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Objectives: The authors evaluated the outcome of adult patients with coronavirus disease 2019 (COVID-19)–related acute respiratory distress syndrome (ARDS) requiring the use of extracorporeal membrane oxygenation (ECMO). Design: Multicenter retrospective, observational study. Setting: Ten tertiary referral university and community hospitals. Participants: Patients with confirmed severe COVID-19–related ARDS. Interventions: Venovenous or venoarterial ECMO. Measurements and Main Results: One hundred thirty-two patients (mean age 51.1 ± 9.7 years, female 17.4%) were treated with ECMO for confirmed severe COVID-19–related ARDS. Before ECMO, the mean Sequential Organ Failure Assessment score was 10.1 ± 4.4, mean pH was 7.23 ± 0.09, and mean PaO₂/fraction of inspired oxygen ratio was 77 ± 50 mmHg. Venovenous ECMO was adopted in 122 patients (92.4%) and venoarterial ECMO in ten patients (7.6%) (mean duration, 14.6 ± 11.0 days). Sixty-three (47.7%) patients died on ECMO and 70 (53.0%) during the index hospitalization. Six-month all-cause mortality was 53.0%. Advanced age (per year, hazard ratio [HR] 1.026, 95% CI 1.000–1–052) and low arterial pH (per unit, HR 0.006, 95% CI 0.000–0.083) before ECMO were the only baseline variables associated with increased risk of six-month mortality. Conclusions: The present findings suggested that about half of adult patients with severe COVID-19–related ARDS can be managed successfully with ECMO with sustained results at six months. Decreased arterial pH before ECMO was associated significantly with early mortality. Therefore, the authors hypothesized that initiation of ECMO therapy before severe metabolic derangements subset may improve survival rates significantly in these patients. These results should be viewed in the light of a strict patient selection policy and may not be replicated in patients with advanced age or multiple comorbidities. Clinical Trial Registration: identifier, NCT04383678.

Objectives: The aim of this study was to identify the risk factors associated with early mortality after postcardiotomy venoarterial extracorporeal membrane oxygenation. Methods: This is an analysis of the postcardiotomy extracorporeal membrane oxygenation registry, a retrospective multicenter cohort study including 781 patients aged more than 18 years who required venoarterial extracorporeal membrane oxygenation for cardiopulmonary failure after cardiac surgery from 2010 to 2018 at 19 cardiac surgery centers. Results: After a mean venoarterial extracorporeal membrane oxygenation therapy of 6.9 ± 6.2 days, hospital and 1–year mortality were 64.4% and 67.2%, respectively. Hospital mortality after venoarterial extracorporeal membrane oxygenation therapy for more than 7 days was 60.5% (P = 0.105). Centers that had treated more than 50 patients with postcardiotomy venoarterial extracorporeal membrane oxygenation had a significantly lower hospital mortality than lower–volume centers (60.7% vs 70.7%, adjusted odds ratio, 0.58; 95% confidence interval, 0.41–0.82). The postcardiotomy extracorporeal membrane oxygenation score was derived by assigning a weighted integer to each independent pre–venoarterial extracorporeal membrane oxygenation predictors of hospital mortality as follows: female gender (1 point), advanced age (60–69 years, 2 points; ≥70 years, 4 points), prior cardiac surgery (1 point), arterial lactate 6.0 mmol/L or greater before venoarterial extracorporeal membrane oxygenation (2 points), aortic arch surgery (4 points), and preoperative stroke/unconsciousness (5 points). The hospital mortality rates according to the postcardiotomy extracorporeal membrane oxygenation score was 0 point, 45.6%; 1 point, 40.5%; 2 points, 51.1%; 3 points, 57.8%; 4 points, 70.7%; 5 points, 68.3%; 6 points, 77.5%; and 7 points or more, 89.7% (P < 0.0001). Conclusions: Age, female gender, prior cardiac surgery, preoperative acute neurologic events, aortic arch surgery, an, PC-ECMO Study Group Collaborators of the PC-ECMO Study Group: Kristiina Pälve, MD, PhD, Vesa Anttila, MD, PhD, MD, Thomas Fux, MD, PhD, Gilles Amr, MD, Nikolaos Kalampokas, MD, Artur Lichtenberg, MD, Anders Jeppsson, MD, PhD, Marco Gabrielli, MD, Daniel Reichart, MD, Sidney Chocron, MD, PhD, Mariafrancesca Fiorentino, MD, Ugolino Livi, MD, Ivan Netuka, MD, Dieter De Keyzer, MD, Krister Mogianos, MD, Zein El Dean, MRCS, LLM, Angelo M. Dell’Aquila, MD, Nicla Settembre, MD, PhD, and Stefano Rosato, MSc.

