Evaluation of patients referred to the spine clinic via telemedicine and the impact on diagnosis and surgical decision-making.

OBJECTIVE: Telemedicine encounters are expanding in utility for outpatient care and evaluation, partially as a necessity during the COVID-19 pandemic. It is unclear if telemedicine evaluation is comparable to in-person assessment of patients with spinal pathology undergoing surgical consultation. The objective of this study was to determine if treatment plans change for spine patients evaluated in person following an initial telemedicine consultation. METHODS: Patients referred to the authors' comprehensive spine center were evaluated first via telemedicine and then in clinic. Telemedicine evaluations were conducted via video evaluation with an attending surgeon. Demographic data including age, gender, and distance traveled from the clinic were retrospectively recorded. A chart review retrieved symptoms, radiographic details, and past medical history. The primary outcome was if the treatment plan changed (plan change [PC]) after seeing the patient in the clinic. Chi-square tests and binary logistical regression produced uni- and multivariate analyses. RESULTS: There were 152 new patients seen via telemedicine and in person. Pathology was present in the cervical (28.3%), thoracic (9.9%), and lumbar (61.8%) spine. The most common symptom was pain (72.4%), followed by radiculopathy (66.4%), weakness (26.3%), myelopathy (15.1%), and claudication (12.5%). There were 37 patients (24.3%) for whom there was a PC after clinic evaluation, and of those, only 5 (3.3%) were due to physical examination (PCPE) findings. On univariate analysis, a longer duration between telemedicine and clinic visit (odds ratio [OR] 1.094 per 7 days, p = 0.003), having pathology in the thoracic spine (OR 3.963, p = 0.018) and lack of sufficient imaging (OR 25.455, p < 0.0001) were predictive of a PC. Having pathology in the cervical spine (OR 9.538, p = 0.047) and adjacent-segment disease (OR 11.471, p = 0.010) were predictive of a PCPE. CONCLUSIONS: This study demonstrates that telemedicine may be an effective modality for the initial evaluation of spine surgical patients, without compromising decision-making in the absence of an in-person physical examination.

The Enhanced Recovery After Surgery pathway for posterior cervical surgery: a retrospective propensity-matched cohort study.

OBJECTIVE: The Enhanced Recovery After Surgery (ERAS) protocol is a comprehensive, multifaceted approach aimed at improving postoperative outcomes. It incorporates a range of strategies to promote early and more effective recovery, including reducing pain, complications, and length of stay, without increasing readmission rate. To date, ERAS for spine surgery patients has been primarily limited to lumbar surgery and anterior cervical decompression and fusion (ACDF). ERAS has not been previously studied for posterior cervical surgery, which may present a greater opportunity for improvement in patient outcomes with ERAS than ACDF. This single-institution, multi-surgeon study assessed the impact of an ERAS protocol in patients undergoing posterior cervical decompression surgery. METHODS: This study included a retrospective consecutive patient cohort with controls that were propensity matched for age, body mass index, sex, home opioid use, surgical levels, Nurick grade, and smoking status. In addition, consecutive patients who underwent posterior cervical decompression surgery for degenerative disease from December 2014 to December 2021 were included. ERAS was implemented in December 2018. Demographic, perioperative, clinical, and radiographic information was gathered. Regression models were created to evaluate length of stay, physiological function, pain levels, and opioid use. The primary focus was length of stay, with secondary outcomes including timing of ambulation, bowel movement, and voiding; daily pain scores; opioid consumption; discharge status; 30-day readmission rates; and reoperation rates. RESULTS: There were 366 patients included in the study, all of whom were included in multivariate models, and 254 (127 in each cohort) were included on the basis of matching. After propensity matching, patient characteristics, operative procedures, and operative duration were similar between groups. The ERAS cohort had a significantly improved length of stay (3.2 vs 4.7 days, p < 0.0001) and home discharge rate (80% vs 50%, p < 0.001) without an increase in readmission rate. The ERAS cohort had an earlier day of the first ambulation (p = 0.003), bowel movement (p = 0.014), and voiding (p = 0.001). ERAS demonstrated a significantly lower composite complication rate (1.1 vs 1.8, p < 0.0001). ERAS resulted in better maximum pain scores (p = 0.043) and trended toward improved mean pain scores (p = 0.072), although total opioid use was similar. CONCLUSIONS: Implementing a novel ERAS protocol significantly improved length of stay, return of physiological function, home discharge, complications, and maximum pain score after posterior cervical surgery.

