Restructuring of an Orthopaedic Surgery Residency Research Rotation Correlates with Increased Academic Productivity in Teaching Faculty.

INTRODUCTION: Contribution toward clinical research is paramount to the education of physician trainees and is required by the Accreditation Council for Graduate Medical Education. From 1987 through 2015, our single institution orthopaedic surgery residency research experience included 2 dedicated research rotations. Because few resident projects were pursued to completion, feedback was used to restructure the curriculum, including the appointment of 2 clinical orthopaedic faculty to serve as codirectors, development of a revised curriculum, use of research teams, and a centralized research database. Our group previously displayed increased resident productivity within 2 years after the 2015 implementation. The aim of this study was to investigate the impact of orthopaedic residency curricular changes on scholarly activity of orthopaedic teaching faculty. METHODS: The curriculum vitae (CVs) of a single institution's orthopaedic teaching faculty were collected and retrospectively reviewed from 2014 through 2018 to determine academic productivity of clinical faculty. Indicators of academic productivity included peer-reviewed publications (including journal impact factors) and podium or poster presentations. RESULTS: Twenty-three of 27 faculty members responded to our request for CVs. One hundred three CVs were reviewed on 23 faculty. All academic indicators increased over 5 years. Multivariate analysis of variance (MANOVA) using a multivariate repeated measures analysis was completed. A sphericity χ2 test was violated for all measures, precluding us from using unadjusted univariate analysis. Univariate MANOVA with repeated measures displays significance regarding impact factor (f < 0.02, p < 0.05) and journal publications (f < 0.004, p < 0.05). Subsequent multivariate analysis shows similar results regarding impact factor (f < 0.0008), journal publications (0.0005), and poster presentations (f < 0.016). CONCLUSIONS: Improved structure of an established resident research rotation combined with enhanced faculty mentorship resulted in a significant increase in academic productivity for clinical teaching faculty of the department of orthopaedic surgery. This increase parallels that seen in orthopaedic resident research productivity; indicating a positive impact on teaching faculty scholarly activity. LEVEL OF EVIDENCE: III.

Proline­rich polypeptide­1 decreases cancer stem cell population by targeting BAFF chromatin­remodeling complexes in human chondrosarcoma JJ012 cells.

Chondrosarcoma is the second most common primary malignant bone tumor and is resistant to chemotherapy and radiation. Inadequate treatment response and poor prognosis requires novel therapeutic approaches. Proline­rich polypeptide­1 (PRP­1), synthesized by brain neurosecretory cells, has demonstrated antitumor properties in JJ012­cells; however, its underlying molecular mechanism remains unclear. The present study aimed to investigate the epigenetic regulation by which PRP­1 inhibits chondrosarcoma cancer stem cell (CSC) proliferation and to elucidate additional CSC biomarkers in human chondrosarcoma other than ALDH1A1. Human chondrosarcoma JJ012­cells were treated with PRP­1 prior to performing an Aldefluor™ assay and fluorescence­activated cell sorting in order to determine aldehyde dehydrogenase (ALDH) expression levels and isolate ALDHhigh and ALDHlow cell populations. ALDH is an established marker of CSCs in several neoplasms, including chondrosarcoma. The cells were collected and lysed for gel electrophoresis, followed by western blot analysis. The Aldefluor™ assay was used to assess the expression levels of well­established CSC biomarkers, including CD133, CD4, CD10, CD144, CD177, CD221, CD271, leucine­rich repeat­containing G protein­coupled receptor 5, SOX2 and B lymphoma Mo­MLV insertion region 1 homolog (BMI­1), within the ALDHhigh population of JJ012 cells. The results confirmed that ALDHA1 was the biomarker for chondrosarcoma CSCs. PRP­1 was demonstrated to inhibit the ALDHhigh population colony and sarcosphere formation; 5 µg/ml PRP­1 was indicated to be the optimum concentration in eliminating colonies formed by JJ012 cells (92%, P<0.001) and by the ALDHhigh CSC­population (80.5%, P<0.001) in the clonogenic dose­response assay. Spheroid growth unequivocally decreased with an increase in PRP­1 dose. In order to determine the molecular mechanism by which PRP­1 decreased the CSC population, the regulation of the mammalian Switch/sucrose non­fermenting (SWI/SNF) complex, also referred to as BRG1­associated factor (BAF) complex, which either activates or represses transcription, thus acting as an oncogene or tumor suppressor in human cells, was analyzed. PRP­1 was demonstrated to decrease the expression levels of BRG, BAF170 and BRM; therefore, in JJ012 cells, these key players of the SWI/SNF (BAF) complex served an oncogenic role. The results of the present study demonstrated that PRP­1 targets chromatin­remodeling complexes; therefore, future efforts will be directed towards determining the interconnection between CSC maintenance, self­renewal capacity and BAF complexes.

Multidisciplinary Management of Spinal Metastasis and Vertebral Instability: A Systematic Review.

OBJECTIVE: The aim of this systematic literature review is to evaluate recent attempts in creating a standardized multidisciplinary approach combining tumor treatment with current vertebral stabilization techniques for palliative treatment of vertebral metastasis in patients who do not fall into the NOMS (neurologic, oncologic, mechanical, systemic) framework. METHODS: We performed a systematic literature search for studies using a tumor modality in conjunction with kyphoplasty or vertebroplasty. In addition, the bibliographies of selected articles were examined for additional studies not viewed in database searches, which led to the use of additional search terms. RESULTS: A total of 563 articles were found after our database search. Eighteen studies fulfilled our inclusion criteria. Articles were then divided into categories based on combinations of tumor modality. Multiple studies reported significant decreases in visual analog scale scores after combined procedures with very low rates of symptomatic complications. Studies that compared their combination with control treatment groups showed greater clinical efficacy. CONCLUSIONS: Although multidisciplinary management of spinal metastasis using a combination of tumor ablation techniques with vertebral stabilization has been recommended in the previous literature, this review shows that no combination of treatment carried demonstrably different results in pain score reduction, reduced analgesic intake, or improved quality of life. In addition, there is no consensus of standardized variables to evaluate efficacy of treatment, limiting the efficacy of treatment results for the analyzed studies. Although not explicitly included in the initial NOMS framework, our results support the consideration of concomitant percutaneous kyphoplasty or vertebroplasty in these patients on a case-by-case basis.

Isolated Recurrence of Diffuse Large B-Cell Lymphoma in Sciatic Nerve.

Sciatica is a common clinical presentation with a number of etiological factors. Many of them are innocuous like prolapsed intervertebral disc or peripheral compression in the sciatic nerve. Occasionally the cause could be of a more serious nature like a nerve sheath tumor or more infrequently, lymphomatosis. We describe recurrent lymphoma in a patient who had been in remission presented with sciatica as result of the involvement of the nerve with metastatic tumor.