Malignant pleural effusion is a common complication in metastatic breast cancer (MBC); however, changes in the pleural microenvironment are poorly characterized, especially with respect to estrogen ...receptor status. Histologically, MBC presents with increased microvessels beneath the parietal and visceral pleura, indicating generalized angiogenic activity. Breast cancer‐associated pleural fluid (BAPF) was collected and cultured with HUVECs to recapitulate the molecular changes in subpleural endothelial cells. The clinical progression of triple‐negative breast cancer (TNBC) is much more aggressive than that of hormone receptor‐positive breast cancer (HPBC). However, BAPF from HPBC (BAPF‐HP) and TNBC (BAPF‐TN) homogeneously induced endothelial proliferation, migration, and angiogenesis. In addition, BAPF elicited negligible changes in the protein marker of endothelial‐mesenchymal transition. Both BAPF‐HP and BAPF‐TN exclusively upregulated JNK signaling among all MAPKs in HUVECs. By contrast, the response to the JNK inhibitor was insignificant in Transwell and tube formation assays of the HUVECs cultured with BAPF‐TN. The distinct contribution of p‐JNK to endothelial angiogenesis was consequently thought to be induced by BAPF‐HP and BAPF‐TN. Due to increased angiogenic factors in HUVECs cultured with BAPF, vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor was applied accordingly. Responses to VEGFR2 blockade were observed in both BAPF‐HP and BAPF‐TN concerning endothelial migration and angiogenesis. In conclusion, the above results revealed microvessel formation in the pleura of MBC and the underlying activation of p‐JNK/VEGFR2 signaling. Distinct responses to blocking p‐JNK and VEGFR2 in HUVECs cultured with BAPF‐HP or BAPF‐TN could lay the groundwork for future investigations in treating MBC based on hormone receptor status.
Current study evaluated the angiogenic response of HUVECs cultured with breast cancer‐associated pleural fluid (BAPF) obtained from hormone positive (HP) and triple negative (TN) breast cancer, respectively. Both BAPF‐HP and BAPF‐TN stimulated endothelial angiogenesis with upregulation of vascular endothelial growth factor receptor 2 (VEGFR2) and p‐JNK expressions. In contrast, application of p‐JNK inhibitor only showed efficacy in HUVECs cultured with BAPF‐HP, but not BAPF‐TN. Blockade of VEGFR2 signaling revealed potent inhibition on endothelial motility and angiogenesis induced by BAPF‐HP and BAPF‐TN.
It has been shown that iron deficiency anemia (IDA) is associated with psychosocial consequences and psychiatric morbidity. However, the association between adults with IDA and psychiatric disorders ...has not been clarified. The purpose of this study was to investigate the psychiatric disorder morbidity of an IDA group in comparison with a non-IDA group and to examine the risk of psychiatric disorders in IDA patients treated with iron supplementation.
All study subjects were 20 years of age or over with newly diagnosed IDA enrolled in the Taiwan National Health Insurance Database from 2000 to 2012. We matched IDA and non-IDA subjects according to age and gender in a 1:2 ratio. Our primary outcome was diagnosis of psychiatric disorders and the patients were monitored until the end of 2013. A multivariate Cox proportional hazards regression model was used to explore the risk of psychiatric disorders in patients with IDA after adjustment for confounders, including demographic characteristics and comorbidities.
The adjusted hazard ratios (aHRs) of psychiatric disorders was 1.52 (95% CI = 1.45-1.59) in the IDA group compared with the non-IDA group. Among the different types of psychiatric disorders, the IDA group was associated with significantly higher incidence and risks of anxiety disorders, depression, sleep disorders, and psychotic disorders (p < 0.05). Furthermore, iron supplementation in IDA subjects was associated with a significantly lower risk of psychiatric disorders compared to non-iron supplementation in IDA patients.
Our study indicates that IDA subjects had an increased risk of psychiatric disorders, regardless of other confounders. In IDA patients, iron supplementation was associated with a decreased risk of psychiatric disorders. Moreover, IDA patients receiving iron supplementation also had a lower risk of sleep disorders.
The most robust and economical method for laboratory diagnosis of tuberculosis (TB) is to identify mycobacteria acid-fast bacilli (AFB) under acid-fast staining, despite its disadvantages of low ...sensitivity and labor intensity. In recent years, artificial intelligence (AI) has been used in TB-smear microscopy to assist medical technologists with routine AFB smear microscopy. In this study, we evaluated the performance of a TB automated system consisting of a microscopic scanner and recognition program powered by artificial intelligence and machine learning. This AI-based system can detect AFB and classify the level from 0 to 4+. A total of 5930 smears were evaluated on the performance of this automatic system in identifying AFB in daily lab practice. At the first stage, 120 images were analyzed per smear, and the accuracy, sensitivity, and specificity were 91.3%, 60.0%, and 95.7%, respectively. In the second stage, 200 images were analyzed per smear, and the accuracy, sensitivity, and specificity were increased to 93.7%, 77.4%, and 96.6%. After removing disqualifying smears caused by poor staining quality and smear preparation, the accuracy, sensitivity, and specificity were improved to 95.2%, 85.7%, and 96.9%, respectively. Furthermore, the automated system recovered 85 positive smears initially identified as negative by manual screening. Our results suggested that the automated TB system could achieve higher sensitivity and laboratory efficiency than manual microscopy under the quality control of smear preparation. Automated TB smear screening systems can serve as a screening tool at the first screen before manual microcopy.
