A single bout of vigorous intensity exercise enhances the efficacy of rituximab against human chronic lymphocytic leukaemia B-cells ex vivo.

Chronic lymphocytic leukaemia (CLL) is characterised by the clonal proliferation and accumulation of mature B-cells and is often treated with rituximab, an anti-CD20 monoclonal antibody immunotherapy. Rituximab often fails to induce stringent disease eradication, due in part to failure of antibody-dependent cellular cytotoxicity (ADCC) which relies on natural killer (NK)-cells binding to rituximab-bound CD20 on B-cells. CLL cells are diffusely spread across lymphoid and other bodily tissues, and ADCC resistance in survival niches may be due to several factors including low NK-cell frequency and a suppressive stromal environment that promotes CLL cell survival. It is well established that exercise bouts induce a transient relocation of NK-cells and B-cells into peripheral blood, which could be harnessed to enhance the efficacy of rituximab in CLL by relocating both target and effector cells together with rituximab in blood. In this pilot study, n = 20 patients with treatment-naïve CLL completed a bout of cycling 15 % above anaerobic threshold for âˆ¼ 30-minutes, with blood samples collected pre-, immediately post-, and 1-hour post-exercise. Flow cytometry revealed that exercise evoked a 254 % increase in effector (CD3-CD56+CD16+) NK-cells in blood, and a 67 % increase in CD5+CD19+CD20+ CLL cells in blood (all p < 0.005). NK-cells were isolated from blood samples pre-, and immediately post-exercise and incubated with primary isolated CLL cells with or without the presence of rituximab to determine specific lysis using a calcein-release assay. Rituximab-mediated cell lysis increased by 129 % following exercise (p < 0.001). Direct NK-cell lysis of CLL cells - independent of rituximab - was unchanged following exercise (p = 0.25). We conclude that exercise improved the efficacy of rituximab-mediated ADCC against autologous CLL cells ex vivo and propose that exercise should be explored as a means of enhancing clinical responses in patients receiving anti-CD20 immunotherapy.

British Society of Echocardiography guideline for the transthoracic echocardiographic assessment of cardiac amyloidosis.

These guidelines form an update of the BSE guideline protocol for the assessment of restrictive cardiomyopathy (Knight et al. in Echo Res Prac, 2013). Since the original recommendations were conceived in 2013, there has been an exponential rise in the diagnosis of cardiac amyloidosis fuelled by increased clinician awareness, improvements in cardiovascular imaging as well as the availability of new and effective disease modifying therapies. The initial diagnosis of cardiac amyloidosis can be challenging and is often not clear-cut on the basis of echocardiography, which for most patients presenting with heart failure symptoms remains the first-line imaging test. The role of a specialist echocardiographer will be to raise the suspicion of cardiac amyloidosis when appropriate, but the formal diagnosis of amyloid sub-type invariably requires further downstream testing. This document seeks to provide a focused review of the literature on echocardiography in cardiac amyloidosis highlighting its important role in the diagnosis, prognosis and screening of at risk individuals, before concluding with a suggested minimum data set, for use as an aide memoire when reporting.

BSE and BCOS Guideline for Transthoracic Echocardiographic Assessment of Adult Cancer Patients Receiving Anthracyclines and/or Trastuzumab.

The subspecialty of cardio-oncology aims to reduce cardiovascular morbidity and mortality in patients with cancer or following cancer treatment. Cancer therapy can lead to a variety of cardiovascular complications, including left ventricular systolic dysfunction, pericardial disease, and valvular heart disease. Echocardiography is a key diagnostic imaging tool in the diagnosis and surveillance for many of these complications. The baseline assessment and subsequent surveillance of patients undergoing treatment with anthracyclines and/or human epidermal growth factor receptor (HER) 2-positive targeted treatment (e.g., trastuzumab and pertuzumab) form a significant proportion of cardio-oncology patients undergoing echocardiography. This guideline from the British Society of Echocardiography and British Cardio-Oncology Society outlines a protocol for baseline and surveillance echocardiography of patients undergoing treatment with anthracyclines and/or trastuzumab. The methodology for acquisition of images and the advantages and disadvantages of techniques are discussed. Echocardiographic definitions for considering cancer therapeutics-related cardiac dysfunction are also presented.

British Society for Echocardiography and British Cardio-Oncology Society guideline for transthoracic echocardiographic assessment of adult cancer patients receiving anthracyclines and/or trastuzumab.

