SummaryBone marrow niches for hematopoietic progenitor cells are not well defined despite their critical role in blood homeostasis. We previously found that cells expressing osteocalcin, a marker of mature osteolineage cells, regulate the production of thymic-seeding T lymphoid progenitors. Here, using a selective cell deletion strategy, we demonstrate that a subset of mesenchymal cells expressing osterix, a marker of bone precursors in the adult, serve to regulate the maturation of early B lymphoid precursors by promoting pro-B to pre-B cell transition through insulin-like growth factor 1 (IGF-1) production. Loss of Osx+ cells or Osx-specific deletion of IGF-1 led to a failure of B cell maturation and the impaired adaptive immune response. These data highlight the notion that bone marrow is a composite of specialized niches formed by pairings of specific mesenchymal cells with parenchymal stem or lineage committed progenitor cells, thereby providing distinctive functional units to regulate hematopoiesis.

Purpose Given the lack of a reference standard diagnostic tool for carpal tunnel syndrome (CTS), we conducted a population-level analysis of patients undergoing carpal tunnel release to characterize utilization of preoperative electrodiagnostic studies (EDS). Secondarily, we sought to determine the impact of EDS utilization on timeliness of surgery, number of preoperative physician visits, and costs. Methods The 2009 to 2013 Truven MarketScan Databases were used to identify a national cohort of adult patients undergoing carpal tunnel release. Three multivariable regression models were designed to evaluate the relationship between preoperative EDS use and timing of surgical release, the number of preoperative physician visits, and total costs for CTS-related visits, while controlling for socio-demographic variables, insurance type, comorbid conditions, and treatment characteristics. Results The final study cohort included 62,894 patients who underwent carpal tunnel release, of whom 58% had preoperative EDS. Patients undergoing EDS waited 36% longer for surgical release than patients without EDS. The mean time between diagnosis and surgery was predicted to be 183 days for patients who underwent preoperative EDS and 135 days for patients who did not. Patients having EDS experienced 1 additional visit, $996 greater total costs, and $112 additional out-of-pocket costs on average. Occupational therapy consultation and steroid injection were also associated with increased time to surgery, but with one-fourth and one-third the added cost of EDS, respectively. Conclusions Based on national practice trends, providers do not consistently agree with the practice of performing EDS prior to carpal tunnel release. Given the uncertain utility of routine EDS prior to carpal tunnel release and its association with delays to surgery and increased costs, further evaluation of EDS in relation to patient preferences and value of care is warranted. Level of Evidence Level II (retrospective prognostic study)

Phase-amplitude coupling (PAC) estimates the statistical dependence between the phase of a low-frequency component and the amplitude of a high-frequency component of local field potentials (LFP). To date PAC has been mainly applied to one signal. In this work, we introduce a new application of PAC to two LFPs and suggest that it can be used to infer the direction and strength of rhythmic neural transmission between distinct brain networks. This hypothesis is based on the accumulating evidence that transmembrane currents related to action potentials contribute a broad-band component to LFP in the high-gamma band, and PAC calculated between the amplitude of high-gamma (>60 Hz) in one LFP and the phase of a low-frequency oscillation (e.g., theta) in another would therefore relate the output (spiking) of one area to the input (somatic/dendritic postsynaptic potentials) of the other. We tested the hypothesis on theta-band long range communications between hippocampus and prefrontal cortex (PFC) and theta-band short range communications between dentate gyrus (DG) and the Ammon’s horn (CA1) within the hippocampus. The ground truth was provided by the known anatomical connections predicting hippocampus → PFC and DG → CA1, i.e., theta transmission is unidirectional in both cases: from hippocampus to PFC and from DG to CA1 along the tri-synaptic pathway within hippocampus. We found that (1) hippocampal high-gamma amplitude was significantly coupled to PFC theta phase, but not vice versa; (2) similarly, DG high-gamma amplitude was significantly coupled to CA1 theta phase, but not vice versa, and (3) the DG high-gamma-CA1 theta PAC was significantly correlated with DG → CA1 Granger causality, a well-established analytical measure of directional neural transmission. These results support the hypothesis that inter-regional PAC (ir-PAC) can be used to relate the output of a rhythmic “driver” network (i.e., high gamma) to the input of a rhythmic “receiver” network (i.e., theta) and thereby establish the direction and strength of rhythmic neural transmission.

