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.

Mitochondrial ferritin upregulation reduced oxidative stress and blood-brain-barrier disruption by maintaining cellular iron homeostasis in a neonatal rat model of germinal matrix hemorrhage.

Germinal matrix hemorrhage (GMH) is a devasting neurological disease in premature newborns. After GMH, brain iron overload associated with hemoglobin degradation contributed to oxidative stress, causing disruption of the already vulnerable blood-brain barrier (BBB). Mitochondrial ferritin (FTMT), a novel mitochondrial outer membrane protein, is crucial in maintaining cellular iron homeostasis. We aimed to investigate the effect of FTMT upregulation on oxidative stress and BBB disruption associated with brain iron overload in rats. A total of 222 Sprague-Dawley neonatal rat pups (7 days old) were used to establish a collagenase-induced GMH model and an iron-overload model of intracerebral FeCl2 injection. Deferiprone was administered via gastric lavage 1 h after GMH and given daily until euthanasia. FTMT CRISPR Knockout and adenovirus (Ad)-FTMT were administered intracerebroventricularly 48 h before GMH and FeCl2 injection, respectively. Neurobehavioral tests, immunofluorescence, Western blot, Malondialdehyde measurement, and brain water content were performed to evaluate neurobehavior deficits, oxidative stress, and BBB disruption, respectively. The results demonstrated that brain expressions of iron exporter Ferroportin (FPN) and antioxidant glutathione peroxidase 4 (GPX4) as well as BBB tight junction proteins including Claudin-5 and Zona Occulta (ZO)-1 were found to be decreased at 72 h after GMH. FTMT agonist Deferiprone attenuated oxidative stress and preserved BBB tight junction proteins after GMH. These effects were partially reversed by FTMT CRISPR Knockout. Iron overload by FeCl2 injection resulted in oxidative stress and BBB disruption, which were improved by Ad-FTMT mediated FTMT overexpression. Collectively, FTMT upregulation is neuroprotective against brain injury associated with iron overload. Deferiprone reduced oxidative stress and BBB disruption by maintaining cellular iron homeostasis partially by the upregulating of FTMT after GMH. Deferiprone may be an effective treatment for patients with GMH.

Flow diverters versus stent-assisted coiling in unruptured intracranial vertebral artery dissecting aneurysms.

OBJECTIVE: Flow diverters (FDs) have been used in unruptured intracranial vertebral artery dissecting aneurysms (IVADAs) with seemingly more favorable outcomes compared with stent-assisted coiling (SAC). However, the benefits of FDs over SAC in unruptured IVADAs need further evaluation. METHODS: This was a propensity score-matched, retrospective cohort study. Consecutive patients with unruptured IVADAs treated with FDs or SAC at the authors' hospital between January 2016 and December 2020 were reviewed. Propensity score matching at 1:1 was based on age, significant stenosis adjacent to aneurysmal dilatation, maximum diameter, and posterior inferior cerebellar artery involvement. Periprocedural cerebrovascular complications and angiographic and clinical outcomes were compared between the two matched groups. RESULTS: A total of 124 unruptured IVADAs in 123 patients (median age 53 [interquartile range 47-59] years; 101 men) were included. The FD and SAC groups included 65 and 59 IVADAs, respectively. Propensity score matching resulted in 47 matched pairs. The rates of immediate complete occlusion were significantly lower in the matched FD group than in the matched SAC group (6.4% vs 68.1%, p < 0.001). The rates of periprocedural cerebrovascular complications were comparable between the two matched groups (6.4% vs 6.4%, p > 0.99). At last follow-up, the rates of complete occlusion (89.4% vs 80.9%, p = 0.39) and favorable clinical outcomes (100.0% vs 97.9%, p > 0.99) were comparable, whereas the rate of recanalization was significantly lower in the matched FD group than in the matched SAC group (0.0% vs 12.8%, p = 0.03). Although the difference between the rates of in-stent stenosis was not statistically significant (17.0% vs 6.4%, p = 0.18), the difference in the effect measures was considerable. CONCLUSIONS: In unruptured IVADAs and compared with SAC, FDs provide comparable rates of periprocedural cerebrovascular complications, favorable clinical outcomes, and follow-up complete occlusion, lower rates of immediate complete occlusion and follow-up recanalization, and likely higher rates of in-stent stenosis.

Combined exposure to multiple metals on hypertension in NHANES under four statistical models.

Metals exposure has gained increasing attention in the hypertension prevention. However, previous studies have focused on the impacts of single or separated metals on hypertension, and the critical metals contributing to the prevalence of hypertension are still under discussion. We collected data from 5092 participants across three consecutive National Health and Nutrition Examination Survey (NHANES) circles (2011-2016). Weighted logistic regression, weighted quantile sum (WQS) regression, quantile-based g-computation (QGC), and Bayesian kernel machine regression (BKMR) analyses were conducted to evaluate the combined and individual effects of 15 urinary metals, as well as to identify the critical metals on the development of hypertension. In our study, the weighted prevalence of hypertension was 37.9%, and the average age was 47.42 years. Manganese, uranium and tin were found as the independent risk factors for hypertension, while barium, lead, and thallium were found to have protective effects against hypertension. Lead, barium, tungsten, uranium, and tin were determined as critical elements for the prediction of hypertension. No significant interaction relationship was detected between multiple metals. There might be potential positive combined effects of urinary metal mixture on hypertension. Tungsten, uranium, and tin were positively associated with hypertension while lead and barium were negatively associated with hypertension. The underlying mechanisms of urinary metal exposure on the risk of hypertension deserve further investigations.

Blood inflammatory biomarkers predict in-hospital pneumonia after endovascular treatment of aneurysm in patients with aneurysmal subarachoid hemorrhage.

The systemic inflammatory response index (SIRI) is a well-known marker of systemic inflammation reflecting the body's inflammatory/immune state. The study aimed to evaluate the relationship between the SIRI on admission and aneurysmal subarachnoid hemorrhage (aSAH)-associated pneumonia and compare with other currently used bio-markers. We reviewed 562 successive patients with aneurysmal SAH who underwent endovascular treatment between January 2019 and September 2021. ASAH-associated pneumonia was diagnosed using the modified Centers for Disease Control and Prevention criteria. The SIRI on admission was calculated as monocyte count × neutrophil count / lymphocyte count. Multiple logistic regression models were used for data analysis. A total of 158 (28.11%) patients developed aSAH-associated pneumonia. Using the Multiple logistic regression analysis, a notable dose-response association was found between the elevated SIRI (fourth quartile) and aSAH-associated pneumonia (adjusted odds ratio = 6.759; 95% confidence interval [CI], 3.280-13.930; p < 0.001 [p for trend < 0.001]). The SIRI (0.701, 95% CI: 0.653-0.749) presented a higher area under the curve (AUC) than systemic immune- inflammation index (SII) (0.669, 95% CI: 0.620-0.718) (p = 0.089); neutrophil-to-lymphocyte ratio (NLR) (0.665, 95% CI: 0.616-0.714) (p = 0.035) and platelet-lymphocyte ratio (PLR) (0.587, 95% CI: 0.534-0.641) (p < 0.001). A higher SIRI on admission was associated with aSAH-associated pneumonia, which may guide further clinical trials of prophylactic antibiotic therapy.

Fractalkine Enhances Hematoma Resolution and Improves Neurological Function via CX3CR1/AMPK/PPARγ Pathway After GMH.

