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Objectives To evaluate the application of black-blood CT (BBCT) in carotid artery wall imaging and its accuracy in disclosing stenosis rate and plaque burden of carotid artery. Methods A total of 110 patients underwent contrast-enhanced CT scan with two phases, and BBCT images were obtained using contrast-enhancement (CE)-boost technology. Two radiologists independently scored subjective image quality on black-blood computerized tomography (BBCT) images using a 4-point scale and then further analyzed plaque types. The artery stenosis rate on BBCT was measured and compared with CTA. The plaque burden on BBCT was compared with that on high-resolution intracranial vessel wall MR imaging (VW-MR imaging). The kappa value and intraclass correlation coefficient (ICC) were used for consistency analysis. The diagnostic accuracy of BBCT for stenosis rate and plaque burden greater than 50% was evaluated by AUC. Results The subjective image quality scores of BBCT had good consistency between the two readers (ICC = 0.836, p  < 0.001). BBCT and CTA had a good consistency in the identification of stenosis rate ( p  < 0.001). There was good consistency between BBCT and VW-MR in diagnosis of plaque burden ( p  < 0.001). As for plaque burden over 50%, BBCT had good sensitivity (93.10%) and specificity (73.33%), with an AUC of 0.950 (95%CI 0.838–0.993). Compared with CTA, BBCT had higher consistency with VW-MR in disclosing low-density plaques and mixed plaques (ICC = 0.931 vs 0.858, p  < 0.001). Conclusions BBCT can not only display the carotid artery wall clearly but also accurately diagnose the stenosis rate and plaque burden of carotid artery. Clinical relevance statement Black-blood CT, as a novel imaging technology, can assist clinicians and radiologists in better visualizing the structure of the vessel wall and plaques, especially for patients with contraindication to MRI. Key Points • Black-blood CT can clearly visualize the carotid artery wall and plaque burden. • Black-blood CT is superior to conventional CTA with more accurate diagnosis of the carotid stenosis rate and plaque burden features.

Clot composition could impact recanalization outcomes of thrombectomy, and preoperative imaging markers may help know about the histological components of thrombus. Consecutive patients who underwent thrombectomy from June 2017 to December 2019 were reviewed. The mean Hounsfield unit (HU) of thrombus (aHU) and contralateral artery (cHU) were recorded based on non-enhanced CT. The relative thrombus density was calculated (dHU=aHU-cHU). Hyperdense artery sign (HAS) was identified if dHU≥ 4HU. The clot perviousness was evaluated via thrombus attenuation increase (δHU) on contrast-enhanced CT compared to non-enhanced CT. Pervious clots were identified when δHU≥ 11HU. Tissue quantification for thrombus was based on Martius Scarlet Blue staining, using the Orbit Imaging Analysis Software. Spearman rank correlations was used to detect the association between imaging markers and clot composition. The differences in clinical characteristics were compared according to the presence of HAS or pervious clots. Fifty-three patients were included. The dHU was positively correlated with erythrocyte fractions (r = 0.337, p = 0.014), while there was no significant association between aHU and erythrocyte components (r = 0.146, p = 0.296). HAS (+) patients showed a comparable proportion of modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3 (94.6% vs. 87.5%, p = 0.740) and modified Rankin Scale score (mRS) 0–2 (35.1% vs. 56.3%, p = 0.152) compared with those HAS (-). Forty-seven cases were available for the analysis of clot perviousness. Clot perviousness was negatively associated with platelet fractions (r = −0.577, p < 0.001). Patients with pervious clots also showed a comparable proportion of mTICI 2b-3 (86.2% vs. 100%, p = 0.283) and mRS 0–2 (37.9% vs. 50.0%, p = 0.416) compared with impervious clots. This study suggests that relative thrombus density was positively correlated with erythrocyte fractions, while clot perviousness showed a negative relationship with platelet components. Yet, the presence of HAS or pervious clots did not show significant associations with recanalization and clinical outcomes. The conclusions should be drawn with caution. •Relative thrombus density was positively correlated with erythrocyte fractions.•Absolute density did not show significant associations with clot composition.•Clot perviousness showed a negative relationship with platelet fractions.•These two imaging markers did not show significant correlation with reperfusion outcomes.

