A single center case series of immune checkpoint inhibitor-induced type 1 diabetes mellitus, patterns of disease onset and long-term clinical outcome

BackgroundType 1 diabetes mellitus (T1DM) is a rare, but serious immune-related adverse event (irAE) of immune checkpoint inhibitors (ICIs). Our goal was to characterize treatment outcomes associated with ICI-induced T1DM through analysis of clinical, immunological and proteomic data.MethodsThis was a single-center case series of patients with solid tumors who received ICIs and subsequently had a new diagnosis of T1DM. ICD codes and C-peptide levels were used to identify patients for chart review to confirm ICI-induced T1DM. Baseline blood specimens were studied for proteomic and immunophenotypic changes.ResultsBetween 2011 and 2023, 18 of 3744 patients treated at Huntsman Cancer Institute with ICIs were confirmed to have ICI-induced T1DM (0.48%). Eleven of the 18 patients received anti-PD1 monotherapy, 4 received anti-PD1 plus chemotherapy or targeted therapy, and 3 received ipilimumab plus nivolumab. The mean time to onset was 218 days (range 22-418 days). Patients had sudden elevated serum glucose within 2-3 weeks prior to diagnosis. Sixteen (89%) presented with diabetic ketoacidosis. Three of 12 patients had positive T1DM-associated autoantibodies. All patients with T1DM became insulin-dependent through follow-up. At median follow-up of 21.9 months (range 8.4-82.4), no patients in the melanoma group had progressed or died from disease. In the melanoma group, best responses were 2 complete response and 2 partial response while on active treatment; none in the adjuvant group had disease recurrence. Proteomic analysis of baseline blood suggested low inflammatory (IL-6, OSMR) markers and high metabolic (GLO1, DXCR) markers in ICI-induced T1DM cohort.ConclusionsOur case series demonstrates rapid onset and irreversibility of ICI-induced T1DM. Melanoma patients with ICI-induced T1DM display excellent clinical response and survival. Limited proteomic data also suggested a unique proteomic profile. Our study helps clinicians to understand the unique clinical presentation and long-term outcomes of this rare irAE for best clinical management

Attitudes About Sex and Marital Sexual Behavior in Hai Duong Province, Vietnam

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74926/1/j.1728-4465.2005.00047.x.pd

Impact of Social Determinants of Health on Medical Conditions Among Transgender Veterans

Introduction Transgender individuals experience pronounced disparities in health (e.g., mood disorders, suicide risk) and in the prevalence of social determinants of housing instability, financial strain, and violence. The objectives of this study were to understand the prevalence of social determinants among transgender veterans and assess their associations with medical conditions. Methods This project was a records review using administrative data from the U.S. Department of Veterans Affairs databases for 1997–2014. Transgender veterans (N=6,308) were defined as patients with any of four ICD-9 diagnosis codes associated with transgender status. Social determinants were operationalized using ICD-9 codes and Department of Veterans Affairs clinical screens indicating violence, housing instability, or financial strain. Multiple logistic regression was used to assess the associations of social determinants with medical conditions: mood disorder, post-traumatic stress disorder, alcohol abuse disorder, illicit drug abuse disorder, tobacco use disorder, suicidal risk, HIV, and hepatitis C. Results After adjusting for sociodemographic variables, housing instability and financial strain were significantly associated with all medical conditions except for HIV, and violence was significantly associated with all medical conditions except for tobacco use disorder and HIV. There was a dose response–like relationship between the increasing number of forms of social determinants being associated with increasing odds for medical conditions. Conclusions Social determinants are prevalent factors in transgender patients’ lives, exhibiting strong associations with medical conditions. Documenting social determinants in electronic health records can help providers to identify and address these factors in treatment goals

Lower frequencies of circulating suppressive regulatory T cells and higher frequencies of CD4+ naïve T cells at baseline are associated with severe immune-related adverse events in immune checkpoint inhibitor-treated melanoma

Background Immune-related adverse events (irAEs) are major barriers of clinical management and further development of immune checkpoint inhibitors (ICIs) for cancer therapy. Therefore, biomarkers associated with the onset of severe irAEs are needed. In this study, we aimed to identify immune features detectable in peripheral blood and associated with the development of severe irAEs that required clinical intervention.Methods We used a 43-marker mass cytometry panel to characterize peripheral blood mononuclear cells from 28 unique patients with melanoma across 29 lines of ICI therapy before treatment (baseline), before the onset of irAEs (pre-irAE) and at the peak of irAEs (irAE-max). In the 29 lines of ICI therapy, 18 resulted in severe irAEs and 11 did not.Results Unsupervised and gated population analysis showed that patients with severe irAEs had a higher frequency of CD4+ naïve T cells and lower frequency of CD16+ natural killer (NK) cells at all time points. Gated population analysis additionally showed that patients with severe irAEs had fewer T cell immunoreceptor with Ig and ITIM domain (TIGIT+) regulatory T cells at baseline and more activated CD38+ CD4+ central memory T cells (TCM) and CD39+ and Human Leukocyte Antigen-DR Isotype (HLA-DR)+ CD8+ TCM at peak of irAEs. The differentiating immune features at baseline were predominantly seen in patients with gastrointestinal and cutaneous irAEs and type 1 diabetes. Higher frequencies of CD4+ naïve T cells and lower frequencies of CD16+ NK cells were also associated with clinical benefit to ICI therapy.Conclusions This study demonstrates that high-dimensional immune profiling can reveal novel blood-based immune signatures associated with risk and mechanism of severe irAEs. Development of severe irAEs in melanoma could be the result of reduced immune inhibitory capacity pre-ICI treatment, resulting in more activated TCM cells after treatment