Citations

ABSTRACT Endoluminal flow diverters are increasingly used to treat cerebral aneurysms. Despite good aneurysm occlusion efficacy, delayed ischemic complications due to side branch or perforator occlusion remain a serious concern. However, the mechanisms leading to side branch occlusion are poorly understood. To investigate these mechanisms, a combination of animal and computational models was utilized. Flow diverters were deployed in four rabbit superior mesenteric artery (SMA) and studied with computational fluid dynamics (CFD) and a previously developed fibrin dynamics model. Subject‐specific vascular models were reconstructed from 3D rotational angiography images and flow conditions were derived from Doppler ultrasound velocity measurements. Flow diverting devices were virtually deployed within the vascular models under guidance from angiography images. Coupled flow and fibrin production, transport, and adhesion simulations were carried out and the effects of fibrin accumulation at the origin of jailed side branches after flow diverter implantation were analyzed. The results of the computational models suggest significant fibrin accumulation across the struts of all flow diverting devices jailing side branches. Larger accumulation was observed at the more distal branches. However, minor flow alterations were produced which were not detectable in angiography sequences. These results were in agreement with experimental observations. On the other hand, fibrin accumulation alone did not explain complete side branch occlusions, which are likely the result of the interaction between initial fibrin accumulation and subsequent cell migration from the peripheral parent artery.

Background: Pulsatile tinnitus (PT) is frequently caused by venous sinus stenosis and may be associated with idiopathic intracranial hypertension (IIH). Venous sinus stenting (VSS) directly addresses venous outflow obstruction and has emerged as a therapeutic option; however, outcome data remain heterogeneous. We performed an updated systematic review and meta-analysis to evaluate the efficacy and durability of VSS for PT and to compare outcomes between IIH-associated and isolated PT. Methods: MEDLINE, Scopus, and Web of Science were searched from inception through December 2025 following PRISMA guidelines. Clinical studies reporting PT outcomes after VSS were included. Random-effects meta-analyses of proportions were conducted to estimate pooled rates of overall improvement, complete resolution, and recurrence. Prespecified subgroup analyses compared IIH versus isolated PT. Results: Thirty-two studies comprising 850 patients were included (641 with IIH; 209 with isolated PT). Venous sinus stenosis accounted for 90.3% of treated etiologies. The pooled rate of overall PT improvement was 89.8% (95% CI, 85.5-92.9). Complete resolution occurred in 87.1% (95% CI, 82.5-90.6). Recurrence at last follow-up was 10.9% (95% CI, 8.3-14.2). Improvement and complete resolution rates did not differ significantly between IIH and isolated PT. Recurrence was higher in IIH (12.0%) than in isolated PT (5.7%), without reaching statistical significance. Conclusions: VSS is associated with high rates of PT improvement and complete resolution with low recurrence. Recurrence trends appear higher in IIH, suggesting underlying pathophysiology may influence durability.

Background: Despite recent advances in cleft care, Vietnam continues to have extensive involvement from international nongovernmental organizations (NGOs), creating a fragmented system with limited coordination. This project seeks to establish a baseline understanding of Vietnam’s cleft care landscape, including major international NGOs and their collaborations with local partners, costs and insurance coverage, and patterns applicable to other low- and middle-income countries with NGO-supported cleft care. Methods: We conducted a mixed-methods study using literature review and semi-structured interviews with surgeons, hospital administrators, and NGO representatives (n = 7). Sources included PubMed, targeted Google searches, and government regulations on NGO involvement, cleft care costs, and insurance policies. Results: Vietnam partners with 17 international NGOs that operate through 3 distinct but complementary models: vertical, horizontal, and diagonal models. These collaborations offer financial support, infrastructure, technology investment, and research development, leading to higher surgical volume, more timely access to care, and implementation of standardized multidisciplinary cleft services in Vietnam. National insurance provides broad coverage but requires a complex referral process with limited benefits for secondary cleft services. Limited awareness of insurance benefits and mistrust of local care further discourage the use of national health insurance. Conclusions: Improving access to comprehensive cleft services in Vietnam requires streamlining insurance referral pathways and decentralizing advanced cleft services to regional centers to ensure continuity of care. Aligning NGO activities with national policies is essential to building a coordinated and sustainable cleft care system in Vietnam and in other low- and middle-income countries with strong insurance frameworks and significant NGO involvement.

