Citations

BACKGROUND: Apelin is an endogenous prepropeptide that regulates cardiac homeostasis and various physiological processes. Intravenous injection has been shown to improve cardiac contractility in patients with heart failure. However, its short half-life prevents studying its impact on left ventricular remodeling in the long term. Here, we aim to study whether microparticle-mediated slow release of apelin improves heart function and left ventricular remodeling in mice with myocardial infarction (MI). METHODS: A cardiac patch was fabricated by embedding apelin-containing microparticles in a fibrin gel scaffold. MI was induced via permanent ligation of the left anterior descending coronary artery in adult C57BL/6J mice followed by epicardial patch placement immediately after (acute MI) or 28 days (chronic MI) post-MI. Four groups were included in this study, namely sham, MI, MI plus empty microparticle-embedded patch treatment, and MI plus apelin-containing microparticle-embedded patch treatment. Cardiac function was assessed by transthoracic echocardiography. Cardiomyocyte morphology, apoptosis, and cardiac fibrosis were evaluated by histology. Cardioprotective pathways were determined by RNA sequencing, quantitative polymerase chain reaction, and Western blot. RESULTS: The level of endogenous apelin was largely reduced in the first 7 days after MI induction and it was normalized by day 28. Apelin-13 encapsulated in poly(lactic-co-glycolic acid) microparticles displayed a sustained release pattern for up to 28 days. Treatment with apelin-containing microparticle-embedded patch inhibited cardiac hypertrophy and reduced scar size in both acute and chronic MI models, which is associated with improved cardiac function. Data from cellular and molecular analyses showed that apelin inhibits the activation and proliferation of cardiac fibroblasts by preventing transforming growth factor-β–mediated activation of Smad2/3 (supporessor of mothers against decapentaplegic 2/3) and downstream profibrotic gene expression. CONCLUSIONS: Poly(lactic-co-glycolic acid) microparticles prolonged the apelin release time in the mouse hearts. Epicardial delivery of the apelin-containing microparticle-embedded patch protects mice from both acute and chronic MI-induced cardiac dysfunction, inhibits cardiac fibrosis, and improves left ventricular remodeling.

OBJECTIVES: This study seeks to evaluate the variability of Medicaid reimbursement and compare it with Medicare reimbursement using the 20 most commonly billed orthopaedic trauma Current Procedural Terminology (CPT) codes nationwide. The authors anticipate significant variability between states and hypothesize that Medicaid payment will be significantly less than Medicare payment. METHODS: The top 20 most common orthopaedic trauma surgery procedural codes were identified from a previous analysis performed by Haglin et al. The Centers for Medicare and Medicaid Services Physician Fee Schedule was used to determine reimbursement rates from Medicare, and state Medicaid fee schedules were used to determine reimbursement rates for Medicaid. State Medicaid rates were compared with their corresponding Medicare rates to determine a dollar difference. In addition, the dollar difference for each CPT code was divided by its respective physician relative value unit. This was used to acknowledge the possible variability in the complexity of orthopaedic procedures and the related physician effort. The Medicare Wage Index was used to adjust Medicaid rates based on the cost of living for the state as well. Coefficients of variation were calculated to represent overall variability in Medicaid and Medicare reimbursement rates. RESULTS: The mean reimbursement rates for Medicaid were lower for all 20 procedures compared with Medicare. On average, Medicaid reimbursed 16.0% less than Medicare and 29.6% less when adjusting for cost of living. MCD reimbursed at a higher rate than MCR for all procedures in only 9 states (Alaska, Arizona, Arkansas, Montana, Nebraska, New Jersey, New Mexico, North Dakota, and South Dakota) while 38 states reimbursed at a lower rate than MCR, on average. The coefficient of variation ranged from 0.24 to 0.34 for the Medicaid unadjusted group and from 0.35 to 0.46 for the Medicare Wage Index–adjusted group. By contrast, the Medicare group was consistent at 0.06 for all 20 procedures. The average dollar difference across the 20 CPT codes for Medicaid reimbursement compared with Medicare reimbursement ranged from −$76.89 to −$225.17, and the dollar difference per relative value unit ranged from −$5.96 to −$15.16. CONCLUSIONS: This study found a high amount of variation between state Medicaid reimbursement rates and average rates that were significantly lower than Medicare reimbursement rates for the top 20 most used orthopaedic trauma CPT codes as identified by Haglin et al. The discrepancy in reimbursement was increased when Medicaid rates were adjusted for state cost of living. LEVEL OF EVIDENCE: Prognostic, Level III. See Instructions for Authors for a complete description of levels of evidence.