Bicuspid Aortic Valve: Current Therapeutic Strategies

Bicuspid aortic valve (BAV) is the most common congenital valvular pathology with an incidence of 1–2% in the general population. It is associated with an ascending aortic aneurysm phenotype in 26–50%, and aortic root (+/− ascending aneurysm) phenotype in up to 20–32% of patients. Bicuspid aortic valve patients present with a spectrum of valvular, ascending, and aortic root aneurysmal pathophysiologies. This variable spectrum has mandated the development of an array of surgical procedures to be able to tailor an individualized approach to BAV syndrome for a typically younger BAV population in which long-term outcomes are especially relevant . This chapter will delineate the current evidence-based surgical therapeutic strategies for patients with a BAV syndrome of aortic valve stenosis or insufficiency phenotype and aortic phenotype pathophysiology and include aortic valve replacement, aortic valve repair, aortic valve and supracoronary ascending aorta replacement (AVRSCAAR), Bentall procedure, and valve-sparing root reimplantation

Increased Production of Outer Membrane Vesicles by Salmonella Interferes with Complement-Mediated Innate Immune Attack

Bacterial outer membrane vesicles (OMVs) enriched with bioactive proteins, toxins, and virulence factors play a critical role in host-pathogen and microbial interactions. The two-component system PhoP-PhoQ (PhoPQ) of Salmonella enterica orchestrates the remodeling of outer membrane lipopolysaccharide (LPS) molecules and concomitantly upregulates OMV production. In this study, we document a novel use of nanoparticle tracking analysis to determine bacterial OMV size and number. Among the PhoPQ-activated genes tested,; pagC; expression had the most significant effect on the upregulation of OMV production. We provide the first evidence that PhoPQ-mediated upregulation of OMV production contributes to bacterial survival by interfering with complement activation. OMVs protected bacteria in a dose-dependent manner, and bacteria were highly susceptible to complement-mediated killing in their absence. OMVs from bacteria expressing PagC bound to complement component C3b in a dose-dependent manner and inactivated it by recruiting complement inhibitor Factor H. As we also found that Factor H binds to PagC, we propose that PagC interferes with complement-mediated killing of Salmonella in the following two steps: first by engaging Factor H, and second, through the production of PagC-enriched OMVs that divert and inactivate the complement away from the bacteria. Since PhoPQ activation occurs intracellularly, the resultant increase in PagC expression and OMV production is suggested to contribute to the local and systemic spread of Salmonella released from dying host cells that supports the infection of new cells.; IMPORTANCE; Bacterial outer membrane vesicles (OMVs) mediate critical bacterium-bacterium and host-microbial interactions that influence pathogenesis through multiple mechanisms, including the elicitation of inflammatory responses, delivery of virulence factors, and enhancement of biofilm formation. As such, there is a growing interest in understanding the underlying mechanisms of OMV production. Recent studies have revealed that OMV biogenesis is a finely tuned physiological process that requires structural organization and selective sorting of outer membrane components into the vesicles. In Salmonella, outer membrane remodeling and OMV production are tightly regulated by its PhoPQ system. In this study, we demonstrate that PhoPQ-regulated OMV production plays a significant role in defense against host innate immune attack. PhoPQ-activated PagC expression recruits the complement inhibitor Factor H and degrades the active C3 component of complement. Our results provide valuable insight into the combination of tools and environmental signals that Salmonella employs to evade complement-mediated lysis, thereby suggesting a strong evolutionary adaptation of this facultative intracellular pathogen to protect itself during its extracellular stage in the host

How to Perfuse: Concepts of Cerebral Protection during Arch Replacement

Arch surgery remains undoubtedly among the most technically and strategically challenging endeavors in cardiovascular surgery. Surgical interventions of thoracic aneurysms involving the aortic arch require complete circulatory arrest in deep hypothermia (DHCA) or elaborate cerebral perfusion strategies with varying degrees of hypothermia to achieve satisfactory protection of the brain from ischemic insults, that is, unilateral/bilateral antegrade cerebral perfusion (ACP) and retrograde cerebral perfusion (RCP). Despite sophisticated and increasingly individualized surgical approaches for complex aortic pathologies, there remains a lack of consensus regarding the optimal method of cerebral protection and circulatory management during the time of arch exclusion. Many recent studies argue in favor of ACP with various degrees of hypothermic arrest during arch reconstruction and its advantages have been widely demonstrated. In fact ACP with more moderate degrees of hypothermia represents a paradigm shift in the cardiac surgery community and is widely adopted as an emergent strategy; however, many centers continue to report good results using other perfusion strategies. Amidst this important discussion we review currently available surgical strategies of cerebral protection management and compare the results of recent European multicenter and single-center data

Trans-sternotomy, snare-assisted thoracic endovascular aortic repair for redirection of a migrated elephant trunk

The two-stage elephant trunk (ET) and thoracic endovascular aortic repair technique for type A and B aortic dissection can result in complications between the two stages. We have presented the case of a patient with an acute-on-chronic type B aortic dissection complicated by ET kinking and migration into the false lumen. We used a hybrid approach consisting of a first stage (retrograde thoracic endovascular aortic repair) and a second stage (“body floss” with antegrade thoracic endovascular aortic repair) to successfully reposition the ET back into the true lumen