Citations

612 Background: EOP, an I-SPY2 sub-study, evaluates the tolerability and activity of novel endocrine strategies in stage 2/3 breast cancer (BC) patients (pts) predicted to have lower chemotherapy benefit. Laso, a selective estrogen receptor modulator (SERM), has shown favorable toxicity profile and activity in HR+/HER2- endocrine-resistant metastatic BC. Methods: Pts with Stage 2/3 HR+/HER2-, MammaPrint (MP) low risk BC were enrolled. Pts with MP High1 BC were included if clinically node-negative. Pts received oral laso 5 mg daily for six 28-day cycles. Laso was continued until the day prior to surgery. Premenopausal pts received ovarian function suppression (OFS) starting C2D1. The primary endpoint was feasibility (>75% of patients completing >75% study therapy). Baseline (T0), 3-wk (T1) biopsies, and the surgical specimen (T3) was assessed centrally for Ki-67. Breast MRI functional tumor volume (FTV) was performed at T0, T1, 12 weeks (T2), and pre-operatively (T3). Blood was collected for tumor informed ctDNA at T0, T1, T2, T3. Advance event (AE) was assessed using CTCAE V5. Results: From 3/2023 to 5/2024, 20 pts were enrolled. Median age 50.5 years, 50% premenopausal, and 1 male pt. 60% cN0, 80% MP low-risk signature. 18 (90%) pts completed >75% study therapy. Two pts discontinued treatment due to pt preference. Median Ki67 at T0 was 14.7%. At T1, 87.5% of pts remained or suppressed Ki67 to <10% and 37.5% suppressed to <2.7%. Ki67 at T1 was similar between pre-and postmenopausal pts despite OFS (Table). The median MRI FTV was 8.4 cc at T0, and 3.4 cc at T3. Median % FTV reduction from T0 to T3 was -47.5%. 2/20 pts (10%) achieved a modified PEPI score of 0. No patients achieved completed pathological response. Of the 16 pts with RCB results, 2 (12.5%) RCB-1, 6 (37.5%) RCB-2, 8 (50%) RCB-3 disease. 14 pts had ctDNA available at T0. 4/14 were ctDNA+ at T0, 2 of whom became ctDNA negative, and 2 remained ctDNA+. 10/14 pts were ctDNA negative at T0, 8 of whom remained negative, 2 became positive at T1 then cleared. All AEs were grade(G) 1 except 1 pt with G2 hot flashes. Most common AEs include hot flashes (85%), constipation (50%), fatigue (50%), and nausea (35%). One pt had G3 hypersensitivity and hypertension, both unrelated to therapy. Conclusions: Neoadjuvant laso demonstrates a favorable AE profile and promising anti-tumor activity in suppressing 3-wk Ki67 and MRI FTV change in pts with HR+ HER2-negative early BC. Ki67 suppression in premenopausal pts was seen in the absence of OFS. Clinical trial information: NCT01042379 . Ki67 expression at pre-treatment, and 3-wk time point. All Patients(n=20) Premenopausal (n=10) Postmenopausal (n=9) Median Ki67 expression Baseline 10.0% 12.5% 10.0% 3-wk 5.1% 3.0% 6.0% Number of pts with Ki67 expression <10% at 3-wk 87.5% 1 87.5% 85.7% Number of pts with Ki67 expression <2.7% at 3-wk 37.5% 50% 28.6% 1 Include the one male pt.

Background The Woven EndoBridge (WEB) device is a prevalent treatment for intracranial aneurysms. While many studies have assessed the obliteration rate post-WEB embolization, few have focused on long-term outcomes in partially thrombosed aneurysms. Objective To assess whether partially thrombosed aneurysms are at higher risk of recurrence or retreatment following WEB embolization compared with non-thrombosed aneurysms. Methods We evaluated data from 22 academic institutions, focusing on previously untreated cerebral aneurysms treated with the WEB device. Logistic regression was utilized to analyze factors predicting long-term aneurysm obliteration and retreatment necessity. Results Among 1303 patients, 26 presented with a partially thrombosed aneurysm. In the partially thrombosed group, the mean aneurysm maximal diameter was 10.7±4 mm with a neck ratio of 1.99±1.19 mm, larger than in the control group where the mean aneurysm maximal diameter was 6.81±2.37 mm with a neck ratio of 1.64±0.51 mm (P<0.001 for both maximal diameter and neck ratio). At the final follow-up, partially thrombosed aneurysms treated by the WEB device had a 38.5% retreatment rate, compared with 7.0% for non-thrombosed aneurysms (P<0.001). Among partially thrombosed aneurysms, the Raymond-Roy type IIIa/b occlusion rate was higher (38.5% vs 9.9%, P<0.001). On multivariate analysis, partially thrombosed aneurysms compared with non-thrombosed aneurysms had an increased rate of retreatment (OR 3.64, 95% CI 1.28 to 10.1). Conclusion Partially thrombosed aneurysms are associated with a poorer occlusion rate and a higher rate of retreatment following WEB embolization. For partially thrombosed aneurysms, the WEB device appears suboptimal as a first-line treatment, and therefore alternative techniques should be prioritized.