The impact of thrombocytopenia on postoperative bleeding and other major adverse events after cardiac surgery is unclear. This issue was investigated in a series of patients who underwent isolated coronary artery bypass grafting (CABG) from the prospective, multicenter E-CABG registry. Preoperative thrombocytopenia was defined as preoperative platelet count <150 × 10⁹/L and it was considered moderate-severe when preoperative platelet count was <100 × 10⁹/L. Multilevel mixed-effects regression analysis was performed to adjust the effect of thrombocytopenia on outcomes for baseline and operative covariates as well as for interinstitutional differences in patient-blood management. Among 7189 patients included in this analysis, 599 (8.3%) had preoperative thrombocytopenia. Patient with preoperative thrombocytopenia had an increased chest drainage output at 12 h (mean, 519 vs. 456 mL, adjusted coeff. 39, 95%CI 18–60) and rates of severe-massive bleeding (Universal Definition of Perioperative Bleeding (UDPB) severity grades 3–4: 12.7% vs. 8.1%, adjusted OR 1.47, 95%CI 1.11–1.93; E-CABG bleeding severity grades 2–3: 10.4% vs. 6.1%, adjusted OR 1.78, 95%CI 1.30–2.43). Thrombocytopenia was associated with an increased risk of hospital/30-day death (3.2% vs. 1.9%, adjusted OR 2.02, 95%CI 1.20–3.42), 1-year death (5.7% vs. 3.4%, adjusted HR 1.68, 95%CI 1.16–2.44), deep sternal wound infection (3.5% vs. 2.4%, adjusted OR 1.65, 95%CI 1.02–2.66), acute kidney injury (28.1% vs. 22.2%, OR 1.45, 1.18–1.78), and prolonged stay in the intensive care unit (mean, 3.6 vs 2.8 days, adjusted coeff. 0.74, 95%CI 0.40–1.09). Similar results were observed in a subset of patients with moderate-severe thrombocytopenia (51 patients, 0.7%). In particular, these patients had a markedly higher rate of acute kidney injury (40%, adjusted OR, 1.94, 95%CI 1.05–3.57), resternotomy for bleeding (7.8%, adjusted OR 3.49, 95%CI 1.20–10.21), and severe-massive bleeding (UDPB severity grades 3–4

Background: We evaluated perioperative bleeding after coronary artery bypass grafting (CABG) in patients preoperatively treated with ticagrelor or clopidogrel, stratified by discontinuation of these P2Y₁₂ inhibitors. Methods: All patients from the prospective, European Multicenter Registry on Coronary Artery Bypass Grafting (E-CABG) treated with ticagrelor or clopidogrel undergoing isolated primary CABG were eligible. The primary outcome measure was severe or massive bleeding defined according to the Universal Definition of Perioperative Bleeding, stratified by P2Y₁₂ inhibitor discontinuation. Secondary outcome measures included four additional definitions of major bleeding. Propensity score matching was performed to adjust for differences in preoperative and perioperative covariates. Results: Of 2,311 patients who were included, 1,293 (55.9%) received clopidogrel and 1,018 (44.1%) ticagrelor preoperatively. Mean time between discontinuation and the operation was 4.5 ± 3.2 days for clopidogrel and 4.9 ± 3.0 days for ticagrelor. In the propensity score–matched cohort, ticagrelor-treated patients had a higher incidence of major bleeding according to Universal Definition of Perioperative Bleeding when ticagrelor was discontinued 0 to 2 days compared with 3 days before the operation (16.0% vs 2.7%, p = 0.003). Clopidogrel-treated patients had a higher incidence of major bleeding according to the Universal Definition of Perioperative Bleeding when clopidogrel was discontinued 0 to 3 days compared with 4 to 5 days before the operation (15.6% vs 8.3%, p = 0.031). Conclusions: In patients receiving ticagrelor 2 days before CABG and in those receiving clopidogrel 3 days before CABG, there was an increased rate of severe bleeding. Postponing nonemergent CABG for at least 3 days after discontinuation of ticagrelor and 4 days after clopidogrel should be considered.

