@article{GuesgenAngerHaueretal.2020, author = {G{\"u}sgen, C. and Anger, F. and Hauer, T. and Willms, A. and Buhr, H. J. and Germer, C.-T. and Schwab, R. and Lock, J. F.}, title = {Fortbildung von Allgemein- und Viszeralchirurgen in der lebensrettenden Notfallchirurgie. Ergebnisse einer Umfrage unter Operationskursteilnehmern}, series = {Der Chirurg}, volume = {91}, journal = {Der Chirurg}, organization = {Chirurgische ArbeitsgemeinschaftMilit{\"a}r- und Notfallchirurgie (CAMIN) der Deutschen Gesellschaft f{\"u}r Allgemein- und Viszeralchirurgie (DGAV)}, issn = {0009-4722}, doi = {10.1007/s00104-020-01170-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235246}, pages = {1044-1052}, year = {2020}, abstract = {Hintergrund Die geringe Anzahl operativ zu versorgender K{\"o}rperh{\"o}hlenverletzungen erfordert ein Umdenken in der chirurgischen Aus- und Weiterbildung. Ein entsprechendes Kursformat wird seit 2014 {\"u}ber die DGAV angeboten. Um Berechtigung, Bedarf, Nutzen und Erfolg eines solchen Kursformates zu erheben, erfolgte eine Evaluation durch die bisherigen Kursteilnehmer. Material und Methoden Kursevaluation und zus{\"a}tzliche Onlinebefragung der bisherigen Kursteilnehmer hinsichtlich Alter, Geschlecht, Ausbildungsstand, Fachrichtung, Versorgungsstufe des Krankenhauses, notfallchirurgischer Erfahrungen, der H{\"a}ufigkeit chirurgischer Notfallversorgungen, Teilnahme an anderen Kursformaten, Erfahrungen nach der Kursteilnahme, Einsch{\"a}tzung der aktuellen Fort- und Weiterbildungssituation und Finanzierung solcher Kurse. Ergebnisse Insgesamt 142 Kursteilnehmer evaluierten ihre Kursteilnahme, zus{\"a}tzlich beantworteten 83 den Onlinefragebogen. {\"U}ber 90 \% berichteten von einem nachhaltigen positiven Einfluss des Kurses auf ihr notfallchirurgisches Handeln. Mehr als die H{\"a}lfte konnte von konkreten Notfallsituationen berichten, die sie aufgrund der Kursteilnahme besser bew{\"a}ltigen konnten. In der Notfallversorgung erfahrene Chirurgen bewerteten den eigenen Lernerfolg durch die Kursteilnahme signifikant h{\"a}ufiger positiv als ihre weniger erfahrenen Kollegen. Keinen Einfluss auf den Lernerfolg hatten eine Ober- oder Chefarztposition, die Versorgungsstufe des Krankenhauses, das Alter oder Geschlecht der Teilnehmer. Die Mehrheit der antwortenden Chirurgen bef{\"u}rwortet die Integration eines solchen Kursformates in die chirurgische Weiterbildung und fordert hierzu eine finanzielle Unterst{\"u}tzung. Schlussfolgerung Kursformate, in denen notfallchirurgische Strategien und F{\"a}higkeiten vermittelt werden, sind etabliert und werden sehr positiv evaluiert. Die Fort- und Weiterbildung in notfallchirurgischen F{\"a}higkeiten und Kenntnissen liegt im gesellschaftlichen Interesse und zumindest anteilig auch in ihrer Verantwortung.}, language = {de} } @article{JuergensBieniussaVoelkeretal.2020, author = {Juergens, Lukas and Bieniussa, Linda and Voelker, Johannes and Hagen, Rudolf and Rak, Kristen}, title = {Spatio-temporal distribution of tubulin-binding cofactors and posttranslational modifications of tubulin in the cochlea of mice}, series = {Histochemistry and Cell Biology}, volume = {154}, journal = {Histochemistry and Cell Biology}, issn = {0948-6143}, doi = {10.1007/s00418-020-01905-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234852}, pages = {671-681}, year = {2020}, abstract = {The five tubulin-binding cofactors (TBC) are involved in tubulin synthesis and the formation of microtubules. Their importance is highlighted by various diseases and syndromes caused by dysfunction or mutation of these proteins. Posttranslational modifications (PTMs) of tubulin promote different characteristics, including stability-creating subpopulations of tubulin. Cell- and time-specific distribution of PTMs has only been investigated in the organ of Corti in gerbils. The aim of the presented study was to investigate the cell type-specific and time-specific expression patterns of TBC proteins and PTMs for the first time in murine cochleae over several developmental stages. For this, murine cochleae were investigated at the postnatal (P) age P1, P7 and P14 by immunofluorescence analysis. The investigations revealed several profound interspecies differences in the distribution of PTMs between gerbil and mouse. Furthermore, this is the first study to describe the spatio-temporal distribution of TBCs in any tissue ever showing a volatile pattern of expression. The expression analysis of TBC proteins and PTMs of tubulin reveals that these proteins play a role in the physiological development of the cochlea and might be essential for hearing.