BACKGROUND: Childbirth can have a substantial impact on maternal health-related quality of life. Cesarean delivery is the most performed inpatient operation, yet little is known about normal postpartum recovery profiles. The primary aim of our study was to longitudinally evaluate global health visual analog scale (GHVAS; 0–100) scores up to 12 weeks after scheduled cesarean delivery and identify the time to plateau of scores. The secondary aims were to evaluate different domains of postpartum recovery using validated patient-reported outcome measures (Obstetric Quality of Recovery score [ObsQoR-10] and 5-level 5-dimensional EuroQol questionnaire [EQ-5D]). METHODS: After institutional review board approval, this single-center, prospective longitudinal study enrolled healthy women scheduled for cesarean delivery. Women were excluded for gestational age <32 weeks, neonatal demise, neonatal intensive care unit admission, inability to read or understand English, and if general anesthesia was used. Women completed baseline surveys before delivery and then at 24 and 48 hours after delivery. After hospital discharge, women completed surveys (including GHVAS, OBsQoR-10, EQ-5D, Edinburgh Postnatal Depression Scale, and activities of daily living) at 1 week, 3 weeks, 6 weeks, and 12 weeks postpartum. One-way repeated measures analysis of variance (ANOVA) was used to detect the difference in GHVAS and postpartum recovery outcomes with different follow-up time points. RESULTS: We enrolled 66 parturients and 3 were withdrawn. Response rates were 95%, 84%, 83%, and 76% at 1, 3, 6, and 12 weeks, respectively. Mean ± standard deviation [SD] GHVAS scores were 78 ± 16 at baseline, 64 ± 17 at 24 hours, 69 ± 15 at 48 hours, 75 ± 19 at 1 week, 88 ± 11 at 3 weeks, 88 ± 15 at 6 weeks, and 90 ± 12 at 12 weeks postpartum ( P < .001). The global health VAS improved up until week 3 and then plateaued close to the maximum score between 3 weeks and 12 weeks postpartum. Mean ± SD ObsQoR-10 scores were 75 ± 15 at 24 hours, 85 ± 10 at 48 hours, and 81 ± 28 at 1 week postpartum ( P = .003). The mean ± SD EQ-5D composite scores improved at 6 weeks (4.9 ± 2.9) and 3 months (4.2 ± 2.6) compared to baseline (6.5 ± 1.8) with usual activities ( P = .001) and pain/discomfort ( P < .001) showing significant improvement over time. ObsQoR-10 score at 24 hours correlated with ObsQoR-10 scores at 48 hours (r = 0.629, P < .001) and 1 week (r = 0.429, P < .001) but did not correlate with EQ-5D scores at 6 weeks and 12 weeks. CONCLUSIONS: Our study demonstrates that GHVAS after scheduled CD plateaus at week 3. This data can be used to inform patients about the anticipated trajectory of key postpartum recovery domains up to 12 weeks postpartum.