Background: There is uncertainty whether venoarterial extracorporeal membrane oxygenation (VA-ECMO) should be used in older patients with cardiopulmonary failure after cardiac surgery. Methods: This was a retrospective multicenter study of 781 patients who required postcardiotomy VA-ECMO for cardiopulmonary failure after adult cardiac surgery from 2010 to 2018 at 19 cardiac surgery centers. A parallel systematic review with meta-analysis of the literature was performed. Results: The hospital mortality in the overall Postcardiotomy Venoarterial Extracorporeal Membrane Oxygenation (PC-ECMO) series was 64.4%. A total of 255 patients were 70 years old or older (32.7%), and their hospital mortality was significantly higher than in younger patients (76.1% vs 58.7%; adjusted odds ratio, 2.199; 95% confidence interval [CI], 1.536 to 3.149). Arterial lactate level greater than 6 mmol/L before starting VA-ECMO was the only predictor of hospital mortality among patients 70 years old or older in univariate analysis (82.6% vs 70.4%; P = 0.029). Meta-analysis of current and previous studies showed that early mortality after postcardiotomy VA-ECMO was significantly higher in patients aged 70 years or older compared with younger patients (odds ratio, 2.09; 95% CI, 1.59 to 2.75; 5 studies including 1547 patients; I², 5.9%). The pooled early mortality rate among patients aged 70 years or older was 78.8% (95% CI, 74.1 to 83.5; 6 studies including 617 patients; I², 41.8%). Two studies reported 1-year mortality (including hospital mortality) of 79.9% and 75.6%, respectively, in patients 70 years old or older. Conclusions: Advanced age should not be considered a contraindication for postcardiotomy VA-ECMO. However, in view of the high risk of early mortality, meaningful scrutiny is needed before using VA-ECMO after cardiac surgery in older patients.

Background: The outcome after weaning from postcardiotomy venoarterial extracorporeal membrane oxygenation (VA-ECMO) is poor. In this study, we investigated the prognostic impact of arterial lactate levels at the time of weaning from postcardiotomy VA. Methods: This analysis included 338 patients from the multicenter PC-ECMO registry with available data on arterial lactate levels at weaning from VA-ECMO. Results: Arterial lactate levels at weaning from VA-ECMO (adjusted OR 1.426, 95%CI 1.157–1.758) was an independent predictor of hospital mortality, and its best cutoff values was 1.6 mmol/L (<1.6 mmol/L, 26.2% vs. ≥ 1.6 mmol/L, 45.0%; adjusted OR 2.489, 95%CI 1.374–4.505). When 261 patients with arterial lactate at VA-ECMO weaning ≤2.0 mmol/L were analyzed, a cutoff of arterial lactate of 1.4 mmol/L for prediction of hospital mortality was identified (<1.4 mmol/L, 24.2% vs. ≥1.4 mmol/L, 38.5%, p = 0.014). Among 87 propensity score-matched pairs, hospital mortality was significantly higher in patients with arterial lactate ≥1.4 mmol/L (39.1% vs. 23.0%, p = 0.029) compared to those with lower arterial lactate. Conclusions: Increased arterial lactate levels at the time of weaning from postcardiotomy VA-ECMO increases significantly the risk of hospital mortality. Arterial lactate may be useful in guiding optimal timing of VA-ECMO weaning.

The perioperative bleeding risk in patients receiving fondaparinux versus low-molecular weight heparin before coronary artery bypass grafting has not been reported. We evaluated perioperative coronary artery bypass grafting -related bleeding in patients with acute coronary syndrome preoperatively treated with fondaparinux or low-molecular weight heparin. All patients with acute coronary syndrome from the prospective, European multicenter registry on Coronary Artery Bypass Grafting (E-CABG) preoperatively treated with fondaparinux or lowmolecular weight heparin undergoing isolated primary CABG were eligible. The primary outcome measure was severe or massive bleeding defined according to the Universal Definition of Perioperative Bleeding stratified by P2Y12 inhibitor discontinuation. Secondary outcome measures included three additional definitions of major bleeding used in cardiac surgery trials. Propensity score matching was performed to adjust for differences in pre- and perioperative covariates. 1525 patients were included, of whom 276 (18.1%) received fondaparinux and 1249 (81.9%) low-molecular weight heparin preoperatively. In the propensity score-matched cohort (245 pairs), the risk of major bleeding according to the Universal Definition of Perioperative Bleeding severe or massive bleeding (11.8 versus 9.0%, p = 0.285) and the three other major bleeding definitions was similar between the fondaparinux and low-molecular weight heparin cohorts. In conclusion, preoperative treatment with fondaparinux compared to low-molecular weight heparin was associated with similar incidence of perioperative bleeding in patients with acute coronary syndrome undergoing coronary artery bypass grafting.

