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High output, persistent ascites (PA) is a common complication following liver transplant (LT). Recent work has identified that platelets help maintain endothelial integrity and can decrease leakage in pathological states. We sought to assess the association of PA following LT with platelet count and platelet function.Clot strength (MA) is a measure of platelet function and was quantified using thrombelastography (TEG). Total drain output following surgery was recorded in 24-h intervals during the same time frame as TEG. PA was considered1 L on POD7, as that much output prohibits drain removal.105 LT recipients with moderate or high volume preoperative ascites were prospectively enrolled. PA occurred in 28%. Platelet transfusions before and after surgery were associated with PA, in addition to POD5 TEG MA and POD5 MELD score. Patients with PA had a longer hospital length of stay and an increased rate of intraabdominal infections.Persistent ascites following liver transplant is relatively common and associated with platelet transfusions, low clot strength, and graft dysfunction.

Severe injury can provoke systemic processes that lead to organ dysfunction, and hemolysis of both native and transfused red blood cells (RBC's) may contribute. Hemolysis can release erythrocyte proteins, such as hemoglobin and arginase-1, the latter with the potential to disrupt arginine metabolism and limit physiologic nitric oxide (NO) production. We aimed to quantify hemolysis and arginine metabolism in trauma patients and measure association with injury severity, transfusions, and outcomes.Blood was collected from injured patients at a Level I Trauma Center enrolled in the COMBAT trial. Proteomics and metabolomics were performed on plasma fractions through liquid chromatography coupled with mass spectrometry. Abundances of erythrocyte proteins comprising a hemolytic profile as well as haptoglobin, L-arginine, ornithine, and L-citrulline (NO surrogate marker) were analyzed at different timepoints and correlated with transfusions and adverse outcomes.More critically injured patients, non-survivors, and those with longer ventilator requirement had higher levels of hemolysis markers with reduced L-arginine and L-citrulline. In logistic regression, elevated hemolysis markers, reduced L-arginine, and reduced L-citrulline were significantly associated with these adverse outcomes. An increased number of blood transfusions was significantly associated with elevated hemolysis markers and reduced L-arginine and L-citrulline independently of new injury severity score and arterial base excess.Severe injury induces intravascular hemolysis, which may mediate post-injury organ dysfunction. In addition to native RBC's, transfused RBC's can lyse and may exacerbate trauma-induced hemolysis. Arginase-1 released from RBC's may contribute to the depletion of L-arginine and the subsequent reduction in the NO necessary to maintain organ perfusion.

Introduction: Severely injured patients develop a dysregulated inflammatory state characterized by vascular endothelial permeability, which contributes to multiple organ failure. To date, however, the mediators of and mechanisms for this permeability are not well established. Endothelial permeability in other inflammatory states such as sepsis is driven primarily by overactivation of the RhoA GTPase. We hypothesized that tissue injury and shock drive endothelial permeability after trauma by increased RhoA activation leading to break down of endothelial tight and adherens junctions. Methods: Human umbilical vein endothelial cells (HUVECs) were grown to confluence, whereas continuous resistance was measured using electrical cell-substrate impedance sensing (ECIS) Z-Theta technology, 10% ex vivo plasma from severely injured trauma patients was added, and resistance measurements continued for 2 hours. Areas under the curve (AUCs) were calculated from resistance curves. For GTPase activity analysis, HUVECs were grown to confluence and incubated with 10% trauma plasma for 5 minutes before harvesting of cell lysates. Rho and Rac activity were determined using a G-LISA assay. Significance was determined using Mann-Whitney tests or Kruskal-Wallis test, and Spearman ρ was calculated for correlations. Results: Plasma from severely injured patients induces endothelial permeability with plasma from patients with both severe injury and shock contributing most to this increased permeability. Surprisingly, Injury Severity Score (ISS) does not correlate with in vitro trauma-induced permeability (-0.05, P0.05), whereas base excess (BE) does correlate with permeability (-0.47, P = 0.0001). The combined impact of shock and injury resulted in a significantly smaller AUC in the injury + shock group (ISS15, BE-9) compared with the injury only (ISS15, BE-9; P = 0.04) or minimally injured (ISS15, BE-9; P = 0.005) groups. In addition, incubation with injury + shock plasma resulted in higher RhoA activation ( P = 0.002) and a trend toward decreased Rac1 activation ( P = 0.07) compared with minimally injured control. Conclusions: Over the past decade, improved early survival in patients with severe trauma and hemorrhagic shock has led to a renewed focus on the endotheliopathy of trauma. This study presents the largest study to date measuring endothelial permeability in vitro using plasma collected from patients after traumatic injury. Here, we demonstrate that plasma from patients who develop shock after severe traumatic injury induces endothelial permeability and increased RhoA activation in vitro . Our ECIS model of trauma-induced permeability using ex vivo plasma has potential as a high throughput screening tool to phenotype endothelial dysfunction, study mediators of trauma-induced permeability, and screen potential interventions.

Background: Blood type O is the most common blood type and has lower von Willebrand factor (vWF) levels (25%-35% lower than non-O blood types). von Willebrand factor is important for initiating platelet attachment and binding factor VIII. We hypothesized that patients with type O blood are at an increased risk of trauma-induced coagulopathy and bleeding post injury. Study Design: Adult trauma activations with known blood type at a level I trauma center with field systolic blood pressure90 mm Hg were studied retrospectively. The relationships of blood group O versus non-O to coagulation assays, massive transfusion (MT), ventilator-free days, and mortality were adjusted for confounders. Hyperfibrinolysis (HF) was defined as thromboelastogram of percent lysis in 30 min3%, and fibrinolysis shutdown was defined as percent lysis in 30 min0.9%. von Willebrand factor activity was quantified on 212 injured patients using a STAGO apparatus. Results: Overall, 268 patients met criteria. Type O patients were more likely to develop HF than non-type O blood patients (43% vs. 29%, P = 0.06) and had significantly lower vWF activity (222% vs. 249%, P = 0.01). After adjustment for New Injury Severity Score and blunt mechanism, type O had higher odds of HF (odds ratio, 1.94, 95% confidence interval, 1.09-3.47) and increased odds of MT (odds ratio, 3.02; 95% confidence interval, 1.22-7.49). Other outcomes were not significantly affected. Conclusion: Type O patients with hypotension had increased HF and MT post injury, and these were associated with lower vWF activity. These findings have implications for the monitoring of HF in patients receiving type O whole-blood transfusions post injury.

