Most Promising Approaches to Improve Brain AVM Management: ARISE I Consensus Recommendations.

Brain arteriovenous malformations (bAVMs) are complex, and rare arteriovenous shunts that present with a wide range of signs and symptoms, with intracerebral hemorrhage being the most severe. Despite prior societal position statements, there is no consensus on the management of these lesions. ARISE (Aneurysm/bAVM/cSDH Roundtable Discussion With Industry and Stroke Experts) was convened to discuss evidence-based approaches and enhance our understanding of these complex lesions. ARISE identified the need to develop scales to predict the risk of rupture of bAVMs, and the use of common data elements to perform prospective registries and clinical studies. Additionally, the group underscored the need for comprehensive patient management with specialized centers with expertise in cranial and spinal microsurgery, neurological endovascular surgery, and stereotactic radiosurgery. The collection of prospective multicenter data and gross specimens was deemed essential for improving bAVM characterization, genetic evaluation, and phenotyping. Finally, bAVMs should be managed within a multidisciplinary framework, with clinical studies and research conducted collaboratively across multiple centers, harnessing the collective expertise and centralization of resources.

ARISE I Consensus Review on the Management of Intracranial Aneurysms.

BACKGROUND: Intracranial aneurysms (IAs) remain a challenging neurological diagnosis associated with significant morbidity and mortality. There is a plethora of microsurgical and endovascular techniques for the treatment of both ruptured and unruptured aneurysms. There is no definitive consensus as to the best treatment option for this cerebrovascular pathology. The Aneurysm, Arteriovenous Malformation, and Chronic Subdural Hematoma Roundtable Discussion With Industry and Stroke Experts discussed best practices and the most promising approaches to improve the management of brain aneurysms. METHODS: A group of experts from academia, industry, and federal regulators convened to discuss updated clinical trials, scientific research on preclinical system models, management options, screening and monitoring, and promising novel device technologies, aiming to improve the outcomes of patients with IA. RESULTS: Aneurysm, Arteriovenous Malformation, and Chronic Subdural Hematoma Roundtable Discussion With Industry and Stroke Experts suggested the incorporation of artificial intelligence to capture sequential aneurysm growth, identify predictors of rupture, and predict the risk of rupture to guide treatment options. The consensus strongly recommended nationwide systemic data collection of unruptured IA radiographic images for the analysis and development of machine learning algorithms for rupture risk. The consensus supported centers of excellence for preclinical multicenter trials in areas such as genetics, cellular composition, and radiogenomics. Optical coherence tomography and magnetic resonance imaging contrast-enhanced 3T vessel wall imaging are promising technologies; however, more data are needed to define their role in IA management. Ruptured aneurysms are best managed at large volume centers, which should include comprehensive patient management with expertise in microsurgery, endovascular surgery, neurology, and neurocritical care. CONCLUSIONS: Clinical and preclinical studies and scientific research on IA should engage high-volume centers and be conducted in multicenter collaborative efforts. The future of IA diagnosis and monitoring could be enhanced by the incorporation of artificial intelligence and national radiographic and biologic registries. A collaborative effort between academic centers, government regulators, and the device industry is paramount for the adequate management of IA and the advancement of the field.

Genetic analysis of polymorphism rs10937405 of TP63 gene in breast and ovarian cancer patients of North Indian Cohort.

Introduction: Ovarian and breast cancers are highly prevalent in the population of Jammu and Kashmir (J&K). However, case-control association studies on breast and ovarian cancers are lacking in this population. Moreover, no case-control study is available on variant rs10937405 of TP63 in breast and ovarian cancers. Thus, we designed to replicate the cancer susceptible variant rs10937405 of TP63 in ovarian and breast cancers in the population of J&K because the TP63 gene act as a tumor suppressor gene and was previously associated with various cancers. Materials and Methods: This case-control association study conducted at the Shri Mata Vaishno Devi University, includes 150 breast, 150 ovarian cancer cases, and 210 healthy controls (age and sex-matched). Variant rs10937405 of the TP63 gene was determined by the TaqMan assay. Hardy-Weinberg equilibrium for the variant was assessed using the Chi-square test. The allele and genotype-specific risks were estimated by odds ratios (ORs) with 95% confidence intervals (CI). Results: In this study, variant rs10937405 of TP63 gene did not show any risk with ovarian and breast cancer with (P-value = 0.70) having OR 0.94, (0.69-1.28 at 95% CI) and (P-value = 0.16) having OR 0.80, (0.59-1.10). Discussion: Our results indicate that the variant rs10937405 of the TP63 gene did not impart any risk of breast and ovarian cancer in the population of J&K. Our results indicate that a larger sample size is needed for further statistical validation. As the study was for a particular variant, it warrants the analysis of other variants of this gene.

Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Wide-Neck Aneurysms - SCENT: 3-year outcomes.

BACKGROUND: To report the 3-year safety and effectiveness of the Surpass Streamline flow diverter in the SCENT trial (Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Wide-Neck Aneurysms). METHODS: The Surpass Streamline flow diverter device was evaluated in a multicenter, prospective, single-arm, non-randomized interventional trial including patients with uncoilable or previously treated but failed aneurysms of the intracranial internal carotid artery. 3-year outcomes were tabulated with descriptive statistics and compared with 1-year outcomes. RESULTS: Of 180 patients in the modified intent-to-treat (mITT) cohort, 36-month clinical and angiographic follow-up was available in 134 and 117 cases, respectively. Effectiveness endpoint of complete aneurysm occlusion without clinically significant stenosis or retreatment was met in 71.8% (79/110, 95% CI 62.4% to 80.0%) of cases. Safety composite endpoint was 12.2% (22/180) over the 3-year period, with two major safety events (ipsilateral ischemic strokes) occurring between 12-36 months. Complete aneurysm occlusion was noted in 77.8% (91/117), and 99.1% (116/117) of the patients demonstrated adequate aneurysm occlusion (complete occlusion or neck residual). There were four cases (2.2%) of aneurysm rupture, all occurring within the first month of the index procedure. Target aneurysm retreatment rate was 2.8% (5/180). CONCLUSION: The present findings support the long-term safety and effectiveness of the Surpass Streamline flow diverter device. TRIAL REGISTRATION: NCT01716117.

Treatment of large and giant posterior communicating artery aneurysms with the Surpass streamline flow diverter: results from the SCENT trial.

BACKGROUND: The Surpass flow diverter was developed to treat intracranial aneurysms not amenable to standard treatment. Indications for use allow placement in the internal carotid artery to the terminus, including the communicating artery segment. METHODS: The Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Wide Neck Aneurysms (SCENT) trial is an international, multicenter, prospective, non-randomized trial comparing the outcomes of Surpass flow diverter treatment with historic control designed to evaluate the effectiveness and safety of Surpass for the treatment of wide neck (≥4 mm) large or giant intracranial aneurysms ≥10 mm. The primary effectiveness endpoint is the percentage of subjects with 100% aneurysm occlusion without significant stenosis of the parent artery and without retreatment of the target aneurysm at 12 months. The primary safety endpoint is the percentage of subjects experiencing neurologic death or major ipsilateral stroke at 12 months. We report the effectiveness and safety of flow diversion in the subgroup of posterior communicating artery (PComA) aneurysms. RESULTS: Of the 180 patients treated, 38 harbored a PComA aneurysm. Mean aneurysm size was 12.2 mm and mean neck width was 4.8 mm. The mean number of Surpass devices used was 1.1 per procedure, with 94.7% of aneurysms treated with one flow diverter. The 12 month primary effectiveness rate was 73.7% (28/38). At 36 months, 68.4% (26/38) of aneurysms remained completely occluded. The 12 month major ipsilateral stroke or neurological death rate was 10.5%. No patients with PComA occlusion after flow diverter placement (54.5%) had clinical sequelae. CONCLUSIONS: SCENT demonstrated acceptable 12 month effectiveness of flow diversion in PComA aneurysms. Despite associated PComA occlusions in many cases, arterial occlusions were clinically silent. TRIAL REGISTRATION NUMBER: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT01716117.

