76 research outputs found
Safety and efficacy of rituximab treatment for vasculitis in hepatitis B virus-associated type II cryoglobulinemia: a case report
Mepolizumab and benralizumab in patients with severe asthma and a history of eosinophilic granulomatosis with polyangiitis
IntroductionAsthma associated with eosinophilic granulomatosis with polyangiitis (EGPA) is often severe and corticosteroid-dependent, leading to significant morbidity. Mepolizumab and benralizumab are humanized monoclonal antibodies targeting interleukin 5 (IL-5) and its receptor, respectively. They have been shown to be effective in steroid-sparing in patients with severe eosinophilic asthma.ObjectiveOur aim was to evaluate the efficacy and safety of mepolizumab and benralizumab prescribed for severe asthma in patients with EGPA under “real-world” conditions.MethodsThis was a retrospective analysis of patients with EGPA and persistent asthma who received either mepolizumab 100 or 300 mg administered every 4 weeks, or benralizumab 30 mg administered every 4 weeks for the initial 3 injections and followed by an injection every 8 weeks thereafter, whilst combined with oral glucocorticoids. The follow-up every 6 ± 3 months included an assessment of clinical manifestations, pulmonary function tests and eosinophil cell count. The primary outcome was the proportion of patients at 12 months receiving a daily oral dose of prednisone or equivalent of 4 mg or less with a BVAS of 0.ResultsTwenty-six patients were included. After 12 months of treatment with mepolizumab or benralizumab, 32% of patients met the primary outcome and were receiving less than 4 mg of prednisone per day with a BVAS of 0. The median dose of prednisone was 10 mg per day at baseline, 9 mg at 6 months, and 5 mg at 12 months (p ≤ 0.01). At 12 months, 23% of patients were weaned off corticosteroids, while an increase or no change in dose was observed in 27% of patients. The median eosinophil count was significantly reduced from 365 cells/mm3 to 55 cells/mm3 at 6 months and 70 cells/mm3 at 12 months, respectively. No significant change was observed in FEV1. After 12 months of treatment, 14% of patients had had an average of 1 exacerbation of asthma, compared with 52% of patients before baseline. The tolerability profile was favorable.ConclusionIn this real-world study in patients with severe asthma and a history of EGPA asthma, mepolizumab and benralizumab had a significant steroid-sparing effect and reduced asthma exacerbation, but no significant effect on lung function
Effects of Genotypes and Treatment on Oxygenscan Parameters in Sickle Cell Disease
(1) Background: The aim of the present study was to compare oxygen gradient ektacytometry parameters between sickle cell patients of different genotypes (SS, SC, and S/β+) or under different treatments (hydroxyurea or chronic red blood cell exchange). (2) Methods: Oxygen gradient ektacytometry was performed in 167 adults and children at steady state. In addition, five SS patients had oxygenscan measurements at steady state and during an acute complication requiring hospitalization. (3) Results: Red blood cell (RBC) deformability upon deoxygenation (EImin) and in normoxia (EImax) was increased, and the susceptibility of RBC to sickle upon deoxygenation was decreased in SC patients when compared to untreated SS patients older than 5 years old. SS patients under chronic red blood cell exchange had higher EImin and EImax and lower susceptibility of RBC to sickle upon deoxygenation compared to untreated SS patients, SS patients younger than 5 years old, and hydroxyurea-treated SS and SC patients. The susceptibility of RBC to sickle upon deoxygenation was increased in the five SS patients during acute complication compared to steady state, although the difference between steady state and acute complication was variable from one patient to another. (4) Conclusions: The present study demonstrates that oxygen gradient ektacytometry parameters are affected by sickle cell disease (SCD) genotype and treatment
Structural basis of ABCF-mediated resistance to pleuromutilin, lincosamide, and streptogramin A antibiotics in Gram-positive pathogens
