Deacetylase SIRT2 Inhibition Promotes Microglial M2 Polarization Through Axl/PI3K/AKT to Alleviate White Matter Injury After Subarachnoid Hemorrhage.

White matter injury (WMI) subsequent to subarachnoid hemorrhage (SAH) frequently leads to an unfavorable patient prognosis. Previous studies have indicated that microglial M1 polarization following SAH results in the accumulation of amyloid precursor protein (APP) and degradation of myelin basic protein (MBP), thereby catalyzing the exacerbation of WMI. Consequently, transitioning microglial polarization towards the M2 phenotype (neuroprotective state) represents a potential therapeutic approach for reversing WMI. The SIRT2 gene is pivotal in neurological disorders such as neurodegeneration and ischemic stroke. However, its function and underlying mechanisms in SAH, particularly how it influences microglial function to ameliorate WMI, remain unclear. Our investigations revealed that in post-SAH, there was a temporal increase in SIRT2 expression, predominantly in the cerebral corpus callosum area, with notable colocalization with microglia. However, following the administration of the SIRT2 inhibitor AK-7, a shift in microglial polarization towards the M2 phenotype and an improvement in both short-term and long-term neuronal functions in rats were observed. Mechanistically, CO-IP experiments confirmed that SIRT2 can interact with the receptor tyrosine kinase Axl within the TAM receptor family and act as a deacetylase to regulate the deacetylation of Axl. Concurrently, the inhibition of SIRT2 by AK-7 can lead to increased expression of Axl and activation of the anti-inflammatory pathway PI3K/Akt signaling pathway, which regulates microglial M2 polarization and consequently reduces WMI. However, when Axl expression was inhibited by the injection of the shAxl virus into the lateral ventricles, the downstream signaling pathways were significantly suppressed. Rescue experiments also confirmed that the neuroprotective effects of AK-7 can be reversed by PI3K inhibitors. These data suggest that SIRT2 influences WMI by affecting microglial polarization through the Axl/PI3K/AKT pathway, and that AK-7 could serve as an effective therapeutic drug for improving neurological functions in SAH patients.

Plasma Proteomics to Identify Drug Targets and Potential Drugs for Retinal Artery Occlusion: An Integrated Analysis in the UK Biobank.

Retinal artery occlusion (RAO), which is positively correlated with acute ischemic stroke (IS) and results in severe visual impairment, lacks effective intervention drugs. This study aims to perform integrated analysis using UK Biobank plasma proteome data of RAO and IS to identify potential targets and preventive drugs. A total of 7191 participants (22 RAO patients, 1457 IS patients, 8 individuals with both RAO and IS, and 5704 healthy age-gender-matched controls) were included in this study. Unique 1461 protein expression profiles of RAO, IS, and the combined data set, extracted from UK Biobank Plasma proteomics projects, were analyzed using both differential expression analysis and elastic network regression (Enet) methods to identify shared key proteins. Subsequent analyses, including single cell type expression assessment, pathway enrichment, and druggability analysis, were conducted for verifying shared key proteins and discovery of new drugs. Five proteins were found to be shared among the samples, with all of them showing upregulation. Notably, adhesion G-protein coupled receptor G1 (ADGRG1) exhibited high expression in glial cells of the brain and eye tissues. Gene set enrichment analysis revealed pathways associated with lipid metabolism and vascular regulation and inflammation. Druggability analysis unveiled 15 drug candidates targeting ADGRG1, which demonstrated protective effects against RAO, especially troglitazone (-8.5 kcal/mol). Our study identified novel risk proteins and therapeutic drugs associated with the rare disease RAO, providing valuable insights into potential intervention strategies.

Microsurgical clipping versus endovascular therapy for treating patients with middle cerebral artery aneurysms presenting with neurological ischemic symptoms.

