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.

Polyetheretherketone Implant Cranioplasty for Large Cranial Defects: A Seven-Year Follow-Up.

BACKGROUND: Goals of a cranioplasty include protection of the brain, restoration of normal appearance, and neurological function improvement. Although choice of materials for cranial remodeling has changed through the years, computer-designed polyetheretherketone (PEEK) implant has gained traction as a preferred material used for cranioplasty. However, long-term outcomes and complications of PEEK implants remain limited. The goal of this study was to report long-term clinical outcomes after PEEK implant cranioplasty. METHODS: A retrospective chart review was performed on patients undergoing PEEK cranioplasty between January 2007 and February 2023. Preoperative, intraoperative, and postoperative data were collected and analyzed. RESULTS: Twenty-two patients were included in this study. Mean postoperative follow-up time was 83.45 months (range: 35.47-173.87). Before PEEK implant cranioplasty, patients with multiple cranial procedures had undergone a mean of 2.95 procedures. PEEK implant cranioplasty indications were prior implant infection (14) and secondary reconstruction of cranial defect (8). The mean implant size was 180.43 cm2 (range: 68.00-333.06). Four patients received a 2-piece implant. Postoperative complications included: perioperative subgaleal self-resolving fluid collection in 1 patient, hematoma in another, and 3 infections resulting in explantations with successful reinsertion in 2 patients. Four of 5 patients with preoperative history of seizures reported improved seizures and all 4 patients with preoperative syndrome of the trephined reported improved symptoms and neurological function. CONCLUSION: At a mean follow-up of 7 years, most PEEK implants continued to provide protection to the brain and consistent symptom relief in patients suffering from prior postcraniectomy/craniotomy sequelae of seizures and syndrome of the trephined.

Racial and Ethnic Disparities in the Medical Management of Poststroke Complications Among Patients With Acute Stroke.

BACKGROUND: To inform clinical practice, we sought to identify racial and ethnic differences in the medical management of common poststroke complications. METHODS AND RESULTS: A cohort of acutely hospitalized, first-time non-Hispanic White (NHW), non-Hispanic Black, and Hispanic patients with stroke was identified from electronic medical records of 51 large health care organizations (January 1, 2003 to December 5, 2022). Matched propensity scores were used to account for baseline differences. Primary outcomes included receipt of medication(s) associated with the management of the following poststroke complications: arousal/fatigue, spasticity, mood, sleep, neurogenic bladder, neurogenic bowel, and seizure. Differences were measured at 14, 90, and 365 days. Subgroup analyses included differences restricted to patients with ischemic stroke, younger age (<65 years), and stratified by decade (2003-2012 and 2013-2022). Before matching, the final cohort consisted of 348 286 patients with first-time stroke. Matching resulted in 63 722 non-Hispanic Black-NHW pairs and 24 009 Hispanic-NHW pairs. Non-Hispanic Black (versus NHW) patients were significantly less likely to be treated for all poststroke complications, with differences largest for arousal/fatigue (relative risk (RR), 0.58 [95% CI, 0.54-0.62]), spasticity (RR, 0.64 [95% CI, 0.0.62-0.67]), and mood disorders (RR, 0.72 [95% CI, 0.70-0.74]) at 14 days. Hispanic-NHW differences were similar, albeit with smaller magnitudes, with the largest differences present for spasticity (RR, 0.67 [95% CI, 0.63-0.72]), arousal/fatigue (RR, 0.77 [95% CI, 0.70-0.85]), and mood disorders (RR, 0.79 [95% CI, 0.77-0.82]). Subgroup analyses revealed similar patterns for ischemic stroke and patients aged <65 years. Disparities for the current decade remained significant but with smaller magnitudes compared with the prior decade. CONCLUSIONS: There are significant racial and ethnic disparities in the treatment of poststroke complications. The differences were greatest at 14 days, outlining the importance of early identification and management.

Application of apophyllite and thomsonite natural zeolite as modified adsorbents for the removal of zinc from acid mine drainage.

