Tuttlefeldman9132

Biventricular support was done in 7 patients. All patients were treated with an HVAD. Mean postoperative intensive care unit stay was 46.3 ± 32.4 days. Mean right heart bypass support time was 10.6 ± 4.3 days. ATPase inhibitor Twelve patients (86%) could be bridged to RV recovery, RV assist device implantation or heart transplantation.

Percutaneous RV mechanical support is feasible, safe and shows acceptable outcome. Early implantation of RV support may contribute to successful outcome after LVAD implantation.

Percutaneous RV mechanical support is feasible, safe and shows acceptable outcome. Early implantation of RV support may contribute to successful outcome after LVAD implantation.Duchenne muscular dystrophy (DMD) is an X-linked genetic disease characterized by severe, progressive muscle wasting. Cardiomyopathy has emerged as a leading cause of death in patients with DMD. The mechanisms contributing to DMD cardiac disease remain under investigation and specific therapies available are lacking. Our prior work has shown that DMD-iPSC derived cardiomyocytes (DMD-iCMs) are vulnerable to oxidative stress injury and chronic exposure to DMD secreted exosomes impaired the cell's ability to protect against stress. In this study, we sought to examine a mechanism by which DMD cardiac exosomes impair cellular response through altering important stress-responsive genes in the recipient cells. Here, we report that DMD-iCMs secrete exosomes containing altered microRNA (miR) profiles in comparison to healthy controls. In particular, miR-339-5p was upregulated in DMD-iCMs, DMD exosomes, and in mdx mouse cardiac tissue. Restoring dystrophin in DMD-iCMs improved the cellular response to stress and was associated with downregulation of miR-339-5p, suggesting that it is disease-specific. Knockdown of miR-339-5p was associated with increased expression of MDM2, GSK3A and MAP2K3, which are genes involved in important stress-responsive signaling pathways. Finally, knockdown of miR-339-5p led to mitochondrial protection and a reduction in cell death in DMD-iCMs, indicating miR-339-5p is involved in direct modulation of stress-responsiveness. Together, these findings identify a potential mechanism by which exosomal miR-339-5p may be modulating cell signaling pathways which are important for robust stress responses. Additionally, these exosomal miRs may provide important disease specific targets for future therapeutic advancements for the management and diagnosis of DMD cardiomyopathy.

The factors contributing to long-term remission in axial spondyloarthritis (axSpA) are unclear. We aimed to characterize individuals with axSpA at 5-year follow-up to identify baseline factors associated with remission.

We included all patients from the DESIR cohort (recent onset axSpA) with available Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP) at 5-year follow-up. Patients in remission (ASDAS-CRP<1.3) were compared to those with active disease by demographic, clinical, biological and imaging characteristics. A logistic model stratified on tumor necrosis factor inhibitor (TNFi) exposure was used.

Overall, 111/449 (25%) patients were in remission after 5 years. Among those never exposed to TNFi, 31% (77/247) were in remission compared to 17% (34/202) of those exposed to TNFi. Patients in remission after 5-years were more likely to be male, HLA-B27+, have a lower body mass index (BMI), and a higher education level. Baseline factors associated with 5-year remission in patients never exposed to TNFi, included lower BASDAI (adjusted odds ratio [ORa] 0.9, 95% confidence interval [95%CI] 0.8-0.9) and history of peripheral arthritis (ORa 2.1, 95%CI 1.2-5.3). In those exposed to TNFi, remission was associated with higher education level (ORa 2.9, 95%CI 1.6-5.1), lower enthesitis index (ORa 0.8, 95%CI 0.7-0.9), lower BASDAI (ORa 0.9, 95%CI 0.9-0.9), and lower BMI (ORa 0.8, 95%CI 0.7-0.9).

This study highlights the difficulty in achieving 5-year remission in those with recent onset axSpA, especially for the more active cases, despite the use of TNFi. Socio-economic factors and BMI are implicated in the outcome at 5 years.

This study highlights the difficulty in achieving 5-year remission in those with recent onset axSpA, especially for the more active cases, despite the use of TNFi. Socio-economic factors and BMI are implicated in the outcome at 5 years.Numerous genome-wide association studies (GWASs) have been conducted for the identification of genetic variants involved with human height. The vast majority of these studies, however, have been conducted in populations of European ancestry. Here, we report the first GWAS of adult height in the Taiwan Biobank using a discovery sample of 14 571 individuals and an independent replication sample of 20 506 individuals. From our analysis we generalize to the Taiwanese population genome-wide significant associations with height and 18 previously identified genes in European and non-Taiwanese East Asian populations. We also identify and replicate, at the genome-wide significance level, associated variants for height in four novel genes at two loci that have not previously been reported RASA2 on chromosome 3 and NABP2, RNF41, and SLC39A5 at 12q13.3 on chromosome 12. RASA2 and RNF41 are strong candidates for having a role in height with copy number and loss of function variants in RASA2 previously found to be associated with short stature disorders, and decreased expression of the RNF41 gene resulting in insulin resistance in skeletal muscle. The results from our analysis of the Taiwan Biobank underscore the potential for the identification of novel genetic discoveries in underrepresented worldwide populations, even for traits, such as height, that have been extensively investigated in large-scale studies of European ancestry populations.Mechanism-based therapy centred on the molecular understanding of disease-causing pathways in a given patient is still the exception rather than the rule in medicine, even in cardiology. However, recent successful drug developments centred around the second messenger cyclic guanosine-3'-5'-monophosphate (cGMP), which is regulating a number of cardiovascular disease modulating pathways, are about to provide novel targets for such a personalised cardiovascular therapy. Whether cGMP breakdown is inhibited or cGMP synthesis is stimulated via guanylyl cyclases or their upstream regulators in different cardiovascular disease phenotypes, the outcomes seem to be so far uniformly protective. Thus, a network of cGMP modulating drugs has evolved that act in a mechanism-based, possibly causal manner in a number of cardiac conditions. What remains a challenge is the detection of cGMPopathy endotypes amongst cardiovascular disease phenotypes. Here we review the growing clinical relevance of cGMP and provide a glimpse into the future on how drugs interfering with this pathway may change how we treat and diagnose cardiovascular diseases altogether.