Nomogram for predicting in-hospital mortality in trauma patients undergoing resuscitative endovascular balloon occlusion of the aorta: a retrospective multicenter study.

Recently, resuscitative endovascular balloon occlusion of the aorta (REBOA) had been introduced as an innovative procedure for severe hemorrhage in the abdomen or pelvis. We aimed to investigate risk factors associated with mortality after REBOA and construct a model for predicting mortality. This multicenter retrospective study collected data from 251 patients admitted at five regional trauma centers across South Korea from 2015 to 2022. The indications for REBOA included patients experiencing hypovolemic shock due to hemorrhage in the abdomen, pelvis, or lower extremities, and those who were non-responders (systolic blood pressure (SBP) < 90 mmHg) to initial fluid treatment. The primary and secondary outcomes were mortality due to exsanguination and overall mortality, respectively. After feature selection using the least absolute shrinkage and selection operator (LASSO) logistic regression model to minimize overfitting, a multivariate logistic regression (MLR) model and nomogram were constructed. In the MLR model using risk factors selected in the LASSO, five risk factors, including initial heart rate (adjusted odds ratio [aOR], 0.99; 95% confidence interval [CI], 0.98-1.00; p = 0.030), initial Glasgow coma scale (aOR, 0.86; 95% CI 0.80-0.93; p < 0.001), RBC transfusion within 4 h (unit, aOR, 1.12; 95% CI 1.07-1.17; p < 0.001), balloon occlusion type (reference: partial occlusion; total occlusion, aOR, 2.53; 95% CI 1.27-5.02; p = 0.008; partial + total occlusion, aOR, 2.04; 95% CI 0.71-5.86; p = 0.187), and post-REBOA systolic blood pressure (SBP) (aOR, 0.98; 95% CI 0.97-0.99; p < 0.001) were significantly associated with mortality due to exsanguination. The prediction model showed an area under curve, sensitivity, and specificity of 0.855, 73.2%, and 83.6%, respectively. Decision curve analysis showed that the predictive model had increased net benefits across a wide range of threshold probabilities. This study developed a novel intuitive nomogram for predicting mortality in patients undergoing REBOA. Our proposed model exhibited excellent performance and revealed that total occlusion was associated with poor outcomes, with post-REBOA SBP potentially being an effective surrogate measure.

Timing to First Whole Blood Transfusion and Survival Following Severe Hemorrhage in Trauma Patients.

Importance: Civilian trauma centers have revived interest in whole-blood (WB) resuscitation for patients with life-threatening bleeding. However, there remains insufficient evidence that the timing of WB transfusion when given as an adjunct to a massive transfusion protocol (MTP) is associated with a difference in patient survival outcome. Objective: To evaluate whether earlier timing of first WB transfusion is associated with improved survival at 24 hours and 30 days for adult trauma patients presenting with severe hemorrhage. Design, Setting, and Participants: This retrospective cohort study used the American College of Surgeons Trauma Quality Improvement Program databank from January 1, 2019, to December 31, 2020, for adult patients presenting to US and Canadian adult civilian level 1 and 2 trauma centers with systolic blood pressure less than 90 mm Hg, with shock index greater than 1, and requiring MTP who received a WB transfusion within the first 24 hours of emergency department (ED) arrival. Patients with burns, prehospital cardiac arrest, deaths within 1 hour of ED arrival, and interfacility transfers were excluded. Data were analyzed from January 3 to October 2, 2023. Exposure: Patients who received WB as an adjunct to MTP (earlier) compared with patients who had yet to receive WB as part of MTP (later) at any given time point within 24 hours of ED arrival. Main Outcomes and Measures: Primary outcomes were survival at 24 hours and 30 days. Results: A total of 1394 patients met the inclusion criteria (1155 male [83%]; median age, 39 years [IQR, 25-51 years]). The study cohort included profoundly injured patients (median Injury Severity Score, 27 [IQR, 17-35]). A survival curve demonstrated a difference in survival within 1 hour of ED presentation and WB transfusion. Whole blood transfusion as an adjunct to MTP given earlier compared with later at each time point was associated with improved survival at 24 hours (adjusted hazard ratio, 0.40; 95% CI, 0.22-0.73; P = .003). Similarly, the survival benefit of earlier WB transfusion remained present at 30 days (adjusted hazard ratio, 0.32; 95% CI, 0.22-0.45; P < .001). Conclusions and Relevance: In this cohort study, receipt of a WB transfusion earlier at any time point within the first 24 hours of ED arrival was associated with improved survival in patients presenting with severe hemorrhage. The survival benefit was noted shortly after transfusion. The findings of this study are clinically important as the earlier timing of WB administration may offer a survival advantage in actively hemorrhaging patients requiring MTP.