Studies comparing different treatment methods in patients with middle cerebral artery (MCA) aneurysms in different subgroups of onset symptoms are lacking. It is necessary to explore the safety and efficacy of open surgical treatment and endovascular therapy in patients with MCA aneurysms in a specific population. This study aimed to compare microsurgical clipping versus endovascular therapy regarding complication rates and outcomes in patients with MCA aneurysms presenting with neurological ischemic symptoms. This was a retrospective cohort study in which 9656 patients with intracranial aneurysms were screened between January 2014 and July 2022. Further, 130 eligible patients were enrolled. The primary outcome was the incidence of serious adverse events (SAEs) within 30 days of treatment, whereas secondary outcomes included postprocedural target vessel-related stroke, disabling stroke or death, mortality, and aneurysm occlusion rate. Among the 130 included patients, 45 were treated with endovascular therapy and 85 with microsurgical clipping. The primary outcome of the incidence of SAEs within 30 days of treatment was significantly higher in the clipping group [clipping: 23.5%(20/85) vs endovascular: 8.9%(4/45), adjusted OR:4.05, 95% CI:1.20-13.70; P = 0.024]. The incidence of any neurological complications related to the treatment was significantly higher in the clipping group [clipping:32.9%(28/85) vs endovascular:15.6%(7/45); adjusted OR:3.49, 95%CI:1.18-10.26; P = 0.023]. Postprocedural target vessel-related stroke, disabling stroke or death, mortality rate, and complete occlusion rate did not differ significantly between the two groups. Endovascular therapy seemed to be safer in treating patients with MCA aneurysms presenting with neurological ischemic symptoms compared with microsurgical clipping, with a significantly lower incidence of SAEs within 30 days of treatment and any neurological complications related to the treatment during follow-up.

Sex-specific social, lifestyle, and physical health risk factors in cataracts development.

BACKGROUND: Cataract is a leading cause of blindness worldwide. However, little is known about sex differences in cataracts. Our study aimed to explore potential sex differences in the relationships between key social, lifestyle, and physical health risk factors and the incidence of cataracts. METHODS: A total of 117,972 participants from the UK Biobank were included in this prospective cohort study. Cox proportional hazard models were used to calculate hazard ratios (HRs) and female-to-male ratios of HRs (RHRs) with 95% confidence intervals (CIs) for cataract risk factors. Poisson regression was used to assess the incidence of cataracts (per 10,000 person-years). RESULTS: A total of 117,972 individuals without preexisting eye diseases were enroled in the analysis. 4172 subjects (54.8% female) were diagnosed with cataracts during follow-up. The crude incidence rates per 10,000 person-years were 35.06 for females and 29.15 for males. The incidence of cataracts increased in both males and females with factors such as Asian or Black ethnicity, smoking status, obesity, diabetes, and myopia. However, males who consumed alcohol or were unemployed suffered a greater risk of cataracts compared to their female counterparts, while high socioeconomic status, elevated blood pressure and metabolic syndrome were associated with a greater risk of cataracts in females than in males. CONCLUSION: This study provides a comprehensive overview of sex differences in the associations between cataracts and various risk factors. Our findings highlight that socioeconomic and lifestyle risk factors are more strongly linked to cataract risk in males, whereas females with systemic diseases face a greater risk of developing cataract.

Self-expanding intracranial drug-eluting stent system in patients with symptomatic intracranial atherosclerotic stenosis: initial experience and midterm angiographic follow-up.

BACKGROUND: Symptomatic intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke worldwide. In patients undergoing endovascular treatment for ICAS, in-stent restenosis (ISR) is associated with ischemic stroke recurrence. OBJECTIVE: Intracranial drug-eluting self-expanding stent systems (COMETIU; Sinomed Neurovita Technology Inc., CHN) are new devices for treating ICAS. This study evaluated the perioperative experience and medium-term outcomes of COMETIU in 16 patients. METHODS: We prospectively analyzed 16 patients with ICAS (≥ 70% stenosis) who underwent intravascular therapy between September 4, 2022, and February 1, 2023. The primary outcome was the incidence of ISR at 6 months postoperatively. The secondary efficacy outcomes were device and technical success rates. The secondary safety outcomes included stroke or death within 30 days after the procedure and the cumulative annual rate of recurrent ischemic stroke in the target-vessel territory from 31 days to 6 months and 1 year. RESULTS: A total of 16 patients with 16 intracranial atherosclerotic lesions were treated with 16 COMETIUs. All procedures were performed under general anesthesia with 100% device and technical success rates, with no cases of periprocedural stroke or death. The mean radiographic follow-up duration was at least 6 months postoperatively, and all patients presented for radiographic and clinical follow-up. There were no reported ischemic or hemorrhagic strokes. Angiographic follow-up for all patients revealed no cases of ISR. CONCLUSION: COMETIU is safe and effective for treating ICAS, with minimal risk during the procedure and a low rate of ISR during medium-term follow-up.

The antioxidant effect of tetrahedral framework nucleic acid-based delivery of small activating RNA targeting DJ-1 on retinal oxidative stress injury.

