Evolution of Precision Medicine and Surgical Strategies for Bicuspid Aortic Valve-Associated Aortopathy

Bicuspid aortic valve (BAV) is a common congenital cardiac malformation affecting 1–2% of people. BAV results from fusion of two adjacent aortic valve cusps, and is associated with dilatation of the aorta, known as bicuspid valve associated aortopathy. Bicuspid valve aortopathy is progressive and associated with catastrophic clinical events, such as aortic dissection and rupture. Therefore, frequent monitoring and early intervention with prophylactic surgical resection of the proximal aorta is often recommended. However, the specific pattern of aortopathy is highly variable among patients, with different segments of the ascending aorta being affected. Individual patient risks are sometimes difficult to predict. Resection strategies are informed by current surgical guidelines which are primarily based on aortic size and growth criteria. These criteria may not optimally reflect the risk of important aortic events. To address these issues in the care of patients with bicuspid valve aortopathy, our translational research group has focused on validating use of novel imaging techniques to establish non-invasive hemodynamic biomarkers for risk-stratifying BAV patients. In this article, we review recent efforts, successes, and ongoing challenges in the development of more precise and individualized surgical approaches for patients with bicuspid aortic valves and associated aortic disease

Do Health and Forensic DNA Databases Increase Racial Disparities?

Peter Chow-White and Troy Duster examine the question of whether the "digital divide" in health and forensic DNA databases is contributing to racial disparities

Glucose and Fatty Acid Metabolism in a 3 Tissue In-Vitro Model Challenged with Normo- and Hyperglycaemia

Nutrient balance in the human body is maintained through systemic signaling between different cells and tissues. Breaking down this circuitry to its most basic elements and reconstructing the metabolic network in-vitro provides a systematic method to gain a better understanding of how cross-talk between the organs contributes to the whole body metabolic profile and of the specific role of each different cell type. To this end, a 3-way connected culture of hepatocytes, adipose tissue and endothelial cells representing a simplified model of energetic substrate metabolism in the visceral region was developed. The 3-way culture was shown to maintain glucose and fatty acid homeostasis in-vitro. Subsequently it was challenged with insulin and high glucose concentrations to simulate hyperglycaemia. The aim was to study the capacity of the 3-way culture to maintain or restore normal circulating glucose concentrations in response to insulin and to investigate the effects these conditions on other metabolites involved in glucose and lipid metabolism. The results show that the system’s metabolic profile changes dramatically in the presence of high concentrations of glucose, and that these changes are modulated by the presence of insulin. Furthermore, we observed an increase in E-selectin levels in hyperglycaemic conditions and increased IL-6 concentrations in insulin-free-hyperglycaemic conditions, indicating, respectively, endothelial injury and proinflammatory stress in the challenged 3-way system

Is food addiction a predictor of treatment outcome among patients with eating disorder?

ObjectivesThe study aimed to examine whether food addiction (FA) was associated with greater severity in both binge eating disorders (BED) and bulimia nervosa and, therefore, to determine if FA was predictive of treatment outcome.MethodSeventy-one adult patients with bulimia nervosa and BED (42 and 29, respectively) participated in the study. FA was assessed by means of the Yale Food Addiction Scale.ResultsThe results confirmed a high prevalence of FA in patients with binge disorders (around 87%) and also its association with a greater severity of the disorder (i.e., related to an increased eating psychopathology and greater frequency of binge eating episodes). Although FA did not appear as a predictor of treatment outcome in general terms, when the diagnostic subtypes were considered separately, FA was associated with poor prognosis in the BED group. In this vein, FA appeared as a mediator in the relationship between ED severity and treatment outcome.DiscussionsOur findings suggest that FA may act as an indicator of ED severity, and it would be a predictor of treatment outcome in BED but not in BN.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152018/1/erv2705.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152018/2/erv2705_am.pd

The science of BAV aortopathy

The aortopathy associated with bicuspid aortic valve (BAV) is an epidemiologically relevant source of chronic and acute aortic disease (aneurysm and dissection). However, its pathogenesis is still the object of scientific uncertainties and debates. Indeed, the mechanisms determining the diseases of the ascending aorta in BAV patients are most likely complex and multifactorial, i.e. resulting from variable modes of interplay between genetic and hemodynamic factors. Although few scientific studies have so far taken into adequate account this complexity, leaving the precise sequence of pathogenetic events still undiscovered, the accumulated evidence from previous research approaches have at least brought about important insights. While genetic studies have so far identified variants relevant to either valve malformation or aortic complications (including those in the genes NOTCH1, TGFBR2, ACTA2, GATA5, NKX2.5, SMAD6, ROBO4), however each explaining not more than 5% of the study population, other investigations have thoroughly described both the flow features, with consequent forces acting on the arterial wall (including skewed flow jet direction, rotational flow, wall shear stress), and the main changes in the molecular and cellular wall structure (including extracellular matrix degradation, smooth muscle cell changes, oxidative stress, unbalance of TGF-beta signaling, aberrant endothelia l-tomesenchymal transition). All of this evidence, together with the recognition of the diverse phenotypes that the aortopathy can assume in BAV patients, holding possible prognostic significance, is reviewed in this chapter. The complex and multifaceted body of knowledge resulting from clinical and basic science studies on BAV aortopathy has the potential to importantly influence modes of clinical management of this disease in the near future. Crown Copyright (c) 2020 Published by Elsevier Inc. All rights reserved