Sclerostin immunohistochemical staining in surgically treated giant cell tumor of bone.

BACKGROUND: Giant cell tumor of bone (GCTB) is a destructive lesion with a high potential for recurrence. RANK-ligand targeted therapy has provided promising, yet mixed results. Sclerostin (SOST) inhibition results in a net anabolic response and is currently used in the treatment of osteoporosis. The application to GCTB is unknown. OBJECTIVES: We sought to determine if GCTB stained for SOST on immunohistochemistry and correlate its expression with predictor variables. METHODS: All patients at a single institution undergoing surgery for GCTB between 1993 and 2008 with a minimum of 6 months follow-up were included. Primary outcomes included the presence of SOST staining, secondary outcomes included the correlation of patient and tumor-specific predictor variables. RESULTS: SOST antibody staining of any cell type was present in 47 of 48 cases (97.9%). Positivity of the stromal cells was present in 39 of 48 cases (81.3%) and was associated with radiographic aggressiveness (p = 0.023), symptomatic presentation (p = 0.032), prior surgery (p = 0.005), and patient age (p = 0.034). Positivity of giant cells was present in 41 of 48 cases (85.4%) and was not significant with predictive factors. CONCLUSIONS: Sclerostin staining in GCTB is a novel finding and warrants further research to define the role of sclerostin as a prognostic factor and therapeutic target.

Distant migration of gluteal augmentation fat presenting as a soft tissue knee mass.

Gluteal augmentation with autologous fat grafting is an increasingly popular procedure. While complication rates are low, the clinical and imaging evaluation of the various complications can be challenging. We report a case of distal migration of a failed gluteal fat graft in a young female patient presenting as a soft tissue mass in the knee, mimicking a soft tissue sarcoma. Surgical resection of the migrated fat graft confirmed the diagnosis. The diagnosis was challenging as the patient was initially reluctant to disclose her surgical history due to perceived negative social stigmas related to cosmetic contouring procedures. This case highlights the imaging findings of a rare complication following autologous fat grafting for gluteal augmentation and the importance of obtaining a thorough medical history.

Sclerostin Immunohistochemical Staining in Aggressive Maxillofacial Giant Cell Lesions: Initial Results and Potential Therapeutic Target.

INTRODUCTION: Maxillofacial (MF) giant cell lesions (GCLs) are benign, often locally aggressive lesions with potential for recurrence. Systemic treatments have included interferon alpha, calcitonin, bisphosphonates, and denosumab. Sclerostin (SOST) is typically thought to be a negative regulator of bone metabolism and anti-SOST agents have been used to treat osteoporosis; however, its role in central giant cell granuloma is unknown. The purpose of this study was to evaluate the expression of SOST in MF GCLs. MATERIALS AND METHODS: This was a retrospective study of patients with MF GCLs treated at a single institution between 1993 and 2008 with a minimum follow-up of 6 months. Representative tissue was used to create a tissue microarray and SOST immunohistochemical (IHC) staining and grading was performed. The primary outcomes were IHC staining of the stromal cells and giant cells. The secondary outcomes included correlation of IHC staining and patient predictor variables including clinically benign and aggressive lesions. All analyses were completed using univariate statistical tests. RESULTS: A total of 37 subjects were included (29 clinically aggressive and 8 clinically benign). Sclerostin staining was present in 30 of 37 subjects (81%). Of these, 22 (60%) had stromal cell staining and 28 (76%) had giant cell staining. The presence or absence of staining, of either cell type, was not associated with aggressiveness, presence of clinical symptoms, tumor size, previous interferon therapy, previous surgery, or the race or age of the patient. DISCUSSION: Maxillofacial GCLs have an overall high level of SOST staining; however, the role of SOST in treatment and prognosis is unknown and warrants further study.

Adjunct diagnostic strategies in improving diagnostic yields in image-guided biopsies of musculoskeletal neoplasms-A cost-effectiveness analysis.

