Faculty Bibliography

BACKGROUND/UNASSIGNED:Solid organ transplant (SOT) recipients undergoing total joint arthroplasty (TJA) may face elevated perioperative risk because of chronic immunosuppression, medical comorbidity, and organ-specific physiologic considerations. Although intravenous tranexamic acid (TXA) is widely used during TJA to reduce perioperative blood loss, evidence regarding outcomes among SOT recipients receiving TXA remains limited. METHODS/UNASSIGNED:A retrospective review was performed of 29,240 consecutive primary TJA patients who all received intraoperative intravenous TXA between June 2011 and March 2025. Patients undergoing unicompartmental knee arthroplasty, hemiarthroplasty, TJA for fracture, bilateral procedures, revision procedures, or those with less than 90 days of postoperative follow-up were excluded. SOT history was identified using diagnosis and procedural codes and verified by manual review. Outcomes included 90-day deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI), operative time, and hospital length of stay (LOS). RESULTS/UNASSIGNED:Sixty-six patients with verified SOT were identified. The most common transplant types were kidney (59%), liver (24%), and heart (9%). One SOT patient experienced a 90-day VTE event compared with 95 control patients (1.5% versus 0.3%, P = 0.20). There were no PEs or MIs in the SOT cohort, compared with PE and MI rates of 0.2% and 0.01% in controls, respectively (P > 0.05 for both). Operative times were similar between groups (100.8 versus 108.5 min, P = 0.11), while LOS was significantly longer among SOT recipients (86.2 versus 43.8 h, P < 0.001). CONCLUSION/UNASSIGNED:In this retrospective cohort of primary TJA patients who all received intraoperative intravenous TXA, SOT recipients had low observed rates of VTE, PE, and MI. Because all patients received TXA and the SOT cohort was small, these findings should be interpreted as comparative observational safety data rather than evidence that TXA independently increases or does not increase thromboembolic risk in this population.

BACKGROUND/UNASSIGNED:Bone metastases from breast cancer cause skeletal-related events (SREs), including pain, fractures, and the need for radiation or surgery. Denosumab and bisphosphonates (BP) reduce these complications, but their relative efficacy and safety remain unclear. METHODS/UNASSIGNED:PubMed, Scopus, Cochrane Library, and Google Scholar were searched through October 2025. Five publications (four unique studies: three randomized trials and one retrospective cohort) were included. Sensitivity analyses were limited to randomized trials when feasible. Outcomes included SRE incidence and skeletal endpoints, plus renal, metabolic, hematologic, musculoskeletal, gastrointestinal, infectious adverse events, osteonecrosis of the jaw (ONJ), and serious, grade ≥ 3, and treatment-related events. RESULTS/UNASSIGNED: = 0.04) were reduced. Other outcomes, including uNTx, ONJ, serious and grade ≥ 3 events, thrombocytopenia, infectious, gastrointestinal, and respiratory events, were comparable. Results were consistent in randomized-only analyses. CONCLUSION/UNASSIGNED:In breast cancer patients with bone metastases, denosumab may benefit those at higher risk of renal toxicity or skeletal complications, while treatment decisions should remain individualized. PROTOCOL REGISTRATION/UNASSIGNED:www.crd.york.ac.uk/PROSPERO identifier is CRD420251231881.

Osteosarcoma is an aggressive malignancy with a 5-year survival below 30% in metastatic disease, highlighting the need for prognostic tools. A review of 93 studies identified consistent prognostic biomarkers. p53 overexpression was associated with reduced overall and disease-free survival, while high Ki-67 correlated with advanced stage, metastasis, and poor outcomes. HER2 positivity increased metastatic risk. HIF-1α, VEGF, and MMP-9 predicted inferior survival. MYC amplification, TP53/RB1 disruption, and loss of H4K20me3 indicated worse prognosis. Epigenetic signatures predicted chemotherapy sensitivity. Non-coding RNAs showed strong prognostic value, with lncRNA models achieving AUCs 0.88. CircRNAs, metabolomic markers, and 18 F-FDG PET/CT metrics refined risk stratification.

