Triple-fusion protein (TriFu): A potent, targeted, enzyme-like inhibitor of all three complement activation pathways.

The introduction of a therapeutic anti-C5 antibody into clinical practice in 2007 inspired a surge into the development of complement-targeted therapies. This has led to the recent approval of a C3 inhibitory peptide, an antibody directed against C1s and a full pipeline of several complement inhibitors in preclinical and clinical development. However, no inhibitor is available that efficiently inhibits all three complement initiation pathways and targets host cell surface markers as well as complement opsonins.

Imidazoquinolines with improved pharmacokinetic properties induce a high IFNα to TNFα ratio and .

TLR Agonists have promising activity in preclinical models of viral infection and cancer. However, clinical use is only in topical application. Systemic uses of TLR-ligands such as Resiquimod, have failed due to adverse effects that limited dose and thus, efficacy.

Selective Inhibitors of Janus Kinase 3 Modify Responses to Lipopolysaccharides by Increasing the Interleukin-10-to-Tumor Necrosis Factor α Ratio.

Janus kinase (JAK) inhibitors act at low doses (., tofacitinib, 0.2-0.

Immune cell targeted fumaric esters support a role of GPR109A as a primary target of monomethyl fumarate in vivo.

Dimethyl fumarate (DMF) is approved as a treatment for multiple sclerosis (MS), however, its mode of action remains unclear. One hypothesis proposes that Michael addition to thiols by DMF, notably glutathione is immunomodulatory. The alternative proposes that monomethyl fumarate (MMF), the hydrolysis product of DMF, is a ligand to the fatty acid receptor GPR109A found in the lysosomes of immune cells.

Isostearic acid is an active component of imiquimod formulations used to induce psoriaform disease models.

Topical imiquimod based creams are indicated as immune stimulants for papillomas and various skin neoplasms. Imiquimod is considered a TLR7 ligand. These creams are also used in research to induce skin inflammation in mice as a model for psoriasis.

Repeatability and reproducibility of cardiac manganese-enhanced magnetic resonance imaging.

Manganese-enhanced magnetic resonance imaging can provide a surrogate measure of myocardial calcium handling. Its repeatability and reproducibility are currently unknown. Sixty-eight participants: 20 healthy volunteers, 20 with acute myocardial infarction, 18 with hypertrophic and 10 with non-ischemic dilated cardiomyopathy underwent manganese-enhanced magnetic resonance imaging.

MRI and CT coronary angiography in survivors of COVID-19.

Objectives: To determine the contribution of comorbidities on the reported widespread myocardial abnormalities in patients with recent COVID-19.

Methods: In a prospective two-centre observational study, patients hospitalised with confirmed COVID-19 underwent gadolinium and manganese-enhanced MRI and CT coronary angiography (CTCA). They were compared with healthy and comorbidity-matched volunteers after blinded analysis.

First-phase ejection fraction by cardiovascular magnetic resonance predicts outcomes in aortic stenosis.

Background: First-phase ejection fraction (EF1; the ejection fraction measured during active systole up to the time of maximal aortic flow) measured by transthoracic echocardiography (TTE) is a powerful predictor of outcomes in patients with aortic stenosis. We aimed to assess whether cardiovascular magnetic resonance (CMR) might provide more precise measurements of EF1 than TTE and to examine the correlation of CMR EF1 with measures of fibrosis.

Methods: In 141 patients with at least mild aortic stenosis, we measured CMR EF1 from a short-axis 3D stack and compared its variability with TTE EF1, and its associations with myocardial fibrosis and clinical outcome (aortic valve replacement (AVR) or death).

Assessment of stunned and viable myocardium using manganese-enhanced MRI.

Objective: In a proof-of-concept study, to quantify myocardial viability in patients with acute myocardial infarction using manganese-enhanced MRI (MEMRI), a measure of intracellular calcium handling.

Methods: Healthy volunteers (n=20) and patients with ST-elevation myocardial infarction (n=20) underwent late gadolinium enhancement (LGE) using gadobutrol and MEMRI using manganese dipyridoxyl diphosphate. Patients were scanned ≤7 days after reperfusion and rescanned after 3 months.

Manganese-enhanced magnetic resonance imaging in dilated cardiomyopathy and hypertrophic cardiomyopathy.

Aims: The aim of this study is to quantify altered myocardial calcium handling in non-ischaemic cardiomyopathy using magnetic resonance imaging.

Methods And Results: Patients with dilated cardiomyopathy (n = 10) or hypertrophic cardiomyopathy (n = 17) underwent both gadolinium and manganese contrast-enhanced magnetic resonance imaging and were compared with healthy volunteers (n = 20). Differential manganese uptake (Ki) was assessed using a two-compartment Patlak model.

Adverse health effects associated with household air pollution: a systematic review, meta-analysis, and burden estimation study.

Background: 3 billion people worldwide rely on polluting fuels and technologies for domestic cooking and heating. We estimate the global, regional, and national health burden associated with exposure to household air pollution.

Methods: For the systematic review and meta-analysis, we systematically searched four databases for studies published from database inception to April 2, 2020, that evaluated the risk of adverse cardiorespiratory, paediatric, and maternal outcomes from exposure to household air pollution, compared with no exposure.

18F-fluoride PET/MR in cardiac amyloid: A comparison study with aortic stenosis and age- and sex-matched controls.

