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Abstract Background Hemodynamic factors play an important role in aneurysm initiation, growth, rupture, and recurrence, while the mechanism of the hemodynamic characteristics is still controversial. A unique model of multiple aneurysms (initiation, growth, rupture, and recurrence) is helpful to avoids the confounders and further explore the possible hemodynamic mechanisms of aneurysm in different states. Methods We present a model with multiple aneurysms, and including the states of initiation, growth, rupture, and recurrence, discuss the proposed mechanisms, and describe computational fluid dynamic model that was used to evaluate the likely hemodynamic effect of different states of the aneurysms. Results The hemodynamic analysis suggests that high flow impingement and high WSS distribution at normal parent artery was found before aneurysmal initiation. The WSS distribution and flow velocity were decreased in the new sac after aneurysmal growth. Low WSS was the risk hemodynamic factor for aneurysmal rupture. High flow concentration region on the neck plane after coil embolization still marked in recanalized aneurysm. Conclusions Associations have been identified between high flow impingement and aneurysm recanalization, while low WSS is linked to the rupture of aneurysms. High flow concentration and high WSS distribution at normal artery associated with aneurysm initiation and growth, while after growth, the high-risk hemodynamics of aneurysm rupture was occurred, which is low WSS at aneurysm dome.

Abstract Background Although flow diverter device (FDD) has brought revolutionized advances in endovascular treatment of intracranial aneurysms, it also presents considerable drawbacks as well, as the innovation for novel device has never stopped. This preclinical research aims to evaluate the safety and efficacy of a newly developed FDD, the EMBOPIPE, through in vivo and in vitro experiments. Methods Aneurysms were induced in 20 New Zealand white rabbits which were randomized to three follow-up groups according to the time elapsed after EMBOPIPE implantation (28, 90, and 180 days). Additional EMBOPIPEs were implanted in the abdominal aorta to cover the renal artery in nine rabbits. Angiography was performed immediately after device placement in all groups. Aneurysm occlusion, patency of renal arteries, and pathological outcomes were assessed. For the in vitro experiments, we measured the thrombogenic potential of EMBOPIPEs (n = 5) compared with bare stents (n = 5) using the Chandler loop model. Evaluation indicators were the platelet counts, macroscopic observations and scanning electron microscopy. Results EMBOPIPEs were successfully deployed in 19 of 20 rabbit aneurysms (95.0%). The rates of complete or near-complete aneurysm occlusion were 73.3%, 83.3%, and 100% in the 28-, 90-, and 180-day groups, respectively. All renal arteries covered by EMBOPIPEs remained patent, and the mean difference in renal artery diameter before and after the device placement in the three groups was 0.07 mm, 0.10 mm, and 0.10 mm, respectively (p = 0.77). Renal pathology was normal in all cases. The pathological findings of the aneurysms were as follows: thickened and adequate neointimal coverage at the aneurysm neck, minimal inflammatory response, near-complete smooth muscle cell layer, and endothelialization along the device. In vitro experiments showed that the platelet counts were significantly higher in EMBOPIPE blood samples than in bare stent samples and that platelet adhesion to the device was lower in the EMBOPIPE stent struts compared with bare stent struts through macroscopic observations and scanning electron microscopy. Conclusions The EMBOPIPE can achieve high rates of aneurysm occlusion while maintaining excellent branch artery patency. It exhibited wonderful pathological results. This novel device with phosphorylcholine surface modification could reduce platelet thrombus attached to the stent struts.

Objective The objective of this study was to investigate how cellulase or/and lactic acid bacteria (LAB) affected the fermentation characteristic and microbial community in wet brewer’s grains (WBG) and corn stover (CS) mixed silage. Methods The WBG was mixed thoroughly with the CS at 7:3 (w/w). Four treatment groups were studied: i) CON, no additives; ii) CEL, added cellulase (120 U/g fresh matter [FM]), iii) LAB, added LAB (2×106 cfu/g FM), and iv) CLA, added cellulase (120 U/g FM) and LAB (2×106 cfu/g FM). Results All additive-treated groups showed higher fermentation quality over the 30 d ensiling period. As these groups exhibited higher (p

Abstract Background Intracranial aneurysms (IAs) pose a significant and intricate challenge. Elucidating the interplay between DNA methylation and IA pathogenesis is paramount to identify potential biomarkers and therapeutic interventions. Methods We employed a comprehensive bioinformatics investigation of DNA methylation in IA, utilizing a transcriptomics-based methodology that encompassed 100 machine learning algorithms, genome-wide association studies (GWAS), Mendelian randomization (MR), and summary-data-based Mendelian randomization (SMR). Our sophisticated analytical strategy allowed for a systematic assessment of differentially methylated genes and their implications on the onset, progression, and rupture of IA. Results We identified DNA methylation-related genes (MRGs) and associated molecular pathways, and the MR and SMR analyses provided evidence for potential causal links between the observed DNA methylation events and IA predisposition. Conclusion These insights not only augment our understanding of the molecular underpinnings of IA but also underscore potential novel biomarkers and therapeutic avenues. Although our study faces inherent limitations and hurdles, it represents a groundbreaking initiative in deciphering the intricate relationship between genetic, epigenetic, and environmental factors implicated in IA pathogenesis. Graphical Abstract

Abstract Background As an antioxidant, hydrogen (H2) can selectively react with the highly toxic hydroxyl radical (·OH) in tumor cells to break the balance of reactive oxygen species (ROS) and cause oxidative stress. However, due to the high diffusibility and storage difficulty of hydrogen, it is impossible to achieve long-term release at the tumor site, which highly limited their therapeutic effect. Results Photosynthetic bacteria (PSB) release a large amount of hydrogen to break the balance of oxidative stress. In addition, as a nontoxic bacterium, PSB could stimulate the immune response and increase the infiltration of CD4+ and CD8+ T cells. More interestingly, we found that hydrogen therapy induced by our live PSB did not lead to the up-regulation of PD-L1 after stimulating the immune response, which could avoid the tumor immune escape. Conclusion Hydrogen-immunotherapy significantly kills tumor cells. We believe that our live microbial hydrogen production system provides a new strategy for cancer hydrogen treatment combining with enhanced immunotherapy without up-regulating PD-L1. Graphical Abstract

Background: Several pharmacological pathways have revealed statin to have a positive role in patients with for intracranial aneurysms. However, prior studies regarding the association between statin use and patients’ outcomes after pipeline embolization device (PED) treatment were not completely supportive. Objectives: To investigate whether statin medication following PED treatment would improve the outcomes of intracranial aneurysm patients in a real-world setting. Design: A retrospective multicenter cohort study. Methods: Patients were selected from the PLUS registry study conducted from November 2014 to October 2019 across 14 centers in China. The population was divided into two groups: those who received statin medication after the PED treatment and those who did not receive statin medication after PED treatment. Study outcomes included angiographic evaluation of aneurysm occlusion, parent arteries stenosis, ischemic and hemorrhage complications, all-cause mortality, neurologic mortality, and functional outcome. Results: 1087 patients with 1168 intracranial aneurysms were eligible; 232 patients were in the statin user group and the other 855 were in the non-statin user group. For the statin user group versus the non-statin user group, no significant difference was found for the primary outcomes of complete occlusion of aneurysm (82.4% versus 84.2%; p = 0.697). Of the secondary outcomes, none had a significant difference including stenosis of parent arteries ≥ 50% (1.4% versus 2.3%; p = 0.739), total subarachnoid hemorrhage (0.9% versus 2.5%; p = 0.215), all-cause mortality (0.0% versus 1.9%; p = 0.204), neurologic mortality (0.0% versus 1.6%; p = 0.280), excellent (95.5% versus 97.2%; p = 0.877), and favorable (98.9% versus 98.4%; p = 0.933) functional outcomes. The total ischemic complication rate (9.0% versus 7.1%; p = 0.401) was higher but not significant in the statin user group. The propensity score-matched cohort showed similar results. Results of binary multivariable logistic regression analysis and propensity score-matched analysis both showed that statin usage was not independently associated with an increased rate of complete occlusion or any other secondary outcomes. Subgroup analysis found the same result in patients who did not use statin before the procedure. Conclusion: Among patients with intracranial aneurysms, statin use after the PED treatment was not significantly associated with better angiographic and clinical outcomes. Well-designed studies are needed to further confirm this finding.

