Association of liver dysfunction with outcomes after percutaneous coronary intervention - a systematic review and meta-analysis.

BACKGROUND: Liver dysfunction is a known risk factor in the cardiovascular field. It specifically increases perioperative risk in patients undergoing coronary bypass surgery. Since percutaneous coronary intervention (PCI) is the much less invasive procedure for the treatment of coronary artery disease, we aimed to assess the relationship of liver dysfunction with outcomes in patients undergoing PCI. METHODS: Three libraries were searched (MEDLINE, Web of Science and The Cochrane Library). We performed a meta-analysis of all studies in patients who underwent PCI that provided information on the presence or absence of liver dysfunction. Primary outcome was short-term mortality. Secondary outcomes were major adverse cardio- and cerebrovascular events (MACCE), bleeding and acute kidney injury. Random-effects model was applied. RESULTS: Five studies were selected and the data from 10,710,317 patients were included in the final analysis. In comparison with the absence of liver dysfunction, patients with liver dysfunction were associated with higher short-term mortality (OR 2.97, 95%CI 1.23-7.18, p = 0.02), higher MACCE (OR 1.42, 95%CI 1.08-1.87, p = 0.01), and higher bleeding (OR 2.23, 95%CI 1.65-3.00, p < 0.01). There was no significant difference regarding acute kidney injury (OR 1.20, 95%CI 0.50-2.87, p = 0.69). CONCLUSIONS: The analysis suggests that liver dysfunction in patients undergoing PCI is independently associated with higher risk of short-term mortality and increased occurrence of MACCE and bleeding. However, there appears to be no association to acute kidney injury.

[Acquired hemophilia - quick diagnosis and treatment can significantly reduce the risk of mortality]. / Förvärvad hemofili ­ tidig diagnos och behandling är avgörande.

This case report of a 73-year-old male with bleedings provides insights into the clinical characteristics, diagnosis och treatment of acquired hemophilia A. It's a dangerous non-hereditary bleeding disorder caused by autoantibodies against coagulation factor VIII, often linked with other autoimmune diseases or malignancies, but it is also often idiopathic. The diagnosis remains a challenge due to its rarity and non-specific symtoms, but should be considered in unexplained bleeding cases with prolonged activated partial thromboplastin time (APTT). Quick  diagnosis and treatment can significantly reduce the risk of serious complications and mortality. The long-term prognosis usually depends on the presence of any underlying disease.

Incidence and characteristics of prehospital fatalities from haemorrhage in Sweden: a nationwide observational study.

BACKGROUND: Haemorrhage is a leading cause of preventable mortality in high-income countries and emergency management presents unique challenges in the prehospital setting. The study aimed to determine incidence and characteristics of fatalities from prehospital haemorrhage in Sweden. METHODS: A nationwide retrospective cohort study 2012-2021 was conducted using data from the Swedish National Board of Health and Welfare. Prehospital fatality from haemorrhage was defined as a cause of death related to haemorrhage (Appendix 1) without a hospital admission on the same day. Primary outcome was age-standardized mortality rate per 100,000 inhabitants. RESULTS: A total of 9801 prehospital fatalities from haemorrhage were identified. Annual age-standardized mortality rate decreased from 10.97 to 8.18 per 100,000 population (coefficient = - 0.28, r2 = 0.85, p = < 0.001). Trauma was the most common cause (3512, 35.83%) with intentional self-harm (X60-X84), transport accidents (V01-V99) and assault (X85-Y09) being the most common mechanisms of injury. Traumatic fatalities were younger and a larger proportion were male compared to non-traumatic causes (p < 0.001). Overall median Charlson Comorbidity Index (Quan) was 0 [0-2] with a lower index noted for traumatic causes (p < 0.001). Trauma resulted in a median of 26.1 [3.65-49.22] years of life lost per patient compared to 0 [0-3.65] for non-traumatic causes (p < 0.001). Regional variations in mortality rate were observed with lower population density correlating with higher mortality rate (ρ = - 0.64, p = 0.002). CONCLUSIONS: Prehospital mortality from haemorrhage decreased between 2012 and 2021. Trauma was the most common cause which resulted in many years of life lost in a population with a low burden of comorbidities. There were considerable regional differences with low population density associated with higher mortality rate from prehospital haemorrhage.

Apixaban, edoxaban and rivaroxaban but not dabigatran are associated with higher mortality compared to vitamin-K antagonists: A retrospective German claims data analysis.

