ABSTRACT
Predicting left atrial appendage thrombus (LAAT) in chronic nonvalvular atrial fibrillation remains challenging despite the fact that several predictive models have been proposed to date. In this study, we sought to develop new and simpler models for LAAT prediction in chronic nonvalvular atrial fibrillation. The study enrolled 144 patients with chronic nonvalvular atrial fibrillation who underwent transesophageal echocardiography for LAAT detection. We examined the association of LAAT incidence with the CHA2DS2-VASc score and echocardiographic parameters pertaining to the left atrium (LA), including diameter, volume index, strain, and strain rate measured on speckle tracking echocardiography. LAAT was found in 24.3% of patients (39/144). The following parameters had good diagnostic performance for LAAT: LA volume index >57 mL (area under the curve (AUC), 0.72; sensitivity, 77.1%; specificity, 64.2%), LA positive strain ≤6.7% in the four-chamber view (AUC, 0.84; sensitivity, 77.1%; specificity, 77.1%), and LA negative strain rate >-0.73 s-1 in the four-chamber view (AUC, 0.83; sensitivity, 85.7%; specificity, 70.6%). The CHA2DS2-VASc score alone had a low predictive value for LAAT in this population (χ 2 = 3.53), whereas the combination of CHA2DS2-VASc score with LA volume index had significant association and better predictive value (χ 2 = 12.03), and the combination of CHA2DS2-VASc score with LA volume index and LA positive strain or negative strain rate in the four-chamber view had the best predictive ability for LAAT (χ 2: 33.47 and 33.48, respectively). We propose two novel and simple models for noninvasive LAAT prediction in patients with chronic nonvalvular atrial fibrillation. These models combine the CHA2DS2-VASc score with LA volume index and LA longitudinal strain parameters measured on speckle tracking echocardiography in the four-chamber view. We hope these simple models can help with decision-making in managing the antithrombotic treatment of such patients, whose risk of stroke cannot be determined solely based on the CHA2DS2-VASc score.
ABSTRACT
Effects of aquatic pollutants on fish are of increasing concern. Pharmaceutical-based contaminants are prioritized for further study in environmental risk assessment using several approaches. Dexamethasone (DEX) was one such contaminant recognised for its effect on fish health status. Thus, we carried out an in vivo experiment to identify potential effects of DEX on rainbow trout. Fish were exposed to 3, 30, 300 and 3000ngL(-1) DEX in a semi-static system over a period of 42d. The concentrations of DEX that fish were exposed to was confirmed by LC-LC-MS/MS. Using hepatic microsomes, we determined cytochrome P450 content, activities of ethoxyresorufin O-deethylase (EROD), p-nitrophenol hydroxylase (PNPH), 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylase (BFCOD) and benzyloxyquinoline O-debenzylase (BQOD), as well as protein expression. Our results showed that fish do not change the catalytic activity of CYP450-mediated reactions after high DEX concentration exposure. These results disagree with mammalian studies, where DEX is a well-known inducer of CYP450. We showed a significant effect of DEX exposure on CYP450-mediated reactions (EROD, BCFOD, BQOD and PNPH) when expressed as amount of product formed per min per nmol total CYP450 at 3, 30 and 300ngL(-1) after 21d exposure. Moreover, BFCOD and BQ activities showed matching trends in all groups. Western blot analysis showed induction of CYP3A-like protein in the presence of the lowest environmentally relevant concentration of DEX. Based on these findings, continued investigation of the effect of DEX on fish using a battery of complementary biomarkers of exposure and effect is highly relevant.