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are the world's leading causes of blindness. The retinal pigment epithelium (RPE) and vascular endothelial cell exposed to oxidative stress is the major cause of AMD and DR. DJ-1, an important endogenous antioxidant, its overexpression is considered as a promising antioxidant treatment for AMD and DR. Here, we modified the tetrahedral frame nucleic acids (tFNAs) with DJ-1 saRNAs as a delivery system, and synthesized a novel nanocomplex (tFNAs-DJ-1 saRNAs). In vitro studies show that tFNAs-DJ-1 saRNAs can efficiently transfer DJ-1 saRNAs to human umbilical vein endothelial cells (HUVECs) and ARPE-19s, and significantly increased their cellular DJ-1 level. Reactive oxygen species expression in H2O2-treated HUVECs and ARPE-19s were decreased, cell viability was enhanced and cell apoptosis were inhibited when tFNAs-DJ-1 saRNAs were delivered. Moreover, tFNAs-DJ-1 saRNAs preserved mitochondrial structure and function under oxidative stress conditions. In the aspect of molecular mechanism, tFNAs-DJ-1 saRNAs activated Erk and Nrf2 pathway, which might contribute to its protective effects against oxidative stress damage. To conclude, this study shows the successfully establishment of a simple but effective delivery system of DJ-1 saRNAs associated with antioxidant effects in AMD and DR, which may be a promising agent for future treatment in oxidative stress-related retinal disorders.

LAMC1 attenuates neuronal apoptosis via FAK/PI3K/AKT signaling pathway after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The poor prognosis in patients with subarachnoid hemorrhage (SAH) is often attributed to neuronal apoptosis. Recent evidence suggests that Laminin subunit gamma 1 (LAMC1) is essential for cell survival and proliferation. However, the effects of LAMC1 on early brain injury after SAH and the underlying mechanisms are unknown. The current study aimed to reveal the anti-neuronal apoptotic effect and the potential mechanism of LAMC1 in the rat and in the in vitro SAH models. METHODS: The SAH model of Sprague-Dawley rats was established by endovascular perforation. Recombinant LAMC1 (rLAMC1) was administered intranasally 30 min after modeling. LAMC1 small interfering RNA (LAMC1 siRNA), focal adhesion kinase (FAK)-specific inhibitor Y15 and PI3K-specific inhibitor LY294002 were administered before SAH modeling to explore the neuroprotection mechanism of rLAMC1. HT22 cells were cultured and stimulated by oxyhemoglobin to establish an in vitro model of SAH. Subsequently, SAH grades, neurobehavioral tests, brain water content, blood-brain barrier permeability, western blotting, immunofluorescence, TUNEL, and Fluoro-Jade C staining were performed. RESULTS: The expression of endogenous LAMC1 was markedly decreased after SAH, both in vitro and in vivo. rLAMC1 significantly reduced the brain water content and blood-brain barrier permeability, improved short- and long-term neurobehavior, and decreased neuronal apoptosis. Furthermore, rLAMC1 treatment significantly increased the expression of p-FAK, p-PI3K, p-AKT, Bcl-XL, and Bcl-2 and decreased the expression of Bax and cleaved caspase -3. Conversely, knockdown of endogenous LAMC1 aggravated the neurological impairment, suppressed the expression of Bcl-XL and Bcl-2, and upregulated the expression of Bax and cleaved caspase-3. Additionally, the administration of Y15 and LY294002 abolished the protective roles of rLAMC1. In vitro, rLAMC1 significantly reduced neuronal apoptosis, and the protective effects were also abolished by Y15 and LY294002. CONCLUSION: Exogenous LAMC1 treatment improved neurological deficits after SAH in rats, and attenuated neuronal apoptosis in both in vitro and in vivo SAH models, at least partially through the FAK/PI3K/AKT pathway.

Use of the Tubridge flow diverter in the treatment of intracranial aneurysms: a single center experience.

