Citations

BACKGROUND AND OBJECTIVES: Unruptured intracranial aneurysms (UIAs) are increasingly detected and require careful management to prevent rupture. No externally validated score currently predicts procedural risk to guide treatment decisions. We developed and validated 2 predictive scores for complications after endovascular treatment (EVT) or neurosurgical treatment (NT) of UIA using routinely collected clinical and aneurysmal features. METHODS: We conducted a multicenter retrospective study including patients with UIA treated with EVT or NT across 15 neurovascular centers (2014-2024). Predictive models were built using multivariable logistic regression, with variables derived from Delphi consensus. The primary outcome was a composite safety end point: new neurological deficits, modified Rankin Scale (mRS) worsening (≥1 point or mRS 2-5 within 30 days), or procedural death. Internal validation used bootstrapping, and external validation was performed temporally and institutionally. Model performance was assessed using area under the receiver operating characteristic curve (AUROC) and calibration. Final scores, named Morbidity and Mortality Associated Risk in the Treatment of UIAs (MARTA)-EVT and MARTA-NT, were compared with existing models identified through systematic review. RESULTS: Among 2647 patients (1907 EVT and 740 NT), procedural complications occurred in 6.3% (EVT) and 12.8% (NT). Independent predictors included age, baseline mRS, aneurysm location, size, morphology, and procedural factors. MARTA-EVT (AUROC = 0.68, 95% CI = 0.57-0.78) and MARTA-NT (AUROC = 0.65, 95% CI = 0.54-0.77) showed moderate discrimination and good calibration. MARTA-EVT outperformed existing models; MARTA-NT performed similarly to SAFETEA. Predictive models are available open-source: https://martascoreapp.shinyapps.io/martascoreapp/. CONCLUSION: MARTA-EVT and MARTA-NT are validated tools for predicting procedural risks in UIA treatment and may support patient counseling and clinical decision making.

Abstract Motivation: Epilepsy is a diverse group of neurological disorders affecting over 50 million people worldwide. While common epilepsy types are well studied, rare epilepsies—often severe and genetically complex—pose significant challenges in diagnosis, research, and treatment. Accurate and interoperable etiology and disease classifications are critical for improving data sharing, supporting clinical decision-making, and advancing rare disease research. Results: To enhance the accuracy of epilepsy-related disease concept representation within the Mondo Disease Ontology (Mondo), we conducted a series of expert-driven workshops in collaboration with the team from the Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP). Specialists in epileptology, genetics, neurodevelopment, biomedical ontology, and patient community advocates systematically reviewed and revised the epilepsy hierarchy in Mondo, aligning it with the International League Against Epilepsy (ILAE) classification system. These updates include reclassification of epilepsy subtypes, including syndromes, age-related epilepsies, and developmental epileptic encephalopathies, resulting in a more granular, standardized, and clinically relevant structure. Mondo now offers an enhanced framework for integrating epilepsy data across resources, enabling improved interoperability and facilitating rare disease research and data curation, with continued efforts underway to further refine and expand this integration.

TPS256 Background: Currently, there are no biomarkers validated prospectively in randomized studies for resected colon cancer (CC) to determine need for adjuvant chemotherapy (AC). However, circulating tumor DNA (ctDNA) represents a highly specific and sensitive approach (especially with serial monitoring) for identifying minimal/molecular residual disease (MRD) post-surgery in CC patients (pts), and may outperform traditional clinical and pathological features in prognosticating risk for recurrence. CC pts who do not have detectable ctDNA (ctDNA-) are at a much lower risk of recurrence and may be spared the toxicities associated with AC. Furthermore, for CC pts with detectable ctDNA (ctDNA+) who are at a very high risk of recurrence, the optimal AC regimen has not been established. We hypothesize that for pts whose CC has been resected, ctDNA status may be used to risk-stratify for making decisions about AC. Methods: In this prospective phase II/III trial, up to 1,912 pts with resected stage IIB, IIC, and III CC will be enrolled. Based on the post-operative ctDNA status using personalized and tumor-informed assay (Signatera, bespoke assay), those who are ctDNA- (Cohort A) will be randomized to immediate AC with fluoropyrimidine (FP)+oxaliplatin (Ox) for 3-6 mos per established guidelines v serial ctDNA monitoring. Patients who are ctDNA+ post-operatively, or with serial monitoring (Cohort B), will be randomized to FP+Ox v more intensive AC with addition of irinotecan (I) for 6 mos. One cycle of chemotherapy is allowed while awaiting ctDNA testing results for cohort assignment. The primary endpoints for Cohort A are time to ctDNA+ status (phase II) and disease-free survival (DFS) (phase III) in the immediate v delayed AC arms. The primary endpoint for Cohort B is DFS in the FP+Ox v FP+Ox+I arms for both phase II and phase III portions of the trial. Secondary endpoints include prevalence of detectable ctDNA post-operatively, time-to-event outcomes (overall survival and time to recurrence) by ctDNA status, and the assessment of compliance to adjuvant therapy. Biospecimens including archival tumor tissue, as well as post-operative plus serial matched/normal blood samples, will be collected for exploratory correlative research. Active enrollment across the NCTN started in June 2022 with CCTG sites joining in August 2023. Current accrual (as of 9-4-2025): 967/1,912. Drs. Lieu and Dasari contributed equally to the development of this trial. Clinical trial information: NCT05174169 .

