The MAP3K1/c-JUN signaling axis regulates glioblastoma stem cell invasion and tumor progression.

Glioblastoma (GBM) stem cells (GSCs) are responsible for GBM initiation, progression, infiltration, standard therapy resistance, and recurrence. However, the mechanisms underlying GSC invasion remain incompletely understood. Using public single-cell RNA-Seq data, we identified MAP3K1 as a master regulator of infiltrative GSCs through c-JUN signaling regulation. MAP3K1 knockdown significantly decreased GSC invasion capacity, proliferation, and stemness in vitro. Moreover, in an orthotopic xenograft model, knockdown of MAP3K1 prominently suppressed GSC infiltration along the corpus callosum and tumor progression and prolonged mouse survival. Mechanistically, MAP3K1 regulates GSC invasion through phosphorylation of downstream c-JUN at serine 63 and 73, as confirmed using the CPTAC phosphoproteome dataset. Furthermore, the c-JUN inhibitor JNK-IN-8 significantly decreased GSC invasion, proliferation, and stemness. Taken together, our study demonstrates that MAP3K1 regulates GSC invasion and tumor progression via activation of c-JUN signaling and indicates that the MAP3K1/c-JUN signaling axis is a therapeutic target for infiltrative GBM.

Fibroblast growth factor 11 (FGF11) promotes non-small cell lung cancer (NSCLC) progression by regulating hypoxia signaling pathway.

BACKGROUND: Accumulating evidence highlights the critical roles of fibroblast growth factors (FGFs) in regulating the progression of multiple human cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the role of FGF11 in the progression of NSCLC. METHODS: Previously published transcriptomic data (GSE75037 and GSE81089) were used to compare FGF11 expression level between NSCLC tumor tissues and adjacent normal tissues. 100 cases of NSCLC tumor tissues and 30 cases of matched adjacent normal tissues were used to validate FGF11 expression at mRNA and protein level by qPCR and immunohistochemistry. Bioinformatics analysis and dual luciferase reporter analysis were performed to confirm the regulatory effect of miR-525-5p on FGF11 expression. CCK-8 assay and transwell migration assay were employed to examine cellular proliferation, migration and invasion. Gene set enrichment analysis (GSEA) was performed to identify the signaling pathway associated with FGF11 expression. Finally, the functional role of FGF11 in NSCLC tumor growth was evaluated by in vivo study. RESULTS: FGF11 was upregulated in NSCLC tumor tissues and tumor cell lines. High FGF11 expression was associated with a poor prognosis in NSCLC patients. In vitro loss- and gain-of function experiments demonstrated that FGF11 knockdown inhibited, whereas FGF11 overexpression promoted the proliferation, migration and invasion of NSCLC cells. Dual luciferase reporter assay confirmed that FGF11 was downregulated by miR-525-5p, and the effect of FGF11 on cell proliferation, migration and invasion could be interfered by miR-525-5p. GSEA analysis further revealed that FGF11 expression was enriched with genes in hypoxia signaling pathway and the oncogenic function of FGF11 could be suppressed by knocking down HIF-1α in NSCLC cells. Moreover, FGF11 knockdown suppressed NSCLC tumor growth whereas FGF11 overexpression promoted tumor growth in vivo. CONCLUSIONS: Our study showed that FGF11 functions as an oncogene in tumor NSCLC progression. miR-525-5p seems to negatively regulate FGF11 and the oncogenic role of FGF11 is dependent on the upregulation of HIF-1α. Our study suggests that targeting FGF11 and HIF-1α may serve as novel strategies for the treatment of NSCLC.

Imaging features and evolution on CT in 100 COVID-19 pneumonia patients in Wuhan, China.

