Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial: study protocol for a multicentre international trial of cardiac output-guided fluid therapy with low-dose inotrope infusion compared with usual care in patients undergoing major elective gastrointestinal surgery.

INTRODUCTION: Postoperative morbidity and mortality in older patients with comorbidities undergoing gastrointestinal surgery are a major burden on healthcare systems. Infections after surgery are common in such patients, prolonging hospitalisation and reducing postoperative short-term and long-term survival. Optimal management of perioperative intravenous fluids and inotropic drugs may reduce infection rates and improve outcomes from surgery. Previous small trials of cardiac-output-guided haemodynamic therapy algorithms suggested a modest reduction in postoperative morbidity. A large definitive trial is needed to confirm or refute this and inform widespread clinical practice. METHODS: The Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial is a multicentre, international, parallel group, open, randomised controlled trial. 2502 high-risk patients undergoing major elective gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intravenous fluid combined with low-dose inotrope infusion, or usual care. The trial intervention will be carried out during and for 4 hours after surgery. The primary outcome is postoperative infection of Clavien-Dindo grade II or higher within 30 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation; however, outcome assessors will be blinded when feasible. Participant recruitment started in January 2017 and is scheduled to last 3 years, within 50 hospitals worldwide. ETHICS/DISSEMINATION: The OPTIMISE II trial has been approved by the UK National Research Ethics Service and has been approved by responsible ethics committees in all participating countries. The findings will be disseminated through publication in a widely accessible peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: ISRCTN39653756.The OPTIMISE II trial is supported by Edwards Lifesciences (Irvine, CA) and the UK National Institute for Health Research through RMP’s NIHR Professorship

Description of clinical and genetic features of 122 patients included in the Spanish Pompe registry

\ua9 2023Pompe disease is a rare genetic disorder with an estimated prevalence of 1:60.000. The two main phenotypes are Infantile Onset Pompe Disease (IOPD) and Late Onset Pompe Disease (LOPD). There is no published data from Spain regarding the existing number of cases, regional distribution, clinical features or, access and response to the treatment. We created a registry to collect all these data from patients with Pompe in Spain. Here, we report the data of the 122 patients registered including nine IOPD and 113 LOPD patients. There was a high variability in how the diagnosis was obtained and how the follow-up was performed among different centres. Seven IOPD patients were still alive being all treated with enzymatic replacement therapy (ERT) at last visit. Ninety four of the 113 LOPD patients had muscle weakness of which 81 were receiving ERT. We observed a progressive decline in the results of muscle function tests during follow-up. Overall, the Spanish Pompe Registry is a valuable resource for understanding the demographics, patient\u27s journey and clinical characteristics of patients in Spain. Our data supports the development of agreed guidelines to ensure that the care provided to the patients is standardized across the country

Correction to: Vena cava filters in patients presenting with major bleeding during anticoagulation for venous thromboembolism (Internal and Emergency Medicine, (2019), 14, 7, (1101-1112), 10.1007/s11739-019-02077-5)

In the original publication, part of the conflict of statement was incorrectly published as “Dr. Bikdeli reports that he was approached by lawyers on behalf of plaintiffs in litigation related to IVC filters”. The correct statement should read as “Dr. Bikdeli reports that he is a consulting expert (on behalf of the plaintiff) for litigation related to a specific type of IVC filters”. In addition, the affiliation of first author was incorrectly published. The corrected affiliation is given in this erratum

Early use of echocardiography in patients with acute pulmonary embolism: Findings from the RIETE registry

Background\u2014Transthoracic echocardiography (TTE) is often considered for risk stratification of patients with acute pulmonary embolism (PE). We sought to determine the contemporary utilization of early TTE (within 72 hours of PE diagnosis) and explored the association between TTE findings and PE-related mortality. Methods and Results\u2014Data from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry, a multicenter registry of consecutive patients with acute PE, were used (2001-July 2017). We used a generalized linear mixed model to determine predictors of early TTE performance. Moreover, the association between 3 TTE variables (right atrial enlargement, right ventricular hypokinesis, and presence of right heart thrombi) and 30-day PE-related mortality was assessed in generalized linear mixed models adjusted for PE severity index, and other comorbidities. Among 35 935 enrollees with acute PE, 15 375 (42.8%) underwent early TTE. There was an increase in early TTE utilization rate over time (P<0.001 for trend). Younger age, female sex, enrollment in countries other than Spain, history of coronary disease, heart failure, atrial fibrillation, tachycardia, and hypotension were the main predictors of early TTE (P<0.01 for all). In multivariable analyses, right atrial enlargement (adjusted odds ratio: 3.74; 95% confidence interval, 2.10-6.66), right ventricular hypokinesis (adjusted odds ratio: 3.11, 95% confidence interval: 1.85-5.21) and right heart thrombi (adjusted odds ratio: 4.39, 95% confidence interval, 1.99-9.71) were associated with increased odds for PErelated mortality. Conclusions\u2014Early TTE is commonly performed for acute PE and utilization rates have increased over time. Right atrial enlargement, right ventricular hypokinesis, and right heart thrombi are predictive of worse outcomes. Clinical Trial Registration\u2014URL: http://www.clinicaltrials.gov. Unique identifier: NCT02832245

Vena cava filters in patients presenting with major bleeding during anticoagulation for venous thromboembolism

The association between inferior vena cava filter (IVC) use and outcome in patients presenting with major bleeding during anticoagulation for venous thromboembolism (VTE) has not been thoroughly investigated. We used the RIETE registry to compare the 30-day outcomes (death, major re-bleeding or VTE recurrences) in VTE patients who bled during the first 3 months of therapy, regarding the insertion of an IVC filter. A propensity score matched (PSM) analysis was performed to adjust for potential confounders. From January 2001 to September 2016, 1065 VTE patients had major bleeding during the first 3 months of anticoagulation (gastrointestinal 370; intracranial 124). Of these, 122 patients (11%) received an IVC filter. Patients receiving a filter restarted anticoagulation later (median, 4 vs. 2 days) and at lower doses (95\u2009\ub1\u200952 IU/kg/day vs. 104\u2009\ub1\u200955 of low-molecular-weight heparin) than those not receiving a filter. During the first 30 days after bleeding (after excluding 246 patients who died within the first 24 h), 283 patients (27%) died, 63 (5.9%) had non-fatal re-bleeding and 19 (1.8%) had recurrent pulmonary embolism (PE). In PSM analysis, patients receiving an IVC filter (n\u2009=\u2009122) had a lower risk for all-cause death (HR 0.49; 95% CI 0.31-0.77) or fatal bleeding (HR 0.16; 95% CI 0.07-0.49) and a similar risk for re-bleeding (HR 0.55; 95% CI 0.23-1.40) or PE recurrences (HR 1.57; 95% CI 0.38-6.36) than those not receiving a filter (n\u2009=\u2009429). In VTE patients experiencing major bleeding during the first 3 months, use of an IVC filter was associated with reduced mortality rates.Clinical Trial Registration NCT02832245

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)