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The study of polymers' rheological properties is of paramount importance both for the problems of their industrial production as well as for their practical application. Two polymers used for embolization of arteriovenous malformations (AVMs) are studied in this work: Onyx-18 ® and Squid-12 ® . Viscosity curve tests and computational fluid dynamics (CFD) were used to uncover viscosity law as a function of shear rate as well as behavior of the polymers in catheter or pathological tissue models. The property of thermal activation of viscosity was demonstrated, namely, the law of dependence of viscosity on temperature in the range from 20 °C to 37 °C was established. A zone of viscosity nonmonotonicity was identified, and a physical interpretation of the dependence of the embolic polymers' viscosity on the shear rate was given on the basis of Cisco's model. The obtained empirical constants will be useful for researchers based on the CFD of AVMs. A description of the process of temperature activation of the embolic polymers' viscosity is important for understanding the mechanics of the embolization process by practicing surgeons as well as for producing new prospective embolic agents.

Numerical modeling is an effective tool for preoperative planning. The present work is devoted to a retrospective analysis of neurosurgical treatments for the occlusion of cerebral aneurysms using flow-diverters and hemodynamic factors affecting stent endothelization. Several different geometric approaches have been considered for virtual flow-diverters deployment. A comparative analysis of hemodynamic parameters as a result of computational modeling has been carried out basing on the four clinical cases: one successful treatment, one with no occlusion and two with in stent stenosis. For the first time, a quantitative assessment of both: the limiting magnitude of shear stresses that are necessary for the occurrence of in stent stenosis (MaxWSS > 1.23) and for conditions in which endothelialization is insufficiently active and occlusion of the cervical part of the aneurysm does not occur (MaxWSS < 1.68)—has been statistacally proven (p < 0.01).

