Patients Who Have Prior Solid Organ Transplants Have Increased Risk Of 10-Year Periprosthetic Joint Infection Revision Following Primary Total Knee Arthroplasty: A Propensity Matched Analysis.

BACKGROUND: Total knee arthroplasty (TKA) for solid organ transplant (SOT) patients is becoming more prominent as life expectancy in this population increases. However, data on long-term (10 year) implant survivorship in this cohort is sparse. The purpose of this study was to compare 90-day, 2-year, 5-year, and 10-year implant survivability following primary TKA in patients who did and did not have prior SOT. METHODS: The PearlDiver database was utilized to query patients who underwent unilateral elective TKA with at least 2 years of active follow-up. These patients were stratified into those who had a SOT before TKA and those who did not. The SOT cohort was propensity-matched to control patients based on age, sex, Charlson Comorbidity Index, and obesity in a 1:2 ratio. Cumulative incidence (CI) rates and hazard ratios (HR) were compared between the SOT, matched, and unmatched cohorts. RESULTS: No difference was observed in 10-year CI and risk of all-cause revision surgery in TKA patients with prior SOT when compared to matched and unmatched controls. Compared to the matched control, the SOT cohort had no difference in the risk of revision when stratified by indication and timing. However, when compared to the unmatched control, patients who had prior SOT had a higher risk for revision due to periprosthetic joint infection (PJI) at 10 years (HR: 1.80; 95% Confidence Interval: 1.17 to 2.76) as well as all-cause revision within 90 days after TKA (HR: 1.93; 95% Confidence Interval: 1.10 to 3.36). CONCLUSION: Prior SOT patients have higher rates of all-cause revision within 90 days and PJI within 10 years when compared to the general population, likely associated with the elevated number of comorbidities in SOT patients and not the transplant itself. Therefore, these patients should be monitored in the preoperative and early postoperative settings to optimize their known comorbidities.

Photoimmunotheranostics of epithelioid sarcoma by targeting CD44 or EGFR.

Epithelioid sarcoma (ES) is a rare soft tissue neoplasm with high recurrence rates. Wide surgical resection remains the only potential curative treatment. ES presents most commonly on the fingers, hands and forearm, making light-based cancer cell-targeted therapies such as near-infrared photoimmunotherapy (NIR-PIT) that is target-specific, but with limited penetration depth, suitable for ES treatment. We established that CD44 and EGFR were overexpressed in ES patient samples and in the VA-ES-BJ human ES cell line. NIR-PIT of VA-ES-BJ cells using antibody photosensitizer conjugates, prepared by conjugating a CD44 or EGFR monoclonal antibody to the photosensitizer IR700, confirmed that NIR-PIT with both conjugates resulted in cell death. Neither treatment with NIR light alone nor treatment with the conjugates but without NIR light were effective. CD44-IR700-PIT resulted in greater cell death than EGFR-IR700-PIT, consistent with the increased expression of CD44 by VA-ES-BJ cells. In tumors, EGFR-IR700 exhibited a higher tumor-to-normal ratio, as determined by in vivo fluorescence imaging, and a higher anti-tumor growth effect, compared to CD44-IR700. No antitumor effect of the EGFR antibody or the photosensitizer conjugate alone was observed in vivo. Our data support evaluating the use of EGFR-IR700-PIT in the management of ES for detecting and eliminating ES cells in surgical margins, and in the treatment of superficial recurrent tumors.

The therapeutic alliance between study participants and intervention facilitators is associated with acute effects and clinical outcomes in a psilocybin-assisted therapy trial for major depressive disorder.

We examined if the therapeutic alliance between study participants and intervention facilitators in a psilocybin-assisted therapy (PAT) trial changed over time and whether there were relationships between alliance, acute psilocybin experiences, and depression outcomes. In a randomized, waiting list-controlled clinical trial for major depressive disorder in adults (N = 24), participants were randomized to an immediate (N = 13) or delayed (N = 11) condition with two oral doses of psilocybin (20mg/70kg and 30mg/70kg). Ratings of therapeutic alliance significantly increased from the final preparation session to one-week post-intervention (p = .03, d = .43). A stronger total alliance at the final preparation session predicted depression scores at 4 weeks (r = -.65, p = .002), 6 months (r = -.47, p = .036), and 12 months (r = -.54, p = .014) post-intervention. A stronger total alliance in the final preparation session was correlated with higher peak ratings of mystical experiences (r = .49, p = .027) and psychological insight (r = .52, p = .040), and peak ratings of mystical experience and psychological insight were correlated with depression scores at 4 weeks (r = -.45, p = .030 for mystical; r = -.75, p < .001 for insight). Stronger total alliance one week after the final psilocybin session predicted depression scores at 4 weeks (r = -.85, p < .001), 3 months (r = -.52, p = .010), 6 months (r = -.77, p < .001), and 12 months (r = -.61, p = .001) post-intervention. These findings highlight the importance of the therapeutic relationship in PAT. Future research should explore therapist and participant characteristics which maximize the therapeutic alliance and evaluate its relationship to treatment outcomes. Trial registration: Registration: Clinicaltrials.gov NCT03181529. https://classic.clinicaltrials.gov/ct2/show/NCT03181529.

