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Serum interleukin-1 (IL-1) are possibly indicative of the inflammation in the intracranial aneurysm (IA) wall. This study aimed to investigate whether IL-1 could discriminate the unstable IAs (ruptured intracranial aneurysms (RIAs) and symptomatic unruptured intracranial aneurysms (UIAs)) from stable, asymptomatic UIAs. IA tissues and blood samples from 35 RIA patients and 35 UIA patients were collected between January 2017 and June 2020 as the derivation cohort. Blood samples from 211 patients with UIAs were collected between January 2021 and June 2022 as the validation cohort (including 63 symptomatic UIAs). Blood samples from 35 non-cerebral-edema meningioma patients (non-inflammatory control) and 19 patients with unknown-cause subarachnoid hemorrhage (hemorrhagic control) were also collected. IL-1β and IL-1.ra (IL-1 receptor antagonist) were measured in serum and IA tissues, and the IL-1 ratio was calculated as log 10 (IL-1.ra/IL-1β). Based on the derivation cohort, multivariate logistic analysis showed that IL-1β (odds ratio, 1.48, P = 0.001) and IL-1.ra (odds ratio, 0.74, P = 0.005) were associated with RIAs. The IL-1 ratio showed an excellent diagnostic accuracy for RIAs (c-statistic, 0.91). Histological analysis confirmed the significant correlation of IL-1 between serum and aneurysm tissues. IL-1 ratio could discriminate UIAs from non-inflammatory controls (c-statistic, 0.84), and RIAs from hemorrhagic controls (c-statistic, 0.95). Based on the validation cohort, the combination of IL-1 ratio and PHASES score had better diagnostic accuracy for symptomatic UIAs than PHASES score alone (c-statistic, 0.88 vs 0.80, P < 0.001). Serum IL-1 levels correlate with aneurysm tissue IL-1 levels and unstable aneurysm status, and could serve as a potential biomarker for IA instability., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Interleukin-1 (IL-1) could induce inflammation of the aneurysm wall, which might be related to intracranial aneurysm rupture. The aim of this study was to investigate whether IL-1 could serve as a biomarker to predict the risk of rebleeding after admission. Data between January 2018 and September 2020 were collected from patients with ruptured intracranial aneurysms (RIAs) and were retrospectively reviewed. The serum IL-1β and IL-1ra levels were detected using a panel, and IL-1 ratio was calculated as the log10 (IL-1ra/IL-1β). The predictive accuracy of IL-1 compared with previous clinical morphology (CM) model and other risk factors were evaluated by the c-statistic. Five hundred thirty-eight patients were finally included in the study, with 86 rebleeding RIAs. The multivariate Cox analysis confirmed aspect ratio (AR) > 1.6 (hazard ratio (HR), 4.89 [95%CI, 2.76-8.64], P < 0.001), size ratio (SR) > 3.0 (HR, 2.40 [95%CI, 1.34-4.29], P = 0.003), higher serum IL-1β (HR, 1.88 [95%CI, 1.27-2.78], P = 0.002), and lower serum IL-1ra (HR, 0.67 [95%CI, 0.56-0.79], P < 0.001) as the independent risk factors for rebleeding after admission. According to the c-statistics, the IL-1 ratio had the highest predictive accuracy (0.82), followed by IL-1ra and IL-1β (0.80), AR > 1.6 (0.79), IL-1ra (0.78), IL-1β (0.74), and SR > 3.0 (0.56), respectively. Subgroup analysis based on AR and SR presented similar results. The model combining IL-1 ratio and CM model showed higher predictive accuracy for the rebleeding after admission (c-statistic, 0.90). Serum IL-1, especially IL-1 ratio, could serve as a biomarker to predict the risk of rebleeding after admission., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Calcium channel blockers (CCBs) are antihypertensive agents with potential vascular protection effects. This study investigated whether CCB usage was associated with a lower incidence of unruptured intracranial aneurysm (UIA) instability (growth and rupture) in patients with hypertension., Methods: UIA patients were included in two prospective, multicenter cohort studies (IARP-CP and 100-Project cohorts). All patients received conservative treatment and were regularly followed up every 6 months by CT angiography for 2 years. Patients taking CCBs at least 5 days per week were considered CCB users; otherwise, they were considered non-CCB users. The primary endpoint was UIA instability (rupture, growth of > 20% and/or 1 mm in any dimension, or appearance of a new dome irregularity on imaging follow-up)., Results: A total of 392 UIA patients with hypertension (191 male, 201 female; median age 57 years) were included with a mean follow-up duration of 21.7 ± 5.2 months. The primary endpoint was met in 81 patients (20.7%) during follow-up, including 68 patients with aneurysms that grew and 13 with aneurysms that ruptured. CCB users had a lower UIA instability rate than non-CCB users (27/237 [11.4%] vs 54/155 [34.8%], p < 0.001). Multivariable Cox analysis demonstrated that CCB use was associated with a lower risk of UIA instability (HR 0.37, 95% CI 0.22-0.61; p < 0.001). The protective effect of CCB use was consistent in patients taking a single antihypertensive agent (HR 0.22, 95% CI 0.12-0.40; p < 0.001) and patients taking > 1 antihypertensive agent (HR 0.42, 95% CI 0.20-0.87; p = 0.021). For patients with controlled hypertension, CCB use was still associated with a lower risk of UIA instability (HR 0.22, 95% CI 0.09-0.52; p = 0.001)., Conclusions: In UIA patients with hypertension, CCB use was associated with a lower incidence of aneurysm instability.