BACKGROUND: Vitamin-K antagonists (VKAs) have widely been replaced by non-VKA oral anticoagulants (NOACs). This includes Austria, Germany and Switzerland, where as VKA, instead of warfarin, the much longer-acting phenprocoumon is used, which was not compared to NOACs in clinical trials. METHODS: Using administrative data from a large German health insurance, we included all anticoagulation-naïve patients with a first prescription of a NOAC or VKA between 2012 and 2020. We analysed overall survival, major adverse cardiac and cerebrovascular events, major thromboembolic events and major bleeding. RESULTS: Overall, 570,137 patients were included (apixaban: 26.9%, dabigatran: 4.6%, edoxaban: 8.8%, rivaroxaban: 39.1% and VKA: 20.7% of these 99.4% phenprocoumon). In the primary analysis using a 1:1 propensity score matching-cohort (PSM-cohort), a significantly higher overall mortality was found for apixaban, edoxaban and rivaroxaban (all p < 0.001) but not for dabigatran (p = 0.13) compared to VKA. In this PSM-cohort, 5-year mortality was 22.7% for apixaban versus 12.7% for VKA, 19.5% for edoxaban versus 11.4% for VKA, 16.0% for rivaroxaban versus 12.3% for VKA (all p < 0.001) and 13.0% for dabigatran versus 12.8% for VKA (p = 0.06). The observed effect was confirmed in sensitivity analyses using un-weighted and three different weighted Fine-Gray regression models on the basis of the entire cohort. CONCLUSIONS: In this large real-world analysis, apixaban, edoxaban and rivaroxaban, but not dabigatran, were associated with worse survival compared to VKA. These findings, consistent with a few other studies including phenprocoumon, cast profound doubts on the unreflected, general use of NOACs. Randomized trials should assess whether phenprocoumon might actually be superior to NOACs.

Epidemiology of Diffuse Alveolar Hemorrhage in Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients.

Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary toxicity that can arise after hematopoietic cell transplantation (HCT). Risk factors and outcomes are not well understood owing to a sparsity of cases spread across multiple centers. The objectives of this epidemiologic study were to characterize the incidence, outcomes, transplantation-related risk factors and comorbid critical care diagnoses associated with post-HCT DAH. Retrospective analysis was performed in a multicenter cohort of 6995 patients age ≤21 years who underwent allogeneic HCT between 2008 and 2014 identified through the Center for International Blood and Marrow Transplant Research registry and cross-matched with the Virtual Pediatric Systems database to obtain critical care characteristics. A multivariable Cox proportional hazard model was used to determine risk factors for DAH. Logistic regression models were used to determine critical care diagnoses associated with DAH. Survival outcomes were analyzed using both a landmark approach and Cox regression, with DAH as a time-varying covariate. DAH occurred in 81 patients at a median of 54 days post-HCT (interquartile range, 23 to 160 days), with a 1-year post-transplantation cumulative incidence probability of 1.0% (95% confidence interval [CI], .81% to 1.3%) and was noted in 7.6% of all pediatric intensive care unit patients. Risk factors included receipt of transplantation for nonmalignant hematologic disease (reference: malignant hematologic disease; hazard ratio [HR], 1.98; 95% CI, 1.22 to 3.22; P = .006), use of a calcineurin inhibitor (CNI) plus mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis (referent: CNI plus methotrexate; HR, 1.89; 95% CI, 1.07 to 3.34; P = .029), and grade III-IV acute GVHD (HR, 2.67; 95% CI, 1.53-4.66; P < .001). Critical care admitted patients with DAH had significantly higher rates of systemic hypertension, pulmonary hypertension, pericardial disease, renal failure, and bacterial/viral/fungal infections (P < .05) than those without DAH. From the time of DAH, median survival was 2.2 months, and 1-year overall survival was 26% (95% CI, 17% to 36%). Among all HCT recipients, the development of DAH when considered was associated with a 7-fold increase in unadjusted all-cause post-HCT mortality (HR, 6.96; 95% CI, 5.42 to 8.94; P < .001). In a landmark analysis of patients alive at 2 months post-HCT, patients who developed DAH had a 1-year overall survival of 33% (95% CI, 18% to 49%), compared to 82% (95% CI, 81% to 83%) for patients without DAH (P < .001). Although DAH is rare, it is associated with high mortality in the post-HCT setting. Our data suggest that clinicians should have a heightened index of suspicion of DAH in patients with pulmonary symptoms in the context of nonmalignant hematologic indication for HCT, use of CNI + MMF as GVHD prophylaxis, and severe acute GVHD. Further investigations and validation of modifiable risk factors are warranted given poor outcomes.

