Active contour configuration model for estimating the posterior ablative margin in image fusion of real-time ultrasound and 3D ultrasound or magnetic resonance images for radiofrequency ablation: an experimental study

Purpose The purpose of this study was to evaluate the accuracy of an active contour model for estimating the posterior ablative margin in images obtained by the fusion of real-time ultrasonography (US) and 3-dimensional (3D) US or magnetic resonance (MR) images of an experimental tumor model for radiofrequency ablation. Methods Chickpeas (n=12) and bovine rump meat (n=12) were used as an experimental tumor model. Grayscale 3D US and T1-weighted MR images were pre-acquired for use as reference datasets. US and MR/3D US fusion was performed for one group (n=4), and US and 3D US fusion only (n=8) was performed for the other group. Half of the models in each group were completely ablated, while the other half were incompletely ablated. Hyperechoic ablation areas were extracted using an active contour model from real-time US images, and the posterior margin of the ablation zone was estimated from the anterior margin. After the experiments, the ablated pieces of bovine rump meat were cut along the electrode path and the cut planes were photographed. The US images with the estimated posterior margin were compared with the photographs and post-ablation MR images. The extracted contours of the ablation zones from 12 US fusion videos and post-ablation MR images were also matched. Results In the four models fused under real-time US with MR/3D US, compression from the transducer and the insertion of an electrode resulted in misregistration between the real-time US and MR images, making the estimation of the ablation zones less accurate than was achieved through fusion between real-time US and 3D US. Eight of the 12 post-ablation 3D US images were graded as good when compared with the sectioned specimens, and 10 of the 12 were graded as good in a comparison with nicotinamide adenine dinucleotide staining and histopathologic results. Conclusion Estimating the posterior ablative margin using an active contour model is a feasible way of predicting the ablation area, and US/3D US fusion was more accurate than US/MR fusion

Elevated IFNA1 and suppressed IL12p40 associated with persistent hyperinflammation in COVID-19 pneumonia

IntroductionDespite of massive endeavors to characterize inflammation in COVID-19 patients, the core network of inflammatory mediators responsible for severe pneumonia stillremain remains elusive. MethodsHere, we performed quantitative and kinetic analysis of 191 inflammatory factors in 955 plasma samples from 80 normal controls (sample n = 80) and 347 confirmed COVID-19 pneumonia patients (sample n = 875), including 8 deceased patients. ResultsDifferential expression analysis showed that 76% of plasmaproteins (145 factors) were upregulated in severe COVID-19 patients comparedwith moderate patients, confirming overt inflammatory responses in severe COVID-19 pneumonia patients. Global correlation analysis of the plasma factorsrevealed two core inflammatory modules, core I and II, comprising mainly myeloid cell and lymphoid cell compartments, respectively, with enhanced impact in a severity-dependent manner. We observed elevated IFNA1 and suppressed IL12p40, presenting a robust inverse correlation in severe patients, which was strongly associated with persistent hyperinflammation in 8.3% of moderate pneumonia patients and 59.4% of severe patients. DiscussionAberrant persistence of pulmonary and systemic inflammation might be associated with long COVID-19 sequelae. Our comprehensive analysis of inflammatory mediators in plasmarevealed the complexity of pneumonic inflammation in COVID-19 patients anddefined critical modules responsible for severe pneumonic progression

Cancer/testis antigen CAGE mediates osimertinib resistance in non-small cell lung cancer cells and predicts poor prognosis in patients with pulmonary adenocarcinoma

Abstract CAGE, a cancer/testis antigen, was originally isolated from the sera of patients with gastric cancers. Previously, we have shown the role of CAGE in resistance to chemotherapy and target therapy. The aim of this study was to investigate the role of CAGE in osimertinib resistance and determine the prognostic value of CAGE in patients with pulmonary adenocarcinomas. The clinicopathological correlation with CAGE and autophagy flux in patients was examined using immunohistochemistry and in situ hybridization. The possible role of autophagy in osimertinib resistance was analyzed using immune blot, immune fluorescence staining and immunohistochemistry. This study found that immunohistochemical staining (IHC) showed CAGE expression in more than 50% of patients with pulmonary adenocarcinomas (pADCs). CAGE expression was increased in pADCs after the acquisition of EGFR-TKIs resistance. High expression of CAGE was correlated with shorter overall survival and progression free survival in patients with pADCs. Thus, CAGE mediates osimertinib resistance and predicts poor prognosis in patients with pADCs. Osimertinib-resistant non-small cell lung cancer cells (PC-9/OSI) were established and mechanistic studies of CAGE-mediated osimertinib resistance were performed. PC-9/OSI cells showed increased autophagic flux and CAGE expression compared with parental sensitive PC-9 cells. PC-9/OSI cells showed higher tumorigenic, metastatic, and angiogenic potential compared with parental PC-9 cells. CAGE CRISPR-Cas9 cell lines showed decreased autophagic flux, invasion, migration potential, and tumorigenic potential compared with PC-9/OSI cells in vitro and in vivo. CAGE plays a crucial role in the cancer progression by modulating autophagy and can predict the poor prognosis of patients with pulmonary adenocarcinomas. Our findings propose CAGE as a potential therapeutic target for developing anticancer drugs that can overcome osimertinib resistance

Twenty-Year Retrospective Study of Post-Enucleation Chemotherapy in High-Risk Patients with Unilateral Retinoblastoma

Primary enucleation is a life-saving treatment for advanced intraocular retinoblastoma, particularly in patients with poor visual potential and functional contralateral eyes. This single-center study presents the treatment outcomes of patients with unilateral retinoblastoma who received primary enucleation and adjuvant chemotherapy with cyclophosphamide, vincristine, doxorubicin, and intrathecal methotrexate (CVDM) between 2000 and 2020. Twenty patients were enrolled in the study. The median age at diagnosis was 26 months (range, 1–45). Eighteen patients (90%) were in group E and two (10%) were in group D, according to the intraocular classification of retinoblastoma guidelines. Excluding one patient with an inadequate specimen, 19 patients (95%) had optic nerve involvement (ONI) at least up to the lamina cribrosa. Eight patients (40%) had choroidal invasion in addition to ONI. Two patients (10%) were surgical resection margin positive. The overall and event-free survival rates were 100% and 95%, respectively, for a median follow-up duration of 102.24 months (range 24.2–202.9). There were no relapses or deaths due to any cause, but one patient developed secondary rhabdomyosarcoma 99.6 months after chemotherapy. Treatment was well tolerated, with minimal hematotoxicity and hepatotoxicity. CVDM as a post-enucleation chemotherapy for advanced intraocular retinoblastoma has excellent outcomes with tolerable toxicity. However, in line with updated treatment trends, further risk stratification and lowering the treatment intensity should be considered. Continued long-term follow-up is required to further determine late effects