Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors

Objective To report the induction of anti-Ma2 antibody-associated paraneoplastic neurologic syndrome (Ma2-PNS) in 6 patients after treatment with immune checkpoint inhibitors (ICIs). We also analyzed (1) patient clinical features compared with a cohort of 44 patients who developed Ma2-PNS without receiving ICI treatment and (2) the frequency of neuronal antibody detection before and after ICI implementation. Methods Retrospective nationwide study of all patients with Ma2-PNS developed during ICI treatment between 2017 and 2018. Results Our series of patients included 5 men and 1 woman (median age, 63 years). The patients were receiving nivolumab (n = 3), pembrolizumab (n = 2), or a combination of nivolumab and ipilimumab (n = 1) for treatment of neoplasms that included lung (n = 4) and kidney (n = 1) cancers and pleural mesothelioma (n = 1). Clinical syndromes comprised a combination of limbic encephalitis and diencephalitis (n = 3), isolated limbic encephalitis (n = 2), and a syndrome characterized by ophthalmoplegia and head drop (n = 1). No significant clinical difference was observed between our 6 patients and the overall cohort of Ma2-PNS cases. Post-ICI Ma2-PNS accounted for 35% of the total 17 Ma2-PNS diagnosed in our center over the 2017-2018 biennium. Eight cases had been detected in the preceding biennium 2015-2016, corresponding to a 112% increase of Ma2-PNS frequency since the implementation of ICIs in France. Despite ICI withdrawal and immunotherapy, 4/6 patients died, and the remaining 2 showed a moderate to severe disability. Conclusions We show a clear association between ICI use and increased diagnosis of Ma2-PNS. Physicians need to be aware that ICIs can trigger Ma2-PNS because clinical presentation can be challenging

Synthèse lipochimique et étude de composés à chaine ramifiée pour lubrifiant. Convention ADEME (AGRICE - CIRAD - VALAGRO - CHRISTOL GREASE n. 95 01 066. Rapport final décembre 1998

Le présent rapport concerne la mise au point de protocoles de synthèse ainsi que la fabrication d'échantillons d'esters à structure ramifiée à partir d'acides gras saturés ou monoinsaturés à chaîne normale, notamment d'origine tournesol oléique. Il associe le CIRAD, un centre technique spécialiste des agroressources VALAGRO et un industriel du domaine de la lubrification CHRISTOL-GREASE. Ce travail qui est centré sur la "voie cétonique" explorée par le CIRAD, permet d'obtenir des esters via la condensation d'acides gras en cétones, l'hydrogénation de ces dernières en alcools secondaires et l'estérification par une deuxième coupe d'acides gras. La procédure de synthèse fait intervenir la catalyse hétérogène pour les deux premières étapes, ne nécessite que l'éthanol et l'eau comme solvants et permet d'atteindre un rendement très élevé en produit fini. Elle est transposable à l'échelle industrielle. Parmi les nombreuses molécules synthétie d'origine 100% végétale dépassant le cadre du présent contrat. De plus la versatilité de la voie de synthèse qui a été peu exploitée au cours de cette première année du programme de recherche devrait permettre d'affiner la structure de l'ester afin d'ajuster les propriétés. Les composés déjà obtenus ou projetés au cours de la phase suivante pourront trouver des applications dans des domaines variés. Le présent rapport dresse d'ailleurs un panorama optimiste du marché potentiel des lubrifiants d'origine végétale. L'approche technico-économique montre que le coût de production estimé de ces composés nouveaux, même à une échelle modeste, resterait compatible avec les exigences du marché. (Résumé d'auteur

Internet users engage more with phatic posts than with health misinformation on Facebook

International audienceSocial media like Facebook are harshly criticized for the propagation of health misinformation. Yet, little research has provided in-depth analysis of real-world data to measure the extent to which Internet users engage with it. This article examines 6.5 million interactions generated by 500 posts on an emblematic case of online health misinformation: the Facebook page Santé + Mag, which generates five times more interactions than the combination of the five best-established French media outlets. Based on the literature on cultural evolution, we tested whether the presence of cognitive factors of attraction, that tap into evolved cognitive preferences, such as information related to sexuality, social relations, threat, disgust or negative emotions, could explain the success of Santé + Mag's posts. Drawing from media studies findings, we hypothesized that their popularity could be driven by Internet users' desire to interact with their friends and family by sharing phatic posts (i.e. statements with no practical information fulfilling a social function such as "hello" or "sister, I love you"). We found that phatic posts were the strongest predictor of interactions, followed by posts with a positive emotional valence. While 50% of the posts were related to social relations, only 28% consisted of health misinformation. Despite its cognitive appeal, health misinformation was a negative predictor of interactions. Sexual content negatively predicted interactions and other factors of attraction such as disgust, threat or negative emotions did not predict interactions. These results strengthen the idea that Facebook is first and foremost a social network used by people to foster their social relations, not to spread online mis-information. We encourage researchers working on misinformation to conduct finer-grained analysis of online content and to adopt interdisciplinary approach to study the phatic dimension of communication, together with positive content, to better understand the cultural evolution dynamics of social media