BACKGROUND:Pediatric supracondylar humeral fractures (SCHFs) are among the most common elbow injuries in children and frequently require operative fixation. Although after-hours surgery is often unavoidable due to emergency presentation patterns, many centers now reserve nighttime intervention for urgent indications such as vascular compromise. Concerns nevertheless persist regarding the potential impact of after-hours surgery on surgical efficiency, technical decision-making, and postoperative outcomes. METHODS:A systematic search of PubMed, Scopus, the Cochrane Library, and Google Scholar was conducted from database inception through December 15, 2025. Comparative studies evaluating operative treatment of pediatric SCHFs performed during daytime working hours versus after-hours were included. Outcomes assessed comprised perioperative characteristics (operative time, time to surgery), intraoperative decision-making (medial pin fixation, open reduction), and postoperative complications (pin migration, alignment-related complications, infection, and iatrogenic postoperative nerve injury). RESULTS:Seven studies encompassing 913 pediatric patients met the inclusion criteria. Operative time did not differ significantly between daytime and after-hours surgery ( P =0.11). Time to surgery was shorter in the after-hours group ( P <0.001). No significant differences were observed in rates of medial pin fixation ( P =0.70) or open reduction ( P =0.80). Postoperative complications, including pin migration, infection, and iatrogenic postoperative nerve injury, were comparable between groups, whereas alignment-related complications were more frequent in the after-hours group ( P =0.04). CONCLUSIONS:Operative fixation of pediatric SCHFs showed broadly comparable perioperative efficiency, technical outcomes, and complication rates when performed during daytime or after-hours, although alignment-related complications were more frequent in the after-hours group. These findings suggest that surgical timing alone may not be the primary determinant of outcome.

INTRODUCTION/BACKGROUND:Ewing sarcoma (EWS) is an aggressive small round blue cell malignancy driven by EWSR1::ETS fusions, with poor survival outcomes in metastatic and relapsed disease. While multimodal chemotherapy remains the cornerstone of therapy, emerging agents hold potential to overcome resistance and improve outcomes. METHODS:A systematic search of PubMed, Scopus, and Google Scholar through February 2026 identified 1,166 records. Following duplicate removal and two-stage screening, 87 preclinical and clinical studies were included. Data were extracted and synthesized narratively, with emphasis on therapeutic class, mechanism of action, side effects, and translational relevance. RESULTS:Across therapeutic classes, several promising avenues emerged. Direct EWS-FLI1 targeting (TK216, trabectedin combinations, CRISPR-based approaches) demonstrated preliminary clinical and robust preclinical efficacy. IGF-1R inhibitors (linsitinib, ganitumab, and figitumumab) showed biological activity, though limited survival benefit in trials. CD99-directed therapies, including monoclonal antibodies and siRNA-nanoparticle conjugates, achieved synergy with chemotherapy in xenografts. PARP inhibitors exhibited preclinical efficacy, particularly in combination regimens, though monotherapy responses were modest in clinical cohorts. Kinase inhibitors targeting WEE1, DNA-PK, and Aurora A kinase, as well as multikinase TKIs (cabozantinib, regorafenib, and anlotinib), revealed varying degrees of cytotoxicity and disease stabilization. Epigenetic therapies, including LSD1, HDAC, and EZH2 inhibitors, attenuated EWS-FLI1 transcriptional programs and enhanced chemosensitivity. Immunotherapeutic approaches (immune checkpoint inhibitors, IGF-1R antibodies, Vigil vaccine) have so far yielded limited responses, though selected strategies showed potential benefit in subsets. Novel agents such as verteporfin, evofosfamide, and proteasome inhibitors further expanded the spectrum of vulnerabilities. CONCLUSIONS:Targeted and molecular therapies in EWS show significant promise, particularly in rational combinations that exploit the tumor's dependence on EWS-FLI1-driven transcriptional dysregulation, DNA damage repair deficiencies, or survival signaling. Future research must prioritize biomarker-driven patient selection, integration of multiomics approaches, and multicenter prospective trials to translate these strategies into clinically meaningful improvements in EWS survival.

