Neovascularization and inflammation are independent biological processes but are linked in response to injury. The role of inflammation-dampening cytokines in the regulation of angiogenesis remains to be clarified. The purpose of this work was to test the hypothesis that IL-19 can induce angiogenesis in the absence of tissue hypoxia and to identify potential mechanisms. Using the aortic ring model of angiogenesis, we found significantly reduced sprouting capacity in aortic rings from IL-19(-/-) compared with wild-type mice. Using an in vivo assay, we found that IL-19(-/-) mice respond to vascular endothelial growth factor (VEGF) significantly less than wild-type mice and demonstrate decreased capillary formation in Matrigel plugs. IL-19 signals through the IL-20 receptor complex, and IL-19 induces IL-20 receptor subunit expression in aortic rings and cultured human vascular smooth muscle cells, but not endothelial cells, in a peroxisome proliferator-activated receptor-γ-dependent mechanism. IL-19 activates STAT3, and IL-19 angiogenic activity in aortic rings is STAT3-dependent. Using a quantitative RT-PCR screening assay, we determined that IL-19 has direct proangiogenic effects on aortic rings by inducing angiogenic gene expression. M2 macrophages participate in angiogenesis, and IL-19 has indirect angiogenic effects, as IL-19-stimulated bone marrow-derived macrophages secrete proangiogenic factors that induce greater sprouting of aortic rings than unstimulated controls. Using a quantitative RT-PCR screen, we determined that IL-19 induces expression of angiogenic cytokines in bone marrow-derived macrophages. Together, these data suggest that IL-19 can promote angiogenesis in the absence of hypoxia by at least two distinct mechanisms: 1) direct effects on vascular cells and 2) indirect effects by stimulation of macrophages.
Background: Coronary artery calcification (CAC) is a common and important incidental finding in low-dose computed tomography (LDCT) performed for lung cancer screening (LCS). The impact of these incidental findings on patient management is unclear. Purpose: The goals of our study were to determine the impact of reporting CAC on patient management and to determine whether standardized reporting of CAC affects the likelihood of future interventions. Methods: In this IRB-approved retrospective study, we queried our LCS database for reports of LDCT performed between January 2016 and September 2018. All reports with significant findings of CAC designated with the letter “S” for any Lung-RADS category were selected. The grading of CAC was extracted from the reports. Medical records were reviewed for each patient to determine demographics, clinical history, medications, and cardiac-related diagnostic and interventional procedures. The changes in management after the report of significant CAC on LDCT were documented. Statistical analysis with Student t test and Pearson χ2 test was performed. Results: A total of 756/3110 patients (mean age: 67±6.4 y; M=466, 61.6%: F=290, 38.4%) were reported to have significant CAC on LDCT for LCS. Of them, 236/756 patients (31.2%) had established coronary artery disease (CAD) at baseline, before the initial LDCT. A change in management was observed in 155/756 patients (20.5%). The most common changes in management included the following: alteration in medication regimen (n=114/155, 73.5%), stress testing (n=65/155, 41.9%), and referral to a cardiologist (36/155, 23.2%). Percutaneous coronary intervention (4, 2.6%) and surgery (3, 1.9%) were uncommon. Changes in management were more common in those without established CAD and in those whose CAC was semiquantitatively graded (35% vs. 25%, P=0.02). Conclusion: CAC is a common significant finding in LDCT for LCS. Reporting of CAC in patients with nonestablished CAD and semiquantitative assessment resulted in changes in management.
Although pneumocystis jiroveci pneumonia was historically associated with HIV/AID patients, there is a recent shift in demographics with increasing incidence in patients with hematologic malignancies and transplants. A granulomatous response to pneumocytis jiroveci infection is uncommon and most commonly presents as multiple randomly distributed nodules on chest imaging. Granulomatous pneumocytis jiroveci pneumonia presents with similar clinical manifestations as typical pneumocytis pneumonia but is usually not detected by bronchoalveolar lavage and may require biopsy for a definitive diagnosis. For this reason, the radiologist may be the first provider to suggest this diagnosis and guide management.
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