he antibiotic target. One class of such proteins are the antibiotic resistance (ARE) ATP-binding cassette (ABC) proteins of the F-subtype (ARE-ABCFs), which are widely distributed throughout Gram-positive bacteria and bind the ribosome to alleviate translational inhibition from antibiotics that target the large ribosomal subunit. Here, we present single-particle cryo-EM structures of ARE-ABCF-ribosome complexes from three Gram-positive pathogens: Enterococcus faecalis LsaA, Staphylococcus haemolyticus VgaALC and Listeria monocytogenes VgaL. Supported by extensive mutagenesis analysis, these structures enable a general model for antibiotic resistance mediated by these ARE-ABCFs to be proposed. In this model, ABCF binding to the antibiotic-stalled ribosome mediates antibiotic release via mechanistically diverse long-range conformational relays that converge on a few conserved ribosomal RNA nucleotides located at the peptidyltransferase center. These insights are important for the future development of antibiotics that overcome such target protection resistance mechanisms
Apport de la biopsie ostéomédullaire dans le diagnostic des fièvres prolongées inexpliquées et des syndromes inflammatoires biologiques persistants de l'adulte (à propos de 180 observations vues en médecine interne)
LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Amylose cardiaque (étude rétrospective descriptive et analyse de survie à partir de 46 dossiers)
LYON1-BU Santé (693882101) / SudocPARIS-Bib. Serv.Santé Armées (751055204) / SudocSudocFranceF
Pratique et respect des recommandations en cas de surdosage en anti-vitamine K en médecine de ville
LYON1-BU Santé (693882101) / SudocSudocFranceF
Long-term follow-up of a multicentric cohort of 101 patients with eosinophilic granulomatosis with polyangiitis
Objectifs : Etudier le devenir à long terme des patients atteints de granulomatose éosinophilique avec polyangéite (EGPA) Méthodes : 101 patients répondant aux critères ACR 1990 du syndrome de Churg-Strauss ont été inclus entre 1990 et 2011 dans 3 centres hospitaliers européens (Cambridge, Lyon et Cagliari). Les antécédents, les caractéristiques cliniques, le statut ANCA et le five-factor score (FFS) des patients ont été recueillis à la prise en charge. La survie globale, la survie sans récidive et les séquelles d'organes ont ensuite été analysées en fonction du statut ANCA et du FFS. Résultats : Plus de la moitié des patients avait un antécédent d'asthme allergique sans distinction du statut ANCA. Les patients ANCA-négatifs avaient reçu davantage de montelukast (p=O.OOS) et avaient plus d'asthme grave (p=0.03). La prévalence de l'atteinte cardiaque n'était pas différente selon le statut ANCA. 79.6% des patients étaient mis en rémission après le traitement d'induction, mais 81.1o/o présentaient au moins une rechute. Les patients ANCA-positifs ne rechutaient pas plus que les patients ANCA-négatifs, mais ils avaient un phénotype plus sévère avec davantage de mononeuropathie multiple (p=0.0004) et d'atteinte rénale (p=0.02), témoins de la vascularite systémique. La nationalité italienne était le seul facteur pronostique associé à une meilleure survie sans récidive (p=0.01) grâce à une immunosuppression plus prolongée. La nécessité du maintien d'une corticothérapie faible au long cours voire à vie reste à définir. La survie globale atteignait 93.1% après une période de suivi moyenne de 7.3 ans. Aucun facteur n'était significativement associé à la mortalité. Cependant, les patients âgés de plus de 65 ans, ayant une atteinte cardiaque ou ANCA-positifs tendaient à avoir une mortalité plus élevée. Les séquelles concernaient 83.2% des patients. L'atteinte ORL était un facteur de bon pronostic sur les morbidités rénale (p=0.04) et cardiaque (p=0.03). Les patients ANCA-positifs développaient plus de maladie rénale chronique (p=0.03) et de séquelles neurologiques périphériques (p=0.02). Conclusions : Les challenges thérapeutiques actuels dans la prise en charge de l'EGPA sont d'une part de réduire le nombre de rechutes, et d'autre part de limiter les séquelles et d'améliorer la qualité de vie des patients. L'existence d'une atteinte ORL au diagnostic pourrait être un facteur de bon pronostic en termes de morbidités rénale et cardiaque. La positivité des ANCA serait un facteur prédictif de séquelles vascularitiques rénale et neurologique. Le choix des traitements devrait être adapté au profil évolutif de chaque patientLYON1-BU Santé (693882101) / SudocSudocFranceF
Pneumocystose pulmonaire chez les patients atteints de tumeurs solides (Ă propos de 23 observations)
LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
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