Cholangiocarcinoma (CCA) presents significant diagnostic challenges, resulting in late patient diagnosis and poor survival rates. Primary Sclerosing Cholangitis (PSC) patients pose a particularly difficult clinical dilemma, since they harbor chronic biliary strictures that are difficult to distinguish from CCA. MicroRNAs (miRs) have recently emerged as a valuable class of diagnostic markers; however, thus far, neither extracellular vesicles (EVs) nor miRs within EVs have been investigated in human bile. We aimed to comprehensively characterize human biliary EVs, including their miR content. Conclusion We have established the presence of extracellular vesicles in human bile. In addition, we have demonstrated that human biliary EVs contain abundant miR species, which are stable and therefore amenable to the development of disease marker panels. Furthermore, we have characterized the protein content, size, numbers and size distribution of human biliary EVs. Utilizing Multivariate Organization of Combinatorial Alterations (MOCA), we defined a novel biliary vesicle miR-based panel for CCA diagnosis which demonstrated a sensitivity of 67% and specificity of 96%. Importantly, our control group contained 13 PSC patients, 16 patients with biliary obstruction of varying etiologies (including benign biliary stricture, papillary stenosis, choledocholithiasis, extrinsic compression from pancreatic cysts, and cholangitis), and 3 patients with bile leak syndromes. Clinically, these types of patients present with a biliary obstructive clinical picture that could be confused with CCA. These findings establish the importance of using extracellular vesicles, rather than whole bile, for developing miR-based disease markers in bile. Finally, we report the development of a novel bile-based CCA diagnostic panel that is stable, reproducible, and has potential clinical utility.

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In a model that resembles atherosclerotic obstruction of peripheral arteries in patients, the i.m. administration of AdCA5 promoted arteriogenic and angiogenic responses.

Mesenteric ischemia is a rare disease associated with high morbidity and mortality. Acute mesenteric ischemia is most commonly secondary to embolism followed by arterial thrombosis, nonocclusive ischemia, and less commonly venous thrombosis. Chronic mesenteric ischemia is almost always caused by atherosclerotic disease, with rare causes including fibromuscular dysplasia and vasculitis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Patients with mesenteric ischemia usually present with nonspecific abdominal symptoms and laboratory findings. This document evaluates and rates the appropriateness of imaging to evaluate patients with clinically suspected mesenteric ischemia. While catheter-based angiography has been considered the reference standard and enables diagnosis and treatment, advances in computed tomography have made it a first-line test in many patients because it is a fast, widely available, and noninvasive study. Abdominal radiographs and ultrasound have a limited role in diagnosing mesenteric ischemia but are commonly the first ordered tests in patients with abdominal pain and may diagnose more common pathologies.