CD147 Sparks Atherosclerosis by Driving M1 Phenotype and Impairing Efferocytosis.

BACKGROUND: Atherosclerosis is a globally prevalent chronic inflammatory disease with high morbidity and mortality. The development of atherosclerotic lesions is determined by macrophages. This study aimed to investigate the specific role of myeloid-derived CD147 (cluster of differentiation 147) in atherosclerosis and its translational significance. METHODS AND RESULTS: We generated mice with a myeloid-specific knockout of CD147 and mice with restricted CD147 overexpression, both in an apoE-deficient (ApoE-/-) background. Here, the myeloid-specific deletion of CD147 ameliorated atherosclerosis and inflammation. Consistent with our in vivo data, macrophages isolated from myeloid-specific CD147 knockout mice exhibited a phenotype shift from proinflammatory to anti-inflammatory macrophage polarization in response to lipopolysaccharide/IFN (interferon)-γ. These macrophages demonstrated a weakened proinflammatory macrophage phenotype, characterized by reduced production of NO and reactive nitrogen species derived from iNOS (inducible NO synthase). Mechanistically, the TRAF6 (tumor necrosis factor receptor-associated factor 6)-IKK (inhibitor of κB kinase)-IRF5 (IFN regulatory factor 5) signaling pathway was essential for the effect of CD147 on proinflammatory responses. Consistent with the reduced size of the necrotic core, myeloid-specific CD147 deficiency diminished the susceptibility of iNOS-mediated late apoptosis, accompanied by enhanced efferocytotic capacity mediated by increased secretion of GAS6 (growth arrest-specific 6) in proinflammatory macrophages. These findings were consistent in a mouse model with myeloid-restricted overexpression of CD147. Furthermore, we developed a new atherosclerosis model in ApoE-/- mice with humanized CD147 transgenic expression and demonstrated that the administration of an anti-human CD147 antibody effectively suppressed atherosclerosis by targeting inflammation and efferocytosis. CONCLUSIONS: Myeloid CD147 plays a crucial role in the growth of plaques by promoting inflammation in a TRAF6-IKK-IRF5-dependent manner and inhibiting efferocytosis by suppressing GAS6 during proinflammatory conditions. Consequently, the use of anti-human CD147 antibodies presents a complementary therapeutic approach to the existing lipid-lowering strategies for treating atherosclerotic diseases.

Solid Pseudopapillary Neoplasms of the Pancreas: Clinicopathologic Analysis and a Predictive Model.

Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare. They are considered low-grade malignancies, and a small percentage of patients experience recurrence or metastasis. It is critical to investigate associated biological behavior and identify patients at a risk of relapse. This was a retrospective study of 486 patients with SPNs who were diagnosed between 2000 and 2021. Their clinicopathologic features, including 23 parameters and prognoses were analyzed. Six patients (1.2%) presented with synchronous liver metastasis. A total of 21 patients experienced recurrence or metastasis postoperatively. The overall and disease-specific survival rates were 99.8% and 100%, respectively. The 5- and 10-year relapse-free survival (RFS) rates were 97.4% and 90.2%, respectively. Tumor size, lymphovascular invasion, and the Ki-67 index were independent predictors of relapse. Furthermore, a Peking Union Medical College Hospital-SPN risk model was built to evaluate the risk of relapse and compared it with the American Joint Committee on Cancer tumor staging system (eighth edition, 2017). Risk factors included 3 parameters: tumor size (>9 cm), lymphovascular invasion status (presence), and Ki-67 index (>1%). Risk grades were available for 345 patients, who were divided into 2 groups: (1) low risk (n = 124) and (2) high risk (n = 221). The group with no risk factors was designated as low risk and had a 10-year RFS of 100%. The group associated with 1 to 3 factors was designated as high risk, with a 10-year RFS of 75.3%. Receiver operating characteristic curves were generated, and the area under the curve was 0.791 for our model and 0.630 for the American Joint Committee on Cancer with respect to the cancer staging system. We validated our model in independent cohorts and demonstrated a sensitivity of 98.3%. In conclusion, SPNs are low-grade malignant neoplasms that rarely metastasize, and the 3 selected pathologic parameters can be used to predict their behavior. A novel Peking Union Medical College Hospital-SPN risk model was proposed for routine application to guide the patient counseling in clinical practice.