Complement activation after trauma promotes hemostasis but is associated with increased morbidity and mortality. However, the specific pathways and downstream mediators remain unclear. Recently, the anaphylatoxin C4a has been shown to bind to thrombin receptors. While plasma-based resuscitation has been shown to modify the endotheliopathy of trauma, it may provide complement zymogens that fuel ongoing inflammatory cascades. We sought to characterize the activation of complement after injury and the effect of fresh frozen plasma (FFP) on this inflammatory response. We hypothesized that trauma induces C4 activation, which is associated with worse outcomes and influenced by FFP resuscitation.Blood was collected from injured patients at a single level I trauma center enrolled in the Control of Major Bleeding after Trauma (COMBAT) randomized clinical trial. Proteomic analyses were performed through targeted liquid chromatography coupled with mass spectrometry. For the present observational study, concentrations of complement proteins were analyzed at multiple time points, compared between treatment groups, and correlated with outcomes.C4 activation occurred over the first 6 hours postinjury with peak activation 6 to 24 hours. Tissue hypoperfusion, defined as base deficit10 mEq/L, and requirement for massive transfusion were associated with greater C4 activation. C4 activation was associated with mortality, multiple organ failure, and longer ventilator requirement. In addition, temporal trends of C1q, factor B, and C3 by outcome groups support the prevailing theory of primary classical pathway activation with alternative pathway amplification. Resuscitation with FFP over the first 6 hours was associated with increased C4 activation at 12 and 24 hours.C4 activation has an important inflammatory role postinjury, and FFP has the potential to augment this complement activation during resuscitation.Prognostic/epidemiological, level III.

Improvised explosive devices have resulted in a unique polytrauma injury pattern termed dismounted complex blast injury (DCBI), which is frequent in the modern military theater. Dismounted complex blast injury is characterized by extremity amputations, junctional vascular injury, and blast traumatic brain injury (bTBI). We developed a combat casualty relevant DCBI swine model, which combines hemorrhagic shock (HS) and tissue injury (TI) with a bTBI, to study interventions in this unique and devastating military injury pattern.A 50-kg male Yorkshire swine were randomized to the DCBI or SHAM group (instrumentation only). Those in the DCBI group were subjected to HS, TI, and bTBI. The blast injury was applied using a 55-psi shock tube wave. Tissue injury was created with bilateral open femur fractures. Hemorrhagic shock was induced by bleeding from femoral arteries to target pressure. A resuscitation protocol modified from the Tactical Combat Casualty Care guidelines simulated battlefield resuscitation for 240 minutes.Eight swine underwent the DCBI model and five were allocated to the SHAM group. In the DCBI model the mean base excess achieved at the end of the HS shock was -8.57 ± 5.13 mmol·L -1 . A significant coagulopathy was detected in the DCBI model as measured by prothrombin time (15.8 seconds DCBI vs. 12.86 seconds SHAM; p = 0.02) and thromboelastography maximum amplitude (68.5 mm DCBI vs. 78.3 mm in SHAM; p = 0.0003). For the DCBI models, intracranial pressure (ICP) increased by a mean of 13 mm Hg, reaching a final ICP of 24 ± 7.7 mm Hg.We created a reproducible large animal model to study the combined effects of severe HS, TI, and bTBI on coagulation and ICP in the setting of DCBI, with significant translational applications for the care of military warfighters. Within the 4-hour observational period, the swine developed a consistent coagulopathy with a concurrent brain injury evidenced by increasing ICP.

BACKGROUND: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients. RESEARCH QUESTION: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe? STUDY DESIGN AND METHODS: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality. RESULTS: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio was significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the Pao2 to Fio2 ratio at 48 h (16.9% [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit. INTERPRETATION: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04357730; URL: www.clinicaltrials.gov.

Fibrinogen is the first coagulation factor to decrease after massive hemorrhage. European massive transfusion guidelines recommend early repletion of fibrinogen; however, this practice has not been widely adopted in the US. We hypothesize that hypofibrinogenemia is common at hospital arrival and is an integral component of trauma-induced coagulopathy.This study entailed review of a prospective observational database of adults meeting the highest-level activation criteria at an urban level 1 trauma center from 2014 through 2020. Resuscitation was initiated with 2:1 red blood cell (RBC) to fresh frozen plasma (FFP) ratios and continued subsequently with goal-directed thrombelastography. Hypofibrinogenemia was defined as fibrinogen below 150 mg/dL. Massive transfusion (MT) was defined as more than 10 units RBC or death after receiving at least 1 unit RBC over the first 6 hours of admission.Of 476 trauma activation patients, 70 (15%) were hypofibrinogenemic on admission, median age was 34 years, 78% were male, median New Injury Severity Score (NISS) was 25, and 72 patients died (15%). Admission fibrinogen level was an independent risk factor for MT (odds ratio [OR] 0.991, 95% CI 0.987-0.996]. After controlling for confounders, NISS (OR 1.034, 95% CI 1.017-1.052), systolic blood pressure (OR 0.991, 95% CI 0.983-0.998), thrombelastography angle (OR 0.925, 95% CI 0.896-0.954), and hyperfibrinolysis (OR 2.530, 95% CI 1.160-5.517) were associated with hypofibrinogenemia. Early cryoprecipitate administration resulted in the fastest correction of hypofibrinogenemia.Hypofibrinogenemia is common after severe injury and predicts MT. Cryoprecipitate transfusion results in the most expeditious correction. Earlier administration of cryoprecipitate should be considered in MT protocols.

Venous thromboembolism (VTE) remains a frequent postinjury complication with well established but nonmodifiable risk factors. We hypothesized that fibrinolysis shutdown (SD) as measured by thromboelastography (TEG) would be an independent risk factor for VTE in trauma patients.A subgroup of patients enrolled in the CLOTT-2 (Consortium of Leaders in the Study of Traumatic Thromboembolism 2), multicenter prospective cohort study had kaolin TEG and tissue plasminogen activator (tPA)-TEG data at 12 and 24 hours postadmission. Patients underwent a screening duplex venous ultrasound examination during the first week unless clot was already detected on computed tomography. Injury factors associated with early fibrinolysis SD (defined as kaolin TEG Ly30 ≤0.3%) and/or tPA resistance (tPA-R) (defined as kaolin TEG with tPA 75 ng Ly302.1%) were investigated as was the association of the TEG measurements with the development of VTE.A total of 141 patients had both TEG measurements at 24 hours, and 135 had both TEG measurements at 12 hours. Shutdown was evident at 12 hours in 71 of 135 (52.6%) patients and in 62 of 141 (44%) at 24 hours. Tissue plasminogen activator resistance was found in 61 of 135 (45.2%) at 12 hours and in 49 of 141 (34.3%) at 24 hours. Factors significantly associated with SD included receiving4 U of FFP in the first 24 hours, the presence of a major brain injury or pelvic fracture, and the need for major surgery. In contrast, factors significantly associated with early tPA-R included4 U of red blood cells transfused in the first 24 hours and the presence of a major chest injury or long bone fracture. Deep vein thrombosis was detected in 15 patients and pulmonary clots in 5 (overall VTE rate, 14.2%). Tissue plasminogen activator resistance at 12 hours was found to be an independent risk factor for VTE (hazard ratio, 5.57; 95% confidence interval, 1.39-22.39).Early development of a hypercoagulable state as defined by tPA-R at 12 hours after admission represents a potentially modifiable risk factor for postinjury VTE.Therapeutic/Care Management; Level II.

