Evaluation of standard breast ultrasonography by adding two-dimensional and three-dimensional shear wave elastography: a prospective, multicenter trial.

OBJECTIVE: To reduce the number of biopsies performed on benign breast lesions categorized as BI-RADS 4-5, we investigated the diagnostic performance of combined two-dimensional and three-dimensional shear wave elastography (2D + 3D SWE) with standard breast ultrasonography (US) for the BI-RADS assessment of breast lesions. METHODS: A total of 897 breast lesions, categorized as BI-RADS 3-5, were subjected to standard breast US and supplemented by 2D SWE only and 2D + 3D SWE analysis. Based on the malignancy rate of less than 2% for BI-RADS 3, lesions assessed by standard breast US were reclassified with SWE assessment. RESULTS: After standard breast US evaluation, 268 (46.1%) participants underwent benign biopsies in BI-RADS 4-5 lesions. By using separated cutoffs for upstaging BI-RADS 3 at 120 kPa and downstaging BI-RADS 4a at 90 kPa in 2D + 3D SWE reclassification, 123 (21.2%) participants underwent benign biopsy, resulting in a 54.1% reduction (123 versus 268). CONCLUSION: Combining 2D + 3D SWE with standard breast US for reclassification of BI-RADS lesions may achieve a reduction in benign biopsies in BI-RADS 4-5 lesions without sacrificing sensitivity unacceptably. CLINICAL RELEVANCE STATEMENT: Combining 2D + 3D SWE with US effectively reduces benign biopsies in breast lesions with categories 4-5, potentially improving diagnostic accuracy of BI-RADS assessment for patients with breast lesions. TRIAL REGISTRATION: ChiCTR1900026556 KEY POINTS: • Reduce benign biopsy is necessary in breast lesions with BI-RADS 4-5 category. • A reduction of 54.1% on benign biopsies in BI-RADS 4-5 lesions was achieved using 2D + 3D SWE reclassification. • Adding 2D + 3D SWE to standard breast US improved the diagnostic performance of BI-RADS assessment on breast lesions: specificity increased from 54 to 79%, and PPV increased from 54 to 71%, with slight loss in sensitivity (97.2% versus 98.7%) and NPV (98.1% versus 98.7%).

Clinical features of aseptic meningitis with varicella zoster virus infection diagnosed by next-generation sequencing: case reports.

BACKGROUND: The aseptic meningitis caused by varicella zoster virus (VZV) reactivation was less described in the literature, most of which were detected by means of polymerase chain reaction. The authors presented 4 adult immunocompetent patients with acute aseptic meningitis with VZV infection diagnosed by next-generation sequencing (NGS). CASE PRESENTATION: Four patients were admitted to the hospital with headache and fever between March 2018 and August 2019. The median ages were 37 years (range 22-52 years). The median symptoms onset to clinic time was 3.5 days (range 3-6 days). Two patients had signs of meningeal irritation. Rash occurred after the meningitis symptoms in 1 patient (time from meningitis symptoms to rash, 2 days). No other sign or symptom was reported. The brain Magnetic resonance imaging and electroencephalography were normal in all patients. Cerebrospinal fluid (CSF) samples were obtained at a median of 4 days (range 3-7 days) from the meningitis symptoms onset. Opening pressure of lumbar puncture after admission were high in these cases (median 256 mm H2O; range 165-400 mm H2O). White blood cell counts and protein levels were significantly elevated in CSF samples (median 317 × 10^6/L, range 147-478 × 10^6/L; median 1.41 g/L, range 0.57-1.79 g/L). The cytology of CSF demonstrated a lymphocytic pleocytosis, and most multinuclear cells. The culture of CSF was negative for all 4 cases, while T-cell spot test was positive for 2 cases, who were administrated with anti-tuberculosis treatment for suspicious tuberculous meningitis. NGS of CSF (the Vision Medical Research Institute) detected specific sequences of VZV in the 4 cases within 72 h after admission. The inappropriate treatment were stopped while acyclovir were continued intravenously for 10-14 days. All patients recovered completely. CONCLUSIONS: VZV is an infectious agent that causes aseptic meningitis in immunocompetent adults and could not be accompanied by skin manifestations. The NGS of CSF is a rapid detection for the identification and differentiation of meningitis in patients, which is of great importance for providing the rapid and accurate diagnosis and the targeted antimicrobial therapy for central nervous system infection.

[The Characteristics of Ultrasonography and Thermal Tomography in Various Molecular Subtypes of Breast Cancer].

OBJECTIVE: To explore the relationship between the imaging features of ultrasonography and thermal tomography and molecular subtypes of breast cancer. METHODS: 404 female breast cancer patients with complete imaging data and pathological findings from January 2014 to June 2017 were reviewed in the West China Hospital of Sichuan University. Breast cancer pathological molecules were classified into Luminal A like type, Luminal B like type, human epidermal growth receptor-2 (HER-2) overexpression type and Basal like type according to the expression of various immune markers. The correlation of ultrasonographic BI-RADS signs, thermal tomography characteristics and immunohistochemical results of breast cancer was analyzed. RESULTS: Breast cancer lesions with regular morphology, sharp margins, and enhanced posterior echo were more common in Basal like type; Microcalcification was more likely tend to appear in HER-2 expression breast cancer than other subtypes; The q-r curve of Luminal A like breast cancer was nearly 30°, and that was more common between 30°and 45° of HER-2 expression and Basal like breast cancer；The ratio of vertical and horizontal ≥1 of tumors and limited lymph node metastasis could not be used for distinguishing between different subtypes. CONCLUSION: Different molecular subtypes of breast cancer may behave routine ultrasound and thermal tomography imaging features.

[Breast Thermal Tomography and High Frequency Ultrasound Imaging in Predicting Breast Cancer: a Preliminary Study].

OBJECTIVE: To determine the clinical value of breast thermal tomography and high frequency ultrasound imaging in diagnosing breast cancer. METHODS: Breast thermal tomography and high frequency ultrasound imaging were performed in 298 patients with breast lumps. The results were compared with pathological diagnosis. RESULTS: The ultrasound imaging had a sensitivity, specificity and the area under the curve (AUC) of 99.02%, 62.78% and 0.814, respectively, compared with 83.33%, 83.16% and 0.830 of thermal tomography, for diagnosing breast cancer. The two imaging results showed statistical significance in the test of non-inferiority (P < 0.001). A combination of the two imaging results produced a sensitivity, specificity and AUC of 83.33%, 89.79% and 0.866, respectively. CONCLUSION: Thermal tomography is not inferior to ultrasonography in detecting breast cancer. The two combined can improve specificity and accuracy of the diagnosis of breast cancer.

[Contrast-enhanced ultrasonography findings for papillary thyroid carcinoma and its pathological bases ].

OBJECTIVE: To investigate the findings of contrast enhanced ultrasound for papillary thyroid carcinoma and its pathological bases. METHODS: Seventy two (72) patients with thyroid nodules underwent routine conventional ultrasound and color Doppler examination, and 86 nodules with TI RADS 3 were examined by contrast-enhanced ultrasound (CEUS . Histopathological examination was kept as standard reference and the findings of CEUS were analyzed. Pathological studies of all nodules were made after post-operative CD34 immunohistochemistry staining examination. RESULTS: Of the total 86 nodules, Adler CDFl classification grades were: grade 0-26. grade I-34. grade II-23 and grade III-3 nodules respectively. Enhancement pattern on CEUS showed that there was low enhancement on 71 nodules, iso enhancement on 12 and high enhancement on 3 nodules. The differences of echo mean intensity. the peak intensity, area under the curve for enhancement intensity and CD34 count between the nodules and surrounding tissue were statistical significant (P < 0. 001). CONCLUSION: Low enhancement pattern on CEUS is the most common finding for papillary thyroid carcinoma, which is related to the difference of microvessel density between the nodules and surrounding tissues in papillary thyroid carcinoma.

[The perfusion pattern of lymphadenopathy in contrast-enhanced ultrasonograph. under different reference conditions ].

OBJECTIVE: To determine the perfusion pattern of lymphadenopathy in contrast-enhanced ultrasonography (CEUS) under different reference conditions. METHODS: The CEUS perfusion patterns of 78 superficial lymph node lesions were compared with their pathology results. Time-intensity curves were used for comparison between benign and malignant lymph nodes. RESULTS: Inhomogeneous hyperenhancement was the main perfusion pattern (7/17, 41. 2%) in metastatic lymph nodes; compared with homogeneous hyperenhancement (2/4, 50. 0%) in lymphoma, homogeneous hyperenhancement and isoenhancement (6/52, 11. 5%) in reactive lymph nodes, and circle enhancement (2/4,50. 0%) in tuberculosis. Benign lymph nodes showed different mean value, peak intensity and area under the curve compared with their surrounding arteries (P<0. 05). But the differences in mean value, rise time, time to peak, peak intensity and the area under the curve between benign lymphadenopathy and their surrounding tissues were not statistically significant (P>0. 05). Malignant lymph nodes showed different mean value and peak intensity compared with their surrounding arteries and tissues (P<0. 05). The differences in time to peak between malignant lymph nodes and their surrounding tissues were also statistically significant (P< 0. 05). CONCLUSION: Different CEUS perfusion patterns are associated with different types of lymph node lesions. Time intensity curves with surrounding tissues as reference condition offer great values for the differential diagnosis of superficial lymphadenopathy.