Background: The prognostic impact of cross-clamp time (XCT) in patients undergoing isolated coronary artery bypass grafting (CABG) has not been thoroughly investigated. Material and Methods: 2957 patients who underwent on-pump isolated CABG from the prospective multicentre E-CABG study were the subjects of this analysis. Results: The mean XCT in this series was 58 ± 25 minutes Cross-clamp time was >60 minutes in 1134 patients (38.3%), >75 minutes in 619 patients (20.9%) and >90 minutes in 296 patients (10.0%). Multivariate analysis showed that XCT was an independent predictor of 30-day mortality (p < 0.0001, OR 1.027, 95%CI 1.015–1.039) along with age (p < 0.0001), female gender (p = 0.001), pulmonary disease (p = 0.001), poor mobility (p = 0.002), urgency status (p = 0.007), critical preoperative status (p = 0.002) and participating centres (p = 0.015). Adjusted risk of 30-day mortality was highest for XCT >75 minutes (2.9% vs. 1.7%, p = 0.002, OR 3.479, 95%CI 1.609–7.520). Analysis of 428 propensity score matched pairs showed that XCT >75 minutes was associated with significantly increased risk of early mortality, prolonged use of inotropes, postoperative use of intra-aortic balloon pump, use of extracorporeal membrane oxygenation, atrial fibrillation, prolonged stay in the intensive care unit and of composite major adverse events. Conclusions: Isolated CABG is currently performed with prolonged XCT in a significant number of patients and this seems to be a determinant of poor early outcome.

Objective: This study was planned to pool existing data on outcome and to evaluate the efficacy of postcardiotomy venoarterial extracorporeal membrane oxygenation (VA-ECMO) in adult patients. Design: Systematic review of the literature and meta-analysis. Setting: Multi-institutional study. Participants: Adult patients with acute heart failure immediately after cardiac surgery. Interventions: VA-ECMO after cardiac surgery. Studies evaluating only heart transplant patients were excluded from this analysis. Measurements and Main Results: A literature search was performed to identify studies published since 2000. Thirty-one studies reported on 2,986 patients (mean age, 58.1 years) who required postcardiotomy VA-ECMO. The weaning rate from VA-ECMO was 59.5% and hospital survival was 36.1% (95% CI 31.5–40.8). The pooled rate of reoperation for bleeding was 42.9%, major neurological event 11.3%, lower limb ischemia 10.8%, deep sternal wound infection/mediastinitis 14.7%, and renal replacement therapy 47.1%. The pooled mean number of transfused red blood cell units was 17.7 (95% CI 13.3–22.1). The mean stay in the intensive care unit was 13.3 days (95% CI 10.2–16.4). Survivors were significantly younger (mean, 55.7 v 63.6 years, p = 0.015) and their blood lactate level before starting VA-ECMO was lower (mean, 7.7 v 10.7 mmol/L, p = 0.028) than patients who died. One-year survival rate was 30.9% (95% CI 24.3–37.5). Conclusions: Pooled data showed that VA-ECMO may salvage one-third of patients unresponsive to any other resuscitative treatment after adult cardiac surgery.

