DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Angio-œdème à l’énalapril : prise en charge d’un cas en Chirurgie buccale

L’œdème angio-neurotique (OAN), ou angio-œdème bradykinique, est une maladie rare touchant une personne sur 150 000 en France. Il est dû à un déficit en inhibiteur de la C1 estérase et comporte des formes héréditaires ou acquises; l’OAN acquis d’origine médicamenteuse toucherait ainsi 0,1 à 0,7 % des patients traités par inhibiteurs de l’enzyme de conversion. Cette atteinte peut entraîner une obstruction des voies aériennes en cas d’atteinte laryngée et aboutir à un décès par asphyxie dans 25 % des cas en l’absence de traitement. L’OAN survient spontanément ou apparait provoqué par différents facteurs tels que les infections dentaires et les traitements chirurgicaux. Cet article décrit la prise en charge de foyers infectieux dentaires multiples chez une patiente ayant présenté des épisodes d’angio-œdème après l’instauration d’un traitement par inhibiteurs de l’enzyme de conversion

Predictive medicine in multiple sclerosis: A systematic review

International audienceBackground:One of the main challenges in multiple sclerosis (MS) is to predict disease progression based on patient characteristics and therapeutic strategies. We therefore performed a systematic review to critically appraise the composite tools available for this purpose.Methods:We performed electronic database searches in MEDLINE, EMBASE, Web of Science and the Cochrane Library. We included studies in English or French that developed and/or validated a predictive model for MS patients. Two reviewers independently screened articles by title and abstract. Three teams of two reviewers assessed the full text of each relevant study.Results:Database searches yielded 6,035 studies after deduplication. Among the 42 screened full texts, 15 articles satisfied the eligibility criteria. Of these, six articles examined the development of predictive tools, six articles aimed to validate existing tools and three articles proposed both development and validation. We identified numerous methodological pitfalls, especially the lack of adequate validations in terms of discrimination and calibration. Only two scoring systems were externally validated several times: the Rio and the modified Rio scores. Nevertheless, their accuracies were highly variable, ranging from 65% to 91%.Conclusions:Overall, there is a lack of validated predictive tools in MS, and further external validation of the existing ones are required. Demonstration of the clinical usefulness is also needed prior to being transferred into clinical practice. Finally, our study illustrates that the MS literature needs to integrate good standards in developing and validating predictive models

Multiple Sclerosis CSF Is Enriched With Follicular T Cells Displaying a Th1/Eomes Signature

International audienceBackground and Objectives Tertiary lymphoid structures and aggregates are reported in the meninges of patients with multiple sclerosis (MS), especially at the progressive stage, and are strongly associated with cortical lesions and disability. Besides B cells, these structures comprise follicular helper T (Tfh) cells that are crucial to support B-cell differentiation. Tfh cells play a pivotal role in amplifying autoreactive B cells and promoting autoantibody production in several autoimmune diseases, but very few are known in MS. In this study, we examined the phenotype, frequency, and transcriptome of circulating cTfh cells in the blood and CSF of patients with relapsing-remitting MS (RRMS). Methods The phenotype and frequency of cTfh cells were analyzed in the blood of 39 healthy controls and 41 untreated patients with RRMS and in the CSF and paired blood of 10 patients with drug-naive RRMS at diagnosis by flow cytometry. Using an in vitro model of blood-brain barrier, we assessed the transendothelial migratory abilities of the different cTfh-cell subsets. Finally, we performed an RNA sequencing analysis of paired CSF cTfh cells and blood cTfh cells in 8 patients sampled at their first demyelinating event. Results The blood phenotype and frequency of cTfh cells were not significantly modified in patients with RRMS. In the CSF, we found an important infiltration of Tfh1 cells, with a high proportion of activated PD1(+) cells. We demonstrated that the specific subset of Tfh1 cells presents increased migration abilities to cross an in vitro model of blood-brain barrier. Of interest, even at the first demyelinating event, cTfh cells in the CSF display specific characteristics with upregulation of EOMES gene and proinflammatory/cytotoxic transcriptomic signature able to efficiently distinguish cTfh cells from the CSF and blood. Finally, interactome analysis revealed potential strong cross talk between pathogenic B cells and CSF cTfh cells, pointing out the CSF as opportune supportive compartment and highlighting the very early implication of B-cell helper T cells in MS pathogenesis. Discussion Overall, CSF enrichment in activated Tfh1 as soon as disease diagnosis, associated with high expression of EOMES, and a predicted high propensity to interact with CSF B cells suggest that these cells probably contribute to disease onset and/or activity

Survivorship Data in Prostate Cancer: Where Are We and Where Do We Need To Be?

Cancer survivorship was recently identified as a prostate cancer (PCa) research priority by PIONEER, a European network of excellence for big data in PCa. Despite being a research priority, cancer survivorship lacks a clear and agreed definition, and there is a distinct paucity of patient-reported outcome (PRO) data available on the subject. Data collection on cancer survivorship depends on the availability and implementation of (validated) routinely collected patient-reported outcome measures (PROMs). There have been recent advances in the availability of such PROMs. For instance, the European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) is developing survivorship questionnaires. This provides an excellent first step in improving the data available on cancer survivorship. However, we propose that an agreed, standardised definition of (prostate) cancer survivorship must first be established. Only then can real-world data on survivorship be collected to strengthen our knowledge base. With more men than ever surviving PCa, this type of research is imperative to ensure that the quality of life of these men is considered as much as their quantity of life. Patient summary: As there are more prostate cancer survivors than ever before, research into cancer survivorship is crucial. We highlight the importance of such research and provide recommendations on how to carry it out. The first step should be establishing agreement on a standardised definition of survivorship. From this, patient-reported outcome measures can then be used to collect important survivorship data