Smaller limbic structures are associated with greater immunosuppression in over 1000 HIV-infected adults across five continents: Findings from the ENIGMA-HIV Working Group

Background: Human immunodeficiency virus type-1 (HIV) infection can be controlled with combination antiretroviral therapy (cART), but neurocognitive impairment remains common even in chronic and treated HIV-infected (HIV+) cohorts. Identifying the neuroanatomical pathways associated with infection has the potential to delineate novel neuropathological processes underlying persisting deficits, yet individual neuroimaging studies have yielded inconsistent findings. The ENIGMA-HIV Working Group was established to harmonize data from diverse studies to identify the common effects of HIV-infection on brain structure. Methods: Data were pooled from 12 independent neuroHIV studies from Africa, Asia, Australia, Europe, and North America. Volume estimates for eight subcortical brain regions were extracted from T1-weighted MRI from 1,044 HIV+ adults (aged 22-81 years; 72.4% on cART; 70.3% male; 41.6% with detectable viral load (dVL)), to identify associations with plasma markers reflecting current immunosuppression (CD4+ T-cell count) or dVL. Follow-up analyses stratified data by cART status and sex. Bonferroni correction was used to determine statistical significance. Findings: LowercurrentCD4+ count was associated with smaller hippocampal (β= 20.3 mm3 per 100 cells/mm3; p = 0.0001) and thalamic volumes (β= 29.3; p = 0.003); in the subset of participants not on cART, it was associated with smaller putamen volumes (β= 65.1; p = 0.0009). On average, a dVL was associated with smaller hippocampal (Cohen’s d = 0.24; p = 0.0003) and amygdala volumes (d = 0.18; p = 0.0058).Interpretation: In HIV+ individuals across five continents, smaller limbic volumes were consistently associated with current plasma markers. As we assessed cohorts with different inclusion/exclusion criteria and demographic distributions, these deficits may represent a generalizable brain-signature of HIV infection in the cART era. Our findings support the importance of achieving viral suppression and immune restoration for maintaining brain health. Funding: This work was supported, in part, by NIH grant U54 EB020403

Association of Immunosuppression and Viral Load With Subcortical Brain Volume in an International Sample of People Living With HIV

International audienceIMPORTANCE Despite more widely accessible combination antiretroviral therapy (cART), HIV-1 infection remains a global public health challenge. Even in treated patients with chronic HIV infection, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in vivo may delineate the neuropathologic processes underlying these deficits. However, published neuroimaging findings from relatively small, heterogeneous cohorts are inconsistent, limiting the generalizability of the conclusions drawnto date.OBJECTIVE To examine structural brain associations with the most commonly collected clinicalassessments of HIV burden (CD4+T-cell count and viral load), which are generalizable acrossdemographically and clinically diverse HIV-infected individuals worldwide.DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study established the HIV WorkingGroup within the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) consortiumto pool and harmonize data from existing HIV neuroimaging studies. In total, data from 1295HIV-positive adults were contributed from 13 studies across Africa, Asia, Australia, Europe, and NorthAmerica. Regional and whole brain segmentations were extracted from data sets as contributingstudies joined the consortium on a rolling basis from November 1, 2014, to December 31, 2019.MAIN OUTCOMES AND MEASURES Volume estimates for 8 subcortical brain regions wereextracted from T1-weighted magnetic resonance images to identify associations with blood plasmamarkers of current immunosuppression (CD4+T-cell counts) or detectable plasma viral load (dVL) inHIV-positive participants. Post hoc sensitivity analyses stratified data by cART status.RESULTS After quality assurance, data from 1203 HIV-positive individuals (mean [SD] age, 45.7 [11.5]years; 880 [73.2%] male; 897 [74.6%] taking cART) remained. Lower current CD4+cell counts wereassociated with smaller hippocampal (mean [SE] β = 16.66 [4.72] mm3per 100 cells/mm3;P< .001)and thalamic (mean [SE] β = 32.24 [8.96] mm3per 100 cells/mm3;P< .001) volumes and largerventricles (mean [SE] β = −391.50 [122.58] mm3per 100 cells/mm3;P= .001); in participants nottaking cART, however, lowercurrent CD4+cell counts were associated with smaller putamen volumes(mean [SE] β = 57.34 [18.78] mm3per 100 cells/mm3;P= .003). A dVL was associated with smallerhippocampal volumes (d= −0.17;P= .005); in participants taking cART, dVL was also associated withsmaller amygdala volumes (d= −0.23;P= .004

