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Osteoid osteoma is a benign tumor that accounts for roughly 10-12% of all benign bone forming tumors. This tumor generally occurs within the first three decades of life and occurs more commonly in males. This lesion is painful and is generally worse at night and has relief of symptoms with the use of NSAIDs. Osteoid osteoma is characterized by the production of osteoid surrounded by a rim of sclerotic bone. These lesions most commonly occur in long bones such as the proximal femur, however they can occur anywhere. Rarely, as with our patient, have these lesions been reported in the acetabulum.

Bisphosphonate (BP) therapy for moderate to severe osteogenesis imperfecta (OI) has become a mainstay of treatment in the last three decades. Given the significant improvements in bone mineral density and theoretical reductions in fracture risk, many patients are treated with bisphosphonates for prolonged periods of time. There currently lacks consensus in the optimal duration of BP therapy for patients with OI, and patients are often treated on a case-by-case basis. Long-term BP therapy has been associated with atypical femur fractures in adult patients treated for osteoporosis. The American Society for Bone and Mineral Research concluded that the median duration of BP therapy in patients with atypical femur fractures was 7 years. The role of long-term BP therapy in OI patients with atypical femur fractures remains unclear. Here, a case report is presented of an adolescent patient with type V OI that sustained a subtrochanteric femur fracture with features of an atypical pattern following treatment with intravenous pamidronate for 10.5 years. At the time of injury, the contralateral femur was also found to have atypical features suggestive of an impending fracture. The completed fracture was treated with closed reduction and cephalomedullary nail fixation. The impending fracture was prophylactically stabilized using the same technique. Prior to the injury, limb-length radiographs obtained to evaluate lower extremity alignment demonstrated features of an impending fracture but went unnoticed. Further studies are needed to clarify the role of long-term BP therapy in patients with OI suffering from atypical femur fractures.

The detection of tumor-specific nucleic acids from blood increasingly is being used as a method of liquid biopsy and minimal residual disease detection. However, achieving high sensitivity and high specificity remains a challenge. Here, we perform a direct comparison of two droplet digital PCR (ddPCR)-based detection methods, circulating plasma tumor RNA and circulating plasma tumor DNA (ptDNA), in blood samples from newly diagnosed Ewing sarcoma patients. First, we developed three specific ddPCR-based assays to detect EWS-FLI1 or EWS-ERG fusion transcripts, which naturally showed superior sensitivity to DNA detection on in vitro control samples. Next, we identified the patient-specific EWS-FLI1 or EWS-ERG breakpoint from five patient tumor samples and designed ddPCR-based, patient-specific ptDNA assays for each patient. These patient-specific assays show that although plasma tumor RNA can be detected in select newly diagnosed patients, positive results are low and statistically unreliable compared with ptDNA assays, which reproducibly detect robust positive results across most patients. Furthermore, the unique disease biology of Ewing sarcoma enabled us to show that most cell-free RNA is not tumor-derived, although cell-free-DNA burden is affected strongly by tumor-derived DNA burden. Here, we conclude that, even with optimized highly sensitive and specific assays, tumor DNA detection is superior to RNA detection in Ewing sarcoma patients.

BACKGROUND: Acute hematogenous musculoskeletal infections are a common cause of hospitalization in children. A locally developed clinical care guideline (CCG) for acute musculoskeletal infections was implemented at our quaternary care pediatric hospital in July 2012. The purpose of this study was to evaluate the long-term sustainability of previously described improvements after CCG implementation. METHODS: Clinical outcomes for children hospitalized with musculoskeletal infections at Children’s Hospital Colorado from June 2009 through September 2018 were retrospectively reviewed. Patients were included if they had an International Classification of Diseases, Ninth Revision or International Classification of Diseases, 10th Revision discharge diagnosis of acute osteomyelitis, septic arthritis, or pyomyositis and were between 6 months and 18 years of age at admission. Patients with underlying medical complexity or nonhematogenous musculoskeletal infections were excluded. Patients were categorized by date of admission as either “pre-CCG” (June 2009 to June 2011) or “sustain-CCG” (July 2014 to September 2018). Primary outcomes were hospital length of stay and intravenous antimicrobial length of therapy. RESULTS: From pre-CCG to sustain-CCG, median length of stay decreased by 1.29 days (5.56 vs 4.27; P < .004) and median length of therapy decreased by 5.04 days (8.33 vs 3.29; P < .0001). Statistical process control charts support that these were sustained improvements many years after CCG implementation. Additional secondary clinical improvements were observed in the sustain-CCG group including faster fever resolution, more consistent blood and source culture acquisition, and decreased central line placement. There was no increase in related readmissions or therapeutic failures in the sustain-CCG group. CONCLUSIONS: Implementation of a CCG to standardize care for musculoskeletal infections can be sustained many years after implementation.

