Comparing right- versus left-first implantation in off-pump sequential double-lung transplantation: an observational cohort study.

Objectives: Historically, the perfusion-guided sequence suggests to first transplant the side with lowest lung perfusion. This sequence is thought to limit right ventricular afterload and prevent acute heart failure after first pneumonectomy. As a paradigm shift, we adopted the right-first implantation sequence, irrespective of lung perfusion.

Recombinant human placental growth factor-2 in post-infarction left ventricular dysfunction: a randomized, placebo-controlled, preclinical study.

Placental growth factor (PlGF)-2 induces angio- and arteriogenesis in rodents but its therapeutic potential in a clinically representative post-infarction left ventricular (LV) dysfunction model remains unclear. We, therefore, investigated the safety and efficacy of recombinant human (rh)PlGF-2 in the infarcted porcine heart in a randomized, placebo-controlled blinded study. We induced myocardial infarction (MI) in pigs using 75 min mid-LAD balloon occlusion followed by reperfusion.

Real-life effectiveness of sacubitril/valsartan in older Belgians with heart failure, reduced ejection fraction and most severe symptoms.

We assessed the real-world effectiveness of sacubitril/valsartan in patients with chronic heart failure (HF) and reduced ejection fraction (HFrEF) with an emphasis on those with older age (≥ 75 years) or with New York Heart Association (NYHA) class IV, for whom greater uncertainty existed regarding clinical outcomes. We conducted a retrospective cohort study based on patient-level linkage of electronic healthcare datasets. Data from all adults with HFrEF in Belgium receiving a prescription for sacubitril/valsartan between 01-November-2016 and 31-December-2018 were collected, with a follow-up of > 6 years.

Treatment of non-constipated irritable bowel syndrome with the histamine 1 receptor antagonist ebastine: a randomised, double-blind, placebo-controlled trial.

Objective: We evaluated the histamine 1 receptor antagonist ebastine as a potential treatment for patients with non-constipated irritable bowel syndrome (IBS) in a randomised, placebo-controlled phase 2 study.

Methods: Non-constipated patients with IBS fulfilling the Rome III criteria were randomly assigned to 20 mg ebastine or placebo for 12 weeks. Subjects scored global relief of symptoms (GRS) and abdominal pain intensity (API).

10-year follow-up results of the European Achalasia Trial: a multicentre randomised controlled trial comparing pneumatic dilation with laparoscopic Heller myotomy.

Objective: As achalasia is a chronic disorder, long-term follow-up data comparing different treatments are essential to select optimal clinical management. Here, we report on the 10-year follow-up of the European Achalasia Trial comparing endoscopic pneumodilation (PD) with laparoscopic Heller myotomy (LHM).

Design: A total of 201 newly diagnosed patients with achalasia were randomised to either a series of PDs (n=96) or LHM (n=105).

Modulation of thromboinflammation in hospitalized COVID-19 patients with aprotinin, low molecular weight heparin, and anakinra: The DAWn-Antico study.

Background: Thromboinflammation plays a central role in severe COVID-19. The kallikrein pathway activates both inflammatory pathways and contact-mediated coagulation. We investigated if modulation of the thromboinflammatory response improves outcomes in hospitalized COVID-19 patients.

Pembrolizumab, radiotherapy, and an immunomodulatory five-drug cocktail in pretreated patients with persistent, recurrent, or metastatic cervical or endometrial carcinoma: Results of the phase II PRIMMO study.

A phase II study (PRIMMO) of patients with pretreated persistent/recurrent/metastatic cervical or endometrial cancer is presented. Patients received an immunomodulatory five-drug cocktail (IDC) consisting of low-dose cyclophosphamide, aspirin, lansoprazole, vitamin D, and curcumin starting 2 weeks before radioimmunotherapy. Pembrolizumab was administered three-weekly from day 15 onwards; one of the tumor lesions was irradiated (8Gyx3) on days 15, 17, and 19.

Azithromycin for treatment of hospitalised COVID-19 patients: a randomised, multicentre, open-label clinical trial (DAWn-AZITHRO).

Background And Objectives: Azithromycin was rapidly adopted as a repurposed drug to treat coronavirus disease 2019 (COVID-19) early in the pandemic. We aimed to evaluate its efficacy in patients hospitalised for COVID-19.

Methods: In a series of randomised, open-label, phase 2 proof-of-concept, multicentre clinical trials (Direct Antivirals Working against the novel coronavirus (DAWn)), several treatments were compared with standard of care.

Early high antibody titre convalescent plasma for hospitalised COVID-19 patients: DAWn-plasma.

Background: Several randomised clinical trials have studied convalescent plasma for coronavirus disease 2019 (COVID-19) using different protocols, with different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibody titres, at different time-points and severities of illness.

Methods: In the prospective multicentre DAWn-plasma trial, adult patients hospitalised with COVID-19 were randomised to 4 units of open-label convalescent plasma combined with standard of care (intervention group) or standard of care alone (control group). Plasma from donors with neutralising antibody titres (50% neutralisation titre (NT)) ≥1/320 was the product of choice for the study.

Ninety-Day Follow-up Is Inadequate for Diagnosis of Fracture-related Infections in Patients with Open Fractures.

