Single-cell profiling reveals unique features of diabetogenic T cells in anti-PD-1-induced type 1 diabetes mice.

Immune-related adverse events (irAEs) are a notable complication of PD-1 cancer immunotherapy. A better understanding of how these iatrogenic diseases compare with naturally arising autoimmune diseases is needed for treatment and monitoring of irAEs. We identified differences in anti-PD-1-induced type 1 diabetes (T1D) and spontaneous T1D in non-obese diabetic (NOD) mice by performing single-cell RNA-seq and TCR-seq on T cells from the pancreas, pancreas-draining lymph node (pLN), and blood of mice with PD-1-induced T1D or spontaneous T1D. In the pancreas, anti-PD-1 resulted in expansion of terminally exhausted/effector-like CD8+ T cells, an increase in T-bethi CD4+FoxP3- T cells, and a decrease in memory CD4+FoxP3- and CD8+ T cells in contrast to spontaneous T1D. Notably, anti-PD-1 caused increased TCR sharing between the pancreas and the periphery. Moreover, T cells in the blood of anti-PD-1-treated mice expressed markers that differed from spontaneous T1D, suggesting that the blood may provide a window to monitor irAEs rather than relying exclusively on the autoimmune target organ.

Utility of Ischemia Testing Prior to Ablation for Sustained Monomorphic Ventricular Tachycardia.

The aim of this study was to determine the relationship between ischemia testing prior to ablation for sustained monomorphic ventricular tachycardia (VT) (SMVT) and post-ablation mortality and VT recurrence. As SMVT is generally caused by myocardial scar and not active ischemia, the utility of ischemia testing prior to SMVT ablation is unclear. Patients who underwent ablation for SMVT at 2 tertiary care centers between January 2016 and July 2018 were included in a retrospective study. A Kaplan-Meier survival analysis was performed, stratifying patients by pre-ablation ischemia testing for the endpoints of mortality and VT recurrence. A Cox multivariable regression analysis was performed to identify predictors of post-ablation VT recurrence. A total of 163 patients were included, with 46 (28%) patients undergoing ischemia testing prior to ablation. Only 5 of the 46 patients (11%) received revascularization pre-ablation. After a median follow-up period of 625 days (interquartile range, 292-982 days) following ablation, 97 of 163 patients (60%) had VT recurrence, and 32 patients (20%) had died. There was no difference in mortality or VT recurrence between patients who did or did not experience ischemia testing or revascularization. In the multivariable regression analysis, predictors of VT recurrence were the number of anti-arrhythmics failed, non-ischemic cardiomyopathy, sex, and cardiac magnetic resonance imaging pre-ablation. Neither ischemia testing nor revascularization was a significant predictor of VT recurrence in univariable or multivariable regression analysis. In conclusion, ischemia testing is frequently ordered prior to SMVT ablation but infrequently leads to revascularization and is not associated with post-ablation outcomes. The findings support adopting an individualized approach rather than performing routine ischemia testing.