Deep Convolutional Neural Network for Dedicated Regions-of-Interest Based Multi-Parameter Quantitative Ultrashort Echo Time (UTE) Magnetic Resonance Imaging of the Knee Joint.

We proposed an end-to-end deep learning convolutional neural network (DCNN) for region-of-interest based multi-parameter quantification (RMQ-Net) to accelerate quantitative ultrashort echo time (UTE) MRI of the knee joint with automatic multi-tissue segmentation and relaxometry mapping. The study involved UTE-based T1 (UTE-T1) and Adiabatic T1ρ (UTE-AdiabT1ρ) mapping of the knee joint of 65 human subjects, including 20 normal controls, 29 with doubtful-minimal osteoarthritis (OA), and 16 with moderate-severe OA. Comparison studies were performed on UTE-T1 and UTE-AdiabT1ρ measurements using 100%, 43%, 26%, and 18% UTE MRI data as the inputs and the effects on the prediction quality of the RMQ-Net. The RMQ-net was modified and retrained accordingly with different combinations of inputs. Both ROI-based and voxel-based Pearson correlation analyses were performed. High Pearson correlation coefficients were achieved between the RMQ-Net predicted UTE-T1 and UTE-AdiabT1ρ results and the ground truth for segmented cartilage with acceleration factors ranging from 2.3 to 5.7. With an acceleration factor of 5.7, the Pearson r-value achieved 0.908 (ROI-based) and 0.945 (voxel-based) for UTE-T1, and 0.733 (ROI-based) and 0.895 (voxel-based) for UTE-AdiabT1ρ, correspondingly. The results demonstrated that RMQ-net can significantly accelerate quantitative UTE imaging with automated segmentation of articular cartilage in the knee joint.

Bone Biomarkers Based on Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is increasingly used to evaluate the microstructural and compositional properties of bone. MRI-based biomarkers can characterize all major compartments of bone: organic, water, fat, and mineral components. However, with a short apparent spin-spin relaxation time (T2*), bone is invisible to conventional MRI sequences that use long echo times. To address this shortcoming, ultrashort echo time MRI sequences have been developed to provide direct imaging of bone and establish a set of MRI-based biomarkers sensitive to the structural and compositional changes of bone. This review article describes the MRI-based bone biomarkers representing total water, pore water, bound water, fat fraction, macromolecular fraction in the organic matrix, and surrogates for mineral density. MRI-based morphological bone imaging techniques are also briefly described.

Whole knee joint mapping using a phase modulated UTE adiabatic T1ρ (PM-UTE-AdiabT1ρ ) sequence.

PURPOSE: To develop a 3D phase modulated UTE adiabatic T1ρ (PM-UTE-AdiabT1ρ ) sequence for whole knee joint mapping on a clinical 3 T scanner. METHODS: This new sequence includes six major features: (1) a magnetization reset module, (2) a train of adiabatic full passage pulses for spin locking, (3) a phase modulation scheme (i.e., RF cycling pair), (4) a fat saturation module, (5) a variable flip angle scheme, and (6) a 3D UTE Cones sequence for data acquisition. A simple exponential fitting was used for T1ρ quantification. Phantom studies were performed to investigate PM-UTE-AdiabT1ρ 's sensitivity to compositional changes and reproducibility as well as its correlation with continuous wave-T1ρ measurement. The PM-UTE-AdiabT1ρ technique was then applied to five ex vivo and five in vivo normal knees to measure T1ρ values of femoral cartilage, meniscus, posterior cruciate ligament, anterior cruciate ligament, patellar tendon, and muscle. RESULTS: The phantom study demonstrated PM-UTE-AdiabT1ρ 's high sensitivity to compositional changes, its high reproducibility, and its strong linear correlation with continuous wave-T1ρ measurement. The ex vivo and in vivo knee studies demonstrated average T1ρ values of 105.6 ± 8.4 and 77.9 ± 3.9 ms for the femoral cartilage, 39.2 ± 5.1 and 30.1 ± 2.2 ms for the meniscus, 51.6 ± 5.3 and 29.2 ± 2.4 ms for the posterior cruciate ligament, 79.0 ± 9.3 and 52.0 ± 3.1 ms for the anterior cruciate ligament, 19.8 ± 4.5 and 17.0 ± 1.8 ms for the patellar tendon, and 91.1 ± 8.8 and 57.6 ± 2.8 ms for the muscle, respectively. CONCLUSION: The 3D PM-UTE-AdiabT1ρ sequence allows volumetric T1ρ assessment for both short and long T2 tissues in the knee joint on a clinical 3 T scanner.

