Sharing Data from the Human Tumor Atlas Network through Standards, Infrastructure, and Community Engagement.

The Data Coordinating Center (DCC) of the Human Tumor Atlas Network (HTAN) has played a crucial role in enabling the broad sharing and effective utilization of HTAN data within the scientific community. Data from the first phase of HTAN are now available publicly. We describe the diverse datasets and modalities shared, multiple access routes to HTAN assay data and metadata, data standards, technical infrastructure and governance approaches, as well as our approach to sustained community engagement. HTAN data can be accessed via the HTAN Portal, explored in visualization tools-including CellxGene, Minerva, and cBioPortal-and analyzed in the cloud through the NCI Cancer Research Data Commons nodes. We have developed a streamlined infrastructure to ingest and disseminate data by leveraging the Synapse platform. Taken together, the HTAN DCC's approach demonstrates a successful model for coordinating, standardizing, and disseminating complex cancer research data via multiple resources in the cancer data ecosystem, offering valuable insights for similar consortia, and researchers looking to leverage HTAN data.

Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer.

Tumors are intrinsically heterogeneous and it is well established that this directs their evolution, hinders their classification and frustrates therapy1-3. Consequently, spatially resolved omics-level analyses are gaining traction4-9. Despite considerable therapeutic interest, tumor metabolism has been lagging behind this development and there is a paucity of data regarding its spatial organization. To address this shortcoming, we set out to study the local metabolic effects of the oncogene c-MYC, a pleiotropic transcription factor that accumulates with tumor progression and influences metabolism10,11. Through correlative mass spectrometry imaging, we show that pantothenic acid (vitamin B5) associates with MYC-high areas within both human and murine mammary tumors, where its conversion to coenzyme A fuels Krebs cycle activity. Mechanistically, we show that this is accomplished by MYC-mediated upregulation of its multivitamin transporter SLC5A6. Notably, we show that SLC5A6 over-expression alone can induce increased cell growth and a shift toward biosynthesis, whereas conversely, dietary restriction of pantothenic acid leads to a reversal of many MYC-mediated metabolic changes and results in hampered tumor growth. Our work thus establishes the availability of vitamins and cofactors as a potential bottleneck in tumor progression, which can be exploited therapeutically. Overall, we show that a spatial understanding of local metabolism facilitates the identification of clinically relevant, tractable metabolic targets.

Addressing persistent challenges in digital image analysis of cancerous tissues.

The National Cancer Institute (NCI) supports many research programs and consortia, many of which use imaging as a major modality for characterizing cancerous tissue. A trans-consortia Image Analysis Working Group (IAWG) was established in 2019 with a mission to disseminate imaging-related work and foster collaborations. In 2022, the IAWG held a virtual hackathon focused on addressing challenges of analyzing high dimensional datasets from fixed cancerous tissues. Standard image processing techniques have automated feature extraction, but the next generation of imaging data requires more advanced methods to fully utilize the available information. In this perspective, we discuss current limitations of the automated analysis of multiplexed tissue images, the first steps toward deeper understanding of these limitations, what possible solutions have been developed, any new or refined approaches that were developed during the Image Analysis Hackathon 2022, and where further effort is required. The outstanding problems addressed in the hackathon fell into three main themes: 1) challenges to cell type classification and assessment, 2) translation and visual representation of spatial aspects of high dimensional data, and 3) scaling digital image analyses to large (multi-TB) datasets. We describe the rationale for each specific challenge and the progress made toward addressing it during the hackathon. We also suggest areas that would benefit from more focus and offer insight into broader challenges that the community will need to address as new technologies are developed and integrated into the broad range of image-based modalities and analytical resources already in use within the cancer research community.

Femoral Head Autograft Can Reliably Reconstruct Dysplastic Acetabula Through the Direct Anterior Approach for Total Hip Arthroplasty.

Background: Bone deficiencies in dysplastic acetabula create technical difficulties during total hip arthroplasty (THA). Bulk femoral head autograft (FHA) is one method to increase cup coverage and bone stock of the true acetabulum; however, only limited data exist on its efficacy through a direct anterior approach (DAA). This study aimed to evaluate the outcomes of FHA during THA via a DAA in dysplastic hips. Methods: Retrospective review of 34 patients (41 hips) with hip dysplasia (Crowe I-III) who underwent primary THA via a DAA with FHA at a single institution was performed. Surgical procedures were performed on a traction table with intraoperative fluoroscopy and highly porous-coated cup placement in the true acetabulum. Patients were assessed clinically and radiographically at a minimum of 2 years postoperatively (range, 2 to 7). Results: The average modified Harris Hip Score improved from 31.9 ± 10.8 to 94.1 ± 5.8, Merle d'Aubigné Hip Score from 7.5 ± 2.8 to 16.6 ± 1.1, and visual analog pain score from 7.9 ± 2.7 to 1.4 ± 1.4 (all P < .001). All hips had an "anatomic" inferomedial cup position postoperatively, with an average increase in horizontal coverage of 43.4%. Mean postoperative limb-length discrepancy improved from 21.8 ± 16.1 mm to 1.6 ± 5.7 mm (P < .001). There were no cases of revision THA, nor complications such as dislocation, infection, or osteolysis. Conclusion: Reconstructing dysplastic acetabula (Crowe I-III) with FHA during THA can be successfully accomplished via the DAA with increased acetabular bone stock and accurate correction of limb-length discrepancy.