Association of Early and Late Hospital Readmissions with a Novel Housing-Based Socioeconomic Measure.

Background: While socioeconomic status has been linked to hospital readmissions for several conditions, reliable measures of individual socioeconomic status are often not available. HOUSES, a new measure of individual socioeconomic status based upon objective public data about one's housing unit, is inversely associated with overall hospitalization rate but it has not been studied with respect to readmissions. Purpose: To determine if patients in the lowest HOUSES quartile are more likely to be readmitted within 30 days (short-term) and 180 days (long-term). Methods: A retrospective cohort study of 11 993 patients having 21 633 admissions was conducted using generalized linear mixed-effects models. Results: HOUSES quartile did not show any significant association with early readmission. However, when compared to the lowest HOUSES quartile, the second quartile (OR = 0.90, 95%CI 0.83-0.98) and the third quartile (OR = 0.91, 95%CI 0.83-0.99) were associated with lower odds of late readmission while the highest quartile (OR = 0.91, 95%CI 0.82-1.01) was not statistically different. Conclusion: HOUSES was associated with late readmission, but not early readmission. This may be because early readmissions are influenced by medical conditions and hospital care while late readmissions are influenced by ambulatory care and home-based factors. Since HOUSES relies on public county assessor data, it is generally available and may be used to focus interventions on those at highest risk for late readmission.

Enhanced recovery after surgery (ERAS) improves return of physiological function in frail patients undergoing one- to two-level TLIFs: an observational retrospective cohort study.

BACKGROUND CONTEXT: The enhanced recovery after surgery (ERAS) protocol is a multimodal approach which has been shown to facilitate recovery of physiological function, and reduce early post-operative pain, complications, and length of stay (LOS) in open one- to two-level TLIF. The benefit of ERAS in specifically frail patients undergoing TLIF has not been demonstrated. Frailty is clinically defined as a syndrome of physiological decline that can predispose patients undergoing surgery to poor outcomes. PURPOSE: This study primarily evaluated the benefit of an ERAS protocol in frail patients undergoing one- or two-level open TLIF compared to frail patients without ERAS. Secondarily, we assessed whether outcomes in frail patients with ERAS approximated those seen in nonfrail patients with ERAS. STUDY DESIGN: Retrospective consecutive patient cohort with controls propensity-matched for age, body mass index, sex, and smoking status. PATIENT SAMPLE: Consecutive patients that underwent one- or two-level open TLIF for degenerative disease from August, 2015 to July, 2021 by a single surgeon. ERAS was implemented in December 2018. OUTCOME MEASURES: Primary outcome measure was return of postoperative physiological function defined as the summation of first day to ambulate, first day to bowel movement, and first day to void. Additional outcome measures included LOS, daily average pain scores, opioid use, discharge disposition, 30-day readmission rate, and reoperation. METHODS: A retrospective analysis of frail patients > 65 years of age undergoing one- to two-level open TLIF post-ERAS were compared to propensity matched frail pre-ERAS patients. Frailty was assessed using the Fried phenotype classification (score >1). Patient demographics, LOS, first-day-to-ambulate (A1), first-day-to-bowel movement (B1), first-day-to-void (V1) were collected. Return of physiological function was defined as A1+B1+V1. Primary analysis was a comparison of frail patients pre-ERAS versus post-ERAS to determine effect of ERAS on return of physiologic function with frailty. Secondary analysis was a comparison of post-ERAS frail versus post-ERAS nonfrail patients to determine if return of physiologic function in frail patients with ERAS approximates that of nonfrail patients. RESULTS: In the primary analysis, 32 frail patients were included with mean age ± standard deviation of 72.8±4.4 years, mean BMI 28.8±5.5, 65.6% were male, 15 pre-ERAS and 17 post-ERAS. Patient characteristics were similar between groups. After ERAS implementation, return of physiological function improved by a mean 3.2 days overall (post-ERAS 3.4 vs. pre-ERAS 6.7 days) (p<.0001), indicating a positive effect of ERAS in frail patients. Additionally, length of stay improved by 1 day (4.8±1.6 vs. 3.8±1.9 days, p<.0001). Total daily intravenous morphine milligram equivalent (MME) as well as average daily pain scores were similar between groups. Secondarily, 26 nonfrail patients post ERAS were used as a comparison group with the 17 post-ERAS frail cohort. Mean age of this cohort was 73.4±4.6 years, mean BMI 27.4±4.9, and 61.9% were male. Return of physiologic function was similar between cohorts (post-ERAS nonfrail 3.5 vs. post-ERAS frail 3.4 days) (p=.938), indicating the benefit with ERAS in frail patients approximates that of nonfrail patients. CONCLUSIONS: ERAS significantly improves return of physiologic function and length of stay in patients with frailty after one- to two-level TLIF, and approximates improved outcomes seen in non-frail patients.

Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation.

The bone marrow niche plays critical roles in hematopoietic recovery and hematopoietic stem cell (HSC) regeneration after myeloablative stress. However, it is not clear whether systemic factors beyond the local niche are required for these essential processes in vivo. Thrombopoietin (THPO) is a key cytokine promoting hematopoietic rebound after myeloablation and its transcripts are expressed by multiple cellular sources. The upregulation of bone marrow-derived THPO has been proposed to be crucial for hematopoietic recovery and HSC regeneration after stress. Nonetheless, the cellular source of THPO in myeloablative stress has never been investigated genetically. We assessed the functional sources of THPO following two common myeloablative perturbations: 5-fluorouracil (5-FU) administration and irradiation. Using a Thpo translational reporter, we found that the liver but not the bone marrow is the major source of THPO protein after myeloablation. Mice with conditional Thpo deletion from osteoblasts and/or bone marrow stromal cells showed normal recovery of HSCs and hematopoiesis after myeloablation. In contrast, mice with conditional Thpo deletion from hepatocytes showed significant defects in HSC regeneration and hematopoietic rebound after myeloablation. Thus, systemic THPO from the liver is necessary for HSC regeneration and hematopoietic recovery in myeloablative stress conditions.

Socioeconomic Implications of Professional Relationships within Modern Care Delivery Systems.

No physician can successfully deliver high-value patient care in the modern-day health care system in isolation. Delivery of effective patient care requires integrated and collaborative systems that depend on dynamic professional relationships among members of the health care team. An overview of the socioeconomic implications of professional relationships within modern care delivery systems and potential employment models is presented.

Cerebral amyloid angiopathy: early presentation in a patient with prior neurosurgical interventions. Case report.

BACKGROUND: Cerebral amyloid angiopathy (CAA) has classically been described as a disease of the elderly. Genetic predisposition has been linked to the APOE e3/e3 allele. Evidence suggests that brain insult in the form of injury, prior surgical intervention, or radiation can exacerbate the clearance of toxic proteins in patients susceptible to CAA. CASE: We describe a unique case of CAA in a 30-year-old male who had prior surgical interventions for spina bifida, Chiari malformation, and hydrocephalus as a child. CONCLUSIONS: The case is used to teach important components regarding diagnosis, clinical suspicion, and highlight the need for further investigation regarding the emerging role of the glymphatic system and its role in clinical pathology.

Cervical Spine Deformity Correction Techniques.

Cervical kyphotic deformity can be a debilitating condition with symptoms ranging from mechanical neck pain, radiculopathy, and myelopathy to impaired swallowing and horizontal gaze. Surgical correction of cervical kyphosis has the potential to halt progression of neurological and clinical deterioration and even restore function. There are various operative approaches and deformity correction techniques. Choosing the optimal strategy is predicated on a fundamental understanding of spine biomechanics. Preoperative characterization of cervical malalignment, assessment of deformity rigidity, and defining postoperative clinical and radiographic objectives are paramount to formulating a surgical plan that balances clinical benefit with morbidity. This review of cervical deformity treatment provides an overview of the biomechanics of cervical kyphosis, radiographic classification, algorithm-based management, surgical techniques, and current surgical outcome studies.

Reimbursement patterns for neurosurgery: Analysis of the NERVES survey results from 2011-2016.