Faster refill in an urban emergency medical services system saves lives: A prospective preliminary evaluation of a prehospital advanced resuscitative care bundle.

INTRODUCTION: Military experience has demonstrated mortality improvement when advanced resuscitative care (ARC) is provided for trauma patients with severe hemorrhage. The benefits of ARC for trauma in civilian emergency medical services (EMS) systems with short transport intervals are still unknown. We hypothesized that ARC implementation in an urban EMS system would reduce in-hospital mortality. METHODS: This was a prospective analysis of ARC bundle administration between 2021 and 2023 in an urban EMS system with 70,000 annual responses. The ARC bundle consisted of calcium, tranexamic acid, and packed red blood cells via a rapid infuser. Advanced resuscitative care patients were compared with trauma registry controls from 2016 to 2019. Included were patients with a penetrating injury and systolic blood pressure ≤90 mm Hg. Excluded were isolated head trauma or prehospital cardiac arrest. In-hospital mortality was the primary outcome of interest. RESULTS: A total of 210 patients (ARC, 61; controls, 149) met the criteria. The median age was 32 years, with no difference in demographics, initial systolic blood pressure or heart rate recorded by EMS, or New Injury Severity Score between groups. At hospital arrival, ARC patients had lower median heart rate and shock index than controls ( p ≤ 0.03). Fewer patients in the ARC group required prehospital advanced airway placement ( p < 0.001). Twenty-four-hour and total in-hospital mortality were lower in the ARC group ( p ≤ 0.04). Multivariable regression revealed an independent reduction in in-hospital mortality with ARC (odds ratio, 0.19; 95% confidence interval, 0.05-0.68; p = 0.01). CONCLUSION: Early ARC in a fast-paced urban EMS system is achievable and may improve physiologic derangements while decreasing patient mortality. Advanced resuscitative care closer to the point of injury warrants consideration. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Maintaining a whole blood-centered transfusion improves survival in hemorrhagic resuscitation.

BACKGROUND: Whole blood (WB) transfusion has been shown to improve mortality in trauma resuscitation. The optimal ratio of packed red blood cells (pRBC) to WB in emergent transfusion has not been determined. We hypothesized that a low pRBC/WB transfusion ratio is associated with improved survival in trauma patients. METHODS: We analyzed the 2021 Trauma Quality Improvement Program (TQIP) database to identify patients who underwent emergent surgery for hemorrhage control and were transfused within 4 hours of hospital arrival, excluding transfers or deaths in the emergency department. We stratified patients based on pRBC/WB ratios. The primary outcome was mortality at 24 hours. Logistic regression was performed to estimate odds of mortality among ratio groups compared with WB alone, adjusting for injury severity, time to intervention, and demographics. RESULTS: Our cohort included 17,562 patients; of those, 13,678 patients had only pRBC transfused and were excluded. Fresh frozen plasma/pRBC ratio was balanced in all groups. Among those who received WB (n = 3,884), there was a significant increase in 24-hour mortality with higher pRBC/WB ratios (WB alone 5.2%, 1:1 10.9%, 2:1 11.8%, 3:1 14.9%, 4:1 20.9%, 5:1 34.1%, p = 0.0001). Using empirical cutpoint estimation, we identified a 3:1 ratio or less as an optimal cutoff point. Adjusted odds ratios of 24-hour mortality for 4:1 and 5:1 groups were 2.85 (95% confidence interval [CI], 1.19-6.81) and 2.89 (95% CI, 1.29-6.49), respectively. Adjusted hazard ratios of 24-hour mortality were 2.83 (95% CI, 1.18-6.77) for 3:1 ratio, 3.67 (95% CI, 1.57-8.57) for 4:1 ratio, and 1.97 (95% CI, 0.91-4.23) for 5:1 ratio. CONCLUSION: Our analysis shows that higher pRBC/WB ratios at 4 hours diminished survival benefits of WB in trauma resuscitation. Further efforts should emphasize this relationship to optimize trauma resuscitation protocols. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Mortality in patients with unresectable gastric cancer complicated with tumor bleeding

