Immunological markers after long-term treatment interruption in chronically HIV-1 infected patients with CD4 cell count above 400 x 10(6) cells/l.

OBJECTIVE: To analyse immunological markers associated with CD4+ lymphocyte T-cell count (CD4+) evolution during 12-month follow-up after treatment discontinuation. METHOD: Prospective observational study of chronically HIV-1 infected patients with CD4+ above 400 x 10(6) cells/l. RESULTS: CD4+ changes took place in two phases: an initial rapid decrease in the first month (-142 x 10(6) cells/l on average), followed by a slow decline (-17 x 10(6) cells/l on average) The second slope of CD4+ decline was not correlated with the first and only baseline plasma HIV RNA was associated with it. The decline in CD4+ during the first month was steeper in patients with higher CD4+ and weaker plasma HIV RNA baseline levels. Moreover, the decline was less pronounced (P < 10(-4)) in patients with CD4+ nadir above 350 x 10(6) cells/l (-65 x 10(6) cells/l per month) in comparison with those below 350 x 10(6) cells/l (-200 x 10(6) cells/l per month). A high number of dendritic cells (DCs) whatever the type was associated with high CD4+ at the time of treatment interruption and its steeper decline over the first month. Moreover, the myeloid DC level was stable whereas the lymphoid DC count, which tended to decrease in association with decrease in CD4+, was negatively correlated with the HIV RNA load slope. CONCLUSIONS: The results support the use of the CD4+ nadir to predict the CD4+ dynamic after treatment interruption and consideration of the CD4+ count after 1-month of interruption merely reflects the 12-month level of CD4+. Although DCs seem to be associated with the CD4+ dynamic, the benefit of monitoring them has still to be defined

Alternative methods to analyse the impact of HIV mutations on virological response to antiviral therapy

<p>Abstract</p> <p>Background</p> <p>Principal component analysis (PCA) and partial least square (PLS) regression may be useful to summarize the HIV genotypic information. Without pre-selection each mutation presented in at least one patient is considered with a different weight. We compared these two strategies with the construction of a usual genotypic score.</p> <p>Methods</p> <p>We used data from the ANRS-CO3 Aquitaine Cohort Zephir sub-study. We used a subset of 87 patients with a complete baseline genotype and plasma HIV-1 RNA available at baseline and at week 12. PCA and PLS components were determined with all mutations that had prevalences >0. For the genotypic score, mutations were selected in two steps: 1) p-value < 0.01 in univariable analysis and prevalences between 10% and 90% and 2) backwards selection procedure based on the Cochran-Armitage Test. The predictive performances were compared by means of the cross-validated area under the receiver operating curve (AUC).</p> <p>Results</p> <p>Virological failure was observed in 46 (53%) patients at week 12. Principal components and PLS components showed a good performance for the prediction of virological response in HIV infected patients. The cross-validated AUCs for the PCA, PLS and genotypic score were 0.880, 0.868 and 0.863, respectively. The strength of the effect of each mutation could be considered through PCA and PLS components. In contrast, each selected mutation contributes with the same weight for the calculation of the genotypic score. Furthermore, PCA and PLS regression helped to describe mutation clusters (e.g. 10, 46, 90).</p> <p>Conclusion</p> <p>In this dataset, PCA and PLS showed a good performance but their predictive ability was not clinically superior to that of the genotypic score.</p

Covichem: A biochemical severity risk score of COVID-19 upon hospital admission

Clinical and laboratory predictors of COVID-19 severity are now well described and combined to propose mortality or severity scores. However, they all necessitate saturable equipment such as scanners, or procedures difficult to implement such as blood gas measures. To provide an easy and fast COVID-19 severity risk score upon hospital admission, and keeping in mind the above limits, we sought for a scoring system needing limited invasive data such as a simple blood test and co-morbidity assessment by anamnesis. A retrospective study of 303 patients (203 from Bordeaux University hospital and an external independent cohort of 100 patients from Paris Pitié-Salpêtrière hospital) collected clinical and biochemical parameters at admission. Using stepwise model selection by Akaike Information Criterion (AIC), we built the severity score Covichem. Among 26 tested variables, 7: obesity, cardiovascular conditions, plasma sodium, albumin, ferritin, LDH and CK were the independent predictors of severity used in Covichem (accuracy 0.87, AUROC 0.91). Accuracy was 0.92 in the external validation cohort (89% sensitivity and 95% specificity). Covichem score could be useful as a rapid, costless and easy to implement severity assessment tool during acute COVID-19 pandemic waves