BACKGROUND:Synthetic composites of calcium phosphate and calcium sulfate have been used for grafting after intralesional curettage of benign bone tumors. However, there are limited studies on the outcomes of children who were grafted with these materials. QUESTIONS/PURPOSES/OBJECTIVE:(1) What proportion of patients with benign pediatric bone lesions who were treated with synthetic calcium phosphate and calcium sulfate bone substitute as a bone void filler experienced radiographic graft resorption by 1 year after treatment? (2) What proportion of patients thus treated experienced recurrence of the tumor or fracture at a minimum follow-up time of 1 year? METHODS:Between 2020 and 2023, a total of 42 patients were surgically treated for benign lytic bone tumors or bone cysts at a single tertiary academic children's hospital. Two were excluded from analysis (one because it was a recurrent aneurysmal bone cyst initially treated with curettage and bone grafting, and one who was treated with aspiration and corticosteroid injection of the cyst at the family's request), leaving 40 who were treated with curettage and grafting using synthetic calcium phosphate and calcium sulfate bone substitute. All had at least 12 months of follow-up (mean ± SD 32 ± 15 months) and were analyzed in this retrospective study. Of the patients, 30% (12 of 40) were female, and the mean age of the cohort was 12 ± 4 years. During this time, adjunctive internal fixation hardware was generally used when there was a pathologic fracture, and based on those indications, 23% (9 of 40) received hardware. To answer our first study question about the proportion of lesions that demonstrated graft resorption by 1 year after treatment, we annotated the lesions and assessed for percent resorption at 6 weeks, 12 weeks, 6 months, 9 months, and 12 months. To answer our second study question, we used a Kaplan-Meier survivorship estimator to determine survivorship free from recurrence and survivorship free from fracture. RESULTS:Eighty-eight percent (35 of 40) developed complete resorption of the graft by 1 year after surgery; 45% (18 of 40) demonstrated this finding by 4 months after surgery. Thirteen percent (5) of patients developed local recurrence. Survivorship free from local recurrence was 88% (95% confidence interval [CI] 77% to 99%) at 1 year, and survivorship free from fracture was 100% (95% CI not estimable) at 1 year. Of those that recurred, there were three aneurysmal bone cysts, one unicameral bone cyst, and one chondroblastoma. CONCLUSION/CONCLUSIONS:The bone substitute was associated with gradual resorption, low recurrence rates, and no fractures in this cohort. With the right indications, patients can start weightbearing at 6 weeks without hardware augmentation. Close monitoring is crucial, especially for aneurysmal bone cysts that have a higher risk of recurrence. Further research may be needed to compare the effectiveness and cost-efficiency of bone substitutes and alternative graft options. LEVEL OF EVIDENCE/METHODS:Level IV, therapeutic study.