Salubrinal protects against inflammatory response in macrophage and attenuates psoriasiform skin inflammation by antagonizing NF-κB signaling pathway.

Psoriasiform skin inflammation is the common chronic skin inflammatory disease with no effective clinical therapy. Salubrinal is a multifunctional molecule playing a protective role in several conditions. Recently, studies have reported that Salubrinal is a potential therapeutic agent for inflammatory diseases. However, the protective role of Salubrinal in psoriasis-like skin inflammation remains unknown. In this article, imiquimod (IMQ)-induced psoriasis models were established in wild-type mice to explore the role of Salubrinal in the development of psoriasis. As a result, the IMQ-induced mouse models exhibited typical skin inflammation, which was alleviated by the administration of Salubrinal. Furthermore, RAW264.7 macrophage was stimulated with Lipopolysaccharide(LPS) in the presence or absence of Salubrinal. LPS stimulation elevated the expression of various inflammatory biomarkers, while the administration of Salubrinal abolished the function of LPS in RAW264.7 macrophages. In addition, the activation of the nuclear factor-kappa B (NF-κB) signaling pathway in both the LPS-stimulated RAW264.7 macrophage and psoriasis mouse models was antagonized by the administration of Salubrinal. Collectively, Salubrinal might be considered as a promising therapeutic agent for psoriasis-like skin inflammation.

Electrochemical Biosensor with Enhanced Antifouling Capability for COVID-19 Nucleic Acid Detection in Complex Biological Media.

Biofouling caused by the accumulation of biomolecules on sensing surfaces is one of the major problems and challenges to realize the practical application of electrochemical biosensors, and an effective way to counter this problem is the construction of antifouling biosensors. Herein, an antifouling electrochemical biosensor was constructed based on electropolymerized polyaniline (PANI) nanowires and newly designed peptides for the detection of the COVID-19 N-gene. The inverted Y-shaped peptides were designed with excellent antifouling properties and two anchoring branches, and their antifouling performances against proteins and complex biological media were investigated using different approaches. Based on the biotin-streptavidin affinity system, biotin-labeled probes specific to the N-gene (nucleocapsid phosphoprotein) of COVID-19 were immobilized onto the peptide-coated PANI nanowires, forming a highly sensitive and antifouling electrochemical sensing interface for the detection of COVID-19 nucleic acid. The antifouling genosensor demonstrated a wide linear range (10-14 to 10-9 M) and an exceptional low detection limit (3.5 fM). The remarkable performance of the genosensor derives from the high peak current of PANI, which is chosen as the sensing signal, and the extraordinary antifouling properties of designed peptides, which guarantee accurate detection in complex systems. These crucial features represent essential elements for future rapid and decentralized clinical testing.

lncRNA BSG-AS1 is hypoxia-responsive and promotes hepatocellular carcinoma by enhancing BSG mRNA stability.

Emerging evidence indicates that aberrant changes of lncRNAs expression induced by hypoxia participate in the development of HCC. The present study aimed to identify novel hypoxia-responsive lncRNAs and reveal its role and mechanism in HCC. Hypoxia exposure in HCC tissues was comprehensively estimated based on public data using multiple hypoxia gene signatures. Huh7 cells were treated with hypoxia and RNA-seq was performed. Then we analyzed the changes of lncRNAs in HCC tissues and cells exposed to hypoxia. We found that lncRNA BSG-AS1 was highly expressed in tissues with high hypoxia score. Then we verified the response of lncRNA BSG-AS1 to hypoxia in the cell hypoxia model in vitro. Through functional phenotypic analysis, we found that lncRNA BSG-AS1 can mediate the promoting effect of hypoxia on the proliferation and migration in HCC cells. RNA-seq was used to find the downstream target genes of lncRNA BSG-AS1. Sequencing data and wet experiments showed that mRNA of BSG decreased after knockout of lncRNA BSG-AS1, and mediated the promotive effect of lncRNA BSG-AS1 on proliferation and migration in HCC cells. The mechanism is that lncRNA BSG-AS1 can enhance the stability of BSG mRNA as antisense lncRNA. Finally, the data based on the public cohort and the cohort we collected suggested that the overexpression of lncRNA BSG-AS1 and BSG are related to the poor prognosis. In conclusion, lncRNA BSG-AS1 is a novel hypoxia-responsive lncRNA. LncRNA BSG-AS1 can positively regulate BSG, by maintaining the mRNA stability of BSG, thus promoting the proliferation and migration of HCC. High expression of lncRNA BSG-AS1 and BSG are risk factors for prognosis.

