Inclisiran: A New Strategy for LDL-C Lowering and Prevention of Atherosclerotic Cardiovascular Disease.

Multiple lines of evidence confirm that the cumulative burden of low-density lipoprotein cholesterol (LDL-C) is causally related to the development of atherosclerotic cardiovascular disease (ASCVD). As such, lowering LDL-C is a central tenet in all ASCVD prevention guidelines, which recommend matching the intensity of LDL-C lowering with the absolute risk of the patient. Unfortunately, issues such as difficulty with long-term adherence to statin therapy and inability to achieve desired LDL-C thresholds with statins alone results in residual elevated ASCVD risk. Non-statin therapies generally provide similar risk reduction per mmol/L of LDL-C reduction and are included by major society guidelines as part of the treatment algorithm for managing LDL-C. Per the 2022 American College of Cardiology Expert Consensus Decision Pathway, patients with ASCVD are recommended to achieve both an LDL-C reduction ≥50% and an LDL-C threshold of <55 mg/dL in patients at very high-risk and <70 mg/dL in those not at very high risk. Patients with familial hypercholesterolemia (FH) but without ASCVD should lower LDL-C to <100 mg/dL. For patients who remain above LDL-C thresholds with maximally tolerated statin therapy plus lifestyle changes, non-statin therapy warrants strong consideration. While several non-statin therapies have been granted FDA approval for managing hypercholesterolemia (eg, ezetimibe, Proprotein Convertase Subtilisin/Kexin 9 [PCSK9] monoclonal antibodies, and bempedoic acid), the focus of the current review is on inclisiran, a novel small interfering RNA therapy that inhibits the production of the PCSK9 protein. Inclisiran is currently FDA approved as an adjunct to statin therapy in patients with clinical ASCVD or heterozygous FH who require additional LDL-lowering. The drug is administered by subcutaneous injection twice a year, after an initial baseline and 3 month dose. In this review, we sought to provide an overview of the use of inclisiran, review current trial data, and outline an approach to potential patient selection.

Pembrolizumab-Induced Diabetes Mellitus Presenting as Diabetic Ketoacidosis in a Patient With Metastatic Colonic Adenocarcinoma.

Immunotherapy drugs are gaining popularity in the treatment of certain malignancies due to the success of these agents in recent clinical trials. Pembrolizumab is an immune checkpoint inhibitor that acts via binding to programmed cell death 1 (PD-1) receptors on T-cells, allowing for the constitutive activation of T-cells to fight malignant tumor cells. Immune checkpoint molecules such as PD-1 act to inhibit T-cell function, promoting tolerance to self-antigens. Inhibition of these molecules may lead to increased T-cell activation against cancer cells, but also against healthy tissue, leading to the side effects of these medications known as immune-related adverse events. In this article, we present the case of a 77-year-old female with a history of metastatic colonic adenocarcinoma presenting with new-onset diabetes mellitus and diabetic ketoacidosis in the setting of receiving pembrolizumab chemotherapy. Our patient was treated with hydration, insulin therapy, and management of her electrolytes, ultimately being discharged with the need for home insulin therapy to manage her new-onset diabetes. There are no current guidelines for the management or surveillance of patients receiving pembrolizumab chemotherapy, and further research should be done to determine which patients are at highest risk to developing this rare but potentially lethal side effect.

Coexisting Cirrhosis Worsens Inpatient Outcomes in Patients With Infective Endocarditis: A Cross-Sectional Analysis of the National Inpatient Sample 2013-2014.

Introduction Cirrhosis is known to be an important prognostic factor in determining morbidity and mortality in preoperative cardiac risk assessment for cardiac surgery. Data is limited on outcomes in patients with infective endocarditis (IE) and comorbid liver cirrhosis. The objective of our study is to evaluate the clinical outcomes in patients suffering from IE both with and without underlying liver cirrhosis as well as to determine rates of in-hospital mortality and factors that contribute to this outcome. Hypothesis Liver cirrhosis worsens clinical outcomes in patients with IE. Materials and methods Patients with a principal diagnosis of IE with and without liver cirrhosis were identified by querying the Healthcare Cost and Utilization (HCUP) database, specifically the National Inpatient Sample for the years 2013 and 2014 using International Classification of Diseases, Ninth Revision (ICD-9) codes. Results During 2013 and 2014, a total of 17,952 patients were admitted with a diagnosis of IE, out of whom 780 had concurrent liver cirrhosis. There was increased in-hospital mortality [15.6% vs 10.2%, aOR = 1.57 (1.27-1.93)], acute kidney injury [41.4% vs 32.6%, aOR = 1.45 (1.24-1.69)], and hematologic complications [32.1 vs 14.7%, aOR = 2.87 (2.44-3.37)] in patients with IE with liver cirrhosis when compared to patients with IE without liver cirrhosis. Patients having IE without liver cirrhosis underwent an increased number of interventions, i.e. aortic (7.2 vs 3.7%, aOR = 0.51 (0.34-0.76)) and mitral (4.9% vs 3.4%, aOR = 0.39 (0.23-0.69)) valvular replacements as compared to those with liver cirrhosis, which may explain the increased mortality seen in patients with liver cirrhosis. Conclusion Liver cirrhosis is an important prognostic risk factor for in-hospital mortality in patients with IE. The coagulopathic state in addition to increased rates of bleeding complications and renal dysfunction make these patients poor surgical candidates thus contributing to higher mortality. Further research into the individual risk factors contributing to the increased mortality rates in patients with IE and cirrhosis is required.