Experimentelle Untersuchungen am porzinen „over-sized coronary stent“-

Experimental investigations at the porcine over-sized coronary stent-model for in-stent-restenosis rate after implantation of uncoated niob-zirkonium stents and niob-zirkonium stents coated with iridiumoxide. Background: The treatment of atherosclerotic stenosis in coronary artery disease with balloon expandable coronary stents has been successfully practised in minimal invasive cardiology in the last two decades. Today almost all commercially coronary stents are made of stainless steel (316L) and there is a great variety in design and coatings available. Until now no interventional procedure has been successful to stop the vicious circle of arterial stenosis, intervention and restenosis. Methods: In 23 pigs (German land breed) Inflow Dynamics Starflex Design Stents were implanted into the LAD and LCX by random for 28 days. In the porcine over-sized coronary stent model three groups were compared: uncoated niob-zirkonium stents, niob-zirkonium stents coated with iridiumoxide and stainless steel stents (control group). The implantation procedure and angiography were documented and histological and histomorphometric studies were performed to interpret the in-stent-restenosis rate. The statistical evaluation of the differences between the test groups was done by the analysis of variance (One Way ANOVA-Test) and specified (Post Hoc-Test). Results: Three animals died postoperatively. 38 stents were evaluated. The implantation procedure in the experimental groups was complicated due to the elastic and plastic properties of the niob-zirkonium stents. The injury score (IS) and the measured neointimal area (NF) were significantly higher in the group of niob-zirkonium stents coated with iridiumoxide. The histomorphometric and angiographic parameters of restenosis did not point out any significant difference between the test groups. The histological response of the arterial wall after stent implanation provided a homogenous appearance of tissue shaped by the score of vascular irritation. Conclusion: A direct comparison in the stents of uncoated niob-zirkonium and niob-zirkonium stents coated with iridiumoxide with stainless steel stents was not possible. No new findings for the in-stent-restenosis rate were provided by the results of the control stents. The prototypes of the uncoated niob-zirkonium stents and the niob-zirkonium stents coated with iridiumoxide have to be optimized in their metallurgical characteristics to guarantee an implantation procedure without complications. The alloy niob-zirkonium and the iridiumoxide-coating are excellently biocompatible. Even SUMMARY 117 after a high vascular irritation the stents are embeded into a neointima with only a minimum of cellular response.Hintergrund: Die Therapie stenosierter Herzkranzgefäße mit ballonexpandierbaren Gefäßstützen (Stents) wird in der minimalinvasiven Kardiologie seit einigen Jahren mit Erfolg praktiziert. Die heute hauptsächlich zum Einsatz kommenden Stents sind aus dem Material 316L (medizinischer Edelstahl). Sie unterscheiden sich in ihrem Design und ihren Oberflächenbeschichtungen. Keinem interventionellen Verfahren ist es bisher gelungen, den Teufelskreis arterielle Stenose, Intervention und Restenose zu durchbrechen. Methoden: 23 Schweinen (Deutsche Landrasse Hybrid) werden für den Versuchszeitraum von 28 Tagen jeweils in die LAD und LCX Stents des „Starfex“-Designs der Fa. Inflow Dynamics implantiert. Am porzinen „over-sized coronary stent“-Modell werden randomisiert in drei Gruppen unbeschichtete Niobzirkonium-Stents oder mit Iridiumoxid beschichtete Niobzikon-Stents oder Stahl-Stents (Kontrolle) verglichen. Zur Beurteilung der In-Stent-Restenose werden der Implantationsverlauf und die Angiographie dokumentiert sowie histologische und histomorphometrische Untersuchungen durchgeführt. Die statistische Auswertung erfolgt mit dem One Way ANOVA-Test und wird mit dem Post Hoc Test spezifiziert. Ergebnisse: Drei Tiere versterben post OP. 38 Stents werden ausgewertet. Die Implantationen der Stents aus Niobzirkonium können nur unter Komplikationen durchgeführt werden, da die elastische und plastische Verformbarkeit während der Dilatation nicht optimal sind. Für den Verletzungsindex (IS) und die ausgemessene neointimale Fläche (NF) ergeben sich in der Gruppe der mit Iridiumoxid beschichteten Niobzirkonium-Stents signifikant erhöhte Werte. Die histomorphometrisch und angiographisch ermittelten Restenoseparameter zeigen keine statistisch signifikanten Unterschiede zwischen den drei Gruppen. Die histologische Reaktion der Gefäßwand auf die Stentimplantation liefert ein einheitliches Gewebebild, das geprägt ist vom Grad der Gefäßwandirritation. Schlussfolgerung: Ein direkter Vergleich der Stents aus Niobzirkonium, mit Iridiumoxid beschichtetem Niobzirkonium und aus medizinischem Edelstahl ist nicht möglich. Die Ergebnisse zur In-Stent-Restenoserate der Kontrollstents ergeben keine neuen Erkenntnisse. Die Prototypen der Stents aus unbeschichtetem und mit Iridiumoxid beschichtetem Niobzikonium müssen in ihren mechanischen Eigenschaften optimiert werden, um eine sichere Implantation zu gewährleisten. Die Legierung Niobzirkonium und die Iridiumoxid-Beschichtung sind sehr gut ZUSAMMENFASSUNG 115 gewebeverträglich. Auch nach starker Gefäßwandverletzung wachsen sie in eine Neointima ein, die nur eine geringgradige zelluläre Entzündungsreaktion zeigt

