Trauma-Induced Coagulopathy: Prevalence and Association with Mortality Persist Twenty Years Later.

INTRODUCTION: A 2003 landmark study identified the prevalence of eTIC at 28% with a strong association with mortality of 8.9%. Over the last 20 years there have been significant advances in both the fundamental understanding of eTIC and therapeutic interventions. METHODS: A retrospective cohort study was performed from 2018-2022 on patients ≥18 using prospectively collected data from two level 1 trauma centers and compared to data from 2003. Demographics, laboratory data and clinical outcomes were obtained. RESULTS: There were 20,107 patients meeting criteria: 65% male, 85% blunt, mean age 54 ± 21 years, median injury severity score (ISS) 10 [10, 18]), 8% of patients were hypotensive on arrival, with an all-cause mortality 6.0%. The prevalence of eTIC remained high at 32% in patients with an abnormal PT and 10% with an abnormal PTT, for an overall combined prevalence of 33.4%. Coagulopathy had a major impact on mortality over all injury severity ranges, with the greatest impact with lower ISS. In a hybrid logistic regression/Classification and Regression Trees analysis, coagulopathy was independently associated with a 2.1-fold increased risk of mortality (95% CI 1.5-2.9); the predictive quality of the model was excellent (AUROC 0.932). CONCLUSION: The presence of eTIC conferred a higher risk of death across all disease severities and was independently associated with a greater risk of death. Biomarkers of coagulopathy associated with eTIC remain strongly predictive of poor outcome despite advances in trauma care.

Out with the old, in with the new? The revised AAST grading schema better predicts splenic salvage but not splenectomy.

BACKGROUND: The revised American Association for the Surgery of Trauma (AAST) organ injury scale (OIS) for splenic injury incorporates radiologic features but the implications of this are unknown. We hypothesized that the revised AAST-OIS would better predict outcomes. METHODS: Patients with a blunt splenic injury admitted to a Level I trauma center were reviewed from 2016 to 2021. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for splenectomy were calculated for high-grade injuries (AAST-OIS grades IV-V) using both schemas. RESULTS: Of the 852 patients analyzed, 48.5% were observed, 24.6% were embolized, and the remaining underwent operative intervention. The median AAST-OIS increased from II to III (p â€‹< â€‹0.01). Sensitivity (38.0% vs. 73.7%) and NPV (80.9% vs. 88.2%) for splenectomy increased for high-grade injuries but specificity (93.5% vs 70.1%) and PPV (67.5% vs 46.7%) decreased. CONCLUSION: The revised AAST-OIS better predicted splenic salvage but is less accurate at predicting need for splenectomy.

INHIBITORS OF INORGANIC POLYPHOSPHATE AND NUCLEIC ACIDS ATTENUATE IN VITRO THROMBIN GENERATION IN PLASMA FROM TRAUMA PATIENTS.

ABSTRACT: Background: Inorganic polyphosphate (polyP) is a procoagulant polyanion. We assessed the impact of polyP inhibition on thrombin generation after trauma using the novel polyP antagonists, macromolecular polyanion inhibitor 8 (MPI 8), and universal heparin reversal agent 8 (UHRA-8). Methods: Plasma thrombin generation (calibrated automated thrombogram, CAT), in 56 trauma patients and 39 controls +/- MPI 8 and UHRA-8 (50 µg/mL), was expressed as lag time (LT, minutes), peak height (PH, nM), and time to peak (ttPeak, minutes), with change in LT (ΔLT) and change in ttPeak (ΔttPeak) quantified. Results expressed in median and quartiles [Q1, Q3], Wilcoxon matched-pairs testing, P < 0.05 significant. Results: Trauma patients had greater baseline PH than controls (182.9 [121.0, 255.2]; 120.5 [62.1, 174.8], P < 0.001). MPI 8 treatment prolonged LT and ttPeak in trauma (7.20 [5.88, 8.75]; 6.46 [5.45, 8.93], P = 0.020; 11.28 [8.96, 13.14]; 11.00 [8.95, 12.94], P = 0.029) and controls (7.67 [6.67, 10.50]; 6.33 [5.33, 8.00], P < 0.001; 13.33 [11.67, 15.33]; 11.67 [10.33, 13.33], P < 0.001). UHRA-8 treatment prolonged LT and ttPeak and decreased PH in trauma (9.09 [7.45, 11.33]; 6.46 [5.45, 8.93]; 14.02 [11.78, 17.08]; 11.00 [8.95, 12.94]; 117.4 [74.5, 178.6]; 182.9 [121.0, 255.2]) and controls (9.83 [8.00, 12.33]; 6.33 [5.33, 8.00]; 16.67 [14.33, 20.00]; 11.67 [10.33, 13.33]; 55.3 [30.2, 95.9]; 120.5 [62.1, 174.8]), all P < 0.001. Inhibitor effects were greater for controls (greater ΔLT and ΔttPeak for both inhibitors, P < 0.001). Conclusion: PolyP inhibition attenuates thrombin generation, though to a lesser degree in trauma than in controls, suggesting that polyP contributes to accelerated thrombin generation after trauma.

