Effect of smoking cessation medications on intracranial aneurysm risk: A Mendelian randomization study.

INTRODUCTION: We aim to assess the association between smoking behavior and intracranial aneurysms (IAs) and the effect of smoking cessation medications on IAs at the genetic level. METHODS: Causal effects of four phenotypes: 1) age at initiation of regular smoking, 2) cigarettes smoked per day, 3) smoking cessation, and 4) smoking initiation on IAs, were analyzed using two-sample inverse-variance weighted Mendelian randomization analyses. The effects of genes interacting with the smoking cessation medications were analyzed using cis-expression quantitative trait loci genetic instruments on IAs using summary statistics-based Mendelian randomization analyses. Colocalization analyses were then used to test whether the genes shared causal variants with IAs. The role of confounding phenotypes as potential causative mechanisms of IAs at these gene loci was tested. RESULTS: Cigarettes smoked per day (OR=2.89; 95% CI:1.85-4.51) and smoking initiation on IAs (OR=4.64; 95% CI: 2.64-8.15) were significantly associated with IA risk. However, age at initiation of regular smoking (OR=0.54; 95% CI: 0.10-2.8) and smoking cessation (OR=6.80; 95% CI: 0.01-4812) had no overall effect on IAs. Of 88 genes that interacted with smoking cessation medications, two had a causal effect on IA risk. Genetic variants affecting HYKK levels showed strong evidence of colocalization with IA risk. Higher HYKK levels in the blood were associated with a lower IA risk. Gene target analyses revealed that cigarettes/day could be a main mediator of HYKK's effect on IA risk. CONCLUSIONS: This study provides evidence supporting that smoking initiation on IAs and cigarettes/day may increase IA risk. Increased HYKK gene expression may reduce IA risk. This can be explained by the increased number of cigarettes consumed daily. HYKK could also reduce IA risk due to the positive effect of continuous abstinence and varenicline therapy on smoking cessation.

Comparison of pipeline embolization device and tubridge flow diverter for posterior circulation aneurysms: A multicentre propensity score matched study.

Rationale and objectives: The off-label use of flow diverters (FDs) has broadened to include treating aneurysms in posterior circulation (PC). A novel flow diverter, the Tubridge flow diverter (TFD), has been created in China specifically for treating PC aneurysms. However, studies comparing between pipeline embolization device (PED) and TFD are rare. Thus, our study aimed to explore the effectiveness of PED and TFD in the treatment of PC aneurysms using a propensity score matched cohort design. Methods: Retrospective data collection was conducted on patients who underwent treatment with either PED or TFD over the period from 2015 through 2020. Propensity score matching (PSM) was employed to calibrate for patient age; history of ischemic stroke; aneurysm size; morphology; location and neck; number of FDs; parent vessel diameter; and the employment of assisted coiling and balloon techniques. Data on previously ruptured aneurysms was not included in the analysis. A comparison was conducted between the two devices to assess perioperative complications, aneurysm occlusion rates, and functional outcomes. Results: A total of 252 PC aneurysms were treated in 248 patients. Clinical and imaging follow-ups were lost in 26 and 47 patients, respectively. Major perioperative complications occurred in 7.5% of the cases, with favorable clinical outcomes in 91.0% and complete occlusion in 79.1%. Eighty-two (32.5%) aneurysms were treated with TFD, while 170 (67.5%) aneurysms were treated with PED. PSM was used to account for these significant variations, producing 82 matched pairs of unruptured aneurysms treated with PED or TFD. In terms of functional and angiographic outcomes, no significant differences were found between PED and TFD (functional outcome, p = 0.594 and angiographic outcome, p = 0.415). However, more perioperative major complications were found in patients treated with TFD (p = 0.005) compared with those receiving PED. Conclusion: The comparative study of PED and TFD in the treatment of PC aneurysms resulted in positive clinical results and sustained occlusion rates, with acceptable perioperative complications. However, higher quality studies are needed to enhance our understanding of the use of FDs for treating of PC aneurysms.

