Mutational Landscape of Secondary Glioblastoma Guides MET-Targeted Trial in Brain Tumor.

Low-grade gliomas almost invariably progress into secondary glioblastoma (sGBM) with limited therapeutic option and poorly understood mechanism. By studying the mutational landscape of 188 sGBMs, we find significant enrichment of TP53 mutations, somatic hypermutation, MET-exon-14-skipping (METex14), PTPRZ1-MET (ZM) fusions, and MET amplification. Strikingly, METex14 frequently co-occurs with ZM fusion and is present in ∼14% of cases with significantly worse prognosis. Subsequent studies show that METex14 promotes glioma progression by prolonging MET activity. Furthermore, we describe a MET kinase inhibitor, PLB-1001, that demonstrates remarkable potency in selectively inhibiting MET-altered tumor cells in preclinical models. Importantly, this compound also shows blood-brain barrier permeability and is subsequently applied in a phase I clinical trial that enrolls MET-altered chemo-resistant glioma patients. Encouragingly, PLB-1001 achieves partial response in at least two advanced sGBM patients with rarely significant side effects, underscoring the clinical potential for precisely treating gliomas using this therapy.

Phosphorylation of Oligopeptides: Design of Ultra-Hydrophilic Zwitterionic Peptides for Anti-Fouling Detection of Nucleic Acids in Saliva.

The construction of low-fouling biosensors for assaying biomarkers in complex biological samples remains a challenge, and the key limitation is the lack of effective anti-fouling materials. Inspired by the biomimetic process of protein phosphorylation, we herein designed a new phosphorylated peptide modified with the dihydrogen phosphate (-PO4H2) group, which significantly increased the hydrophilicity and anti-fouling capability of the peptide when compared with natural and normal peptides. Molecular simulation (MS) illustrated that, compared with the -COOH and -NH2 groups, the -PO4H2 group formed the most numbers of hydrogen bonds and stronger hydrogen bonds with water molecules. As a result, the PO4H2-oligopeptide was proved by MS to be able to attract the greatest number of water molecules, so as to form a compact layer of H2O to resist further adsorption of nonspecific biomolecules. The modification of electrodes with the designed PO4H2-oligopeptides, in addition to the adoption of neutral peptide nucleic acids (PNAs) as the sensing probes, ensured the fabrication of anti-fouling electrochemical biosensors capable of detecting nucleic acids in complex saliva. The constructed anti-fouling biosensor was able to detect the nucleic acid of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in undiluted saliva, with a wide linear response range (0.01 pM-0.01 µM) and a low limit of detection (LOD) of 3.4 fM (S/N = 3). The phosphorylation of oligopeptides offers an effective strategy to designing ultra-hydrophilic peptides suitable for the construction of promising anti-biofouling biosensors and bioelectronics.

An MRI radiomics approach to predict survival and tumour-infiltrating macrophages in gliomas.

Preoperative MRI is one of the most important clinical results for the diagnosis and treatment of glioma patients. The objective of this study was to construct a stable and validatable preoperative T2-weighted MRI-based radiomics model for predicting the survival of gliomas. A total of 652 glioma patients across three independent cohorts were covered in this study including their preoperative T2-weighted MRI images, RNA-seq and clinical data. Radiomic features (1731) were extracted from preoperative T2-weighted MRI images of 167 gliomas (discovery cohort) collected from Beijing Tiantan Hospital and then used to develop a radiomics prediction model through a machine learning-based method. The performance of the radiomics prediction model was validated in two independent cohorts including 261 gliomas from the The Cancer Genomae Atlas database (external validation cohort) and 224 gliomas collected in the prospective study from Beijing Tiantan Hospital (prospective validation cohort). RNA-seq data of gliomas from discovery and external validation cohorts were applied to establish the relationship between biological function and the key radiomics features, which were further validated by single-cell sequencing and immunohistochemical staining. The 14 radiomic features-based prediction model was constructed from preoperative T2-weighted MRI images in the discovery cohort, and showed highly robust predictive power for overall survival of gliomas in external and prospective validation cohorts. The radiomic features in the prediction model were associated with immune response, especially tumour macrophage infiltration. The preoperative T2-weighted MRI radiomics prediction model can stably predict the survival of glioma patients and assist in preoperatively assessing the extent of macrophage infiltration in glioma tumours.