Mortality reduction by post-dilution online-haemodiafiltration : A cause-specific analysis

Background. From an individual participant data (IPD) meta-analysis from four randomized controlled trials comparing haemodialysis (HD) with post-dilution online-haemodiafiltration (ol-HDF), previously it appeared that HDF decreases all-cause mortality by 14% (95% confidence interval 25; 1) and fatal cardiovascular disease (CVD) by 23% (39; 3). Significant differences were not found for fatal infections and sudden death. So far, it is unclear, however, whether the reduced mortality risk of HDF is only due to a decrease in CVD events and if so, which CVD in particular is prevented, if compared with HD. Methods. The IPD base was used for the present study. Hazard ratios and 95% confidence intervals for cause-specific mortality overall and in thirds of the convection volume were calculated using the Cox proportional hazard regression models. Annualized mortality and numbers needed to treat (NNT) were calculated as well. Results. Besides 554 patients dying from CVD, fatal infections and sudden death, 215 participants died from 'other causes', such as withdrawal from treatment and malignancies. In this group, the mortality risk was comparable between HD and ol-HDF patients, both overall and in thirds of the convection volume. Subdivision of CVD mortality in fatal cardiac, non-cardiac and unclassified CVD showed that ol-HDF was only associated with a lower risk of cardiac casualties [0.64 (0.61; 0.90)]. Annual mortality rates also suggest that the reduction in CVD death is mainly due to a decrease in cardiac fatalities, including both ischaemic heart disease and congestion. Overall, 32 and 75 patients, respectively, need to be treated by high-volume HDF (HV-HDF) to prevent one all-cause and one CVD death, respectively, per year. Conclusion. The beneficial effect of ol-HDF on all-cause and CVD mortality appears to be mainly due to a reduction in fatal cardiac events, including ischaemic heart disease as well as congestion. In HV-HDF, the NNT to prevent one CVD death is 75 per year

Mortality reduction by post-dilution online-haemodiafiltration : A cause-specific analysis

Background. From an individual participant data (IPD) meta-analysis from four randomized controlled trials comparing haemodialysis (HD) with post-dilution online-haemodiafiltration (ol-HDF), previously it appeared that HDF decreases all-cause mortality by 14% (95% confidence interval 25; 1) and fatal cardiovascular disease (CVD) by 23% (39; 3). Significant differences were not found for fatal infections and sudden death. So far, it is unclear, however, whether the reduced mortality risk of HDF is only due to a decrease in CVD events and if so, which CVD in particular is prevented, if compared with HD. Methods. The IPD base was used for the present study. Hazard ratios and 95% confidence intervals for cause-specific mortality overall and in thirds of the convection volume were calculated using the Cox proportional hazard regression models. Annualized mortality and numbers needed to treat (NNT) were calculated as well. Results. Besides 554 patients dying from CVD, fatal infections and sudden death, 215 participants died from 'other causes', such as withdrawal from treatment and malignancies. In this group, the mortality risk was comparable between HD and ol-HDF patients, both overall and in thirds of the convection volume. Subdivision of CVD mortality in fatal cardiac, non-cardiac and unclassified CVD showed that ol-HDF was only associated with a lower risk of cardiac casualties [0.64 (0.61; 0.90)]. Annual mortality rates also suggest that the reduction in CVD death is mainly due to a decrease in cardiac fatalities, including both ischaemic heart disease and congestion. Overall, 32 and 75 patients, respectively, need to be treated by high-volume HDF (HV-HDF) to prevent one all-cause and one CVD death, respectively, per year. Conclusion. The beneficial effect of ol-HDF on all-cause and CVD mortality appears to be mainly due to a reduction in fatal cardiac events, including ischaemic heart disease as well as congestion. In HV-HDF, the NNT to prevent one CVD death is 75 per year