Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Tenosynovial giant cell tumour (TGCT) is a locally aggressive neoplasm for which few systemic treatment options exist. This study evaluated the efficacy and safety of vimseltinib, an oral, switch-control, CSF1R inhibitor, in patients with symptomatic TGCT not amenable to surgery. METHODS: MOTION is a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial done in 35 specialised hospitals in 13 countries. Eligible patients were adults (aged ≥18 years) with a histologically confirmed diagnosis of TGCT for which surgical resection could potentially worsen functional limitation or cause severe morbidity. Patients were randomly assigned (2:1) with interactive response technology to vimseltinib (30 mg orally twice weekly) or placebo, administrated in 28-day cycles for 24 weeks. Patients and site personnel were masked to treatment assignment until week 25, unless progressive disease was confirmed earlier. The primary endpoint was objective response rate by independent radiological review using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) at week 25 in the intention-to-treat population. Safety was assessed in all patients who received the study drug. The trial is registered with ClinicalTrials.gov, NCT05059262, and enrolment is complete. FINDINGS: Between Jan 21, 2022, and Feb 21, 2023, 123 patients were randomly assigned (83 to vimseltinib and 40 to placebo). 73 (59%) patients were female and 50 (41%) were male. Nine (11%) of 83 patients assigned to vimseltinib and five (13%) of 40 patients assigned to placebo discontinued treatment before week 25; one patient in the placebo group did not receive any study drug. Objective response rate per RECIST was 40% (33 of 83 patients) in the vimseltinib group vs 0% (none of 40) in the placebo group (difference 40% [95% CI 29-51]; p<0·0001). Most treatment-emergent adverse events (TEAEs) were grade 1 or 2; the only grade 3 or 4 TEAE that occurred in more than 5% of patients receiving vimseltinib was increased blood creatine phosphokinase (eight [10%] of 83). One patient in the vimseltinib group had a treatment-related serious TEAE of subcutaneous abscess. No evidence of cholestatic hepatotoxicity or drug-induced liver injury was noted. INTERPRETATION: Vimseltinib produced a significant objective response rate and clinically meaningful functional and symptomatic improvement in patients with TGCT, providing an effective treatment option for these patients. FUNDING: Deciphera Pharmaceuticals.

Hip Preservation and Capanna Reconstruction for Pediatric Proximal Femur Ewing Sarcoma: A Report of 2 Cases.

CASE: This is a first report describing preservation of the femoral head by transcervical resection of proximal femoral Ewing sarcoma in 2 pediatric patients. A unique Capanna reconstruction supported joint salvage. At 1 year, Pediatric Outcomes Data Collection Instrument and Pediatric Toronto Extremity Salvage Score outcomes were excellent. Surveillance magnetic resonance imaging was without evidence of recurrence or impaired perfusion to the femoral head. CONCLUSION: We demonstrate the feasibility of hip joint preservation and maintenance of femoral head viability after transcervical resection of pediatric proximal femur bone sarcomas while preserving the medial circumflex femoral artery. This technique may be a preferred option over joint sacrifice and endoprosthetic replacement in young patients when tumor margins permit.

Antibiotic calcium sulphate beads lower the bacterial burden and prevent infection in a mouse model of periprosthetic joint infection.

Aims: Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. Methods: A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 105 colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs. Results: The mean in vivo bioluminescence in the VB group was significantly lower on POD 8 and POD 10 compared with the other groups. There was a significant 1.3-log10 (95%) and 1.5-log10 (97%) reduction in mean soft-tissue CFUs in the VB group compared with the VP and IC groups (3.6 × 103 vs 7.0 × 104; p = 0.022; 3.6 × 103 vs 1.0 × 105; p = 0.007, respectively) at POD 21. There was a significant 1.6-log10 (98%) reduction in mean implant CFUs in the VB group compared with the IC group (1.3 × 100 vs 4.7 × 101, respectively; p = 0.038). Combined soft-tissue and implant infection was prevented in 10 of 19 mice (53%) in the VB group as opposed to 5 of 21 (24%) in the VP group, 3 of 15 (20%) in the IC group, and 0% in the SV group. Conclusion: In our in vivo mouse model, antibiotic-releasing calcium sulphate beads appeared to outperform vancomycin powder alone in lowering the bacterial burden and preventing soft-tissue and implant infections.

