Background and Purpose Vascular endothelial growth factor (VEGF) expression is elevated in human brain arteriovenous malformations (bAVM). We have developed a bAVM model in the adult mouse by focal Alk1 gene deletion and human VEGF stimulation. We hypothesized that once the abnormal vasculature has been established; tonic VEGF stimulation is necessary to maintain the abnormal phenotype and VEGF antagonism by bevacizumab (Avastin) would reduce vessel density and attenuate the dysplastic vascular phenotype. Methods Angiogenesis and bAVM were induced by injection of adeno-associated viral vector expressing human VEGF (AAV-VEGF) alone into the brain of wild-type (WT) mice or with adenoviral vector expressing Cre recombinase (Ad-Cre) into Alk12f/2fmice. Six weeks later, bevacizumab or trastuzumab (Herceptin, bevacizumab control) were administered. Vessel density (VD), dysplasia index (DI), vascular cell proliferation and apoptosis, and human IgG were assessed (n=6/group). Results Compared to trastuzumab (15 mg/kg), administration of 5, 10 and 15 mg/kg of bevacizumab to AAV-VEGF treated WT mice reduced focal VD (p<0.05); administration of 5 mg/kg bevacizumab decreased proliferating vascular cells (p=0.04) and increased TUNEL-positive vascular cells (p=0.03). More importantly, bevacizumab (5 mg/kg) treatment reduced both VD (p=0.01) and DI (p=0.02) in our bAVM model. Human IgG was detected in the vessel wall and the parenchyma in the angiogenic foci of bevacizumab treated mice. Conclusions We provide proof-of-principle that, once abnormal AVM vessels have formed, VEGF antagonism may reduce the number of dysplastic vessels and should be further evaluated as a therapeutic strategy for the human disease.
The high prevalence of sleep-related breathing disorders demands the development of ambulatory recording devices that can handle data with a high degree of selectivity and are easy to use and to interpret. A digital device based on the recording of heart rate and breathing sounds was developed. Patients with sleep-related breathing disorders can be preselected before they undergo sleep laboratory investigations. Treatment control can be achieved ambulatory, having an initial recording.
Introduction:We examined the characteristics and financial outcomes of online crowdfunding campaigns for patients with major urological cancers in the U.S.Methods: This cross-sectional study analyzed publicly available data from GoFundMe, the largest online medical crowdfunding service, via automated web scraping. Online campaigns from 2010 to 2018 with the following primary cancer types were included: kidney, prostate, bladder and testicular. Financial outcomes were compared using Kruskal-Wallis and Wilcoxon rank-sum tests. Multivariable analyses were utilized to identify predictors of campaign financial outcomes.Results: Kidney cancers were the most frequent online campaign type (478), followed by prostate (379), bladder (202) and testicular (175) malignancies. Urological cancer campaign recipients frequently requested funding for medical expenses (71%) during active treatment (57%). After adjustment, testicular cancer and children's cancer campaigns generated more donations than other urological and adult cancer campaigns (p <0.05). Family and friend-authored campaigns generated more donations and average donation amounts than self-authored campaigns (p <0.05). Campaign narratives focused on disheartening circumstances received fewer donations than narratives focused on the recipient's high moral character or contributions to society (p <0.05), and unclear narratives received the smallest donation amounts (p <0.05).Conclusions: Urological cancer crowdfunding in the U.S. is primarily used to finance uncovered costs associated with medical care during active treatment. Crowdfunding financial outcomes are likely related to the campaign recipient's age, malignancy type, social network and primary appeal of the narrative. Urologists should be aware of trends in medical crowdfunding in order to better understand the financial burden this patient population faces.
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