Purpose To conduct a population-level analysis of practice trends and probability of surgery based on the number of steroid injections for common hand conditions. Methods Patients at least 18 years old receiving injection or surgery for carpal tunnel syndrome (CTS), trigger finger (TF), or De Quervain tenovaginitis (DQ) were identified for inclusion using the 2009–2013 Truven MarketScan databases. The number of injections performed was counted, and time between injection and operation was calculated for patients receiving both treatments. A multivariable logistic regression model was created to evaluate the odds of undergoing surgery based on the number of injections performed, controlling for patient age, sex, comorbidities, and insurance type. Results The study sample included 251,030 patients who underwent steroid injection or operative release for CTS (n=129,917), TF (n=102,778), and DQ (n=18,335). The majority of CTS patients were managed with immediate surgery (71%), whereas most patients with TF and DQ were managed initially with injection (74% and 84%, respectively). Among patients receiving both an injection and an operation, a single injection was the most common practice prior to surgery (69%, 58%, and 67% of patients with CTS, TF, and DQ, respectively). Multiple injections for DQ and TF were associated with relatively low predicted probability of surgery (17% and 26%, respectively, after 2 injections). However, the predicted probability of surgery after two injections was higher in patients with CTS (44%). Conclusions Given the associated probability of surgery after multiple injections for the three hand conditions examined, the practice of repeat injections should be critically examined to determine whether underuse or overuse is present and whether efficiency and resource utilization can be improved upon. Level of Evidence Level II (retrospective prognostic study)

Phase-amplitude coupling (PAC) estimates the statistical dependence between the phase of a low-frequency and the amplitude of a high-frequency component of local field potentials (LFP). Characterizing the relationship between nested oscillations in LFPs, PAC has become a powerful tool for understanding neural dynamics in both animals and humans. In this work, we introduce a new application for this measure to two LFPs to infer the direction and strength of rhythmic neural transmission between distinct networks. Based on recently accumulating evidence that transmembrane currents related to action potentials contribute a broad-band component to LFP in the highgamma band, we hypothesized that PAC calculated between high-gamma in one LFP and low-frequencyoscillations in another would relate the output (spiking) of one area to the input (soma/dendritic postsynaptic potentials) of the other. We tested this hypothesis on theta-band long range communications between hippocampus and prefrontal cortex (PFC) and theta-band short range communications between different regions within the hippocampus. The results were interpreted within the known anatomical connections predicting hippocampus→PFC and DG→CA3→CA1, i.e., theta transmission is unidirectional in both cases: from hippocampus to PFC and along the tri-synaptic pathway within hippocampus. We found that (1) hippocampal highgamma amplitude was significantly coupled to theta phase in PFC, but not vice versa; (2) similarly, high-gamma amplitude in DG was significantly coupled to CA1 theta phase, but not vice versa, and (3) the DG high-gamma-CA1 theta PAC was significantly correlated with DG→CA1 Granger causality, a well-established analytical measure of directional neural transmission. These results support the hypothesis that inter-regional PAC (ir-PAC) can be used to relate the output of a "driver" network (i.e., high gamma) to the input of a "receiver" network (i.e., theta) and thereby establish the direction and strength of rhythmic neural transmission.