Inpatient outcomes of NSTEMI among patients with immune thrombocytopenia: a propensity matched national study.

Patients with immune thrombocytopenia (ITP) admitted for non-ST elevation myocardial infarction (NSTEMI) present a unique therapeutic challenge due to the increased risk of bleeding with antiplatelet and anticoagulation therapies. There is limited evidence studying hospital mortality and complications in this population. The study included a patient cohort from the 2018-2021 National Inpatient Sample database. Propensity score matched NSTEMI patients with and without ITP using a 1:1 matching ratio. Outcomes analyzed were in-hospital mortality, rates of diagnostic angiogram, percutaneous coronary intervention (PCI), acute kidney injury (AKI), congestive heart failure (CHF), cardiogenic shock, cardiac arrest, mechanical ventilation, tracheal intubation, ventricular tachycardia (VT), ventricular fibrillation (VF), major bleeding, need for blood and platelet transfusion, length of stay (LOS), and total hospitalization charges. A total of 1,699,020 patients met inclusion criteria (660,490 females [39%], predominantly Caucasian 1,198,415 (70.5%); mean [SD] age 67, [3.1], including 2,615 (0.1%) patients with ITP. Following the propensity matching, 1,020 NSTEMI patients with and without ITP were matched. ITP patients had higher rates of inpatient mortality (aOR 1.98, 95% CI 1.11-3.50, p 0.02), cardiogenic shock, AKI, mechanical ventilation, tracheal intubation, red blood cells and platelet transfusions, longer LOS, and higher total hospitalization charges. The rates of diagnostic angiogram, PCI, CHF, VT, VF, and major bleeding were not different between the two groups. Patients with ITP demonstrated higher odds of in-hospital mortality for NSTEMI and need for platelet transfusion with no difference in rates of diagnostic angiogram or PCI.

Analysis of early death in critically ill patients with acute promyelocytic leukaemia in the HICU.

This study was conducted to identify the characteristics and risk factors for early death in critically ill acute promyelocytic leukaemia (APL) patients in the Hemato-oncology ICU (HICU). A total of 44 APL patients from 2017 to 2023 were included. The mortality among APL patients in the HICU was high (27/44, 61.36%). Compared with patients who survived, nonsurvivors had a longer prothrombin time (P = 0.002), lower fibrinogen (P = 0.022), higher white blood cell count (P = 0.004) and higher creatinine (P = 0.037) on hosipital admission. Severe bleeding was the most frequent complication (34 cases, 77.27%), which occurred either preinduction or on Day 5 (IQR 3-7.5 days) of induction. Cerebral bleeding associated with consciousness disturbance was the main reason for HICU admission (18 cases, 40.9%). The leading cause of death was fatal haemorrhage (18/34, 52.94%), which occurred either preinduction or on Day 4 (IQR 3-7 days) of induction. Another common cause of death was sepsis (8/18, 44.44%), which occurred on Day 12 (IQR 9.5-24.75 days) during induction. In conclusion, the main cause of death in APL patients treated in the HICU was primary being attributed to fatal bleeding, followed by sepsis.

Retroperitoneal and lower extremities muscle bleeding in acquired haemophilia A (AHA): Risk factors and implications in disability and survival.