Objectives/Goals: Aspiration causes or aggravates lung diseases. While bedside swallow evaluations are not sensitive/specific, gold standard tests for aspiration are invasive, uncomfortable, expose patients to radiation, and are resource intensive. We propose the development and validation of an AI model that analyzes voice to noninvasively predict aspiration. Methods/Study Population: Retrospectively recorded [i] phonations from 163 unique ENT patients were analyzed for acoustic features including jitter, shimmer, harmonic to noise ratio (HNR), etc. Patients were classified into three groups: aspirators (Penetration-Aspiration Scale, PAS 6–8), probable (PAS 3–5), and non-aspirators (PAS 1–2) based on video fluoroscopic swallow (VFSS) findings. Multivariate analysis evaluated patient demographics, history of head and neck surgery, radiation, neurological illness, obstructive sleep apnea, esophageal disease, body mass index, and vocal cord dysfunction. Supervised machine learning using five folds cross-validated neural additive network modelling (NAM) was performed on the phonations of aspirator versus non-aspirators. The model was then validated using an independent, external database. Results/Anticipated Results: Aspirators were found to have quantifiably worse quality of sound with higher jitter and shimmer but lower harmonics noise ratio. NAM modeling classified aspirators and non-aspirators as distinct groups (aspirator NAM risk score 0.528+0.2478 (mean + std) vs. non-aspirator (control) risk score of 0.252+0.241 (mean + std); p Discussion/Significance of Impact: We report the use of voice as a novel, noninvasive biomarker to detect aspiration risk using machine learning techniques. This tool has the potential to be used for the safe and early detection of aspiration in a variety of clinical settings including intensive care units, wards, outpatient clinics, and remote monitoring.

Background Neuropsychiatric symptoms (NPS) are frequent in Alzheimer's disease (AD) dementia, but a higher NPS burden is found in dementia with Lewy bodies (DLB). Lewy body (LB) pathology frequently co-occurs with AD pathology and may not meet neuropathological criteria for DLB (ADLB). NPS trajectories over disease course in these subgroups is not well understood. Objective We investigated changes in NPS severity over time, at two time points, comparing clinicopathologically defined cohorts of AD (without LB), ADLB, DLB, and controls. Methods Cases with two available Neuropsychiatric Inventory-Questionnaire (NPIQ), at the time of enrollment and within 2.5 years of death, were selected from the Arizona Study of Aging and Neurodegenerative Disorders. Differences and rate of change in NPIQ scores were compared between AD (n = 75), ADLB (n = 48) DLB (n = 65), and controls (n = 32) with covariates for age, sex, and cognition. Results First NPIQ scores were highest in ADLB when compared to AD (p = 0.04) and controls (p = 0.01) but not different from DLB. A significant increase in NPS severity was observed in DLB and AD (p < 0.001) over a mean follow up time of 4.9 ± 3.0 years, and the rate of change was significantly greater in DLB when compared to other groups. Final NPIQ scores were highest in DLB when compared to AD (p = 0.03) but not ADLB, and in DLB, ADLB, and AD than controls ( all p < 0.001). Conclusions Early NPS burden as well as NPS severity progression rate, independently of cognitive status, might be useful clinical metrics and may help predict underlying pathological diagnoses.

Background Mechanical thrombectomy (MT) is established as an effective treatment for large vessel occlusion strokes, but its efficacy and safety for medium vessel occlusions (MeVOs) remain less clear. This study examines the impact of periprocedural embolization to a new vascular territory (ENT) on clinical outcomes in patients with MeVO stroke treated with MT. Methods A multicenter, retrospective analysis was conducted using the MAD-MT (Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy) registry, including 2122 patients with MeVO stroke w­ho underwent MT between September 2017 and July 2023. ENT was defined as filling defects in previously unaffected territories, excluding embolization near the original occlusion, observed on final angiographic runs after retrieval of the primary thrombus. The associations between ENT, procedural variables, and 90-day clinical outcomes were evaluated, including functional independence (modified Rankin Scale (mRS) scores of 0–2), excellent outcomes (mRS 0–1), mortality, and hemorrhagic complications. Results ENT occurred in 2.9% (63/2122) of patients. Longer onset-to-arterial puncture time (adjusted OR 1.03; 95% CI 1.01 to 1.05; P=0.002) and a greater number of passes (adjusted OR 1.15; 95% CI 1.01 to 1.32; P=0.032) were associated with increased ENT risk, while excellent recanalization (thrombolysis in cerebral infarction (TICI) scale score 2c–3) was associated with reduced ENT risk (adjusted OR 0.41; 95% CI 0.23 to 0.72; P=0.002). ENT was not associated with poorer functional independence, mortality, or hemorrhagic complications. Conclusions ENT during MT for MeVO stroke occurs infrequently and does not significantly affect the clinical outcomes. These findings suggest ENT risk should not deter clinicians from performing MT in patients with MeVO. Further prospective studies are needed to validate these results.