Introduction: The endovascular stent-assisted coiling approach for the treatment of cerebral aneurysms is evolving rapidly with the availability of new stent devices. It remains unknown how each type of stent affects the safety and efficacy of the stent-coiling procedure., Methods: This study compared the outcomes of endovascular coiling of cerebral aneurysms using Neuroform (NEU), Enterprise (EP), and Low-profile Visualized Intraluminal Support (LVIS) stents. Patient characteristics, treatment details and angiographic results using the Raymond-Roy grade scale (RRGS), and procedural complications were analyzed in our study., Results: Our study included 659 patients with 670 cerebral aneurysms treated with stent-assisted coiling (NEU, n=182; EP, n=158; LVIS, n=330) that were retrospectively collected from six academic centers. Patient characteristics included mean age 56.3±12.1 years old, female prevalence 73.9%, and aneurysm rupture on initial presentation of 18.8%. We found differences in complete occlusion on baseline imaging, defined as RRGS I, among the three stents: LVIS 64.4%, 210/326; NEU 56.2%, 95/169; EP 47.6%, 68/143; P=0.008. The difference of complete occlusion on 10.5 months (mean) and 8 months (median) angiographic follow-up remained significant: LVIS 84%, 251/299; NEU 78%, 117/150; EP 67%, 83/123; P=0.004. There were 7% (47/670) intra-procedural complications and 11.5% (73/632) post-procedural-related complications in our cohort. Furthermore, procedure-related complications were higher in the braided-stents vs laser-cut, P=0.002., Conclusions: There was a great variability in techniques and choice of stent type for stent-assisted coiling among the participating centers. The type of stent was associated with immediate and long-term angiographic outcomes. Randomized prospective trials comparing the different types of stents are warranted., Competing Interests: Competing interests: Mokin: reports consultant: Cerebrotech, Canon Medical, Imperative Care; stock options – Serenity Medical, Inc. Fiorella: reports grants, non-financial support, and other from Penumbra; non-financial support and other from Cerenovous and Medtronic; grants and non-financial support from Siemens and Microvention; and stock in Vascular Simulations and Neurogami. Rai: reports other from Penumbra; and non-financial support from Microvention and Stryker. Mocco: reports other from Penumbra, Cerebrotech, Rebound Therapeutics, TSP, Lazarus Effect, Medina, Pulsar Vascular, and Blockade. DeLeacy: reports other and non-financial support from Penumbra; and non-financial support from Cerenovus and Siemens. Turner: consultant for Penumbra, Medtronic, Microvention, Codman, Pulsar Vascular, Q’Apel, Rebound Medical, and Blockade Medical. Guilherme Dabus is a consultant for Medtronic, Microvention, and Penumbra and a shareholder in Surpass/Stryker, InNeuroCo, and Medina/Medtronic. Chaudry: reports other, grants, and non-financial support from Penumbra and Pulsar Vascular; grants and non-financial support from Medtronic, Microvention, and Codman; non-financial support and other from Blockade and non-financial support from Siemens. Turk: reports other, grants, and non-financial support from Penumbra and Pulsar Vascular; grants and non-financial support from Codman, Microvention, and Medtronic; non-financial support and other from Blockade; and non-financial support from Siemens., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Intracranial aneurysms located in the distal vessels are rare and remain a challenge to treat through surgical or endovascular interventions., Objective: To describe a multicenter approach with flow diversion using the pipeline embolization device (PED) for treatment of distal intracranial aneurysms., Methods: Cases of distal intracranial aneurysms defined as starting on or beyond the A2 anterior cerebral artery, M2 middle cerebral artery, and P2 posterior cerebral artery segments were included in the final analysis., Results: 65 patients with distal aneurysms treated with the PED were analyzed. Median aneurysm size at the largest diameter was 7.0 mm, 60% were of a saccular morphology, and 9/65 (13.8%) patients presented in the setting of acute rupture. Angiographic follow-up data were available for 53 patients, with a median follow-up time of 6 months: 44/53 (83%) aneurysms showed complete obliteration, 7/53 (13.2%) showed reduced filling, and 2/53 (3%) showed persistent filling. There was no association between patient characteristics, including aneurysm size (P=0.36), parent vessel diameter (P=0.27), location (P=0.81), morphology (P=0.63), ruptured status on admission (P=0.57), or evidence of angiographic occlusion at the end of the embolization procedure (P=0.49). Clinical outcome data were available for 60/65 patients: 95% (57/60) had good clinical outcome (modified Rankin Scale score of 0-2) at 3 months., Conclusions: This large multicenter study of patients with A2, M2, and P2 distal aneurysms treated with the PED showed that flow diversion may be an effective treatment approach for this rare type of vascular pathology. The procedural compilation rate of 7.7% indicates the need for further studies as the flow diversion technology constantly evolves., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Since appearance of the balloon-remodeling technique and stent-assisted coiling, complex aneurysms have been treated successfully by endovascular means worldwide. Although these two techniques have been widely proven, the combination of both traditionally made the procedures more complicated technically. The aim of our study was to determine the technical success, safety, and efficacy of the low-profile stents delivered through double lumen balloons., Methods: Clinical, procedural, and angiographic data were analyzed., Results: Eighty-four patients (55 women; age range 20-81 years) harboring 86 aneurysms were included in this study. Aneurysm maximal diameter ranged from 2 to 26 mm, with mean 7.5 mm. There were 62 unruptured, 15 recanalized, and 9 acutely ruptured aneurysms. Aneurysm locations were ACoA (31), MCA (36), supraclinoid ICA (4), carotid bifurcation (2), basilar (7), PCA (3), PICA (2), and VA (1). Ninety-three devices were implanted (63 LVIS jr, 15 LEO Baby, 14 ACCLINO Flex and 1 Neuroform Atlas) through the double lumen balloons (Scepter C or XC and Eclipse 2 L). We found 2 minor clinical events (2.4%) and 1 major event (1.2%). Total intra-procedural technical complication rate was 11.6%. Follow-up was available for 71 patients with an average follow-up of 7 months. Complete and near complete occlusion was 90.1%. Residual aneurysms were seen in 9.9%., Conclusion: The "combined remodeling technique" with low-profile stents delivered through double-lumen balloons is technically feasible, safe, and effective for the treatment of intracranial aneurysms. This technique allows the operator to avoid extra maneuvers.