BACKGROUND: Hematoma clearance has been a proposed therapeutic strategy for hemorrhagic stroke. This study investigated the impact of CX3CR1 (CX3C chemokine receptor 1) activation mediated by r-FKN (recombinant fractalkine) on hematoma resolution, neuroinflammation, and the underlying mechanisms involving AMPK (AMP-activated protein kinase)/PPARγ (peroxisome proliferator-activated receptor gamma) pathway after experimental germinal matrix hemorrhage (GMH). METHODS: A total of 313 postnatal day 7 Sprague Dawley rat pups were used. GMH was induced using bacterial collagenase by a stereotactically guided infusion. r-FKN was administered intranasally at 1, 25, and 49 hours after GMH for short-term neurological evaluation. Long-term neurobehavioral tests (water maze, rotarod, and foot-fault test) were performed 24 to 28 days after GMH with the treatment of r-FKN once daily for 7 days. To elucidate the underlying mechanism, CX3CR1 CRISPR, or selective CX3CR1 inhibitor AZD8797, was administered intracerebroventricularly 24 hours preinduction of GMH. Selective inhibition of AMPK/PPARγ signaling in microglia via intracerebroventricularly delivery of liposome-encapsulated specific AMPK (Lipo-Dorsomorphin), PPARγ (Lipo-GW9662) inhibitor. Western blot, Immunofluorescence staining, Nissl staining, Hemoglobin assay, and ELISA assay were performed. RESULTS: The brain expression of FKN and CX3CR1 were elevated after GMH. FKN was expressed on both neurons and microglia, whereas CX3CR1 was mainly expressed on microglia after GMH. Intranasal administration of r-FKN improved the short- and long-term neurobehavioral deficits and promoted M2 microglia polarization, thereby attenuating neuroinflammation and enhancing hematoma clearance, which was accompanied by an increased ratio of p-AMPK (phosphorylation of AMPK)/AMPK, Nrf2 (nuclear factor erythroid 2-related factor 2), PPARγ, CD36 (cluster of differentiation 36), CD163 (hemoglobin scavenger receptor), CD206 (the mannose receptor), and IL (interleukin)-10 expression, and decreased CD68 (cluster of differentiation 68), IL-1ß, and TNF (tumor necrosis factor) α expression. The administration of CX3CR1 CRISPR or CX3CR1 inhibitor (AZD8797) abolished the protective effect of FKN. Furthermore, selective inhibition of microglial AMPK/PPARγ signaling abrogated the anti-inflammation effects of r-FKN after GMH. CONCLUSIONS: CX3CR1 activation by r-FKN promoted hematoma resolution, attenuated neuroinflammation, and neurological deficits partially through the AMPK/PPARγ signaling pathway, which promoted M1/M2 microglial polarization. Activating CX3CR1 by r-FKN may provide a promising therapeutic approach for treating patients with GMH.

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.

Association between smoking and intracranial artery dissection in patients aged less than 50 years: A propensity score-matched analysis.

INTRODUCTION: Smoking is a common risk factor for stroke in the young population. Intracranial artery dissection (ICAD) is a major cause of stroke in this population. However, the association between smoking and ICAD in young patients is not well characterized. We aimed to evaluate the association between smoking and ICAD in young individuals using propensity score-matched analysis. METHODS: We conducted a retrospective study of consecutive patients aged <50 years with ICAD who were admitted to Beijing Tiantan Hospital between January 2016 and December 2020. Patients with other non-atherosclerotic/non-aneurysmal cerebrovascular diseases were selected as controls. Propensity score matching was based on age and sex. Smoking and other vascular risk factors were compared between the two groups. RESULTS: The ICAD and control group included 120 and 197 patients, respectively. Propensity score matching resulted in 70 matched pairs. Smoking was the only significant factor association with ICAD in the matched cohort (p=0.031). CONCLUSIONS: In this propensity score-matched analysis, smoking showed a positive association with ICAD in young patients with common cerebrovascular diseases that were neither atherosclerotic nor aneurysmal. Further studies are required to investigate the predictive role of smoking for ICAD in the young population.

