BackgroundRisk stratification of patients in the emergency department can be strengthened using prognostic biomarkers, but the impact on patient prognosis is unknown. The aim of the TRIAGE III trial was to investigate whether the introduction of the prognostic and nonspecific biomarker: soluble urokinase plasminogen activator receptor (suPAR) for risk stratification in the emergency department reduces mortality in acutely admitted patients.MethodsThe TRIAGE III trial was a cluster-randomized interventional trial conducted at emergency departments in the Capitol Region of Denmark. Eligible hospitals were required to have an emergency department with an intake of acute medical and surgical patients and no previous access to suPAR measurement. Three emergency departments were randomized; one withdrew shortly after the trial began. The inclusion period was from January through June of 2016 consisting of twelve cluster-periods of 3-weeks alternating between intervention and control and a subsequent follow-up of ten months. Patients were allocated to the intervention if they arrived in interventional periods, where suPAR measurement was routinely analysed at arrival. In the control periods suPAR measurement was not performed. The main outcome was all-cause mortality 10 months after arrival of the last patient in the inclusion period. Secondary outcomes included 30-day mortality.ResultsThe trial enrolled a consecutive cohort of 16,801 acutely admitted patients; all were included in the analyses. The intervention group consisted of 6 cluster periods with 8900 patients and the control group consisted of 6 cluster periods with 7901 patients. After a median follow-up of 362 days, death occurred in 1241 patients (13.9%) in the intervention group and in 1126 patients (14.3%) in the control group.The weighted Cox model found a hazard ratio of 0.97 (95% confidence interval, 0.89 to 1.07; p = 0.57). Analysis of all subgroups and of 30-day all-cause mortality showed similar results.ConclusionsThe TRIAGE III trial found no effect of introducing the nonspecific and prognostic biomarker suPAR in emergency departments on short- or long-term all-cause mortality among acutely admitted patients. Further research is required to evaluate how prognostic biomarkers can be implemented in routine clinical practice.Trial registrationclinicaltrials.gov, NCT02643459. Registered 31 December 2015.Electronic supplementary materialThe online version of this article (10.1186/s13049-018-0539-5) contains supplementary material, which is available to authorized users.

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Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Fonden Background Cardiogenic shock (CS) is seen in up to 10% of patients with ST-elevation myocardial infarction (STEMI) and is associated with a high mortality rate of up to 50%. Approximately 1/3 of STEMI-patients developing CS are not in overt shock at time of hospital admission but will develop hemodynamical instability within the following hours to days. Patients at risk of CS development may be clinically stable but with normal lactate levels (Society for Cardiovascular Angiography and Interventions classification, SCAI A/B). The Observatoire Régional Breton sur l'Infarctus (ORBI) clinical risk score has recently been developed and validated for predicting the risk of in-hospital (late) CS. STEMI-patients with an ORBI score >=10 have a risk of in-hospital CS development of more than 8-10%. NTproBNP is a biomarker released from the myocardium reflecting neurohormonal activation which is strongly correlated with hemodynamic parameters. Neurohormonal activation as well as a systemic inflammatory response are present acutely at hospital admission in STEMI patients developing late CS compared to non-CS patients suggesting an early subclinical hemodynamic deterioration. Dobutamine induces significant positive inotropic- and dose-dependent chronotropic effects and decreases afterload by peripheral vasodilatation, which increases cardiac output and organ perfusion. The interleukin-6 receptor antagonist Tocilizumab has been shown to reduce troponin leakage and increase myocardial salvage in acute MI patients. The effects of Dobutamine and Tocilizumab in a high-risk population have not previously been investigated. Methods DOBERMANN is an investigator-initiated, double blinded randomized clinical trial. Consecutive patients with acute MI admitted for acute coronary angiography and treated with percutaneous coronary intervention are screened with the ORBI risk score in the catheterization laboratory. One hundred adult patients presenting without CS at hospital admission with an intermediate-high risk of CS development (ORBI risk score of >=10) will be randomized 2x2 to receive a continuous intravenous infusion of dobutamine (5 micrograms/kg/minute, 24h) vs. placebo, and a single dose of Tocilizumab (280 mg, 1h) vs. placebo. NTproBNP as a proxy for development of CS and hemodynamic instability will be sampled for primary endpoint analysis. Effects on clinical parameters, mortality, morbidity as well as specific indicators of inflammation, cardiac function, and infarct size will secondarily be assessed noninvasively at 48h and at three months follow-up. Enrollment began in March 2022 and is commencing as planned. Discussion We hypothesize that inflammatory and neurohormonal responses are associated with subclinical hemodynamic instability in patients with AMI with intermediate/high risk of CS. The potentially unstable condition may be targeted pharmacologically as an add-on to existing therapy.