Bone Health Management in Elective Orthopaedic Surgery: A Claims-Based Observational Study.

Introduction: There are limited data on the management of bone health, including bone mineral density (BMD) evaluation and osteoporosis (OP) treatment, in patients undergoing elective orthopaedic surgeries. Methods: This was a retrospective cohort study using administrative claims data from Symphony Health, PatientSource for patients aged ≥50 years with documented kyphoplasty/vertebroplasty (KP/VP), total knee arthroplasty (TKA), and total hip arthroplasty (THA). Risk stratification to identify patients at very high risk for fracture (VHRFx) was based on clinical practice guideline recommendations to the extent information on variables of interest were available from the claims database. Results: A total of 251 919 patients met inclusion criteria: KP/VP (31 018), TKA (149 849), and THA (71 052). The majority were female (80.3%) with a mean (SD) age of 68.5 (7.5) years. Patients undergoing KP/VP were older and had a greater comorbidity burden associated with risk for falls, mobility issues, muscle weakness, and respiratory and cardiovascular diseases. In the 6 months before surgery, 11.8% of patients were tested and/or received treatment for OP. Patients undergoing KP/VP were more likely to be tested and/or treated (17.5%) than patients undergoing TKA (11.0%) or THA (10.9%). Overall, men had a lower rate of testing and/or treatment than women (4.6% vs 13.5%). In the 12 months before surgery, patients with an OP diagnosis and at VHRFx (30.8%) had a higher rate of treatment and/or testing than those without OP (11.5%), or those without OP but with a fracture in the year preceding surgery (10.2%). Conclusions: Bone health management is suboptimal in patients undergoing elective orthopaedic surgeries and is worse in men than in women. Proper management of OP before and after surgery may improve outcomes.

Proceedings of the 2022 Santa Fe Bone Symposium: Current Concepts in the Care of Patients with Osteoporosis and Metabolic Bone Diseases.

The 22nd Annual Santa Fe Bone Symposium (SFBS) was a hybrid meeting held August 5-6, 2022, with in-person and virtual attendees. Altogether, over 400 individuals registered, a majority of whom attended in-person, representing many states in the USA plus 7 other countries. The SFBS included 10 plenary presentations, 2 faculty panel discussions, satellite symposia, Bone Health & Osteoporosis Foundation Fracture Liaison Service Boot Camp, and a Project ECHO workshop, with lively interactive discussions for all events. Topics of interest included fracture prevention at different stages of life; how to treat and when to change therapy; skeletal health in cancer patients; advanced imaging to assess bone strength; the state of healthcare in the USA; osteosarcopenia; vitamin D update; perioperative bone health care; new guidelines for managing primary hyperparathyroidism; new concepts on bone modeling and remodeling; and an overview on the care of rare bone diseases, including hypophosphatasia, X-linked hypophosphatemia, tumor induced osteomalacia, osteogenesis imperfecta, fibrodysplasia ossificans progressiva, and osteopetrosis. The SFBS was preceded by the Santa Fe Fellows Workshop on Osteoporosis and Metabolic Bone Diseases, a collaboration of the Endocrine Fellows Foundation and the Osteoporosis Foundation of New Mexico. From the Workshop, 4 participating fellows were selected to give oral presentations at the bone symposium. These proceedings represent the clinical highlights of 2022 SFBS presentations and the discussions that followed, all with the aim of optimizing skeletal health and minimizing the consequences of fragile bones.