Materials composed of natural zeolite have the potential to serve as highly effective adsorbents in the treatment of wastewater. The present study explores zeolite resin-based Apophyllite and Thomsonite as adsorbents for removing Zinc from acid mine drainage solution. The characteristics of the natural zeolites (Apophyllites and Thomsonite) are investigated using X-ray diffraction, Fourier-transform infrared spectroscopy and Field emission scanning electron microscopy analysis. The removal of Zinc from AMD is explored, and the influence of metal ion concentration, resin dose, and pH is investigated using a batch exchange resin-based experimental method. Maximum zinc removal occurs in the pH range of 2-6 with an initial zinc content of 50-250 mg/L and a resin dosage of 25-700 mg/L, indicating that the adsorption process is pH-dependent. Various isotherm models, including those proposed by Freundlich and Langmuir as well as Redlich-Peterson, Dubinin, and Temkin, are used to verify the results of the experimental research. All these isotherm models' constants are determined. Both resins showed different sorption efficiencies at different operating conditions. However, highest Zn removal efficiency of 86.2% was observed for the Thomsonite zeolite resin whereas Apophyllite zeolite resin showed maximum Zn uptake of 81.6%. Thus, Thomsonite was found to be an effective sorbent.

Theoretical investigations on electronic structure and optoelectronic properties of vinyl fused monomeric and oligomeric benzimidazole derivatives using DFT and TDDFT techniques.

CONTEXT: The present work encompasses the theoretical investigation of 14 benzimidazole-based (seven vinyl fused monomeric benzimidazole (VFMBI) and seven vinyl fused oligomeric benzimidazole (VFOBI)) derivatives using density functional theory (DFT) and time-dependent density functional theory (TD-DFT) techniques. The effects of electron donor and acceptor groups on the electronic structure such as HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energies, HOMO-LUMO energy gap, ionization potentials (IPs), electron affinities (EAs), internal reorganization energies of holes and electrons (λh/e), and excited state properties have been explored in the present work. In addition, natural bond orbital (NBO) analysis of these compounds has been investigated to reveal the typical stabilization interactions in these molecules. Hence, the aim of the present work is to explore the electronic structures and optoelectronic properties of the title molecules on the basis of the DFT quantum chemical calculations and to make an idea on the parameters influencing the optoelectronic efficiency toward a better understanding of the structure-property relationships. Moreover, the calculated results reveal the suitable optoelectronic properties of benzimidazole oligomer derivatives using theoretical techniques. Of the investigated molecules, 4_MABIMCY and 4_MABIOCY show potential optoelectronic properties and can be used as a potential charge transport material due to their narrow band gap, high hyperpolarizability, low ionization potential, and high electron affinity. The larger λab and λem values favor the system to be used as a potential optoelectronic material with better optical properties. METHODS: All quantum chemical calculations were carried out using Gaussian09 theoretical chemistry code. Ground state calculations were made using the B3LYP/6-31+G(d,p) method. All excited state calculations had been computed using TDB3P86/6-311++(d,p). The initial structure for excited state calculations was optimized using the AM1 semi-empirical method.

Landfill leachate treatment using fungi and fungal enzymes: a review.

Landfill leachate raises a huge risk to human health and the environment as it contains a high concentration of organic and inorganic contaminants, heavy metals, ammonia, and refractory substances. Among leachate treatment techniques, the biological methods are more environmentally benign and less expensive than the physical-chemical treatment methods. Over the last few years, fungal-based treatment processes have become popular due to their ability to produce powerful oxidative enzymes like peroxidases and laccases. Fungi have shown better removal efficiency in terms of color, ammonia, and COD. However, their use in the treatment of leachate is relatively recent and still needs to be investigated. This review article assesses the potential of fungi and fungal-derived enzymes in treating landfill leachate. The review also compares different enzymes involved in the fungal catabolism of organic pollutants and the enzyme degradation mechanisms. The effect of parameters like pH, temperature, contact time, dosage variation, heavy metals and ammonia are discussed. The paper also explores the reactor configuration used in the fungal treatment and the techniques used to improve leachate treatment efficacy, like pretreatment and fungi immobilisation. Finally, the review summarises the limitations and the future direction of work required to adapt the fungal application for leachate treatment on a large scale.

Interface engineering of heterogeneous NiMn layered double hydroxide/vertically aligned NiCo2S4 nanosheet as highly efficient hybrid electrocatalyst for overall seawater splitting.