Abstract Background Brain arteriovenous malformations (BAVMs) are abnormal vessels that are apt to rupture, causing life-threatening intracranial hemorrhage (ICH). The estimated prevalence of BAVMs is 0.05% among otherwise healthy individuals. In this study, we aim to investigate the mutational spectrum of syndromic genes in sporadic BAVM. Methods We recruited a cohort of 150 patients with BAVM and performed whole-exome sequencing on their peripheral blood DNA. To explore the mutational spectrum of syndromic genes in sporadic brain arteriovenous malformation, we selected six genes according to the Online Mendelian Inheritance in Man (OMIM) and literature. All variants in the six candidate genes were extracted and underwent filtering for qualifying variants. Results There are a total of four patients with rare variants in hereditary hemorrhagic telangiectasia-related genes. In addition, we identified two patients have the variant of RASA1 gene in our database, which are also rare mutations that are absent from population databases. However, we did not find any patients with GNAQ mutations in our database. Conclusions In conclusion, we demonstrated that variants in syndromic vascular malformations play important roles in the etiology of sporadic BAVM.

BackgroundWe aimed to investigate the effects of high on-treatment platelet reactivity (HPR) and antiplatelet therapy adjustment on high-risk radiomic features in patients with antiplatelet therapy adjustment on acute silent cerebral infarction (ASCI) who had unruptured intracranial aneurysms (UIA) after stent placement.MethodsThis single-institution study prospectively included 230 UIA patients who had ACSI after stent placement in our hospital between January 2015 and July 2020. All patients underwent magnetic resonance imaging with diffusion-weighted imaging (MRI-DWI) after stent placement and 1,485 radiomic features were extracted from each patient. The least absolute shrinkage and selection operator regression methods were used for selection of high-risk radiomic features associated with clinical symptoms. In addition, 199 patients with ASCI were classified into three groups: controls without HPR (n = 113), HPR patients with standard antiplatelet therapy (n = 63) and HPR patients with antiplatelet therapy adjustment (n = 23). We compared high-risk radiomic features between three groups.ResultsOf the patients who had acute infarction after MRI-DWI, 31 (13.5%) exhibited clinical symptoms. Eight risk radiomic features associated with clinical symptoms were selected, and the radiomics signature exhibited good performance. In ASCI patients, compared with controls, the radiomic characteristics of ischemic lesion in HPR patients were consistent with the following high-risk radiomic features associated with clinical symptoms: higher gray-level values, greater variance in intensity values, and greater homogeneity. However, the adjustment of antiplatelet therapy in HPR patients modified the high-risk radiomic features, which showed lower gray-level values, less variance in intensity values, and more heterogeneous texture. The radiomic shape feature of elongation showed no notable difference between three groups.ConclusionAdjustment of antiplatelet therapy might reduce the high-risk radiomic features of UIA patients with HPR after stent placement.

Hypoxia is a prominent feature of malignant tumors and contributes to tumor proliferation, metastasis, and drug resistance in various solid tumors. Therefore, improving tumor oxygenation is crucial for curing tumors. To date, multiple strategies, including oxygen delivering and producing materials, have been designed to increase the oxygen concentration in hypoxic tumors. However, the unsustainable supply of oxygen is still the main obstacle, resulting in a suboptimal outcome in treating oxygen-deprived tumors. Thus, a sufficient oxygen supply is highly desirable in the treatment of hypoxic tumors. Photosynthesis, as the main source of oxygen in nature through the conversion of light energy into chemical energy and oxygen, has been widely studied in scientific research. Moreover, photosynthetic microorganisms have been increasingly applied in cancer therapy by increasing oxygenation, which improves the therapeutic effect of oxygen-consuming tumor therapeutic tools such as radiotherapy and photodynamic therapy. In this review, we summarize recent advances in the design and manufacture of live bacteria as oxygen shuttles for a new generation of hypoxic tumor treatment strategies. Finally, current challenges and future directions are also discussed for successfully addressing hypoxic tumor issues.

Abstract Background We compared the treatment of small unruptured intracranial aneurysms (UIAs) with flow diverter and LVIS-assisted coiling to determine the effects of hemodynamic changes caused by different stent and coil packing in endovascular treatment. Methods Fifty-one UIAs in 51 patients treated with pipeline embolization device (PED) were included in this study and defined as the PED group. We matched controls 1:1 and enrolled 51 UIAs who were treated with LVIS stent, which were defined as the LVIS group. Computational fluid dynamics were performed to assess hemodynamic alterations between PED and LVIS. Clinical analysis was also performed between these two groups after the match. Results There was no difference in procedural complications between the two groups (P = 0.558). At the first angiographic follow-up, the complete occlusion rate was significantly higher in the LVIS group compared with that in the PED group (98.0% vs. 82.4%, P = 0.027). However, during the further angiographic follow-up, the complete occlusion rate in the PED group achieved 100%, which was higher than that in the LVIS group (98.0%). Compared with the LVIS group after treatment, cases in the PED group showed a higher value of velocity in the aneurysm (0.03 ± 0.09 vs. 0.01 ± 0.01, P = 0.037) and WSS on the aneurysm (2.32 ± 5.40 vs. 0.33 ± 0.47, P = 0.011). Consequently, the reduction ratios of these two parameters also showed statistical differences. These parameters in the LVIS group showed much higher reduction ratios. However, the reduction ratio of the velocity on the neck plane was comparable between two groups. Conclusions Both LVIS and PED were safe and effective for the treatment of small UIAs. However, LVIS-assisted coiling produced greater hemodynamic alterations in the aneurysm sac compared with PED. The hemodynamics in the aneurysm neck may be a key factor for aneurysm outcome.

This study investigated the effects of applying cellulase and starch on the fermentation characteristics and microbial communities of Napier grass silage after ensiling for 30 d. Three groups were studied: No additives (control); added cellulase (Group 1); and added cellulase and starch (Group 2). The results showed that the addition of cellulase and starch decreased the crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF) and pH significantly (p < 0.05) and increased water-soluble carbohydrate (WSC) content (p < 0.05). The addition of additives in two treated groups exerted a positive effect on the lactic acid (LA) content, lactic acid bacteria (LAB) population, and lactic acid / acetic acid (LA/AA) ratio, even the changes were not significant (p > 0.05). Calculation of Flieg’s scores indicated that cellulase application increased silage quality to some extent, while the application of cellulase and starch together significantly improved fermentation (p < 0.05). Compared with the control, both additive groups showed increased microbial diversity after ensiling with an abundance of favorable bacteria including Firmicutes and Weissella, and the bacteria including Proteobacteria, Bacteroidetes, Acinetobacter increased as well. For alpha diversity analysis, the combined application of cellulase and starch in Group 2 gave significant increases in all indices (p < 0.05). The study demonstrated that the application of cellulase and starch can increase the quality of Napier grass preserved as silage.

Abstract Background The aim of this study was to comprehensively evaluate the risk factors of periprocedural ischemic stroke associated with endovascular treatment of intracranial aneurysms using a real-world database. Methods From August 2016 to March 2017, 167 patients were enrolled. Univariate analysis and multivariate logistic regression analysis were used to examine the risk factors for periprocedural ischemic stroke. Results Among the 167 cases, periprocedural ischemic stroke occurred in 20 cases (11.98%). After univariate analysis, the ischemic group had a higher proportion of large (≥ 10 mm) aneurysms than the control group (45.0% vs. 23.1%, p = 0.036). The incidence of periprocedural ischemic stroke was higher in cases treated by flow diverter (21.6%) or stent-assisted coiling (11.8%) than in cases treated by coiling only (2.7%), and the differences were statistically significant (p = 0.043). After multivariate logistic regression analysis, treatment modality was the independent risk factor for periprocedural ischemic stroke. Compared with the coiling-only procedure, flow diverter therapy was associated with a significantly higher rate of periprocedural ischemic stroke (OR 9.931; 95% CI 1.174–84.038; p = 0.035). Conclusions Aneurysm size and treatment modality were associated with periprocedural ischemic stroke. Larger aneurysms were associated with increased risk of periprocedural ischemic stroke. Flow diverter therapy was associated with significantly more periprocedural ischemic stroke than the coiling procedure alone.