Gait outcomes following proximal tibial tumor resection and endoprosthetic reconstruction.

BACKGROUND: Despite the proximal tibia being a common site of primary malignant bone tumors, there is limited information about gait function following proximal tibial tumor resection and endoprosthetic reconstruction (PTR). RESEARCH QUESTION: What is the impact of PTR on gait and quality of life? METHODS: This was a cross-sectional study of patients ≥18 years old who were ≥2 years post-PTR compared to a control group of similar age and sex distribution. Eighteen participants (9 PTR, 9 Control) were recruited. Gait spatial-temporal data, joint kinematics and kinetics were collected at preferred and fast walking speeds. Community walking cadence, health-related quality of life (SF-36) and knee joint torque were assessed. Comparisons were performed using one-way ANOVAs with Bonferroni corrections for multiple comparisons. Nonparametric tests were used for data not normally distributed. RESULTS: Mean age was 31 years for each group (PTR range = 18-42 yrs, Control range = 18-44 yrs). Compared to both control and nonsurgical limbs, the surgical limb exhibited significantly decreased % single limb support time, reduced heel rise during terminal stance and an absence of normally occurring knee flexion angles, extensor moments and power generation during initial double limb support. Additionally, a reduced peak plantar flexor moment was found for the surgical as compared to the control limb. The number of gait abnormalities increased during fast walking. Significantly reduced surgical knee extensor torque on isokinetic testing and weakness of the knee and ankle on clinical examination support gait findings. During community walking, the number of low frequency strides was an average of 5.3 % greater for the PTR group (p <  0.05). Norm-based PTR group SF-36 component scores were within normal values (53.4 physical, 56.5 mental). SIGNIFICANCE: Gait abnormalities were consistent with ankle muscle resection and transposition and knee extensor mechanism disruption. Despite these deficits, walking speed and quality of life were relatively normal.

Prediction of soft tissue sarcoma response to radiotherapy using longitudinal diffusion MRI and a deep neural network with generative adversarial network-based data augmentation.

PURPOSE: The goal of this study was to predict soft tissue sarcoma response to radiotherapy (RT) using longitudinal diffusion-weighted MRI (DWI). A novel deep-learning prediction framework along with generative adversarial network (GAN)-based data augmentation was investigated for the response prediction. METHODS: Thirty soft tissue sarcoma patients who were treated with five-fraction hypofractionated radiation therapy (RT, 6Gy×5) underwent diffusion-weighted MRI three times throughout the RT course using an MR-guided radiotherapy system. Pathologic treatment effect (TE) scores, ranging from 0-100%, were obtained from the post-RT surgical specimen as a surrogate of patient treatment response. Patients were divided into three classes based on the TE score (TE ≤ 20%, 20% < TE < 90%, TE ≥ 90%). Apparent diffusion coefficient (ADC) maps of the tumor from the three time points were combined as 3-channel images. An auxiliary classifier generative adversarial network (ACGAN) was trained on 20 patients to augment the data size. A total of 15,000 synthetic images were generated for each class. A prediction model based on a previously described VGG-19 network was trained using the synthesized data, validated on five unseen validation patients, and tested on the remaining five test patients. The entire process was repeated seven times, each time shuffling the training, validation, and testing datasets such that each patient was tested at least once during the independent test stage. Prediction performance for slice-based prediction and patient-based prediction was evaluated. RESULTS: The average training and validation accuracies were 86.5% ± 1.6% and 84.8% ± 1.8%, respectively, indicating that the generated samples were good representations of the original patient data. Among the seven rounds of testing, slice by slice prediction accuracy ranged from 81.6% to 86.8%. The overall accuracy of the independent test sets was 83.3%. For patient-based prediction, 80% was achieved in one round and 100% was achieved in the remaining six rounds. The mean accuracy was 97.1%. CONCLUSION: This study demonstrated the potential to use deep learning to predict the pathologic treatment effect from longitudinal DWI. Accuracies of 83.3% and 97.1% were achieved on independent test sets for slice-based and patient-based prediction respectively.

