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.

DETECTION OF MORPHOLOGIC PATTERNS OF DIABETIC MACULAR EDEMA USING A DEEP LEARNING APPROACH BASED ON OPTICAL COHERENCE TOMOGRAPHY IMAGES.

PURPOSE: To develop a deep learning (DL) model to detect morphologic patterns of diabetic macular edema (DME) based on optical coherence tomography (OCT) images. METHODS: In the training set, 12,365 OCT images were extracted from a public data set and an ophthalmic center. A total of 656 OCT images were extracted from another ophthalmic center for external validation. The presence or absence of three OCT patterns of DME, including diffused retinal thickening, cystoid macular edema, and serous retinal detachment, was labeled with 1 or 0, respectively. A DL model was trained to detect three OCT patterns of DME. The occlusion test was applied for the visualization of the DL model. RESULTS: Applying 5-fold cross-validation method in internal validation, the area under the receiver operating characteristic curve for the detection of three OCT patterns (i.e., diffused retinal thickening, cystoid macular edema, and serous retinal detachment) was 0.971, 0.974, and 0.994, respectively, with an accuracy of 93.0%, 95.1%, and 98.8%, respectively, a sensitivity of 93.5%, 94.5%, and 96.7%, respectively, and a specificity of 92.3%, 95.6%, and 99.3%, respectively. In external validation, the area under the receiver operating characteristic curve was 0.970, 0.997, and 0.997, respectively, with an accuracy of 90.2%, 95.4%, and 95.9%, respectively, a sensitivity of 80.1%, 93.4%, and 94.9%, respectively, and a specificity of 97.6%, 97.2%, and 96.5%, respectively. The occlusion test showed that the DL model could successfully identify the pathologic regions most critical for detection. CONCLUSION: Our DL model demonstrated high accuracy and transparency in the detection of OCT patterns of DME. These results emphasized the potential of artificial intelligence in assisting clinical decision-making processes in patients with DME.

Retinal microvasculature impairment in patients with congenital heart disease investigated by optical coherence tomography angiography.

IMPORTANCE: A high prevalence of retinal abnormalities have been reported in congenital heart disease (CHD), but quantitative analysis of retinal vasculature is scarce. Optical coherence tomography angiography (OCTA) is a noninvasive method to quantitatively assess the retinal microvasculature. BACKGROUND: To investigate the retinal microvasculature changes in CHD patients by using OCTA. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 158 participants including 57 cyanotic CHD (CCHD) patients, 60 acyanotic CHD (ACHD) patients and 41 control subjects were included. METHODS: All participants underwent a comprehensive ophthalmologic examination, including refraction measurement, intraocular pressure measurement and OCTA. MAIN OUTCOME MEASURES: Vessel density (VD) was measured within the radial peripapillary capillary (RPC), superficial capillary plexus (SCP) and deep capillary plexus (DCP) of the macula. RESULTS: CCHD patients had significantly lower VD in the RPC, SCP and DCP (all P < .01) compared to control subjects, and significantly lower VD in the RPC and DCP (both P < .05) compared to ACHD patients. Besides, among the CHD group, VD in the RPC was positively correlated with oxygen saturation (whole image, ρ = 0.45; peripapillary, ρ = 0.48) and negatively correlated with haematocrit (whole image, ρ = 0.55; peripapillary, ρ = 0.55) (all P < .001). CONCLUSIONS AND RELEVANCE: Retinal VD might be a surrogate to reflect the effect of chronic systemic hypoxemia in CHD patients. OCTA could be a convenient and noninvasive tool to evaluate the retinal structure and function in CHD patients.

Comparison of clinical outcomes of different components of diabetic macular edema on optical coherence tomography.

PURPOSE: To evaluate the edema reduction after intravitreal injection of ranibizumab (IVR) in two diabetic macular edema (DME) components in the same eye using optical coherence tomography (OCT). METHODS: Totally 113 eyes with mixed OCT pattern of DME were included. All the eyes underwent best-corrected visual acuity (BCVA) examination and OCT scanning at baseline and follow-up visits (1, 3, and 6 months after 3 monthly consecutive IVR). The mixed OCT pattern of DME was classified into 2 OCT components: serous retinal detachment (SRD) component and non-SRD component. Foveal thickness of the SRD component (SRDFT) and the non-SRD component (NSRDFT) was compared between baseline and follow-up visits. Reduction and reduction ratio of the SRDFT and the NSRDFT at each follow-up were compared. When calculating the NSRDFT reduction ratio, we innovatively optimized a commonly used formula by subtracting the normal foveal thickness from the baseline NSRDFT. RESULTS: SRDFT was 265.6 ± 175.4 µm at baseline and was significantly decreased to 126.7 ± 114.4 µm at 1 month, to 110.5 ± 103.4 µm at 3 months, and to 110.4 ± 89.6 µm at 6 months (all P < 0.001). NSRDFT was 409.5 ± 173.1 µm at baseline and was significantly decreased to 274.1 ± 140.4 µm at 1 month, to 249.1 ± 95.9 µm at 3 months, and to 254.1 ± 90.4 µm at 6 months (all P < 0.001). There was no significant difference in reduction or reduction ratio between NSRDFT and SRDFT during follow-up (all P > 0.05). The correlation between BCVA and SRDFT was most significant at baseline (r = 0.366, P < 0.001) and the correlation between BCVA and NSRDFT was most significant at 6 months (r = 0.426, P < 0.001). BCVA improvement was more significantly correlated with reduction or reduction ratio of SRDFT at each follow-up timepoint (r = 0.271-0.426, all P < 0.01). CONCLUSIONS: IVR was effective in reducing both the SRD and non-SRD components of DME according to our optimized formula. The association between BCVA improvement and edema reduction was more significant in the SRD component.

