Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.Peer reviewe

A clinical comparison of Atlas and LVIS Jr stent-assisted aneurysm coiling

BACKGROUND: Case series have described the safety and efficacy of LVIS Jr and Atlas stent-assisted aneurysm coiling, but their comparative clinical performance has not yet been formally studied. OBJECTIVE: To clinically compare LVIS Jr and Atlas stents, emphasizing comparative rates of technical success and complications. METHODS: Our institutional endovascular database was queried for aneurysms treated by stent-assisted coiling with either the LVIS Jr or Atlas stents. Demographic data, aneurysm information, treatment technique, periprocedural and device-related complications, and initial and follow-up angiographic results were evaluated. RESULTS: Thirty-seven patients underwent Atlas stent placement and 27 patients underwent LVIS Jr stent placement for aneurysm coiling. There was no significant difference in aneurysm location, size, coiling technique, and coil packing density between the two cohorts. The rate of initial Raymond 1 occlusion was significantly greater in the Atlas cohort (57% vs 41%, P=0.03). The rate of postoperative ischemic complications, both clinically apparent and as defined on postoperative MRI diffusion-weighted imaging, did not significantly differ between the two groups. Follow-up DSA demonstrated a significantly greater rate of Raymond 1 or 2 occlusion for the Atlas cohort (100% vs 81%, P=0.04), and a significantly lower rate of in-stent stenosis (0% vs 19%, P=0.04). CONCLUSION: This institutional analysis demonstrates greater obliteration rates and lower in-stent stenosis rates for aneurysms treated via Atlas stent-assisted coiling as compared with those treated via LVIS Jr stent-assisted coiling

Abstract Number ‐ 39: Comparison of Clinical and Radiographic Efficacy of Particles versus nBCA/Onyx in MMA Embolization for cSDH

Introduction Middle meningeal artery (MMA) embolization has emerged as a minimally invasive alternative to open surgery for treatment of chronic subdural hematoma (cSDH). Different embolic materials are utilized in this procedure per operators’ discretion; however, limited data currently exists regarding the clinical and radiographic efficacy of these embolic materials, with available studies lumping Onyx and N‐Butyl cyanoacrylate (n‐BCA) into a single group of liquid embolic material. Methods Series of consecutive patients undergoing MMA embolization (MMAE) for cSDH at 2 North American centers (2019‐2021) were included. The primary outcomes included cSDH radiographic resolution of cSDH with at least 50% reduction of hematoma thickness to be considered treatment success. Clinical outcomes were defined as the proportion of patients requiring additional unplanned surgical intervention. These outcomes compared between the particles group, the liquid group which were further subdivided into the n‐BCA and Onyx groups. Results Overall, 185 patients undergoing 198 MMAE procedures (median age 72 years, 27.5% women) were included in this analysis. In this cohort, 42.6% of the procedures were performed utilizing particles embolic material, while n‐BCA and Onyx were utilized in 29.5% and 26.8% of procedures, respectively. On last follow‐up imaging (median 3.5 months), ≥ 50% reduction in hematoma thickness was achieved in 67.7%, 71.1%, and 72.3% in the particles, Onyx and the n‐BCA group, respectively (p = 0.2). There were no differences in the proportion of patients requiring additional unplanned surgery between the groups (p = 0.6). Similarly, there was no difference in procedural complications between the 3 embolic materials groups. Conclusions MMAE for cSDH utilizing particles and liquid embolic materials (including Onyx and n‐BCA) appears to have an overall equivalent safety and efficacy profiles in cSDH treatment. Further studies with larger sample sizes and longer follow‐up are warranted