Background: Fracture-related infection (FRI) is a challenging complication in musculoskeletal trauma surgery and often complicates the management of open fractures. The CDC currently advocates a surveillance period of 90 days after fracture fixation, but it is unclear what duration of follow-up constitutes adequate surveillance for FRI. Inadequate follow-up will underestimate infections and, in clinical research, will make any interventions studied appear better than they really are, thereby resulting in misleading conclusions.

Endurance exercise and the risk of cardiovascular pathology in men: a comparison between lifelong and late-onset endurance training and a non-athletic lifestyle - rationale and design of the Master@Heart study, a prospective cohort trial.

Introduction: Low and moderate endurance exercise is associated with better control of cardiovascular risk factors, a decreased risk of coronary artery disease and atrial fibrillation (AF). There is, however, a growing proportion of individuals regularly performing strenuous and prolonged endurance exercise in which the health benefits have been challenged. Higher doses of endurance exercise have been associated with a greater coronary atherosclerotic plaque burden, risk of AF and myocardial fibrosis (MF).

Itraconazole for COVID-19: preclinical studies and a proof-of-concept randomized clinical trial.

Background: The antifungal drug itraconazole exerts in vitro activity against SARS-CoV-2 in Vero and human Caco-2 cells. Preclinical and clinical studies are required to investigate if itraconazole is effective for the treatment and/or prevention of COVID-19.

Methods: Due to the initial absence of preclinical models, the effect of itraconazole was explored in a clinical, proof-of-concept, open-label, single-center study, in which hospitalized COVID-19 patients were randomly assigned to standard of care with or without itraconazole.

Direct antivirals working against the novel coronavirus: azithromycin (DAWn-AZITHRO), a randomized, multicenter, open-label, adaptive, proof-of-concept clinical trial of new antivirals working against SARS-CoV-2-azithromycin trial.

Background: The rapid emergence and the high disease burden of the novel coronavirus SARS-CoV-2 have created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against SARS-CoV-2 in vitro and acts on cytokine signaling pathways that have been implicated in COVID-19.

Patient satisfaction with intravenous regional anaesthesia or an axillary block for minor ambulatory hand surgery: A randomised controlled study.

Background: Intravenous regional anesthesia (IVRA) and the axillary brachial plexus block are popular alternatives to general anaesthesia in ambulatory hand surgery. Although both have proven their effectiveness, patients' preferences have never been evaluated.

Objectives: We investigated patient satisfaction with both techniques and hypothesised that satisfaction after IVRA is noninferior compared with axillary brachial plexus block.

The effect of intracoronary infusion of bone marrow-derived mononuclear cells on all-cause mortality in acute myocardial infarction: the BAMI trial.

Aims: Bone marrow-derived mononuclear cell (BM-MNC) therapy may improve myocardial recovery in patients following acute myocardial infarction (AMI), though existing trial results are inconsistent.

Methods And Results: Originally an open-label, multicentre Phase III trial, BAMI was designed to demonstrate the safety and efficacy of intracoronary infusion of BM-MNCs in reducing the time to all-cause mortality in patients with reduced left ventricular ejection fraction (LVEF, ≤45%) after primary angioplasty (PPCI) for ST-elevation AMI. Unexpectedly low recruitment means the trial no longer qualifies as a hypothesis-testing trial, but is instead an observational study with no definitive conclusions possible from statistical analysis.

Optimum Blood Pressure in Patients With Shock After Acute Myocardial Infarction and Cardiac Arrest.

Background: In patients with shock after acute myocardial infarction (AMI), the optimal level of pharmacologic support is unknown. Whereas higher doses may increase myocardial oxygen consumption and induce arrhythmias, diastolic hypotension may reduce coronary perfusion and increase infarct size.

Objectives: This study aimed to determine the optimal mean arterial pressure (MAP) in patients with AMI and shock after cardiac arrest.

Impact of duration of perioperative antibiotic prophylaxis on development of fracture-related infection in open fractures.

Introduction: Infection is a common complication of open fractures potentially leading to nonunion, functional loss, and even amputation. Perioperative antibiotic prophylaxis (PAP) is standard practice for infection prevention in the management of open fractures. However, optimal duration of PAP remains controversial.

Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo - a post-hoc analysis of the BACE randomized controlled trial.

Background: In the BACE trial, a 3-month (3 m) intervention with azithromycin, initiated at the onset of an infectious COPD exacerbation requiring hospitalization, decreased the rate of a first treatment failure (TF); the composite of treatment intensification (TI), step-up in hospital care (SH) and mortality.

Objectives: (1) To investigate the intervention's effect on recurrent events, and (2) to identify clinical subgroups most likely to benefit, determined from the incidence rate of TF and hospital readmissions.

Methods: Enrolment criteria included the diagnosis of COPD, a smoking history of ≥10 pack-years and ≥ 1 exacerbation in the previous year.

Azithromycin during Acute Chronic Obstructive Pulmonary Disease Exacerbations Requiring Hospitalization (BACE). A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial.

Azithromycin prevents acute exacerbations of chronic obstructive pulmonary disease (AECOPDs); however, its value in the treatment of an AECOPD requiring hospitalization remains to be defined. We investigated whether a 3-month intervention with low-dose azithromycin could decrease treatment failure (TF) when initiated at hospital admission and added to standard care. In an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, patients who had been hospitalized for an AECOPD and had a smoking history of ≥10 pack-years and one or more exacerbations in the previous year were randomized (1:1) within 48 hours of hospital admission to azithromycin or placebo.