A Case Report of Invasive Lobular Carcinoma of Breast with Multiple Gastrointestinal and Cutaneous Metastases.

BACKGROUND: The metastasis of primary breast invasive lobular carcinoma to the gastrointestinal tract and skin is a rare phenomenon, with the simultaneous occurrence of both transfers being more uncommon. CASE PRESENTATION: This article reports a case of a patient with hormone receptor-positive, HER2-negative breast invasive lobular carcinoma with gastrointestinal tract and skin metastases. The patient was assessed by a second-look ultrasound and diagnosed by subsequent ultrasound-guided needle biopsy. Following endocrine therapy, a favorable effect was observed, with significant regression of the primary breast lesion, cutaneous metastases, and gastrointestinal metastases. CONCLUSION: Patients with breast invasive lobular carcinoma should be alert to the possibility of breast cancer metastasis, even if there are no obvious symptoms or signs, when they encounter rapidly progressive cutaneous nodules or plaques, or if they possess gastrointestinal abnormalities. For patients with negative breast ultrasonography for the first time, after combining mammography, Contrast-enhanced Spectral Mammography (CESM) or Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) examinations, if breast cancer is highly suspected, second-look ultrasound is particularly crucial at this juncture, which is the key prerequisite for breast needle biopsy and obtaining the gold standard of pathology.

Extrachromosomal circular DNA landscape of breast cancer with lymph node metastasis.

Breast cancer (BC) is a complex disease with diverse manifestations, often resulting in lymph node metastasis (LNM) and impacting patient prognosis. Extrachromosomal circular DNA (eccDNA) has emerged as a key player in tumorigenesis, yet its contribution to BC LNM remains elusive. Here, we examined primary tumors and matched LNM tissues from 19 BC patients using the Circle-Seq method. We identified a median count of 44,682 eccDNA in primary tumor tissues and 38,057 in their paired LNM tissues. Furthermore, a ladder-like size distribution is observed in both primary tumor and LNM tissues. Meanwhile, similar repeat sequence distribution and GC content are identified from both primary tissue and LNM tissues. Finally, we found that eccDNA from both groups are flanked with palindromic trinucleotide motifs. These observations indicate that eccDNA of primary tumor and LNM tissues are from similar chromosomal origins. However, a subset of miRNA-associated eccDNA displayed selective enrichment in metastatic lesions, such as miR-6730 and miR-548AA1 genes. This observation implicates the function of miRNA-related eccDNA in the metastatic cascade. Our study uncovers the potential significance of these unique eccDNA molecules, shedding light on their role in cancer metastasis.

The ultrasonography and pathological features of primary hepatic pleomorphic undifferentiated sarcoma.

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Mammographically detected breast clustered microcalcifications localized by chest thin-section computed tomography.

BACKGROUND: To explore the capability and clinical significance of chest thin-section computed tomography (CT) for localization of mammographically detected clustered microcalcifications. METHODS: A total of 69 patients with 71 mammographically detected clustered microcalcifications received surgical biopsy under the guidance of mammography (MG), CT was used to localize calcifications combined with MG if calcifications can be seen on CT. Intraoperative mammography of the specimens were performed in all cases for identification of the resected microcalcifications. The clinical, imaging and pathological information of these patients were analyzed. RESULTS: A total of 42 (59.15%) cases of calcifications were localized by CT + MG, 29 (40.85%) cases were guided only by the mammography. All suspicious calcifications on the mammography were successfully removed. Pathological results showed 42 cases were cancer, 23 cases were benign, and 6 cases were atypical hyperplasia. The mean age in the CT + MG group was older than that of the MG group (54.12 vs. 49.27 years; P = 0.014). The maximum diameter of clusters of microcalcifications on mammography in the CT + MG group was larger than that of the MG group [(cranio-caudal view, 1.52 vs. 0.61 mm, P = 0.000; mediolateral oblique (MLO) view, 1.53 vs. 0.62 mm, P = 0.000)]. The gray value ratio (calcified area / paraglandular; MLO, P = 0.004) and the gray value difference (calcified area - paraglandular; MLO, P = 0.005) in the CT + MG group was higher than that of the MG group. Multivariate analysis showed that the max diameter of clusters of microcalcifications (MLO view) was a significant predictive factor of localization by CT in total patients (P = 0.001). CONCLUSIONS: About half of the mammographically detected clustered microcalcifications could be localized by thin-section CT. Maximum diameter of clusters of microcalcifications (MLO view) was a predictor of visibility of calcifications by CT. Chest thin-section CT may be useful for localization of calcifications in some patients, especially for calcifications that are only visible in one view on the mammography.

