ABSTRACT
BACKGROUND: Computed tomography coronary angiography (CTCA) is an established modality for the diagnosis and assessment of cardiovascular disease. However, price and space pressure have mostly necessitated outsourcing CTCA to external radiology providers. Advara HeartCare has recently integrated CT services within local clinical networks across Australia. This study examined the benefits of the presence (integrated) or absence (pre-integrated) of this "in-house" CTCA service in real-world clinical practice. METHODS: De-identified patient data from electronic medical records were used to create an Advara HeartCare CTCA database. Data analysis included clinical history, demographics, CTCA procedure, and 30-day outcomes post-CTCA from two age-matched cohorts: integrated (n â= â495) and pre-integrated (n â= â456). RESULTS: Data capture was more comprehensive and standardised across the integrated cohort. There was a 21% increase in referrals for CTCA from cardiologists observed for the integration cohort vs. pre-integration [n â= â332 (72.8%) pre-integration vs. n â= â465 (93.9%) post-integration, p â< â0.0001] with a parallel increase in diagnostic assessments including blood tests [n â= â209 (45.8%) vs. n â= â387 (78.1%), respectively, p â< â0.0001]. The integrated cohort received lower total dose length product [Median 212 (interquartile range 136-418) mGy∗cm vs. 244 (141.5, 339.3) mGy∗cm, p â= â0.004] during the CTCA procedure. 30-days after CTCA scan, there was a significantly higher use of lipid-lowering therapies in the integrated cohort [n â= â133 (50.5%) vs. n â= â179 (60.6%), p â= â0.04], along with a significant decrease in the number of stress echocardiograms performed [n â= â14 (10.6%) vs. n â= â5 (11.6%), p â= â0.01]. CONCLUSION: Integrated CTCA has salient benefits in patient management, including increased pathology tests, statin usage, and decreased post-CTCA stress echocardiography utilisation. Our ongoing work will examine the effect of integration on cardiovascular outcomes.
Subject(s)
Cardiology , Coronary Artery Disease , Humans , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Sensitivity and Specificity , Predictive Value of Tests , Tomography, X-Ray Computed/methods , Computed Tomography Angiography , Disease ManagementABSTRACT
The growth and metabolic actions of growth hormone (GH) are believed to be mediated through the GH receptor (GHR) by JAK2 activation. The GHR exists as a constitutive homodimer, with signal transduction by ligand-induced realignment of receptor subunits. Based on the crystal structures, we identify a conformational change in the F'G' loop of the lower cytokine module, which results from binding of hGH but not G120R hGH antagonist. Mutations disabling this conformational change cause impairment of ERK but not JAK2 and STAT5 activation by the GHR in FDC-P1 cells. This results from the use of two associated tyrosine kinases by the GHR, with JAK2 activating STAT5, and Lyn activating ERK1/2. We provide evidence that Lyn signals through phospholipase C gamma, leading to activation of Ras. Accordingly, mice with mutations in the JAK2 association motif respond to GH with activation of hepatic Src and ERK1/2, but not JAK2/STAT5. We suggest that F'G' loop movement alters the signalling choice between JAK2 and a Src family kinase by regulating TMD realignment. Our findings could explain debilitated ERK but not STAT5 signalling in some GH-resistant dwarfs and suggest pathway-specific cytokine agonists.