Progressive Improvement in 5-Year Survival Rates for Extremity Soft Tissue Sarcomas from 1999 to 2019.

Background: Extremity soft-tissue sarcoma (ESTS) is a group of rare, heterogeneous malignancies. Previous studies have demonstrated a progressive improvement in 5-year survival rate over time, but recent trends are unknown. Therefore, this study aimed to provide an update on the clinical characteristics and 5-year survival rate of ESTS from 1999 to 2019. Methods: This retrospective cohort study used the Surveillance, Epidemiology, and End Results (SEER) database. Overall, 5,654 patients over the age of 15 years with primary ESTS diagnosed between 1999 and 2019 were included. Data on patient demographics, clinical characteristics, and survival were extracted. Patients were grouped by year of diagnosis: 1999-2005, 2006-2012, and 2013-2019. Kaplan-Meier and Cox proportional hazards regression analyses were performed. Results: ESTS occurred primarily in the lower extremity (76.1%) and was frequently grade III (58.3%), >5 cm in size (69.9%), and without metastasis (77.9%) at diagnosis. Furthermore, there was a significant increase in the proportion of patients over age 60 (p < 0.001) and without metastasis (p < 0.001) over the study period. The 5-year survival rate successively improved, from 47% in 1999-2005, to 61% in 2006-2012, to 78% in 2013-2019. Similarly, in multivariate analysis, the mortality rate progressively declined from a hazard ratio (HR) of 3.4 in 1999-2005 to an HR of 2.1 in 2006-2012, with the 2013-2019 group having the best overall survival (p < 0.001). Age, tumor size, grade, and metastasis were negative prognostic factors for survival; radiation and surgery were positive prognostic factors. Conclusions: The 5-year overall survival rate for ESTS progressively improved over the 20-year study period, perhaps due to an increasing proportion of older patients diagnosed with local disease. These findings may also be related to earlier detection or more effective treatment over the study period.

Screening for Asymptomatic Osteonecrosis of the Hip in Systemic Lupus Erythematous: A Systematic Review and Meta-Analysis of MRI-Based Prevalence.

Objective. This paper aims to estimate asymptomatic hip osteonecrosis prevalence in SLE patients using MRI examination and to determine the prevalence among higher risk subpopulations. Materials and Methods. PubMed, Embase, Cochrane, and SCOPUS were searched from inception to May 9th, 2023. Studies on patients who were clinically diagnosed with systemic lupus erythematosus without reported symptoms attributable to hip osteonecrosis were included. Two independent reviewers extracted data and assessed the risk of bias. Data collected from each study include the study year, the number of hips screened, the number of hips with osteonecrosis, demographics, laboratory data, medications, follow-up time, radiological protocols, and MRI-based osteonecrosis detection and grading criteria. Results. Eleven eligible studies including 503 participants (15-35 years old; 74-100% female) with SLE were identified. Significant risk of bias was determined in one study. The overall prevalence of osteonecrosis of the hip was found to be 14% (184/1006 hip joints, 95% confidence interval: 7-22%, number needed to scan: 7.1). SLE patients who received corticosteroid treatment had a higher prevalence of asymptomatic hip osteonecrosis (18%) compared to non-corticosteroid users (0%, p-value < 0.01). Additionally, meta-regression results revealed that daily corticosteroid dose was associated with increased prevalence of asymptomatic osteonecrosis (0.5%/milligram, p-value < 0.01). Conclusions. The high prevalence of asymptomatic hip osteonecrosis in SLE patients raises concerns about the timeliness of interventions. The limitations of this study include a relatively low number of identified studies; and one study lacked full-text availability.

Life Expectancy After Treatment of Metastatic Bone Disease: An International Trend Analysis.