OBJECTIVES: To investigate CT images of 100 confirmed COVID-19 pneumonia patients to describe the lesion distribution, CT signs, and evolution during different courses. METHODS: A retrospective study of 100 COVID-19 pneumonia patients without ARDS was performed, and CT scans were reviewed. A COVID-19 pneumonia course diagram was drawn. Mann-Whitney U test was used to compare the lesion distribution and CT scores, χ2 test was used to compare the CT findings between different stages. RESULTS: A total of 272 CT scans from 100 patients (mean age, 52.3 years ± 13.1) were investigated. Four patients with lung abnormalities on CT first showed negative RT-PCR result and turned positive afterwards. One hundred sixty-nine (62.1%) showed predominantly peripheral distribution. The CT scores of the upper zone (3.4 ± 3.6) were significantly lower than those of the middle (5.0 ± 3.9) and lower (4.8 ± 3.6) zones (p < 0.001). The CT scores of the anterior zones (4.9 ± 4.7) were significantly lower than those of the posterior zones (8.4 ± 6.2) (p < 0.001). In the early rapid progressive stage (1~7 days), ground glass opacity (GGO) plus reticular pattern (58.1%), GGO plus consolidation (43.0%), and GGO (41.9%) were all common. In the advanced stage (8~14 days), GGO plus consolidation (79.8%) and repairing CT signs (subpleural line, bronchus distortion, and fibrotic strips) showed a significant increase (p < 0.05). In the absorption stage, GGO plus consolidation (9.1%) sharply decreased (p < 0.05). CONCLUSION: CT imaging of COVID-19 pneumonia showed a predominantly peripheral, middle and lower, and posterior distribution. The early rapid progressive stage is 1~7 days from symptom onset, the advanced stage with peak levels of abnormalities on CT is 8~14 days, and the abnormalities started to improve after 14 days. KEY POINTS: • The course of COVID-19 pneumonia consists of three stages: 1~7 days is the early rapid progressive stage, 8~14 days is the advanced stage, and after 14 days, the abnormalities started to decrease. • In the early rapid progressive stage, GGO plus a reticular pattern, GGO plus consolidation, and GGO were all common signs; in the advanced stage, signs of progression and absorption coexisted; lung abnormalities showed an asynchronous process with parts with absorption and parts progressing. • Lung abnormalities mainly showed predominantly peripheral, middle, and lower distribution.

Initial CT findings and temporal changes in patients with the novel coronavirus pneumonia (2019-nCoV): a study of 63 patients in Wuhan, China.

OBJECTIVES: The purpose of this study was to observe the imaging characteristics of the novel coronavirus pneumonia. METHODS: Sixty-three confirmed patients were enrolled from December 30, 2019 to January 31, 2020. High-resolution CT (HRCT) of the chest was performed. The number of affected lobes, ground glass nodules (GGO), patchy/punctate ground glass opacities, patchy consolidation, fibrous stripes and irregular solid nodules in each patient's chest CT image were recorded. Additionally, we performed imaging follow-up of these patients. RESULTS: CT images of 63 confirmed patients were collected. M/F ratio: 33/30. The mean age was 44.9 ± 15.2 years. The mean number of affected lobes was 3.3 ± 1.8. Nineteen (30.2%) patients had one affected lobe, five (7.9%) patients had two affected lobes, four (6.3%) patients had three affected lobes, seven (11.1%) patients had four affected lobes while 28 (44.4%) patients had 5 affected lobes. Fifty-four (85.7%) patients had patchy/punctate ground glass opacities, 14 (22.2%) patients had GGO, 12 (19.0%) patients had patchy consolidation, 11 (17.5%) patients had fibrous stripes and 8 (12.7%) patients had irregular solid nodules. Fifty-four (85.7%) patients progressed, including single GGO increased, enlarged and consolidated; fibrous stripe enlarged, while solid nodules increased and enlarged. CONCLUSIONS: Imaging changes in novel viral pneumonia are rapid. The manifestations of the novel coronavirus pneumonia are diverse. Imaging changes of typical viral pneumonia and some specific imaging features were observed. Therefore, we need to strengthen the recognition of image changes to help clinicians to diagnose quickly and accurately. KEY POINTS: • High-resolution CT (HRCT) of the chest is critical for early detection, evaluation of disease severity and follow-up of patients with the novel coronavirus pneumonia. • The manifestations of the novel coronavirus pneumonia are diverse and change rapidly. • Radiologists should be aware of the various features of the disease and temporal changes.

CT Features of Coronavirus Disease 2019 (COVID-19) Pneumonia in 62 Patients in Wuhan, China.

OBJECTIVE. The purpose of this study was to investigate 62 subjects in Wuhan, China, with laboratory-confirmed coronavirus disease (COVID-19) pneumonia and describe the CT features of this epidemic disease. MATERIALS AND METHODS. A retrospective study of 62 consecutive patients with laboratory-confirmed COVID-19 pneumonia was performed. CT images and clinical data were reviewed. Two thoracic radiologists evaluated the distribution and CT signs of the lesions and also scored the extent of involvement of the CT signs. The Mann-Whitney U test was used to compare lesion distribution and CT scores. The chi-square test was used to compare the CT signs of early-phase versus advanced-phase COVID-19 pneumonia. RESULTS. A total of 62 patients (39 men and 23 women; mean [± SD] age, 52.8 ± 12.2 years; range, 30-77 years) with COVID-19 pneumonia were evaluated. Twenty-four of 30 patients who underwent routine blood tests (80.0%) had a decreased lymphocyte count. Of 27 patients who had their erythrocyte sedimentation rate and high-sensitivity C-reactive protein level assessed, 18 (66.7%) had an increased erythrocyte sedimentation rate, and all 27 (100.0%) had an elevated high-sensitivity C-reactive protein level. Multiple lesions were seen on the initial CT scan of 52 of 62 patients (83.9%). Forty-eight of 62 patients (77.4%) had predominantly peripheral distribution of lesions. The mean CT score for the upper zone (3.0 ± 3.4) was significantly lower than that for the middle (4.5 ± 3.8) and lower (4.5 ± 3.7) zones (p = 0.022 and p = 0.020, respectively), and there was no significant difference in the mean CT score of the middle and lower zones (p = 1.00). The mean CT score for the anterior area (4.4 ± 4.1) was significantly lower than that for the posterior area (7.7 ± 6.3) (p = 0.003). CT findings for the patients were as follows: 25 patients (40.3%) had ground-glass opacities (GGO), 21 (33.9%), consolidation; 39 (62.9%), GGO plus a reticular pattern; 34 (54.8%), vacuolar sign; 28 (45.2%), microvascular dilation sign; 35 (56.5%), fibrotic streaks; 21 (33.9%), a subpleural line; and 33 (53.2%), a subpleural transparent line. With regard to bronchial changes seen on CT, 45 patients (72.6%) had air bronchogram, and 11 (17.7%) had bronchus distortion. In terms of pleural changes, CT showed that 30 patients (48.4%) had pleural thickening, 35 (56.5%) had pleural retraction sign, and six (9.7%) had pleural effusion. Compared with early-phase disease (≤ 7 days after the onset of symptoms), advanced-phase disease (8-14 days after the onset of symptoms) was characterized by significantly increased frequencies of GGO plus a reticular pattern, vacuolar sign, fibrotic streaks, a subpleural line, a subpleural transparent line, air bronchogram, bronchus distortion, and pleural effusion; however, GGO significantly decreased in advanced-phase disease. CONCLUSION. CT examination of patients with COVID-19 pneumonia showed a mixed and diverse pattern with both lung parenchyma and the interstitium involved. Identification of GGO and a single lesion on the initial CT scan suggested early-phase disease. CT signs of aggravation and repair coexisted in advanced-phase disease. Lesions presented with a characteristic multifocal distribution in the middle and lower lung regions and in the posterior lung area. A decreased lymphocyte count and an increased high-sensitivity C-reactive protein level were the most common laboratory findings.

Present Status and Advances in Chimeric Antigen Receptor T Cell Therapy for Glioblastoma.

Adoptive chimeric antigen receptor (CAR) T cells designed to recognize specific tumor antigens have shown promising results in cancer therapy. While CAR T cell therapy has demonstrated notable clinical effectiveness for hematologic disease, efforts to develop therapies for solid tumors, including glioblastoma (GBM), have been hampered by heterogeneity, an immunosuppressive tumor microenvironment, and difficulty in trafficking. Several specific tumor antigens, such as IL13Rα2, EGFRvIII, and HER2, have been attempted in clinical trials; however, limited efficacy has been observed. In this review, we discuss the current status of CAR T therapy for GBM in clinical trials and highlight the potential target antigens for CAR T cells. Additionally, we summarize the mechanisms used to enhance their efficacy and explore the challenges and future prospects of CAR T cell therapy for GBM.

Combined bulk RNA and single-cell RNA analyses reveal TXNL4A as a new biomarker for hepatocellular carcinoma.

