TY - JOUR A1 - Moll, Heidrun A1 - Müller, Christoph A1 - Gillitzer, Reinhard A1 - Fuchs, Harald A1 - Röllinghoff, Martin A1 - Simon, Markus M. A1 - Kramer, Michael D. T1 - Expression of T-cell-associated serine proteinase-1 during murine Leishmania major infection correlates with susceptibility to disease N2 - The expression of T-cell-associated serine proteinase 1 (MTSP-1) in vivo during Leishmania major infection was analyzed in genetically resistant C57BL/6 mice and in genetically susceptible BALB/c mice. Using a monoclonal antibody as well as an RNA probe specific for MTSP-1 to stain tissue sections, we found T cells expressing MTSP-1 in skin lesions and spleens of mice of both strains. In skin lesions, MTSP-1-positive T cells could be detected as early as 3 days after infection. Most importantly, the frequency of T cells expressing MTSP-1 was significantly higher in susceptible BALB/c mice than in resistant C57BL/6 mice. These findings suggest that MTSP-1 is associated with disease-promoting T cells and that it may be an effector molecule involved in the pathogenesis of cutaneous leishmaniasis. KW - Biologie KW - Immunologie Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61311 ER - TY - JOUR A1 - Kleinschnitz, Christoph A1 - Grund, Henrike A1 - Wingler, Kirstin A1 - Armitage, Melanie E. A1 - Jones, Emma A1 - Mittal, Manish A1 - Barit, David A1 - Schwarz, Tobias A1 - Geis, Christian A1 - Kraft, Peter A1 - Barthel, Konstanze A1 - Schuhmann, Michael K. A1 - Herrmann, Alexander M. A1 - Meuth, Sven G. A1 - Stoll, Guido A1 - Meurer, Sabine A1 - Schrewe, Anja A1 - Becker, Lore A1 - Gailus-Durner, Valerie A1 - Fuchs, Helmut A1 - Klopstock, Thomas A1 - de Angelis, Martin Hrabe A1 - Jandeleit-Dahm, Karin A1 - Shah, Ajay M. A1 - Weissmann, Norbert A1 - Schmidt, Harald H. H. W. T1 - Post-Stroke Inhibition of Induced NADPH Oxidase Type 4 Prevents Oxidative Stress and Neurodegeneration N2 - Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox42/2) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox42/2 mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy. KW - Schlaganfall Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68416 ER - TY - JOUR A1 - Jordan, Martin C. A1 - Jovic, Sebastian A1 - Gilbert, Fabian A1 - Kunz, Andreas A1 - Ertl, Maximilian A1 - Strobl, Ute A1 - Jakubietz, Rafael G. A1 - Jakubietz, Michael G. A1 - Meffert, Rainer H. A1 - Fuchs, Konrad F. T1 - Qualitätssteigerung der Abrechnungsprüfung durch Smartphone-basierte Fotodokumentation in der Unfall-, Hand-, und Plastischen Chirurgie JF - Der Unfallchirurg N2 - Hintergrund Die Fotodokumentation von offenen Frakturen, Wunden, Dekubitalulzera, Tumoren oder Infektionen ist ein wichtiger Bestandteil der digitalen Patientenakte. Bisher ist unklar, welchen Stellenwert diese Fotodokumentation bei der Abrechnungsprüfung durch den Medizinischen Dienst der Krankenkassen (MDK) hat. Fragestellung Kann eine Smartphone-basierte Fotodokumentation die Verteidigung von erlösrelevanten Diagnosen und Prozeduren sowie der Verweildauer verbessern? Material und Methoden Ausstattung der Mitarbeiter mit digitalen Endgeräten (Smartphone/Tablet) in den Bereichen Notaufnahme, Schockraum, OP, Sprechstunden sowie auf den Stationen. Retrospektive Auswertung der Abrechnungsprüfung im Jahr 2019 und Identifikation aller Fallbesprechungen, in denen die Fotodokumentation eine Erlösveränderung bewirkt hat. Ergebnisse Von insgesamt 372 Fallbesprechungen half die Fotodokumentation in 27 Fällen (7,2 %) zur Bestätigung eines Operationen- und Prozedurenschlüssels (OPS) (n = 5; 1,3 %), einer Hauptdiagnose (n = 10; 2,7 %), einer Nebendiagnose (n = 3; 0,8 %) oder der Krankenhausverweildauer (n = 9; 2,4 %). Pro oben genanntem Fall mit Fotodokumentation ergab sich eine durchschnittliche Erlössteigerung von 2119 €. Inklusive Aufwandpauschale für die Verhandlungen wurde somit ein Gesamtbetrag von 65.328 € verteidigt. Diskussion Der Einsatz einer Smartphone-basierten Fotodokumentation kann die Qualität der Dokumentation verbessern