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Introduction: While balloon guide catheters (BGCs) enhance safety and efficacy of mechanical thrombectomy in large vessel occlusions, their impact on distal medium vessel occlusion (DMVO) remains underexplored. This study aimed to compare the outcomes of BGC vs non-BGC in DMVO thrombectomy. Methods: This retrospective study focused on DMVO cases defined as occlusions in M2-M4 middle cerebral artery, anterior cerebral artery, and posterior cerebral artery. Baseline characteristics and technical and clinical outcomes were compared between the two groups, with subgroup analysis in first-line thrombectomy techniques, including ADAPT, stent retriever, and Solumbra. First pass effect (FPE) was defined as a modified Thrombolysis in Cerebral Infarction (mTICI) score ≥ 2C after the first pass. Results: A total of 1,508 patients were included, of whom 231 (15.3%) were in the BGC group and 1,277 (84.7%) were in the Non-BGC group. The BGC group was associated with a lower mTICI score ≥ 2C (overall: 43.2% vs. 52.7%, p = 0.01; ADAPT: 42.2% vs. 57.1%, p = 0.01; Solumbra: 32.4% vs. 51.4%, p = 0.005), longer puncture to intracranial access time (overall: 15 vs. 8 min, p < 0.001; ADAPT: 17 vs. 8 min, p < 0.001; Solumbra: 12 vs. 8 min, p = 0.02), and longer puncture to recanalization time (overall: 97 vs. 35 min, p < 0.001; ADAPT: 100 vs. 28 min, p < 0.001; Solumbra: 78 vs. 46 min, p < 0.001; Stent retriever: 95 vs. 45 min, p < 0.001 ). The BGC group also had a lower FPE rate (17.4% vs. 30.7%, p = 0.03) in the Solumbra subgroup. In terms of clinical outcomes, the BGC group had a lower rate of distal embolization (overall: 8.8% vs. 14.9%, p = 0.02), but there were no significant differences in other clinical outcomes between the two groups in first-line thrombectomy techniques. Conclusions: Our findings showed that the use of BGC in DMVO had a lower mTICI score, reduced FPE rates, decreased distal embolization, and longer procedure times. Figure 1: Figure 2:

Introduction: The efficacy of mechanical thrombectomy (MT) for tandem vertebrobasilar occlusion (tVBO) is not well established in patients with basilar artery occlusion (BAO). Objective: To investigate the treatment outcomes of MT in tVBO. Method: This international, multicenter, retrospective cohort included patients with MT for tVBO and isolated BAO from 2013 to 2023. The primary outcome was the 90-day modified Rankin Scale (mRS) score 0-2. Secondary outcomes included complete recanalization (modified Thrombolysis in Cerebral Ischemia [mTICI] ≥ 2C) and 90-day mortality rate. These outcomes were compared between tVBO and isolated BAO groups. Adjustment factors were age, sex, admission National Institutes of Health Stroke Scale (NIHSS), pre-morbid mRS, onset to groin duration, and intravenous tissue plasminogen activator. Results: Among 10,229 patients, 689 had BAO. Of those, 61 (9.7%) had a tVBO. Median age was 61 [IQR 53-74] years and 29 (47.5%) patients were female. Compared to isolated BAO, tVBO group had lower age (61 [53-74] versus 68 [58-79], P<0.001) and lower admission NIHSS (15 [7 - 22] versus 17 [9-26], P≤0.05). There was no significant difference in the rate of complete recanalization between the two groups (adjusted odds ratio [aOR]: 0.83; 95% CI: 0.39-1.79; P=0.60) However, the tVBO group had significantly lower odds of a favorable outcome compared to the isolated BAO group (aOR: 0.35; 95% CI: 0.13-0.83; P=0.023) and higher odds of 90-day mortality (aOR: 3.51; 95% CI: 1.59-7.85; P=0.002). Binary regression analysis revealed that age (OR 0.98; 95% CI 0.96 - 1.00; P=0.019), admission NIHSS (OR 0.90; 95% CI 0.87-0.93; P<0.001), premorbid mRS (OR 0.71; 95% CI 0.53-0.93; P=0.016), successful recanalization (OR 2.94; 95% CI 1.71-5.15; P<0.001), and tVBO (OR 0.33; 95% CI 0.11-0.86; P=0.031) were significant predictors of 90-day favorable outcome. Conclusion: tVBO was associated with poor outcomes. Further efforts should be aimed at improving outcomes for this subpopulation.