Introduction: Hepatocellular carcinoma (HCC) has a high mortality rate worldwide. The dysregulation of RNA splicing is a major event leading to the occurrence, progression, and drug resistance of cancer. Therefore, it is important to identify new biomarkers of HCC from the RNA splicing pathway. Methods: We performed the differential expression and prognostic analyses of RNA splicing-related genes (RRGs) using The Cancer Genome Atlas-liver hepatocellular carcinoma (LIHC). The International Cancer Genome Consortium (ICGC)-LIHC dataset was used to construct and validate prognostic models, and the PubMed database was used to explore genes in the models to identify new markers. The screened genes were subjected to genomic analyses, including differential, prognostic, enrichment, and immunocorrelation analyses. Single-cell RNA (scRNA) data were used to further validate the immunogenetic relationship. Results: Of 215 RRGs, we identified 75 differentially expressed prognosis-related genes, and a prognostic model incorporating thioredoxin like 4A (TXNL4A) was identified using least absolute shrinkage and selection operator regression analysis. ICGC-LIHC was used as a validation dataset to confirm the validity of the model. PubMed failed to retrieve HCC-related studies on TXNL4A. TXNL4A was highly expressed in most tumors and was associated with HCC survival. Chi-squared analyses indicated that TXNL4A expression positively correlated positively with the clinical features of HCC. Multivariate analyses revealed that high TXNL4A expression was an independent risk factor for HCC. Immunocorrelation and scRNA data analyses indicated that TXNL4A was correlated with CD8 T cell infiltration in HCC. Conclusion: Therefore, we identified a prognostic and immune-related marker for HCC from the RNA splicing pathway.

EGFR-TKIs plus stereotactic body radiation therapy (SBRT) for stage IV Non-small cell lung cancer (NSCLC): A prospective, multicenter, randomized, controlled phase II study.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have a significant therapeutic effect in the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR mutations. However, the acquired resistance greatly limits the survival benefit of EGFR-TKIs for EGFR-mutant NSCLC patients. We aimed to assess the efficacy and safety of stereotactic body radiotherapy (SBRT) plus EGFR-TKIs in these patients. METHODS: In this prospective, randomized, controlled, phase 2 study, participants were recruited from 4 different hospitals in Wuhan, China. Eligible patients were histologically confirmed to have NSCLC with an EGFR-sensitive mutation (19DEL or 21L858R) and diagnosed at stage IV. Patients who had received first-line EGFR-TKIs treatment including gefitinib, erlotinib, and icotinib and achieved stable disease or partial response were enrolled after three months. Eligible participants were randomly assigned (1:1) to receive SBRT plus EGFR-TKIs or EGFR-TKIs treatment alone. In the combination-group, different tumor sites were irradiated at doses ranging from 30-50 Gy in five fractions. Considering the short duration of SBRT, the TKIs were continued during the radiotherapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and safety. This study was registered at ClinicalTrials.gov, with the registration number of NCT03595644. RESULTS: Between May 4, 2018 and Dec 20, 2019, 74 patients were screened, of whom 62 patients were enrolled and randomized. The study was closed early with 62/72 patients due to slow accrual. The enrolled patients were randomly assigned to receive SBRT plus EGFR-TKI(n = 31) or EGFR-TKI alone (n = 31). One patient who was randomized to the SBRT plus EGFR-TKI group refused to receive SBRT during the treatment, and, 61 patients were included the modified intention-to-treat (mITT) analysis, with 30 in the SBRT plus EGFR-TKI and 31 in the EGFR-TKI group. As of the clinical cutoff date (Feb 14, 2022), the median follow-up was 29.4 months (IQR 6.9-38.9). The median PFS of the EGFR-TKI group and SBRT combination group was 9.0 vs 17.6 months (hazard ratio [HR] = 0.52, 95% confidence interval [95%CI], 0.31-0.89, P = 0.016). Meanwhile, the median OS was 23.2 vs 33.6 months (HR [95%CI], 0.53(0.30-0.95); P = 0.026). There was no grade 3 or greater toxicity observed in either group, the grade 2 adverse events were 50% in the EGFR-TKIs + SBRT group while the percentage was 45.2% in the EGFR-TKIs group. CONCLUSIONS: The addition of SBRT significantly delayed the onset of acquired resistance to EGFR-TKIs and prolonged the PFS and OS of patients. Radiotherapy of the primary lesion alone might be superior to metastatic sites. Further confirmatory studies are needed to confirm our findings.

IGFBP5 is an ROR1 ligand promoting glioblastoma invasion via ROR1/HER2-CREB signaling axis.

Diffuse infiltration is the main reason for therapeutic resistance and recurrence in glioblastoma (GBM). However, potential targeted therapies for GBM stem-like cell (GSC) which is responsible for GBM invasion are limited. Herein, we report Insulin-like Growth Factor-Binding Protein 5 (IGFBP5) is a ligand for Receptor tyrosine kinase like Orphan Receptor 1 (ROR1), as a promising target for GSC invasion. Using a GSC-derived brain tumor model, GSCs were characterized into invasive or non-invasive subtypes, and RNA sequencing analysis revealed that IGFBP5 was differentially expressed between these two subtypes. GSC invasion capacity was inhibited by IGFBP5 knockdown and enhanced by IGFBP5 overexpression both in vitro and in vivo, particularly in a patient-derived xenograft model. IGFBP5 binds to ROR1 and facilitates ROR1/HER2 heterodimer formation, followed by inducing CREB-mediated ETV5 and FBXW9 expression, thereby promoting GSC invasion and tumorigenesis. Importantly, using a tumor-specific targeting and penetrating nanocapsule-mediated delivery of CRISPR/Cas9-based IGFBP5 gene editing significantly suppressed GSC invasion and downstream gene expression, and prolonged the survival of orthotopic tumor-bearing mice. Collectively, our data reveal that IGFBP5-ROR1/HER2-CREB signaling axis as a potential GBM therapeutic target.

A comparison of radiographic features between non-survivors and survivors from ICU.

The clinical and imaging data of 121 ICU patients with SARS-CoV-2 infection (63 survivors and 58 non-survivors) were retrospectively reviewed. The clinical results and radiographic features were compared between survivors and non-survivors. Compared with survivors, non-survivors were more likely to develop ARDS (53 [91 %] vs. 22 [35 %], P < 0.0001), shock (6 [10 %] vs. 0, P = 0.009), cardiac injury(18 [31 %] vs. 6 [10 %], P = 0.003), acute kidney injury(21 [36 %] vs. 10 [16 %], P = 0.01), and pneumothorax(5 [9%] vs. 0, P = 0.017). There were typical radiographic features for ICU patients with SARS-CoV-2 pneumonia. Extensive air-space opacities could be seen in all patients. Middle and lower lung involvement was significantly more serious than upper lung (score 6.8 ±â€¯1.9, 7.2 ±â€¯2.1, and 5.7 ±â€¯1.7, respectively, P < 0.0001). Based on X-ray involvement score, non-survivors were in a more critical condition than survivors (20.3 ±â€¯4.6 vs. 19.1 ±â€¯3.1, P = 0.038).

Assessment of relationships among clinicopathological characteristics, morphological computer tomography features, and tumor cell proliferation in stage I lung adenocarcinoma.

BACKGROUND: Surgically resected stage I lung adenocarcinoma (ADC) has wide variation in prognosis. It is significant to identify high-risk patients and optimize therapeutic strategy. This study aimed to investigate the relationships among histological grade, serum tumor marker index (TMI), morphological computer tomography (CT) features, and a well-established prognosticator cell proliferation (Ki-67) in stage I ADC. METHODS: Preoperative CT was performed in 182 patients with stage I ADC confirmed by pathology. The Ki-67 expression was acquired by immunohistochemistry. TMI was the square root of standardized serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) values. Tumor shadow disappearance rate (TDR) and other morphological CT features were interpreted by two radiologists. Histological grade, TMI, CT features were statistically evaluated to explore the associations with Ki-67 expression. RESULTS: In univariate analysis, gender, smoking history, pack-year, histological grade, TNM stage (IA and IB), serum CEA and CYFRA 21-1 status, TMI status, as well as TDR, long-axis diameter, short-axis diameter, lobulation, spiculation, attenuation types, vacuolation, vascular invasion, vascular convergence, thickened bronchovascular bundles, pleural attachment and peripheral fibrosis were significantly associated with Ki-67 expression (all P<0.05). Solid-predominant ADC had the highest Ki-67 expression, followed by micropapillary, papillary and acinar-predominant ADC, while lepidic-predominant ADC had the lowest Ki-67 expression (P<0.001). TDR was negatively correlated with Ki-67 (r =-0.478, P<0.001). Multivariate logistic regression analysis revealed that gender, histological grade, TDR and attenuation types were independent factors associated with Ki-67 expression. CONCLUSIONS: Ki-67 expression differed distinctly according to ADC histological subtypes. High Ki-67 expression is independently associated with male patients of stage I ADC with worse differentiation, lower TDR and solid tumors, which might be of prognostic value for poor prognosis in stage I ADC.

