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PURPOSE Detection of bone marrow disease has been a major component of rhabdomyosarcoma (RMS) staging with bilateral bone marrow aspirates/biopsies (BMAB) from the iliac crests considered the diagnostic gold standard. This study's goal was to determine if 2- 18 F-labeled fluorodeoxyglucose positron emission tomography/computed tomography ([ 18 F]FDG PET/CT) or PET/magnetic resonance imaging (MRI) may replace BMAB in RMS staging. METHODS Patients were recruited in Europe and North America. Medical records, FDG PET/CT or FDG PET/MRI (PET), and BMAB reports were collected retrospectively. Images were re-reviewed by nuclear medicine physicians at the patients' home institutions if PET reports indicated increased FDG uptake at bone/bone marrow sites or if tumor cells were detected in bone marrow samples. RESULTS PET imaging and BMAB were performed before chemotherapy and tumor resection in 301 patients with FDG-avid RMS. Bone marrow metastases were detected by PET and BMAB in 54, by PET only in 24, and by BMAB only in one of 301 patients with FDG-avid primary tumors. Absence of bone marrow metastases was confirmed by PET and BMAB in 222 of 301 patients. These observations translated into 98% sensitivity and 90% specificity for PET in detecting bone marrow metastases when BMAB was considered as gold standard. FDG-avid marrow disease was patchy (1-5 foci) in one third of cases. Patients with marrow disease indicated by PET and BMAB had more FDG-avid bone marrow foci, more metastatic sites, and lower survival than those with marrow disease indicated by PET only, suggesting more advanced disease stages. CONCLUSION Bone marrow sampling may be omitted in patients without evidence of FDG-avid bone marrow disease by PET. If there are FDG-avid bone marrow lesions, further investigation by MRI and/or biopsy should be considered.

ABSTRACT Background and Objectives Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal, but the contribution of nonbiological factors to long‐term survival is unclear. We evaluated demographic, socioeconomic, clinical, treatment, and care‐delivery factors associated with 3‐year survival and whether these associations persisted at 5 years. Methods National Cancer Database patients with stage I–III PDAC diagnosed from 2012 to 2022 were analyzed using multivariable logistic regression adjusted for treatment pathway. Results Among 57,053 patients, 51,071 were eligible for a 3‐year analysis, and 12,205 (23.9%) survived. Compared with chemotherapy alone, surgery with chemotherapy (OR, 7.12; 95% CI, 6.64–7.63) and surgery alone (OR, 3.84; 95% CI, 3.49–4.23) had the strongest associations with survival. Younger age, lower comorbidity, Asian race, Spanish/Hispanic ethnicity, private insurance, lower grade, body or tail location, and lower nodal burden were independently associated with survival. Black race and treatment timing were not significant after adjustment. Findings were directionally consistent at 5 years. Conclusion Demographic, socioeconomic, and clinical factors independently influence 3‐year survival in PDAC. These findings underscore the need to complement biologic and therapeutic advances with structural interventions, such as insurance expansion and improved access to high‐quality centers, to mitigate disparities and improve outcomes in this highly lethal cancer.

Background: Dancers are at risk of femoroacetabular impingement (FAI) owing to supraphysiologic range of motion and associated demands placed on their hips. There remains a paucity of literature on midterm outcomes in dancers who undergo primary arthroscopy and labral repair for FAI. Purpose: To determine the rate of return to dance and patient-reported outcome measures in competitive dancers after hip arthroscopy with labral repair for FAI with minimum 2-year follow-up. Study Design: Case series; Level of evidence, 4. Methods: This study included dancers with FAI undergoing primary hip arthroscopy with labral repair from 2010 to 2022. Patient-reported outcome measures were collected at 2-year minimum follow-up: modified Harris Hip Score (overall, activities of daily living, gait, pain), Hip Outcome Score (activities of daily living, sports-specific subscale), Tegner Activity Scale, visual analog scale for pain, and surgery satisfaction. Patients were evaluated for preoperative radiographic measurements, postoperative return to sport, and revision surgery. Return to dance was evaluated. Results: Thirty-seven dancers were followed for a mean 7.4 years (range, 3.2-12.2) postoperatively (36 female and 1 male; mean ± SD age, 21 ± 7 years; mean body mass index, 23.3 ± 4.5). All outcome scores significantly improved postoperatively as compared with preoperatively ( P ≤ .037). Twenty dancers (71%) returned to dance. Of those who returned to dance, 17 (85%) returned to sport at the same or higher level as compared with the preoperative level. At final follow-up, 45% of dancers who initially returned to dance continued to dance. Of the dancers who no longer participated in dance at final follow-up, 7 (65%) quit dancing for nonhip-related reasons. Mean surgery satisfaction (0-10) at final follow-up was 7.1. Four patients (10%) underwent revision hip arthroscopy with revision labral repair. Conclusion: Hip arthroscopy with labral repair in dancers results in sustained improvements in function and pain at minimum 2-year follow-up. Most dancers return to their prior levels of dance, and nearly half remain active several years later. Notably, discontinuation of dance was often unrelated to hip symptoms, underscoring the importance of counseling patients on clinical and lifestyle factors influencing return to sport.