Objective: To determine whether first pass effect (FPE) after mechanical thrombectomy (MT) for anterior circulation large vessel occlusion acute ischemic stroke (LVO-AIS) is modified by procedural time (PT). Methods: The Stroke Thrombectomy and Aneurysm Registry (STAR), a multi-center international dataset, was retrospectively analyzed for anterior circulation LVO-AIS treated by MT who achieved excellent reperfusion (TICI 2c/3). The primary outcome was good functional outcome as defined by a 90-day modified Rankin Scale (mRS) 0-2. The primary study exposure was first pass success (FPS, 1 pass vs ≥2 passes) and the secondary exposure was PT. Logistic regression models were fit-adjusted and marginal effects used to assess the interaction of PT (≤30 vs >30 minutes) and FPS, adjusting for potential confounders including time from last known well to start of MT. Results: A total of 1,310 patients had excellent reperfusion. These patients were divided into two cohorts based on PT: ≤30 minutes (777 patients, 59.3%) and > 30 minutes (533 patients, 40.7%). Good functional outcome was observed in 658 patients (50.2%). The interaction term between FPS and PT was significant (p=0.018). Individuals with FPS in ≤30 minutes had 11.5% higher adjusted predicted probability of good outcome compared with those who required ≥2 passes (58.2% vs. 46.7%, p=0.001). However, there was no significant difference in the adjusted predicted probability of good outcome based on FPS in individuals with PT >30 minutes (p=0.763). This relationship appeared identical in models with PT treated as a continuous variable. Conclusion: In a large, real-world, multi-national dataset, we find that FPE is importantly modified by PT. The added clinical benefit of FPE is lost in longer procedures (>30 minutes). These data argue for a new metric for MT procedures, namely, FPE 30 , that better represents the ideal of fast, complete reperfusion with a single pass of a thrombectomy device.

314 Background: Prostate cancer patients (PC) face an elevated risk of both developing atherosclerotic cardiovascular disease (ASCVD). The American College of Cardiology Pooled Cohort Equations (PCE) for ASCVD predictions may lack accuracy. Methods: Males ≥18 years, diagnosed with PC between 2005-2012 at a hybrid academic-community practice were included. Using XGBoost algorithm we developed using a training subset of the cohort (50% train + 25% test), ranked 33 covariates (including demographic, treatment-related and social determinants of health (SDOH) information) for ASCVD prediction using SHAP (Shapley additive explanations) values. The top 10 predictors were transformed in a predictive equation using logistic regression models. This equation was tested in the cohort validation subset (25%), and subsequently compared to the PCE risk score. Results: We included 1,506 patients, with a median age of 67 (IQR 60-74) years, 13.8% had advanced stage disease (TNM III-IV), 1.5% had high risk PC (Gleason 8-10), and 20.5% received androgen deprivation therapy (ADT). Of those, 10.4% had a 10-year ASCVD risk. The PCE had an area under the curve (AUC)=0.61 and underestimated ASCVD in 0.9% (mean risk=20.1% [95% CI 17.2-23.0] vs. mean predicted risk=19.2% [95% CI 18.6-19.8]). The equation pooled from the top-10 predictors of the ML algorithm (C-index=0.78 [95% CI 0.75-0.81]) achieved an AUC=0.71 (Table). Conclusions: Conventional PCE tend to underestimate ASCVD risk in males with PC. A cancer-specific model inclusive of SDOH exhibits good performance for predicting ASCVD risk in this population. [Table: see text]