Study Design: This was a cross-sectional study. Objective: The objective of this study is to report the impact of COVID-19 on spine surgery fellow education and readiness for practice. Summary of Background Data: COVID-19 has emerged as one of the most devastating global health crises of our time. To minimize transmission risk and to ensure availability of health resources, many hospitals have cancelled elective surgeries. There may be unintended consequences of this decision on the education and preparedness of current surgical trainees. Materials and Methods: A multidimensional survey was created and distributed to all current AO Spine fellows and fellowship directors across the United States and Canada. Results: Forty-five spine surgery fellows and 25 fellowship directors completed the survey. 62.2% of fellows reported >50% decrease in overall case volume since cancellation of elective surgeries. Mean hours worked per week decreased by 56.2%. Fellows reported completing a mean of 188.4±64.8 cases before the COVID-19 crisis and 84.1% expect at least an 11%–25% reduction in case volume compared with previous spine fellows. In all, 95.5% of fellows did not expect COVID-19 to impact their ability to complete fellowship. Only 2 directors were concerned about their fellows successfully completing fellowship; however, 32% of directors reported hearing concerns regarding preparedness from their fellows and 25% of fellows were concerned about job opportunities. Conclusions: COVID-19 has universally impacted work hours and case volume for spine surgery fellows set to complete fellowship in the middle of 2020. Nevertheless, spine surgery fellows generally feel ready to enter practice and are supported by the confidence of their fellowship directors. The survey highlights a number of opportunities for improvement and innovation in the future training of spine surgeons. Level of Evidence: Level III.

Background Traumatic finger/thumb amputations are some of the most prevalent traumatic injuries affecting Americans each year. Rates of replantation after traumatic finger/thumb amputation, however, have been steadily declining across U.S. hospitals, which may make these procedures less accessible to minorities and vulnerable populations. The specific aim of this study was to examine racial variation in finger replantation after traumatic finger/thumb amputation. Methods Using a two-level hierarchical model, we retrospectively compared replantation rates for African-American patients with those of Whites, adjusting for patient and hospital characteristics. Patients younger than 65 with traumatic finger/thumb amputation injuries who sought care at a U.S. trauma center between 2007 and 2012 were included in the study sample. Results We analyzed 13,129 patients under 65 years of age with traumatic finger/thumb amputation. Replantation rates declined over time from 19% to 14% (p = 0.004). Adjusting for patient and hospital characteristics, African-Americans (OR=0.81; CI: 0.66–0.99; p = 0.049) were less likely to undergo replantation procedures than Whites, and uninsured patients (OR=0.73; CI: 0.62–0.84; p < 0.0001) were less likely than those who were privately insured. Conclusions Despite advancements in microsurgical techniques and the increasing use of reconstructive surgery in other fields, finger/thumb replantation rates are declining in the U.S. and vulnerable populations are less likely to undergo replantation after amputation injuries. Regionalization of care for these injuries may not only provide a higher quality care but also reduce variations in treatment.

Purpose Spine surgeons around the world have been universally impacted by COVID-19. The current study addressed whether prior experience with disease epidemics among the spine surgeon community had an impact on preparedness and response toward COVID-19. Methods A 73-item survey was distributed to spine surgeons worldwide via AO Spine. Questions focused on: demographics, COVID-19 preparedness, response, and impact. Respondents with and without prior epidemic experience (e.g., SARS, H1NI, MERS) were assessed on preparedness and response via univariate and multivariate modeling. Results of the survey were compared against the Global Health Security Index. Results Totally, 902 surgeons from 7 global regions completed the survey. 24.2% of respondents had prior experience with global health crises. Only 49.6% reported adequate access to personal protective equipment. There were no differences in preparedness reported by respondents with prior epidemic exposure. Government and hospital responses were fairly consistent around the world. Prior epidemic experience did not impact the presence of preparedness guidelines. There were subtle differences in sources of stress, coping strategies, performance of elective surgeries, and impact on income driven by prior epidemic exposure. 94.7% expressed a need for formal, international guidelines to help mitigate the impact of the current and future pandemics. Conclusions This is the first study to note that prior experience with infectious disease crises did not appear to help spine surgeons prepare for the current COVID-19 pandemic. Based on survey results, the GHSI was not an effective measure of COVID-19 preparedness. Formal international guidelines for crisis preparedness are needed to mitigate future pandemics.