Polycythemia vera is characterized by erythrocytosis and increased risk of thrombosis. Sapablursen is an antisense oligonucleotide that suppresses transmembrane serine protease 6 (TMPRSS6), increases hepcidin production, and reduces iron availability for erythropoiesis. IMPRSSION; an ongoing phase 2a, randomized, open-label study includes patients meeting 2016 WHO criteria for polycythemia vera, requiring ≥3 phlebotomies within 6 months of screening and ≥1 phlebotomy within the last 12 weeks. Cohort A (120 or 80 mg) and Cohort B (40 mg) received sapablursen subcutaneously once every 4 weeks (Q4W). The primary efficacy endpoint was the reduction in phlebotomy frequency from baseline to weeks 17-37 in patients who received ≥1 dose. Forty-nine patients received ≥1 sapablursen dose (median age 61 years; 82% male). The baseline mean±SD weekly phlebotomy rate was 0.15±0.07 in Cohort A; 0.17±0.07 in Cohort B and was reduced by -0.10 (95%CI, -0.13, -0.07; n=32;p<0.0001) in Cohort A; -0.10 (95%CI, -0.14, -0.06; n=17;p=0.0001) in Cohort B. Sapablursen reduced the median (IQR) number of phlebotomies from 5.0 (3.0-6.0,Cohort A; 3.5-6.5,Cohort B) at baseline (26-weeks) to 0 (0-1.0) in the efficacy evaluation window (20-weeks) in Cohort A and 1.5 (0-2.5) in Cohort B. Most adverse events were mild or moderate; anemia and fatigue were most common. The mean change in MPN-SAF-TSS at week 37 was -6.21 points (95%CI: -10.56, -1.85, p=0.0052) in Cohort A; -2.71 points in Cohort B (95% CI: -8.33, 2.91, p=0.34). Sapablursen reduced phlebotomy need, improved symptoms, and was safe and well-tolerated in patients with polycythemia vera. (Funded by Ionis Pharmaceuticals; ClinicalTrials.gov: NCT05143957)

Aneuploidy is a hallmark of cancer often associated with inferior prognosis. Copy number gains of chromosome 8 (chr8) are recurrent in multiple cancers, including breast, prostate, colorectal cancers, and sarcomas such as malignant peripheral nerve sheath tumors (MPNSTs). MPNSTs are aggressive, hard-to-treat sarcomas frequently linked to the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. To investigate the role of chr8 gain in MPNST pathogenesis, we performed a CRISPR knockout screen and identified 58 essential genes on chr8, including PTK2, which encodes focal adhesion kinase (FAK). We evaluated FAK as a therapeutic target and tested small-molecule FAK inhibitors (FAKi) alone or combined with RAF/MEK inhibitors (RAF/MEKi), a class of agents relevant to NF1-deficient tumors with ERK pathway hyperactivation. Both pharmacological and genetic inhibition of FAK reduced MPNST cell proliferation in vitro and tumor growth in vivo. Combined FAKi and RAF/MEKi treatment further suppressed phosphorylation of FAK, STAT3, and AKT while increasing cleaved caspase-3 and PARP-1, indicating enhanced apoptosis. In MPNST patient-derived xenograft (PDX) models, combination therapy significantly reduced tumor growth, showing superior efficacy, particularly in chr8 gain MPNST-PDX. These results support FAK/RAF/MEK co-targeting as a promising therapeutic strategy for chr8 gain MPNST and related tumors.

