The recently described VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is caused by somatic mutations in UBA1. Patients with VEXAS display late-onset autoinflammatory symptoms, usually refractory to treatment, and hematologic abnormalities. The identification of an easily-accessible specific marker (UBA1 mutations) is of particular interest as it allows the convergence of various inflammatory and hematological symptoms in a unique clinico-biological entity and gives the opportunity to design specific treatment strategies. Here we retrospectively identified 6 patients with VEXAS who underwent allogeneic hematopoietic stem cell transplantation (ASCT). To date, no treatment guidelines have been validated. In four patients, ASCT was guided by life-threatening autoinflammatory symptoms that were refractory to multiple therapies. Three patients are in durable complete remission, 32, 38 and 37 months after ASCT. Two others are in complete remission response after 3 and 5 months. One unfortunately died post-ASCT. This report suggests that ASCT could be a curative option in patients with VEXAS and severe manifestations. Considering the complications and side effects of the procedure as well as the existence of other potential treatment, clinical trials are needed to define the subgroup of patients who will benefit from this strategy and its place in the therapeutic arsenal against VEXAS.
26Necrophagous flies breeding on carcasses face high selection pressures and therefore 27 provide interesting opportunities to study social adaptations. We postulated that blowfly 28 necrophagous larvae gregariousness is an adaptive response to the environmental 29 constraints of fresh carcasses. Cooperation is indeed believed to be a key to the global 30 success of social species. To test this idea, the development of Lucilia sericata 31 (Diptera: Calliphoridae) larvae growing on low-or high-digestibility food substrate 32 (control or trypsin-added ground beef muscle, respectively) at different larval densities 33 was monitored. Results showed that larvae developed faster and had decreased 34 mortality at high larval density compared with low larval density. Furthermore,
35aggregation had no deleterious effect on the morphological characteristics (e.g., size)
36of post-feeding larvae and flies. We concluded that increased density positively 37 affected population fitness, which is a conclusion consistent with the predictions of the 38 Allee effect. Compared with regular food, larvae fed on high-digestibility food had 39 reduced mortality and faster development on average. According to these results, we 40 postulated that collective exodigestion might be an adaptive response allowing 41 blowflies to colonise fresh carcasses before the arrival of other insects and the 42 multiplication of microbes. This hypothesis is consistent with the idea that cooperation 43 may enable species to expand their niches. 44 45
A better understanding of immune-related adverse events is essential for the early detection and appropriate management of these phenomena. We conducted an observational study of cases recorded at the French reference center for hypereosinophilic syndromes and in the French national pharmacovigilance database. Thirty-seven reports of eosinophilia induced by treatment with immune checkpoint inhibitors (ICIs) were included. The median [range] time to the absolute eosinophil count (AEC) peak was 15 [4─139] weeks. The median AEC was 2.7 [0.8─90.9] G/L. Eosinophil-related manifestations were reported in 21 of the 37 cases (57%). If administered, corticosteroids were always effective (n = 10 out of 10). Partial or complete remission of eosinophilia was obtained in some patients not treated with corticosteroids, after discontinuation (n = 12) or with continuation (n = 4) of the ICI. The AEC should be monitored in ICI-treated patients. If required by oncologic indications, continuation of ICI may be an option in asymptomatic hypereosinophilic patients, and in corticosteroid responders.
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