Politiques de développement rural et niveaux de décision : une approche organisationnelle

National audienceDue to their own complexity, related with the stakes' and actors' variety and interdependency, rural development concerns account for more and more sophisticated action settings, which contents is defined not only beforehand but also all along the implementation stage. This paper puts an analysis grid which accounts for the multi level organization of these action settings. This grid is then used to show the construction at different levels of the European Agricultural Fund for Rural Development (EAFRD) setting. Prospects are finally suggested about the conception of action settings in this field.De par leur complexité propre, liée à la diversité et à l'interdépendance des enjeux et des acteurs concernés, les questions de développement rural motivent la conception de dispositifs d'action publique de plus en plus élaborés, dont le contenu n'est pas défini seulement à l'amont mais aussi tout au long de la phase de mise en ½uvre. Cet article propose une grille de lecture permettant de rendre compte de l'organisation à différentes échelles de ces dispositifs d'action. Cette grille est ensuite utilisée pour présenter la construction du dispositif relatif au Fonds européen agricole de développement rural (FEADER). Des perspectives sont suggérées concernant la conception des dispositifs d'action dans ce domaine

Politiques de développement rural et niveaux de décision : une approche organisationnelle

[Departement_IRSTEA]GT [TR1_IRSTEA]RURAMEN / AMANDENational audienceDue to their own complexity, related with the stakes' and actors' variety and interdependency, rural development concerns account for more and more sophisticated action settings, which contents is defined not only beforehand but also all along the implementation stage. This paper puts an analysis grid which accounts for the multi level organization of these action settings. This grid is then used to show the construction at different levels of the European Agricultural Fund for Rural Development (EAFRD) setting. Prospects are finally suggested about the conception of action settings in this field.De par leur complexité propre, liée à la diversité et à l'interdépendance des enjeux et des acteurs concernés, les questions de développement rural motivent la conception de dispositifs d'action publique de plus en plus élaborés, dont le contenu n'est pas défini seulement à l'amont mais aussi tout au long de la phase de mise en ½uvre. Cet article propose une grille de lecture permettant de rendre compte de l'organisation à différentes échelles de ces dispositifs d'action. Cette grille est ensuite utilisée pour présenter la construction du dispositif relatif au Fonds européen agricole de développement rural (FEADER). Des perspectives sont suggérées concernant la conception des dispositifs d'action dans ce domaine

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Complete genome sequence of the fish pathogen Flavobacterium psychrophilum

International audienceWe report here the complete genome sequence of the virulent strain JIP02/86 (ATCC 49511) of Flavobacterium psychrophilum, a widely distributed pathogen of wild and cultured salmonid fish. The genome consists of a 2,861,988–base pair (bp) circular chromosome with 2,432 predicted protein-coding genes. Among these predicted proteins, stress response mediators, gliding motility proteins, adhesins and many putative secreted proteases are probably involved in colonization, invasion and destruction of the host tissues. The genome sequence provides the basis for explaining the relationships of the pathogen to the host and opens new perspectives for the development of more efficient disease control strategies. It also allows for a better understanding of the physiology and evolution of a significant representative of the family Flavobacteriaceae, whose members are associated with an interesting diversity of lifestyles and habitat

Teriflunomide and Time to Clinical Multiple Sclerosis in Patients With Radiologically Isolated Syndrome: The TERIS Randomized Clinical Trial.

