Identification and characterization of new candidates for abdominal aortic aneurysm screening in patients outside of current accepted guidelines.

BACKGROUND: Previous studies have identified groups of patients with abdominal aortic aneurysm (AAA) that fall outside of currently accepted screening guidelines. Population-based studies have found AAA screening would be cost-effective at a prevalence of 0.5% to 1.0%. The goal of this study was to determine the prevalence of AAA in patients that fall outside of the current screening guidelines. In addition, we analyzed outcomes of the groups with a prevalence of greater than 1%. METHODS: Using the TriNetX Analytics Network, several patient cohorts were abstracted with a diagnosis of ruptured or unruptured AAA based on previously identified groups with a potentially high risk for AAA that fall outside of currently accepted screening guidelines. Groups were also stratified by sex. For groups found to have a prevalence of greater than 1%, the unruptured patients were further analyzed for long-term rates of rupture and included male ever-smokers aged 45 to 65, male never-smokers aged 65 to 75, male never-smokers aged greater than 75, and female ever-smokers aged 65 or greater. Long-term mortality, stroke, and myocardial infarction rates were compared in patients with treated and untreated AAA after propensity score matching. RESULTS: We identified 148,279 patients across the four groups with a prevalence of AAA of greater than 1% with female ever-smokers aged 65 or older being the most prevalent (2.73%). In each of the four groups, the rate of AAA rupture increased every 5 years and all had rupture rates of greater than 1% at 10 years. Meanwhile, controls for each of these four subgroups without a previous AAA diagnosis had rupture rates between 0.090% and 0.013% at 10 years. Those who underwent repair of their AAA had decreased incidence of mortality, stroke, and myocardial infarction. Specifically, male ever-smokers aged 45 to 64 had a significant difference in incidence of mortality and myocardial infarction at 5 years and stroke at 1 and 5 years. CONCLUSIONS: Our analysis suggests male ever-smokers aged 45 to 65, male never-smokers aged 65 to 75, male never-smokers aged greater than 75, and female ever-smokers aged 65 or greater have a more than 1% prevalence of AAA and, therefore, may benefit from screening. Outcomes were significantly worse compared with well-matched controls in these groups.

Exported Epoxide Hydrolases Modulate Erythrocyte Vasoactive Lipids during Plasmodium falciparum Infection.

Erythrocytes are reservoirs of important epoxide-containing lipid signaling molecules, including epoxyeicosatrienoic acids (EETs). EETs function as vasodilators and anti-inflammatory modulators in the bloodstream. Bioactive EETs are hydrolyzed to less active diols (dihydroxyeicosatrienoic acids) by epoxide hydrolases (EHs). The malaria parasite Plasmodium falciparum infects host red blood cells (RBCs) and exports hundreds of proteins into the RBC compartment. In this study, we show that two parasite epoxide hydrolases, P falciparum epoxide hydrolases 1 (PfEH1) and 2 (PfEH2), both with noncanonical serine nucleophiles, are exported to the periphery of infected RBCs. PfEH1 and PfEH2 were successfully expressed in Escherichia coli, and they hydrolyzed physiologically relevant erythrocyte EETs. Mutations in active site residues of PfEH1 ablated the ability of the enzyme to hydrolyze an epoxide substrate. Overexpression of PfEH1 or PfEH2 in parasite-infected RBCs resulted in a significant alteration in the epoxide fatty acids stored in RBC phospholipids. We hypothesize that the parasite disruption of epoxide-containing signaling lipids leads to perturbed vascular function, creating favorable conditions for binding and sequestration of infected RBCs to the microvascular endothelium. IMPORTANCE: The malaria parasite exports hundreds of proteins into the erythrocyte compartment. However, for most of these proteins, their physiological function is unknown. In this study, we investigate two "hypothetical" proteins of the α/ß-hydrolase fold family that share sequence similarity with epoxide hydrolases (EHs)-enzymes that destroy bioactive epoxides. Altering EH expression in parasite-infected erythrocytes resulted in a significant change in the epoxide fatty acids stored in the host cell. We propose that these EH enzymes may help the parasite to manipulate host blood vessel opening and inflame the vessel walls as they pass through the circulation system. Understanding how the malaria parasite interacts with its host RBCs will aid in our ability to combat this deadly disease.