Experimentelle Untersuchungen am porzinen „over-sized coronary stent“-

Experimental investigations at the porcine over-sized coronary stent-model for in-stent-restenosis rate after implantation of uncoated niob-zirkonium stents and niob-zirkonium stents coated with iridiumoxide. Background: The treatment of atherosclerotic stenosis in coronary artery disease with balloon expandable coronary stents has been successfully practised in minimal invasive cardiology in the last two decades. Today almost all commercially coronary stents are made of stainless steel (316L) and there is a great variety in design and coatings available. Until now no interventional procedure has been successful to stop the vicious circle of arterial stenosis, intervention and restenosis. Methods: In 23 pigs (German land breed) Inflow Dynamics Starflex Design Stents were implanted into the LAD and LCX by random for 28 days. In the porcine over-sized coronary stent model three groups were compared: uncoated niob-zirkonium stents, niob-zirkonium stents coated with iridiumoxide and stainless steel stents (control group). The implantation procedure and angiography were documented and histological and histomorphometric studies were performed to interpret the in-stent-restenosis rate. The statistical evaluation of the differences between the test groups was done by the analysis of variance (One Way ANOVA-Test) and specified (Post Hoc-Test). Results: Three animals died postoperatively. 38 stents were evaluated. The implantation procedure in the experimental groups was complicated due to the elastic and plastic properties of the niob-zirkonium stents. The injury score (IS) and the measured neointimal area (NF) were significantly higher in the group of niob-zirkonium stents coated with iridiumoxide. The histomorphometric and angiographic parameters of restenosis did not point out any significant difference between the test groups. The histological response of the arterial wall after stent implanation provided a homogenous appearance of tissue shaped by the score of vascular irritation. Conclusion: A direct comparison in the stents of uncoated niob-zirkonium and niob-zirkonium stents coated with iridiumoxide with stainless steel stents was not possible. No new findings for the in-stent-restenosis rate were provided by the results of the control stents. The prototypes of the uncoated niob-zirkonium stents and the niob-zirkonium stents coated with iridiumoxide have to be optimized in their metallurgical characteristics to guarantee an implantation procedure without complications. The alloy niob-zirkonium and the iridiumoxide-coating are excellently biocompatible. Even SUMMARY 117 after a high vascular irritation the stents are embeded into a neointima with only a minimum of cellular response.Hintergrund: Die Therapie stenosierter Herzkranzgefäße mit ballonexpandierbaren Gefäßstützen (Stents) wird in der minimalinvasiven Kardiologie seit einigen Jahren mit Erfolg praktiziert. Die heute hauptsächlich zum Einsatz kommenden Stents sind aus dem Material 316L (medizinischer Edelstahl). Sie unterscheiden sich in ihrem Design und ihren Oberflächenbeschichtungen. Keinem interventionellen Verfahren ist es bisher gelungen, den Teufelskreis arterielle Stenose, Intervention und Restenose zu durchbrechen. Methoden: 23 Schweinen (Deutsche Landrasse Hybrid) werden für den Versuchszeitraum von 28 Tagen jeweils in die LAD und LCX Stents des „Starfex“-Designs der Fa. Inflow Dynamics implantiert. Am porzinen „over-sized coronary stent“-Modell werden randomisiert in drei Gruppen unbeschichtete Niobzirkonium-Stents oder mit Iridiumoxid beschichtete Niobzikon-Stents oder Stahl-Stents (Kontrolle) verglichen. Zur Beurteilung der In-Stent-Restenose werden der Implantationsverlauf und die Angiographie dokumentiert sowie histologische und histomorphometrische Untersuchungen durchgeführt. Die statistische Auswertung erfolgt mit dem One Way ANOVA-Test und wird mit dem Post Hoc Test spezifiziert. Ergebnisse: Drei Tiere versterben post OP. 38 Stents werden ausgewertet. Die Implantationen der Stents aus Niobzirkonium können nur unter Komplikationen durchgeführt werden, da die elastische und plastische Verformbarkeit während der Dilatation nicht optimal sind. Für den Verletzungsindex (IS) und die ausgemessene neointimale Fläche (NF) ergeben sich in der Gruppe der mit Iridiumoxid beschichteten Niobzirkonium-Stents signifikant erhöhte Werte. Die histomorphometrisch und angiographisch ermittelten Restenoseparameter zeigen keine statistisch signifikanten Unterschiede zwischen den drei Gruppen. Die histologische Reaktion der Gefäßwand auf die Stentimplantation liefert ein einheitliches Gewebebild, das geprägt ist vom Grad der Gefäßwandirritation. Schlussfolgerung: Ein direkter Vergleich der Stents aus Niobzirkonium, mit Iridiumoxid beschichtetem Niobzirkonium und aus medizinischem Edelstahl ist nicht möglich. Die Ergebnisse zur In-Stent-Restenoserate der Kontrollstents ergeben keine neuen Erkenntnisse. Die Prototypen der Stents aus unbeschichtetem und mit Iridiumoxid beschichtetem Niobzikonium müssen in ihren mechanischen Eigenschaften optimiert werden, um eine sichere Implantation zu gewährleisten. Die Legierung Niobzirkonium und die Iridiumoxid-Beschichtung sind sehr gut ZUSAMMENFASSUNG 115 gewebeverträglich. Auch nach starker Gefäßwandverletzung wachsen sie in eine Neointima ein, die nur eine geringgradige zelluläre Entzündungsreaktion zeigt