Amyloid-targeting therapies (ATTs), including donanemab and lecanemab, are FDA-approved disease-modifying therapies for Alzheimer’s disease in the mild cognitive impairment or mild dementia stages. Early initiation is important for optimal outcomes. This article summarizes practical strategies for implementing ATTs in clinical practice, focusing on leadership alignment and infrastructure development, as well as patient identification, diagnosis, and monitoring protocols. Key recommendations include establishing appropriate patient tracking systems, infusion and imaging protocols, and interprofessional collaboration. Approaches for systematic patient routing (e.g., hub-and-spoke models, fast-track mechanisms) and biomarker-integrated assessments are critical to facilitating timely diagnosis and treatment. Education for patients, care partners, and clinicians is crucial for managing the risks associated with amyloid-related imaging abnormalities. Successful ATT implementation requires coordinated systems, timely diagnosis, and robust safety monitoring. These measures can enable frameworks for ATT administration to optimize outcomes for patients, care partners, and health systems.

Abstract The liver is organized into tightly regulated zones with distinct metabolic functions but zonation erodes with age. Cellular senescence contributes to aging and liver diseases, however, its impact on aging biology is ill-defined. As part of The Cellular Senescence Network Consortium, we used multiple spatial transcriptomics approaches (GeoMx, Visium, CosMx) with snRNA-seq to profile senescence signatures, zonation markers, and metabolic pathways in livers from wild-type (WT) mice of multiple ages. We observed a loss of canonical zone signatures in aged mouse livers characterized by “expansion” of midlobular (zone 2) marker gene expression, accompanied by diminished expression of zone 3 marker genes by middle-age (18 months), indicative of loss of cell identity. Multiple analytic approaches identified distinct age-, zone- and sex-specific senescence signatures, which were significantly associated with zonation markers changes. This was recapitulated in Ercc1 mutant models of accelerated senescence, supporting a causal role of senescent cells in liver aging. A “no-zone” hepatocyte-like cluster expanded with age and with the strongest Senescence-Associated Secretory Phenotype (SASP) profile. Gene expression profiles from senescent hepatocytes implicate decreased WNT signaling and increased BMP as contributing to age-related loss of zonation. Together, these data elucidate the role of senescent cells in driving aging biology in non-diseased liver through disruption of cell:cell signaling and the loss of metabolic and cell identity gene expression necessary for hepatocyte function.

PURPOSE Cancer care capacity in sub-Saharan Africa (SSA) is constrained by late diagnosis and limited treatment access. Few funding mechanisms support innovative, locally led programs to address these challenges. A collaborative initiative was developed to strengthen oncology care through quality improvement (QI) projects. MATERIALS AND METHODS The program was developed by Global Bridges Oncology (GBO) at Mayo Clinic, Pfizer Global Medical Grants, and the African Organisation for Research and Training in Cancer. A committee composed primarily of African oncology experts guided the process. An RFP was disseminated across SSA in English, French, and Portuguese, inviting applications to improve diagnostic and therapeutic cancer care. Applications underwent a structured, two-stage review, with GBO providing technical support, expert guidance, and training resources. RESULTS The RFP generated 218 applications reflecting strong demand for oncology QI funding in SSA. After review, 17 projects representing 10 African countries were selected and awarded $1.1 million USD. Funded initiatives reflected four themes: oncology training and clinical practice improvements, early detection and accurate diagnostics, pediatric cancer care, and oncology nursing and palliative medicine. As of March 2026, 11 (65%) of 17 projects are complete, with 4,565 health care professionals engaged through direct training, conference dissemination, system adoption, and sensitization activities, and program-supported services were delivered to more than 47,300 patients. CONCLUSION This initiative demonstrates the feasibility of a competitive, regionally guided grant program to strengthen cancer care capacity. Early implementation outcomes, including measurable improvements in diagnostic delay, treatment adherence, and care network expansion, confirm that locally led QI initiatives can generate meaningful results across diverse institutional settings. By centering African leadership and supporting diverse QI projects, it advances equitable access to funding, capacity building, and sustainability planning.