BackgroundVertebrobasilar dissecting aneurysms (VBDAs) with an intramural hematoma (IMH) usually cause symptoms because of mass effect and grow in size over time. Clinical outcomes are generally poor.ObjectiveThis study aimed to examine outcomes of reconstructive endovascular treatment (EVT) in patients with VBDAs with IMH. Safety and effectiveness were compared between flow diverters (FDs) and conventional stents.MethodsWe retrospectively analyzed the clinical and radiological data of 36 VBDAs with IMH in 36 patients who underwent EVT with either FDs or conventional stents from January 2012 to December 2020 at our institution.ResultsAmong the 36 study patients, 20 were treated with FDs and 16 with conventional stents. Incidence of procedure-related complications did not significantly differ between the two stents. IMH growth occurred after EVT in a significantly higher proportion of conventional stent group aneurysms (zero vs. 31.3% [5/16]; p = 0.012). Among the five aneurysms with IMHs that grew, all recurred. Change in IMH size after EVT was significantly lower in the FD group (−2.7 vs. +8.1%, p = 0.036). However, after the recurrent aneurysms were removed from the conventional stent group, change in IMH size did not significantly differ between the two groups (−2.7 vs. +1.0%, p = 0.332). The proportion of patients who experienced an improvement in mRS score after EVT was significantly higher in the FD group (60 vs. 25%, p = 0.036).ConclusionIMHs in VBDAs stop growing after successful reconstructive EVT. Although both FD and conventional stent treatment are effective, FD treatment may be superior based on clinical outcomes and effect on IMH size.

Objective:Intracranial fusiform aneurysms are uncommon and can occur in vessels of the anterior circulation (AC) or posterior circulation (PC). While flow diversion is one treatment option, research into Pipeline Embolization Device (PED) treatment is lacking. This study explored the efficacy and safety of PED treatment for intracranial fusiform aneurysms, and compared therapeutic effects between AC and PC aneurysms.MethodsIn the post-market multi-center cohort study of embolization of intracranial aneurysms with PED in China (PLUS) registry study, we retrospectively analyzed 71 fusiform aneurysms in 67 patients among 1,171 patients treated with a PED from November 2014 to October 2019. The general characteristics, perioperative status, aneurysm occlusion rate at the last follow-up angiography, and changes in modified Rankin Scale scores were analyzed. Aneurysms were divided into AC and PC groups, and univariate and multivariate analyses were conducted.ResultsThe study included 26 AC (25 patients) and 45 PC (42 patients) aneurysms. A total of 75 PEDs were used, an average of 1.1 PEDs were used, and the median follow-up was 6.7 months. Fifty aneurysms (71.4%) were occluded and twenty (28.5%) were incompletely occluded. There were significantly more occluded aneurysms in the PC group than in the AC group (12 vs. 38; P = 0.001). Risk factors for incomplete occlusion were AC aneurysms (P = 0.001) and a perforating artery originating from the aneurysm (P = 0.006). The mean modified Rankin Scale score was significantly lower at the last follow up than preoperatively (0.58 vs. 0.21; P = 0.0001).ConclusionNon-overlapping PED is a safe and effective treatment for both AC and PC fusiform aneurysms. The occlusion rate of AC fusiform aneurysms is lower than that of PC.

BackgroundThe Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial primarily demonstrated the safety and efficacy of the implantation of multiple pipeline embolization devices (multi-PEDs) for large/giant intracranial aneurysms. However, no study has focused on when, why, or how to apply multi-PEDs.ObjectiveThe purpose of this study was to investigate the indications and strategies of using multi-PEDs for complex intracranial aneurysms.MethodsPatients who had been treated with two or more PEDs were included in the post-market multicenter registry study from 2014 to 2019, across 14 centers in China. Indications, strategies, perioperative safety, and clinical outcomes were retrospectively analyzed. The modified Rankin scale (mRS) score was used to evaluate clinical outcomes comprehensively, and the O’Kelly–Marotta (OKM) grading scale was used to evaluate aneurysm healing results.ResultsA total of 55 intracranial aneurysms were treated with multi-PEDs. There were 20 fusiform aneurysms with a large range, 25 large/giant saccular aneurysms, six aneurysms with failed treatment, and four aneurysms with greatly varied diameters of the parent artery. The strategies included telescope techniques in 40 patients and overlap techniques in 15 patients. In total, 120 stents were deployed in 55 patients. The operation styles included 25 patients (55.6%) with two PEDs, 21 patients (38.2%) with two PEDs combined with coiling, four patients (7.3%) with three PEDs, four patients (7.3%) with three PEDs combined with coiling, and one patient (1.8%) with four PEDs. Angiography revealed OKM D in two, OKM C in seven, and OKM A and B in 46 cases after surgery. During the perioperative period, eight patients developed neurological dysfunction, three of whom died. A total of thirty-four patients were followed up with digital subtraction angiography for 2–45 (8.2 ± 8.0) months. Angiography revealed OKM D in 26, OKM C in five, and OKM B in three. At the last follow-up, the mRS score was 0–1 in 52 patients.ConclusionThe treatment of anterior circulation aneurysms with multi-PEDs is safe and effective. The implantation of multi-PEDs could be considered for large-scale fusiform aneurysms, large/giant saccular aneurysms with a jet-sign, salvage of failed PED treatments, and in cases where the diameter of the parent artery varies greatly.

Abstract Background The Tubridge™ flow diverter (TFD) was recently developed in China; however, its safety and efficacy in treating large cavernous carotid artery aneurysms (LCCAs) are unclear. Our objective was to evaluate the safety and efficacy of the TFD in patients receiving TFDs to treat LCCAs (10–25 mm). Methods Between June 2013 and May 2014, seven patients with LCCAs were enrolled in our study, and all seven patients underwent TFD implantation combined with coils. Results Angiographic follow-up images were available for all seven patients at a median of 57.5 ± 16.7 (range, 6–69) months. Seven patients obtained favorable angiographic results defined as O’Kelly–Marotta Scale C and D. Clinical follow-up data were available for all seven patients at a median of 73.32 ± 3.6 (range, 66–78) months. No patients developed new neurological deficits. Six patients achieved a modified Rankin scale score of 0, and diplopia improved in the remaining patient. Conclusions The results were excellent for the aneurysms treated with TFDs in our patients with LCCAs. TFDs are feasible for the treatment of LCCAs, but a multicenter, controlled clinical trial is needed to evaluate the long-term safety and efficacy of the TFD to treat LCCAs.

ObjectiveThe purpose of this work was to summarize the real-world safety and efficacy of Pipeline Embolization Device (PED) therapy for small and medium-sized intracranial aneurysms in China.MethodsPatients from the PED in China post-market multi-center registry study (PLUS) with aneurysms smaller than 12 mm were selected. Radiographic outcomes were assessed using digital subtraction angiography. Clinical outcomes included functional outcomes (modified Rankin Scale, MRS) in the early postoperative period ( ≤ 30 days) and early postoperative complications associated with PED therapy.ResultsA total of 652 patients with a combined 754 aneurysms were included in this study (mean age of 53.9 ± 10.3 years, 68.7% women). Mean aneurysm diameter was 6.78 ± 2.67 mm. Of the 687 stents deployed, 99.7% (685/689) were successfully deployed. In this study, 64.7% (488/754) of aneurysms were treated with only the PED, whereas 35.3% (266/754) were subjected to PED-assisted therapy. Radiographic outcome at the last follow-up (median time: seven months) was available for 64.3% (485/754) of the aneurysms. 82.5% (400/485) of aneurysms demonstrated complete occlusion (Raymond Roy Grade I). 81.4% (395/485) of aneurysms were found to meet the study's primary effectiveness outcome. At the early postoperative period, the mRS score was determined to be 0–2 vs. 3-6 in 98.2% (640/652) vs. 1.8% (12/652) of the cases, respectively. The combined major morbidity and mortality rate was 3.2% (21/652).ConclusionIn the largest study of PED therapy for small and medium-sized intracranial aneurysms to date, pipeline-assisted coil embolization was chosen more often than multiple stent implantation for aneurysm treatment, demonstrating good results, high surgical success rates, high occlusion rates, and low morbidity and mortality.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT03831672.

BackgroundAssessing rupture risk in patients with unruptured intracranial aneurysms (UIAs) remains challenging. Hemodynamics plays an important role in the natural history of intracranial aneurysms. This study aimed to compare aneurysmal hemodynamic features between patients with different rupture risk as determined by PHASES score.MethodsWe retrospectively examined 238 patients who harbored a solitary saccular UIA. Patients were stratified by rupture risk into low-, intermediate-, and high-risk groups according to PHASES score. Flow simulations were performed to compare differences in hemodynamics among the groups.ResultsAneurysmal time-averaged wall shear stress (WSSa) and normalized WSS (WSSn) decreased progressively as PHASES score increased. WSSa and WSSn significantly differed among the low-, intermediate-, and high-risk groups (p < 0.001). WSSa was significantly lower in the high-risk group than the low-risk group (p < 0.001) and the intermediate-risk group (p = 0.004). WSSn was also significantly lower in the high-risk group than the low-risk group (p < 0.001) and the intermediate-risk group (p = 0.001).ConclusionsLow WSS was significantly associated with higher risk of intracranial aneurysm rupture as determined by PHASES score, indicating that hemodynamics may play an important role in aneurysmal rupture. In the future, a multidimensional rupture risk prediction model that includes hemodynamic parameters should be investigated.

Introduction Vertebrobasilar dissecting aneurysms (VBDAs) are associated with serious complications and a poor prognosis. It is believed that inflammation of the aneurysm wall may be the main cause of rupture or deterioration. Atorvastatin has been shown to inhibit inflammation and may be a suitable drug candidate. Here, we report a clinical research study protocol to investigate whether atorvastatin inhibits inflammation of the aneurysm wall, as measured by signal index enhancement.Methods and analysis We have designed a single-centre, randomised, double-blind, blank-controlled clinical trial. 40 patients with non-ruptured VBDAs with enhancement aneurysm walls will be enrolled in Beijing Tiantan Hospital. Eligible patients will be randomly divided into two treatment groups, at a ratio of 1:1, to receive atorvastatin 20 mg orally for 6 months or no treatment. The primary assessment outcome will be the change in aneurysm wall enhancement, as measured by the signal index during the 6-month treatment period. The secondary assessment outcomes will be the aneurysm morphology (intramural haematoma, dissection valve and false lumen) and changes in the concentrations of inflammatory factors, including C reactive protein, tumour necrosis factor-α, interleukin (IL)-1β and IL-6.Ethics and dissemination The protocol has been approved by the medical ethics committee of the Beijing Tiantan Hospital at which the work will be conducted (Approval No. KY 2019-024-02). Written informed consent will be obtained from all participants. Findings from the study will be submitted for publication in a peer-reviewed journal.Trial registration number NCT04943783.

Summary: Tumor immunotherapy has been convincingly demonstrated as a feasible approach for treating cancers. Although promising, the immunosuppressive tumor microenvironment (TME) has been recognized as a major obstacle in tumor immunotherapy. It is highly desirable to release an immunosuppressive “brake” for improving cancer immunotherapy. Among tumor-infiltrated immune cells, tumor-associated macrophages (TAMs) play an important role in the growth, invasion, and metastasis of tumors. The polarization of TAMs (M2) into the M1 type can alleviate the immunosuppression of the TME and enhance the effect of immunotherapy. Inspired by this, we constructed a therapeutic exosomal vaccine from antigen-stimulated M1-type macrophages (M1OVA-Exos). M1OVA-Exos are capable of polarizing TAMs into M1 type through downregulation of the Wnt signaling pathway. Mediating the TME further activates the immune response and inhibits tumor growth and metastasis via the exosomal vaccine. Our study provides a new strategy for the polarization of TAMs, which augments cancer vaccine therapy efficacy.

Background and Purpose: The utilization of flow diversion for ruptured intracerebral aneurysms (IAs) is still limited. We aimed to demonstrate our multicenter experience using the pipeline embolization device (PED) for ruptured IAs that were difficult to treat by clipping and coiling.Methods: Thirty-eight patients with ruptured IAs who underwent PED treatment from 2015 to 2020 were retrospectively reviewed. Factors associated with procedure-related stroke (ischemic and hemorrhagic) and clinical and angiography outcomes were analyzed.Results: There were 14 (36.8%) saccular IAs, 12 (31.6%) blister-like IAs, and 12 (31.6%) dissecting IAs. Perforator involvement was noted in 10 (26.3%) IAs. Early PED placement ( ≤ 15 days) and adjunctive coiling treatment were performed in 27 (71.1%) and 22 (57.9%) cases, respectively. The overall rate of stroke-related complications was 31.6% (12/38) (including rates of 10.5% for procedure-related hemorrhagic complications and 15.8% for procedure-related infarction). The mortality rate was 13.2% (5/38), and 84.2% of patients (32/38) had favorable outcomes. Thirty-two (84.2%) patients underwent follow-up angiographic evaluations; of these, 84.4% (27 patients) had complete occlusion and 15.6% had incomplete obliteration. Multivariate analysis revealed that early PED placement was not associated with a high risk of procedure-related stroke or an unfavorable outcome. Adjunctive coiling exhibited an association with procedure-related stroke (p = 0.073). Procedure-related hemorrhagic complications were significantly associated with an unfavorable outcome (p = 0.003). Immediate contrast stasis in the venous phase was associated with complete occlusion during follow-up (p = 0.050).Conclusion: The PED is a feasible and effective treatment to prevent rebleeding and achieve aneurysm occlusion, but it is associated with a substantial risk of periprocedural hemorrhage and ischemic complications in acute ruptured IAs. Therefore, the PED should be used selectively for acutely ruptured IAs. Additionally, adjunctive coiling might increase procedure-related stroke; however, it may reduce aneurysm rebleeding in acutely ruptured IAs. Patients with immediate contrast stasis in the venous phase were more likely to achieve total occlusion. A prospective study with a larger sample size should be performed to verify our results.

Background and purpose: Although grading scales for angiography outcomes following cerebral aneurysm treatment with flow diversion have been published, physicians have not widely adopted these scales in practice. The aim of this study is to propose and validate a novel Flow diversion Predictive Score (4F-FPS) grading scale based on previously established scales that is simple and reliable. Methods: We retrospectively analyzed consecutive patients who underwent endovascular treatment for cerebral aneurysms with flow diversion between January 2014 and September 2019. The included patients were randomly divided into the derivation and validation group in a 70/30 ratio, respectively. Aneurysms were classified as incomplete or complete occlusion based on final angiography outcomes. 4F-FPS was derived to predict aneurysm occlusion from multivariate logistic regression analyses in the derivation group and validated with previously published grading scales in the validation group. Results: Overall, 662 patients [mean age, 53.8 years; 72.5% (480/662) female] with 662 aneurysms treated with the Pipeline TM flow diverter were included [69.9% (463/662) derivation group, 30.1% (199/662) validation group]. The incidence of aneurysm occlusion was 82.7%. 4F-FPS demonstrated significant discrimination in 10-fold cross validation [mean receiver operating characteristic (ROC) area, 0.862 ± 0.055] and calibration (Cox & Snell R 2 , 0.251; Nagelkerke R 2 , 0.413) in the derivation group. The ROC area of 4F-FPS score in both the derivation and validation groups is the largest compared with previously published grading scales/scores ( p

Background: Flow diverters and conventional coiling are established modalities for the retreatment of intracranial recurrent aneurysms after initial endovascular treatment. We aimed to compare the efficacy of these techniques.Methods: We retrospectively analyzed data for patients with recurrent aneurysms after initial endovascular treatment retreated in our center with either a pipeline embolization device (PED) or conventional coil embolization from January 2012 to July 2020. We performed 1:2 propensity score matching (PSM) using the nearest neighbor method. We controlled for: initial treatment strategy, aneurysm size, neck diameter, symptom presentation, history of aneurysm rupture, age, sex, fusiform-dissecting aneurysm, bifurcation aneurysm, and aneurysm location. The clinical and morphological factors of all patients at initial treatment and the angiographic and clinical results at the second treatment were collected and compared between the propensity-matched pairs.Results: A total of 105 intracranial aneurysms were identified; 18 patients (17.1%) were treated with a PED, and 87 (82.9%) were treated via conventional coil embolization. PSM resulted in 12 matched pairs (12 patients in the PED group and 24 in the coiling group). There was no significant difference of ischemic and hemorrhagic complications between the groups, the obliteration rate of branches covered by stent, or modified Rankin Scale scores at the last clinical follow-up. Importantly, the retreatment strategy in the PED group provided significantly different results vs. the coiling group (P < 0.001), with a lower recurrence rate (0.0 vs. 29.2%, respectively; P = 0.037). However, the procedural failure rate and the parent artery stenosis were more frequently in PED group compared with coiling group (both were 16.7 vs. 0.0%; P = 0.040).Conclusions: Endovascular retreatment for recurrent aneurysms after initial endovascular treatment might be safe and effective. Flow diverters might be associated with reduced risk of recanalization and an increased risk of procedural failure and mild parent artery stenosis.

