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The original CHESS database of human genes was assembled from nearly 10,000 RNA sequencing experiments in 53 human body sites produced by the Genotype-Tissue Expression (GTEx) project, and then augmented with genes from other databases to yield a comprehensive collection of protein-coding and noncoding transcripts. The construction of the new CHESS 3 database employed improved transcript assembly algorithms, a new machine learning classifier, and protein structure predictions to identify genes and transcripts likely to be functional and to eliminate those that appeared more likely to represent noise. The new catalog contains 41,356 genes on the GRCh38 reference human genome, of which 19,839 are protein-coding, and a total of 158,377 transcripts. These include 14,863 novel protein-coding transcripts. The total number of transcripts is substantially smaller than earlier versions due to improved transcriptome assembly methods and to a stricter protocol for filtering out noisy transcripts. Notably, CHESS 3 contains all of the transcripts in the MANE database, and at least one transcript corresponding to the vast majority of protein-coding genes in the RefSeq and GENCODE databases. CHESS 3 has also been mapped onto the complete CHM13 human genome, which gives a more-complete gene count of 43,773 genes and 19,968 protein-coding genes. The CHESS database is available athttp://ccb.jhu.edu/chess.

The human Y chromosome has been notoriously difficult to sequence and assemble because of its complex repeat structure including long palindromes, tandem repeats, and segmental duplications. As a result, more than half of the Y chromosome is missing from the GRCh38 reference sequence and it remains the last human chromosome to be finished. Here, the Telomere-to-Telomere (T2T) consortium presents the complete 62,460,029 base pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference, revealing the complete ampliconic structures ofTSPY, DAZ, andRBMY; 42 additional protein-coding genes, mostly from theTSPYgene family; and an alternating pattern of human satellite 1 and 3 blocks in the heterochromatic Yq12 region. We have combined T2T-Y with a prior assembly of the CHM13 genome and mapped available population variation, clinical variants, and functional genomics data to produce a complete and comprehensive reference sequence for all 24 human chromosomes.

The numerical calculation of local mass distributions in membrane systems by computational fluid dynamics (CFD) offers indispensable benefits. However, the concept to calculate such distributions in response to separate variations of operation conditions (OCs) makes it difficult to address overall, flow-physics-related questions, which require the consideration of the collective interaction of OCs. It is shown that such understanding-related relationships can be obtained by the analytical solution of the advection–diffusion equation considered. A Fourier series model (FSM) is presented, which provides exact solutions of an advection–diffusion equation for a wide range of OCs. On this basis, a new zeroth-order model is developed, which is very simple and as accurate as the complete FSM for all conditions of practical relevance. Advection-dominated blocked and diffusion-dominated unblocked flow regimes are identified (depending on a Péclet number which compares the flow geometry with a length scale imposed by the flow), which implies relevant requirements for the use of lab results for pilot- and full-scale applications. Analyses reveal the equivalence of variations of OCs, which offers a variety of options to accomplish desired flow regime changes.

Until 2019, the human genome was available in only one fully annotated version, GRCh38, which was the result of 18 years of continuous improvement and revision. Despite dramatic improvements in sequencing technology, no other genome was available as an annotated reference until 2019, when the genome of an Ashkenazi individual, Ash1, was released. In this study, we describe the assembly and annotation of a second individual genome, from a Puerto Rican individual whose DNA was collected as part of the Human Pangenome project. The new genome, called PR1, is the first true reference genome created from an individual of African descent. Due to recent improvements in both sequencing and assembly technology, and particularly to the use of the recently completed CHM13 human genome as a guide to assembly, PR1 is more complete and more contiguous than either GRCh38 or Ash1. Annotation revealed 37,755 genes (of which 19,999 are protein coding), including 12 additional gene copies that are present in PR1 and missing from CHM13. Fifty-seven genes have fewer copies in PR1 than in CHM13, 9 map only partially, and 3 genes (all noncoding) from CHM13 are entirely missing from PR1.