Atomistic Insights into the Effect of Functional Groups on the Adsorption of Water by Activated Carbon for Heat Energy Storage.

Adsorption heat storage holds great promise for solar energy applications. The development of new adsorbent materials is currently the research focus in this area. The present work designs several activated carbon models with different functional groups, including -OH, -NH2, -COOH, and -SO3H, and explores the influence of functional groups' categories and numbers on the water adsorption capacity of the activated carbon using the GCMC method. The adsorption mechanism between functional groups and water molecules is analyzed using density functional theory. The results show that the functional groups could significantly improve the water adsorption capacity of activated carbon due to the hydrogen bond between functional groups and water molecules. In the scope of this paper, under low pressure, the activated carbon with -SO3H exhibits the best adsorption capacity, followed by the activated carbon with -COOH. Under low and medium pressure, increasing the number of -SO3H functional groups could increase the water adsorption capacity; however, when the pressure is high, increasing the functional group numbers might decrease the water adsorption capacity. As the temperature increases, the water adsorption capacity of activated carbons decreases, and the activated carbon with -SO3H is proven to have excellent application prospects in heat energy storage.

Clinical characteristics and surgical outcomes of ependymomas in the upper cervical spinal cord: a single-center experience of 155 consecutive patients.

Ependymomas occurring in the upper cervical spinal cord (above the level of the C4 segment) are rare entities with great therapeutic challenges. This study was aimed to investigate the clinicoradiological characteristics and the prognosis in a large cohort of upper cervical ependymomas from a single institution. This retrospective study enrolled 155 patients with primary ependymomas in the upper cervical spinal cord. The pre- and post-operative clinical and magnetic resonance imaging profiles were collected. The neurological outcomes and survival events were evaluated, and potential independent risk factors were analyzed. There were 82 females and 73 males, with an average age of 43.1 ± 11.3 years. Immediately post-operatively, 118 (76.1%) patients experienced neurological deterioration and 32 (20.7%) patients remained unchanged. Three months after surgery, 61 (39.4%) patients showed deteriorated neurological functions compared to the pre-operative baseline levels. After an average follow-up period of 56.0 ± 24.7 months, the neurological functions were worse than the baseline status in 37 (23.9%) patients and improved in 33 (21.3%) patients, respectively. Logistic regression analysis identified that lower age (≤ 42 years) and lower pre-operative MMS (I-II) were independent protective factors for predicting favorable neurological functions. Multivariate Cox regression analysis revealed that incomplete resection was the only independent risk factor associated with a shorter progression-free survival. Age and pre-operative functional status affect the long-term neurological outcomes, and incomplete resection was associated with a shorter survival. Our findings indicate that gross total resection should be the goal of surgical treatment of upper cervical ependymomas.

Gridding Microsurgical Anatomy of Far Lateral Approach in the Three-Dimensional Model.

OBJECTIVE: The far lateral craniotomy involves osteotomy of various portions of occipital condyle. Intracranial operation exposing clivus encounters complicated neurovascular anatomy. The aim of the present study was to make refinement for the anatomy of far lateral approach by gridding route in the 3-dimensional model. METHODS: Computed tomography and magnetic resonance imaging data were used to construct 3-dimensional model containing osseous and neurovascular structures of skull base. Then, far lateral approach was simulated by triangular prism and divided into gridding surgical route. The relationship of surgical route and osseous and neurovascular structures was observed. Measurement of volume was performed to evaluate surgical exposure. RESULTS: Observation of 3-dimensional model showed bony drilling of far lateral approach started with the occipital condyle and passed through the lateral edge of foramen magnum. The cerebellum and medulla oblongata were exempted from the surgical route exposing clivus. The anatomy variances of operative space, osseous, and neurovascular structures in the gridding route were displayed clearly and compared objectively. CONCLUSION: The gridding operative spaces for the far lateral approach are useful to disclose the detailed discrepancy in the different surgical region. The volumetric measurement provides quantified information to facilitate a better understanding of the anatomy variance.

Quantification of Microsurgical Anatomy in Three-Dimensional Model: Transfrontal Approach for Anterior Portion of the Thalamus.