Quality Assurance for Carotid Stenting in the CREST-2 Registry

The CREST-2 Registry (C2R) was approved by National Institute of Neurological Disorders and Stroke–National Institutes of Health in September 2014 with Centers for Medicare & Medicaid Services, U.S. Food and Drug Administration, and industry collaboration to enroll patients undergoing CAS. The registry credentials interventionists and promotes optimal patient selection, procedural-technique, and outcomes. This study reports periprocedural outcomes in a cohort of carotid artery stenting (CAS) performed for asymptomatic and symptomatic carotid stenosis. Asymptomatic patients with ≥70% and symptomatic patients with ≥50% carotid stenosis, ≤80 years of age, and at standard or high risk for carotid endarterectomy are eligible for enrollment. Interventionists are credentialed by a multispecialty committee that reviews experience, lesion selection, technique, and outcomes. The primary endpoint was a composite of stroke and death (S/D) in the 30-day periprocedural period. Myocardial infarction and access-site complications were assessed as secondary outcomes. As of December 2018, 187 interventionists from 98 sites in the United States performed 2,219 CAS procedures in 2,141 patients with primary atherosclerosis (78 were bilateral). The mean age of the cohort was 68 years, 65% were male, and 92% were white; 1,180 (55%) were for asymptomatic disease, and 961 (45%) were for symptomatic disease. All U.S. Food and Drug Administration–approved stents and embolic protection devices were represented. The 30-day rate of S/D was 1.4% for asymptomatic, 2.8% for symptomatic, and 2.0% for all patients. C2R is the first national registry for CAS cosponsored by federal and industry partners. CAS was performed by experienced operators using appropriate patient selection and optimal technique. In that setting, a broad group of interventionists achieved very low periprocedural S/D rates for asymptomatic and symptomatic patients. [Display omitted

Pivotal Trial of the Neuroform Atlas Stent for Treatment of Anterior Circulation Aneurysms: One-Year Outcomes.

Background and purposeStent-assisted coil embolization using the new generation Neuroform Atlas Stent System has shown promising safety and efficacy. The primary study results of the anterior circulation aneurysm cohort of the treatment of wide-neck, saccular, intracranial, aneurysms with the Neuroform Atlas Stent System (ATLAS trial [Safety and Effectiveness of the Treatment of Wide Neck, Saccular Intracranial Aneurysms With the Neuroform Atlas Stent System]) are presented.MethodsATLAS IDE trial (Investigational Device Exemption) is a prospective, multicenter, single-arm, open-label study of wide-neck (neck ≥4 mm or dome-to-neck ratio <2) intracranial aneurysms in the anterior circulation treated with the Neuroform Atlas Stent and approved coils. The primary efficacy end point was complete aneurysm occlusion (Raymond-Roy class 1) on 12-month angiography, in the absence of retreatment or parent artery stenosis (>50%) at the target location. The primary safety end point was any major stroke or ipsilateral stroke or neurological death within 12 months. Adjudication of the primary end points was performed by an independent Imaging Core Laboratory and the Clinical Events Committee.ResultsA total of 182 patients with wide-neck anterior circulation aneurysms at 25 US centers were enrolled. The mean age was 60.3±11.4 years, 73.1% (133/182) women, and 80.8% (147/182) white. Mean aneurysm size was 6.1±2.2 mm, mean neck width was 4.1±1.2 mm, and mean dome-to-neck ratio was 1.2±0.3. The most frequent aneurysm locations were the anterior communicating artery (64/182, 35.2%), internal carotid artery ophthalmic artery segment (29/182, 15.9%), and middle cerebral artery bifurcation (27/182, 14.8%). Stents were placed in the anticipated anatomic location in all patients. The study met both primary safety and efficacy end points. The composite primary efficacy end point of complete aneurysm occlusion (Raymond-Roy 1) without parent artery stenosis or aneurysm retreatment was achieved in 84.7% (95% CI, 78.6%-90.9%) of patients. Overall, 4.4% (8/182, 95% CI, 1.9%-8.5%) of patients experienced a primary safety end point of major ipsilateral stroke or neurological death.ConclusionsIn the ATLAS IDE anterior circulation aneurysm cohort premarket approval study, the Neuroform Atlas stent with adjunctive coiling met the primary end points and demonstrated high rates of long-term complete aneurysm occlusion at 12 months, with 100% technical success and <5% morbidity. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02340585