To investigate the safety and effect of Tubridge flow diverter deployment for the treatment of intracranial aneurysms, 85 patients with intracranial aneurysms treated with the Tubridge flow diverter were retrospectively enrolled. The clinical data including the baseline data, aneurysm parameters before and after treatment, and follow-up outcomes were assessed. Among 85 patients, there were 35 (41.2%) males and 50 females (58.8%) aged 17-77 (mean 56.7 ± 11.1) years with 110 aneurysms. Five (5.9%) patients initially presented with subarachnoid hemorrhage from aneurysm rupture. The aneurysm size was 2-30 (mean 8.6) mm, and the aneurysm neck was 2-10.6 (mean 5.7 ± 2.3) mm. Ninety-three Tubridge stents were deployed. Twenty-five (29.4%) patients experienced adjunctive loose coiling. Blood flow was significantly reduced from entering the aneurysm after stent deployment. Periprocedural complications occurred in three (3.5%) patients, including in-stent thrombosis during embolization in one patient (1.2%), conjunctiva edema on the right in one patient (1.2%), and acute multiple cerebral infarctions in one patient (1.2%). Angiographic follow-up was conducted in 67 (78.8%) patients 3-36 (mean 15.3 ± 5.6) months later. In 11 (16.4% or 11/67) patients, blood flow still entered the aneurysm with the O'Kelly-Marotta (OKM) grade B in two (3.0%) patients and grade C in nine (13.4%), whereas complete occlusion (OKM grade D) was achieved in the other 56 (83.6% or 56/67) aneurysms. In-stent stenosis was present in five (7.5%) patients with approximately 25% stenosis in three (4.5%) patients and 50% in two (3.0%). In conclusion, the Tubridge flow diverter can be safely and efficiently applied in the treatment of small and large intracranial aneurysms, with a low periprocedural complication rate, a high occlusion degree, and a low in-stent stenosis rate at follow-up even though large aneurysms may necessitate a longer surgical time and adjunctive coiling.

Risk Factors for Cerebral Hyperperfusion Syndrome After Combined Revascularization in Adult Patients with Moyamoya Disease.

BACKGROUND: Cerebral hyperperfusion syndrome (CHS) is known as a complication after bypass surgery for Moyamoya disease (MMD). However, the incidence of CHS has not been accurately reported, and there is no consensus on the risk factors associated with it. AIM: The aim of this study was to determine the risk factors associated with postoperative CHS after surgical combined revascularization used to treat adult patients with MMD. OBJECTIVE: To assess the frequency and characteristics of CHS in patients with MMD after revascularization operations. METHODS: Patients who received combined revascularization from Jan 2021 to Nov 2022 were retrospectively reviewed. Preoperative clinical characteristics and radiographic features were recorded. Postoperative CHS after surgery were examined. Multivariate logistic regression analyses were performed to identify the risk factors for CHS. RESULTS: A total of 133 patients (141 hemispheres) were included in this study. Postoperative CHS were observed in 28 hemispheres (19.8%), including focal cerebral hyperperfusion syndrome (FCHS) in 20 hemispheres (14.2%), hemorrhage in 4 (2.8%) hemispheres, seizures in 4 (2.8%) hemispheres. The results of multivariate logistic regression analysis indicated that preoperative hypertension (OR 4.705, 95% CI 1.323 ~ 12.554, p = 0.014), cerebral hemorrhage onset (OR 5.390, 95% CI 1.408 ~ 20.642, p = 0.014) and higher Hct level (OR 1.171, 95% CI 1.051 ~ 1.305, p = 0.004) were significantly associated with CHS after combined revascularization. CONCLUSIONS: Preoperative hypertension, cerebral hemorrhage onset, and higher Hct level were independent risk factors for CHS after combined revascularization.

Long-term outcomes of anti-VEGF treatment with 5+PRN regimen for macular edema due to central retinal vein occlusion.

AIM: To assess the long-term outcomes of treating macular edema (ME) associated with central retinal vein occlusion (CRVO) with a regimen of "5+pro re nata (PRN)". METHODS: This retrospective study included 27 eyes of 27 patients with ME associated with non-ischemic CRVO (non-iCRVO group, n=15) and ischemic CRVO (iCRVO group, n=12). The eyes were treated with five consecutive intravitreal injections of conbercept or ranibizumab, followed by reinjections as needed or PRN. Retinal laser photocoagulation or intravitreal dexamethasone implants (DEX) were implemented in both groups when necessary. The best-corrected visual acuity (BCVA, logMAR) and central retinal thickness (CRT) were recorded at baseline, at 1, 2, 3, 4, 5, 6, and 12mo, and at the final visit. The efficacy rates of BCVA and CRT before and after treatment were calculated. The number of injections at each visit and the incidence of adverse events were also recorded. RESULTS: The patients, aged 59.4±15.1y, were followed up for 24.7±8.8mo (range: 15-42mo). After treatment, BCVA improved significantly from 1.04±0.56 logMAR at baseline to 0.59±0.36 logMAR (P=0.038) at the final visit in all patients. Both the non-iCRVO and the iCRVO groups achieved improved BCVA compared to the baseline at all visit points, but there was no statistical significance (P=0.197 and 0.33, respectively). The mean CRT was statistically reduced compared to baseline at all visit points in all the eyes and in both groups (all P<0.001). The apparent effective rate was 22.22% for BCVA and 37.04% for CRT after the first injection, 48.15% for BCVA and 62.96% for CRT after 5 consecutive injections, and 74.08% for BCVA and 100% for CRT at the end of follow up. The average number of injections in all patients was 9.0±2.4 at 12mo and 14.9±8.1 finally with no statistical significance between both groups (P>0.05). Laser treatment was applied to all eyes in the iCRVO group, while only 5 patients in the non-iCRVO group. Six patients in the non-iCRVO group and 3 patients in the iCRVO group had a drug switch. DEX was applied to 4 eyes in the non-iCRVO group and 5 eyes in the iCRVO group. CONCLUSION: The 5+PRN anti-vascular endothelial growth factor (VEGF) regimen is found to be safe and effective for both iCRVO and non-iCRVO, especially in the iCRVO group. The best regimen for such patients needs to be further investigated. Adjuvant laser therapy and DEX are necessary in some cases.