We report the fabrication of a heterogeneous catalyst through vertically aligned NiCo2S4/Ni3S2 nanosheet with encapsulation of ultrathin NiMn layered double hydroxide over self-standing nickel foam (NM/NCS/NS/NF) via two-step hydrothermal processes. Benefiting from more adequate catalytic active centres and copious interfacial charge transfer channels, NM/NCS/NS/NF electrode demonstrates superior bifunctional activity for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) processes under alkaline fresh/simulated seawater electrolyte conditions. As a result, NM/NCS/NS/NF electrode requires the smallest overpotentials of 282 & 312 mV (OER) and 171 & 204 mV (HER) to attain current densities of 30 & 50 mA cm-2 respectively under alkaline simulated seawater electrolyte conditions. Besides, the presence of amorphous NiMn LDH layers over crystalline NiCo2S4/Ni3S2 catalyst stimulates surface adsorption of oxygen intermediate species, water dissociate ability on catalytic active centres, and mass transport with electron transfer at the interface. Further, the two-electrode configuration assisted electrolyser system delivers an efficient overall water splitting activity with minimum cell voltages of 1.54 V (in 1 M KOH) and 1.56 V (in 1 M KOH+0.5 M NaCl) at a current density of 10 mA cm-2. Besides, a fabricated electrolyser cell provides a more sustained water electrolysis process and robust durability for 20 h which displays NM/NCS/NS/NF electrode is a vibrant and potential candidate for realistic seawater electrolysis. Therefore, our proposed heterogeneous electrocatalyst could open up a new platform for developing efficient large-scale efficient seawater electrolysis.

A Transcriptomic Comparative Study of Cranial Vasculature.

In genetic studies of cerebrovascular diseases, the optimal vessels to use as controls remain unclear. Our goal is to compare the transcriptomic profiles among 3 different types of control vessels: superficial temporal artery (STA), middle cerebral arteries (MCA), and arteries from the circle of Willis obtained from autopsies (AU). We examined the transcriptomic profiles of STA, MCA, and AU using RNAseq. We also investigated the effects of using these control groups on the results of the comparisons between aneurysms and the control arteries. Our study showed that when comparing pathological cerebral arteries to control groups, all control groups presented similar responses in the activation of immunological processes, the regulation of intracellular signaling pathways, and extracellular matrix productions, despite their intrinsic biological differences. When compared to STA, AU exhibited upregulation of stress and apoptosis genes, whereas MCA showed upregulation of genes associated with tRNA/rRNA processing. Moreover, our results suggest that the matched case-control study design, which involves control STA samples collected from the same subjects of matched aneurysm samples in our study, can improve the identification of non-inherited disease-associated genes. Given the challenges associated with obtaining fresh intracranial arteries from healthy individuals, our study suggests that using MCA, AU, or paired STA samples as controls are feasible strategies for future large-scale studies investigating cerebral vasculopathies. However, the intrinsic differences of each type of control should be taken into consideration when interpreting the results. With the limitations of each control type, it may be most optimal to use multiple tissues as controls.

Understanding Auger recombination in perovskite solar cells.

Enhanced radiative efficiency, long carrier lifetimes, and high carrier mobilities are hallmarks of perovskite solar cells. Considering this, complete cells experience large nonradiative recombination losses that restrict their VOC considerably below the Shockley-Queisser limit. Auger recombination, which involves two free photo-induced carriers and a trapped charge carrier, is one potential mechanism. Herein, the effects of Auger capture coefficients in mixed-cation perovskites are analyzed employing SCAPS-1D computations. It is demonstrated that VOC and FF are severely decreased with an increase in the acceptor concentration and Auger capture coefficients of perovskites, thus reducing the device performance. When the Auger capture coefficient is increased to 10-20 cm6 s-1 under the acceptor concentration of 1016 cm-3, the performance is drastically lowered from 21.5% (without taking Auger recombination into account) to 9.9%. The findings suggest that in order to increase the efficiency of perovskite solar cells and prevent the effects of Auger recombination, the Auger recombination coefficients should be less than 10-24 cm6 s-1.

