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Objective: To assess the link between retinal vascular health and cognitive performance in a diverse population, using a novel mobile laboratory platform and portable color fundus photography. Background: The retina is an accessible window into brain health. Studies that had highlighted the link between retinal vasculature and cognition included clinical populations or narrowly defined research cohorts, with limited generalizability. To address the need to expand this research to demographic and geographic diverse communities, we launched a mobile laboratory platform across rural and urban Arizona zip codes. Methods: 240 subjects were recruited in our prospective community-based study. We assessed cognition using the MindCrowd web-based testing platform and analyzed verbal paired associates (VPA) task, a validated measure of verbal associative memory sensitive to age-related cognitive decline. Non-mydriatic color fundus photographs were obtained using the portable hand-held Aurora camera (Optomed), two images per eye (disc- and macula-centered). Image processing and vascular feature quantification were automatically conducted using Automorph software. Linear regression models examined the associations between retinal vascular metrics and VPA, adjusting for age, sex, education attainment, and risk factors. Results: Our cohort’s mean age was 45 +/-16.7 years, 32.9% were male and 39.5% had a college degree. In disc-centered fundus images, fractal dimension strongly associated with chronological age (p = 1.04E-10). Greater artery tortuosity in the retinal zones B and C was associated with lower VPA (p = 0.02 and p = 0.004, respectively). In macula-centered images, fractal dimension showed the strongest association with age (p = 4.31E-11), reinforcing its utility as a robust biomarker of vascular aging. Males had wider average artery caliber in zone B (p=0.02). Zone B vein fractal dimension (p=0.002) and vein vessel density (p=0.006) were the strongest predictors of VPA. Conclusions: This study demonstrates the safety, feasibility, and utility of a mobile laboratory to collect high-quality non-mydriatic color photos and cognitive data across a geographically diverse cohort. Arterial tortuosity and venous fractal dimension and density, particularly in retinal zone B, were predictive of cognitive performance, after adjusting for vascular health covariates. Retina may become a scalable and accessible platform for studying brain aging in the general population.

476 Background: Outcomes remain poor for patients with advanced/metastatic CCA treated with first-line gemcitabine-cisplatin +/- anti-PD(L)1. Lirafugratinib is the first highly selective, irreversible FGFR2 inhibitor designed to target oncogenic FGFR2 driver alterations and resistance mutations. ReFocus (NCT04526106) is an open-label, multicenter phase 1/2 study in patients with advanced/metastatic CCA and other solid tumors with FGFRok2 alterations. Methods: Pivotal cohort of patients (n=116) with advanced/metastatic CCA harboring FGFR2 f/r previously treated with ≥1 systemic therapy and FGFR i-naive were treated with oral lirafugratinib 70 mg once daily until disease progression or unacceptable toxicity. The primary endpoint was confirmed ORR per RECIST v1.1 by independent review committee (IRC). Key secondary endpoint was duration of response (DOR); other secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and quality of life per EORTC QLC-C30. Results: As of 27SEP2024, the primary efficacy analysis of IRC-assessed data (n=114) and the secondary analysis of investigator-assessed data (n=116) set was done. The primary efficacy analysis excluded 2 patients as not available. Median age 57 years with 61.4% female. IRC-assessed ORR was 47%, and median DOR was 11.8 months (mos) (95% CI, 7.5-13.0), where 76.2% of responses lasted >6 mos. Median PFS was 11.3 mos (95% CI, 9.2, 14.8), with 12-month rate of 49.2%. Median OS was 22.8 mos (95% CI, 17.3-27.2), with 12-month rate of 74.6%. DCR was 96.5%. Common grade ≥3 on-target, off-tumor treatment-related adverse events (TRAEs) included palmar-plantar erythrodysesthesia (32.8%) and stomatitis (12.1%). TRAEs led to dose reductions of 75.9%, dose interruption of 82.8%, and treatment discontinuation of 4.3%. QoL was maintained. Conclusions: Lirafugratinib demonstrated clinically meaningful anti-tumor activity (ORR, DOR, and PFS), manageable and tolerable safety in CCA FGFR2 f/r patients. Clinical trial information: NCT04526106 . Best Overall Response, n (%) IRC c Investigator d Complete Response Partial Response Stable Disease Progression Disease Not Evaluable 3 (2.6)50 (43.9)57 (50.0)3 (2.6)1 (0.9) 061 (52.6)51 (44.0)3 (2.6)1 (0.9) ORR a , n (%)95% CI 53 (46.5)37.1, 56.1 61 (52.6)43.1, 61.9 DCR b , n (%)95% CI 110 (96.5)91.3, 99.0 112 (96.6)91.4, 99.1 a ORR defined as proportion achieving confirmed response of complete response or partial response per RECIST v1.1. b DCR defined as proportion with confirmed response of complete response, partial response, or stable disease per RECIST v1.1. c Primary Efficacy Analysis Set. d Secondary Efficacy Analysis Set. Percentages based on number of patients in the analysis set for each treatment arm. Exact Clopper-Pearson used for 95% CI. IRC and investigator assessments are based on different populations and cannot compare directly.

This Practice Advisory presents a comprehensive and evidence-based set of position statements and recommendations for the use of contrast media in interventional pain procedures. The advisory was established by an international panel of experts under the auspices of 11 multinational and multispecialty organizations based on a comprehensive review of the literature up to December 31, 2019. The advisory discusses the risks of using gadolinium-based contrast agents. These include nephrogenic systemic fibrosis, gadolinium brain deposition/retention, and encephalopathy and death after an unintentional intrathecal gadolinium injection. The advisory provides recommendations on the selection of a specific gadolinium-based contrast agent in patients with renal insufficiency, those who had multiple gadolinium-enhanced magnetic resonance imaging examinations, and in cases of paraspinal injections. Additionally, recommendations are made for patients who have a history of mild, moderate, or severe hypersensitivity reactions to contrast medium.