The thalamus located in the deep site of cerebrum with the risk of internal capsule injury during operation. The purpose of this study was to compare the anatomy for exposure and injury using simulative surgical corridor of 3-dimensional model. The 3-dimensional anatomy model of thalamus in cerebrum was created based on magnetic resonance imaging performed for 15 patients with trigeminal neuralgia. The midpoint of line between anterior edge and top of thalamus was the target exposed. Axis connecting the target with the anterior edge and top of caudate head was used to outline the cylinder, respectively, simulating surgical corridors 1 and 2 of transfrontal approach. Cerebral tissues involved in the corridors were observed, measured, and compared. Incision of cortex was made on the anterior portion of inferior frontal gyrus through corridor 1 and middle frontal gyrus through corridor 2. Both of the 2 corridors passed the caudate nucleus, the anterior limb and genu of internal capsule, ultimately reached the upper anterior portion of thalamus. The volumes of white matter, caudate head, and thalamus in the corridor 1 were more than those in corridor 2. Conversely, the volumes of cortex, internal capsule in corridor 2 were more than those in corridor 1. In conclusion, surgical anatomy-specific volume is helpful to postulate the intraoperative injury of transfrontal approach exposing anterior portion of the thalamus. The detailed information in the quantification of microsurgical anatomy will be used to develop minimally invasive operation.

Prognostic value of a microRNA signature as a novel biomarker in patients with lower-grade gliomas.

MicroRNAs (miRNAs) may act as prognostic biomarkers in a variety of cancers. The aim of this study was to identify and evaluate a prognostic miRNA signature in patients with lower-grade gliomas (LGGs). miRNA expression profiles and clinical data of patients with LGGs from the Chinese Glioma Genome Atlas (CGGA; the training cohort) and The Cancer Genome Atlas (TCGA; the validation cohort) were analyzed, and the least absolute shrinkage and selection operator Cox regression model was used to identify the miRNA signature, which was combined with clinical prognostic factors to develop an individualized survival prediction model. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to reveal the biological implications of the signature. We identified a four-miRNA signature that stratified patients in the training cohort into low- or high-risk groups according to overall survival time, a finding that was verified in the validation cohort. Multivariate Cox regression analysis indicated that the four-miRNA signature was an independent prognostic biomarker, and a nomogram combining this miRNA signature with clinicopathological and molecular factors showed high prognostic accuracy for individualized survival prediction in both TCGA (C-index = 0.83) and CGGA (C-index = 0.68) cohorts. Functional annotation indicated that the major biological processes of this prognostic miRNA signature were enriched in cell cycle and DNA repair-associated biological processes. Our findings indicated that our newly discovered four-miRNA signature may be an effective independent prognostic factor for the prediction of patients with LGGs.

MRI features can predict EGFR expression in lower grade gliomas: A voxel-based radiomic analysis.

OBJECTIVE: To identify the magnetic resonance imaging (MRI) features associated with epidermal growth factor (EGFR) expression level in lower grade gliomas using radiomic analysis. METHODS: 270 lower grade glioma patients with known EGFR expression status were randomly assigned into training (n=200) and validation (n=70) sets, and were subjected to feature extraction. Using a logistic regression model, a signature of MRI features was identified to be predictive of the EGFR expression level in lower grade gliomas in the training set, and the accuracy of prediction was assessed in the validation set. RESULTS: A signature of 41 MRI features achieved accuracies of 82.5% (area under the curve [AUC] = 0.90) in the training set and 90.0% (AUC = 0.95) in the validation set. This radiomic signature consisted of 25 first-order statistics or related wavelet features (including range, standard deviation, uniformity, variance), one shape and size-based feature (spherical disproportion), and 15 textural features or related wavelet features (including sum variance, sum entropy, run percentage). CONCLUSIONS: A radiomic signature allowing for the prediction of the EGFR expression level in patients with lower grade glioma was identified, suggesting that using tumour-derived radiological features for predicting genomic information is feasible. KEY POINTS: • EGFR expression status is an important biomarker for gliomas. • EGFR in lower grade gliomas could be predicted using radiogenomic analysis. • A logistic regression model is an efficient approach for analysing radiomic features.

Genotype prediction of ATRX mutation in lower-grade gliomas using an MRI radiomics signature.

