Search

Data on next-day discharge (NDD) after transcatheter aortic valve replacement (TAVR) are limited. This study investigated the feasibility and safety of NDD as a first-line option (the very-early discharge [VED] strategy) compared with the early-discharge (ED) strategy (2-3 days as a first-line option) after TAVR.We reviewed 611 consecutive patients who had minimalist TAVR (transfemoral approach under conscious sedation) and no in-hospital mortality; a total of 418 patients underwent ED strategy (since December 2013) and 193 patients underwent VED strategy (as part of a hospital initiative to reduce length of stay, since August 2016). NDD in the VED strategy was performed with heart team consensus in patients without significant complications. The primary outcome was a composite of 30-day all-cause mortality/rehospitalization.Sixty-five patients (33.7%) in the VED strategy and 10 patients (2.4%) in the ED strategy were discharged the next day (P.001). NDD patients had received balloon-expandable (n = 30) or self-expanding valves (n = 45) and showed a similar primary outcome rate compared with non-NDD patients. After adjustment using propensity score matching (172 pairs), post-TAVR length of stay was significantly shorter in the VED group (3.2 ± 3.1 days) than in the ED group (3.5 ± 2.7 days; P.01). The primary outcome did not differ between the two groups (7.0% vs 11.6%; P=.14), with comparable 30-day mortality rate (1.2% vs 2.3%; P=.68) and rehospitalization rate (5.8% vs 11.1%; P=.08).Utilization of NDD as a first-line option after minimalist TAVR is feasible and safe, and leads to further reduction in length of stay compared with an ED strategy.

Summary Background : For patients with coeliac disease (CD), compliance with a gluten-free diet, when eating food not prepared at home may be difficult. Aims : We assessed whether there are differences in the eating habits of coeliac patients when compared to the general public. In addition, we compared chefs' knowledge with the public's knowledge about CD. Method : A questionnaire survey about CD was performed on coeliac patients, chefs and the general public from the United Kingdom (UK). Results : Three hundred and nineteen coeliac patients [mean age 53.8 years, 65.8% female], 513 members of the public [49.2 years, 62.6% female] and 322 chefs [37.6 years, 15.2% female] were interviewed. Chefs were less likely to have heard of CD when compared to the public (17.1% (55/322) versus 44.2% (227/513), respectively, P 0.0001 ). Coeliac patients ate less frequently at a friend's house than the general public ( P = 0.003 ). Coeliac patients ate less frequently from take-away establishments ( P 0.0001 ). However, coeliac patients' ate as frequently in restaurants ( P = 0.078 ). Conclusions : In the UK, chefs appear to know less about CD than the general public. Patients with CD feel justifiably cautious when eating food not prepared at home. Educating chefs about a gluten-free diet may alleviate the social restrictions on coeliac patients.

Fatty acids cause endothelial dysfunction involving increased ROS (reactive oxygen species) and reduced NO (nitric oxide) bioavailability. We show that in MAECs (mouse aortic endothelial cells), the PPARß/d (peroxisome- proliferator-activated receptor ß/d) agonist GW0742 prevented the decreased A23187-stimulated NO production, phosphorylation of eNOS (endothelial nitric oxide synthase) at Ser1177 and increased intracellular ROS levels caused by exposure to palmitate in vitro. The impaired endothelium-dependent relaxation to acetylcholine in mouse aorta induced by palmitate was restored by GW0742. In vivo, GW0742 treatment prevented the reduced aortic relaxation, phosphorylation of eNOS at Ser1177, and increased ROS production and NADPH oxidase in mice fed on a high-fat diet. The PPARß/d antagonist GSK0660 abolished all of these protective effects induced by GW0742. This agonist enhanced the expression of CPT (carnitine palmitoyltransferase)-1. The effects of GW0742 on acetylcholine- induced relaxation in aorta and on NO and ROS production in MAECs exposed to palmitate were abolished by the CPT-1 inhibitor etomoxir or by siRNA targeting CPT-1. GW0742 also inhibited the increase in DAG (diacylglycerol), PKCa/ßII (protein kinase Ca/ßII) activation, and phosphorylation of eNOS at Thr495 induced by palmitate in MAECs, which were abolished by etomoxir. In conclusion, PPARß/d activation restored the lipid-induced endothelial dysfunction by up-regulation of CPT-1, thus reducing DAG accumulation and the subsequent PKC-mediated ROS production and eNOS inhibition.