Abstract Background Subarachnoid hemorrhage (SAH) accounts for 4.4% of cerebral vascular disease, which is one of the leading causes of death in China. Rupture of intracranial aneurysms (IAs) is the most common cause of SAH. The natural history of unruptured IAs (UIAs) and the risk factors for rupture are among the key issues regarding the pathogenesis of IA and SAH that remain unclear in the Chinese population. Methods The China Intracranial Aneurysm Project (CIAP) is a prospective, observational, multicenter registry study of the natural courses, risk factors for the onset and rupture, treatment methods, comorbidity management and other aspects of intracranial aneurysms. To date, there are five studies in the CIAP. CIAP-1 is a prospective observational cohort study of UIAs. More than 5000 patients who will be followed for at least 1 year are expected to be enrolled in this cohort. These participants come from more than 20 centers that represent different regions in China. Enrollment began on May 1, 2017, and will take approximately 5 years. A nationwide online database of UIAs will be built. Participants’ basic, lifestyle, clinical and follow-up information will be collected. The blood samples will be stored in the Central Biological Specimen Bank. Strict standards have been established and will be followed in this study to ensure efficient implementation. Discussion The natural course of UIAs in the Chinese population will be explored in this registry study. In addition, the risk factors for the rupture of the UIAs and the joint effect of those factors will be analyzed. The present study aims to create a nationwide database of UIAs and investigate the natural course of UIAs in China. Trial registration The Natural Course of Unruptured Intracranial Aneurysms in a Chinese Cohort (ClinicalTrials.gov Identifier: NCT03117803). Registered: July 5, 2017

Abstract Background Flow diverter devices are increasingly used for endovascular treatment of internal carotid artery aneurysms. Treatment of ophthalmic segment aneurysms with flow diverter devices also includes coverage of the ophthalmic artery but may result in complications. It is unclear, however, whether these devices mechanically block blood flow in the ophthalmic artery. Also unclear is the relationship between deployment of a flow diverter device and post-treatment occlusion. We studied hemodynamic changes in the ophthalmic artery after deployment of a flow diverter device to determine the relationship between those changes and post-stent occlusion of the artery. Methods We analyzed hemodynamic modifications in the ophthalmic artery in 21 patients (19 women, 2 men; mean age 53.43 ± 7.32 years) treated by a single pipeline embolization device. Patient-specific geometries were determined from three-dimensional digital subtraction angiography and the stenting process was simulated. Computational fluid dynamics technology was used to analyze the change in ophthalmic artery hemodynamics. We compared pre-treatment and post-treatment flow velocity of the ophthalmic artery. Results Among the 21 patients with aneurysms located in the ophthalmic segment, no ophthalmic artery occlusion was found during immediate or follow-up angiography. Post-stent flow velocity in the ophthalmic artery decreased from 0.35 ± 0.19 to 0.33 ± 0.20 m/s, with the difference not being statistically significant (P = 0.106). Conclusion Our results showed no significant change in ophthalmic artery blood flow after pipeline embolization device deployment. Hence, post-stent occlusion of the ophthalmic artery could not be explained by reduced blood flow. Delayed thrombosis and neointimal formation maybe the keys to ophthalmic artery occlusion and need further investigation.

Objective To demonstrate the application value of high-resolution vessel wall magnetic resonance imaging (HR-VW-MRI) for depicting the imaging features of unruptured intracranial vertebrobasilar dissecting aneurysms (VBDAs). Methods HR-VW-MRI data of 49 patients with suspected unruptured VBDAs were retrospectively analyzed. The presence of intramural hematomas (IMH), double lumens, intimal flaps, and outer diameter enlargements were recorded. Specificity and sensitivity were calculated for both two-dimensional (2D) and three-dimensional (3D) sequences. Additionally, IMH volumes were measured and posterior inferior cerebellar artery (PICA) involvement was analyzed. Results Thirty-five VBDAs were confirmed in 34 patients. The overall sensitivity and specificity were 0.889 (95% confidence interval [CI]: 0.730–0.964) and 0.769 (95% CI: 0.460–0.938) for 2D sequences, and 0.917 (95% CI: 0.764–0.978) and 0.846 (95% CI: 0.537–0.973) for 3D sequences, respectively. Intimal flaps were detected in 57.1%, 87.5%, and 71.4% of all cases on 2D pre-contrast T1-weighted, contrast-enhanced T1-weighted, and 3D T1-weighted black-blood (BB) images, respectively. There was no significant difference in IMH volume between 3D T1-weighted BB and magnetization-prepared rapid gradient-echo sequences. PICA involvement was best visualized using 3D T1 sequences. Conclusion 3D T1-weighted BB MRI provided good visualization of VBDA features, with large coverage, and was useful for detecting dissection flaps.

Background and Purpose: Stability stratification of intracranial aneurysms (IAs) is crucial for individualized clinical management, especially for small IAs. We aim to develop and validate a nomogram based on clinical and morphological risk factors for individualized instability stratification of small IAs.Methods: Six hundred fifty-eight patients with unstable (n = 293) and stable (n = 416) IAs

Background and purpose A large proportion of patients with unruptured intracranial aneurysm (IA) are not suitable for surgical clipping and endovascular treatment. For these patients, anti-inflammatory medications are worth exploring due to inflammation of aneurysmal wall being a major factor in higher risk of rupture. Statin has been proven to reduce inflammation of atherosclerosis and maybe a suitable candidate. This study aimed to evaluate whether atorvastatin will reduce inflammatory of the aneurysm wall measured by the signal index of aneurysm wall enhancement.Methods and analysis The Statin Treatment for UnruptureD Intracranial anEurysms Study is a single-centre, phase 2, randomised, controlled, double-blind clinical trial. 60 patients with unruptured IAs with aneurysm wall enhancement will be enrolled in Beijing Tiantan Hospital. The patients will be randomised to receive atorvastatin 20 mg or placebo orally per day for 12 months. The primary outcome will be the change in aneurysm wall enhancement measured by the signal index during the 12 months treatment with atorvastatin. The secondary study outcomes will be the change in aneurysm wall enhancement measured by the signal index at 3 months, the changes in aneurysmal morphology and inflammation-related factors (C reactive protein, tumour necrosis factor-α, interleukin-1β and interleukin-6) at 3 and 12 months. This study is the first to explore the role of atorvastatin in reducing inflammation in unruptured IA, which could lay the groundwork for future phase III trial.Ethics and dissemination Beijing Tiantan Hospital’s Ethics committee approved the research and written informed consents would be obtained from all participant or representative included in this study.Trial registration number NCT04149483

Objective: To investigate the safety and efficacy of low-profile visualized intraluminal support (LVIS) stent-assisted coiling of intracranial tiny aneurysms using a “compressed” stent technique.Methods: We retrospectively analyzed patients with tiny aneurysms treated in our hospital with LVIS devices using a compressed stent technique. We analyzed patients' imaging outcomes, clinical outcomes, and complications.Results: Forty-two tiny aneurysms in 42 patients were included in this study cohort; 8 patients presented with subarachnoid hemorrhage at admission. The immediate postoperative complete embolization rate was 76.2% (32/42). After an average of 8.5 months of imaging follow-up, the complete embolization rate was 90.5% (38/42), and no aneurysm recanalization occurred. After an average of 24.4 months of clinical follow-up, 95.2% (40/42) of the patients achieved favorable clinical outcomes (modified Rankin scale = 0/1). Operation-related complications occurred in two patients (4.8%); one intraoperative acute thrombosis, and one significant unilateral decreased vision during the postoperative follow-up.Conclusion: LVIS stent-assisted coiling of intracranial tiny aneurysms using a compressed stent technique is safe and effective. Combined stent compression technology is beneficial to maximize the complete embolization of aneurysms and reduce aneurysm recanalization. This study expands the clinical applicability of LVIS stents.

