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

Signification environnementale de guano de salanganes et de chiroptères de Nouvelle-Calédonie. Premiers résultats

sera mis en ligne en texte intégral en septembre 2019International audienceGuano accumulated in caves by bats or birds contains a stratigraphic record of the environment which may supplement or supply conventionnal terrestrial sedimentary records like lacustrine/palustrine deposits or peat. Thus, guano study allows the understanding of recent or past climate and environment changes, which ability has expanded recently with the development of more sophisticated analytical tools, based on proxies that are indirect measures of past climates or environments preserved in natural archives. In New Caledonia, diurnal cave swiftlet Collocalia spodiopygia and nocturnal Chiroptera Micropterus robustior, both insectivores, share very often the same cavities. The comparison of the content of pollen and isotopes δ13C and δD in their respective guano, shows a great variability of constituents which reflects the sources of the feeding grounds of the eaten preys and their interaction with the ecosystem, more particularly the vegetation. The high richness of pollen taxa, identical to 50 % between the two guanos, underlines the respective food resource areas. The pollen content also shows seasonal variations probably in response to changes in food availability and in turn environmental change, if not climatic changes. This paper presents a preliminary set of results obtained on the 92cm-long core HAK1 retrieved in a guano mound taken under a cave swiftlet roost site in Hama Cave from Lifou (Loyalty Islands). The comparison between yearly mean daily rainfall, carbon (δ13C) and hydrogen (δD) isotopes compositions of high-molecular weight n-alkane (n-C29) from guano shows a good covariation, which is interpreted as a proxy of ENSO occurrences. Our work confirms that the guano piles are promising records for palaeoenvironmental change studies at high temporal resolution.L'intérêt est grandissant pour le potentiel présenté par les acccumulations cavernicoles de guano de chauves-souris et d'oiseaux en tant qu'enregistrements stratigraphiques continentaux, complémentaires voire alternatifs aux archives étudiées générale-ment (sédiments lacustres, palustres, tourbeux, etc.). Ces dépôts permettent des reconstructions de la variabilité climatique à haute résolution pour des échelles de temps récentes à plus anciennes, grâce à la calibration de nouveaux proxies susceptibles d'enregistrer ces variations. Ainsi la comparaison du contenu pollinique et des traceurs isotopiques δ13 C et δD des n-alcanes du guano de différents animaux insectivores, les salanganes diurnes (Collocalia spodiopygia) et les chiroptères nocturnes (Micropterus robustior) cohabitant dans de nombreuses grottes de Nouvelle-Calédonie, met en évidence une grande variabilité. Celle-ci est à l'image des cibles de nourrissage des proies appétées et de leur interaction avec les composantes de l'écosystème, en particulier les plantes. La grande richesse du contenu pollinique observée dans les deux types de guano, bien que présentant 50 % de taxons communs, souligne des aires de nourrissage préférentielles. Elle montre aussi des fluctuations interannuelles, marqueurs probables de changements environnementaux, sinon climatiques. Cet article présente des premiers résultats obtenus sur le sondage HAK1 prélévé dans un amas de guano de salanganes de la grotte Hama sur l'île de Lifou, l'une des îles Loyautés. La comparaison entre les données de géochimie isotopique moléculaire (isotopes du carbone δ13C et de l'hydrogène δD du n-alcane C29) et les données pluviométriques met en évidence une bonne covariation interprétée comme marqueur du signal climatique ENSO contemporain des dépôts de guano analysés. Ce travail préliminaire confirme le fort potentiel des amas de guano cavernicoles pour étudier à haute résolution les changements paléo-environnementaux

Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases

© 2020, American Society for Clinical Investigation. BACKGROUND. Undifferentiated systemic autoinflammatory diseases (USAIDs) present diagnostic and therapeutic challenges. Chronic interferon (IFN) signaling and cytokine dysregulation may identify diseases with available targeted treatments. METHODS. Sixty-six consecutively referred USAID patients underwent underwent screening for the presence of an interferon signature using a standardized type-I IFN-response-gene score (IRG-S), cytokine profiling, and genetic evaluation by next-generation sequencing. RESULTS. Thirty-six USAID patients (55%) had elevated IRG-S. Neutrophilic panniculitis (40% vs. 0%), basal ganglia calcifications (46% vs. 0%), interstitial lung disease (47% vs. 5%), and myositis (60% vs. 10%) were more prevalent in patients with elevated IRG-S. Moderate IRG-S elevation and highly elevated serum IL-18 distinguished 8 patients with pulmonary alveolar proteinosis (PAP) and recurrent macrophage activation syndrome (MAS). Among patients with panniculitis and progressive cytopenias, 2 patients were compound heterozygous for potentially novel LRBA mutations, 4 patients harbored potentially novel splice variants in IKBKG (which encodes NF-κB essential modulator [NEMO]), and 6 patients had de novo frameshift mutations in SAMD9L. Of additional 12 patients with elevated IRG-S and CANDLE-, SAVI- or Aicardi-Goutières syndrome-like (AGS-like) phenotypes, 5 patients carried mutations in either SAMHD1, TREX1, PSMB8, or PSMG2. Two patients had anti-MDA5 autoantibody-positive juvenile dermatomyositis, and 7 could not be classified. Patients with LRBA, IKBKG, and SAMD9L mutations showed a pattern of IRG elevation that suggests prominent NF-κB activation different from the canonical interferonopathies CANDLE, SAVI, and AGS. CONCLUSIONS. In patients with elevated IRG-S, we identified characteristic clinical features and 3 additional autoinflammatory diseases: IL-18-mediated PAP and recurrent MAS (IL-18PAP-MAS), NEMO deleted exon 5-autoinflammatory syndrome (NEMO-NDAS), and SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD). The IRG-S expands the diagnostic armamentarium in evaluating USAIDs and points to different pathways regulating IRG expression

Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases

BACKGROUND. Undifferentiated systemic autoinflammatory diseases (USAIDs) present diagnostic and therapeutic challenges. Chronic interferon (IFN) signaling and cytokine dysregulation may identify diseases with available targeted treatments. METHODS. Sixty-six consecutively referred USAID patients underwent underwent screening for the presence of an interferon signature using a standardized type-I IFN-response-gene score (IRG-S), cytokine profiling, and genetic evaluation by next-generation sequencing. RESULTS. Thirty-six USAID patients (55%) had elevated IRG-S. Neutrophilic panniculitis (40% vs. 0%), basal ganglia calcifications (46% vs. 0%), interstitial lung disease (47% vs. 5%), and myositis (60% vs. 10%) were more prevalent in patients with elevated IRG-S. Moderate IRG-S elevation and highly elevated serum IL-18 distinguished 8 patients with pulmonary alveolar proteinosis (PAP) and recurrent macrophage activation syndrome (MAS). Among patients with panniculitis and progressive cytopenias, 2 patients were compound heterozygous for potentially novel LRBA mutations, 4 patients harbored potentially novel splice variants in IKBKG (which encodes NF-κB essential modulator [NEMO]), and 6 patients had de novo frameshift mutations in SAMD9L. Of additional 12 patients with elevated IRG-S and CANDLE-, SAVI- or Aicardi-Goutières syndrome-like (AGS-like) phenotypes, 5 patients carried mutations in either SAMHD1, TREX1, PSMB8, or PSMG2. Two patients had anti-MDA5 autoantibody-positive juvenile dermatomyositis, and 7 could not be classified. Patients with LRBA, IKBKG, and SAMD9L mutations showed a pattern of IRG elevation that suggests prominent NF-κB activation different from the canonical interferonopathies CANDLE, SAVI, and AGS. CONCLUSIONS. In patients with elevated IRG-S, we identified characteristic clinical features and 3 additional autoinflammatory diseases: IL-18-mediated PAP and recurrent MAS (IL-18PAP-MAS), NEMO deleted exon 5-autoinflammatory syndrome (NEMO-NDAS), and SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD). The IRG-S expands the diagnostic armamentarium in evaluating USAIDs and points to different pathways regulating IRG expression

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer

International audienc