Development of celecoxib-derived antifungals for crop protection.

Selective COX-2 inhibitor celecoxib was found directly inhibiting the growth of tested phytopathogenic fungi with the inhibitory rate ranging from 30 to 40% at 100 µg/ml. Lead optimization of celecoxib led to the identification of compound 12 among its derivatives as the most active antifungal candidate. The antifungal effect of compound 12 was supposed to be independent of COX-2 inhibition. Transcriptome profiling analysis of Fusarium graminearium (PH-1) treated with compound 12 brought about 406 up-regulated and 572 down-regulated differentially express genes (DEGs) respectively.

Neddylation inhibition upregulates PD-L1 expression and enhances the efficacy of immune checkpoint blockade in glioblastoma.

Pevonedistat (MLN4924), a specific NEDD8-activating enzyme inhibitor, has been considered as a promising treatment for glioblastoma, which is currently in Phase I/II clinical trials. On the other hand, inhibition of neddylation pathway substantially upregulates the expression of T cell negative regulator programmed death-ligand 1 (PD-L1), which might account for the potential resistance via evasion of immune surveillance checkpoints. Whether administration of anti-PD-L1 enhances the efficacy of pevonedistat through a cytotoxic T cell-dependent mechanism in glioblastoma needs to be investigated. Here, we report that depletion of neddylation pathway key enzymes markedly elevates PD-L1 expression in glioblastoma cancer cells. Consistently, neddylation inhibitor pevonedistat significantly enhances PD-L1 expression in both glioblastoma cancer cell lines and animal models. Mechanistically, pevonedistat increases PD-L1 mRNA levels mainly through inhibiting Cullin1-F-box and WD repeat domain-containing 7 E3 ligase activity and accumulating c-MYC proteins, a direct transcriptional activator of PD-L1 gene expression. In addition, inhibition of Cullin3 activity by pevonedistat also blocks PD-L1 protein degradation. Importantly, pevonedistat attenuates T cell killing through PD-L1 induction, and blockade of PD-L1 restores the sensitivity of pevonedistat-treated glioblastoma cancer cells to T cell killing. The combination of pevonedistat and anti-PD-L1 therapy compared to each agent alone significantly increased the therapeutic efficacy in vivo. Our study demonstrates inhibition of neddylation pathway suppresses cancer-associated immunity and provides solid evidence to support the combination of pevonedistat and PD-L1/programmed cell death protein 1 immune checkpoint blockade as a potential therapeutic strategy to treat glioblastoma.

Ubiquitin-independent, Proteasome-mediated targeted degradation of KRAS in pancreatic adenocarcinoma cells using an engineered ornithine decarboxylase/antizyme system.