Background: Precipitating hydrophobic injectable liquid is a newly introduced liquid embolic agent for endovascular embolization with some technical advantages over other liquid embolic agents. We present our initial experience with precipitating hydrophobic injectable liquid in the endovascular treatment of cerebral arteriovenous malformations., Methods: From October 2015 to January 2018, 27 patients harboring cerebral arteriovenous malformations underwent endovascular embolization with precipitating hydrophobic injectable liquid 25. Clinical features, angiographic results, procedural details, complications, and follow-up details were retrospectively analyzed., Results: Twenty-seven patients with cerebral arteriovenous malformations were included. Total obliteration in one endovascular session was confirmed for 14/27 (52%) patients. Partial embolization was attained in 13 patients (48%) in whom staged treatment with following radiosurgery or surgery was planned. No mortality was recorded in this series. Complications during or after the embolization occurred in six of 27 (22.2%) patients., Conclusion: In our initial experience, precipitating hydrophobic injectable liquid has acceptable clinical outcome comparable to other liquid embolic agents. Although this is the largest reported study in arteriovenous malformation treatment with precipitating hydrophobic injectable liquid, further studies are needed to validate its safety and efficacy.

Objective: We performed prospective randomized comparison of clinical and surgical outcomes of flow diversion versus PVO and bypass in patients with complex anterior circulation aneurysms., Patients and Methods: Open, prospective, randomized, parallel group, multicenter study of complex intracranial aneurysms treatment was conducted. Patients with complex intracranial aneurysms of anterior circulation with neck is more than 4 mm wide, dome/neck ratio is equal or less than 2:1, which is suitable for flow diversion and occlusion with bypass were included in the study. A total of 111 potential participants were enrolled since March 2015. Additional propensity score matching was performed with 40 patients in each group selected for analysis., Results: 39 out of 40 patients (97.5%) from matched FD group reached good clinical outcome. In the matched bypass group acceptable outcome was achieved in 32 (80%) out of 40 patients (difference between groups p = 0.029). The morbidity and mortality rates were 15% and 5%, respectively. Difference in the rates of favorable outcomes, compared by χ2 met statistical significance (p = 0.014). The rate of complete aneurysm occlusion at 6 months was 42.5% in the FD group and 95% in surgical group (p < 0.0001). The rate of complete occlusion at 12 months was 65% in the FD group and 97.5% in surgical group. The difference between groups was still significant (p = 0.001). There were no significant differences between groups by occurrence of ischemic (p = 0.108) and hemorrhagic (p = 0.615) complications., Conclusion: The study demonstrated superior clinical outcomes for endovascular flow diversion in comparison with bypass surgery in treatment of complex aneurysms. Though, both techniques grant similar percentage of major neurologic complications and comparable cure rate for cranial neuropathy. Nevertheless, flow diversion is associated with significantly lower early obliteration rate, thus possesses patient for risks of prolonged dual antiplatelet regimen and delayed rupture. Hence, it's important to stratify patient by the natural risk of aneurysm rupture prior to treatment selection., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Utilization of flow diverting devices is accompanied with dual antiplatelet therapy to reduce the risk of thromboembolic events, even though this increases the risk of hemorrhagic complications. The updated Pipeline Flex embolization device with Shield Technology has been created using a phosphorylcholine coating that reduces thrombogenicity and possibly reduces the need for dual antiplatelet therapy. However, because of the potential risk to patients of utilizing a pipeline embolization device without dual antiplatelet therapy, the pipeline embolization device with Shield Technology has not been tested in human subjects without dual antiplatelet therapy, and its contribution to preventing thromboembolic events is therefore unknown. We report a case in which a patient, following complications that limited his absorption of dual antiplatelet therapy, had low levels of dual antiplatelet therapy medications in his bloodstream following treatment for an intracranial aneurysm with a pipeline embolization device with Shield Technology. The patient recovered without signs of luminal stenosis or thromboembolic event.

Purpose and Methods: Superselective transvenous embolization (TVE) with liquid embolic agents is a new concept in treatment of vein of Galen aneurysmal malformations (VGAM). We performed ten sessions of TVE in VGAM patients with restricted transarterial access. In this paper, we assessed clinical and angiographic outcomes of the proposed treatment and discussed three different TVE techniques with regard to morphology of the shunt and outflow tract. Safety and avoidance-of-complication tips were also discussed., Results: Patient age ranged from 4 to 51 months. There were eight patients with choroidal VGAMs, seven of them were successfully treated with Onyx, and in one case, transvenous catheterization failed. In three cases, adjunctive coiling of draining vein was performed. In three cases, normal deep cerebral veins were connected to the outflow part of malformation; they were preserved during embolization in all cases. Six-month follow-up angiography demonstrated angiographic cure in six cases, and partial occlusion in one. There were two patients with mural VGAMs: both were treated with n-BCA. Partial occlusion was achieved in both cases. There was no procedure-related permanent morbidity or mortality. Oculomotor deficit due to quadrigeminal ischemia occurred in one case, and resolved completely after 3 weeks., Conclusion: TVE with liquid embolic agents is a safe and effective salvage method for VGAMs with restricted transarterial access, previously considered as poor candidates for endovascular treatment.

Endovascular embolization is an important modality in the treatment of brain AVMs. Nowadays staged embolization is the method of choice for the prevention of perioperative hemorrhagic complications. Current theory suggests that simultaneous occlusion of more than 60% of AVM volume induces significant redistribution local blood flow. That, in turn, may lead to hemorrhage due to AVM rupture. Aside from angiographic findings, there is still no method that predicts the degree of safe partial embolization. Intraluminal measurement of flow velocity and pressure in the vicinity of the AVM nidus might allow detecting the changes in local hemodynamics. That can provide a valuable data and shed the light on the origin of vascular catastrophes. Ten patients underwent 12 embolization sessions with intraluminal flow velocity and pressure monitoring. The measurements were performed by dual-sensor guidewire. The "Combomap" (Volcano) system with Combowire microguidewires was chosen for measurements, as there is a documented experience of safe use of said guidewires in the cerebral vasculature. The findings observed during the study matched empirical data as well as the current physiological hypothesis of AVM hemorrhage. In conjunction with DSA runs, intraluminal flow velocity and pressure monitoring has the potential to become a valuable tool in AVM treatment., (© The Author(s) 2015 Reprints and permissions:]br]sagepub.co.uk/journalsPermissions.nav.)

Introduction: The multimodal approach to treatment of arteriovenous malformations yields good results. However, small and deep malformations still pose a big problem for surgeons. Transvenous embolization was designed as an alternative for the cases when endovascular treatment is required and conventional transarterial embolization is not available., Case Study: A 41-year-old patient with binodal malformation in the subcortical nuclei of the left hemisphere of the brain, which had previously become a source of massive parenchymal ventricular hemorrhage, was operated on using the transarterial and, for the first time in our clinic, transvenous approaches. Transarterial embolization of the thalamic node of malformation was performed as the first step. After 6 months, transvenous embolization of the hypothalamic node of malformations was performed as the second step. Successful operation was ensured by using a stable coaxial guiding catheter system with the maximum distal approach and intranidal positioning of a microcatheter with detachable distal portion upon temporary occlusion of afferent vessels of the malformations using a balloon catheter. The operation resulted in total thrombosis of the malformation. No perioperative complications were observed. Control examination in 6 months did not reveal recanalization of the malformation., Conclusion: The transvenous approach can be successfully used in endovascular treatment of small and deep arteriovenous malformations with a single drainage vein, which are inaccessible to direct surgery. It can also be used when radiosurgery is associated with a high risk in cases where transarterial embolization is infeasible.