1. Nathan Donaldson, DO* 2. Julia Sanders, MD* 3. Jason Child, PharmD† 4. Sarah Parker, MD‡ 1. *Division of Orthopedic Surgery and 2. ‡Division of Infectious Diseases, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, CO 3. †Department of Pharmacy, Children’s Hospital Colorado, Aurora, CO * Abbreviations: ADE: : adverse drug event CRMO: : chronic recurrent multifocal osteomyelitis CRP: : C-reactive protein CT: : computed tomography ESR: : erythrocyte sedimentation rate MRI: : magnetic resonance imaging MRSA: : methicillin-resistant Staphylococcus aureus MSSA: : methicillin-susceptible Staphylococcus aureus OAI: : osteoarticular infection WBC: : white blood cell Management of pediatric acute hematogenous osteoarticular infections has changed in various ways during the past decade, including the description of new pathogens and updated diagnostic and treatment strategies (such as infected source sampling and an early switch to oral therapy). After completing this article, readers should be able to: 1. Understand what predisposes children of different age groups to acute hematogenous osteoarticular infections (OAIs), particularly the role of anatomy and differing pathogenic susceptibilities. 2. Recognize the symptoms present in children with OAIs and their most common differential diagnoses. 3. Understand the most effective imaging techniques and laboratory tests/cultures to diagnose an OAI and how to interpret them. 4. Understand the benefits and limitations of therapeutic surgery and source sampling (biopsy/aspirate) and when to commence antimicrobial drug therapy. 5. Recognize the most common causative pathogens and the most effective antimicrobial drugs for their treatment. 6. Determine how long a patient should be taking intravenous and oral therapy and under what conditions they should switch from intravenous to oral antimicrobial agents. 7. Understand the recommended follow-up after diagnosis, including when to expect normalization of laboratory values in patients with uncomplicated OAIs. 8. Recognize complicated OAIs and their possible long-term sequelae. Pediatric osteoarticular infections (OAIs) include infections of the bones (osteomyelitis) and joints (septic arthritis). Pathogenic organisms may be introduced into these normally sterile sites via direct inoculation (eg, trauma or surgery) or via erosion from a contiguously infected source (eg, chronic ulcer), but organisms are mostly hematogenously delivered. Bacteria are the most common pathogens to cause OAIs, but mycobacteria, fungi, and viruses can also infect these tissues. If diagnosed in the first 10 to 14 days, these infections are …

Objectives Identifying the causative bacterial pathogen for children with acute hematogenous musculoskeletal infections (MSKIs) allows for improved care. The purpose of our study was to determine if clinical markers could predict which patients will have a causative pathogen found on source culture alone, thus being highest yield to undergo operative diagnostic procedures. Methods A single-center, retrospective cohort study was performed. Medical records for patients between 6 months and 18 years of age admitted between July 2014 and September 2018 with a discharge diagnosis of acute osteomyelitis, septic arthritis, or pyomyositis were reviewed. Patients were stratified based on results of blood and source cultures. Predictors of interest were screened on a univariable basis with significant predictors retained in a multivariate analysis. Results There were 170 patients included. No predictors were significantly associated with increased odds of having a causative pathogen found on source culture alone. Degree of C-reactive protein elevation and history of fever were associated with decreased odds of being source culture positive, OR (95% CI); 0.92 (0.87, 0.98) and 0.39 (0.19, 0.81), respectively. Conclusions Predictive modeling failed to identify children with MSKIs whose causative pathogen was found by source culture alone. It is difficult to predict which MSKI patients will be highest yield for operative diagnostic procedures.