Background: Bilateral internal mammary artery (BIMA) grafting is increasingly used in elderly patients without evidence of its risks or benefits compared with single internal mammary artery (SIMA) grafting. Methods: In all, 2,899 patients aged 70 years or older (855 [29.5%] underwent BIMA grafting) operated on from January 2015 to December 2016 and included in the prospective multicenter Outcome After Coronary Artery Bypass Grafting (E-CABG) study were considered in this analysis. Results: One-to-one propensity matching resulted in 804 pairs with similar preoperative risk profile. Propensity score matched analysis showed that BIMA grafting was associated with a nonstatistically significant increased risk of inhospital death (2.7% versus 1.6%, p = 0.117). The BIMA grafting cohort had a significantly increased risk of any sternal wound infection (7.7% versus 5.1%, p = 0.031) as well as higher risk of deep sternal wound infection/mediastinitis (4.0% versus 2.2%, p = 0.048). The BIMA grafting cohort required more frequently extracorporeal membrane oxygenation (1.0% versus 0.1%, p = 0.02), and the intensive care unit stay (mean 3.6 versus 2.6 days, p < 0.001) and inhospital stay (mean 11.3 versus 10.0 days, p < 0.001) were significantly longer compared with the SIMA grafting cohort. Test for interaction showed that urgent operation in patients undergoing BIMA grafting was associated with higher risk of inhospital death (5.6% versus 1.3%, p = 0.009). Conclusions: Bilateral internal mammary artery grafting in elderly patients seems to be associated with a worse early outcome compared with SIMA grafting, particularly in patients undergoing urgent operation. Until more conclusive results are gathered, BIMA grafting should be reserved only for elderly patients with stable coronary artery disease, without significant baseline comorbidities and with long life expectancy.

Objectives: The aim of this study was to assess the impact of frailty on the outcome after coronary artery bypass grafting (CABG) and whether it may improve the predictive ability of European System for Cardiac Operative Risk Evaluation (EuroSCORE II). Methods: The Clinical Frailty Scale (CFS) was assessed preoperatively in patients undergoing isolated CABG from the multicentre E-CABG registry, and patients were stratified into 3 classes: scores 1–2, scores 3–4 and scores 5–7. Results: Of the 6156 patients enrolled, 39.2% had CFS scores 1–2, 57.6% scores 3–4, and 3.2% scores 5–7. Logistic regression adjusted for multiple covariates showed that the CFS was an independent predictor of hospital/30-day mortality [CFS scores 3–4, odds ratio (OR) 3.95, 95% confidence interval (CI) 2.19–7.14; CFS scores 5–7, OR 5.90, 95% CI 2.67–13.05] and resulted in an Integrated Improvement Index of 1.3 (P < 0.001) and a Net Reclassification Index of 55.6 (P < 0.001) for prediction of hospital/30-day mortality. Adding the CFS classes to EuroSCORE II resulted in an Integrated Improvement Index of 0.9 (P < 0.001) and Net Reclassification Index of 59.6 (P < 0.001) for prediction of hospital/30-day mortality with a significantly larger area under the receiver operating characteristics curve (0.809 vs 0.781, P = 0.028). The CFS was an independent predictor of mid-term mortality [CFS scores 3–4, hazard ratio (HR) 2.05, 95% CI 1.43–2.85; CFS scores 5–7, HR 3.05, 95% CI 1.83–5.06]. Conclusions: The CFS predicted early- and mid-term mortality in patients undergoing isolated CABG. Further studies are needed to evaluate whether frailty may improve the estimation of the operative risk of patients undergoing adult cardiac surgery.

Background: Multiple percutaneous coronary interventions (PCIs) are considered determinant of poor outcome in patients undergoing coronary artery bypass grafting (CABG), but scarce data exist to substantiate this. Methods and results: Patients who underwent CABG without history of prior PCI or with PCI performed >30 days before surgery were selected for the present analysis from the prospective, multicenter E‐CABG (European Multicenter Study on Coronary Artery Bypass Grafting) registry. Out of 6563 patients with data on preoperative SYNTAX (Synergy between PCI With Taxus and Cardiac Surgery) score, 1181 patients (18.0%) had undergone PCI >30 days before CABG. Of these, 11.6% underwent a single PCI, 4.4% 2 PCIs, and 2.1% ≥3 PCIs. PCI of a single main coronary vessel was performed in 11.3%, of 2 main vessels in 4.9%, and of 3 main vessels in 1.6% of patients. Multivariable analysis showed that differences in early mortality and other outcomes were not significantly different in the study cohorts. The adjusted hospital/30‐day mortality rate was 1.8% in patients without history of prior PCI, 1.9% in those with a history of 1 PCI, 1.4% after 2 PCIs, and 2.5% after ≥3 PCIs (adjusted P=0.8). The adjusted hospital/30‐day mortality rate was 2.0% in those who had undergone PCI of 1 main coronary vessel, 1.3% after PCI of 2 main vessels, and 3.1% after PCI of 3 main coronary vessels (adjusted P=0.6). Conclusions: Multiple prior PCIs are not associated with increased risk of early adverse events in patients undergoing isolated CABG. The present results are conditional to survival after PCI and should not be viewed as a support for a policy of multiple PCI as opposed to earlier CABG. Clinical trial registration: URL: http://www.Clinicaltrials.gov. Unique identifier: NCT02319083. ( J Am Heart Assoc. 2018;7: e010089. DOI: 10.1161/JAHA.118.010089.)