AIM: To assess risk factors of retroperitoneal and lower extremity musculoskeletal bleed in acquired haemophilia (AHA) and perform an objective assessment of disability and influence on survival. METHODS: We included 49 patients with AHA from November 2017 to May 2023. The occurrence of any retroperitoneal or/and lower extremities bleeding manifestation was investigated. On clinical follow-up, we search for compressive femoral neuropathy and quadriceps amyotrophy. The lower extremity functional scale (LEFS) was carried out one year after the last bleeding event in all AHA patients. RESULTS: A 61.2% of patients in our AHA cohort presented with any retroperitoneal and/or lower extremities musculoskeletal manifestation. Those patients had higher percentage of major bleeding EACH2/ISTH criteria (90% vs. 57%, p = .01), needs of blood transfusions (86% vs. 57% of patients, p = .03), and haemostatic by-pass products (90% vs. 63%, p = .02). Hypertension (HR 2.6, 95% CI 1.1-5.9, p = .02), presence of autoimmune disease (HR 13, 95% CI 1.7-99, p = .01), and inhibitor level > 20 BU (HR 2.6 95% CI 1.0-6.8, p = .04) significantly predicted retroperitoneal/lower extremities clinical manifestations. Most frequent sequelae were quad atrophy (30.6%) and femoral nerve palsy (20.4%). Quad atrophy and LEFS scores under 50 were associated with increased mortality (HR 3, 95% CI 1.1-8.6 and HR 12, 95% CI 3.3-45, respectively). CONCLUSION: AHA with retroperitoneal/lower extremities bleeding involvement is of greater severity and shows high disability and worst survival outcomes. Quadriceps atrophy and LEFS scale scoring under 50 predicted mortality in our AHA patients.

Life-threatening hemorrhage as defined by the critical administration threshold in nontraumatic critical bleeding: A descriptive observational study.

BACKGROUND: Evaluations of critical bleeding and massive transfusion have focused on traumatic hemorrhage. However, most critical bleeding in hospitalized patients occurs outside trauma. The purpose of this study was to provide an in-depth description examining the critical administration threshold (CAT; ≥3 units red blood cells (RBCs) in a 1-h period) occurrences in nontraumatic hemorrhage. This will assist in establishing the framework for future investigations in nontraumatic hemorrhage. METHODS: This is an observational cohort study of adults experiencing critical bleeding defined as being CAT+ during hospitalization from 2016 to 2021 at a single academic institution. A CAT episode started with administration of the first qualifying RBC unit and ended at the time of completion of the last allogeneic unit prior to a ≥4-h gap without subsequent transfusion. The primary goal was to describe demographic, clinical and transfusion characteristics of participants with nontraumatic critical bleeding. RESULTS: 2433 patients suffered critical bleeding, most often occurring in the operating room (71.1%) followed by the intensive care unit (20.8%). 57% occurred on the initial day of hospitalization, with a median duration of 138 (36, 303) minutes. The median number of RBCs transfused during the episode was 5 (4, 8), with median total allogeneic units of 9 (4, 9). Hospital mortality was 19.2%. The most common cause of death was multi-organ failure (50.3%), however death within 24 h was due to exsanguination (72.7%). DISCUSSION: The critical administration threshold may be employed to identify critical bleeding in non-trauma settings of life-threatening hemorrhage, with a mortality rate of approximately 20%.

Comparative analysis of COVID-19-associated venous thromboembolism outcomes: evolution from 2020 to 2021-2022.

Patients with COVID-19 are at an increased risk for venous thromboembolism (VTE). With the advent of vaccinations and novel treatments from 2020 through 2022, the landscape of COVID-19 has evolved. Notably, the effects of such interventions on the outcomes of COVID-19-associated VTE have not been thoroughly examined. Data from the RIETE registry were analyzed to evaluate 90-day VTE-related outcomes (all-cause mortality, major bleeding, and VTE recurrences) in patients with COVID-19-associated VTE. We compared the periods before and after the widespread introduction of COVID-19 vaccines: March to December 2020 (pre-vaccine period) and March 2021 to December 2022 (post-vaccine period). Statistical analysis included mixed-effects parametric survival-time models. Among 1,620 patients with COVID-19-associated VTE, most (74.1%) were identified during 2020 period. The analysis revealed a more than two-fold increase in the risk of death within 90 days (adjusted hazard ratio [HR]: 2.27; 95% confidence interval, CI: 1.18-4.38) and major bleeding (adjusted HR: 2.91; 95%CI: 1.08-7.84) for patients from the 2020 period compared to those from the 2021-2022 period. Inpatient subgroup analysis confirmed the observed mortality differences. The frequency of recurrent VTE was low (1.1 vs. 0.7%, respectively), and did not show significant variation between the two periods. Our research provides a comparative perspective on the clinical outcomes of COVID-19-associated VTE before and after the introduction of vaccines. Our findings reveal a significant decrease in the incidence of 90-day mortality and major bleeding in patients with COVID-19-associated VTE in the 2021-2022 period.

Increasing the Threshold to Perform Preperitoneal Pelvic Packing Decreases Morbidity Without Affecting Mortality.

