SLC30A8 polymorphism and BMI complement HLA-A*24 as risk factors for poor graft function in islet allograft recipients

Transplantation and autoimmunit

HLA-A*24 Carrier Status and Autoantibody Surges Posttransplantation Associate With Poor Functional Outcome in Recipients of an Islet Allograft

Surgical oncolog

Transformations in Victor Hugo's cosmic poetry

Victor Hugo's verse draws on ideas about reincarnation, future harmony, the chain of being, and the rejection of hell set out by contemporaries such as Ballanche and Reynaud. This article shows how two related poetic texts by Hugo, ‘Ce que dit la bouche d'ombre’ from Les Contemplations and the end of the ‘L'Océan d'en haut’ section of Dieu, not only transpose such ideas into visionary images but also use the resources of poetry to enact the very transformations and movements that are their subject matter. Close analysis of key passages shows how Hugo describes the structure of the cosmos in terms of motion, uses verbal metaphors to emphasize change as process, and plays on organic metaphors to suggest that evil will inevitably turn into good. He thus transposes into verse the Romantic tendency to privilege the idea of life and, in versifying movement, he dynamizes poetry

Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review

Objective: To better define the rare adverse event (AE) of diabetes mellitus associated with immune checkpoint inhibitors (ICIs).Design and methods: We report the case of a lung cancer patient with diabetic ketoacidosis (DKA) and autoimmune thyroiditis during pembrolizumab treatment. We provide a systematic review of all published cases (PubMed/Web of Science/Cochrane, through November 2018) of autoimmune diabetes mellitus related to blockade of the cytotoxic T-lymphocyte antigen 4 (CTLA-4)-, programmed cell death 1 (PD-1) receptor or its ligand (PD-L1) or combination (ICI) therapy.Results: Our literature search identified 90 patient cases (our case excluded). Most patients were treated with anti-PD-1 or anti-PD-L1 as monotherapy (79%) or in combination with CTLA-4 blockade (15%). On average, diabetes mellitus was diagnosed after 4.5 cycles; earlier for combination ICI at 2.7 cycles. Early-onset diabetes mellitus (after one or two cycles) was observed during all treatment regimens. Diabetic ketoacidosis was present in 71%, while elevated lipase levels were detected in 52% (13/25). Islet autoantibodies were positive in 53% of patients with a predominance of glutamic acid decarboxylase antibodies. Susceptible HLA genotypes were present in 65% (mostly DR4). Thyroid dysfunction was the most frequent other endocrine AE at 24% incidence in this patient population.Conclusion: ICI-related diabetes mellitus is a rare but often life-threatening metabolic urgency of which health-care professionals and patients should be aware. Close monitoring of blood glucose and prompt endocrine investigation in case of hyperglycemia is advisable. Predisposing factors such as HLA genotype might explain why some individuals are at risk.Diabetes mellitus: pathophysiological changes and therap

HLA-A∗24 carrier status and autoantibody surges posttransplantation associate with poor functional outcome in recipients of an islet allograft

OBJECTIVE We investigated whether changes in islet autoantibody profile and presence of HLA risk markers, reported to predict rapid β- cell loss in pre-type 1 diabetes, associate with poor functional outcome in islet allograft recipients. RESEARCH DESIGN AND METHODS Forty- one patients received ≥2.3 million β-cells/kg body wt in one to two intraportal implantations. Outcome after 6-18 months was assessed by C-peptide (random and stimulated), insulin dose, and HbA1c .RESULTS Patients carrying HLA-A∗24-positive or experiencing a significant autoantibody surge within 6 months after the first transplantation (n 5 19) had lower C-peptide levels (P ≤ 0.003) and higher insulin needs (P < 0.001) despite higher HbA1c levels (P ≤ 0.018). They became less often insulin independent (16% vs. 68%, P 5 0.002) and remained less often C- peptide positive (47% vs. 100%, P < 0.001) than recipients lacking both risk factors. HLA-A∗24 positivity or an autoantibody surge predicted insulin dependence (P 5 0.007). CONCLUSIONS HLA-A∗24 and early autoantibody surge after islet implantation associate with poor functional graft outcome.SCOPUS: ar.jinfo:eu-repo/semantics/publishe