The spinal cord plays a central role in the pathophysiology and clinical manifestations of multiple sclerosis (MS), yet remains under-studied compared with the brain. This review summarizes key insights from the 2025 North American Imaging in MS Spinal Cord Imaging Workshop, highlighting recent advances, ongoing challenges, and future opportunities in MS spinal cord imaging. We review pathological studies and outline the clinical relevance of spinal cord lesions and atrophy for diagnosis, prognosis, and disease monitoring, highlighting emerging biomarkers of progression independent of relapse activity. Correlations between magnetic resonance imaging, histopathology, and clinical outcomes support the validation and translational potential of advanced spinal cord imaging techniques. Finally, we discuss spinal cord–specific processing pipelines and reproducibility challenges. Collectively, these insights underscore the need to integrate advanced and quantitative spinal cord imaging into clinical trials, research studies, and—when feasible—clinical care, to fully capture the extent of MS pathology, and ultimately improve patient outcomes.

TPS3675 Background: Multi-agent chemotherapy regimens (eg, mFOLFOX6) ± anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor regimens are currently the standard of care for patients (pts) with mCRC without targetable mutations. However, the 5-year survival rate remains low at approximately 16% (SEER, 2025). The addition of biological therapies (eg, bevacizumab [bev], an anti-VEGF monoclonal antibody) to immune checkpoint inhibitors (ICIs) has demonstrated a synergistic antitumor effect in solid tumors. However, ICI monotherapy has limited activity in mismatch repair proficient (pMMR)/microsatellite stable (MSS) mCRC. Simultaneous bispecific targeting of programmed death 1 (PD-1) and VEGF in conjunction with cytotoxic chemotherapy has the potential to enhance antitumor activity. PF-08634404 is a fully human immunoglobulin G4 (IgG4) bispecific antibody targeting PD-1 and VEGF. A phase 2 study of PF-08634404 with XELOX or mFOLFOX6 demonstrated promising antitumor activity with a manageable safety profile in first-line (1L) mCRC (Xu X, ESMO 2025; Abstract 796P). Methods: Symbiotic-GI-03 (NCT07222800) is an ongoing, double-blind, randomized, phase 3 study evaluating the efficacy and safety of 1L PF-08634404 + mFOLFOX6 vs bev + mFOLFOX6. Inclusion criteria are age ≥18 y; mCRC with measurable disease per RECIST 1.1; no prior systemic therapy for metastatic disease; ECOG PS 0 or 1; and adequate hematologic, hepatic, and renal function. Pts with BRAF V600E-mutant or mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) CRC, active central nervous system metastases, or clinically significant risk of hemorrhage/fistula will be excluded. Approximately 800 pts will be randomized 1:1 to receive PF-08634404 + mFOLFOX6 or bev + mFOLFOX6 until disease progression, unacceptable toxicity, withdrawal of consent, or death. Randomization will be stratified by region (North America, Europe, or rest of world), RAS status (mutant or wildtype), and presence of liver metastasis (yes or no). The dual primary endpoints are progression-free survival (PFS) by blinded independent central review and overall survival; for each, a stratified log-rank test will be used to compare arms. Hazard ratios with corresponding 2-sided 95% CIs will be estimated using a stratified Cox proportional hazards model, and medians will be estimated using the Kaplan-Meier method with corresponding 2-sided 95% CIs calculated using the log(-log) method. Secondary endpoints include PFS by investigator, objective response rate, duration of response, PFS after next-line therapy, safety/tolerability, pharmacokinetics, immunogenicity, and patient-reported outcomes. Enrollment began in December 2025. Clinical trial information: NCT07222800 .

