Citations

ABSTRACT Background and Objectives Non‐rhabdomyosarcoma soft tissue sarcomas (NRSTS) account for less than 4% of pediatric cancers. Treatment and outcomes have been described in adults, but pediatric data are lacking. The purpose of this study is to review our institution's outcomes of extremity NRSTS in pediatric patients. Methods Ninety‐eight (56 male: 42 female) pediatric patients with NRSTS of the extremity at our institution were reviewed. Mean age at diagnosis was 11 ± 5 years, and mean follow‐up was 12 ± 10 years. The most common diagnosis was synovial sarcoma (27%), and 60% were high‐grade. Results Treatment included surgical resection in all patients, with 33% receiving radiation and 37% receiving systemic therapy. 20‐year local recurrence‐ (LRFS) and metastatic disease‐free survival (MDFS) were 91% and 91%, respectively, with 92% disease specific survival (DSS). High grade tumors were associated with lower LRFS ( p = 0.02) and DSS ( p = 0.03). Tumor size < 5 cm demonstrated improved MDFS ( p = 0.03), and stage 3 tumors showed worse MDFS ( p < 0.01). Conclusions Treatment of pediatric NRSTS was variable, with large, deep, high‐grade tumors more likely to receive neoadjuvant and adjuvant treatments. Multidisciplinary treatment was associated with high rates of local control and durable survival. This study provides an extended follow‐up of pediatric patients to identify late complications.

ABSTRACT Introduction Chronic gastroduodenal disorders remain challenging to manage, and new diagnostic approaches are needed to better delineate underlying causes and guide therapeutic decisions. Body Surface Gastric Mapping (BSGM) technologies combine high‐resolution gastric myoelectrical activity measurements with symptom and psychological profiling to provide mechanistic insights into gastric motor and sensory dysfunction. An International Working Group convened to derive the first consensus classification of BSGM phenotypes (the “Auckland Classification”). Methods A Technical Group conducted a systematic literature and clinical database review to identify objective test biomarkers and candidate disease mechanisms. Evidence was synthesized across 50 studies (primarily in gastroparesis, chronic nausea and vomiting, and functional dyspepsia), and BSGM phenotypes were mapped to existing treatment guidelines. Subsequently, iterative review and development of consensus was performed by a Consensus Group composed of international clinical experts familiar with BSGM. Eleven statements underlying the classification were then derived and circulated as a final survey to establish agreement. Results Six BSGM phenotypes were endorsed: three defined by myoelectrical abnormalities (Dysrhythmic, High Frequency, and Low Meal Response) and three by characteristic symptom associations (Sensorimotor, Continuous, and Delayed Onset Symptoms). Published studies plausibly linked these phenotypes to mechanisms including interstitial cell of Cajal depletion, vagal impairment, hypomotility, visceral hypersensitivity, gut‐brain dysregulation, and small bowel dysfunction. Phenotypes were also mapped to existing mechanism‐based treatment guidelines. Ten out of the eleven statements had > 80% agreement. Conclusions The Auckland Classification, derived by international consensus, presents a structured framework for BSGM‐defined patient phenotypes. Evidence and mechanism‐based treatment options are suggested for each phenotype to provide a foundation for research, further validation, and a pathway for integrating BSGM into clinical care.

Summary Background Postoperative nausea and vomiting (PONV) is a common consequence of anaesthesia, affecting up to 30% of postoperative patients. Female sex is one of the strongest risk factors for PONV, yet no dedicated analysis has examined how this association varies across surgical settings and timepoints. This systematic review and meta-analysis aimed to quantify sex differences in PONV incidence across different surgical contexts. Methods A systematic search was conducted using PRISMA guidelines across Medline and Embase from inception to September 1, 2025. Eligible studies were observational cohort studies (n≥500) of adult patients that conducted multivariate regression analyses including sex as a variable. Two reviewers independently screened, extracted data, and assessed risk of bias using ROBINS-E. A random-effects meta-analysis was performed. Subgroup analyses and multiple sensitivity analyses were completed. Results From 4620 identified studies, 23 met the inclusion criteria, including 462,828 patients across various surgical settings and specialties (52% female). The pooled incidence of PONV was 21% (95% CI[16-27%]), with high heterogeneity (I 2 =99.9%). Meta-analysis confirmed females had a higher risk of developing PONV compared to males (pooled OR=2.40, 95% CI[2.06-2.79], I 2 =93.1%, p<0.0001). Sensitivity analyses confirmed robustness of pooled estimates. Subgroup analyses demonstrated consistently elevated risk of PONV for females at all three timepoints (PACU, 24-hour, 48-hour post-operative) and across studies including and excluding female-only surgeries. Studies were generally at high risk of bias. Discussion Female sex is a strong risk factor for PONV across surgical settings. Further research into precise subgroups, underlying mechanisms of sex-differences, and the use of prophylaxis may help improve this inequity.