Improving fast auto-focus with event polarity.

Fast and accurate auto-focus in adverse conditions remains an arduous task. The emergence of event cameras has opened up new possibilities for addressing the challenge. This paper presents a new high-speed and accurate event-based focusing algorithm. Specifically, the symmetrical relationship between the event polarities in focusing is investigated, and the event-based focus evaluation function is proposed based on the principles of the event cameras and the imaging model in the focusing process. Comprehensive experiments on the public event-based autofocus dataset (EAD) show the robustness of the model. Furthermore, precise focus with less than one depth of focus is achieved within 0.004 seconds on our self-built high-speed focusing platform. The dataset and code will be made publicly available.

Epstein-Barr virus-associated B-cell lymphoproliferative disorder meeting the definition of CAEBV B cell disease: a case report.

BACKGROUND: Chronic active Epstein-Barr virus infection (CAEBV) is a systemic EBV-positive lymphoproliferative disorder (EBV-LPD) considered to be associated with a genetic immunological abnormality, although its cause is still unclear. EBV is usually detected in T cells or NK cells in CAEBV patients with only a few cases involving B cells described in East Asia, which may be due to differences in genetic and environmental factors. CASE DESCRIPTION: A 16-year-old boy who seemed to be diagnosed as CAEBV of B cell type was studied. The patient had IM-like symptoms persisting for more than 3 months, high levels of EBV DNA in the PB, and positive EBER in situ hybridization in B cells. In addition, to exclude underlying genetic disorders, we performed next-generation sequencing (NGS) and whole-exome sequencing (WES), which identified the missense mutation in PIK3CD (E1021K), ADA (S85L) and CD3D (Q140K) in the patient while no same genetic mutation was detected in his parents and sister. However, there is no diagnosis of CAEBV of B cell type in the most recent World Health Organization classification of tumors of hematopoietic and lymphoid tissues, therefore we finally diagnosed this patient as EBV-B-LPD. CONCLUSIONS: This study shows a rare case of a patient meeting the definition of CAEBV B-cell disease in East Asia. Meanwhile, the case indicates that the missense mutation and the disease are related.

Outcomes of programmed death protein-1 inhibitors treatment of chronic active Epstein Barr virus infection: A single center retrospective analysis.

Introduction: Chronic active Epstein-Barr virus (CAEBV) disease is a high-mortality disease, which is characterized by persistent infectious mononucleosis-like symptoms. There is no standard treatment for CAEBV and allogeneic hematopoietic stem cell transplantation (HSCT) was considered the only potentially therapeutic approach. PD-1 inhibitors have achieved high response in many Epstein-Barr virus-related diseases. In this single-center retrospective analysis, we report the outcomes of PD-1 inhibitors treatment of CAEBV. Methods: All CAEBV patients without hemophagocytic lymphohistiocytosis (HLH), who were treated with PD-1 inhibitors in our center between 6/1/2017 and 12/31/2021, were retrospectively analyzed. The efficacy and safety of the PD-1 inhibitors were evaluated. Results: Among the sixteen patients with a median age at onset of 33 years (range, 11-67 years), twelve patients responded to PD-1 inhibitors and the median progression-free survival (PFS) was 11.1 months (range, 4.9-54.8 months). Three achieved clinical complete response (clinical CR), as well as molecular CR. Five patients achieved and remained partial response (PR), and four converted from PR to no response (NR). For three CR patients, the median time and cycles from the first application of PD-1 inhibitor to clinical CR were 6 weeks (range, 4-10 weeks) and 3 cycles (range, 2-4 cycles), and molecular CR was achieved after a median of 16.7 weeks (range, 6.1-18.4 weeks) and 5 cycles (range, 3-6 cycles) of PD-1 inhibitor infusion. No immune-related adverse events have been observed except for one patient who suffered immune-related pancreatitis. There was no correlation of treatment outcome with blood count, liver function, LDH, cytokine or ferritin levels. NK cell function, PD-L1 expression in tumor tissue and gene mutation possibly correlated with treatment response. Discussion: In patients with CAEBV, PD-1 inhibitors have tolerable toxicity and comparable outcomes while improving quality of life and financial toxicity. Larger prospective studies and longer follow-up time is needed to be conducted.

Effects of an mHealth Intervention for Pulmonary Tuberculosis Self-management Based on the Integrated Theory of Health Behavior Change: Randomized Controlled Trial.