Size of Splenic Subcapsular Hematoma Is Associated With Varying Outcomes of Nonoperative Management.

The presence of a splenic subcapsular hematoma (SCH) has been associated with higher rates of failure of nonoperative management (FNOM) in patients with blunt splenic injury (BSI), with rates up to 80%. We hypothesized that contemporary rates are lower. A retrospective review was conducted of patients admitted with BSI to a level I trauma center (2016-2021). Patients with SCH who had FNOM were compared to those who did not. There were 661 BSI patients, of which 102 (15.4%) had SCH. Among the SCH patients, 8 (7.8%) had FNOM. Failure of nonoperative management was higher in patients who had a SCH measuring 15 mm or greater. To the best of our knowledge, this is the largest study to date examining the relationship between SCH and FNOM. The presence of a SCH alone is not associated with a high risk for FNOM contrary to previous literature. However, SCH thickness was larger in those who failed.

A pseudo-dilemma: Are we over-diagnosing and over-treating traumatic splenic intraparenchymal pseudoaneurysms?

BACKGROUND: Splenic embolization for traumatic vascular abnormalities in stable patients is a common practice. We hypothesize that modern contrast-enhanced computed tomography (CT) over diagnoses posttraumatic splenic vascular lesions, such as intraparenchymal pseudoaneurysms (PSA) that may not require embolization. METHODS: We reviewed the experience at our high-volume center with endovascular management of blunt splenic injuries from January 2016 to December 2021. Multidisciplinary review was used to compared initial CT findings with subsequent angiography, analyzing management and outcomes of identified vascular lesions. RESULTS: Of 853 splenic injuries managed overall during the study period, 255 (29.9%) underwent angiography of the spleen at any point during hospitalization. Vascular lesions were identified on 58% of initial CTs; extravasation (12.2%) and PSA (51.0%). Angiography was performed a mean of 22 hours after admission, with 38% done within 6 hours. Embolization was performed for 90.5% (231) of patients. Among the 130 patients with PSA on initial CT, 36 (27.7%) had no visible lesion on subsequent angiogram. From the 125 individuals who did not have a PSA identified on their initial CT, 67 (54%) had a PSA seen on subsequent angiography. On postembolization CT at 48 hours to 72 hours, persistently perfused splenic PSAs were seen in 41.0% (48/117) of those with and 22.2% (2/9) without embolization. Only one of 24 (4.1%) patients with PSA on angiography observed without embolization required delayed splenectomy, whereas 6.9% (16/231) in the embolized group had splenectomy at a mean of 5.5 ± 4 days after admission. CONCLUSION: There is a high rate of discordance between CT and angiographic identification of splenic PSAs. Even when identified at angiogram and embolized, close to half will remain perfused on follow-up imaging. These findings question the use of routine angioembolization for all splenic PSAs. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

A murine multiple-injury model for the study of thromboinflammation.