Impact of Stent Size Selection and Vessel Evaluation on Skull Base Cerebrovascular Diseases Treated With Willis Covered Stents: A Multicenter Retrospective Analysis.

PURPOSE: This study aimed to evaluate the impact of the diverse stent size selection on the clinical and angiographic outcomes of Willis covered stent (WCS) for the treatment of skull base cerebrovascular diseases. MATERIALS AND METHODS: A total of 147 patients with 151 skull base cerebrovascular diseases treated with WCS in 3 centers between January 2015 and July 2022 were included in this study. Several parameters depicting stent size and parent artery condition were incorporated into the analysis of the outcomes. RESULTS: Complete occlusion was found in 106 cases (68.2%) immediately after deployment and 126 cases (83.4%) after technical adjustment. In the multivariate logistics analysis, the difference between stent diameter and parent artery diameter (DD) was significantly associated with immediate endoleak without adjustment (odds ratio [OR]=0.410; p=0.005) and late endoleak (OR=0.275; p=0.028). In addition, differences between stent diameter and parent artery diameter at wide landing point (DSW) and differences between stent diameter and parent artery diameter at narrow landing point (DSN) was also was significant associated with immediate endoleak without adjustment and balloon re-dilation respectively. CONCLUSIONS: This study demonstrated that the diameter selection of the WCS was associated with the occurrence of endoleak during the treatment of skull base cerebrovascular diseases. Precise selection and evaluation of stent size and vessel condition were significant factors for skull base cerebrovascular diseases treated by WCS. CLINICAL IMPACT: This study demonstrates a significant association between the diameter selection of the Willis covered stent (WCS) and the occurrence of endoleak in the management of skull base cerebrovascular diseases. The results offer valuable medical evidence that can inform stent selection for WCS. The study emphasizes the significance of precise evaluation of stent size and vessel condition as crucial factors in WCS procedures. These findings underscore the importance of meticulous consideration and individualized approaches to stent selection, ultimately improving treatment outcomes in clinical practice.

Comparison of a covered stent and pipeline embolization device in intracranial aneurysm: a propensity score matching analysis.

BACKGROUND: The Willis covered stent (WCS) and pipeline embolization device (PED) have partly overlapping therapeutic indications. However, the differences of effect between these two treatments remain unclear. OBJECTIVE: To compare clinical outcome, angiographic outcome, and complications following treatment with a WCS versus PED. METHODS: Patients with intracranial aneurysms treated by a WCS or PED between January 2015 and December 2020 were included. The primary outcomes were complications, clinical outcome (modified Rankin Scale score >2), and angiographic outcome (incomplete aneurysm occlusion). Propensity score matching was conducted to adjust for potential confounding factors. RESULTS: A total of 94 aneurysms treated by WCS and 698 aneurysms by PED were included. Compared with the PED group, patients in the WCS group are younger, a greater number have a poor condition at admission, a larger proportion of ruptured, non-saccular, and anterior circulation aneurysms, a smaller aneurysm neck width, and less coiling assistance is required. A total of 42 (44.7%) branches were covered by WCS. After adjustment for age, sex, aneurysm type, rupture status, neck size, aneurysm location, and coiling, 50 WCS and PED pairs were examined for internal carotid artery aneurysms. No significant differences were observed in clinical (10.4% vs 2.1%, P=0.206) and angiographic outcomes (12.8% vs 18.2%, P=0.713). However, 27 branches covered by WCS, including 22 ophthalmic arteries and five posterior communicating arteries. Patients in the WCS group had a higher intraoperative complication rate than those in the PED group (28% vs 6%, P=0.008), especially in the occlusion rate of covered branches (51.9% vs 11.1%, P<0.001). CONCLUSION: The comparable clinical and angiographic outcomes of WCS or PED demonstrate the therapeutic potential of WCS as a viable alternative for aneurysms. However, the complication of occlusion of covered branches might not be negligible.

