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

Dramatic Tunability of the Glass Transition Temperature and Fragility of Low Molecular Weight Polystyrene by Initiator Fragments Located at Chain Ends

Important, yet unexplored effects of chemically distinct initiator fragments incorporated at chain ends in linear polymer are investigated in depth. Polystyrene (PS) samples of a wide range of molecular weight (MW) were synthesized by conventional free radical polymerization and controlled radical polymerization using seven different initiators and compared with anionically polymerized PS. The initiator fragments incorporated during polymerization have major consequences on the glass transition temperature (Tg) and dynamic fragility of low MW PS. For example, with ∼4 kg/mol PS, the Tg onset value and fragility can be tuned from ∼334 K and ∼65, respectively, with dodecanethiol and hydrogen atom chain ends to ∼367 K and ∼130, respectively, with cyanopentanoic acid chain ends. A similar high Tg and high fragility were measured with isobutyric acid/SG1 nitroxide chain ends. These remarkable effects, with a greater than 30 K difference in Tg and a factor of 2 difference in fragility, indicate that chain ends in low MW PS homopolymer play an “outsize” role in comparison to comonomer units in perturbing properties that are sensitive to the density of chain ends. The Tg results also provide further direct evidence against any correlation between the MW at which the Tg–MW dependence saturates and entanglement MW. Instead, the perturbation of Tg by the combined effects of a reduction in MW (increase in chain-end density) and chain-end structure correlates one-to-one within error with the perturbation of fragility. These results suggest that the susceptibility of fragility to be perturbed is key to the susceptibility of Tg to be perturbed

Mental Health of Transgender Veterans in US States With and Without Discrimination and Hate Crime Legal Protection

Objectives. To examine whether indicators of community- and state-level lesbian, gay, bisexual, and transgender equality are associated with transgender veterans’ mental health. Methods. We extracted Veterans Administration data for patients who were diagnosed with gender identity disorder, had at least 1 visit in 2013, and lived in a zip code with a Municipality Equality Index score (n = 1640). We examined the associations of whether a state included transgender status in employment nondiscrimination laws and in hate crimes laws with mood disorders; alcohol, illicit drug, and tobacco use disorders; posttraumatic stress disorder; and suicidal ideation or attempt. Results. Nearly half (47.3%) of the sample lived in states with employment discrimination protection, and 44.8% lived in states with hate crimes protection. Employment nondiscrimination protection was associated with 26% decreased odds of mood disorders (adjusted odds ratio [AOR] = 0.74; 95% confidence interval [CI] = 0.59, 0.93) and 43% decreased odds of self-directed violence (AOR = 0.57; 95% CI = 0.34, 0.95). Conclusions. Understanding lesbian, gay, bisexual, and transgender social stressors can inform treatment and care coordination for transgender populations. </jats:p

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