Périartérite noueuse ou vascularite cryoglobulinémique associée au virus de l'hépatite C (deux diagnostics différentiels difficiles)

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Tuberculose disséminée de l'adulte jeune (épidémiologie, gènes de susceptibilité et déficits immunogénétiques impliqués, modalités de prise en charge en service non spécialisé; revue de la littérature à propos d'un cas)

PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Incidence de la maladie thrombo-embolique veineuse au cours de la primo-infection à C.M.V. (coïncidence ou lien de causalité ?)

PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Un exemple de complication dégénérative de la drépanocytose homozygote de l'adulte jeune : le rein drépanocytaire (revue de la littérature à propos d'une obseravation clinique)

[Résumé français]La drépanocytose est une vasculopathie d'origine génétique au grand polymorphisme d'expression, avec des complications aiguës et chroniques souvent sévères chez le patient homozygote. Malgré l'amélioration de la prise en charge pédiatrique ces dix dernières années, trop de complications à l'âge adulte ne sont dépistées qu'à l'occasion de décompensations aiguës. Nous exposons ici le cas clinique d'une jeune patiente drépanocytaire homozygote qui a présenté une insuffisance rénale aiguë révélant un syndrome néphrotique majeur. L'analyse histologique a permis le diagnostic. Le rein drépanocytaire de l'adulte est une complication évolutive, dont la physiopathologie est de mieux en mieux comprise. L'atteinte rénale reflète des années d'hyperfonctionnement des néphrons. Une meilleure connaissance de la sémiologie clinique permet une prise en charge thérapeutique précoce. En effet, le pronostic fonctionnel rénal est souvent précaire, pouvant évoluer vers l'insuffisance rénale chronique terminale. Les patients drépanocytaires doivent bénéficier, dès l'adolescence, d'une prise en charge préventive par un suivi clinique annuel et une stratégie thérapeutique adaptée. L'utilisation d'outils de surveillance simples permettraient d'améliorer leur qualité de vie et leur espérance de vie.PARIS13-BU Serge Lebovici (930082101) / SudocSudocFranceF

Fièvre boutonneuse méditerranéenne compliquée d'hémophagocytose dans le bassin parisien (une pathologie d'importation sévère, cible de l'emporiatrie)

La fièvre boutonneuse méditerranéenne, maladie éruptive vectorielle due à un agent bactérien intracellulaire,Rickettsia conorii, transmis par la tique,Rhipicephalus sanguineus, est endémique dans le bassin méditerranéen. Le diagnostic de deux cas en région parisienne, compliqués d'un syndrome d'activation macrophagique, pose le problème des formes graves de cette pathologie méconnue hors zone endémique, engageant potentiellement le pronostic vital. Dès lors la précocité d un diagnostic s impose, visant l instauration rapide des thérapeutiques antibactériennes ciblées,voire dans les formes sévères des immunoglobulines. L'émergence multifactorielle de ces pathologies d'importation dans le bassin parisien redonne à la prévention une place prépondérante, reposant sur la formation, la lutte anti-vectorielle et les mesures prophylactiques. Au delà des emporiatres, l'ensemble du corps médical dont les généralistes doit être mieux formé et informé pour une meilleure prise en charge des voyageurs.ST QUENTIN EN YVELINES-BU (782972101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Hydroxychloroquine in mild-to-moderate coronavirus disease 2019: a placebo-controlled double blind trial

International audienceObjectives: To determine whether hydroxychloroquine decreases the risk of adverse outcome in patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk of worsening. Methods: We conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: need for supplemental oxygen, age 75 years, age between 60 and 74 years and presence of at least one co-morbidity. Severely ill patients requiring oxygen therapy >3 L/min or intensive care were excluded. Eligible patients were randomized in a 1:1 ratio to receive either 800 mg hydroxychloroquine on day 0 followed by 400 mg per day for 8 days or a placebo. The primary end point was a composite of death or start of invasive mechanical ventilation within 14 days following randomization. Secondary end points included mortality and clinical evolution at days 14 and 28, and viral shedding at days 5 and 10. Results: The trial was stopped after 250 patients were included because of a slowing down of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placeboand hydroxychloroquine groups, respectively. The median age was 77 years (interquartile range 58-86 years) and 151/250 (60.4%) patients required oxygen therapy. The primary end point occurred in 9/124 (7.3%) patients in the hydroxychloroquine group and 8/123 (6.5%) patients in the placebo group (relative risk 1.12; 95% CI 0.45e2.80). The rates of positive SARS-CoV-2 RT-PCR tests at days 5 and 10 were 72.8% (75/103) and 57.1% (52/91) in the hydroxychloroquine group, versus 73.0% (73/100) and 56.6% (47/83) in the placebo group, respectively. No difference was observed between the two groups in any of the other secondary end points. Conclusion: In this underpowered trial involving mainly older patients with mild to moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo

A placebo-controlled double blind trial of hydroxychloroquine in mild-to-moderate COVID-19

AbstractBackgroundThe efficacy of hydroxychloroquine in coronavirus disease 2019 (COVID-19) remains controversial.MethodsWe conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: age ≥75 years, age between 60 and 74 years, and presence of at least one comorbidity, or need for supplemental oxygen (≤3 L/min). Eligible patients were randomized in a 1:1 ratio to receive either 800mg hydroxychloroquine on Day 0 followed by 400mg per day for 8 days or a placebo. The primary endpoint was a composite of death or tracheal intubation within 14 days following randomization. Secondary endpoints included mortality and clinical evolution at Day 14 and 28, viral shedding at Day 5 and 10.ResultsThe trial was stopped after 250 patients were included due to a slowdown of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years and 151 patients required oxygen therapy. The primary endpoint occurred in nine patients in the hydroxychloroquine group and eight patients in the placebo group (relative risk 1.12; 95% confidence interval 0.45– 2.80; P=0.82). No difference was observed between the two groups in any of the secondary endpoints.ConclusionIn this trial involving mainly older patients with mild-to-moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo.</jats:sec

Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection

BACKGROUND: The management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear. METHODS: We performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure. The primary outcome was persistent infection (defined as the persistence or recurrence of infection with the initial causative bacteria, with an antibiotic susceptibility pattern that was phenotypically indistinguishable from that at enrollment) within 2 years after the completion of antibiotic therapy. Noninferiority of 6 weeks of therapy to 12 weeks of therapy would be shown if the upper boundary of the 95% confidence interval for the absolute between-group difference (the value in the 6-week group minus the value in the 12-week group) in the percentage of patients with persistent infection within 2 years was not greater than 10 percentage points. RESULTS: A total of 410 patients from 28 French centers were randomly assigned to receive antibiotic therapy for 6 weeks (205 patients) or for 12 weeks (205 patients). Six patients who withdrew consent were not included in the analysis. In the main analysis, 20 patients who died during follow-up were excluded, and missing outcomes for 6 patients who were lost to follow-up were considered to be persistent infection. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group (risk difference, 8.7 percentage points; 95% confidence interval, 1.8 to 15.6); thus, noninferiority was not shown. Noninferiority was also not shown in the per-protocol and sensitivity analyses. We found no evidence of between-group differences in the percentage of patients with treatment failure due to a new infection, probable treatment failure, or serious adverse events. CONCLUSIONS: Among patients with microbiologically confirmed prosthetic joint infections that were managed with standard surgical procedures, antibiotic therapy for 6 weeks was not shown to be noninferior to antibiotic therapy for 12 weeks and resulted in a higher percentage of patients with unfavorable outcomes. (Funded by Programme Hospitalier de Recherche Clinique, French Ministry of Health; DATIPO ClinicalTrials.gov number, NCT01816009.)

Efficacy of oral 20-hydroxyecdysone (BIO101), a MAS receptor activator, in adults with severe COVID-19 (COVA): a&nbsp;randomized, placebo-controlled, phase 2/3 trial.

BACKGROUND: SARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due to COVID-19. The aim of the study was to test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore the Renin-Angiotensin System equilibrium and limit the frequency of respiratory failure and mortality in adults hospitalized with severe COVID-19. METHODS: Double-blind, randomized, placebo-controlled phase 2/3 trial. Randomization: 1:1 oral BIO101 (350&nbsp;mg BID) or placebo, up to 28 days or until an endpoint was reached. Primary endpoint: mortality or respiratory failure requiring high-flow oxygen, mechanical ventilation, or extra-corporeal membrane oxygenation. Key secondary endpoint: hospital discharge following recovery (ClinicalTrials.gov Number, NCT04472728). FINDINGS: Due to low recruitment the planned sample size of 310 was not reached and 238 patients were randomized between August 26, 2020 and March 8, 2022. In the modified ITT population (233 patients; 126 BIO101 and 107 placebo), respiratory failure or early death by day 28 was 11.4% lower in the BIO101 (13.5%) than in the placebo (24.3%) group, (p&nbsp;=&nbsp;0.0426). At day 28, proportions of patients discharged following recovery were 80.1%, and 70.9% in the BIO101 and placebo group respectively, (adjusted difference 11.0%, 95% CI [-0.4%, 22.4%], p&nbsp;=&nbsp;0.0586). Hazard Ratio for time to death over 90 days: 0.554 (95% CI [0.285, 1.077]), a 44.6% mortality reduction in the BIO101 group (not statistically significant). Treatment emergent adverse events of respiratory failure were more frequent in the placebo group. INTERPRETATION: BIO101 significantly reduced the risk of death or respiratory failure supporting its use in adults hospitalized with severe respiratory symptoms due to COVID-19. FUNDING: Biophytis