Matthew D. Neal

Acute kidney injury (AKI) develops in 20% to 40% of patients with injuries and contributes to poor outcomes. In sepsis and critical illness, dysregulated coagulation and fibrinolysis are linked to microangiopathic kidney dysfunction, but similar relationships in trauma remain poorly characterized. We performed a secondary analysis of a single-center randomized controlled trial of adult patients with severe traumatic injuries. Plasma thrombin-antithrombin (TAT), plasmin-α2-antiplasmin (PAP), and fibrinogen levels were measured within 2 hours of injury and 6 hours later. AKI was defined by the Risk, Injury, Failure, Loss, and End-stage kidney disease criteria. Adjusted logistic regression models evaluated biomarker associations with AKI and receiver operating characteristic analyses identified discriminatory thresholds. Among 149 patients, 30 (20.1%) developed AKI. Patients with AKI had higher TAT and PAP concentrations and lower fibrinogen levels at both time points. The 6-hour TAT-to-fibrinogen ratio was independently associated with AKI (adjusted odds ratio, 7.17; 95% confidence interval, 2.34-21.9; P = .001; area under the curve = 0.88). Supplemental analyses demonstrated consistent associations for TAT and fibrinogen levels individually, whereas PAP level was not independently predictive. A 6-hour TAT level of 173 mg/dL showed a low likelihood of AKI (NPV, 88.2%). Elevated TAT and reduced fibrinogen levels measured 6 hours after injury were independently associated with AKI. This suggests that early coagulation imbalance may reflect evolving microvascular kidney dysfunction in patients with injuries and warrants the evaluation of the TAT-to-fibrinogen ratio as an early marker of trauma-related AKI. This trial was registered at www.clinicaltrials.gov as NCT02535949.

BACKGROUND: Fibrinolytic phenotypes have been implicated in postinjury pathophysiology and outcomes. While prehospital tranexamic acid (TXA) administration has demonstrated survival benefits, the interaction between TXA administration and distinct fibrinolytic profiles remains poorly defined. METHODS: We analyzed data from a harmonized dataset combining 2 prospective trials evaluating prehospital TXA use in trauma (Prehospital Tranexamic Acid Use for Traumatic Brain Injury and the Study of Tranexamic Acid During Air and Ground Medical Prehospital Transport Trial). Patients were stratified by initial thromboelastographic (TEG) LY30 into fibrinolytic shutdown (3%), and physiological fibrinolysis (0.9–3%). The primary outcome was 30-day mortality. Secondary outcomes included 24-hour mortality and adverse events. Multivariable regression adjusted for TXA administration, fibrinolysis phenotypes, age, mechanism of injury, injury severity score, and shock index on presentation to the hospital. RESULTS: Among 1,249 patients, 30-day mortality was 14.5% in the fibrinolytic shutdown group, 6.7% in the hyperfibrinolysis group, and 6.5% in the physiological fibrinolysis group. After multivariable regression, hyperfibrinolysis was associated with increased risk of death (HR 2.87; 95% CI: 1.10–7.53; p 0.03). Patients with fibrinolytic shutdown who were randomized to TXA had decreased risk of death (HR 0.32; 95% CI: 0.11–0.91; p =0.03). CONCLUSIONS: This multitrial analysis revealed greater statistically significant differences between fibrinolytic phenotypes than analysis of each trial alone. Fibrinolytic phenotypes were independently associated with mortality. Fibrinolytic shutdown in patients randomized to receive TXA was associated with lower risk of death. These findings support the relevance of fibrinolysis profiling during early trauma care and underscore the need for larger studies to further elucidate the prognostic and therapeutic implications in trauma. LEVEL OF EVIDENCE: II (Subanalysis of Randomized Controlled Trials).

BACKGROUND: Postoperative venous thromboembolism (VTE) remains a major cause of surgical morbidity despite guideline-based prophylaxis. Whether VTE timing and thromboprophylaxis patterns differ across surgical subspecialties is incompletely characterized. STUDY DESIGN: Retrospective cohort study of adults with imaging-confirmed postoperative VTE during the index admission within a multihospital healthcare system (2013 to 2019). VTE events were identified using natural language processing and confirmed by chart review. The primary outcome was time to postoperative VTE; the secondary outcome was time to thromboprophylaxis. Kaplan–Meier analyses and multivariable Cox proportional hazards models evaluated associations across surgical specialties. RESULTS: Among 1,520 patients with postoperative VTE, 24.9% had deep vein thrombosis only, 67.2% pulmonary embolism only, and 7.9% both. Median time to VTE was 4 days (interquartile range 2.0 to 8.0); pulmonary embolism occurred earlier than deep vein thrombosis (3 vs 6 days; p < 0.001). Neurosurgery had the highest VTE incidence (0.23% of neurosurgical cases), whereas orthopaedic surgery demonstrated the highest adjusted hazard for postoperative VTE. Overall, 76% received postoperative thromboprophylaxis beginning a median of 1.3 days after surgery (interquartile range 0.8 to 1.7). Patients without thromboprophylaxis developed VTE earlier than those receiving prophylaxis (2.0 vs 4.0 days; p < 0.001). Cardiac surgery demonstrated the lowest adjusted likelihood of thromboprophylaxis, whereas thoracic surgery had the highest (hazard ratio 5.8, 95% CI 2.8 to 12.1; reference cardiac), and trauma patients were less likely to receive prophylaxis (hazard ratio 0.44, 95% CI 0.34 to 0.57). CONCLUSIONS: Postoperative VTE risk, timing, and thromboprophylaxis practices vary substantially across surgical subspecialties. These findings support specialty-specific VTE risk assessment, prophylaxis strategies, and postoperative surveillance.

