Steroids and Immunomodulatory Therapies for Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is characterized by a dysregulated immune response to infection or injury. This framework has driven long-standing interest in immunomodulatory therapies as treatments for ARDS. In this narrative review, we first define what constitutes a dysregulated immune response in ARDS.

Mitral regurgitation assessment by cardiovascular magnetic resonance imaging during continuous in-scanner exercise: a feasibility study.

Purpose: Exercise imaging using current modalities can be challenging. This was patient focused study to establish the feasibility and reproducibility of exercise-cardiovascular magnetic resonance imaging (EX-CMR) acquired during continuous in-scanner exercise in asymptomatic patients with primary mitral regurgitation (MR).

Methods: This was a prospective, feasibility study.

Neurological outcome following out of hospital cardiac arrest: Evaluation of performance of existing risk prediction models in a UK cohort.

Introduction: Out of hospital cardiac arrest (OHCA) is a common problem. Rates of survival are low and a proportion of survivors are left with an unfavourable neurological outcome. Four models have been developed to predict risk of unfavourable outcome at the time of critical care admission - the Cardiac Arrest Hospital Prognosis (CAHP), MIRACLE, Out of Hospital Cardiac Arrest (OHCA), and Targeted Temperature Management (TTM) models.

4D Flow Cardiac MR in Primary Mitral Regurgitation.

Background: Four-dimensional-flow cardiac MR (4DF-MR) offers advantages in primary mitral regurgitation. The relationship between 4DF-MR-derived mitral regurgitant volume (MR-Rvol) and the post-operative left ventricular (LV) reverse remodeling has not yet been established.

Purpose: To ascertain if the 4DF-MR-derived MR-Rvol correlates with the LV reverse remodeling in primary mitral regurgitation.

Cardiac reverse remodeling in primary mitral regurgitation: mitral valve replacement vs. mitral valve repair.

Background: When feasible, guidelines recommend mitral valve repair (MVr) over mitral valve replacement (MVR) to treat primary mitral regurgitation (MR), based upon historic outcome studies and transthoracic echocardiography (TTE) reverse remodeling studies. Cardiovascular magnetic resonance (CMR) offers reference standard biventricular assessment with superior MR quantification compared to TTE. Using serial CMR in primary MR patients, we aimed to investigate cardiac reverse remodeling and residual MR post-MVr vs MVR with chordal preservation.

Cardiovascular magnetic resonance phenotyping of heart failure with mildly reduced ejection fraction.

Aims: The 2016 European Society of Cardiology Heart Failure Guidelines defined a new category: heart failure with mid-range ejection fraction (HFmrEF) of 40-49%. This new category was highlighted as having limited evidence and research was advocated into underlying characteristics, pathophysiology, and diagnosis. We used multi-parametric cardiovascular magnetic resonance (CMR) to define the cardiac phenotype of presumed non-ischaemic HFmrEF.

Prospective Longitudinal Characterization of the Relationship between Diabetes and Cardiac Structural and Functional Changes.

Objectives: In a cohort of type 2 diabetic (T2D) patients who underwent baseline cardiac magnetic resonance (CMR) and biomarker testing, during a median follow-up of 6 years, we aimed to determine longitudinal changes in the phenotypic expression of heart disease in diabetes, report clinical outcomes, and compare baseline clinical characteristics and CMR findings of patients who experienced major adverse cardiovascular events (MACE) to those remaining MACE free.

Background: T2D increases the risk of heart failure (HF) and cardiovascular mortality. The long-term impact of T2D on cardiac phenotype in the absence of cardiovascular disease and other clinical events is unknown.

Empagliflozin Treatment Is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of major adverse cardiovascular (CV) events and hospitalization for heart failure (HF) in patients with type 2 diabetes (T2D). Using CV MRI (CMR) and P-MRS in a longitudinal cohort study, we aimed to investigate the effects of the selective SGLT2 inhibitor empagliflozin on myocardial energetics and cellular volume, function, and perfusion. Eighteen patients with T2D underwent CMR and P-MRS scans before and after 12 weeks' empagliflozin treatment.

Systematic review of studies investigating ventilator associated pneumonia diagnostics in intensive care.

Background: Ventilator-associated pneumonia (VAP) is an important diagnosis in critical care. VAP research is complicated by the lack of agreed diagnostic criteria and reference standard test criteria. Our aim was to review which reference standard tests are used to evaluate novel index tests for suspected VAP.

Detrimental Immediate- and Medium-Term Clinical Effects of Right Ventricular Pacing in Patients With Myocardial Fibrosis.

Background: Long-term right ventricular (RV) pacing leads to heart failure or a decline in left ventricular (LV) function in up to a fifth of patients. We aimed to establish whether patients with focal fibrosis detected on late gadolinium enhancement cardiovascular magnetic resonance (CMR) have deterioration in LV function after RV pacing.

Methods: We recruited 84 patients with LV ejection fraction ≥40% into 2 observational CMR studies.

A comparison of standard and high dose adenosine protocols in routine vasodilator stress cardiovascular magnetic resonance: dosage affects hyperaemic myocardial blood flow in patients with severe left ventricular systolic impairment.

Background: Adenosine stress perfusion cardiovascular magnetic resonance (CMR) is commonly used in the assessment of patients with suspected ischaemia. Accepted protocols recommend administration of adenosine at a dose of 140 µg/kg/min increased up to 210 µg/kg/min if required. Conventionally, adequate stress has been assessed using change in heart rate, however, recent studies have suggested that these peripheral measurements may not reflect hyperaemia and can be blunted, in particular, in patients with heart failure.