INTRODUCTION/BACKGROUND:While the number of absolute and relative contraindications to total joint arthroplasty (TJA) has gradually decreased, active cancer patients have traditionally been challenging surgical candidates. We sought to compare perioperative and two-year postoperative clinical outcomes of patients with and without active cancer. METHODS:Patients over 18 years with active cancer undergoing primary, unilateral TJA from 2017 to 2023 at a single urban academic center were reviewed for a minimum two-year follow-up. Cancer status, type, and stage were confirmed manually. 68 cancer patients were propensity-matched 3:1 to 204 non-cancer patients from a pool of 9,382 based on age, sex, BMI, smoking status, race, and ASA class. Demographic, perioperative, and clinical data were analyzed using t-tests, Chi-square, and ANOVA. Subgroup analyses compared cancer patients receiving active therapy versus those not on treatment. RESULTS:There were no significant demographic differences between groups, except Charlson Comorbidity Index (P < 0.001). The most common cancers were breast (22%) and prostate (20%). There were no differences in discharge disposition (P = 0.20), operative time (P = 0.87), or length of stay (P = 0.29). The all-cause revision rate (including infection) was higher in patients with active cancer (7.4% vs. 2.5%), though not statistically significant (P = 0.15; Power = 46.5%). Of the various causes for revision, infection was significantly more likely in cancer patients than other causes compared (4.4% vs. 0%, P = 0.003). When analyzing only the active cancer group, those receiving cancer therapy had higher revision rates, though this was not statistically significant (11.1% vs. 6.0%, P = 0.487). DISCUSSION/CONCLUSION/CONCLUSIONS:Despite often being excluded from arthroplasty studies, active cancer patients demonstrated comparable overall outcomes after primary TJA. Although infection-related revisions were more common, they were effectively treated. With proper preoperative optimization and multidisciplinary care, TJA can be safely performed in selected active cancer patients.

INTRODUCTION/BACKGROUND:Distal radius fractures are the most common fractures seen in the emergency department in children in the USA. However, no established or standardised guidelines exist for the optimal management of completely displaced fractures in younger children. The proposed multicentre randomised trial will compare functional outcomes between children treated with fracture reduction under sedation versus children treated with simple immobilisation. METHODS AND ANALYSIS/METHODS:Participants aged 4-10 years presenting to the emergency department with 100% dorsally translated metaphyseal fractures of the radius less than 5 cm from the distal radial physis will be recruited for the study. Those patients with open fractures, other ipsilateral arm fractures (excluding ulna), pathologic fractures, bone diseases, or neuromuscular or metabolic conditions will be excluded. Participants who agree to enrol in the trial will be randomly assigned via a minimal sufficient balance algorithm to either sedated reduction or in situ immobilisation. A sample size of 167 participants per arm will provide at least 90% power to detect a difference in the primary outcome of Patient-Reported Outcomes Measurement Information System Upper Extremity computer adaptive test scores of 4 points at 1 year from treatment. Primary analyses will employ a linear mixed model to estimate the treatment effect at 1 year. Secondary outcomes include additional measures of perceived pain, complications, radiographic angulation, satisfaction and additional procedures (revisions, refractures, reductions and reoperations). ETHICS AND DISSEMINATION/BACKGROUND:Ethical approval was obtained from the following local Institutional Review Boards: Advarra, serving as the single Institutional Review Board, approved the study (Pro00062090) in April 2022. The Hospital for Sick Children (Toronto, ON, Canada) did not rely on Advarra and received separate approval from their local Research Ethics Board (REB; REB number: 1000079992) on 19 July 2023. Results will be disseminated through publication in peer-reviewed journals and presentations at international conference meetings. TRIAL REGISTRATION NUMBER/BACKGROUND:NCT05131685.

» Multifactorial Pathogenesis: Legg-Calvé-Perthes disease (LCPD) may result from a complex interplay of genetic, epigenetic, and environmental factors, culminating in avascular necrosis of the femoral head in children aged 4 to 10 years.» Genetic Contributions: Mutations in COL2A1 weaken cartilage integrity, and polymorphisms in IL6 drive inflammatory responses, exacerbating bone resorption and necrosis.» Role of Epigenetics: Epigenetic mechanisms, such as altered DNA methylation and miRNA dysregulation, may modulate disease progression by linking genetic susceptibility to environmental influences.» Environmental Amplifiers: Key environmental risk factors, including maternal smoking, low birth weight, and socioeconomic deprivation, may exacerbate the genetic and epigenetic predisposition to LCPD.» Future Directions: Advancements in genetic screening and epigenetic therapies, such as miRNA modulators and DNA methylation inhibitors, combined with preventive measures like improved prenatal care and reduced smoke exposure, may offer promising avenues for optimizing outcomes in LCPD.