}, language = {en} } @book{Reuter2020, author = {Reuter, Oliver M.}, title = {Erfahrungsverankerte Rezeption : Eine Methode zur Verzahnung von Produktion und Rezeption}, edition = {1. Auflage}, publisher = {kopaed}, isbn = {978-3-86736-580-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-345281}, publisher = {Universit{\"a}t W{\"u}rzburg}, pages = {210}, year = {2020}, abstract = {Eine Rezeption auf den von Kindern und Jugendlichen selbst gemachten Erfahrungen aufzubauen, ist das zentrale Anliegen der ausgef{\"u}hrten Methode zur Verschr{\"a}nkung von produktiven und rezeptiven Anteilen im Kunstunterricht. Indem vor der Rezeption eine bildnerische Praxis stattfindet, k{\"o}nnen Ideen und Vorstellungen selbst{\"a}ndig und individuell entwickelt und in Bilder {\"u}bersetzt werden. Bei der erfahrungsverankerten Vermittlung basiert die Rezeption auf einer Schnittmenge zwischen eigenen Handlungen im bildnerischen oder darstellenden Prozess und zentralen Aspekten des Werks. Solche Referenzpunkte zwischen der Produktion und der Rezeption k{\"o}nnen im Material, im Thema, in der Gattung, im bildnerischen Verfahren oder in einer k{\"u}nstlerischen Strategie ausfindig gemacht werden. Sie dienen dazu, Einsichten, Einstellungen, Kenntnisse und Wissen aus der Produktion in die Rezeption mitzunehmen. Somit ist die Methode der erfahrungsverankerten Rezeption gleichermaßen geeignet f{\"u}r die Vermittlung historischer wie f{\"u}r zeitgen{\"o}ssischer Kunst. Nach der Darlegung und Konturierung der Konzeption zeigt die Publikation Wege auf, die erfahrungsverankerte Rezeption in Unterricht zu {\"u}berf{\"u}hren. Exemplarische Unterrichtsskizzen illustrieren die Umsetzung im Kunstunterricht.}, subject = {Erfahrung}, language = {de} } @article{HerrmannAdamNotzetal.2020, author = {Herrmann, Johannes and Adam, Elisabeth Hannah and Notz, Quirin and Helmer, Philipp and Sonntagbauer, Michael and Ungemach-Papenberg, Peter and Sanns, Andreas and Zausig, York and Steinfeldt, Thorsten and Torje, Iuliu and Schmid, Benedikt and Schlesinger, Tobias and Rolfes, Caroline and Reyher, Christian and Kredel, Markus and Stumpner, Jan and Brack, Alexander and Wurmb, Thomas and Gill-Schuster, Daniel and Kranke, Peter and Weismann, Dirk and Klinker, Hartwig and Heuschmann, Peter and R{\"u}cker, Viktoria and Frantz, Stefan and Ertl, Georg and Muellenbach, Ralf Michael and Mutlak, Haitham and Meybohm, Patrick and Zacharowski, Kai and Lotz, Christopher}, title = {COVID-19 Induced Acute Respiratory Distress Syndrome — A Multicenter Observational Study}, series = {Frontiers in Medicine}, volume = {7}, journal = {Frontiers in Medicine}, issn = {2296-858X}, doi = {10.3389/fmed.2020.599533}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219834}, year = {2020}, abstract = {Background: Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS). Methods: This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals. All patients consecutively admitted to the intensive care unit (ICU) in any of the participating hospitals between March 12 and May 4, 2020 with a COVID-19 induced ARDS were included. Results: A total of 106 ICU patients were treated for COVID-19 induced ARDS, whereas severe ARDS was present in the majority of cases. Survival of ICU treatment was 65.0\%. Median duration of ICU treatment was 11 days; median duration of mechanical ventilation was 9 days. The majority of ICU treated patients (75.5\%) did not receive any antiviral or anti-inflammatory therapies. Venovenous (vv) ECMO was utilized in 16.3\%. ICU triage with population-level decision making was not necessary at any time. Univariate analysis associated older age, diabetes mellitus or a higher SOFA score on admission with non-survival during ICU stay. Conclusions: A high level of care adhering to standard ARDS treatments lead to a good outcome in critically ill COVID-19 patients.