MORTALITE PRECOCE DES VASCULARITES NECROSANTES (FACTEURS PRONOSTIQUES, CAUSE DU DECES ; ANALYSE RETROSPECTIVE DE 60 CAS)

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Le syndrome de réactivation paradoxale de la tuberculose chez le patient infecté par le VIH lors de la restauration immunitaire sous traitement antirétroviral (étude rétrospective et comparative de 9 dossiers)

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Aggravations paradoxales des tuberculoses acquises sous anti-TNFa (description et facteurs de risque)

Les aggravations paradoxales de tuberculose, connues sous le nom de syndrome de reconstitution immunitaire inflammatoire (IRIS), sont récemment rapportées à l arrêt de l anti-TNF chez des patients ayant développé une tuberculose sous biothérapie. Nous rapportons la première série d IRIS de tuberculoses à l arrêt des anti TNF.Les cas d IRIS ont été recueillis à partir du registre RATIO et d un appel national à observations et comparés à des tuberculoses sous anti-TNF sans IRIS. Entre 2001 et 2010, 14 cas d IRIS ont été recueillis. Les patients, âgés de 52 ans (IQR: 41-67), souffrent d arthrites inflammatoires (10), de vascularites (3) et de psoriasis (1) et sont traités par anticorps monoclonaux (13) et récepteurs solubles (1). Au diagnostic de tuberculose, le plus souvent disséminée (12), tous les anti-TNFa sont stoppés, les antibiotiques et une corticothérapie (8) sont introduits. L IRIS est diagnostiqué, 62 jours (IQR: 22.00-131.00) après le début des antituberculeux, devant la réapparition de fièvre, l apparition, l augmentation de taille ou la fistulisation d adénopathies, l apparition d abcès froids, de tuberculomes, de péricardite, pleurésie, de cavernes pulmonaires. Les IRIS ont été traités par corticoïdes (9), rituximab (1), reprise d une quadrithérapie (2) et chirurgie (4) avec une évolution toujours favorable. L étude cas-témoins a trouvé comme facteurs de risque : la dissémination initiale de la tuberculose, et la profondeur de l immunodépression induite par les anti-TNFa. L IRIS, de diagnostic difficile, est source d une morbidité importante : traitement significativement plus long, hospitalisations à répétitions, chirurgies et corticothérapie prolongée.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Evolution clinique et diagnostique des patients de plus de 65 ans atteints d'anémie ferriprive, sans diagnostic étiologique après explorations endoscopiques digestives non contributives (Etude retrospective multicentrique)

STRASBOURG-Medecine (674822101) / SudocSudocFranceF

From furnace to casting moulds: an exceptional 14th century copper-metallurgy workshop studied in the light of refractory ceramic materials

International audienc

Latent Tuberculosis Infection Screening and 2-Year Outcome in Antiretroviral-Naive HIV-Infected Patients in a Low-Prevalence Country

International audienceBackground - Diagnosis and treatment of latent tuberculous infection decrease the incidence of tuberculosis (TB) in HIV-infected patients. Objectives - To evaluate the diagnostic yield of two IFN-γ release assays and tuberculin skin testing for the screening of latent infection in HIV-infected patients. Methods - We performed a prospective study in 29 referral centers for HIV care in France. Asymptomatic, antiretroviral-naive patients infected with HIV-1 who consented to participate underwent two commercial tests (T-SPOT.TB and QuantiFERON-TB Gold In-Tube ELISA test [QFT]) and skin test at enrollment and were followed up for clinical events during 24 months. Results - Between March 2009 and 2011, 506 patients were included, of whom 415 performed the three tests. Median age was 38 years (interquartile range, 31-45 yr), with median CD4 cell count of 466/μL (337-615 μL), and HIV viral load of 4.5 log10 copies/ml (3.6-4.9 log10 copies/ml). At least one IFN-γ release assay was positive for 55 (13.5%) patients: QFT (n = 43), T-SPOT.TB (n = 34), both (n = 22). Skin test was positive (>5 mm) in 66 (15.9%) patients, with intertest agreement at 81 to 86%. On multivariate analysis, positive IFN-γ release assay was only correlated with country of birth (8.4% for France vs. 17.9% for high-prevalence countries, P = 0.004). Of the 55 patients with positive IFN-γ release assay, 8 (14.5%) developed active TB, all within 120 days. No other case of active TB was diagnosed. Once active TB was excluded, IFN-γ release assay-based latent infection prevalence was 11.8%. Conclusions - Systematic screening for latent TB infection by IFN-γ release assay identifies a population at high risk of active TB over the next months. An extensive diagnostic work-up for active TB must follow positive IFN-γ release assay, before considering treatment of latent infection. Clinical trial registered with www.clinicaltrials.gov (NCT00805272)

