INTRODUCTION: There is a paucity of published data on the clinical experience with trans-catheter aortic valve implantation (TAVI) in the Republic of Ireland. We sought to examine the clinical outcomes of patients with medium-term follow-up treated with TAVI at our institution. METHODS: A prospective TAVI registry was used to assess the baseline demographics, procedural variables and clinical outcomes of patients treated with TAVI between the inception of the programme in 2008 and November 2017. RESULTS: A total of 354 patients (mean age 80.9 ± 8.1 years, 58% male, mean STS score 6.1 ± 4.3%) were treated during the study period. Major in-hospital outcomes included in-lab death (n = 2, 0.6%), stroke (n = 8, 2.2%), device embolisation (n = 4, 1.2%), permanent pacemaker implantation (n = 22, 6.2%) and major vascular complication (n = 2, 0.6%). The median length of hospital stay was 4 days (IQR 2-8 days). The Kaplan-Meier estimate of freedom from death at 30 days and 1 year for the entire cohort was 97 ± 1% and 85.4 ± 2.3%, respectively. Trans-femoral access was associated with a significantly lower rate of death and/or stroke at 1 year compared to trans-apical access (84.9 ± 2.4% versus 60 ± 8.9%, p = 0.0005). There was no significant difference in freedom from death and/or stroke at 1 year between balloon-expandable and self-expanding valves (81.6 ± 2.6% versus 84.4 ± 7.4%, p = 0.63). CONCLUSION: This study documents low complication rates and favourable rates of survival following TAVI in a consecutive series of patients undergoing TAVI at a tertiary referral centre in the Republic of Ireland. These data support the application of this therapy in the Irish context.

• MeSH
• aortální chlopeň chirurgie   MeSH
• aortální stenóza chirurgie   MeSH
• centra terciární péče MeSH
• cévní mozková příhoda mortalita   MeSH
• Kaplanův-Meierův odhad MeSH
• kohortové studie MeSH
• lidé MeSH
• prospektivní studie MeSH
• registrace MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transkatetrální implantace aortální chlopně metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Irsko MeSH

The high incidence of cystic fibrosis (CF) is due to the frequency of the c.1521_1523delCTT variant in the cystic fibrosis transmembrane conductance regulator (CFTR), but its age and origin are uncertain. This gap limits attempts to shed light on the presumed heterozygote selective advantage that accounts for the variant's high prevalence among Caucasian Europeans and Europe-derived populations. In addition, explaining the nature of heterozygosity to screened individuals with one c.1521_1523delCTT variant is challenging when families raise questions about these issues. To address this gap, we obtained DNA samples from 190 patients bearing c.1521_1523delCTT and their parents residing in geographically distinct European populations plus a Germany-derived population in the USA. We identified microsatellites spanning CFTR and reconstructed haplotypes at 10 loci to estimate the time/age of the most recent common ancestor (tMRCA) with the Estiage program. We found that the age estimates differ between northwestern populations, where the mean tMRCA values vary between 4600 and 4725 years, and the southeastern populations where c.1521_1523delCTT seems to have been introduced only about 1000 years ago. The tMRCA values of Central Europeans were intermediate. Thus, our data resolve a controversy by establishing an early Bronze Age origin of the c.1521_1523delCTT allele and demonstrating its likely spread from northwest to southeast during ancient migrations. Moreover, taking the archeological record into account, our results introduce a novel concept by suggesting that Bell Beaker folk were the probable migrating population responsible for the early dissemination of c.1521_1523delCTT in prehistoric Europe.

• MeSH
• cystická fibróza epidemiologie   genetika   MeSH
• lidé MeSH
• migrace lidstva MeSH
• mikrosatelitní repetice MeSH
• populace genetika   MeSH
• protein CFTR genetika   MeSH
• rodokmen * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Evropa MeSH

Background The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. Methods We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. Results We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10(-14)). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. Conclusions We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.).

• MeSH
• adaptorové proteiny signální transdukční genetika   MeSH
• chromozomální delece * MeSH
• dánio pruhované MeSH
• DiGeorgeův syndrom genetika   MeSH
• dítě MeSH
• exom MeSH
• haploinsuficience * MeSH
• heterozygot MeSH
• jaderné proteiny genetika   MeSH
• kojenec MeSH
• ledviny abnormality   MeSH
• lidé MeSH
• lidské chromozomy, pár 22 MeSH
• mladiství MeSH
• mladý dospělý MeSH
• močové ústrojí abnormality   MeSH
• modely u zvířat MeSH
• myši MeSH
• novorozenec MeSH
• sekvenční analýza DNA MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• myši MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH