Optimal Woven EndoBridge (WEB) Device Size Selection Using Automated Volumetric Software.

INTRODUCTION: Selecting the appropriate Woven EndoBridge (WEB) device sizing for the treatment of wide-neck bifurcation aneurysms (WNBAs) remains challenging. The aim of this study was to evaluate different volumetric-based imaging methodologies to predict an accurate WEB device size selection to result in a successful implantation. METHODS: All consecutive patients treated with WEB devices for intracranial aneurysms from January 2019 to June 2020 were included. Aneurysm dimensions to calculate aneurysm volumes were measured using three different modalities: automated three-dimensional (3D) digital subtraction angiography (DSA), manual 3D DSA, and two-dimensional (2D) DSA. The device-aneurysm volume (DAV) ratio was defined as device volume divided by the aneurysm volume. WEB volumes and the DAV ratios were used for assessing the device implantation success and follow-up angiographic outcomes at six months. Pearson correlation, Wilcoxon Rank Sum test, and density approximations were used for estimating the WEB volumes and the imaging modality volumes for successful implantation. RESULTS: A total of 41 patients with 43 aneurysms were included in the study. WEB device and aneurysm volume correlation coefficient was highest for 3D automatic (r = 0.943), followed by 3D manual (r = 0.919), and 2D DSA (r = 0.882) measurements. Measured median volumes were significantly different for 3D automatic and 2D DSA (p = 0.017). The highest rate of successful implantation (87.5%) was between 0.6 and 0.8 DAV ratio. CONCLUSION: Pre-procedural assessment of DAV ratios may increase WEB device implantation success. Our results suggest that volumetric measurements, especially using automated 3D volumes of the aneurysms, can assist in accurate WEB device size selection.

Safety and Feasibility of Symptomatic Carotid Artery Stent-Assisted Revascularization within 48 Hours after Symptoms Onset.

OBJECTIVE: We aimed to evaluate the safety and feasibility of carotid artery stenting (CAS) performed in the hyperacute period. METHODS: We analyzed a retrospective database of CAS patients from our center. We included patients with symptomatic isolated ipsilateral extracranial carotid stenosis and acute tandem occlusions who underwent CAS. Hyperacute CAS (HCAS) and acute CAS (ACAS) groups were defined as CAS within 48 hours and >48 hours to 14 days from symptoms onset, respectively. The primary outcome was a composite of any stroke, myocardial infarction, or death at 3 months of follow-up. Secondary outcomes were periprocedural complications and restenosis or occlusion rates. RESULTS: We included 97 patients, 39 with HCAS and 58 with ACAS. There was no significant difference between groups for the primary outcome (HCAS 3.3% vs. ACAS 6.1%; p = 1). There were no differences in the rate of perioperative complications between groups although a trend was observed (HCAS 15.3% vs. ACAS 3.4%; p = .057). The rate of restenosis or occlusion between groups (HCAS 8.1% vs. ACAS 9,1%; log-rank test p = .8) was similar with a median time of follow-up of 13.7 months. CONCLUSION: Based on this study, CAS may be feasible in the hyperacute period. However, there are potential higher rates of perioperative complications in the hyperacute group, primarily occurring in MT patients with acute tandem occlusion. A larger multicenter study may be needed to further corroborate our findings.

G-quadruplex-binding small molecules ameliorate C9orf72 FTD/ALS pathology in vitro and in vivo.

Intronic GGGGCC repeat expansions in C9orf72 are the most common known cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), which are characterised by degeneration of cortical and motor neurons, respectively. Repeat expansions have been proposed to cause disease by both the repeat RNA forming foci that sequester RNA-binding proteins and through toxic dipeptide repeat proteins generated by repeat-associated non-ATG translation. GGGGCC repeat RNA folds into a G-quadruplex secondary structure, and we investigated whether targeting this structure is a potential therapeutic strategy. We performed a screen that identified three structurally related small molecules that specifically stabilise GGGGCC repeat G-quadruplex RNA We investigated their effect in C9orf72 patient iPSC-derived motor and cortical neurons and show that they significantly reduce RNA foci burden and the levels of dipeptide repeat proteins. Furthermore, they also reduce dipeptide repeat proteins and improve survival in vivo, in GGGGCC repeat-expressing Drosophila Therefore, small molecules that target GGGGCC repeat G-quadruplexes can ameliorate the two key pathologies associated with C9orf72 FTD/ALS These data provide proof of principle that targeting GGGGCC repeat G-quadruplexes has therapeutic potential.