Immunostimulant In Situ Fibrin Gel for Post-operative Glioblastoma Treatment by Macrophage Reprogramming and Photo-Chemo-Immunotherapy.

Tumor recurrence remains the leading cause of treatment failure following surgical resection of glioblastoma (GBM). M2-like tumor-associated macrophages (TAMs) infiltrating the tumor tissue promote tumor progression and seriously impair the efficacy of chemotherapy and immunotherapy. In addition, designing drugs capable of crossing the blood-brain barrier and eliciting the applicable organic response is an ambitious challenge. Here, we propose an injectable nanoparticle-hydrogel system that uses doxorubicin (DOX)-loaded mesoporous polydopamine (MPDA) nanoparticles encapsulated in M1 macrophage-derived nanovesicles (M1NVs) as effectors and fibrin hydrogels as in situ delivery vehicles. In vivo fluorescence imaging shows that the hydrogel system triggers photo-chemo-immunotherapy to destroy remaining tumor cells when delivered to the tumor cavity of a model of subtotal GBM resection. Concomitantly, the result of flow cytometry indicated that M1NVs comprehensively improved the immune microenvironment by reprogramming M2-like TAMs to M1-like TAMs. This hydrogel system combined with a near-infrared laser effectively promoted the continuous infiltration of T cells, restored T cell effector function, inhibited the infiltration of myeloid-derived suppressor cells and regulatory T cells, and thereby exhibited a strong antitumor immune response and significantly inhibited tumor growth. Hence, MPDA-DOX-NVs@Gel (MD-NVs@Gel) presents a unique clinical strategy for the treatment of GBM recurrence.

Effects of different stent size selection on pipeline embolization device treatment of intracranial aneurysms.

Background: Pipeline embolization device (PED) is becoming increasingly common in therapeutic practice. In idealized model studies, treatment effectiveness may vary with different stent sizes in the same vasculature. The true effect of stent size selection in the clinical setting remains unknown, however. Objective: To determine the true effect of stent size selection in the clinical setting. Design: It is a retrospective review. Methods: A retrospective review was conducted on consecutive patients with aneurysms treated with a PED at our institution. The primary exposures were the difference between the diameter of the stent and the parent artery (DD) and the difference between the length of the stent and the aneurysm neck (DL). The outcomes were the clinical and angiographic results, perioperative complications, balloon application, and in-stent stenosis. The results were generated using univariable and multivariable logistic regression and restricted cubic spline (RCS) curves. Results: A larger DD was significantly associated with incomplete occlusion [odds ratio (OR) = 2.37; 95% confidence interval (CI) = 1.43-3.98; p < 0.001], while a larger DL was significantly associated with balloon application (OR = 1.12; 95% CI = 1.02-1.23; p = 0.021) and in-stent stenosis (>25%) (OR = 1.07; 95% CI = 1.01-1.16; p = 0.042). The RCS curve indicated that the risk of incomplete occlusion increased as the DD became larger, the possibility of balloon application increased as the DL increased when the DL was >5.7 mm, and the risk of in-stent stenosis (>25%) increased as the DL increased. Conclusion: In the clinical setting, stent selection was associated with treatment effectiveness and may add to the treatment burden. These occurrences should be considered for aneurysms treated with PED.

In-depth investigation of formic acid pretreatment for various biomasses: Chemical properties, structural features, and enzymatic hydrolysis.

Formic acid pretreatment is a promising approach for fractionating biomass, and it has the advantages of efficient recycling and removal of hemicellulose and lignin. Biomass is one of the most plentiful resources on earth, yet its chemical structure differs significantly between woody and herbaceous biomass. The influence of formic acid pretreatment on the fractionation of woody and herbaceous biomasses, as well as changes in physical-chemical properties, was investigated in this study. The results indicated that formic acid is universal in the biorefinery of different biomass, however, herbaceous biomass had greater xylan and lignin removal than woody biomass (especially softwood). Formic acid pretreatment not only considerably improved the enzymatic efficiency of herbaceous biomass, but also had a good effect on the enzymatic efficiency of poplar. This study also found that the correlation between residual xylan content and enzymatic efficiency after pretreatment was much higher than that of lignin content.