Resuming Training in High-Level Athletes After Mild COVID-19 Infection: A Multicenter Prospective Study (ASCCOVID-19)

BACKGROUND: There is a paucity of data on cardiovascular sequelae of asymptomatic/mildly symptomatic SARS-Cov-2 infections (COVID). OBJECTIVES: The aim of this prospective study was to characterize the cardiovascular sequelae of asymptomatic/mildly symptomatic COVID-19 among high/elite-level athletes. METHODS: 950 athletes (779 professional French National Rugby League (F-NRL) players; 171 student athletes) were included. SARS-Cov-2 testing was performed at inclusion, and F-NRL athletes were intensely followed-up for incident COVID-19. Athletes underwent ECG and biomarker profiling (D-Dimer, troponin, C-reactive protein). COVID(+) athletes underwent additional exercise testing, echocardiography and cardiac magnetic resonance imaging (CMR). RESULTS: 285/950 athletes (30.0%) had mild/asymptomatic COVID-19 [79 (8.3%) at inclusion (COVID(+)(prevalent)); 206 (28.3%) during follow-up (COVID(+)(incident))]. 2.6% COVID(+) athletes had abnormal ECGs, while 0.4% had an abnormal echocardiogram. During stress testing (following 7-day rest), COVID(+) athletes had a functional capacity of 12.8 ± 2.7 METS with only stress-induced premature ventricular ectopy in 10 (4.3%). Prevalence of CMR scar was comparable between COVID(+) athletes and controls [COVID(+) vs. COVID(-); 1/102 (1.0%) vs 1/28 (3.6%)]. During 289 ± 56 days follow-up, one athlete had ventricular tachycardia, with no obvious link with a SARS-CoV-2 infection. The proportion with troponin I and CRP values above the upper-limit threshold was comparable between pre- and post-infection (5.9% vs 5.9%, and 5.6% vs 8.7%, respectively). The proportion with D-Dimer values above the upper-limit threshold increased when comparing pre- and post-infection (7.9% vs 17.3%, P = 0.01). CONCLUSION: The absence of cardiac sequelae in pauci/asymptomatic COVID(+) athletes is reassuring and argues against the need for systematic cardiac assessment prior to resumption of training (clinicaltrials.gov; NCT04936503).L'Institut de Rythmologie et modélisation Cardiaqu

BMJ Open

INTRODUCTION: Sarcomas are rare tumours of connective tissue. The exact overall incidence of sarcomas is unknown due to diagnostic difficulties and the various histological subtypes (over 80 subtypes). However, the apparent increasing incidence of sarcomas suggests environmental causes such as pesticides. Except for some specific factors (ie, ionising radiation, vinyl chloride, dioxin and genetic predispositions) the scientific knowledge on the aetiology of sarcomas is sparse and inconsistent. France is a particularly appropriate country to set up a study investigating the causes of sarcoma occurrence due to the French organisation in treatment and care of sarcoma patients, which is highly structured and revolved around national expert networks. The main objective of the ETIOlogy of SARcomas (ETIOSARC) project is to study the role of lifestyle, environmental and occupational factors in the occurrence of sarcomas among adults from a multicentric population-based case-control study. METHODS AND ANALYSIS: Cases will be all incident patients (older than 18 years) prospectively identified in 15 districts of France covered by a general population-based cancer registry and/or a reference centre in sarcoma's patient care over a 3-year period with an inclusion start date ranging from February 2019 to January 2020 and histologically confirmed by a second review of the diagnosis. Two controls will be individually matched by sex, age (5 years group) and districts of residence and randomly selected from electoral rolls. A standardised questionnaire will be administered by a trained interviewer in order to gather information about occupational and residential history, demographic and socioeconomic characteristics and lifestyle factors. At the end of the interview, a saliva sample will be systematically proposed. This study will permit to validate or identify already suspected risk factors for sarcomas such as phenoxyherbicides, chlorophenol and to generate new hypothesis to increase our understanding about the genetic and environmental contributions in the carcinogenicity process. ETHICS AND DISSEMINATION: The present study is promoted by the French National Institute of Health and Medical Research (identification number C17-03). This study received National French Ethic committee (CPP Sud Mediterrannee I) approval (identification number 18-31) and French Data Protection Authority (CNIL) approval (identification number 918171). Results of this study will be published in international peer-reviewed journals. Technical appendix, statistical code and dataset will be available in the Dryad repository when collection data are completed. TRIAL REGISTRATION NUMBER: NCT03670927