}, language = {en} } @article{GabbertDillingMeybohmetal.2020, author = {Gabbert, Lydia and Dilling, Christina and Meybohm, Patrick and Burek, Malgorzata}, title = {Deletion of Protocadherin Gamma C3 Induces Phenotypic and Functional Changes in Brain Microvascular Endothelial Cells In Vitro}, series = {Frontiers in Pharmacology}, volume = {11}, journal = {Frontiers in Pharmacology}, issn = {1663-9812}, doi = {10.3389/fphar.2020.590144}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219828}, year = {2020}, abstract = {Inflammation of the central nervous system (CNS) is associated with diseases such as multiple sclerosis, stroke and neurodegenerative diseases. Compromised integrity of the blood-brain barrier (BBB) and increased migration of immune cells into the CNS are the main characteristics of brain inflammation. Clustered protocadherins (Pcdhs) belong to a large family of cadherin-related molecules. Pcdhs are highly expressed in the CNS in neurons, astrocytes, pericytes and epithelial cells of the choroid plexus and, as we have recently demonstrated, in brain microvascular endothelial cells (BMECs). Knockout of a member of the Pcdh subfamily, PcdhgC3, resulted in significant changes in the barrier integrity of BMECs. Here we characterized the endothelial PcdhgC3 knockout (KO) cells using paracellular permeability measurements, proliferation assay, wound healing assay, inhibition of signaling pathways, oxygen/glucose deprivation (OGD) and a pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) treatment. PcdhgC3 KO showed an increased paracellular permeability, a faster proliferation rate, an altered expression of efflux pumps, transporters, cellular receptors, signaling and inflammatory molecules. Serum starvation led to significantly higher phosphorylation of extracellular signal-regulated kinases (Erk) in KO cells, while no changes in phosphorylated Akt kinase levels were found. PcdhgC3 KO cells migrated faster in the wound healing assay and this migration was significantly inhibited by respective inhibitors of the MAPK-, β-catenin/Wnt-, mTOR- signaling pathways (SL327, XAV939, or Torin 2). PcdhgC3 KO cells responded stronger to OGD and TNFα by significantly higher induction of interleukin 6 mRNA than wild type cells. These results suggest that PcdhgC3 is involved in the regulation of major signaling pathways and the inflammatory response of BMECs.}, language = {en} } @article{LotzMuellenbachMeybohmetal.2020, author = {Lotz, C. and Muellenbach, R. M. and Meybohm, P. and Rolfes, C. and Reyher, C.}, title = {Pr{\"a}klinisches Management bei Herz-Kreislauf-Stillstand - extrakorporale kardiopulmonale Reanimation}, series = {Der Anaesthesist}, volume = {69}, journal = {Der Anaesthesist}, issn = {0003-2417}, doi = {10.1007/s00101-020-00787-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232525}, pages = {404-413}, year = {2020}, abstract = {Hintergrund Die {\"U}berlebenschancen nach pr{\"a}klinischem Herz-Kreislauf-Stillstand sind weiterhin sehr gering. Trotz intensiver Bem{\"u}hungen bleibt das Outcome seit vielen Jahren weitestgehend konstant. Neue Technologien wie die extrakorporale kardiopulmonale Reanimation (eCPR) k{\"o}nnen in bestimmten Situationen m{\"o}glicherweise das {\"U}berleben mit gutem neurologischen Outcome signifikant verbessern. Fragestellung Beeinflusst die sofortige Reperfusion und Reoxygenierung des K{\"o}rpers mittels eCPR das {\"U}berleben nach Herz-Kreislauf-Stillstand? Bedarf es einer Erweiterung der „chain of survival" um die eCPR? Material und Methoden Diskussion aktueller Studienergebnisse und Leitlinienempfehlungen. Ergebnisse Die {\"U}berlebensraten nach pr{\"a}klinischem Herz-Kreislauf-Stillstand sind weltweit seit vielen Jahren unver{\"a}ndert bei 10-30 \%. Trotz geringer Fallzahlen zeigen neuere retrospektive Studien, dass