Malignancy in giant cell tumor of bone: analysis of an open-label phase 2 study of denosumab.

BACKGROUND: Giant cell tumor of bone (GCTB) is a rare osteoclastogenic stromal tumor. GCTB can rarely undergo malignant transformation. This post hoc analysis evaluated and classified malignancies in patients with GCTB who received denosumab. METHODS: This analysis was conducted on patients with pathologically confirmed GCTB and measurable active disease treated with denosumab 120 mg subcutaneously once every 4 weeks, with loading doses on study days 8 and 15, as part of a phase 2, open-label, multicenter study. We identified potential cases of malignancy related to GCTB through an independent multidisciplinary review or medical history, associated imaging or histopathologic reports, and disease course. The findings were summarized and no statistical analysis was performed. RESULTS: Twenty of five hundred twenty-six patients (3.8%) who received at least one dose of denosumab were misdiagnosed with GCTB that was later discovered to be malignancies: five primary malignant GCTB, five secondary malignant GCTB, four sarcomatous transformations, and six patients with other malignancies (giant cell-rich osteosarcoma, undifferentiated pleomorphic sarcoma, spindle cell sarcoma, osteogenic sarcoma, phosphaturic mesenchymal tumor of mixed connective tissue type, and fibrosarcoma/malignant fibrous histiocytoma). Many malignancies were present before denosumab was initiated (8 definitive cases, 7 likely cases), excluding potential involvement of denosumab in these cases. Signs associated with potential misdiagnoses of GCTB included poor mineralization with denosumab treatment, rapid relapse in pain, or a failure of the typical dramatic improvement in pain normally observed with denosumab. CONCLUSIONS: Although rare, GCTB can undergo malignant transformation, and rates in this study were consistent with previous reports. Signs of poor mineralization or lack of response to denosumab treatment may warrant close monitoring. TRIAL REGISTRATION: clinicaltrials.gov , ( NCT00680992 ). Registered May 20, 2008.

Denosumab Treatment for Giant Cell Tumor of the Spine Including the Sacrum.

STUDY DESIGN: This was a subanalysis of an international, multicenter, open-label study. OBJECTIVE: The aim of this study was to assess the efficacy and safety of denosumab in a subset of patients with giant cell tumors of bone (GCTB) of the spine including the sacrum from an international, open-label, single-arm, phase 2 study (ClinicalTrials.gov: NCT00680992). SUMMARY OF BACKGROUND DATA: Standard GCTB treatment is surgical removal, either by curettage or resection, combined with intraoperative adjuvant therapy; however, some sites may not be amenable to resection (e.g., skull, spine). METHODS: Adults or skeletally mature adolescents with pathologically confirmed GCTB of the spine including the sacrum, and radiologically measurable evidence of active disease, were included. Patients received denosumab (120 mg subcutaneously) once every 4 weeks during the treatment phase, with loading doses on days 8 and 15 of the first cycle. Patients had surgically unsalvageable GCTB (Cohort 1), had planned surgery expected to result in severe morbidity (Cohort 2), or were enrolled from a previous GCTB study (Cohort 3). RESULTS: Overall, 132 patients were included in the safety analysis (103 in Cohort 1, 24 in Cohort 2, and five in Cohort 3); 131 patients were included in the efficacy analysis. Kaplan-Meier estimated probabilities of disease progression or recurrence were 3% (95% confidence interval [CI], 0.0-6.2) at year 1 and 7.4% (95% CI, 2.1-12.7) at years 3 and 5 in Cohort 1, and not estimable in Cohorts 2 and 3. Of 23 patients (Cohort 2) with surgery planned at baseline, 10 (43%) had on-study surgery; of these, one patient had reported disease progression or recurrence after the on-study surgery. Clinical benefit was reported in 83% of patients overall (all cohorts). CONCLUSION: Results from the analysis suggest that denosumab is potentially effective treatment for patients with GCTB of the spine including the sacrum. The adverse event profile was consistent with the full study population.Level of Evidence: 2.