BACKGROUND Transit-time flow measurement (TTFM) should be routinely used in CABG surgery to verify graft function. Most recently, a 2D high-frequency-ultrasound (HF-US) epicardial imaging probe has been released (MiraQ™, Medistim, Oslo, Norway), which allows to evaluate the cannulation/clamping site of the aorta morphologically and to evaluate the completed anastomosis. We aimed to evaluate the use of TTFM and HF-US on surgical strategy during CABG surgery. METHODS A total of 65 consecutive patients undergoing CABG surgery were evaluated. The target vessels, the clamping/cannulation site and the anastomosis were evaluated by HF-US. TTFM was performed on all grafts and the mean flow (mL/min) and pulsatility indices (PI) were recorded. Troponin-I levels (ng/L) were obtained within the first 4 postoperative days. RESULTS A total of 3.3±0.9 grafts were performed, with 98.5% LIMA use and a sequential graft was performed in 55.4%. The mean PI and flow (mL/min) were 2.3±2.7 and 70.8±50.6 for the right coronary artery system, 2.4±2.2 and 82.0±47.6 for the circumflex system, and 2.1±1.2 and 78.0±35.0 for the LAD system, respectively. Postoperative troponin-I levels showed a maximum on postoperative day 1. A surgical strategy change, based on imaging, was done in 15%. Moreover, we observed a correlation of PI and flow with maximum postoperative troponin-I levels. CONCLUSIONS The present study evaluated the combination of TTFM and HF-US in CABG surgery. Epicardial scanning was helpful to evaluate the potential opening site of the vessel, to evaluate the completed anastomosis or to evaluate the clamping or cannulation site. Troponin-I levels were directly correlated to mean graft flow and PI levels.

Objectives: Patients with thoracic aneurysmal disease involving the arch and the descending or thoracoabdominal aorta may require more than one surgical intervention. The results of one-stage repair using a hybrid stent-graft in the frozen elephant trunk manner are presented. Methods: Between January 2005 and March 2012, 113 (age 67 ± 10 years) of 358 registered patients in the International E-Vita Open® Registry were operated on for combined arch and descending and thoracoabdominal aortic aneurysm. Thirty-one (27%) patients had a previous cardiothoracic, abdominal aortic surgery or endovascular repair. The E-Vita Open® hybrid stent-graft was used in all cases. Postoperatively and during the follow-up (100%), aortic image examinations were performed. Results: Combined arch replacement and antegrade stent-grafting distally (graft diameter 34 ± 4 mm) were performed under selective cerebral perfusion (72 ± 27 min) and hypothermic visceral ischaemia (65 ± 27 min). Postoperatively, aneurysm exclusion was completely and partially achieved in 80% and 20%, respectively. In-hospital mortality and survival rate after 5 years were 12% (13 of 113) and 78%, respectively. Latest aortic imaging demonstrated 93% complete aneurysm exclusion. Freedom from secondary endovascular intervention and open surgery were 88 and 90%, respectively. CONCLUSIONS: In multisegmental thoracic aneurysmal disease, combined arch replacement with distal repair by a hybrid stent-graft enables one-stage treatment with acceptable mortality. Aneurysm exclusion by the stent-graft seems to be primarily curative and allows easier access for distal open or endovascular reintervention. © The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Thoracic endovascular aortic repair (TEVAR) is an emerging treatment modality, which has been rapidly embraced by clinicians treating thoracic aortic disease.1–4 Fundamentally, it is a far less invasive approach than open surgery and its availability and relative ease of application has changed and extended management options in thoracic aortic disease, including in those patients deemed unfit or unsuitable for open surgery. In the operating room, this requires considerable perceptual, cognitive and psychomotor demands on the operators. The dramatic expansion of TEVAR activity has necessarily prompted a requirement to systematically consider the indications, appropriateness, limitations and delivery of this treatment, which has been adopted by many specialties including cardiologists, cardiovascular surgeons, radiologists and vascular surgeons.5 Our task has been to generate a multidisciplinary position statement that supports and advises all clinicians utilizing this technological advance. This document focuses on the main diagnoses—thoracic aortic aneurysm (TAA), thoracic aortic dissection (TAD) of the descending aorta (type B according to the Stanford classification) and thoracic aortic injury (TAI)—indications and applicability of TEVAR and includes information regarding its limitations and complications. It acts as a position statement for both societies that reflects current understanding of thoracic aortic endovascular therapy. ### Evaluation of symptoms and patient status Symptoms in patients with TAA and chronic dissection are rare and non-specific.6,7 New onset of hoarseness or dysphagia may suggest a developing aneurysm in the distal aortic arch and proximal descending aorta. Most asymptomatic cases are discovered incidentally, while symptomatic patients have usually developed complications. Even in patients with acute aortic syndromes, chest pain, back pain and signs of malperfusion are often misinterpreted due to lack of awareness. In cases of clinical suspicion, a computed tomography (CT)-angiography is the diagnostic modality of first choice. ### Multidisciplinary consultation Patient selection should be performed on an individual basis according to anatomy, pathology, comorbidity and …