IgG4-Related Disease: A Retrospective Chinese Study of Features and Treatment Response of 98 Patients Including 4 Rare Cases.

The features and treatment of 98 Chinese patients with immunoglobulin G4 (IgG4)-related disease (IgG4-RD) referred to a single tertiary referring centre were reviewed. Patients diagnosed with IgG4-RD according to the comprehensive diagnostic criteria (CDC) were included in the retrospective study from May 2012 to March 2019. We collected data on clinical, laboratory, imaging, histological features and treatment. Totally, 98 patients with IgG4-RD were enrolled. The common clinical manifestations included abdominal pain, salivary gland swelling and lymphadenopathy. 51% of the patients had multiple organs involvement. Lymph nodes, pancreas and salivary glands were most commonly involved. Four rare sites including ulna, cerebellum, scalp, and mammary gland were found. The serum IgG4 level was increased by 85.7%. The serum IgG4 level was positively correlated with the number of involved organs, IgG and IgG4/IgG. Low C3 and C4 levels were observed in 37.5% and 12.2% patients respectively, and all patients with kidney involvement had hypocomplementemia. A total of 54 patients underwent tissue biopsies, and 55.6%, 31.5% and 11.1% cases were diagnosed as definite, probable and possible IgG4-RD, respectively. Eighty-eight patients received glucocorticoids (GCs) therapy. Five patients underwent radical surgery to remove the lesion. 73% of them presented a complete or partial remission. IgG4-RD is a systemic fibroinflammatory disease with involvement of multiple organs throughout the body including some rare sites. Most IgG4-RD patients had increased serum IgG4 levels and patients with kidney involvement showed hypocomplementemia. GCs therapy is effective. More research is needed to provide a more reliable basis for the diagnosis and treatment of patients.

Whole-Lesion DCE-MRI Intensity Histogram Analysis for Diagnosis in Patients with Suspected Lung Cancer.

RATIONALE AND OBJECTIVES: To explore the diagnostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) intensity histogram metrics, relative to time intensity curve (TIC)-derived metrics, in patients with suspected lung cancer. MATERIALS AND METHODS: This retrospective study enrolled 49 patients with suspected lung cancer on routine CT imaging who underwent DCE-MRI scans and had final histopathologic diagnosis. Three TIC-derived metrics (maximum enhancement ratio, peak time [Tmax] and slope) and eight intensity histogram metrics (volume, integral, maximum, minimum, median, coefficient of variation [CoV], skewness, and kurtosis) were extracted from DCE-MRI images. TIC-derived and intensity histogram metrics were compared between benignity versus malignancy using the Wilcoxon rank-sum test. Associations between imaging metrics and malignancy risk were assessed by univariate and multivariate logistic regression odds ratios (ORs). RESULTS: There were 33 malignant lesions and 16 benign lesions based on histopathology. Lower CoV (OR = 0.2 per 1-SD increase, p = 0.0006), lower Tmax (OR = 0.4 per 1-SD increase, p = 0.005), and steeper slope (OR = 2.4 per 1-SD increase, p = 0.010) were significantly associated with increased risk of malignancy. Under multivariate analysis, CoV was significantly independently associated with malignancy likelihood after accounting for either Tmax (OR = 0.3 per 1-SD increase, p = 0.007) or slope (OR = 0.3 per 1-SD increase, p = 0.011). CONCLUSION: This initial study found that DCE-MRI CoV was independently associated with malignancy in patients with suspected lung cancer. CoV has the potential to help diagnose indeterminate pulmonary lesions and may complement TIC-derived DCE-MRI metrics. Further studies are warranted to validate the diagnostic value of DCE-MRI intensity histogram analysis.

A Comparative Study of Chest Computed Tomography Features in Young and Older Adults With Corona Virus Disease (COVID-19).