OBJECTIVES: To predict ATRX mutation status in patients with lower-grade gliomas using radiomic analysis. METHODS: Cancer Genome Atlas (TCGA) patients with lower-grade gliomas were randomly allocated into training (n = 63) and validation (n = 32) sets. An independent external-validation set (n = 91) was built based on the Chinese Genome Atlas (CGGA) database. After feature extraction, an ATRX-related signature was constructed. Subsequently, the radiomic signature was combined with a support vector machine to predict ATRX mutation status in training, validation and external-validation sets. Predictive performance was assessed by receiver operating characteristic curve analysis. Correlations between the selected features were also evaluated. RESULTS: Nine radiomic features were screened as an ATRX-associated radiomic signature of lower-grade gliomas based on the LASSO regression model. All nine radiomic features were texture-associated (e.g. sum average and variance). The predictive efficiencies measured by the area under the curve were 94.0 %, 92.5 % and 72.5 % in the training, validation and external-validation sets, respectively. The overall correlations between the nine radiomic features were low in both TCGA and CGGA databases. CONCLUSIONS: Using radiomic analysis, we achieved efficient prediction of ATRX genotype in lower-grade gliomas, and our model was effective in two independent databases. KEY POINTS: • ATRX in lower-grade gliomas could be predicted using radiomic analysis. • The LASSO regression algorithm and SVM performed well in radiomic analysis. • Nine radiomic features were screened as an ATRX-predictive radiomic signature. • The machine-learning model for ATRX-prediction was validated by an independent database.

Quantification of Surgical Route Parameters for Exposure of the Jugular Foramen Via a Trans-Mastoidal Approach Exposing Jugular Foramen in Three-Dimensional Visualization Model.

OBJECTIVE: Surgical operation within the region of the jugular foramen presents a great challenge. The authors characterized the quantitative impact of surgical window parameters on the exposure of the jugular foramen via a trans-mastoidal approach. METHODS: Computed tomography and magnetic resonance imaging data were used to establish a 3-dimensional model of the jugular foramen region. The mastoidale, posterior edge of the mastoid, and the superior edge of the bony external acoustic meatus were selected as points a, b, and c. The anterior edge of the tuberculum jugulare was selected as point d. The midpoints of line segments ab, ac, and bc were selected as points e, f, and g. Triangle abc was divided into triangles aef, beg, cfg, and efg. Surgical corridors of the triangular pyramid were outlined by connecting the above triangles to point d. Anatomic exposure was evaluated by measuring the area and volume of various structures within each route. Statistical comparisons were performed via analysis of variance. RESULTS: The model allowed for adequate visualization of all structures. The areas of triangles beg and efg were greater than those of triangles aef and cfg (P < 0.05). The volumes of triangular pyramids d-beg and d-cfg were greater than those of triangular pyramids d-aef and d-efg (P = 0.000). Statistically significant differences were also observed for volumes of osseous, venous, and cranial nerve structures in all divided routes (P = 0.000). CONCLUSION: Our results indicate that 3-dimensional modeling may aid in the quantification of surgical exposure and that division of the craniotomy window may allow for more precise operation.

Virtual Reality Model of the Three-Dimensional Anatomy of the Cavernous Sinus Based on a Cadaveric Image and Dissection.

OBJECTIVE: Studying the three-dimensional (3D) anatomy of the cavernous sinus is essential for treating lesions in this region with skull base surgeries. Cadaver dissection is a conventional method that has insurmountable flaws with regard to understanding spatial anatomy. The authors' research aimed to build an image model of the cavernous sinus region in a virtual reality system to precisely, individually and objectively elucidate the complete and local stereo-anatomy. METHODS: Computed tomography and magnetic resonance imaging scans were performed on 5 adult cadaver heads. Latex mixed with contrast agent was injected into the arterial system and then into the venous system. Computed tomography scans were performed again following the 2 injections. Magnetic resonance imaging scans were performed again after the cranial nerves were exposed. Image data were input into a virtual reality system to establish a model of the cavernous sinus. Observation results of the image models were compared with those of the cadaver heads. RESULTS: Visualization of the cavernous sinus region models built using the virtual reality system was good for all the cadavers. High resolutions were achieved for the images of different tissues. The observed results were consistent with those of the cadaver head. The spatial architecture and modality of the cavernous sinus were clearly displayed in the 3D model by rotating the model and conveniently changing its transparency. CONCLUSION: A 3D virtual reality model of the cavernous sinus region is helpful for globally and objectively understanding anatomy. The observation procedure was accurate, convenient, noninvasive, and time and specimen saving.