Triple therapy versus dual-antiplatelet therapy for dolichoectatic vertebrobasilar fusiform aneurysms treated with flow diverters.

BACKGROUND: Dolichoectatic vertebrobasilar fusiform aneurysms (DVBFAs) have poor natural history when left untreated and high morbimortality when treated with microsurgery. Flow diversion (FD) with dual-antiplatelet therapy (DAPT) is feasible but carries high risk of perforator occlusion and progression of brainstem compression. Elaborate antithrombotic strategies are needed to preserve perforator patency while vessel remodeling occurs. We compared triple therapy (TT (DAPT plus oral anticoagulation)) and DAPT alone in patients with DVBFAs treated with FD. METHODS: Retrospective comparison of DAPT and TT in patients with DVBFAs treated with FD at eight US centers. RESULTS: The groups (DAPT=13, TT=14) were similar in age, sex, clinical presentation, baseline disability, and aneurysm characteristics. Radial access use was significantly higher in the TT group (71.4% vs 15.3%; P=0.006). Median number of flow diverters and adjunctive coiling use were non-different between groups. Acute ischemic stroke rate during the oral anticoagulation period was lower in the TT group than the DAPT group (7.1% vs 30.8%; P=0.167). Modified Rankin Scale score decline was significantly lower in the TT group (7.1% vs 69.2%; P=0.001). Overall rates of hemorrhagic complications (TT, 28.6% vs DAPT, 7.7%; P=0.162) and complete occlusion (TT, 25% vs DAPT, 54.4%; P=0.213) were non-different between the groups. Rate of moderate-to-severe disability at last follow-up was significantly lower in the TT group (21.4% vs 76.9%; P=0.007). CONCLUSIONS: Patients with DVBFAs treated with FD in the TT group had fewer ischemic strokes, less symptom progression, and overall better outcomes at last follow-up than similar patients in the DAPT group.

Safety of the APOLLO Onyx delivery microcatheter for embolization of brain arteriovenous malformations: results from a prospective post-market study.

BACKGROUND: Catheter retention and difficulty in retrieval have been observed during embolization of brain arteriovenous malformations (bAVMs) with the Onyx liquid embolic system (Onyx). The Apollo Onyx delivery microcatheter (Apollo) is a single lumen catheter designed for controlled delivery of Onyx into the neurovasculature, with a detachable distal tip to aid catheter retrieval. This study evaluates the safety of the Apollo for delivery of Onyx during embolization of bAVMs. METHODS: This was a prospective, non-randomized, single-arm, multicenter, post-market study of patients with a bAVM who underwent Onyx embolization with the Apollo between May 2015 and February 2018. The primary endpoint was any catheter-related adverse event (AE) at 30 days, such as unintentional tip detachment or malfunction with clinical sequelae, or retained catheter. Procedure-related AEs (untoward medical occurrence, disease, injury, or clinical signs) and serious AEs (life threatening illness or injury, permanent physiological impairment, hospitalization, or requiring intervention) were also recorded. RESULTS: A total of 112 patients were enrolled (mean age 44.1±17.6 years, 56.3% men), and 201 Apollo devices were used in 142 embolization procedures. The mean Spetzler-Martin grade was 2.38. The primary endpoint was not observed (0/112, 0%). The catheter tip detached during 83 (58.5%) procedures, of which 2 (2.4%) were unintentional and did not result in clinical sequelae. At 30 days, procedure related AEs occurred in 26 (23.2%) patients, and procedure-related serious AEs in 12 (10.7%). At 12 months, there were 3 (2.7%) mortalities, including 2 (1.8%) neurological deaths, none of which were device-related. CONCLUSION: This study demonstrates the safety of Apollo for Onyx embolization of bAVMs. CLINICAL TRIAL REGISTRATION: CNCT02378883.

International teleproctoring in neurointerventional surgery and its potential impact on clinical trials in the era of COVID-19: legal and technical considerations.

BACKGROUND: Existing travel restrictions limit the mobility of proctors, significantly delaying clinical trials and the introduction of new neurointerventional devices. We aim to describe in detail technical and legal considerations regarding international teleproctoring, a tool that could waive the need for in-person supervision during procedures. METHODS: International teleproctoring was chosen to provide remote supervision during the first three intracranial aneurysm treatments with a new flow diverter (currently subject of a clinical trial) in the US. Real-time, high-resolution transmission software streamed audiovisual data to a proctor located in Canada. The software allowed the transmission of images in a de-identified, HIPAA-compliant manner. RESULTS: All three flow diverters were implanted as desired by operator and proctor and without complication. The proctor could swap between images from multiple sources and reported complete spatial and situational awareness, without any significant lag or delay in communication. Procedural times and radiologic dose were similar to those of uncomplicated, routine flow diversion cases at our institution. CONCLUSIONS: International teleproctoring was successfully implemented in our clinical practice. Its first use provided important insights for establishing this tool in our field. With no clear horizon for lifting the current travel restrictions, teleproctoring has the potential to remove the need for proctor presence in the angiography suite, thereby allowing the field to advance through the continuation of trials and the introduction of new devices in clinical practice. In order for this tool to be used safely and effectively, highly reliable connection and high-resolution equipment is necessary, and multiple legal nuances have to be considered.

Five-year results of randomized bioactive versus bare metal coils in the treatment of intracranial aneurysms: the Matrix and Platinum Science (MAPS) Trial.

BACKGROUND: No randomized trial of intracranial aneurysm coiling has compared long-term efficacy of polymer-modified coils to bare metal coils (BMCs). We report 5-year results comparing Matrix2 coils to BMCs. The primary objective was to compare the rates of target aneurysm recurrence (TAR) at 12 months. Secondary objectives included angiographic outcomes at TAR or 12 months and TAR at 5 years. METHODS: A total of 626 patients were randomized to BMCs or Matrix2 coils. Detailed methods and 1-year results have been published previously. RESULTS: Of 580 patients eligible for 5-year follow-up, 431 (74.3%) completed follow-up or reached TAR. Matrix2 coils were non-inferior to BMCs (P=0.8) but did not confer any benefit. Core lab reported post-treatment residual aneurysm filling (Raymond III) correlated with TAR (P<0.0001) and with aneurysm hemorrhage after treatment (P<0.008). Repeat aneurysmal hemorrhage after treatment, but before hospital discharge, occurred in three patients treated for acutely ruptured aneurysms. Additionally, two patients treated for unruptured aneurysms experienced a first hemorrhage during follow-up. All five hemorrhages resulted from aneurysms with Raymond III residual aneurysm filling persisting after initial treatment. After 5 years follow-up, 2/626 (0.3%) patients are known to have had target aneurysm rupture following hospital discharge. The annualized rate of delayed hemorrhage after coiling was 2/398/5=0.001 (0.1%) per year for unruptured aneurysms and 0 for ruptured aneurysms. CONCLUSIONS: After 5 years Matrix2 coils were non-inferior to BMCs but no benefit was demonstrated. Post-treatment residual angiographic aneurysm filling (Raymond III) is strongly associated with TAR (P<0.0001) and post-treatment aneurysmal hemorrhage (P=0.008).

Review of current intracranial aneurysm flow diversion technology and clinical use.

Endovascular treatment of intracranial aneurysms (IAs) has evolved considerably over the past decades. The technological advances have been driven by the experience that coils fail to completely exclude all IAs from the blood circulation, the need to treat the diseased parent vessel segment leading to the aneurysm formation, and expansion of endovascular therapy to treat more complex IAs. Stents were initially developed to support the placement of coils inside wide neck aneurysms. However, early work on stent-like tubular braided structure led to a more sophisticated construct that then later was coined as a flow diverter (FD) and found its way into clinical application. Although FDs were initially used to treat wide-neck large and giant internal carotid artery aneurysms only amenable to surgical trap with or without a bypass or endovascular vessel sacrifice, its use in other types of IAs and cerebrovascular pathology promptly followed. Lately, we have witnessed an explosion in the application of FDs and subsequently their modifications leading to their ubiquitous use in endovascular therapy. In this review we aim to compile the available FD technology, evaluate the devices' peculiarities from the authors' perspective, and analyze the current literature to support initial and expanded indications, recognizing that this may be outdated soon.