Aneurysm wall remodeling (AWR) is an important pathological characteristic in aneurysm wall, which was characterized by abnormal histological structure and inflammation infiltration. In the present study, the aim is to determine the relationships of morphological-hemodynamic characteristics, inflammation, and AWR in intracranial aneurysms (IAs), as well as the pathological basis of morphological-hemodynamic predictors to achieve IA development. For this end, 113 unruptured IAs were prospectively collected from 110 cases. In addition, patient-specific computational fluid dynamics and geometry were adopted to determine hemodynamic and morphological parameters. Moreover, Hematoxylin-Eosin staining was performed to identify the AWR. By performing immunofluorescence, the inflammatory markers were detected. Masson staining was conducted to characterize the characteristics of atherosclerosis in aneurysm wall. To demonstrate the parameters regarding the AWR, a multivariate logistic analysis was conducted. Besides, correlation analyses were conducted to verify the relationship between morphological-hemodynamic and pathological characteristics. For 113 unruptured IAs, no difference was identified in baseline information. AWR was demonstrated in 92 (81.4%) IAs. To be specific, the aneurysm size (odds ratio (OR), 2.63; confidence interval (CI), 1.04-6.67; P = 0.041), size ratio (SR; OR, 1.95; CI, 1.38-2.76; P < 0.001), normalized wall shear stress average (NWSSA; OR, 0.05; CI, 0.01-0.15; P = 0.007), and relative resident time (RRT; OR, 1.28; CI, 1.07-1.53; P = 0.007) were proved as the factors of AWR. As revealed from the results of immunofluorescence, aneurysm size, SR, NWSSA, and RRT were significantly correlated with the level of inflammation in IA tissues. Furthermore, Masson staining revealed that atherosclerosis area in IA tissues and NWSSA was correlated with RRT. In this study, SR, NWSSA, and RRT were demonstrated as the risk factors of AWR. The mentioned parameters could also reflect the characteristics of inflammation and atherosclerosis in aneurysm wall as well. This study revealed that biomechanical stress and inflammation in aneurysm wall are correlated, which might suggest the pathological evidence of morphological-hemodynamic predictors for IA development., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The stability of intracranial aneurysms (IAs) may involve in multidimensional factors. Backpropagation (BP) neural network could be adopted to support clinical work. This preliminary study aimed to delve into the feasibility of BP neural network in assessing the risk of IA rupture/growth and to prove the advantage of multidimensional model over single/double-dimensional model., Methods: Thirty-six IA patients were recruited from a prospective registration study (ChiCTR1900024547). All patients were followed up until aneurysm ruptured/grew or 36 months after being diagnosed with the IAs. The multidimensional data regarding clinical, morphological, and hemodynamic characteristics were acquired. Hemodynamic analyses were conducted with patient-specific models. Based on these characteristics, seven models were built with BP neural network (the ratio of training set to validation set as 8:1). The area under curves (AUC) was calculated for subsequent comparison., Results: Forty-five characteristics were determined from 36 patients with 37 IAs. In the models based on the single dimension of IA characteristics, only morphological characteristics exhibited high performance in assessing 3-year IA stability (AUC = 0.703, P = 0.035). Among the models integrating two dimensions of IA characteristics, clinical-morphological (AUC = 0.731, P = 0.016), clinical-hemodynamic (AUC = 0.702, P = 0.036), and morphological-hemodynamic (AUC = 0.785, P = 0.003) models were capable of assessing the risk of 3-year IA rupture/growth. Moreover, the models including all three dimensions exhibited the maximum predicting significance (AUC = 0.811, P = 0.001)., Conclusion: The present preliminary study reported that BP neural network might support assessing the 3-year stability of IAs. Models based on multidimensional characteristics could improve the assessment accuracy for IA rupture/growth., (© 2021. Fondazione Società Italiana di Neurologia.)

