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We investigated whether RV function recovers in children with pulmonary arterial hypertension (PAH) and RV failure undergoing lung transplantation (LuTx). The major research questions were how completely and how quickly after LuTx systolic RV function recovers in children with PAH. Prospective observational study of 15 consecutive children (age range: 1.9-17.6 years) with severe PAH who underwent bilateral lung transplantation between December 2013 and January 2021. We performed advanced echocardiography (Echo) and cardiac magnetic resonance imaging (MRI), followed by conventional and strain analysis, pre and ∼6 weeks post LuTx. All patients had PAH, i.e. group 1 pulmonary hypertension: idiopathic (n=6), heritable (n=4), PAH-congenital heart disease (n=2), pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis (PVOD/PCH; n=3). Six weeks after LuTx, RV/LV endsystolic diameter ratio (Echo), RV volumes and systolic RV function (RVEF 63 vs. 30 %; p<0.05) by MRI completely normalized, even in children with severe RV failure (RVEF < 40%). The echocardiographic end-systolic LV eccentricity index nearly normalized post LuTx (1.0 vs. 2.0, p<0.0001) while RV hypertrophy regressed more slowly and was still evident. We found especially the end-systolic RV/LV ratios by Echo (RV/LV diameter; 0.6 vs. 2.6) or MRI (RV/LV volumes: 0.8 vs. 3.4 excellent diagnostic tools (p<0.05): Together with RVEF by MRI, these ratios were superior to tricuspid annular plane systolic excursion (TAPSE; p>0.05) in assessing global systolic RV dysfunction. Moreover, children with severe PAH had reduced RV 2D longitudinal strain (Echo, MRI; p<0.05) and decreased RV 2D radial and circumferential strain (MRI; p<0.01), all of which greatly improved following LuTx. One year survival after LuTx for PAH was 100% (15/15 patients alive; 1 retransplant 9 months status post LuTx because of cellular rejection). No PAH LuTx candidate died on the transplant waiting list. We demonstrate full recovery of RV systolic function in children within two months after LuTx for severe PAH, independently of the patients' age, weight, and hemodynamic compromise preceding the LuTx. Even in end-stage pediatric PAH with poor RV function and low cardiac output, LuTx should be preferred over heart-lung transplantation. [ABSTRACT FROM AUTHOR]

The European Pediatric Pulmonary Vascular Disease Network (EPPVDN) developed in 2019 a pediatric pulmonary hypertension (PH) risk score to assess the risk and severity of PH in children and young adults. This prospective observational study seeks to validate the EPPVDN pediatric PH risk score by correlations with suitable and independent variables from cardiac magnetic resonance imaging (CMR) and speckle tracking echocardiography. Twenty children with PAH were enrolled into the study (age: 10.8±1.0, range 4.0- 17.6 years). During the same inpatient stay the invasive and non-invasive EPPVDN pediatric PH risk scores were determined and a protocol-driven CMR study was performed. Subsequently, we correlated the risk scores with conventional and strain CMR variables and advanced echocardiographic variables, including strain analysis (speckle-tracking). In addition, we applied the risk score to 9 children with PAH who received add-on selexipag therapy. Before and approximately 6 months after selexipag start the risk score and echocardiographic RV strain were determined and delta-changes of both were correlated. We observed significant (p<0.001) and strong correlations of conventional CMR (r=0.69-0.88), CMR strain (r=0.71-0.88), advanced echocardiographic (r=0.65-0.88) and echocardiographic strain variables (r=0.67-0.86), with the EPPVDN PHrisk score. The EPPVDN higher risk scores correlated stronger with the CMR-, ECHO-, and CMR-strain variables, when compared to the lower risk scores. In the add-on selexipag cohort, the change in ECHO-derived RV strain correlated most strongly and significantly with the change in the invasive higher risk score (r= -0.72, p<0.004). We found strong correlations of conventional, outcome-relevant CMR and strain variables (CMR, ECHO) with the EPPVDN pediatric PH risk scores, and thus validated the score via independent methods. The novel EPPVDN pediatric PH risk score will be very useful in routine clinical care, and can now be applied in larger prospective, pharma-interventional PAH studies in children and young adults. According open access online tools for rapid, comprehensive risk assement are in preparation. [ABSTRACT FROM AUTHOR]

Ozone oxidation is proven to be an effective solution for the degradation of selected oestrogenic active substances detected in secondary wastewaters such as β-oestradiol, oestrone, oestriol, 17-α-ethinyloestradiol, mestranol, daidzeine, β-sitosterol, bisphenol A, norethisterone, 4-tertoctylphenol and 4-iso-nonylphenol, up to their limit of detection. The matrix-effect of wastewater was investigated performing ozone experiments under batch mode and continuous mode using drinking water and a wastewater issued from a local plant both spiked with the non-detected substances. The results obtained indicate that the wastewater matrix greatly affects the kinetics of ozone reaction with these substances but does not really change the related reactivity scale. The ozone dose corresponding to the full conversion of target EDCs consequently increases as their oxidation takes place competing with reactions of background pollutants represented by the COD and DOC content. However, a usual dose close to 12 mg/L was found sufficient to provide high degradation yields for all substances studied while 35% of COD was removed. This is a contribution to the numerous current works focused on technologies able to improve the quality of water discharged from wastewater treatment plants, both considering conventional parameters and emerging contaminants. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor (PPAR)-γ is reduced in pulmonary arteries (PAs) of patients with PA hypertension (PAH), and we reported that deletion of PPAR-y in smooth muscle cells (SMCs) of transgenic mice results in PAH. However, the sequelae of loss of PPAR-γ in PA endothelial cells (ECs) are unknown. Therefore, we bred Tie2-Cre mice with PPARγflox/flox mice to induce EC loss of PPARγ (Tie2 PPAR-γ-/-), and we assessed PAH by right ventricular systolic pressure (RVSP), RV hypertrophy (RVH), and muscularized distal PAs in room air (RA), after chronic hypoxia (CH), and after 4 wk of recovery in RA (Rec-RA). The Tie2 PPARγ-/- mice developed spontaneous PAH in RA with increased RVSP, RVH, and muscularized PAs vs. wild type (WT); both genotypes exhibited a similar degree of PAH following chronic hypoxia, but Tie2 PPARγ-/- mice had more residual PAH compared with WT mice after Rec-RA. The Tie2 PPARγ-/- vs. WT mice in RA had increased platelet-derived growth factor receptor-β (PDGF-Rβ) expression and signaling, despite an elevation in the PPARγ target apolipoprotein E, an inhibitor of PDGF signaling. Inhibition of PDGF-Rγ signaling with imatinib, however, was sufficient to reverse the PAH observed in the Tie2 PPARγ-/- mice. Thus the disruption of PPARγ signaling in EC is sufficient to cause mild PAH and to impair recovery from CH-induced PAH. Inhibition of heightened PDGF-Rβ signaling is sufficient to reverse PAH in this genetic model. [ABSTRACT FROM AUTHOR]