Comparison of the treatment strategies for symptomatic chronic internal carotid artery occlusion.

OBJECTIVE: The best management of symptomatic chronic internal carotid artery occlusion (CICAO) has been controversial. This systematic review and meta-analysis were to compare the outcomes of different treatment strategies for symptomatic CICAO. METHODS: Two independent researchers conducted a search of articles on the treatment of CICAO published between January 2000 and October 2023 in PubMed, Web of Science, Embase, and The Cochrane Library. Twenty-two articles were eligible for meta-analysis using a random effects model to combine and analyze the data for the pooled rates of stroke and death, and the rates of procedural success and significant restenosis/occlusion. RESULTS: A total of 1193 patients from 22 publications were included in this study. Six of them had bilateral internal carotid artery occlusion. The 30-day stroke and death rates were 1.1% (95% confidence interval [CI], 0%-4.4%) in the best medical treatment (BMT) group, 4.1% (95% CI, 0.7%-9.3%; I2 = 71.4%) in the extracranial-intracranial (EC-IC) bypass group, 4.4% (95% CI, 2.4%-6.8%; I2 = 0%) in the carotid artery stenting (CAS) group, and 1.2% (95% CI, 0%-3.4%; I2 = 0%) in the combined carotid endarterectomy (CEA) and stenting (CEA + CAS) group. During follow-up of 16.5 (±16.3) months, the stroke and death rates were 19.5%, 1.2%, 6.6%, and 2.4% in the BMT, EC-IC, CAS, and CEA + CAS groups respectively. The surgical success rate was 99.7% (95% CI, 98.5%-100%; I2 = 0%) in the EC-IC group, 70.1% (95% CI, 62.3%-77.5%; I2 = 64%) in the CAS group, and 86.4% (95% CI, 78.8%-92.7%; I2 = 60%) in the CEA + CAS group. The rate of post-procedural significant restenosis or occlusion was 3.6% in the EC-IC group, 18.7% in the CAS group, and 5.7% in the CEA + CSA group. The surgical success rate was negatively associated by the length of internal carotid artery (ICA) occlusion. Surgical success rate was significantly higher in the patients with occlusive lesion within C1 to C4 segments, compared with those with occlusion distal to C4 segment (odds ratio, 11.3; 95% CI, 5.0-25.53; P < .001). A proximal stump of ICA is a favorable sign for CAS. The success rate of CAS was significantly higher in the patients with an ICA stump than that in the patients without (odds ratio, 11.36; 95% CI, 4.84-26.64; P < .01). However, the success rate of CEA + CAS was not affected by the proximal ICA stump. CONCLUSIONS: For the management of symptomatic CICAO, BMT alone is associated with the highest risk of mid- and long-term stroke and death. EC-IC bypass surgery and CEA + CAS should be considered as the choice of treatment based on operator's expertise and patient's anatomy. CAS may be employed as an alternative option in high surgical risk patients, especially when proximal ICA stump exists.

Identification of metabolic components of carotid plaque in high-risk patients utilizing liquid chromatography-tandem mass spectrometry.

OBJECTIVE: Carotid atherosclerosis is a chronic progressive vascular disease that can be complicated by stroke in severe cases. Prompt diagnosis and treatment of high-risk patients are quite difficult due to the lack of reliable clinical biomarkers. This study aimed to explore potential plaque metabolic markers of stroke-prone risk and relevant targets for pharmacological intervention. METHOD: Carotid intima and plaque sample tissues were obtained from 20 patients with cerebrovascular symptoms of carotid origin. An untargeted metabolomics approach based on liquid chromatography-tandem mass spectrometry was utilized to characterize the metabolic profiles of the tissues. Multivariate and univariate analysis tools were used. RESULTS: A total of 154 metabolites were significantly altered in carotid plaque when compared with thickened intima. Of these, 62 metabolites were upregulated, whereas 92 metabolites were downregulated. Support vector machines identified the 15 most important metabolites, such as N-(cyclopropylmethyl)-N'-phenylurea, 9(S)-HOTrE, ACar 12:2, quinoxaline-2,3-dithiol, and l-thyroxine, as biomarkers for high-risk plaques. Metabolic pathway analysis showed that abnormal purine and nucleotide metabolism, amino acid metabolism, glutathione metabolism, and vitamin metabolism may contribute to the occurrence and progression of carotid atherosclerotic plaque. CONCLUSIONS: Our study identifies the biomarkers and related metabolic mechanisms of carotid plaque, which is stroke-prone, and provides insights and ideas for the precise prevention and targeted intervention of the disease.

Development and validation of bioanalytical assays for the quantification of 9MW2821, a nectin-4-targeting antibody-drug conjugate.

We designed and developed 9MW2821, an anti-Nectin-4 antibody-drug conjugate (ADC) with an enzymatically cleavable valine-citrulline linker and monomethyl auristatin E (MMAE) as the payload. Four bioanalytical assays for total antibodies, conjugated antibodies, conjugated payload, and free payload were then developed and validated for the comprehensive evaluation of the multiple drug forms of 9MW2821. Specific sandwich enzyme-linked immunosorbent assays were used to quantify total antibodies and conjugated antibody, showing good drug-to-antibody ratio (DAR) tolerance. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine free MMAE, and conjugated MMAE was quantified using a combination of ligand-binding assay (LBA) and LC-MS/MS. Based on these four assays, we studied the serum stability and monkey pharmacokinetic profiles of 9MW2821, and the in vivo DAR of 9MW2821 was calculated and dynamically monitored. In conclusion, we developed and validated series of bioanalytical assays to quantify multiple forms of 9MW2821, a new ADC, and used the assays to evaluate the serum stability and monkey pharmacokinetic characteristics. The results indicate good linker stability and suggest that the developed assays can be further used in clinical settings.