The underlying mechanisms leading to aortic dissection are poorly understood. The present paper describes a unique device for aortic wall testing during open heart surgery which allows to directly predict the risk of aortic dissection.Samples of the aortic wall were taken during surgery of the aortic valve and ascending aorta in 35 patients. Disruption of the samples was performed by using the dissectometer (patent pending). The output signal of the actuator was visualized by a "tensile strain curve". Seven destinctive curve parameters were compared by parametric or nonparametric evaluation with regard to the results of the normality test.Variations of all seven parameters in each patient differed not significantly; however, significant differences could be observed between the 35 patients. All parameters proved to be consistent and reproducible intra-individually. Histological analysis showed the integrity of the surface and localization of dissection in the external layer of tunica media.The dissectometer proved to be a suitable device to predict aortic wall consistence intraoperatively. Statistical analysis confirmed that a single sample of aorta is sufficient for assessment of aortic wall quality. A valid statistical discrimination between "healthy" and pathological aortas could only be assumed by generation of a large database of patients.

Acute aortic dissection is a life threatening disease, which is occasionally limited to an ascending aorta only (DeBakey type II). In majority of patients it involves the aortic arch and entire rest of the aorta (DeBakey type I). The standardized cannulation and operation strategy can not be used in cases, when aortic arch branches are involved in dissection (complex aortic arch dissection) or in cases with malperfusion or severely compromised hemodynamics (tamponade or heart failure due to severe aortic valve insufficiency). The aim of this present review is to present the "Essen" treatment concept of complicated acute aortic arch dissection from diagnostics to operation strategy.

The aim of the present study was to evaluate and compare the in vitro and flow dynamics of the Magna (MB) and the Magna Ease aortic valve bioprosthesis (MEB) within the ascending aorta. A 2D-particle-image-velocimetry (2D-PIV) study was performed to compare the flow dynamics induced by each pericardial Carpentier-Edwards Magna and Magna Ease aortic valve prosthesis in the aortic flow field directly behind the valve. Both prostheses (diameter 23 mm) were placed inside an artificial aorta under pulsatile flow conditions (70 Hz and 70 ml stroke volume). The flow field was evaluated according to velocity, shear strength, and vorticity. Both prostheses showed a jet flow type profile with a maximum velocity of 0.97±0.09 m/s for MB and 0.83±1.8 m/s for MEB. Flow fields of both valves were similar in acceleration, peak flow deceleration and leakage phase. Maximum shear strength was 20,285±11,774 l/s2 for MB and 17,006±8453 l/s2 for MEB. Vorticity was nearly similar for counterclockwise and clockwise rotation in both prostheses, but slightly higher with MB (251±41 l/s and -250±39 l/s vs. 225±48 l/s and -232±48 l/s). The point-of-interest (POI)-analysis revealed a higher velocity for left-sided aortic wall compared to right-sided at MB (0.12±0.09 m/s vs. 0.18±0.10 m/s, p

