Colorectal Cancer Risk Factors and Screening Among the Uninsured of Tampa Bay: A Free Clinic Study.

INTRODUCTION: Uninsured patients with low socioeconomic status are at high risk for developing colorectal cancer (CRC), and data on risk factors and prevalence of CRC in this population are limited. The purpose of this study was to assess the risk factors for CRC in uninsured patients from free clinics in the Tampa Bay area of Florida. METHODS: We conducted a retrospective cohort study among patients 50 years or older who were provided service at 9 free clinics in the Tampa Bay area between 2016 and 2018. Demographics, chronic disease characteristics, and screening data were collected via a query of paper and electronic medical records. RESULTS: Of the 13,982 patients seen, 5,139 (36.8%) were aged 50 years or older. Most were female (56.8%), non-Hispanic White (41.1%), and unemployed (54.9%). Patients with CRC screening were more likely to be employed compared with patients without CRC screening (54.4% vs 44.4%, P = .01). Within the cohort, 725 (22.7%) patients were active smokers, 771 (29.2%) patients currently consumed alcohol, and 23 patients (0.4%) had a history of inflammatory bowel disease. Patients had a median body mass index of 29.4 (interquartile range, 25.4-34.2) kg/m2, and 1,455 (28.3%) had diabetes. Documented CRC screening was found among 341 (6.6%) patients. CONCLUSION: Uninsured patients had a high prevalence of CRC risk factors but a low reported screening rate for CRC. Free clinics are uniquely positioned to provide patients at high risk for CRC with strategies to decrease their risk and to be screened for CRC.

Focal adhesion kinase and Src mediate microvascular hyperpermeability caused by fibrinogen- γC- terminal fragments.

OBJECTIVES: We previously reported microvascular leakage resulting from fibrinogen-γ chain C-terminal products (γC) occurred via a RhoA-dependent mechanism. The objective of this study was to further elucidate the signaling mechanism by which γC induces endothelial hyperpermeability. Since it is known that γC binds and activates endothelial αvß3, a transmembrane integrin receptor involved in intracellular signaling mediated by the tyrosine kinases FAK and Src, we hypothesized that γC alters endothelial barrier function by activating the FAK-Src pathway leading to junction dissociation and RhoA driven cytoskeletal stress-fiber formation. METHODS AND RESULTS: Using intravital microscopy of rat mesenteric microvessels, we show increased extravasation of plasma protein (albumin) resulting from γC administration. In addition, capillary fluid filtration coefficient (Kfc) indicated γC-induced elevated lung vascular permeability. Furthermore, γC decreased transendothelial barrier resistance in a time-dependent and dose-related fashion in cultured rat lung microvascular endothelial cells (RLMVECs), accompanied by increased FAK/Src phosphorylation detection by western blot. Experiments with pharmacological inhibition or gene silencing of FAK showed significantly reduced γC-induced albumin and fluid leakage across microvessels, stress-fiber formation, VE-cadherin tyrosine phosphorylation, and improved γC-induced endothelial barrier dysfunction, indicating the involvement of FAK in γC mediated hyperpermeability. Comparable results were found when Src was targeted in a similar manner, however inhibition of FAK prevented Src activation, suggesting that FAK is upstream of Src in γC-mediated hyperpermeability. In addition, γC-induced cytoskeletal stress-fiber formation was attenuated during inhibition or silencing of these tyrosine kinases, concomitantly with RhoA inhibition. CONCLUSION: The FAK-Src pathway contributes to γC-induced microvascular barrier dysfunction, junction protein phosphorylation and disorganization in a manner that involves RhoA and stress-fiber formation.