The oncogene KRAS not only promotes the tumorigenesis of pancreatic cancers but also is required for the malignant progression and metastasis of these cancers. Many methods have been explored to influence the malignant biological behavior of these cancers by targeting mutant KRAS. The ornithine decarboxylase/antizyme (ODC/AZ) system is another protein degradation pathway that exists in nature. The formation of an ODC and protein substrate complex through direct combination can promote its degradation by the 26S proteasome without ubiquitination, and this process can be catalyzed by AZ. In this study, we designed and reconstructed a chimeric fusion protein (named RC-ODC). The engineered fusion protein RC-ODC was confirmed to interact with the mutant KRAS oncoprotein in a co-immunoprecipitation assay, and the introduction of both RC-ODC and AZ resulted in degradation of the exogenous and endogenous mutant KRAS oncoprotein at the post-translational level independent of ubiquitination in vitro. Along with a decreased KRAS level, suppression of PANC-1 cell proliferation was detected in vitro and in vivo, and meanwhile downregulation of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) was also observed. Targeted degradation of the KRAS oncoprotein through the ODC/AZ pathway at the post-translational level may reflect a more effective future therapeutic strategy for pancreatic cancer patients. © 2018 The Authors. IUBMB Life published by Wiley Periodicals,Inc. on behalf of International Union of Biochemistry and Molecular Biology, 71(1):57-65, 2019.

Mitofusin 2 Exerts a Protective Role in Ischemia Reperfusion Injury Through Increasing Autophagy.

BACKGROUND/AIMS: Autophagy is essential for maintaining cellular homeostasis and the survival of terminally differentiated cells as neurons. In this study, we aim to investigate whether mitofusin 2, a mitochondrial fusion protein, mediates autophagy in cerebral ischemia/reperfusion (I/R) injury. METHODS: Primary cultured neurons were treated with oxygen-glucose deprivation/reperfusion to mimic cerebral I/R injury in vitro. Autophagosomes were visualized upon TEM. Autophagy-markers were then detected to monitor autophagy by western-blot and real-time PCR, and the autophagic flux was tracked with a mRFP-GFP-LC3 construct by fluorescence as well as autophagy inhibitors and agonists. The up- and downregulation of Mfn2 were through transfecting a lentivirusexpression vector respectively. And neuronal injury was detected by cell counting kit and TUNEL assay. RESULTS: Results showed I/R increased autophagosome formation and inhibited autolysosome degradation. Furthermore, use of autophagy related agents demonstrated that I/R injury was caused by insufficient autophagy and aggravated by impaired autophagic degradation. The results also indicated that mitofusin 2 could ameliorate I/R injury through increasing autophagosome formation and promoting the fusion of autophagosomes and lysosomes. In contrast, downregulation of mitofusin 2 aggravated the I/R injury by inhibiting autophagosome formation and the fusion of autophagosomes and lysosomes. Additionly, mitofusin 2 overexpression did not lead to autolysosome accumulation induced by I/R. CONCLUSIONS: In summary, this study explicitly demonstrated that mitofusin 2 could ameliorate I/R injury mainly through promoting autophagy, which represented a potential novel strategy for neuroprotection against cerebral I/R damage.

Initial changes in alveolar bone volume for sham-operated and ovariectomized rats in ligature-induced experimental periodontitis.

OBJECTIVES: Osteoporosis is a disease characterized by a reduction in bone mass, poor bone strength, and microarchitectural deterioration primarily in postmenopausal women. With respect to periodontal disease, osteoporosis is thought to contribute to pre-existing alveolar degeneration although the association between both diseases is not fully characterized. The aim of the present study was to observe the initial changes in mandibular alveolar bone for sham-operated and ovariectomized (OVX) rats in ligature-induced experimental periodontitis. MATERIALS AND METHODS: A total of 64 Wistar rats (7 weeks of age, 180-200 g) were used in this study (32 control sham-operated animals + ligature placement, 32 OVX animals + ligature placement). Following an 8-week period to induce an OVX model, micro-CT analysis was performed to calculate vertical and furcation bone loss of mandibular first molars at time points 0, 3, 7, and 11 days following ligature placement (six animals per group per time point). Furthermore, histological analysis was performed to calculate the loss of alveolar bone crest height from the cemento-enamel junction, and tartrate-resistant acid phosphatase (TRAP) staining was utilized to calculate the number of osteoclasts. RESULTS: The results from the present study demonstrate that OVX animals showed significant vertical bone loss at all time points when compared to control sham-operated animals. In the furcation area, no significant difference in bone loss was observed between sham-operated and OVX animals at 0, 3, and 7 days; however by 11 days, a significant decrease in bone volume/total volume and trabecular thickness was observed in the OVX group. The histological analysis also revealed that alveolar bone crest height was significantly reduced in OVX animals, and TRAP staining further revealed the greater number of multinucleated osteoclasts peaking at 3 days postligature placement. CONCLUSION: The results from the present study demonstrate a direct correlation between the osteoporotic phenotype and the progression of periodontal breakdown in a diseased-induced animal model. CLINICAL RELEVANCE: It may be suggested that an osteoporotic phenotype has the potential to speed periodontal breakdown and thus contributes to the overall degeneration of the periodontium in patients suffering from postmenopausal bone loss. Future research from human clinical studies are necessary to further understand the relationship between periodontal disease and osteoporosis.

