Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial.

BACKGROUND: Infections with SARS-CoV-2 continue to cause significant morbidity and mortality. Interleukin (IL)-1 and IL-6 blockade have been proposed as therapeutic strategies in COVID-19, but study outcomes have been conflicting. We sought to study whether blockade of the IL-6 or IL-1 pathway shortened the time to clinical improvement in patients with COVID-19, hypoxic respiratory failure, and signs of systemic cytokine release syndrome. METHODS: We did a prospective, multicentre, open-label, randomised, controlled trial, in hospitalised patients with COVID-19, hypoxia, and signs of a cytokine release syndrome across 16 hospitals in Belgium. Eligible patients had a proven diagnosis of COVID-19 with symptoms between 6 and 16 days, a ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO(2):FiO(2)) of less than 350 mm Hg on room air or less than 280 mm Hg on supplemental oxygen, and signs of a cytokine release syndrome in their serum (either a single ferritin measurement of more than 2000 μg/L and immediately requiring high flow oxygen or mechanical ventilation, or a ferritin concentration of more than 1000 μg/L, which had been increasing over the previous 24 h, or lymphopenia below 800/mL with two of the following criteria: an increasing ferritin concentration of more than 700 μg/L, an increasing lactate dehydrogenase concentration of more than 300 international units per L, an increasing C-reactive protein concentration of more than 70 mg/L, or an increasing D-dimers concentration of more than 1000 ng/mL). The COV-AID trial has a 2 × 2 factorial design to evaluate IL-1 blockade versus no IL-1 blockade and IL-6 blockade versus no IL-6 blockade. Patients were randomly assigned by means of permuted block randomisation with varying block size and stratification by centre. In a first randomisation, patients were assigned to receive subcutaneous anakinra once daily (100 mg) for 28 days or until discharge, or to receive no IL-1 blockade (1:2). In a second randomisation step, patients were allocated to receive a single dose of siltuximab (11 mg/kg) intravenously, or a single dose of tocilizumab (8 mg/kg) intravenously, or to receive no IL-6 blockade (1:1:1). The primary outcome was the time to clinical improvement, defined as time from randomisation to an increase of at least two points on a 6-category ordinal scale or to discharge from hospital alive. The primary and supportive efficacy endpoints were assessed in the intention-to-treat population. Safety was assessed in the safety population. This study is registered online with ClinicalTrials.gov (NCT04330638) and EudraCT (2020-001500-41) and is complete. FINDINGS: Between April 4, and Dec 6, 2020, 342 patients were randomly assigned to IL-1 blockade (n=112) or no IL-1 blockade (n=230) and simultaneously randomly assigned to IL-6 blockade (n=227; 114 for tocilizumab and 113 for siltuximab) or no IL-6 blockade (n=115). Most patients were male (265 [77%] of 342), median age was 65 years (IQR 54-73), and median Systematic Organ Failure Assessment (SOFA) score at randomisation was 3 (2-4). All 342 patients were included in the primary intention-to-treat analysis. The estimated median time to clinical improvement was 12 days (95% CI 10-16) in the IL-1 blockade group versus 12 days (10-15) in the no IL-1 blockade group (hazard ratio [HR] 0·94 [95% CI 0·73-1·21]). For the IL-6 blockade group, the estimated median time to clinical improvement was 11 days (95% CI 10-16) versus 12 days (11-16) in the no IL-6 blockade group (HR 1·00 [0·78-1·29]). 55 patients died during the study, but no evidence for differences in mortality between treatment groups was found. The incidence of serious adverse events and serious infections was similar across study groups. INTERPRETATION: Drugs targeting IL-1 or IL-6 did not shorten the time to clinical improvement in this sample of patients with COVID-19, hypoxic respiratory failure, low SOFA score, and low baseline mortality risk. FUNDING: Belgian Health Care Knowledge Center and VIB Grand Challenges program

L’alcoolisme au tournant du XXe siècle :les positions belges dans les débats européens

En Europe, entre 1880 et 1914, l’alcoolisme, un des trois fléaux sociaux, constitue plus que jamais une inquiétude chez les bourgeois bien pensants pour les ravages qu’il cause dans leur classe populaire. Dans ce climat, deux écoles " anti-alcooliques " s’affrontent sur la politique à suivre :condamner seulement l’eau-de-vie ou toute forme de boisson alcoolisée. La Belgique, nation de la bière, est partie intégrante dans ce houleux débat...info:eu-repo/semantics/publishe

L'alcoolisme au tournant du XXe siècle: les positions belges dans les débats européens

In Europe, between 1880 and 1914, the alcoolism, one of the three social ills, represents more than ever a concern among the society's leaders against the ravages it causes in their working class. In this context, two schools of " antialcoholism " clash to policy matters :To prevent to only spirits or any form of alcohol beverage. Belgium, land of beer, forms an integral part of the debate...SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Le nodule thyroïdien: Bénin ou malin?