Malignant pleural effusion (MPE) and paramalignant pleural effusion (PPE) remain debilitating complications in lung cancer patients with poor prognosis and limited treatment options. The role of ...vascular endothelial cells has not been explored in the pleural environment of lung cancer. By integrating MPE and PPE as malignant‐associated pleural fluid (MAPF), the current study aimed to evaluate the effect of MAPF on cell proliferation, migration and angiogenesis of HUVEC. First, increased capillaries were identified in the subpleural layer of lung adenocarcinoma. Compatible with pathological observations, the ubiquitous elevation of HUVEC survival was identified in MAPF culture regardless of the underlying cancer type, the driver gene mutation, prior treatments and evidence of malignant cells in pleural fluid. Moreover, MAPF enhanced HUVEC motility with the formation of lamellipodia and filopodia and focal adhesion complex. Tube formation assay revealed angiogenic behavior with the observation of sheet‐like structures. HUVEC cultured with MAPF resulted in a significant increase in MAPK phosphorylation. Accompanied with VEGFR2 upregulation in MAPF culture, there was increased expressions of p‐STAT3, HIF‐1α and Nf‐kB. VEGF/VEGFR2 blockade regressed endothelial migration and angiogenesis but not cell proliferation. Our data indicate the angiogenic activities of MAPF on vascular endothelial cells that revealed increased pleural capillaries in lung cancer. Targeting the VEGF/VEGFR2 pathway might modulate the angiogenic propensity of MAPF in future clinical investigations.
Increased microvessel formation manifested in the subpleural layer of lung carcinoma specimens. In addition, the potency of MAPF to promote endothelial viability and motility was universal regardless of the histological type of cancer, the presence of malignant cells in pleural fluid, and whether or not patients harbored gene mutations. Blockade of VEGFR2 signaling did not compromise MAPF‐induced endothelial viability, and more bioactive factors were, thus, needed to investigate the drug development of MAPF.
Schwannomas are rare slow-growing benign tumors arising from Schwann cells lining the nerve sheaths. Head and neck schwannomas account for about one-third of all cases, and only 4% of them arise from ...the sinonasal tract. Its diagnosis is based on histology and immunohistochemistry. Complete surgical excision is the most recommended treatment option, and endoscopic surgery has been widely performed in recent years. In this study, we presented a case of a 55-year-old female with schwannoma arising from the lateral wall of the nasal cavity, causing epistaxis and rhinorrhea. The patient underwent endoscopic excision with prompt resolution of symptoms. The reported cases of nasal cavity schwannoma were reviewed and summarized for educational purposes.
Objective
To develop a risk predictor model in evaluation of tomosynthesis-detected architectural distortion (AD) based on characteristics of contrast-enhanced digital mammography (CEDM).
Methods
...Ninety-four AD lesions on CEDM in combination with tomosynthesis were retrospectively reviewed from 92 consecutive women (mean age, 52.4 years ± 7.9) with abnormal diagnostic or screening mammography. CEDM results were correlated with histology of ADs using cross-tabulation for statistical analysis. Predictors for risk of malignancy from CEDM characteristics (background parenchyma enhancement, degree of AD enhancement, enhancing morphology, size of enhancement, and enhancing spiculations) and patient’s age were evaluated using logistic regression. We propose a sum score, termed AD score (ADS), for risk stratification and corresponding suggested BI-RADS category.
Results
Thirty-three of ninety-four (35.1%) of detected AD lesions were malignant. The sensitivity, specificity, PPV, and NPV of CEDM in evaluation of malignant AD are 100%, 42.6%, 48.5%, and 100%, respectively. Absence of AD enhancement on CEDM is highly indicative of no underlying malignancy. On multivariate analysis, the predictors on CEDM with statistical significance are (1) marked intensity of AD enhancement (OR, 22.6; 95%CI 3.1, 166.6;
p
= .002); and (2) presence of enhancing spiculations (OR, 9.1; 95%CI 2.2, 36.5;
p
= .002). A prediction model whose scores (ADS) given by ranking of OR of all predictors with AUC of 0.934 and Brier score of 0.0956 was developed.
