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Nivolumab is a programmed cell death receptor (PD-1) inhibitor that is increasingly used for various malignancies, both as a first line agent and as salvage therapy. Being a PD-1/PD-1 ligand checkpoint inhibitor, it is known to cause autoimmune inflammation of various organs and has been associated with thyroiditis, insulitis, colitis, hepatitis and encephalitis to name a few. There are increasing reports of nivolumab leading to acute onset fulminant type 1 diabetes and diabetic ketoacidosis (DKA). We present a case of a 68-year-old man who developed DKA after 2 doses of nivolumab for metastatic melanoma. He was found to have type 1 diabetes, but no diabetes related antibodies were positive. He recovered from diabetes and continues to use insulin 1 year after his diagnosis. This case and associated review illustrates the importance of educating and monitoring patients who start nivolumab therapy regarding this potentially life threatening complication.

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Introduction: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening clinical syndrome characterized by microangiopathy and a variable degree of end-organ ischemic damage. Cardiac involvement has been recognized as a major cause of mortality in these patients (Patschan et al, Nephrol Dial Transplant, 2006; Benhamou et al, J Thromb. Haemost, 2015). In this study, we aim to investigate clinical predictors and outcomes of acute coronary syndrome in the setting of TTP admissions. Methods: The National Inpatient Sample (NIS) was queried for all hospitalizations with a primary diagnosis of thrombotic microangiopathy (ICD- 9-CM code 4466 and ICD-10-CM code M3.11) from 2002 to 2017. Using ICD-9-CM procedure codes (9972), (9971), and (9979), as well as ICD-10-CM procedure codes (6A551Z3) and (6A550Z3) we identified patients who received plasma exchange (PLEX) during the same admission. Due to the wide spectrum of thrombotic microangiopathy diseases, we decided to include only those who received PLEX to get a more specific subpopulation who were presumed to have TTP. We stratified patients based on whether or not they had acute coronary syndrome (ACS) during the admission, defined as presence of any ICD code for either ST-segment elevation myocardial infarction (STEMI), Non-STEMI, or unstable angina. Baseline characteristics and inpatient outcomes were compared between groups. Statistical analysis was performed using SPSS v26 (IBM Corp, Armonk, NY, USA). The odds ratio (OR) and 95% confidence interval (CI) were calculated using the Cochran-Mantel-Haenszel test. A multivariate regression model was deployed to assess predictors of inpatient mortality. Complex weights were used throughout all calculations, enabling appropriate national projections. Results: A total of 15,640 patients with the diagnosis of thrombotic microangiopathy were identified during the studied period. Of those, 6,214 patients had received PLEX treatment during their admission (39.7%). The annual admission rate for TTP was ranging between 5-7/100,000 admissions. Patients had a mean age of 47.8 years; 67% were females, and 46.5% were Caucasian. Stratifying by geographic region, 24% were from the Northeast, 21% from the Midwest, 42% from the South, and 13% from the West. The most common primary payer was private insurance (42.7%). Overall inpatient mortality was 9.1%. The most common complications reported included acute kidney injury (42.5%), followed by acute respiratory failure (14.9%), incident dialysis (14.3%), acute encephalopathy (7.7%), acute heart failure (7.3%), acute cerebrovascular accident (7.2%), and acute coronary syndrome (6.3%). ACS was documented in 6.7% of patients. Compared with patients without ACS, those with ACS were relatively older and had a relatively higher prevalence of coronary artery disease, dyslipidemia, diabetes mellitus, essential hypertension, chronic kidney disease, and heart failure. Patients with ACS had a 3-fold higher in-hospital mortality and a longer mean hospital stay (19 days vs. 15 days, P<0.001). Using stepwise logistic regression, we identified age (aOR 1.03; 95% CI, 1.02 - 1.03; P <0.001), history of heart failure (aOR 2.02; 95% CI, 1.53-2.67; P <0.001), and history of coronary artery disease (aOR 2.69; 95% CI, 2.03 - 3.57; P <0.001) as independent predictors of ACS among patients hospitalized with TTP. On another regression analysis, certain complications were more prevalent in the ACS group including acute cerebrovascular accidents, acute heart failure, acute kidney injury, cardiogenic shock, and respiratory failure. Conclusion: Despite wider utilization of therapeutic plasmapheresis and improved supportive treatments for patients with TTP, associated morbidity and mortality remain significant. We demonstrate from this large retrospective cohort that ACS is an independent predictor of higher morbidity and mortality in TTP patients. We identified older age, history of heart failure, and history of coronary artery disease as independent predictors of ACS among patients admitted with TTP. Further studies are warranted to develop risk stratification models for patients with TTP. Figure Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.