RU.521 mitigates subarachnoid hemorrhage-induced brain injury via regulating microglial polarization and neuroinflammation mediated by the cGAS/STING/NF-κB pathway.

BACKGROUND: The poor prognosis of subarachnoid hemorrhage (SAH) is often attributed to neuroinflammation. The cGAS-STING axis, a cytoplasmic pathway responsible for detecting dsDNA, plays a significant role in mediating neuroinflammation in neurological diseases. However, the effects of inhibiting cGAS with the selective small molecule inhibitor RU.521 on brain injury and the underlying mechanisms after SAH are still unclear. METHODS: The expression and microglial localization of cGAS following SAH were investigated with western blot analysis and immunofluorescent double-staining, respectively. RU.521 was administered after SAH. 2'3'-cGAMP, a second messenger converted by activated cGAS, was used to activate cGAS-STING. The assessments were carried out by adopting various techniques including neurological function scores, brain water content, blood-brain barrier permeability, western blot analysis, TUNEL staining, Nissl staining, immunofluorescence, morphological analysis, Morris water maze test, Golgi staining, CCK8, flow cytometry in the in vivo and in vitro settings. RESULTS: Following SAH, there was an observed increase in the expression levels of cGAS in rat brain tissue, with peak levels observed at 24 h post-SAH. RU.521 resulted in a reduction of brain water content and blood-brain barrier permeability, leading to an improvement in neurological deficits after SAH. RU.521 had beneficial effects on neuronal apoptosis and microglia activation, as well as improvements in microglial morphology. Additionally, RU.521 prompted a shift in microglial phenotype from M1 to M2. We also noted a decrease in the production of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, and an increase in the level of the anti-inflammatory cytokine IL-10. Finally, RU.521 treatment was associated with improvements in cognitive function and an increase in the number of dendritic spines in the hippocampus. The therapeutic effects were mediated by the cGAS/STING/NF-κB pathway and were found to be abolished by 2'3'-cGAMP. In vitro, RU.521 significantly reduced apoptosis and neuroinflammation. CONCLUSION: The study showed that SAH leads to neuroinflammation caused by microglial activation, which contributes to early brain injury. RU.521 improved neurological outcomes and reduced neuroinflammation by regulating microglial polarization through the cGAS/STING/NF-κB pathway in early brain injury after SAH. RU.521 may be a promising candidate for the treatment of neuroinflammatory pathology after SAH. Video Abstract.

Complications after endovascular treatment of large basilar trunk aneurysms.

BACKGROUND AND PURPOSE: Large basilar trunk aneurysms (BTAs) have a poor natural history if left untreated and always pose a significant challenge to endovascular treatment. The present study aimed to analyze the complications after endovascular treatment of large BTAs. METHODS: This was a retrospective, observational, cohort study. Between January 2015 and September 2022, 9116 patients with intracranial aneurysms came to our institution for management, of which 34 patients with 34 large (≥10 mm) BTAs were treated with endovascular treatment. Postprocedural complications, clinical, and angiographic outcomes were evaluated. RESULTS: All 34 patients (34 aneurysms) were successfully treated, of which 13 aneurysms were treated with flow diversion (FD), and 21 aneurysms were treated with stent-assisted coiling. Neurological complications occurred in 12 (35.3%) patients, with 7 (20.6%) deaths. Ischemic complications occurred in 10 (29.4%) patients, and 4 (11.8%) patients experienced hemorrhagic events. The incidences of favorable outcomes at discharge and last follow-up were 85.3% and 75.8%, respectively. The cumulative survival rates at 1 and 3 years were 86.5% and 71.4%, respectively. Unilateral vertebral artery sacrifice was associated with postprocedural complications (hazard ratio: 3.74, 95% confidence interval: 1.06-13.25, p = 0.041). The postprocedural complication rates were comparable between patients treated with FD and stent-assisted coiling (5/13, 38.5% vs. 7/21, 33.3%, p > 0.99). Angiography follow-up was available for 21 patients, and complete aneurysm occlusion was observed in 16/21 (76.2%) aneurysms. CONCLUSIONS: Endovascular treatment might be a feasible option for treating large BTAs. However, clinicians should be alerted to procedure-related complications, especially ischemic complications that cause disability or death. Unilateral vertebral artery sacrifice might be associated with postprocedural complications.