Background: gastric cancer (GC) is a gastrointestinal (GI) neoplasia which often complicates with GI bleeding. It is uncertain if bleeding worsens mortality in this group of patients. Aims: to compare 30- and 90-day mortality in patients with unresectable GC (uGC) and tumor bleeding versus patients with the same neoplasia without bleeding. Methods: a retrospective analysis of patients with uGC, with and without tumor bleeding was performed. Survival analysis for 30- and 90-days mortality was performed using Cox regression. Logistic regression was used to identify risk factors associated with mortality and first bleeding episode. Results: 202 patients were included in the analysis (105 cases). Mortality at 90 days was 37.14 % for cases and 20.62 % for controls (p = 0.04). There was a significant difference in hazard ratio (HR) at 90 days for cases compared to controls (HR 1.95, 95 % CI 1.14-3.34, p = 0.02). Cases without palliative chemotherapy had the highest 90-days mortality (HR 5.43, 95 % CI 2.12-13.87, p < 0.01), compared to controls treated with chemotherapy. Predictors for first tumor bleeding were clinical stage IV (OR 2.93, 95 % CI 1.04-8.26, p = 0.04), Helicobacter pylori infection (OR 2.80, 95 % CI 1.35-5.80, p < 0.01) and histologic intestinal-subtype (OR 2.14, 95 % CI 1.07-4.30, p = 0.03). Conclusions: tumor bleeding increases 90-days mortality in patients with uGC. Prevention of the first bleeding episode might improve outcome in these patients and the recognition of high-risk patients might help decision-making. (AU)

Muerte materna asociada a una malformación arteriovenosa uterina / Maternal death associated with uterine arteriovenous malformation

La malformación arteriovenosa uterina (MAVU), para algunos autores considerada como fístula arteriovenosa, representa entre el 1 y 2% de la hemorragia genital e intraperitoneal como resultado de la rotura vascular espontánea o provocada posterior a una intervención quirúrgica.Exponemos un caso de muerte materna ocurrida durante una caminata sobre una pendiente, presentando metrorragia y desvanecimiento con desenlace letal. La autopsia médico legal demostró un útero gestante con hemorragia del miometrio y múltiples coágulos hemáticos, diagnosticada anatomopatológicamente como MAVU.La muerte materna es un problema de salud pública multifactorial en los países subdesarrollados, la MAVU es una causa poco frecuente, sin embargo, algunos autores la consideran subdiagnosticada; han aumentado el reporte de casos en los últimos años y en los países en desarrollo puede ser letal. (AU)

Uterine arteriovenous malformation (UAMM) for some authors, considered an arteriovenous fistula, represents between 1% and 2% of genital and intraperitoneal hemorrhage as a result of spontaneous or provoked vascular rupture after a surgical intervention.We present a case of maternal death that occurred during a walk on a slope, presenting metrorrhagia and fainting with a fatal outcome. The medico-legal autopsy showed a pregnancy uterus with myometrial hemorrhage and multiple blood clots, diagnosed pathologically as a uterine arteriovenous malformation.Maternal death is a multifactorial public health problem in underdeveloped countries. Uterine arteriovenous malformation is a rare cause, however some authors consider it underdiagnosed; reported cases have increased in recent years and in developing countries it can be lethal. (AU)

Effect of special operational forces surgical resuscitation teams on combat casualty survival: A narrative review.

