Hierarchical online contrastive anomaly detection for fetal arrhythmia diagnosis in ultrasound.

Arrhythmia is a major cardiac abnormality in fetuses. Therefore, early diagnosis of arrhythmia is clinically crucial. Pulsed-wave Doppler ultrasound is a commonly used diagnostic tool for fetal arrhythmia. Its key step for diagnosis involves identifying adjacent measurable cardiac cycles (MCCs). As cardiac activity is complex and the experience of sonographers is often varied, automation can improve user-independence and diagnostic-validity. However, arrhythmias pose several challenges for automation because of complex waveform variations, which can cause major localization bias and missed or false detection of MCCs. Filtering out non-MCC anomalies is difficult because of large intra-class and small inter-class variations between MCCs and non-MCCs caused by agnostic morphological waveform variations. Moreover, rare arrhythmia cases are insufficient for classification algorithms to adequately learn discriminative features. Using only normal cases for training, we propose a novel hierarchical online contrastive anomaly detection (HOCAD) framework for arrhythmia diagnosis during test time. The contribution of this study is three-fold. First, we develop a coarse-to-fine framework inspired by hierarchical diagnostic logic, which can refine localization and avoid missed detection of MCCs. Second, we propose an online learning-based contrastive anomaly detection with two new anomaly scores, which can adaptively filter out non-MCC anomalies on a single image during testing. With these complementary efforts, we precisely determine MCCs for correct measurements and diagnosis. Third, to the best of our knowledge, this is the first reported study investigating intelligent diagnosis of fetal arrhythmia on a large-scale and multi-center ultrasound dataset. Extensive experiments on 3850 cases, including 266 cases covering three typical types of arrhythmias, demonstrate the effectiveness of the proposed framework.

An intelligent quantification system for fetal heart rhythm assessment: A multicenter prospective study.

BACKGROUND: The motion relationship and time intervals of the pulsed-wave Doppler (PWD) spectrum are essential for diagnosing fetal arrhythmia. However, few technologies currently are available to automatically calculate fetal cardiac time intervals (CTIs). OBJECTIVE: The purpose of this study was to develop a fetal heart rhythm intelligent quantification system (HR-IQS) for the automatic extraction of CTIs and establish the normal reference range for fetal CTIs. METHODS: A total of 6498 PWD spectrums of 2630 fetuses over the junction between the left ventricular inflow and outflow tracts were recorded across 14 centers. E, A, and V waves were manually labeled by 3 experienced fetal cardiologists, with 17 CTIs extracted. Five-fold cross-validation was performed for training and testing of the deep learning model. Agreement between the manual and HR-IQS-based values was evaluated using the intraclass correlation coefficient and Spearman's rank correlation coefficient. The Jarque-Bera test was applied to evaluate the normality of CTIs' distributions, and the normal reference range of 17 CTIs was established with quantile regression. Arrhythmia subset was compared with the non-arrhythmia subset using the Mann-Whitney U test. RESULTS: Significant positive correlation (P <.001) and moderate-to-excellent consistency (P <.001) between the manual and HR-IQS automated measurements of CTIs was found. The distribution of CTIs was non-normal (P <.001). The normal range (2.5th to 97.5th percentiles) was successfully established for the 17 CTIs. CONCLUSIONS: Using our HR-IQS is feasible for the automated calculation of CTIs in practice and thus could provide a promising tool for the assessment of fetal rhythm and function.

The value of conventional ultrasound combined with superb microvascular imaging and color Doppler flow imaging in the diagnosis of thyroid malignant nodules: a systematic review and meta-analysis.