Dissertation, Universität Duisburg-Essen, 2015 Einleitung: In der vorliegenden Arbeit berichten wir über die ersten tierexperimentellen und humanen Transkatheteraortenklappenimplantationen (TAVI) unter Verwendung der transapikalen, selbst-expandierbaren Symetis Acurate TA Transkatheterherzklappe am Westdeutschen Herz- und Gefäßzentrum Essen. Material und Methoden: Diese neuartige Transkatheterherzklappe besteht aus einer procinen Bioprothese, die in einen selbst-expandierbaren Nitinolstent montiert ist und eine anatomisch korrekte, einfache Implantation der Prothese ermöglicht. Zwischen Juli 2010 und April 2015 wurden insgesamt 105 Hochrisikopatienten mit symptomatischer Aortenklappenstenose und/oder Aorteninsuffizienz in die vorliegende Studie eingeschlossen. Klinische und hämodynamische Parameter wurde prospektiv erhoben und gemäß der VARC Definitionen ausgewertet. Die hämodynamische Funktion der Prothese wurde mittels Echokardiographie präoperativ, zum Zeitpunkt von 30 Tagen und nach 12 Monaten bestimmt. Fragestellung: Wie ist die Durchführbarkeit und Handhabung des neuartigen Symetis Acurate TA Systems und die Sicherheit in Bezug auf intra- und postoperative Komplikationen, sowohl im Tiermodell, als auch im Patienten? Wie stellen sich Implantationsergebnisse und hämodynamische Eigenschaften dar, und wie sind die mittel- und langfristigen Ergebnisse im Verlauf über einen Beobachtungszeitraum von 12 Monaten? Ergebnisse: Zunächst konnte die Handhabung und Sicherheit des neuartigen Transkatheterklappensystems in 6 Hausschweinen überprüft werden. Alle 6 Implantationen verliefen erfolgreich und es kam in keinem Fall zu schwerwiegenden Komplikationen. Die Erkenntnis auf eine schnelle Schrittmacherstimulation während der Freisetzung der Prothese verzichten zu können, genauso wie die sichere Implantierbarkeit ohne Vorhandensein einer kalzifizierten Stenose konnte anschließend direkt bei den Implantationen am Patienten angewandt werden. Das mittlere Alter der Patienten betrug 79,0±7,1 Jahre (MW±SD) und 54% der Patienten waren weiblich. Der logistische EuroSCORE war 32,3±13,4% und der STS-Score lag im Mittel bei 6,9±3,0%. Alle bis auf eine Implantation verliefen erfolgreich (99%). Eine Nachdilatation der Prothese war bei 28% notwendig. Der mittlere Druckgradient über der Aortenklappe von präoperativ 41,2±19.3mmHg fiel auf 13,0±6,6mmHg nach 30 Tagen und blieb mit 10,3±5,8mmHg nach 12 Monaten stabil. Die 30-Tage Letalität betrug 3,8% und die Kaplan-Meier-Überlebensrate nach 6- und 12 Monaten betrug 90 und 89%. Innerhalb des Beobachtungszeitraums von 12 Monaten betrug die Schlaganfallsrate 3,8%, die Schrittmacherneuimplantationsrate lag bei 6,6%. Paravalvuläre Leckagen waren bei 59% der Patienten nicht zu beobachten, und bei 37% mild (Grad 1) und 4 % moderat (Grad 2). Kein Patient hatte eine schwere (Grad 3) paravalvuläre Leckage. Schlussfolgerung: Die weltweit erstmalige Anwendung der transapikalen, selbst-expandierbaren 2.-Generations Transkatheterklappe zeigt im akuten Schweinemodell exzellente Ergebnisse. Die monozentrischen Ergebnisse bei Hochrisikopatienten zeigen sehr gute hämodynamische Eigenschaften, eine niedrige Rate an postoperativen paravalvuläre Leckagen und insgesamt sehr gute klinische Ergebnisse über einen Beobachtungszeitraum von 12 Monaten.