334 Background: Sarcopenia, or decreased skeletal muscle mass, has been associated with worse surgical and oncologic outcomes across multiple malignancies. This study investigates the impact of sarcopenia on outcomes after multimodal therapy for esophageal cancer. Methods: Retrospective observational cohort study including adult patients who underwent neoadjuvant therapy followed by esophagectomy for primary esophageal cancer from January 2000 - December 2021. A fully automated abdominal segmentation using deep convolutional neural network was utilized to calculate skeletal muscle index (SMI) from preoperative CT scans performed at our institution. Males with SMI <52.4 cm 2 /m 2 and females with SMI <38.5 cm 2 /m 2 at any point before surgery were classified as sarcopenic. The relationship between sarcopenia and patient demographics, operative details, and complications were explored using chi-square tests. The relationship between sarcopenia and disease-free survival and overall survival were investigated using parsimonious multivariable analysis retaining variables with p-value <0.05 using backward selection method. Results: We identified 200 patients meeting the study criteria with 142 (71%) having sarcopenia at any time prior to surgery. Patients with sarcopenia were significantly older [65.2 (59.6, 71.2) vs 63 (53.6, 67.5), p = .023] and more likely to have had open surgery [129 (90.8%) vs 46 (79.3%), p = .034]. There were no significant differences in sex, history of diabetes, coronary artery disease, renal disease, smoking, cancer type, cancer stage, tumor size, tumor location, or margin status between sarcopenic groups ( p > .05). Sarcopenic patients were significantly more likely to require blood transfusion ≥3 units after esophagectomy [79 (55.6%) vs 8 (13.8%), p < .001] or to experience complications requiring surgical intervention [36 (24.6%) vs 7 (12.1%), p = .048]. Multivariate analysis revealed that sarcopenia was associated with disease-free and overall survival (Table). Conclusions: Sarcopenia is a prognostic factor in patients undergoing multimodal therapy for esophageal cancer. Interventions that aim to prevent decreases in SMI after initiating neoadjuvant therapy should be investigated. Multivariate analysis with sarcopenia predicting outcomes. Disease free survivalHR (95% CI) p-value Overall survivalHR (95% CI) p-value Age 1.04 (1.02, 1.06) < .001 1.04 (1.02, 1.07) < .001 Epicenter Middle Upper 1.88 (1.21, 2.86)3.16 (1.67, 5.98) .001.005< .001 1.96 (1.26, 3.04)4.00 (1.90, 8.44) < .001.003< .001 Stage Stage II Stage III Stage IV 1.88 (0.95, 3.71)2.90 (1.46, 5.75)16.02 (6.12, 41.93) < .001.069.002< .001 1.65 (0.83, 3.25)2.76 (1.37, 5.55)10.14 (4.03, 25.53) < .001.151.005< .001 Cancer type - - 1.76 (1.03, 3.02) .039 Transfusion > 3 pRBC - - 1.54 (0.99, 2.40) .057 BMI prior to cancer diagnosis - - 0.98 (0.94, 1.01 .208 Sarcopenic 1.76 (1.16, 2.67) .007 1.64 (1.04, 2.60) .033