INTRODUCTION: The decision to treat metastatic bone disease (MBD) surgically depends in part on patient life expectancy. We are unaware of an international analysis of how life expectancy among these patients has changed over time. Therefore, we asked (1) how has the life expectancy for patients treated for MBD changed over time, and (2) which, if any, of the common primary cancer types are associated with longer survival after treatment of MBD? METHODS: We reviewed data collected from 2000 to 2022 in an international MBD database, as well as data used for survival model validation. We included 3,353 adults who underwent surgery and/or radiation. No patients were excluded. Patients were grouped by treatment date into period 1 (2000 to 2009), period 2 (2010 to 2019), and period 3 (2020 to 2022). Cumulative survival was portrayed using Kaplan-Meier curves; log-rank tests were used to determine significance at P < 0.05. Subgroup analyses by primary cancer diagnosis were performed. RESULTS: Median survival in period 2 was longer than in period 1 ( P < 0.001). Median survival (at which point 50% of patients survived) had not been reached for period 3. Median survival was longer in period 2 for all cancer types ( P < 0.001) except thyroid. Only lung cancer reached median survival in period 3, which was longer compared with periods 1 and 2 ( P < 0.001). Slow-growth, moderate-growth, and rapid-growth tumors all demonstrated longer median survival from period 1 to period 2; only rapid-growth tumors reached median survival for period 3, which was longer compared with periods 1 and 2 ( P < 0.001). DISCUSSION: Median duration of survival after treatment of MBD has increased, which was a consistent finding in nearly all cancer types. Longer survival is likely attributable to improvements in both medical and surgical treatments. As life expectancy for patients with MBD increases, surgical methods should be selected with this in mind. LEVEL OF EVIDENCE: VI.

Symptomatic Neuroma Development following En Bloc Resection of Skeletal and Soft-Tissue Tumors: A Retrospective Analysis of 331 Cases.

BACKGROUND: Although symptomatic neuroma formation has been described in other patient populations, these data have not been studied in patients undergoing resection of musculoskeletal tumors. This study aimed to characterize the incidence and risk factors of symptomatic neuroma formation following en bloc resection in this population. METHODS: The authors retrospectively reviewed adults undergoing en bloc resections for musculoskeletal tumors at a high-volume sarcoma center from 2014 to 2019. The authors included en bloc resections for an oncologic indication and excluded non-en bloc resections, primary amputations, and patients with insufficient follow-up. Data are provided as descriptive statistics, and multivariable regression modeling was performed. RESULTS: The authors included 231 patients undergoing 331 en bloc resections (female, 46%; mean age, 52 years). Nerve transection was documented in 87 resections (26%). There were 81 symptomatic neuromas (25%) meeting criteria of Tinel sign or pain on examination and neuropathy in the distribution of suspected nerve injury. Factors associated with symptomatic neuroma formation included age 18 to 39 [adjusted OR (aOR), 3.6; 95% CI, 1.5 to 8.4; P < 0.01] and 40 to 64 (aOR, 2.2; 95% CI, 1.1 to 4.6; P = 0.04), multiple resections (aOR, 3.2; 95% CI, 1.7 to 5.9; P < 0.001), preoperative neuromodulator requirement (aOR, 2.7; 95% CI, 1.2 to 6.0; P = 0.01), and resection of fascia or muscle (aOR, 0.5; 95% CI, 0.3 to 1.0; P = 0.045). CONCLUSION: The authors' results highlight the importance of adequate preoperative optimization of pain control and intraoperative prophylaxis for neuroma prevention following en bloc resection of tumors, particularly for younger patients with a recurrent tumor burden. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Nodular cystic fat necrosis: a distinctive rare soft-tissue mass.