OBJECTIVES: To determine the effectiveness of an updated protocol that increased the transfusion threshold to perform preperitoneal pelvic packing in patients with pelvic ring injuries and hemodynamic instability (HDI). DESIGN: Retrospective review. SETTING: Urban level 1 trauma center. PATIENTS SELECTION CRITERIA: Severely injured (injury severity score > 15) patients with pelvic ring injuries treated before and after increasing the threshold to perform preperitoneal pelvic packing from 2 to 4 units of red blood cells (RBCs). HDI was defined as a systolic blood pressure <90 mm Hg. OUTCOME MEASURES AND COMPARISONS: Mortality from hemorrhage, anterior pelvic space infections, and venous thromboembolisms before and after increasing preperitoneal pelvic packing threshold. RESULTS: One hundred sixty-six patients were included: 93 treated under the historical protocol and 73 treated under the updated protocol. HDI was present in 46.2% (n = 43) of the historical protocol group and 49.3% (n = 36) of the updated protocol group (P = 0.69). The median age of patients with HDI was 35.0 years (interquartile range 26.0-52.0), 74.7% (n = 59) were men, and the median injury severity score was 41.0 (interquartile range 29.0-50.0). Patients with HDI in the updated protocol group had a lower heart rate on presentation (105.0 vs. 120.0; P = 0.004), required less units of RBCs over the first 24 hours (6.0 vs. 8.0, P = 0.03), and did not differ in age, injury severity score, systolic blood pressure on arrival, base deficit or lactate on arrival, resuscitative endovascular balloon occlusion of the aorta, resuscitative thoracotomy, angioembolization, or anterior pelvis open reduction internal fixation (P > 0.05). The number of PPPs performed decreased under the new protocol (8.3% vs. 65.1%, P < 0.0001), and there were fewer anterior pelvic infections (0.0% vs. 13.9%, P = 0.02), fewer VTEs (8.3% vs. 30.2%; P = 0.02), and no difference in deaths from acute hemorrhagic shock (5.6% vs. 7.0%, P = 1.00). CONCLUSIONS: Increasing the transfusion threshold from 2 to 4 units of red blood cells to perform pelvic packing in severely injured patients with pelvic ring injuries decreased anterior pelvic space infections and venous thromboembolisms without affecting deaths from acute hemorrhage. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Deaths and major cardiovascular events in patients with lymphoma: Analysis from a French nationwide hospitalization database.

BACKGROUND: There are few data assessing the risk of death and cardiovascular events in patients with lymphoma. AIM: Using a nationwide hospitalization database, we aimed to address cardiovascular outcomes in patients with lymphoma. METHODS: From 01 January to 31 December 2013, 3,381,472 adults were hospitalized in French hospitals; 22,544 of these patients had a lymphoma. The outcome analysis (all-cause or cardiovascular death, myocardial infarction, ischaemic stroke, bleedings, new-onset heart failure and new-onset atrial fibrillation) was performed over a 5-year follow-up period. Each patient with lymphoma was matched with a patient without a lymphoma or other cancer (1:1). A competing risk analysis was also performed. RESULTS: After adjustment on all risk factors, cardiovascular and non-cardiovascular co-morbidities, the subdistribution hazard ratios for all-cause death, major bleeding, intracranial bleeding, new-onset heart failure and new-onset atrial fibrillation were higher in patients with lymphoma; conversely, the subdistribution hazard ratios for cardiovascular death, myocardial infarction and ischaemic stroke were lower in patients with lymphoma. In the matched analysis, the risk of all-cause death (subdistribution hazard ratio 1.936, 95% confidence interval 1.881-1.992) and major bleeding (subdistribution hazard ratio 1.117, 95% confidence interval 1.049-1.188) remained higher in patients with lymphoma. CONCLUSION: In this large nationwide cohort study, patients with lymphoma had a higher incidence of all-cause death and major bleeding.

Preperitoneal pelvic packing in isolated severe pelvic fractures is associated with higher mortality and venous thromboembolism: A matched-cohort study.

INTRODUCTION: Preperitoneal pelvic packing (PPP) has been advocated as a damage control procedure for pelvic fracture bleeding, despite of weak evidence. METHODS: Matched cohort study, TQIP database. Patients with isolated severe blunt pelvic fractures (pelvis abbreviated injury score [AIS] â€‹≥ â€‹3, AIS ≤2 in all other body regions) were included. Patients who underwent PPP were matched to patients with no PPP, 1:3 nearest propensity score. Matching was performed based on demographics, vital signs on admission, comorbidities, injury characteristics, type and timing of initiation of VTE prophylaxis, and additional procedures including laparotomy, REBOA, and angioembolization. RESULTS: 64 patients with PPP were matched with 182 patients with No-PPP. PPP patients had higher in-hospital mortality (14.1 â€‹% vs 2.2 â€‹% p â€‹< â€‹0.001) and higher rates of VTE and DVT (VTE: 14.1 â€‹% vs 4.4 â€‹% p â€‹= â€‹0.018, DVT: 10.9 â€‹% vs 2.2 â€‹% p â€‹= â€‹0.008). CONCLUSION: PPP is associated with worse survival outcomes and increased rate of VTE and DVT complications.

Use of resuscitative endovascular balloon occlusion of the aorta (REBOA) for trauma and its performance in Japan over the past 18 years: a nationwide descriptive study.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been used to control massive hemorrhages. Although there is no consensus on the efficacy of REBOA, it remains an option as a bridging therapy in non-trauma centers where trauma surgeons are not available. To better understand the current landscape of REBOA application, we examined changes in its usage, target population, and treatment outcomes in Japan, where immediate hemostasis procedures sometimes cannot be performed. METHODS: This retrospective observational study used the Japan Trauma Data Bank data. All cases in which REBOA was performed between January 2004 and December 2021 were included. The primary outcome was the in-hospital mortality rate. We analyzed mortality trends over time according to the number of cases, number of centers, severity of injury, and overall and subgroup mortality associated with REBOA usage. We performed a logistic analysis of mortality trends over time, adjusting for probability of survival based on the trauma and injury severity score. RESULTS: Overall, 2557 patients were treated with REBOA and were deemed eligible for inclusion. The median age of the participants was 55 years, and male patients constituted 65.3% of the study population. Blunt trauma accounted for approximately 93.0% of the cases. The number of cases and facilities that used REBOA increased until 2019. While the injury severity score and revised trauma score did not change throughout the observation period, the hospital mortality rate decreased from 91.3 to 50.9%. The REBOA group without severe head or spine injuries showed greater improvement in mortality than the all-patient group using REBOA and all-trauma patient group. The greatest improvement in mortality was observed in patients with systolic blood pressure ≥ 80 mmHg. The adjusted odds ratios for hospital mortality steadily declined, even after adjusting for the probability of survival. CONCLUSIONS: While there was no significant change in patient severity, mortality of patients treated with REBOA decreased over time. Further research is required to determine the reasons for these improvements in trauma care.

Causes of death in patients with atrial fibrillation anticoagulated with rivaroxaban: a pooled analysis of XANTUS.

AIMS: Anticoagulation can prevent stroke and prolong lives in patients with atrial fibrillation (AF). However, anticoagulated patients with AF remain at risk of death. The aim of this study was to investigate the causes of death and factors associated with all-cause and cardiovascular death in the XANTUS population. METHODS AND RESULTS: Causes of death occurring within a year after rivaroxaban initiation in patients in the XANTUS programme studies were adjudicated by a central adjudication committee and classified following international guidance. Baseline characteristics associated with all-cause or cardiovascular death were identified. Of 11 040 patients, 187 (1.7%) died. Almost half of these deaths were due to cardiovascular causes other than bleeding (n = 82, 43.9%), particularly heart failure (n = 38, 20.3%) and sudden or unwitnessed death (n = 24, 12.8%). Fatal stroke (n = 8, 4.3%), which was classified as a type of cardiovascular death, and fatal bleeding (n = 17, 9.1%) were less common causes of death. Independent factors associated with all-cause or cardiovascular death included age, AF type, body mass index, left ventricular ejection fraction, hospitalization at baseline, rivaroxaban dose, and anaemia. CONCLUSION: The overall risk of death due to stroke or bleeding was low in XANTUS. Anticoagulated patients with AF remain at risk of death due to heart failure and sudden death. Potential interventions to reduce cardiovascular deaths in anticoagulated patients with AF require further investigation, e.g. early rhythm control therapy and AF ablation. TRIAL REGISTRATION NUMBERS: NCT01606995, NCT01750788, NCT01800006.

Development of a two-hit lethal liver injury model in swine.