[Sonography of male breast lesions and the pathological diagnosis: a retrospective study of 10 years and literature review].

The sonographic features of male breast lesions, which underwent ultrasound examination in our hospital for the past 10 years, were retrospectively analyzed. Sonographic features of these lesions were standardized as BI RADS image lexicon. The differences in ultrasonic malignant signs were assessed between the benign and the malig nant diseases. Between the two groups, incomplete boundary was statistically different. The specificity was above 95% within the two groups in terms of speculated margin, echogenic halo, calcification, axillary lymphadenopathy, thickening of skin and eccentric of mass to the nipple. High-frequency sonographic examination has a high level of differential diagnosis for male breast lesions.

Metagenomic next-generation sequencing for diagnosis of infectious encephalitis and meningitis: a retrospective study of 90 patients.

BACKGROUND: Infections of the central nervous system (CNS) are potentially life-threatening and can cause serious morbidity. We evaluated the clinical value of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis and explored the factors affecting the results of mNGS. METHODS: Patients with suspected cases of encephalitis or meningitis who presented in Northern Jiangsu People's Hospital from 1 March 2018 to 30 September 2022 were collected. Demographic, historical, and clinical information were obtained, and cerebrospinal fluid (CSF) samples were treated with mNGS. The pathogen was identified using National Center for Biotechnology Information (NCBI) GenBank sequence data. RESULTS: Ninety-six patients were screened and finally 90 subjects enrolled. Of the 90 enrolled cases, 67 (74.4%) were diagnosed with central nervous system infections, which included 48 cases (71.6%) of viral infection, 11 (12.2%) of bacterial infection, 5 (7.5%) of mycobacterium tuberculosis, 2 (3.0%) of fungal infection, and 1 (1.5%) of rickettsia infection. From these cases, mNGS identified 40 (44.4%) true-positive cases, 3 (3.3%) false-positive case, 22 (24.4%) true-negative cases, and 25 (27.8%) false-negative cases. The sensitivity and specificity of mNGS were 61.5% and 88%, respectively. mNGS of CSF could show a higher positive rate in patients with marked CSF abnormalities, including elevated protein concentrations and monocyte counts. CONCLUSION: mNGS of CSF is an effective method for detecting infectious encephalitis and meningitis, and the results should be analyzed combined with conventional microbiological testing results.

Inhibition of YAP/TAZ pathway contributes to the cytotoxicity of silibinin in MCF-7 and MDA-MB-231 human breast cancer cells.

Breast cancer is one of the most common cancers threatening women's health. Our previous study found that silibinin induced the death of MCF-7 and MDA-MB-231 human breast cancer cells. We noticed that silibinin-induced cell damage was accompanied by morphological changes, including the increased cell aspect ratio (cell length/width) and decreased cell area. Besides, the cytoskeleton is also destroyed in cells treated with silibinin. YAP/TAZ, a mechanical signal sensor interacted with extracellular pressure, cell adhesion area and cytoskeleton, is also closely associated with cell survival, proliferation and migration. Thus, the involvement of YAP/TAZ in the cytotoxicity of silibinin in breast cancer cells has attracted our interests. Excitingly, we find that silibinin inhibits the nuclear translocation of YAP/TAZ in MCF-7 and MDA-MB-231 cells, and reduces the mRNA expressions of YAP/TAZ target genes, ACVR1, MnSOD and ANKRD. More importantly, expression of YAP1 gene is negatively correlated with the survival of the patients with breast cancers. Molecular docking analysis reveals high probabilities for binding of silibinin to the proteins in the YAP pathways. DARTS and CETSA results confirm the binding abilities of silibinin to YAP and LATS. Inhibiting YAP pathway either by addition of verteporfin, an inhibitor of YAP/TAZ-TEAD, or by transfection of si-RNAs targeting YAP or TAZ further enhances silibinin-induced cell damage. While enhancing YAP activity by silencing LATS1/2 or overexpressing YAPS127/397A, an active form of YAP, attenuates silibinin-induced cell damage. These findings demonstrate that inhibition of the YAP/TAZ pathway contributes to cytotoxicity of silibinin in breast cancers, shedding lights on YAP/TAZ-targeted cancer therapies.