Chronologie et spatialisation de retombées de cendres volcaniques tardiglaciaires dans les massifs des Vosges et du Jura, et le plateau suisse

L’établissement d’une chronologie précise des différents événements climatiques du Tardiglaciaire et de l’Holocène nécessite l’emploi de différents moyens de datation. Parmi ceux-ci, la téphrochronologie apparaît comme un outil permettant à la fois une datation précise et une synchronisation à l’échelle inter-régionale de ces événements. Dans le cadre de l’étude de l’enregistrement des variations du climat ayant régné en Europe de l’Ouest durant les 20 000 dernières années, des niveaux de téphras et de « cryptotéphras » ont été détectés dans des remplissages de lacs situés dans les massifs du Jura, des Vosges et sur le Plateau suisse. Certains de ces niveaux étant invisibles à l’œil nu, leur détection a été rendue possible grâce à l’emploi de la mesure de la susceptibilité magnétique à un pas de 5 mm. Nos observations permettent de compléter l’extension géographique de la bordure ouest du nuage de dispersion méridional du Laacher See Tephra (env. 12900 ans, Eifel, Allemagne) déjà observé dans d’autres remplissages lacustres du Jura et de l’Europe de l’Ouest et du Nord. Dans les sites étudiés, les échardes de verre volcanique présentent des compositions chimiques comparables à celles des phases les plus jeunes du Laacher See Tephra. D’autres niveaux de téphras, non répertoriés jusqu’à présent dans cette région, ont été détectés et caractérisés. Deux niveaux, très discrets et uniquement présents dans les sites du massif du Jura et du Plateau suisse, sont caractérisés par des âges et compositions chimiques de phénocristaux compatibles avec les produits émis par le Puy de la Nugère (Chaîne des Puys, France) pendant l’Allerød (autour de 13300 ans). Les sites du massif des Vosges, quant à eux, sont caractérisés par l’occurence d’un téphra rhyolitique, le Vedde Ash (env. 12000 ans), déposé durant le Dryas récent. Actuellement, il s’agit là de l’occurence la plus méridio‑occidentale de ce téphra. Nos résultats complètent la téphrochronologie tardiglaciaire de l’Est de la France et offrent donc un « pont » chronologique supplémentaire entre les séquences sédimentaires nord- et centreeuropéennes et celles situées plus à l’ouest. Ils soulignent l’importance du Laacher See Tephra et du Vedde Ash pour les études paléoenvironnementales dans cette partie de l’Europe puisque ces deux téphras encadrent la limite Allerød - Dryas récent et permettent, pour cet intervalle de temps, de pallier l’absence de données radiochronologiques.Establishment of a precise chronicle of the lateglacial and holocene climatic variations requires the use of various dating methods. Among them, tephrochronology allows high-resolution dating and synchronization of these events at a regional scale and sometimes at a continental scale. Study of the record of the climatic variations occuring in western Europe since twenty thousands years leads to the discovery of tephras levels and “cryptotephras” in sediments cored in lakes from the Jura and Vosges mountains, and the Swiss plateau. Some of these levels are invisible to the naked eye. Their detection was obtained using magnetic susceptibility measurement with a 5 mm step along the cores. Our observations allow to complete the western boundary of the southern distribution of the Laacher See Tephra (ca. 12,900 yr, Eifel, Germany). This tephra has been already described in others lacustrine sequences from the Jura and the western and northern Europe. In the sites we have studied, the volcanic glass shards show geochemical compositions comparable to those of the youngest phases of the Laacher See Tephra eruption. Other tephra levels, never described in this region until then, have been detected and characterized. Two very discrete tephra levels, only observed in sites from the Jura and the Swiss plateau, present ages, mineral assemblages and chemical compositions close to those of tephras that were emitted by the Puy de la Nugère (Chaîne des Puys, France) during the Alleröd (about 13,300 yr). Sites from the Vosges mountains are characterized by the occurrence of the rhyolitic Vedde Ash (ca. 12,000 yr, from the icelandic Katla volcano), deposited during the Younger Dryas. Presently, this is the most southwestern occurrence of the Vedde Ash. Our data make up the Eastern France Lateglacial tephrochrology and offer an additional chronological bridge between sedimentary sequences from northern and central Europe and those situated more westerly. They show the importance of the Laacher See Tephra and the Vedde Ash for palaeoenvironmental studies in western Europe since they are flanking the AllerödYounger Dryas transition and allow to compensate the lack of radiochronological data