OBJECTIVE: To analyze the most common computed tomography (CT) findings of pneumonia caused by new coronavirus in younger patients (60 and younger) and older adults (older than 60). MATERIALS AND METHODS: The chest CT images of 72 symptomatic patients with corona virus disease (COVID-19) were analyzed retrospectively, including 44 younger patients (47.5±8.7 y old) and 28 older patients (68.4±6.0 y old). CT findings including density (pure ground-glass opacities, ground-glass opacities with consolidation, consolidation), the number of lobes involved, lesion distribution, and the main accompanying signs were analyzed and compared. RESULTS: Characteristic CT findings included the lobes of bilateral lung extensively involved, ground-glass opacity and ground-glass opacity with consolidation in the peripheral area, sometimes accompanied by interlobular septal thickening, and subpleural line and pleural thickening. Compared with the younger group, the proportion of extensive involvement of lung lobes was higher in the elderly group (71.4% vs. 36.4%, P=0.009), and subpleural line and pleural thickening were more likely to occur (50.0% vs. 25.0%, and 71.4% vs. 40.9%, P=0.030 and 0.011, respectively). CONCLUSION: Elderly and younger patients with corona virus disease have some common CT features, but older patients are more likely to have extensive lung lobe involvement, and subpleural line and pleural thickening. These differentiated characteristics may be related to the progress and prognosis of the disease.

Chest CT imaging features and severity scores as biomarkers for prognostic prediction in patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a pandemic. Few studies have explored the role of chest computed tomography (CT) features and severity scores for prognostic prediction. In this study, we aimed to investigate the role of chest CT severity score and imaging features in the prediction of the prognosis of COVID-19 patients. METHODS: A total of 134 patients (62 recovered and 72 deceased patients) with confirmed COVID-19 were enrolled. The clinical, laboratory, and chest CT (316 scans) data were retrospectively reviewed. Demographics, symptoms, comorbidities, and temporal changes of laboratory results, CT features, and severity scores were compared between recovered and deceased groups using the Mann-Whitney U test and logistic regression to identify the risk factors for poor prognosis. RESULTS: Median age was 48 and 58 years for recovered and deceased patients, respectively. More patients had at least one comorbidity in the deceased group than the recovered group (60% vs. 29%). Leukocytes, neutrophil, high-sensitivity C-reactive protein (hsCRP), prothrombin, D-dimer, serum ferritin, interleukin (IL)-2, and IL-6 were significantly elevated in the deceased group than the recovered group at different stages. The total CT score at the peak stage was significantly greater in the deceased group than the recovered group (20 vs. 11 points). The optimal cutoff value of the total CT scores was 16.5 points, achieving 69.4% sensitivity and 82.2% specificity for the prognostic prediction. The crazy-paving pattern and consolidation were more common in the deceased patients than those in the recovered patients. Linear opacities significantly increased with the disease course in the recovered patients. Sex, age, neutrophil, IL-2, IL-6, and total CT scores were independent risk factors for the prognosis with odds ratios of 3.8 to 8.7. CONCLUSIONS: Sex (male), older age (>60 years), elevated neutrophil, IL-2, IL-6 level, and total CT scores (≥16) were independent risk factors for poor prognosis in patients with COVID-19. Temporal changes of chest CT features and severity scores could be valuable for early identification of severe cases and eventually reducing the mortality rate of COVID-19.

A prediction model of outcome of SARS-CoV-2 pneumonia based on laboratory findings.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in thousands of deaths in the world. Information about prediction model of prognosis of SARS-CoV-2 infection is scarce. We used machine learning for processing laboratory findings of 110 patients with SARS-CoV-2 pneumonia (including 51 non-survivors and 59 discharged patients). The maximum relevance minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator logistic regression model were used for selection of laboratory features. Seven laboratory features selected in the model were: prothrombin activity, urea, white blood cell, interleukin-2 receptor, indirect bilirubin, myoglobin, and fibrinogen degradation products. The signature constructed using the seven features had 98% [93%, 100%] sensitivity and 91% [84%, 99%] specificity in predicting outcome of SARS-CoV-2 pneumonia. Thus it is feasible to establish an accurate prediction model of outcome of SARS-CoV-2 pneumonia based on laboratory findings.

Clinical course of coronavirus disease 2019 in 11 patients after thoracic surgery and challenges in diagnosis.