durch die eCPR eine Verbesserung des Outcome erzielt werden kann. In selektionierten Patientenkollektiven ist ein {\"U}berleben mit gutem neurologischen Outcome von 38 \% m{\"o}glich. Schlussfolgerung Ob und mit welcher Lebensqualit{\"a}t ein Herz-Kreislauf-Stillstand {\"u}berlebt werden kann, ist von vielen unterschiedlichen Faktoren abh{\"a}ngig. Der Faktor Zeit, also die Vermeidung einer „No-flow-Phase" und die Reduktion der „Low-flow-Phase", ist von zentraler Bedeutung. Durch die sofortige Wiederherstellung von Zirkulation und Sauerstoffversorgung kann durch die eCPR das {\"U}berleben signifikant verbessert werden. Große kontrollierte, randomisierte Studien hierzu fehlen jedoch bisher.}, language = {de} } @article{LotzNotzKrankeetal.2020, author = {Lotz, Christopher and Notz, Quirin and Kranke, Peter and Kredel, Markus and Meybohm, Patrick}, title = {Unconventional approaches to mechanical ventilation - step-by-step through the COVID-19 crisis}, series = {Critical Care}, volume = {24}, journal = {Critical Care}, doi = {10.1186/s13054-020-02954-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229868}, year = {2020}, abstract = {No abstract available.}, language = {en} } @article{AverdunkBernhagenFehnleetal.2020, author = {Averdunk, Luisa and Bernhagen, J{\"u}rgen and Fehnle, Karl and Surowy, Harald and L{\"u}decke, Hermann-Josef and Mucha, S{\"o}ren and Meybohm, Patrick and Wieczorek, Dagmar and Leng, Lin and Marx, Gernot and Leaf, David E. and Zarbock, Alexander and Zacharowski, Kai and Bucala, Richard and Stoppe, Christian}, title = {The Macrophage Migration Inhibitory Factor (MIF) promoter polymorphisms (rs3063368, rs755622) predict acute kidney injury and death after cardiac surgery}, series = {Journal of Clinical Medicine}, volume = {9}, journal = {Journal of Clinical Medicine}, number = {9}, issn = {2077-0383}, doi = {10.3390/jcm9092936}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213126}, year = {2020}, abstract = {Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT\(_{5-7}\) (rs5844572/rs3063368,"-794") and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT\(_7\)) had a significantly higher risk of acute kidney injury (AKI) compared to others (23\% vs. 13\%; OR 2.01 (1.40-2.88), p = 0.0001). Carriers of CATT\(_7\) were also at higher risk of death (1.8\% vs. 0.4\%; OR 5.12 (0.99-33.14), p = 0.026). The GC genotype was associated with AKI (20\% vs. GG/CC:13\%, OR 1.71 (1.20-2.43), p = 0.003). Multivariate analyses identified CATT\(_7\) predictive for AKI (OR 2.13 (1.46-3.09), p < 0.001) and death (OR 5.58 (1.29-24.04), p = 0.021). CATT\(_7\) was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). Conclusion: The CATT\(_7\) allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance.}, language = {en} } @article{CurtazSchmittHerbertetal.2020, author = {Curtaz, Carolin J. and Schmitt, Constanze and Herbert, Saskia-Laureen and Feldheim, Jonas and Schlegel, Nicolas and Gosselet, Fabien and Hagemann, Carsten and Roewer, Norbert and Meybohm, Patrick and W{\"o}ckel, Achim and Burek, Malgorzata}, title = {Serum-derived factors of breast cancer patients with brain metastases alter permeability of a human blood-brain barrier model}, series = {Fluids and Barriers of the CNS}, volume = {17}, journal = {Fluids and Barriers of the CNS}, doi = {10.1186/s12987-020-00192-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229940}, year = {2020}, abstract = {Background The most threatening metastases in breast cancer are brain metastases, which correlate with a very poor overall survival, but also a limited quality of life. A key event for the metastatic progression of breast cancer into the brain is the migration of cancer cells across the blood-brain barrier (BBB). Methods We adapted and validated the CD34\(^+\) cells-derived human in vitro BBB model (brain-like endothelial cells, BLECs) to analyse the effects of patient serum on BBB properties. We collected serum samples from healthy donors, breast cancer patients with primary cancer, and breast cancer patients with, bone, visceral or cerebral metastases. We analysed