We report the case of a 34-year-old female who was evaluated for a right lower extremity soft-tissue mass, found to be a large cystic lesion bound by fibrous tissue containing innumerable, freely mobile nodules of fat. Her presentation suggested the diagnosis of nodular cystic fat necrosis (NCFN), a rare entity that likely represents a morphological subset of fat necrosis potentially caused by vascular insufficiency secondary to local trauma. Her lesion was best visualized using MRI, which revealed characteristic imaging features of NCFN including nodular lipid-signal foci that suppress on fat-saturated sequences, intralesional fluid with high signal intensity on T2-weighted imaging, and a contrast-enhancing outer capsule with low signal intensity on T1-weighted imaging. Ultrasound imaging offered the advantage of showing mobile hyperechogenic foci within the anechoic cystic structure, and the lesion was otherwise visualized on radiography as a nonspecific soft-tissue radiopacity. She was managed with complete surgical excision with pathologic evaluation demonstrating, similar to the radiologic features, innumerable free-floating, 1-5 mm, smooth, nearly uniform spherical nodules of mature fat with widespread necrosis contained within a thick fibrous pseudocapsule. Follow-up imaging revealed no evidence of remaining or recurrent disease on postoperative follow-up MRI. The differential diagnosis includes lipoma with fat necrosis, lipoma variant, atypical lipomatous tumor, and a Morel-Lavallée lesion. There is overlap in the imaging features between fat necrosis and both benign and malignant adipocytic tumors, occasionally making this distinction based solely on imaging findings challenging. To our knowledge, this is the largest example of NCFN ever reported.

Impact of Consolidative Radiation on Overall and Progression-Free Survival in Pediatric, Adolescent, and Young Adult Metastatic Bone and Soft Tissue Sarcoma.

PURPOSE: To determine the association between consolidative radiation (RT) and survival in children, adolescents, and young adults with metastatic sarcoma. METHODS AND MATERIALS: Eligibility criteria included patients aged ≤39 years with newly diagnosed metastatic bone or soft tissue sarcoma who completed local control of the primary tumor without disease progression. Consolidative RT was defined as RT to all known sites of metastatic disease. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). The least absolute shrinkage and selection operator Cox provided adjusted estimates. To account for immortal time bias, consolidative RT was used as a time-varying covariate in a time dependent Cox model. Distant failure was estimated using the Fine-Gray model. RESULTS: Patients (n = 85) had a median age at diagnosis of 14.8 years. Most common histology was Ewing Sarcoma (45.9%) followed by rhabdomyosarcoma (40.0%). Receipt of consolidative RT was associated with Ewing Sarcoma (P < .001) and local control modality as those who underwent local control with surgery and RT compared with surgery alone were more likely to be treated with consolidative RT (P = .034). Consolidative RT was independently associated with improved OS (hazard ratio [HR], 0.41; 95% CI, 0.17-0.98; P = .045) and improved PFS (HR, 0.37; 95% CI, 0.16-0.88; P = .024) after adjusting for confounding variables and immortal time bias. Patients treated with consolidative RT also experienced a lower risk of distant failure (HR, 0.33; 95% CI, 0.17-0.64; P = .001). In an independent data set of patients with metachronous progression (n = 36), consolidative RT remained independently associated with improved OS. CONCLUSIONS: Consolidative RT was independently associated with improved OS and PFS and decreased risk of distant failure in child, adolescent, and young adult patients with metastatic sarcoma. Future work should evaluate biomarkers to optimize patient selection, timing, and dose for consolidative RT.

The use of weakly supervised machine learning for necrosis assessment in patients with osteosarcoma: A pilot study.

Percent necrosis (PN) following chemotherapy is a prognostic factor for survival in osteosarcoma. Pathologists estimate PN by calculating tumor viability over an average of whole-slide images (WSIs). This non-standardized, labor-intensive process requires specialized training and has high interobserver variability. Therefore, we aimed to develop a machine-learning model capable of calculating PN in osteosarcoma with similar accuracy to that of a musculoskeletal pathologist. In this proof-of-concept study, we retrospectively obtained six WSIs from two patients with conventional osteosarcomas. A weakly supervised learning model was trained by using coarse and incomplete annotations of viable tumor, necrotic tumor, and nontumor tissue in WSIs. Weakly supervised learning refers to processes capable of creating predictive models on the basis of partially and imprecisely annotated data. Once "trained," the model segmented areas of tissue and determined PN of the same six WSIs. To assess model fidelity, the pathologist also estimated PN of each WSI, and we compared the estimates using Pearson's correlation and mean absolute error (MAE). MAE was 15% over the six samples, and 6.4% when an outlier was removed, for which the model inaccurately labeled cartilaginous tissue. The model and pathologist estimates were strongly, positively correlated (r = 0.85). Thus, we created and trained a weakly supervised machine learning model to segment viable tumor, necrotic tumor, and nontumor and to calculate PN with accuracy similar to that of a musculoskeletal pathologist. We expect improvement can be achieved by annotating cartilaginous and other mesenchymal tissue for better representation of the histological heterogeneity in osteosarcoma.

Predicting Risk of 30-day Postoperative Morbidity Using the Pathologic Fracture Mortality Index.