Radiomic features predict Ki-67 expression level and survival in lower grade gliomas.

To investigate the radiomic features associated with Ki-67 expression in lower grade gliomas and assess the prognostic values of these features. Patients with lower grade gliomas (n = 117) were randomly assigned into the training (n = 78) and validation (n = 39) sets. A total of 431 radiological features were extracted from each patient. Differential radiological features between the low and high Ki-67 expression groups were screened by significance analysis of microarrays. Then, generalized linear analysis was performed to select features that could predict the Ki-67 expression level. Predictive efficiencies were further evaluated in the validation set. Cox regression analysis was performed to investigate the prognostic values of Ki-67 expression level and Ki-67-related radiological features. A group of nine radiological features were screened for prediction of Ki-67 expression status; these achieved accuracies of 83.3% and 88.6% (areas under the curves, 0.91 and 0.93) in the training and validation sets, respectively. Of these features, only spherical disproportion (SD) was found to be a prognostic factor. Patients in the high SD group exhibited worse outcomes in the whole cohort (overall survival, p < 0.0001; progression-free survival, p < 0.0001). Ki-67 expression level and SD were independent prognostic factors in the multivariate Cox regression analysis. This study identified a radiomic signature for prediction of Ki-67 expression level as well as a prognostic radiological feature in patients with lower grade gliomas.

Assessment of Risk of Aneurysmal Rupture in Patients with Normotensives, Controlled Hypertension, and Uncontrolled Hypertension.

BACKGROUND: The prevalence of hypertension in patients with intracranial aneurysms has been an increased concern, but it is not well understood if uncontrolled hypertension has impact on aneurysmal rupture. The aim of this study was to determine whether the risk of aneurysmal rupture is higher in uncontrolled hypertensive cohorts than in controlled hypertensive cohorts and normotensive cohorts. METHODS: We retrospectively analyzed the records and angiographies of 456 patients with aneurysms who were treated at our center between June 2013 and June 2014. Three groups of patients were included in the study following the ESH-ESC (European Society of Hypertension-European Society of Cardiology) 2013 guidelines: normotensive group (n = 229), controlled hypertension group (n = 127), and uncontrolled hypertension group (n = 100). Paired comparisons of these 3 groups were analyzed with the Nemenyi test. Multivariate logistic regression analysis was used to exclude the impact of possible confounding factors. RESULTS: The results of the univariate analysis showed that hypertension, smoking, and size of the aneurysms were significantly associated with intracranial aneurysmal rupture (P < .05). The multivariate logistic regression analysis containing clinical and aneurysmal characteristics showed that uncontrolled hypertension, smoking, and aneurysm size were statistically significant predictors of intracranial aneurysmal rupture (P < .05). The paired comparisons of 3 groups showed that the risk of rupture of intracranial aneurysms in the uncontrolled hypertension group was significantly greater than that in the normotensive group (P < .05) and in the controlled hypertension group (P < .05). CONCLUSIONS: Uncontrolled hypertension is associated with increased risk of rupture of intracranial aneurysms. Given that aneurysmal rupture is a potentially fatal-but preventable-complication, these findings are of clinical relevance.

ADAM9 Expression Is Associate with Glioma Tumor Grade and Histological Type, and Acts as a Prognostic Factor in Lower-Grade Gliomas.

The A disintegrin and metalloproteinase 9 (ADAM9) protein has been suggested to promote carcinoma invasion and appears to be overexpressed in various human cancers. However, its role has rarely been investigated in gliomas and, thus, in the current study we have evaluated ADAM9 expression in gliomas and examined the relevance of its expression in the prognosis of glioma patients. Clinical characteristics, RNA sequence data, and the case follow-ups were reviewed for 303 patients who had histological, confirmed gliomas. The ADAM9 expression between lower-grade glioma (LGG) and glioblastoma (GBM) patients was compared and its association with progression-free survival (PFS) and overall survival (OS) was assessed to evaluate its prognostic value. Our data suggested that GBM patients had significantly higher expression of ADAM9 in comparison to LGG patients (p < 0.001, t-test). In addition, among the LGG patients, aggressive astrocytic tumors displayed significantly higher ADAM9 expression than oligodendroglial tumors (p < 0.001, t-test). Moreover, high ADAM9 expression also correlated with poor clinical outcome (p < 0.001 and p < 0.001, log-rank test, for PFS and OS, respectively) in LGG patients. Further, multivariate analysis suggested ADAM9 expression to be an independent marker of poor survival (p = 0.002 and p = 0.003, for PFS and OS, respectively). These results suggest that ADAM9 mRNA expression is associated with tumor grade and histological type in gliomas and can serve as an independent prognostic factor, specifically in LGG patients.