cytokine levels in these sera utilizing immunoassays and correlated them with clinical data. We used paracellular permeability measurements, immunofluorescence staining, Western blot and mRNA analysis to examine the effects of patient sera on the properties of BBB in vitro. Results The BLECs cultured together with brain pericytes in transwells developed a tight monolayer with a correct localization of claudin-5 at the tight junctions (TJ). Several BBB marker proteins such as the TJ proteins claudin-5 and occludin, the glucose transporter GLUT-1 or the efflux pumps PG-P and BCRP were upregulated in these cultures. This was accompanied by a reduced paracellular permeability for fluorescein (400 Da). We then used this model for the treatment with the patient sera. Only the sera of breast cancer patients with cerebral metastases had significantly increased levels of the cytokines fractalkine (CX3CL1) and BCA-1 (CXCL13). The increased levels of fractalkine were associated with the estrogen/progesterone receptor status of the tumour. The treatment of BLECs with these sera selectively increased the expression of CXCL13 and TJ protein occludin. In addition, the permeability of fluorescein was increased after serum treatment. Conclusion We demonstrate that the CD34\(^+\) cell-derived human in vitro BBB model can be used as a tool to study the molecular mechanisms underlying cerebrovascular pathologies. We showed that serum from patients with cerebral metastases may affect the integrity of the BBB in vitro, associated with elevated concentrations of specific cytokines such as CX3CL1 and CXCL13.}, language = {en} } @article{SchlesingerWeissbrichWedekinketal.2020, author = {Schlesinger, Tobias and Weißbrich, Benedikt and Wedekink, Florian and Notz, Quirin and Herrmann, Johannes and Krone, Manuel and Sitter, Magdalena and Schmid, Benedikt and Kredel, Markus and Stumpner, Jan and D{\"o}lken, Lars and Wischhusen, J{\"o}rg and Kranke, Peter and Meybohm, Patrick and Lotz, Christpher}, title = {Biodistribution and serologic response in SARS-CoV-2 induced ARDS: A cohort study}, series = {PLoS One}, volume = {15, 2020}, journal = {PLoS One}, number = {11}, doi = {10.1371/journal.pone.0242917}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231348}, year = {2020}, abstract = {Background The viral load and tissue distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain important questions. The current study investigated SARS-CoV-2 viral load, biodistribution and anti-SARS-CoV-2 antibody formation in patients suffering from severe corona virus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). Methods This is a retrospective single-center study in 23 patients with COVID-19-induced ARDS. Data were collected within routine intensive care. SARS-CoV-2 viral load was assessed via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Overall, 478 virology samples were taken. Anti-SARS-CoV-2-Spike-receptor binding domain (RBD) antibody detection of blood samples was performed with an enzyme-linked immunosorbent assay. Results Most patients (91\%) suffered from severe ARDS during ICU treatment with a 30-day mortality of 30\%. None of the patients received antiviral treatment. Tracheal aspirates tested positive for SARS-CoV-2 in 100\% of the cases, oropharyngeal swabs only in 77\%. Blood samples were positive in 26\% of the patients. No difference of viral load was found in tracheal or blood samples with regard to 30-day survival or disease severity. SARS-CoV-2 was never found in dialysate. Serologic testing revealed significantly lower concentrations of SARS-CoV-2 neutralizing IgM and IgA antibodies in survivors compared to non-survivors (p = 0.009). Conclusions COVID-19 induced ARDS is accompanied by a high viral load of SARS-CoV-2 in tracheal aspirates, which remained detectable in the majority throughout intensive care treatment. Remarkably, SARS-CoV-2 RNA was never detected in dialysate even in patients with RNAemia. Viral load or the buildup of neutralizing antibodies was not associated with 30-day survival or disease severity.}, language = {en} }