ABSTRACT Introduction Community health workers (CHWs) help patients navigate community resources. CHW programs can improve health outcomes and reduce healthcare utilization, but identifying eligible patients is challenging. We developed an electronic health record (EHR)‐based algorithm trained to predict referrals to a CHW program. Our objective was to evaluate whether an algorithm trained on historical referrals identifies a subgroup of patients that differs from the subgroup identified through questionnaire‐based health‐related social needs (HRSN) screening alone. Methods This analysis used data from Mayo Clinic primary care patients in Southeast Minnesota. We developed a gradient boosted time‐to‐event model that incorporated demographics, diagnoses, HRSN questionnaire responses, and HRSNs derived from clinical notes using natural language processing. We compared the characteristics of algorithm‐identified patients with those identified through questionnaires and assessed the variable importance of model features. Results The algorithm had AUC: 0.87 in the training and 0.92 in the hold out set. Patients flagged by the algorithm tended to use interpreter services more commonly (12.6% vs. 1.3%), have a non‐English preferred language (14.1% vs. 2.3%), and have more instances of health literacy documented (5.36 vs. 1.29) compared to patients identified by the HRSN questionnaire. Only 47.0% of patients flagged by the algorithm had responded to the HRSN questionnaire within 2 years. Variable importance was highest for health literacy and financial strain from unstructured notes. Conclusions The algorithm is a chart‐review prioritization tool for referral to the CHW program for patients that may overcome challenges to identifying patients with HRSNs, especially when questionnaire data is incomplete.

ABSTRACT Introduction The proximal tibia is a common location for bone tumors. Two contemporary reconstruction techniques for limb salvage are endoprosthetic replacement (EPR) and allograft‐prosthesis composite (APC). This study aimed to compare the long‐term oncologic and functional outcomes of EPR and APC reconstructions. Methods Thirty‐eight (19 APC and 19 EPR) patients underwent oncologic proximal tibia resection and reconstruction were reviewed. Patients undergoing APC reconstruction were younger than the EPR group (31 vs. 44 years, p = 0.049), and patients in the EPR group were more likely to have a diagnosis of metastatic disease (32% vs. 0%, p = 0.019). Results For all patients, the 10‐year disease‐specific survival was 63%. With death a competing risk, there was no difference in the 10‐year cumulative risk of failure (41% vs. 26%, p = 0.171) or amputation (11% vs. 19%, p = 0.690) between APC or EPR. There was no difference comparing EPR to APC in the proportion of patients with an extensor lag > 10° (42% vs. 26%, p = 0.495) or 10‐year knee society scores (85 vs. 85, p = 0.710). Conclusion EPR and APC have a similar complication profile and functional outcomes following proximal tibial resection and reconstruction.

Abstract Introduction: Targeted therapy yields deep and durable response in histiocytic neoplasms.However, relapse rate following interruption is high at 75-77%, with a median time to relapse 6-9 months in previous studies. Outcomes after discontinuation in those who have already achieved a durable response are not well understood and are the focus of this study. Methods: We performed a multicenter retrospective study, including 4 US centers, including patients with histiocytic disorders treated with BRAF inhibitor (BRAFi), MEK inhibitor (MEKi), or combination BRAF/MEKi, and whose therapy was interrupted after ≥12 months of therapy following a best response of partial (PR) or complete response (CR). Progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier method. Cox regression was performed to identify clinical and molecular factors that are associated with PFS. Results: 26 patients were included (median age 55 [range 12-72]; male 53.8%; Caucasian 69.2%). Most predominant histology was Erdheim-Chester Disease (ECD) (n=15, 57.5%), followed by mixed histiocytosis (n=5, 19.2%). Rosai-Dorfman Disease (RDD) (n=4, 15.4%), and Langerhans Cell Histiocytosis (LCH) (n=2, 7.7%). All had BRAF V600E analysis and 10 (38.5%) were positive. 19 patients underwent additional molecular testing; alternative mutations identified included MAP2K1/2 (n=6, 23.1%), NRAS (n=1, 3.8%), RAF1 (n=1, 3.8%), ASXL1 (n=1, 3.8%), and SRSF2 (n=1, 3.8%). Targeted therapy was given as frontline therapy (n=8, 30.8%) or in the relapsed refractory setting (n=18, 69.2%) with median 1 prior line of therapy (range 0-7). Targeted therapies include BRAFi (n=5, 19.2%; 2 dabrafenib, 3 vemurafenib), MEKi (n=17, 65.4%; 14 cobimetinib, 3 trametinib), and BRAF/MEKi (n=4, 15.4%; 3 dabrafenib/trametinib, 1 vemurafenib/cobimetinib). PR and CR occurred in 8 (30.8%) and 18 (69.2%) patients, respectively. The median duration of treatment was 32 months (range 13-60) (12-24 months: 9 [34.6%]; 24-36 months: 7 [26.9%]; &gt;36 months: 10 [38.5%]). Median time from initiation of targeted therapy to best response was 6 months (&lt;6 months: 14 [53.8%]; 6-12 months: 5 [19.2%]; &gt;12 months: 7 [26.9%]). Median duration from best response to drug discontinuation was 19 months (12-24 months: 14 [53.8%]; 24-36 months: 7 [26.9%]; &gt;36 months: 5[19.2%]). Reasons for drug discontinuation include toxicity (n=8, 30.8%), patient preference (n=13, 50.0%), cost prohibition (n=1, 3.8%), and other critical medical conditions (n= 4,15.4%). Eleven patients (42.3%) experienced disease progression after discontinuation of targeted therapy, 5 patients progressed within 6 months. Systemic and CNS progression were captured by PET/CT and MRI brain, respectively. At median follow-up of 33.0 months (95%CI 24.3-47.1), median PFS, defined by time from targeted therapy discontinuation to progression or death, was 29 months (95% confidence interval [CI] not estimable). Median OS was not reached. In Cox regression model, BRAF V600E mutation (hazard ratio [HR] 4.16, 95% CI 1.10-15.70, p 0.036) and CNS involvement (HR 4.64, 95% CI 1.21-17.67, p 0.025) were associated with inferior PFS. MEKi containing regimen trended toward improved PFS (HR 0.35, 95%CI 0.10-1.21, p 0.097). There was no difference in PFS when assessing demographics, histology, prior therapies, best response to targeted therapy, treatment duration, or time from best response to discontinuation. Of the 11 patients with progression, 9 were re-challenged with targeted therapy (7 switched class), 2 did not receive next line therapy (1 transitioned to hospice and passed from progression, 1 has pending evaluation for next line therapy). Of 6 with response assessments, all recaptured response (1 CR, 5 PR), and none had progressed by data cutoff. Conclusions: In patients with histiocytic neoplasm and prior durable response to targeted therapy, ~40% experienced disease progression after treatment discontinuation. BRAF V600E mutation and CNS disease are associated with inferior PFS, suggesting these subgroups may not be appropriate for limited duration of treatment. Novel approaches are needed in these high-risk patients.