Fecal occult blood testing (FOBT) is proven an efficient way of reducing mortality from colorectal cancer but has a relatively low positive predictive value (PPV). This study evaluated the ability to detect K-ras mutations in stool DNA from FOBT cards and to improve the PPV of the screening process. Two hundred and five consecutive positive FOBT cards and an arbitrary sample of 38 negative cards from a population-based screening program were included. K-ras mutations in FOBT card stool were sought using allele-specific hybridization. DNA was successfully amplified from 87.2% of cards. In 130 cases with positive FOBT and amplifiable DNA 23 malignancies and 25 adenomas were detected. In 34.8% of the malignancies, a mutation in K-ras was detected. The PPV for malignancies increased from 17.7% (all positive cards) to 60.0% if cards with four or more fields were positive and K-ras was positive (RR=2.66, 95% CI: 1.2-6.1). Testing for K-ras mutations in DNA extracted from stool from positive FOBT cards is feasible. Sequential detection of cancer-associated genetic markers from FOBT-based stool samples may potentially help separate true from false positives in a FOBT-based screening process.

Colorectal cancer is one of the most common malignancies in the western world, including Israel. An important step in progression includes induction of activating mutations in the protooncogene K-ras. This event is very frequent and is detected in about 40% of colorectal carcinomas. Previous studies of a variety of genetic disorders revealed unique gene mutation prevalence in Jewish populations, attributed both to differences in genetic background and to variability in environmental exposure. To determine the incidence and molecular subtypes of K-ras mutations in colorectal cancer in Israel, compared with other countries, DNA was isolated from a random collection of 105 colorectal carcinoma samples, and K-ras mutations were detected by an improved designed RFLP and direct sequencing. K-ras sporadic mutations in colorectal cancer in Israel are relatively frequent, with a higher fraction in codon 13 than reported thus far. Comparison with other countries shows a vast heterogeneity in terms of the relative abundance of the affected K-ras codon and in type and representation of specific mutations. The heterogeneous distribution found may be due to a variable genetic background and different environmental factors involved in the initiation and propagation of sporadic colorectal cancer.

Colorectal cancer is one of the most common malignancies in the western world. About 60,000 Americans die of colorectal cancer each year. The annual incidence rate in Israel is 40 per 100,000 persons, namely a total of 2,000 new cases each year. An important step in the progression of colorectal cancer includes induction of activating mutations in the proto-oncogene K-ras. The mutations in K-ras appear early during tumorigenesis, at the intermediate adenoma stage, and thus can be used as a biomarker for early detection in about 40% of colonic tumors. A large yet unknown number of mutated cells are shed from the developing tumor during its progression. Indeed, K-ras mutations were detected in DNA isolated from stool obtained from symptomatic and asymptomatic patients with colorectal cancer, suggesting a novel approach for a noninvasive screening procedure. However, severe difficulties in obtaining reproducible yields of amplifiable DNA from stool, and usage of nonquantitative, time-consuming procedures, hampered further progress in the utilization of K-ras mutations for the early detection of colorectal cancer. Apparently a novel protocol is required that provides reproducible output of amplifiable DNA from small amounts of stool, detects if K-ras mutated DNA is present, and determines the quantity of K-ras mutated cells in the stool sample. In addition, this protocol should be simple, robotics compatible, and thus suitable for cost-effective, large-scale mutation screening. Molecular assays for detecting K-ras mutations and additional biomarkers in stool DNA promise to be highly sensitive, specific, and cost-effective. As such they should be very effective when used in chemoprevention studies and screening protocols for colorectal cancer.