•The history of stroke or TIA and occlusion in the terminal ICA were independent predictor for SE.•Patients with SE have significantly higher proportion of RBCs in thrombus than those without SE.•Imaging markers (thrombus density and perviousness) did not show an association with SE.•SE might increase the risk of incomplete recanalization and the number of maneuvers. Secondary embolism (SE) is a common adverse event during mechanical thrombectomy (MT) for acute intracranial large vessel occlusion, which could lead to incomplete revascularization and increased maneuvers. However, the mechanisms behind SE are still unclear. In this study, we aimed to investigate the risk factors of SE, with a focus on clot composition. Consecutive patients with retrieved clots were reviewed. Histologic examination for thrombus included Hematoxylin and eosin, Martius Scarlet Blue, immunohistochemistry for von Willebrand factor (VWF). Patients included were assigned to SE or no SE group. The differences in histological composition and clinical characteristics were compared, and logistic regression was conducted for predictors of SE. Fifty-four patients were included, of which 19 were identified as having an SE. For patients with SE, there was more history of stroke or transient cerebral ischemia (TIA) (57.9 % vs. 28.6 %, p = 0.035), more occlusion located in terminal internal carotid artery (ICA) (63.2 % vs. 25.7 %, p = 0.007), relatively more contact aspiration used as frontline strategy (68.4 % vs. 45.7 %, p = 0.110), and less eTICI2c-3 recanalization achieved (52.6 % vs. 91.4 %, p = 0.003). As for histologic composition, the clots in SE group showed a higher proportion of erythrocyte fractions (42.9 % vs. 26.8 %, p = 0.045), while the other components were comparable with the non-SE group. Multivariate analysis suggested that a history of stroke or TIA (OR 6.45, 95 %CI 1.41–29.44, p = 0.016) and ICA occlusion (OR 8.05, 95 %CI 1.80–36.10, p = 0.006) could independently predict SE. History of TIA or stroke and occlusion in the terminal ICA were found to be independent predictors for SE. Thrombus with a higher erythrocyte fractions might be more fragile. Further studies are needed.

Purpose: The aim of this study was to verify the value of collateral circulation and B-type natriuretic peptide (BNP) in predicting clinical outcomes of patients with acute ischemic stroke (AIS) and their biomarker value for stroke subtypes before endovascular treatment (EVT). Patients and Methods: In this retrospective study, 182 patients who underwent EVT for unilateral anterior circulation large-vessel occlusion between March 2016 and January 2022 were analyzed. The modified collateral circulation scoring system on four-dimensional computed tomography angiography (4D CTA-CS) was used to assess collateral status, and stroke subtypes were determined according to the TOAST classification criteria. Patients were divided into good (mRS ≤ 2) and poor outcome (mRS > 2) groups based on their modified Rankin Scale (mRS) score at 3 months. Results: 4D CTA-CS was an independent predictor of the clinical outcome for all AIS patients (odds ratio = 0.253; 95% CI, 0.147–0.437; p < 0.001), CE stroke patients (odds ratio = 0.513; 95% CI, 0.280–0.939; p = 0.030), and LAA stroke patients (odds ratio = 0.148; 95% CI, 0.049–0.447; p = 0.001). The BNP was a biomarker for clinical outcome prediction in CE (odds ratio = 1.004; 95% CI, 1.001–1.008; p = 0.005) but not in LAA patients. Combined with BNP, 4D CTA-CS improved predictive values for clinical outcomes (p < 0.05). Conclusion: Collateral status and BNP could be used as independent predictors of clinical outcomes in AIS patients and could determine stroke subtypes (CE stroke or LAA stroke). In addition, the model of 4D CTA-CS combined with BNP was the most effective in predicting clinical outcomes compared with collateral status or BNP alone.

This study aimed to identify independent predictors for the risk of hemorrhagic transformation (HT) in arterial ischemic stroke (AIS) patients. Consecutive patients with AIS due to large artery occlusion in the anterior circulation treated with mechanical thrombectomy (MT) were enrolled in a tertiary stroke center. Demographic and medical history data, admission lab results, and Circle of Willis (CoW) variations were collected from all patients. Altogether, 90 patients were included in this study; among them, 34 (37.8%) had HT after MT. The final pruned decision tree (DT) model consisted of collateral score and platelet to lymphocyte ratios (PLR) as predictors. Confusion matrix analysis showed that 82.2% (74/90) were correctly classified by the model (sensitivity, 79.4%; specificity, 83.9%). The area under the ROC curve (AUC) was 81.7%. The DT model demonstrated that participants with collateral scores of 2-4 had a 75.0% probability of HT. For participants with collateral scores of 0-1, if PLR at admission was <302, participants had a 13.0% probability of HT; otherwise, participants had an 75.0% probability of HT. The final adjusted multivariate logistic regression analysis indicated that collateral score 0-1 (OR, 10.186; 95% CI, 3.029-34.248; p < 0.001), PLR (OR, 1.005; 95% CI, 1.001-1.010; p = 0.040), and NIHSS at admission (OR, 1.106; 95% CI, 1.014-1.205; p = 0.022) could be used to predict HT. The AUC for the model was 0.855, with 83.3% (75/90) were correctly classified (sensitivity, 79.4%; specificity, 87.3%). Less patients with HT achieved independent outcomes (mRS, 0-2) in 90 days (20.6% vs. 64.3%, p < 0.001). Rate of poor outcomes (mRS, 4-6) was significantly higher in patients with HT (73.5% vs. 19.6%; p < 0.001). Both the DT model and multivariate logistic regression model confirmed that the lower collateral status and the higher PLR were significantly associated with an increased risk for HT in AIS patients after MT. PLR may be one of the cost-effective and practical predictors for HT. Further prospective multicenter studies are needed to validate our findings.