IMPORTANCE Radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS) punctuated by incidental magnetic resonance imaging (MRI) white matter anomalies within the central nervous system. OBJECTIVE To determine the time to onset of symptoms consistent with MS. DESIGN, SETTING, AND PARTICIPANTS From September 2017 to October 2022, this multicenter, double-blind, phase 3, randomized clinical trial investigated the efficacy of teriflunomide in delaying MS in individuals with RIS, with a 3-year follow-up. The setting included referral centers in France, Switzerland, and Turkey. Participants older than 18 years meeting 2009 RIS criteria were randomly assigned (1:1) to oral teriflunomide, 14 mg daily, or placebo up to week 96 or, optionally, to week 144. INTERVENTIONS Clinical, MRI, and patient-reported outcomes (PROs) were collected at baseline and yearly until week 96, with an optional third year in the allocated arm if no symptoms have occurred. MAIN OUTCOMES Primary analysis was performed in the intention-to-treat population, and safety was assessed accordingly. Secondary end points included MRI outcomes and PROs. RESULTS Among 124 individuals assessed for eligibility, 35 were excluded for declining to participate, not meeting inclusion criteria, or loss of follow-up. Eighty-nine participants (mean [SD] age, 37.8 [12.1] years; 63 female [70.8%]) were enrolled (placebo, 45 [50.6%]; teriflunomide, 44 [49.4%]). Eighteen participants (placebo, 9 [50.0%]; teriflunomide, 9 [50.0%]) discontinued the study, resulting in a dropout rate of 20% for adverse events (3 [16.7%]), consent withdrawal (4 [22.2%]), loss to follow-up (5 [27.8%]), voluntary withdrawal (4 [22.2%]), pregnancy (1 [5.6%]), and study termination (1 [5.6%]). The time to the first clinical event was significantly extended in the teriflunomide arm compared with placebo, in both the unadjusted (hazard ratio [HR], 0.37; 95% CI, 0.16-0.84; P = .02) and adjusted (HR, 0.28; 95% CI, 0.11-0.71; P = .007) analysis. Secondary imaging end point outcomes including the comparison of the cumulative number of new or newly enlarging T2 lesions (rate ratio [RR], 0.57; 95% CI, 0.27-1.20; P = .14), new gadolinium-enhancing lesions (RR, 0.33; 95% CI, 0.09-1.17; P = .09), and the proportion of participants with new lesions (odds ratio, 0.72; 95% CI, 0.25-2.06; P = .54) were not significant. CONCLUSION AND RELEVANCE Treatment with teriflunomide resulted in an unadjusted risk reduction of 63% and an adjusted risk reduction of 72%, relative to placebo, in preventing a first clinical demyelinating event. These data suggest a benefit to early treatment in the MS disease spectrum. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03122652