Presurgical discrimination of blood blister-like aneurysms (BBAs) can assist neurosurgeons in clinical decision-making. The aim of this study was to investigate the characteristics of BBAs and construct a useful tool to distinguish BBAs. This study reviewed patients with small/median, hemispherical, and wide-necked aneurysms of the internal carotid artery in our institution. BBAs were identified via their intraoperative findings. A hemodynamic analysis was performed using a patient-specific model. The independent risk factors of BBAs were investigated using a logistic analysis. A scoring system was then established to discriminate BBAs, in which its predicting value was analyzed using receiver operating characteristic (ROC) analysis. A total of 67 aneurysms comprising 21 BBAs were enrolled. Comparing features between BBAs and non-BBAs, statistical significances were found in the aspect ratio (AR), height-to-width ratio, aneurysm angle (AA), wall shear stress gradient (WSSG), and normalized wall shear stress average. A multivariate logistic analysis identified AR (OR = 0.29, p = 0.021), WSSG (OR = 1.54, p = 0.017) and AA (OR = 2.49, p = 0.039) as independent risk factors for BBAs. A scoring system was constructed using these parameters, effectively distinguishing BBAs (AUC = 0.931, p < 0.01). Our multidimensional scoring system may effectively assist in the discrimination of BBAs from wide-necked non-BBAs., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Objective: Intraoperative aneurysm rupture (IAR) could cause a poor outcome. This study aimed to investigate the relationship between IARs and postoperative cerebral infarctions (CIs)., Method: We retrospectively reviewed patients with asymptomatic unruptured intracranial aneurysms (UIAs) who received microsurgical clipping in two neurosurgical centers from January 2016 to June 2019. A propensity score matching was done to constitute a cohort. The data were collected regarding the clinical and radiological characteristics. The CI at 1-2 weeks and the functional outcome at two weeks after clipping were recorded. Differences between IAR patients with CIs and without CIs were compared. The relationship between the IARs and postoperative CIs was investigated by using logistic regression analysis., Results: This study yielded 96 UIAs patients, including 48 patients undergoing IARs and 48 patients not. Twenty patients with CIs at 1-2 weeks after clipping were identified. The rate of CIs in patients undergoing IARs was higher than that in patients not undergoing IARs (OR, 2.88; p = 0.038); moreover, the mRS was also worse in patients undergoing IARs (OR, 1.58; p = 0.015). For patients undergoing IARs, the significance was found in ischemic cerebrovascular disease (OR, 6.40; p = 0.048), Essen stroke risk score (OR, 2.14; p = 0.026), and severity of intraoperative rupture (OR, 5.63; p = 0.023). The multivariate logistic analysis demonstrated the major IARs (OR, 6.09; CI, 1.18-31.53; p = 0.031) as the independent risk factor related to postoperative CI., Conclusion: IARs could increase the risk of postoperative CIs and worsen the functional outcome, and major IAR was the independent risk factor related to the postoperative CIs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Objective: Aneurysm rebleeding after rupture can result in a catastrophic outcome with high mortality and morbidity. In this study, we evaluated the correlation of IARS (intracranial aneurysm rupture score) and aneurysm rebleeding. The aim of this study was to explore the clinical utility of IARS for better clinical decision-making., Method: The patients with ruptured intracranial aneurysms between January 2017 and September 2018 were reviewed. Propensity scoring match was performed to construct a cohort. The morphological and hemodynamic parameters were obtained. The difference between stable aneurysms and rebleeding aneurysms was compared. Subsequently, the correlation of IARS and