Active surveillance of diffuse-type tenosynovial giant cell tumors: A retrospective, multicenter cohort study.

BACKGROUND: Diffuse-type tenosynovial giant cell tumor (D-TGCT) is a mono-articular, soft-tissue tumor. Although it can behave locally aggressively, D-TGCT is a non-malignant disease. This is the first study describing the natural course of D-TGCT and evaluating active surveillance as possible treatment strategy. METHODS: This retrospective, multicenter study included therapy naïve patients with D-TGCT from eight sarcoma centers worldwide between 2000 and 2019. Patients initially managed by active surveillance following their first consultation were eligible. Data regarding the radiological and clinical course and subsequent treatments were collected. RESULTS: Sixty-one patients with primary D-TGCT were initially managed by active surveillance. Fifty-nine patients had an MRI performed around first consultation: D-TGCT was located intra-articular in most patients (n = 56; 95 %) and extra-articular in 14 cases (24 %). At baseline, osteoarthritis was observed in 13 patients (22 %) on MRI. Most of the patients' reported symptoms: pain (n = 43; 70 %), swelling (n = 33; 54 %). Eight patients (13 %) were asymptomatic. Follow-up data were available for 58 patients; the median follow-up was 28 months. Twenty-one patients (36 %) had radiological progression after 21 months (median). Eight of 45 patients (18 %) without osteoarthritis at baseline developed osteoarthritis during follow-up. Thirty-seven patients (64 %) did not clinically deteriorate during follow-up. Finally, eighteen patients (31 %) required a subsequent treatment. CONCLUSION: Active surveillance can be considered adequate for selected therapy naïve D-TGCT patients. Although follow-up data was limited, almost two-thirds of the patients remained progression-free, and 69 % did not need treatment during the follow-up period. However, one-fifth of patients developed secondary osteoarthritis. Prospective studies on active surveillance are warranted.

The MOTION study: a randomized, phase III study of vimseltinib for the treatment of tenosynovial giant cell tumor.

Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive neoplasm that occurs in the synovium of joints, bursae, or tendon sheaths and is caused by upregulation of the CSF1 gene. Vimseltinib is an oral switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit the CSF1 receptor. Here, we describe the rationale and design for the phase III MOTION trial (NCT05059262), which aims to evaluate the efficacy and safety of vimseltinib in participants with TGCT not amenable to surgical resection. In part 1, participants are randomized to receive vimseltinib 30 mg twice weekly or matching placebo for ≤24 weeks. Part 2 is a long-term treatment phase in which participants will receive open-label vimseltinib.

Tenosynovial giant cell tumor (or TGCT) is a rare, noncancerous tumor that grows in the soft tissue lining the spaces of joints and bursae (fluid-filled sacs that work to reduce friction in the joints). These tumors are linked to increased levels of a protein called CSF1. While this condition is typically treated with surgery, some patients may not be candidates for surgical removal of the tumor due to factors such as location or complexity of the tumor; therefore, drug treatments are needed to help these patients. Vimseltinib is an investigational oral drug specifically designed to inhibit the receptor to which the CSF1 protein binds. In this article, we describe the rationale and design for a phase III clinical trial that will test how well vimseltinib works in participants with TGCT who are not candidates for surgery. In the first part of the study, participants are randomly assigned to receive vimseltinib 30 mg twice weekly or a matching placebo (inactive substance) for up to 24 weeks. This first part is blinded, so participants will not know if they are receiving vimseltinib or the placebo. The second part of the study is a long-term treatment phase in which all participants will receive vimseltinib (unblinded). Clinical Trial Registration: NCT05059262 (ClinicalTrials.gov).

Prosthetic Limb Attachment via Electromagnetic Attraction through a Closed Skin Envelope.