Efficacy of Chest CT for COVID-19 Pneumonia Diagnosis in France

International audienceThe role and performance of chest CT in the diagnosis of the coronavirus disease 2019 (COVID-19) pandemic remains under active investigation. Purpose To evaluate the French national experience using chest CT for COVID-19, results of chest CT and reverse transcription polymerase chain reaction (RT-PCR) assays were compared together and with the final discharge diagnosis used as the reference standard. Materials and Methods A structured CT scan survey (NCT04339686) was sent to 26 hospital radiology departments in France between March 2, 2020, and April 24, 2020. These dates correspond to the peak of the national COVID-19 epidemic. Radiology departments were selected to reflect the estimated geographic prevalence heterogeneities of the epidemic. All symptomatic patients suspected of having COVID-19 pneumonia who underwent both initial chest CT and at least one RT-PCR test within 48 hours were included. The final discharge diagnosis, based on multiparametric items, was recorded. Data for each center were prospectively collected and gathered each week. Test efficacy was determined by using the Mann-Whitney test, Student t test, χ2 test, and Pearson correlation coefficient. P < .05 indicated a significant difference. Results Twenty-six of 26 hospital radiology departments responded to the survey, with 7500 patients entered; 2652 did not have RT-PCR test results or had unknown or excess delay between the RT-PCR test and CT. After exclusions, 4824 patients (mean age, 64 years ± 19 [standard deviation], 2669 male) were included. With final diagnosis as the reference, 2564 of the 4824 patients had COVID-19 (53%). Sensitivity, specificity, negative predictive value, and positive predictive value of chest CT in the diagnosis of COVID-19 were 2319 of 2564 (90%; 95% CI: 89, 91), 2056 of 2260 (91%; 95% CI: 91, 92), 2056 of 2300 (89%; 95% CI: 87, 90), and 2319 of 2524 (92%; 95% CI: 91, 93), respectively. There was no significant difference for chest CT efficacy among the 26 geographically separate sites, each with varying amounts of disease prevalence. Conclusion Use of chest CT for the initial diagnosis and triage of patients suspected of having coronavirus disease 2019 was successful

Teriflunomide and Time to Clinical Multiple Sclerosis in Patients With Radiologically Isolated Syndrome

International audienceImportance Radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS) punctuated by incidental magnetic resonance imaging (MRI) white matter anomalies within the central nervous system. Objective To determine the time to onset of symptoms consistent with MS. Design, Setting, and Participants From September 2017 to October 2022, this multicenter, double-blind, phase 3, randomized clinical trial investigated the efficacy of teriflunomide in delaying MS in individuals with RIS, with a 3-year follow-up. The setting included referral centers in France, Switzerland, and Turkey. Participants older than 18 years meeting 2009 RIS criteria were randomly assigned (1:1) to oral teriflunomide, 14 mg daily, or placebo up to week 96 or, optionally, to week 144. Interventions Clinical, MRI, and patient-reported outcomes (PROs) were collected at baseline and yearly until week 96, with an optional third year in the allocated arm if no symptoms have occurred. Main outcomes Primary analysis was performed in the intention-to-treat population, and safety was assessed accordingly. Secondary end points included MRI outcomes and PROs. Results Among 124 individuals assessed for eligibility, 35 were excluded for declining to participate, not meeting inclusion criteria, or loss of follow-up. Eighty-nine participants (mean [SD] age, 37.8 [12.1] years; 63 female [70.8%]) were enrolled (placebo, 45 [50.6%]; teriflunomide, 44 [49.4%]). Eighteen participants (placebo, 9 [50.0%]; teriflunomide, 9 [50.0%]) discontinued the study, resulting in a dropout rate of 20% for adverse events (3 [16.7%]), consent withdrawal (4 [22.2%]), loss to follow-up (5 [27.8%]), voluntary withdrawal (4 [22.2%]), pregnancy (1 [5.6%]), and study termination (1 [5.6%]). The time to the first clinical event was significantly extended in the teriflunomide arm compared with placebo, in both the unadjusted (hazard ratio [HR], 0.37; 95% CI, 0.16-0.84; P = .02) and adjusted (HR, 0.28; 95% CI, 0.11-0.71; P = .007) analysis. Secondary imaging end point outcomes including the comparison of the cumulative number of new or newly enlarging T2 lesions (rate ratio [RR], 0.57; 95% CI, 0.27-1.20; P = .14), new gadolinium-enhancing lesions (RR, 0.33; 95% CI, 0.09-1.17; P = .09), and the proportion of participants with new lesions (odds ratio, 0.72; 95% CI, 0.25-2.06; P = .54) were not significant. Conclusion and Relevance Treatment with teriflunomide resulted in an unadjusted risk reduction of 63% and an adjusted risk reduction of 72%, relative to placebo, in preventing a first clinical demyelinating event. These data suggest a benefit to early treatment in the MS disease spectrum. Trial Registration ClinicalTrials.gov Identifier: NCT0312265