PURPOSE: Noncompressible truncal hemorrhage remains a leading cause of preventable death in the prehospital setting. Standardized and reproducible large animal models are essential to test new therapeutic strategies. However, existing injury models vary significantly in consistency and clinical accuracy. This study aims to develop a lethal porcine model to test hemostatic agents targeting noncompressible abdominal hemorrhages. METHODS: We developed a two-hit injury model in Yorkshire swine, consisting of a grade IV liver injury combined with hemodilution. The hemodilution was induced by controlled exsanguination of 30% of the total blood volume and a 3:1 resuscitation with crystalloids. Subsequently, a grade IV liver injury was performed by sharp transection of both median lobes of the liver, resulting in major bleeding and severe hypotension. The abdominal incision was closed within 60 s from the injury. The endpoints included mortality, survival time, serum lab values, and blood loss within the abdomen. RESULTS: This model was lethal in all animals (5/5), with a mean survival time of 24.4 ± 3.8 min. The standardized liver resection was uniform at 14.4 ± 2.1% of the total liver weight. Following the injury, the MAP dropped by 27 ± 8mmHg within the first 10 min. The use of a mixed injury model (i.e., open injury, closed hemorrhage) was instrumental in creating a standardized injury while allowing for a clinically significant hemorrhage. CONCLUSION: This novel highly lethal, consistent, and clinically relevant translational model can be used to test and develop life-saving interventions for massive noncompressible abdominal hemorrhage.

Every minute matters: Improving outcomes for penetrating trauma through prehospital advanced resuscitative care.

BACKGROUND: Prehospital resuscitation with blood products is gaining popularity for patients with traumatic hemorrhage. The MEDEVAC trial demonstrated a survival benefit exclusively among patients who received blood or plasma within 15 minutes of air medical evacuation. In fast-paced urban EMS systems with a high incidence of penetrating trauma, mortality data based on the timing to first blood administration is scarce. We hypothesize a survival benefit in patients with severe hemorrhage when blood is administered within the first 15 minutes of EMS patient contact. METHODS: This was a retrospective analysis of a prospective database of prehospital blood (PHB) administration between 2021 and 2023 in an urban EMS system facing increasing rates of gun violence. Prehospital blood patients were compared with trauma registry controls from an era before prehospital blood utilization (2016-2019). Included were patients with penetrating injury and SBP ≤ 90 mm Hg at initial EMS evaluation that received at least one unit of blood product after injury. Excluded were isolated head trauma or prehospital cardiac arrest. Time to initiation of blood administration before and after PHB implementation and in-hospital mortality were the primary variables of interest. RESULTS: A total of 143 patients (PHB = 61, controls = 82) were included for analysis. Median age was 34 years with no difference in demographics. Median scene and transport intervals were longer in the PHB cohort, with a 5-minute increase in total prehospital time. Time to administration of first unit of blood was significantly lower in the PHB vs. control group (8 min vs. 27 min; p < 0.01). In-hospital mortality was lower in the PHB vs. control group (7% vs. 29%; p < 0.01). When controlling for patient age, NISS, tachycardia on EMS evaluation, and total prehospital time interval, multivariate regression revealed an independent increase in mortality by 11% with each minute delay to blood administration following injury (OR 1.11, 95%CI 1.04-1.19). CONCLUSION: Compared with patients with penetrating trauma and hypotension who first received blood after hospital arrival, resuscitation with blood products was started 19 minutes earlier after initiation of a PHB program despite a 5-minute increase in prehospital time. A survival for early PHB use was demonstrated, with an 11% mortality increase for each minute delay to blood administration. Interventions such as PHB may improve patient outcomes by helping capture opportunities to improve trauma resuscitation closer to the point of injury. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Bleeding and Thrombosis in Patients With Out-of-Hospital Ventricular Tachycardia/Ventricular Fibrillation Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation improves outcomes after out-of-hospital cardiac arrest. However, bleeding and thrombosis are common complications. We aimed to describe the incidence and predictors of bleeding and thrombosis and their association with in-hospital mortality. METHODS AND RESULTS: Consecutive patients presenting with refractory ventricular tachycardia/ventricular fibrillation out-of-hospital cardiac arrest between December 2015 and March 2022 who met the criteria for extracorporeal cardiopulmonary resuscitation initiation at our center were included. Major bleeding was defined by the Extracorporeal Life Support Organization's criteria. Adjusted analyses were done to seek out risk factors for bleeding and thrombosis and evaluate their association with mortality. Major bleeding occurred in 135 of 200 patients (67.5%), with traumatic bleeding from cardiopulmonary resuscitation in 73 (36.5%). Baseline demographics and arrest characteristics were similar between groups. In multivariable analysis, decreasing levels of fibrinogen were independently associated with bleeding (adjusted hazard ratio [aHR], 0.98 per every 10 mg/dL rise [95% CI, 0.96-0.99]). Patients who died had a higher rate of bleeds per day (0.21 versus 0.03, P<0.001) though bleeding was not significantly associated with in-hospital death (aHR, 0.81 [95% CI. 0.55-1.19]). A thrombotic event occurred in 23.5% (47/200) of patients. Venous thromboembolism occurred in 11% (22/200) and arterial thrombi in 15.5% (31/200). Clinical characteristics were comparable between groups. In adjusted analyses, no risk factors for thrombosis were identified. Thrombosis was not associated with in-hospital death (aHR, 0.65 [95% CI, 0.42-1.03]). CONCLUSIONS: Bleeding is a frequent complication of extracorporeal cardiopulmonary resuscitation that is associated with decreased fibrinogen levels on admission whereas thrombosis is less common. Neither bleeding nor thrombosis was significantly associated with in-hospital mortality.