IMPORTANCE: The most common cause of preventable death on the conventional battlefield or on special operations force (SOF) missions is hemorrhage. SOF missions may take place in remote and austere locations. Many preventable deaths in combat occur within 30 min of wounding. Therefore, SOF damage control resuscitation (DCR) and damage control surgery (DCS) teams may improve combat casualty survival in the SOF environment. OBJECTIVE: To determine the effect of SOF DCR and DCS teams on combat casualty survival. Also, to describe commonalities in team structure, logistics, and blood product usage. DESIGN: A narrative review of the English literature used a Medline and Embase search strategy. The authors were contacted for more details as required. The risk of bias was assessed using the Cochrane Collaboration's ROBINS-I tool. Pooling of data was not done to the heterogeneity of studies. RESULTS: Weak evidence was identified showing a clinical benefit of SOF DCR and DCS teams. Conflicting evidence from less rigorous studies was also found. The overall risk of bias using ROBINS-I was serious to critical. Several commonalities in team structure, training, and logistics were found. CONCLUSIONS AND RELEVANCE: There is conflicting evidence regarding the effect SOF DCR and DCS teams have on combat casualty survival. There is no strong evidence that SOF DCR and DCS teams cause harm. More robust data collection is recommended to evaluate these teams.

Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Randomized Clinical Trial.

IMPORTANCE: The optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain. OBJECTIVE: To determine whether early use of moderate hypothermia (33-34 °C) compared with strict normothermia (36-37 °C) improves mortality in patients with cardiogenic shock receiving venoarterial ECMO. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for <6 hours) conducted in the intensive care units at 20 French cardiac shock care centers between October 2016 and July 2019. Of 786 eligible patients, 374 were randomized. Final follow-up occurred in November 2019. INTERVENTIONS: Early moderate hypothermia (33-34 °C; n = 168) for 24 hours or strict normothermia (36-37 °C; n = 166). MAIN OUTCOMES AND MEASURES: The primary outcome was mortality at 30 days. There were 31 secondary outcomes including mortality at days 7, 60, and 180; a composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at days 30, 60, and 180; and days without requiring a ventilator or kidney replacement therapy at days 30, 60, and 180. Adverse events included rates of severe bleeding, sepsis, and number of units of packed red blood cells transfused during venoarterial ECMO. RESULTS: Among the 374 patients who were randomized, 334 completed the trial (mean age, 58 [SD, 12] years; 24% women) and were included in the primary analysis. At 30 days, 71 patients (42%) in the moderate hypothermia group had died vs 84 patients (51%) in the normothermia group (adjusted odds ratio, 0.71 [95% CI, 0.45 to 1.13], P = .15; risk difference, -8.3% [95% CI, -16.3% to -0.3%]). For the composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at day 30, the adjusted odds ratio was 0.61 (95% CI, 0.39 to 0.96; P = .03) for the moderate hypothermia group compared with the normothermia group and the risk difference was -11.5% (95% CI, -23.2% to 0.2%). Of the 31 secondary outcomes, 30 were inconclusive. The incidence of moderate or severe bleeding was 41% in the moderate hypothermia group vs 42% in the normothermia group. The incidence of infections was 52% in both groups. The incidence of bacteremia was 20% in the moderate hypothermia group vs 30% in the normothermia group. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial involving patients with refractory cardiogenic shock treated with venoarterial ECMO, early application of moderate hypothermia for 24 hours did not significantly increase survival compared with normothermia. However, because the 95% CI was wide and included a potentially important effect size, these findings should be considered inconclusive. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02754193.

The risk of fatal bleeding complications in jugular catheterization in patients with coagulopathy: A retrospective analysis of death cases in closed claims and the Medical Accident Investigating System in Japan.