OBJECTIVE: Current socket-based methods of prosthetic limb attachment are responsible for many of the dominant problems reported by persons with amputation. In this work, we introduce a new paradigm for attachment via electromagnetic attraction between a bone-anchored ferromagnetic implant and an external electromagnet. Our objective was to develop a design framework for electromagnetic attachment, and to evaluate this framework in the context of transfemoral amputation. METHODS: We first used inverse dynamics to calculate the forces required to suspend a knee-ankle-foot prosthesis during gait. We then conducted cadaveric dissections to inform implant geometry and design a surgical methodology for covering the implant. We also developed an in silico framework to investigate how electromagnet design affects system performance. Simulations were validated against benchtop testing of a custom-built electromagnet. RESULTS: The physical electromagnet matched simulations, with a root-mean-square percentage error of 4.2% between measured and predicted forces. Using this electromagnet, we estimate that suspension of a prosthesis during gait would require 33 W of average power. After 200 and 1000 steps of simulated walking, the temperature at the skin would increase 2.3℃ and 15.4℃ relative to ambient, respectively. CONCLUSION: Our design framework produced an implant and electromagnet that could feasibly suspend a knee-ankle-foot prosthesis during short walking bouts. Future work will focus on optimization of this system to reduce heating during longer bouts. SIGNIFICANCE: This work demonstrates the initial feasibility of an electromagnetic prosthetic attachment paradigm that has the potential to increase comfort and improve residual limb health for persons with amputation.

Thematic analysis of online discussion forums for soft tissue sarcomas.

BACKGROUND AND OBJECTIVES: As there is an increasing reliance on the internet for medical information, patients diagnosed with rare diseases have turned to online community forums to share information about their diagnoses. These forums help patients to gather and share information about their experience with disease. Additionally, these platforms enable patients to build unique connections based on their shared experiences. The objective of this study was to review shared posts in online community forums by individuals with soft tissue sarcomas to better understand commonly discussed themes. This information may improve the physicians' understanding of patients' concerns and feelings at the time of diagnosis and treatment. METHODS: We entered "sarcoma discussion forum" in search engines to identify internet discussion boards. Four major discussion forums were analyzed, and posts written between January 1, 2017 through May 1, 2022 addressing soft tissue sarcomas present in the upper and lower extremities were collected. Each post was analyzed by the two investigators in three steps (open coding, axial coding, and selective coding). RESULTS: A total of 506 posts were included in the final analysis. We used twenty-seven axial codes and four selective codes. Emotional Aspects/Connecting with Others was the most common theme (77 % of posts) followed by Information Support: Treatment (38 % of posts), Information Support: Diagnosis (24 % of posts) and Information Support: Recovery (21 % of posts). CONCLUSIONS: The most prevalent theme was centered on emotional aspects of these patients' journeys, highlighting the importance of providing resources to address emotional support for patients with soft tissue sarcoma and their families. LEVEL IV: Qualitative research study.

Monoclonal Antibody Disrupts Biofilm Structure and Restores Antibiotic Susceptibility in an Orthopedic Implant Infection Model.

Bacterial biofilms on orthopedic implants are resistant to the host immune response and to traditional systemic antibiotics. Novel therapies are needed to improve patient outcomes. TRL1068 is a human monoclonal antibody (mAb) against a biofilm anchoring protein. For assessment of this agent in an orthopedic implant infection model, efficacy was measured by reduction in bacterial burden of Staphylococcus aureus, the most common pathogen for prosthetic joint infections (PJI). Systemic treatment with the biofilm disrupting mAb TRL1068 in conjunction with vancomycin eradicated S. aureus from steel pins implanted in the spine for 26 of 27 mice, significantly more than for vancomycin alone. The mechanism of action was elucidated by two microscopy studies. First, TRL1068 was localized to biofilm using a fluorescent antibody tag. Second, a qualitative effect on biofilm structure was observed using scanning electron microscopy (SEM) to examine steel pins that had been treated in vivo. SEM images of implants retrieved from control mice showed abundant three-dimensional biofilms, whereas those from mice treated with TRL1068 did not. Clinical Significance: TRL1068 binds at high affinity to S. aureus biofilms, thereby disrupting the three-dimensional structure and significantly reducing implant CFUs in a well-characterized orthopedic model for which prior tested agents have shown only partial efficacy. TRL1068 represents a promising systemic treatment for orthopedic implant infection.

Approach to the Treatment of Expansile Metacarpal Aneurysmal Bone Cysts: A Report of Two Cases.