INTRODUCTION: The purpose of this study was to evaluate the ability of the Pathologic Fracture Mortality Index (PFMI) to predict the risk of 30-day morbidity after pathologic fracture fixation and compare its efficacy with those of the American Society of Anesthesiologists (ASA) physical status, modified Charlson Comorbidity Index (mCCI), and modified frailty index (mFI-5). METHODS: Cohorts of 1,723 patients in the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2020 and 159 patients from a tertiary cancer referral center who underwent fixation for impending or completed pathologic fractures of long bones were retrospectively analyzed. National Surgical Quality Improvement Program morbidity variables were categorized into medical, surgical, utilization, and all-cause. PFMI, ASA, mCCI, and mFI-5 scores were calculated for each patient. Area under the curve (AUC) was used to compare efficacies. RESULTS: AUCs predicting all-cause morbidity were 0.62, 0.54, and 0.56 for the PFMI, ASA, and mFI-5, respectively. The PFMI outperformed the ASA and mFI-5 in predicting all-cause ( P < 0.01), medical ( P = 0.01), and utilization ( P < 0.01) morbidities. In the 2005 to 2012 subset, the PFMI outperformed the ASA, mFI-5, and mCCI in predicting all-cause ( P = 0.01), medical ( P = 0.03), and surgical ( P = 0.05) morbidities but performed similarly to utilization morbidity ( P = 0.19). In our institutional cohort, the AUC for the PFMI in morbidity stratification was 0.68. The PFMI was associated with all-cause (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.12 to 1.51; P < 0.001), medical (OR, 1.19; 95% CI, 1.03 to 1.40; P = 0.046), and utilization (OR, 1.32; 95% CI, 1.14 to 1.52; P < 0.001) morbidities but not significantly associated with surgical morbidity (OR, 1.21; 95% CI, 0.98 to 1.49; P = 0.08) in this cohort. DISCUSSION: The PFMI is an advancement in postoperative morbidity risk stratification of patients with pathologic fracture from metastatic disease. LEVEL OF EVIDENCE: III.

The efficacy and safety of direct oral anticoagulants compared with low-molecular-weight heparin for venous thromboembolism prophylaxis after surgical resection of primary lower extremity bone or soft-tissue sarcoma.

INTRODUCTION: The incidence of postoperative venous thromboembolism (VTE) and wound complications is greater after sarcoma resection. We sought to identify differences in postoperative VTE and bleeding complications with direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) following resection of lower extremity primary bone or soft tissue sarcoma. METHODS: We retrospectively identified 2083 patients from the PearlDiver database who underwent resection of primary bone or soft tissue sarcoma of the lower extremity from January 2010 to October 2021 and prescribed LMWH or DOAC within 90-days postoperatively. The primary outcomes were comparison of postoperative incidence and odds of deep venous thrombosis (DVT), pulmonary embolism (PE), and bleeding complications within 90-days following resection. RESULTS: Patients prescribed DOACs had a greater odds of DVT (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.06-2.41; p = 0.024) and PE (OR: 3.38; 95% CI: 1.96-5.86; p < 0.001) within 90-days following resection of bone sarcoma when compared with the LMWH cohort. Patients undergoing resection of soft tissue sarcomas also had greater odds DVT (OR: 1.65; 95% CI: 1.09-2.49; p = 0.016) and PE (OR: 2.62; 95% CI: 1.52-4.54; p < 0.001) in the DOAC cohort. There was no difference in the odds of bleeding complications. CONCLUSION: This study demonstrated an increased incidence and odds of VTE, but not bleeding complications, when using DOACs versus LMWH after primary bone or soft tissue sarcoma resection. LEVEL OF EVIDENCE: Level III.

The low and disproportionate utilization of antiresorptive therapy in patients with osseous metastasis.