Antitumor therapies based on adoptively transferred T cells or oncolytic viruses have made significant progress in recent years, but the limited efficiency of their infiltration into solid tumors makes it difficult to achieve desired antitumor effects when used alone. In this study, an oncolytic virus (rVSV-LCMVG) that is not prone to induce virus-neutralizing antibodies was designed and combined with adoptively transferred T cells. By transforming the immunosuppressive tumor microenvironment into an immunosensitive one, in B16 tumor-bearing mice, combination therapy showed superior antitumor effects than monotherapy. This occurred whether the OV was administered intratumorally or intravenously. Combination therapy significantly increased cytokine and chemokine levels within tumors and recruited CD8 + T cells to the TME to trigger antitumor immune responses. Pretreatment with adoptively transferred T cells and subsequent oncolytic virotherapy sensitizes refractory tumors by boosting T-cell recruitment, down-regulating the expression of PD-1, and restoring effector T-cell function. To offer a combination therapy with greater translational value, mRNA vaccines were introduced to induce tumor-specific T cells instead of adoptively transferred T cells. The combination of OVs and mRNA vaccine also displays a significant reduction in tumor burden and prolonged survival. This study proposed a rational combination therapy of OVs with adoptive T-cell transfer or mRNA vaccines encoding tumor-associated antigens, in terms of synergistic efficacy and mechanism.

Background Pectus excavatum, the most common chest wall deformity, is frequently treated with Nuss procedure. Here we will describe non-invasive procedure and analyze the variables associated vacuum bell therapy for patients with pectus excavatum. Methods Retrospective case–control study in a single center between July 2018 and February 2022, including patients with pectus excavatum treated with vacuum bell. Follow-up was continued to September 2022. The Haller index and Correction index was calculated before and after treatment to analysis the effectiveness of vacuum bell therapy. Results There were 98 patients enrolled in the treatment group, with 72 available for analysis, and the follow-up period ranged from 1.1 to 4.4 years (mean 3.3 years). When analyzing with the Haller Index, 18 patients (25.0%) showed excellent correction, 13 patients (18.1%) achieved good correction, and 4 patients (5.6%) had fair correction. The remaining patients had a poor outcome. Characteristics predicting a non-poor prognosis included initial age ≤ 11 years (OR = 3.94, p  = 0.013) and patients with use over 24 consecutive months (OR = 3.95, p  = 0.013). A total of 9 patients (12.5%) achieved a CI reduction below 10. Patients who started vacuum bell therapy at age > 11 had significantly less change compared to those who started at age ≤ 11 ( P  < 0.05). Complications included chest pain (5.6%), swollen skin (6.9%), chest tightness (1.4%) and erythema (15.3%). Conclusions A certain percentage of patients with pectus excavatum can achieve excellent correction when treated with pectus excavatum therapy. Variables predicting better outcome including initial age ≤ 11 years both in HI and CI and vacuum bell use over 24 consecutive months in HI. In summary, pectus excavatum is an emerging non-invasive therapy for pectus excavatum and will be widely performed in a certain group of patients.

Background Oncolytic viruses are now well recognized as potential immunotherapeutic agents against cancer. However, the first FDA-approved oncolytic herpes simplex virus 1 (HSV-1), T-VEC, showed limited benefits in some patients in clinical trials. Thus, the identification of novel oncolytic viruses that can strengthen oncolytic virus therapy is warranted. Here, we identified a live-attenuated swine pseudorabies virus (PRV-LAV) as a promising oncolytic agent with broad-spectrum antitumor activity in vitro and in vivo. Methods PRV cytotoxicity against tumor cells and normal cells was tested in vitro using a CCK8 cell viability assay. A cell kinase inhibitor library was used to screen for key targets that affect the proliferation of PRV-LAV. The potential therapeutic efficacy of PRV-LAV was tested against syngeneic tumors in immunocompetent mice, and against subcutaneous xenografts of human cancer cell lines in nude mice. Cytometry by time of flight (CyTOF) and flow cytometry were used to uncover the immunological mechanism of PRV-LAV treatment in regulating the tumor immune microenvironment. Results Through various tumor-specific analyses, we show that PRV-LAV infects cancer cells via the NRP1/EGFR signaling pathway, which is commonly overexpressed in cancer. Further, we show that PRV-LAV kills cancer cells by inducing endoplasmic reticulum (ER) stress. Moreover, PRV-LAV is responsible for reprogramming the tumor microenvironment from immunologically naïve (“cold”) to inflamed (“hot”), thereby increasing immune cell infiltration and restoring CD8 + T cell function against cancer. When delivered in combination with immune checkpoint inhibitors (ICIs), the anti-tumor response is augmented, suggestive of synergistic activity. Conclusions PRV-LAV can infect cancer cells via NRP1/EGFR signaling and induce cancer cells apoptosis via ER stress. PRV-LAV treatment also restores CD8 + T cell function against cancer. The combination of PRV-LAV and immune checkpoint inhibitors has a significant synergistic effect. Overall, these findings point to PRV-LAV as a serious potential candidate for the treatment of NRP1/EGFR pathway-associated tumors.