The inflow angle of intracranial aneurysms (IAs) can impact the hemodynamics of IAs, therefore it is likely to contribute to IA clinical rupture risk stratification. This study aimed to assess the effect of inflow angle on the hemodynamics of IAs, as well as its potential ability to predict IA rupture risk. A novel algorithm was developed to build a series of inflow angle models on patient-specific IA models, which were reconstructed from IA 3DRA image data of eleven clinical patients. Fully coupled fluid-structure interaction (FSI) simulations were performed to quantify hemodynamic characteristics of the established IA models with various inflow angles. Hemodynamic parameters including wall shear stress (WSS), flow velocity, flow pattern, inflow zone, impingement region, pressure, and energy loss (EL) were calculated and analyzed. It was demonstrated from the analysis that a rise in the IA inflow angle is associated with the following hemodynamic changes: more direct blood flowed into the aneurysm sac, higher velocity at the upside of the aneurysm, upregulated flow velocity and WSS in the aneurysm, more complicated flow patterns, extended inflow zone, the impingement region moving upward from the neck to the apex of the aneurysm, and higher WSS and larger flow velocity at the inflow zone of the IAs. Therefore, the proposed method may be helpful in exploring the hemodynamic variations of IAs with inflow angles. The findings could be conducive to hemodynamic studies on the association between IA inflow angle and its rupture risk.

Background and Purpose: The Pipeline Embolization Device (PED, Covidien/Medtronic) is widely used to treat intracranial aneurysms. This PED in China post-market multi-center registry study (PLUS) investigated safety and effectiveness of the PED for intracranial aneurysms in the Chinese population. Methods: This was a panoramic, consecutive, real-world cohort registry study. Patients treated with PED with or without coils between November 2014 and October 2019 at 14 centers in China were included, and those treated by parent vessel occlusion or other stents were excluded. Study outcomes included angiographic evaluation of aneurysm occlusion, complications, in-stent stenosis, and predictors of aneurysm occlusion. A central committee reviewed all imaging and endpoint events. Results: In total, 1171 patients with 1322 intracranial aneurysms were included. The total occlusion rate was 81.4% (787/967) at mean follow-up of 8.96 ± 7.50 months, with 77.1% (380/493) occlusion in the PED alone and 85.9% (407/474) in the PED plus coiling group. On multi-variate analysis, female sex, hyperlipidemia, vertebral aneurysms, PED plus coiling, and blood flow detained to venous phase were significant predictors of aneurysm occlusion. In posterior circulation cohort, there was no variable associated with aneurysm occlusion. In-stent stenosis predictors included current smoking and cerebral sclerosis/stenosis. Conclusion: In the largest series on PED of multi-center date of China, data suggest that treatment with the flow-diverting PED in intracranial aneurysms was efficacious. The treatment of PED combined coiling and blood flow detained to venous phase after PED implant were associated with aneurysmal occlusion. The occlusion rate of vertebral aneurysms was higher than other location aneurysms. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT03831672.

Objective: To evaluate effectiveness and safety of Pipeline embolization device (PED) for large or giant verterbrobasilar aneurysms (LGVBAs), and to compare the therapeutic effects of PED with and without adjunctive coils.Methods: We retrospectively analyzed 21 cases of unruptured LGVBAs who were treated in our hospital with PED. These cases were divided into “PED group” and “PED with adjunctive coils group.” We compared the aneurysm characteristics and treatment outcomes between the two groups.Results: The overall neurological complication rate was 28.6% (6/21) and the mortality rate was 4.8% (1/21). There were 12 patients in the PED group and nine in the PED with adjunctive coils group. There were no significant differences in age, smoking, hypertension, aneurysm size, aneurysm location, or operation time between the two groups. The complete aneurysm embolization rate and favorable outcome rate (modified Rankin Scale = 0,1) of the PED with adjunctive coils group was 78% (7/9) and 100% (9/9), respectively, which were both better compared with the PED group with 63.6% (7/11) and 83% (10/12), respectively. However, these differences were not statistically significant.Conclusion: The effectiveness and safety of PED for LGVBAs is acceptable. Treatment results did not differ between the PED and PED with adjunctive coils groups; therefore, whether coils should be used may depend the operator. Our results suggest that correct use of the coils does not increase complications. We suggest that PED with adjunctive coils should be used for some selected LGVBAs.

Background The management of bilateral intracranial vertebral artery dissecting aneurysms (IVADAs) is controversial, and requires the development of endovascular treatment modalities and principles. We aim to investigate the endovascular treatment strategy and outcomes of bilateral IVADAs.Methods We identified all bilateral IVADAs at a high-volume neurointerventional centre over a 10-year period (from January 2009 to December 2018). Radiographic and clinical data were recorded, and a treatment algorithm was derived.Results Twenty-seven patients with bilateral IVADAs (54 IVADAs in total, 51 unruptured, 3 ruptured) were diagnosed. Four patients (14.8%) received single-stage endovascular treatment, 12 patients (44.4%) with staged endovascular treatment and 11 patients (40.8%) with unilateral endovascular treatment of bilateral IVADAs. Thirty-six IVADAs (85.7%) have complete obliteration at the follow-up angiography. Two of three ruptured IVADAs with stent-assisted coiling recanalised, and had further recoiling. Three patients (11.1%) have intraprocedural or postprocedural complications (two in single-stage and one in staged). Twenty-five patients (92.6%) had a favourable clinical outcome, and two patients (7.4%, all in single-stage) showed an unfavourable clinical outcome at follow-up. For the patients with unilateral reconstructive endovascular treatment, the contralateral untreated IVADAs were stable and had no growth or ruptured during follow-up period. None of all IVADAs had rebleeding during the clinical follow-up.Conclusions Endovascular treatment can be performed in bilateral IVADAs with high technical success, high complete obliteration rates and acceptable morbidity/mortality. Contralateral IVADAs had low rates of aneurysm growth and haemorrhage when treated in a staged/delayed fashion.

Background: Endovascular therapy of intracranial aneurysms has a high recurrence rate. This study aimed to evaluate the risk factors of recurrence after endovascular coil embolization of intracranial aneurysms.Methods: From January 2014 to May 2015, 504 patients with 558 intracranial aneurysms who were treated by endovascular therapy were recruited from four high-volume centers. We used multivariate Cox proportional hazard regression to evaluate the risk factors associated with the angiographic recurrence of intracranial saccular aneurysms after endovascular coil embolization.Results: Angiographic follow-up was available for 504 patients (558 aneurysms), with a mean duration of 11.42 months. Of the 558 aneurysms, 57 (10.2%) aneurysms showed recurrence. Aneurysm size (p = 0.028), therapy (non-stent assisted coiling or stent-assisted coiling) (p = 0.008), the Raymond scale (p = 0.040), aneurysm rupture status (p < 0.001), and packing density (p < 0.001) showed significant associations with angiographic follow-up outcome. A low packing density was independently associated with aneurysmal recurrence after multivariate Cox proportional hazard regression analysis (p < 0.001).Conclusion: Endovascular treatment is effective for these lesions. Multiple factors could attribute to the aneurysmal recurrence after endovascular coil embolization. The low packing density is the independent risk factor for aneurysmal recurrence. These findings should be verified by larger multicenter and multi-population studies.

Pediatric intracranial dissecting aneurysms are rare (1), and treating this type of aneurysm in the vertebrobasilar circulation is more difficult. As an off-label application, pipeline embolization devices (PEDs) for posterior circulation dissecting aneurysms are reported to have good therapeutic effect (2). However, studies have found that PEDs for large or giant vertebrobasilar dissecting aneurysms have a poor effect and are associated with disastrous consequences for patients (3). PEDs are feasible for vertebrobasilar dissecting aneurysms (4); however, few reports discuss using PEDs to span the entire segment of the basilar artery. Because there are more perforating arteries in the basilar artery, it is more prudent to use PEDs in this artery. We report a case of a pediatric patient with a giant vertebrobasilar dissecting aneurysm successfully treated with three PEDs combined with right vertebral artery occlusion, without complications. The patient's headache symptoms resolved fully 3 months after the procedure, and the aneurysm was completely healed and excellent reconstruction of the left vertebral artery was seen 4 months post-procedure, using digital subtraction angiography.

Braided stents were widely used to treat cerebral aneurysms and computational fluid dynamics (CFD) was used to evaluate the therapeutic effects. But the aneurysm-artery geometry used in CFD were usually undeformed which is inconsistent with clinical findings. Our team developed a finite element modeling workflow to simulate implantation of braided stents in patient-specific aneurysm-artery model. An LVIS-based braided stent was deployed into an aneurysm-artery model. The stent fully expanded, causing obvious deformation on the aneurysm-artery model. The workflow which we developed could provide reasonable deformed geometries of aneurysm-artery and braided stent for CFD computation and possibly assist surgical planning.

