Cardiovascular diseases (CVDs) remain the leading cause of death in the world and in most developed countries. Patients with type 2 diabetes mellitus (T2DM) suffer from both microvascular and macrovascular diseases and therefore have higher rates of morbidity and mortality compared to those without T2DM. If current trends continue, the Center for Disease Control and Prevention estimates that 1 in 3 Americans will have T2DM by year 2050. As a consequence of the controversy surrounding rosiglitazone and the increasing prevalence of diabetes and CVDs, in 2008 the Food and Drug Administration (FDA) established new expectations for the evaluation of new antidiabetic agents, advising for pre and, in some cases, post-marketing data on major cardiovascular events. As a direct consequence, there has been a paradigm shift in new antidiabetic agents that has given birth to the recently published American Diabetes Association/European Association for the Study of Diabetes consensus statement recommending sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon like peptide-1 receptor agonists (GLP-1RA) in patients with T2DM and established CVD. As a result of over a decade of randomized placebo controlled cardiovascular outcome trials, the aforementioned drugs have received FDA approval for risk reduction of cardiovascular (CV) events in patients with T2DM and established CV disease. SGLT2i have been shown to have a stronger benefit in patients with congestive heart failure and diabetic kidney disease when compared to their GLP-1RA counterparts. These benefits are not withstanding additional considerations such as cost and the multiple FDA Black Box warnings. This topic is currently an emerging research area and this mini-review paper examines the role of these two novel classes of drugs in patients with T2DM with both confirmed, and at risk for, CVD.

Introduction Diabetes is the leading cause of end-stage renal disease (ESRD) in the United States (US), with 37 million having chronic kidney disease. Despite national guidelines recommendations for diabetic nephropathy screening with urine albumin-to-creatinine ratio (UACR), less than 50% receive full screening. Our Internal Medicine residents led a quality improvement project to increase diabetic nephropathy screening rate with UACR in our resident clinic by 50% in one academic year. Methods We conducted the resident-led quality improvement project from July 2021 to April 2022. We reviewed the electronic medical records (EMR) from our clinic pre-intervention July 2020 to June 2021 and compared this to post intervention July 2021 to March 2022 determining the nephropathy screening rates in patients with diabetes. Our interventions included resident education, pre and post surveys to test foundational knowledge, adding UACR in the affordable laboratory order form and establishing normal reference range of UACR in the EMR. Results We collected 217 patients with diabetes, 27% were uninsured, 38% had Medicare/Medicaid and 90% identified as Hispanic. Comparing pre to post intervention, there was a significant change of 45 (20.7%) vs 71 (32.7%) patients screened for diabetic nephropathy with a UACR. The correct average score of knowledge-based questions was 82% on the pre survey, which increased to 88% in the post survey. Conclusion Our study showed promising results on improving diabetic nephropathy screening. The comprehensive approach including resident education about diabetic nephropathy screening with UACR and more so facilitating the order set in the EMR were key to achieve this goal.

COVID-19 pandemic brought difficult scenarios that patients and families are facing about end- of-life decisions. This exposed some weak areas in the healthcare system where we can continue improve in reducing disparities and emphasizing advance care planning from a primary level of care. We present a case of challenges in end-of-life decision-making in a Latino patient.

e14013 Background: Despite the success in hematological malignancies, immunotherapy of solid tumors using redirected T cells such as CAR-T remains challenging due to the lack of a unique tumor antigen, inefficient trafficking of CAR T cells to tumor sites and the presence of immunosuppressive tumor microenvironment. ET140202 is a novel T-cell platform that targets AFP/MHC complex with GPC3-guided co-stimulation aiming to improve the specificity and efficacy. Herein we report a case study of ET140202 for a subject with AFP+ recurrent HCC previous treated with surgery and 2 TACE therapies. Baseline imaging showed multiple nodules on segment 7 of right lobe with enlarged lymph nodes in hepatic hilar region. Methods: From 9/25/18 to 1/29/19 the subject first received 2 intra-hepatic artery infusions (i.a.) of ET140202 T cells at the dose of 3×106 cells/kg followed by 4 i.v. infusions at the dose of 6×106 cells/kg. No lymphodepleting chemotherapy was given prior to T-cell infusion. Vital signs, blood cell count, and blood chemistry were monitored on Days 1, 3, 7, and 14. Clinical responses were assessed at Month 1, 2, 3, 4, 6, 9, 12 and 24. Results: Vital signs are normal after each infusion. No treatment-related Grade 2 or higher AEs observed. Grade 1 events that were possibly attributable to therapy included transient elevation of AST and bilirubin 58 days post the 1st infusion. Both events resolved in 4 days without treatment. The subject did not experience any clinical signs of CRS or neurotoxicity. Month 1, 2, and 3 follow-ups showed that the number and size of the liver nodules slowly increased overtime. Month 4 follow-up showed that the size of liver nodules decreased more than 50% of baseline and resulted in PR based on RECIST criteria. The AFP level elevated in the subject after infusion and reached the peak of 2097 ng/mL 55 days post 1st infusion, gradually dropped to 905 ng/mL on day 67, elevated to the 2nd peak of 2660 ng/mL and gradually decreased to 1235 ng/mL at the last follow-up on day 130. Conclusions: Repeated infusion of ET140202 T cells via i.a. and i.v. routes is safe and shows early sign of efficacy 4 months post initiation of the treatment in AFP+/HLA-A2+ HCC subject.