Emergency general surgery (EGS) represents a significant portion of admissions to hospitals and overall surgical care delivery, yet comprehensive outcome tracking and quality improvement efforts have lagged behind elective surgery and trauma care. This article outlines the gap in data and provides three practical solutions to registry development: third-party registry software with dedicated registrars, leveraging existing National Surgical Quality Improvement Program (NSQIP) infrastructure through the EGS-NSQIP module, and automated data extraction from electronic medical records. Each approach offers unique advantages in addressing the dual challenges of case identification and risk-adjusted outcome measurement for both local quality improvement and national benchmarking. The aim of this white paper is to provide pragmatic, scalable data solutions for EGS leaders seeking to implement contemporary quality improvement and verification efforts.

Background: The Early Cold Stored Platelet Transfusion Following Severe Trauma Injury Trial evaluated the safety and efficacy of cold stored platelet (CSP) transfusion in injured patients at risk of hemorrhagic shock. It was a phase II, multicenter, randomized clinical trial conducted from June 2022 to September 2023 at five US level 1 trauma centers. A total of 200 adult patients at risk of hemorrhagic shock (102 CSP, 98 standard care (SC)) were included. Median age was 34±13 years, 85% were males, and injury severity was similar between groups. The original frequentist analysis did not demonstrate a statistically significant difference in 24-hour mortality between CSP (5.9%) transfusion and SC (10.2%, p=0.28). Methods: To provide further insight into these findings, a Bayesian logistic regression outcome model with an uninformative prior was performed. To validate the findings further, a sensitivity analysis was performed in addition to analysis using a beta-binomial Bayesian model. Results: The Bayesian logistic regression model yielded an 89.1% posterior probability that CSP transfusion reduced 24-hour mortality (ß ₁ =−0.668, 95% highest posterior density interval: −1.7 to 0.48). This posterior distribution indicates it is 8.1 times more likely that CSP transfusion improves 24-hour mortality than not. Sensitivity analyses across a spectrum of priors consistently produced posterior probabilities >81%. The beta-binomial model demonstrated a similar 86.2% probability that CSP transfusion reduced 24-hour mortality. Conclusion: These findings suggest a high likelihood of mortality benefit with early CSP transfusion in injured patients at risk of hemorrhagic shock and illustrate the added interpretive value of Bayesian analysis in trauma trials with low event rates. Level of evidence: Level II—therapeutic/care management.

Introduction: To support the development of the National Trauma Research Repository (NTRR), a multidisciplinary workgroup focused on prehospital trauma care used a consensus-driven approach to review established data elements and recommend basic common data elements (CDEs) for inclusion in the NTRR data dictionary. Methods: A 13-member workgroup of military and civilian trauma researchers and data scientists located and reviewed databases, codebooks, data collection forms, and published articles for data elements relevant to prehospital trauma care. Identified data elements were reviewed in a three-round Delphi survey and during monthly workgroup meetings. Consensus during the Delphi survey was determined with an 80% agreement threshold. Results: Twenty-one sources were reviewed for prehospital data elements. Following three rounds and workgroup discussions, 52 elements (84%) reached consensus for inclusion, two elements (3%) were excluded, and eight elements (13%) did not reach consensus. Discussion: The Delphi process proved effective in achieving expert consensus on basic CDEs for prehospital trauma care research. The resulting standardized basic CDEs will improve data harmonization and support consistent data collection in the NTRR. These CDEs represent an initial framework and serve as a foundational starting point for prehospital data collection within the NTRR. As researchers use the NTRR, the list of CDEs will grow and evolve to meet the needs of the trauma research community.