Objectives: Cardiac MR is widely used to diagnose cardiac amyloid, but cannot differentiate AL and ATTR subtypes: an important distinction given their differing treatments and prognoses. We used PET/MR imaging to quantify myocardial uptake of 18F-fluoride in ATTR and AL amyloid patients, as well as participants with aortic stenosis and age/sex-matched controls.

Methods: In this prospective multicenter study, patients were recruited in Edinburgh and New York and underwent 18F-fluoride PET/MR imaging.

Quantification of Macrophage-Driven Inflammation During Myocardial Infarction with F-LW223, a Novel TSPO Radiotracer with Binding Independent of the rs6971 Human Polymorphism.

Myocardial infarction (MI) is one of the leading causes of death worldwide, and inflammation is central to tissue response and patient outcomes. The 18-kDa translocator protein (TSPO) has been used in PET as an inflammatory biomarker. The aims of this study were to screen novel, fluorinated, TSPO radiotracers for susceptibility to the rs6971 genetic polymorphism using in vitro competition binding assays in human brain and heart; assess whether the in vivo characteristics of our lead radiotracer, F-LW223, are suitable for clinical translation; and validate whether F-LW223 can detect macrophage-driven inflammation in a rat MI model.

Short-term exposure to carbon monoxide and myocardial infarction: A systematic review and meta-analysis.

Background: Previous studies suggest an association between short-term exposure to carbon monoxide and myocardial infarction. We performed a systematic review and meta-analysis to assess current evidence on this association to support the update of the World Health Organization (WHO) Global Air Quality Guidelines.

Methods: We searched Medline, Embase and Cochrane Central Register of Controlled Trials to update the evidence published in a previous systematic review up to 30th September 2018 for studies investigating the association between short-term exposure to ambient carbon monoxide (up to lag of seven days) and emergency department visits or hospital admissions and mortality due to myocardial infarction.

Determinants and prognostic value of echocardiographic first-phase ejection fraction in aortic stenosis.

Objective: First-phase ejection fraction (EF1) is a novel measure of early left ventricular systolic dysfunction. We investigated determinants of EF1 and its prognostic value in aortic stenosis.

Methods: EF1 was measured retrospectively in participants of an echocardiography/cardiovascular magnetic resonance cohort study which recruited patients with aortic stenosis (peak aortic velocity of ≥2 m/s) between 2012 and 2014.

Manganese-enhanced T mapping to quantify myocardial viability: validation with F-fluorodeoxyglucose positron emission tomography.

Gadolinium chelates are widely used in cardiovascular magnetic resonance imaging (MRI) as passive intravascular and extracellular space markers. Manganese, a biologically active paramagnetic calcium analogue, provides novel intracellular myocardial tissue characterisation. We previously showed manganese-enhanced MRI (MEMRI) more accurately quantifies myocardial infarction than gadolinium delayed-enhancement MRI (DEMRI).

Manganese-enhanced MRI of the myocardium.

Gadolinium-based contrast media are widely used in cardiovascular MRI to identify and to highlight the intravascular and extracellular space. After gadolinium, manganese has the second highest paramagnetic moment and was one of the first MRI contrast agents assessed in humans. Over the last 50 years, manganese-enhanced MRI (MEMRI) has emerged as a complementary approach enabling intracellular myocardial contrast imaging that can identify functional myocardium through its ability to act as a calcium analogue.

Complications and prognosis of patients undergoing apical or septal right ventricular pacing.

Objectives: Optimal right ventricular lead placement remains controversial. Large studies investigating the safety and long-term prognosis of apical and septal right ventricular lead placement have been lacking.

Methods: Consecutive patients undergoing pacemaker insertion for high-degree atrioventricular block at Edinburgh Heart Centre were investigated.

Myocardial and Systemic Inflammation in Acute Stress-Induced (Takotsubo) Cardiomyopathy.

Background: Acute stress-induced (takotsubo) cardiomyopathy can result in a heart failure phenotype with a prognosis comparable with that of myocardial infarction. In this study, we hypothesized that inflammation is central to the pathophysiology and natural history of takotsubo cardiomyopathy.

Methods: In a multicenter study, we prospectively recruited 55 patients with takotsubo cardiomyopathy and 51 age-, sex-, and comorbidity-matched control subjects.

Manganese-Enhanced T Mapping in the Myocardium of Normal and Infarcted Hearts.

Background: Manganese-enhanced MRI (MEMRI) has the potential to identify viable myocardium and quantify calcium influx and handling. Two distinct manganese contrast media have been developed for clinical application, mangafodipir and EVP1001-1, employing different strategies to mitigate against adverse effects resulting from calcium-channel agonism. Mangafodipir delivers manganese ions as a chelate, and EVP1001-1 coadministers calcium gluconate.

Absence of Myocardial Fibrosis Predicts Favorable Long-Term Survival in New-Onset Heart Failure.

Background: Myocardial fibrosis, identified by late gadolinium enhancement cardiovascular magnetic resonance, predicts outcomes in chronic heart failure (HF). Its prognostic significance in new-onset HF and reduced left ventricular ejection fraction (LVEF) is unclear. We investigated whether the pattern and extent of fibrosis predict survival in new-onset HF and reduced LVEF of initially uncertain pathogenesis.

Myocardial inflammation, injury and infarction during on-pump coronary artery bypass graft surgery.

Background: Myocardial inflammation and injury occur during coronary artery bypass graft (CABG) surgery. We aimed to characterise these processes during routine CABG surgery to inform the diagnosis of type 5 myocardial infarction.

Methods: We assessed 87 patients with stable coronary artery disease who underwent elective CABG surgery.