Parent artery occlusion after pipeline embolization device implantation of intracranial saccular and fusiform aneurysms.

BACKGROUND: Studies reporting parent artery occlusion (PAO) after pipeline embolization device (PED) implantation are limited. The aim of this study was to investigate the incidence rate and risk factors of PAO after PED implantation. METHODS: In this retrospective study, we enrolled consecutive patients with intracranial saccular and fusiform aneurysms treated with PED implantation at our institution. Multivariate logistic regression analysis was subsequently performed to determine the risk factors for PAO. RESULTS: A total of 588 saccular and fusiform aneurysms were finally enrolled in the study. PAO was found in 14 (2.38%) aneurysms. The aneurysm complete occlusion rate was 79.6%. Compared with the non-PAO group, aneurysms in the PAO group were larger in size (20.08 vs 9.61 mm; p<0.001), had a greater neck diameter (9.92 vs 6.15 mm; p=0.001), and had higher frequencies of adjunctive coils (64.3% vs 35.7%; p=0.028). In the multivariate logistic analysis, aneurysm size (OR 1.12, 95% CI 1.02 to 1.24; p=0.016) and the presence of poor wall apposition after balloon angioplasty (OR 7.74, 95% CI 1.28 to 46.82; p=0.026) were associated with PAO occurrence after adjusting for confounding factors. CONCLUSIONS: In this study, the incidence rate of PAO following PED implantation was 2.38% in intracranial saccular and fusiform aneurysms. Aneurysm size and residual presence of poor wall apposition after balloon angioplasty were risk factors for PAO. Further research is required to better understand the mechanisms of PAO.

Economic evaluation of intravenous alteplase for stroke with the time of onset between 4.5 and 9 hours.

BACKGROUND: A clinical trial proved the clinical effectiveness of perfusion imaging-guided intravenous thrombolysis with alteplase for patients with acute ischemic stroke (AIS) with the time of onset between 4.5 and 9 hours. This study aimed to assess the lifetime cost-effectiveness of alteplase versus placebo from the perspective of Chinese and United States (US) healthcare payers. METHODS: A decision-analytic model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) associated with alteplase or placebo. Model inputs were extracted from published sources. Incremental costs, incremental QALYs, and incremental cost-effectiveness ratio (ICER) were calculated to evaluate the base-case scenario. One-way and probabilistic sensitivity analysis were performed to evaluate uncertainty in the results. RESULTS: In China, alteplase yielded an additional lifetime QALY of 0.126 with an additional cost of Chinese Yuan (¥) ¥9552 compared with placebo, and the ICER was ¥83 950 (US$12 157)/QALY. In the US, alteplase had a higher QALY (difference: 0.193) with a lower cost (difference: US$-2024) compared with placebo. In probabilistic sensitivity analyses, alteplase had a 42.54% to 78.3% probability of being cost-effective compared with placebo in China when the willingness-to-pay (WTP) threshold ranged from ¥72 447/QALY to ¥217 341/QALY. In the US, alteplase had a 93.47% to 93.57% probability of being cost-effective under the WTP threshold of US$100 000/QALY to US$150 000/QALY. These findings remained robust under one-way sensitivity analysis. CONCLUSION: For patients with AIS with a time of onset between 4.5 and 9 hours, perfusion imaging-guided intravenous alteplase was likely to be cost-effective in China and was cost-effective in the US when compared with placebo.

Morphological characteristics associated with ruptured intracranial vertebral artery dissecting aneurysms.