OBJECTIVES: To illustrate the clinical course and difficulties in early diagnosis of coronavirus disease 2019 (COVID-19) in patients after thoracic surgery. METHODS: We retrospectively analyzed the clinical course of the first 11 patients diagnosed with COVID-19 after thoracic surgery in early January 2020. Postoperative clinical, laboratory, and radiologic records and the time line of clinical course were summarized. Potential prognostic factors were evaluated. RESULTS: In the 11 confirmed cases (3 female, 8 male), median days from symptom onset to case detection was 8. Insidious symptom onset and misinterpreted postoperative changes on chest computed tomography (CT) resulted in delay in diagnosis. There were 3 fatalities due to respiratory failure, whereas 4 severe and 4 mild cases recovered and were discharged. All patients had once experienced leukocytosis and eosinopenia. Remittent fever and resected lung segments ≥5 were associated with fatality. CONCLUSIONS: The case fatality rate of postsurgical patients subsequently diagnosed with COVID-19 was 27.3%. Insidious symptom onset, postoperative leukocytosis with lymphopenia, and postsurgical CT changes overshadowed the early signs of viral pneumonia. Dynamic symptom monitoring, serial chest CTs, and tests for viral RNA and serum antibody improve the chance for prompt detection of COVID-19. Consideration should be given to preadmission and preoperative screening and strict contact isolation during the postoperative period.

Application of Low Tube Voltage, Low-concentration Contrast Agent Using a 320-row CT in Coronary CT Angiography: Evaluation of Image Quality, Radiation Dose and Iodine Intake.

The effect of low voltage and low concentration contrast agent on image quality of coronary CT angiography, radiation dose and iodine intake was evaluated. A total of 121 patients with body mass index (BMI) <26 kg/m2 and heart rate (HR) <70 beats/min were randomly divided into four groups: group A (n=31, 80 kVp, 270 mgI/mL); group B (n=33, 100 kVp, 270 mgI/mL); group C (n=30, 100 kVp, 320 mgI/mL); group D (n=27, 100 kVp, 400 mgI/mL). The automatic current modulation system and the iterative algorithm for reconstruction were adopted in each group. The CT values and SD values of the aortic root (AR), subcutaneous fat, left coronary artery opening (LCA), and right coronary artery opening (RCA) were measured in all groups, the signal-to-noise ratio (SNR) and contrast noise ratio (CNR) were calculated, and effective radiation dose and iodine intake were recorded. The subjective assessment for image quality was performed by two physicians using a 4-point scale. The results were compared using the one-way ANOVA and rank sum tests. The image quality of the four groups met the clinical diagnostic requirements. The CT values of AR in groups A, B, C, and D were 537.6±71.4, 447.2±81.9, 445.2±64.9 and 518.5±94.9 Hu, respectively, with no significant difference between group A and group D, or between group B and group C, while CT values in groups B and C were significantly lower than those in groups A and D (P<0.05). In groups A, B, C, and D, the LCA SNR values were 22.7±9.1, 23.3±9.1, 23.3±7.7 and 26.6±8.9, and the RCA CNR values were 26.9±9.8, 28.5±11.4, 27.7±8.8 and 32.1±10.6, respectively. The AR visual scores in groups A, B, C and D were 3.8±0.2, 3.9±0.3, 3.9±0.3 and 4.0±0.3, respectively. There were no significant differences in SNR, CNR and visual score among the four groups (P>0.05). The radiation doses in groups A, B, C and D were 2.6±1.4, 3.6±1.8, 4.9±3.5 and 4.9±2.8 mSv, respectively. The radiation dose in group A was significantly less than that in the rest three groups (P<0.05). The iodine intakes in groups A, B, C and D were 14.9±1.5, 15.0±1.5, 17.7±2.0 and 18.1±2.5 g, respectively. There was no significant difference in the intake of iodine between groups C and D, or between groups A and B, while iodine intake in groups A and B were significantly reduced as compared with that in groups C and D (P<0.05). It was concluded that for patients with low BMI and controlled HR, compared to 100 kVp tube voltage combined with multiple concentration contrast agents, 80 kVp combined with 270 mgI/mL contrast agent is enough to ensure the quality of the images, and can reduce the radiation dose significantly, while reducing the amount of iodine intake notably, thus reducing the incidence of adverse reaction.