Abstract Background Ruptured aneurysms, the commonest cause of nontraumatic subarachnoid hemorrhage, can be catastrophic; the mortality and morbidity of affected patients being very high. Some risk factors, such as smoking, hypertension and female sex have been identified, whereas others, such as hemodynamics, imaging, and genomics, remain unclear. Currently, no accurate model that includes all factors for predicting such rupture is available. We plan to use data from a large cohort of Chinese individuals to set up a multidimensional model for predicting risk of rupture of unruptured intracranial aneurysms (UIAs). Methods The China Intracranial Aneurysm Project-2 (CIAP-2) will comprise screening of a cohort of 500 patients with UIA (From CIAP-1) and focus on hemodynamic factors, high resolution magnetic resonance imaging (HRMRI) findings, genetic factors, and biomarkers. Possible risk factors for rupture of UIA, including genetic factors, biomarkers, HRMRI, and hemodynamic factors, will be analyzed. The first project of the China Intracranial Aneurysm Project (CIAP-1; chaired by the Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China) will prospectively collect a cohort of 5000 patients with UIA from 20 centers in China, and collect baseline information for each patient. Multidimensional data will be acquired in follow-up assessments. Statistically significant clinical features in the UIA cohort will also be analyzed and integrated into the model for predicting risk of UIA rupture. After the model has been set up, the resultant evidence-based prediction will provide a preliminary theoretical basis for treating aneurysms at high risk of rupture. Discussion This study will explore the risk of rupture of aneurysms and develop a scientific multidimensional model for predicting rupture of unruptured intracranial aneurysms. Clinical Trials registration A Study on a Multidimensional Prediction Model for Rupture Risk of Unruptured Intracranial Aneurysms (CIAP-2), NCT03133624. Registered: 16 April 2017. https://clinicaltrials.gov/ct2/show/NCT03133624

Abstract Background The low-profile visualized intraluminal support (LVIS) stent has become a promising endovascular option for treating intracranial aneurysms. To achieve better treatment of aneurysms using LVIS, we developed a fast virtual stenting technique for use with LVIS (F-LVIS) to evaluate hemodynamic changes in the aneurysm and validate its reliability. Methods A patient-specific aneurysm was selected for making comparisons between the real LVIS (R-LVIS) and the F-LVIS. To perform R-LVIS stenting, a hollow phantom based on a patient-specific aneurysm was fabricated using a three-dimensional printer. An R-LVIS was released in the phantom according to standard procedure. F-LVIS was then applied successfully in this aneurysm model. The computational fluid dynamics (CFD) values were calculated for both the F-LVIS and R-LVIS models. Qualitative and quantitative comparisons of the two models focused on hemodynamic parameters. Results The hemodynamic characteristics for R-LVIS and F-LVIS were well matched. Representative contours of velocities and wall shear stress (WSS) were consistently similar in both distribution and magnitude. The velocity vectors also showed high similarity, although the R-LVIS model showed faster and more fluid streams entering the aneurysm. Variation tendencies of the velocity in the aneurysm and the WSS on the aneurysm wall were also similar in the two models, with no statistically significant differences in either velocity or WSS. Conclusions The results of the computational hemodynamics indicate that F-LVIS is suitable for evaluating hemodynamic factors. This novel F-LVIS is considered efficient, practical, and effective.

Background/Aims: Our previous microarray results identified numerous microRNAs (miRNAs), including miR-29b, that were differentially expressed in the serum of intracranial aneurysm (IA) patients. The current study aimed to investigate whether miR-29b downregulation in IA could promote the phenotypic modulation of vascular smooth muscle cells (VSMCs) involved in the pathogenesis of aneurysm by activating ATG14-mediated autophagy. Methods: First, the levels of miR-29b and autophagy related genes (ATGs) between IA patients and normal subjects were compared. Next, we modified the level of miR-29b via lentivirus particles in the VSMCs and examined the effects of miR-29b on proliferation, migration, and phenotypic modulation of VSMCs from a contractile phenotype to a synthetic phenotype, as well as the levels of autophagy. Finally, the binding of miR-29b to the 3’UTR of ATG14 mRNA and its effects on ATG14 expression were analysed by a luciferase reporter assay and Western blot, respectively. Results: The level of miR-29b was decreased, and autophagy markers were increased in the IA patients compared to that of the normal subjects. Knockdown of miR-29b significantly promoted VSMCs proliferation and migration and, more importantly, induced the phenotypic modulation associated with autophagy activation, whereas miR-29b overexpression showed the opposite effects. The luciferase reporter assay demonstrated that ATG14 was a functional target gene of miR-29b. Notably, knockdown of ATG14 by siRNA apparently abrogated miR-29b inhibition-mediated phenotypic modulation. Conclusion: Downregulation of miR-29b induced VSMCs phenotypic modulation by directly activating ATG14-mediated autophagy, which is associated with the formation, growth and rupture of IAs.

Background: Mass effect associated with large or giant aneurysms is an intractable problem for traditional endovascular treatments. Preventing recurrence of aneurysms requires dense coiling, which may aggravate the mass effect. However, the flow diverter (FD) is a new device that avoids the need for dense coiling. This study was performed to investigate whether use of FDs with adjunctive coil embolization can relieve the aneurysmal mass effect and to explore the factors that affect the variation of compressional symptoms.Methods: We retrospectively evaluated patients with compressional symptoms caused by unruptured aneurysms who underwent endovascular treatment with an FD with adjunctive coil embolization at our center from January 2015 to December 2017. Imaging follow-up included digital subtraction angiography (DSA) ranging from 11 to 14 months and magnetic resonance imaging (MRI) ranging from 24 to 30 months; the former was used to evaluate the intracavitary volume, and the latter was used to measure the variation of the mass effect. Follow-up physical examinations were performed to observe variations of symptoms.Results: In total, 22 patients with 22 aneurysms were treated by an FD combined with coil embolization. All 22 patients underwent the last clinical follow-up. Regarding compressional symptoms, 12 (54.54%) patients showed improvement, 6 (27.27%) were fully recovered, and 6 (27.27%) showed improvement but with incomplete cranial palsy. However, five (22.72%) patients showed no change, four (18.18%) showed worsening symptoms compared with their preoperative state, and one (4.55%) died of delayed rupture. Seventeen of the 22 patients underwent MRI. Of these 17 patients, the aneurysm shrank in 13 (76.47%) and no significant change occurred in 4 (23.53%). In the multivariate analysis, a short duration from symptom occurrence to treatment (p = 0.03) and younger patient age (p = 0.038) were statistically significant factors benefiting symptom improvement, and shrinkage of the aneurysm was associated with favorable clinical outcomes (p = 0.006).Conclusions: Use of the FD with adjunctive loose coil embolization might help to alleviate the compressional symptoms caused by intracranial aneurysms. Shrinkage of the aneurysm, a short duration of symptoms, and younger patient age might contribute to favorable outcomes of mass effect-related symptoms.

BackgroundEndovascular treatment of large or giant non-saccular vertebrobasilar aneurysms (VBAs) by conventional stents is difficult and has unsatisfactory outcomes.ObjectThis study was performed to retrospectively analyze the safety and efficacy of a flow diverter in treating large and giant non-saccular VBAs.MethodsWe identified 78 patients with 83 large or giant non-saccular VBAs who accepted endovascular treatment with a pipeline embolization device (PED) or conventional stent from January 2014 to June 2018. The technical details of the procedure, procedure-associated complications, angiographic outcomes, and clinical outcomes were evaluated.ResultsForty-two patients (53.8%, 42/78) with 44 aneurysms (53.0%, 44/83) underwent endovascular treatment with PEDs. Thirty-six patients (46.2%, 36/78) with 39 aneurysms (47.0%, 39/83) underwent endovascular treatment with conventional stents. The complication rate of PED group and conventional stent group was 7.1% (3/42) and 5.6% (2/36), respectively (odds ratio, 0.765; 95% confidence interval, 0.121–4.851; P = 0.776). During a median follow-up time of 28.8 months, the complete occlusion rate in the PED group and conventional stent group was 90.2% (37/41) and 70.3% (26/37), respectively (odds ratio, 3.913; 95% confidence interval, 1.122–13.652; P = 0.032).ConclusionEndovascular treatment with a PED is a promising and safe modality for large and giant non-saccular VBAs, and the complication rate is acceptable, compared with conventional endovascular treatment.