Purpose: To evaluate and compare the value of conventional ultrasound-based superb microvascular imaging (SMI) and color Doppler flow imaging (CDFI) in the diagnosis of malignant thyroid nodule by meta-analysis. Methods: The literature included in the Cochrane Library, PubMed, and Embase were searched by using " superb microvascular imaging (SMI), color Doppler flow imaging (CDFI), ultrasound, thyroid nodules" as the keywords from inception through February 1, 2023. According to the inclusion and exclusion criteria, the clinical studies using SMI and CDFI to diagnose thyroid nodules were selected, and histopathology of thyroid nodules was used as reference standard. The diagnostic accuracy research quality assessment tool (QUADAS-2) was used to evaluate the quality of included literature, and the Review Manager 5.4 was used to make the quality evaluation chart. The heterogeneity test was performed on the literature that met the requirements, the combined sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were pooled, and a comprehensive ROC curve analysis was performed. Meta-DiSc version 1.4, StataSE 12, and Review Manager 5.4 software were used. Results: Finally, 13 studies were included in this meta-analysis. A total of 815 thyroid malignant nodules were assessed. All thyroid nodules were histologically confirmed after SMI or CDFI. The combined sensitivity, specificity, PLR, NLR, DOR, and area under the SROC curve of SMI for the diagnosis of malignant thyroid nodules were 0.80(95%CI: 0.77-0.83), 0.79(95%CI: 0.77-0.82), 4.37(95%CI: 3.0-6.36), 0.23(95%CI: 0.15-0.35), 22.29(95%CI: 12.18-40.78), and 0.8944, respectively; the corresponding values of CDFI were 0.62(95%CI: 0.57-0.67), 0.81(95%CI: 0.78-0.85), 3.33(95%CI: 2.18-5.07), 0.41(95%CI: 0.27-0.64), 8.93(95%CI: 3.96-20.16), and 0.8498. Deek funnel pattern showed no significant publication bias. Conclusion: The diagnostic efficiency of SMI for malignant thyroid nodules is better than CDFI, and SMI technology can provide significantly more information on vascularity, make up for the deficiency of CDFI, and has better clinical application value. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023402064.

Older Age and Abnormal Pulmonary Ventilation Function Do Not Increase the Risk of Pulmonary Hemorrhage Caused by CT-Guided Percutaneous Core Needle Biopsy.

Purpose: The aim of this study was to analyze the differences in risk factors for pulmonary hemorrhage in elderly and young patients with percutaneous computed tomography-guided needle biopsies (PCNBs). The correlations between the incidence of pulmonary hemorrhage and pulmonary function indicators before CT-guided PCNB were also discussed. Methods: Between January 2018 and December 2019, 1,100 consecutive patients underwent CT-guided PCNBs at Qilu Hospital. Both univariate and multivariate logistic regression analyses identified risk factors for hemorrhage. Results: The occurrence of pulmonary hemorrhage was 22.1% in elderly patients and was 22.6% in young patients. In elderly patients, pulmonary hemorrhage was significantly influenced by needle depth to the lesion and dwell time, while in young patients, pulmonary hemorrhage was independently associated with lesion size, needle depth to the lesion, and dwell time. However, pulmonary function parameters, including FVC (% pred), FEV1 (% pred), FEV1/FVC ratio (%), small airway function parameters (FEF50%, FEF75%, and FEF25-75%), and large airway function parameters (MVV, PEF, and FEF25%), were not risk factors for hemorrhage. Furthermore, the incidence of pulmonary hemorrhage was not associated with different types of pulmonary dysfunctions. The risk of pulmonary hemorrhage did not increase with the severity of pulmonary dysfunctions. Conclusions: In this study, age is no longer a risk factor in evaluating pulmonary hemorrhage. Longer needle depth to the lesion and longer dwell time were significantly high risk factors of hemorrhage in both elderly patients and young patients. Patients with severe pulmonary dysfunctions did not show increased risks of pulmonary hemorrhage here.

Elevated ß-catenin and C-myc promote malignancy, relapse, and indicate poor prognosis in patients with relapsed glioma.

Context: Extensive studies have shown that ß-catenin and C-myc have been linked to a number of human cancers. However, the role of ß-catenin and C-myc in relapse glioma remains unclear. Aims: The aims of this study were to investigate the role of ß-catenin and C-myc in relapsed glioma patients and to explore the possible impact of malignancy, relapse, and prognosis. Materials and Methods: We collected surgical samples of 100 patients with primary and relapsed glioma treated at our institution. Immunohistochemistry (IHC) staining was used to evaluate the expressions of ß-catenin and C-myc. The impact of the differences on disease-free interval (DFI), initial overall survival (iOS), and overall survival from the time of glioma relapse (rOS) of the patients was analyzed. Kaplan-Meier survival functions were used to plot survival time, and a log-rank test was used for analyzing statistical significance. Cox multivariate regression analysis was used to determine independent prognostic parameters. Results: Compared to primary tumors, relapsed gliomas had higher expressions of ß-catenin and C-myc (P < 0.05). Furthermore, the expressions of ß-catenin and C-myc were significantly correlated with glioma grade (P < 0.05). These changes in expression at the time of relapse were independent of radiotherapy use. In multivariate Cox analysis, we found that ß-catenin and C-myc were independent prognostic factors for rOS (P < 0.05). Conclusions: Elevated ß-catenin and C-myc promote malignancy, relapse, and indicate poor prognosis in patients with relapsed glioma. The elevated levels of ß-catenin and c-myc in relapsed glioma were not affected by radiation therapy. The results of this study may provide a new therapeutic target for patients with relapsed glioma.

TMEM60 Promotes the Proliferation and Migration and Inhibits the Apoptosis of Glioma through Modulating AKT Signaling.

Glioma is a highly fatal malignancy with aggressive proliferation, migration, and invasion metastasis due to aberrant genetic regulation. This work aimed to determine the function of transmembrane protein 60 (TMEM60) during glioma development. The level of TMEM60 in glioma tissues and normal tissues and its correlation with glioma prognosis were checked in The Cancer Genome Atlas (TCGA) database. The levels of TMEM60 in glioma cell lines and normal astrocytes were determined by quantitative real-time PCR and western blotting assay. TMEM60 knockdown and overexpression were conducted, followed by detection of cell viability, migration, invasion, and apoptosis. CCK-8 and colony formation assay were adopted to detect cell viability proliferation. Transwell assay was performed to measure cell migration and invasion. Cell apoptosis was evaluated by flow cytometry. The alternation of key proteins in the PI3K/Akt signaling pathway was measured by western blotting. TMEM60 expression was significantly higher in glioma tissues than that in the healthy control and was correlated with poor overall survival of patients. The protein and mRNA levels of TMEM60 were both elevated in glioma cell lines in comparison with the normal cell lines. Elevated level of TMEM60 led to enhanced proliferation, migration, and invasion and suppressed cell apoptosis. TMEM60 promoted the activation of PI3K/Akt signaling. Our data suggested that TMEM60 plays an oncogenic role in glioma progression via activating the PI3K/Akt signaling pathway.

Conventional ultrasonography and elastosonography in diagnosis of malignant thyroid nodules: A systematic review and meta-analysis.

Purpose: To evaluate the diagnostic value of conventional ultrasound and elastosonography in malignant thyroid nodules by meta-analysis. Methods: The literature included in the Cochrane Library, PubMed, and Embase were searched by using "elastosonography, ultrasonography, thyroid nodules" as the keywords. The clinical studies using elastosonography and conventional ultrasound to diagnose thyroid nodules were selected, and histopathology of thyroid nodules was used as reference standards. The quality evaluation and heterogeneity test were performed on the literature that met the requirements, the combined specificity and sensitivity were pooled, and a comprehensive ROC curve analysis was performed. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was utilized to evaluate the quality of each included study. Meta-DiSc version 1.4, StataSE 12 and Review Manager 5.4 were used. Results: A total of nine studies assessed 3066 thyroid nodules (2043 benign and 1023 malignant). The pooled sensitivity, specificity, PLR, NLR, and DOR of conventional ultrasound for the diagnose of malignant thyroid nodules were 0.833 (95% CI 0.809-0.855), 0.818 (95% CI 0.801-0.835), 4.85 (95% CI 4.36-5.39), 0.20 (95% CI 0.17-0.23), and 29.38 (95% CI 23.28-37.08), respectively, with an AUC of 0.9068. Also, the pooled sensitivity, specificity, PLR, NLR, and DOR of elastosonography were 0.774 (95% CI 0.741-0.804), 0.737 (95% CI 0.715-0.758), 3.14(95% CI 2.85-3.47), 0.29 (95% CI 0.25-0.34), and 9.35 (95% CI 7.63-11.46), respectively, with an AUC of 0.8801. Three studies provided data regarding the conventional ultrasound and elastosonography. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.902 (95% CI 0.870-0.928), 0.649 (95% CI 0.616-0.681), 2.72 (95% CI 2.46-3.00), 0.14 (95% CI 0.11-0.19), 25.51 (95%CI 17.11-38.03), and 0.9294. Conclusion: The existing evidence shows that elastosonography cannot completely replace conventional ultrasound in the diagnosis of malignant thyroid nodules, and the combination of elastosonography and conventional ultrasound gives a better diagnostic precision. Systematic review registration: www.crd.york.ac.uk, identifier PROSPERO CRD42022375808.