INTRODUCTION: Neutrophil extracellular traps (NETs) contribute to trauma-induced coagulopathy. We aimed to develop a murine multiple-injury model that induces thrombo-inflammatory response, that is, NETosis and accelerated thrombin generation. METHODS: Wild-type male mice (n = 10, aged 8-12 weeks) underwent multiple injuries (gastrocnemius crush, femur fracture, and laparotomy) and were compared with an uninjured control group (n = 10). Mice were euthanized by cardiac puncture performed 3 hours after injury. Whole blood samples were immediately processed to platelet poor plasma for thrombin generation kinetics (calibrated automated thrombogram), myeloperoxidase (MPO), and von Willebrand factor quantification. Immunohistochemistry of lung tissue was performed to assess for citrullinated histone 3 (CitH3) and MPO. A NETosis cluster was defined as 3+ neutrophils staining for CitH3 at 400× magnification (CitH3 cluster). Data were presented either as mean (SD) or median (interquartile range) with p < 0.05 significant. Sham and trauma treated animals were compared by the two-sample Wilcoxon rank-sum test. RESULTS: Animals subjected to multiple injuries had accelerated thrombin generation compared with controls with greater peak height (61.3 [41.2-73.2] vs. 28.4 [19.5-37.5] nM, p = 0.035) and shorter time to peak (3.37 [2.81-3.81] vs. 4.5 [4.08-4.75] minutes, p = 0.046). Markers of neutrophil activation were greater following multiple injuries than in controls (MPO, 961.1 [858.1-1116.8] vs. 481.3 [438.0-648.9] ng/mL; p = 0.004). NETosis, as evidenced by the aforementioned defined number of CitH3 clusters in the lung, was greater in multiple-injury animals than in controls (mean [SD], 3 [2.9] vs. 0.2 [0.7]; p = 0.009). CONCLUSION: This is the first study to demonstrate that NETosis and accelerated thrombin generation can be induced using a murine multiple-injury model, as early as 3 hours following injury.

Early lyophilized cryoprecipitate enhances the ADAMTS13/VWF ratio to reduce systemic endotheliopathy and lessen lung injury in a mouse multiple-trauma hemorrhage model.

BACKGROUND: Recent studies in severely injured patients suggest an important role of von Willebrand Factor (VWF) and ADAMTS13 in the endotheliopathy of trauma (EoT). We hypothesized that the early use of cryoprecipitate would be effective as an endothelial protector by supplementing physiologic VWF and ADAMTS13 to reverse the EoT. We tested a pathogen-reduced lyophilized cryoprecipitate (LPRC) that could expedite the early administration of cryoprecipitate in the battlefield. METHODS: A mouse multiple-trauma model with uncontrolled hemorrhage (UCH) from liver injury was utilized followed by hypotensive resuscitation (mean arterial pressure, 55-60) × 3 hours with lactated Ringer's (LR), fresh frozen plasma (FFP), conventional pathogen-reduced cryoprecipitate (CC), and LPRC. Blood was collected for measurement of syndecan-1, VWF, and ADAMTS13 by ELISA. Lungs were stained for histopathologic injury and syndecan-1 and bronchial alveolar lavage (BAL) fluid harvested for protein as an indicator of permeability. Statistical analysis was by ANOVA followed by Bonferroni correction. RESULTS: Following multiple trauma and UCH, blood loss was similar across groups. Mean volume of resuscitation was higher in the LR group compared with the other resuscitation groups. Lung histopathologic injury, syndecan-1 immunostaining and BAL protein were higher with LR compared with resuscitation with FFP and CC, while LPRC further reduced BAL compared with FFP and CC. The ADAMTS13/VWF ratio was significantly lower in LR but improved with FFP and CC, comparable to shams while LPRC further increased this ratio. CONCLUSION: The protective effects of CC and LPRC were comparable to FFP in ameliorating the EoT in our murine multiple trauma and UCH model. Lyophilized cryoprecipitate may also provide additional benefit by enhancing the ADAMTS13/VWF ratio. These data provide evidence of the safety and efficacy of LPRC and warrants further investigation for its potential application in military settings once approved for human administration.

Contemporary management and outcomes of penetrating colon injuries: Validation of the 2020 AAST Colon Organ Injury Scale.

INTRODUCTION: The American Association for the Surgery of Trauma Colon Organ Injury Scale (OIS) was updated in 2020 to include a separate OIS for penetrating colon injuries and included imaging criteria. In this multicenter study, we describe the contemporary management and outcomes of penetrating colon injuries and hypothesize that the 2020 OIS system correlates with operative management, complications, and outcomes. METHODS: This was a retrospective study of patients presenting to 12 Level 1 trauma centers between 2016 and 2020 with penetrating colon injuries and Abbreviated Injury Scale score of <3 in other body regions. We assessed the association of the new OIS with surgical management and clinical outcomes and the association of OIS imaging criteria with operative criteria. Bivariate analysis was done with χ 2 , analysis of variance, and Kruskal-Wallis, where appropriate. Multivariable models were constructed in a stepwise selection fashion. RESULTS: We identified 573 patients with penetrating colon injuries. Patients were young and predominantly male; 79% suffered a gunshot injury, 11% had a grade V destructive injury, 19% required ≥6 U of transfusion, 24% had an Injury Severity Score of >15, and 42% had moderate-to-large contamination. Higher OIS was independently associated with a lower likelihood of primary repair, higher likelihood of resection with anastomosis and/or diversion, need for damage-control laparotomy, and higher incidence of abscess, wound infection, extra-abdominal infections, acute kidney injury, and lung injury. Damage control was independently associated with diversion and intra-abdominal and extra-abdominal infections. Preoperative imaging in 152 (27%) cases had a low correlation with operative findings ( κ coefficient, 0.13). CONCLUSION: This is the largest study to date of penetrating colon injuries and the first multicenter validation of the new OIS specific to these injuries. While imaging criteria alone lacked strong predictive value, operative American Association for the Surgery of Trauma OIS colon grade strongly predicted type of interventions and outcomes, supporting use of this grading scale for research and clinical practice. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Time to Splenic Angioembolization Does Not Impact Splenic Salvage Rates.

We aimed to determine whether early (<6 hours) vs delayed (≥6 hours) splenic angioembolization (SAE) after blunt splenic trauma (grades II-V) impacted splenic salvage rates at a level I trauma center (2016-2021). The primary outcome was delayed splenectomy by timing of SAE. Mean time of SAE was determined for those who failed vs those who had successful splenic salvage. We retrospectively identified 226 individuals, from which 76 (33.6%) were in the early group and 150 (66.4%) were in the delayed group. The early group had higher AAST grade, greater amount of hemoperitoneum on CT, and 3.9x greater odds of undergoing delayed splenectomy (P = .046). Time to embolization was shorter in the group that failed splenic salvage (5 vs 10 hours, P = .051). On multivariate analysis, timing of SAE had no effect on splenic salvage. This study supports performing SAE on an urgent rather than emergent basis in stable patients after blunt splenic injury.

A Cautionary Tale: The Use of Propensity Matching to Evaluate Hemorrhage-Related Trauma Mortality in the American College of Surgeons TQIP Database.

BACKGROUND: Propensity-matched methods are increasingly being applied to the American College of Surgeons TQIP database to evaluate hemorrhage control interventions. We used variation in systolic blood pressure (SBP) to demonstrate flaws in this approach. STUDY DESIGN: Patients were divided into groups based on initial SBP (iSBP) and SBP at 1 hour (2017 to 2019). Groups were defined as follows: iSBP 90 mmHg or less who decompensated to 60 mmHg or less (immediate decompensation [ID]), iSBP 90 mmHg or less who remained greater than 60 mmHg (stable hypotension [SH]), and iSBP greater than 90 mmHg who decompensated to 60 mmHg or less (delayed decompensation [DD]). Individuals with Head or Spine Abbreviated Injury Scale score 3 or greater were excluded. Propensity score was assigned using demographic and clinical variables. Outcomes of interest were in-hospital mortality, emergency department death, and overall length of stay. RESULTS: Propensity matching yielded 4,640 patients per group in analysis #1 (SH vs DD) and 5,250 patients per group in analysis #2 (SH vs ID). The DD and ID groups had 2-fold higher in-hospital mortality than the SH group (DD 30% vs 15%, p < 0.001; ID 41% vs 18%, p < 0.001). Emergency department death rate was 3 times higher in the DD group and 5 times higher in the ID group (p < 0.001), and length of stay was 4 days shorter in the DD group and 1 day shorter in the ID group (p < 0.001). Odds of death were 2.6 times higher for the DD vs SH group and 3.2 times higher for the ID vs SH group (p < 0.001). CONCLUSIONS: Differences in mortality rate by SBP variation underscore the difficulty of identifying individuals with a similar degree of hemorrhagic shock using the American College of Surgeons TQIP database despite propensity matching. Large databases lack the detailed data needed to rigorously evaluate hemorrhage control interventions.