BACKGROUND: Routine use of adjunct intraprocedural fresh frozen biopsy (FFP) or point-of-care (POC) cytology at the time of image-guided biopsy can improve diagnostic tissue yields for musculoskeletal neoplasms, but these are associated with increased costs. OBJECTIVE: This study aimed to ascertain the most cost-effective adjunctive test for image-guided biopsies of musculoskeletal neoplasms. METHODS: This expected value cost-effectiveness microsimulation compared the payoffs of cost (2020 United States dollars) and effectiveness (quality-adjusted life, in days) on each of the competing strategies. A literature review and institutional data were used to ascertain probabilities, diagnostic yields, utility values, and direct medical costs associated with each strategy. Payer and societal perspectives are presented. One- and two-way sensitivity analyses evaluated model uncertainties. RESULTS: The total cost and effectiveness for each of the strategies were $1248.98, $1414.09, $1980.53, and 80.31, 79.74, 79.69 days for the use of FFP, permanent pathology only, and POC cytology, respectively. The use of FFP dominated the competing strategies. Sensitivity analyses revealed FFP as the most cost-effective across all clinically plausible values. CONCLUSIONS: Adjunct FFP is most cost-effective in improving the diagnostic yield of image-guided biopsies for musculoskeletal neoplasms. These findings are robust to sensitivity analyses using clinically plausible probabilities.

Oncological and Functional Outcomes in Joint-sparing Resections of the Proximal Femur for Malignant Primary Bone Tumors.

BACKGROUND: Joint-sparing resections (JSR) of the proximal femur allow for preservation of the proximal femoral growth plate and native hip joint, but whether this offers fewer complications or better function and longevity of the reconstruction remains unknown. In this study, we compared the functional outcomes of pediatric patients with bone sarcomas undergoing JSR of the proximal femur with intercalary allograft (ICA) reconstruction to those undergoing proximal femoral resections (PFR) with allograft-prosthetic composite (APC) reconstructions. METHODS: We retrospectively reviewed all patients undergoing JSR with ICA reconstruction and PFR with APC reconstructions between 1995 and 2013 at a tertiary pediatric referral center. Primary outcomes included major and minor complications and secondary outcomes included the need for a secondary procedure, presence of local or distant relapse, survival status, and the presence of pain and ambulatory status (limp, assistive device, highest level of function). We assessed differences in outcomes using the Fisher exact and Wilcoxon rank-sum tests. RESULTS: Eight patients underwent a JSR and ICA reconstruction, while 7 patients underwent a PFR with APC reconstruction. Median patient follow-up was 60.4 months (interquartile range: 36.8 to 112.9) Patients undergoing JSR and ICA reconstruction were younger than patients undergoing PFR with APC reconstruction (7.7 vs. 11.7 y, P=0.043); however, we found no other statistically significant differences in patient demographics. There were no statistically significant differences in primary or secondary outcomes between the study groups; however, patients who underwent JSR with ICA had more major complications (62.5% vs. 42.9%, P=0.29) and a lower rate of minor complications (25% vs. 28.6%, P=0.22). CONCLUSION: Treatment of proximal femoral bone sarcomas in pediatric and adolescent patients remains a challenging enterprise. JSR with ICA reconstruction in the proximal femur, when feasible, may provide a similar function and risk of intermediate-term major and minor complications when compared with PFR with APC reconstruction. Further long-term studies are required to determine the impact of the native femoral head retention with respect to revision rates. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Person-environment interaction in a new secure forensic state psychiatric hospital.

This study examined the person-environment interaction effects of environmental design on ward climate, safety, job satisfaction, and treatment outcomes within a new high security forensic psychiatric facility. Participants included male and female adult psychiatric inpatients and staff members at different security stages. Data were collected once before and twice after the experimental group moved into the new building. The control group remained in the same facilities. Contrary to expectations, the new building had limited effects on the measured variables.

Mechanical performance of spider orb webs is tuned for high-speed prey.