BACKGROUND: Patients with cervical artery dissection (CeAD) may experience a recurrent dissection, but its frequency, risk factors, and clinical implications are not well defined. We aimed to determine the risk, associated factors, and clinical impact of recurrent CeAD. METHODS: The STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection) was a multicenter international retrospective observational study of patients with CeAD treated between January 2015 and June 2022. Recurrent dissection was defined as a CeAD occurring at least 7 days after the diagnosis of the index event that affects a different artery or a different segment of the same artery. Patients were followed from day 7 up to 2 years. The absolute risk of recurrent CeAD over time was calculated using Kaplan-Meier survival estimates. Multivariable logistic and Cox regression models were used to assess predictors of CeAD recurrence. RESULTS: Of the 4023 patients included in STOP-CAD, 3836 (median age 46 years, 45% women) were eligible for this analysis. During a median (interquartile range) follow-up of 295 (97–720) days, 88 (2.29%) patients had a CeAD recurrence. Median time-to-recurrent CeAD was 53 (interquartile range, 18–157) days. The estimated risk of recurrent CeAD at 2 years was 3.22% (95% CI, 2.59%–4.00%). In multivariable analyses, younger age (adjusted odds ratios, 0.98 [95% CI, 0.96–0.99]), migraine (adjusted odds ratio, 1.88 [95% CI, 1.14–3.07]), and fibromuscular dysplasia (adjusted odds ratio, 2.90 [95% CI, 1.66–5.06]) were associated with CeAD recurrence, while presenting with an ischemic stroke was associated with a lower likelihood of recurrence (adjusted odds ratio, 0.47 [95% CI, 0.29–0.75]). These associations with CeAD recurrence over time were confirmed by Cox regression analyses. Among the 88 patients with recurrent CeAD, only 5 had accompanying ischemic events (3 strokes, 2 transient ischemic attacks). CONCLUSIONS: In this retrospective study, recurrent CeAD was uncommon, approximately half of the events were diagnosed within the first 2 months of the index event, and recurrent events rarely caused new ischemic events. Younger age, migraine, absence of ischemic stroke at presentation, and signs of fibromuscular dysplasia may help identify high-risk patients.

Abstract Background Cytomegalovirus (CMV) infection remains one of the most prevalent and important infections following solid organ transplant (SOT). Treatment is often challenging, especially when dealing with refractory and resistant CMV infections.Table 1:Univariable logistic regression analyses of associations with early refractory CMV infectionTable 2:Univariable logistic regression analyses of associations with resistant CMV infection Methods We performed a retrospective cohort study of SOT recipients with clinically significant CMV infection (csCMVi) at a tertiary transplant center in the US during 2010-2016. The primary outcome was early refractory CMV infection and secondary outcomes were drug resistance, CMV recurrence, and mortality. Kaplan-Meier estimation, univariable logistic regression analysis, and multivariable Cox regression were used for outcome analysis.Table 3:Multivariable Cox regression analysis of associations with recurrent CMV infection after primary treatment endedNote: Refractory CMV was not included in the model for recurrent CMV as no patients with refractory infection had recurrence. Results A total of 145 SOT recipients with csCMVi were included. Most patients were recipients of liver (49%), followed by kidney (22.1%), heart (6.9%), lung (5.5%), and pancreas (4.1%). Multiple organ transplants accounted for 12.4% of the cohort. Most common induction was an anti-IL-2 antibody (43.9%) followed by ATG (29.5%). 82 (56.5%) had CMV D+/R- mismatch. In total, 34 (23.4%) had CMV syndrome, 38 (26.2%) had tissue-invasive CMV disease, while the rest (50.3%) were asymptomatic. After the initial 3 weeks of antiviral therapy, 13 (8.9%) patients had probable refractory csCMVi; most of them (10 [76.9%]) were CMV D+/R- mismatch. Longer time after transplant had lower risk (OR 0.68; CI 0.48-0.95, p=0.029) while lower absolute lymphocyte count (ALC) was higher risk of early refractory csCMVi (OR 1.54; CI 1.01-2.44, p=0.048) (Table 1). Drug-resistant CMV occurred in 7 patients (4.8%); a high initial CMV DNA level was associated with resistant csCMVi (OR 2; CI 1.08-3.93, p=0.031) (Table 2). Of 144 patients with post-treatment follow-up, 25 (17.2%) experienced recurrent csCMVi within 6 months. Table 3 shows the associations with recurrence of csCMVi after initial treatment. 30 patients (20.7%) died during a median follow-up of 4 years, but refractory, resistant or recurrent CMV were not associated with mortality. Conclusion Refractory csCMVi is associated with low ALC and an earlier onset post-transplant. Resistant csCMVi is associated with high levels of initial CMV DNA. Recurrence of csCMVi is common and possibly associated with low ALC at the end of antiviral treatment. Disclosures All Authors: No reported disclosures