BACKGROUND: Improving the health self-management level of patients with tuberculosis (TB) is significant for reducing drug resistance, improving the cure rate, and controlling the prevalence of TB. Mobile health (mHealth) interventions based on behavioral science theories may be promising to achieve this goal. OBJECTIVE: This study aims to explore and conduct an mHealth intervention based on the Integrated Theory of Health Behavior Change (ITHBC) in patients with pulmonary TB to increase their ability of self-care management. METHODS: A prospective randomized controlled study was conducted from May to November 2020. A total of 114 patients who were admitted consecutively to the TB clinic of Harbin Chest Hospital, China from May 2020 to August 2020 were recruited by convenience sampling. Patients were divided into the control group and intervention group, and all received a 3-month intervention. Patients in the intervention group and the control group received routine medical and nursing care in the TB clinic, including the supervision of their medications. In addition, pharmacist-assisted mHealth (WeChat) intervention based on the ITHBC theory about TB management was provided to the intervention group. The primary outcome was self-management behavior, while the secondary outcomes were TB awareness, self-efficacy, social support, and degree of satisfaction with health education. The outcomes were measured using web-based self-designed and standard questionnaires administered at baseline and at the end point of the study. Intergroup data were assessed using the Mann-Whitney U test, whereas intragroup data were assessed with the Wilcoxon test (for paired samples). RESULTS: A total of 112 patients (59 in intervention group and 53 in control group) completed the study. After the intervention, a statistically significant increase was noted in the scores of each item of self-care management behaviors compared with the scores at the baseline (P<.001) in the intervention group. The scores of all self-care management behaviors of the control group were lower than those of all self-care management behaviors in the intervention group (all P<.05), except for the item "cover your mouth and nose when coughing or sneezing" (P=.23) and item "wash hands properly" (P=.60), which had no statistically significant difference from those in the intervention group. Compared with those at baseline, TB knowledge awareness, self-efficacy, social support, and degree of satisfaction with health education in the intervention group increased significantly (P<.001), and the intervention group had significantly higher scores than the control group (P<.001). CONCLUSIONS: mHealth intervention for TB self-management based on ITHBC could deepen the understanding of patients with TB about their disease and improve their objective initiative and self-care management behaviors, which were beneficial for promoting compliance behavior and quality of prevention and control for pulmonary TB. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200055557; https://tinyurl.com/4ray3xnw.

The superiority of Epstein-Barr virus DNA in plasma over in peripheral blood mononuclear cells for monitoring EBV-positive NK-cell lymphoproliferative diseases.

Epstein-Barr virus (EBV), characterized as an omnipresent virus, has been found able to infect NK cells and leads to NK-cell type EBV-positive lymphoproliferative diseases (EBV-NK-LPDs). We retrospective analyzed 202 EBV-NK-LPDs (including 64 CAEBV-NK, 27 aggressive natural killer-cell leukemia (ANKL), and 111 extranodal NK/T-cell lymphoma (ENKTL)) patients' relationships between EBV DNA copies laboratory test results and clinical features. In CAEBV-NK cohort, EBV DNA loads in either plasma or PBMCs had significant differences between the active state and the inactive state. Receiver operating characteristic curves were used to measure the diagnosis accuracy of EBV DNA copies. After comparing the area under the curve, EBV DNA loads in plasma had significantly higher accuracy in distinguishing disease activation than in PBMCs. Therefore, we propose redefining CAEBV-NK diagnosis criteria as increased EBV DNA copies in plasma (over 7.1 × 102 copies/ml) instead of in peripheral blood. In ANKL and ENKTL cohorts, patients who received effective therapy had significantly lower EBV DNA copies in plasma & PBMCs than in those with ineffective therapy. The significant and consistent decline indicated EBV DNA loads in plasma being a more sensitive biomarker in monitoring EBV-NK-LPDs therapy responses. Hemophagocytic lymphohistiocytosis (HLH) can occur secondary to EBV-NK-LPDs, mostly associated with a poor prognosis, so we try to estimate the combination of HLH by monitoring EBV DNA copies. When comparing the Receiver operating characteristic curves of EBV DNA copies, EBV DNA loads in plasma had higher diagnosis accuracy. When the copies level over 4.16 × 103 copies/ml, it might indicate combining with HLH.

Self-medication in Chinese residents and the related factors of whether or not they would take suggestions from medical staff as an important consideration during self-medication.

Objective: To investigate the status of Chinese residents' self-medication behavior and the important factors to consider when purchasing OTC drugs, and to explore the related factors of the possibility that Chinese residents take medical staff's suggestions as important factors to consider when purchasing OTC drugs. Study design: A cross-sectional survey. Methods: A questionnaire was developed for exploring the sociodemographic characteristics of the respondents, their self-medication status, and important considerations. The questionnaire includes several scales including Health Literacy Scale-Short Form (HLS-SF), EQ-5D Visual Analog Scale (EQ-5D-VAS), Big Five Inventary-10 Items (BFI-10), and New General Self Efficacy Scale (NGSES). After carrying out a multi-stage sampling method, the questionnaire was conducted nationwide from July 10 to September 15, 2021. Next, descriptive statistics were conducted to analyze the general features. Logistic regression was then used to analyze the related factors of the possibility that the respondents took the suggestions of medical staff as an important consideration when purchasing OTC drugs. Results: Nine thousand two hundred fifty-six qualified questionnaires were received. 99.06% of Chinese adults had self-medication behaviors. The types of OTC drugs purchased most by the respondents were NSAIDs (5,421/9,256 people, 58.57%) and vitamins/minerals (4,851/9,256 people, 52.41%). 86.2% of the respondents took the suggestions of medical staff as an important consideration when purchasing OTC drugs. The results of multi-factor logistic regression showed that women, those living in the central and western regions of China, those suffering from chronic diseases, those with high agreeableness, high conscientiousness, high neuroticism and openness, high health literacy, high EQ-5D-VAS, and those with high self-efficacy are more likely to take medical staff's suggestions as important factors to consider. Conclusion: The vast majority of Chinese adults have self-medication behavior. Important considerations when purchasing OTC drugs include medical staff's suggestions, drug safety and drug efficacy. Whether residents take the suggestions of medical staff as an important consideration is related to their sociological characteristics, agreeableness, conscientiousness, neuroticism, openness, health literacy, self-assessment health status, and self-efficacy. When purchasing and using OTC drugs, residents should carefully listen to the suggestions from medical staff. They should also carefully consider their own conditions before buying OTC drugs.

Chronic active Epstein-Barr virus infection progresses to aggressive NK cell leukemia with a poor prognosis.

Epstein-Barr virus (EBV) associated T/NK-cell lymphoproliferative diseases (EBV-T/NK-LPDs) are a cluster of diseases that include chronic active EBV infection (CAEBV) and aggressive NK cell leukemia (ANKL). The pathogenesis of EBV-T/NK-LPDs is largely unclear and the treatment is difficult and in most cases a hematopoietic stem cell transplantation is needed. Hemophagocytic lymphohistiocytosis (HLH) is known to affect the prognosis of patients with EBV-T/NK-LPDs. This study reports a case of a 20-year-old male patient with repeated infectious mononucleosis (IM)-like symptoms such as high fever, splenomegaly, lymphadenopathy for more than two years. The patient had a high EBV-DNA load (NK cells were the main target cells). He was first diagnosed as CAEBV. However, the disease gradually progressed and the patient developed with high ferritin, phagocytosis and monoclonal NK cells in bone marrow, pancytopenia, increased cytokines, and elevated expression of Ki-67. Also, his NK cells had abnormal immunophenotypes and impaired function. The patient had a typical clinical course of progression from CAEBV to ANKL, accompanied by HLH complications and a poor prognosis. Herein, the detailed diagnostic and differential diagnostic process of EBV infection was shown in this report.

Case Report: Post-CAR-T Infusion HBV Reactivation in Two Lymphoma Patients Despite Entecavir Preventive Therapy.

Hepatitis B virus (HBV) reactivation is a common complication in chronic or resolved HBV infection patients undergoing immunosuppressive chemotherapy. Furthermore, few articles have been published regarding the risk of HBV reactivation in lymphoma patients receiving chimeric antigen receptor (CAR) T-cell therapy and anti-HBV prophylaxis. Few guidelines or clear optimal strategies are available for managing these patients. Here, we present two cases of patients who underwent CAR-T-cell cocktail therapy with anti-CD19 and anti-CD22 CAR (CAR19/22) T cell for lymphoma. Patients had previous history of HBV infection, and blood tests on initial admission indicated positive results for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and antibody to hepatitis B e antigen (anti-HBe), while serum HBV DNA level was undetectable. Therefore, two patients received entecavir as antiviral prophylactic therapy during their entire treatment. They were diagnosed with HBV reactivation based on positive serum HBV DNA test results, 2 weeks after CAR-T-cell infusion. Liver function assay indicated elevated levels of alanine transaminase (ALT) and aspartate transaminase (AST), combined with increased levels of total bilirubin (TBIL) and direct bilirubin (DBIL). Subsequently, they received anti-HBV treatment with entecavir and tenofovir. As a result, their serum HBV DNA copies and AST/ALT levels returned to normal after 1 week. These cases show that there is a risk of HBV reactivation in lymphoma patients with CAR-T-cell therapy despite entecavir preventive therapy, and combination treatment of entecavir and tenofovir may be an effective treatment option for such patients with HBV reactivation.