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Bone is the most common site of breast cancer metastasis and once established, it is frequently incurable. Critical to our ability to prevent and treat bone metastasis is the identification of the key factors mediating its establishment and understanding their biological function. To address this issue we previously carried out an in vivo selection process to isolate murine mammary tumor sublines possessing an enhanced ability to colonize the bone. A comparison of gene expression between parental cells and sublines by genome-wide cDNA microarray analysis revealed several potential mediators of bone metastasis, including the pyrophosphate-generating ectoenzyme Enpp1. By qRT-PCR and Western analysis we found that expression of Enpp1 was elevated in human breast cancer cell lines known to produce bone metastasis in animal models compared to non-metastatic and normal mammary epithelial cell lines. Further, in clinical specimens, levels of Enpp1 were significantly elevated in human primary breast tumors relative to normal mammary epithelium, with highest levels observed in breast-bone metastasis as determined by qRT-PCR and immunohistochemical analysis. To examine the potential role of Enpp1 in the development of bone metastasis, Enpp1 expression was stably increased in the breast cancer cell line MDA-MB-231 and the ability to colonize the bone following intracardiac and direct intratibial injection of athymic nude mice was determined. By both routes of administration, increased expression of Enpp1 enhanced the ability of MDA-MB-231 cells to form tumors in the bone relative to cells expressing vector alone, as determined by digital radiography and histological analysis. Taken together, these data suggest a potential role for Enpp1 in the development of breast cancer bone metastasis.

A water vapor micropulse differential absorption lidar (DIAL) instrument was developed collaboratively by the National Center for Atmospheric Research (NCAR) and Montana State University (MSU). This innovative, eye-safe, low-power, diode-laser-based system has demonstrated the ability to obtain unattended continuous observations in both day and night. Data comparisons with well-established water vapor observing systems, including radiosondes, Atmospheric Emitted Radiance Interferometers (AERIs), microwave radiometer profilers (MWRPs), and ground-based global positioning system (GPS) receivers, show excellent agreement. The Pearson’s correlation coefficient for the DIAL and radiosondes is consistently greater than 0.6 from 300 m up to 4.5 km AGL at night and up to 3.5 km AGL during the day. The Pearson’s correlation coefficient for the DIAL and AERI is greater than 0.6 from 300 m up to 2.25 km at night and from 300 m up to 2.0 km during the day. Further comparison with the continuously operating GPS instrumentation illustrates consistent temporal trends when integrating the DIAL measurements up to 6 km AGL.

Non-dispersive infrared (NDIR) sensors are a low-cost way to observe carbon dioxide concentrations in air, but their specified accuracy and precision are not sufficient for some scientific applications. An initial evaluation of six SenseAir K30 carbon dioxide NDIR sensors in a lab setting showed that without any calibration or correction, the sensors have an individual root mean square error (RMSE) between  ∼ 5 and 21 parts per million (ppm) compared to a research-grade greenhouse gas analyzer using cavity enhanced laser absorption spectroscopy. Through further evaluation, after correcting for environmental variables with coefficients determined through a multivariate linear regression analysis, the calculated difference between the each of six individual K30 NDIR sensors and the higher-precision instrument had an RMSE of between 1.7 and 4.3 ppm for 1 min data. The median RMSE improved from 9.6 for off-the-shelf sensors to 1.9 ppm after correction and calibration, demonstrating the potential to provide useful information for ambient air monitoring.

CD8+ T cell dysfunction impedes antitumor immunity in solid cancers, but the underlying mechanisms are diverse and poorly understood. Extracellular matrix (ECM) composition has been linked to impaired T cell migration and enhanced tumor progression; however, impacts of individual ECM molecules on T cell function in the tumor microenvironment (TME) are only beginning to be elucidated. Upstream regulators of aberrant ECM deposition and organization in solid tumors are equally ill-defined. Therefore, we investigated how ECM composition modulates CD8+ T cell function in undifferentiated pleomorphic sarcoma (UPS), an immunologically active desmoplastic tumor. Using an autochthonous murine model of UPS and data from multiple human patient cohorts, we discovered a multifaceted mechanism wherein the transcriptional coactivator YAP1 promotes collagen VI (COLVI) deposition in the UPS TME. In turn, COLVI induces CD8+ T cell dysfunction and immune evasion by remodeling fibrillar collagen and inhibiting T cell autophagic flux. Unexpectedly, collagen I (COLI) opposed COLVI in this setting, promoting CD8+ T cell function and acting as a tumor suppressor. Thus, CD8+ T cell responses in sarcoma depend on oncogene-mediated ECM composition and remodeling.

