Citations

Abstract Brain arteriovenous malformations (AVMs) result from abnormal growth of vascular structures. AVMs pose a significant rupture risk, and its treatment is challenging due to the complex hemodynamics within the tangled nidus. Currently, investigating AVM hemodynamics remains a challenge due to the low resolution of clinical imaging modalities. In this study, a high-fidelity Computational Fluid Dynamics (CFD) simulation of a brain AVM from a KRAS-mutated mouse model is developed from micro-CT images. Brain AVMs were induced in mice through systemic delivery of AAV-BR1-CAG vector encoding KRASG12V-GFP transgene to cerebral endothelial cells. High-resolution microCT imaging at 6.551 𝜇𝑚 pixel size captured the complex vascular anatomy. The cerebral arteries were reconstructed using the 3D Slicer and Blender software. The curvilinear immersed boundary (CURVIB) method was employed with approximately 65 million grid points and spatial resolution of 0.7−2.3 𝜇𝑚. Our preliminary results reveal heterogeneous flow distribution through the nidus, with blood channeling through two primary pathways. The extremely low Reynolds number (0.038) indicates viscous-dominated flow characteristic of microcirculation. Our work presents the first high-resolution CFD simulation of brain AVM in the literature, providing a foundation for investigating flow-mediated vascular remodeling, rupture risk assessment, and therapeutic intervention planning in future.

This cross-sectional study examines sexual orientation-related discrimination among lesbian, gay, bisexual, and nonheterosexual (LGB+) medical students with disabilities.

PURPOSE Cholangiocarcinoma is a rare cancer associated with poor prognosis. Pemigatinib was the first FGFR1-3 inhibitor approved for second-line therapy and beyond, on the basis of the phase II FIGHT-202 trial. Here, we assess efficacy and safety of first-line pemigatinib. METHODS FIGHT-302 is a phase III, randomized, global trial evaluating pemigatinib as first-line therapy (ClinicalTrials.gov identifier: NCT03656536 ). Adults with advanced cholangiocarcinoma with FGFR2 rearrangement were randomized 1:1 to receive pemigatinib (13.5 mg once daily) or chemotherapy (1,000 mg/m 2 gemcitabine plus 25 mg/m 2 cisplatin once per day on days 1 and 8 of every 3-week cycle for ≤8 cycles) and were stratified by prior receipt of chemotherapy, geographic region, and tumor burden. Pemigatinib crossover was allowed for patients progressing on chemotherapy. The primary end point was progression-free survival (PFS). Secondary efficacy, safety, and exploratory end points were also analyzed. RESULTS Overall, 4,563 patients were prescreened, 196 were screened, and 167 randomly assigned to receive pemigatinib (n = 83) or chemotherapy (n = 84) before early closure of the study because of a change in standard of care. The median PFS was 8.3 months in the pemigatinib group versus 6.8 months in the chemotherapy group (hazard ratio, 0.58 [95% CI, 0.39 to 0.87]; nominal P = .0078); objective response rate was 47% versus 15%, and the median duration of response was 14.2 versus 6.3 months. Median overall survival was similar (24.4 v 25.0 months, respectively). In the crossover group (n = 42, second-line pemigatinib), the median PFS was 8.1 months. Safety was consistent with the known profile of pemigatinib. CONCLUSION To our knowledge, this was the largest, first-line, randomized, phase III trial of a targeted therapy for advanced FGFR2- rearranged cholangiocarcinoma. Pemigatinib demonstrated prolonged median PFS compared with chemotherapy, with no new safety findings.