BACKGROUND Resuscitative endovascular occlusion of the aorta (REBOA) is used for temporary aortic occlusion of trauma patients in the management of noncompressible hemorrhage. Previous studies have focused on how to properly perform REBOA in the trauma environment to improve survival rates, but high-grade evidence defining the ideal patient population does not yet exist. This post hoc analysis of the Emergent Truncal Hemorrhage Control Study seeks to identify the most important clinical factors for physicians to consider when selecting for REBOA candidates and their potential survival following REBOA. METHODS Post hoc analysis of a large, multicenter, prospective observational study conducted at six level 1 trauma centers, 2017 to 2018, was performed. An onsite data collector documented all time points for REBOA patients since admission. Candidate predictors were demographics; injury severity; physiology preprocedure, during procedure, and postprocedure; cardiopulmonary resuscitation; and REBOA-specific variables (time to procedure, procedure-related time intervals, access site, technique, sheath size, catheter length, balloon volume, deployment zone). Predictive models for survival at three different time points along the trauma triage and REBOA process timeline ("Admission," "REBOA Initiation," and "Postaortic Occlusion") were devised by logistic regression. RESULTS Eighty-eight patients had REBOA placement. The Admission model selected age, Glasgow Coma Scale, and admission systolic blood pressure as significant predictors of survival (area under the receiver operating characteristic curve [AUROC], 0.86; 95% CI, 0.77-0.94). The REBOA Initiation and Postaortic Occlusion models selected age, Glasgow Coma Scale, and the systolic blood pressure measured just before balloon inflation as predictors for survival (AUROC, 0.87 [95% CI, 0.78-0.97] and AUROC, 0.90 [95% CI, 0.81-0.99], respectively). No REBOA procedural variables were identified as predictors of patient survival. CONCLUSION Only patient-specific criteria of age, neurologic status, and severity of shock predicted survival. The hemodynamic stability of the patient at the time REBOA is initiated is more important than how REBOA is initiated. These findings suggest that earlier preparation for REBOA placement may be a key to improved survival. LEVEL OF EVIDENCE Therapeutic, level IV.

BACKGROUND Prospective studies of surgical stabilization of rib fractures (SSRF) have excluded elderly patients, and no study has exclusively addressed the ≥80-year-old subgroup. We hypothesized that SSRF is associated with decreased mortality in trauma patients 80 years or older. METHODS Multicenter retrospective cohort study involving eight centers. Patients who underwent SSRF from 2015 to 2020 were matched to controls by study center, age, injury severity score, and presence of intracranial hemorrhage. Patients with chest Abbreviated Injury Scale score less than 3, head Abbreviated Injury Scale score greater than 2, death within 24 hours, and desire for no escalation of care were excluded. A subgroup analysis compared early (0-2 days postinjury) to late (3-7 days postinjury) SSRF. Poisson regression accounting for clustered data by center calculated the relative risk (RR) of the primary outcome of mortality for SSRF versus nonoperative management. RESULTS Of 360 patients, 133 (36.9%) underwent SSRF. Compared with nonoperative patients, SSRF patients were more severely injured and more likely to receive locoregional analgesia. There were 31 hospital deaths among the entire sample (8.6%). Multivariable regression demonstrated a decreased risk of mortality for the SSRF group, as compared with the nonoperative group (RR, 0.41; 95% confidence interval, 0.24-0.69; p < 0.01). However, SSRF patients were more likely to develop pneumonia, and had an increased duration of both mechanical ventilation and intensive care unit stay. There were no differences in discharge destination, although the SSRF group was less likely to be discharged on narcotics (RR, 0.66; 95% confidence interval, 0.48-0.90; p = 0.01). There was no difference in adjusted mortality between the early and late SSRF subgroups. CONCLUSION Patients selected for SSRF were substantially more injured versus those managed nonoperatively. Despite this, SSRF was independently associated with decreased mortality. With careful patient selection, SSRF may be considered a viable treatment option in octogenarian/nonagenarians. LEVEL OF EVIDENCE Therapeutic, Level IV.

Tissue injury (TI) and hemorrhagic shock (HS) are the major contributors to trauma-induced coagulopathy (TIC). However, the individual contributions of these insults are difficult to discern clinically because they typically coexist. TI has been reported to release procoagulants, while HS has been associated with bleeding. We developed a large animal model to isolate TI and HS and characterize their individual mechanistic pathways. We hypothesized that while TI and HS are both drivers of TIC, they provoke different pathways; specifically, TI reduces time to clotting, whereas, HS decreases clot strength stimulates hyperfibrinolysis.After induction of general anesthesia, 50 kg male, Yorkshire swine underwent isolated TI (bilateral muscle cutdown of quadriceps, bilateral femur fractures) or isolated HS (controlled bleeding to a base excess target of - 5 mmol/l) and observed for 240 min. Thrombelastography (TEG), calcium levels, thrombin activatable fibrinolysis inhibitor (TAFI), protein C, plasminogen activator inhibitor 1 (PAI-1), and plasminogen activator inhibitor 1/tissue-type plasminogen activator complex (PAI-1-tPA) were analyzed at pre-selected timepoints. Linear mixed models for repeated measures were used to compare results throughout the model.TI resulted in elevated histone release which peaked at 120 min (p = 0.02), and this was associated with reduced time to clot formation (R time) by 240 min (p = 0.006). HS decreased clot strength at time 30 min (p = 0.003), with a significant decline in calcium (p = 0.001). At study completion, HS animals had elevated PAI-1 (p = 0.01) and PAI-1-tPA (p = 0.04), showing a trend toward hyperfibrinolysis, while TI animals had suppressed fibrinolysis. Protein C, TAFI and skeletal myosin were not different among the groups.Isolated injury in animal models can help elucidate the mechanistic pathways leading to TIC. Our results suggest that isolated TI leads to early histone release and a hypercoagulable state, with suppressed fibrinolysis. In contrast, HS promotes poor clot strength and hyperfibrinolysis resulting in hypocoagulability.

