ESET histone methyltransferase is essential to hypertrophic differentiation of growth plate chondrocytes and formation of epiphyseal plates

AbstractThe 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

50+ years of replantation surgery experience: are we progressing or regressing?

The first successful digit replantation was reported in 1965 and accepted enthusiastically by hand surgeons. The decade that immediately followed saw a surge of interest in this complex surgery, fueling significant improvements in success rates and the rise of hand and microsurgeons who were highly proficient in replantation. The decades that followed, however, showed a stable field lacking any significant changes or advancements. More recently, and especially in the United States, the frequency with which surgeons even attempt replantation and the rate of survival have plummeted. If this trend continues, successful replantation surgery will become all too rare of an event. It is critical that we evaluate the state of replantation surgery today, identify the primary causes, and work to not only revive the field but allow it to advance similar to other areas of medicine

Complex upper extremity injuries: targeted muscle reinnervation, free functional muscle transfer, and vascularized composite allotransplantation

Restoration of upper extremity function poses a unique surgical challenge. With considerations ranging from ensuring appropriate skeletal support and musculotendinous and ligamentous anatomy, restoring adequate vascularity and innervation, and providing sufficient soft tissue coverage, upper extremity injuries present a diverse range of reconstructive problems. Recent history has been marked by an expansion of novel techniques for addressing these complex issues. Sophisticated modalities, such as targeted muscle reinnervation, free functional muscle transfer, and vascularized composite allotransplantation, have become some of the most powerful tools in the armamentarium of the reconstructive surgeon. This review article aims to define the distinguishing features of each of these modalities and reviews some of their unique advantages and limitations

Influence of Corticosteroid Injections on Postoperative Infections in Carpal Tunnel Release.

PURPOSE: Corticosteroid injections (CSIs) are commonly used in carpal tunnel syndrome; however, recent literature has demonstrated risk of postoperative infection associated with preoperative CSIs in other orthopedic fields. The aim of this study was to assess the relationship of CSIs and postoperative infection following carpal tunnel release (CTR). METHODS: A single-center retrospective review was conducted from 2010 to 2019 to identify patients who underwent CTR with subsequent antibiotic prescription for chart-documented wound infection. A demographically-matched cohort of 100 patients was identified for comparison. Information on patient demographics, comorbidities, injection history, and presence of postoperative infection was collected. RESULTS: Thirty-nine patients (0.67% of all CTR patients) were identified with postoperative infections, 3 of which (0.05% of all CTR patients) were deep infections. In the infection cohort, 16 of 39 (41%) patients received an injection prior to surgery, whereas 16 of 100 (16%) patients in the control cohort received an injection. History of CSI was significantly more common in patients with postoperative infection, and patients in the infection cohort had a significantly shorter average time from injection to surgery by approximately 55 days. CONCLUSIONS: Corticosteroid injections in the preoperative period are associated with postoperative infection after CTR. Proximity of injection to time of surgery plays a role, although comorbidities, the corticosteroid dose, and frequency of injection require further study to determine risk contribution. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic III

Distal Radius Fracture Management: Surgeon Factors Markedly Influence Decision Making

IntroductionIt is our hypothesis that physician-specific variables affect the management of distal radius (DR) fractures in addition to patient-specific factors.MethodsA prospective cohort study was conducted evaluating treatment differences between Certificate of Additional Qualification hand surgeons (CAQh) and board-certified orthopaedic surgeons who treat patients at level 1 or level 2 trauma centers (non-CAQh). After institutional review board approval, 30 DR fractures were selected and classified (15 AO/OTA type A and B and 15 AO/OTA type C) to create a standardized patient data set. The patient-specific demographics and surgeon's information regarding the volume of DR fractures treated per year, practice setting, and years posttraining were obtained. Statistical analysis was done using chi-square analysis with a postanalysis regression model.ResultsA notable difference was observed between CAQh and non-CAQh surgeons. Surgeons in practice longer than 10 years or who treat >100 DR fractures/year were more likely to choose surgical intervention and obtain a preoperative CT scan. The two most influential factors in decision making were the patients' age and medical comorbidities, with physician-specific factors being the third most influential in medical decision making.DiscussionPhysician-specific variables have a notable effect on decision making and are critical for the development of consistent treatment algorithms for DR fractures