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Recent advancements in computed tomography have significantly transformed the clinical application of this technique in diagnosing and managing coronary artery disease (CAD). Computed tomography coronary angiography (CTCA) has emerged as a leading non-invasive imaging modality, often serving as the first-line investigation to exclude obstructive CAD in patients with chronic coronary syndrome. Beyond its utility in diagnosing CAD, CTCA has become instrumental in procedural planning for percutaneous coronary intervention (PCI), particularly in complex cases such as left main stem (LMS) interventions, where peri-procedural risks are elevated. This review highlights the evolving role of CTCA in LMS PCI, underscoring its clinical utility in improving procedural precision and, subsequently, patient outcomes. Recent technological advancements, including detailed multiplanar and three-dimensional (3D) reconstructions, CT-derived fractional flow reserve (CTFFR), and the integration of artificial intelligence (AI) algorithms, have expanded the capabilities of CTCA. These innovations allow for comprehensive anatomical and functional assessments, enabling precise plaque morphology, lesion complexity, and bifurcation anatomy evaluations alongside PCI simulations. By offering detailed insights into coronary vasculature and lesion characteristics, CTCA provides critical information for optimising LMS PCI strategies. This review explores the current applications and future potential of CTCA in guiding LMS PCI, highlighting its role in improving procedural planning, risk assessment, and overall management of this challenging patient population.

e17064 Background: Analyses of clinical trials data suggest thatBlack men have equal or even improved overall survival (OS) with certain treatments for mCRPC compared with other races. Moreover, retrospective analysis of the PROCEED registry indicated that Black men who received Sip-T, an autologous cellular immunotherapy, had longer survival compared with other men with mCRPC. The Abi Race and PANTHER clinical trials prospectively assessed the effect of ARPIs on clinical outcomes among Black and White patient (pt) cohorts, and included pts who had received Sip-T either prior to or during study. We combined data from Abi Race and PANTHER to investigate associations between OS, Sip-T and race. Methods: Data from the Abi Race (N=100) and PANTHER (N=93) studies were retrospectively pooled for this analysis. Propensity scores for Sip-T treatment were calculated based on Karnofsky performance status, race, Gleason score, and study. Kaplan-Meier estimates for OS, with and without inverse propensity score weighting, were generated and stratified by Sip-T use. This analysis was stratified by race to examine whether the relationship between Sip-T use and OS differed by race. Results: Of the 93 Black pts and 100 White patients included from both studies, 123 patients did not receive Sip-T, while 70 patients did (60 before study, 10 on study). Pts who received Sip-T had a median OS (mOS) of 44 months (95% Confidence Interval (CI) 39, NR) compared to 36 months (95% CI 31, 48) for those who did not. Weighted by propensity scores, Black men who received Sip-T had a mOS of 72 months (95% CI 43, NR), while those who did not had a mOS of 38 months (95% CI 30, NR). Among White men, patients who received Sip-T had a mOS of 39 months (95% CI 30, NR), while those who did not had a mOS of 32 months (95% CI 29, 48) (see Table). Conclusions: Our findings from an investigator-led retrospective analysis independent of sponsors provide independent clinical trial support of prior retrospective findings that suggest Black men with mCRPC who receive Sip-T may have a greater OS than White men. While our analysis controlled for factors that may influence the use of Sip-T, it is limited by potential unmeasured confounders or timing of Sip-T. Further, adequately powered prospective trials specifically evaluating outcomes with Sip-T by race in earlier clinical settings are needed. Drug support and funding for Abi Race and PANTHER were provided by Janssen Scientific Affairs, LLC. Death counts and median overall survival (mOS) in months by race and Sipuleucel-T use. Black Men White Men Sipuleucel-T use Deaths / Total N No 36 / 64 38 / 59 Yes 12 / 29 24 / 41 Unweighted mOS (95% CI) No 36 (29, NR) 32 (29, 48) Yes 72 (43, NR) 39 (31, NR) Weighted mOS (95% CI) No 38 (30, NR) 32 (29, 48) Yes 72 (43, NR) 39 (30, NR) NR = not reached, mOS = median overall survival, CI = confidence interval.