Abstract To report clinical and functional outcomes, including patient-reported outcome measures (PROMs), complications, reoperation rates, and arthritic progression in patients who sustained a knee dislocation (KD) type V fracture dislocation at minimum 2-year follow-up. A retrospective review from a prospectively collected database was performed to identify all patients with a KD type V fracture dislocation between 2001 and 2022 at a single institution. Patient demographics, pre- and postoperative clinical examination findings, intraoperative details, and postoperative complication rates were obtained from medical records. PROMs, including Visual Analog Scale (VAS), Tegner Activity Scale, Lysholm score, and International Knee Documentation Committee Subjective (IKDC) score were analyzed. A total of 11 patients (mean age: 33.9 ± 7.6, mean BMI: 33.5 ± 6.4 kg/m2) were included with a mean follow-up of 6.4 ± 5.4 years. Seven patients (64%) had a tibial plateau fracture involving the weight-bearing surface. Four patients (36%) had a concomitant nerve injury, one patient (9%) had a concomitant vascular injury, three patients (27%) had a concomitant cartilage injury (ICRS grade 3 + ), and seven patients (64%) had a concomitant meniscus injury. In all, 10 patients (82%) underwent fracture fixation. The mean postoperative Kellgren-Lawrence (KL) grade was 3.0 ± 1.0. Postoperative PROMs included VAS at rest of 2.0 ± 2.3, VAS with activity of 3.3 ± 3.2, IKDC of 68.3 ± 22.1, Lysholm of 79.0 ± 23.6, and Tegner of 4.3 ± 1.7. Nine patients (83%) experienced a complication, with four (36%) patients requiring a subsequent reoperation. Patients with a KD V fracture dislocation who underwent surgical management demonstrated high complication and reoperation rates with advanced radiographic evidence of osteoarthritis but ultimately satisfactory functional outcomes at mid-term follow-up. These findings underscore the complexity of KD V injuries and the importance of early recognition, multidisciplinary surgical planning, and patient counseling regarding the prolonged recovery and likelihood of residual symptoms. Level of evidence is IV—retrospective case series.

Abstract Introduction Microglia are the resident immune cells of the central nervous system, classically studied for neuroinflammation. A specialized subset, vessel-associated microglia (VAM), whose somata directly contact capillaries, constitutes ∼30% of microglia in the naïve brain. Only recently have VAM been recognized as regulators of brain circulation, influencing blood—brain barrier (BBB) integrity and cerebral blood flow, yet their role in pathological vascular remodeling remains unclear. To address this gap, we used glioma models in which peritumoral capillaries undergo extensive vascular remodeling and BBB dysfunction, providing an in vivo platform to probe capillary vulnerability and vascular stability. Methods We combined pharmacological microglial ablation via CSF1R inhibitors with longitudinal in vivo two-photon imaging to visualize microglia—capillary interactions. Behavioral testing, survival analysis, T2-weighted MRI, and immunostaining were performed in parallel. Results Over half of the microglia-depleted mice developed acute, lethal paralysis by 15 days, whereas control tumor-bearing mice remained asymptomatic and survived 30 days. MRI revealed large intracranial hemorrhages and severe edema, and two-photon imaging showed nodular, abnormal vasculature at paralysis onset. The peritumoral region contained dense capillary networks with a marked increase in VAMs (>60%). Genetic lineage tracing confirmed these cells were microglia, exhibiting elongated, vessel-wrapping morphology, also observed following single-vessel photothrombosis and consistent with a response to capillary injury. Conclusion Our findings identify VAMs as critical neurovascular stabilizers that preserve peritumoral capillary integrity and prevent lethal hemorrhage in glioma, highlighting an essential immune role in brain vascular homeostasis. Notably, intracranial hemorrhage has repeatedly emerged across clinical trials of CSF1R inhibitors, raising important safety considerations for CSF1R-targeted therapies in the diseased brain. Funding Source AHA postdoc fellowship (26POST1560008) (J.Z.) Topic Categories Neuroimmunology (NEUR)