MassArray analysis of genomic susceptibility variants in ovarian cancer.

Ovarian cancer (OC), a multifaceted and genetically heterogeneous malignancy is one of the most common cancers among women. The aim of the study is to unravel the genetic factors associated with OC and the extent of genetic heterogeneity in the populations of Jammu and Kashmir (J&K).Using the high throughput Agena MassARRAY platform, present case control study was designed which comprises 200 histopathological confirmed OC patients and 400 age and ethnicity matched healthy controls to ascertain the association of previously reported eleven single nucleotide polymorphisms (SNPs) spread over ten genes (DNMT3A, PIK3CA, FGFR2, GSTP1, ERCC5, AKT1, CASC16, CYP19A1, BCL2 and ERCC1) within the OC population of Jammu and Kashmir, India. The association of each variant was estimated using logistic regression analyses. Out of the 11 SNPs the odds ratio observed for three SNPs; rs2699887 was (1.72 at 95% CI: 1.19-2.48, p = 0.004), rs1695 was (1.87 at 95% CI: 1.28-2.71, p = 0.001), and rs2298881 was (0.66 at 95% CI: 0.46-0.96, p = 0.03) were found significantly associated with the OC after correction with confounding factors i.e. age & BMI. Furthermore, the estimation of interactive analyses was performed and odds ratio observed was 2.44 (1.72-3.47), p value < 0. 001 suggests that there was a strong existence of interplay between the selected genetic variants in OC, which demonstrate that interactive analysis highlights the role of gene-gene interaction that provides an insight among multiple little effects of various polymorphisms in OC.

Trends in academic productivity in the COVID-19 era: analysis of neurosurgical, stroke neurology, and neurointerventional literature.

BACKGROUND: Academic physicians aim to provide clinical and surgical care to their patients while actively contributing to a growing body of scientific literature. The coronavirus disease 2019 (COVID-19) pandemic has resulted in procedural-based specialties across the United States witnessing a sharp decline in their clinical volume and surgical cases. OBJECTIVE: To assess the impact of COVID-19 on neurosurgical, stroke neurology, and neurointerventional academic productivity. METHODS: The study compared the neurosurgical, stroke neurology, and neurointerventional academic output during the pandemic lockdown with the same time period in previous years. Editors from a sample of neurosurgical, stroke neurology, and neurointerventional journals provided the total number of original manuscript submissions, broken down by months, from the year 2016 to 2020. Manuscript submission was used as a surrogate metric for academic productivity. RESULTS: 8 journals were represented. The aggregated data from all eight journals as a whole showed that a combined average increase of 42.3% was observed on original submissions for 2020. As the average yearly percent increase using the 2016-2019 data for each journal exhibited a combined average increase of 11.2%, the rise in the yearly increase for 2020 in comparison was nearly fourfold. For the same journals in the same time period, the average percent of COVID-19 related publications from January to June of 2020 was 6.87%. CONCLUSION: There was a momentous increase in the number of original submissions for the year 2020, and its effects were uniformly experienced across all of our represented journals.

First clinical experience with the new Surpass Evolve flow diverter: technical and clinical considerations.

OBJECTIVE: To describe the results in patients treated with the Surpass Evolve (SE) device, the new generation of Surpass flow diverters. METHODS: Twenty-five consecutive patients (20 women, average age 58 years), with anterior or posterior circulation aneurysms treated with SEs in two early-user centers, were included. Device properties and related technical properties, imaging and clinical follow-up data, and intraprocedural, early (<30 days) and delayed (>30 days) neurological complications, further divided into minor (silent/non-permanent) and major (permanent) complications, were recorded and analyzed. RESULTS: Twenty-nine SEs were successfully implanted in all subjects to treat 26 aneurysms using an 0.027" microcatheter with an average of 1.2 stents per patient. No intraprocedural thromboembolic or hemorrhagic complications were seen. At clinical follow-up, 24/25 (96%) patients had a modified Rankin Score of 0-2. Mortality was 0%. Imaging follow-up, available in 22/25 (88%) patients (median follow-up time 4 months), showed a complete aneurysm occlusion in 13/23 (57%) imaged lesions. Minor, transitory neurological deficits were recorded in 5/25 (20%) patients. One (4%) major complication was seen in one patient (4%) with a left-sided hemispheric stroke on postprocedural day 4 due to an acute stent thrombosis. CONCLUSIONS: Preliminary experience in patients demonstrates a good performance of the SE. This newly designed implant maintains the engineering characteristics of Surpass flow diverters, including precise placement due to its lower foreshortening and a high mesh density, yet can be deployed through a significantly lower-profile delivery system.