Abstract Oscillations in the high gamma and ripple frequency ranges are known to coordinate local hippocampal and neocortical neuronal assemblies during memory encoding and recall. Here, we explored spatiotemporal dynamics and the role of global coordination of these fast oscillatory discharges across the sensory and associational cortical areas in distinct phases of memory processing. Individual bursts of high frequency oscillations were detected in intracranial recordings from epilepsy patients remembering word lists for immediate free recall. We found constant coincident bursting across visual and higher order processing areas, peaking before recall and elevated during encoding of words. This global co-bursting was modulated by memory processing, engaged approximately half of the recorded electrode sites, and clustered into a sequence of multiple consecutive bursting discharges. Our results suggest a general role of global coincident high frequency oscillations in organizing large-scale information processing across the brain necessary especially, but not exclusively, for memory functions.

Abstract Leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of Rab GTPases that regulate receptor trafficking; activating mutations in LRRK2 are linked to Parkinson’s disease. Rab phosphorylation is a transient event that can be reversed by phosphatases, including PPM1H, that acts on phosphoRab8A and phosphoRab10. Here we report a phosphatome-wide siRNA screen that identified PPM1M as a phosphoRab12-preferring phosphatase that also acts on phosphoRab8A and phosphoRab10. Upon knockout from cells or mice, PPM1M displays selectivity for phosphoRab12. As shown previously for mice harboring LRRK2 pathway mutations, knockout of Ppm1m leads to primary cilia loss in striatal cholinergic interneurons. We have also identified a rare PPM1M mutation in patients with Parkinson’s disease that is catalytically inactive when tested in vitro and in cells. These findings identify PPM1M as a key player in the LRRK2 signaling pathway and provide a new therapeutic target for the possible benefit of patients with Parkinson’s disease. Teaser Parkinson’s linked Rab phosphorylation is reversed by PPM1M; the inactive D440N variant is implicated in rare patient cases.

INTRODUCTION: Immune-modifying therapies in pediatric inflammatory bowel disease (IBD) increase infection risks, including varicella. METHODS: Using Optum's deidentified Clinformatics Data Mart Database, a nationwide US commercial insurance claims database (2007–2022), we conducted a retrospective study of 5,368 patients with IBD aged 21 years or younger matched to a non-IBD cohort. The primary outcome was incidence of varicella. RESULTS: Varicella incidence was low in both groups (IBD: 0.570 vs non-IBD: 0.297 per 1,000 person-years, P = 0.23). At year 4, cumulative varicella incidence was 0.27% for IBD and 0.18% for non-IBD ( P = 0.24). No hospitalizations or deaths occurred. DISCUSSION: Despite immune-modifying therapy, pediatric patients with IBD demonstrate low varicella incidence.

Abstract This retrospective analysis aimed to provide evidence-based risk stratification of TP53-mutated (TP53mut) myeloid neoplasms (MNs). Of 580 MNs harboring TP53mut with variant allele frequency (VAF) ≥2%, 219 (37.8%), 194 (33.4%), 92 (15.9%), and 75 (12.9%) were classified as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) with low blasts (MDS-LB), MDS with excess blasts (MDS-EB)-2, and -EB1 according to the revised fourth edition of the World Health Organization (WHO) classification, respectively. Hierarchical analysis identified the following 4 risk groups with distinct survival: (1) MDS-LB, (2) MDS-EB1/EB2/AML VAF <10%, (3) MDS-EB1/EB2 VAF ≥10%, and (4) AML VAF ≥10%. We next evaluated the impact of allelic status, VAF, and complex karyotype (CK). In our cohort, the significance of biallelic status was limited to MDS with <5% blasts and not for blasts 5% to 9%, as proposed by the International Consensus Classification (ICC), or 5% to 19%, as proposed by the fifth edition of the WHO (WHO-5). MDS-EB1 and -EB2 with VAF ≥10% had comparable survival (9.6 vs 7.2 months; P = .12), regardless of allelic status. Contrary to the ICC proposal, MDS-EB1/EB2 with VAF <10% and CK had poor survival compared with those without CK, comparable to MDS-EB1/EB2 with VAF ≥10% (5.6 vs 26.2 vs 6.3 months; P = .003). Survival of TP53mut AML was poor (median 3.9 months) regardless of allelic/CK status. Thus, using ICC or WHO-5 may underestimate prognosis of MDS with blasts 5% to 19% and 5% to 9%, respectively. Collectively, the hierarchical model acknowledges poor survival of 91.9% TP53mut MDS and AML compared with 36.5% and 80.7% by WHO-5 and ICC, respectively.

