Clinical outcome and hemodynamic behavior of the Labcor Dokimos Plus aortic valve

Background The Labcor Dokimos Plus (LDP) is a stented externally mounted pericardial aortic bioprosthesis, which was recently introduced in Europe. Aims of the study are evaluation of operative and postoperative results as well as hemodynamic performance. Methods One hundred consecutive patients with a mean age of 65.9 ± 10.7 years (range 35–87) and a mean EuroSCORE II of 3.1 ± 3.9 (range 0.67–24.5) underwent aortic valve replacement with the LDP. Mean valve-size was 25.2 ± 1.7 mm. Concomitant procedures were performed in 34% of the cases. Postoperative clinical data were analyzed and hemodynamic performance of the prostheses was evaluated by transthoracic echocardiography. Clinical follow-up was 100%, echocardiographic follow-up was 93% complete. Results Intraoperatively no peculiarities occurred. Mean cross clamp times for isolated and complex procedures were 74.5 ± 20.0 min and 103.7 ± 37.1 min, respectively. Patients were extubated after a mean of 9.4 ± 15.8 h. There were no perioperative strokes. Bleeding events occurred in 4 patients. 30-day- mortality was 2%. One case of early endocarditis occurred. Echocardiography showed maximum and mean pressure gradients of 18.1 ± 6.4 and 9.6 ± 3.7 mmHg, respectively. Correspondingly to valve sizes 21, 23, 25 and 27 mm, mean pressure gradients were 17.3, 9.5, 8.5 and 10.2 mmHg, effective orifice areas were 1.92, 1.79, 2.0, 2.16 cm2 and indexed effective orifice areas were 1.08, 0.95, 0.99 and 1.01 cm2/m2, respectively. No relevant regurgitations occurred. Conclusions The LDP showed operatively no peculiarities and a satisfactory clinical outcome with low perioperative morbidity and mortality. The hemodynamic performance of the implanted valve sizes was satisfactory

Noninvasive monitoring of cardiac function in a chronic ischemic heart failure model in the rat: Assessment with tissue Doppler and non-Doppler 2D strain echocardiography

<p>Abstract</p> <p>Objectives</p> <p>Feasibility of noninvasive monitoring of cardiac function after surgically induced ischemic cardiomyopathy with tissue Doppler and non-Doppler 2D strain echocardiography in rats.</p> <p>Background</p> <p>The optimal method for quantitative assessment of global and regional ventricular function in rats with chronic heart failure for research purposes remains unclear.</p> <p>Methods</p> <p>20 rats underwent suture ligation of the left anterior descending coronary artery via a left thoracotomy to induce ischemic cardiomyopathy. Echocardiographic examination with estimation of left ventricular wall thickness, diameters, fractional shortening, ejection fraction, wall velocities as well as radial strain were performed before and 4 weeks after surgery.</p> <p>Results</p> <p>Mean LVEF decreased from 70 ± 6% to 40 ± 8% (p < 0.0001) one month after the operation. LVEDD increased from 7 ± 1 mm to 9 ± 1 mm (p < 0.0001), systolic anterior velocity decreased from 0.79 ± 0.25 cm/s to 0.18 ± 0.19 cm/s (p < 0.0001). Radial 2D strain was significantly reduced after myocardial infarction of the septal (18.2 ± 6.6% vs 7.0 ± 5.9%, p < 0.001), anteroseptal (17.3 ± 5.2% vs 4.6 ± 3.0%, p < 0.0001), anterior (18.9 ± 5.9% vs 5.6 ± 2.5%, p < 0.0001), lateral (21.4 ± 4.9% vs 8.1 ± 3.5%, p < 0.0001) as well as posterior myocardial segments (19.3 ± 5.2% vs 15.4 ± 5.5%, p < 0.01). Inferior segments (19.2 ± 7.9% vs 17.8 ± 7.9%, ns) did not change at all.</p> <p>Conclusion</p> <p>It is feasible to assess dimensions, global function, and regional contractility with echocardiography in rats suffering from chronic heart failure after myocardial infarction. Particularly regional function can be exactly evaluated if tissue Doppler and 2D strain is used.</p

Correction to: Solving patients with rare diseases through programmatic reanalysis of genome-phenome data

In the original publication of the article, consortium author lists were missing in the articl

Correction to: Solve-RD: systematic pan-European data sharing and collaborative analysis to solve rare diseases

In the original publication of the article, consortium author list was missing in the article

Solving patients with rare diseases through programmatic reanalysis of genome-phenome data.

