ABSTRACT
BackgroundThis study evaluated the safety and immunogenicity of an AS03-adjuvanted SARS-CoV-2 recombinant protein candidate vaccine, CoV2 preS dTM. MethodsThis Phase 2, modified double-blind, parallel-group study (NCT04762680) was conducted in adults, including those at increased risk of severe COVID-19. Participants were randomised 1:1:1, stratified by age (18-59/[≥]60 years), rapid serodiagnostic test (positive/negative) and high-risk medical conditions (yes/no), to receive two injections (day [D]1 and D22) of 5g, 10g or 15g of CoV2 preS dTM antigen with fixed AS03 content. Interim safety and reactogenicity results (to D43) and neutralising antibodies (NAbs) against the D614G variant are presented (primary objectives). FindingsOf 722 participants enrolled and randomised between 24 February and 8 March 2021, 721 received [≥]1 injections (5g, n=240; 10g, n=239; 15g, n=242). Four participants reported unsolicited immediate adverse events (AEs), two were vaccine-related (investigator assessment). Five participants reported seven vaccine-related medically-attended AEs. No vaccine-related serious AEs and no AEs of special interest were reported. Solicited reactions (local and systemic) were reported at similar frequencies between study groups; these were mostly mild to moderate and transient, with higher frequency and intensity post-injection 2 than post-injection 1. In SARS-CoV-2 naive participants at D36, 96{middle dot}9%, 97.0% and 97{middle dot}6% of participants had [≥]4-fold-rise in NAb titres from baseline in the 5g-, 10g- and 15g-dose groups, respectively. NAb titres increased with antigen dose in younger (GMTs: 2954, 3951 and 5142 for 5g-, 10g- and 15g-dose groups) but not older adults (GMTs: 1628, 1393 and 1736, respectively). NAb titres in non-naive adults after one injection were higher than titres after two injections in naive adults. InterpretationTwo injections of CoV2 preS dTM-AS03 demonstrated acceptable safety and reactogenicity, and robust immunogenicity in SARS-CoV-2 naive and non-naive adults. These results informed antigen dose selection for progression to Phase 3 evaluation of primary and booster vaccination.
ABSTRACT
Objective@#To explore the value of CT texture analysis (CTTA) in differentiating the pathological grade of urothelial carcinoma of the bladder (UCB).@*Methods@#A total of 53 lesions from 43 patients with bladder cancer confirmed by postoperative pathology were retrospectively analyzed, including 27 cases of high-grade urothelial carcinoma (HGUC) and 26 cases of low-grade urothelial carcinoma (LGUC). All the patients took pelvic CT and enhanced scanning in the same CT scanner with same scanning parameters. Lesions on both plain and enhanced CT images were delineated on software by two radiologists to extract the corresponding volumes of interest (VOI) and then 92 parameters based on feature classes were generated. The average values of two radiologists were obtained. The difference parameters between HGUC group and LGUC group were screened by nonparametric test, and the receiver operating characteristic (ROC) was drawn. The corresponding optimal thresholds were determined and diagnostic effect was assessed.@*Results@#Nine difference texture parameters between HGUC group and LGUC group were selected, including 5 parameters on unenhanced images, namely, skewness, root mean squared, cluster shade, zone percentage and large area high gray level emphasis. There were 4 parameters on enhanced images, namely, skewness, kurtosis, cluster shade and zone percentage. The largest area under curve of 0.840±0.058 (95% CI 0.726-0.955) was obtained from skewness generated by VOI of unenhanced images. The cut-off value of skewness was 0.186 5, which permitted the diagnosis of HGUC with sensitivity of 92.59%, specificity of 73.08%, positive predictive value of 78.13%, negative predictive value of 90.48% and accuracy of 83.02%.@*Conclusion@#CTTA can effectively distinguish between LGUC and HGUC. Skewness from unenhanced CT images had the optimal diagnostic performance.