BACKGROUND: Venous thromboembolism chemoprophylaxis (VTE-CHEMO) is often delayed in patients with traumatic brain injury because of the concern for intracranial hemorrhage (ICH) progression. We hypothesize that (1) late time to VTE-CHEMO (≥48h) is associated with higher incidence of VTE, and (2) VTE-CHEMO use does not correlate with ICH progression. MATERIALS AND METHODS: This is a multiinstitutional retrospective study of patients with traumatic brain injury admitted between 2014 and 2016. Inclusion criteria were head Abbreviated Injury Code ≥2, ICH present on initial head computed tomography, and two or more head computed tomography scans after admission. The primary outcome was VTE, and the secondary outcome was ICH progression. Patients were classified as receiving VTE-CHEMO early (30 (hazard ratio [HR], 1.05; P = 0.002), Injury Severity Score (HR, 1.004; P < 0.001), pelvic or femur fractures (HR, 1.05; P < 0.0001), spinal cord injury (HR, 1.28; P = 0.02), and missed VTE-CHEMO doses (HR, 1.08; P = 0.01) were significant predictors of VTE. In those who required neurosurgery, late VTE-CHEMO predicted VTE (HR, 1.21; P = 0.0001). Overall, 32% patients experienced ICH progression, which did not correlate with VTE-CHEMO use or timing. CONCLUSIONS: This multicenter study highlights benefits from early VTE-CHEMO and identifies high-risk groups who may benefit from more aggressive prophylaxis. These data also emphasize risk to patients by withholding VTE-CHEMO.

Medical-legal partnerships (MLPs) add legal professionals, trained specifically to tackle health-related social needs (HRSN), to the health care team. We evaluated the impact on health outcomes and health care utilization of a MLP housed in a large federally qualified health center in Colorado (MLP-CO). Clients screened for I-HELP (Income, Housing, Employment, Legal status, Personal stability) needs were surveyed at baseline and six months post-enrollment. Reasons for legal aid were legal immigration status (46.5%), income (30.8%), personal/family stability (14.8%), housing (4.8%), and education (1.2%). Overall, 61.4% attributed great/moderate improvements in their health care experience to the MLP-CO. Statistically significant improvements were noted for days with poor physical/mental health, and feelings of stress/worry. There was a reduction in emergency department visits, hospitalization days, and missed appointments, but only the latter was statistically significant. In conclusion, MLPs are a promising innovation to achieve the Institute for Healthcare Improvement's quadruple aim.

Debate continues as to whether choledochoduodenostomy (CDD) can be used instead of Roux-en-Y choledochojejunostomy (CDJ) when duct-to-duct (DTD) is not an option. We hypothesized that CDD and CDJ had similar rates of complications. All deceased-donor liver transplantations from September 2011 to March 2020 were categorized by biliary reconstruction. Primary outcomes were bleeding, bile leak, anastomotic stricture, and cholangitis. Of the 1,086 patients, 812 (74.8%) received a DTD; 225 (20.7%) received a CDD; and 49 (4.5%) received a CDJ. Cholangitis was significantly higher in CDJ compared to DTD and CDD (26.5% vs 6% vs 13.8%, p 0.0001). When controlling for significant confounders, CDJ had 10.2 higher odds of cholangitis (95% CI 4.4-23.2) compared to DTD, and 3.3 higher odds compared to CDD (95% CI 1.4-7.8). When compared to DTD, CDJ and CDD had significantly lower odds of stricture. CDD continues to be a safe alternative for biliary reconstruction in deceased-donor liver transplantation.

OBJECTIVES: Identify the metabolites that are increased in the plasma of severely injured patients that developed ARDS versus severely injured patients that did not, and assay if these increased metabolites prime PMNs and induce pulmonary sequestration in an animal model of ARDS. We hypothesize that metabolic derangement due to advanced shock in critically injured patients leads to the pulmonary sequestration of neutrophils (PMNs), which serves as the first event in the acute respiratory distress syndrome (ARDS). SUMMARY BACKGROUND DATA: Intracellular metabolites accumulate in the plasma of severely injured patients. METHODS: Untargeted metabolomics profiling of 67 critically injured patients was completed to establish a metabolic signature associated with ARDS development. Metabolites that signficantly increased were assayed for PMN priming activity in vitro. The metabolites that primed PMNs were tested in a two-event animal model of ARDS to identify a molecular link between circulating metabolites and clinical risk for ARDS. RESULTS: After controlling for confounders, four metabolites significantly increased: creatine, dehydroascorbate, fumarate, and succinate in trauma patients who developed ARDS (p

Objective To address the clinical and regulatory challenges of optimal primary endpoints for bleeding patients by developing consensus-based recommendations for primary clinical outcomes for pivotal trials in patients within 6 categories of significant bleeding, (1) traumatic injury, (2) intracranial hemorrhage, (3) cardiac surgery, (4) gastrointestinal hemorrhage, (5) inherited bleeding disorders, and (6) hypoproliferative thrombocytopenia. Background A standardized primary outcome in clinical trials evaluating hemostatic products and strategies for the treatment of clinically significant bleeding will facilitate the conduct, interpretation, and translation into clinical practice of hemostasis research and support alignment among funders, investigators, clinicians, and regulators. Methods An international panel of experts was convened by the National Heart Lung and Blood Institute and the United States Department of Defense on September 23 and 24, 2019. For patients suffering hemorrhagic shock, the 26 trauma working-group members met for almost a year, utilizing biweekly phone conferences and then an in-person meeting, evaluating the strengths and weaknesses of previous high quality studies. The selection of the recommended primary outcome was guided by goals of patient-centeredness, expected or demonstrated sensitivity to beneficial treatment effects, biologic plausibility, clinical and logistical feasibility, and broad applicability. Conclusions For patients suffering hemorrhagic shock, and especially from truncal hemorrhage, the recommended primary outcome was 3 to 6-hour all-cause mortality, chosen to coincide with the physiology of hemorrhagic death and to avoid bias from competing risks. Particular attention was recommended to injury and treatment time, as well as robust assessments of multiple safety related outcomes.