The two cases presented demonstrate the management of aneurysmal bone cysts of the metacarpal, which destroyed the normal bone architecture. Treatment of both cases included wide resection and metacarpal reconstruction with an intercalary fibular allograft. Denosumab use contrasts these two cases and is helpful in reestablishment of a cortical rim for fixation in the absence of a 1-cm margin proximally or distally to preserve the native carpometacarpal and metacarpophalangeal joints. Surgical resection and allograft reconstruction is a viable treatment for expansile metacarpal aneurysmal bone cysts, and neoadjuvant denosumab has utility in creating an ossified margin for fixation.

Arthroscopic debridement for acute hemorrhagic subacromial bursitis following COVID-19 vaccine administration: A case report.

The rapid rollout of vaccinations in response to the COVID-19 pandemic has led to their widespread distribution and administration throughout the world. The benefit of these vaccinations in preventing the spread of the disease and diminishing symptoms in patients who contract COVID-19 has been fervently studied and reported. While vaccinations remain an effective and generally safe method of limiting disease transmission and virus-related mortality, vaccine administration is not completely without risk. Shoulder injuries related to vaccine administration (SIRVA) have been described with previously available vaccines but have yet to be widely reported in the COVID-19 vaccination population. We present a case report of a young, high-functioning patient who presented with acute subacromial bursitis after COVID-19 vaccine administration due to improper vaccination technique. The patient was treated with arthroscopic shoulder surgery and had near immediate relief of shoulder symptoms.

The microbial profile of infected endoprosthetic reconstructions after wide excision for patients with musculoskeletal tumors: A call for pathogen-based practices.

BACKGROUND AND OBJECTIVES: Periprosthetic infection is a devastating complication following endoprosthetic reconstruction. This study utilized a large database of endoprostheses to describe the incidence, risk factors, and microbial profile of such infections to better catalogue and understand these catastrophic events. METHODS: A retrospective review of endoprosthetic reconstructions for an oncologic indication from January 1, 1981 to December 31, 2020 was performed. Demographic, oncologic, procedural and outcome data was analyzed. Multivariable logistic regression was used to identify potential risk factors for infection with significance defined as p < 0.05. RESULTS: Forty four out of 712 (6.2%) reconstructions resulted in infection at a mean time of 39.9 ± 44.5 months. Revision surgery (odds ratio [OR] 6.14, p < 0.001) or having a postoperative wound complication (OR 7.67, p < 0.001) were significantly associated with infection. Staphylococcus aureus and Staphylococcus epidermidis were the most commonly cultured organisms at a rate of 34.1% (15/44) and 22.7% (10/44), respectively. Ten infections resulted in amputation; five due to antimicrobial-resistant infections and three due to polymicrobial infections. CONCLUSION: Understanding the microbial profile of patients undergoing endoprosthetic reconstruction is paramount. This study demonstrates a relatively high rate of polymicrobial and antibiotic-resistant infections that portend worse outcomes, thus suggesting that pathogen-specific infectious practices may be warranted. LEVEL OF EVIDENCE: Retrospective cohort study, level III.

Multimodal management of tenosynovial giant cell tumors (TGCT) in the landscape of new druggable targets.

Tenosynovial giant cell tumor (TGCT) is a rare, benign, locally aggressive synovial based neoplastic process that can result in functional debilitation and end-stage arthrtitis. Although surgical resection is the primary treatment modality, novel systemic therapies are emerging as part of the multimodal armamentarium for patients with unresectable or complex disease burden. This review discusses the pathogenesis of TGCT, potential druggable targets and therapeutic approaches. It also evaluates the safety and efficacy of different systemic therapies.

Risk Factors for All-Cause Early Reoperation Following Tumor Resection and Endoprosthetic Reconstruction: A Secondary Analysis from the PARITY Trial.