Téphras et séquences quaternaires

Journée AFEQ / SGF (6 novembre 2006

Chronic use of inhaled corticosteroids in patients admitted for respiratory virus infections: a 6-year prospective multicenter study

International audienceInhaled corticosteroids (ICS) have been associated with increased risk of pneumonia. Their impact on respiratory virus infections is unclear. We performed a post-hoc analysis of the FLUVAC cohort, a multicenter prospective cohort study of adults hospitalized with influenza-like illness (ILI) during six consecutive influenza seasons (2012–2018). All patients were tested for respiratory virus infection by multiplex PCR on nasopharyngeal swabs and/or bronchoalveolar lavage. Risk factors were identified by logistic regression analysis. Among the 2658 patients included, 537 (20.2%) were treated with ICS before admission, of whom 282 (52.5%, 282/537) tested positive for at least one respiratory virus. Patients on ICS were more likely to test positive for non-influenza respiratory viruses (25.1% vs. 19.5%, P = 0.004), especially for adenovirus (aOR 2.36, 95% CI 1.18–4.58), and respiratory syncytial virus (aOR 2.08, 95% CI 1.39–3.09). Complications were reported in 55.9% of patients on ICS (300/537), primarily pneumonia (171/535, 32%). Among patients on chronic ICS who tested positive for respiratory virus, 14.2% (40/282) were admitted to intensive care unit, and in-hospital mortality rate was 2.8% (8/282). Chronic use of ICS is associated with an increased risk of adenovirus or RSV infections in patients admitted for ILI

Successful Thrombectomy Improves Functional Outcome in Tandem Occlusions with a Large Ischemic Core

International audienceBackground: Emergent stenting in tandem occlusions and mechanical thrombectomy (MT) of acute ischemic stroke related to large vessel occlusion (LVO-AIS) with a large core are tested independently. We aim to assess the impact of reperfusion with MT in patients with LVO-AIS with a large core and a tandem occlusion and to compare the safety of reperfusion between large core with tandem and nontandem occlusions in current practice. Methods: We analyzed data of all consecutive patients included in the prospective Endovascular Treatment in Ischemic Stroke Registry in France between January 2015 and March 2023 who presented with a pretreatment ASPECTS (Alberta Stroke Program Early CT Score) of 0–5 and angiographically proven tandem occlusion. The primary end point was a favorable outcome defined by a modified Rankin Scale (mRS) score of 0–3 at 90 days. Results: Among 262 included patients with a tandem occlusion and ASPECTS 0–5, 203 patients (77.5%) had a successful reperfusion (modified Thrombolysis in Cerebral Infarction grade 2b-3). Reperfused patients had a favorable shift in the overall mRS score distribution (adjusted odds ratio [aOR], 1.57 [1.22–2.03]; P < 0.001), higher rates of mRS score 0–3 (aOR, 7.03 [2.60–19.01]; P < 0.001) and mRS score 0–2 at 90 days (aOR, 3.85 [1.39–10.68]; P = 0.009) compared with nonreperfused. There was a trend between the occurrence of successful reperfusion and a decreased rate of symptomatic intracranial hemorrhage (aOR, 0.5 [0.22–1.13]; P = 0.096). Similar safety outcomes were observed after large core reperfusion in tandem and nontandem occlusions. Conclusions: Successful reperfusion was associated with a higher rate of favorable outcome in large core LVO-AIS with a tandem occlusion, with a safety profile similar to nontandem occlusion

Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia

International audienceImportance Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19).Objective To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia.Design, Setting, and Particpants This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes.Interventions Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants.Main Outcomes and Measures Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events.Results Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21).Conclusions and Relevance In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care unit, TCZ did not reduce WHO-CPS scores lower than 5 at day 4 but might have reduced the risk of NIV, MV, or death by day 14. No difference on day 28 mortality was found. Further studies are necessary for confirming these preliminary results.Trial Registration ClinicalTrials.gov Identifier: NCT0433180

Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial

International audienc

Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

International audienc

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old