LBA531 Background: Muscle-invasive urothelial carcinoma (MIUC) is an aggressive disease with high relapse rates. Neoadjuvant platinum-based chemotherapy (NAC) is the standard of care in patients (pts) who are cisplatin (Cis)-eligible. However, many pts are Cis-ineligible or have persistent muscle-invasive disease after NAC and surgery. We evaluated pembrolizumab (Pembro) as adjuvant therapy in pts with high-risk MIUC following surgical resection. Methods: The AMBASSADOR study is an open-label, randomized, phase III trial that enrolled pts with histologically confirmed MIUC of the bladder, upper tract, or urethra who (1) had ≥ pT2 and/or pN+ or margins+ at surgery (radical cystectomy, nephrectomy, nephroureterectomy, or ureterectomy) following NAC or (2) ≥ pT3 and/or pN+ or margins+ at surgery without NAC and were either Cis-ineligible or declined adjuvant Cis-based therapy. Pts were registered ≥4 to 16 weeks after surgery and randomized 1:1 to receive Pembro 200 mg every 3 weeks for 1 year or observation (Obs). Randomization was stratified by pathologic stage, centrally tested PD-L1 status, and prior NAC. The dual primary endpoints were disease-free survival (DFS) and overall survival (OS) with a target sample size of 739 pts and required 387 DFS and 320 OS events for final analysis. Secondary objectives included evaluation of DFS and OS in PD-L1-positive and -negative pts and assessing safety. Here we present the interim DFS and OS results. Results: Between 09/2017 and 08/2021 a total of 702 pts were randomized prior to early closure due to US FDA approval of nivolumab for MIUC pts: 354 pts to Pembro and 348 pts to Obs; 13.0% vs 21.6% withdrew from study without event in the Pembro vs Obs arms, respectively. 74 pts (21%) in the Obs arm received an immune checkpoint inhibitor. Median follow-up was 22.3 months (mos) for DFS and 36.9 mos for OS. The DFS endpoint (based on 319 events needed for interim analysis) crossed the efficacy boundary. Median DFS was 29.0 months (95% confidence interval (CI) 21.8‒not evaluable (NE)) with Pembro and 14.0 months (95% CI 9.7‒20.20) with Obs (hazard ratio (HR) 0.69 [95% CI 0.55–0.87]; p=0.0013). At the interim analysis (n = 257 events), median OS was 50.9 months (95% CI 43.9‒NE) with Pembro and 55.8 months (95% CI 53.3‒NE) with Obs (HR 0.98 [95% CI 0.76–1.26]; p=0.88). Grade 3+ adverse events occurred in 48.4% and 31.8% of pts in the Pembro and Obs arms, respectively. Conclusions: Adjuvant Pembro demonstrated a statistically significant and clinically meaningful improvement in DFS vs Obs for high-risk MIUC pts after radical surgery. The OS endpoint may have been impacted by pts on the Obs arm receiving a checkpoint inhibitor. Pembro was tolerable with no new safety signals. These results support adjuvant Pembro as a new therapeutic option for pts with MIUC with high risk for recurrence. Additional follow-up is ongoing for the final DFS/OS, PD-L1 subgroups, and ctDNA analyses. Clinical trial information: NCT03244384 .

AbstractBackgroundThe impact of chronic kidney disease (CKD) on atrial fibrillation outcomes (AF) is not well understood.MethodsWe conducted analyses of comorbid AF and CKD related death in the United States from 1999 to 2020 using descriptive epidemiology.ResultsAge‐adjusted mortality rates (AAMR) per 100,000 increased from 0.39 in 1999 to 1.65 in 2020. Non‐Hispanic populations (1.01) and nonmetropolitan areas (1.08) had higher AAMRs compared to Hispanic (0.62) and metropolitan (0.97) areas. Midwestern (1.11) and Western (1.13) US regions recorded the highest AAMRs.ConclusionsThese findings highlight the need for interventions to address AF death disparities in patients with CKD.

Objectives The objective of this case study is to raise awareness of potential 123I-FP-CIT SPECT interference by lisdexafetamine dimesylate, a prodrug of d-amphetamine. Methods A 69-year-old man with Rapid Eye Movement sleep behavior disorder and mild cognitive impairment had been treated with lisdexafetamine dimesylate for attention-deficit/hyperactivity disorder. The patient had annual or biennial 123I-FP-CIT SPECT evaluations after their baseline visit at 69 years old. Nigrostriatal dopamine transporter uptake was semiquantitatively evaluated with 123I-FP-CIT SPECT using DaTQUANT 2.0 software. Lisdexafetamine dimesylate was discontinued 3 months before the sixth-year visit (76 years old) by his primary care provider. Results The patient had 4 123I-FP-CIT SPECT scans with lisdexafetamine dimesylate and 2 scans after the discontinuation of lisdexafetamine dimesylate. The DaTQUANT z-scores of the putamen declined from −1.36 at the baseline visit to −3.02 at the fifth-year visit. After the discontinuation of lisdexafetamine dimesylate, DaTQUANT z-scores of the putamen increased to −0.63 at the sixth-year visit and remained in the normal range of −0.71 at the seventh-year visit. Conclusions This case suggests that lisdexafetamine dimesylate may have a strong interference with 123I-FP-CIT SPECT, decreasing the tracer binding to the dopamine transporter and presenting false positive results.