BACKGROUND: Oncologic resection and endoprosthetic reconstruction of lower-extremity musculoskeletal tumors are complex procedures fraught with multiple modes of failure. A robust assessment of factors contributing to early reoperation in this population has not been performed in a large prospective cohort. The aim of the present study was to assess risk factors for early reoperation in patients who underwent tumor excision and endoprosthetic reconstruction, with use of data from the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial. METHODS: Baseline characteristics were assessed, including age, sex, tumor type, tumor location, presence of a soft-tissue mass, diabetes, smoking status, chemotherapy use, and neutropenia. Operative factors were recorded, including operative time, topical antibiotics, silver-coated prosthetics, endoprosthetic fixation, extra-articular resection, length of bone resected, margins, tranexamic acid, postoperative antibiotics, negative-pressure wound therapy, and length of stay. Univariate analysis was utilized to explore the differences between patients who did and did not undergo reoperation within 1 year postoperatively, and a multivariate Cox proportional hazards regression model was utilized to explore the predictors of reoperation within 1 year. RESULTS: A total of 155 (25.7%) of 604 patients underwent ≥1 reoperation. In univariate analysis, tumor type (p < 0.001), presence of a soft-tissue mass (p = 0.045), operative time (p < 0.001), use of negative-pressure wound therapy (p = 0.010), and hospital length of stay (p < 0.001) were all significantly associated with reoperation. On multivariate assessment, tumor type (benign aggressive bone tumor versus primary bone malignancy; hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.63; p = 0.01), operative time (HR per hour, 1.15; 95% CI, 1.10 to 1.23; p < 0.001), and use of negative-pressure wound therapy (HR, 1.93; 95% CI, 1.30 to 2.90; p = 0.002) remained significant predictors of reoperation within 1 year. CONCLUSIONS: Independent variables associated with reoperation within 1 year in patients who underwent tumor resection and endoprosthetic reconstruction included tumor type (benign aggressive bone tumor versus primary bone malignancy), operative time, and use of negative-pressure wound therapy. These results will help to inform patients and surgeons regarding the risk of reoperation by diagnosis and reinforce operative time as a factor influencing reoperation. These results also support further investigation into the use of negative-pressure wound therapy at the time of surgery in this patient population. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Most Patients With Bone Sarcomas Seek Emotional Support and Information About Other Patients' Experiences: A Thematic Analysis.

BACKGROUND: Online discussion forums allow individuals who otherwise may be strangers to create a community where they can seek and share information. Patients with bone sarcomas and their support networks use discussion forums dedicated to cancer support. There is a paucity of published reports regarding the care experience of patients with bone sarcomas because studies on online discussion groups have primarily focused on some of the more common cancers, including breast and prostate cancer. Understanding commonly discussed themes among patients with bone sarcomas would allow treating physicians to have a better understanding of patient concerns when providing patient education and counseling. QUESTION/PURPOSE: We performed this study to review posts from bone sarcoma internet discussion boards to establish common themes related to the care experience of patients with sarcomas. METHODS: Online discussion forums were identified using the search term "sarcoma discussion forum." After identifying 12 websites, we excluded closed forum groups, websites with missing or invalid links to forums, and nonpublic forums, such as groups on Facebook. These websites include profiles and photos that are personal, and sufficient author anonymity could not be achieved for this study. Posts written between January 1, 2012, and May 1, 2022, posted on five discussion boards were reviewed and collected until we reached a point of data saturation in which we agreed that the collection of additional posts would not reveal new themes. Discussion threads were filtered to identify posts pertaining to the most common bone sarcomas: chondrosarcoma, Ewing sarcoma, and osteosarcoma. Grounded theory-the methodology of repeated analyses of qualitative data to identify recurring themes or concepts-was used to analyze posts. Caregiver posts were delineated from patient posts and categorized separately for subgroup analysis. Grounded theory, although a qualitative method, endeavors to integrate the strengths inherent in quantitative methods with qualitative approaches. Grounded theory categorizes words, language, and the meanings these imply and seeks to organize and reduce the data gathered into themes or essences, which, in turn, can be fed into descriptions, models, or theories. Our analysis used three reviews of text to assign and group codes based on repeating ideas or concepts. The first review (open coding) aims to assign codes based on the verbatim text included by the author to capture the specific thoughts and ideas of the post. The second review (axial coding) aims to consolidate the ideas of posts by applying broader concepts to each post. The third and final review (selective coding) aims to further consolidate the themes of each post by trying to embody the main message contained in a post. A total of 570 posts from 139 threads were collected and analyzed using grounded theory. Twenty-five axial codes and four selective codes were created. We defined data saturation by the absence of a new open code in the analysis of a block of 50 posts to ensure that signals of saturation were not accepted too early in the analysis. RESULTS: The four selective codes included emotional aspects or connecting with others, information support: diagnosis, information support: treatment, and information support: recovery. Of these four codes, emotional aspects and connecting with others was the most prevalent theme (78% [445 of 570] of posts) followed by information support: treatment (49% [282 of 570] of posts). Information support: diagnosis and information support: recovery were each captured in 15% of posts. CONCLUSION: Analysis of posts reveals that the two most common themes involve seeking out emotional support and information about the experiences of others with various treatment modalities. Although most of the posts we assessed contained experiential information and emotional support rather than directed medical advice, future studies should assess the accuracy of information shared among online sarcoma forums. CLINICAL RELEVANCE: Physicians caring for patients with sarcomas should not only address patient concerns related to medical care, but also provide emotional support directly and assist patients by providing resources to peer support outlets, including online discussion forums. Although we cannot ascertain the proportion of patients who use online sites given the anonymity of posts included, these findings suggest common experiential themes across patients with sarcomas outside their doctors' offices. It is important that providers be aware of reputable forums to provide as resources for their patients. The Musculoskeletal Tumor Society may further benefit from endorsing one or more of these forums and providing physician oversight to monitor misinformation.