The subspecialty of cardio-oncology aims to reduce cardiovascular morbidity and mortality in patients with cancer or following cancer treatment. Cancer therapy can lead to a variety of cardiovascular complications, including left ventricular systolic dysfunction, pericardial disease, and valvular heart disease. Echocardiography is a key diagnostic imaging tool in the diagnosis and surveillance for many of these complications. The baseline assessment and subsequent surveillance of patients undergoing treatment with anthracyclines and/or human epidermal growth factor (EGF) receptor (HER) 2-positive targeted treatment (e.g. trastuzumab and pertuzumab) form a significant proportion of cardio-oncology patients undergoing echocardiography. This guideline from the British Society of Echocardiography and British Cardio-Oncology Society outlines a protocol for baseline and surveillance echocardiography of patients undergoing treatment with anthracyclines and/or trastuzumab. The methodology for acquisition of images and the advantages and disadvantages of techniques are discussed. Echocardiographic definitions for considering cancer therapeutics-related cardiac dysfunction are also presented.

The assessment of mitral valve disease: a guideline from the British Society of Echocardiography.

Mitral valve disease is common. Mitral regurgitation is the second most frequent indication for valve surgery in Europe and despite the decline of rheumatic fever in Western societies, mitral stenosis of any aetiology is a regular finding in all echo departments. Mitral valve disease is, therefore, one of the most common pathologies encountered by echocardiographers, as both a primary indication for echocardiography and a secondary finding when investigating other cardiovascular disease processes. Transthoracic, transoesophageal and exercise stress echocardiography play a crucial role in the assessment of mitral valve disease and are essential to identifying the aetiology, mechanism and severity of disease, and for helping to determine the appropriate timing and method of intervention. This guideline from the British Society of Echocardiography (BSE) describes the assessment of mitral regurgitation and mitral stenosis, and replaces previous BSE guidelines that describe the echocardiographic assessment of mitral anatomy prior to mitral valve repair surgery and percutaneous mitral valvuloplasty. It provides a comprehensive description of the imaging techniques (and their limitations) employed in the assessment of mitral valve disease. It describes a step-wise approach to identifying: aetiology and mechanism, disease severity, reparability and secondary effects on chamber geometry, function and pressures. Advanced echocardiographic techniques are described for both transthoracic and transoesophageal modalities, including TOE and exercise testing.

Characterizing Regional Methane Emissions from Natural Gas Liquid Unloading.

A "bottom-up" probabilistic model was developed using engineering first-principles to quantify annualized throughput normalized methane emissions (TNME) from natural gas liquid unloading activities for 18 basins in the United States in 2016. For each basin, six discrete liquid-unloading scenarios are considered, consisting of combinations of well types (conventional and unconventional) and liquid-unloading systems (nonplunger, manual plunger lift, and automatic plunger lift). Analysis reveals that methane emissions from liquids unloading are highly variable, with mean TNMEs ranging from 0.0093% to 0.38% across basins. Automatic plunger-lift systems are found to have significantly higher per-well methane emissions rates relative to manual plunger-lift or non-plunger systems and on average constitute 28% of annual methane emissions from liquids unloading over all basins despite representing only ∼0.43% of total natural gas well count. While previous work has advocated that operational malfunctions and abnormal process conditions explain the existence of super-emitters in the natural gas supply chain, this work finds that super-emitters can arise naturally due to variability in underlying component processes. Additionally, average cumulative methane emissions from liquids unloading, attributed to the natural gas supply chain, across all basins are ∼4.8 times higher than those inferred from the 2016 Greenhouse Gas Reporting Program (GHGRP). Our new model highlights the importance of technological disaggregation, uncertainty quantification, and regionalization in estimating episodic methane emissions from liquids unloading. These insights can help reconcile discrepancies between "top-down" (regional or atmospheric studies) and "bottom-up" (component or facility-level) studies.

Lost without Occam's razor: Escherichia coli tricuspid valve endocarditis in a non-intravenous drug user.

The unusual case of a 31-year-old woman who developed tricuspid valve endocarditis with positive blood cultures for Escherichia coli is presented. The patient had no underlying cardiac disease or predisposing conditions that could have made her susceptible to the native valve infection. Despite a lengthy course of intravenous antibiotics only a partial response was achieved. The patient underwent cardiac surgery and had a good postoperative recovery.

Austrian syndrome: a case report and review of the literature.

A usually fit and well 69-year-old woman presented with headache and altered consciousness. Initial clinical findings and investigations were consistent with a diagnosis of pneumococcal meningitis and pneumonia. Cultures of blood and cerebrospinal fluid grew Streptococcus pneumoniae. The patient continued to spike temperatures and developed cardiac failure. A transoesophageal echocardiogram demonstrated a large vegetation of the aortic valve causing severe aortic regurgitation. A diagnosis of Austrian syndrome, the triad of pneumococcal meningitis, pneumonia and endocarditis, was made. The patient has completed a course of appropriate antibiotic therapy and is awaiting aortic valve surgery.