Surveillance Imaging Associated With Delayed Splenectomy in High-Grade Blunt Splenic Trauma.

This retrospective, single-site study at a level I trauma center (2016-2021) sought to determine whether repeat CT had an impact on clinical decision making after splenic angioembolization following blunt splenic trauma (grades II-V). The primary outcome was need for intervention after subsequent imaging (defined as angioembolization and/or splenectomy) by high- or low-grade injury. Of the 400 individuals examined, 78 (19.5%) underwent intervention after repeat CT, from which 17% were in the low-grade group (grades II and III) and 22% were in the high-grade group (grades IV and V). Individuals in the high-grade group were 3.6 times more likely to undergo delayed splenectomy than those in the low-grade group (P = .006). Delayed intervention after surveillance imaging in blunt splenic injury is driven mostly by the identification of new vascular lesions and leads to greater rates of splenectomy in high-grade injuries. Surveillance imaging should be considered for all AAST injury grades II or higher.

Surgical Science and the Evolution of Critical Care Medicine.

Surgical science has driven innovation and inquiry across adult and pediatric disciplines that provide critical care regardless of location. Surgically originated but broadly applicable knowledge has been globally shared within the pages Critical Care Medicine over the last 50 years.

Contemporary Management and Outcomes of Injuries to the Inferior Vena Cava: A Prospective Multicenter Trial From PROspective Observational Vascular Injury Treatment.

INTRODUCTION: Injuries to the inferior vena cava (IVC), while uncommon, have a high mortality despite modern advances. The goal of this study is to describe the diagnosis and management in the largest available prospective data set of vascular injuries across anatomic levels of IVC injury. METHODS: The American Association for the Surgery of Trauma PROspective Observational Vascular Injury Treatment (PROOVIT) registry was queried from November 2013 to January 2019. Demographics, diagnostic modalities, injury patterns, and management strategies were recorded and analyzed. Comparisons between anatomic levels were made using non-parametric Wilcoxon rank-sum statistics. RESULTS: 140 patients from 19 institutions were identified; median age was 30 years old (IQR 23-41), 75% were male, and 62% had penetrating mechanism. The suprarenal IVC group was associated with blunt mechanism (53% vs 32%, P = .02), had lower admission systolic blood pressure, pH, Glasgow Coma Scale (GCS), and higher ISS and thorax and abdomen AIS than the infrarenal injury group. Injuries were managed with open repair (70%) and ligation (30% overall; infrarenal 37% vs suprarenal 13%, P = .01). Endovascular therapy was used in 2% of cases. Overall mortality was 42% (infrarenal 33% vs suprarenal 66%, P<.001). Among survivors, there was no difference in first 24-hour PRBC transfusion requirement, or hospital or ICU length of stay. CONCLUSIONS: Current PROOVIT registry data demonstrate continued use of ligation extending to the suprarenal IVC, limited adoption of endovascular management, and no dramatic increase in overall survival compared to previously published studies. Survival is likely related to IVC injury location and total injury burden.

DNASE-MEDIATED DISSOLUTION OF NEUTROPHIL EXTRACELLULAR TRAPS ACCELERATES IN VITRO THROMBIN GENERATION KINETICS IN TRAUMA PATIENTS.