Introduction: Antiresorptive therapies are commonly utilized to mitigate and prevent skeletal-related-events in patients with metastatic osseous disease. However, limited data exists on the incidence or factors associated with prescription of antiresorptives or their effects on the incidence of pathologic fractures in patients with osseous metastatic disease. The aims of this study were to determine 1) the proportion of patients with osseous metastasis who receive antiresorptive therapy and sustain a pathologic fracture within 2-years of a new diagnosis, 2) factors associated with sustaining a pathologic fracture, and 3) factors are associated with the likelihood of receiving antiresorptive therapy. Methods: Between January 2010 and October 2021, 1,492,301 patients with a new diagnosis of osseous metastasis were captured in the Mariner dataset of the PearlDiver database. Patients were identified using International Classification of Disease (ICD) 10 codes for osseous metastasis. We excluded patients with a prior diagnosis of osseous metastasis and if they had less than two-years of follow-up. There were 696,459 patients (46.7 %) included for analysis. Of these patients, 63 % (N = 437,716) were over the age of 65, 46 % were women, and 5.6 % had Medicaid insurance. We identified patients who were prescribed antiresorptive therapy within 2-years of a new diagnosis of osseous metastasis. Cox proportional hazard ratio models were created to predict factors associated with 1) pathologic fracture and 2) receiving antiresorptive therapy within 2-years of a new diagnosis of osseous metastasis, respectively. Results: The incidence of antiresorptive therapy prescription was 7.7 % in our cohort. The incidence of pathologic fracture within 2-years of a new diagnosis was 7.3 %. The risk of sustaining a pathologic fracture was higher for patients aged 35-44 (HR 1.27 [95 % CI 1.08-1.51]; p = 0.004), those with primary kidney cancer (HR 1.78 [95 % CI 1.71-1.85]; p < 0.001), p = 0.005), multiple myeloma (HR 2.49 [95 % CI 2.39-2.59]; p < 0.001), and Medicaid insurance (HR 1.17 [95 % CI 1.13-1.21]; p < 0.001). The risk of sustaining a pathologic fracture was lower for patients on antiresorptive therapy (HR 0.71 [95 % CI 0.66-0.83]; p < 0.001). Increasing age was an independent predictor for antiresorptive therapy prescription (HR 1.77-16.38, all p < 0.05). Male sex as well as diagnosis of primary prostate, lung, or kidney cancer and Medicaid insurance were negative predictors for antiresorptive prescription (HR 0.15-0.87, all p < 0.001). Conclusions: The utilization of antiresorptive therapy in patients with osseous metastases remains unacceptably low, with only 7.7% patients being prescribed these therapies, despite shown efficacy in reduction of pathologic fractures incidences. This study identified younger patients, males, and those diagnosed with primary prostate, kidney, and lung cancers to be at increased risk of not being prescribed antiresorptive therapy, suggesting possible bias in prescription patterns. Greater efforts are needed by providers who care for this vulnerable population to increase the utilization and reduce disparities of prescribing antiresorptive therapy.

Functional outcomes after open reconstruction or nonoperative management of 81 pathologic acetabular fractures from metastatic bone disease.

Background: Pathologic acetabular fracture secondary to skeletal metastasis may result in debilitating pain, inability to ambulate, and impaired quality of life, which may mark the first period of dependent care in cancer patients. Acetabular reconstruction may involve morbid procedures with increased complication rates. This study aimed to evaluate the evolution of pain, performance status, and ambulation following nonoperative management or open reconstruction of pathologic acetabular fractures. Methods: A retrospective cohort of 2630 adult patients with osseous metastatic disease treated at a high-volume cancer center between 2005 and 2021 was screened for pathologic fractures of the acetabulum. The study outcomes were pain, performance status, and the ability to ambulate. We identified 78 patients (median age, 60 years; 37 female patients [46%]) with 81 fractures. Of these, treatment consisted of open reconstruction (n = 34) or nonoperative management alone (n = 47). The mean follow-up in surviving patients was 3.4 years. Results: Open reconstruction was performed more frequently for displaced fractures (P < 0.01), Harrington class III or IV acetabula (P < 0.01), and patients with a performance status ≥3 at hospitalization (P = 0.00). Open reconstruction was associated with clinically meaningful improvements in pain (adjusted odds ratio [aOR], 8.3; 95% CI, 1.4-50.6; P = 0.02) and performance status (aOR, 10.9; 95% CI, 1.7-71.0; P = 0.01) at discharge and a restoration of ambulation (aOR, 7.5; 95% CI, 1.9-29.8; P < 0.01) at final follow-up. Conclusions: In patients with pathologic acetabular fracture due to osseous metastatic disease, functional improvements in pain, performance status, and ambulation were observed following open acetabular reconstruction in carefully selected patients, with no impact on survival, while noninferior improvements were observed in patients receiving nonoperative management when considering their larger clinical context. Level of evidence: Level III, therapeutic study.

Metastatic sarcomatoid carcinoma to bone.