Low prevalence (0.13%) of COVID-19 infection in asymptomatic pre-operative/pre-procedure patients at a large, academic medical center informs approaches to perioperative care.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in reduced performance of elective surgeries and procedures at medical centers across the United States. Awareness of the prevalence of asymptomatic disease is critical for guiding safe approaches to operative/procedural services. As COVID-19 polymerase chain reaction (PCR) testing has been limited largely to symptomatic patients, health care workers, or to those in communal care centers, data regarding asymptomatic viral disease carriage are limited. METHODS: In this retrospective observational case series evaluating UCLA Health patients enrolled in pre-operative/pre-procedure protocol COVID-19 reverse transcriptase (RT)-PCR testing between April 7, 2020 and May 21, 2020, we determine the prevalence of COVID-19 infection in asymptomatic patients scheduled for surgeries and procedures. RESULTS: Primary outcomes include the prevalence of COVID-19 infection in this asymptomatic population. Secondary data analysis includes overall population testing results and population demographics. Eighteen of 4,751 (0.38%) patients scheduled for upcoming surgeries and high-risk procedures had abnormal (positive/inconclusive) COVID-19 RT-PCR testing results. Six of 18 patients were confirmed asymptomatic and had positive test results. Four of 18 were confirmed asymptomtic and had inconclusive results. Eight of 18 had positive results in the setting of recent symptoms or known COVID-19 infection. The prevalence of asymptomatic COVID-19 infection was 0.13%. More than 90% of patients had residential addresses within a 67-mile geographic radius of our medical center, the median age was 58, and there was equal male/female distribution. CONCLUSION: These data demonstrating low levels (0.13% prevalence) of COVID-19 infection in an asymptomatic population of patients undergoing scheduled surgeries/procedures in a large urban area have helped to inform perioperative protocols during the COVID-19 pandemic. Testing protocols like ours may prove valuable for other health systems in their approaches to safe procedural practices during COVID-19.

Treatment of an Acromial Stress Fracture After Reverse Total Shoulder Arthroplasty With Teriparatide: A Case Report.

CASE: A 78-year-old woman who underwent reverse total shoulder arthroplasty (RTSA) for proximal humerus fracture developed a Type-3 acromial stress fracture, resulting in increased pain and decreased function 9 months post-op. She was managed nonoperatively with adjunctive teriparatide (FORTEO), and after a 4-month course, she had regained excellent motion and achieved union. CONCLUSION: Teriparatide is a viable adjunct in treating patients nonoperatively with acromial stress fractures after RTSA.

Treatment effect prediction for sarcoma patients treated with preoperative radiotherapy using radiomics features from longitudinal diffusion-weighted MRIs.

The objective of this study was to explore radiomics features from longitudinal diffusion-weighted MRIs (DWIs) for pathologic treatment effect prediction in patients with localized soft tissue sarcoma (STS) undergoing hypofractionated preoperative radiotherapy (RT). Thirty patients with localized STS treated with preoperative hypofractionated RT were recruited to this longitudinal imaging study. DWIs were acquired at three time points using a 0.35 T MRI-guided radiotherapy system. Treatment effect score (TES) was obtained from the post-surgery pathology as a surrogate of treatment outcome. Patients were divided into two groups based on TES. Response prediction was first performed using a support vector machine (SVM) with only mean apparent diffusion coefficient (ADC) or delta ADC to serve as the benchmark. Radiomics features were then extracted from tumor ADC maps at each of the three time points. Logistic regression and SVM were constructed to predict the TES group using features selected by univariate analysis and sequential forward selection. Classification performance using SVM with features from different time points and with or without delta radiomics were evaluated. Prediction performance using only mean ADC or delta ADC was poor (area under the curve (AUC) < 0.7). For the radiomics study using features from all time points and corresponding delta radiomics, SVM significantly outperformed logistic regression (AUC of 0.91 ± 0.05 v.s. 0.85 ± 0.06). Prediction AUC values using single or multiple time points without delta radiomics were all below 0.74. Including delta radiomics of mid- or post-treatment relative to the baseline drastically boosted the prediction. In this work, an SVM model was built to predict the TES using radiomics features from longitudinal DWI. Based on this study, we found that use of mean ADC, delta ADC, or radiomics features alone was not sufficient for response prediction, and including delta radiomics features of mid- or post-treatment relative to the baseline can optimize the prediction of TES, a pathologic and clinical endpoint.

