN OUTCOMES AND MEASURES: Conditional logistic regression models were fit to estimate associations between specific patient factors and the odds of undergoing appendectomy within 30 days after initiating antibiotics. A sensitivity analysis was performed excluding participants who underwent appendectomy within 30 days for nonclinical reasons. RESULTS: Of 776 participants initiating antibiotics (mean [SD] age, 38.3 [13.4] years; 286 [37%] women and 490 [63%] men), 735 participants had 30-day outcomes, including 154 participants (21%) who underwent appendectomy within 30 days. After adjustment for other factors, female sex (odds ratio [OR], 1.53; 95% CI, 1.01-2.31), radiographic finding of wider appendiceal diameter (OR per 1-mm increase, 1.09; 95% CI, 1.00-1.18), and presence of appendicolith (OR, 1.99; 95% CI, 1.28-3.10) were associated with increased odds of undergoing appendectomy within 30 days. Characteristics that are often associated with increased risk of complications (eg, advanced age, comorbid conditions) and those clinicians often use to describe appendicitis severity (eg, fever: OR, 1.28; 95% CI, 0.82-1.98) were not associated with odds of 30-day appendectomy. The sensitivity analysis limited to appendectomies performed for clinical reasons provided similar results regarding appendicolith (adjusted OR, 2.41; 95% CI, 1.49-3.91). CONCLUSIONS AND RELEVANCE: This cohort study found that presence of an appendicolith was associated with a nearly 2-fold increased risk of undergoing appendectomy within 30 days of initiating antibiotics. Clinical characteristics often used to describe severity of appendicitis were not associated with odds of 30-day appendectomy. This information may help guide more individualized decision-making for people with appendicitis.

Utility and Outcome of Angioembolization for High-Grade Renal Trauma Management in a Large Hospital-Based Trauma Registry.

PURPOSE: We evaluated angioembolization (AE) use for high-grade renal trauma (HGRT) management and compared AE vs surgical repair (SR) in requiring nephrectomy. MATERIALS AND METHODS: Using National Trauma Data Bank® 2013-2018, we identified patients with HGRT who underwent AE or SR as initial management. Therapy failure was defined as performing subsequent nephrectomy, partial nephrectomy, SR or AE. Logistic regression was performed to assess the association between intervention type (AE vs SR) and nephrectomy. Analysis was repeated in a propensity score-matched cohort constructed by matching AE to SR patients on American Association for the Surgery of Trauma (AAST) grade, injury mechanism (blunt vs penetrating) and hemodynamic instability (systolic blood pressure <90 mmHg). RESULTS: There were 266 patients in the AE group and 215 in the SR group. Median age was 29.5 years and 212 patients (44.1%) had penetrating injuries. AE was successful in 94.2% and 85.3% of grade IV and V injuries, respectively, whereas SR was successful in 82.1% and 56%, respectively. Grade V injury was associated with AE failure in the adjusted analysis (OR 3.55, 95% CI 1.22-10.2, p=0.02). Nephrectomy was less likely to be performed after AE vs after SR in HGRT (6.4% vs 17.2%, p=0.01), AAST grade IV (4.2% vs 13.7%, p=0.001) and AAST grade V (12% vs 44%, p=0.001). The matched cohort comprised 528 patients. In post-match regression, AE, compared to SR, was associated with lower odds of nephrectomy (OR 0.18, 95% CI 0.04-0.70, p=0.013). CONCLUSIONS: AE achieved superior kidney salvage compared to SR in this observational cohort. These results inform both clinical practice and future prospective trials.

Multi-center validation of the Bowel Injury Predictive Score (BIPS) for the early identification of need to operate in blunt bowel and mesenteric injuries.

INTRODUCTION: The Bowel Injury Prediction Score (BIPS) is a tool for identifying patients at risk for blunt bowel and mesenteric injury (BBMI) requiring surgery. BIPS is calculated by assigning one point for each of the following: (1) WBC ≥ 17,000, (2) abdominal tenderness, and (3) injury grade ≥ 4 (mesenteric contusion or hematoma with bowel wall thickening or adjacent interloop fluid collection) on CT scan. A total score ≥ 2 is associated with BBMI requiring surgery. We aimed to validate the BIPS as a predictor for patients with BBMIs requiring operative intervention in a multi-center prospective study. MATERIALS AND METHODS: Patients were prospectively enrolled at 15 U.S. trauma centers following blunt trauma with suspicion of BBMI on CT scan between July 1, 2018 and July 31, 2019. The BIPS was calculated for each patient enrolled in the study. RESULTS: Of 313 patients, 38% had BBMI requiring operative intervention. Patients were significantly more likely to require surgery in the presence of abdominal tenderness (OR, 3.6; 95% CI, 1.6-8.0) and CT grade ≥ 4 (OR, 11.7; 95% CI, 5.7-23.7). Patients with a BIPS ≥ 2 were more than ten times more likely to require laparotomy than those with a BIPS < 2 (OR, 10.1; 95% CI, 5.0-20.4). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a BIPS ≥ 2 for BBMI requiring surgery was 72% (CI 0.6-0.8), 78% (CI 0.7-0.8), 67% (CI 0.6-0.8), and 82% (CI 0.8-0.9), respectively. The AUROC curve for BIPS ≥ 2 was 0.75. The sensitivity, specificity, PPV, and NPV of a BIPS ≥ 2 for BBMI requiring surgery in patients with severe alteration in mental status (GCS 3-8) was 70% (CI 0.5-0.9), 92% (CI 0.8-1.0), 82% (CI 0.6-1.0), and 86% (CI 0.7-1.0), respectively. CONCLUSION: This prospective multi-center trial validates BIPS as a predictor of BBMI requiring surgery. Calculation of BIPS during the initial evaluation of trauma patients is a useful adjunct to help general surgeons taking trauma call determine operative versus non-operative management of patients with BBMI including those with severe alteration in mental status.