Increased linezolid plasma concentrations are associated with the development of severe toxicity in MDR-TB treatment.

Auteurs : the LZDM groupInternational audienceAbstract Background Treatment of multidrug-resistant (MDR) tuberculosis with linezolid is characterized by high rates of adverse events. Evidence on therapeutic drug monitoring to predict drug toxicity is scarce. This study aimed to evaluate the association of linezolid trough concentrations with severe toxicity. Methods We retrospectively assessed consecutive patients started on linezolid for MDR tuberculosis between 2011 and 2017. The primary outcome was severe mitochondrial toxicity (SMT) due to linezolid, defined as neurotoxicity or myelotoxicity leading to drug discontinuation. The impact of plasma linezolid trough concentrations >2 mg/L was assessed in multivariate Cox proportional hazards models including time-varying covariates. Results SMT occurred in 57 of 146 included patients (39%) at an incidence rate of 0.38 per person-year (95% confidence interval, .30–.49). A maximum linezolid trough concentration >2 mg/L was detected in 52 patients (35.6%), while the mean trough concentration was >2 mg/L in 22 (15%). The adjusted hazard ratio for SMT was 2.35 (95% confidence interval, 1.26–4.38; P = .01) in patients with a mean trough concentration >2 mg/L and 2.63 (1.55–4.47; P < .01) for SMT after the first detection of a trough concentration >2 mg/L. In an exploratory analysis, higher maximum trough concentrations were dose-dependently associated with toxicity, while lowering elevated trough concentrations did not restore baseline risk. Conclusions Linezolid trough concentrations >2 mg/L are strongly associated with the development of severe treatment-emergent toxicity in patients treated for MDR tuberculosis. Pending further prospective evidence, an individual risk-benefit assessment on the continuation of linezolid treatment is warranted in any patient with trough concentrations >2 mg/L

Recommandations pratiques pour l’utilisation et l’interprétation des tests de détection de l’interféron gamma dans le diagnostic de l’infection tuberculeuse latente et de la tuberculose maladie

International audienc

Tocilizumab-treated convalescent COVID-19 patients retain the cross-neutralization potential against SARS-CoV-2 variants

International audienceAlthough tocilizumab treatment in severe and critical coronavirus disease 2019 (COVID-19) patients has proven its efficacy at the clinical level, there is little evidence supporting the effect of short-term use of interleukin-6 receptor blocking therapy on the B cell sub-populations and the cross-neutralization of SARS-CoV-2 variants in convalescent COVID-19 patients. We performed immunological profiling of 69 tocilizumab-treated and non-treated convalescent COVID-19 patients in total. We observed that SARS-CoV-2-specific IgG1 titers depended on disease severity but not on tocilizumab treatment. The plasma of both treated and non-treated patients infected with the ancestral variant exhibit strong neutralizing activity against the ancestral virus and the Alpha, Beta, and Delta variants of SARS-CoV-2, whereas the Gamma and Omicron viruses were less sensitive to seroneutralization. Overall, we observed that, despite the clinical benefits of short-term tocilizumab therapy in modifying the cytokine storm associated with COVID-19 infections, there were no modifications in the robustness of B cell and IgG responses to Spike antigens