Self-Administration of Aspirin After Chest Pain for the Prevention of Premature Cardiovascular Mortality in the United States: A Population-Based Analysis.

BACKGROUND: Aspirin, an effective, low-cost pharmaceutical, can significantly reduce mortality if used promptly after acute myocardial infarction (AMI). However, many AMI survivors do not receive aspirin within a few hours of symptom onset. Our aim was to quantify the mortality benefit of self-administering aspirin at chest pain onset, considering the increased risk of bleeding and costs associated with widespread use. METHODS AND RESULTS: We developed a population simulation model to determine the impact of self-administering 325 mg aspirin within 4 hours of severe chest pain onset. We created a synthetic cohort of adults ≥ 40 years old experiencing severe chest pain using 2019 US population estimates, AMI incidence, and sensitivity/specificity of chest pain for AMI. The number of annual deaths delayed was estimated using evidence from a large, randomized trial. We also estimated the years of life saved (YOLS), costs, and cost per YOLS. Initiating aspirin within 4 hours of severe chest pain onset delayed 13 016 (95% CI, 11 643-14 574) deaths annually, after accounting for deaths due to bleeding (963; 926-1003). This translated to an estimated 166 309 YOLS (149391-185 505) at the cost of $643 235 (633 944-653 010) per year, leading to a cost-effectiveness ratio of $3.70 (3.32-4.12) per YOLS. CONCLUSIONS: For <$4 per YOLS, self-administration of aspirin within 4 hours of severe chest pain onset has the potential to save 13 000 lives per year in the US population. Benefits of reducing deaths post-AMI outweighed the risk of bleeding deaths from aspirin 10 times over.

[Cause of Death after Severe Trauma: 30 Years Experience from TraumaRegister DGU]. / Woran stirbt der schwerverletzte Patient: eine Analyse aus 30 Jahren TraumaRegister DGU.

Every year, thousands of people in Germany succumb to severe injuries. But what causes the death of these patients? In addition to the trauma, pre-traumatic health status, age, and other influencing factors play a role in the outcome after trauma. This study aims to answer the question of what causes the death of a severely injured patient.For this publication, in addition to previously published results, we examined current data from patients in German hospitals from the years 2015-2022 (8 years) documented in the TraumaRegister DGU®. The feature "Presumed Cause of Death", introduced in 2015, was considered. Patients transferred out early (< 48 h) as well as patients with minor injuries were excluded from this analysis.The number of fatalities decreases over time and does not correspond to a traditionally postulated tri-modal mortality distribution. Instead, over time, the distribution of causes of death shows significant variation. In over half of the cases (54%), traumatic brain injury (TBI) was the presumed cause of death, followed by organ failure (24%) and haemorrhage (9%). TBI dominates, especially in the first week, haemorrhage in the first 24 h, and organ failure as a cause steadily increases over time.In summary, it can be observed that the risk of death due to trauma-related consequences is highest in the first minutes, hours, and days, decreasing steadily over time. Particularly, the extent of injuries, head injuries, and significant blood loss are early risk factors.