Most blunt splenic injuries (BSI) are treated with nonoperative management (NOM) or embolization (EMBO). Little is known about the hematologic changes associated with these treatments. We aim to assess the temporal changes of hematologic markers in trauma patients who undergo splenectomy (SPL), packing and splenorrhaphy (P/S), EMBO, or NOM. We hypothesize that differences in trends of hematologic markers exist in patients undergoing EMBO or SPL, compared to NOM.An 8-year review of adult patients with BSI and underwent SPL, EMBO, P/S, or NOM. White blood cell count (WBC), hematocrit (HCT) and platelet count (PLT) at presentation to 14 days post-admission were analyzed; post-procedural complications were reviewed. Temporal trends were compared using linear mixed-effects models.478 patients sustained BSI, 298 (62.3%) underwent NOM, 100 (29.2%) SPL, 42 (8.8%) EMBO, and 38 (8.0%) P/S. After adjustment for age, ISS and splenic injury grade, SPL patients had a significantly higher upward trend compared to other management strategies (p 0.05). Infection further increased this trend. Starting on day 6, SPL patients with infections had significantly higher WBC than those without infection. SPL and P/S were more likely than NOM to develop infections after adjustment for confounders (HR = 3.64; 95%CI: 1.79-7.39 and HR = 2.59; 95%CI: 1.21-5.55, respectively). Day 6 WBC16,000 cells/ml post-SPL had a positive predictive value (PPV) of 65.2% and negative predictive value (NPV) of 76.9% for infections. Among P/S, Day 6 WBC10,200 cells/ml had a PPV = 50% and NPV = 86.7% for infections.We observed distinct patterns of hematologic markers following BSI managed with SPL, EMBO, P/S, and NOM. Day 6 WBC increases after SPL or P/S should raise suspicion of infections and trigger a diagnostic investigation.

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) was first described in the 1950s, but early attempts at REBOA faced several technical challenges. Subsequent advances in endovascular technologies led to renewed interest in employing REBOA for management of hemorrhagic shock. However, REBOA usage remains infrequent, and indications for REBOA implementation remain unclear. We evaluated current opinions of trauma surgeons toward the use of REBOA for control of trauma-related hemorrhage and other causes of hemorrhagic shock. We hypothesize, that despite heightened interest in REBOA, implementation remains limited. A 25-question survey was thus created to query institutional and surgeon-specific training and practice patterns related to REBOA usage. The anonymized survey was distributed via email to a national trauma surgeon database and responses were recorded online. 992 subjects were invited to participate, of whom 31% (n=311) responded. Of these, 89% reported to be a trauma or acute care surgeon at a Level I trauma center, 50% reported practicing for ≥20 years. Two-thirds (68%) reported REBOA use at their institution, and the majority (59%) employed REBOA at least once. However, most (78%) performed ≤5 REBOA placements last year. Respondents supported REBOA usage in non-trauma causes of shock including gastrointestinal bleeding (60%), post-partum hemorrhage (83%), and ruptured abdominal aortic aneurysm (69%). A significant minority (20.3%) reported either only slight confidence or no confidence in their ability to deploy REBOA, and thus 21% reported being 'very interested' in attending a REBOA skills course.We thus conclude that REBOA has gained wide interest among trauma surgeons. However, placement remains infrequent with most providers placing a few annually. Educational courses are needed to disseminate the necessary skills for REBOA utilization.

INTRODUCTION: Several disease processes trigger prolonged activation of the alternative complement pathway. Crosslinks between complement activation and physiologic changes in platelets and neutrophils have been identified, but how this interplay alters the hemostatic potential in humans remains undefined. We hypothesize that activation of the alternative pathway triggers a hypercoagulable state. METHODS: C3/C5 convertase Cobra Venom Factor (CVF, 10 Units/mL) was employed to activate the alternative complement pathway in whole blood. Complement inhibition was completed with inhibitors for C3/C3b (Compstatin, 25 and 50 μM), C3a receptor (SB290157, 300 nM, C3aR), and C5a receptor (W54011, 6 nM, C5aR). Coagulation was assessed using native thrombelastography which produces the following: reaction time (R time); angle; maximum amplitude (MA); percent fibrinolysis at 30-minutes post-MA (LY30). RESULTS: Inhibition with C3aR and C5aR inhibitors did not alter clot formation (R time, 11.2 vs 11.6 min, p=0.36), clot strength (MA, 52.0 vs 52.3 mm, p=0.43) or fibrinolysis (LY30, 1.6 vs 4.0%, p=0.19). Compstatin did not influence clot formation or clot strength but did induce a dose-dependent increase in fibrinolysis (control LY30 3.0 vs 7.8% and 12.4% for 25 and 50 μM respectively, p=0.0002). CVF increased MA (58.0 vs 62.8 mm, p

Introduction High alcohol consumption has been associated with decreased fibrinolysis and enhanced thrombosis risk in cardiovascular disease. In trauma, alcohol has been associated with poor clot formation; however, its effect on fibrinolysis has not been fully investigated. We assessed the association of blood alcohol levels and fibrinolysis in trauma activation patients. Methods We queried our prospective registry of trauma activations from 2014 to 2016. Associations between viscoelastic measurements [rapid thrombelastography (rTEG)] and blood alcohol level (BAL) were determined and adjusted for confounders by a multinomial logistic regression. Lysis phenotypes were defined by the % lysis in 30 min (LY30) as follows: hyperfibrinolysis ≥ 3%, physiologic 0.9–2.9%, and fibrinolysis shutdown 150 mg/dL. BAL had a moderate, but significant inverse correlation with LY30 (Rho = − 0.315, p 150 mg/dL were independently associated with a threefold increase in the odds of shutdown compared to undetectable BAL (OR 3.37, 95% CI 1.04–8.05, p = 0.006). High BAL was also significantly associated with higher odds of shutdown compared to low BAL (OR 2.63, 95% CI 1.15–6.06). Compared to physiologic fibrinolysis, fibrinolysis shutdown was associated with increased mortality (OR 2.87, 95% CI 1.41–5.83) and VFD

