Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Evaluation de la prise en charge des traumatisés crâniens légers

Le traumatisme crânien léger (TCL) est un motif fréquent de consultation dans les services d urgence (SU). La difficulté de leur prise en charge repose sur l identification des patients à risque de lésion post traumatique. La Société Française de Médecine d Urgence (SFMU) a publié des recommandations en Juin 2011, définissant les critères de recours à l'imagerie et à l'hospitalisation. Elles insistent particulièrement sur le risque accru de complication immédiate et secondaire sous traitements antithrombotiques. Une évaluation des pratiques professionnelles a été menée dans le SU du CHU d'Angers. L objectif était d analyser la conformité des prises en charge des TCL par rapport aux recommandations de la SFMU. Une analyse spécifique des TCL sous antithrombotique était également menée (impact sur le devenir fonctionnel et la prescritpion des antithrombotiques) 253 TCL ont été inclus dans notre étude avec des caractéristiques épidémiologiques comparables à la littérature. Notre étude objective un respect partiel du recours à l'imagerie (63%) et à l'hospitalisation (61%) en présence d'un facteur de risque identifié. Seul 38% des patients sous antiagrégant plaquettaire et 71% sous anti-vitamine K ont bénéficié de la prise en charge recommandée. Un défaut d'information concernant la surveillance post traumatique a été également pointé pour deux tiers des TCL retournant à domicile. Par ailleurs, au décours du traumatisme, la majorité des médecins traitants ont procédé à une remise en question de leurs prescriptions d antithrombotique, conscient du risque encouru par leur patient; débouchant sur une part non négligeable (18,5%) d arrêt de prescription.Minor head trauma (MHT) is a common presentation in emergency rooms. These patients can be difficult to assess and their management depends on the identification of post traumatic lesion. SFMU's recommendations published in June 2011 define criteria for computed tomographic scanning and hospitalisation decisions. The serious risk of early and secondary complications is highlighted for patient with antithrombotic therapies. This study has been conducted by the CHU d'Angers in the emergency service. The goal of the evaluation of professional practice in minor head trauma management is to analyse the conformity with the published guidelines. A specific analyse of patients with antithrombotic therapies has also been carried out to demonstrate the impact of these practice on the physical complication and on the antithrombotic's prescription. 253 patients with MHT and epidemiologic characteristic similar to the medical literature were including. It result a partial compliance regarding imaging performance (63%) and hospitalisation (61%) when a risk factor was identified. Only 38% patient taking antiplatelet medication and 71% patient receiving oral anticoagulant received a recommended management. A lake of information about the post traumatic survey has also been pointed out for two-third of the patient leaving. In addition, following the trauma, a majority of the referring physician put into question their antithrombotic's prescription, aware of the potential risk; generating a significant part of them to stop the treatment (18.5%).ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Onderscheid in gedrags- en emotionele problemen bij kinderen van het type 1,3 en 8 : een onderzoek met de teacher's report form /

Diss. lic. pedagogische wetenschappen: orthopedagogie

Development of temporal lobe epilepsy during maintenance electroconvulsive therapy: A case of human kindling?

We describe a patient with new-onset temporal lobe epilepsy during prolonged maintenance electroconvulsive therapy. We suggest a possible causal relationship with maintenance electroconvulsive therapy through electrical kindling of the temporal lobe.status: Published onlin

Development of temporal lobe epilepsy during maintenance electroconvulsive therapy: A case of human kindling?

We describe a patient with new-onset temporal lobe epilepsy during prolonged maintenance electroconvulsive therapy. We suggest a possible causal relationship with maintenance electroconvulsive therapy through electrical kindling of the temporal lobe.Circuits and System

Neoantigen landscape dynamics during human melanoma-T cell interactions

Recognition of neoantigens that are formed as a consequence of DNA damage is likely to form a major driving force behind the clinical activity of cancer immunotherapies such as T-cell checkpoint blockade and adoptive T-cell therapy(1-7). Therefore, strategies to selectively enhance T-cell reactivity against genetically defined neoantigens(1,8-11) are currently under development. In mouse models, T-cell pressure can sculpt the antigenicity of tumours, resulting in the emergence of tumours that lack defined mutant antigens(12,13). However, whether the T-cell-recognized neoantigen repertoire in human cancers is constant over time is unclear. Here we analyse the stability of neoantigen-specific T-cell responses and the antigens they recognize in two patients with stage IV melanoma treated by adoptive T-cell transfer. The T-cell-recognized neoantigens can be selectively lost from the tumour cell population, either by overall reduced expression of the genes or loss of the mutant alleles. Notably, loss of expression of T-cell-recognized neoantigens was accompanied by development of neoantigen-specific T-cell reactivity in tumour-infiltrating lymphocytes. These data demonstrate the dynamic interactions between cancer cells and T cells, which suggest that T cells mediate neoantigen immunoediting, and indicate that the therapeutic induction of broad neoantigen-specific T-cell responses should be used to avoid tumour resistanc