PPARβ enhances insulin sensitivity in adipocytes and skeletal muscle cells, but its effects on insulin signalling in endothelial cells are not known. We analysed the effects of the PPARβ/δ (PPARβ) agonists, GW0742 and L165041, on impaired insulin signalling induced by high glucose in HUVECs and aortic and mesenteric arteries from diabetic rats.Insulin-stimulated NO production, Akt-Ser(473) and eNOS-Ser(1177) phosphorylation, and reactive oxygen species (ROS) production were studied in HUVECs incubated in low- or high-glucose medium. Insulin-stimulated relaxations and protein phosphorylation in vessels from streptozotocin (STZ)-induced diabetic rats were also analysed.HUVECs incubated in high-glucose medium showed a significant reduction in insulin-stimulated production of NO. High glucose also reduced insulin-induced Akt-Ser(473) and eNOS-Ser(1177) phosphorylation, increased IRS-1-Ser(636) and ERK1/2-Thr(183) -Tyr(185) phosphorylation and increased ROS production. The co-incubation with the PPARβ agonists GW0742 or L165041 prevented all these effects induced by high glucose. In turn, the effects induced by the agonists were suppressed when HUVEC were also incubated with the PPARβ antagonist GSK0660, the pyruvate dehydrogenase kinase (PDK)4 inhibitor dichloroacetate or after knockdown of both PPARβ and PDK4 with siRNA. The ERK1/2 inhibitor PD98059, ROS scavenger catalase, inhibitor of complex II thenoyltrifluoroacetone or uncoupler of oxidative phosphorylation, carbonyl cyanide m-chlorophenylhydrazone, also prevented glucose-induced insulin resistance. In STZ diabetic rats, oral GW0742 also improved insulin signalling and the impaired NO-mediated vascular relaxation.PPARβ activation in vitro and in vivo restores the endothelial function, preserving the insulin-Akt-eNOS pathway impaired by high glucose, at least in part, through PDK4 activation.

Background: The increasing prevalence of type 2 diabetes in general and in younger people in particular has led to an increasing numbers of pregnancies with the complication of gestational hyperglycaemias. All complications associated with gestational hyperglycaemias are potentially preventable. The aim of this study is to monitor longitudinal changes in blood glucose levels in pregnancy and to co-relate it with various maternal and foetal outcomes. Material and Methods: The study was conducted in 93 pregnant women. Venous blood was collected and post prandial blood glucose (PP2BG) level was estimated by glucose oxidase-peroxidase enzyme method once in every trimester. Pregnancy outcomes including the mode of delivery (spontaneous vaginal delivery or assisted delivery), birth weight of the baby and the neonatal morbidity like asphyxia, hypoglycaemias were noted. Results: We found 6% of the women in the study group have gestational hyperglycaemias in the first trimester and 27% in the second trimester. The percentages of gestational hyperglycaemias are reduced to 11% in the third trimester. Maternal post prandial blood glucose levels affect the birth weight of the baby and also mode of delivery. Numbers of neonatal complications are higher in subjects with higher blood glucose levels. Conclusion: We recommend that estimation of maternal PP2 BG levels should be carried out in all pregnant women at the first antenatal visit and at least once in every trimester. This would help to reduce adverse perinatal outcomes.

International audience

Thoracic aortic aneurysm, as occurs in Marfan syndrome, is generally asymptomatic until dissection or rupture, requiring surgical intervention as the only available treatment. Here, we show that nitric oxide (NO) signaling dysregulates actin cytoskeleton dynamics in Marfan Syndrome smooth muscle cells and that NO-donors induce Marfan-like aortopathy in wild-type mice, indicating that a marked increase in NO suffices to induce aortopathy. Levels of nitrated proteins are higher in plasma from Marfan patients and mice and in aortic tissue from Marfan mice than in control samples, indicating elevated circulating and tissue NO. Soluble guanylate cyclase and cGMP-dependent protein kinase are both activated in Marfan patients and mice and in wild-type mice treated with NO-donors, as shown by increased plasma cGMP and pVASP-S239 staining in aortic tissue. Marfan aortopathy in mice is reverted by pharmacological inhibition of soluble guanylate cyclase and cGMP-dependent protein kinase and lentiviral-mediated Prkg1 silencing. These findings identify potential biomarkers for monitoring Marfan Syndrome in patients and urge evaluation of cGMP-dependent protein kinase and soluble guanylate cyclase as therapeutic targets., “La Caixa” Banking Foundation under project codes HR18-00068 (to M.R.C. and J.M.R.) and HR17-00247 (to J.V.); Spanish Ministerio de Ciencia e Innovación grants RTI2018-099246-B-I00 (MICIU/AEI/FEDER, UE) and SAF2015-636333R (MINECO/FEDER, UE) to J.M.R., SAF2017-88881R (MINECO/AEI/FEDER, UE) to M.R.C., and BIO2015-67580-P and PGC2018-097019-B-I00 to J.V.; the Comunidad de Madrid