arrEYE : a customized platform for high-resolution copy number analysis of coding and noncoding regions of known and candidate retinal dystrophy genes and retinal noncoding RNAs

Purpose: Our goal was to design a customized microarray, arrEYE, for high-resolution copy number variant (CNV) analysis of known and candidate genes for inherited retinal dystrophy (iRD) and retina expressed noncoding RNAs (ncRNAs). Methods: arrEYE contains probes for the full genomic region of 106 known iRD genes, including those implicated in retinitis pigmentosa (RP) (the most frequent iRD), cone rod dystrophies, macular dystrophies, and an additional 60 candidate iRD genes and 196 ncRNAs. Eight CNVs in iRD genes identified by other techniques were used as positive controls. The test cohort consisted of 57 patients with autosomal dominant, X-linked, or simplex RP. Results: In an RP patient, a novel heterozygous deletion of exons 7 and 8 of the HGSNAT gene was identified: c.634-408_820+338delins AGAATATG, p.(G1u2 I 2Glyfs*2). A known variant was found on the second allele: c.1843G>A, p.(A1a615Thr). Furthermore, we expanded the allelic spectrum of USH2A and RCBTB1 with novel CNVs. Conclusion: The arrEYE platform revealed subtle single-exon to larger CNVs in iRD genes that could be characterized at the nucleotide level, facilitated by the high resolution of the platform. We report the first CNV in HGSNAT that, combined with another mutation, leads to RP, further supporting its recently identified role in nonsyndromic iRD

Incidence, determinants and consequences of delirium in older patients after transcatheter aortic valve implantation

Background: delirium is an event leading to negative health outcomes and increased mortality in patients. The aim of this study is to investigate the incidence, determinants and consequences of post-operative delirium (POD) in older patients undergoing transcatheter aortic valve implantation (TAVI). Methods: The TAVI Care and Cure program is a prospective, observational registry in patients referred for TAVI at Erasmus University Medical Centre. The presence of delirium was evaluated by daily clinical assessment by a geriatrician pre- and up to 3 days post-TAVI. Mortality data were obtained from the Dutch Civil Registry. Results: A total of 543 patients underwent TAVI between January 2014 and December 2017. Overall, the incidence of POD was 14% (75/543 patients) but declined from 18% in 2014 to 7% in 2017 (P = 0.009). Patients who developed POD were older (81.9 ± 5.8 versus 78.6 ± 8.3 years, P < 0.001), had higher prevalence of renal dysfunction and prior stroke (54% versus 40%, P = 0.02; 31% versus 18%, P = 0.01) and were more often frail (32% versus 25%, P = 0.02). From a procedural perspective, general anesthesia (odds ratios (OR), 2.31; 95% CI, 1.40–3.83; P = 0.001), non-transfemoral access (OR, 2.37; 95% CI, 1.20–4.70; P = 0.01) and longer procedural time (OR, 1.01; 95% CI, 1.01–1.02; P < 0.001) were significantly associated with POD. One-year survival rate was 68% among patients who had suffered a POD and was 85% in patients without a POD (hazard ratio’s 1.8 (95% CI 1.01–3.10), P = 0.045). Conclusion: POD frequently occurs after TAVI and is associated with increased mortality. It might be speculated that patient selection and the minimalistic approach of TAVI may reduce the frequency of delirium

Long-term follow-up of quality of life in high-risk patients undergoing transcatheter aortic valve implantation for symptomatic aortic valve stenosis

Background Transcatheter aortic valve implantation (TAVI) has become the standard treatment for patients with severe symptomatic aortic stenosis (AS) considered at very high risk for surgical aortic valve replacement. The purpose of this sub-study was to evaluate long-term (> 4 years) health-related quality of life (QoL) in octogenarians who underwent TAVI. Methods A single center observational registry in twenty patients who underwent frame analysis assessment = 4 years after TAVI. Health-related QoL was evaluated, using the Short Form-36 (SF-36), the EuroQoL-5D (EQ-5D) and the visual analogue score (EQ-VAS) questionnaires. Results The mean SF-36 subscale scores at follow-up were physical functioning 40.8 ± 26.3, role physical functioning 67.7 ± 34.9, vitality 54.6 ± 21.6, general health 52.1 ± 20.4, social functioning 63.8 ± 37.7, role emotional functioning 70.2 ± 36.0, mental health 73.2 ± 23.3 and bodily pain 80.9 ± 22.9. The mean EQ-VAS score > 4 years after TAVI was 64.7 ± 15.1. With respect to functional class, 80% of the patients were in NYHA class I/II at follow-up compared to 15% prior to TAVI. Conclusions This sub-study reports a significant improvement in functional class (NYHA) in a selected group of very elderly patients > 4 years after TAVI. Furthermore, all patients showed a satisfactory QoL despite their age and multiple comorbidities. In addition, our study reveals a lower QoL when compared with the general age matched Dutch population

arrEYE: a customized platform for high-resolution copy number analysis of coding and noncoding regions of known and candidate retinal dystrophy genes and retinal noncoding RNAs

Purpose: Our goal was to design a customized microarray, arrEYE, for high-resolution copy number variant (CNV) analysis of known and candidate genes for inherited retinal dystrophy (iRD) and retina expressed noncoding RNAs (ncRNAs). Methods: arrEYE contains probes for the full genomic region of 106 known iRD genes, including those implicated in retinitis pigmentosa (RP) (the most frequent iRD), cone rod dystrophies, macular dystrophies, and an additional 60 candidate iRD genes and 196 ncRNAs. Eight CNVs in iRD genes identified by other techniques were used as positive controls. The test cohort consisted of 57 patients with autosomal dominant, X-linked, or simplex RP. Results: In an RP patient, a novel heterozygous deletion of exons 7 and 8 of the HGSNAT gene was identified: c.634-408_820+338delins AGAATATG, p.(G1u2 I 2Glyfs*2). A known variant was found on the second allele: c.1843G>A, p.(A1a615Thr). Furthermore, we expanded the allelic spectrum of USH2A and RCBTB1 with novel CNVs. Conclusion: The arrEYE platform revealed subtle single-exon to larger CNVs in iRD genes that could be characterized at the nucleotide level, facilitated by the high resolution of the platform. We report the first CNV in HGSNAT that, combined with another mutation, leads to RP, further supporting its recently identified role in nonsyndromic iRD