IMproving PULmonary hypertension Screening by Echocardiography: IMPULSE.

Background The world symposium on pulmonary hypertension (PH) has proposed that PH be defined as a mean pulmonary artery pressure (mPAP) > 20 mmHg as assessed by right heart catheterisation (RHC). Transthoracic echocardiography (TTE) is an established screening tool used for suspected PH. International guidelines recommend a multi-parameter assessment of the TTE PH probability although effectiveness has not been established using real world data. Study aims To determine accuracy of the European Society of Cardiology (ESC) and British Society of Echocardiography (BSE) TTE probability algorithm in detecting PH in patients attending a UK PH centre. To identify echocardiographic markers and revised algorithms to improve the detection of PH in those with low/intermediate BSE/ESC TTE PH probability. Methods TTE followed by RHC (within 4 months after) was undertaken in patients for suspected but previously unconfirmed PH. BSE/ESC PH TTE probabilities were calculated alongside additional markers of right ventricular (RV) longitudinal and radial function, and RV diastolic function. A refined IMPULSE algorithm was devised and evaluated in patients with low and/or intermediate ESC/BSE TTE PH probability. Results Of 310 patients assessed, 236 (76%) had RHC-confirmed PH (average mPAP 42.8 ± 11.7). Sensitivity and specificity for detecting PH using the BSE/ESC recommendations was 89% and 68%, respectively. 36% of those with low BSE/ESC TTE probability had RHC-confirmed PH and BSE/ESC PH probability parameters did not differ amongst those with and without PH in the low probability group. Conversely, RV free wall longitudinal strain (RVFWLS) was lower in patients with vs. without PH in low BSE/ESC probability group (− 20.6 ± 4.1% vs − 23.8 ± 3.9%) (P < 0.02). Incorporating RVFWLS and TTE features of RV radial and diastolic function (RVFAC and IVRT) within the IMPULSE algorithm reduced false negatives in patients with low BSE/ESC PH probability by 29%. The IMPULSE algorithm had excellent specificity and positive predictive value in those with low (93%/80%, respectively) or intermediate (82%/86%, respectively) PH probability. Conclusion Existing TTE PH probability guidelines lack sensitivity to detect patients with milder haemodynamic forms of PH. Combining additional TTE makers assessing RV radial, longitudinal and diastolic function enhance identification of milder forms of PH, particularly in those who have a low BSE/ESC TTE PH probability

Stimulatory effect of Echinacea purpurea extract on the trafficking activity of mouse dendritic cells: revealed by genomic and proteomic analyses

<p>Abstract</p> <p>Background</p> <p>Several <it>Echinacea </it>species have been used as nutraceuticals or botanical drugs for "immunostimulation", but scientific evidence supporting their therapeutic use is still controversial. In this study, a phytocompound mixture extracted from the butanol fraction (BF) of a stem and leaf (S+L) extract of <it>E. purpurea </it>([BF/S+L/Ep]) containing stringently defined bioactive phytocompounds was obtained using standardized and published procedures. The transcriptomic and proteomic effects of this phytoextract on mouse bone marrow-derived dendritic cells (BMDCs) were analyzed using primary cultures.</p> <p>Results</p> <p>Treatment of BMDCs with [BF/S+L/Ep] did not significantly influence the phenotypic maturation activity of dendritic cells (DCs). Affymetrix DNA microarray and bioinformatics analyses of genes differentially expressed in DCs treated with [BF/S+L/Ep] for 4 or 12 h revealed that the majority of responsive genes were related to cell adhesion or motility (<it>Cdh10</it>, <it>Itga6</it>, <it>Cdh1</it>, <it>Gja1 </it>and <it>Mmp8</it>), or were chemokines (<it>Cxcl2, Cxcl7) </it>or signaling molecules (<it>Nrxn1, Pkce </it>and <it>Acss1</it>). TRANSPATH database analyses of gene expression and related signaling pathways in treated-DCs predicted the JNK, PP2C-α, AKT, ERK1/2 or MAPKAPK pathways as the putative targets of [BF/S+L/Ep]. In parallel, proteomic analysis showed that the expressions of metabolic-, cytoskeleton- or NF-κB signaling-related proteins were regulated by treatment with [BF/S+L/Ep]. <it>In vitro </it>flow cytometry analysis of chemotaxis-related receptors and <it>in vivo </it>cell trafficking assay further showed that DCs treated with [BF/S+L/Ep] were able to migrate more effectively to peripheral lymph node and spleen tissues than DCs treated as control groups.</p> <p>Conclusion</p> <p>Results from this study suggest that [BF/S+L/Ep] modulates DC mobility and related cellular physiology in the mouse immune system. Moreover, the signaling networks and molecules highlighted here are potential targets for nutritional or clinical application of <it>Echinacea </it>or other candidate medicinal plants.</p