Deliberately Staged Combined Endovascular Embolization and Subsequent Microsurgery Resection for the Treatment of Cerebral Arteriovenous Malformations.

OBJECTIVE: Complex cerebral arteriovenous malformations (AVMs) require a combined therapy of endovascular embolization and microsurgical resection to eliminate the lesion and maximize neurological protection, while a deliberate time interval might contribute to optimal clinical outcomes. The present study aimed to explore the feasibility of this paradigm. METHODS: All patients who underwent deliberately planned presurgery embolization and microsurgery resection between 2015 and 2023 were reviewed, with baseline data, postoperative complications, and follow-up outcomes recorded. The modified Rankin scale (mRS) was used to evaluate clinical outcomes, with mRS 0-2 defined as good. RESULTS: A total of 30 patients were included in the study (15 were ruptured AVMs). The median Spetzler-Martin grade of baseline AVMs was 3 (interquartile range: 2-3). The median interval between the last embolization and microsurgery was 5 days (interquartile range: 2.25-7). The complete removal rate was 100%, and the overall permanent complication rate was 16.67%. At the last follow-up, 26 patients achieved mRS 0-2, while 28 had improved or unaltered mRS. The last follow-up mRS significantly improved from baseline and discharge (P = 0.0006 and P = 0.006). The last follow-up mRS decreased by 0.65 for each additional day of time interval before the 4.4-day inflection point (ß = -0.65, P = 0.02) in the AVM ruptured cohort. CONCLUSIONS: The deliberately staged combined procedure of embolization and microsurgery might be a safe and efficacious strategy for Spetzler-Martin grade 2-5 AVMs, 4-5 days might be an appropriate staged time interval for ruptured AVMs, although further studies are needed to substantiate these findings.

Impact of qualifying artery on the efficacy of stenting plus medical therapy versus medical therapy alone in patients with symptomatic intracranial stenosis: a post-hoc analysis of the CASSISS trial.

BACKGROUND: A recent trial failed to show any benefit of stenting plus medical therapy over medical therapy alone in patients with symptomatic intracranial stenosis. We aimed to examine whether the symptomatic qualifying artery modifies the effect of stenting plus medical therapy. METHODS: This is a post-hoc analysis of the CASSISS trial that included patients with symptomatic intracranial stenosis, randomly assigned to undergo stenting plus medical therapy or medical therapy alone; 358/380 patients were included. Multivariable logistic regression analysis was used with an interaction term to estimate the altered treatment effect by the qualifying artery. The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The five secondary outcomes included stroke or death related to the qualifying artery territory at 2 and 3 years. RESULTS: No significant treatment allocation-by-stenosis site interaction was observed (Pinteraction=0.435). Compared with medical therapy alone, the adjusted ORs for stenting plus medical therapy were 2.73 (95% CI 0.42 to 17.65) for internal carotid artery stenosis, 1.20 (95% CI 0.29 to 4.99) for M1 stenosis, 0.23 (95% CI 0.02 to 2.31) for vertebral artery stenosis, and 1.33 (95% CI 0.34 to 5.28) for basilar artery stenosis. Of the five secondary outcomes, none showed a significant treatment allocation-by-stenosis site interaction including stroke in the qualifying artery territory at 2 years (Pinteraction=0.659) and 3 years (Pinteraction=0.493). CONCLUSIONS: Among patients with transient ischemic attacks or ischemic stroke due to severe intracranial atherosclerotic stenosis, there was no evidence that the symptomatic qualifying artery could determine the addition of stenting to medical therapy.

Low-profile visualized intraluminal support-within-Enterprise overlapping-stent technique versus flow diversion in the treatment of intracranial vertebrobasilar trunk dissecting aneurysms.