Y‐Stent–Assisted Coiling of Wide‐Necked Intracranial Aneurysms With the Neuroform Atlas Stent System

Background Endovascular management of wide‐necked bifurcation aneurysms poses a therapeutic challenge, as coiling often requires the use of multiple adjunctive stent constructs to achieve successful embolization without compromising parent vessel integrity. The Neuroform Atlas Stent System is a novel low‐profile, intraluminal remodeling device. The study aims to investigate the safety and efficacy of Y‐stent–assisted coiling configuration constructs using the next generation stent for aneurysm coil embolization. Methods Subjects undergoing Y‐stent–assisted coiling in the ATLAS IDE (Safety and Effectiveness of the Treatment of Wide Neck, Saccular Intracranial Aneurysms with the Neuroform Atlas Stent System Investigational Device Exception) trial were identified for subgroup analysis. Enrollment in the trial was not stratified on the basis of the procedural stenting technique used. The primary efficacy end point was complete aneurysm occlusion (Raymond–Roy class 1) on 12‐month angiography, in the absence of re‐treatment or parent artery stenosis (>50%) at the target location. The primary safety end point was any major stroke or ipsilateral stroke or neurological death within 12 months. Adjudication of the primary end points was performed by an independent imaging core laboratory and the clinical events committee. Results A total of 60 subjects were identified. The mean age was 59, and 28.3% were men. The median aneurysm size was 6.7 mm, with a median neck size of 4.3 mm. Frequently reported aneurysm locations included the basilar apex (56.7%), anterior communicating artery (20.0%), and middle cerebral artery bifurcation (11.7%). The composite primary efficacy end point was achieved in 81.1% of subjects. Overall, 1.7% of subjects experienced a primary safety endpoint of major ipsilateral stroke or neurological death. Conclusion In the ATLAS IDE aneurysm cohort premarket approval study, Y‐stent–assisted coiling with Neuroform demonstrated high rates of complete aneurysm occlusion at 12 months, with low rates of morbidity

Pivotal trial of the Neuroform Atlas stent for treatment of posterior circulation aneurysms: one-year outcomes.

BACKGROUND: Stent-assisted coiling of wide-necked intracranial aneurysms (IAs) using the Neuroform Atlas Stent System (Atlas) has shown promising results. OBJECTIVE: To present the primary efficacy and safety results of the ATLAS Investigational Device Exemption (IDE) trial in a cohort of patients with posterior circulation IAs. METHODS: The ATLAS trial is a prospective, multicenter, single-arm, open-label study of unruptured, wide-necked, IAs treated with the Atlas stent and adjunctive coiling. This study reports the results of patients with posterior circulation IAs. The primary efficacy endpoint was complete aneurysm occlusion (Raymond-Roy (RR) class I) on 12-month angiography, in the absence of re-treatment or parent artery stenosis >50%. The primary safety endpoint was any major ipsilateral stroke or neurological death within 12 months. Adjudication of the primary endpoints was performed by an imaging core laboratory and a Clinical Events Committee. RESULTS: The ATLAS trial enrolled and treated 116 patients at 25 medical centers with unruptured, wide-necked, posterior circulation IAs (mean age 60.2±10.5 years, 81.0% (94/116) female). Stents were placed in all patients with 100% technical success rate. A total of 95/116 (81.9%) patients had complete angiographic follow-up at 12 months, of whom 81 (85.3%) had complete aneurysm occlusion (RR class I). The primary effectiveness outcome was achieved in 76.7% (95% CI 67.0% to 86.5%) of patients. Overall, major ipsilateral stroke and secondary persistent neurological deficit occurred in 4.3% (5/116) and 1.7% (2/116) of patients, respectively. CONCLUSIONS: In the ATLAS IDE posterior circulation cohort, the Neuroform Atlas Stent System with adjunctive coiling demonstrated high rates of technical and safety performance. Trial registration number https://clinicaltrials.gov/ct2/show/NCT02340585