OBJECTIVE: Morphological risk factors for the rupture of intracranial vertebral artery dissecting aneurysms (IVADAs) have not been well characterized. In this study, we aim to identify morphological characteristics associated with IVADA rupture. METHODS: We conducted a retrospective study of 249 consecutive patients with single IVADAs (31 ruptured and 218 unruptured) admitted to Beijing Tiantan Hospital between January 2016 and December 2020. Various morphological parameters were measured using three-dimensional digital subtraction angiography images. Univariate and multivariate logistic regression analyses were performed to identify morphological characteristics associated with IVADA rupture. RESULTS: Univariate regression analysis revealed that the coexistence of significant proximal and distal stenosis and posterior inferior cerebellar artery (PICA) involvement were associated with IVADA rupture, while the origin from the dominant vertebral artery was inversely associated with the rupture. Multivariate regression analysis demonstrated that the coexistence of significant proximal and distal stenosis (OR 22.00, 95% CI 5.60 to 86.70, p<0.001) and PICA involvement (OR 4.55, 95% CI 1.36 to 15.20, p=0.014) were independently associated with IVADA rupture. CONCLUSION: The coexistence of significant proximal and distal stenosis and PICA involvement were independently associated with IVADA rupture. These morphological characteristics may facilitate the assessment of rupture risk in patients with IVADAs.

Flow diversion treatment for giant intracranial serpentine aneurysms.

Background: Giant serpentine aneurysms (GSAs) are among the most complex and challenging type of intracranial aneurysms. Surgical clipping, bypass, or endovascular parent artery occlusion has been the main treatment of GSAs in the past. However, studies on flow diversion (FD) are limited. Therefore, we reported our experience with patients with GSAs treated with FD. Methods: Patients with GSAs treated with FD from 2012 to 2020 in our single center were retrospectively reviewed. Angiographic outcomes were graded according to the O'Kelly-Marotta scale as complete occlusion (D), trace filling (C), entry remnant (B), or aneurysm filling (A). Clinical outcomes were assessed using the modified Rankin scale (mRS) score. We also collected the patients' treatment details and perioperative complications. Results: Thirteen patients with 14 aneurysms were included, including three in the anterior circulation and 11 in the posterior circulation. Grades B-D were found in 72.7% (8/11) of the GSAs. Good prognosis (mRS score, 0-2) was found in 66.7% (8/12) and 50.0% (6/12) of the patients at the 6-month and latest follow-up, respectively. Parent artery occlusion was found in three cases of GSAs. Five postoperative complications were observed, including two minor complications and three major complications. Conclusion: Although reconstructive treatment with FD could be considered as one of the treatment strategies for patients with both anterior and posterior circulation GSAs, however, the risk of complications and parent artery occlusion should be considered.

Periprocedural cerebrovascular complications and 30-day outcomes of endovascular treatment for intracranial vertebral artery dissecting aneurysms.

