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 < 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

Lot 1: Reduction of gear impact and discards in deep sea fisheries. Final report

This report presents the results of laboratory developments, field experiments and data analyses carried out in the contract MARE/2011/07 - "Studies on the Common Fisheries Policy" - Lot 1 "Reduction of gear impact and discards in deep sea fisheries". The contractual objectives were "(I) to identify and study trawl modification and alternative gear that aim at reducing the impact of the gear on the sea bottom when engaged in deep-sea fisheries, and (II) to identify and study a measure for discard reduction in deep-sea fisheries or fisheries having deep-sea species as a by-catch, pursued with trawls or nets. The measure could consist in gear modifications or catch purification based on the skipper’s strategy to avoid unwanted fish.

Impact of a Pre-Discharge Education Session on Stroke Knowledge: a Randomized Trial

International audienceBackground and purposes: Stroke knowledge, awareness of risk factors and stroke warning symptoms is very poor among stroke survivors. We investigated whether a pre-discharge education intervention in the stroke unit could improve stroke knowledge in patients with TIA or minor stroke. Methods: We performed a prospective single-center, randomized controlled trial (2013-2016) in patients with TIA or minor stroke. The intervention consisted in an interactive group session focused on stroke education, within the stroke unit before hospital discharge. Primary outcome was the 3-month change in stroke knowledge score (SKS) from randomization. Secondary outcomes were the 12-month change in SKS, the number of risk factors and warning signs named, control of risk factors and self-reported adherence. Results: A total of 199 patients (mean [SD] age, 63.5 [12.4] years; 67 [33.7%] women) were randomized (99 in stroke education session). Intervention was associated with a greater improvement in SKS than in the control group (baseline-adjusted mean between-group difference, 1.6 point [95%CI, 1.4 to 1.9]; p=0.001). This difference was significantly maintained at 12 months. The number of risk factors and warning signs named were significantly increased in the intervention group at 3 months. Control of risk factors and self-reported adherence did not differ significantly between the two groups. Conclusions: An interactive education session in the stroke unit significantly improved stroke knowledge at 3 months and 12 months in patients with TIA or minor stroke

Protocol for the e-POWUS Project: multicentre blinded-randomised controlled trial of ultrasound speed choice to improve sonography quality in pregnant women with obesity

International audienceIntroduction During pregnancy, maternal obesity increases the risk of fetal abnormalities. Despite advances in ultrasound imaging, the assessment of fetal anatomy is less thorough among these women. Currently, the construction of ultrasound images uses a conventional ultrasound propagation velocity (1540 m/s), which does not correspond to the slower speed of propagation in fat tissue. The main objective of this randomised study is to compare the completeness of fetal ultrasonography according to whether the operator could choose the ultrasound velocity (1420, 1480 or 1540 m/s) or was required to apply the 1540 m/s velocity. Methods and analysis This randomised trial is an impact study to compare a diagnostic innovation with the reference technique. The trial inclusion criteria require that a pregnant woman with obesity be undergoing a fetal morphology examination by ultrasound from 20 +0 to 25 +0 gestational weeks. Randomisation will allocate women into two groups. The first will be the ‘modulable speed’ group, in which operators can choose the speed of ultrasound propagation to be considered for the morphological analysis: 1420, 1480 or 1540 m/s. In the second ‘conventional speed’ group, operators will perform the morphological examination with the ultrasound speed fixed at 1540 m/s. The adjudication committee, two independent experts, will validate the completeness of each examination and the quality of the images. Ethics and dissemination This research protocol does not change the standard management. The only possible impact is an improvement of the ultrasound examination by improving the quality of the image and the completeness of morphological examination. The Agence du Médicament et produits de santé approved this study (2018-A03478-47). The anonymised data will be available on request from the principal investigator. Results will be reported in peer-reviewed journals and at scientific meetings. Trial registration number ClinicalTrials.gov ( http://www.clinicaltrials.gov ) Registry ( NCT04212234 )

New Surge of Syphilis among Patients Living with Human Immunodeficiency Virus in Martinique in 2015

International audienceA syphilis outbreak began in Martinique, French Antilles, in 2004, initially among men who had sex with men (MSM) and who were living with human immunodeficiency virus (HIV). The outbreak subsequently affected all groups at risk, leading to a first epidemic peak in 2008. After an initial decrease, the outbreak started growing again in 2014 among patients living with HIV with unprecedented incidence among MSM. Herein, we describe the change in medical and social parameters of the outbreak since 2005

Individual Mapping of Innate Immune Cell Activation Is a Candidate Marker of Patient-Specific Trajectories of Worsening Disability in Multiple Sclerosis

