JAK inhibition in Aicardi-Goutières syndrome: a monocentric multidisciplinary real-world approach study

International audienceThe paradigm type I interferonopathy Aicardi-Goutières syndrome (AGS) is most typically characterized by severe neurological involvement. AGS is considered an immune-mediated disease, poorly responsive to conventional immunosuppression. Premised on a chronic enhancement of type I interferon signaling, JAK1/2 inhibition has been trialed in AGS, with clear improvements in cutaneous and systemic disease manifestations. Contrastingly, treatment efficacy at the level of the neurological system has been less conclusive. Here, we report our real-word approach study of JAK1/2 inhibition in 11 patients with AGS, providing extensive assessments of clinical and radiological status; interferon signaling, including in cerebrospinal fluid (CSF); and drug concentrations in blood and CSF. Over a median follow-up of 17 months, we observed a clear benefit of JAK1/2 inhibition on certain systemic features of AGS, and reproduced results reported using the AGS neurologic severity scale. In contrast, there was no change in other scales assessing neurological status; using the caregiver scale, only patient comfort, but no other domain of everyday-life care, was improved. Serious bacterial infections occurred in 4 out of the 11 patients. Overall, our data lead us to conclude that other approaches to treatment are urgently required for the neurologic features of AGS. We suggest that earlier diagnosis and adequate central nervous system penetration likely remain the major factors determining the efficacy of therapy in preventing irreversible brain damage, implying the importance of early and rapid genetic testing and the consideration of intrathecal drug delivery

Une soeur de charité dans le monde : madame Barrère / par Mlle Clarisse Bader

Avec mode text

Le journal de Melle d'Arvers : nouvelle écrite en français / par Toru Dutt,... ; ouvrage précédé d'une Etude sur la vie & les oeuvres de Toru Duttpar Melle Clarisse Bader

Comprend : Étude sur la vie & les oeuvres de Toru DuttAvec mode text

Analyzing Toru Dutt’s Oeuvre Today : How a Transnational Literary-Educational Case from Colonial India Can Enrich Our Conception of Transnational History

Bagchi argues that our conceptualization of the transnational in educational history is enriched by examining the multicentric histories and educational trajectories of Toru Dutt. She analyzes the transnational educational history of Dutt’s life as writer-in-the-making. A teenage prodigy who produced an astonishingly varied and rich corpus in a life that spanned India and Europe, before dying at the age of twenty-one, Dutt created a transnational literary and cultural space for her own work. Bagchi demonstrates that, using a feminist lens, we can recognize the character and enriching quality of such transnational female friendships and networks. While Dutt can be situated in the concepts of imperial as well as critical and vernacular cosmopolitanism, cosmopolitanisms need to be seen as important in our conceptualization of the transnational