Activated neutrophil fluorescent imaging technique for human lungs.

Neutrophil activation is an integral process to acute inflammation and is associated with adverse clinical sequelae. Identification of neutrophil activation in real time in the lungs of patients may permit biological stratification of patients in otherwise heterogenous cohorts typically defined by clinical criteria. No methods for identifying neutrophil activation in real time in the lungs of patients currently exist.

Exercise cardiovascular magnetic resonance: feasibility and development of biventricular function and great vessel flow assessment, during continuous exercise accelerated by Compressed SENSE: preliminary results in healthy volunteers.

Purpose: Exercise cardiovascular magnetic resonance (Ex-CMR) typically requires complex post-processing or transient exercise cessation, decreasing clinical utility. We aimed to demonstrate the feasibility of assessing biventricular volumes and great vessel flow during continuous in-scanner Ex-CMR, using vendor provided Compressed SENSE (C-SENSE) sequences and commercial analysis software (Cvi42).

Methods: 12 healthy volunteers (8-male, age: 35 ± 9 years) underwent continuous supine cycle ergometer (Lode-BV) Ex-CMR (1.

Exercise cardiovascular magnetic resonance: development, current utility and future applications.

Stress cardiac imaging is the current first line investigation for coronary artery disease diagnosis and decision making and an adjunctive tool in a range of non-ischaemic cardiovascular diseases. Exercise cardiovascular magnetic resonance (Ex-CMR) has developed over the past 25 years to combine the superior image qualities of CMR with the preferred method of exercise stress. Presently, numerous exercise methods exist, from performing stress on an adjacent CMR compatible treadmill to in-scanner exercise, most commonly on a supine cycle ergometer.

Feasibility and reproducibility of a cardiovascular magnetic resonance free-breathing, multi-shot, navigated image acquisition technique for ventricular volume quantification during continuous exercise.

Background: Cardiovascular magnetic resonance (CMR) image acquisition techniques during exercise typically requires either transient cessation of exercise or complex post-processing, potentially compromising clinical utility. We evaluated the feasibility and reproducibility of a navigated image acquisition method for ventricular volumes assessment during continuous physical exercise.

Methods: Ten healthy volunteers underwent supine cycle ergometer (Lode) exercise CMR on two separate occasions using a free-breathing, multi-shot, navigated, balanced steady-state free precession cine pulse sequence.

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.

Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.

Design, Setting, And Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin.

Direct oral anticoagulants compared to vitamin K antagonist for the management of left ventricular thrombus.

Aims: Left ventricular (LV) thrombus is increasingly detected in patients with and without ischaemic heart disease due to the increased availability of cardiac magnetic resonance imaging. Risk factors include anterior ST elevation myocardial infarction, delayed reperfusion therapy, and non-ischaemic cardiomyopathy with severe LV systolic dysfunction. We aimed to report the characteristics and outcomes of patients with LV thrombus treated with either vitamin K antagonist (VKA) or direct oral anticoagulants (DOAC) with a view to describing differences in efficacy, specifically, subsequent thromboembolic events, thrombus resolution, and also side effects of therapy including clinically significant bleeding.

Insight Into Myocardial Microstructure of Athletes and Hypertrophic Cardiomyopathy Patients Using Diffusion Tensor Imaging.

Background: Hypertrophic cardiomyopathy (HCM) remains the commonest cause of sudden cardiac death among young athletes. Differentiating between physiologically adaptive left ventricular (LV) hypertrophy observed in athletes' hearts and pathological HCM remains challenging. By quantifying the diffusion of water molecules, diffusion tensor imaging (DTI) MRI allows voxelwise characterization of myocardial microstructure.

Enhanced avidity from a multivalent fluorescent antimicrobial peptide enables pathogen detection in a human lung model.

Rapid in situ detection of pathogens coupled with high resolution imaging in the distal human lung has the potential to provide new insights and diagnostic utility in patients in whom pneumonia is suspected. We have previously described an antimicrobial peptide (AMP) Ubiquicidin (fragment UBI) labelled with an environmentally sensitive fluorophore that optically detected bacteria in vitro but not ex vivo. Here, we describe further chemical development of this compound and demonstrate that altering the secondary structure of the AMP to generate a tri-branched dendrimeric scaffold provides enhanced signal in vitro and ex vivo and consequently allows the rapid detection of pathogens in situ in an explanted human lung.

In situ identification of Gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid A.

Respiratory infections in mechanically ventilated patients caused by Gram-negative bacteria are a major cause of morbidity. Rapid and unequivocal determination of the presence, localization, and abundance of bacteria is critical for positive resolution of the infections and could be used for patient stratification and for monitoring treatment efficacy. Here, we developed an in situ approach to visualize Gram-negative bacterial species and cellular infiltrates in distal human lungs in real time.

Super-silent FRET Sensor Enables Live Cell Imaging and Flow Cytometric Stratification of Intracellular Serine Protease Activity in Neutrophils.

Serine proteases are released by neutrophils to act primarily as antimicrobial proteins but excessive and unbalanced serine protease activity results in serious host tissue damage. Here the synthesis of a novel chemical sensor based on a multi-branched fluorescence quencher is reported. It is super-silent, exhibiting no fluorescence until de-quenched by the exemplar serine protease human neutrophil elastase, rapidly enters human neutrophils, and is inhibited by serine protease inhibitors.