aneurysm rebleeding was studied., Results: The matching process constructed a cohort, including 5 rebleeding aneurysms and 15 stable aneurysms. By comparing the difference between stable aneurysms and rebleeding aneurysms, the statistical significance was found in diameter of neck (p = 0.036), aspect ratio (p = 0.004) and size ratio (p = 0.029), normalized wall shear stress average (p = 0.026), low shear area ratio (p = 0.028), oscillatory shear index (OSI) (p = 0.031), and deviated angle (p = 0.025). The IARS here had a strong correlation with the aneurysm rebleeding, and the interval from the first bleeding to the rebleeding tended to shorten with the increase of IARS (R = 0.715, p = 0.027). IARS had a good predicting value for the aneurysm rebleeding (area under the curve = 0.756, p < 0.001)., Conclusion: Based on this preliminary study, intracranial aneurysm rupture score may correlate to the rebleeding in ruptured aneurysms. For ruptured aneurysms with high IARS scores, surgery should be given priority, and medical treatment is not recommended.

The underlying pathophysiological mechanisms involved in cerebral aneurysms rupture remain unclear. This study was performed to investigate the differentially expressed proteins between ruptured and unruptured aneurysms using quantitative proteomics. The aneurysmal walls of six ruptured aneurysms and six unruptured aneurysms were collected during the surgical operation. The isobaric tags for relative and absolute quantification (iTRAQ) were used to identify the differentially expressed proteins and western blotting was performed to validate the expression of the proteins of interest. Bioinformatics analysis of the differentially expressed proteins was also performed using the KEGG database and GO database. Between ruptured and unruptured aneurysms, 169 proteins were found differently expressed, including 74 up-regulated proteins and 95 down-regulated proteins with a fold change ≥ 2 and p value ≤ .05. KEGG pathway analysis revealed that phagosome, focal adhesion and ECM-receptor interaction were the most common pathways involved in aneurysm rupture. In addition, the differential expressions of ITGB3, CRABP1 and S100A9 were validated by western blotting. Through the iTRAQ method, we found that inflammatory responses and cell-matrix interactions may play a significant role in the rupture of cerebral aneurysms. These findings provide a basis for better understanding of pathophysiological mechanisms associated with aneurysm rupture., Biological Significance: Intracranial aneurysm is the leading cause of life-threating subarachnoid hemorrhage which can cause 45% patients die within 30 days and severe morbidity in long-term survivors. With a high prevalence ranging from 1% to 5% in general population, cerebral aneurysm has become a widespread health hazard over past decades. Though great advances have been achieved in the diagnosis and treatment of this disease, the underlying pathophysiological mechanisms of aneurysm rupture remains undetermined and a lot of uncertainty still exists surrounding the treatment of unruptured cerebral aneurysms. Clarifying the mechanism associated with aneurysm rupture is important for estimating the rupture risk, as well as the development of new treatment strategy. Some previous studies have analyzed the molecular differences between ruptured and unruptured IAs at gene and mRNA levels, but further comprehensive proteomic studies are relatively rare. Here we performed a comparative proteomics study to investigate the differentially expressed proteins between ruptured IAs (RIAs) and unruptured IAs (UIAs). Results of our present study will provide more insights into the pathogenesis of aneurysm rupture at protein level. With a better understanding of pathophysiological mechanisms associated with aneurysm rupture, some noninvasive treatment strategies may be developed in the future., (Copyright © 2018 Elsevier B.V. All rights reserved.)