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

Antimicrobial for 7 or 14 Days for Febrile Urinary Tract Infection in Men: A Multicenter Noninferiority Double-Blind, Placebo-Controlled, Randomized Clinical Trial

International audienceThe optimal duration of antimicrobial therapy for urinary tract infections (UTIs) in men remains controversial. Methods To compare 7 days to 14 days of total antibiotic treatment for febrile UTIs in men, this multicenter randomized, double-blind. placebo-controlled noninferiority trial enrolled 282 men from 27 centers in France. Men were eligible if they had a febrile UTI and urine culture showing a single uropathogen. Participants were treated with ofloxacin or a third-generation cephalosporin at day 1, then randomized at day 3–4 to either continue ofloxacin for 14 days total treatment, or for 7 days followed by placebo until day 14. The primary endpoint was treatment success, defined as a negative urine culture and the absence of fever and of subsequent antibiotic treatment between the end of treatment and 6 weeks after day 1. Secondary endpoints included recurrent UTI within weeks 6 and 12 after day 1, rectal carriage of antimicrobial-resistant Enterobacterales, and drug-related events. Results Two hundred forty participants were randomly assigned to receive antibiotic therapy for 7 days (115 participants) or 14 days (125 participants). In the intention-to-treat analysis, treatment success occurred in 64 participants (55.7%) in the 7-day group and in 97 participants (77.6%) in the 14-day group (risk difference, –21.9 [95% confidence interval, −33.3 to −10.1]), demonstrating inferiority. Adverse events during antibiotic therapy were reported in 4 participants in the 7-day arm and 7 in the 14-day arm. Rectal carriage of resistant Enterobacterales did not differ between both groups. Conclusions A treatment with ofloxacin for 7 days was inferior to 14 days for febrile UTI in men and should therefore not be recommended. Clinical Trials Registration NCT02424461; Eudra-CT: 2013-001647-32

Kawasaki disease in adults: observations in France and literature review Short title: Kawasaki disease in adults in France

International audienceObjective Kawasaki disease (KD) is a vasculitis that mostly occurs in young children and rarely in adults. We analyzed the characteristics of adult-onset KD (AKD) in France. Methods We collected retrospective and prospective data for patients with a diagnosis of KD occurring after the age of 18 years. Cases were obtained via various French medical networks and identified from the international literature. Results We included 43 patients of AKD at 26 institution from 1992 to 2015, with mean (SD) age 30 (11) years (range 18–68) and sex ratio (M/F) 1.2; 34 patients met the American Heart Association criteria and 9 were incomplete AKD. The median time to diagnosis was 13 days (interquartile range 8–21). The main symptoms were fever (100%), exanthema (98%), changes in the extremities (91%), conjunctivitis (77%), oral cavity changes (89%), cervical adenitis (55%) and cardiac abnormalities (45%). Overall, 35% of patients showed large-vessel vasculitis: coronary vasculitis (26%) and coronary aneurysm (19%). Treatment was mostly intravenous immunoglobulins (79%) and aspirin (81%). Four patients showed myocardial infarction due to coronary vasculitis, but none were treated with IVIg because of late diagnosis. After a median follow-up of 5 months (range 1–117), persistent aneurysm was noted in 9% of cases. Damage was significantly lower with early treatment than late or no treatment (p = 0.01). Conclusion Given the high frequency of cardiac involvement and complications in this series of AKD, diagnosis and treatment should not be delayed, and early IVIg treatment seems to improve the outcom

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old