Background: It is necessary to explore the safety and efficacy of various endovascular treatment techniques in the treatment of patients with intracranial vertebrobasilar trunk dissecting aneurysms (VBTDAs). This study sought to compare the clinical and angiographic outcomes of patients with intracranial VBTDAs following low-profile visualized intraluminal support (LVIS)-within-Enterprise overlapping-stent technique with those of flow diversion (FD). Methods: This was a retrospective, observational, cohort study. Between January 2014 and March 2022, 9,147 patients with intracranial aneurysms were screened, and 91 patients with 95 VBTDAs who underwent LVIS-within-Enterprise overlapping-stent assisted-coiling technique or FD were included in the analysis. The primary outcome was the complete occlusion rate at the last angiographic follow-up. The secondary outcomes included adequate aneurysm occlusion, in-stent stenosis/thrombosis, general neurological complications, neurological complications within 30 days after the procedure, the mortality rate, and unfavorable outcomes. Results: Among the 91 included patients, 55 were treated with LVIS-within-Enterprise overlapping-stent technique (the LE group) and 36 were treated with FD (the FD group). The angiography results at the median follow-up time of 8 months showed complete occlusion rates of 90.0% and 60.9% for the LE and FD groups, respectively, with an adjusted odds ratio of 5.79 (95% CI: 1.35-24.85; P=0.01). Adequate aneurysm occlusion (P=0.98), in-stent stenosis/thrombosis (P=0.46), general neurological complications (P=0.22), neurological complications within 30 days after the procedure (P=0.63), mortality rate (P=0.31), and unfavorable outcomes (P=0.07) at the last clinical follow-up did not differ significantly between the 2 groups. Conclusions: A significantly higher complete occlusion rate for VBTDAs was found following LVIS-within-Enterprise overlapping-stent technique as compared with FD. The 2 treatment modalities have comparable adequate occlusion rates and safety profiles.

Comparison of pipeline classic and flex embolization devices in endovascular performance for intracranial aneurysms.

To investigate the endovascular performance of the Pipeline Classic embolization device (PED Classic) and PED Flex device (PED Flex) in the treatment of intracranial aneurysms. Fifty-three patients with intracranial aneurysms treated with the PED Classic were retrospectively enrolled into the PED Classic group, and 118 patients with intracranial aneurysms treated with the PED Flex were enrolled into the PED Flex group. The Procedure time, contrast dosage, fluoroscopy time, and perioperative complications were analyzed. The success rate of the stenting procedure was 100% in both groups. In the PED Classic group, 58 PED Classic devices were implanted, and 26 aneurysms underwent coil embolization. In the PED Flex group, 126 PED Flex devices were implanted, and 35 aneurysms underwent concomitant coil embolization. The procedure time was significantly (P < .001) greater in the PED Classic (159.0 ±â€…42.0 minutes) than in the PED Flex (121.9 ±â€…4.0 minutes) group. The dosage of contrast agent (156.4 ±â€…39.4 vs 110.1 ±â€…38.5 mL) and the total fluoroscopic time (34.7 ±â€…5.7 minutes vs 22.8 ±â€…7.6 minutes) were significantly (P < .001) greater in the PED Classic than in the PED Flex group. Peri-procedural complications occurred in 5 (9.4%) patients in the PED Classic group and in 3 (2.5%) patients in the Flex group, without a statistically significant (P = .11) difference. The performance of the PED Flex device may be safer and easier than that of the PED Classic device in the treatment of intracranial aneurysms despite some serious complications which remain to be prevented.

LVIS-within-enterprise double-stent technique with coil embolization in the treatment of patients with acutely ruptured intracranial vertebrobasilar artery-dissecting aneurysms.