Severe perioperative bleeding after coronary artery bypass grafting (CABG) is associated with poor outcome. An additive score for prediction of severe bleeding was derived (n=2494) and validated (n=1250) in patients from the E-CABG registry. Severe bleeding was defined as E-CABG bleeding grades 2–3 (transfusion of >4 units of red blood cells or reoperation for bleeding). The overall incidence of severe bleeding was 6.4 %. Preoperative anaemia (3 points), female gender (2 points), eGFR <45 ml/min/1.73 m² (3 points), potent antiplatelet drugs discontinued less than five days (2 points), critical preoperative state (5 points), acute coronary syndrome (2 points), use of low-molecular-weight heparin/fondaparinux/unfractionated heparin (1 point) were independent predictors of severe bleeding. The WILL-BLEED score was associated with increasing rates of severe bleeding in both the derivation and validation cohorts (scores 0–3: 2.9 % vs 3.4 %; scores 4–6: 6.8 % vs 7.5 %; scores>6: 24.6 % vs 24.2 %, both p<0.0001). The WILL-BLEED score had a better discriminatory ability (AUC 0.725) for prediction of severe bleeding compared to the ACTION (AUC 0.671), CRUSADE (AUC 0.642), Papworth (AUC 0.605), TRUST (AUC 0.660) and TRACK (AUC 0.640) bleeding scores. The net reclassification index and integrated discrimination improvement using the WILL-BLEED score as opposed to the other bleeding scores were significant (p<0.0001). The decision curve analysis demonstrated a net benefit with the WILL-BLEED score compared to the other bleeding scores. In conclusion, the WILL-BLEED risk score is a simple risk stratification method which allows the identification of patients at high risk of severe bleeding after CABG.

Perioperative bleeding is a determinant of poor outcome in patients undergoing coronary artery bypass grafting (CABG), but there is a lack of adequate stratification of its severity. The ability of the European registry of Coronary Artery Bypass Grafting (E-CABG), Universal Definition of Perioperative Bleeding (UDPB), Study of Platelet Inhibition and Patient Outcomes (PLATO), Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events−Seventh Organization to Assess Strategies in Ischemic Syndromes (CURRENT-OASIS 7), Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q Wave Coronary Events (ESSENCE), and SafeTy and Efficacy of Enoxaparin in Percutaneous coronary intervention patients, an internationaL randomized Evaluation (STEEPLE) bleeding classifications to predict early mortality, stroke, acute kidney injury (AKI) stage 3, and deep sternal wound infection/mediastinitis was investigated in 3,730 patients from the prospective, multicentre E-CABG registry. Increasing grades of the E-CABG, UDPB, PLATO, and CURRENT-OASIS 7 classifications were associated with increasing risks of early mortality, had similar receiver-operating characteristic area under the curves (>0.7), and were predictive also when adjusted for EuroSCORE II. The E-CABG and UDPB classifications had satisfactory area under the curves (>0.6) in predicting stroke, AKI stage 3, and deep sternal wound infection/mediastinitis even when adjusted for EuroSCORE II. The PLATO and CURRENT-OASIS 7 classifications had similar predictive ability for stroke and AKI stage 3 as confirmed by multivariate analysis adjusted for EuroSCORE II but showed inferior ability in predicting severe wound infection compared to the E-CABG and UDPB classifications. The STEEPLE and ESSENCE classifications had a poor ability of predicting all these adverse events. Decision curve analysis showed a benefit of the E-CABG bleeding classification over the other classifications in predicting all adverse events. In concl