Proximal Femur Replacements for an Oncologic Indication Offer a Durable Endoprosthetic Reconstruction Option: A 40-year Experience.

BACKGROUND: Proximal femur replacements (PFRs) are an effective surgical option to treat primary and metastatic tumors causing large bony defects in the proximal femur. Given the relative rarity of these indications, current studies on PFR for oncologic indications are generally limited by patient volume or relatively short-term follow-up. Because recent advances in systemic therapy have improved the prognosis of patients who undergo limb salvage surgery for musculoskeletal tumors, data on the long-term durability of endoprosthetic reconstructions have become increasingly important. QUESTIONS/PURPOSES: (1) How does the long-term survival of cemented bipolar PFRs compare with patient survival in patients who underwent PFR for benign, aggressive, and metastatic tumors? (2) What are common reasons for revisions of primary PFRs? (3) Which factors are associated with survival of primary PFRs? (4) What is the survivorship free from conversion of bipolar PFRs to THA? METHODS: Between January 1, 1980, and December 31, 2020, we treated 812 patients with an endoprosthetic reconstruction for an oncologic indication. All patients who underwent a primary PFR for an oncologic indication were included in this study. The study cohort consisted of 122 patients receiving a primary PFR. Eighteen patients did not reach a censored endpoint such as death, revision, or amputation within 2 years. Thirty-three patients died within 2 years of their surgery. Of the 122 patients with primary PFRs, 39 did not reach a censored endpoint and have not been seen within the past 5 years. However, the mean follow-up time for these patients was longer than 10 years. The Social Security Death Index was queried to identify any patients who may have died but might not have been captured by our database To allow for adequate follow-up, endoprosthetic reconstructions performed after December 31, 2020 were excluded. The mean age at the time of the index surgery was 48 ± 22 years. The mean follow-up time of surviving patients was 7 ± 8 years. All PFRs were performed using a bipolar hemiarthroplasty with a cemented stem, and all implants were considered comparable. Demographic, oncologic, procedural, and outcome data including prosthesis survival, patient survival, complication rates, and rates of conversion to THA were analyzed. Patient, prosthesis, and limb salvage survival rates were generated, with implant revision as the endpoint and death as a competing risk. Statistical significance was defined as p < 0.05. RESULTS: Generally, patients with benign or low-grade (Stage I) disease outlived their implants (100% patient survival through 30 years; p = 0.02), whereas the opposite was true in patients with high-grade, localized Stage II disease (64% patient survival at 5 years [95% CI 49% to 76%]; p = 0.001) or widespread Stage III metastatic disease (6.2% patient survival at 5 years [95% CI 0.5% to 24%]; p < 0.001). Primary PFR implant survival at 5, 10, 20, and 30 years was 97% (95% CI 90% to 99%), 81% (95% CI 67% to 90%), 69% (95% CI 46% to 84%), and 51% (95% CI 24% to 73%), respectively. Eight percent (10 of 122) of primary PFRs were revised for any reason. The most common causes of revision were aseptic loosening (3% [four of 122]), infection (3% [three of 122]), breakage of the implant (2% [two of 122]), and tumor progression (1% [one of 122]). Follow-up time was the only factor that was associated with revision of primary PFRs. Neither segment length nor stem length were associated with revision of primary. Six percent (seven of 122) of PFRs were converted to THA at a mean 15 ± 8 years from the index procedure. Survivorship free from conversion to THA (accounting for death as a competing risk) was 94% (95% CI 85% to 99%), 86% (95% CI 68% to 94%). and 77% (95% CI 51% to 91%) at 10, 20, and 30 years, respectively. CONCLUSION: Cemented bipolar PFRs for an oncologic indication are a relatively durable reconstruction technique. Given the relative longevity and efficacy of PFRs demonstrated in our study, especially in patients with high-grade or metastatic disease where implant survival until all-cause revision was longer than patient survival, surgeons should continue to seriously consider PFRs in appropriate patients. The relative rarity of these reconstructions limits the number of patients in this study as well as in current research; thus, further multi-institutional collaborations are needed to provide the most accurate prognostic data for our patients. LEVEL OF EVIDENCE: Level III, therapeutic study.

