Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Performance des glottiscopes (une étude comparative randomisée menée sur simulateur d'intubation difficile)

Nous avons comparé la performance de 4 glottiscopes : Airtraq® (AQ), GlideScope® (GS), McGrath® (MG), LMA CTrach® (CT) avec celle du laryngoscope de Macintosh (LM) en simulation d intubation difficile dans une étude prospective avec l ordre des outils d intubation choisi de manière aléatoire. 52 médecins seniors devaient réaliser, une fois la courbe d apprentissage des glottiscopes finalisée, 2 séries de 5 intubations sur le mannequin Airman®. En situation d intubation standard, la qualité de la vision glottique et les durées d apnée étaient identiques entre les 5 outils. Les durées d intubation étaient comparables entre LM, GS et MG. Elles étaient significativement plus courtes avec AQ et plus longues avec CT. En simulation d intubation difficile, les 4 glottiscopes étaient supérieurs au LM pour améliorer la vision glottique, diminuer la durée d intubation et réduire le temps d apnée L indice de performance pour l intubation difficile avec les glottiscopes était maximal pour l AQ et le CT, significativement plus élevé que celui du GS et du MG. L AQ était le plus facile à utiliser en situation d intubation difficile.We have prospectively compared simulated-difficult tracheal intubation characteristics of 4 glottiscopes: Airtraq (AQ), GlideScope (GS), McGrath (MG), LMA CTrach (CT) with that of the conventional Macintosh laryngoscope (ML) in a prospective study with the airway devices proposed in a randomly assigned order. Fifty two physicians were requested, after the learning curve of each airway device was completed, to perform 2 series of 5 tracheal intubations on the manikin Airman . During standard situation, laryngeal exposure quality and apnea duration were similar with the 5 airway devices. As compared to the ML, GS, MG, tracheal intubation duration was significantly shorter with the AQ and longer with the CT. During difficult tracheal intubation simulation, laryngeal exposure and tracheal intubation duration were of better quality and shorter with the 4 glottiscopes as compared to that of ML, respectively. Performance index during difficult tracheal intubation simulation was significantly more important with the AQ and the CT. AQ was the simplest airway device to manage a simulated difficult tracheal intubation.PARIS13-BU Serge Lebovici (930082101) / SudocSudocFranceF

Développement d'une nouvelle génération de détecteurs micro-structurés à base de semi-conducteurs pour l'imagerie médicale de rayons X

L amélioration des performances des détecteurs (au niveau de la résolution en énergie et de la résolution spatiale) pour la radiographie X médicale par l utilisation d un semi-conducteur montre l intérêt de remplacer les détecteurs à base de cristaux scintillateurs (majorité des systèmes commerciaux) par un détecteur à base de semi-conducteur. Avec une perspective de respect environnemental, ces travaux portent sur le développement d une nouvelle génération de détecteurs à base de semi-conducteur, différent du CdTe, pour l imagerie médicale de rayons X fonctionnant en mode comptage, ce qui permet la réduction de la dose de rayonnement envoyée sur le patient. Deux axes de recherches en découlent, avec le choix d un nouveau matériau semi-conducteur, le GaAs semi-isolant et d une nouvelle géométrie de détection, la géométrie 3D.Ces travaux ont consisté à évaluer expérimentalement le semi-conducteur, afin de choisir un matériau (fournisseur, croissance) et une électrode métallique qui ont la capacité de compter des photons. Puis, la structure de détection, au travers de caractérisations des procédés technologiques nécessaires pour la réalisation de la géométrie 3D (usinage des électrodes, dépôt des électrodes, connexion à un circuit électronique) et de la validation du concept avec un dispositif de test, a été également étudiée. Enfin, les premiers résultats d un détecteur 3D à base de GaAs semi-isolant, montrant la concrétisation de ces objectifs, sont proposés.In X-ray medical imaging, semi-conductors tend to replace scintillator crystals (most of the commercial devices), thank to their higher spatial resolution and energy resolution. Counting mode is another tendency, because it allows reducing the radiation dose delivered to the patient. This work aims at developing a new generation of semi-conductor detectors, different from CdTe / CdZnTe for environmental concerns, and associated with a new detection structure (3D geometry). Semi-insulating GaAs from specific growth and supplier, with adapted metallic electrodes, shows the ability to count photons. Then, a proof of concept of the 3D geometry is provided, through the characterization of electrodes machining in bulk material, metal deposition and connection to a read-out electronic circuit. Finally, the achievement of these objectives is reflected in the preliminary characterization of 3D detector based on semi-insulating GaAs.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Higher Frequency of Dipeptidyl Peptidase-4 Inhibitor Intake in Bullous Pemphigoid Patients than in the French General Population