Ongoing Geometric Remodeling of the Parent Artery After Flow-Diverter Stent Reconstruction in Cerebral Aneurysms: The Device Design Matters.

OBJECTIVE: Configuration changes of the parent artery (PA) after flow-diverter (FD) stent reconstruction, caused by the bending force of the device, may have an additional role in aneurysm occlusion as a result of the secondary alteration of intra-aneurysmal hemodynamics related to the geometry alteration of the vessel. To determine the degree of PA deformation and aneurysm occlusion rates after deployment of 2 different types of FD. METHODS: Patients treated with 2 different designs of cobalt-chromium braid (48 and 64 wire braid) structure FD were subject to analysis. Vascular angle changes at the level of the reconstructed segment immediately after FD deployment and at 1 year follow-up were measured and the potential relationship with aneurysmal occlusion rate was analyzed. RESULTS: Forty-two patients harboring 48 aneurysms were included in the present study. The aneurysms were divided into side wall (85.4%) and bifurcation types (14.6%). Twenty-six aneurysms were treated using the Pipeline FD (48 wire braid; 54.2%) and 22 using the Evolve FD (64 wire braid; 45.8%). Of the 48 aneurysms, 42 (87.5%) met the primary end point of complete occlusion at 12 months. The median postdeployment angle change was 7.04°± 4.59° for the Pipeline and 5.05°± 2.49° for the Evolve, whereas the median 12 months follow-up angle change was 15.49°± 10.99° and 10.01°± 8.83°, respectively. PA angle changes were significantly higher in the bifurcation group compared with the side wall group both during procedure and at 12 months follow-up. Angle change had a statistically nonsignificant association with complete aneurysm occlusion. CONCLUSIONS: PA deformation starts immediately after deployment and remodeling continues for 1 year after. Aneurysms located in the vessel bifurcation were more prone to PA straightening after FD deployment than were side wall aneurysms. Furthermore, Pipeline seemed to be more prone to inducing vascular deformation, compared with Evolve.

Endovascular treatment of intracranial dural arteriovenous fistulas with Onyx: A consecutive series of 62 patients from a single-center.

OBJECTIVE: Intracranial intracranial dural arteriovenous fistulas (DAVFs) are mainly treated with an endovascular approach and various embolic agents. The aim of this study was to investigate the efficacy and safety of Onyx embolization in the treatment of DAVFs and characterize the factors as sociated with complete obliteration. METHODS: This retrospective study was based on 62 patients with DAVFs who underwent endovascular treatment with Onyx alone or in combination with coils at our institution. Clinical and imaging data were collected and analyzed. RESULTS: A total of 62 patients with 64 DAVFs were treated with endovascular embolization. The most common primary symptom was ophthalmological signs with a rate of 37.1%. Cognard type III was the most commonly seen subtype (32.8%). The immediate complete occlusion and follow-up rate was 92.2% and 93.5%, respectively. Transvenous balloon-assisted sinus protection was used in 12 patients (18.8%). The pressure cooker technique was used in eight patients (12.5%). Complications were seen in five patients including intracerebral hemorrhage (n = 2), venous thrombotic events (n = 2), and glued microcatheter (n = 1). CONCLUSIONS: Endovascular Onyx alone or in combination with coils embolization is a safe and effective therapy for DAVFs. Favorable angiographic and clinical outcomes can be achieved using different endovascular approaches. Transvenous balloon-assisted sinus protection and the pressure cooker technique may help achieve complete occlusion of DAVFs.