Treatment of Early Breast Cancer Patients: Evidence, Controversies, Consensus: Focusing on Systemic Therapy - German Experts' Opinions for the 16th International St. Gallen Consensus Conference (Vienna 2019)

A German working group of leading breast cancer experts have discussed the votes at the International St. Gallen Consensus Conference in Vienna for the treatment of primary breast cancer with regard to the German AGO (Ar-beitsgemeinschaft Gynakologische Onkologie) recommendations for clinical practice in Germany. Three of the German breast cancer experts were also members of this year's St. Gallen panel. Comparing the St. Gallen recommendations with the annually updated treatment recommendations of the Gynecological Oncology Working Group (AGO Mamma 2019) and the German S3 Guideline is useful, because the recommendations of the St. Gallen panel are based on expert opinions of different countries and disciplines. The focus of this article is on systemic therapy. The motto of this year's 16th St. Gallen Consensus Conference was Estimating the magnitude of clinical benefit. The rationale behind this motto is that, for every treatment decision, a benefit-risk assessment must be taken into consideration for each patient

Early Pliocene increase in thermohaline overturning : a precondition for the development of the modern equatorial Pacific cold tongue

Author Posting. © American Geophysical Union, 2010. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 25 (2010): PA2202, doi:10.1029/2008PA001645.Unraveling the processes responsible for Earth's climate transition from an “El Niño–like state” during the warm early Pliocene into a modern-like “La Niña–dominated state” currently challenges the scientific community. Recently, the Pliocene climate switch has been linked to oceanic thermocline shoaling at ∼3 million years ago along with Earth's final transition into a bipolar icehouse world. Here we present Pliocene proxy data and climate model results, which suggest an earlier timing of the Pliocene climate switch and a different chain of forcing mechanisms. We show that the increase in North Atlantic meridional overturning circulation between 4.8 and 4.0 million years ago, initiated by the progressive closure of the Central American Seaway, triggered overall shoaling of the tropical thermocline. This preconditioned the turnaround from a warm eastern equatorial Pacific to the modern equatorial cold tongue state about 1 million years earlier than previously assumed. Since ∼3.6–3.5 million years ago, the intensification of Northern Hemisphere glaciation resulted in a strengthening of the trade winds, thereby amplifying upwelling and biogenic productivity at low latitudes.Funding for this research was provided by the Deutsche Forschungsgemeinschaft (DFG) through projects Ti 240/7, Ti 240/12 (being part of the DFG Research Unit, FOR 451: Impact of Gateways on Ocean Circulation, Climate, and Evolution at Kiel University), and Ti 240/17 and through the DFG Research Center/Excellence Cluster “The Ocean in the Earth System” at the University of Bremen. A. Timmermann is supported by the Japan Agency for Marine-Earth Science and Technology through its sponsorship of the International Pacific Research Center