Background/rationale Image-guided needle biopsies are commonly used to diagnose musculoskeletal tumors, but nondiagnostic (ND) results can delay diagnosis and treatment. It is important to understand which factors or diagnoses predispose to a ND result so that appropriate patient education or a possible change in the clinical plan can be made. Currently it is unclear which factors or specific lesions are more likely to lead to a ND result after image-guided needle biopsy. Questions/purposes We therefore identified specific factors and diagnoses most likely to yield ND results. We also asked whether an image-guided needle biopsy of bone and soft tissue lesions is an accurate and clinically useful tool. Methods We retrospectively reviewed data from a prospectively collected database for a case-control study of 508 image-guided needle biopsies of patients with suspected musculoskeletal tumors between 2003 and 2008. Results The interpretations of 453 of the 508 (89%) needle biopsies were accurate and clinically useful. Forty-five biopsies (9%) were ND and 10 (2%) were incorrect (IC). Bone lesions had a higher ND rate than soft tissue lesions (13% vs. 4%). The specific diagnosis with the highest ND rate was histiocytosis. Elbow and forearm locations had higher ND rates than average. Malignant tumors had a higher IC rate than benign tumors (5% vs. 0%); fibromyxoid sarcoma and rare subtypes of osteosarcoma had higher IC rates than other diagnoses. Repeat needle or open biopsies were performed in 71 (14%) patients. Bone lesions were more likely than soft tissue lesions to require repeat biopsies (18% vs. 9%). Conclusions A high rate of accuracy and clinical usefulness is possible with image-guided needle biopsies of musculoskeletal lesions. We believe these biopsies appropriate in selected circumstances but a key factor for appropriate use is an experienced musculoskeletal tumor team with frequent communication to correlate clinical, radiographic, and histologic information for each patient. Level of Evidence Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Orthopedics is the least diverse medical specialty. From residents to faculty, the representation of women and underrepresented minorities lags behind that of all other specialties. The crux of the disparity stems from the pipeline, as medical students who are female and are underrepresented minorities are simply not applying to orthopedic surgery. Grassroots efforts providing early exposure to orthopedics have led to a considerable proportion of alumnae pursuing science majors and eventually medical school. Institutions with a stated commitment to diversity have successfully produced residency classes with greater diversity. The culture should be one that combats biases, dispels misconceptions about orthopedics, and prioritizes recruiting/retaining diverse providers. [ Orthopedics . 2020;43(3):e134–e140.]

Women are underrepresented across the field of orthopedic surgery and may face barriers to academic advancement. Research presentation at national meetings and publication record are important drivers of advancement in academic orthopedic surgery. However, little is known regarding potential gender differences in publication after orthopedic conference research presentation. This investigation analyzed research presentations at the Annual Meeting of the American Academy of Orthopaedic Surgeons in 2016 and 2017. Author gender was determined through a search of institutional and professional networking websites for gender-specific pronouns. Resulting publications were identified using a systematic search of PubMed and Google Scholar databases. A total of 1696 of 1803 (94.1%) abstracts from 2016 to 2017 had identifiable gender for both the first and last authors, with 1213 (71.5%) abstracts ultimately being published. There were no differences in average sample size or level of evidence between genders. Abstracts authored by women were significantly less likely to lead to publication compared with those by men (67.1% vs 72.1%, P=.023), with articles authored by women having a longer median time to publication (median, 20 months [interquartile range, 19] vs 17 months [interquartile range, 15]; P=.003). This discrepancy was most apparent in adult reconstruction, with women having a 15.5% lower rate of publication (55.1% [27/49] vs 70.6% [307/435]; P=.026) and lower publication journal impact factor (2.7±1.4 vs 3.4±3.4, P=.040) than men. Potential reasons for these discrepancies, including disproportionate domestic obligations, inadequate mentorship, and bias against female researchers, should be addressed. [Orthopedics. 20XX;XX(X):xx–xx.]