Garbage enzyme-mediated treatment of landfill leachate: A sustainable approach.

The study evaluates the soluble chemical oxygen demand (sCOD) removal efficiency from landfill leachate by treating it with four different garbage enzymes at two temperatures (room temperature 27 ± 3 °C and higher temperature 42 ± 3 °C). The four different garbage enzymes were prepared by fermenting fruit peels such as pineapple, banana, orange, and lemon peels and treated with landfill leachate at different mixing ratios of 5%, 10%, 15% and 20%. The results show that garbage enzymes made from orange (10%) and lemon (15%) have maximum sCOD reduction of 68.24% and 67.89%, respectively, at room temperature. The maximum solubilization was found in the pineapple and lemon garbage enzyme at 5% concentration. The samples kept at room temperature showed better solubilization and sCOD removal compared to the samples at higher temperatures. The study demonstrates that the garbage enzyme could be used to increase the bioavailability of organics in leachate.

Deep-learning-enabled brain hemodynamic mapping using resting-state fMRI.

Cerebrovascular disease is a leading cause of death globally. Prevention and early intervention are known to be the most effective forms of its management. Non-invasive imaging methods hold great promises for early stratification, but at present lack the sensitivity for personalized prognosis. Resting-state functional magnetic resonance imaging (rs-fMRI), a powerful tool previously used for mapping neural activity, is available in most hospitals. Here we show that rs-fMRI can be used to map cerebral hemodynamic function and delineate impairment. By exploiting time variations in breathing pattern during rs-fMRI, deep learning enables reproducible mapping of cerebrovascular reactivity (CVR) and bolus arrival time (BAT) of the human brain using resting-state CO2 fluctuations as a natural "contrast media". The deep-learning network is trained with CVR and BAT maps obtained with a reference method of CO2-inhalation MRI, which includes data from young and older healthy subjects and patients with Moyamoya disease and brain tumors. We demonstrate the performance of deep-learning cerebrovascular mapping in the detection of vascular abnormalities, evaluation of revascularization effects, and vascular alterations in normal aging. In addition, cerebrovascular maps obtained with the proposed method exhibit excellent reproducibility in both healthy volunteers and stroke patients. Deep-learning resting-state vascular imaging has the potential to become a useful tool in clinical cerebrovascular imaging.

Variability in the Transition of Care to Poststroke Rehabilitation During the First Wave of COVID-19.

OBJECTIVE: The aim of the study is to evaluate transitions of acute stroke and inpatient rehabilitation facility care during the first wave of COVID-19. DESIGN: This is a retrospective observational study (3 comprehensive stroke centers with hospital-based inpatient rehabilitation facilities) between January 1, 2019, and May 31, 2019 (acute stroke = 584, inpatient rehabilitation facility = 210) and January 1, 2020, and May 31, 2020 (acute stroke = 534, inpatient rehabilitation facility = 186). Acute stroke characteristics included stroke type, demographics, and medical comorbidities. The proportion of patients admitted for acute stroke and inpatient rehabilitation facility care was analyzed graphically and using t test assuming unequal variances. RESULTS: The proportion of intracerebral hemorrhage patients (28.5% vs. 20.5%, P = 0.035) and those with history of transient ischemic attack (29% vs. 23.9%; P = 0.049) increased during the COVID-19 first wave in 2020. Uninsured acute stroke admissions decreased (7.3% vs. 16.6%) while commercially insured increased (42.7% vs. 33.4%, P < 0.001).Acute stroke admissions decreased from 116.5 per month in 2019 to 98.8 per month in 2020 ( P = 0.008) with no significant difference in inpatient rehabilitation facility admissions (39 per month in 2019, 34.5 per month in 2020; P = 0.66).In 2019, monthly changes in acute stroke admissions coincided with inpatient rehabilitation facility admissions.In 2020, acute stroke admissions decreased 80.6% from January to February, while inpatient rehabilitation facility admissions remained stable. Acute stroke admissions increased 12.8% in March 2020 and remained stable in April, while inpatient rehabilitation facility admissions decreased by 92%. CONCLUSIONS: Acute stroke hospitalizations significantly decreased per month during the first wave of COVID-19, with a delayed effect on the transition from acute stroke to inpatient rehabilitation facility care.