Clinical efficacy, bone density, and follow-up in implant and orthodontic treatment for inclined adjacent teeth.

BACKGROUND: Tooth defects can cause elongation of occlusal teeth, leading to insufficient repair space. The combination of dental implant restoration and orthodontic treatment of oblique adjacent teeth has a significant therapeutic effect. AIM: To explore clinical efficacy, bone density, and follow-up of implant and orthodontic treatment for patients with inclined adjacent teeth. METHODS: In total, 98 patients with oblique adjacent teeth were randomly assigned to implant restoration combined with orthodontic treatment (group A, n = 49) or to receive implant restoration alone (group B, n = 49). Changes in alveolar ridge bone density and apical bone density were observed before and after treatment in the two groups. Changes in chewing function and language function were compared between the two groups of patients. Follow-up lasted for 12 mo after repair to observe any adverse reactions in the oral cavity. RESULTS: The clinical effective rates of group A and group B were 97.96% and 85.71%, respectively, with group A having a higher clinical effective rate than group B. After treatment, the bone density of the alveolar ridge and apical bone in both groups decreased compared to before treatment, while the chewing and language functions improved. The changes in various indicators in group A were more significant. After treatment, the satisfaction rate of group A (97.96%) was higher than that of group B (79.59%). The incidence of adverse reactions in group A (2.04%) was lower than that in group B (24.49%). CONCLUSION: The amalgamation of implant restoration and orthodontic treatment for adjacent tilted teeth demonstrates notable clinical efficacy, diminishes alveolar bone resorption, and fosters patient functional rehabilitation while exhibiting negligible adverse reactions.

Study the local metabolic changes of aneurysms through microcatheter sampling.

Intracranial aneurysm is the primary cause of nontraumatic subarachnoid hemorrhage. To assess aneurysm metabolism, we present a method of intra-operatively collecting blood samples from the aneurysm neck, as well as the proximal and distal responsible vessels, using microcatheters. Through these paired comparisons, we can eliminate the interpatient variation usually observed in plasma samples taken from the peripheral vein. We utilized 39 plasma samples from 13 intracranial patients to characterize the metabolite profiles using untargeted liquid chromatography-mass spectrometry. Our findings revealed that L-tyrosine is upregulated at relatively high levels at the aneurysm neck than the proximal and distal aneurysm, whereas phenylpyruvic acid, L-cystine, and L-ornithine are downregulated. Based on this, there was also a significant decrease in arginine within small aneurysm of the internal carotid artery. The 6-month follow-up indicated that patients who experienced good recovery had lower levels of biliverdin, bilirubin, and metabolites of coenzyme Q within the aneurysm. In conclusion, our investigation provides a comprehensive overview of plasma metabolites in patients with intracranial aneurysms, shedding light on potential pathogenetic mechanisms in unruptured intracranial aneurysms. Moreover, the study proposes innovative ideas for establishing postoperative follow-up timelines for flow diverter devices.

Neoadjuvant camrelizumab followed by concurrent camrelizumab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: a single-arm, phase II study.