A Phase II Trial of 5-Day Neoadjuvant Radiotherapy for Patients with High-Risk Primary Soft Tissue Sarcoma.

PURPOSE: In a single-institution phase II study, we evaluated the safety of a 5-day dose-equivalent neoadjuvant radiotherapy (RT) regimen for high-risk primary soft tissue sarcoma. PATIENTS AND METHODS: Patients received neoadjuvant RT alone (30 Gy in five fractions) to the primary tumor with standard margins. The primary endpoint was grade ≥2 late-radiation toxicity. Major wound complications, local recurrences, and distant metastases were also examined. In exploratory analysis, we evaluated germline biomarkers for wound toxicity and the effects of the study on treatment utilization. RESULTS: Over 2 years, 52 patients were enrolled with median follow-up of 29 months. Seven of 44 evaluable patients (16%) developed grade ≥2 late toxicity. Major wound complications occurred in 16 of 50 patients (32%); a signature defined by 19 germline SNPs in miRNA-binding sites of immune and DNA damage response genes, in addition to lower extremity tumor location, demonstrated strong predictive performance for major wound complications. Compared with the preceding 2-year period, the number of patients treated with neoadjuvant RT alone at our institution increased 3-fold, with a concomitant increase in the catchment area. CONCLUSIONS: A shorter 5-day neoadjuvant RT regimen results in favorable rates of wound complications and grade ≥2 toxicity after 2-year follow-up. Five-day RT significantly increased utilization of neoadjuvant RT at our high-volume sarcoma center. With further validation, a putative germline biomarker for wound complications may guide safer RT utilization.

Use of Denosumab in Children With Osteoclast Bone Dysplasias: Report of Three Cases.

Denosumab has been used successfully to treat disease-associated osteoclast overactivity, including giant cell tumor of bone. Given its mechanism of action, denosumab is a potent potential treatment of other osteoclast bone dysplasias including central giant cell granuloma (CGCG), aneurysmal bone cyst (ABC), and cherubism. Relatively little is known about the safety and efficacy of denosumab in patients with these conditions, especially in children. We report on 3 pediatric patients treated with denosumab over a 3-year period at UCLA Medical Center (Los Angeles and Santa Monica, CA, USA): a 12-year-old with recurrent ABC of the pelvis, a 14-year-old with CGCG of the mandible, and a 12-year-old with cherubism. All were started on a 1-year course of 15 doses 120 mg s.c., given monthly with two loading doses on day 8 and 15. All patients demonstrated rapid and pronounced clinical improvement while on denosumab, including a significant reduction in pain and sclerosis of lytic lesions on radiographs. Within 1 month of initiating therapy, 2 patients experienced hypocalcemia (Common Terminology Criteria for Adverse Events [CTCAE] grade 2) and hypophosphatemia, with 1 patient experiencing symptoms. One patient went on to experience symptomatic rebound hypercalcemia (CTCAE grade 4) 5 months after completing therapy, requiring bisphosphonates and calcitonin. For the second patient, we developed a schedule to wean denosumab involving the progressive lengthening of time between doses from 1 to 4 months in 1-month increments before cessation. We found that denosumab therapy results in significant clinical and radiographic improvement for pediatric patients with nonresectable ABC, CGCG, and cherubism. Problems with serum calcium may be more common in younger patients, with symptomatic and protracted rebound hypercalcemia after cessation of therapy the most significant. We present a potential solution to this problem with progressive spacing of doses. Potential serious adverse events from alterations in calcium homeostasis should be explored in prospective clinical trials. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Standardized Hospital-Based Care Programs Improve Geriatric Hip Fracture Outcomes: An Analysis of the ACS NSQIP Targeted Hip Fracture Series.