6028 Background: RET alterations are targetable oncogenic drivers in multiple solid tumors and TCs. Pralsetinib is an oral, potent, selective RET inhibitor granted accelerated approval by the FDA for adults and children aged ≥12 y with advanced/metastatic RET fusion-positive TC who require systemic therapy and are radioactive iodine-refractory, based on ARROW trial (NCT03037385) results. Accelerated approval for medullary TC (MTC) was withdrawn by the sponsor in 2023 due to recruitment challenges in the confirmatory trial. We report final efficacy and safety in ARROW patients with RET -altered TC and MTC. Methods: Phase 2 ARROW patients were enrolled from 84 sites in 13 countries. Primary end points were overall response rate (ORR; per RECIST v1.1) and safety. Progression-free survival (PFS), overall survival (OS), and safety were assessed in patients with advanced/metastatic TC and MTC who received ≥1 dose of pralsetinib (Efficacy Population [EP]). ORR and duration of response (DOR) were assessed in the Measurable Disease Population (MDP). Results: At the May 20, 2024, data lock, 28 patients with RET -altered TC and prior systemic treatment and 145 patients with RET -altered MTC received pralsetinib 400 mg/d (median treatment duration: 24.7 mo [TC]; and 35.4 mo [MTC]). In the TC and MTC groups, median age was 58 and 57 y; 39% and 64% were male; median (range) prior lines of treatment was 2 (1, 9) and 1 (1, 6). 53.8% of MTC patients had prior systemic treatment. In TC and MTC patients, ORRs (95% CI) were 91.7% (73.0, 99.0) and 68.2% (59.5, 76.0) (Table). Treatment-related adverse events (TRAEs) occurred in 27 (96%) TC and 142 (98%) MTC patients; 68% and 67% had grade ≥3. TRAEs in ≥35% of TC and MTC patients were increased AST (50% and 38%) and ALT (43% and 30%), decreased white blood cell count (39% and 30%), and anemia (39% each). Death due to a TRAE occurred in 1 TC patient (liver injury) and 1 MTC patient (pneumonia). Safety was consistent with prior reports. Conclusions: The final analysis of ARROW confirms that pralsetinib yields clinically meaningful and durable responses in patients with RET -altered TC and MTC with a manageable safety profile consistent with prior reports. Clinical trial information: NCT03037385 . Efficacy summary. All MTC MTCPrior Cabozantinib/Vandetanib MTC Treatment-Naïve TCPrior Systemic Treatment MDP, n 132 60 62 24 ORR, % (95% CI) 68.2(59.5, 76.0) 56.7(43.2, 69.4) 79.0(66.8, 88.3) 91.7(73.0, 99.0) Complete response, n (%) 12 (9.1) 2 (3.3) 7 (11.3) 4 (16.7) Partial response, n (%) 78 (59.1) 32 (53.3) 42 (67.7) 18 (75.0) DOR, median, mo (95% CI) 39.6(29.4, NE) 21.7(15.1, 34.8) NR(36.8, NE) NR(16.0, NE) DOR follow-up, median, mo (95% CI) 45.7(41.0, 48.4) 48.9(36.9, 58.7) 45.1(40.4, 47.8) 35.4(26.9, 40.0) EP, n 145 67 67 28 OS, median, mo (95% CI) NR(54.6, NE) 42.2(31.2, NE) NR(NE, NE) NR(25.4, NE) PFS, median, mo (95% CI) 37.2(27.5, 55.5) 24.9(19.9, 35.0) 55.3(36.8, NE) NR(14.7, NE) NE, not evaluable; NR, not reached.