Background: Neoadjuvant therapy combining camrelizumab with chemotherapy has emerged as a promising approach for treating locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal strategy for integrating immunotherapy with chemotherapy remains to be fully defined. This single-arm phase II study aimed to evaluate the efficacy and safety of neoadjuvant therapy with camrelizumab induction followed by camrelizumab plus chemotherapy in locally advanced ESCC. Methods: Patients with clinical stage cT2-4N0M0 or cTxN1-3M0 ESCC were enrolled in the study. Patients received one dose of camrelizumab (200 mg) followed by docetaxel (75 mg/m2) and nedaplatin (75 mg/m2) plus camrelizumab (200 mg) every 3 weeks for two cycles, and then underwent surgery within 3-4 weeks. The primary endpoint was the major pathological response (MPR) rate. The secondary endpoints included the pathological complete response (pCR) rate, R0 resection rate, downstaging rate, disease-free survival (DFS), overall survival (OS), and safety. Results: In total, 55 patients were enrolled in the study between 16 April 2020 and 30 October 2021. Of these 55 patients, 53 (96.4%) completed neoadjuvant therapy, and 48 (87.3%) underwent surgery. The MPR rate was 77.1% [37/48, 95% confidence interval (CI): 62.7-88.0%]. The pCR (ypT0N0) rate was 39.6% (19/48, 95% CI: 25.8-54.7%). All the patients had R0 resections. Primary tumor downstaging occurred in 44 (91.7%) patients, and nodal downstaging occurred in 19 (39.6%) patients. The 2-year DFS rate was 68.9% (95% CI: 53.0-80.4%), and the 2-year OS rate was 74.7% (95% CI: 60.2-84.6%). Grade ≥3 treatment-related adverse events (TRAEs) were observed in 7 (12.7%) patients. Conclusions: In conclusion, neoadjuvant camrelizumab followed by camrelizumab plus chemotherapy showed promising efficacy in treating locally advanced ESCC and had a manageable safety profile.

Benchmarking the CoW with the TopCoW Challenge: Topology-Aware Anatomical Segmentation of the Circle of Willis for CTA and MRA.

The Circle of Willis (CoW) is an important network of arteries connecting major circulations of the brain. Its vascular architecture is believed to affect the risk, severity, and clinical outcome of serious neuro-vascular diseases. However, characterizing the highly variable CoW anatomy is still a manual and time-consuming expert task. The CoW is usually imaged by two angiographic imaging modalities, magnetic resonance angiography (MRA) and computed tomography angiography (CTA), but there exist limited public datasets with annotations on CoW anatomy, especially for CTA. Therefore we organized the TopCoW Challenge in 2023 with the release of an annotated CoW dataset. The TopCoW dataset was the first public dataset with voxel-level annotations for thirteen possible CoW vessel components, enabled by virtual-reality (VR) technology. It was also the first large dataset with paired MRA and CTA from the same patients. TopCoW challenge formalized the CoW characterization problem as a multiclass anatomical segmentation task with an emphasis on topological metrics. We invited submissions worldwide for the CoW segmentation task, which attracted over 140 registered participants from four continents. The top performing teams managed to segment many CoW components to Dice scores around 90%, but with lower scores for communicating arteries and rare variants. There were also topological mistakes for predictions with high Dice scores. Additional topological analysis revealed further areas for improvement in detecting certain CoW components and matching CoW variant topology accurately. TopCoW represented a first attempt at benchmarking the CoW anatomical segmentation task for MRA and CTA, both morphologically and topologically.

Endovascular Treatment of a Traumatic Carotid Cavernous Fistula Concomitant with Intracranial Pseudoaneurysm by Flow Diverter, 2-Dimensional Operative Video.

Traumatic carotid cavernous fistulas (TCCFs) and traumatic intracranial pseudoaneurysms are uncommon vascular anomalies associated with head trauma.1,2 Detachable balloons, covered stents, or liquid embolic agents can be used to treat TCCFs in some conditions.3,4 TCCF concomitant with pseudoaneurysm is an extremely rare occurrence in the literature.5,6 In Video 1, we present a unique case of a TCCF concomitant with a giant pseudoaneurysm of the posterior communicating segment of the left internal carotid artery in a young patient. Both lesions were successfully managed with an endovascular treatment using a Tubridge flow diverter (MicroPort Medical Company, Shanghai, China), coils, and Onyx 18 (Medtronic, Bridgeton, Missouri, USA). No neurologic complications occurred due to the procedures. Six-month follow-up angiography illustrated complete resolution of fistula and pseudoaneurysm. This video shows a new treatment method for TCCF concomitant with a pseudoaneurysm. The patient consented to the procedure.