Spiders in the Orbiculariae spin orb webs that dissipate the mechanical energy of their flying prey, bringing the insects to rest and retaining them long enough for the spider to attack and subdue their meals. Small prey are easily stopped by webs but provide little energetic gain. While larger prey offer substantial nourishment, they are also challenging to capture and can damage the web if they escape. We therefore hypothesized that spider orb webs exhibit properties that improve their probability of stopping larger insects while minimizing damage when the mechanical energy of those prey exceeds the web's capacity. Large insects are typically both heavier and faster flying than smaller prey, but speed plays a disproportionate role in determining total kinetic energy, so we predicted that orb webs may dissipate energy more effectively under faster impacts, independent of kinetic energy per se. We used high-speed video to visualize the impact of wooden pellets fired into orb webs to simulate prey strikes and tested how capture probability varied as a function of pellet size and speed. Capture probability was virtually nil above speeds of ~3 m s(-1). However, successful captures do not directly measure the maximum possible energy dissipation by orb webs because these events include lower-energy impacts that may not significantly challenge orb web performance. Therefore, we also compared the total kinetic energy removed from projectiles that escaped orb webs by breaking through the silk, asking whether more energy was removed at faster speeds. Over a range of speeds relevant to insect flight, the amount of energy absorbed by orb webs increases with the speed of prey (i.e. the rates at which webs are stretched). Orb webs therefore respond to faster - and hence higher kinetic energy - prey with better performance, suggesting adaptation to capture larger and faster flying insect prey. This speed-dependent toughness of a complex structure suggests the utility of the intrinsic toughness of spider silk and/or features of the macro-design of webs for high-velocity industrial or military applications, such as ballistic energy absorption.

Under-represented minorities in emergency medicine.

BACKGROUND: According to the Association of American Medical Colleges and the Institute of Medicine, promoting diversity in the health care workforce is a national priority. The under-representation of minorities in health care contributes significantly to the problem of health disparities currently facing racial and ethnic minority groups in the United States (US). Evidence shows that improved diversity among medical providers contributes to higher satisfaction for minority patients and better educational experiences for trainees. OBJECTIVE: Our aim was to describe the racial and ethnic composition of medical students, Emergency Medicine residents, and practicing Emergency Medicine Physicians as compared with other specialties and the US population. METHODS: A cross-sectional analysis of the most recent data available from the Association of American Medical Colleges and the US Census were used to determine the racial and ethnic distribution of the US population, medical students, residents, and practicing physicians. The Association of American Medical Colleges' definition of under-represented minorities (URMs) for the years studied included individuals of black, Latino, and Native-American race and ethnicity. Proportions with 95% confidence intervals were calculated. χ(2) analysis was used to compare groups. RESULTS: URMs comprised 30% of the total US population, yet only 6% of all practicing physicians and 9% of Emergency Physicians self-identified as URMs. By comparison, 15% of medical students, 17% of all residents, and 14% of Emergency Medicine residents were URMs (p < 0.0001). CONCLUSIONS: Emergency Medicine, like other specialties, lacks the racial and ethnic diversity seen in the US population. Efforts to improve diversity at the resident level are limited by the number of URM students in medical school, and should include steps aimed at addressing this issue.

Critical Review of Oncologic Medical Malpractice Claims Against Orthopaedic Surgeons.

INTRODUCTION: The purpose of this study was to determine the most common allegations for malpractice litigation brought against orthopaedic surgeons for oncologic matters and the resulting verdicts. METHODS: The Westlaw Legal research database was queried for malpractice cases filed against orthopaedic surgeons for oncologic matters in the United States after 1980. Plaintiff demographics, state of filing, allegations, and outcomes of lawsuits were recorded and reported accordingly. RESULTS: A total of 36 cases met the inclusion and exclusion criteria and were subsequently included in the final analysis. The overall rate of cases filed remained consistent through the past four decades and was primarily related to a primary sarcoma diagnosis in adult women. The primary reason for litigation was failure to diagnose a primary malignant sarcoma (42%) followed by failure to diagnose unrelated carcinoma (19%). The most common states of filing were primarily located in the Northeast (47%), where a plaintiff verdict was also more commonly encountered as compared with other regions. Damages awarded averaged $1,672,500 with a range of $134, 231 to $6,250,000 and a median of $918,750. CONCLUSION: Failure to diagnose primary malignant sarcoma and unrelated carcinoma was the most common reason for oncologic litigation brought against orthopaedic surgeons. Although most of the cases ruled in favor of the defendant surgeon, it is important for orthopaedic surgeons to be aware of the potential errors that not only prevent litigation but also improve patient care.

Management of limb length discrepancy after bone sarcoma resection about the knee in the skeletally immature.