Conclusion
ADS-based lesion characterization on CEDM enables risk assessment of tomosynthesis-detected AD lesions.
Key Points
• Architecture distortions presenting with marked enhancement intensity and presence of enhancing spiculations are highly associated with risk of malignancy.
• Absence of architecture distortion enhancement in minimal or mild background parenchyma enhancement on CEDM indicates low risk of breast malignancy (NPV = 100%).
Gouty arthritis is the one of the most painful arthritis and is caused by an inflammatory reaction. This study investigated whether astaxanthin (AXT), which has documented anti‐inflammatory and ...antioxidant properties, exhibits protective effects against monosodium urate (MSU) crystal‐induced inflammation. Cell viability of J774A.1 murine macrophages was assessed by AXT dose‐dependent incubation by MTT assays, and expression levels of iNOS and COX‐2 proteins as well as secretion of IL‐1β were also analyzed under MSU crystals stimulation with or without AXT treatment. The production of inflammatory mediators was found to significantly decrease with AXT treatment, and the formation of the inflammasome complex was also attenuated when cells were co‐stimulated with MSU crystals and AXT. Furthermore, we found that expression of the MAPK pathway was downregulated in J774A.1 cells. AXT also inhibited the induction of COX‐2 and IL‐6 in human chondrocytes and synovial fibroblasts by western blots. Finally, an MSU crystal intra‐articular injection rat model for gouty arthritis was utilized in which treatment groups received 5‐daily intraperitoneal injections of AXT prior to MSU crystal stimulation, or once intra‐articular injections of AXT following MSU crystal stimulation for 6 hours. Results of synovitis score analysis revealed that inflammation was significantly attenuated in the group which received intraperitoneal AXT injection prior to MSU crystal stimulation compared to the group which received MSU only. These results indicate that AXT attenuates the effects of MSU crystal‐induced inflammation by suppressing the production of pro‐inflammatory cytokines and inflammatory mediators. Our findings that the anti‐inflammatory activities of AXT may be beneficial in the treatment of MSU crystal‐induced arthritis.
Previous research has suggested an association between antidepressants use and clinical restless legs syndrome (RLS) in patients, but there has never been a single study investigating the risk of RLS ...in irritable bowel syndrome (IBS) patients treated with antidepressants. Hence, we aimed to explore the association between IBS and RLS and to examine the risk of RLS in IBS patients treated with antidepressants. With the use of the National Health Insurance Research Database of Taiwan, 27,437 adults aged ≥ 20 years with newly diagnosed IBS (ICD-9-CM Code 564.1) and gender- and age-matched 54,874 controls without IBS were enrolled between 2000 and 2012. All patients were followed-up until RLS diagnosis, withdrawal from the National Health Insurance program, or end of 2013. We used the Cox proportional hazards model to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of RLS. RLS was more prevalent in IBS patients than in the non-IBS group (7.57 versus 3.36 per 10,000 person-years), with an increased risk of RLS (adjusted HR aHR, 1.91; 95% CI, 1.52-2.40). Multivariate Cox proportional hazards analysis identified older age (age, 51-65 years; aHR, 1.67; 95% CI, 1.09-2.56; and age > 65; aHR, 1.59; 95% CI, 1.02-2.48), hypothyroidism (aHR, 4.24; 95% CI, 1.92-9.37), CAD (aHR, 1.70; 95% CI, 1.17-2.48), and depression (aHR, 3.15; 95% CI, 2.14-4.64) as independent RLS risk factors in IBS patients. In addition, the male SSRIs users were associated with significantly higher risk of RLS (aHR, 3.05 95% CI, 1.34-6.92). Our study showed that the IBS group has higher risk of RLS. Moreover, SSRIs use may increase the risk of RLS in male IBS patients.
Gout is one of the most painful disease conditions. The central mechanism of pain processing in this condition remains elusive. Cerebral blood volume (CBV) responses are faithful correlates of brain ...activity changes; the application of CBV-weighted functional magnetic resonance imaging (fMRI) may shed light on the issue of interest. Transient receptor potential vanilloid 1 (TRPV1) is a critical ion channel expressed both peripherally in nociceptors and centrally in the brain. Whether TRPV1 plays a critical role in gout pain was also explored. Results showed that, in rats with gouty arthritis, noxious stimulation induced CBV increases in the primary somatosensory cortex and thalamus. These increases were correlated with up-regulated TRPV1 protein expression and pain behavior. Selective blockage of central TRPV1 channel activity by intrathecal administration of AMG9810 reversed the induced pain, and abolished the induced CBV increase in thalamocortical regions. The findings support that TRPV1 activation in the central pain pathway is crucial to the augmentation of pain in gouty conditions. This new information supports the development of TRPV1-based drugs for treating gout pain, while fMRI can be useful for repeated evaluation of brain activity changes induced by gout.
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