A thyroid nodule is a frequent occurrence. Its prevalence in a general adult population is about 50% and can even reach 67% when a cervical echography is performed. Only 5% of these nodules are cancers, and it is therefore important to avoid an useless and riskful surgery. This presentation is based on the Medical Guidelines for Clinical Practice :American Association of Clinical Endocrinologists (AACE), Associazione Medici Endocrinologi (AME) and European Thyroid Association (ETA) in 2010 for the Diagnosis and Management of Thyroid Nodules. In the absence of prospective randomized studies, these recommendations are established on the best evidence level. The patient history and clinical signs give some informations about potential risks. Thyroid tests not only evaluate thyroid functional status but TSH value and the presence of antithyroglobuline antibody seem to be associated with a higher risk of malignancy. A thyroid scintigraphy detects the presence of hot thyroid nodules. The thyroid echography is a key element before fine needle aspiration cytology. Some echographic criteria in the TIRADS (Thyroid Imaging Reporting and Data System), classification can reach an 88% sensitivity, a 49% specificity, a 49% positive predictive value, an 88% negative predictive value and a 94% diagnostic accuracy. The fine needle aspiration cytology performed with echography will be crucial to decide if the patient is to be eligible for surgery. In 70 to 80% of the cases, nodules can be classified as benign or malignant with a 92% negative predictive value for a benign diagnosis and a 100% positive predictive value for a diagnosis of cancer. The discovery of a follicular proliferation (cancer incidence of 20-30%) is a grey zone. Follicular proliferation and definite cancer lead of course to a surgical option. A decisional tree summarizes the different steps leading to a therapeutic decision.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Histoire d'une toux chronique.

A 64 years old woman was admitted for persistent dry cough. The cough was lasting for one month and was associated with throat clearing, asthenia and low fever mainly at night. A thorough anamnesis also revealed the existence of mild occipital headache. Empirical antibiotic therapy (clarithromycine) had previously been administered without any clinical improvement. Physical examination was normal. However, the blood tests showed an inflammatory syndrome. The diagnostic approach was focused on the lungs, sinuses and digestive tract and did not show any acute disease. The bronchoscopy demonstrated an edematous bronchial mucosa without endoluminal lesion. The results of bacteriological tests performed were negative. Given the age of the patient and the persistence of an inflammatory syndrome of unknown origin, the diagnosis of giant cell arteritis should be excluded, despite an unusual clinical presentation. This hypothesis was supported by a diagnostic biopsy of the right temporal artery, which histological analysis showed characteristic pattern.Case ReportsEnglish AbstractJournal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Une nécrolyse épidermique induite par pembrolizumab chez un patient atteint d’un cancer pulmonaire

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Autoimmune polyendocrine syndrome and thrombocytosis

We describe a woman aged 37 years, affected with Hashimoto's thyroiditis, detected since the age of 17, with gonadic insufficiency with anti-ovarian antibodies since the age of 22 years and Addison's disease since 24 years old. At that moment, the diagnosis of autoimmune polyendocrine syndrome (APS) was made. Concomitant to this diagnosis, thrombocytosis was detected and aetiological assessment revealed an atrophy of the spleen. Differential diagnoses of APS and hyposplenism will be discussed. We will look at a possible association between these two pathologies. Indeed, asplenism is found in approximately 20% of adults affected by type 1 APS, also called auto-immune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) syndrome. The most likely aetiology for this atrophy of the spleen is a destruction of auto-immunological origin. However, in our patient, the search for a mutation of the autoimmune regulator (AIRE) gene proved negative. This mutation is commonly, but not systematically, present in type 1 APS. A type 2 APS should then be considered.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Amiodarone et dysthyroidies - Etude prospective et revue de la litterature

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Doxycyline and hepatotoxicity

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