The effects of radiation therapy and laminectomy on the growing spine have been well documented. Due to compromised bone quality after irradiation, spinal fusion has a high failure rate. The aim of this study was to evaluate treatment of post-laminectomy and post-irradiation kyphosis in children using a vascularized rib graft (VRG) to augment anterior spinal fusion and posterior spinal fusion. Data were collected retrospectively from electronic medical records for all patients treated at a single institution for post-laminectomy and post-irradiation kyphosis who underwent VRG to augment spinal fusions done between December 2003 and August 2015. Five patients were included in the analysis. Imaging studies were analyzed by 2 senior pediatric orthopedic surgeons and a pediatric orthopedic surgery fellow. The outcome for all 5 patients who underwent VRG were considered successful at most recent clinical follow-up. Success was defined as the following: complete fusion evident through computed tomography scan, no implant failure, and no kyphosis progression. Follow-up ranged from 21 to 63 months. One patient experienced 2 complications: esophageal tear and deep infection. Spinal fusion with a VRG is a viable treatment option for children who have developed kyphosis following laminectomy and irradiation. On long-term follow-up, there has been no evidence of progression of kyphosis for patients who were treated with VRG in either the primary fusion procedure or in subsequent revision procedures. A VRG provides a non-irradiated, vascularized bone graft to bridge the irradiated segments, increasing the stability of the spine. [ Orthopedics . 2021;44(4):e563–e569.]

Ewing sarcoma (ES) is the second most common bone cancer in children, accounting for 2% of pediatric cancer diagnoses. Patients who present with metastatic disease at the time of diagnosis have a dismal prognosis, compared to the >70% 5-year survival of those with localized disease. Here, we utilized single-cell RNA sequencing (scRNA-seq) to characterize the transcriptional landscape of primary ES tumors, and to identify circulating tumor cells (CTCs) in peripheral blood at the time of diagnosis in order to further understand ES transcriptional heterogeneity and factors that drive metastasis. Methods: Viably frozen primary tumor and peripheral blood samples were obtained from 7 ES patients at the time of diagnosis and prior to the initiation of treatment. Tumors were dissociated into a single cell suspension and sorted for viability using FACS (fluorescence activated cell sorting) whereas peripheral blood samples were subjected to a size-based selection with the CellSieve microfiltration system. ScRNA-seq was performed using the 10xChromium platform and count matrices were generated using 10x Genomics Cell Ranger software. Quality control, integration, and cluster analysis was performed with Seurat. Results: Cluster analysis of integrated, primary tumor samples demonstrated that candidate ES cell clusters express FLI1 and ES marker NKX2-2 and cluster separately from immune cell populations. Additionally, using inferCNV, ES clusters were demonstrated to harbor chromosomal copy number alterations known to be associated with ES and that were previously identified clinically on preliminary pathology reports for each patient; further GSEA analysis showed significant overlap between published ES gene sets and genes upregulated in ES clusters. Further analysis of ES cells demonstrated that cell-cycle phase determined a cluster enriched in pro-proliferation gene signatures, and overall heterogeneity of expression of previously known therapeutic targets. Candidate ES CTCs were identified among the peripheral blood samples among clusters which corresponded with distinct immune cell populations. The candidate ES CTCs expressed NKX2-2 and demonstrated enrichment in oncogenic gene signatures. Conclusion: ScRNA-seq of primary ES tumors is feasible and demonstrates that ES tumor cells are largely homogeneous in nature; and candidate ES CTCs can be identified in peripheral blood at the time of diagnosis in ES patient and warrant further investigation as to their utility as a biomarker of metastatic disease. Citation Format: Sarah K. Nelson-Taylor, Avery Bodlack, Andrew Goodspeed, Amy Treece, Nathan Donaldson, Carrye Cost, Tim Garrington, Brian Greffe, Sandra Luna-Fineman, Jenna Sopfe, Masanori Hayashi. Single cell RNA sequencing of primary Ewing sarcoma tumors and identification of circulating tumor cells in patient-matched peripheral blood samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1681.

This paper traces the history of the Oxford Magnetic Suspension and Balance System, from its initial development in the 1960s through to current times. Developed in conjunction with the Oxford Low Density Tunnel, the balance has been a key instrument throughout its history for investigating aerodynamic forces at high Mach numbers, low density flows across the continuum, slip and transition regimes. An initial balance was developed as a 2-axis system with control over only lift and drag. Following its success, a second balance was designed to control lift, drag and additionally pitch. This enabled more complex geometries, such as a re-entry Aerobrake model and NASA’s X-43 hypersonic demonstrator to be investigated. The evolution of the electro-mechanical design of each balance and the associated model attitude detection systems are described in this paper. Operational issues encountered with the system and sample results from past studies are also presented and discussed. The paper concludes with an outlook to the future development and application of the magnetic suspension balance system within the Oxford Low Density Tunnel.