Stent-assisted coiling of very small wide-necked intracranial aneurysms: Complications, anatomical results and clinical outcomes.

BACKGROUND AND OBJECTIVE: Treatment of very small (≤3mm) wide-necked intracranial aneurysms remains controversial, we investigated the efficacy and safety of stent-assisted coiling of such aneurysms. METHODS: From September 2008 to December 2012, 112 very small wide-necked intracranial aneurysms in 108 patients were embolized with stent-assisted coiling. We assessed the initial neurological conditions, complications and anatomic results. The follow-up results were evaluated with DSA and mRS. RESULTS: Stent deployment was successful in 104 of 108 procedures (96.3%). 11 complications (10.2%) occurred during procedures, including 5 events of aneurysm rupture, 3 events of thromboembolism. The rate of complication, rupture and thromboembolism was not statistically different between the ruptured and unruptured patients (P=0.452, P=0.369, P=1.000, respectively). The initial aneurysmal occlusion was Raymond scale (RS) 1 in 34 patients (31.5%), RS2 in 53 patients (49.1%), and RS3 in 21 patients (19.4%). 79 aneurysms were available for anatomic follow-up of 12-47 months, stable occlusion in 45 aneurysms (57.0%), progressive complete occlusion in 34 aneurysms (43.0%). 95 patients(88.0%) were available for a clinical follow-up of 12-52 months, 92 patients (96.8%) had favorable clinical outcomes (mRS ≤2), 3 patients (3.2%) had morbidity (mRS: 3-5). The morbidity was not statistically different between the ruptured and unruptured patients (P=1.000). CONCLUSIONS: Stent-assisted coiling of very small wide-necked intracranial aneurysms may be effective and safe. Because of low risk of rupture in such aneurysms, the coiling of unruptured such aneurysms must be selective. The long-term efficacy and safety of coiling such aneurysms remains to be determined in larger prospective series.

Enterprise stent-assisted coiling for wide-necked intracranial aneurysms during ultra-early (48hours) subarachnoid hemorrhage: a single-center experience in 59 consecutive patients.

BACKGROUND AND OBJECTIVE: Accumulated experience and improvement of stents dedicated to intracranial use have significantly widened the applicability of stent-assisted coiling (SAC) to ruptured wide-necked aneurysms. This retrospective study was designed to evaluate the safety and efficacy of SAC using the Enterprise stent for ruptured wide-necked intracranial aneurysms during ultra-early subarachnoid hemorrhage. METHOD: We reviewed data from 59 consecutive patients with ruptured wide-necked aneurysms who had SAC using the Enterprise stent performed within 48hours of onset. Data collected and analyzed included: patient demographics; morphologic features of the aneurysm; treatment results and follow-up results. Clinical outcomes were evaluated by modified Rankin Scale (mRS). RESULTS: In all 59 cases, SAC using the Enterprise stent was performed successfully, with no significant technical difficulties. Initial angiographic results were: complete occlusion in 38 cases; near occlusion in 17; and partial occlusion in four. Angiographic follow-up of 48 patients showed that 46 (95.8%) remained stable or improved, without regrowth, while regrowth was imaged in two patients. Medium-term clinical follow-up of 54 patients (mean, 26.9months) showed that 88.9% had a good outcome (mRS: 0 in 34; 1 in eight; and 2 in six), and 11.1% poor outcomes (mRS: 3 in four; and 4 in two). CONCLUSION: Enterprise SAC is a safe and viable option for treatment of ruptured wide-necked aneurysms within 48hours of ictus.

Impact of hypertension and smoking on the rupture of intracranial aneurysms and their joint effect.