2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

AIM: The "2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage" replaces the 2012 "Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage." The 2023 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with aneurysmal subarachnoid hemorrhage. METHODS: A comprehensive search for literature published since the 2012 guideline, derived from research principally involving human subjects, published in English, and indexed in MEDLINE, PubMed, Cochrane Library, and other selected databases relevant to this guideline, was conducted between March 2022 and June 2022. In addition, the guideline writing group reviewed documents on related subject matter previously published by the American Heart Association. Newer studies published between July 2022 and November 2022 that affected recommendation content, Class of Recommendation, or Level of Evidence were included if appropriate. Structure: Aneurysmal subarachnoid hemorrhage is a significant global public health threat and a severely morbid and often deadly condition. The 2023 aneurysmal subarachnoid hemorrhage guideline provides recommendations based on current evidence for the treatment of these patients. The recommendations present an evidence-based approach to preventing, diagnosing, and managing patients with aneurysmal subarachnoid hemorrhage, with the intent to improve quality of care and align with patients' and their families' and caregivers' interests. Many recommendations from the previous aneurysmal subarachnoid hemorrhage guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Vulnerable newborn types: analysis of subnational, population-based birth cohorts for 541 285 live births in 23 countries, 2000-2021.

OBJECTIVE: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021. POPULATION: Liveborn infants. METHODS: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study. RESULTS: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%). CONCLUSIONS: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs.

Outcomes of accelerated collagen cross linking in progressive paediatric keratoconus.

Purpose: To determine the efficacy and safety of pediatric accelerated cross linking (CXL). Methods: A prospective study on progressive keratoconus (KC) cases under ≤18 years of age. Sixty four eyes of thirty nine cases underwent epithelium-off accelerated CXL protocol. Visual acuity (VA), slit-lamp examination, refraction, pentacam reading of keratometry (K), corneal thickness, and thinnest location pachymetry were noted. Cases were followed up on days 1, 5, and at 1st, 3rd, 6th, and 12th-month post procedure. Results: Statistically, significant improvement of the mean aided VA, K, and mean corneal astigmatism (p < 0.0001) was noted. Mean Kmax reading reduced from 55.5 ± 5.64 (47.4-70.4) diopter (D) preoperatively to 54.41 ± 5.51 (46-68.3) D at 12 months postaccelerated CXL. Two cases had progression. Complications encountered were sterile infiltrate and persistent haze. Conclusion: Accelerated CXL is effective and efficacious in pediatric KC.

Effect of inpatient rehabilitation facility care on ninety day modified Rankin score in ischemic stroke patients.

OBJECTIVE: To determine Inpatient Rehabilitation Facility (IRF) treatment effect on modified Rankin Scale (mRS) scores at 90 days in acute ischemic stroke (AIS) patients. MATERIALS AND METHODS: This prospective cross-sectional study included 738 AIS patients admitted 1/1/2018-12/31/2020 to a Comprehensive Stroke Center with a Stroke Rehabilitation program. We compared outcomes for patients who went directly home versus went to IRF at hospital discharge: (1) acute care length of stay (LOS), (2) National Institutes of Health Stroke Scale (NIHSS) score, (3) mRS score at hospital discharge and 90 days, (4) the proportion of mRS scores ≤ 2 from hospital discharge to 90 days. RESULTS: Among 738 patients, 499 went home, and 239 went to IRF. IRF patients were more likely to have increased acute LOS (10.7 vs 3.9 days; t-test, P<0.0001), increased mean NIHSS score (7.8 vs 4.8; t-test, P<0.0001) and higher median mRS score (3 vs 1, t-test, P<0.0001) compared to patients who went home. At 90 days, ischemic stroke patients who received IRF care were more likely to progress to a mRS ≤ 2 (18.7% increase) compared to patients discharged home from acute care (16.3% decrease). Home patients experienced a one-point decrease in mRS at 90 days compared to those who received IRF treatment (median mRS of 3 vs. 2, t-test, P<0.05). CONCLUSIONS: In ischemic stroke patients, IRF treatment increased the likelihood of achieving mRS ≤ 2 at 90 days indicating the ability to live independently, and decreased the likelihood of mRS decrease, compared with patients discharged directly home after acute stroke care.