OBJECTIVE: In response to rising national health expenditures, the Patient Protection and Affordable Care Act (ACA) was passed in 2010, with major provisions implemented in 2014. Due to increasing concerns about workload and compensation among neurosurgeons, we evaluated trends in neurosurgical reimbursement, productivity and compensation before and after the implementation of the major provisions of the ACA. PATIENTS AND METHODS: Results from Neurosurgery Executives' Resource Value and Education Society (NERVES) annual surveys were collected, representing data from 2011 to 2016. Responses from different practice settings across the six years were categorized into groups, and inverse variance-weighted averaging was performed within the frameworks of a one-way ANOVA model with year. Data from 2011 to 2013 and 2014-2016 were analyzed similarly for differences among practice setting and region. RESULTS: The NERVES survey response rates ranged from 20% to 36%. Median values for compensation decreased by 3.66%, 6.42%, and 10.34% within private, hospital, and academic practices respectively after 2014 although these trends did not reach statistical significance. Median work RVUs had a trend to decrease by 5.67%, 13.08%, and 19.44% within private, hospital, and academic practices respectively after 2014. Academic practices showed statistically significant decreases in annual total RVUs, total gross charges and collections. CONCLUSION: These data demonstrate neurosurgical reimbursement and productivity have trended down during a time that increases in productivity and reimbursement were predicted. This phenomenon is most notable in academic practices compared to private or hospital based practices. Prospective analyses of the impact of healthcare policy reform on neurosurgical productivity are urgently needed.

The effects of hyperglycemia on outcomes in surgical high-grade glioma patients.

OBJECTIVE: To define the glucose values associated with an increase in complication rates in post-operative brain tumor patients. PATIENTS AND METHODS: Patients who underwent craniotomy for resection of WHO Grade III or IV glioma from 2011 to 2014 were retrospectively reviewed. Post-operative blood glucose values were recorded for post-operative day #0, #1, and #2. Medians were obtained and assessed for significance. Multivariate analysis was performed to assess patient demographics, pre-operative findings, steroid use, and blood glucose values with respect to post-operative complications and to 30-day readmission. RESULTS: 108 patients underwent craniotomy for resection of high-grade glioma and had postoperative blood glucose values documented. Median blood glucose values greater than 167 mg/dL were associated with increased serious post-operative complications, and values greater than 163 mg/dL were associated with increased 30-day readmissions. CONCLUSION: Post-operative hyperglycemia in patients with high-grade gliomas places this vulnerable patient population to undue post-operative complications and readmissions, potentially delaying further treatment of their disease.

Hepatic thrombopoietin is required for bone marrow hematopoietic stem cell maintenance.

Hematopoietic stem cell (HSC) maintenance depends on extrinsic cues. Currently, only local signals arising from the bone marrow niche have been shown to maintain HSCs. However, it is not known whether systemic factors also sustain HSCs. We assessed the physiological source of thrombopoietin (TPO), a key cytokine required for maintaining HSCs. Using TpoDsRed-CreER knock-in mice, we showed that TPO is expressed by hepatocytes but not by bone marrow cells. Deletion of Tpo from hematopoietic cells, osteoblasts, or bone marrow mesenchymal stromal cells does not affect HSC number or function. However, when Tpo is deleted from hepatocytes, bone marrow HSCs are depleted. Thus, a cross-organ factor, circulating TPO made in the liver by hepatocytes, is required for bone marrow HSC maintenance. Our results demonstrate that systemic factors, in addition to the local niche, are a critical extrinsic component for HSC maintenance.

Bone Marrow Micro-Environment in Normal and Deranged Hematopoiesis: Opportunities for Regenerative Medicine and Therapies.

Various cell types cooperate to create a highly organized and dynamic micro-environmental niche in the bone marrow. Over the past several years, the field has increasingly recognized the critical roles of the interplay between bone marrow environment and hematopoietic cells in normal and deranged hematopoiesis. These advances rely on several new technologies that have allowed us to characterize the identity and roles of these niches in great detail. Here, we review the progress of the last several years, list some of the outstanding questions in the field and propose ways to target the diseased environment to better treat hematologic diseases. Understanding the extrinsic regulation by the niche will help boost hematopoiesis for regenerative medicine. Based on natural development of hematologic malignancies, we propose that combinatory targeting the niche and hematopoietic intrinsic mechanisms in early stages of hematopoietic malignancies may help eliminate minimal residual disease and have the highest efficacy.

Extrinsic regulation of hematopoietic stem cells in development, homeostasis and diseases.

Lifelong generation of blood and immune cells depends on hematopoietic stem cells (HSCs). Their function is precisely regulated by complex molecular networks that integrate and respond to ever changing physiological demands of the body. Over the past several years, significant advances have been made in understanding the extrinsic regulation of HSCs during development and in homeostasis. Propelled by technical advances in the field, the cellular and molecular components of the microenvironment that support HSCs in vivo are emerging. In addition, the interaction of HSCs with their niches is appreciated as a critical contributor to the pathogenesis of a number of hematologic disorders. Here, we review these advances in detail and highlight the extrinsic regulation of HSCs in the context of development, homeostasis, and diseases. WIREs Dev Biol 2017, 6:e279. doi: 10.1002/wdev.279 For further resources related to this article, please visit the WIREs website.