Funder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health); doi: https://doi.org/10.13039/100011272; Grant(s): 305444, 305444Funder: Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness); doi: https://doi.org/10.13039/501100003329Funder: Generalitat de Catalunya (Government of Catalonia); doi: https://doi.org/10.13039/501100002809Funder: EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj); doi: https://doi.org/10.13039/501100008530Funder: Instituto Nacional de Bioinformática ELIXIR Implementation Studies Centro de Excelencia Severo OchoaFunder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health)Reanalysis of inconclusive exome/genome sequencing data increases the diagnosis yield of patients with rare diseases. However, the cost and efforts required for reanalysis prevent its routine implementation in research and clinical environments. The Solve-RD project aims to reveal the molecular causes underlying undiagnosed rare diseases. One of the goals is to implement innovative approaches to reanalyse the exomes and genomes from thousands of well-studied undiagnosed cases. The raw genomic data is submitted to Solve-RD through the RD-Connect Genome-Phenome Analysis Platform (GPAP) together with standardised phenotypic and pedigree data. We have developed a programmatic workflow to reanalyse genome-phenome data. It uses the RD-Connect GPAP's Application Programming Interface (API) and relies on the big-data technologies upon which the system is built. We have applied the workflow to prioritise rare known pathogenic variants from 4411 undiagnosed cases. The queries returned an average of 1.45 variants per case, which first were evaluated in bulk by a panel of disease experts and afterwards specifically by the submitter of each case. A total of 120 index cases (21.2% of prioritised cases, 2.7% of all exome/genome-negative samples) have already been solved, with others being under investigation. The implementation of solutions as the one described here provide the technical framework to enable periodic case-level data re-evaluation in clinical settings, as recommended by the American College of Medical Genetics

Solve-RD: systematic pan-European data sharing and collaborative analysis to solve rare diseases.

For the first time in Europe hundreds of rare disease (RD) experts team up to actively share and jointly analyse existing patient's data. Solve-RD is a Horizon 2020-supported EU flagship project bringing together >300 clinicians, scientists, and patient representatives of 51 sites from 15 countries. Solve-RD is built upon a core group of four European Reference Networks (ERNs; ERN-ITHACA, ERN-RND, ERN-Euro NMD, ERN-GENTURIS) which annually see more than 270,000 RD patients with respective pathologies. The main ambition is to solve unsolved rare diseases for which a molecular cause is not yet known. This is achieved through an innovative clinical research environment that introduces novel ways to organise expertise and data. Two major approaches are being pursued (i) massive data re-analysis of >19,000 unsolved rare disease patients and (ii) novel combined -omics approaches. The minimum requirement to be eligible for the analysis activities is an inconclusive exome that can be shared with controlled access. The first preliminary data re-analysis has already diagnosed 255 cases form 8393 exomes/genome datasets. This unprecedented degree of collaboration focused on sharing of data and expertise shall identify many new disease genes and enable diagnosis of many so far undiagnosed patients from all over Europe

Solving unsolved rare neurological diseases-a Solve-RD viewpoint.

Funder: Durch Princess Beatrix Muscle Fund Durch Speeren voor Spieren Muscle FundFunder: University of Tübingen Medical Faculty PATE programFunder: European Reference Network for Rare Neurological Diseases | 739510Funder: European Joint Program on Rare Diseases (EJP-RD COFUND-EJP) | 44140962

Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock