BACKGROUND:Despite two large randomized controlled trials (RCT) designed to assess tranexamic acid (TXA) for traumatic brain injury (TBI) patients, its use and optimal dosing strategy in TBI remains uncertain. We sought to assess functional and mortality outcomes associated with prehospital TXA administration for TBI patients using Bayesian techniques. METHODS:We performed a post hoc analysis of the prehospital TXA for TBI RCT where TBI patients received TXA as a 1-g bolus followed by a 1-g infusion (standard), 2-g bolus (bolus), or placebo. Bayesian regression models were created to assess the association of early prehospital TXA administration in TBI patients using posterior probabilities for 6-month functional outcomes, as well as 28-day and 6-month mortality. RESULTS:Patients receiving prehospital TXA (standard or bolus) displayed a 78.1% probability of having improved functional neurologic outcomes at 6 months compared with placebo. When compared with placebo, the Bolus cohort displayed a 95.3% probability of improved functional neurologic outcomes at 6 months, a 95.3% probability of decreased mortality at 28 days, and a 70.7% probability of decreased mortality at 6 months. The Standard cohort displayed a less than 50% probability of benefit compared with placebo for all outcomes measured. CONCLUSION:A prehospital 2 g TXA bolus dosing strategy demonstrated a high probability of benefit compared with both placebo and Standard cohorts for functional neurologic and mortality outcomes in patients with moderate to severe TBI. ( J Trauma Acute Care Surg . 2026;100: 879-885. © 2026 American Association for the Surgery of Trauma.). LEVEL OF EVIDENCE:Therapeutic; Level III.

BACKGROUND:Thrombotic and thromboembolic events are a common and potentially preventable complication in multitrauma patients, and substantial quality improvement efforts are directed at prevention. The results of several randomized controlled trials (RCTs) related to the association between tranexamic acid (TXA) and thrombotic/thromboembolic events have demonstrated conflicting results. We aimed to address this by examining whether prehospital TXA was associated with higher rates of thrombotic/thromboembolic events in a harmonized data set from three large multicenter RCTs. METHODS:We analyzed data using a harmonized data set from three RCTs examining the effects of prehospital TXA: The Pre-Hospital Anti-fibrinolytics for Traumatic Coagulopathy and Hemorrhage Study (PATCH trial), Study of Tranexamic Acid During Air and Ground Medical Prehospital Transport Trial (STAAMP trial) and the Prehospital TXA for TBI trial, part of the Resuscitation Outcomes Consortium (ROC trial). Outcomes included deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, stroke, combined venous thrombotic/thromboembolic events (VTE), and combined arterial thrombotic/thromboembolic events. Multivariable regression was used to adjust for TXA administration, sex, age, injury severity score, Glasgow Coma Scale, shock index, and 24-hour red cell transfusion. RESULTS:There were no differences in myocardial infarction, stroke, arterial thrombotic/thromboembolic events, DVT, PE, or VTE in patients who were randomized to TXA compared with those who were not. On univariate analysis, rates of PE, DVT and VTE were significantly higher in the PATCH cohort compared with STAAMP and ROC cohorts, but patients in PATCH had significantly higher injury severity scores and chest trauma when compared with those in ROC and STAAMP. CONCLUSION:This multicenter database combining three large RCTs showed that randomization to TXA was not associated with higher rates of arterial and VTE. The higher rates of thrombotic/thromboembolic events observed in the PATCH trial may be explained by higher injury severity as well as protocolized screening. ( J Trauma Acute Care Surg. 2026;101: 48-56. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). LEVEL OF EVIDENCE:Sub-analysis of randomized controlled trials; Level II.

BACKGROUND AND PURPOSE:Tranexamic acid (TXA) may reduce the progression of vasogenic edema in traumatic brain injury (TBI), potentially providing a survival benefit in specific patients. This study evaluates a CT-based quantitative imaging tool for identifying patients with acute TBI who may benefit from prehospital TXA. MATERIALS AND METHODS:This is a post hoc analysis of the Prehospital Tranexamic Acid Use for Traumatic Brain Injury trial, a multicenter, placebo-controlled trial that randomized patients with moderate or severe TBI to either a 1-g TXA bolus followed by 1-g infusion, a 2-g TXA bolus, or a placebo. CT images were analyzed using a novel Matlab-based algorithm to calculate the percentage of voxels within various density ranges. The region of interest was defined as the entire brain parenchyma after skull removal. The 10-20 HU range, identified as most representative of vasogenic edema based on correlation with mean ADC values in a subset of 102 patients, was used for further analysis. Logistic regression was performed to evaluate the relationship between voxel percentages in the 10-20 HU range and in-hospital mortality. Threshold analysis identified the minimum voxel percentage within the 10-20 HU range associated with significant TXA survival benefit. Relative risk reduction in mortality was calculated for patients above and below this threshold. RESULTS:In a cohort of 550 patients, logistic regression showed that the association between TXA use and in-hospital survival varied with the percentage of brain voxels in the 10-20 HU range (interaction P = .04). Threshold analysis identified a cutoff of 3% of brain parenchymal voxels in the 10-20 HU range, corresponding to approximately 40 mL of vasogenic edema, beyond which TXA administration was associated with a significant survival benefit (P = .04). In this subgroup, TXA was associated with a relative risk of mortality of 0.41 (95% CI, 0.17-0.99) compared with a placebo. CONCLUSIONS:A voxel percentage of ≥3% within the 10-20 HU CT density range serves as a promising imaging biomarker associated with a survival benefit from TXA in patients with acute TBI in the prehospital setting. Prospective validation is required to confirm these findings before integrating this biomarker into clinical decision-making for personalized TBI management.

BACKGROUND:Injured older adults account for nearly 25% of trauma admissions nationwide with increased morbidity and mortality compared with younger adults. Endothelial dysfunction has been associated with poor outcomes in trauma patients. We hypothesized that posttraumatic endothelial changes in older versus younger adult trauma patients will be different with worse outcomes in older adults. METHODS:This is a retrospective secondary analysis of the "Tranexamic Acid (TXA) in Traumatic Brain Injury" prehospital database (2015-2017). We studied patients with admission endothelial biomarkers: intercellular adhesion molecule 1, angiotensin 1, thrombomodulin, vascular cell adhesion molecule 1 (VCAM 1), angiotensin 2, syndecan-1, and thrombospondin. We divided patients into age quartiles and compared the oldest quartile (older age [OA] group) with the three youngest quartiles (younger age [YA] group). In-hospital, discharge, and mortality outcomes were compared. Significance was set at p < 0.05. RESULTS:A total of 436 patients were included. The mean age in OA group was 66 years (55-88 years, n = 108). The YA mean age was 30 years (15-54 years, n = 328). There was no difference between OA and YA in rates of blunt trauma (98.1% vs. 96.3%, p = 0.61), head abbreviated injury scale (mean, 2.83 vs. 2.93; p = 0.582), or Injury Severity Score (mean, 21 vs. 19; p = 0.29). Tranexamic acid dosing was not different between cohorts ( p = 0.571). Overall, the OA group had higher thrombomodulin (median, 693.3 vs. 592.9 pg/mL; p = 0.0008), VCAM 1 (median, 70,852 vs. 59,738 pg/mL; p = 0.0015), and angiotensin 2 (median, 165.3 vs. 134.2 pg/mL; p = 0.005). When comparing endothelial biomarkers of OA to each YA age quartile subsets, in the 2g TXA group OA patients had significantly higher syndecan-1 levels from a subset of YA (37 to 54-year-olds, p = 0.034). In the 2g TXA group OA patients had significantly lower plasma thrombomodulin, angiotensin 2, and VCAM 1 ( p = 0.00001, p = 0.0032, and p = 0.0002, respectively) than patients in the placebo group. None of the biomarkers were independent predictors of 28-day mortality. CONCLUSION:Despite similar injury patterns, OA presented with higher admission endothelial plasma biomarkers. The OA patients receiving 2 g of TXA had significantly different endothelial biomarker levels versus YA group. These differences suggest that OA patients have a different baseline endothelial function prior to injury and that TXA may have a more pronounced effect on injured OA versus YA endothelium. LEVEL OF EVIDENCE:Therapeutic Care Management; Level IV.

BACKGROUND:Although a prehospital 2 g bolus of tranexamic acid (TXA) has been associated with decreased mortality in patients with traumatic intracranial hemorrhage (ICH), the underlying mechanism remains controversial. We investigated whether early coagulation biomarkers are associated with ICH type, prehospital TXA treatment, and outcomes in patients with early traumatic brain injury (TBI). METHODS:We conducted a secondary analysis of the Prehospital TXA for TBI trial (Glasgow Coma Scale score of <13 and systolic blood pressure of ≥90 mm Hg in patients blindly randomized prehospital to either a 2 g TXA bolus, 1 g TXA bolus plus 1 g TXA infusion, or placebo bolus plus infusion). Intracranial hemorrhage types were categorized as extradural, subdural, subarachnoid, intraventricular, intraparenchymal, mixed, any ICH, and no ICH. Outcomes including Glasgow Outcome Score-Extended, Disability Rating Score, and mortality were examined at discharge and 6 months. Associations between biomarkers, ICH type, TXA treatment group, and outcomes were examined. RESULTS:Of 783 patients, 464 had ICH (5 extradural, 40 subdural, 84 subarachnoid, 7 intraventricular, 26 intraparenchymal, 302 mixed, 464 any ICH), and 319 had no ICH. Three markers of fibrinolytic activity (D-dimer, plasmin-α2-antiplasmin complex [PAP], and thrombin-antithrombin complex [TAT]) were significantly increased in the presence of any ICH and mixed ICH. Higher D-dimer, PAP, and TAT levels were associated with increased mortality, and worse Glasgow Outcome Score-Extended and Disability Rating Score at discharge and 6 months. Plasmin-α2-antiplasmin complex was associated with TXA treatment, with lower PAP levels associated with the higher initial TXA bolus dose. CONCLUSION:In patients with early TBI, D-dimer, PAP, and TAT are associated with the presence of any ICH and mixed ICH. Higher D-dimer, PAP, and TAT levels are associated with neurologic outcomes. Only PAP is associated with TXA treatment. Future studies should examine the utility of PAP as a potential marker for TXA responsiveness. LEVEL OF EVIDENCE:Therapeutic/Care Management; Level III.

To introduce the UChicago PBI Imaging score, a novel characterization of imaging features using head computed tomography (HCT) in patients with gunshot wounds to the head (GSWH) resulting in penetrating brain injury (PBI) and to quantify the association with mortality. We retrospectively collected and analyzed data from 230 patients with GSWH admitted to our Level 1 trauma center between May 1, 2018, and October 31, 2023. HCT images obtained on hospital arrival were evaluated for predefined imaging features by two blinded readers and arbitrated, when needed, by a third. The average contribution of each radiological feature to mortality at hospital discharge was assessed using a SuperLearner ensemble model trained on ∼77% of the cohort. Each feature's contribution was scaled to ensure the additive final score per patient ranged between 0 and 100. The HCT features predicting in-hospital mortality, ranked from highest to lowest importance, were transhemispheric projectile below the level of the third ventricle (18 [16.8, 19.9]), presence of blood in the lateral ventricles (ventricles casted) (18[16.8, 19.6]), brainstem involvement (14 [12.7, 15.1]), transhemispheric projectile above the level of the third ventricle (11 [9.7, 11.6]), presence of any amount of blood in the ambient cistern (9[8.2, 10]), presence of any amount of blood in the lateral ventricles (9 [7.9, 9.8]), cerebellar involvement (9 [7.9, 9.5]), any evidence of ventricular effacement (4 [3.4, 4.6]), midline shift (MLS) >0 mm (4 [3.4, 4.4]), perforating injury (3 [2.4, 3.2]), and presence of an intracerebral hematoma (ICH) >20 mm in the largest diameter (2 [1.4, 1.9]). The UChicago PBI Imaging score showed a strong performance, achieving an area under the curve (AUC) of 0.86 (95% CI: [0.77, 0.96]) on a test set of 56 patients who were not included in model training. This indicates better prediction accuracy compared to both the Rotterdam score (AUC 0.8, 95% CI: [0.68, 0.96]) and the Marshall score (AUC 0.66, 95% CI: [0.52, 0.81]). Our model performed particularly well for patients with a Glasgow Coma Scale (GCS) score between 5 and 9. In this range, our model's performance (AUC 0.86) remained stable, while the Rotterdam and Marshall Scores showed notably lower predictive accuracy, with AUCs of 0.61 and 0.52, respectively. A dedicated evaluation of GSWH HCT reveals an association between disease burden, as quantified by unique features not native to blunt TBI imaging models, and mortality. Specifically, transhemispheric injury below the level of the third ventricle along with blood-casting bilateral ventricles and brainstem involvement was highly associated with mortality. The model is optimized for intermediate GCS scores where greater prognostic uncertainty exists. This study parallels efforts to refine TBI classification, underscoring the necessity for precise imaging-based classification in PBI to identify imaging biomarkers and ultimately enhance prognostication and targeted treatment.

BACKGROUND Traumatic brain injury (TBI) contributes to substantial morbidity and mortality worldwide. Tranexamic acid (TXA) has been shown to reduce mortality in patients with traumatic intracranial hemorrhage (ICH) when given within 2 hours of injury. Although TXA is an antifibrinolytic, most studies have observed no difference in ICH progression; recent studies suggest that TXA may reduce cerebral edema in TBI. Our objective was to determine if prehospital TXA administered within 2 hours of injury is associated with surrogates of cerebral edema in patients with moderate or severe TBI. METHODS We performed a retrospective analysis of a multinational prehospital trial of TXA administered within 2 hours of injury in patients with moderate or severe TBI. Patients with prehospital Glasgow Coma Scale score of <13 and systolic blood pressure of >90 mm Hg were randomized to placebo, 2-g TXA bolus, or 1-g TXA bolus followed by 1 g 8-hour TXA infusion. Patients who received an intracranial pressure (ICP) monitor were selected for analysis. Baseline demographic, injury severity, and infusion characteristics were compared between TXA dosing cohorts. Proportion of hours spent with ICP of >20 mm Hg, cerebral perfusion pressure (CPP) of <60 mm Hg, and need for craniectomy were compared between groups. RESULTS A total of 108 patients with ICP monitors made up the study population (placebo, n = 31; 1 g + 1 g, n = 38; 2-g bolus, n = 39). No differences were identified in age, sex, Abbreviated Injury Scale head, Glasgow Coma Scale, Injury Severity Score, crystalloid and blood product infused in first 24 hours, Marshall score, ICH, or mortality between the three treatment arms. No differences in proportions of hours in which ICP of >20 mm Hg or CPP of <60 mm Hg were identified between treatment arms; rate of craniectomy was also similar. CONCLUSION No association could be identified between TXA treatment and ICP elevation, CPP depression, or need for craniectomy. These results question TXA's potential impact on cerebral edema. Further study is needed to confirm this finding based on the exploratory nature and limited number of subjects in this study. LEVEL OF EVIDENCE Therapeutic/Care Management; Level IV.

INTRODUCTION:Tranexamic acid (TXA) is an antifibrinolytic drug that has been demonstrated to reduce head injury-related mortality when given within 2 h of injury in patients with traumatic brain injury and intracranial hemorrhage. It is usually administered via intravenous (IV) access, which can be difficult to obtain in prehospital and austere settings. Intraosseous (IO) access is fast and offers an alternative when IV access proves challenging; however, TXA administration via IO access has never been studied in humans. We sought to determine if the total drug exposure of TXA given in the prehospital setting in patients with moderate or severe brain injury differs based on route of administration. METHODS:We performed a retrospective analysis of prospectively collected data from the prehospital TXA for traumatic brain injury trial (NCT01990768). Participants who received TXA via IO administration were compared to those who received TXA via IV administration and stratified by renal function category based on the Kidney Disease Improving Global Outcomes criteria. The area under the plasma drug concentration-time curve (AUC) was calculated using the trapezoidal rule (Phoenix WinNonlin 8.3, Certara, Princeton NJ) to obtain total drug exposure. The inverse variance method was used to combine observations within strata and calculate mean differences. RESULTS:Of the 966 participants enrolled in the trial, 345 participants received a 2-g TXA prehospital bolus (11 IO, 334 IV); 312 participants received a 1-g TXA prehospital bolus followed by a 1-g TXA infusion in-hospital over 8 h (13 IO, 299 IV). After exclusion because of missing data and extreme estimated AUC, 233 IV and eight IO participants in the 2-g bolus arm and 152 IV and eight IO participants in the 1-g bolus 1-g infusion arm remained. Participants did not differ by age, sex, race, ethnicity, body mass index, serum creatinine, estimated glomerular filtration rate, or clot lysis at 30 min on thromboelastography. No difference in the mean AUCs were observed between IV and IO for either the 2-g bolus group (-2.6 μ g/mL/h [IO] compared to IV, 95% confidence interval: -28.4 to 23.3 μ g/mL/h) or the 1-g bolus/1-g infusion group (-13.0 μ g/mL/h [IO] compared to IV, 95% confidence interval: -236.2 to 210.3 μ g/mL/h). CONCLUSIONS:These preliminary data suggest that the administration of TXA via IO and IV routes may result in similar total drug exposure. Further studies incorporating larger numbers with clinical outcomes are needed to confirm this finding.

INTRODUCTION:Recent randomized clinical trials have demonstrated that prehospital tranexamic acid (TXA) administration following injury is safe and improves survival. However, the effect of prehospital TXA on adverse events, transfusion requirements, and any dose-response relationships require further elucidation. METHODS:A secondary analysis was performed using harmonized data from two large, double-blinded, randomized prehospital TXA trials. Outcomes, including 28-day mortality, pertinent adverse events, and 24-hour red cell transfusion requirements, were compared between TXA and placebo groups. Regression analyses were used to determine the independent associations of TXA after adjusting for study enrollment, injury characteristics, and shock severity across a broad spectrum of injured patients. Dose-response relationships were similarly characterized based upon grams of prehospital TXA administered. RESULTS:A total of 1,744 patients had data available for secondary analysis and were included in the current harmonized secondary analysis. The study cohort had an overall mortality of 11.2% and a median Injury Severity Score of 16 (interquartile range, 5-26). Tranexamic acid was independently associated with a lower risk of 28-day mortality (hazard ratio, 0.72; 95% confidence interval [CI], 0.54-0.96; p = 0.03). Prehospital TXA also demonstrated an independent 22% lower risk of mortality for every gram of prehospital TXA administered (hazard ratio, 0.78; 95% CI, 0.63-0.96; p = 0.02). Multivariable linear regression verified that patients who received TXA were independently associated with lower 24-hour red cell transfusion requirements ( β= - 0.31; 95% CI, -0.61 to -0.01; p = 0.04) with a dose-response relationship ( β= - 0.24; 95% CI, -0.45 to -0.02; p = 0.03). There was no independent association of prehospital TXA administration on thromboembolism, seizure, or stroke. CONCLUSION:In this secondary analysis of harmonized data from two large randomized interventional trials, prehospital TXA administration across a broad spectrum of injured patients is safe. Prehospital TXA is associated with a significant 28-day survival benefit and lower red cell transfusion requirements at 24 hours and demonstrates a dose-response relationship. LEVEL OF EVIDENCE:Therapeutic/Care Management; Level III.

The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) model is a widely recognized prognostic model applied after traumatic brain injury (TBI). However, it was developed with patient cohorts that may not reflect modern practice patterns in North America. We analyzed data from two sources: the placebo arm of the phase II double-blinded, multicenter, randomized controlled trial Prehospital Tranexamic Acid for TBI (TXA) cohort and an observational cohort with similar inclusion/exclusion criteria (Predictors of Low-risk Phenotypes after Traumatic Brain Injury Incorporating Proteomic Biomarker Signatures [PROTIPS] cohort). All three versions of the IMPACT model-core, extended, and laboratory-were evaluated for 6-month mortality (Glasgow Outcome Scale Extended [GOSE] = 1) and unfavorable outcomes (GOSE = 1-4). Calibration (intercept and slope) and discrimination (area under the receiver operating characteristic curve [ROC-AUC]) were used to assess model performance. We then compared three model updating methods-recalibration in the large, logistic recalibration, and coefficient update-with the best update method determined by likelihood ratio tests. In our calibration analysis, recalibration improved both intercepts and slopes, indicating more accurate predicted probabilities when recalibration was done. Discriminative performance of the IMPACT models, measured by AUC, showed mortality prediction ROCs between 0.61 and 0.82 for the TXA cohort, with the coefficient updated Lab model achieving the highest at 0.84. Unfavorable outcomes had lower AUCs, ranging from 0.60 to 0.79. Similarly, in the PROTIPS cohort, AUCs for mortality ranged from 0.75 to 0.82, with the coefficient updated Lab model also showing superior performance (AUC 0.84). Unfavorable outcomes in this cohort presented AUCs from 0.67 to 0.73, consistently lower than mortality predictions. The closed testing procedure using likelihood ratio tests consistently identified the coefficient update model as superior, outperforming the original and recalibrated models across all cohorts. In our comprehensive evaluation of the IMPACT model, the coefficient updated models were the best performing across all cohorts through a structured closed testing procedure. Thus, standardization of model updating procedures is needed to reproducibly determine the best performing versions of IMPACT that reflect the specific characteristics of a dataset.

BACKGROUND Brain specific biomarkers such as glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), and microtubule-associated protein-2 (MAP-2) have been identified as tools for diagnosis in traumatic brain injury (TBI). Tranexamic acid (TXA) has been shown to decrease mortality in patients with intracranial hemorrhage (ICH). The effect of TXA on these biomarkers is unknown. We investigated whether TXA affects levels of GFAP, UCH-L1, and MAP-2, and whether biomarker levels are associated with mortality in patients receiving TXA.METHODS Patients enrolled in the prehospital TXA for TBI trial had GFAP, UCHL-1 and MAP-2 levels drawn at 0 hour and 24 hours postinjury (n = 422). Patients with ICH from blunt trauma with a GCS <13 and SBP >90 were randomized to placebo, 2 g TXA bolus, or 1 g bolus +1 g/8 hours TXA infusion. Associations of TXA and 24-hour biomarker change were assessed with multivariate linear regression. Association of biomarkers with 28-day mortality was assessed with multivariate logistic regression. All models were controlled for age, GCS, ISS, and AIS head.RESULTS Administration of TXA was not associated with a change in biomarkers over 24 hours postinjury. Changes in biomarker levels were associated with AIS head and age. On admission, higher GFAP (odds ratio [OR], 1.75; confidence interval [CI], 1.31-2.38; p < 0.001) was associated with increased 28-day mortality. At 24 hours postinjury, higher levels of GFAP (OR, 2.09; CI, 1.37-3.30; p < 0.001 and UCHL-1 (OR, 2.98; CI, 1.77-5.25; p < 0.001) were associated with mortality. A change in UCH levels from 0 hour to 24 hours postinjury was also associated with increased mortality (OR, 1.68; CI, 1.15-2.49; p < 0.01).CONCLUSION Administration of TXA does not impact change in GFAP, UCHL-1, or MAP-2 during the first 24 hours after blunt TBI with ICH. Higher levels of GFAP and UCH early after injury may help identify patients at high risk for 28-day mortality.LEVEL OF EVIDENCE Therapeutic/Care Management; Level III.

Introduction Tranexamic acid (TXA) administered within 2 h of injury reduces mortality in traumatic brain injury (TBI) with intracranial hemorrhage. TXA also reduces the seizure threshold in a dose-dependent manner. We examined whether a 2-g bolus of prehospital TXA administered in moderate or severe TBI is associated with seizure activity within 72 h of injury. Methods Patients from the prehospital TXA for TBI trial with Glasgow Coma Scale < 13, blunt head injury, and time-of-seizure data were included in this analysis. The original trial randomized patients with suspected TBI to placebo, 1-g TXA bolus + 1-g 8-h TXA infusion, or 2-g TXA bolus within 2 h of injury. In this secondary analysis, multivariable logistic regression was performed to examine the association of treatment group with seizure incidence. The model controlled for age, Glasgow Coma Scale, Injury Severity Score, intracranial hemorrhage, Abbreviated Injury Scale-head, and home antiseizure medication use. Results Of the 786 patients who met the inclusion criteria, 19 had seizures within 72 h (five in placebo, two in 1-g bolus/1-g infusion, and 12 in 2-g bolus). The 2-g TXA bolus was not associated with increased seizures compared to placebo (odds ratio 0.41, 95% confidence interval 0.12-1.18, P = 0.12). Home antiseizure medication use was associated with increased seizures (odds ratio 15.95, 95% confidence interval 3.79-60.57, P < 0.001). Conclusions A prehospital 2-g TXA bolus in moderate or severe TBI was not associated with increased seizure activity during the first 72 h after injury; however, limited power, limited use of continuous electroencephalography, and unavailable seizure prophylaxis data highlight the need for further study.