Zone 1 resuscitative endovascular balloon occlusion of the aorta has been recommended for refractory shock after a dismounted complex blast injury for the austere combat scenario. While resuscitative endovascular balloon occlusion of the aorta should enhance coronary perfusion, there is a potential risk of secondary brain injury due to loss of cerebral autoregulation. We developed a combat casualty relevant dismounted complex blast injury swine model to evaluate the effects of resuscitative endovascular balloon occlusion of the aorta zone I on intracranial pressure and cerebral edema. We hypothesized that zone 1 aortic occlusion with resuscitative endovascular balloon occlusion of the aorta would increase mean arterial pressure transmitted in excessive intracranial pressure, thereby worsening brain injury.50 kg male Yorkshire swine were subjected to a combination dismounted complex blast injury model consisting of blast traumatic brain injury (50 psi, ARA Mobile Shock Laboratory), tissue injury (bilateral femur fractures), and hemorrhagic shock (controlled bleeding to a base deficit goal of 10 mEq/L). During the shock phase, pigs were randomized to no aortic occlusion (n = 8) or to 30 minutes of zone 1 resuscitative endovascular balloon occlusion of the aorta (zone 1 aortic occlusion group, n = 6). After shock, pigs in both groups received a modified Tactical Combat Casualty Care-based resuscitation and were monitored for an additional 240 minutes until euthanasia/death for a total of 6 hours. Intracranial pressure was monitored throughout, and brains were harvested for water content. Linear mixed models for repeated measures were used to compare mean arterial pressure and intracranial pressure between zone 1 aortic occlusion and no aortic occlusion groups.After dismounted complex blast injury, the zone 1 group had a significantly higher mean arterial pressure during hemorrhagic shock compared to the control group (41.2 mm Hg vs 16.7 mm Hg, P = .002). During balloon occlusion, intracranial pressure was not significantly elevated in the zone 1 aortic occlusion group vs control, but intracranial pressure was significantly lower in the zone 1 group at the end of the observation period. In addition, the zone 1 aortic occlusion group did not have increased brain water content (zone 1 aortic occlusion: 3.95 ± 0.1g vs no aortic occlusion: 3.95 ± 0.3 g, P = .87). Troponin levels significantly increased in the no aortic occlusion group but did not in the zone 1 aortic occlusion group.Zone 1 aortic occlusion using resuscitative endovascular balloon occlusion of the aorta in a large animal dismounted complex blast injury model improved proximal mean arterial pressure while not significantly increasing intracranial pressure during balloon inflation. Observation up to 240 minutes postresuscitation did not show clinical signs of worsening brain injury or cardiac injury. These data suggest that in a dismounted complex blast injury swine model, resuscitative endovascular balloon occlusion of the aorta in zone 1 may provide neuro- and cardioprotection in the setting of blast traumatic brain injury. However, longer monitoring periods may be needed to confirm that the neuroprotection is lasting.

Objective(s): Understanding patient goals of care is essential in any setting, and especially so in an urban, safety net trauma centers’ Surgical Intensive Care Units (SICU). This underscores the need for implementation of palliative care principles and practices, such as identification of surrogate decision makers, goals-of-care discussions, and CPR directives, in the SICU. Methods: A pragmatic, quality improvement study utilizing a retrospective, pre- and post-intervention continuum analysis. Interventions included a surgeon champion, resident education, and an electronic medical record template, called the Advanced Care Planning (ACP) Note, for use on daily rounds. We reviewed the charts of all adults admitted to the SICU before, during, and after these interventions to identify the incidence of surrogate decision maker documentation by SICU residents. Results: There was an early and enthusiastic adoption in ACP note utilization by SICU residents over the study period. Rates of documenting surrogate decision makers increased throughout the study period ( p

ImportanceAortic occlusion (AO) is a lifesaving therapy for the treatment of severe traumatic hemorrhagic shock; however, there remains controversy whether AO should be accomplished via resuscitative thoracotomy (RT) or via endovascular balloon occlusion of the aorta (REBOA) in zone 1.ObjectiveTo compare outcomes of AO via RT vs REBOA zone 1.Design, Setting, and ParticipantsThis was a comparative effectiveness research study using a multicenter registry of postinjury AO from October 2013 to September 2021. AO via REBOA zone 1 (above celiac artery) was compared with RT performed in the emergency department of facilities experienced in both procedures and documented in the prospective multicenter Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery (AORTA) registry. Propensity score matching (PSM) with exact institution matching was used, in addition to subgroup multivariate analysis to control for confounders. The study setting included the ED, where AO via RT or REBOA was performed, and participants were adult trauma patients 16 years or older.ExposuresAO via REBOA zone 1 vs RT.Main Outcomes and MeasuresThe primary outcome was survival. Secondary outcomes were ventilation-free days (VFDs), intensive care unit (ICU)–free days, discharge Glasgow Coma Scale score, and Glasgow Outcome Score (GOS).ResultsA total of 991 patients (median [IQR] age, 32 [25-48] years; 808 male individuals [81.9%]) with a median (IQR) Injury Severity Score of 29 (18-50) were included. Of the total participants, 306 (30.9%) had AO via REBOA zone 1, and 685 (69.1%) had AO via RT. PSM selected 112 comparable patients (56 pairs). REBOA zone 1 was associated with a statistically significant lower mortality compared with RT (78.6% [44] vs 92.9% [52]; P = .03). There were no significant differences in VFD greater than 0 (REBOA, 18.5% [10] vs RT, 7.1% [4]; P = .07), ICU-free days greater than 0 (REBOA, 18.2% [10] vs RT, 7.1% [4]; P = .08), or discharge GOS of 5 or more (REBOA, 7.5% [4] vs RT, 3.6% [2]; P = .38). Multivariate analysis confirmed the survival benefit of REBOA zone 1 after adjustment for significant confounders (relative risk [RR], 1.25; 95% CI, 1.15-1.36). In all subgroup analyses (cardiopulmonary resuscitation on arrival, traumatic brain injury, chest injury, pelvic injury, blunt/penetrating mechanism, systolic blood pressure ≤60 mm Hg on AO initiation), REBOA zone 1 offered an either similar or superior survival.Conclusions and RelevanceResults of this comparative effectiveness research suggest that REBOA zone 1 provided better or similar survival than RT for patients requiring AO postinjury. These findings provide the ethically necessary equipoise between these therapeutic approaches to allow the planning of a randomized controlled trial to establish the safety and effectiveness of REBOA zone 1 for AO in trauma resuscitation.

Prehospital identification of the injured patient likely to require emergent care remains a challenge. End-tidal carbon dioxide (ETCO2) has been used in the prehospital setting to monitor respiratory physiology and confirmation of endotracheal tube placement. Low levels of ETCO2 have been demonstrated to correlate with injury severity and mortality in a number of in-hospital studies. We hypothesized that prehospital ETCO2 values would be predictive of mortality and need for massive transfusion (MT) in intubated patients.This was a retrospective multicenter trial with 24 participating centers. Prehospital, emergency department, and hospital values were collected. Receiver operating characteristic curves were created and compared. Massive transfusion defined as10 U of blood in 6 hours or death in 6 hours with at least 1 U of blood transfused.A total of 1,324 patients were enrolled. ETCO2 (area under the receiver operating characteristic curve [AUROC], 0.67; confidence interval [CI], 0.63-0.71) was better in predicting mortality than shock index (SI) (AUROC, 0.55; CI, 0.50-0.60) and systolic blood pressure (SBP) (AUROC, 0.58; CI, 0.53-0.62) (p0.0005). Prehospital lowest ETCO2 (AUROC, 0.69; CI, 0.64-0.75), SBP (AUROC, 0.75; CI, 0.70-0.81), and SI (AUROC, 0.74; CI, 0.68-0.79) were all predictive of MT. Analysis of patients with normotension demonstrated lowest prehospital ETCO2 (AUROC, 0.66; CI, 0.61-0.71), which was more predictive of mortality than SBP (AUROC, 0.52; CI, 0.47-0.58) or SI (AUROC, 0.56; CI, 0.50-0.62) (p0.001). Lowest prehospital ETCO2 (AUROC, 0.75; CI, 0.65-0.84), SBP (AUROC, 0.63; CI, 0.54-0.74), and SI (AUROC, 0.64; CI, 0.54-0.75) were predictive of MT in normotensive patients. ETCO2 cutoff for MT was 26 mm Hg. The positive predictive value was 16.1%, and negative predictive value was high at 98.1%.Prehospital ETCO2 is predictive of mortality and MT. ETCO2 outperformed traditional measures such as SBP and SI in the prediction of mortality. ETCO2 may outperform traditional measures in predicting need for transfusion in occult shock.Diagnostic test, level III.