Acute type I aortic dissection (AD) complicated by true lumen (TL) collapse and malperfusion downstream is associated with devastating prognosis. The study reports an institutional mid-term experience with TL stabilization by uncovered stents to restore perfusion as a supplement to proximal thoracic aortic surgery. Between January 2007 and May 2017, 181 out of 270 acute type A AD patients were operated on type I AD. Eighteen uncovered stents (10%) were used to expand the aortic TL in presence of visceral and/or peripheral malperfusion. The procedures took place in a hybrid operating room and were combined with proximal aortic surgery. During follow-up (mean ± standard deviation 3.44 ± 2.1 years), the fate of AD was evaluated by computed tomography. Indication for TL stenting included visceral (44%) or peripheral malperfusion (11%) or both (45%). Stenting of aortic branches followed in 33%. All patients underwent proximal repair and were combined with frozen elephant trunk (67%) or retrograde descending aorta stent grafting (11%). Thirty-day mortality was 16.7%. Two-year survival was 71.8%. The false lumen around the uncovered stents remained patent in 89% and the aortic diameter increased 0.1 cm/y. No intimal rupture or occlusion of arteries occurred. In 1 patient, the stented aortic lumen was visualized after 6.3 years and neointima ingrowth covering the nitinol frame was found. In acute type I AD, combined endovascular-surgical procedures in a hybrid operation room setting can be used safely to resolve distal malperfusion. Encapsulation of uncovered stents within the intimal wall provides a stable fundament for endovascular techniques to close entry tears and false lumen.

Objectives The treatment of patients with extensive thoracic aortic disease involving the arch and descending aorta is often performed, using the frozen elephant trunk (FET) technique. We retrospectively analysed early outcomes with this technique, using a prospective database. Methods A total of 509 patients (mean age: 61 ± 11 years) were registered between January 2005 and January 2014 in a multicentre database after FET surgery. Acute or chronic aortic dissection (AD) was the indication for surgery in 350 (68.8%) patients and degenerative or atherosclerotic aneurysm (DA) accounted for 159 (31.2%) patients. A logistic regression model was created to identify independent predictors of in-hospital mortality and neurological complications. Results The average in-hospital mortality was 15.9% (n = 81) with 17.1% for AD patients and 13.2% for DA patients (P = 0.2). Independent predictors of in-hospital mortality were haemodynamic instability [odds ratio (OR): 2.7, P = 0.005], peripheral vascular disease (OR: 2.6, P = 0.002), diabetes (OR: 2.1, P = 0.05) and selective cerebral perfusion time >60 min (OR: 2.2, P = 0.005). Patients under 60 years of age and the use of guide wire during FET implantation were protective for early survival. Stroke occurred in 7.7% (n = 39) of patients. Paraplegia or paraparesis occurred in 7.5% (n = 38) of patients. A distal landing zone lower than T10 was an independent predictor for spinal cord injury (OR: 2.3, P = 0.03). Conclusions Techniques for faster arch replacement and controlled FET placement should be considered in order to reduce the early mortality and neurological complications after FET surgery. For distal aortic lesions, a two-staged approach is suggested, rather than the FET landing lower than T10.

Duisburg, Essen, Univ., Diss., 2012

Duisburg, Essen, Univ., Diss., 2012

Duisburg, Essen, Univ., Diss., 2010

Duisburg-Essen, Univ., Diss. 2009

Duisburg, Essen, Univ., Diss., 2006

Duisburg, Essen, Univ., Diss., 2006