ABSTRACT: Introduction: Neutrophil extracellular traps (NETs) trigger thrombin generation. We aimed to characterize the effects of deoxyribonuclease (DNAse) on NET components (cell-free DNA [cfDNA] and histones) and thrombin generation after trauma. Methods: Citrated plasma samples were collected from trauma patients and healthy volunteers. Thrombin generation (calibrated automated thrombogram) was measured as lag time (LT, in minutes), peak height (in nM), and time to peak thrombin generation (in minutes). Citrullinated histone 3 (CitH3) and 4 (CitH4) were measured by enzyme-linked immunosorbent assay; cfDNA by PicoGreen (all in nanograms per milliliter). Samples analyzed +/- DNAse (1,000 U/mL). Results expressed as median and quartiles [Q1, Q3], Wilcoxon testing, P < 0.05 significant. Results: We enrolled 46 patients (age, 48 [31, 67] years; 67% male) and 21 volunteers (age, 45 [28, 53] years; 43% male). Deoxyribonuclease treatment of trauma plasma led to shorter LT (3.11 [2.67, 3.52] min; 2.93 [2.67, 3.19] min), shorter time to peak thrombin generation (6.00 [5.30, 6.67] min; 5.48 [5.00, 6.00] min), greater peak height (273.7 [230.7, 300.5] nM; 288.7 [257.6, 319.2] nM), decreased cfDNA (576.9 [503.3, 803.1] ng/mL; 456.0 [393.5, 626.7] ng/mL), decreased CitH3 (4.54 [2.23, 10.01] ng/mL; 3.59 [1.93, 7.98] ng/mL), and increased H4 (1.30 [0.64, 6.36] ng/mL; 1.75 [0.83, 9.67] ng/mL), all P < 0.001. The effect of DNAse was greater on trauma patients as compared with volunteers for LT (ΔLT, -0.21 vs. -0.02 min, P = 0.007), cfDNA (ΔcfDNA -133.4 vs. -84.9 ng/mL, P < 0.001), and CitH3 (ΔCitH3, -0.65 vs. -0.11 ng/mL, P = 0.004). Conclusion: Deoxyribonuclease treatment accelerates thrombin generation kinetics in trauma patient samples as compared with healthy volunteers. These findings suggest that NETs may contribute to the hypercoagulable state observed in trauma patients.

Biomarkers of endothelial cell dysfunction persist beyond resuscitation in patients with hemorrhagic shock.

BACKGROUND: It has been shown that microRNA-19b (miR-19b) binds to and degrades syndecan-1 after hemorrhagic shock (HS) and contributes to endothelial dysfunction in vitro and in vivo. The objective of the current study was to assess longitudinal changes in miR-19b and syndecan-1 in HS patients. METHODS: Blood samples from HS patients (blood pressure <90 mm Hg and ≥2 U blood) were collected upon admission, completion of hemostasis, and after 24 hours for miR-19b (quantitative reverse transcription PCR) and syndecan-1 (enzyme-linked immunosorbent assay) and compared with controls and minimally injured (Injury Severity Score, ≤9). Inflammatory cytokines were measured (Luminex [Thermo Fisher, Waltham, MA]). Correlations between syndecan-1, miR-19b, inflammatory markers, and patient outcomes were performed. Logistic regression models were developed for outcomes. RESULTS: Thirty-four HS patients were studied: age, 46 (19-89) years; male, 82%; penetrating, 35%; Injury Severity Score, 24 ± 10; and blood products at 24 hours, 21 ± 19 U. MicroRNA-19b was increased upon arrival and further increased over time: 4.6 → 6.7 → 24.1-fold change compared with 0.1 and 1.2 for minimally injured patients and controls, respectively. Syndecan-1 was increased to 42.6 → 50 → 51.5 ng/mL over time compared with 14.7 and 23.5 for minimally injured and controls, respectively. Values for both biomarkers remained significantly increased through 24 hours and were associated with a persistent increase in inflammatory cytokines. Admission syndecan-1 significantly predicted mortality, coagulopathy, and massive transfusion. CONCLUSION: We have shown for the first time that miR-19b and syndecan-1 were biomarkers for endothelial dysfunction independent of resuscitation. MicroRNA-19b did not demonstrate a strong correlation with syndecan-1 nor outcomes. Admission syndecan-1, however, remains a strong prognostic marker, but its elevation over time suggests a versatile role following HS that requires further investigation. LEVEL OF EVIDENCE: Prognostic/Epidemiological; Level II.

