Immune checkpoint inhibitors such as CTLA-4 and PD-1 inhibitors mediate T-cell induced tumor cell destruction by blocking malignant cells' ability to negatively regulate T cell activity. In addition to its anti-tumor effect, checkpoint inhibition can lead to loss of maintenance of self-tolerance, leading to immune-mediated adverse events (irAEs). These events can affect any organ, with pneumonitis, hepatitis, and colitis among the most commonly reported events. A rare and life-threatening reported side effect is cytokine release syndrome (CRS). CRS is a systemic inflammatory response described in a number of cancer immunotherapies, including CAR T-cell and bispecific T-cell engagers (BiTEs). The primary pathophysiology involves activation of bystander immune and non-immune cells (such as endothelial cells) leading to a massive release of inflammatory cytokines. CRS can present as a benign, flu-like syndrome, or as an overwhelming, life-threatening systemic disease characterized by hypotension, capillary leakage, disseminated intravascular coagulopathy, and multi-organ failure. IL-6 appears to play a critical role in CRS through activation of the complement and coagulation cascade. The IL-6 inhibitor tocilizumab is the only FDA-approved treatment for CRS. There have been several reported cases of checkpoint inhibitor-induced CRS reported in the literature, including a 25-year-old patient with Hodgkin's Lymphoma (Zhao L, et al. Immunotherapy 2018) and a 29-year-old patient with sarcoma (Rotz SJ, et al. Pediatr Blood Cancer 2017). CRS developed in these cases after the first and second doses of nivolumab, respectively. We now present an additional rare case of CRS from nivolumab therapy that occurred months after initiation of treatment. We present a 71-year-old male with stage IV melanoma on cycle 17 of nivolumab with a partial response who was admitted to our institution with altered mental status, hypotension, tachycardia, fever up to 104.9°F, and hypoxia requiring BiPAP. On physical exam, he was noted to have a grade 3 maculopapular rash. Lab work on presentation was notable for serum creatinine of 1.68, platelet count of 86, d-dimer > 35, and CRP of 16.1. He was started on vancomycin and piperacillin-tazobactam for suspected sepsis. After 24 hours with no improvement, he was started on 1 mg/kg methylprednisolone due to growing concern that symptoms were immune-mediated. After another 24 hours with no improvement, tocilizumab was administered for the suspicion of CRS. The patient's clinical status began to improve within one hour of treatment with resolution of fever and hypotension, as well as improvement in hypoxia and mental status. Over the next several days, his platelet count and kidney function significantly improved as well. Decreased CRP levels suggesting a blunting of his inflammatory response, and increased IL-6 levels from IL-6 receptor blockade were seen as well. He was discharged from the hospital in good condition on day 6 post-treatment after stabilization of unrelated comorbid conditions, and followed up one week after discharge at his baseline level of function. He unfortunately developed another episode of CRS six weeks after discharge and passed away despite attempted treatment with tocilizumab. CRS remains a rare, potentially life-threatening condition that requires early diagnosis and management. Although initial investigations may point to more common conditions such as infection and sepsis, a low threshold for consideration of irAEs and CRS should exist where the clinical picture warrants. There are likely many more cases in which the diagnosis is missed and appropriate treatment not given due to lack of clinical awareness. Had our patient's symptoms not been clinically recognized as CRS by the inpatient hematology team, his condition would have likely been terminal due to the presumed diagnosis of sepsis. Physician education, particularly in the ED and ICU, early consultation, and prompt implementation of specific testing and treatment with tocilizumab can lead to significantly improved outcomes as our case shows. The unfortunate second CRS event and failure to repeatedly respond to tocilizumab with his second episode reinforces the need for continued research for additional treatment options for CRS, especially in recurrent cases. Disclosures No relevant conflicts of interest to declare.

Introduction: Infective endocarditis (IE) is a life-threatening condition with an annual mortality of up to 40%. Vegetations are the hallmark of IE, however, factors that affect the initial size and changes in size remain unclear. Our study aims to investigate the natural history of cardiac vegetation, including changes in size and/or resolution with adequate treatment, and to analyze factors that influence size and potential for persistence.Material and methods: We conducted a retrospective review of 102 patients admitted with native-valve endocarditis at Henry Ford Health System from September 1, 2017, to June 30, 2019. We included patients treated with six weeks of intravenous antibiotics who had both a diagnostic and a follow-up echocardiogram after antibiotic completion.The primary outcome was the change in vegetation size. Secondary measures included pathogen identification, valve involvement, number of complications, associated IV drug use, and co-infection with hepatitis B/C. Results: Of the 102 patients reviewed, 30 patients matched the inclusion criteria. There was a significant decrease in vegetation size after adequate antibiotic treatment. However, complete resolution was not often seen. A statistically significant relationship was seen between vegetation size, IV drug use, and Staphylococcal species (including both methicillin-susceptible Staphylococcus aureus [MSSA] and methicillin-resistant S. aureus [MRSA]), whereas a history of hepatitis B or C was not significantly related to vegetation size. Conclusion: Large vegetation may predict a higher risk of embolic complications and can be reduced with IV antibiotics, although complete resolution is not likely. IV drug use and Staphylococcal endocarditis influence vegetation size and embolic complications. We argue that these subgroups should be prioritized for early surgical intervention.

Background The purpose of our study was to assess the natural history of cardiac vegetations in native valves(NVIE) including changes in size and/or resolution with adequate treatment, as well as analyze factors that influence initial size. Methods We did a retrospective review of 102 patients discharged with a diagnosis NVIE at a community hospital. These patients were then screened to see if they received an adequate course of antimicrobial therapy and had follow up echocardiograms. The primary outcome measured was the change in vegetation size. We also assessed secondary measures including pathogen identified, the valve involved, complications, and associated IDU and any co-infections. Results 31 patients fulfilled the study criteria and showed an initial mean vegetation size of 170mm upon initial echocardiography. The follow-up size after antibiotic treatment was 78mm suggesting a statistically significant relationship between antibiotic completion and reduction in vegetation size. (p-value 0.005). T-Test was used for subgroup analysis and showed that the initial size of vegetations was significantly larger in IDUs (311) when compared to non-IDU (92)(p-value= 0.026).Patients who had embolic phenomena had significantly larger initial vegetations than those with no embolic complication. Initial vegetation size was significantly larger for people with embolic complications (308 mm vs 82.65 mm, p-value 0.013).We also found that patients with Staphylococcal endocarditis had larger vegetations than those with non-staphylococcal endocarditis (264 vs 39, p-value 0.001). and treatment led to a larger decrease in vegetation size (152 vs 7, p value 0.007) Conclusion Our small study suggests that successful treatment of NVIE does lead to a decrease in vegetation size though resolution of the vegetation does not occur. We also found that embolic phenomenon tended to occur with larger vegetations with our study suggesting that a vegetation > 3 cm was more likely to embolize. Our study also shows that vegetations in NVIE in injection drug users were larger than those in non-IDU and vegetation size is larger in patients with staphylococcal endocarditis however successful treatment in these patients also leads to a larger decrease in size of these vegetations Disclosures All Authors: No reported disclosures