The hemodynamic effects of in-tandem carotid artery stenosis: implications for carotid endarterectomy.

OBJECTIVES: It remains controversial whether patients with severe disease of the internal carotid artery and a coexisting stenotic lesion downstream would benefit from a carotid endarterectomy (CEA) of the proximal lesion. The aim of this study was to simulate the hemodynamic and wall shear effects of in-tandem internal carotid artery stenosis using a computational fluid dynamic (CFD) idealized model to give insight into the possible consequences of CEA on these lesions. METHODS: A CFD model of steady viscous flow in a rigid tube with two asymmetric stenoses was introduced to simulate blood flow in arteries with multiple constrictions. The effect of varying the distance between the two stenoses, and the severity of the upstream stenosis on the pressure and wall shear stress (WSS) distributions on the second plaque, was investigated. The influence of the relative positions of the two stenoses was also assessed. RESULTS: The distance between the plaques was found to have minimal influence on the overall hemodynamic effect except for the presence of a zone of low WSS (range -20 to 30 dyne/cm2) adjacent to both lesions when the two stenoses were sufficiently close (<4 times the arterial diameter). The upstream stenosis was protective if it was larger than the downstream stenosis. The relative positions of the stenoses were found to influence the WSS but not the pressure distribution. CONCLUSIONS: The geometry and positions of the lesions need to be considered when considering the hemodynamic effects of an in-tandem stenosis. Low WSS is thought to cause endothelial dysfunction and initiate atheroma formation. The fact that there was a flow recirculation zone with low WSS in between the two stenoses may demonstrate how two closely positioned plaques may merge into one larger lesion. Decision making for CEA may need to take into account the hemodynamic situation when an in-tandem stenosis is found. CFD may aid in the risk stratification of patients with this problem.

Spread of Salmonella enterica in the body during systemic infection: unravelling host and pathogen determinants.

Salmonella enterica causes a range of life-threatening diseases in humans and animals worldwide. Current treatments for S. enterica infections are not sufficiently effective, and there is a need to develop new vaccines and therapeutics. An understanding of how S. enterica spreads in tissues has very important implications for targeting bacteria with vaccine-induced immune responses and antimicrobial drugs. Development of new control strategies would benefit from a more sophisticated evaluation of bacterial location, spatiotemporal patterns of spread and distribution in the tissues, and sites of microbial persistence. We review here recent studies of S. enterica serovar Typhimurium (S. Typhimurium) infections in mice, an established model of systemic typhoid fever in humans, which suggest that continuous bacterial spread to new infection foci and host phagocytes is an essential trait in the virulence of S. enterica during systemic infections. We further highlight how infections within host tissues are truly heterogeneous processes despite the fact that they are caused by the expansion of a genetically homogeneous microbial population. We conclude by discussing how understanding the within-host quantitative, spatial and temporal dynamics of S. enterica infections might aid the development of novel targeted preventative measures and drug regimens.