BackgroundMagnetic resonance imaging (MRI) plays a critical role in disease characterization of intra-articular tenosynovial giant cell tumor.ObjectiveTo characterize the MRI features of intra-articular tenosynovial giant cell tumor in children with respect to disease subtype and anatomical location.Materials and methodsThis retrospective study included children with tenosynovial giant cell tumor who underwent preoperative MRI between January 2006 and May 2020. Two radiologists reviewed each examination to determine disease subtype, signal intensities and the presence of an effusion, osseous changes, chondromalacia, juxtacapsular disease and concomitant joint involvement. Fisher exact, Mann-Whitney U, and Kruskal-Wallis H tests were used to compare findings between subtypes and locations.ResultsTwenty-four children (16 girls, 8 boys; mean age: 13.1±3.8 years) with 19 knee and 5 ankle-hindfoot tenosynovial giant cell tumor had either diffuse (n=15) or localized (n=9) disease. An effusion (P=0.004) was significantly more common with diffuse than localized disease. There was no significant difference in MRI signal (P-range: 0.09–1) or other imaging findings (P-range: 0.12–0.67) between subtypes. Children with knee involvement were significantly more likely to present with diffuse disease while those with ankle-hindfoot involvement all presented with focal disease (P=0.004). Juxtacapsular (n=4) and concomitant proximal tibiofibular joint involvement (n=5) were observed with diffuse disease in the knee. Erosions (P=0.01) were significantly more common in the ankle than in the knee.ConclusionIn our study, diffuse tenosynovial giant cell tumor was more common than localized disease, particularly in the knee where juxtacapsular and concomitant proximal tibiofibular joint disease can occur.

ObjectivesThe COVID-19 pandemic is unprecedented as a global crisis over the last century. How do specialist surgeons make decisions about patient care in these unprecedent times?DesignBetween April and May 2020, we conducted an international qualitative study. Sarcoma surgeons from diverse global settings participated in 60 min interviews exploring surgical decision making during COVID-19. Interview data were analysed using an inductive thematic analysis approach.SettingParticipants represented public and private hospitals in 14 countries, in different phases of the first wave of the pandemic: Australia, Argentina, Canada, India, Italy, Japan, Nigeria, Singapore, Spain, South Africa, Switzerland, Turkey, UK and USA.ParticipantsFrom 22 invited sarcoma surgeons, 18 surgeons participated. Participants had an average of 19 years experience as a sarcoma surgeon.Results17/18 participants described a decision they had made about patient care since the start of the pandemic that was unique to them, that is, without precedence. Common to ‘unique’ decisions about patient care was uncertainty about what was going on and what would happen in the future (theme 1: the context of uncertainty), the impact of the pandemic on resources or threat of the pandemic to overwhelm resources (theme 2: limited resources), perceived increased risk to self (theme 3: duty of care) and least-worst decision making, in which none of the options were perceived as ideal and participants settled on the least-worst option at that point in time (theme 4: least-worst decision making).ConclusionsIn the context of rapidly changing standards of justice and beneficence in patient care, traditional decision-making frameworks may no longer apply. Based on the experiences of surgeons in this study, we describe a framework of least-worst decision making. This framework gives rise to actionable strategies that can support decision making in sarcoma and other specialised fields of surgery, both during the current crisis and beyond.

Wound complications represent a major source of morbidity in patients undergoing radiation therapy (RT) and surgical resection of soft tissue sarcomas (STS). We investigated whether factors related to RT, surgery, patient comorbidities, and tumor histopathology predict the development of wound complications. An observational study of patients who underwent STS resection and RT was performed. The primary outcome was the occurrence of any wound complication up to four months postoperatively. Significant predictors of wound complications were identified using multivariable logistic regression. Sixty-five patients representing 67 cases of STS were identified. Median age was 59 years (range 22–90) and 34 (52%) patients were female. The rates of major wound complications and any wound complications were 21% and 33%, respectively. After adjusting for radiation timing, diabetes (OR 9.6; 95% CI 1.4–64.8; P=0.02), grade ≥2 radiation dermatitis (OR 4.8; 95% CI 1.2–19.2; P=0.03), and the use of 3D conformal RT (OR 4.6; 95% CI 1.1–20.0; P=0.04) were associated with an increased risk of any wound complication on multivariable analysis. These data suggest that radiation dermatitis and radiation modality are predictors of wound complications in patients with STS.