Leptin-receptor-expressing bone marrow stromal cells are myofibroblasts in primary myelofibrosis.

Bone marrow fibrosis is a critical component of primary myelofibrosis (PMF). However, the origin of the myofibroblasts that drive fibrosis is unknown. Using genetic fate mapping we found that bone marrow leptin receptor (Lepr)-expressing mesenchymal stromal lineage cells expanded extensively and were the fibrogenic cells in PMF. These stromal cells downregulated the expression of key haematopoietic-stem-cell-supporting factors and upregulated genes associated with fibrosis and osteogenesis, indicating fibrogenic conversion. Administration of imatinib or conditional deletion of platelet-derived growth factor receptor a (Pdgfra) from Lepr+ stromal cells suppressed their expansion and ameliorated bone marrow fibrosis. Conversely, activation of the PDGFRA pathway in bone marrow Lepr+ cells led to expansion of these cells and extramedullary haematopoiesis, features of PMF. Our data identify Lepr+ stromal lineage cells as the origin of myofibroblasts in PMF and suggest that targeting PDGFRA signalling could be an effective way to treat bone marrow fibrosis.

Effects of Perioperative Acetyl Salicylic Acid on Clinical Outcomes in Patients Undergoing Craniotomy for Brain Tumor.

OBJECTIVE: To evaluate the safety of continuing acetyl salicylic acid (ASA) in patients undergoing brain tumor resection. Many patients are on antiplatelet agents that are withheld before elective neurosurgical procedures to reduce bleeding risk. Cessation of ASA in patients with cardiovascular disease is associated with a known increased risk of thrombotic events, especially in patients with coronary stents. METHODS: The medical records of patients who underwent surgical resection of a brain tumor at the University of Florida from 2010 to 2014 were evaluated. The patients were separated into groups based on preoperative ASA use and whether or not it was stopped before surgery. Patients were evaluated for thrombotic complications, postoperative hemorrhage, estimated blood loss, length of hospital stay, and discharge disposition. RESULTS: Of the 452 patients analyzed, 368 patients were not on chronic ASA therapy, 55 patients had their ASA discontinued before surgery, and 28 patients were continued on ASA perioperatively. The patients on preoperative ASA were comparable on all collected demographic variables. There were no statistical differences detected between the groups for outcomes including bleeding complications, need for reoperation, or thrombotic complications. CONCLUSIONS: In this analysis, perioperative low dose ASA use was not associated with increased risk of perioperative complications.

Attitudes Toward LGBT Patients Among Students in the Health Professions: Influence of Demographics and Discipline.

PURPOSE: Health providers' personal and professional experiences may predict attitudes toward lesbian, gay, bisexual, and transgender (LGBT) individuals and can therefore serve as key targets for health professions training aimed at decreasing barriers to high-quality patient care. This study explored the relationship between professional, demographic, and training characteristics and health professions student attitudes toward LGBT patients. METHODS: Students from a health sciences university and applied mental health programs in Georgia (N=475) completed a survey that included a modified version of the Attitudes Toward LGBT Patients Scale (ATLPS). RESULTS: Profession, sexual orientation, current financial status, religion, religiosity, spirituality, and self-reported familiarity with various religious perspectives on sex were associated with ATLPS scores. However, religiosity and self-reported familiarity with various religious perspectives on sex were the only significant predictors of ATLPS scores when these variables were included in one general linear model. CONCLUSIONS: Health professions students with higher levels of religiosity and lower levels of self-reported familiarity with various religious perspectives on sex reported less positive attitudes toward LGBT individuals. Results suggest that personal factors may be important to address in interprofessional curriculum related to LGBT patient care. Self-report biases and other factors may limit the accuracy and generalizability of the findings.

Depression screening in Black Americans with multiple sclerosis.