BACKGROUND AND OBJECTIVES: Distinguishing sarcomatoid carcinoma from primary sarcoma is clinically important. We sought to characterize metastatic sarcomatoid bone disease and its management. METHODS: We analyzed the characteristics of all cases of sarcomatoid carcinoma to bone at a single institution from 2001 to 2021, excluding patients with nonosseous metastases. Survival was evaluated using the Kaplan-Meier method. RESULTS: We identified 15 cases of metastatic sarcomatoid carcinoma to bone. In seven cases the primary cancer was unknown at presentation. Renal cell carcinoma was suspected or confirmed in nine cases. Nine patients presented with pathologic fracture and two with concomitant visceral metastases. All patients underwent image-guided core needle or open biopsy. Ten required surgery for discrete osseous metastases; in four cases definitive surgery was delayed (median delay, 19 days) due to inability to rule out sarcoma with frozen section. No patients required reoperation or had construct failure. Thirteen died of disease; median survival was 17.5 months (interquartile range, 6.2-25.1). CONCLUSIONS: Metastatic sarcomatoid carcinoma is a clinically challenging entity. Multidisciplinary input and communication are key to identifying the primary carcinoma, locating osseous metastases, and defining an operative fixation that will survive the remainder of the patient's life.

Incidence of and Risk Factors for Thromboembolism After Endoprosthetic Reconstruction in Musculoskeletal Oncology Patients.

BACKGROUND: The aim of the present study was to assess the incidence of and risk factors for thromboembolic events-including assessment of the intraoperative use of tranexamic acid and postoperative use of chemical thromboprophylaxis-in patients undergoing operative treatment of primary bone or soft-tissue sarcoma or oligometastatic bone disease. METHODS: This study was performed as a secondary analysis of prospective data collected from the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) randomized controlled trial, which included 604 patients ≥12 years old who underwent surgical resection and endoprosthetic reconstruction for either primary bone or soft-tissue sarcoma or oligometastatic disease of the femur or tibia. We determined the incidence of thromboembolic events in these patients and evaluated potential risk factors, including patient age, sex, antibiotic treatment group, type of tumor (i.e., primary bone or soft-tissue sarcoma or metastatic bone disease), intraoperative tranexamic acid, tourniquet use, operative time, pathologic characteristics (i.e., American Joint Committee on Cancer grade, vascular invasion, and percent necrosis), postoperative chemical thromboprophylaxis regimen, and surgical site infection. Continuous variables were assessed with use of the Student t test. Categorical variables were assessed with use of the Pearson chi-square test, except when the expected cell counts were <5, in which case the Fisher exact test was utilized. Significance was set at 0.05. RESULTS: Postoperative thromboembolic events occurred in 11 (1.8%) of 604 patients. Patients who experienced a thromboembolic event had a significantly higher mean (± standard deviation) age (59.6 ± 17.5 years) than those who did not experience a thromboembolic event (40.9 ± 21.8; p = 0.002). Patients randomized to the long-term antibiotic group had a significantly higher incidence of thromboembolic events (9 of 293; 3.1%) than those randomized to the short-term antibiotic group (2 of 311; 0.64%; p = 0.03). Neither intraoperative tranexamic acid nor postoperative chemical thromboprophylaxis were significantly associated with the occurrence of a thromboembolic event. CONCLUSIONS: Although relatively rare in the PARITY cohort, thromboembolic events were more likely to occur in older patients and those receiving long-term prophylactic antibiotics. Intraoperative tranexamic acid and postoperative chemical thromboprophylaxis were not associated with a greater incidence of thromboembolic events. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Does the Use of Negative Pressure Wound Therapy and Postoperative Drains Impact the Development of Surgical Site Infections?: A PARITY Trial Secondary Analysis.