OBJECTIVE: To determine relative complication rates and outcome measures in patients treated under a standardized hip fracture program (SHFP). METHODS: The American College of Surgeons National Surgical Quality Improvement Program was queried to identify patients who underwent operative fixation of femoral neck, intertrochanteric hip, and subtrochanteric hip fractures in 2016. Cohorts of patients who were and were not treated under a documented SHFP were identified. Relevant perioperative clinical and outcomes data were collected. Multivariate regression was used to assess risk-adjusted complication rates and outcomes for patients treated in SHFPs. RESULTS: A total of 9360 hip fracture patients were identified of whom 5070 (54.2%) were treated under a documented SHFP. Median age was 84 years, and 69.9% of patients were women. Patients in an SHFP had a lower risk-adjusted incidence of postoperative deep vein thrombosis [odds ratio (OR) 0.48 (0.32-0.72), P < 0.001]. Rates of other medical and surgical complications and 30-day mortality were statistically comparable. Risk-adjusted evaluation showed that SHFP patients were less likely to be discharged to an inpatient facility versus home [OR 0.72 (0.63-0.81), P < 0.001] and had a lower 30-day readmission rate [OR 0.83 (0.71-0.97), P = 0.023]. Furthermore, the SHFP patients had higher rates of immediate postoperative weight-bearing as tolerated [OR 1.23 (1.10-1.37), P < 0.001], adherence to deep vein thrombosis prophylaxis at 28 days [OR 1.27 (1.16-1.38), P < 0.001], and initiation of bone protective medications [OR 1.79 (1.64-1.96), P < 0.001]. CONCLUSIONS: Care in a modern hospital-based SHFP is associated with improved short-term outcome measures. Further development and widespread implementation of organized, multidisciplinary orthogeriatric hip fracture protocols is recommended. LEVEL OF EVIDENCE: Therapeutic Level III.

The measurement of physical functioning among patients with Tenosynovial Giant Cell Tumor (TGCT) using the Patient-Reported Outcomes Measurement Information System (PROMIS).

BACKGROUND: Tenosynovial giant cell tumor (TGCT), a rare, locally aggressive neoplasm of the synovium of joints and tendon sheaths, is associated with joint destruction, pain and swelling. Impacts on physical function (PF) vary depending on tumor size and location. The aim of this study was to identify relevant items, and demonstrate the content validity of custom measures of lower extremity PF from the Patient-Reported Outcomes Measurement Information System Physical Function Physical Function (PROMIS-PF) item bank among patients with TGCT. METHODS: Patients were recruited for qualitative research interviews to identify predominant TGCT symptoms and impacts. Patients completed a checklist to evaluate the relevance of each PROMIS-PF item. The publicly available PROMIS-PF item response theory (IRT) parameters were used to select items representing the range of the latent PF trait. RESULTS: Participants (n = 20) were 75% female, mean age 42.5 years. TGCTs were located in the knee (n = 15), hip (n = 3), and ankle (n = 2). Fifty-four PROMIS-PF items were identified as relevant by ≥20% of the participants. PF concepts discussed by participants during the qualitative interviews were also used to select relevant items. Selected items (n = 13) were used to create a physical function subscale specific to lower extremity tumors. CONCLUSIONS: We describe a novel method of combining qualitative research and IRT-based item information to select a relevant and content valid subset of PROMIS-PF items to assess heterogeneous impacts on PF in TGCT, a rare disease population.

Bisphosphonate-related atypical femoral fracture: Managing a rare but serious complication.

