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SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published

Chronic thromboembolic pulmonary hypertension (CTEPH) is a type of pulmonary hypertension, resulting from fibrotic transformation of pulmonary artery clots causing chronic obstruction in macroscopic pulmonary arteries and associated vascular remodelling in the microvasculature.Pulmonary endarterectomy (PEA) offers the best chance of symptomatic and prognostic improvement in eligible patients; in expert centres, it has excellent results. Current in-hospital mortality rates are <5% and survival is >90% at 1 year and >70% at 10 years. However, PEA, is a complex procedure and relies on a multidisciplinary CTEPH team led by an experienced surgeon to decide on an individual's operability, which is determined primarily by lesion location and the haemodynamic parameters. Therefore, treatment of patients with CTEPH depends largely on subjective judgements of eligibility for surgery by the CTEPH team.Other controversies discussed in this article include eligibility for PEA versus balloon pulmonary angioplasty, the new treatment algorithm in the European Society of Cardiology/European Respiratory Society guidelines and the definition of an "expert centre" for the management of this condition.

Background: Following positive results from the Phase III CHEST-1 study in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), the Phase IIIb CTEPH early access study (EAS) was designed to assess the safety and tolerability of riociguat in real-world clinical practice, as well as to provide patients with early access to riociguat before launch. Riociguat is approved for the treatment of inoperable and persistent/recurrent CTEPH. Methods: We performed an open-label, uncontrolled, single-arm, early access study in which 300 adult patients with inoperable or persistent/recurrent CTEPH received riociguat adjusted from 1 mg three times daily (tid) to a maximum of 2.5 mg tid. Patients switching from unsatisfactory prior pulmonary arterial hypertension (PAH)-targeted therapy (n=84) underwent a washout period of at least 3 days before initiating riociguat. The primary aim was to assess the safety and tolerability of riociguat, with World Health Organization functional class and 6-min walking distance (6MWD) as exploratory efficacy endpoints. Results: In total, 262 patients (87%) completed study treatment and entered the safety follow-up (median treatment duration 47 weeks). Adverse events were reported in 273 patients (91%). The most frequently reported serious adverse events were syncope (6%), right ventricular failure (3%), and pneumonia (2%). There were five deaths, none of which was considered related to study medication. The safety and tolerability of riociguat was similar in patients switched from other PAH-targeted therapies and those who were treatment naïve. In patients with data available, mean±standard deviation 6MWD had increased by 33±42 m at Week 12 with no clinically relevant differences between the switched and treatment-naïve subgroups. Conclusions: Riociguat was well tolerated in patients with CTEPH who were treatment naïve, and in those who were switched from other PAH-targeted therapies. No new safety s, SCOPUS: ar.j, info:eu-repo/semantics/published

Giovanbattista Ippoliti,1,2 Andrea Maria D'Armini,2 Marco Lucioni,3 Mazen Marjieh,1 Mario Viganò21UO Medicina Interna, Policlinico di Monza, Monza, Italy; 2Department of Surgical Sciences, Charles Dubost Transplant Center, Fondazione IRCCS San Matteo Hospital, 3Anatomic Pathology, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, ItalyAbstract: The development of new immunosuppressive drugs for kidney transplantation resulted both in better short-term outcomes and in decreased metabolic, cardiovascular, and nephrotoxicity risk. Belatacept belongs to a new class of immunosuppressive drugs that selectively inhibits T-cell activation by preventing CD28 activation and by binding its ligands B7-1 and B7-2. The result is an inactivation of costimulatory pathways. A comparative analysis of the BENEFIT and BENEFIT-EXT datasets showed belatacept regimens resulted in better cardiovascular and metabolic risk profiles than did cyclosporin A (CsA) regimens: belatacept likewise outperformed CsA in terms of lower blood pressure and serum lipids and less new onset diabetes after transplantation. About 20% of belatacept-treated patients developed adverse effects which included anemia, pyrexia, neutropenia, diarrhea, urinary tract infection, headache, and peripheral edema. At present, belatacept does not seem to predispose patients to a higher rate of infection than CsA maintenance immunosuppression. The risk of posttransplant lymphoproliferative diseases was higher in Epstein–Barr virus (EBV)-seronegative patients than in EBV-seropositive patients, but the risk may be reduced by use of a less intensive regimen and avoidance of EBV-negative patients and of patients whose pretransplant EBV serology is unknown. Belatacept provides a new option for immunosuppressive therapy in kidney transplantation, but needs further evaluation in terms of the late effects that may derive from prolonged blockage of the costimulatory system and the inducti