BACKGROUND: Surgical site infections (SSIs) represent a major complication following oncologic reconstructions. Our objectives were (1) to assess whether the use of postoperative drains and/or negative pressure wound therapy (NPWT) were associated with SSIs following lower-extremity oncologic reconstruction and (2) to identify factors associated with the duration of postoperative drains and with the duration of NPWT. METHODS: This is a secondary analysis of the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial, a multi-institution randomized controlled trial of lower-extremity oncologic reconstructions. Data were recorded regarding the use of drains alone, NPWT alone, or both NPWT and drains, including the total duration of each postoperatively. We analyzed postoperative drain duration and associations with tourniquet use, intraoperative thromboprophylaxis or antifibrinolytic use, incision length, resection length, and total operative time, through use of a linear regression model. A Cox proportional hazards model was used to evaluate the independent predictors of SSI. RESULTS: Overall, 604 patients were included and the incidence of SSI was 15.9%. Postoperative drains alone were used in 409 patients (67.7%), NPWT alone was used in 15 patients (2.5%), and both postoperative drains and NPWT were used in 68 patients (11.3%). The median (and interquartile range [IQR]) duration of drains and of NPWT was 3 days (IQR, 2 to 5 days) and 6 days (IQR, 4 to 8 days), respectively. The use of postoperative drains alone, NPWT alone, or both drains and NPWT was not associated with SSI (p = 0.14). Increased postoperative drain duration was associated with longer operative times and no intraoperative tourniquet use, as shown on linear regression analysis (p < 0.001 and p = 0.03, respectively). A postoperative drain duration of ≥14 days (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.3 to 9.6; p = 0.01) and an operative time of ≥8 hours (HR, 4.5; 95% CI, 1.7 to 11.9; p = 0.002) were independent predictors of SSI following lower-extremity oncologic reconstruction. CONCLUSIONS: A postoperative drain duration of ≥14 days and an operative time of ≥8 hours were independent predictors of SSI following lower-extremity oncologic reconstruction. Neither the use of postoperative drains nor the use of NPWT was a predictor of SSI. Future research is required to delineate the association of the combined use of postoperative drains and NPWT with SSI. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Complex/cryptic EWSR1::FLI1/ERG Gene Fusions and 1q Jumping Translocation in Pediatric Ewing Sarcomas.

Ewing sarcomas (ES) are rare small round cell sarcomas often affecting children and characterized by gene fusions involving one member of the FET family of genes (usually EWSR1) and a member of the ETS family of transcription factors (usually FLI1 or ERG). The detection of EWSR1 rearrangements has important diagnostic value. Here, we conducted a retrospective review of 218 consecutive pediatric ES at diagnosis and found eight patients having data from chromosome analysis, FISH/microarray, and gene-fusion assay. Three of these eight ES had novel complex/cryptic EWSR1 rearrangements/fusions by chromosome analysis. One case had a t(9;11;22)(q22;q24;q12) three-way translocation involving EWSR1::FLI1 fusion and 1q jumping translocation. Two cases had cryptic EWSR1 rearrangements/fusions, including one case with a cryptic t(4;11;22)(q35;q24;q12) three-way translocation involving EWSR1::FLI1 fusion, and the other had a cryptic EWSR1::ERG rearrangement/fusion on an abnormal chromosome 22. All patients in this study had various aneuploidies with a gain of chromosome 8 (75%), the most common, followed by a gain of chromosomes 20 (50%) and 4 (37.5%), respectively. Recognition of complex and/or cryptic EWSR1 gene rearrangements/fusions and other chromosome abnormalities (such as jumping translocation and aneuploidies) using a combination of various genetic methods is important for accurate diagnosis, prognosis, and treatment outcomes of pediatric ES.

Study protocol of an open-label proof-of-concept trial examining the safety and clinical efficacy of psilocybin-assisted therapy for veterans with PTSD.

INTRODUCTION: Psilocybin-assisted therapy has shown significant promise in treating the cluster of mood and anxiety symptoms that comprise post-traumatic stress disorder (PTSD) but has yet to be tested specifically in this condition. Furthermore, current pharmacological and psychotherapeutic treatments for PTSD are difficult to tolerate and limited in efficacy, especially in the US Military Veteran (USMV) population. This open-label pilot study will examine the safety and efficacy of two psilocybin administration sessions (15 mg and 25 mg), combined with psychotherapy, among USMVs with severe, treatment resistant PTSD. METHODS AND ANALYSIS: We will recruit 15 USMVs with severe, treatment resistant PTSD. Participants will receive one low dose (15 mg) and one moderate/high dose (25 mg) of psilocybin in conjunction with preparatory and post-psilocybin therapy sessions. The primary safety outcome will be the type, severity and frequency of adverse events and suicidal ideation/behaviour, as measured by the Columbia Suicide Severity Rating Scale. The primary outcome measure for PTSD will be the Clinician Administered PTSD Scale-5. The primary endpoint will be 1 month following the second psilocybin administration session, and the total follow-up time will be 6 months. ETHICS AND DISSEMINATION: All participants will be required to provide written informed consent. The trial has been authorised by the Ohio State University Institutional Review Board (study number: 2022H0280). Dissemination of results will occur via a peer-reviewed publication and other relevant media. TRIAL REGISTRATION NUMBER: NCT05554094.