Risk of pneumothorax caused by computerized tomography-guided percutaneous core needle biopsy of the lung in elderly and young patients.

CONTEXT: The incidences and risk factors caused by computed tomography (CT)-guided percutaneous computed tomography-guided needle biopsies (PCNBs) in elderly and young patients were not very clear. AIMS: This study explored the different incidences of pneumothorax caused by PCNBs and related risk factors in elderly and young patients. SETTINGS AND DESIGN: The medical records of 1100 patients who underwent CT-guided PCNBs in a hospital from January 2018 to December 2019 were retrospectively reviewed. SUBJECTS AND METHODS: Data relating to the patients, lesions, techniques, and diagnoses were collected according to the ethical standards of the institutional research committee (registration number: KYLL-202008-145). STATISTICAL ANALYSIS USED: The variables were significant by univariate analysis and further analyzed by multivariate logistic regression analysis. RESULTS: In the 1100 patients with PCNBs, the incidence of pneumothorax in groups ≥65 years old and <65 years old was 15.2% and 12.9%, respectively. There was no significant difference in the incidence of pneumothorax between the young and elderly patients. In elderly and young patients, emphysema along the needle path and dwell time was independent predictors. However, in young patients, lesion-abutting pleura was an independent risk factor for pneumothorax, but not in elderly patients. CONCLUSIONS: The risk of pneumothorax caused by CT-guided percutaneous core needle biopsy of the lung does not increase in elderly patients. Emphysema along the needle path and dwell time is independent predictors of pneumothorax in elderly and young patients.

The role of clinical characteristics and pulmonary function testing in predicting risk of pneumothorax by CT-guided percutaneous core needle biopsy of the lung.

BACKGROUND: We aim to analyze the risk factors for pneumothorax associated with computed tomography (CT)-guided percutaneous core needle biopsy (PCNB) of the lung. Whether the lung function characteristics are related to pneumothorax is unclear. METHODS: We retrospectively evaluated 343 patients who received CT-guided pulmonary PCNBs and underwent preoperative pulmonary function testing. Demographical, lesion-related, procedure-related features and histopathological diagnosis, as well as results of pulmonary function test were analyzed as risk factors of pneumothorax RESULTS: Variables associated with higher rate of pneumothorax were location of lesion, presence of emphysema, and dwell time. The proportion of middle lobe, lingular, or lower lobe lesions in pneumothorax group (30/50, 60.0%) is higher than non-pneumothorax group (113/293, 38.6%). The incidence of emphysema in pneumothorax group was significantly higher than that in non-pneumothorax group (34.0% vs. 7.5%). Obstructive pulmonary function abnormalities, not restrictive, mixed ventilation function abnormalities and small airway dysfunction, correlated with pneumothorax. Multivariate logistic regression analysis showed lower location of lesion sampled and presence of emphysema were independent predictors of pneumothorax. Although dwell time, FEV1/FVC ratio, FEF50%, FEF75% and FEF25-75% were significantly correlated with pneumothorax on univariate analysis, these were not confirmed to be independent predictors. CONCLUSIONS: Patients with obstructive pulmonary dysfunction have a higher risk of pneumothorax. Presence of emphysema was the most important predictor of pneumothorax, followed by location of lesion.