BACKGROUND: To prevent recurrence of medical accidents, the Medical Accident Investigating System was implemented in October 2015 by the Japan Medical Safety Research Organization (Medsafe Japan) to target deaths from medical care that were unforeseen by the administrator. Medsafe Japan analyzed the 10 cases of central venous catheterization-related deaths reported in the system and published recommendations in March 2017. However, the particular emphasis for the prevention of central venous catheterization-related deaths is unclear. METHODS: This study aimed to identify the recommendation points that should be emphasized to prevent recurrence of central venous catheterization-related deaths. We assessed central venous catheterization in 8530 closed-claim cases between January 2002 and December 2016 covered by the medical insurer Sompo-Japan. Moreover, we compared central venous catheterization-related death in closed-claim cases with death in reported cases. RESULTS: The background, error type, anatomic insertion site, and fatal complication data were evaluated for 37 closed-claim cases, of which 12 (32.4%) were death cases. Of the 12 closed-claim cases and 10 reported cases, 9 (75.0%) closed-claim cases and 9 (90.0%) reported cases were related to vascular access. Among these, 5 closed-claim cases (41.7%) and 7 reported cases (77.8%) were related to internal jugular vein catheterization (p = 0.28). Coagulopathy was observed in 3 (60.0%) of 5 closed-claim cases and 6 (85.7%) of 7 reported cases. CONCLUSIONS: The risk of internal jugular catheterization in patients with coagulopathy must be carefully considered.

Temporal Transitions in Fibrinolysis after Trauma: Adverse Outcome Is Principally Related to Late Hypofibrinolysis.

BACKGROUND: The relationship between late clinical outcomes after injury and early dynamic changes between fibrinolytic states is not fully understood. The authors hypothesized that temporal transitions in fibrinolysis states using rotational thromboelastometry (ROTEM) would aid stratification of adverse late clinical outcomes and improve understanding of how tranexamic acid modulates the fibrinolytic response and impacts mortality. METHODS: The authors conducted a secondary analysis of previously collected data from trauma patients enrolled into an ongoing prospective cohort study (International Standard Randomised Controlled Trial Number [ISRCTN] 12962642) at a major trauma center in the United Kingdom. ROTEM was performed on admission and at 24 h with patients retrospectively grouped into three fibrinolysis categories: tissue factor-activated ROTEM maximum lysis of less than 5% (low); tissue factor-activated ROTEM maximum lysis of 5 to 15% (normal); or tissue factor-activated ROTEM maximum lysis of more than 15% (high). Primary outcomes were multiorgan dysfunction syndrome and 28-day mortality. RESULTS: Seven-hundred thirty-one patients were included: 299 (41%) were treated with tranexamic acid and 432 (59%) were untreated. Two different cohorts with low-maximum lysis at 24 h were identified: (1) severe brain injury and (2) admission shock and hemorrhage. Multiple organ dysfunction syndrome was greatest in those with low-maximum lysis on admission and at 24 h, and late mortality was four times higher than in patients who remained normal during the first 24 h (7 of 42 [17%] vs. 9 of 223 [4%]; P = 0.029). Patients that transitioned to or remained in low-maximum lysis had increased odds of organ dysfunction (5.43 [95% CI, 1.43 to 20.61] and 4.85 [95% CI, 1.83 to 12.83], respectively). Tranexamic acid abolished ROTEM hyperfibrinolysis (high) on admission, increased the frequency of persistent low-maximum lysis (67 of 195 [34%]) vs. 8 of 79 [10%]; P = 0.002), and was associated with reduced early mortality (28 of 195 [14%] vs. 23 of 79 [29%]; P = 0.015). No increase in late deaths, regardless of fibrinolysis transition patterns, was observed. CONCLUSIONS: Adverse late outcomes are more closely related to 24-h maximum lysis, irrespective of admission levels. Tranexamic acid alters early fibrinolysis transition patterns, but late mortality in patients with low-maximum lysis at 24 h is not increased.

CHA2DS2-VASc and has-BLED scores do not accurately stratify risk for stroke or bleed in fall victims with atrial fibrillation.