Objective: Pipeline embolization devices (PEDs) are widely used to exclude intracranial aneurysms from their parent arteries. Side branches covered by PEDs, however, sometimes experience occlusion and related symptoms. Thus, predictors of branch occlusion and the patency and clinical outcomes of these branches are concerning.Methods: We conducted a retrospective review of consecutive patients who had been treated with PEDs in our institution during 2015–2018 to identify those in whom one or more branches were involved. Pretreatment and follow-up angiograms were assessed to determine patency of the involved branches. Demographic and clinical data, treatment strategies, and comorbidities were collected to investigate their relations with branch occlusion.Results: Altogether, 173 branches [24 (13.9%) occluded), 29 (16.8%) with diminished flow] in 126 patients were studied. Five patients (OphA involved) presented with blurred vision and 1 patient (ACA involved) presented with headache. None of the other patients had neurologic complications or clinical strokes related to branch occlusion. Multivariate analysis identified that small PED diameter [p = 0.003, odds ratio (OR) = 0.168], branches arising from the aneurysm (p = 0.004, OR = 6.614), and involvement of the anterior cerebral artery (ACA) (p < 0.001, OR = 25.656) significantly predicted branch occlusion.Conclusion: Branch occlusion rate after PED deployment was low and most occlusions was asymptomatic. Branches with rich collateral supply were more likely to occlude, especially the ACA. Smaller PED diameter, branches arising from the aneurysm, and ACA involvement were significant predictors of branch occlusion after PED treatment.

Objective: To evaluate whether the presenting symptoms of VBD predict outcomes following endovascular treatment.Methods: We retrospectively reviewed our institutional clinical database and identified 22 patients (all men; mean age: 52.6 years, range: 11–73 years) with a diagnosis of VBD, who underwent endovascular treatment from January 2010 to December 2017.Results: After analyzing the clinical and imaging data, we evaluated data for 22 symptomatic patients with VBD. At the time of VBD diagnosis, 13 patients (59%) had compressive symptoms, four (18%) had hemorrhagic symptoms, and five (23%) had ischemic symptoms. Nine of the 22 patients (41%), who presented with hemorrhagic and ischemic symptoms, achieved a satisfactory clinical and/or digital subtraction angiography imaging outcome after endovascular treatment. However, of the 13 patients who presented with compressive symptoms, seven (54%, 7/13) died from severe brainstem compression during follow-up; furthermore, magnetic resonance imaging showed worsening of the mass effect in eight patients with compressive symptoms (62%, 8/13).Conclusions: VBD is considered a challenging lesion without an ideal treatment modality. Endovascular treatment of VBD in patients presenting with compressive symptoms at diagnosis may not be beneficial. However, long-term outcomes following endovascular treatment may be acceptable in patients with non-compressive symptoms at diagnosis compared with those with compressive symptoms.

Objective: Flow diverter devices are increasingly used in the treatment of posterior circulation aneurysms, sometimes necessarily involving ostia of side branches and perforators. The aim of this study was to identify the hemodynamic influence of flow diverters on side branches and perforators of the posterior circulation.Methods: We performed a retrospective study of consecutive patients treated by a flow diverter device for posterior circulation aneurysms with anterior inferior cerebellar artery (AICA) or posterior inferior cerebellar artery (PICA) involvement. Computational fluid dynamics (CFD) were used to discern hemodynamic changes of branches after deployment of the flow diverter.Results: We studied 18 branches from 17 patients (mean age, 50.72 ± 8.17 years). No branches were occluded on immediate angiography and later follow-up. Average flow velocity in aneurysms decreased from 0.077 ± 0.065 m/s to 0.025 ± 0.025 m/s (p < 0.01). Average flow velocity in branch ostia decreased from 0.29 ± 0.14 m/s to 0.27 ± 0.16 m/s (p = 0.189). The difference in flow velocity reduction ratio between aneurysms and branches was statistically significant (68.8 vs. 9.5%; p < 0.001). The mean pressure in branch ostia increased from 10,717.4 ± 489.0 to 10,859.0 ± 643.4 Pa (p < 0.01).Conclusion: While a flow diverter device is capable of slowing down aneurysmal inflow, it is unable to block the flow into branches and perforators when used in the treatment of posterior circulation aneurysms; flow velocity in branches even increased in some cases. With a low branch occlusion ratio, it may be acceptable to cover posterior circulation branches and perforators if unavoidable.

Background: We conducted a computational fluid dynamics (CFD) study and compared the treatment of medium-sized intracranial aneurysms with LVIS and Enterprise stent-assisted coil embolization (SACE) to determine the effects of hemodynamic changes caused by different stent and coil packing densities (PDs) in endovascular treatment.Methods: We enrolled 87 consecutive patients, with 87 medium-sized intracranial aneurysms (≥7, ≤ 12 mm), who underwent LVIS or Enterprise SACE. Aneurysms treated with LVIS SACE were allocated to the LVIS group, and the remainder were allocated to the Enterprise group. CFD were performed to assess hemodynamic alterations between before treatment, after stent deployment, and after SACE.Results: One aneurysm recanalized in the LVIS group (n = 42), and five recanalized in the Enterprise group (n = 45) (recanalization rate: 2.4 vs. 11.1%, respectively; P = 0.108). Higher complete obliteration rate (P = 0.069) was found in the LVIS group. Velocity at the neck plane showed a greater reduction ratio than velocity and WSS of the aneurysm in both groups after stent deployment, while velocity and WSS of the aneurysm showed a greater reduction ratio after coil placement. Further, there was a greater reduction in velocity at the neck plane (59.52 vs. 39.81%), aneurysmal velocity (88.46 vs. 69.45%), and wall shear stress (WSS) (85.45 vs. 69.49%) on the aneurysm in the LVIS group (P < 0.001 for all). Specifically, the reduction ratio of velocity at the neck plane showed significant difference between the groups in the multivariate analysis (P = 0.013).Conclusions : LVIS SACE showed a lower recanalization for endovascular treatment of medium-sized intracranial aneurysms, and the greater hemodynamic alterations might be the key factors.

Objective: To evaluate the feasibility and effectiveness of the pipeline embolization device (PED) for the treatment of pediatric giant vertebrobasilar dissecting aneurysms (VBDAs).Methods: We retrospectively reviewed our institutional clinical database and identified 2,706 patients who presented with a diagnosis of intracranial aneurysms from January 2016 to June 2018. Among this group, 153 patients were diagnosed with VBDAs, and 54 of these patients underwent PED therapy. The PED technique was used in four patients who were 18 years old or younger at the time of presentation (two males, two females; mean age 9.25 years; age range 8–11 years).Results: All four included pediatric patients were managed with the PED. One patient (25%) was treated with the PED alone, while three (75%) were treated with the PED and coils. One patient died from brainstem infarction or compression of the brainstem, while follow-up of the other three patients revealed favorable outcomes. The mass effect was reduced in cases 1, 2, and 3 on follow-up MRI performed 6 months after the PED procedure.Conclusions: PEDs could be feasible in the treatment of pediatric giant VBDAs. However, the safety and efficacy of this method have not been clarified in this special pediatric population, and long-term follow-up is still necessary.

BackgroundWe aimed to evaluate the risk factors of recurrence after stent(s)-assisted coiling (SAC) of intracranial vertebrobasilar dissecting aneurysms (VBDAs) based on 168 consecutive patients.MethodsBetween January 2011 and December 2015, 168 consecutive patients with 170 intracranial VBDAs, which were treated by SAC, were recruited from four high-volume centers. We used multivariate logistic regression to examine factors that affected recurrence of VBDAs.ResultsThe mean duration of clinical follow-up of the 168 patients was 7.81 months (range, 3–24 months). Of the 168 patients, 4 (2.38%) suffered from intraoperative complications and 16 (9.52%) had postoperative complications. Two (1.19%) had severe disability. Imaging follow-up was available for 168 patients (170 VBDAs), with a mean duration 7.81 months, and 24 (14.12%) cases of recurrence of aneurysms were noted. Aneurysm size and metal coverage of stent(s) at the neck were independent predictors of recurrence after SAC by logistic regression analysis.ConclusionThis multicenter cohort study shows that aneurysm size and the metal coverage of stent(s) at aneurysmal neck are independent factors associated with recurrence of VBDAs after SAC.