ImportanceData on the performance of traumatic brain injury (TBI) biomarkers within minutes of injury are lacking.ObjectivesTo examine the performance of glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and microtubule-associated protein 2 (MAP-2) within 30 and 60 minutes of TBI in identifying intracranial lesions on computed tomography (CT) scan, need for neurosurgical intervention (NSI), and clinically important early outcomes (CIEO).Design, Setting, and ParticipantsThis cohort study is a biomarker analysis of a multicenter prehospital TBI cohort from the Prehospital Tranexamic Acid Use for TBI clinical trial conducted across 20 centers and 39 emergency medical systems in North America from May 2015 to March 2017. Prehospital hemodynamically stable adult patients with traumatic injury and suspected moderate to severe TBI were included. Blood samples were measured for GFAP, UCH-L1, and MAP-2. Data were analyzed from December 1, 2023, to March 15, 2024.Main Outcomes and MeasuresThe presence of CT lesions, diffuse injury severity on CT, NSI within 24 hours of injury, and CIEO (composite outcome including early death, neurosurgery, or prolonged mechanical ventilation ≥7 days) within 7 days of injury.ResultsOf 966 patients enrolled, 804 patients (mean [SD] age, 41 [19] years; 418 [74.2%] male) had blood samples, including 563 within 60 minutes and 375 within 30 minutes of injury. Among patients with blood drawn within 30 minutes of injury, 212 patients (56.5%) had CT lesions, 61 patients (16.3%) had NSI, and 112 patients (30.0%) had CIEO. Among those with blood drawn within 60 minutes, 316 patients (56.1%) had CT lesions, 95 patients (16.9%) had NSI, and 172 patients (30.6%) had CIEO. All biomarkers showed significant elevations with worsening diffuse injury on CT within 30 and 60 minutes of injury. Among blood samples taken within 30 minutes, GFAP had the highest area under the receiver operating characteristic curve (AUC) to detect CT lesions, at 0.88 (95% CI, 0.85-0.92), followed by MAP-2 (AUC, 0.78; 95% CI, 0.73-0.83) and UCH-L1 (AUC, 0.75; 95% CI, 0.70-0.80). Among blood samples taken within 60 minutes, AUCs for CT lesions were 0.89 (95% CI, 0.86-0.92) for GFAP, 0.76 (95% CI, 0.72-0.80) for MAP-2, and 0.73 (95% CI, 0.69-0.77) for UCH-L1. Among blood samples taken within 30 minutes, AUCs for NSI were 0.78 (95% CI, 0.72-0.84) for GFAP, 0.75 (95% CI, 0.68-0.81) for MAP-2, and 0.69 (95% CI, 0.63-0.75) for UCH-L1; and for CIEO, AUCs were 0.89 (95% CI, 0.85-0.93) for GFAP, 0.83 (95% CI, 0.78-0.87) for MAP-2, and 0.77 (95% CI, 0.72-0.82) for UCH-L1. Combining the biomarkers was no better than GFAP alone for all outcomes. At GFAP of 30 pg/mL within 30 minutes, sensitivity for CT lesions was 98.1% (95% CI, 94.9%-99.4%) and specificity was 34.4% (95% CI, 27.2%-42.2%). GFAP levels greater than 6200 pg/mL were associated with high risk of NSI and CIEO.Conclusions and RelevanceIn this cohort study of prehospital patients with TBI, GFAP, UCH-L1, and MAP-2 measured within 30 and 60 minutes of injury were significantly associated with traumatic intracranial lesions and diffuse injury severity on CT scan, 24-hour NSI, and 7-day CIEO. GFAP was the strongest independent marker associated with all outcomes. This study sets a precedent for the early utility of GFAP in the first 30 minutes from injury in future clinical and research endeavors.

BACKGROUND:In the prehospital tranexamic acid (TXA) for traumatic brain injury (TBI) trial, TXA administered within 2 hours of injury in the out-of-hospital setting did not reduce mortality in all patients with moderate/severe traumatic brain injury (TBI). We examined the association between TXA dosing arms, neurologic outcome, and mortality in patients with intracranial hemorrhage (ICH) on computed tomography (CT). METHODS:This was a secondary analysis of the Prehospital Tranexamic Acid for TBI Trial ( ClinicalTrials.gov [NCT01990768]) that randomized adults with moderate/severe TBI (Glasgow Coma Scale score < 13) and systolic blood pressure ≥ 90 mm Hg within 2 hours of injury to a 2-g out-of-hospital TXA bolus followed by an in-hospital saline infusion, a 1-g out-of-hospital TXA bolus/1-g in-hospital TXA infusion, or an out-of-hospital saline bolus/in-hospital saline infusion (placebo). This analysis included the subgroup with ICH on initial CT. Primary outcomes included 28-day mortality, 6-month Glasgow Outcome Scale-Extended (GOSE) ≤ 4, and 6-month Disability Rating Scale (DRS). Outcomes were modeled using linear regression with robust standard errors. RESULTS:The primary trial included 966 patients. Among 541 participants with ICH, 28-day mortality was lower in the 2-g TXA bolus group (17%) compared with the other two groups (1-g bolus/1-g infusion 26%, placebo 27%). The estimated adjusted difference between the 2-g bolus and placebo groups was -8·5 percentage points (95% confidence interval [CI], -15.9 to -1.0) and between the 2-g bolus and 1-g bolus/1-g infusion groups was -10.2 percentage points (95% CI, -17.6 to -2.9). Disability Rating Scale at 6 months was lower in the 2-g TXA bolus group than the 1-g bolus/1-g infusion (estimated difference - 2.1 [95% CI, -4.2 to -0.02]) and placebo groups (-2.2 [95% CI, -4.3, -0.2]). Six-month GOSE did not differ among groups. CONCLUSION:A 2-g out-of-hospital TXA bolus in patients with moderate/severe TBI and ICH resulted in lower 28-day mortality and lower 6-month DRS than placebo and standard TXA dosing. LEVEL OF EVIDENCE:Therapeutic/Care Management; Level II.

Progression of intracranial hemorrhage is a common, potentially devastating complication after moderate/severe traumatic brain injury (TBI). Clinicians have few tools to predict which patients with traumatic intracranial hemorrhage on their initial head computed tomography (hCT) scan will progress. The objective of this investigation was to identify clinical, imaging, and/or protein biomarkers associated with progression of intracranial hemorrhage (PICH) after moderate/severe TBI and to create an accurate predictive model of PICH based on clinical features available at presentation. We analyzed a subset of subjects from the phase II double-blind, multi-center, randomized "Prehospital Tranexamic Acid Use for TBI" trial. This subset was limited to the placebo arm of the parent trial with evidence of hemorrhage on the initial hCT and a follow-up hCT 6 h after. PICH was defined as an increase in hemorrhage size by 30% or more, or the development of new hemorrhage in the intra- and extra-axial intracranial vault between the initial and the follow-up hCT. Two independent radiologists evaluated each hCT, and conflicts were adjudicated by a third. Clinical and radiographic characteristics were collected, along with plasma protein biomarkers at admission. Principal component analysis (PCA) was performed, and each principal component (PC) was interrogated for its association with PICH. Finally, expert opinion and recursive feature extraction (RFE) were used to select input features for the construction of several supervised classification models. Their ability to predict PICH was quantified and compared. In this subset of subjects (n = 104), 46% (n = 48) demonstrated PICH. Univariate analyses showed no association between PICH and age, sex, admission Glasgow Coma Scale (GCS), GCS motor subscore, presence of midline shift, admission platelet count or admission INR. Radiographic severity scores (Marshall score [p = 0.007], Rotterdam score [p = 0.004]), and initial hematoma volume [p = 0.005] were associated with PICH. Higher levels of admission glial fibrillary acidic protein (p < 0.001) and MAP (p = 0.011) were also associated with PICH. Of the PCs, PC1 was significantly associated with PICH (p = 0.0125). Using multimodal data input, machine learning classifiers successfully discriminated patients with or without PICH. Models composed of machine-selected features performed better than models composed of expert-selected variables (reaching an average of 77% accuracy, AUC = 0.78 versus AUC = 0.68 for the expert-selected variables). Predictive models utilizing variables measured at admission can accurately predict PICH, confirmed by the 6-hour follow-up hCT. Our best-performing models must now be externally validated in a separate cohort of TBI patients with low GCS and initial hCT positive for hemorrhage.

BACKGROUND: Despite representing 4% of the global population, the US has the fifth highest number of intentional homicides in the world. Peripartum people represent a unique and vulnerable subset of homicide victims. This study aimed to understand the risk factors for peripartum homicide. STUDY DESIGN: We used data from the 2018 to 2020 National Violent Death Reporting System to compare homicide rates of peripartum and nonperipartum people capable of becoming pregnant (12 to 50 years of age). Peripartum was defined as currently pregnant or within 1-year postpartum. We additionally compared state-level peripartum homicide rates between states categorized as restrictive, neutral, or protective of abortion. Pearson's chi-square and Wilcoxon rank-sum tests were used. RESULTS: There were 496 peripartum compared with 8,644 nonperipartum homicide victims. The peripartum group was younger (27.4 +/- 71 vs 33.0 +/- 9.6, p < 0.001). Intimate partner violence causing the homicide was more common in the peripartum group (39.9% vs 26.4%, p < 0.001). Firearms were used in 63.4% of homicides among the peripartum group compared with 49.5% in the comparison (p < 0.001). A significant difference was observed in peripartum homicide between states based on policies regarding abortion access (protective 0.37, neutral 0.45, restrictive 0.64; p < 0.01); the same trend was not seen with male homicides. CONCLUSIONS: Compared with nonperipartum peers, peripartum people are at increased risk for homicide due to intimate partner violence, specifically due to firearm violence. Increasing rates of peripartum homicide occur in states with policies that are restrictive to abortion access. There is a dire need for universal screening and interventions for peripartum patients. Research and policies to reduce violence against pregnant people must also consider the important role that abortion access plays in protecting safety. (c) 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.