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 (4.4%) hemispheres, seizures in 4 (4.4%) hemispheres. The results of multivariate logistic regression analysis indicated that preoperative hypertension (OR 3.940, 95% CI 1.275 ~ 12.180, p = 0.017), cerebral hemorrhage onset (OR 5.489, 95% CI 1.443 ~ 20.884, p = 0.013) and higher Hct level (OR 1.166, 95% CI 1.047 ~ 1.298, p = 0.005) 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.

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.

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.

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.

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.

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.

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.

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.

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.

Development and validation of a deep learning system to classify aetiology and predict anatomical outcomes of macular hole.

AIMS: To develop a deep learning (DL) model for automatic classification of macular hole (MH) aetiology (idiopathic or secondary), and a multimodal deep fusion network (MDFN) model for reliable prediction of MH status (closed or open) at 1 month after vitrectomy and internal limiting membrane peeling (VILMP). METHODS: In this multicentre retrospective cohort study, a total of 330 MH eyes with 1082 optical coherence tomography (OCT) images and 3300 clinical data enrolled from four ophthalmic centres were used to train, validate and externally test the DL and MDFN models. 266 eyes from three centres were randomly split by eye-level into a training set (80%) and a validation set (20%). In the external testing dataset, 64 eyes were included from the remaining centre. All eyes underwent macular OCT scanning at baseline and 1 month after VILMP. The area under the receiver operated characteristic curve (AUC), accuracy, specificity and sensitivity were used to evaluate the performance of the models. RESULTS: In the external testing set, the AUC, accuracy, specificity and sensitivity of the MH aetiology classification model were 0.965, 0.950, 0.870 and 0.938, respectively; the AUC, accuracy, specificity and sensitivity of the postoperative MH status prediction model were 0.904, 0.825, 0.977 and 0.766, respectively; the AUC, accuracy, specificity and sensitivity of the postoperative idiopathic MH status prediction model were 0.947, 0.875, 0.815 and 0.979, respectively. CONCLUSION: Our DL-based models can accurately classify the MH aetiology and predict the MH status after VILMP. These models would help ophthalmologists in diagnosis and surgical planning of MH.

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.

Spontaneous healing and complete disappearance of an intracranial vertebral artery dissecting aneurysm: A case report.

RATIONALE: Intracranial vertebrobasilar dissecting aneurysms (VBDAs) are associated with a greater tendency to rupture and a greater risk of worse outcomes than anterior circulation aneurysms. Spontaneous healing of a VBDA is very rare, and there have been very few case reports of spontaneous healing of an aneurysm. We describe a case of intracranial vertebral artery dissecting aneurysm that healed spontaneously and disappeared completely on follow-up images. PATIENT CONCERNS: A 40-years-old woman was referred to the neurology department because of a persistent headache, especially in the left occiput. DIAGNOSES: Magnetic resonance angiography and computed tomography angiography showed a left vertebral artery dissection-like aneurysm (4.5 × 2.0 × 2.5 mm in size) with proximal parent artery mild stenosis (40%). INTERVENTIONS: Flunarizine hydrochloride was administered for symptomatic treatment and follow-up angiography was performed. OUTCOMES: Digital subtraction angiography and magnetic resonance angiography showed that the aneurysm had completely disappeared at 3 months follow-up. High-resolution magnetic resonance vessel wall imaging revealed intimal thickening and mild stenosis in the left intracranial vertebral artery without an aneurysm signal. In addition, enhancement scanning revealed that the aneurysm area was moderately enhanced. MR-vessel wall imaging at 7 months follow-up showed that the enhancement was slightly reduced compared with the previous time. LESSONS: This case illustrates the relatively plastic nature of a vertebral dissecting aneurysm, indicating that spontaneous healing remains possible.

Conservative Therapy vs. Endovascular Approach for Intracranial Vertebrobasilar Artery Trunk Large Aneurysms: A Prospective Multicenter Cohort Study.

Background: Intracranial vertebrobasilar trunk large (≥10 mm) aneurysms (IVBTLAs) are rare and challenging to manage. In this study, we describe the natural prognosis and evaluate the safety and efficacy of endovascular treatment of IVBTLAs compared with conservative therapy. Methods: This prospective multicenter cohort study included patients with IVBTLAs, who chose either endovascular treatment (endovascular group) or conservative therapy (conservative group) after discussion with their doctors. The primary endpoint was the incidence of serious adverse events (SAEs) related to the target vessel, while secondary endpoints included target vessel-related mortality, major stroke, other serious adverse events, and aneurysm occlusion rate. Results: In total, 258 patients were referred to our two centers for the management of vertebrobasilar aneurysms, and 69 patients had IVBTLAs. Among them, 51 patients underwent endovascular treatment, and 18 patients received conservative therapy. The incidence of target vessel-related SAEs was 15.7% (8/51) in the endovascular group and 44.4% (8/18) in the conservative group (P = 0.031). The target vessel-related mortality was 2.0% (1/51) in the endovascular group and 38.9% (7/18) in the conservative group (P < 0.001). The cumulative survival rates in the endovascular group and conservative group within 1-year, 3-year, and 5-year were 98.0% vs. 83.3%, P = 0.020; 98.0% vs. 66.7%, P = 0.001; and 98.0% vs. 35.6%, P < 0.001, respectively. Multivariate analysis revealed conservative therapy, giant aneurysm, and ischemic onset as risks factor for SAEs. Conclusions: Compared with conservative treatment, endovascular treatment of the IVBTLAs may be associated with a lower incidence of SAEs, with higher 1-year, 3-year, and 5-year survival rates. Conservative therapy, giant aneurysm, and ischemic onset were associated with a high risk of SAEs.