International audienceDipeptidyl peptidase-4 inhibitors have been suspected to induce bullous pemphigoid (BP). The objective of this study was to compare the observed frequency of gliptin intake in a large sample of 1,787 BP patients diagnosed between 2012 and 2015 in France, with the expected frequency after indirect age standardization on 225,412 individuals extracted from the database of the National Healthcare Insurance Agency. The secondary objective was to assess the clinical characteristics and the course of gliptin-associated BP, depending on whether gliptin was continued or stopped. The observed frequencies of intake of the whole gliptin class and that of vildagliptin in the BP population were higher than those in the general population after age standardization (whole gliptin class: 6.0%; 95% confidence interval = 4.9-7.1% vs. 3.6%, observed-to-expected drug intake ratio = 1.7; 95% confidence interval = 1.4-2.0; P < 0.0001; vildagliptin = 3.3%; 95% confidence interval = 2.5-4.1% vs. 0.7%, ratio = 4.4; 95% confidence interval = 3.5-5.7; P < 0.0001). The association of any gliptin+metformin was also higher than in the general population, ratio = 1.8 (95% confidence interval = 1.3-2.4; P < 0.0001). Gliptin-associated BP had no specific clinical characteristics. Gliptin was stopped in 48 (45.3%) cases. Median duration to achieve disease control, rate, and delay of relapse were not different whether gliptin was stopped or continued. This study strongly supports the association between gliptin intake, particularly vildagliptin, and the onset of BP

First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial.

IF 44.002International audienceBackground High doses of corticosteroids are considered the standard treatment for pemphigus. Because long-term corticosteroid treatment can cause severe and even life-threatening side-effects in patients with this disease, we assessed whether first-line use of rituximab as adjuvant therapy could improve the proportion of patients achieving complete remission off-therapy, compared with corticosteroid treatment alone, while decreasing treatment side-effects of corticosteroids.Methods We did a prospective, multicentre, parallel-group, open-label, randomised trial in 25 dermatology hospital departments in France (Ritux 3). Eligible participants were patients with newly diagnosed pemphigus aged 18-80 years being treated for the first time (not at the time of a relapse). We randomly assigned participants (1: 1) to receive either oral prednisone alone, 1.0 or 1.5 mg/kg per day tapered over 12 or 18 months (prednisone alone group), or 1000 mg of intravenous rituximab on days 0 and 14, and 500 mg at months 12 and 18, combined with a short-term prednisone regimen, 0.5 or 1.0 mg/kg per day tapered over 3 or 6 months (rituximab plus short-term prednisone group). Follow-up was for 3 years (study visits were scheduled weekly during the first month of the study, then monthly until month 24, then an additional visit at month 36). Treatment was assigned through central computer-generated randomisation, with stratification according to disease-severity (severe or moderate, based on Harman's criteria). The primary endpoint was the proportion of patients who achieved complete remission off-therapy at month 24 (intention-to-treat analysis). This study is registered with ClinicalTrials.gov, number NCT00784589.Findings Between May 10, 2010, and Dec 7, 2012, we enrolled 91 patients and randomly assigned 90 to treatment (90 were analysed; 1 patient withdrew consent before the random assignment). At month 24, 41 (89%) of 46 patients assigned to rituximab plus short-term prednisone were in complete remission off-therapy versus 15 (34%) of 44 assigned to prednisone alone (absolute difference 55 percentage points, 95% CI 38.4-71.7; p<0.0001. This difference corresponded to a relative risk of success of 2.61 (95% CI 1.71-3.99, p<0.0001), corresponding to 1.82 patients (95% CI 1.39-2.60) who would need to be treated with rituximab plus prednisone (rather than prednisone alone) for one additional success. No patient died during the study. More severe adverse events of grade 3-4 were reported in the prednisone-alone group (53 events in 29 patients; mean 1.20 [SD 1.25]) than in the rituximab plus prednisone group (27 events in 16 patients; mean 0.59 [1.15]; p=0.0021). The most common of these events in both groups were diabetes and endocrine disorder (11 [21%] with prednisone alone vs six [22%] with rituximab plus prednisone), myopathy (ten [19%] vs three [11%]), and bone disorders (five [9%] vs five [19%]).Interpretation Data from our trial suggest that first-line use of rituximab plus short-term prednisone for patients with pemphigus is more effective than using prednisone alone, with fewer adverse events

Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid‐sparing effect

International audienc

Factors Associated With Short-term Relapse in Patients With Pemphigus Who Receive Rituximab as First-line Therapy

International audienceImportance: Rituximab and short-term corticosteroid therapy are the criterion standard treatments for patients with newly diagnosed moderate to severe pemphigus.Objective: To examine factors associated with short-term relapse in patients with pemphigus treated with rituximab.Design, setting, and participants: This post hoc analysis of a randomized clinical trial (Comparison Between Rituximab Treatment and Oral Corticosteroid Treatment in Patients With Pemphigus [RITUX 3]) conducted from January 1, 2010, to December 31, 2015, included patients from 20 dermatology departments of tertiary care centers in France from the RITUX 3 trial and 3 newly diagnosed patients treated according to the trial protocol. Data analysis was performed from February 1 to June 30, 2019.Exposure: Patients randomly assigned to the rituximab group in the RITUX 3 trial and the 3 additional patients were treated with 1000 mg of intravenous rituximab on days 0 and 14 and 500 mg at months 12 and 18 combined with a short-term prednisone regimen.Main outcomes and measures: Baseline (pretreatment) clinical and biological characteristics (Pemphigus Disease Area Index [PDAI] score, ranging from 0-250 points, with higher values indicating more severe disease) and changes in anti-desmoglein (DSG) 1 and anti-DSG3 values as measured by enzyme-linked immunosorbent assay during the 3 months after rituximab treatment were compared between patients with disease relapse and those who maintained clinical remission during the first 12 months after treatment. The positive and negative predictive values of these factors were calculated.Results: Among 47 patients (mean [SD] age, 54.3 [17.0] years; 17 [36%] male and 30 [64%] female) included in the study, the mean (SD) baseline PDAI score for patients with relapsing disease was higher than that of the patients with nonrelapsing disease (54 [33] vs 28 [24]; P = .03). At month 3, 7 of 11 patients with relapsing disease (64%) vs 7 of 36 patients with nonrelapsing disease (19%) had persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher (P = .01). A PDAI score of 45 or higher defining severe pemphigus and/or persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher at month 3 provided a positive predictive value of 50% (95% CI, 27%-73%) and a negative predictive value of 94% (95% CI, 73%-100%) for the occurrence of relapse after rituximab.Conclusions and relevance: The findings suggest that initial PDAI score and changes in anti-DSG antibody values after the initial cycle of rituximab might help differentiate a subgroup of patients with high risk of relapse who might benefit from maintenance rituximab infusion at month 6 from a subgroup of patients with low risk of relapse who do not need early maintenance therapy.Trial registration: NCT00784589