G protein gamma 7 suppresses progression of lung adenocarcinoma by inhibiting E2F transcription factor 1.

G protein gamma 7 (GNG7) has been found to be aberrantly expressed in some kinds of malignant tumors. In this study, we mainly discuss the antitumor role of it in lung adenocarcinoma (LUAD) cells. Protein levels of GNG7 in LUAD tissues were measured by western blot and immunohistochemical analysis. Cell proliferation, invasion and migration were detected by CCK-8 assay, 5-ethynyl-2'-deoxyuridine (EdU), and Transwell assay. In our study, GNG7 was down-regulated in LUAD, which significantly correlated with survival of LUAD patients. Functional experiments revealed that GNG7 significantly inhibited LUAD cell proliferation, migration, and invasion in vitro and E2F1 overexpression reversed these properties. GNG7 suppressed xenograft tumorigenesis in nude mice models in vivo. In conclusion, GNG7 functions as a tumor suppressor in LUAD cells through inhibiting E2F1.

Increased expression of MMP-2 and MMP-9 indicates poor prognosis in glioma recurrence.

The main characteristic of glioma is recurrence, even after intensive multidisciplinary treatment. Studies show that enhanced invasive ability will increase the ability of tumor cells to escape from the primary tumor mass, which is a key factor contributing to tumor relapse and recurrence. In this study, we assessed the expression of MMP-2, MMP-9, two important matrix metallopeptidases that increase the invasive ability of glioma, and their suppressors, TIMP-1, TIMP-2 in glioma tissues from primary and recurrent glioma patients by immunohistochemistry. Glioma cells and nude mice were used for in vitro and in vivo studies. Results showed that the expression of MMP-2 and MMP-9 in recurrent gliomas were significantly higher than those in primary gliomas (P = 3.075 × 10-11, P = 1.510 × 10-5, respectively). We also found that radiotherapy increased the expression of MMP-9, but had no effect on MMP-2 and TIMP-1/2. With glioma cell line U251, we found that irradiation increased the expression of MMP-9 in vitro. Tumor tissues from an orthotopic xenograft model showed that after irradiation treatment, the expression of MMP-9 increased significantly in vivo. We also found that knocking down MMP-9 decreased irradiation-induced invasion obviously. Above all, we concluded that higher expressions of MMP-2/-9 indicate poor prognosis in glioma recurrence. The increased expression of MMP-9 after radiotherapy suggests that MMP-9 might be an important target in the radiosensitization of glioma.

miR­494 inhibits cancer­initiating cell phenotypes and reverses resistance to lapatinib by downregulating FGFR2 in HER2­positive gastric cancer.

In gastric cancer, >15% of cases are associated with the amplification of human epidermal growth factor receptor 2 (HER2), which leads to poor clinical outcomes. Lapatinib, a potent ATP­competitive inhibitor, is a small, orally active molecule, which inhibits the tyrosine kinases of HER2 and epidermal growth factor receptor type 1. The activation of receptor tyrosine kinases can contribute to lapatinib resistance in HER2­positive gastric cancer. The aim of the present study was to explore the effects of miR­494 and FGFR2 in regulation of cancer­initiating cell phenotypes and therapeutic efficiency of lapatinib in HER2­positive gastric cancer. Western blot analysis was used to identify that the expression of fibroblast growth factor receptor 2 (FGFR2), a receptor tyrosine kinase, was upregulated in gastric cancer tissues. Formation of cancer initiating cells (CICs) and resistance to lapatinib were determined using sphere growth assay and MTT assay, respectively. The overexpression of FGFR2 promoted the generation of cancer­initiating cells (CICs) and resistance to lapatinib in HER2­positive gastric cancer YCC1 cells. In addition, it was observed that overexpression of microRNA (miR)­494 downregulated the protein expression of FGFR2, inhibited the formation of CICs and reversed lapatinib resistance in YCC1­F cells (HER2­positive, FGFR2 overexpressing and lapatinib­resistant gastric cancer cells). Therefore, it was concluded that miR­494 inhibited the CIC phenotype and reversed resistance to lapatinib by inhibiting FGFR2 in HER2­positive gastric cancer.

