Coxsackievirus type B (CVB) infection of the pancreas induces a massive cellular infiltrate composed of natural killer cells, T cells, and macrophages and leads to the destruction of exocrine tissue. The physiological manifestations of pancreatic CVB infection are correlated with viral tropism; the virus infects acinar cells but spares the islets of Langerhans. Here we evaluate the mechanisms underlying pancreatic inflammation and destruction and identify the determinants of viral tropism. T-cell-mediated immunopathology has been invoked, along with direct virus-mediated cytopathicity, to explain certain aspects of CVB-induced pancreatic disease. However, we show here that in the pancreas, the extent of inflammation and tissue destruction appears unaltered in the absence of the cytolytic protein perforin; these findings exclude any requirement for perforin-mediated lysis by natural killer cells or cytotoxic T cells in CVB3-induced pancreatic damage. Furthermore, perforin-mediated cytotoxic T-cell activity does not contribute to the control of CVB infection in this organ. In addition, we demonstrate that the recently identified coxsackie-adenovirus receptor is expressed at high levels in acinar cells but is barely detectable in islets, which is consistent with its being a major determinant of virus tropism and, therefore, of disease. However, further studies using various cell lines of pancreatic origin reveal secondary determinants of virus tropism.

Coronary computed tomography angiography (CTA) allows coronary artery visualization and the detection of coronary stenoses. In addition; it has been suggested as a novel, noninvasive modality for coronary atherosclerotic plaque detection, characterization, and quantification. Emerging data show that coronary CTA-based semiquantitative plaque characterization and quantification are sufficiently reproducible for clinical purposes, and fully quantitative approaches may be appropriate for use in clinical trials. Furthermore, several lines of investigation have validated plaque imaging by coronary CTA against other imaging modalities such as intravascular ultrasound/"virtual histology" and optical coherence tomography, and there are emerging data using biochemical modalities such as near-infrared spectroscopy. Finally, clinical validation in patients with acute coronary syndrome and in the outpatient setting has shown incremental value of CTA-based plaque characterization for the prediction of major cardiovascular events. With recent developments in image acquisition and reconstruction technologies, coronary CTA can be performed with relatively low radiation exposure. With further technological innovation and clinical research, coronary CTA may become an important tool in the quest to identify vulnerable plaques and the at-risk patient.

No abstract

No abstract

Coronary computed tomography angiography (CTA) is an increasingly utilized, highly accurate noninvasive test for the diagnosis of coronary artery disease. Accumulating data have convincingly demonstrated that the presence, extent, and location of both obstructive and nonobstructive coronary atherosclerosis visualized on coronary CTA conveys powerful prognostic information, incremental to that provided by clinical variables and coronary calcium scoring. Proposed markers of future plaque instability and coronary risk, such as the degree of vessel remodeling and low-attenuation plaque volume, as well as measures of CT myocardial perfusion, may further improve the prognostic value of CTA. Ultimately, studies are needed to assess whether the prognostic information provided by coronary CTA testing results in sustained changes in patient and provider behaviors that cost effectively improve patient outcomes.

We sought to assess the prognostic value of coronary computed tomography angiography (CCTA) among military health care system beneficiaries. We identified 1,125 consecutive symptomatic patients without known coronary artery disease (CAD) referred for 64-slice CCTA (2006-2010) at a single center. CAD was assessed as none, < 50%, or > or = 50% (obstructive) coronary stenosis. A combined endpoint of major adverse events (death, myocardial infarction [MI], coronary revascularization > 90 days after CCTA) was assessed by Kaplan-Meier and Cox proportional hazards. The mean age was 50 +/- 12 years, 59% were male, and 617 (55%) had no CAD, 411 (37%) nonobstructive CAD, and 97 (9%) obstructive CAD on CCTA. During 2.0 +/- 1.1-year follow-up, there were 6 deaths, 3 MIs, and 6 revascularizations. There was 1 event in the no-CAD group (0.08%/year), 4 events in the nonobstructive group (0.5%/year), and 9 events in patients with obstructive CAD (4.5%/year) (p < 0.001). Patients with obstructive CAD had significantly increased combined adverse events. Increasing angina typicality and risk factors (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.05-1.46; p = 0.01) and obstructive CAD (HR 12.1, 95% CI 3.99-36.9; p < 0.001) were independently predictive of events. Absence of CAD was associated with very low event rates, providing military health care system patients and providers confidence in regards to cardiovascular risk, future deployments, and occupational assignments.

Coronary CT angiography has gained increasingly widespread acceptance as a highly accurate method for the diagnosis of coronary artery disease. Beyond its usefulness as a diagnostic test to identify coronary artery stenoses in appropriately selected patients, multiple studies have consistently demonstrated that the extent and severity of coronary atherosclerosis visualized using coronary CT angiography conveys robust prognostic information. The majority of studies to date examining clinical outcomes following coronary CT angiography have documented coronary artery disease either as the presence of any coronary plaque or through the number of vessels with ≥50% (obstructive) stenosis. In the future, advanced, semi-quantitative measures of coronary atherosclerotic disease burden, plaque morphology, and composition may provide additional prognostic information. It is imperative that patients undergoing coronary CT angiography and their providers understand the prognostic information inherent to modern coronary CT angiography so that the maximal yield may be realized. Herein, we review the currently available prognostic studies of coronary CT angiography.