Genetic variants of DNAH11 and LRFN2 genes and their association with ovarian and breast cancer.

OBJECTIVE: To investigate the association of newly identified genetic variants G>A (rs2285947) of the DNAH11 gene and G>A (rs2494938) of the LRFN2 gene with ovarian and breast cancers in women belonging to Jammu and Kashmir state, where the prevalence of ovarian and breast cancers is remarkably high in the population. METHODS: A candidate gene prospective case-control association study design was adopted, in which 354 cases (219 cases of ovarian cancer and 135 cases of breast cancer) were histopathologically confirmed and 330 healthy controls matched for age and ethnicity were recruited. The details of cases and controls were also recorded in a predesigned pro forma after their written informed consent. Both variants were genotyped by TaqMan allele discrimination assay using real-time polymerase chain reaction. Logistic regression analysis was performed to estimate the corrected odds ratio (OR), confidence interval (CI), and level of significance (P value) for potential confounding factors. RESULTS: The rs2285947 variant of DNAH11 was found to be significantly associated with both ovarian and breast cancers with adjusted ORs of 1.7 (95% CI 1.2-2.4; P=0.004) and 1.70 (95% CI 1.13-2.54; P=0.0009), respectively. However, no significant association of variant rs2494938 of LRFN2 was observed with ovarian cancer (estimated OR 0.9, 95% CI 0.6-1.4; P=0.919) or breast cancer (estimated OR 1.27, 95% CI 0.8-1.9; P=0.216). CONCLUSIONS: The collected data proposed that the variant rs2285947 of DNAH11 gene is a potential risk factor for ovarian and breast cancers in the studied population.

Flow diversion treatment for acutely ruptured aneurysms.

BACKGROUND AND PURPOSE: Flow diverters are sometimes used in the setting of acutely ruptured aneurysms. However, thromboembolic and hemorrhagic complications are feared and evidence regarding safety is limited. Therefore, in this multicenter study we evaluated complications, clinical, and angiographic outcomes of patients treated with a flow diverter for acutely ruptured aneurysms. METHODS: We conducted a retrospective observational study of 44 consecutive patients who underwent flow diverter treatment within 15 days after rupture of an intracranial aneurysm at six centers. The primary end point was good clinical outcome, defined as modified Rankin Scale score (mRS) 0-2. Secondary endpoints were procedure-related complications and complete aneurysm occlusion at follow-up. RESULTS: At follow-up (median 3.4 months) 20 patients (45%) had a good clinical outcome. In 20 patients (45%), 25 procedure-related complications occurred. These resulted in permanent neurologic deficits in 12 patients (27%). In 5 patients (11%) aneurysm re-rupture occurred. Eight patients died resulting in an all-cause mortality rate of 18%. Procedure-related complications were associated with a poor clinical outcome (mRS 3-6; OR 5.1(95% CI 1.0 to 24.9), p=0.04). Large aneurysms were prone to re-rupture with rebleed rates of 60% (3/5) vs 5% (2/39) (p=0.01) for aneurysms with a size ≥20 mm and <20 mm, respectively. Follow-up angiography in 29 patients (median 9.7 months) showed complete aneurysm occlusion in 27 (93%). CONCLUSION: Flow diverter treatment of ruptured intracranial aneurysms was associated with high rates of procedure-related complications including aneurysm re-ruptures. Complications were associated with poor clinical outcome. In patients with available angiographic follow-up, a high occlusion rate was observed.