OBJECTIVE: The authors undertook an evaluation of periprocedural cerebrovascular complications and 30-day outcomes of endovascular treatment for intracranial vertebral artery dissecting aneurysms (IVADAs) and assessed the relevant risk factors. METHODS: The authors included a series of 195 patients who had undergone endovascular treatment for 198 IVADAs. Clinical data, morphological characteristics, treatment details, and periprocedural cerebrovascular complications including intraprocedural rupture, intraprocedural thrombosis, intracranial hemorrhage (ICH), transient ischemic attack (TIA), and ischemic stroke (IS) were recorded. After evaluation of the 30-day modified Rankin Scale (mRS) scores, the authors applied univariate and multivariate logistic regression analyses to identify the risk factors for complications and 30-day unfavorable clinical outcomes. RESULTS: There were no intraprocedural ruptures, but the authors recorded intraprocedural thrombosis (n = 5), ICH (n = 3), TIA (n = 1), and IS (n = 13), comprising an 11.1% (22/198) complication rate. Multivariate logistic regression analysis indicated that hyperlipidemia (odds ratio [OR] 3.17, 95% confidence interval [CI] 1.20-8.41, p = 0.020), IS history (OR 5.55, 95% CI 1.46-21.01, p = 0.012), and subarachnoid hemorrhage (SAH) (OR 4.48, 95% CI 1.52-13.20, p = 0.007) were risk factors for overall complications, whereas aneurysmal height (OR 0.77, 95% CI 0.61-0.98, p = 0.032) was a protective factor. SAH (OR 6.44, 95% CI 1.54-26.89, p = 0.011) and preprocedural mRS score > 2 (OR 5.07, 95% CI 1.01-25.59, p = 0.049) were independent risk factors for perforator occlusion stroke. Periprocedural cerebrovascular complications (OR 32.09, 95% CI 3.00-343.94, p = 0.004) and preprocedural mRS score > 2 (OR 319.92, 95% CI 30.28-3379.98, p < 0.001) were independent risk factors for 30-day unfavorable clinical outcomes. CONCLUSIONS: Hyperlipidemia, IS history, and SAH were independent predictors for overall periprocedural cerebrovascular complications of endovascular treatment for IVADAs, but aneurysmal height was an independent protective factor. SAH and preprocedural mRS score > 2 were independent risk factors for perforator occlusion stroke. Preprocedural mRS score > 2 and periprocedural complications were independent risk factors for 30-day unfavorable clinical outcomes.

Cost-effectiveness of recombinant tissue-type plasminogen activator for acute ischaemic stroke with unknown time of onset: a Markov modelling analysis from the Chinese and US perspectives.

OBJECTIVE: The effectiveness of MRI-guided intravenous recombinant tissue-type plasminogen activator (r-tPA) for acute ischaemic stroke (AIS) with an unknown time of onset has been demonstrated by the WAKE-UP Trial. We aim to evaluate its long-term cost-effectiveness from the perspective of Chinese and US healthcare payers. METHODS: A combination of decision tree and Markov model was built to project lifetime costs and quality-adjusted life-years (QALYs) associated with intravenous r-tPA or placebo treatment. Model inputs including the transition probabilities, costs and utilities were derived from the WAKE-UP Trial, similar cost-effectiveness studies and other published sources. To compare intravenous r-tPA to placebo, we calculated incremental costs, incremental QALYs and incremental cost-effectiveness ratio (ICER). One-way sensitivity, probabilistic sensitivity and subgroup analyses were performed to evaluate uncertainty in the results. RESULTS: In China, intravenous r-tPA gained an additional lifetime QALY of 0.293 with an additional cost of the Chinese Yuan (¥) of 7871 when compared with placebo, resulting in an ICER of ¥26 870 (US$3894)/QALY. In the USA, intravenous r-tPA yielded a higher QALY (difference: 0.430) and lower cost (difference: ¥-4563) when compared with placebo. In probabilistic sensitivity analyses, intravenous r-tPA had a 97.8% and 99.8% probability of being cost-effective or cost-saving in China and the USA, respectively. These findings remained robust under one-way sensitivity and subgroup analysis except for patients with a National Institute of Health Stroke Scale Score of less than 4, between 11 and 16, and over 16. CONCLUSIONS: MRI-guided intravenous r-tPA for patients with AIS with an unknown time of onset is cost-effective in China and cost-saving in the USA.

Phase I/II trial of local interstitial chemotherapy with arsenic trioxide in patients with newly diagnosed glioma.

