Background: Post-pulmonary embolism (Post-PE) syndrome, comprising persistent dyspnea, impaired exercise capacity and chronic thromboembolic pulmonary hypertension, is a long-term complication of pulmonary embolism (PE). Post-PE syndrome is associated with decreased quality of life (QoL) and prevention is of great importance. Direct oral anticoagulants (DOACs) have a more stable pharmacologic profile than vitamin K antagonists (VKA) and may lead to improved thrombus resolution. We therefore hypothesized that treatment of PE with edoxaban compared to VKA (both preceded by heparin), would lead to an improved long-term QoL of PE patients. Aim: To assess long-term generic and PE-specific QoL following PE, in patients treated with edoxaban vs. warfarin. Methods: This is a follow-up study of the original HOKUSAI VTE trial (NCT00986154) and we are collecting data from previously enrolled patients at least 5 years after the index PE. The primary outcome is the QoL, generated by the validated generic (SF-36) and PE-specific (PEmb-QoL) questionnaire. We will compare QoL between both treatment arms. Ethical approval was granted in all participating centers and patients signed informed consent. Results: Up to now, 24 of 76 (32%) of the centers that were invited managed to participate and we have currently included 245 patients. The analyses will be performed after completion of data collection (May 2020). Summary: So far, we have included 245 patients. Inclusions will continue until May 2020 and at the ERS 2020 we will be able to present our results on QoL after PE in patients treated with edoxaban compared to patients treated with warfarin.
Background:Cell therapy is a therapeutic option for patients presenting with nonrevascularizable critical limb ischemia (CLI). However there is a lack of firm evidence on its efficacy because of the paucity of randomized controlled trials.
Potassium-sparing diuretics have different effects on angiogenesis that may mediate some abilities to treat cardiovascular diseases. The aim of the current study was to compare the effects of spironolactone and an active metabolite, canrenone, or a derivative, eplerenone, and amiloride, a diuretic without affecting mineralocorticoid activity, on the proliferation of human umbilical vein endothelial cells (HUVEC) and on angiogenesis in fibrin gel chambers implanted in rats.We measured the effects of spironolactone, canrenone, eplerenone, and amiloride on the proliferation of HUVEC in the presence or absence of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). We also examined the effects of these compounds on migration and capillary tube formation by HUVEC. Finally, the effects of the compounds on neovessel formation in vivo were investigated by implanting Wistar rats for 14 days with perforated Plexiglas chambers containing rat fibrin.Spironolactone and amiloride inhibited the proliferation of HUVEC, but canrenone and eplerenone had no effect. The inhibitory effect of spironolactone was not prevented by VEGF or bFGF. Aldosterone had no effect on spironolactone-induced inhibition of HUVEC proliferation. Spironolactone induced a dose-dependent reduction of both cell chemotaxis and capillary tube formation. In fibrin gel chambers, spironolactone and amiloride significantly reduced the numbers of both peripheral and central neovessels. Canrenone and eplerenone, in contrast, had no antiangiogenic effect.Spironolactone and amiloride significantly inhibited angiogenesis in vitro and in the fibrin gel chamber in vivo. Spironolactone antiangiogenic effects are unrelated to antimineralocorticoid activity.
To study the effect of systemic hyperbaric oxygenation (HBO) therapy on the healing course of nonischemic chronic diabetic foot ulcers.From 1999 to 2000, 28 patients (average age 60.2 +/- 9.7 years, diabetes duration 18.2 +/- 6.6 years), of whom 87% had type 2 diabetes, demonstrating chronic Wagner grades I-III foot ulcers without clinical symptoms of arteriopathy, were studied. They were randomized to undergo HBO because their ulcers did not improve over 3 months of full standard treatment. All the patients demonstrated signs of neuropathy. HBO was applied twice a day, 5 days a week for 2 weeks; each session lasted 90 min at 2.5 ATA (absolute temperature air). The main parameter studied was the size of the foot ulcer measured on tracing graphs with a computer. It was evaluated before HBO and at day 15 and 30 after the baseline.HBO was well tolerated in all but one patient (barotraumatic otitis). The transcutaneous oxygen pressure (TcPO(2)) measured on the dorsum of the feet of the patients was 45.6 +/- 18.1 mmHg (room air). During HBO, the TcPO(2) measured around the ulcer increased significantly from 21.9 +/- 12.1 to 454.2 +/- 128.1 mmHg (P < 0.001). At day 15 (i.e., after completion of HBO), the size of ulcers decreased significantly in the HBO group (41.8 +/- 25.5 vs. 21.7 +/- 16.9% in the control group [P = 0.037]). Such a difference could no longer be observed at day 30 (48.1 +/- 30.3 vs. 41.7 +/- 27.3%). Four weeks later, complete healing was observed in two patients having undergone HBO and none in the control group.In addition to standard multidisciplinary management, HBO doubles the mean healing rate of nonischemic chronic foot ulcers in selected diabetic patients. The time dependence of the effect of HBO warrants further investigations.