Few therapies exist to treat severe COVID-19 respiratory failure once it develops. Given known diffuse pulmonary microthrombi on autopsy studies of COVID-19 patients, we hypothesized that tissue plasminogen activator (tPA) may improve pulmonary function in COVID-19 respiratory failure.A multicenter, retrospective, observational study of patients with confirmed COVID-19 and severe respiratory failure who received systemic tPA (alteplase) was performed. Seventy-nine adults from seven medical centers were included in the final analysis after institutional review boards' approval; 23 were excluded from analysis because tPA was administered for pulmonary macroembolism or deep venous thrombosis. The primary outcome was improvement in the PaOtPA was associated with significant PaOThese data suggest tPA is associated with significant improvement in pulmonary function in severe COVID-19 respiratory failure, especially in patients whose pulmonary function is in decline, and has an acceptable safety profile in this patient population.

Objective Investigate whether safe infant sleep prioritization by states through the Title V Maternal and Child Block Grant in 2010 differentially impacted maternal report of supine sleep positioning (SSP) for Non-Hispanic White (NHW) and Non-Hispanic Black (NHB) U.S.-born infants. Methods We analyzed retrospective cross-sectional data from the Pregnancy Risk Assessment Monitoring System (PRAMS) from 2005 to 2015 from 4 states: WV and OK (Intervention) and AR and UT (Control). PRAMS is a population-based surveillance system of maternal perinatal experiences which is linked to infant birth certificates. Piece-wise survey linear regression models were used to estimate the difference in the change in slopes of SSP percents in the pre- (2005-2009) and post- (2011-2015) periods, controlling for maternal and infant characteristics. Models were also stratified by race/ethnicity. Results From 2005 to 2015, for NHW infants, SSP improved from 61.5% and 70.2% to 82.8% and 82.3% for intervention and control states, respectively. For NHB infants, SSP improved from 30.6% and 26.5% to 64.5% and 53.1% for intervention and control states, respectively. After adjustment for maternal characteristics, there was no difference in the rate of SSP change from the pre- to post- intervention periods for either NHW or NHB infants in intervention or control groups. Conclusions and relevance Compared with control states that did not prioritize safe infant sleep in their 2010 Title V Block Grant needs assessment, intervention states experienced no difference in SSP improvement rates for NHW and NHB infants. While SSP increased for all infants during the study period, there was no causal relationship between states' prioritization of safe infant sleep and SSP improvement. More targeted approaches may be needed to reduce the racial/ethnic disparity in SSP and reduce the risk for sleep-associated infant death. Key points · Supine sleep positioning improved for Black and White infants in the U.S.. · State prioritization of safe infant sleep did not directly impact SSP for NHB or NHW infants.. · More targeted approaches may be needed to reduce racial/ethnic disparities in safe sleep practices.

BACKGROUND The rationale for resuscitative endovascular balloon occlusion of the aorta (REBOA) is to control life-threatening subdiaphragmatic bleeding and facilitate resuscitation; however, incorporating this into the resuscitative practices of a trauma service remains challenging. The objective of this study is to describe the process of successful implementation of REBOA use in an academic urban Level I trauma center. All REBOA procedures from April 2014 through December 2019 were evaluated; REBOA was implemented after surgical faculty attended a required and internally developed Advanced Endovascular Strategies for Trauma Surgeons course. Success was defined by sustained early adoption rates. METHODS An institutional protocol was published, and a REBOA supply cart was placed in the emergency department with posters attached to depict technical and procedural details. A focused professional practice evaluation was utilized for the first three REBOA procedures performed by each faculty member, leading to internal privileging. RESULTS Resuscitative endovascular balloon occlusion of the aorta was performed in 97 patients by nine trauma surgeons, which is 1% of the total trauma admissions during this time. Each surgeon performed a median of 12 REBOAs (interquartile range, 5-14). Blunt (77/97, 81%) or penetrating abdominopelvic injuries (15/97, 15%) comprised the main injury mechanisms; 4% were placed for other reasons (4/97), including ruptured abdominal aortic aneurysms (n = 3) and preoperatively for a surgical oncologic resection (n = 1). Overall survival was 65% (63/97) with a steady early adoption trend that resulted in participation in a Department of Defense multicenter trial. CONCLUSION Strategies for how departments adopt new procedures require clinical guidelines, a training program focused on competence, and a hospital education and privileging process for those acquiring new skills. LEVEL OF EVIDENCE Therapeutic, level V.

Resuscitative endovascular occlusion of the aorta (REBOA) is used for temporary aortic occlusion of trauma patients in the management of noncompressible hemorrhage. Previous studies have focused on how to properly perform REBOA in the trauma environment to improve survival rates, but high-grade evidence defining the ideal patient population does not yet exist. This post hoc analysis of the Emergent Truncal Hemorrhage Control Study seeks to identify the most important clinical factors for physicians to consider when selecting for REBOA candidates and their potential survival following REBOA.Post hoc analysis of a large, multicenter, prospective observational study conducted at six level 1 trauma centers, 2017 to 2018, was performed. An onsite data collector documented all time points for REBOA patients since admission. Candidate predictors were demographics; injury severity; physiology preprocedure, during procedure, and postprocedure; cardiopulmonary resuscitation; and REBOA-specific variables (time to procedure, procedure-related time intervals, access site, technique, sheath size, catheter length, balloon volume, deployment zone). Predictive models for survival at three different time points along the trauma triage and REBOA process timeline ("Admission," "REBOA Initiation," and "Postaortic Occlusion") were devised by logistic regression.Eighty-eight patients had REBOA placement. The Admission model selected age, Glasgow Coma Scale, and admission systolic blood pressure as significant predictors of survival (area under the receiver operating characteristic curve [AUROC], 0.86; 95% CI, 0.77-0.94). The REBOA Initiation and Postaortic Occlusion models selected age, Glasgow Coma Scale, and the systolic blood pressure measured just before balloon inflation as predictors for survival (AUROC, 0.87 [95% CI, 0.78-0.97] and AUROC, 0.90 [95% CI, 0.81-0.99], respectively). No REBOA procedural variables were identified as predictors of patient survival.Only patient-specific criteria of age, neurologic status, and severity of shock predicted survival. The hemodynamic stability of the patient at the time REBOA is initiated is more important than how REBOA is initiated. These findings suggest that earlier preparation for REBOA placement may be a key to improved survival.Therapeutic, level IV.