The effects of aneurysmal subarachnoid hemorrhage on cerebral vessel diameter and flow velocity.

BACKGROUND: Transcranial Doppler flow velocity is used to monitor for cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Generally, blood flow velocities appear inversely related to the square of vessel diameter representing local fluid dynamics. However, studies of flow velocity-diameter relationships are few, and may identify vessels for which diameter changes are better correlated with Doppler velocity. We therefore studied a large retrospective cohort with concurrent transcranial Doppler velocities and angiographic vessel diameters. METHODS: This is a single-site, retrospective, cohort study of adult patients with aneurysmal subarachnoid hemorrhage, approved by the UT Southwestern Medical Center Institutional Review Board. Study inclusion required transcranial Doppler measurements within 1.1, R2>0.9). Furthermore, velocity and diameter changed (P<0.033) consistent with the signature time course of cerebral vasospasm. CONCLUSIONS: These results suggest that middle cerebral artery velocity-diameter relationships are most influenced by local fluid dynamics, which supports these vessels as preferred endpoints in Doppler detection of cerebral vasospasm. Other vessels showed less influence of local fluid dynamics, pointing to greater role of factors outside the local vessel segment in determining flow velocity.

Technical Nuances and Outcomes of Telescoping Pipeline Flow Diverters: A Multicenter Study.

BACKGROUND: "Telescoping" multiple overlapping Pipeline Embolization Devices (PEDs; Medtronic) has increased their utility by allowing for more impermeable coverage and providing the ability to off-set landing zone sites and extend treatment constructs. OBJECTIVE: To consider the technical nuances and challenges of telescoping PEDs for the treatment of intracranial aneurysms. METHODS: Databases from 3 U.S. academic neurovascular centers were retrospectively queried to identify patients with intracranial aneurysms treated with multiple PED constructs. Data on patient and aneurysm characteristics, as well as outcomes including Raymond-Roy occlusion classification, modified Rankin Scale score, and complications, were gathered. RESULTS: Forty-six patients had 48 intracranial aneurysms treated, including 16 (33%) in whom placement of telescoping PEDs was planned. Fourteen (30%) patients presented with a ruptured aneurysm. Twenty-one aneurysms (44%) were treated with proximal extension, 13 (27%) with distal extension, and 14 (29%) with PED placement inside one another. Thirty (70%) patients had complete aneurysm occlusion at follow-up. Two (4%) patients had to be retreated. Three patients with unruptured and 1 with ruptured aneurysm had a permanent intraprocedural complication. We present descriptive cases illustrating PEDs that were placed inside one another, proximally, distally, and to improve wall apposition because of vessel tortuosity. CONCLUSION: Our data indicate a higher than expected complication rate that is likely because of the technical complexity of these cases. The case illustrations presented demonstrate the indications and challenging aspects of telescoping PEDs.

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.

Somatic Variants in SVIL in Cerebral Aneurysms.

Background and Objectives: While somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms. Methods: We performed whole-exome sequencing on aneurysm tissues and paired peripheral blood. RNA sequencing and the CRISPR/Cas9 system were then used to perform functional validation of our results. Results: Somatic variants involved in supervillin (SVIL) or its regulation were found in 17% of aneurysm tissues. In the presence of a mutation in the SVIL gene, the expression level of SVIL was downregulated in the aneurysm tissue compared with normal control vessels. Downstream signaling pathways that were induced by knockdown of SVIL via the CRISPR/Cas9 system in vascular smooth muscle cells (vSMCs) were determined by evaluating changes in gene expression and protein kinase phosphorylation. We found that SVIL regulated the phenotypic modulation of vSMCs to the synthetic phenotype via Krüppel-like factor 4 and platelet-derived growth factor and affected cell migration of vSMCs via the RhoA/ROCK pathway. Discussion: We propose that somatic variants form a novel mechanism for the development of cerebral aneurysms. Specifically, somatic variants in SVIL result in the phenotypic modulation of vSMCs, which increases the susceptibility to aneurysm formation. This finding suggests a new avenue for the therapeutic intervention and prevention of cerebral aneurysms.