BACKGROUND: In general population, the prevalence of intracranial aneurysm reaches as high as three percent. The goal of the study was to analyze retrospectively the independent risk factors for the rupture of intracranial aneurysms and their joint effect. METHODS: The records and angiographies of continuous 519 intracranial aneurysm patients treated at our center between February 2013 and July 2014 were retrospectively analyzed. Ruptured group and unruptured group were included in the study according to their clinical and imaging information. Univariate analysis and multivariate logistic regression analysis was used to identified independent risk factors for the rupture of intracranial aneurysms. We assessed the joint effect of independent risk factors for the rupture of intracranial aneurysms with an additional logistic regression analysis. RESULTS: The results of multivariate analysis show that hypertension (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.05-2.18) and smoking (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.06-2.33) were independent risk factors for rupture of intracranial aneurysms. The joint risk of hypertension and smoking was higher (OR, 2.28; 95% CI, 1.29-4.02) than the risks of hypertension (OR, 1.74; 95% CI, 1.11-2.72) and smoking (OR, 1.86; 95% CI, 1.05-3.29) independently. CONCLUSIONS: Hypertension and smoking increase of the rupture risk of intracranial aneurysms. And the joint risk of hypertension and smoking was higher than the risks of hypertension and smoking independently.

Onyx embolization of cavernous sinus dural arteriovenous fistulas via direct transorbital puncture under the guidance of three-dimensional reconstructed skull image (reports of six cases).

BACKGROUND: Because of complex angioarchitecture, the transarterial or venous pathway is not feasible for some cavernous sinus dural arteriovenous fistulas (CS DAVFs). We present six cases in which onyx embolization of a CS DAVFs was made possible through direct transorbital puncture. METHODS: In the present study, all patients were penetrated through one third of the medial-lateral of the inferior orbital rim under the guidance of fluoroscopy superimposed on the three-dimensional reconstructed skull image to complete embolization (onyx with or without coils). The records of patient demographics, clinical manifestation, fistula features, procedures, clinical outcome and angiographic outcome were reviewed and analyzed. RESULTS: In our series of six patients, the immediate angiographic result showed complete occlusion in all patients. The six patients experienced retrobulbarhematoma and eye swelling right after embolization, while the swelling significantly subsided after 3-5 days of conservative treatment. During the postoperative angiography and clinical follow-up (4-10 months), one of the patients had decreased visual acuity; the other five patients did not have neurological dysfunction. CONCLUSIONS: Onyx embolization via direct transorbital puncture provides a method to be considered to treat CS DAVFs when the conventional transvenous approaches are inaccessible.

[Hemodynamic analyses of large intracranial aneurysms].

OBJECTIVE: To simulate the computational hemodynamics of large intracranial aneurysms and analyze the hemodynamics of three types of large intracranial aneurysms. METHODS: A total of 32 patient-specific models of large intracranial aneurysms were constructed with the data of DSA (digital subtraction angiography). According to the location of outflow vessel, plane of main vortex and impact zone, large intracranial aneurysms were classified into type A (outflow vessel in the plane of main vortex), type B1 (outflow vessel out of plane of main vortex, impact zone at the lateral wall of aneurysm) and type B2 (outflow vessel out of plane of main vortex, impact zone at the dome of aneurysm). Blood flow was assumed to be laminar and incompressible and blood Newtonian fluid. The time-dependent pulsatile boundary condition was deployed at inlet. CFD ICEM and Fluent software packages were used to simulate the computational hemodynamics of large intracranial aneurysms. RESULTS: The distributions of hemodynamic variables during the cardiac cycle were analyzed for wall shear stress, velocity and streamlines. The velocity ratio (ratio of aneurysmal flow velocity to parent artery flow velocity) of type A, B1 and B2 was 0.186 ± 0.019, 0.706 ± 0.077 and 0.208 ± 0.041 respectively. The wall shear stress ratio (ratio of aneurysmal wall shear stress to parent artery wall shear stress) of types A, B1 and B2 was 0.081 ± 0.029, 1.019 ± 0.139 and 0.103 ± 0.031 respectively. The flow velocity and wall shear stress were the highest in type B1 group, followed by those in type B2 group and the lowest in type A group. CONCLUSION: As reflected by the location of impact zone, the location of outflow vessel and inflow-angle can influence the level of blood flow in aneurysm sac.