Patients with bone sarcomas increasingly choose limb salvage. This can lead to issues with limb length discrepancy (LLD) for the skeletally immature. We synthesize management options into an algorithm and report our results. Patients with bone sarcomas involving any location from the femoral diaphysis to the tibial diaphysis 12 years or younger were reviewed. Our clinical pathway prescribed patients with metadiaphyseal lesions to intercalary allograft reconstruction, epiphyseal lesions and less than 5 cm expected LLD to osteoarticular allograft and patients with more than 5 cm expected LLD to extendable prosthesis. Twenty patients met inclusion criteria: 11 with osteoarticular allografts, 5 with extendable prostheses and 4 with intercalary allografts; median age 11.5 years; median follow-up 8.2 years; and final median LLD 1.6 cm. Five patients had contralateral epiphysiodesis, two patients underwent contralateral femoral shortening and a median of 6 (range 4-8) lengthenings were performed for extendable prostheses. Four patients had residual LLD over 3 cm. There were 13 revisions in 8 patients and 2 amputations. Limb-salvage in paediatric bone sarcoma of the knee can be managed with multiple techniques producing satisfactory results in regards to LLD. Careful pre-operative planning and shared decision making is a requisite given the high rate of secondary procedures for both LLD and reconstructive failures. Level of evidence: Level III Retrospective Comparative Study.

The impact of radiotherapy on survival after surgical resection of chordoma with minimum five-year follow-up.

BACKGROUND CONTEXT: Local control remains a vexing problem in the management of chordoma despite advances in operative techniques and radiotherapy (RT) protocols. Existing studies show satisfactory local control rates with different treatment modalities. However, those studies with minimum follow-up more than 4 years demonstrate increasing rates of local failure. Therefore, mid-term local survival rates may be inadvertently elevated by studies with less than 4 years follow-up. PURPOSE: The purpose of this study is to report the mid-term results of primary spinal chordoma treated with en bloc resection and proton-based RT with minimum 5 years of follow-up. STUDY DESIGN/SETTING: Retrospective, single-center, cohort study. PATIENT SAMPLE: Patients undergoing primary surgical excision of a spine or sacral chordoma tumor between 1990 and 2016 at a single-institution were included. Patients were included if they had a local failure at any time, or they had a minimum of 5 years of follow up with no local failure. Patients were excluded if a prior surgical excision was performed or metastases were present at the time of referral. OUTCOME MEASURES: The outcome measures were local recurrence-free interval (LRFI) and overall survival (OS). METHODS: Demographic, clinical, oncologic and surgical variables, including margin status, as well as radiation doses and schedule (neoadjuvant, adjuvant, or both) were compared using Wilcoxon rank-sum or chi-squared testing. The goal RT dose was 70 Gray (total) and patients were stratified based on completing (C70) or receiving incomplete (I70) dosing. Overall survival (OS) and local-recurrence free interval (LRFI) were calculated using the Kaplan-Meier method. FUNDING STATEMENT: No funding was obtained for this work. RESULTS: Seventy-six patients were included in the final analysis. All patients had a minimum of 5-year follow-up (median 9.3 years, range 5.1-24.7 years). There were no significant clinical differences between the C70 and I70 RT groups. OS was greater for the C70 RT group (5-year OS 82% vs. 63%, p=.001). There was similar OS for the positive margin group (5-year OS 70% vs. 61%, p=.266). LRFI was greater for the C70 RT group (5-year OS 93% vs. 78%, p=.017). There was similar LRFI for the positive margin group (5-year OS 90% versus 87%, p=.810). CONCLUSION: Chordoma outcomes trend towards diminishing LRFI rates in the literature. Here we report the results of the operative management of primary spinal chordoma with minimum five year follow-up, the addition of C70 RT to surgical excision conferred a benefit to OS and local recurrence.

COVID-19 surge readiness: use cases demonstrating how hospitals leveraged digital identity access management for infection control and pandemic response.