Blood transfusion before arrival at a hospital reduces mortality from traumatic hemorrhage and shock. Whether transfusion with whole blood is more beneficial than transfusion with blood components is uncertain, as are the effects of the length of time that blood products are in storage between donation and transfusion. In this pragmatic, multicenter, phase 3, cluster-randomized trial, we assigned 44 air medical bases in a 2:1 ratio to the use of up to 2 units of whole blood or as-indicated blood components (plasma, red cells, or both) for prehospital transfusion in trauma patients during 1-month blocks. The primary outcome was death from any cause within 30 days after randomization. An observational substudy assessed outcomes according to the storage age of whole blood. Of 1020 eligible patients transported to hospitals by the air bases, 715 were assigned to receive whole blood and 305 to receive blood components; 695 and 298, respectively, were included in the primary analysis. Mortality at 30 days was 25.9% in the whole-blood group and 20.5% in the component group (adjusted odds ratio, 1.24; 95% confidence interval [CI], 0.87 to 1.76; P = 0.24). No substantial between-group differences in adverse events were observed. In the observational substudy, 30-day mortality was 27.1% among 210 patients who received whole blood with a storage age of 15 to 21 days and 26.4% among 443 patients who received whole blood with a storage age of 1 to 14 days (adjusted odds ratio, 0.99; 95% CI, 0.74 to 1.32). In injured patients with hemorrhagic shock, the use of whole blood for prehospital transfusion did not result in lower 30-day mortality than the use of blood components. (Funded by the Congressionally Directed Medical Research Programs and the U.S. Army Medical Research Acquisition Activity; TOWAR ClinicalTrials.gov number, NCT04684719.).

Background: COVID‐19 and other respiratory viral infections can cause cardiovascular complications. SARS‐CoV‐2 virions are found in the blood, and circulating viral RNA levels are associated with death. We hypothesized that viremia can induce thrombotic endotheliopathy that contributes to death and studied this relationship in patients hospitalized for COVID‐19 and enrolled in the ACTIV‐4a (Accelerating COVID‐19 Therapeutic Interventions and Vaccines) randomized trial of antithrombotic therapy. Methods: We quantified SARS‐CoV‐2 nucleocapsid RNA and protein in plasma and measured their associations with clinical outcomes and biomarkers of thromboinflammation and endotheliopathy. We used Cox regression and Fine–Gray competing risk models to analyze survival and thrombosis. We conducted causal mediation analysis to explore whether thrombotic endotheliopathy mediates the relationship between viral RNA and death. Results: In 93 patients, SARS‐CoV‐2 RNA and N‐antigen were higher in nonsurvivors. Baseline viral RNA levels were associated with increased 90‐day death (hazard ratio [HR], 1.31 [95% CI, 1.17–1.46]) and thrombosis (HR, 1.35 [95% CI, 1.24–1.47]). Viral RNA more effectively predicted survivorship than N‐antigen levels. Soluble thrombomodulin, a biomarker of thrombotic endotheliopathy, positively correlated with viral RNA levels. Mediation analysis revealed that soluble thrombomodulin accounts for 12.2% (95% CI, 0.1%–32.3%; P =0.048) after adjustment for age and sex of the relationship between viral RNA and the 90‐day mortality rate. Conclusions: Elevated plasma SARS‐CoV‐2 RNA levels are associated with death in ACTIV‐4a, which is causally mediated in part by soluble thrombomodulin. We propose that lung–blood viral dissemination is a potential mechanism for cardiovascular complications of respiratory viruses. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT04505774.

BACKGROUND: Traumatic brain injury (TBI) patients on antiplatelet medications lack definitive treatment for reversal of platelet inhibition and restoration of injury-induced platelet dysfunction. The use of platelet transfusions in this patient population remains controversial. Cold-stored platelets (CSPs) may be hemostatically superior to their room temperature platelet (RTP) counterparts for hemostatic resuscitation, but their impact on post-transfusion platelet function has yet to be assessed clinically. We aimed to evaluate the effect of CSP or RTP on post-transfusion platelet function in TBI patients on antiplatelet medications. We hypothesized that CSP would better restore platelet function based on the extensive in vitro data suggesting hemostatic superiority. METHODS: We performed a post hoc analysis of a randomized controlled trial comparing CSP and RTP in TBI patients on antiplatelet medications. Platelet hemostatic function was determined pretransfusion and posttransfusion using VerifyNow or thromboelastography with platelet mapping (TEG-PM). Clinical outcomes included 30-day mortality, need for neurosurgical intervention, and follow-up Rotterdam scores. RESULTS: Of the 94 patients with available data, 49 received CSP and 45 received RTP. Baseline characteristics and pre-transfusion assay measurements were similar between groups. Cold-stored platelet recipients had fewer neurosurgical procedures compared with RTP recipients (4.1% vs. 20.0%, p = 0.016). Room temperature platelet recipients showed a greater increase in TEG-PM kaolin maximum amplitude after transfusion compared with CSP recipients (2.4 mm vs. 0.6 mm, p = 0.004). No other differences were observed between RTP and CSP transfusions. CONCLUSION: Despite a reduction in neurosurgical events, CSP did not significantly improve observed platelet function in TBI patients on antiplatelet medications. Our findings highlight the disconnect between platelet function assays and clinical results and suggest transfusion of CSP versus RTP has minimal effect on platelet hemostatic function. A definitive trial is needed to assess the efficacy of differentially stored products in the bleeding patient, with consideration placed on how platelet hemostatic function is assessed. LEVEL OF EVIDENCE: Prognostic/epidemiologic; Level III.