OBJECTIVE Tobacco smoking is among the factors known to significantly augment the risk of untreated intracranial aneurysm (IA) growth and rupture. Smoking appears to have a variable effect on different endovascular treatment modalities. The impact of smoking on the safety, efficacy, and outcomes of Woven EndoBridge (WEB) device use for wide-neck IAs has not been evaluated. This study aimed to investigate the outcomes of WEB devices by smoking status. METHODS A retrospective multicenter analysis was conducted on the data of patients from 36 sites worldwide treated with the WEB device for intracranial saccular aneurysms. Patients were stratified based on smoking status (current, former, and never smokers). The Student t-test and chi-square test were performed for continuous and categorical variables, respectively. Multivariable logistic regression was used to adjust for confounders. RESULTS Of 1376 patients with available smoking status, 504 were current smokers, 358 were former smokers, and 514 were never smokers. Upon adjusting for significant confounders, no association was found between smoking and recurrence outcomes (OR 1.39, 95% CI 0.69–2.80; p = 0.36), thromboembolic and hemorrhagic complications, and mortality among IAs treated with the WEB device. There was no statistically significant difference in outcomes between former and never smokers (OR 1.23, 95% CI 0.70–2.18; p = 0.46). The location of aneurysms differed between smoking groups, with former smokers having more anterior circulation aneurysms compared with current and never smokers (99.0% vs 96.9% vs 95.3%; p = 0.01). In terms of clinical symptoms, headache and dizziness were more common in the never smokers compared with current and former smokers (13.9% vs 8.9% vs 7.7%, p = 0.01). CONCLUSIONS This large-scale study suggests no significant correlation between smoking and the recurrence of IAs treated with the WEB device. Biological studies are warranted to better understand the biological impact of smoking on the growth and rupture of treated IAs.

AbstractBackgroundAnti‐amyloid monoclonal antibody therapies for AD have documented plaque removal on amyloid PET scans. We evaluate the findings for amyloid PET, tau PET, FDG PET and volumetric MRI over the course the open label extension (OLE) for the DIAN‐TU gantenerumab treatment, compared to the last imaging obtained prior to the OLE (to evaluate for potential rebound effects) and in comparison to longitudinal imaging in the DIAN Observational study.MethodThis double‐blind, phase 2/3 trial (2012‐2019), followed by open‐label extension (OLE), investigated varying gantenerumab doses up to 1500 mg SQ q2 weeks [NCT NCT01760005]. We report long‐term amyloid‐plaque removal by PET and findings for metabolic FDG PET and tau PET, and additionally changes of atrophy on volumetric MRI. Imaging measures were secondary outcome analyses. Comparison is made between the treatment cohort and controls (DB placebo participants who didn’t enter OLE, plus external controls from the DIAN OBS). Estimated years to onset was included as a covariate. The gap period of ∼1 year is specifically analyzed to estimate any “rebound” effect on amyloid or tau accumulation or neurodegeneration. Volumetric MRI measures include hippocampal volumes, lateral ventricular volumes, and white matter hyperintensities.ResultIn participants who were asymptomatic at baseline and treated with gantenerumab (n = 53), amyloid‐plaque removal measured by PIB‐PET in Centiloids was dose‐dependent. Few participants had reached completely negative levels (below 24). No statistical significance was found for FDG PET, tau PET, or volumetric MRI, including hippocampal volumes. Impact of the gap period of ∼1 year (gap in treatment) on the rate of amyloid accumulation compared to the rate of accumulation predicted in observational studies of this cohort is under evaluation, as are the other imaging measures.ConclusionWhile no overall effect was observed in the total group for non‐amyloid measures, results suggest dose dependent clearance of amyloid plaque in asymptomatic DIAD mutation carriers following long‐term, high‐dose gantenerumab. The potential “rebound effect” of elevated amyloid accumulation for participants for whom there was a significant gap in therapy between the trial and the OLE is under evaluation and will be presented, as will the variables for FDG PET, tau PET, and volumetric MRI.