BACKGROUND: Surging volumes of patients with COVID-19 and the high infectiousness of SARS-CoV-2 challenged hospital infection control/safety, staffing, care delivery and operations as few crises have. Imperatives to ensure security of patient information, defend against cybersecurity threats and accurately identify/authenticate patients and staff were undiminished, which fostered creative use cases where hospitals leveraged identity access and management (IAM) technologies to improve infection control and minimise disruption of clinical and administrative workflows. METHODS: Working with a leading IAM solution provider, implementation personnel in the USA and UK identified all hospitals/health systems where an innovative use of IAM technology improved facility infection control and pandemic response management. Interviews/communications with hospital clinical informatics leaders collected information describing the use case deployed. RESULTS: Eight innovative/valuable hospital use cases are described: symptom-free attestation by clinicians at shift start; detection of clinician exposure/contact tracing; reporting of clinician temperature checks; inpatient telehealth consults in isolation units; virtual visits between isolated patients and families; touchless single sign-on authentication; secure access enabled for rapid expansion of personnel working remotely; and monitoring of temporary worker attendance. DISCUSSION: No systematic, comprehensive survey of all implemented IAM client sites was conducted, and other use cases may be undetected. A standardised reporting/information sharing vehicle is needed whereby IAM use cases aiding facility pandemic response and infection control can be disseminated. CONCLUSIONS: Clinical care, infection control and facility operations were improved using IAM solutions during COVID-19. Facility end-user innovation in how IAM solutions are deployed can improve infection control/patient safety, care delivery and clinical workflows during surges of epidemic infectious diseases.

Biology and Cellular Tropism of a Unique Astrovirus Strain: Murine Astrovirus 2.

Murine astrovirus 2 (MuAstV2) is a novel murine astrovirus recently identified in laboratory and wild mice. MuAstV2 readily transmits between immunocompetent mice yet fails to transmit to highly immunocompromised mouse strains-a unique characteristic when contrasted with other murine viruses including other astroviruses. We characterized the viral shedding kinetics and tissue tropism of MuAstV2 in immunocompetent C57BL/6NCrl mice and evaluated the apparent resistance of highly immunocompromised NOD- Prkdcem26Cd52Il2rgem26Cd22 /NjuCrl mice to MuAstV2 after oral inoculation. Temporal patterns of viral shedding were determined by serially measuring fecal viral RNA. Tissue tropism and viral load were characterized and quantified by using in-situ hybridization (ISH) targeting viral RNA. Cellular tropism was characterized by evaluating fluorescent colocalization of viral ISH with various immunohistochemical markers. We found a rapid increase of fecal viral RNA in B6 mice, which peaked at 5 d after inoculation (dpi) followed by cessation of shedding by 168 dpi. The small intestine had the highest percentage of hybridization (3.09% of tissue area) of all tissues in which hybridization occurred at 5 dpi. The thymus displayed the next highest degree of hybridization (2.3%) at 7 dpi, indicating extraintestinal viral spread. MuAstV2 RNA hybridization was found to colocalize with only 3 of the markers evaluated: CD3 (T cells), Iba1 (macrophages), and cytokeratin (enterocytes). A higher percentage of CD3 cells and Iba1 cells hybridized with MuAstV2 as compared with cytokeratin at 2 dpi (CD3, 59%; Iba1, 46%; cytokeratin, 6%) and 35 dpi (CD3, 14%; Iba1, 55%; cytokeratin, 3%). Neither fecal viral RNA nor viral hybridization was noted in NCG mice at the time points examined. In addition, mice of mixed genetic background were inoculated, and only those with a functioning Il2rg gene shed MuAstV2. Results from this study suggest that infection of, or interaction with, the immune system is required for infection by or replication of MuAstV2.

Mechanical and structural properties of major ampullate silk from spiders fed carbon nanomaterials.

The dragline silk of spiders is of particular interest to science due to its unique properties that make it an exceptional biomaterial that has both high tensile strength and elasticity. To improve these natural fibers, researchers have begun to try infusing metals and carbon nanomaterials to improve mechanical properties of spider silk. The objective of this study was to incorporate carbon nanomaterials into the silk of an orb-weaving spider, Nephila pilipes, by feeding them solutions containing graphene and carbon nanotubes. Spiders were collected from the field and in the lab were fed solutions by pipette containing either graphene sheets or nanotubes. Major ampullate silk was collected and a tensile tester was used to determine mechanical properties for pre- and post-treatment samples. Raman spectroscopy was then used to test for the presence of nanomaterials in silk samples. There was no apparent incorporation of carbon nanomaterials in the silk fibers that could be detected with Raman spectroscopy and there were no significant improvements in mechanical properties. This study represents an example for the importance of attempting to replicate previously published research. Researchers should be encouraged to continue to do these types of investigations in order to build a strong consensus and solid foundation for how to go forward with these new methods for creating novel biomaterials.