AGO Recommendations for the surgical therapy of breast cancer: update 2022

The recommendations of the AGO Breast Committee on the surgical therapy of breast cancer were last updated in March 2022 (www.ago-online.de). Since surgical therapy is one of several partial steps in the treatment of breast cancer, extensive diagnostic and oncological expertise of a breast surgeon and good interdisciplinary cooperation with diagnostic radiologists is of great importance. The most important changes concern localization techniques, resection margins, axillary management in the neoadjuvant setting and the evaluation of the meshes in reconstructive surgery. Based on meta-analyses of randomized studies, the level of recommendation of an intraoperative breast ultrasound for the localization of non-palpable lesions was elevated to “++”. Thus, the technique is considered to be equivalent to wire localization, provided that it is a lesion which can be well represented by sonography, the surgeon has extensive experience in breast ultrasound and has access to a suitable ultrasound device during the operation. In invasive breast cancer, the aim is to reach negative resection margins (“no tumor on ink”), regardless of whether an extensive intraductal component is present or not. Oncoplastic operations can also replace a mastectomy in selected cases due to the large number of existing techniques, and are equivalent to segmental resection in terms of oncological safety at comparable rates of complications. Sentinel node excision is recommended for patients with cN0 status receiving neoadjuvant chemotherapy after completion of chemotherapy. Minimally invasive biopsy is recommended for initially suspect lymph nodes. After neoadjuvant chemotherapy, patients with initially 1 – 3 suspicious lymph nodes and a good response (ycN0) can receive the targeted axillary dissection and the axillary dissection as equivalent options

AGO recommendations for the surgical therapy of the axilla after neoadjuvant chemotherapy: 2021 Update

For many decades, the standard procedure to treat breast cancer included complete dissection of the axillary lymph nodes. The aim was to determine histological node status, which was then used as the basis for adjuvant therapy, and to ensure locoregional tumour control. In addition to the debate on how to optimise the therapeutic strategies of systemic treatment and radiotherapy, the current discussion focuses on improving surgical procedures to treat breast cancer. As neoadjuvant chemotherapy is becoming increasingly important, the surgical procedures used to treat breast cancer, whether they are breast surgery or axillary dissection, are changing. Based on the currently available data, carrying out SLNE prior to neoadjuvant chemotherapy is not recommended. In contrast, surgical axillary management after neoadjuvant chemotherapy is considered the procedure of choice for axillary staging and can range from SLNE to TAD and ALND. To reduce the rate of false negatives during surgical staging of the axilla in pN+(CNB) stage before NACT and ycN0 after NACT, targeted axillary dissection (TAD), the removal of > 2 SLNs (SLNE, no untargeted axillary sampling), immunohistochemistry to detect isolated tumour cells and micro-metastases, and marking positive lymph nodes before NACT should be the standard approach. This most recent update on surgical axillary management describes the significance of isolated tumour cells and micro-metastasis after neoadjuvant chemotherapy and the clinical consequences of low volume residual disease diagnosed using SLNE and TAD and provides an overview of this year's AGO recommendations for surgical management of the axilla during primary surgery and in relation to neoadjuvant chemotherapy

Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign

Abstract: In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M ⊙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87’s spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded

Advanced Numerical Methods and Software Solutions for Aircraft Design and Analysis

To significantly contribute to the EU target of climate neutrality in 2050 while concurrently maintaining safety standards and competitiveness, the aviation sector faces a transformation that will affect the design of aircraft. The design and optimization process need to be substantially accelerated and to mitigate the high financial risks in order to deliver new, emission-reduced aircraft timely to market. This is achievable with an extensive and integrated usage of digital tools throughout the design and analysis process. The introduction of high-fidelity numerical methods permits a reliable evaluation of new technologies and designs especially at the early stages of the design process and avoids expensive and time-consuming testing on physical demonstrators. The development and industrialization of disciplinary methods for external aerodynamics include turbulence and transition modeling, scale-resolving simulation methods, numerical algorithms and surrogate modeling. Based on these methods as well as on other disciplines, multi-disciplinary applications (MDA) and optimizations (MDO) are ¬¬¬¬developed and demonstrated for relevant aircraft configurations by making use of high-performance computing (HPC) resources. Our established software products like the DLR-TAU Code [1] are widely used in European research and aviation industries. The SMARTy toolbox [2] covers more recent requirements for reduced order and surrogate modeling including AI-based methods as well as uncertainty quantification for robust design. The next-generation CFD-code CODA [3], jointly developed by DLR, ONERA and Airbus, is based on modern software engineering, integrates advanced numerical algorithms and exploits current and future HPC architectures. For the integration and efficient interaction of disciplines to enable e.g. virtual flight testing, the FlowSimulator [4] is used as a platform jointly developed by several European partners. This talk gives an overview of the disciplinary and multi-disciplinary numerical methods and software solutions developed at the C²A²S²E department of the German Aerospace Center to address digital aircraft design and analysis