Atypical femoral fracture is a rare but serious complication of long-term bisphosphonate therapy. Although the benefit of preventing osteoporotic fractures greatly outweighs the risk of atypical fracture in bisphosphonate users, concern about atypical fracture risk has led to a decrease in bisphosphonate use. What are the risks, and how do we treat atypical femoral fracture?

Tenosynovial giant cell tumor: case report of a patient effectively treated with pexidartinib (PLX3397) and review of the literature.

BACKGROUND: Tenosynovial giant cell tumors (TGCTs) or giant cell tumors of tendon sheath are neoplasms that arise in the synovium. They can be categorized as nodular (localized) or diffuse type (D-TGCT). Historically, surgery has been the mainstay of therapy, but diffuse type disease recurs at a high rate and treatment often requires increasingly morbid procedures. Elucidation of the importance of the colony-stimulating factor (CSF1)/CSF1 receptor (CSF1R) pathway in the pathogenesis of this disease has created significant interest in targeting this pathway as a novel TGCT treatment approach. Pexidartinib, a selective tyrosine kinase inhibitor against CSF1R, showed an 83% disease control rate (52% with partial response and 31% with stable disease) in a recent phase 1 study of patients with TGCT. CASE PRESENTATION: We present an illustrative example of a TGCT patient who would have required a morbid operation who derived considerable clinical benefit from pexidartinib treatment. Her tumor volume decreased by 48% after 4 months of treatment, and 55 months after starting treatment the patient exhibits continued disease stability with minimal clinical symptoms, and significant improvement in functional status. CONCLUSIONS: This case illustrates the effectiveness of systemic therapy in controlling a disease associated with high surgical morbidity. This approach may be especially useful in the treatment of extra-articular disease which often invades neurovascular bundles; as the effectiveness in metastatic disease is still unknown. In the future, systemic treatment for TGCT may be appropriate for the neoadjuvant setting to decrease disease burden prior to surgery with the aim of decreasing recurrence rates. However, properly designed prospective studies will need to be carried out to answer these questions.

Long-term Outcomes With Ifosfamide-based Hypofractionated Preoperative Chemoradiotherapy for Extremity Soft Tissue Sarcomas.

OBJECTIVES: The objective of this study was to analyze outcomes for patients with soft tissue sarcoma of the extremities using neoadjuvant ifosfamide-based chemotherapy and hypofractionated reduced dose radiotherapy, followed by limb-sparing surgery. MATERIALS AND METHODS: An Institutional Review Board (IRB)-approved retrospective review of patients treated at a single institution between 1990 and 2013 was performed. In total, 116 patients were identified who received neoadjuvant ifosfamide-based chemotherapy and 28 Gy in 8 fractions of preoperative radiation (equivalent dose in 2 Gray fractions, 31.5 Gy [α/ß 10] 36.4 Gy [α/ß 3]) followed by limb-sparing surgery. Local recurrence (LR), distant failure (DF), and overall survival (OS) were calculated. Univariate and multivariate analysis for LR, DF, and OS were performed using Cox analysis. Statistical significance was set at a P<0.05. RESULTS: Median follow-up was 5.9 years (range, 0.3 to 24 y). Actuarial LR at 3/6 years was 11%/17%, DF at 3/6 years was 25%/35%, and OS at 3/6 years was 82%/67%. On multivariate analysis, only a positive surgical margin was significantly correlated with worse local control (P=0.005; hazard ratio [HR], 18.33; 95% confidence interval (CI), 2.41-139.34). Age over 60 years (P=0.03; HR, 2.34; 95% CI, 1.10-4.98) and tumor size over 10 cm compared with tumor size ≤5 cm (P=0.03; HR, 3.32; 95% CI, 1.15-9.61) were associated with worse OS. CONCLUSIONS: Soft tissue extremity sarcoma patients treated using reduced dose hypofractionated preoperative radiotherapy in combination with ifosfamide-based chemotherapy shows acceptable local control and warrants further investigation.