DNA base excision repair genes variants rs25487 (X-ray repair cross-complementing 1) and rs1052133 (human 8-oxoguanine glycosylase 1) with susceptibility to ovarian cancer in the population of the Jammu region, India.

BACKGROUND: Ovarian cancer is highly prevalent in the population of Jammu, in India; the ovarian cancer ranks third among other types of cancer prevalent in females. However, association studies on ovarian cancer are lacking in this region. We aimed to investigate the disease susceptible variants rs1052133 (human 8-oxoguanine glycosylase 1 [hOGG1]) and rs25487 (X-ray repair cross-complementing 1 [XRCC1]) with ovarian cancer in population of Jammu, India. MATERIALS AND METHODS: The study conducted in the Shri Mata Vaishno Devi University is a 3-year study which included a total of 280 well-characterized samples (130 ovarian cancer cases and 150 healthy controls). hOGG1 and XRCC1 polymorphisms were determined by polymerase chain reaction-based restriction fragment length polymorphism, and these genotyping results were confirmed by Sanger sequencing. Hardy-Weinberg equilibrium for both single-nucleotide polymorphisms (SNPs) was assessed using the Chi-square test. The allele and genotype-specific risks were estimated by odds ratios with 95% confidence intervals. RESULTS: In this preliminary study, SNP rs1052133 showed protection with ovarian cancer (P = 0.042). The SNP rs25487 was not found associated with ovarian cancer (P = 0.271). CONCLUSION: Our results indicate that the G allele of rs1052133 imparts protection to the population whereas variant rs25487 was not associated with ovarian cancer in population from the Jammu region, indicating that larger sample size is needed for further statistical validation. Further, association of other SNPs in these genes should also be carried out as their role cannot be ruled out.

Treatment of blood blister aneurysms of the internal carotid artery with flow diversion.

BACKGROUND: Blood blister aneurysms (BBA) are a rare subset of intracranial aneurysms that represent a therapeutic challenge from both a surgical and endovascular perspective. OBJECTIVE: To report multicenter experience with flow diversion exclusively for BBA, located at non-branching segments along the anteromedial wall of the supraclinoidal internal carotid artery (ICA). METHODS: Consecutive cases of BBA located at non-branching segments along the anteromedial wall of the supraclinoidal ICA treated with flow diversion were included in the final analysis. RESULTS: 49 patients with 51 BBA of the ICA treated with devices to achieve the flow diversion effect were identified. 43 patients with 45 BBA of the ICA were treated with the pipeline embolization device and were included in the final analysis. Angiographic follow-up data were available for 30 patients (32 aneurysms in total); 87.5% of aneurysms (28/32) showed complete obliteration, 9.4% (3/32) showed reduced filling, and 3.1% (1/32) persistent filling. There was no difference between the size of aneurysm (≤2 mm vs >2 mm) or the use of adjunct coiling and complete occlusion of the aneurysm on follow-up (P=0.354 and P=0.865, respectively). Clinical follow-up data were available for 38 of 43 patients. 68% of patients (26/38) had a good clinical outcome (modified Rankin scale score of 0-2) at 3 months. There were 7 (16%) immediate procedural and 2 (5%) delayed complications, with 1 case of fatal delayed re-rupture after the initial treatment. CONCLUSIONS: Our data support the use of a flow diversion technique as a safe and effective therapeutic modality for BBA of the supraclinoid ICA.

Use of the Pipeline embolization device for recurrent and residual cerebral aneurysms: a safety and efficacy analysis with short-term follow-up.