BACKGROUND: Falls are the leading cause of morbidity and mortality in the elderly. Non-valvular Atrial fibrillation (AF) is present in up to 9% of this group and often requires oral anticoagulation (OAC). The CHA2DS2-VASc and HAS-BLED scores are validated tools assessing risk of ischemic stroke from AF and major bleeding (MB) from OAC. It is unclear if these predictions remain accurate in post-fall patients. This study seeks to determine the stroke and major bleeding rate in atrial fibrillation patients after a ground level fall and identify if validated risk scoring systems accurately stratify risk in this cohort. METHODS: Retrospective review of patients with AF presented to the emergency department after a fall. CHA2DS2-VASc and HAS-BLED scores were calculated. Follow up information was reviewed to 1 year. Patients were grouped according to discharge thromboprophylaxis plan (DTP): no treatment, Anti-platelet (AP), OAC, and AP + OAC. Outcomes were ischemic stroke, MB, or death at 1 year. Ischemic stroke and MB rates were calculated. Kruskal-Wallis, Χ2, Fisher's exact, and multivariable logistic regression were used to evaluate for clinical associations. RESULTS: 192 patients were included. MB rate was 14.5 bleeds/100 person-years, and ischemic stroke rate was 10.9/100 person-years. There were no observed differences between DTPs. Overall, one-year mortality was 22.1%. On unadjusted analysis, CHA2DS2-VASc did associate with ischemic stroke (p = 0.03); HAS-BLED did not associate with MB (p = 0.17). After logistic regression accounting for known risk factors, neither system associated with ischemic stroke or MB. CONCLUSIONS: Fall patients are at higher risk for both ischemic stroke and MB compared to previously published reports. Current risk assessment tools should be used with caution. Further study of risk factors is warranted to guide medication decisions in these patients.

TANK prevents IFN-dependent fatal diffuse alveolar hemorrhage by suppressing DNA-cGAS aggregation.

Diffuse alveolar hemorrhage (DAH) is one of the serious complications associated with systemic lupus erythematosus, an autoimmune disease whose pathogenesis involves type I IFNs and cytokines. Here, we show that TANK, a negative regulator of the NF-κB signaling via suppression of TRAF6 ubiquitination, is critical for the amelioration of fatal DAH caused by lung vascular endothelial cell death in a mouse model of systemic lupus erythematosus. The development of fatal DAH in the absence of TANK is mediated by type I IFN signaling, but not IL-6. We further uncover that STING, an adaptor essential for the signaling of cytoplasmic DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS), plays a critical role in DAH under Tank deficiency. TANK controls cGAS-mediated cGAMP production and suppresses DNA-mediated induction of IFN-stimulated genes in macrophages by inhibiting the formation of DNA-cGAS aggregates containing ubiquitin. Collectively, TANK inhibits the cGAS-dependent recognition of cytoplasmic DNA to prevent fatal DAH in the murine lupus model.

Eastern Association for the Surgery of Trauma Multicenter Trial: Comparison of pre-injury antithrombotic use and reversal strategies among severe traumatic brain injury patients.

BACKGROUND: Trauma teams are often faced with patients on antithrombotic (AT) drugs, which is challenging when bleeding occurs. We sought to compare the effects of different AT medications on head injury severity and hypothesized that AT reversal would not improve mortality in severe traumatic brain injury (TBI) patients. METHODS: An Eastern Association for the Surgery of Trauma-sponsored prospective, multicentered, observational study of 15 trauma centers was performed. Patient demographics, injury burden, comorbidities, AT agents, and reversal attempts were collected. Outcomes of interest were head injury severity and in-hospital mortality. RESULTS: Analysis was performed on 2,793 patients. The majority of patients were on aspirin (acetylsalicylic acid [ASA], 46.1%). Patients on a platelet chemoreceptor blocker (P2Y12) had the highest mean Injury Severity Score (9.1 ± 8.1). Patients taking P2Y12 inhibitors ± ASA, and ASA-warfarin had the highest head Abbreviated Injury Scale (AIS) mean (1.2 ± 1.6). On risk-adjusted analysis, warfarin-ASA was associated with a higher head AIS (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.34-4.42) after controlling for Injury Severity Score, Charlson Comorbidity Index, initial Glasgow Coma Scale score, and initial systolic blood pressure. Among patients with severe TBI (head AIS score, ≥3) on antiplatelet therapy, reversal with desmopressin (DDAVP) and/or platelet transfusion did not improve survival (82.9% reversal vs. 90.4% none, p = 0.30). In severe TBI patients taking Xa inhibitors who received prothrombin complex concentrate, survival was not improved (84.6% reversal vs. 84.6% none, p = 0.68). With risk adjustment as described previously, mortality was not improved with reversal attempts (antiplatelet agents: OR 0.83; 85% CI, 0.12-5.9 [p = 0.85]; Xa inhibitors: OR, 0.76; 95% CI, 0.12-4.64; p = 0.77). CONCLUSION: Reversal attempts appear to confer no mortality benefit in severe TBI patients on antiplatelet agents or Xa inhibitors. Combination therapy was associated with severity of head injury among patients taking preinjury AT therapy, with ASA-warfarin possessing the greatest risk. LEVEL OF EVIDENCE: Prognostic, level II.

Preoperative clopidogrel and outcomes in patients with acute coronary syndrome undergoing coronary artery bypass surgery.

OBJECTIVE: The optimal preoperative antiplatelet strategy for patients with acute coronary syndrome (ACS) requiring surgical revascularization remains unclear because of competing risks of bleeding and ischemic events. We evaluated the effect of clopidogrel within 5 days before coronary artery bypass grafting (CABG) on outcomes in patients with ACS. METHODS: Consecutive patients with ACS who underwent isolated CABG at a single center were included in this retrospective study. The primary outcome was a composite of death, myocardial infarction, and stroke within 30 days after surgery. Secondary outcomes were CABG-related major bleeding and perioperative transfusion. Inverse probability weighting using propensity score was performed to evaluate the risk-adjusted effect of preoperative clopidogrel on outcomes. RESULTS: Of 5543 patients with ACS, 820 (14.8%) patients continued clopidogrel within 5 days before CABG. After adjustment for differences in baseline factors, clopidogrel use ≤5 days before CABG was associated with significantly increased odds of the primary composite outcome (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.16-2.29; P = .005), stroke (OR, 3.13; 95% CI, 1.82-5.39; P < .001), major bleeding (OR, 2.01; 95% CI, 1.56-2.58; P < .001), and transfusion (OR, 2.05; 95% CI, 1.82-2.30; P < .001). The effects of preoperative clopidogrel use ≤5 days on primary outcome and major bleeding were greater in patients older than 65 years. CONCLUSIONS: Among patients with ACS undergoing CABG, clopidogrel therapy within 5 days before surgery was associated with increased odds of major cardiac and cerebrovascular events and bleeding complications than discontinuing clopidogrel for >5 days.

Does Gender Matter: A Multi-Institutional Analysis of Viscoelastic Profiles for 1565 Trauma Patients With Severe Hemorrhage.

BACKGROUND: Viscoelastic tests including thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are being used in patients with severe hemorrhage at trauma centers to guide resuscitation. Several recent studies demonstrated hypercoagulability in female trauma patients that was associated with a survival advantage. The objective of our study was to elucidate the effects of gender differences in TEG/ROTEM values on survival in trauma patients with severe hemorrhage. METHODS: A retrospective review of consecutive adult patients receiving massive transfusion protocol (MTP) at 7 Level I trauma centers was performed from 2013 to 2018. Data were stratified by gender and then further examined by TEG or ROTEM parameters. Results were analyzed using univariate and multi-variate analyses. RESULTS: A total of 1565 patients were included with 70.9% male gender (n = 1110/1565). Female trauma patients were older than male patients (43.5 ± .9 vs 41.1 ± .6 years, P = .01). On TEG, females had longer reaction times (6.1 ± .9 min vs 4.8 ± .2 min, P = .03), increased alpha angle (68.6 ± .8 vs 65.7 ± .4, P < .001), and higher maximum amplitude (59.8 ± .8 vs 56.3 ± .4, P < .001). On ROTEM, females had significantly longer clot time (99.2 ± 13.7 vs 75.1 ± 2.6 sec, P = .09) and clot formation time (153.6 ± 10.6 sec vs 106.9 ± 3.8 sec, P < .001). When comparing by gender, no difference for in-hospital mortality was found for patients in the TEG or ROTEM group (P > .05). Multivariate analysis showed no survival difference for female patients (OR 1.11, 95% CI .83-1.50, P = .48). CONCLUSIONS: Although a difference between male and females was found on TEG/ROTEM for certain clotting parameters, no difference in mortality was observed. Prospective multi-institutional studies are needed.