Abstract Background Atypical clinical presentations of Alzheimer's disease (AD) are associated with heterogeneous patterns of cortical tau‐PET uptake. The medial‐temporal (MTL) meta‐ROI is typically used to determine tau‐PET abnormality in AD, but this approach may not detect focal uptake in atypical patients. Our goal was to develop regional tau‐PET cut‐points and determine whether the number of positive regions better captures positive tau‐PET signal in atypical AD. Method 127 amyloid‐positive atypical AD (visual=68, language=39, motor=15, others=5) and 62 amyloid‐negative cognitively unimpaired (CU) individuals were recruited by the Neurodegenerative Research Group, Mayo Clinic, and underwent, amyloid‐PET and 18 F‐AV‐1451(tau)‐PET. Images were parcellated using the modified Harvard‐Oxford atlas and we focused on 67 AD‐specific regions. Rather than using the average SUVR across voxels within a region to quantify uptake, we used the 95 th percentile of SUVR values across voxels within a region to capture focal cases. We then used receiver operating characteristic (ROC) methods and a Youden threshold to define regional abnormality. The number of abnormal regions was calculated for each participant and used to discriminate between CU and atypical AD at the individual level. Result Across 64 regions, our approach showed excellent (AUROC>0.90) differentiation between atypical AD and CU. The temporal‐fusiform, parahippocampal gyrus and inferior temporal gyrus showed the best differentiation (Figure 1). All 67 regions showed excellent specificity (>85%), with 63 regions showing excellent sensitivity (≥80%). The lateral occipital cortex, temporal‐fusiform and parahippocampal gyrus showed the best specificity and sensitivity (Figure 2). The distribution of the number of tau‐elevated regions is shown in Figure 3. 74% of CU had no positive regions, while 43% of the atypical AD patients had all 67 regions affected. An optimal threshold of 7 tau‐elevated regions classified all CU below, and 123 (97%) atypical AD above threshold. Using a standard approach based on the average SUVR in the MTL meta‐ROI, only 116 (91%) atypical AD patients were tau‐PET positive. Conclusion Tau uptake in temporal regions showed the greatest group‐level differentiation. However, examining regional tau‐positivity may offer better sensitivity in atypical AD patients compared to the temporal meta‐ROI, likely due to the presence of focal non‐temporal patterns of uptake.

Abstract Background The tau PET imaging with 18F‐flortacipir (18F‐FTP) has focused interest in accurately tracking longitudinal tau changes in Alzheimer's disease [1]. Thus, minimizing variability is critical. Off‐target signal has the potential to complicate interpretation of tau‐PET imaging due to potential spillover or bleed‐in effects, with increased effects seen in later stages of Alzheimer's due to cerebral atrophy and proximity of off‐target areas to relevant cortical areas[2]. Previously, we demonstrated the effect of uptake period activity on 18F‐FTP signal. With increasing recent interest in demographic factors that may affect off‐target binding, we investigated the effect of age in extra‐cerebral off‐target signal in 18F‐FTP PET imaging. Method Standard 18F‐FTP PET protocol was performed in 330 participants. Two independent readers measured tau uptake in predetermined off‐target regions, including extraocular muscle, meninges, and occipital bone among others. Linear regression models assessed the relationship between participants’ age, sex, and tau uptake values (SUV and SUVr) (SUV = (Tissue radioactivity concentration / Injected dose) / Body weight & SUVr = SUV of target region/ SUV of reference region.) Result Sex had a significant effect on off‐target signal in most brain regions, with variable positive or negative correlation based on area. Notably, SUV in the eyeball‐retina, occipital bone, upper skull meninges all showed significant positive correlation with sex, with ‘male’ status generally associated with lower SUV. The greatest effect of sex was observed in superior skull meninges, occipital bone, and internal carotid artery ( p <0.001). Age showed minimally affected SUV and SUVr in off‐target regions. SUVr values show a significant correlation with SUV values of upper skull meninges in sex. Cognitive status did not significantly affect off‐target SUV. Conclusion We observed that sex significantly affected extra‐brain off‐target signal in 18F‐FTP PET imaging, while age has minimal effect, adding to previous evidence of off‐target binding within brain regions. Further evaluation is necessary to understand the age‐related effects on off‐target regions. As a result, the variability introduced by sex may pose challenges to studying tau accumulation.