Depression is prevalent in Multiple Sclerosis (MS) and impacts treatment adherence. Depression screening may be a useful mechanism to identify Blacks at risk for depression in an MS setting, as they frequently experience more disabling MS disease and also may be less likely than Whites to be accurately diagnosed with depression, which can further impact MS disease and diminish quality of life. The purpose of this study was to compare the clinical presentation (e.g. psychiatric histories, current symptoms, and provider treatment recommendations) of Black and White MS patients identified as at risk for depression using a validated depression screening instrument. Secondary analysis of an archival chart data-set of 279 MS patients (90 Blacks) indicated that Black patients were less likely than Whites to have a past mental health diagnosis (X(2) = 12.794, p < .001), prior experience with psychotropics (X(2) = 11.394, p < .001), or be prescribed psychotropics at the time of screening (X(2) = 10.225, p < .001). No differences in depression scores were observed between Black and White patients. Approximately 44% of patients received provider treatment recommendations following a positive screening with no between group differences in the likelihood of receiving at least one recommendation. Consistent with the literature, our Black patient sample was less likely than Whites to have a history of mental health diagnosis or to have been treated with psychotropics. Although more research is needed, screening programs for depression in MS may facilitate access to services for all MS patients while reducing health disparities in Black American patients and removing barriers to early intervention and ongoing care.

A critical role for AID in the initiation of reprogramming to induced pluripotent stem cells.

Mechanistic insights into the reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs) are limited, particularly for early acting molecular regulators. Here we use an acute loss of function approach to demonstrate that activation-induced deaminase (AID) activity is necessary for the initiation of reprogramming to iPSCs. While AID is well known for antibody diversification, it has also recently been shown to have a role in active DNA demethylation in reprogramming toward pluripotency and development. These findings suggested a potential role for AID in iPSC generation, yet, iPSC yield from AID-knockout mouse fibroblasts was similar to that of wild-type (WT) fibroblasts. We reasoned that an acute loss of AID function might reveal effects masked by compensatory mechanisms during development, as reported for other proteins. Accordingly, we induced an acute reduction (>50%) in AID levels using 4 different shRNAs and determined that reprogramming to iPSCs was significantly impaired by 79 ± 7%. The deaminase activity of AID was critical, as coexpression of WT but not a catalytic mutant AID rescued reprogramming. Notably, AID was required only during a 72-h time window at the onset of iPSC reprogramming. Our findings show a critical role for AID activity in the initiation of reprogramming to iPSCs.

The Ewing's sarcoma fusion protein, EWS-FLI, binds Runx2 and blocks osteoblast differentiation.

Ewing's sarcomas are highly aggressive round cell tumors of bone and soft tissues that afflict children and young adults. The majority of these tumors harbor the t(11;22) translocation and express the fusion protein EWS-FLI. Modern molecular profiling experiments indicate that Ewing's tumors originate from mesenchymal precursors in young individuals. EWS-FLI alters the morphology of mesenchymal cells and prevents lineage specification; however, the molecular mechanisms for differentiation arrest are unclear. We recently showed that EWS-FLI binds Runx2, a master regulator of osteoblast differentiation. In this report, we demonstrate that FLI sequences within EWS-FLI are responsible for interactions with Runx2. EWS-FLI blocks the expression of osteoblastic genes in a multipotent progenitor cell line that requires Runx2 to integrate bone morphogenic protein (Bmp)2 signaling while increasing proliferation and altering cell morphology. These results demonstrate that EWS-FLI blocks the ability of Runx2 to induce osteoblast specification of a mesenchymal progenitor cell. Disrupting interactions between Runx2 and EWS-FLI1 may promote differentiation of the tumor cell.

TEThered to Runx: novel binding partners for runx factors.

RUNX transcription factors reside in the nuclear matrix where they integrate numerous signaling pathways to regulate gene expression and affect tissue development, regeneration, and tumorigenesis. An affinity purification and proteomic experiment was performed to identify novel Runx2 binding partners. The interactions between Runx2 and two nuclear factors (Ddx5 and CoAA) identified in this screen were previously described. Coactivator activator (CoAA) bound the DNA binding domain of Runx2 and prevented Runx-driven gene expression. The YxxQ motif in CoAA was required for Runx2 interactions. Members of the FET/TET family of proteins, including FUS/TLS and EWSR1, contain a similar motif and were hypothesized to interact with Runx2. Here, we provide evidence that FUS/TLS, EWSR1, and the Ewing's sarcoma t(12;21) fusion protein EWS-FLI bind Runx2 and alter its transcriptional activity. Potential roles of protein complexes containing FET/TET and RUNX family members during tumor formation and mesenchymal progenitor cell differentiation are discussed.