Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Ma thèse : 'Physiologie orale des personnes âgées, troubles et conseils alimentaires'

Interview de Mathilde Descamps relative à sa thèse de doctorat dans l'émission de radio "3 minutes pour la science" sur le site internet http://www.courtdujour.ch

Impact de la physiologie orale de la personne âgée sur sa prise alimentaire; quelles solutions pour maintenir le statut nutritionnel ?

Context. In human, oral food intake is the ultimate stage of food supply chain and the beginning of food disintegration and the digestion process. During aging, the oral health changes and sometimes eating food can be a real challenge as food can be hard to masticate, humidify or swallow.Objective. The aim of the present study is to determine which oral factors (salivary, dental, tongue strength) have an impact on physiological – ability to form a food bolus – and psychological – pleasure to eat – dimensions of food oral processing in order to select culinary techniques and help elderlies maintaining an appropriate protein intake in spite of the occurrence of poor oral health.Material and method. Resting and stimulated salivary flow, oral status, the ability to form a food bolus, the pleasure induced by food consumption and the nutritional status were measured on 108 elderly people (65-92 years old, living at home, with no acute pathology at the time of the study). In parallel, culinary technics that aimed at improving meat texture were developed and evaluated throughout physical measurements and oral comfort assessment by the elderly volunteers.Results and conclusion. Multivariate analysis highlighted the fact that oral factors (salivary, dental, muscular) play different roles in food oral processing and eating behavior in elderly people. Moreover, the assessment of oral comfort on the culinary technics showed that some technics improve significantly meat tenderness and juiciness. Those results will help the development of food offer tailored to elderly people with or without oral health impairments.Contexte. Chez l’homme, la mise en bouche d’un aliment est l’étape ultime de la chaîne alimentaire et le début du processus de dégradation et de digestion. Avec l’âge la santé orale évolue et peut parfois rendre l’acte alimentaire difficile.Objectif. L’objectif de cette étude est de déterminer les facteurs (salivaire, dentaire, musculaire) impactant sur les dimensions physiologiques (faculté à former un bol alimentaire, libération et perception de la flaveur) de l’acte alimentaire et/ou la prise alimentaire et la corpulence des séniors. Ceci permettra de d’identifier des techniques culinaires permettant d’adapter la texture des aliments aux problèmes bucco-dentaires.Matériel et méthode. 108 séniors (>65 ans) vivant à domicile et ne présentant pas de pathologie chronique ont été recrutés et caractérisés sur la base des dimensions suivantes : santé orale (examen clinique), auto-évaluation de la santé orale, perceptions sensorielles, faculté à former un bol alimentaire, comportement alimentaire, état de santé général. En parallèle, des techniques culinaires permettant d’améliorer la texture de la viande ont été testées. Leur efficacité a été évaluée via des mesures rhéologiques et la perception du confort en bouche par les séniors eux-mêmes.Résultats et conclusion. L’analyse multidimensionnelle des données montre que les facteurs de santé orale (dentition, salivation, force musculaire) jouent des rôles différents dans les processus de mastication et de prise alimentaire chez les personnes âgées. De plus, l’étude du confort en bouche a permis de sélectionner des techniques culinaires optimisant la tendreté et la jutosité de la viande. Ces résultats permettront de développer une offre alimentaire adaptée aux troubles oraux survenant avec l’âge

Le confort en bouche : Un concept pour mieux comprendre les attentes des consommateurs: Restitution du projet AlimaSSenS

National audienc

Pairing a beer with a soundtrack: Is it guided by geographical identity?

International audienceIn French gastronomy, food and beverage pairing is a traditional practice set down by pairing principles. Among these, some studies highlighted the principle of "geographical identity": pairing two products related to the same area. While this concept has been explored for food-food and food-beverage paring, there is less investigation across different senses e.g. auditory and flavory; specifically when flavory stimuli belong to the same food category. Yet it is well known that the auditory environment interacts with food behavior. We can wonder whether the pairing principles identified for food and beverage are relevant for a soundtrack and a beverage and more precisely whether the shared geographical identity of a beverage and a soundtrack drive their association. The aim of the present study is to explore multisensory interaction through the investigation of geographical identity association between a complex beverage - a beer - and a complex soundtrack (i.e. stimuli with a perceived complexity). The results showed that familiarity and hedonic evaluation of pairs as well as of soundtracks were strongly correlated to harmony evaluation of pairs while familiarity and hedonic evaluation of beers were correlated together. In addition, the results seem to highlight that soundtracks dominate the evaluation of pairs. The present study attempts to demonstrate that pairing multisensory stimuli is complex and the related principles refer to some of the already highlighted pairing principles for food-food pairing: geographical identity but also perceptual principles

Changes of cerebral functional connectivity induced by foot reflexology in a RCT

Abstract Non-Pharmacological Interventions (NPIs) are increasingly being introduced into healthcare, but their mechanisms are unclear. In this study, 30 healthy participants received foot reflexology (FR) and sham massage, and went through a resting-state functional magnetic resonance imaging (rs-fMRI) to evaluate NPIs effect on brain. Rs-fMRI revealed an effect of both NPIs on functional connectivity with changes occurring in the default-mode network, the sensorimotor network and a Neural Network Correlates of Pain (NNCP—a newly discovered network showing great robustness). Even if no differences were found between FR and SM, this study allowed to report brain biomarkers of well-being as well as the safety of NPIs. In further research, it could be relevant to study it in patients to look for a true reflexology induced-effect dependent of patient reported outcomes. Overall, these findings enrich the understanding of the neural correlates of well-being experienced with NPIs and provided insight into the basis of the mechanisms of NPIs

Comment concevoir et proposer à la personne âgée souffrant de trouble de la salivation et de la mastication une offre alimentaire innovante combinant plaisir à manger et valeur nutritionnelle ? Stratégies et approches scientifiques

International audienceAging is frequently accompanied by a decrease in appetite and food intake, which predisposes the elderly to weight loss and increases the risk of malnutrition. One of the physiological reasons explaining this decrease in food intake is the strong deterioration of the oral health of the elderly making the act of eating painful. Considering the challenge of malnutrition in terms of quality of life and public health, it is essential to develop a food supply that meets the nutritional needs of seniors while satisfying their enjoyment of eating. In this context, the objective of this article is to present an overview of the results obtained within the framework of the ANR AlimaSSenS project whose objective was, via an interdisciplinary and systemic approach centered on Food Oral Processing and bolus formation, the development of food products with high nutritional quality and adapted to the oral capacities of the elderly