The role of the G-coupled receptor kinase 2 in sevofluran-induced postconditioning after myocardial ischaemia

Kardiale Ischämien sind die häufigste Todesursache in Deutschland. Aufgrund bisheri-ger Fortschritte in der Therapie und Entwicklung neuer präventiver Prozesse, gewinnen die Erkenntnisse kardioprotektiver Strategien zunehmend an Bedeutung und gelangen in den Mittelpunkt gegenwärtiger Forschung. Der Ablauf molekularer Vorgänge und die subzellulären Veränderungen im Rahmen der APost könnten zu einem möglichen Erklä-rungsansatz beitragen. Die APost wurde im Tiermodell bisher in diversen Spezies gezeigt und konnte experimentell etabliert werden. Diese Arbeit beschäftigt sich mit der Frage, ob die Veränderungen der GRK2 auf molekularer Ebene einer der Gründe für den kardioprotektiven Mechanismus der APost sein könnte. Die GRK2 ist eine myokardspezfische Kinase, die bereits im Rahmen von Herzinsuffizenzmodellen mit kardioprotektiven Eigenschaften in Zusammenhang gebracht worden ist. Ob die GRK2 ebenfalls im Ischämie/Reperfusionsmodell den letalen Reperfusionsschaden und die Infarktgöße beeinflusst, wird in dieser Arbeit in-vivo untersucht. Zusammenfassend lassen sich aus dieser Studie folgende Erkenntnisse gewinnen: Die Infarktgröße lässt sich durch Applikation von Sevofluran signifikant senken. Die medikamentöse GRK2-Inhibition resultiert in einer signifikant verkleinerten In-farktgröße. Der Proteingehalt von ADRB2 steigt signifikant an bei Applikation von Sevofluran zusammen mit dem GRK2-Inhibitor βARK1. Der Proteingehalt von b-Arrestin steigt signifikant an bei Applikation von Sevofluran zusammen mit dem GRK2-Inhibitor βARK1. Diese Daten im Ischämie/Reperfusionsmodell zu reproduzieren und translational weiterzuentwickeln, sollte ein fokussiertes Ziel der Grundlagenforschung und Organprotektion werden, da unter Berücksichtigung des demographischen Wandels und der Lebenszeitprävalenzen zu KHK und Herzinfarkten ein gezieltes pharmakologisches Target im Fokus stehen sollte.Myocardial ischaemia is one of the leading death causes worldwide. By applying anesthetic-induced postconditioning the reperfusion injury after perioperative ischaemia can be mediated. This dissertation investigates the role of the G-coupled receptor kinase 2 in sevofluran-induced postconditioning after myocardial ischaemia

Use of Process Modelling for Optimization of Molecular Tumor Boards

In Molecular Tumor Boards, a team of experts discuss the individual therapy options of a cancer patient based on their individual molecular profile. The process—from recommendation request, through molecular diagnosis, to a personalized therapy recommendation—is complex and time-consuming. Therefore, process optimization is needed to decrease the workload of physicians and to standardize the process. For this purpose, we modeled the current workflow of the Molecular Tumor Board at the University Hospital Hamburg-Eppendorf on Service-Oriented Architecture using Business Process Modeling and Notation to highlight areas for improvement. This identified many manual tasks and an extensive workload for the physician. We then created a novel, simplified, more efficient workflow in which the physician is supported by additional software. In summary, we show that the use of Service-Oriented Architecture using Business Process Modeling and Notation for Molecular Tumor Board processes promotes rapid adaptability, standardization, interoperability, quality assurance, and facilitates collaboration

Major influencing factors on routine implementation of shared decision-making in cancer care: qualitative process evaluation of a stepped-wedge cluster randomized trial

Abstract Background Shared decision-making (SDM) is highly relevant in oncology but rarely implemented in routine care. In a stepped-wedge cluster randomized implementation trial, the outcome evaluation of a theoretically and empirically based multi-component SDM implementation program did not show a statistically significant effect on patient-reported SDM uptake. Within this SDM implementation trial, a thorough a priori planned process evaluation was conducted. Thus, the aim of this study was to investigate factors influencing SDM implementation in the context of a multi-component SDM implementation program. Methods We conducted qualitative process evaluation of a stepped-wedge SDM implementation trial. Qualitative data included interviews with nurses and physicians of participating departments, field notes by the study team, and meeting minutes. Data were analyzed via deductive and inductive qualitative content analysis on basis of the Consolidated Framework for Implementation Research (CFIR). Results Transcripts of 107 interviews with 126 nurses and physicians, 304 pages of field note documentation, and 125 pages of meeting minutes were analyzed. Major factors influencing SDM implementation were found for all domains of the CFIR: a) four regarding characteristics of the individuals involved (e.g., perceived personal relevance, individual motivation to change), b) eleven regarding the inner setting (e.g., leadership engagement, networks and communication, available resources, compatibility with clinical practice), c) two regarding the outer setting (e.g., culture of health care delivery), d) eight regarding characteristics of the intervention (e.g., relative advantage, adaptability), and e) three regarding the implementation process (e.g., integration into existing structures). Furthermore, we found strong interrelations between several of the influencing factors within and between domains. Conclusions This comprehensive process evaluation complements the outcome evaluation of the SDM implementation trial and adds to its interpretation. The identified influencing factors can be used for planning, conducting, and evaluating SDM implementation in the future. Trial registration clinicaltrials.gov, NCT03393351, registered 8 January 2018, https://clinicaltrials.gov/ct2/show/NCT0339335