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

Ultrasensitive serum interferon-α quantification during SLE remission identifies patients at risk for relapse

International audienceObjectives Maintenance of remission has become central in the management of systemic lupus erythematosus (SLE). The importance of interferon-alpha (IFN-α) in the pathogenesis of SLE notwithstanding, its expression in remission has been poorly studied as yet. To study its expression in remission and its prognostic value in the prediction of a disease relapse, serum IFN-α levels were determined using an ultrasensitive single-molecule array digital immunoassay which enables the measurement of cytokines at physiological concentrations.Methods A total of 254 SLE patients in remission, according to the Definition of Remission in SLE classification, were included in the study. Serum IFN-α concentrations were determined at baseline and patients were followed up for 1 year. Lupus flares were defined according to the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index Flare Index, whereas the Kaplan-Meier analysis and Cox regression analysis were used to estimate the time to relapse and to identify baseline factors associated with time to relapse, respectively.Results Of all patients in remission, 26% displayed abnormally high IFN-α serum levels that were associated with the presence of antibodies specific for ribonucleoprotein (RNP), double stranded (ds)DNA and Ro/SSA60, as well as young age. Importantly, elevated-baseline IFN-α serum levels and remission duration were associated in an independent fashion, with shorter time to relapse, while low serum levels of complement component 3 and anti-dsDNA Abs were not.Conclusion Direct serum IFN-α assessment with highly sensitive digital immunoassay permits clinicians to identify a subgroup of SLE patients, clinically in remission, but at higher risk of relapse

Critically Ill Patients with Visceral Nocardia Infection, France and Belgium, 2004-2023.

peer reviewedWe studied 50 patients with invasive nocardiosis treated during 2004-2023 in intensive care centers in France and Belgium. Most (65%) died in the intensive care unit or in the year after admission. Nocardia infections should be included in the differential diagnoses for patients in the intensive care setting

Sjögren's syndrome: State of the art on clinical practice guidelines

Sjögren's syndrome (SS) is a complex autoimmune rheumatic disease that specifically targets salivary and lachrymal glands. As such, patients typically had ocular and oral dryness and salivary gland swelling. Moreover, skin, nasal and vaginal dryness are frequently present. In addition to dryness, musculoskeletal pain and fatigue are the hallmarks of this disease and constitute the classic symptom triad presented by the vast majority of patients. Up to 30% to 50 % of patients with SS may present systemic disease; moreover, there is an increased risk for the development of non-Hodgkin's lymphoma that occurs in a minority of patients. The present work was developed in the framework of the European Reference Network (ERN) dedicated to Rare and Complex Connective Tissue and Musculoskeletal Diseases (ReCONNET). In line with its goals of aiming to improve early diagnosis, treatment and care of rare connective and musculoskeletal diseases, ERN-ReCONNET set to review the current state of clinical practice guidelines (CPGs) in the rare and complex connective tissue diseases of interest of the network. Therefore, the present work was aimed at providing a state of the art of CPGs for SS

New Challenges in Diagnosis, Prognosis and Management of Rare Immunological Disorders in Intensive Care Unit

Les maladies immunologiques systémiques rares sont un ensemble de pathologies pouvant être responsables de l’atteinte concomitante ou asynchrone de plusieurs organes. Leur origine procède d’une altération de la réponse/régulation immunitaire ou inflammatoire. Elles partagent des caractéristiques qui justifient de les regrouper pour les étudier. Ces affections peuvent être responsables de défaillances d’organes et conduire à une admission en soins critiques. Le diagnostic et le traitement en réanimation en sont particulièrement complexes et spécifiques, justifiant d’être un champ d’étude à part entière. L’objectif de ce travail est de faire progresser les connaissances sur ces affections dans leur globalité puis en étudiant spécifiquement certaines maladies. L’un des temps majeurs de ce travail est la description d’une nouvelle entité : la myocardite associée aux anticorps anti-ARN-polymérase-III. Il s’agit de la survenue chez de jeunes femmes, porteuses d’anticorps ciblant l’anticorps anti-ARN-polymérase-III, de myocardites et/ou de péricardites liées à des virus à ARN comme la grippe ou la COVID-19. Leur présentation clinique est très grave et justifie dans la majorité des cas un séjour en réanimation, avec un recours fréquent à l’assistance circulatoire extracorporelle. Ces myocardites sont récidivantes selon un intervalle variable. L’étude du profil cytokinique révèle une réponse antivirale médiée par l’interféron-2 à la différence d’autres formes de myocardites. Entre deux épisodes de myocardites les patientes sont asymptomatiques et la grande majorité des malades ne présente pas de sclérodermie systémique. Les maladies systémiques sont un cadre nosologique en constante évolution. De nouvelles maladies continuent d’apparaitre, fruits des avancées des méthodes diagnostiques générant leur cortège de manifestations graves. La physiopathologie de nombreuses maladies systémiques résiste encore aux avancées de la recherche translationnelle faisant de l’étude de ces affections, particulièrement dans leurs formes les plus sévères, un sujet d’actualité et d’avenir.Rare immunological systemic diseases is a group of disorders defined by their ability to affect several organs concomitantly or asynchronously. They proceed from an altered or dysregulated immune or inflammatory response. They share common characteristics that makes appropriate to study them altogether. These conditions can be responsible for organ failures requiring intensive care unit admission. Their diagnosis and treatment in intensive care is difficult and misleading needing to be specifically investigated. Our work aims to expand the knowledge on the severe manifestations of these conditions studying them firstly altogether, then specifically investigating some on them. One of our major findings is the description of a new condition: the myocarditis associated with anti-RNA-polymerase-III antibodies. It is defined by the occurrence in mainly young female, with detectable serum anti-RNA-polymerase-III antibodies, of severe myocarditis and/or pericarditis related to RNA virus infections (i.e. the flu or COVID-19). Myocarditis are usually severe, responsible for intensive care unit admission, and frequent need for temporary circulatory support. These myocarditis often relapse with a variable time interval. The cytokine profiling revealed an interferon-a2-mediated response, conversely to other forms of myocarditis. In between episodes, patients are asymptomatic, the vast majority having no sign of systemic sclerosis. Rare immunological systemic diseases is an ever evolving group of diseases. New conditions are regularly being discovered, owing advances in diagnostic methods, with their share of severe clinical manifestations. The pathophysiology of a significant number of these diseases still remains elusive. Further investigating critically-ill patients with rare immunological systemic diseases is a urgently needed

