Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

Hemodialysis without systemic anticoagulation: a prospective randomized trial to evaluate 3 strategies in patients at risk of bleeding.

In this clinical trial, we aimed to compare three means of performing chronic hemodialysis in patients with contra-indication to systemic heparinization.This open-label monocentric randomized « n-of-one » trial, conducted in a single tertiary care center, recruited chronic hemodialysis patients with a contra-indication to systemic heparinization for at least 3 consecutive sessions. All patients underwent hemodialysis with an AN69ST dialyzer, and were administered three alternative dialysis procedures in a random sequence: intermittent saline flushes, constant saline infusion, or pre-dialysis heparin coating of the membrane. The primary outcome was the need to interrupt the dialysis session because of clotting events due to either (i) a complete coagulation of the circuit; (ii) a partial coagulation of the circuit; (iii) a>50% rise over baseline in the venous pressure.At the end of the inclusion period (May, 2007 to December, 2008), the number of patients to include (n=75) was not reached: only 46 patients were included and underwent randomization. The study was terminated, and statistical analysis took into account 224 hemodialysis sessions performed in 44 patients with analyzable data. Heparin adsorption was associated with a significant reduction of the need to interrupt the dialysis session because of clotting events: odds ratio 0.3 (CI 95% 0.2 to 0.6; p3 h dialysis sessions and for having complete blood restitution. There were no significant effects of the dialysis procedure on weight loss, online ionic dialysance, and adverse events.Heparin-coated AN69ST dialysis membrane is a safe and effective method to avoid or delay per-dialytic clotting events in patients with contra-indication to systemic anticoagulation. However, results are not generalizable safely to patients with active bleeding, since weak heparinemia, not assessed in this study, may occur.ClinicalTrials.gov NCT00473109

Post-retirement surveillance of workers exposed to asbestos or wood dust: first results of the French national SPIRALE Program.

International audienceObjectives: in France, 15 000-20 000 cancers attributable to occupational exposure occur each year. These cancers appear most often after the worker has retired. Since 1995, a system of post-retirement medical surveillance (PRMS) has been set up for former workers, but it remains largely underused. Design: the SPIRALE program is a public health intervention aimed at identifying the former workers having been exposed to asbestos or wood dust during their working life and to propose thema PRMS. Additionally, it is also an epidemiologic research on the longterm effects of occupational exposure.We report the results of first years of the program conducted in 2006-2008, in 13 districts. Setting and participants: a self-administered questionnaire was sent to 50 000 newly retired men, to identify potential past occupational carcinogen exposure. For respondents detected as possibly exposed, exposure was assessed in Health Screening Centres and a PRMS was recommended if necessary. Main outcome measures: participation rate, rate of confirmed exposure, increased rate of PRMS, satisfaction about the program. Results: the participation rate was 24%. From 12 002 questionnaires analysed, 72% of respondents were identified as possibly exposed: 3%to wood dust, 50%to asbestos and 19%to both exposures. Exposure to asbestos was confirmed for 73.4%, and according to the level of exposure, PRMSwas recommended for 47.1%. Wood dust exposurewas confirmed for 56.7%. In these districts, PRMS for asbestos increased by 45% and for wood dust by 600%. Additional surveys showed that participants showed a high degree of satisfaction about the program. Conclusions:The results are positive in terms of detection, information andmedical surveillance of exposed workers

Suivi des retraités exposés à l'amiante ou aux poussières de boions pendant leur vie professionnelle :premier bilan de la phase pilote du projet Spirale

National audienceSummary The estimation of new cancers due to professional exposures each year in France is between 15,000 and 20,000; about 25% of retired males have been professionally exposed to asbestos, and 8% to wood dust. Since 1995, a post-professional medical followup (SPP) exists, but is widely unknown. The Spirale program follows two aims: of public health, identifying eligible persons for SPP and taking them to it, and of epidemiological research on professional exposures long time effects and advantages from SPP. Spirale is leaded by the Inserm/CNAMTS 687 Unit which locates former employees exposed to carcinogens during their professional life course, using a self questionnaire, and the Assurance maladie (National Health Insurance) Health care centers (CES) which evaluate and confirm exposures and help people to obtain SPP. The Spirale pilot period took place in 13 CES in 2006 and 2007, targeting about 50000 new retired males; it identified 1,751 asbestos professional exposures and 684 wood dust ones. It raised asbestos SPP requests by 45% and wood dust ones by 600%. Besides, about 85% of exposed persons have agreed for an epidemiological follow-up. Looking for a whole territory spread order, the Assurance maladie decided to continue Spirale in 2008 in the 13 pilot CES

Dialysis efficiency and tolerance.

<p>CI: confidence interval. OR: Odd Ratio, RC: Regression coefficient, ref: reference OR were computed using a two levels hierarchical logistic mixed model and regression coefficient with a two levels hierarchical linear mixed mode.</p><p>*missing data for 48 sessions;</p><p>**missing data for 23 sessions.</p><p>***p = 0.69 by Fisher’s exact test.</p

Flow Diagram.

<p>Flow Diagram.</p

Characteristics of the 44 patients at inclusion.

<p>Characteristics of the 44 patients at inclusion.</p