TRAUMA-DERIVED EXTRACELLULAR VESICLES ARE SUFFICIENT TO INDUCE ENDOTHELIAL DYSFUNCTION AND COAGULOPATHY.

ABSTRACTINTRODUCTION: Although a number of studies have demonstrated increased release of extracellular vesicles (EVs) and changes in their origin differentials after trauma, the biologic significance of EVs is not well understood. We hypothesized that EVs released after trauma/hemorrhagic shock (HS) contribute to endotheliopathy and coagulopathy. To test this hypothesis, adoptive transfer experiments were performed to determine whether EVs derived from severely injured patients in shock were sufficient to induce endothelial dysfunction and coagulopathy. Methods: Total EVs were enriched from plasma of severely injured trauma/HS patients or minimally injured patients by ultracentrifugation and characterized for size and numbers. Under isoflurane anesthesia, noninjured naive C57BL/6J mice were administered EVs at varying concentrations and compared with mice receiving equal volume vehicle (phosphate-buffered saline (PBS)) or to mice receiving EVs from minimally injured patients. Thirty minutes after injection, mice were sacrificed, and blood was collected for thrombin generation (thrombin-antithrombin, thrombin-antithrombin complex [TAT] assay) and syndecan-1 by enzyme-linked immunoabsorbent assay (ELISA). Lungs were harvested for examination of histopathologic injury and costained with von Willebrand factor and fibrin to identify intravascular coagulation. Bronchial alveolar lavage fluid was aspirated from lungs for protein measurement as an indicator of the endothelial permeability. Data are presented as mean ± SD, P < 0.05 was considered significant, and t test was used. Results: An initial proof-of-concept experiment was performed in naive mice receiving EVs purified from severely injured trauma/HS patients (Injury Severity Score [ISS], 34 ± 7) at different concentrations (5 × 106 to 3.1 × 109/100 µL/mouse) and compared with PBS (control) mice. Neither TAT nor syndecan-1 levels were significantly different between groups at 30 minutes after EV infusion. However, lung vascular permeability and histopathologic injury were significantly higher in the EV group, and lung tissues demonstrated intravascular fibrin deposition. Based on these data, EVs from severely injured trauma/HS patients (ISS, 32 ± 6) or EVs from minimally injured patients (ISS, 8 ± 3) were administered to naive mice at higher concentrations (1 × 109 to 1 × 1010 EV/100 µL/mouse). Compared with mice receiving EVs from minimally injured patients, plasma TAT and syndecan-1 levels were significantly higher in the trauma/HS EV group. Similarly, bronchial alveolar lavage protein and lung histopathologic injury were higher in the trauma/HS EV group, and lung tissues demonstrated enhanced intravascular fibrin deposition. Conclusion: These data demonstrate that trauma/HS results in the systemic release of EVs, which are capable of inducing endotheliopathy as demonstrated by elevated syndecan-1 and increased permeability and coagulopathy as demonstrated by increased TAT and intravascular fibrin deposition. Targeting trauma-induced EVs may represent a novel therapeutic strategy.

Validation of the American Association for the Surgery of Trauma Organ Injury Scale for Penetrating Colon Injuries.

In 2020, the American Association for the Surgery of Trauma (AAST) published a revision of the organ injury scale (OIS) for bowel injuries. The update included for the first time a separate OIS for penetrating colon injuries as well as imaging criteria. To validate the new OIS and its correlation with outcomes, we performed a retrospective review of patients with penetrating colon injuries (AIS<3 in other body regions) between 2016 and 2020 at a single institution. Sixty-six patients met inclusion criteria. Most were young (29 years median) and male (90%). All underwent operative intervention and 23 (34%) had pre-operative imaging. Imaging grade was higher than operative grade in 11 patients (48%). Higher AAST operative grade was associated with a higher likelihood of resection and anastomosis or colostomy, need for damage control laparotomy, and development of intra-abdominal abscess and acute kidney injury. A multicenter study is underway to confirm these findings.