OBJECTIVE The objective was to evaluate the trajectories of hematoma resolution and functional improvement after middle meningeal artery embolization (MMAE) for chronic subdural hematoma (cSDH), model the temporal pattern of cSDH resolution, and identify factors associated with favorable outcomes. METHODS This real-world multicenter retrospective study included cSDH patients treated with MMAE at 24 centers between 2019 and 2024. Hematoma thickness was measured at baseline and at follow-up intervals (1–4 weeks, 1–3 months, 3–6 months, 6–12 months, and > 12 months after embolization). Resolution patterns were modeled using exponential decay functions. Modified Rankin Scale (mRS) scores assessed functional outcomes. Good functional outcome was defined as mRS score ≤ 2. Resolution patterns were modeled using exponential decay functions to estimate time to 50% and 80% reduction. Patients were categorized as complete resolution (≥ 99%) or by quartile of the remaining distribution (substantial [73%–98%], moderate [53%–73%], partial [27%–53%], minimal [< 27%]). The primary outcome was good functional status (mRS score ≤ 2). RESULTS The authors analyzed a total of 1781 patients with 2295 cSDHs who underwent MMAE. The mean ± SD age was 72.8 ± 12.4 years and 68.1% of patients were male. The initial mean hematoma thickness was 15.31 ± 6.53 mm, decreasing to 5.24 ± 5.91 mm at final follow-up (mean reduction 64.3% ± 42.1%). Resolution followed an exponential decay pattern, with an estimated time to 50% reduction of 1.8 months and to 80% reduction of 8.9 months. Complete resolution occurred in 1031 of 2224 patients (46.4%) with complete follow-up. The median (IQR) mRS score improved from 1 (0–3) at baseline to 0 (0–2) at > 12 months. Good functional outcomes were more common in patients with complete versus minimal resolution (68.9% vs 35.0%, p < 0.001). Achieving ≥ 73% resolution within 90 days was associated with better outcomes (good outcome in 76.9% of those with ≥ 73% resolution vs 67.3% in those without, p < 0.001). Neurological deterioration was the strongest predictor of lack of good outcome (23.7% in patients with neurological deterioration vs 82.4% without, p < 0.001). CONCLUSIONS After MMAE for cSDH, reduction in hematoma thickness follows a predictable exponential decay pattern. Greater extent (≥ 80%) and faster timing (within 90 days) of resolution are valuable prognostic indicators. Functional outcomes improve progressively through 6–12 months after the procedure. The relationship between resolution extent and functional outcomes provides quantitative benchmarks for evaluating treatment response.

Abstract Aims SCN5A-E1784K (c.5350G&gt;A) is the most common variant associated with the long QT (LQTS) and Brugada syndromes (BrS). It can manifest variably as LQTS, BrS, and/or conduction disorders. This presents a challenge for risk stratification. We aimed to describe clinical and ECG characteristics and identify risk markers that associate with arrhythmic events. Methods and results We undertook a retrospective observational multicentre study of a large cohort of 231 subjects with SCN5A-E1784K from Europe, USA, and Japan. Comprehensive demographic and clinical data, including initial presentation ECG and follow-up, were collected. ‘Lethal events’ were defined as sudden death, non-fatal cardiac arrest, and documented sustained VT or VF. ‘Cardiac events’ were defined as arrhythmic syncope plus any lethal events. Clinical characteristics and ECG parameters corrected for age were investigated for association with lethal and/or cardiac events. Fourteen (6%) subjects experienced a lethal event and 45 (19%) a cardiac event. PR interval and QRS duration were associated with lethal and cardiac events. In multivariable models, both PR interval and QRS duration were associated with lethal events, but only QRS duration was associated with cardiac events. Only age-corrected QRS (rQRS) was associated with lethal and cardiac event-free survival from birth after correction for multiple testing. Conclusion Ventricular myocardial conduction appears likely to play a role in the risk of arrhythmic events in patients with SCN5A-E1784K. This provides an important opportunity for the personalization of management and has the potential to guide preventative therapies.

Background/Objectives: Characterizing spinal cord multiple sclerosis (MS) lesions in MRI is critical for diagnosis, monitoring, and treatment evaluation. However, current automated approaches for lesion detection and segmentation are typically designed for specific MRI contrasts or acquisition sites, limiting their generalizability in real-world clinical settings where imaging protocols vary widely. This work proposes a robust multi-site, multi-contrast segmentation framework for spinal cord lesions. Methods: The segmentation model was trained and evaluated on a large-scale dataset comprising 4428 annotated images from 1849 persons with MS across 23 imaging centers, encompassing six MRI contrasts (T1w, T2w, T2*w, PSIR, STIR, and UNIT1) acquired at 1.5 tesla (T), 3 T, and 7 T. Results: Likert-type assessment performed by neuroradiologist ratings demonstrated superior generalization of the model compared to existing contrast-specific pipelines ( p < 0.01). Additional experiments evaluated robustness across spinal levels, acquisition resolutions, binarization thresholds, and quantitative evaluation on external labeled datasets. Conclusions: The proposed model can achieve accurate and reliable spinal cord MS lesion segmentation across heterogeneous MRI data, addressing a key barrier to clinical translation. The model is available in the Spinal Cord Toolbox v7.2 and higher. Code repository: https://github.com/ivadomed/seg-sc-ms-lesion-multicontrast