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.
Dancing on pointe and relevé requires extreme plantar flexion of the talo-crural joint. Hence, these positions may lead to posterior ankle impingement syndrome (PAIS). PAIS often coincides with flexor hallucis longus tendinopathy (FHL tendinopathy, or "dancers' tendinitis"). Both injuries can appear in isolation as well. The goal of this review is to evaluate the results and the available levels of evidence of conservative and operative treatment (both open and endoscopic) of PAIS and FHL tendinopathy in dancers. It also offers an insight into the history of dance medical publications on this subject. In October 2016, a systematic search of PubMed, Embase, Cochrane, CINAHL, Web of Science, and (in French) ScienceDirect databases was undertaken. Five hundred and seventy-six publications were found, of which a total of 27 reported the results of operative treatment in 376 ankles (344 open, 32 endoscopic) in 324 dancers. The outcome was good to excellent in most cases (89%). The mean period of return to dance for all surgeries combined (PAIS and FHL tendinopathy, open and endo) was 11 weeks (range: 4 to 36 weeks), and for isolated FHL tendinopathy 16 weeks (range: 8 to 36 weeks). Only six publications reported the results of conservative treatment in 33 ankles (13 PAIS, 20 FHL tendinopathy) of 28 dancers, which does not allow for any evidence-based recommendations. Most studies failed to include dance-specific baseline characteristics, like dance style and level of participation. We concluded that only retrospective studies with levels of evidence four and five show that operative treatment for PAIS and FHL tendinopathy is successful with few complications. Since isolated PAIS, PAIS combined with FHL tendinopathy, and isolated FHL injuries appear to be different pathological entities, more research taking into account demography, dance type, and level of participation is needed to find out in which cases early operative management should be considered or avoided. The same applies to defining the place of endoscopic surgery in dancers and being able better to predict which pathology is likely to produce worse outcomes or delay the return to dance. Future research should have a prospective design, including dance-specific outcome scores both preand post-treatment. Furthermore, preferably a prospective randomized controlled design should be used to compare different conservative and operative treatment options.
Background Gliomas are rare, with a dismal outcome and an obvious impact on quality of life, because of neurological, physical and cognitive problems, as well as personality and behavioral changes. These latter changes may affect the lives of both patients and their relatives in a profound way, but it is unclear how often this occurs and to what extent. Methods We performed a systematic review to determine the prevalence of changes in personality and behavior in glioma patients. Searches were conducted in PubMed/Medline, PsycINFO, Cochrane, CINAHL and Embase. Based on predetermined in- and exclusion criteria, papers were screened for eligibility. Information on the topics of interest were extracted from the full-text papers. Results The search yielded 9895 papers, of which 18 were found to be eligible; 9 qualitative and 9 quantitative studies. The reported prevalence rates of changes in personality and/or behavior varied from 8%–67% in glioma patients, and was 100% in a case series with bilateral gliomas. Moreover, these changes were associated with distress and a lower quality of life of patients as well as informal caregivers. Methods of measurement of personality and behavioral changes differed considerably, as did the description of these changes. Conclusion To determine the true prevalence of changes in behavior and personality, present but poorly labeled in the reported studies, prospective studies are needed using proper definitions of personality and behavioral changes and validated measurement tools. Ultimately, these findings may result in improved supportive care of both patients and caregivers, during the disease trajectory.
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