Acquired thrombotic thrombocytopenic purpura without detectable anti-ADAMTS13 antibodies: a possible underlying autoimmune mechanism.

In up to 25% of patients with acquired TTP, anti-ADAMTS13 antibodies are not identified, the mechanism resulting from ADAMTS13 deficiency remains unidentified (uTTP). In this study, we provide further insights on clinical presentation and outcome of uTTP. In patients with baseline undetectable anti-ADAMTS13 antibodies, usual features of iTTP (young age, cerebral involvement, severe thrombocytopenia) with no other associated context than a history of systemic autoimmune disease or pregnancy, should prompt to consider the diagnosis of iTTP

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/)

Effective dose of nefopam in 80% of patients (ED80): a study using the continual reassessment method

What is already known about this subjectDixon's up-and-down technique allows the calculation of the median effective dose (ED50) of a drug with a limited number of patients.However, it is not possible to calculate the effective dose in more than 50%, i.e. in 80% or 90% (ED80 or ED90) of the patients with this technique.What this study addsWe used the continual reassessment method, which is a Bayesian method to determine ED80, the dose of nefopam relieving pain in 80% of postoperative patients. The ED80 was close to 60 mg, higher than the usual dose of 20 mg

Efficacious switching from subcutaneous to intravenous tocilizumab in patients with non-infectious non-anterior uveitis

Abstract Purpose The efficacy of tocilizumab in refractory chronic noninfectious uveitis has been previously reported, but no data comparing intravenous and subcutaneous tocilizumab in uveitis are available. Results We report a case series of patients with chronic noninfectious uveitis with incomplete efficacy of subcutaneous tocilizumab, improved after switching to intravenous routes. Improvement of visual acuity was observed with intravenous tocilizumab for all patients. Half of the patients could stop corticosteroids. Rapid efficacy of intravenous tocilizumab was observed, between 2 and 3 months. Conclusion In uveitis, tocilizumab administration could be optimized by a switching from a subcutaneous to an intravenous administration route

Comparison of conventional immunosuppressive drugs versus anti-TNF-α agents in non-infectious non-anterior uveitis

International audienceObjective: To compare the efficacy and safety of Disease-modifying antirheumatic drugs (DMARDs) and anti-TNF-α agents in patients with non-infectious non-anterior uveitis.Methods: Single center retrospective study including adult patients with non-infectious intermediate, posterior or pan-uveitis. Outcomes were compared between patients treated with DMARDs or anti-TNF-α agents. The primary outcome was treatment failure or occurrence of serious adverse events. Treatment failure was determined by ophthalmologic criteria.Results: Seventy-three patients were included, mostly female (52%). Among them, 39 were treated with DMARDs and 34 with anti-TNF-α agents. The main uveitis causes were idiopathic (30%), birdshot chorio-retinopathy (25%), sarcoidosis (16%) and Behçet's disease (14%). The primary outcome was observed in 56% of patients treated with anti-TNF-α agents versus 59% of patients treated with DMARDs (p = 0.82). Median time to observe the primary outcome was 16 months (anti-TNF-α group) versus 21 months (p = 0.52). There was no significant difference between the two groups in terms of treatment failure, corticosteroid sparing effect, visual acuity improvement or adverse events. Earlier control of ocular inflammation was achieved with anti-TNF-α agents than with DMARDs (p = 0.006). In relapsing patients, anti-TNF-α agents allowed better corticosteroid sparing (p = 0.06).Conclusion: DMARDs could still be used as first-line therapy for non-infectious non-anterior uveitis after corticosteroid therapy. However, anti-TNF-α agents could be proposed as an alternative in cases of severe inflammation or initial high level of steroid dependency

Development and validation of a questionnaire assessing fears and beliefs of patients with knee osteoarthritis: the Knee Osteoarthritis Fears and Beliefs Questionnaire (KOFBeQ).

ObjectiveWe aimed to develop a questionnaire assessing fears and beliefs of patients with knee OA.DesignWe sent a detailed document reporting on a qualitative analysis of interviews of patients with knee OA to experts, and a Delphi procedure was adopted for item generation. Then, 80 physicians recruited 566 patients with knee OA to test the provisional questionnaire. Items were reduced according to their metric properties and exploratory factor analysis. Reliability was tested by the Cronbach α coefficient. Construct validity was tested by divergent validity and confirmatory factor analysis. Test-retest reliability was assessed by the intra-class correlation coefficient (ICC) and the Bland and Altman technique.Results137 items were extracted from analysis of the interview data. Three Delphi rounds were needed to obtain consensus on a 25-item provisional questionnaire. The item-reduction process resulted in an 11-item questionnaire. Selected items represented fears and beliefs about daily living activities (3 items), fears and beliefs about physicians (4 items), fears and beliefs about the disease (2 items), and fears and beliefs about sports and leisure activities (2 items). The Cronbach α coefficient of global score was 0.85. We observed expected divergent validity. Confirmation factor analyses confirmed higher intra-factor than inter-factor correlations. Test-retest reliability was good, with an ICC of 0.81, and Bland and Altman analysis did not reveal a systematic trend.ConclusionsWe propose an 11-item questionnaire assessing patients' fears and beliefs concerning knee OA with good content and construct validity

Comparing the efficacy and safety of cyclophosphamide, infliximab and methotrexate in neurosarcoidosis: a multicenter retrospective study

International audienceIntroduction: Neurosarcoidosis is a granulomatous disease affecting 10% of patients with sarcoidosis. In lack of standardized guidelines, various therapeutic strategies exist. Beyond corticosteroids, cyclophosphamide, infliximab, or methotrexate are available options. This study compared the efficacy and safety of these agents as firstline therapy.Methods: This multicenter, retrospective, study included patients with definite or probable neurosarcoidosis (1999-2022). Primary endpoint was relapse rate at the end of follow-up, after first-line therapy with cyclophosphamide, infliximab or methotrexate. Relapse was defined as a≥1-point increase in the Extrapulmonary Organ Severity Tool score following initial improvement.Results: Fifty-two patients were included: 18 (34.6%) received cyclophosphamide, 10 (19.2%) infliximab and 24 (46.2%) methotrexate. Multivisceral impairment was observed in 63% of patients, and neurological involvement at diagnosis in 67% of patients. Main neurological localizations were the brain (60%), meninges (48%) and cranial nerves (46%). Sixteen patients (30.7%) relapsed: 56% with cyclophosphamide, 6% with infliximab and 38% with methotrexate (p = 0.06). Median relapse-free survival was 48 months in patients treated with cyclophosphamide, and not estimable for infliximab or methotrexate (p = 0.07). Relapse was associated with brain involvement (p = 0.006) and younger age (p = 0.04). At 12 months, response rate was 100% for infliximab-treated patients, 89% for cyclophosphamide and 87% for methotrexate. All treatments demonstrated a corticosteroid-sparing effect, with infliximab achieving the highest proportion of patients (80%) reaching ≤ 5 mg/day at 12 months (p = 0.07). Infections were more frequent with cyclophosphamide (p = 0.01), however two deadly infections occured with methotrexate.Conclusion: Infliximab and methotrexate appear as effective and safe options for relapse prevention in neurosarcoidosis