Single antiplatelet regimen in flow diverter treatment of cerebral aneurysms: The drug matters. A systematic review and meta-analysis.

BACKGROUND: Hemorrhagic and thromboembolic complications (TECs) are the main concerns in the endovascular treatment of intracranial aneurysms using flow diverter devices (FDs). The clinical demand for single antiplatelet therapy (SAPT) is increasing especially with the development of devices with lower thrombogenicity profile. However, the safety of SAPT is not well established. OBJECTIVE: To analyze the safety and efficacy of SAPT in terms of ischemic and hemorrhagic complications in patients undergoing FDs treatment for cerebral aneurysms. METHODS: A systematic literature search and meta-analysis were conducted in PubMed, Ovid MEDLINE, Ovid Embase, and Web of Science from January 2010 until October 2022. Twelve articles which reported SAPT and data on hemorrhagic, TECs, and mortality following FDs treatment were included. RESULTS: Overall, the 12 studies involved 237 patients with 295 aneurysms. Five investigated the safety and efficacy of SAPT in 202 unruptured aneurysms. Six studies focused on 57 ruptured aneurysms. One study included both ruptured and unruptured aneurysms. Among the 237 patients, prasugrel was most often used as SAPT in 168 cases (70.9%), followed by aspirin in 42 (17.7%) patients, and by ticagrelor in 27 (11.4%). Overall, the hemorrhagic complication rate was 0.1% (95% CI 0% to 1.8%). The TEC rate was 7.6% (95% CI 1.7% to 16.1%). In the subgroup analysis, the TEC rates of prasugrel monotherapy of 2.4% (95% CI 0% to 9.3%) and ticagrelor monotherapy of 4.2% (95% CI 0.1% to 21.1%) were lower than of aspirin monotherapy 20.2% (95% CI 5.9% to 38.6%). The overall mortality rate was 1.3% (95% CI 0% to 6.1%). CONCLUSION: According to the available data, SAPT regimen in patients undergoing FDs treatment for cerebral aneurysms has an acceptable safety profile, especially with the use of ADP-receptor antagonists.

Efficiency of endovascular management with a combination of Onyx and coils for direct and indirect carotid cavernous fistula treatment: Experience of a single center.

BACKGROUND: To evaluate the safety and efficacy of endovascular treatment with a combination of Onyx and coils for carotid cavernous fistulas (CCFs), and to characterize the factors associated with clinical and angiographic outcomes for direct and indirect CCFs. METHODS: This retrospective study included 31 patients with CCF treated with an endovascular procedure between December 2017 and March 2022. RESULTS: Direct and indirect CCFs were found in 14 (45.2%) and 17 (54.8%) cases, respectively. Direct CCFs included eleven traumatic carotid cavernous fistulas. The most common symptom on admission was chemosis, which was seen in 17 (54.8%) patients. Eight (25.7%) cases were treated by the transarterial approach. Fourteen (45.2%) cases were treated using the femoral vein-inferior petrosal sinus approach. Seven (22.6%) were treated by direct puncture of the superior ophthalmic vein. Two (6.5%) were treated by the femoral vein-facial vein approach. Immediate complete occlusion and follow-up rates were 93.5% and 96.7%, respectively. Twenty-nine (96.7%) patients experienced an improvement in their symptoms at clinical follow-up. Chemosis was significantly improved or resolved in 15 patients. Ophthalmoplegia was improved or resolved in 10 patients. Visual impairment was improved in 6 patients. Proptosis was improved or resolved in 5 patients. One case (3.2%) experienced procedure-related complication presented with transient oculomotor nerve palsy. In univariate subgroup analysis, use of balloon, treatment approach, and history of head trauma were significantly different between the direct and indirect CCF groups. CONCLUSIONS: Endovascular treatment with a combination of Onyx and coils is a safe and effective therapy for CCFs. In this study, the transarterial approach was a favorable option for embolization of direct CCFs. In contrast, the transvenous approach may be the first choice of treatment for indirect CCFs.