Objective: This study aimed to evaluate the feasibility of the low-profile visualized intraluminal support (LVIS)-within-enterprise double-stent technique for patients with acutely ruptured intracranial vertebrobasilar artery-dissecting aneurysms (ari-VBDAs). Methods: A total of 30 patients with ari-VBDAs who underwent reconstructive treatment using LVIS-within-enterprise double-stent technique with coil embolization between January 2014 and May 2022 were retrospectively enrolled. Patients' characteristics and clinical and imaging outcomes were reviewed. The functional outcomes were assessed using the modified Rankin scale (mRS). Results: A total of 34 ari-VBDAs were identified, including seven (20.6%) basilar artery aneurysms and 27 (79.4%) vertebral artery aneurysms. All aneurysms were successfully treated in the acute phase. In total, six (20.0%) patients experienced in-hospital serious adverse events, including two deaths (6.7%). The median clinical follow-up time of the remaining 28 patients was 20.0 (IQR, 7.3-40.8) months. The incidences of dependency or death (mRS score of 3-6) at discharge and at the last follow-up were 16.7% and 14.3%, respectively. Aneurysm rebleeding occurred in one (3.3%) patient periprocedurally. In total, three (10.0%) patients had ischemic events, one of which occurred during the periprocedural period and two occurred during follow-up. A total of two patients (6.7%) underwent ventriculoperitoneal shunt. Imaging follow-up was available for 14 patients at the median of 12.0 (IQR, 7.0-12.3) months, with a complete occlusion rate of 93.3% (14/15). In total, one patient experienced parent artery occlusion, and no aneurysm was recanalized. Conclusion: LVIS-within-enterprise double-stent technique with coil embolization for the treatment of patients with ari-VBDAs could be performed with a good safety profile and high technical success rate. The rate of complete aneurysm occlusion during follow-up seemed to be satisfactory.

Safety and effect of pipeline flex embolization device for complex unruptured intracranial aneurysms.

To investigate the safety and short-term effect of Pipeline Flex devices in the treatment of complex unruptured intracranial aneurysms, a retrospective study was performed for patients with complex unruptured intracranial aneurysms who were treated with the Pipeline Flex embolization device (PED Flex device) combined with or without coiling. The clinical, endovascular, and follow-up data were analyzed. One hundred and thirty-one patients with 159 complex unruptured cerebral aneurysms were treated with the PED Flex device, with 144 Flex devices deployed. Periprocedural complications occurred in four patients, resulting in the complication rate of 3.1%, including ischemic complications in three patients (2.3%) and hemorrhagic complication in one (0.8%). At discharge, the mRS was 0 in 101 (77.1%) patients, 1 in 25 (19.1%), 2 in four (3.1%), and 4 in one (0.8%), with the good prognosis rate (mRS 0-2) of 99.2%. Clinical follow-up was carried out in 87 (66.4%) patients 3-42 months after the procedure, with the mRS of 0 in 78 (89.7%), 1 in five (5.7%), 2 in three (3.4%), and 4 in one (1.1%). No significant (P = 0.16) difference existed in the mRS at discharge compared with that at clinical follow-up. Angiographic follow-up was performed in 61 (46.7%) patients with 80 (50.3%) aneurysms at 3-40 months, with the OKM grade of D in 57 (71.3%) aneurysms, C in eight (10%), and B in 15 (18.8%). Asymptomatic instent stenosis occurred in four patients (6.6%). In conclusion: The treatment of complex intracranial aneurysms with the Pipeline Flex embolization device may be safe and effective, with a high complete occlusion rate, a decreased complication rate, and a good prognosis rate at medium follow-up.

Measurement of Foveal Retinal Thickness in Myopic Patients Using Different Display Modes on Optical Coherence Tomography: A Retrospective, Cross-Sectional Study.

INTRODUCTION: The aim of this work is to investigate the differences in the measurement of foveal retinal thickness in myopic patients between two display modes (1:1 pixel and 1:1 micron) on optical coherence tomography (OCT). METHODS: Horizontal OCT line scan through the central fovea was used for manual measurement of foveal retinal thickness under the two display modes, and the values were compared using Wilcoxon signed-rank test. Correlations between the OCT image tilting angle (OCT ITA) and differences in OCT measurement were analyzed by Spearman's test. RESULTS: 127 participants with a median age of 28 years, a median spherical equivalent (SE) of - 8.5 D, and a median axial length (AL) of 27.04 mm. There were significant differences between the two display modes, with a median absolute difference (median relative difference) of 13.33 µm (2.75%) for the central foveal thickness (CFT), 5.33 µm (1.28%) for the Henle fiber and outer nuclear layer thickness (HFL + ONL), 3 µm (6.47%) for the external limiting membrane to ellipsoid zone distance (ELM-EZ), and 4 µm (8.77%) for the ellipsoid zone to retinal pigment epithelium distance (EZ-RPE) (all p < 0.05). The differences in foveal retinal thickness between the two display modes were significantly correlated with the OCT ITA (r = 0.732 for CFT, 0.561 for HFL + ONL, 0.642 for ELM-EZ, and 0.471 for EZ-RPE, all p < 0.05). CONCLUSIONS: Disparities between the two display modes were found in the manual measurement of foveal retinal thickness and correlated to the OCT ITA.