Comparative study on clinical outcomes and cost-effectiveness of chronic subdural hematomas treated by middle meningeal artery embolization and conventional treatment: a national cross-sectional study.

BACKGROUND: The authors compared the efficacy and cost-effectiveness of middle meningeal artery embolization (MMAE) and conventional treatment for chronic subdural hematomas (cSDH). METHODS: The Nationwide Readmissions Database of 9963 patients (27.2% women) with cSDH between 2016 and 2020 was analyzed. Finally, 9532 patients were included (95.7%, treated conventionally; 4.3%, treated with MMAE). Baseline demographics, comorbidities, adverse events, treatment strategies, and outcomes were compared between patients treated with MMAE and conventional treatment. After propensity score matching, the authors compared primary outcomes, including the 90-day treatment rate, functional outcome, length of hospital stays, and cost. A Markov model estimated lifetime costs and quality-adjusted life years (QALYs) associated with different treatments. The incremental cost-effectiveness ratio (ICER) was calculated to evaluate the base-case scenario. One-way, two-way, and probabilistic sensitivity analyses were performed to evaluate the uncertainty in the results. RESULTS: After propensity score matching, MMAE had a lower 90-day retreatment rate (2.6 vs. 9.0%, P =0.001), shorter length of hospital stays (4.61±6.19 vs. 5.73±5.76 days, P =0.037), similar functional outcomes compared (favorable outcomes, 80.9 vs. 74.8%, P =0.224) but higher costs ($119 757.71±90 378.70 vs. $75 745.55±100 701.28, P <0.001) with conventional treatment. MMAE was associated with an additional cost of US$19 280.0 with additional QALY of 1.3. Its ICER was US$15199.8/QALY. CONCLUSION: MMAE is more effective in treating cSDH than conventional treatment. Based on real-world data, though MMAE incurs higher overall costs, the Markov model showed it to be cost-effective compared to conventional treatment under the American healthcare system. These comparative and economic analyses further support the consideration of a paradigm shift in cSDH treatment.

Early administration of multiple vasopressors is associated with better survival in patients with sepsis: a propensity score-weighted study.

BACKGROUND: The association between the timing of administration of multiple vasopressors and patient outcomes has not been investigated. METHODS: This study used data from the MIMIC-IV database. Patients with sepsis who were administered two or more vasopressors were included. The principal exposure was the last norepinephrine dose when adding a second vasopressor. The cohort was divided into early (last norepinephrine dose < 0.25 µg/kg/min) and normal (last norepinephrine dose ≥ 0.25 µg/kg/min) groups. The primary outcome was 28-day mortality. Multivariable Cox analyses, propensity score matching, stabilized inverse probability of treatment weighting (sIPTW), and restricted cubic spline (RCS) curves were used. RESULTS: Overall, 1,437 patients who received multiple vasopressors were included. Patients in the early group had lower 28-day mortality (HR: 0.76; 95% CI: 0.65-0.89; p < 0.001) than those in the single group, with similar results in the propensity score-matched (HR: 0.80; 95% CI: 0.68-0.94; p = 0.006) and sIPTW (HR: 0.75; 95% CI: 0.63-0.88; p < 0.001) cohorts. RCS curves showed that the risk of 28-day mortality increased as the last norepinephrine dose increased. CONCLUSIONS: The timing of secondary vasopressor administration is strongly associated with the outcomes of patients with sepsis.

Coiling embolization strategy for medium-to-giant-sized intracranial aneurysms treated with pipeline embolization device: a propensity score-weighted study.