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation Background Previous studies have found lower survival rate and neurological outcomes for female patients with out-of-hospital cardiac arrest (OHCA) compared to males. Recently, the effect of liberal or restrictive oxygenation and lower or higher mean arterial blood-pressures (MAP) on outcome in comatose OHCA patients were investigated; showing no differences between the target groups. Evidence concerning sex differences in outcome after appropriate oxygenation and different MAP levels in comatose OHCA patients is limited. Purpose The aim of this study was to investigate whether female sex was associated with higher rates of unfavourable outcome after treatment with oxygenation and MAP in comatose patients after OHCA related to outcome. Methods Adult comatose OHCA patients (age ≥18 years) of presumed cardiac cause were included in a dual-center, double-blind, randomized trial with a 2-by-2 factorial design. Patients were allocated by a 1:1:1:1 ratio into a MAP target of 63 mm Hg or 77 mm Hg and arterial oxygen concentration during mechanical ventilation of 9–10 kPa (restrictive) or 13–14 kPa (liberal). The primary outcome was a composite of all causes of death within a year or hospital discharge with a cerebral performance category (CPC) of 3 or 4. Results Of the 789 included comatose OHCA patients, 152 (19%) were women. Mean age of women and men were similar, 61±14 years and 63±13 years, respectively. Comorbidities and characteristics of the cardiac arrest were comparable between sexes except for ischemic heart disease, which was more frequent in men (12% women, 24% men) and pulseless electrical activity, which was more frequent in women (8% women, 4% men). CPC 3 or 4 occurred equally in women and men (both 3%). Women had a higher, but non-significant one-year all-cause mortality (women: 42%, men: 35%), Figure 1. In a univariate Cox regression model, the difference in all-cause mortality was not significant (HR: 1.25, CI: 0.95-1.63), but showed significance after adjustment for age (HR: 1.31, CI: 1.004-1.72). Conclusion Men and women in comatose after OHCA had similar unfavourable outcome when treated in the same manner with oxygenation and MAP.

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Funding Acknowledgements Type of funding sources: None. Background Differences in outcome between men and women among patients with acute myocardial infarction (AMI) have previously been investigated[1–4], while evidence concerning sex differences in patients with AMI complicated by cardiogenic shock (AMICS) is limited. Purpose The aim of this study was to investigate sex differences in patients with AMICS related to demographics, treatment and long-term outcome. Methods All adult patients (age ≥18 years) with AMICS hospitalized at one of two tertiary heart centers with a catchment area corresponding to 4 million citizens were included in this study. In the study period from January 1st, 2010 to December 31st, 2017, a total of 1716 AMICS patients were identified following individual validation. Data regarding patient characteristics, treatment and clinical outcome including short-term follow-up were extracted from medical records and an 8,5-year long-term follow-up were obtained from the national patients registry. A multivariate cox regression model was used to adjust for significant sex differences known to be associated with outcome in AMICS including age and an out-of-hospital cardiac arrest (OHCA) presentation. Results Of the 1716 included AMICS patients, 438 (26%) were women. Women were older than men, 71±12 years and 66±11 years, P=<0.0001, respectively. Patients characteristics were similar between sex except for hypertension which was more common among women. Women were more often initially admitted to a local hospital (41% women and 30% men, P=<0.0001), while more men presented with OHCA (25% women and 48% men, P=<0.0001), which persisted after adjustment for age. At the time of shock development, women and men were comparable regarding blood pressure (mean: both 82 mmHg, P=0.44), heart rate (mean: 88 vs. 85 bpm, P=0.10), p-lactate (median: 5.2 vs. 5.5 mM, P=0.07), and left ventricular ejection fraction (median: both 30%, P=0.11). However, fewer women were treated with mechanical circulatory support (19% women and 26% men, P=0.002), which persisted following multivariate adjustment. Additionally, women were associated with a lower use of acute revascularization (83% women and 88% men, P=0.006) including percutaneous coronary intervention (n=1405) and coronary artery bypass graft (n=101) and mechanical ventilation (67% women and 82% men, P=<0.0001). These significant signals did not remain following cox regression analysis. Women had a significantly higher short-term as well as long-term mortality rate, which persisted in the multivariate model (Figure 1). Conclusion Women were associated with lower use of mechanical circulatory support devices among AMICS patients. Women had a significantly higher short- and long-term mortality rate compared to men.