Diagnostic accuracy of MRI-guided percutaneous transthoracic needle biopsy of solitary pulmonary nodules.

OBJECTIVE: The purpose of our study was to evaluate the diagnostic accuracy of MRI-guided percutaneous transthoracic needle biopsy (PTNB) of solitary pulmonary nodules (SPNs). METHODS: Retrospective review of 69 patients who underwent MR-guided PTNB of SPNs was performed. Each case was reviewed for complications. The final diagnosis was established by surgical pathology of the nodule or clinical and imaging follow-up. Pneumothorax rate and diagnostic accuracy were compared between two groups according to nodule diameter (≤2 vs. >2 cm) using χ (2) chest and Fisher's exact test, respectively. RESULTS: The success rate of single puncture was 95.6 %. Twelve (17.4 %) patients had pneumothorax, with 1 (1.4 %) requiring chest tube insertion. Mild hemoptysis occurred in 7 (7.2 %) patients. All of the sample material was sufficient for histological diagnostic evaluation. Pathological analysis of biopsy specimens showed 46 malignant, 22 benign, and 1 nondiagnostic nodule. The final diagnoses were 49 malignant nodules and 20 benign nodules basing on postoperative histopathology and clinical follow-up data. One nondiagnostic sample was excluded from calculating diagnostic performance. A sensitivity, specificity, accuracy, positive predictive value, and negative predictive value in diagnosing SPNs were 95.8, 100, 97.0, 100, and 90.9 %, respectively. Pneumothorax rate, diagnostic sensitivity, and accuracy were not significantly different between the two groups (P > 0.05). CONCLUSIONS: MRI-guided PTNB is safe, feasible, and high accurate diagnostic technique for pathologic diagnosis of pulmonary nodules.

[Correlations between MRI apparent diffusion coefficient and histological grade and molecular biology of breast invasive ductal carcinoma].

OBJECTIVE: To study the correlation between the MRI apparent diffusion coefficient (ADC) value and histological grade and molecular biology of breast invasive ductal carcinoma (IDC). METHODS: This retrospective study included 125 patients with IDC verified by pathology from February 2010 to February 2013. Conventional MRI and diffusion-weighted imaging (DWI) examination were performed using a 3.0T scanner with diffusion factor of 0 and 800 s/mm(2). The region of interest (ROI) was drawn on the largest lesion and/or its two adjacent slices. The ADC value of the whole tumor was calculated as the mean ADC value. The correlation between mean ADCs and histological grade and biological factors was analyzed. RESULTS: The mean ADC of pathological grade I, II and III IDC was (1.152 ± 0.072)×10(-3) mm(2)/s, (1.102 ± 0.101)×10(-3) mm(2)/s, and (1.035 ± 0.107)×10(-3) mm(2)/s, respectively. There was a statistically significant difference among them (P = 0.003). Statistically a significant difference was observed between grade III and I (P = 0.034), grade III and II (P = 0.006), but not between grade I and II (P = 0.741). A significant correlation was observed between ADC value and pathological grade (r = -0.342, P < 0.001). The median ADC values were significantly higher in the ER-negative than in the ER-positive cases [(1.130 ± 0.115)×10(-3) mm(2)/s vs. (1.060 ± 0.089) ×10(-3) mm(2)/s, P < 0.001)], in PR-negative than in PR-positive cases [(1.121 ± 0.106)×10(-3) mm(2)/s vs. (1.055 ± 0.096) ×10(-3) mm(2)/s, P < 0.001)], and in Ki-67-negative than in Ki-67-positive cases [(1.153 ± 0.090)×10(-3) mm(2)/s vs. (1.063 ± 0.101) ×10(-3) mm(2)/s, P < 0.001]. A statistically significant correlation was observed between ADC value and expressions of ER, PR, and Ki-67 (r = -0.311, r = -0.317, r = -0.414, P < 0.001). CONCLUSION: ADC value of breast invasive ductal carcinoma is correlated with histological grade, and expression of ER, PR and Ki-67.