AbstractINTRODUCTIONThe implications of positive tau positron emission tomography (T) with negative beta amyloid positron emission tomography (A) are not well understood. We investigated cognitive performance in participants who were T+ but A‐.METHODSWe evaluated 98 participants from the Mayo Clinic who were T+ and A‐. Participants were matched 2:1 to A‐ and T‐ cognitively unimpaired (CU) controls. Cognitive test scores were compared between different groups.RESULTSThe A‐T+ group demonstrated lower performance than the A‐T‐ group on the Mini‐Mental Status Exam (MMSE) (p < 0.001), Wechsler Memory Scale‐Revised Logical Memory I (p < 0.001) and Logical Memory II (p < 0.001), Auditory Verbal Learning Test (AVLT) delayed recall (p = 0.004), category fluency (animals p = 0.005; vegetables p = 0.021), Trail Making Test A and B (p < 0.001), and others. There were no significant differences in demographic features or apolipoprotein E (APOE) e4 genotype between CU A‐T+ and CI A‐T+.DISCUSSIONA‐T+ participants show an association with lower cognitive performance.

Selpercatinib is indicated for locally advanced/metastatic RET-activated solid tumors after progression or following prior systemic therapies. Until the recently published data from LIBRETTO-431 and LIBRETTO-531, there were limited effectiveness data comparing selpercatinib with other first-line treatments in RET-activated non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC), and thyroid cancer (TC). This study analyzed patient data from LIBRETTO-001 and compared the outcomes (time to treatment discontinuation {TTD}, time to next treatment or death {TTNT-D}, time to progression {TTP}, and the objective response rate {ORR}) of first-line selpercatinib (selpercatinib arm) use with the outcomes of first-line standard therapies in patients who then received selpercatinib in later lines of treatment (comparator arm). Overall, the first-line selpercatinib arm had a longer TTD, TTNT-D, and TTP versus the first-line comparator arm. The hazard ratios (HRs) for TTD were 0.29 (NSCLC), 0.15 (MTC), 0.08 (TC); for TTNT-D, the HRs were 0.48 (NSCLC), 0.11 (MTC), 0.09 (TC); and for TTP, the HRs were 0.54 (NSCLC), 0.15 (MTC), and 0.12 (TC). The ORR was higher for first-line selpercatinib versus the first-line comparator (NSCLC: 85.3% vs. 39.7%; MTC: 82.6% vs. 15.2%; and TC: 81.8% vs. 31.8%). First-line selpercatinib use is associated with improved outcomes compared to first-line comparator therapies for patients with advanced/metastatic RET-activated cancers.

AbstractBackgroundThe implications of a positive tau (T) Positron Emission Tomography (PET) with a negative beta amyloid (A) PET are not well understood. We investigated cognitive performance in participants who were positive on tau PET but negative on beta amyloid PET.MethodWe evaluated 98 participants from the Mayo Clinic Study of Aging (MCSA) and the Mayo Clinic Alzheimer’s Disease Research Center (ADRC) who were positive for Flortaucipir (FTP) and negative for PiB PET. Participants were classified as A‐ and T+ based on Standardized Uptake Value Ratios (SUVr) of FTP and PiB PET scans, and were matched 2:1 to amyloid negative and tau negative cognitively unimpaired controls from the MCSA. Cognitive test scores were compared between the combined ADRC/MCSA group and MCSA only group. We also examined clinical diagnoses in our cohort. The most common were Alzheimer’s Disease, mild cognitive impairment (MCI), Dementia with Lewy Bodies (DLB) and Frontotemporal dementia (FTD) amongst others.ResultThere were no significant differences in demographic features or PiB SUVr between groups. There were significant differences in APOE genotype between groups. In the combined ADRC/MCSA group, 25% of A‐T‐ and 13% of A‐T+ were APOE e4 carriers (p = 0.016), and in the MCSA only group, 27% of A‐T‐and 10% of A‐T+ were APOE e4 carriers (p = 0.010). In the combined ADRC/MCSA group, the A‐T+ group demonstrated lower performance than the A‐T‐ group on the Mini Mental Status Exam (MMSE) (p<0.001), Wechsler Memory Scale‐Revised Logical Memory I (p<0.001) and Logical Memory II (p<0.001), Auditory verbal Learning Test Delayed Recall (AVLT) (p = 0.004), Category fluency animals (p = 0.005), Category fluency vegetables (p = 0.021), Trailmaking test A (p<0.001), Trail making test B (p<0.001), Wechsler Adult Intelligence Scale‐IV (WAIS‐IV) (p = 0.002), and Unified Parkinson’s Disease Rating Scale part III (UPDRS III) (p = 0.003). In the MCSA only group, the A‐T+ group had lower scores on Logical Memory II (p = 0.022), AVLT delated recall (p = 0.04), and WAIS‐R block design (p = 0.035) compared to the A‐T‐group.ConclusionPositive tau PET in the absence of beta‐amyloid positivity is associated with lower cognitive performance.