The Role of CT Angiography in Evaluating Lower Extremity Trauma: 157 Patient Case Series at a Military Treatment Facility.

INTRODUCTION: Physical exam and angiography have important roles in the diagnosis of traumatic lower extremity vascular injury with similar reported high rates of sensitivity and specificity. It has been previously shown that CTA is not universally indicated in the setting of acute lower extremity trauma when a reliable physical examination is obtained. As such, the purpose of this study was to determine if obtaining a CTA following physical examination altered the clinical care of patients following high-energy lower extremity trauma and the generalizability to the military population. MATERIALS AND METHODS: Retrospective review of all patients who underwent lower extremity CTA during the initial trauma evaluation at a Level 1 Trauma Center from 2007 to 2014. RESULTS: One hundred and fifty-seven patients met inclusion criteria. One hundred and seventeen patient's initial physical exam excluded limb ischemia with 67 vascular injuries on CTA (9 underwent angiogram in the OR) with no reperfusions required. 40 patients had hard signs of ischemia or ABI's <0.90, 29 had injuries on CTA, and fifteen underwent a vascular reperfusion procedure for acute vascular injury. Ten of 15 reperfusions required no further angiography after CTA. The sensitivity and negative predictive value of physical exam for needed reperfusion were both 100%. There were no instances of missed vascular injury or readmission and 53 patients were discharged directly from the emergency room after a negative CTA. CONCLUSIONS: This study suggests that physical exam alone achieves a high sensitivity for vascular injury in lower extremity trauma. Physical exam excluded all lower extremity ischemia without the need for advanced imaging. While CTA was useful to confirm and localize the source of acute vascular injury, the majority of vascular injuries identified on CTA did not affect immediate clinical care and lead to additional unnecessary procedures. However, in patients with suspected vascular injury, a negative CTA was also used as rationale for immediate discharge from the emergency department without further clinical observation. When applied to the deployed military setting the results of this study support the use of physical exam to accurately diagnose limb threatening ischemia at the time of injury or Role 1 facilities with CTA reserved for diagnosing the level of the vascular injury and for potential patient clearance prior to prolonged evacuation.

Corrigendum to "Bilateral Proximal Tibia Stress Fractures through Persistent Physes".

[This corrects the article DOI: 10.1155/2018/8181547.].

The Eight Cs: a guide to success in an international emergency medicine educational collaboration.

The Tuscan Emergency Medicine Initiative (TEMI) is a comprehensive emergency medicine (EM) training program designed to build an EM training infrastructure in Tuscany, Italy. The program has successfully trained a team of instructors using a train-the-trainers model, certified 350 physicians who are already practicing in emergency departments (EDs), and established a master's program as a bridge to specialty training at the region's three universities. Using lessons learned from this program, the authors identify eight factors (The Eight Cs) that can serve as a guide to implementing a collaborative EM program in other environments: collaboration, context, culture, credibility, consulting, consistency, critique, and conclusion. Each of these topics is described in detail and may be useful to other international interventions.

Bilateral Proximal Tibia Stress Fractures through Persistent Physes.

INTRODUCTION: Fatigue fractures are stress fractures resulting from repetitive trauma in areas of stress concentration. Prior case reports and studies have described stress fractures through persistent physes about the olecranon and distal fibula, as evidenced by hyaline cartilage on histologic analysis. However, there have been no documented proximal tibia stress fractures through persistent physes. CASE PRESENTATION: A 29-year-old military male basic trainee with varus alignment about his knees suffered bilateral medial tibial plateau stress fractures several weeks into military basic training. He underwent radiographic and laboratory evaluation of his stress fractures and eventual operative fixation of his bilateral tibial plateau fractures. Intraoperative specimens obtained from the fracture sites distal to the articular surface demonstrated abnormal fibrous appearing tissue. Histology demonstrated the presence of hyaline cartilage. DISCUSSION: A 29-year-old military male basic trainee had bilateral proximal tibia stress fractures through persistent physes confirmed with biopsies demonstrating hyaline cartilage. Our belief is that the patient's persistent physes placed him at a greater risk for stress fractures and these may benefit from fixation in soldiers and athletes.