Aims The aim of this study was to achieve consensus for important topics related to periprosthetic infection (PJI) in orthopaedic oncology, and to identify areas for future research. Methods In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) held in Birmingham, UK, gathered 309 delegates from 53 countries to debate 20 consensus statements on PJI in orthopaedic oncology using a modified Delphi process. Results Of 20 questions and statements on PJI in orthopaedic oncology, none achieved unanimous consensus, 18 achieved strong consensus, one achieved moderate consensus, and one achieved weak consensus. The statements that reached consensus with notable agreement were on the prophylaxis of infection, management of leaking wounds, and surgical strategies for the treatment of PJI. Short-duration antibiotic prophylaxis was deemed as effective as longer courses for lower-risk reconstructions, and aggressive management was recommended for wounds draining beyond five to seven days to prevent deep infection. Furthermore, single-stage, two-stage, and 1.5-stage revision were recognized as valid strategies, with two-stage revision remaining the most reliable. The statements that did not achieve consensus were on the role of debridement, antibiotics, and implant retention and prolonged antibiotic use post-revision. Conclusion The BOOM meeting achieved consensus for important topics on periprosthetic infection in orthopaedic oncology, but highlighted the low quality of the underlying evidence. This study has provided recommendations for the treatment of leaky wounds, duration of postoperative antibiotic prophylaxis, and choice of revision strategy. Cite this article: Bone Joint J 2025;107-B(12):1352–1359.

Background: Myxofibrosarcomas are notoriously highly infiltrative soft-tissue sarcomas, making negative surgical margins difficult to obtain. Recently, vacuum-assisted closure (VAC) is used to delay wound closure until a negative margin has been achieved; however, this can delay care and increase costs. Our institution has historically performed single-stage resections with intraoperative frozen margin analysis and reconstruction in these patients. The purpose of this study is to report the outcomes of this technique. Methods: We reviewed 112 patients (62 males, mean age 70 ± 14 years) with superficial myxofibrosarcoma. Eighty-eight patients received preoperative radiation. All patients underwent surgical resection with intraoperative frozen margin analysis, and the planned reconstruction was performed in a single anesthetic. Results: The 10-year local recurrence-free survival was 90%; positive intraoperative frozen section (HR 7.44, p = 0.004) and final permanent margins (HR 8.53, p = 0.007) were associated with local recurrence. Intraoperative margins were negative in 103 (92%) of patients, 1 of which was positive on final permanent section. There were nine cases of microscopically positive margins, of which seven underwent immediate re-excision to a negative margin. The accuracy of frozen margin assessment for myxofibrosarcoma was between 92.92 and 98.23%. All patients underwent reconstruction at the time of resection, with 19% needing an additional procedure, most commonly due to a wound complication (12%). Conclusions: Multidisciplinary single-stage excision with intraoperative frozen margin assessment and soft-tissue reconstruction yields low rates of local recurrence in patients with superficial myxofibrosarcoma.