An Orthopedic Surgeon's Dental Examination: Reducing Unnecessary Delays in Joint Replacement Surgery for Marginalized Patients in a Safety Net Hospital System.

BACKGROUND: Selective dental clearance before total joint arthroplasty (TJA) has been proposed; however, effective strategies of carrying out this practice are lacking. This study aims to determine the positive predictive value (PPV) of a novel oral examination performed by an orthopedic surgeon to better direct limited resources for marginalized patients in a safety net hospital system. METHODS: A retrospective review was conducted on 105 consecutive patients who had an oral examination performed by a single surgeon before elective TJA. Patients who screened negative proceeded to surgery without further formal dental clearance. Patients who screened positive underwent formal examination/intervention by a dentist before surgery. The rate of correct referral that resulted in patients undergoing an oral surgical intervention was determined. Complications during a minimum 90-day postoperative follow-up period were collected and compared. RESULTS: Thirty patients (28.6%) screened positive while 75 patients (71.4%) screened negative and proceeded to surgery without referral. The PPV of the screening test was high, with 73.3% of patients receiving a major surgical oral intervention before TJA. Patients sent for formal referral required 89.1 more days to receive their surgery than those that screened negative (54.9 days ± 4.24 vs 144.0 days ± 82.4, P < .001). CONCLUSION: An orthopedic surgeon's oral examination demonstrates a high PPV to identify high-risk patients in need of an oral surgical intervention before TJA. This provides a unique solution regarding over-referral for preoperative dental clearance and avoids delays for marginalized patients considering elective TJA in a safety net hospital system.

Implementation of an enhanced recovery protocol at a safety net hospital : a silver lining to COVID-19?

AIMS: This study aimed to evaluate whether an enhanced recovery protocol (ERP) for arthroplasty established during the COVID-19 pandemic at a safety net hospital can be associated with a decrease in hospital length of stay (LOS) and an increase in same-day discharges (SDDs) without increasing acute adverse events. METHODS: A retrospective review of 124 consecutive primary arthroplasty procedures performed after resuming elective procedures on 11 May 2020 were compared to the previous 124 consecutive patients treated prior to 17 March 2020, at a single urban safety net hospital. Revision arthroplasty and patients with < 90-day follow-up were excluded. The primary outcome measures were hospital LOS and the number of SDDs. Secondary outcome measures included 90-day complications, 90-day readmissions, and 30day emergency department (ED) visits. RESULTS: The mean LOS was significantly reduced from 2.02 days (SD 0.80) in the pre-COVID cohort to 1.03 days (SD 0.65) in the post-COVID cohort (p < 0.001). No patients in the pre-COVID group were discharged on the day of surgery compared to 60 patients (48.4%) in the post-COVID group (p < 0.001). There were no significant differences in 90-day complications (13.7% (n = 17) vs 9.7% (n = 12); p = 0.429), 30-day ED visits (1.6% (n = 2) vs 3.2% (n = 4); p = 0.683), or 90-day readmissions (2.4% (n = 3) vs 1.6% (n = 2); p = 1.000) between the pre-COVID and post-COVID groups, respectively. CONCLUSION: Through use of an ERP, arthroplasty procedures were successfully resumed at a safety net hospital with a shorter LOS and increased SDDs without a difference in acute adverse events. The resulting increase in healthcare value therefore may be considered a 'silver lining' to the moratorium on elective arthroplasty during the COVID-19 pandemic. These improved efficiencies are expected to continue in post-pandemic era. Cite this article: Bone Jt Open 2021;2(10):871-878.

Combined Motor and Sensory Intraoperative Neuromonitoring for Cervical Spondylotic Myelopathy Surgery Causes Confusion: A Level-1 Diagnostic Study.

STUDY DESIGN: Level-1 diagnostic study. OBJECTIVE: The purpose of this study was to evaluate the sensitivity and specificity of combined motor and sensory intraoperative neuromonitoring (IONM) for cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: Intraoperative neuromonitoring during spine surgery began with sensory modalities with the goal of reducing neurological complications. Motor monitoring was later added and purported to further increase sensitivity and specificity when used in concert with sensory monitoring. Debate continues, however, as to whether neuromonitoring reliably detects reversible neurologic changes during surgery or simply adds set-up time, cost, or mere medicolegal reassurance. METHODS: Neuromonitoring data using combined motor and sensory evoked potentials for 540 patients with CSM undergoing anterior or posterior decompressive surgery were collected prospectively. Patients were examined postoperatively to determine the clinical occurrence of new neurologic deficit which correlated with monitoring alerts recorded per established standard criteria. RESULTS: The overall incidence of positive IONM alerts was 1.3% (N = 7) all of which were motor alerts. All were false positives as no patient had clinical neurological deterioration post-operatively. The false-positive rate was 1.4% (N = 146) for anterior surgeries and 1.3% (N = 394) for posteriors with no statistical difference between them (P = 1.0, Fisher exact test). There were no false-negative alerts, and all negatives were true negatives (N = 533). The overall sensitivity of detecting a new neurologic deficit was 0%, overall specificity 98.7%. CONCLUSION: Combined motor and sensory neuromonitoring for CSM patients created a confusing choice between the motor or sensory data when in disagreement in 1.3% of surgical patients. Criterion standard clinical examinations confirmed all motor alerts were false positives. Surgical plan was negatively altered by following false motor alerts early on, but disregarded in later cases in favor of sensory data. Neuromonitoring added set-up time and cost, but without clear benefit in this series.Level of Evidence: 4.

Anterior Total Hip Arthroplasty With Bulk Femoral Head Autograft in a Patient With Camurati-Engelmann Disease.

Camurati-Engelmann disease (CED) is an extremely rare, sclerosing bone disorder of intramedullary ossification with only 300 reported cases worldwide. The pathogenesis is related to activating mutations in transforming growth factor beta 1, which results in bilateral, symmetric hyperostosis affecting primarily the diaphysis of long bones. Despite effective pharmacological treatment options, the diagnosis of CED is problematic owning to its rarity and variability of clinical presentation. We present a patient with known CED with advanced early hip osteoarthritis, secondary to underlying hip dysplasia, for which she underwent a successful total hip arthroplasty via a direct anterior approach with the use of bulk femoral head autograft to reconstruct her native acetabulum.

Factors Influencing the Reparability and Healing Rates of Rotator Cuff Tears.

PURPOSE OF THE REVIEW: To discuss tear- and patient-related factors that influence the healing potential of rotator cuff tears and to clarify the terminology surrounding this topic. RECENT FINDINGS: Over the last few years, further insight has been gained regarding rotator cuff tear features that are associated with poor healing rates after rotator cuff repair. Some of these features have been incorporated in prediction models developed to accurately predict rotator cuff healing rates utilizing preoperative risk factors weighted by importance. Rotator cuff tears may be considered functionally irreparable based on their size, chronicity, absence of adequate tendon length, atrophy, and fatty infiltration. Furthermore, advanced age, use of tobacco products, diabetes, and other patient-related factors may impair tendon healing. Careful analysis and discussion of all these factors with patients is essential to determine if surgical repair of a rotator cuff tear should be recommended, or if it is best to proceed with one of the several salvage procedures reviewed in this topical collection, including augmentation of the repair, superior capsular reconstruction, tendon transfers, and other.

Perceptions of the Educational and Institutional Impact of the Orthopaedic Fellowship Interview Process.

INTRODUCTION: The time spent applying and interviewing for an orthopaedic fellowship has notable financial, educational, and workflow consequences on both residents and their respective residency programs. The purpose of this study was to assess the perceptions regarding the fellowship interview process to suggest changes that could be implemented. METHODS: Mixed-response questionnaires were sent to orthopaedic surgery residency program directors (PDs) and PGY-4 to PGY-6 residents at the 164 accredited allopathic orthopaedic surgery residency programs in the United States (August 2017). RESULTS: Significantly more PDs believed that time away for fellowship interviews negatively affected resident education compared with residents (68% versus 25%, 48 of 65 versus 28 of 113; P < 0.001). About half of all PDs and residents noted a specific amount of time granted for interviews (range, 3 to 20 days). Seventy-one percent of residents included in this study would favor regionally coordinated interview dates. CONCLUSIONS: Orthopaedic surgery residents and PDs perceive differences in the impact of the fellowship interview process on resident education and means for improvement of the process. Two-tiered or regionally coordinated interviews are favored as changes that could be implemented.

Direct and Asymmetric Nickel(II)-Catalyzed Construction of Carbon-Carbon Bonds from N-Acyl Thiazinanethiones.

A wide array of new N-acyl thiazinanethiones are employed in a number of direct and enantioselective carbon-carbon-bond-forming reactions catalyzed by nickel(II) complexes. The electrophilic species are mostly prepared in situ from ortho esters, methyl ethers, acetals, and ketals, which makes the overall process highly efficient and experimentally straightforward. Theoretical calculations indicate that the reactions proceed through an open transition state in a SN1-like mechanism. The utility of this novel procedure has been demonstrated by the asymmetric preparation of synthetically useful intermediates and the total synthesis of peperomin D.