OBJECTIVES: We aim to investigate associations between different coil strategies and outcomes in the aneurysms treated by a pipeline embolization device (PED). METHODS: Patients with medium-to-giant-sized aneurysms treated by PED were included. The total cohort was divided into PED-alone and PED-coiling groups, and the PED-coiling group was further divided into loose and dense packing subgroups. Multivariate logistic analyses and stabilized inverse probability of treatment weighting (sIPTW) were performed to investigate the relationships between coiling strategies and outcomes. Restricted cubic spline (RCS) curves were used to describe the coiling degree and angiographic outcome relationship. RESULTS: A total of 398 patients with 410 aneurysms were included. Aneurysms treated with PED coiling had a lower incomplete occlusion rate (15.3% vs. 30.3%, p = 0.002), higher total perioperative complication rate (14.2% vs. 3.5%, p = 0.001), longer production time (142.14 min vs. 101.26 min, p < 0.001), and higher total cost ($45,158.63 vs. $34,680.91, p < 0.001) than those treated with PED alone. There were no differences in outcomes between the loose and dense packing subgroups. However, the total cost was higher in the dense packing group ($43,787.46 vs. $47,288.32, p = 0.001) than in the loose packing group. The result was still robust in the multivariate and sIPTW analyses. The RCS curves showed "L-shape" relationships between the coil degree and angiographic outcomes. CONCLUSION: Compared with PED alone, PED coiling could improve aneurysm occlusion. However, it could also increase the total complication risk, prolong procedure time, and increase the total cost. Compared with loose packing, dense packing did not enhance the treatment effectiveness but increased the treatment cost. CLINICAL RELEVANCE STATEMENT: The additional treatment effect from coiling embolization declines sharply after a certain point. Specifically, the aneurysm occlusion rate is roughly stable when the coil number is greater than 3 or the total coil length is longer than 150 cm. KEY POINTS: • Compared with pipeline embolization device (PED) alone, PED combined with coiling can improve aneurysm occlusion. • Compared with PED alone, PED combined with coiling increases the total complication risk, cost, and prolongs procedure time. • Compared with loose packing, dense packing did not increase the treatment effectiveness but increased the cost.

Flow diversion for posterior circulation aneurysms: a multicenter retrospective study.

Background: The prevalence of intracranial aneurysms is approximately 3% worldwide. Posterior circulation (PC) aneurysms have a higher risk of treatment complications than anterior circulation aneurysms. Improving the survival rate and quality of life of patients with PC aneurysms remains one of the most important issues in the field. Objectives: Flow diverter (FD) treatment of PC aneurysms remains controversial. We aimed to investigate the effects of FD treatment and analyze differences among different application methods or aneurysm types in PC aneurysms. Design: This is a multicenter retrospective study. Methods: Patients with PC aneurysms treated with the pipeline embolization device (PED) or Tubridge embolization device (TED) between 2015 and 2020 in five neurovascular centers were retrospectively enrolled. The primary outcomes were major perioperative complication, clinical outcome, and aneurysm occlusion rates. Univariable and multivariable logistic regression analyses were used to determine the risk factors of each outcome. Results: In total, 252 aneurysms were included. Major perioperative complication, favorable clinical outcome, and complete occlusion rates were 7.5%, 91.0%, and 79.1%, respectively. Compared with other types of aneurysms, dissecting aneurysms had the best clinical outcome and highest occlusion rate. Both clinical and angiographic outcomes were independently associated with the aneurysm location at the basilar artery. Aneurysm size was not associated with any outcome. TED had similar clinical and angiographic outcomes compared with PED but more perioperative major complications. Tandem treatment and coiling assistance may have poorer clinical outcomes but similar occlusion rates. Single- and multiple-stent treatments had similar outcomes. Conclusion: FD treatment of PC aneurysms achieved favorable clinical outcomes and long-term aneurysm occlusion rates with acceptable perioperative complication rates, especially in dissecting and non-basilar artery aneurysms. There was no additional improvement in outcomes with coiling assistance, multi-stent application, or tandem treatment. Therefore, the use of PC aneurysms should be carefully considered.