Battements et design sonore d’avion: Mesures subjectives et propositions pour minimiser le désagrément

Réduire le désagrément lié au bruit généré par les passages d’avions à proximité des aéroports est une préoccupation majeure de l’industrie aéronautique. En complément de la réduction du niveau d’exposition au bruit, il est notamment important de comprendre et d’évaluer les effets liés aux phénomènes de rugosité ou de battements qui pourraient être générés par la présence de fréquences pures proches. Cet article décrit le protocole mis en place afin d’évaluer le désagrément de potentielles configurations d’avions futurs pouvant présenter cette spécificité. Un ensemble de stimuli correspondant à des survols d’avions ont été créés en partie par synthèse sonore. La restitution sonore a été réalisée au casque. Les 48 auditeurs ont évalué le désagrément sur une échelle continue de 0 à 10. Cet article rapporte les résultats d’évaluation du désagrément de stimuli et propose des recommandations quant aux écarts fréquentiels pour minimiser le désagrément

La dermatite atopique chez l'enfant (facteurs de risque environnementaux, traitements et conseils aux patients)

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Activation immunitaire au cours de l'infection par le VIH (caractérisation, causes et conséquences)

Depuis l'introduction des thérapies antirétrovirales efficaces, l'infection par le VIH n'est plus considérée comme une infection létale à court terme, mais comme une maladie chronique. Si le nombre de lymphocytes T CD4 représente un élément fondamental dans le suivi de l'infection par le VIH, le niveau d'activation immunitaire est un puissant facteur prédictif de progression vers le SIDA. Indépendamment de la charge virale, l'activation des lymphocytes T CD8, exprimant le CD38 et/ou le HLA/DR, est associée à la progression et au déclin des lymphocytes T CD4 chez les patients non traités ainsi quà un gain inférieur de lymphocytes T CD4 chez les patients traités. Dans la plupart des infections virales aiguës, l'activation du système immunitaire est une réponse normale et nécessaire à l'éradication des agents pathogènes. Sa chronicité au cours de l'infection par le VIH est aberrante et représente la caractéristique majeure qui la différencie du modèle d'infection non pathogène par le virus de l'immunodéficience simienne. Les principales causes de l'activation immunitaire sont le VIH, ses protéines libres circulantes, la translocation microbienne digestive secondaire à la déplétion des lymphocytes T CD4 muqueux, la réactivation des herpès virus latents et la co-infection avec le VHC. Sur le plan clinique, les conséquences de l'activation sur l'organisme sont nombreuses et participent aux comorbidités liées à l'inflammation chronique observées au cours du vieillissement. Ainsi, l'immunosénescence, l'athérosclérose accélérée, l'ostéoporose, les détériorations cognitives, et les néphropathies sont fréquentes chez les patients infectés par le VIH sous multithérapie efficace, dont le niveau d'activation immunitaire diminue sans se normaliser. Les thérapeutiques à visée anti-inflammatoire ont pour l'instant montré des bénéfices limités, mais semblent être une stratégie prometteuse pour l'optimisation de la prise en charge de ces patients.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF