Outcomes of listing for lung and heart–lung transplantation in pulmonary hypertension: comparative experience in France and the UK

\ua9 The authors 2024.Background Lung or heart–lung transplantation (LT/HLT) for severe pulmonary hypertension (PH) as the primary disease indication carries a high risk of waiting list mortality and post-transplant complications. France and the UK both have coordinated PH patient services but with different referral pathways for accessing LT services. Methods We conducted a comparative analysis of adult PH patients listed for LT/HLT in the UK and France. Results We included 211 PH patients in France (2006–2018) and 170 in the UK (2010–2019). Cumulative incidence of transplant, delisting and waiting list death within 3 years were 81%, 4% and 11% in France versus 58%, 10% and 15% in the UK (p<0.001 for transplant and delisting; p=0.1 for death). Median nonpriority waiting time was 45 days in France versus 165 days in the UK (p<0.001). High-priority listing occurred in 54% and 51% of transplanted patients respectively in France and the UK (p=0.8). Factors associated with achieving transplantation related to recipients’ height, male sex, clinical severity and priority listing status. 1-year post-transplant survival was 78% in France and 72% in the UK (p= 0.04). Conclusion Access to transplantation for PH patients is better in France than in the UK where more patients were delisted due to clinical deterioration because of longer waiting time. High rates of priority listing occurred in both countries. Survival for those achieving transplantation was slightly better in France. Ensuring optimal outcomes after transplant listing for PH patients is challenging and may involve early listing of higher risk patients, increasing donor lung utilisation and improving allocation rules for these specific patients

Oral Treprostinil is Associated with Improved Survival in FREEDOM-EV and its Open-Label Extension

\ua9 2023, The Author(s).Introduction: In the event-driven FREEDOM-EV trial, oral treprostinil delayed clinical worsening in patients with pulmonary arterial hypertension (PAH). Open-label extension studies offer additional data about tolerability, efficacy, and survival, especially for those initially assigned placebo. The aim of the current study was to determine if oral treprostinil changed survival when considering the parent and extension study, if treprostinil provides functional benefits for participants initially assigned to placebo, and if the benefits observed for those treated with treprostinil were durable. Methods: Both active and placebo participants from FREEDOM-EV could enroll in the FREEDOM-EV open-label extension (OLE) study after experiencing an investigator-assessed clinical worsening event or after parent study closure. All participants in the OLE were offered open-label oral treprostinil. Previously assigned placebo participants titrated to maximally tolerated doses; previously assigned treprostinil participants continued dose titration. We repeated assessments including functional class and 6-min walk distance (6MWD) at 12-week intervals and measured N-terminal pro-brain natriuretic peptide (NT-proBNP) at week 48. Survival was estimated by Kaplan–Meier analysis, and we estimated hazard ratio (HR) using Cox proportional hazards. Results: Of 690 FREEDOM-EV participants, 470 enrolled in the OLE; vital status was available for 89% of initial Freedom-EV participants. When considering the combined parent and open-label data, initial assignment to oral treprostinil reduced mortality (HR 0.64, 95% confidence interval 0.46–0.91, p = 0.013); absolute risk reduction was 9%. Participants randomized to placebo who initiated oral treprostinil after clinical worsening and tolerated treatment through week 48 demonstrated favorable shifts in functional class (p < 0.0001), 6MWD improvements of + 84 m (p < 0.0001), and a reduction in NT-proBNP of − 778 pg/mL (p = 0.02), compared to OLE baseline. Modest trends toward benefit were measured for those initially assigned placebo who did not have clinical worsening, and 132/144 (92%) of treprostinil assigned participants without clinical worsening remained on drug at week 48 in the OLE study. Adverse events were consistent with FREEDOM-EV. Conclusion: Initial treprostinil assignment improved survival in the entire data set; those who began treprostinil after a clinical worsening in the placebo arm and tolerated drug to week 48 enjoyed substantial functional gains. Clinical Trial Registration: ClinicalTrials.gov identifier NCT01560637

Guidelines for the definition of operational management units

The objective of fisheries management is the sustainable exploitation of the fish resources over the extent of their spatial distribution. Along with the Common Fisheries Policy (CFP) objectives, the socio-economic viability of the fisheries exploiting the resource is also to be achieved. To reach these aims, managers need to define the management units they are going to work with. For the purpose of GEPETO project, we define a management unit (MU) as the set of fishing fleets exploiting a common pool of fish resources with strong spatial overlapping and sharing of habitats, which make them being typically fished together. In other words, a MU is the set of fishing fleets exploiting a common fish community over their spatial distribution. MUs have to be defined by the fish community, by the spatial range of distribution of the fish community, and by the set of fishing fleets sharing the exploitation of the fish communityL'objectif de gestion de la pêche est l'exploitation durable des ressources halieutiques sur l'étendue de leur répartition spatiale. Avec la nouvelle Politique Commune de la pêche (PCP) l' objectif de la viabilité socio-économique des pêcheries exploitant la ressource doit également être réalisé. Pour l'atteindre, les gestionnaires doivent définir des unités de gestion. Les partenaires du projet GEPETO, définissent une unité de gestion (MU) comme l'ensemble des flottes de pêche exploitant un pool commun de ressources halieutiques disponibles dans des habitats communs, ce qui les rend très imbriquées. En d'autres termes, un MU est l'ensemble des flottes de pêche exploitant une communauté de poissons ordinaires sur leur répartition spatiale. La MU peu être définie par la communauté de poissons, par la gamme spatiale de la distribution de la communauté de poissons, et par l'ensemble des flottes de pêche qui partagent l'exploitation de la communauté de poissons

Predictors of outcomes in mild pulmonary hypertension according to 2022 ESC/ERS guidelines: the EVIDENCE-PAH UK study

Background and Aims Interventional studies in pulmonary arterial hypertension completed to date have shown to be effective in symptomatic patients with significantly elevated mean pulmonary artery pressure (mPAP) (≥25 mmHg) and pulmonary vascular resistance (PVR) > 3 Wood Unit (WU). However, in health the mPAP does not exceed 20 mmHg and PVR is 2 WU or lower, at rest. The ESC/ERS guidelines have recently been updated to reflect this. There is limited published data on the nature of these newly defined populations (mPAP 21–24 mmHg and PVR >2–≤3 WU) and the role of comorbidity in determining their natural history. With the change in guidelines, there is a need to understand this population and the impact of the ESC/ERS guidelines in greater detail. Methods A retrospective nationwide evaluation of the role of pulmonary haemodynamics and comorbidity in predicting survival among patients referred to the UK pulmonary hypertension (PH) centres between 2009 and 2017. In total, 2929 patients were included in the study. Patients were stratified by mPAP ( 2–≤3 WU, and >3 WU), with 968 (33.0%) in the mPAP <21 mmHg group, 689 (23.5%) in the mPAP 21–24 mmHg group, and 1272 (43.4%) in the mPAP ≥25 mmHg group. Results Survival was negatively correlated with mPAP and PVR in the population as a whole. Survival in patients with mildly elevated mPAP (21–24 mmHg) or PVR (>2–≤3WU) was lower than among those with normal pressures (mPAP <21 mmHg) and normal PVR (PVR ≤ 2WU) independent of comorbid lung and heart disease [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.14–1.61, P = .0004 for mPAP vs. HR 1.28, 95% CI 1.10–1.49, P = .0012 for PVR]. Among patients with mildly elevated mPAP, a mildly elevated PVR remained an independent predictor of survival when adjusted for comorbid lung and heart disease (HR 1.33, 95% CI 1.01–1.75, P = .042 vs. HR 1.4, 95% CI 1.06–1.86, P = .019). 68.2% of patients with a mPAP 21–24 mmHg had evidence of underlying heart or lung disease. Patients with mildly abnormal haemodynamics were not more symptomatic than patients with normal haemodynamics. Excluding patients with heart and lung disease, connective tissue disease was associated with a poorer survival among those with PH. In this subpopulation evaluating those with a mPAP of 21–24 mmHg, survival curves only diverged after 5 years. Conclusions This study supports the change in diagnostic category of the ESC/ERS guidelines in a PH population. The newly included patients have an increased mortality independent of significant lung or heart disease. The majority of patients in this new category have underlying heart or lung disease rather than an isolated pulmonary vasculopathy. Mortality is higher if comorbidity is present. Rigorous phenotyping will be pivotal to determine which patients are at risk of progressive vasculopathic disease and in whom surveillance and recruitment to studies may be of benefit. This study provides an insight into the population defined by the new guidelines

Advancing fishery-independent stock assessments for the Norway lobster (Nephrops norvegicus) with new monitoring techn

The Norway lobster, Nephrops norvegicus, supports a key European fishery. Stock assessments for this species are mostly based on trawling and UnderWater TeleVision (UWTV) surveys. However, N. norvegicus are burrowing organisms and these survey methods are unable to sample or observe individuals in their burrows. To account for this, UWTV surveys generally assume that “1 burrow system = 1 animal”, due to the territorial behavior of N. norvegicus. Nevertheless, this assumption still requires in-situ validation. Here, we outline how to improve the accuracy of current stock assessments for N. norvegicus with novel ecological monitoring technologies, including: robotic fixed and mobile camera-platforms, telemetry, environmental DNA (eDNA), and Artificial Intelligence (AI). First, we outline the present status and threat for overexploitation in N. norvegicus stocks. Then, we discuss how the burrowing behavior of N. norvegicus biases current stock assessment methods. We propose that state-of-the-art stationary and mobile robotic platforms endowed with innovative sensors and complemented with AI tools could be used to count both animals and burrows systems in-situ, as well as to provide key insights into burrowing behavior. Next, we illustrate how multiparametric monitoring can be incorporated into assessments of physiology and burrowing behavior. Finally, we develop a flowchart for the appropriate treatment of multiparametric biological and environmental data required to improve current stock assessment methods

Pulmonary Hypertension: Intensification and Personalization of Combination Rx (PHoenix): A phase IV randomized trial for the evaluation of dose-response and clinical efficacy of riociguat and selexipag using implanted technologies

\ua9 2024 The Authors. Pulmonary Circulation published by John Wiley &amp; Sons Ltd on behalf of Pulmonary Vascular Research Institute.Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type-5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate-cyclase stimulator (sGCS; riociguat). The clinical equipoise between these therapeutic choices provides the opportunity for evaluation of individualized therapeutic effects. Traditionally, invasive/hospital-based investigations are required to comprehensively assess disease severity and demonstrate treatment benefits. Regulatory-approved, minimally invasive monitors enable equivalent measurements to be obtained while patients are at home. In this 2 7 2 randomized crossover trial, patients with PAH established on guideline-recommended dual therapy and implanted with CardioMEMS™ (a wireless pulmonary artery sensor) and ConfirmRx™ (an insertable cardiac rhythm monitor), will receive ERA + sGCS, or PDEi + ERA + IP agonist. The study will evaluate clinical efficacy via established clinical investigations and remote monitoring technologies, with remote data relayed through regulatory-approved online clinical portals. The primary aim will be the change in right ventricular systolic volume measured by magnetic resonance imaging (MRI) from baseline to maximal tolerated dose with each therapy. Using data from MRI and other outcomes, including hemodynamics, physical activity, physiological measurements, quality of life, and side effect reporting, we will determine whether remote technology facilitates early evaluation of clinical efficacy, and investigate intra-patient efficacy of the two treatment approaches