Faculty Bibliography

BACKGROUND:Distal radius fractures treated with open reduction and internal fixation are commonly stabilized with a volar locking plate; however, more complex fracture patterns may require supplemental fixation with fragment-specific implants. The objective of this study was to evaluate the outcomes of distal radius fractures treated with radial column plates. METHODS:A consecutive series of 61 patients who sustained distal radius fractures underwent radial column plating alone or in conjunction with other implants between August 2006 and January 2014. Thirty-one patients returned for follow-up or returned a mailed questionnaire at an average of 4.1 years. The outcomes measures included Visual Analog Scale (VAS); Disabilities of the Arm, Shoulder and Hand (DASH); and Patient-Rated Wrist Evaluation (PRWE) scores. RESULTS:Sixty-one patients with a mean age of 55 years (range, 20-87) met inclusion criteria and were available for follow-up or chart review at an average of 5.2 years (range, 1.6-9.0 years). Seventeen of 61 (28%) underwent radial column plate removal. Twenty patients returned for final follow-up examination, and 11 completed questionnaires via mail. Subjective scores included a mean postoperative VAS of 0.72, DASH score of 17.2, and PRWE score of 15.7. Hardware sensitivity and wrist stiffness were the most common complications at final follow-up. CONCLUSIONS:Radial column plating of the distal radius is a safe treatment modality and a valuable adjunct in the setting of complex distal radius fractures, but patients should be counseled that there is a 28% chance that hardware removal may be required. Our retrospective review found evidence of few complications and objective scores consistent with return to normal function.

BACKGROUND: Although median nerve neuropathy and carpal tunnel syndrome (CTS) are known complications of both untreated and acutely treated distal radius fracture, median neuropathy after correction of distal radius malunion is not commonly reported in hand surgery literature. We describe a patient with severe CTS after corrective osteotomy, open reduction internal fixation (ORIF) with a volar locking plate (VLP), and bone grafting for distal radius malunion. METHODS: We report a case of severe acute CTS as a complication of corrective osteotomy with bone grafting for distal radius malunion. RESULTS: The patient was treated with surgical exploration of the median nerve and carpal tunnel release. CONCLUSION: The authors report a case of acute CTS after ORIF with VLP for a distal radius malunion warranting surgical exploration and carpal tunnel release. Treatment teams must be aware of this potential complication so that the threshold for reoperation is low and irreversible damage to the median nerve is prevented.

PURPOSE: Dupuytren disease is a common benign fibroproliferative disorder causing thickening and shortening of the palmar fascia of the hand. The exact etiology of the disease is unclear but known risk factors such as increased age, male sex, and northern European ethnicity have been established. A link between body mass index (BMI) and Dupuytren disease has not been established previously. The purpose of this study was to test the hypothesis that lower BMI is associated with increased risk for Dupuytren disease diagnosis. METHODS: After we obtained institutional review board approval, we performed a retrospective review using an electronic medical record and an administrative database from Kaiser Permanente Southern California to identify all enrolled patients there between 2007 and 2014 who were diagnosed with Dupuytren disease. Basic demographic data including age, sex, ethnicity, and BMI were collected. Bivariate and multivariable logistical regression analyses were performed to evaluate for associations between Dupuytren disease and BMI. RESULTS: A total of 2,049,803 patients aged 18 years and older were enrolled in Kaiser Permanente Southern California from 2007 to 2014. During that period, 14,844 patients were identified as having Dupuytren disease. The data were consistent with well-defined demographic trends in Dupuytren disease, with increased rates seen in males, Caucasians, and patients aged 50 years and older. In the multivariable analysis, when controlling for age, race, and sex, the risk of Dupuytren disease was inversely proportional to BMI. CONCLUSIONS: The current study showed that higher BMI is associated with decreased odds of having Dupuytren disease. Further work will be required to determine the cause for the apparent relationship between Dupuytren disease and BMI and whether physiologic factors related to obesity may be protective against the development of Dupuytren disease. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

To investigate the effects of histone methyltransferase ESET (also known as SETDB1) on bone metabolism, we analyzed osteoblasts and osteoclasts in ESET knockout animals, and performed osteogenesis assays using ESET-null mesenchymal stem cells. We found that ESET deletion severely impairs osteoblast differentiation but has no effect on osteoclastogenesis, that co-transfection of ESET represses Runx2-mediated luciferase reporter while siRNA knockdown of ESET activates the luciferase reporter in mesenchymal cells, and that ESET is required for postnatal expression of Indian hedgehog protein in the growth plate. As the bone phenotype in ESET-null mice is 100% penetrant, these results support ESET as a critical regulator of osteoblast differentiation during bone development.

The exact molecular mechanisms governing articular chondrocytes remain unknown in skeletal biology. In this study, we have found that ESET (an ERG-associated protein with a SET domain, also called SETDB1) histone methyltransferase is expressed in articular cartilage. To test whether ESET regulates articular chondrocytes, we carried out mesenchyme-specific deletion of the ESET gene in mice. ESET knock-out did not affect generation of articular chondrocytes during embryonic development. Two weeks after birth, there was minimal qualitative difference at the knee joints between wild-type and ESET knock-out animals. At 1 month, ectopic hypertrophy, proliferation, and apoptosis of articular chondrocytes were seen in the articular cartilage of ESET-null animals. At 3 months, additional signs of terminal differentiation such as increased alkaline phosphatase activity and an elevated level of matrix metalloproteinase (MMP)-13 were found in ESET-null cartilage. Staining for type II collagen and proteoglycan revealed that cartilage degeneration became progressively worse from 2 weeks to 12 months at the knee joints of ESET knock-out mutants. Analysis of over 14 pairs of age- and sex-matched wild-type and knock-out mice indicated that the articular chondrocyte phenotype in ESET-null mutants is 100% penetrant. Our results demonstrate that expression of ESET plays an essential role in the maintenance of articular cartilage by preventing articular chondrocytes from terminal differentiation and may have implications in joint diseases such as osteoarthritis.

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.