Immunomodulating Therapies in Acute Myocarditis and Recurrent/Acute Pericarditis

The field of inflammatory disease of the heart or "cardio-immunology " is rapidly evolving due to the wider use of non-invasive diagnostic tools able to detect and monitor myocardial inflammation. In acute myocarditis, recent data on the use of immunomodulating therapies have been reported both in the setting of systemic autoimmune disorders and in the setting of isolated forms, especially in patients with specific histology (e.g., eosinophilic myocarditis) or with an arrhythmicburden. A role for immunosuppressive therapies has been also shown in severe cases of coronavirus disease 2019 (COVID-19), a condition that can be associated with cardiac injury and acute myocarditis. Furthermore, ongoing clinical trials are assessing the role of high dosage methylprednisolone in the context of acute myocarditis complicated by heart failure or fulminant presentation or the role of anakinra to treat patients with acute myocarditis excluding patients with hemodynamically unstable conditions. In addition, the explosion of immune-mediated therapies in oncology has introduced new pathophysiological entities, such as immune-checkpoint inhibitor-associated myocarditis and new basic research models to understand the interaction between the cardiac and immune systems. Here we provide a broad overview of evolving areas in cardio-immunology. We summarize the use of new imaging tools in combination with endomyocardial biopsy and laboratory parameters such as high sensitivity troponin to monitor the response to immunomodulating therapies based on recent evidence and clinical experience. Concerning pericarditis, the normal composition of pericardial fluid has been recently elucidated, allowing to assess the actual presence of inflammation; indeed, normal pericardial fluid is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Importantly, recent findings showed how innate immunity plays a pivotal role in the pathogenesis of recurrent pericarditis with raised C-reactive protein, with inflammasome and IL-1 overproduction as drivers for systemic inflammatory response. In the era of tailored medicine, anti-IL-1 agents such as anakinra and rilonacept have been demonstrated highly effective in patients with recurrent pericarditis associated with an inflammatory phenotype.Peer reviewe

Mass balance of the Greenland Ice Sheet from 1992 to 2018

In recent decades, the Greenland Ice Sheet has been a major contributor to global sea-level rise1,2, and it is expected to be so in the future3. Although increases in glacier flow4–6 and surface melting7–9 have been driven by oceanic10–12 and atmospheric13,14 warming, the degree and trajectory of today’s imbalance remain uncertain. Here we compare and combine 26 individual satellite measurements of changes in the ice sheet’s volume, flow and gravitational potential to produce a reconciled estimate of its mass balance. Although the ice sheet was close to a state of balance in the 1990s, annual losses have risen since then, peaking at 335 ± 62 billion tonnes per year in 2011. In all, Greenland lost 3,800 ± 339 billion tonnes of ice between 1992 and 2018, causing the mean sea level to rise by 10.6 ± 0.9 millimetres. Using three regional climate models, we show that reduced surface mass balance has driven 1,971 ± 555 billion tonnes (52%) of the ice loss owing to increased meltwater runoff. The remaining 1,827 ± 538 billion tonnes (48%) of ice loss was due to increased glacier discharge, which rose from 41 ± 37 billion tonnes per year in the 1990s to 87 ± 25 billion tonnes per year since then. Between 2013 and 2017, the total rate of ice loss slowed to 217 ± 32 billion tonnes per year, on average, as atmospheric circulation favoured cooler conditions15 and as ocean temperatures fell at the terminus of Jakobshavn Isbræ16. Cumulative ice losses from Greenland as a whole have been close to the IPCC’s predicted rates for their high-end climate warming scenario17, which forecast an additional 50 to 120 millimetres of global sea-level rise by 2100 when compared to their central estimate

(A Critical Appraisal of) Classification of Hypereosinophilic Disorders

Hypereosinophilia (HE) is a heterogeneous condition that can be reported in various (namely inflammatory, allergic, infectious, or neoplastic) diseases with distinct pathophysiological pathways. In 1975, Chusid et al. published the first diagnostic criteria of hypereosinophilic syndromes (HES). Over the years, as both basic and clinical knowledge improved, several updates have been suggested, with a focus on better distinguishing isolated or asymptomatic eosinophilia from diseases with specific eosinophil-related organ damage. Moreover, underlying molecular and cellular mechanisms of eosinophilia gradually became the cornerstone of successive attempts to classify HE-related diseases. In 2011, the International Cooperative Working Group on Eosinophil Disorders criteria emerged from a multidisciplinary Working Conference on Eosinophil Disorders and Syndromes, and provided substantial contribution to the clarification of general concepts and definitions in the field of HE. Yet, owing to the low prevalence of HE/HES, to the numerous diseases encompassed in the spectrum of HE-related disorders (with sometimes overlapping phenotypes), many questions are left unanswered (e.g., the need to better standardize the use of modern molecular tools, or the clinical relevance of distinguishing different subtypes of idiopathic HES). Here, we review the current state of knowledge in the fields of classification and diagnosis criteria of HE-related diseases, with emphasis on the analysis of both strengths and weaknesses of present concepts and their usefulness in daily practice

Eosinophilic granulomatosis with polyangiitis: the multifaceted spectrum of clinical manifestations at different stages of the disease

International audienceIntroduction: Eosinophilic granulomatosis with polyangiitis (EGPA) usually occurs in patients with late-onset asthma and sustained peripheral blood eosinophilia and classically presents with a clinical multifaceted spectrum of manifestations, which may vary at the different stages of the natural history of the disease.Areas covered: We reviewed EGPA clinical presentation, focusing on clinical manifestations at three different phases of the disease: 1/before the development of overt vasculitis, 2/at vasculitis diagnosis and 3/during the long-term follow-up. An update on current classification criteria and recent therapeutic advances has been provided as well.Expert opinion: Asthma, chronic rhinosinusitis and blood eosinophilia could anticipate the overt vasculitis for years. An atopic background may be present in a subset of patients (25-30%), while ANCA presence varies between 10 and 40%. Systemic vasculitis rapidly occurs and clinical features demonstrating vasculitis processes (neuropathy, purpura, scleritis, alveolar hemorrhage and glomerulonephritis) develop along with systemic symptoms (50%). After vasculitis resolution, asthma remains severe in up to 50% of patients and incidence of isolated-asthma and rhinosinus exacerbations remains constantly high. Different sets of classification criteria have been published so far, and DCVAS diagnostic criteria will be presented soon. Interleukin-5 blockers seem to be promising to control the disease and to spare corticosteroids