The definition of hyperfibrinolysis based on thrombelastogram LY30 measurements should vary with trauma patient characteristics, i.e., as anatomic injury or shock severity increase, the ability to tolerate even mild degrees of fibrinolysis is markedly reduced. This trend is independent of institutional practice patterns. The management of hyperfibrinolysis, particularly with anti-fibrinolytics administration, should be interpreted in the context of injury severity/shock and managed on an individual patient basis.

Background Trauma patients with hypersensitivity to tissue plasminogen activator mediated fibrinolysis quantified by tissue plasminogen activator thromboelastography are at increased risk of massive transfusion. The tissue plasminogen activator thromboelastography assay has been tested in trauma patients using native thromboelastography with no exogenous activator. We hypothesize that adding an activator will expedite the time to results. Methods Healthy whole blood was assayed with and without exogenous plasmin, which acts to deplete inhibitors of fibrinolysis, mimicking trauma blood. Samples were assessed using native, kaolin, and rapid thromboelastography with and without tissue plasminogen activator. The tissue plasminogen activator thromboelastography indices of time to maximum amplitude and lysis at 30 minutes were contrasted between healthy blood with and without plasmin using the three different activators. The activators were then used with a tissue plasminogen activator thromboelastography in 100 trauma patients to assess performance in predicting massive transfusion. Results In healthy blood, regardless of activator, lysis at 30 minutes did not increase with plasmin alone, but did increase with tissue plasminogen activator (P = .012). Adding tissue plasminogen activator and plasmin increased lysis at 30 minutes (P = .036). Time to maximum amplitude was reduced with tissue plasminogen activator and plasmin compared with tissue plasminogen activator alone (P = .012). Activated thromboelastographies had increased lysis at 30 minutes (P = .002), but no difference in time to maximum amplitude compared with native thromboelastographies. In trauma patients, native tissue plasminogen activator thromboelastography had greater performance in predicting massive transfusion than activated tissue plasminogen activator thromboelastographies with no difference in time to maximum amplitude. Conclusion Adding an activator to tissue plasminogen activator thromboelastography does not expedite time to maximum amplitude in healthy blood depleted of fibrinolysis inhibitors. Activated tissue plasminogen activator thromboelastographies are inferior to native tissue plasminogen activator thromboelastography for predicting massive transfusion and do not reduce the time to results.

Stroke secondary to blunt cerebrovascular injury (BCVI) most often occurs before initiation of antithrombotic therapy. Earlier treatment, especially in multiply injured patients with relative contraindications to antithrombotic agents, could be facilitated with improved risk stratification; furthermore, the relationship between BCVI-attributed stroke and hypercoagulability remains unknown. We hypothesized that patients who suffer BCVI-related stroke are hypercoagulable compared with those with BCVI who do not stroke.Rapid thromboelastography (TEG) was evaluated for patients with BCVI-attributed stroke at an urban Level I trauma center from 2011 to 2018. Contemporary controls who had BCVI but did not stroke were selected for comparison using propensity-score matching with 20% caliper that accounted for age, sex, injury severity, and BCVI location and grade.During the study period, 15,347 patients were admitted following blunt trauma. Blunt cerebrovascular injury was identified in 435 (3%) patients, of whom 28 experienced associated stroke and had a TEG within 24 hours of arrival. Forty-nine patients who had BCVI but did not suffer stroke served as matched controls. Stroke patients formed clots faster as evident in their larger angle (77.5 degrees vs. 74.6 degrees, p = 0.03) and had greater clot strength as indicated by their higher maximum amplitude (MA) (66.9 mm vs. 61.9 mm, p0.01). Activated clotting time was shorter among stroke patients but not significantly (113 seconds vs. 121 seconds, p0.05). Increased angle and elevated MA were significant predictors of stroke with odds ratios of 2.97 for angle greater than 77.3 degrees and 4.30 for MA greater than 63.0 mm.Patients who suffer BCVI-related stroke are hypercoagulable compared with those with BCVI who remain asymptomatic. Increased angle or MA should be considered when assessing the risk of thrombosis and determining the optimal time to initiate antithrombotic therapy in patients with BCVI.Prognostic, Level III.

BACKGROUND: Morbid obesity is associated with an increased risk of thrombotic events, which has been attributed to increased thrombotic activity. Multiple mechanisms have been proposed to explain this increased risk, including an inflammatory state with upregulation of procoagulant and antifibrinolytic proteins. We therefore hypothesize that patients with morbid obesity are hypercoagulable and will revert to normal after bariatric surgery. OBJECTIVES: To evaluate changes in the hypercoagulable state after bariatric surgery. SETTING: University Hospital, Bariatric Center of Excellence, United States. METHODS: Thromboelastography (TEG) data were collected on 72 subjects with morbid obesity, with 36 who had 6 months of follow-up after bariatric surgery. TEG data of 75 healthy subjects (HS) without obesity, recent trauma or surgery, acute infection, or chronic conditions (e.g., liver, cardiovascular, or kidney disease; cancer; diabetes; autoimmune or inflammatory disorders; and disorders of coagulation) were used for comparison. TEG was performed alone and with the addition of 75 and 150 ng/mL tissue plasminogen activator (tPA) to quantify fibrinolysis resistance (tPA-challenged TEG). RESULTS: The bariatric surgery cohort had a median age of 40.5 years, a median body mass index of 44.6 kg/m(2), and 90% female patients. Median body mass index reduced significantly 6 months post surgery but remained elevated compared with the HS group (31.4 versus 25.4 kg/m(2), P < .0001). At 6 months post surgery, subjects had longer reaction time (mean difference, 1.3; P = .02), lower maximum amplitude (−2.4, P = .01), and increased fibrinolysis with low-dose (3.1, P < .0001) and high-dose tPA-challenged TEG (9, P < .0001). Compared with HS, the postsurgery TEG values were still more likely to be abnormal (all P < .05). CONCLUSIONS: Patients with morbid obesity form stronger clots more rapidly and are more resistant to fibrinolysis than subjects without obesity. Bariatric surgery significantly improved the hypercoagulable