Background Acute pediatric musculoskeletal infections are common, leading to significant use of resources and antimicrobial exposure. In order to decrease variability and improve the quality of care, Children's Hospital Colorado implemented a clinical care guideline (CCG) for these infections. The purpose of this study is to evaluate clinical and resource outcomes PRE and POST this CCG. Methods Retrospective chart review evaluated patients admitted to a large pediatric quaternary referral center (CHCO) diagnosed with acute osteomyelitis, septic arthritis, pyomyositis, and/or musculoskeletal abscess prior to and after guideline implementation. Primary outcomes included length of stay and overall antibiotic use, with additional secondary clinical, process, and therapeutic outcomes examined. Results 82 patients were identified in both the pre-CCG and post-CCG cohorts. There was a reduction in the median of all primary outcomes, including length of stay (0.6 median days decrease, P = .04), length of IV antibiotic therapy (4.9 median days decrease, P < .0001), and days of IV antibiotic therapy (6.4 median days decrease, P = .0004). Our median length of stay post-CCG was 4.9 days, the shortest reported length of stay for pediatric acute musculoskeletal infections to date. Additionally, there was a 24.5 hour reduction in median length of fever (P = .02), faster CRP normalization (P < .0001), 50% decrease in the number of related readmissions (P = .02), 34% decrease in central venous catheters placed (P < .0001), decreased time to first culture (P = .02), and 79% pathogen identification post-CCG (P = .056). Conclusions Implementation of a CCG for acute musculoskeletal infections improves patient, process and resource outcomes.

Case A 19-year-old adolescent with Kniest dysplasia was incidentally found to have osteosarcoma of the proximal aspect of the humerus after having a chest radiograph for evaluation of an upper respiratory infection. He underwent chemotherapy and resection of the tumor, and there was no evidence of metastasis at the 16-month follow-up. Conclusion Patients with osteochondrodysplasias often have multiple orthopaedic symptoms. Changes in chronic pain symptoms should be investigated to rule out insidious secondary causes of musculoskeletal pain, such as osteosarcoma.

Background Pathogen detection in pediatric patients with musculoskeletal infections relies on conventional bacterial culture, which is slow and can delay antimicrobial optimization. The ability to rapidly identify causative agents and antimicrobial resistance genes in these infections may improve clinical care. Methods Convenience specimens from bone and joint samples submitted for culture to Children's Hospital Colorado (CHCO) from June 2012 to October 2016 were evaluated using a “Musculoskeletal Diagnostic Panel” (MDP) consisting of the Xpert MRSA/SA SSTI real-time PCR (qPCR, Cepheid) and laboratory-developed qPCRs for Kingella kingae detection and erm genes A, B, and C which confer clindamycin resistance. Results from the MDP were compared to culture and antimicrobial susceptibility testing (AST) results. Results A total of 184 source specimens from 125 patients were tested. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the Xpert MRSA/SA SSTI compared to culture and AST results were 85%, 98%, 93%, and 95% respectively for MSSA and 82%, 100%, 100%, and 99% for MRSA. Compared to phenotypic clindamycin resistance in S. aureus isolates, the erm A, B, and C gene PCRs collectively demonstrated a sensitivity, specificity, PPV, and NPV of 80%, 96%, 67%, and 98%. In comparison to clinical truth, Kingella PCR had a sensitivity, specificity, PPV, and NPV of 100%, 99.5%, 100%, and 100%. Conclusions This novel MDP offers a rapid, sensitive, and specific option for pathogen detection in pediatric patients with musculoskeletal infections.

Patients with congenital pseudarthrosis of the tibia do not have a normal tibia. In such patients, the entire tibia is abnormal (even outside of the established pseudarthrosis site); the bone does not have a normal healing response to injury or osteotomy, and the proximal growth plate typically has

Solid organ transplant recipients are at increased risk of malignancy. Pediatric transplant recipients particularly have a potentially higher risk given the young age of immunosuppression initiation. Posttransplant malignancies are the main cause of death in 5%–16% of liver transplantation patients. The frequency of de novo malignancies in pediatric liver transplant recipients has been reported to be 13%. Synovial sarcoma is a malignant mesenchymal neoplasm that has not been previously reported after liver transplantation. We report the case of an adolescent liver transplant recipient who was diagnosed with synovial sarcoma 14 years after liver transplantation.

