Objective Transluminal in vitro resection of severely calcified human aortic valves has already been successfully carried out by our group. The aim of this study was to analyze endovascular ...laser-assisted resection of human aortic valves in situ in 10 human cadavers. Material and Methods After anterolateral minithoracotomy, the aortic valve isolation chamber system was inserted into the descending aorta and pushed forward transluminally into the aortic position to generate a separate operation space between the subvalvular and the proximal ascending aortic area. After deployment and sealing of the chamber, stable function with a continuous chamber lavage of 1.58 L/min saline solution was established (8/10 cases). The endoscopically guided laser fiber was delivered via the right carotid artery. After fixation of a leaflet by a forceps catheter, the native leaflets were resected each by a thulium:YAG laser with 20-W power rating. Macropathology and micropathology of surrounding anatomic structures were analyzed. Results The duration of transluminal positioning and deployment of the aortic valve isolation chamber took 7.3 ± 5.8 minutes. Fluoroscopy confirmed sealed chambers. The resection was completed in all leaflets and took, on average, 6.0 ± 3.5 minutes per leaflet. The aortic wall was moderately injured in 4 of 10 cases and the aortic annulus in two cases with one aortic wall perforation. The surrounding tissue, the coronary ostia, the mitral valve, and the left ventricular outflow tract remained unaffected. Conclusion This study demonstrates the feasibility of endovascular resection of human aortic valves in situ. This is a subsequent step toward complete percutaneous replacement (resection and implantation) of human aortic valves.
Transapical mitral valved stent implantation Lozonschi, Lucian; Quaden, Rene; Edwards, Niloo M ...
The Annals of thoracic surgery,
09/2008, Letnik:
86, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Transcatheter aortic and pulmonary valve replacement is currently being tested in human trials. Efforts to create a valved stent to replace the atrioventricular valves have shown limited success. ...This is due to their their complex anatomy and function.
A self-expanding valved stent was created for transapical replacement of the atrioventricular valve. Ten pigs underwent transapical off-pump mitral valved stent implantation. Data were gathered to assess the animals' hemodynamic stability for 60 minutes after implantation. The valved stent function was assessed by transesophageal echocardiography (TEE) and contrast left ventriculogram.
All animals exhibited normal hemodynamics immediately after mitral valved stent implantation and maintained stability for the entire period of monitoring. Accurate positioning of the valved stent was established in all animals. Mild paravalvular regurgitation was found in three out of ten animals by TEE and in two animals during left ventriculogram. No left ventricular outflow tract obstruction was encountered.
Transapical off-pump mitral valved stent implantation is feasible in an acute experimental setting. Long-term function of the new valved stent remains to be established.
Anxiety disorders are common and often disabling. The goal of this study was to examine the genetic architecture of anxiety disorders and anxiety symptoms, which are also frequently comorbid with ...other mental disorders, such as major depressive disorder.
Using one of the world's largest biobanks including genetic, environmental, and medical information, the Million Veteran Program, the authors performed a genome-wide association study (GWAS) of a continuous trait for anxiety (based on score on the Generalized Anxiety Disorder 2-item scale GAD-2, N=199,611) as the primary analysis and self-report of physician diagnosis of anxiety disorder (N=224,330) as a secondary analysis.
The authors identified five genome-wide significant signals for European Americans and one for African Americans on GAD-2 score. The strongest were on chromosome 3 (rs4603973) near
, a global regulator of gene expression, and on chromosome 6 (rs6557168) near
, which encodes an estrogen receptor. The locus identified on chromosome 7 (rs56226325, MAF=0.17) near
was previously identified in GWASs of bipolar disorder and schizophrenia. The authors replicated these findings in the summary statistics of two major published GWASs for anxiety, and also found evidence of significant genetic correlation between the GAD-2 score results and previous GWASs for anxiety (r
=0.75), depression (r
=0.81), and neuroticism (r
=0.75).
This is the largest GWAS of anxiety traits to date. The authors identified novel genome-wide significant associations near genes involved with global regulation of gene expression (
) and the estrogen receptor alpha (
). Additionally, the authors identified a locus (
) that may have implications for genetic vulnerability across several psychiatric disorders. This work provides new insights into genetic risk mechanisms underpinning anxiety and related psychiatric disorders.
Post-traumatic stress disorder (PTSD) is a major problem among military veterans and civilians alike, yet its pathophysiology remains poorly understood. We performed a genome-wide association study ...and bioinformatic analyses, which included 146,660 European Americans and 19,983 African Americans in the US Million Veteran Program, to identify genetic risk factors relevant to intrusive reexperiencing of trauma, which is the most characteristic symptom cluster of PTSD. In European Americans, eight distinct significant regions were identified. Three regions had values of P < 5 × 10
: CAMKV; chromosome 17 closest to KANSL1, but within a large high linkage disequilibrium region that also includes CRHR1; and TCF4. Associations were enriched with respect to the transcriptomic profiles of striatal medium spiny neurons. No significant associations were observed in the African American cohort of the sample. Results in European Americans were replicated in the UK Biobank data. These results provide new insights into the biology of PTSD in a well-powered genome-wide association study.
As recreational use of cannabis is being decriminalized in many places and medical use widely sanctioned, there are growing concerns about increases in cannabis use disorder (CanUD), which is ...associated with numerous medical comorbidities. Here we performed a genome-wide association study of CanUD in the Million Veteran Program (MVP), followed by meta-analysis in 1,054,365 individuals (n
= 64,314) from four broad ancestries designated by the reference panel used for assignment (European n = 886,025, African n = 123,208, admixed American n = 38,289 and East Asian n = 6,843). Population-specific methods were applied to calculate single nucleotide polymorphism-based heritability within each ancestry. Statistically significant single nucleotide polymorphism-based heritability for CanUD was observed in all but the smallest population (East Asian). We discovered genome-wide significant loci unique to each ancestry: 22 in European, 2 each in African and East Asian, and 1 in admixed American ancestries. A genetically informed causal relationship analysis indicated a possible effect of genetic liability for CanUD on lung cancer risk, suggesting potential unanticipated future medical and psychiatric public health consequences that require further study to disentangle from other known risk factors such as cigarette smoking.
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