Immune checkpoint inhibitors (ICI) such as program cell death protein 1 (PD-1) inhibitors are widely used for the treatment of patients with recurrent, locally advanced or metastatic, gastric or gastroesophageal (GE) junction adenocarcinoma. Immune-related adverse events (irAE) such as endocrinopathies have been reported after patients received ICI. We report a case of pembrolizumab-induced hyperthyroidism and type 1 diabetes mellitus (DM1) presenting with diabetic ketoacidosis (DKA). A 53-year-old African American male with no history of diabetes or hyperthyroidism was treated with two cycles of pembrolizumab for recurrent GE junction adenocarcinoma after which he was admitted with hyperthyroidism (thyroid stimulating hormone [TSH] 0.070mIU/L, free thyroxine 1.85mIU/L) and DKA (pH 7.06, glucose 583 mg/dL, beta-hydroxybutyrate 8.63 mmol/L, anion gap 27 meq/L). The patient was treated with intravenous insulin and aggressively hydrated. Given the lack of other precipitating factors for the two endocrinopathies, it was determined that the most likely etiology was recent treatment with pembrolizumab (a PD-1 inhibitor). In our case, pembrolizumab monotherapy developed two irAE (hyperthyroidism and DKA), which is unique as most combined immunotherapy regimens are associated with the development of multiple endocrinopathies. Our case emphasizes the importance of baseline monitoring of thyroid function and blood glucose prior to the start of ICI to monitor and evaluate patients with immune-related adverse events, including endocrinopathies.
Funding Acknowledgements
Type of funding sources: None.
Background
Central retinal artery occlusion (CRAO) is a devastating event and atrial fibrillation (AF) is a recognized cause that may not be present at the time of the event.
Purpose
We performed a meta-analysis for the association of CRAO with the risk of new-onset AF and stroke during follow-up.
Methods
We searched the databases MEDLINE, Embase and SCOPUS from inception to May 2022 for the terms ‘atrial fibrillation’ and ‘retinal artery occlusion’ and identified 205 studies. We excluded duplicates, non-relevant studies and those not reporting new-onset AF after CRAO. We used random effects models to calculate the pooled odds ratio (OR) and 95% confidence intervals (CI) of AF risk in patients with CRAO or stroke in comparison to control groups. Analysis was performed with RevMan 5.4.1 (Cochrane 2020).
Results
We included 7 studies with 1.476 patients with CRAO compared to a control group without CRAO (n=9.843) and a group with stroke (n=7.058). There were 196 new AF cases (13.4%) in 18 months after CRAO. CRAO was associated with a higher risk for new-onset AF (OR:1.59, CI:1.20-2.11, p=0.001) and stroke (OR:2.46, CI:1.74-3.47, p<0.001) when compared to controls. However, the risk for AF after CRAO was similar to that after a stroke (OR:0.83, CI:0.41-1.71, p=0.62).
Conclusions
CRAO is associated with a higher risk for new-onset AF and stroke. AF risk after CRAO though is similar to that after stroke. Thus, CRAO should be regarded as cryptogenic stroke and mandate a closer follow-up with screening for AF and evaluation of early anticoagulation.
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