Venoarterial extracorporeal membrane oxygenation in cardiogenic shock: indications, mode of operation, and current evidence

International audiencePURPOSE OF REVIEW: Temporary circulatory support (TCS) with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a salvage therapy for patients with refractory cardiogenic shock. This article provides an overview of VA-ECMO principles, indications, management, complications, and discusses the results of recent case series and trials.RECENT FINDINGS: VA-ECMO is utilized as a bridge to 'decision' that includes weaning after cardiac function recovery, transplantation, long-term mechanical circulatory support, and withdrawal in case of futility. VA-ECMO is considered the first-line TCS as it allows rapid improvement in oxygenation, is less expensive, and is also suitable for patients with biventricular failure. Combining Impella (Abiomed, Danvers, MA, USA) or intra-aortic balloon pump support with VA-ECMO might decrease left ventricular pressure and improve outcomes. Massive pulmonary embolism, sepsis-associated cardiomyopathy, and refractory cardiac arrest are among emerging indications for TCS.SUMMARY: TCS have become the cornerstone of the management of patients with cardiogenic shock, although the evidence supporting their efficacy is limited. VA-ECMO is considered the first-line option, with a growing number of accepted and emerging indications. Randomized clinical trials are now needed to determine the place VA-ECMO in cardiogenic shock treatment strategies

What’s new in cardiogenic shock?

International audiencePurpose of review: Temporary circulatory support (TCS) devices are increasingly used as a salvage therapy for patients with refractory cardiogenic shock. The exact place of the different TCS devices in the management of cardiogenic shock patients remains unclear and intensely debated. This article provides an overview on new cardiogenic shock classification, currently available devices, place of TCS in the management of cardiogenic shock patients, and discusses the results of recent case series and trials in this setting.Recent finding: A new classification system for cardiogenic shock has recently been proposed to homogenize definitions of cardiogenic shock and appropriately differentiate patient subsets in clinical trials and registries. Although the routine use of intraaortic balloon pump is no more recommended, other TCS are increasingly used and investigated but many advantages favor the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) as the first-line TCS.Summary: TCS devices have become the cornerstone of the management of patients with refractory cardiogenic shock. VA-ECMO has emerged as the first-line support system in this setting, with a growing number of accepted indications. Large adequately powered randomized controlled trials are now underway and should help to determine the respective place of different TCS devices in strategies to treat cardiogenic shock patients

Idiopathic lung fibrosis and anti myeloperoxidase glomerulonephritis: the tree that hides the forest

International audienceBackground: Although anti-neutrophil cytoplasmic antibodies [ANCA] are frequently found in patients diagnosed with idiopathic pulmonary fibrosis [IPF], current guidance does not recommend serologic testing for vasculitis. Case presentation: A 71-year old Caucasian male, diagnosed with IPF three years earlier, presented with rapidly progressive glomerulonephritis. ANCA were found both in current and historical sera. A kidney biopsy sample was taken, which revealed a pauci-immune glomerulonephritis, but also areas of glomerular fibrosis, hence strongly suggesting unrecognized flares of an indolent vasculitis in his past. This made the diagnosis of " idiopathic " pulmonary fibrosis very unlikely. Conclusion: As nephrologists, we argue that testing for ANCA should be performed on a systematic basis, at least in elderly patients, even in the absence of extra-pulmonary signs of vasculitis at presentation

Response to: ‘Presence of anti-phospholipid antibodies in COVID-19: a case series study’ by Amezcua-Guerra et al

International audienc

Antibiotic stewardship in the ICU: time to shift into overdrive

Abstract Antibiotic resistance is a major health problem and will be probably one of the leading causes of deaths in the coming years. One of the most effective ways to fight against resistance is to decrease antibiotic consumption. Intensive care units (ICUs) are places where antibiotics are widely prescribed, and where multidrug-resistant pathogens are frequently encountered. However, ICU physicians may have opportunities to decrease antibiotics consumption and to apply antimicrobial stewardship programs. The main measures that may be implemented include refraining from immediate prescription of antibiotics when infection is suspected (except in patients with shock, where immediate administration of antibiotics is essential); limiting empiric broad-spectrum antibiotics (including anti-MRSA antibiotics) in patients without risk factors for multidrug-resistant pathogens; switching to monotherapy instead of combination therapy and narrowing spectrum when culture and susceptibility tests results are available; limiting the use of carbapenems to extended-spectrum beta-lactamase-producing Enterobacteriaceae, and new beta-lactams to difficult-to-treat pathogen (when these news beta-lactams are the only available option); and shortening the duration of antimicrobial treatment, the use of procalcitonin being one tool to attain this goal. Antimicrobial stewardship programs should combine these measures rather than applying a single one. ICUs and ICU physicians should be at the frontline for developing antimicrobial stewardship programs