Faculty Bibliography

The ESET (also called SETDB1) protein contains an N-terminal tudor domain that mediates protein-protein interactions and a C-terminal SET domain that catalyzes methylation of histone H3 at lysine 9. We report here that ESET protein is transiently upregulated in prehypertrophic chondrocytes in newborn mice. To investigate the in vivo effects of ESET on chondrocyte differentiation, we generated conditional knockout mice to specifically eliminate the catalytic SET domain of ESET protein only in mesenchymal cells. Such deletion of the ESET gene caused acceleration of chondrocyte hypertrophy in both embryos and young animals, depleting chondrocytes that are otherwise available to form epiphyseal plates for endochondral bone growth. ESET-deficient mice are thus characterized by defective long bone growth and trabecular bone formation. To understand the underlying mechanism for ESET regulation of chondrocytes, we carried out co-expression experiments and found that ESET associates with histone deacetylase 4 to bind and inhibit the activity of Runx2, a hypertrophy-promoting transcription factor. Repression of Runx2-mediated gene transactivation by ESET is dependent on its H3-K9 methyltransferase activity as well as its associated histone deacetylase activity. In addition, knockout of ESET is associated with repression of Indian hedgehog gene in pre- and early hypertrophic chondrocytes. Together, these results provide clear evidence that ESET controls hypertrophic differentiation of growth plate chondrocytes and endochondral ossification during embryogenesis and postnatal development.

STUDY DESIGN: Multivariate analysis of prospectively collected registry data. OBJECTIVE: To determine the effect of payor status on complication rates after spine surgery. SUMMARY OF BACKGROUND DATA: Understanding the risk of perioperative complications is an essential aspect in improving patient outcomes. Previous studies have looked at complication rates after spine surgery and factors related to increased perioperative complications. In other areas of medicine, there has been a growing body of evidence gathered to evaluate the role of payor status on outcomes and complications. Several studies have found increased complication rates and inferior outcomes in the uninsured and Medicaid insured. METHODS: The Spine End Results Registry (2003-2004) is a collection of prospectively collected data on all patients who underwent spine surgery at our 2 institutions. Extensive demographic data, including payor status, and medical information were prospectively recorded as described previously by Mirza et al. Medical complications were defined in detail a priori and were prospectively recorded for at least 2 years after surgery. Using univariate and multivariate analysis, we determined risk of postoperative medical complications dependent on payor status. RESULTS: A total of 1591 patients underwent spine surgery in 2003 and 2004 that met our criteria and were included in our analysis. With the multivariate analysis and by controlling for age, patients whose insurer was Medicaid had a 1.68 odds ratio (95% confidence interval: 1.23-2.29; P = 0.001) of having any adverse event when compared with the privately insured. CONCLUSION: After univariate and multivariate analyses, Medicaid insurance status was found to be a risk factor for postoperative complications. This corresponds to an ever-growing body of medical literature that has shown similar trends and raises the concern of underinsurance.