Background: Glioma is the most common primary brain tumor in adults with poor prognosis. The glioma patients benefit from STUPP strategy, including maximum and safe resection and adjuvant radiotherapy and chemotherapy. Arsenic trioxide could inhibit various tumors. However, it is a challenge to evaluate the efficiency and safety of srsenic trioxide in glioma patients. Objective: The arsenic trioxide has the potent therapeutic effect on glioma. However, the safety and efficacy of local interstitial chemotherapy with arsenic trioxide in newly diagnosed glioma patients is unclear. Methods: All patients received partial or complete tumor resection and intraoperative implantation of Ommaya reservoirs followed by standard radiotherapy. Arsenic trioxide with the starting dose 0.3 mg was administered via an Ommaya reservoir catheter inserted into the tumor cavity for 5 consecutive days every 3 months for a total of eight cycles unless tumor progression or excessive toxicity was observed. Results: No hematological or grade 4 non-hematological toxicity was observed in any patient during arsenic trioxide treatment. The maximum tolerated dose of 1.5 mg of arsenic trioxide was safe and well tolerated. The median overall survival for WHO grade 3 glioma was 33.6 months, and for glioblastoma was 13.9 months. The median progression-free survival for WHO grade 2 glioma was 40.3 months, for grade 3 glioma was 21.5 months, and for glioblastoma was 9.5 months. Conclusion: These results suggest that arsenic trioxide is safe and well tolerated with local delivery into the tumor cavity of the brain, and the dose recommended for a phase II trial is 1.5 mg.

Efficient transfer hydrogenation of ketones using molybdenum complexes by comprehensively verifying the auxiliary ligands.

Molybdenum complexes ligated with N1,N1-dialkyl-N2-(5,6,7,8-tetrahydroquinolin-8-yl)ethane-1,2-diamines and auxiliary ligands, providing various structural features, were developed: [NNH/NNHN]Mo(CO)4/3 (Mo1-Mo3), [NNHN]Mo(CO)2Br (Mo4-Mo5), [NNH]Mo(CO)(η3-C3H5)Br (Mo6) and [NNHN/S]Mo(CO)(PPh3)2 (Mo7-Mo8). All the complexes were highly active in the transfer hydrogenation (TH) of a model substrate (acetophenone), providing excellent yields of 1-phenylethanol. The structural variation in the ligand framework had a modest effect on the catalyst performance as compared to the changes in the auxiliary ligands Br, PPh3 and CO. This structural evolution provided the complex [Mo(NNH)(η3-C3H5)(CO)2Br] (Mo6) as the most effective catalyst not only for the transfer hydrogenation of acetophenone but also for a wide range of diverse ketones (up to 43 examples). Moreover, easy purification of the products by only removing the acetone byproduct is another noteworthy feature of this environmentally friendly route.

Economic Evaluation of Ticagrelor Plus Aspirin Versus Aspirin Alone for Acute Ischemic Stroke and Transient Ischemic Attack.

Background: Although ticagrelor plus aspirin is more effective than aspirin alone in preventing the 30-day risk of a composite of stroke or death in patients with an acute mild-to-moderate ischemic stroke (IS) or transient ischemic attack (TIA), the cost-effectiveness of this combination therapy remains unknown. This study aims to determine the cost-effectiveness of ticagrelor plus aspirin compared with aspirin alone. Methods: A combination of decision tree and Markov model was built to estimate the expected costs and quality-adjusted life-years (QALYs) associated with ticagrelor plus aspirin and aspirin alone in the treatment of patients with an acute mild-to-moderate IS or TIA. Model inputs were extracted from published sources. One-way sensitivity, probabilistic sensitivity, and subgroup analyses were performed to test the robustness of the findings. Results: Compared with aspirin alone, ticagrelor plus aspirin gained an additional lifetime QALY of 0.018 at an additional cost of the Chinese Yuan Renminbi (¥) of 269, yielding an incremental cost-effectiveness ratio of ¥15,006 (US$2,207)/QALY. Probabilistic sensitivity analysis showed that ticagrelor plus aspirin had a probability of 99.99% being highly cost-effective versus aspirin alone at the current willingness-to-pay threshold of ¥72,447 (US$10,500)/QALY in China. These findings remain robust under one-way sensitivity and subgroup analyses. Conclusions: The results indicated that early treatment with a 30-days ticagrelor plus aspirin for an acute mild-to-moderate IS or TIA is highly cost-effective in a Chinese setting.