Defining and understanding the "extra-corporeal membrane oxygenation gap" in the veno-venous configuration: Timing and causes of death.

In-hospital mortality of adult veno-venous extracorporeal membrane oxygenation (V-V ECMO) patients remains invariably high. However, little is known regarding timing and causes of in-hospital death, either on-ECMO or after weaning. The current review aims to investigate the timing and causes of death of adult patients during hospital admittance for V-V ECMO, and to define the V-V ECMO gap, which is represented by the patients that are successfully weaned of ECMO but still die during hospital stay. A systematic search was performed using electronic MEDLINE and EMBASE databases through PubMed. Studies reporting on adult V-V ECMO patients from January 2006 to December 2020 were screened. Studies that did not report on at least on-ECMO mortality and discharge rate were excluded from analysis as they could not provide the required information regarding the proposed V-V ECMO-gap. Mortality rates on-ECMO and after weaning, as well as weaning and discharge rates, were analyzed as primary outcomes. Secondary outcomes were the causes of death and complications. Initially, 35 studies were finally included in this review. Merely 24 of these studies (comprising 975 patients) reported on prespecified V-V ECMO outcomes (on-ECMO mortality and discharge rate). Mortality on V-V ECMO support was 27.8% (95% confidence interval (CI) 22.5%-33.2%), whereas mortality after successful weaning was 12.7% (95% CI 8.8%-16.6%, defining the V-V ECMO gap). 72.2% of patients (95% CI 66.8%-77.5%) were weaned successfully from support and 56.8% (95% CI 49.9%-63.8%) of patients were discharged from hospital. The most common causes of death on ECMO were multiple organ failure, bleeding, and sepsis. Most common causes of death after weaning were multiorgan failure and sepsis. Although the majority of patients are weaned successfully from V-V ECMO support, a significant proportion of subjects still die during hospital stay, defining the V-V ECMO gap. Overall, timing and causes of death are poorly reported in current literature. Future studies on V-V ECMO should describe morbidity and mortality outcomes in more detail in relation to the timing of the events, to improve patient management, due to enhanced understanding of the clinical course.

Impact of major bleeding and thrombosis on 180-day survival in patients with severe COVID-19 supported with veno-venous extracorporeal membrane oxygenation in the United Kingdom: a multicentre observational study.

Bleeding and thrombosis are major complications in patients supported with extracorporeal membrane oxygenation (ECMO). In this multicentre observational study of 152 consecutive patients (≥18 years) with severe COVID-19 supported by veno-venous (VV) ECMO in four UK commissioned centres during the first wave of the COVID-19 pandemic (1 March to 31 May 2020), we assessed the incidence of major bleeding and thrombosis and their association with 180-day mortality. Median age (range) was 47 years (23-65) and 75% were male. Overall, the 180-day survival was 70·4% (107/152). The rate of major bleeding was 30·9% (47/152), of which intracranial bleeding (ICH) was 34% (16/47). There were 96 thrombotic events (63·1%) consisting of venous 44·7% [68/152 of which 66·2% were pulmonary embolism (PE)], arterial 18·6% (13/152) and ECMO circuit thrombosis 9·9% (15/152). In multivariate analysis, only raised lactate dehydrogenase (LDH) at the initiation of VV ECMO was associated with an increased risk of thrombosis [hazard ratio (HR) 1·92, 95% CI 1·21-3·03]. Major bleeding and ICH were associated with 3·87-fold (95% CI 2·10-7·23) and 5·97-fold [95% confidence interval (CI) 2·36-15·04] increased risk of mortality and PE with a 2·00-fold (95% CI1·09-3·56) risk of mortality. This highlights the difficult balancing act often encountered when managing coagulopathy in COVID-19 patients supported with ECMO.

Noninfectious complications of hematopoietic cell transplantation.

Noninfectious lung diseases contribute to nonrelapse mortality. They constitute a spectrum of diseases that can affect the parenchyma, airways, or vascular pulmonary components and specifically exclude cardiac and renal causes. The differential diagnoses of these entities differ as a function of time after hematopoietic cell transplantation. Specific diagnosis, prognosis, and optimal treatment remain challenging, although progress has been made in recent decades.