Early identification of life-threatening soft-tissue infection using dynamic fluorescence imaging: first-in-kind clinical study of first-pass kinetics.

Necrotizing soft-tissue infections (NSTIs) are aggressive and deadly. Immediate surgical debridement is standard-of-care, but patients often present with non-specific symptoms, thereby delaying treatment. Because NSTIs cause microvascular thrombosis, we hypothesized that perfusion imaging using indocyanine green (ICG) would show diminished fluorescence signal in NSTI-affected tissues, particularly compared to non-necrotizing, superficial infections. Through a first-in-kind clinical study, we performed first-pass ICG fluorescence perfusion imaging of patients with suspected NSTIs. Early results support our hypothesis that ICG signal voids occur in NSTI-affected tissues and that dynamic contrast-enhanced fluorescence parameters reveal tissue kinetics that may be related to disease progression and extent.

The Role of Denosumab in the Treatment of Primary Tumors of Bone.

Many hand surgeons treat benign bone tumors without referral to orthopedic oncologists. However, there have been considerable advances in medical therapy for some of these tumors, with which hand surgeons may not be as familiar. This review focuses on the mechanism and uses of denosumab in the treatment of benign tumors of bone. Although the hand surgeon may not be directly prescribing this therapy, they are often the only physician treating the patient for these conditions. As such, awareness regarding the use of this therapy in reducing pain, decreasing tumor volume, and treatment of potential lung metastases is critical to those taking on these cases without the support of an orthopedic oncologist. This article aims to familiarize hand surgeons with denosumab to help promote knowledge of this therapeutic option and the potential role of this medication in the treatment of primary bone tumors in the hand.

Tenosynovial Giant Cell Tumor Observational Platform Project (TOPP) Registry: A 2-Year Analysis of Patient-Reported Outcomes and Treatment Strategies.

BACKGROUND: The Tenosynovial giant cell tumor Observational Platform Project (TOPP) registry is an international prospective study that -previously described the impact of diffuse-type tenosynovial giant cell tumour (D-TGCT) on patient-reported outcomes (PROs) from a baseline snapshot. This analysis describes the impact of D-TGCT at 2-year follow-up based on treatment strategies. MATERIAL AND METHODS: TOPP was conducted at 12 sites (EU: 10; US: 2). Captured PRO measurements assessed at baseline, 1-year, and 2-year follow-ups were Brief Pain Inventory (BPI), Pain Interference, BPI Pain Severity, Worst Pain, EQ-5D-5L, Worst Stiffness, and -Patient-Reported Outcomes Measurement Information System. Treatment interventions were no current/planned treatment (Off-Treatment) and systemic treatment/surgery (On-Treatment). RESULTS: A total of 176 patients (mean age: 43.5 years) were included in the full analysis set. For patients without active treatment strategy -(Off-Treatment) at baseline (n = 79), BPI Pain Interference (1.00 vs. 2.86) and BPI Pain Severity scores (1.50 vs. 3.00) were numerically favorable in patients remaining Off-Treatment compared with those who switched to an active treatment strategy at year 1. From 1-year to 2-year -follow-ups, patients who remained Off-Treatment had better BPI Pain Interference (0.57 vs. 2.57) and Worst Pain (2.0 vs. 4.5) scores compared with patients who switched to an alternative treatment strategy. In addition, EQ-5D VAS scores (80.0 vs. 65.0) were higher in patients who remained -Off-Treatment between 1-year and 2-year follow-ups compared with patients who changed treatment strategy. For patients receiving systemic treatment at baseline, numerically favorable scores were seen in patients remaining on systemic therapy at 1-year follow-up: BPI Pain Interference (2.79 vs. 5.93), BPI Pain Severity (3.63 vs. 6.38), Worst Pain (4.5 vs. 7.5), and Worst Stiffness (4.0 vs. 7.5). From 1-year to 2-year follow-up, EQ-5D VAS scores (77.5 vs. 65.0) were higher in patients who changed from systemic treatment to a different treatment strategy. CONCLUSION: These findings highlight the impact D-TGCT has on patient quality of life, and how treatment strategies may be influenced by these outcome measures. (ClinicalTrials.gov number: NCT02948088).