International audienceOur objective was to develop a novel approach to generate individual maps of white matter (WM) innate immune cell activation using 18F-DPA-714 translocator protein PET and to explore the relationship between these maps and individual trajectories of worsening disability in patients with multiple sclerosis (MS). Methods: Patients with MS (n = 37), whose trajectories of worsening disability over the 2 y preceding study entry were calculated, and healthy controls (n = 19) underwent MRI and 18F-DPA-714 PET. A threshold for significant activation of 18F-DPA-714 binding was calculated with a voxelwise randomized permutation-based comparison between patients and controls and used to classify each WM voxel in all subjects as characterized by a significant activation of innate immune cells (DPA+) or not. Individual maps of innate immune cell activation in the WM were used to calculate the extent of activation in WM regions of interests and to classify each WM lesion as DPA-active, DPA-inactive, or unclassified. Results: Compared with the WM of healthy controls, patients with MS had a significantly higher percentage of DPA+ voxels in the normal-appearing WM (NAWM) (NAWM in patients, 24.6% ± 1.4%; WM in controls, 14.6% ± 2.0%; P < 0.001). In patients with MS, the percentage of DPA+ voxels increased significantly from the NAWM to the perilesional areas, T2 hyperintense lesions, and T1 hypointense lesions (38.1% ± 2.6%, 45.0% ± 2.6%, 51.8% ± 2.6%, respectively; P < 0.001). Among the 1,379 T2 lesions identified, 512 were defined as DPA-active and 258 as DPA-inactive. A higher number of lesions classified as DPA-active (odds ratio, 1.13; P = 0.009), a higher percentage of DPA+ voxels in the NAWM (odds ratio, 1.16; P = 0.009), and a higher percentage of DPA+ voxels in T1 spin-echo lesions (odds ratio, 1.06; P = 0.036) were significantly associated with a retrospectively more severe clinical trajectory in patients with MS. Conclusion: A more severe trajectory of disability worsening in MS is associated with innate immune cell activation inside and around WM lesions. 18F-DPA-714 PET may provide a promising biomarker to identify patients at risk of a severe clinical trajectory

Structural and Clinical Correlates of a Periventricular Gradient of Neuroinflammation in Multiple Sclerosis

International audienceObjectives: To explore in-vivo innate immune cell activation as a function of the distance from ventricular CSF in patients with Multiple Sclerosis (MS) using [18F]-DPA714 PET, and to investigate its relationship with periventricular microstructural damage, evaluated by magnetization transfer ratio (MTR), and with trajectories of disability worsening.Methods: Thirty-seven MS patients and nineteen healthy controls underwent MRI and [18F]-DPA714 TSPO dynamic PET, from which individual maps of voxels characterized by innate immune cell activation (DPA+) were generated. White matter (WM) was divided in 3mm-thick concentric rings radiating from the ventricular surface toward the cortex, and the percentage of DPA+ voxels and mean MTR were extracted from each ring. Two-year trajectories of disability worsening were collected to identify patients with and without recent disability worsening.Results: The percentage of DPA+ voxels was higher in patients compared to controls in the periventricular WM (p=6.10e-6), and declined with increasing distance from ventricular surface, with a steeper gradient in patients compared to controls (p=0.001). This gradient was found both in periventricular lesions and normal-appearing WM. In the total WM, it correlated with a gradient of microstructural tissue damage measured by MTR (rs=-0.65, p=1.0e-3). When compared to clinically stable patients, patients with disability worsening were characterized by a higher percentage of DPA+ voxels in the periventricular normal-appearing WM (p=0.025).Conclusions: Our results demonstrate that in MS the innate immune cell activation predominates in periventricular regions and associates with microstructural damage and disability worsening. This could result from the diffusion of pro-inflammatory CSF-derived factors into surrounding tissues

Frontières des hommes, frontières des plantes cultivées: des territoires de l'agro-diversité

Trois hypothèses principales peuvent être posées pour expliquer les facteurs qui organisent dans l’espace la diversité des plantes cultivées. Elles sous-tendent les textes présentés dans ce premier volume

An EZH2 blocker sensitizes histone mutated diffuse midline glioma to cholesterol metabolism inhibitors through an off-target effect

International audienceAbstract Background Diffuse Midline Glioma, H3K27M-mutant (DMG) is a rare, highly aggressive pediatric tumor affecting the brainstem, and is one of the deadliest cancers. Currently available treatment options such as chemotherapy and radiotherapy do only modestly prolong survival. In this pathology, H3K27 mutations deregulate Polycomb Repressive Complex 2 (PRC2), including enzymatic activity of EZH2, which is therefore under investigation as a therapeutic target. Methods We used a chemical EZH2 inhibitor, GSK126, small interfering RNAs and a CRISPR/Cas9 knockout approaches in a series of DMG tumor cell lines to investigate metabolic treatment responses by proteomic analysis. A combination strategy was elaborated and studied in primary and established DMG cells, spheroid 3D cultures and in vivo in a chick chorio-allantoic membrane DMG assay and an orthotopic intracranial DMG mouse model. Results GSK126 shows significant (p&lt;0.05-0.001) inhibitory effects in in vitro cell proliferation assays and induces apoptosis. Chemical targeting of EZH2 induced expression of proteins implicated in cholesterol metabolism. Low-dose GSK126 treatment together with statins revealed strong growth inhibition in combinatorial treatments, but not in single treatments, both in DMG cells in vitro, in DMG spheroid cultures and in chick and mouse in vivo models (p&lt;0.05). All statistical tests were two-sided. Conclusions Our results reveal an unexpected GSK126-inducible sensitivity to cholesterol biosynthesis inhibitors in highly aggressive pediatric glioma that warrants further evaluation as treatment strategy. This combinatorial therapy should have few side effects because of the low doses used to achieve significant anti-tumor activity