OBJECTIVE: Evaluation of the safety and efficacy of the Pipeline embolization device (PED) when used as second-line treatment for recurrent or residual, pretreated ruptured and unruptured intracranial aneurysms (IAs). METHODS: Retrospective review of our database to include all patients who were treated with a PED for recurrent or residual IAs following surgical clipping or coiling. We evaluated neurological outcome and angiograms at discharge, 6- and 12-months' follow-up and assessed intimal hyperplasia at follow-up. RESULTS: Twenty-four patients met our inclusion criteria. Most IAs were located in the anterior circulation (n=21). No change of preprocedure modified Rankin Scale score was seen at discharge or at any scheduled follow-up. Complete or near-complete aneurysm occlusion on 6- and 12-month angiograms was seen in 94.4% (17/18 cases) and 93.3% (14/15 cases), respectively. Complete or near-complete occlusion was seen in 100% of previously ruptured and 85.7% (6/7 cases) and 83.3% (5/6 cases) of previously unruptured cases at the 6- and 12-months' follow-up, respectively. One case of moderate intimal hyperplasia was observed at 6 months and decreased to mild at the 12-months' follow-up. No difference in device performance was observed among pretreated unruptured or ruptured IAs. CONCLUSIONS: Treatment of recurrent or residual IAs with a PED after previous coiling or clipping is feasible and safe. There is no difference in device performance between ruptured or unruptured IAs.

In situ tissue engineering: endothelial growth patterns as a function of flow diverter design.

BACKGROUND: Vascular remodeling in response to implantation of a tissue engineering scaffold such as a flow diverter (FD) leads to the cure of intracranial aneurysms. We hypothesize that the vascular response is dependent on FD design, and CD34+ progenitor cells play an important role in the endothelialization of the implant. METHODS: Sixteen rabbit aneurysms were randomly treated with two different single-layer braided FDs made of cobalt-chrome alloys. The FD-48 and FD-72 devices had 48 and 72 wires, respectively. Aneurysm occlusion rate was assessed during the final digital subtraction angiogram at 10, 20, 30, and 60 days (n=2 per device per time point). Implanted vessels were analyzed with scanning electron microscopy for tissue coverage, endothelialization, and immuno-gold labeling for CD34+ cells. RESULTS: Complete aneurysm occlusion rates were similar between the devices; however, complete or near complete occlusion was more frequently observed in aneurysms with neck ≤4.2 mm (p=0.008). Total tissue coverage at 10 days over the surface of the FD-48 and FD-72 devices was 56.4±11.6% and 76.6±3.6%, respectively. Endothelial cell growth over the surface was time-dependent for the FD-72 device (Spearman's r=0.86, p=0.013) but not for the FD-48 device (Spearman's r=-0.59, p=0.094). The endothelialization score was marginally correlated with the distance from the aneurysm neck for the FD-48 device (Spearman's r=1, p=0.083) but not for the FD-72 device (Spearman's r=0.8, p=0.33). CD34+ cells were present along the entirety of both devices at all time points. CONCLUSIONS: This study gives preliminary evidence that temporal and spatial endothelialization is dependent on FD design. Circulating CD34+ progenitor cells contribute to endothelialization throughout the healing process.

Treatment of complex anterior cerebral artery aneurysms with Pipeline flow diversion: mid-term results.

BACKGROUND: The off-label use of flow diverters in the treatment of distal aneurysms continues to be debated. OBJECTIVE: To report our multicenter experience in the treatment of complex anterior cerebral artery aneurysms with the Pipeline embolization device (PED). METHODS: The neurointerventional databases of the four participating institutions were retrospectively reviewed for aneurysms treated with PED between October 2011 and January of 2016. All patients treated for anterior cerebral artery aneurysms were included in the analysis. Clinical presentation, location, type, vessel size, procedural complications, clinical and imaging follow-up were included in the analysis. RESULTS: Twenty patients (13 female) with 20 aneurysms met the inclusion criteria in our study. Fifteen aneurysms were classified as saccular and five as fusiform (mean size 7.3 mm). Thirteen aneurysms were located in the anterior communicating region (ACOM or A1/2 junction), six were A2-pericallosal, and one was located in the A1 segment. Six patients had presented previously with subarachnoid hemorrhage and had their aneurysms initially clipped or coiled. There was one minor event (a small caudate infarct) and one major event (intraparenchymal hemorrhage). Sixteen of the 20 patients had angiographic follow-up (mean 10 months). Eleven aneurysms were completely occluded, one had residual neck, and four had residual aneurysm filling. CONCLUSIONS: The treatment of complex anterior cerebral artery aneurysms with the PED as an alternative for patients who are not good candidates for conventional methods is technically feasible and safe. Mid-term results are promising but larger series with long-term follow-up are required to assess its effectiveness.