What are the indications and survivorship of tumor endoprosthetic reconstructions for patients with extremity metastatic bone disease?

BACKGROUND AND OBJECTIVES: Given advances in therapies, endoprosthetic reconstruction (EPR) in metastatic bone disease (MBD) may be increasingly indicated. The objectives were to review the indications, and implant and patient survivorship in patients undergoing EPR for MBD. METHODS: A review of patients undergoing EPR for extremity MBD between 1992 and 2022 at two centers was performed. Surgical data, implant survival, patient survival, and implant failure modes were examined. RESULTS: One hundred fifteen patients were included with a median follow-up of 14.9 months (95% confidence interval [CI]: 9.2-19.3) and survival of 19.4 months (95% CI: 13.6-26.1). The most common diagnosis was renal cell carcinoma (34/115, 29.6%) and the most common location was proximal femur (43/115, 37.4%). Indications included: actualized fracture (58/115, 50.4%), impending fracture (30/115, 26.1%), and failed fixation (27/115, 23.5%). Implant failure was uncommon (10/115, 8.7%). Patients undergoing EPR for failed fixation were more likely to have renal or lung cancer (p = 0.006). CONCLUSIONS: EPRs were performed most frequently for renal cell carcinoma and in patients with a relatively favorable survival. EPR was indicated for failed previous fixation in 23.5% of cases, emphasizing the importance of predictive survival modeling. EPR can be a reliable and durable surgical option for patients with MBD.

One-Stage Synovectomies Result in Improved Short-Term Outcomes Compared to Two-Stage Synovectomies of Diffuse-Type Tenosynovial Giant Cell Tumor (D-TGCT) of the Knee: A Multicenter, Retrospective, Cohort Study.

Diffuse-type tenosynovial giant cell tumors' (D-TGCTs) intra- and extra-articular expansion about the knee often necessitates an anterior and posterior surgical approach to facilitate an extensive synovectomy. There is no consensus on whether two-sided synovectomies should be performed in one or two stages. This retrospective study included 191 D-TGCT patients from nine sarcoma centers worldwide to compare the postoperative short-term outcomes between both treatments. Secondary outcomes were rates of radiological progression and subsequent treatments. Between 2000 and 2020, 117 patients underwent one-stage and 74 patients underwent two-stage synovectomies. The maximum range of motion achieved within one year postoperatively was similar (flexion 123-120°, p = 0.109; extension 0°, p = 0.093). Patients undergoing two-stage synovectomies stayed longer in the hospital (6 vs. 4 days, p < 0.0001). Complications occurred more often after two-stage synovectomies, although this was not statistically different (36% vs. 24%, p = 0.095). Patients treated with two-stage synovectomies exhibited more radiological progression and required subsequent treatments more often than patients treated with one-stage synovectomies (52% vs. 37%, p = 0.036) (54% vs. 34%, p = 0.007). In conclusion, D-TGCT of the knee requiring two-side synovectomies should be treated by one-stage synovectomies if feasible, since patients achieve a similar range of motion, do not have more complications, but stay for a shorter time in the hospital.