Purpose We present a surgical technique for chest wall reconstruction using custom-designed titanium implants developed for two female patients to provide both chest wall symmetry and adequate stability for staged breast reconstruction. Methods A retrospective review was performed for two adolescent female patients with large chest wall defects who underwent the described technique. The etiology of the chest wall deficiency was secondary to Poland's syndrome in one patient, and secondary to surgical resection of osteosarcoma in the other patient. For each patient, a fine-cut computed tomography scan was obtained to assist with implant design. After fabrication of the prosthesis, reconstruction was performed though a curvilinear thoracotomy approach with attachment of the implant to the adjacent ribs and sternum. Wound closure was obtained with use of synthetic graft material, local soft tissue procedures, and flap procedures as necessary. Results The two patients were followed post-operatively for 35 and 38 months, respectively. No intra-operative or post-operative complications were identified. Mild scoliosis that had developed in the patient following chest wall resection for osteosarcoma did not demonstrate any further progression following reconstruction. Conclusions We conclude that this technique was successful at providing a stable chest wall reconstruction with satisfactory cosmetic results in our patients.

Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) are a heterogeneous group of sarcomas that encompass over 35 histologies. With an incidence of ∼500 cases per year in the United States in those20 years of age, NRSTS are rare and therefore difficult to study in pediatric populations. We used the large Surveillance, Epidemiology, and End Results (SEER) database to validate the prognostic ability of the Children's Oncology Group (COG) risk classification system and to define patient, tumor, and treatment characteristics.From SEER data from 1988 to 2007, we identified patients ≤18 years of age with NRSTS. Data for age, sex, year of diagnosis, race, registry, histology, grade, primary size, primary site, stage, radiation therapy, and survival outcomes were analyzed. Patients with nonmetastatic grossly resected low-grade tumors of any size or high-grade tumors ≤5 cm were considered low risk. Cases of nonmetastatic tumors that were high grade,5 cm, or unresectable were considered intermediate risk. Patients with nodal or distant metastases were considered high risk.A total of 941 patients met the review criteria. On univariate analysis, black race, malignant peripheral nerve sheath (MPNST) histology, tumors5 cm, nonextremity primary, lymph node involvement, radiation therapy, and higher risk group were associated with significantly worse overall survival (OS) and cancer-specific survival (CSS). On multivariate analysis, MPNST histology, chemotherapy-resistant histology, and higher risk group were significantly poor prognostic factors for OS and CSS. Compared to low-risk patients, intermediate patients showed poorer OS (hazard ratio [HR]: 6.08, 95% confidence interval [CI]: 3.53-10.47, P.001) and CSS (HR: 6.27; 95% CI: 3.44-11.43, P.001), and high-risk patients had the worst OS (HR: 13.35, 95% CI: 8.18-21.76, P.001) and CSS (HR: 14.65, 95% CI: 8.49-25.28, P.001).The current COG risk group stratification for children with NRSTS has been validated with a large number of children in the SEER database.

Over the last three years the authors have been involved in three experiments that were or will be launched on sounding rockets and high altitude balloons with the REXUS/BEXUS program (Rocket-borne / Balloon-borne Experiments for University Students). The first experiment, called Suaineadh was launched from Esrange (Kiruna, Sweden) onboard REXUS 12 in March 2012. Suaineadh had the purpose of deploying a web in space by using centrifugal forces. The payload was lost during re-entry but was recovered 18 month later in early September 2013. StrathSat-R is the second experiment, which had the purpose of deploying two cube satellites with inflatable structures from the REXUS 13 sounding rocket, was launched first in May 2013 and will be launched a second time in spring 2014. The last experiment is the iSEDE experiment which has the goal of deploying an inflatable structure with disaggregated electronics from the high altitude balloon BEXUS15/16 in October 2013. All these experiments have been designed, built and flown in a timeframe of one and a half to two years. This paper will present the lessons learned in project management, outreach, experiment design, fabrication and manufacturing, software design and implementation, testing and validation as well as launch, flight and post-flight. Furthermore, the lessons learned during the recovery mission of Suaineadh will be discussed as well. All these experiments were designed, built and tested by a large group of university students of various disciplines and different nationalities. StrathSat-R and iSEDE were built completely at Strathclyde but the Suaineadh experiment was a joint project between Glasgow and Stockholm which was especially tricky during integration while approaching the experiment delivery deadline. This paper should help students and professionals across various disciplines to build and organise these kinds of projects more efficiently without making the same, sometimes expensive, mistakes all over again.