und Erlöseinbußen bei der Abrechnungsprüfung verhindern. Die Implementierung digitaler Endgeräte mit entsprechender Software ist ein wichtiger Teil des digitalen Strukturwandels in Kliniken. N2 - Background Photographic documentation of wounds, decubitus ulcers, tumors, open fractures and infections is an important part of digital patient files. It is unclear whether the photographic documentation has an effect on medical accounting with health insurance companies. Objective It was hypothesized that Smartphone-based systematic photographic documentation can improve the confirmation of proceeds-relevant diagnoses and procedures as well as the duration. Material and methods Staff in the emergency room, operating theater, outpatient clinic and on the wards were equipped with digital devices (Smartphone, tablet) including a photo-app. Medical accounting with the health insurance companies and identification of all case conferences in which the photographic documentation had effected a change in proceeds were analyzed for 2019 in a retrospective manner. Results Overall, 372 cases were discussed of which 27 cases were affected by the digital photographic documentation. Photographic documentation was used for clarification of the operative procedure (n = 5), primary diagnosis (n = 10), secondary diagnosis (n = 3), and length of hospitalization (n = 9). An average of 2119 € was negotiated and added per case affected by photographic documentation. Hereby, a level 1 trauma center gained an estimated 65,328 € in revenue. Discussion The use of Smartphone based photographic documentation can improve the overall quality of patient files and thus avoid loss of revenue. The implementation of digital devices with corresponding software is an important component of the digital structural change in hospitals. KW - Digitalisierung KW - Gesundheits-App KW - Künstliche Intelligenz KW - Plattform KW - Strukturwandel KW - artificial intelligence KW - database KW - digital transformation KW - photo app KW - surgery Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232415 SN - 0177-5537 VL - 124 ER - TY - JOUR A1 - Gerhard-Hartmann, Elena A1 - Goergen, Helen A1 - Bröckelmann, Paul J. A1 - Mottok, Anja A1 - Steinmüller, Tabea A1 - Grund, Johanna A1 - Zamò, Alberto A1 - Ben-Neriah, Susana A1 - Sasse, Stephanie A1 - Borchmann, Sven A1 - Fuchs, Michael A1 - Borchmann, Peter A1 - Reinke, Sarah A1 - Engert, Andreas A1 - Veldman, Johanna A1 - Diepstra, Arjan A1 - Klapper, Wolfram A1 - Rosenwald, Andreas T1 - 9p24.1 alterations and programmed cell death 1 ligand 1 expression in early stage unfavourable classical Hodgkin lymphoma: an analysis from the German Hodgkin Study Group NIVAHL trial JF - British Journal of Haematology N2 - High programmed cell death 1 ligand 1 (PD-L1) protein expression and copy number alterations (CNAs) of the corresponding genomic locus 9p24.1 in Hodgkin- and Reed–Sternberg cells (HRSC) have been shown to be associated with favourable response to anti-PD-1 checkpoint inhibition in relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In the present study, we investigated baseline 9p24.1 status as well as PD-L1 and major histocompatibility complex (MHC) class I and II protein expression in 82 biopsies from patients with early stage unfavourable cHL treated with anti-PD-1-based first-line treatment in the German Hodgkin Study Group (GHSG) NIVAHL trial (ClinicalTrials.gov Identifier: NCT03004833). All evaluated specimens showed 9p24.1 CNA in HRSC to some extent, but with high intratumoral heterogeneity and an overall smaller range of alterations than reported in advanced-stage or r/r cHL. All but two cases (97%) showed PD-L1 expression by the tumour cells in variable amounts. While MHC-I was rarely expressed in >50% of HRSC, MHC-II expression in >50% of HRSC was found more frequently. No obvious impact of 9p24.1 CNA or PD-L1 and MHC-I/II expression on early response to the highly effective anti-PD-1-based NIVAHL first-line treatment was observed. Further studies evaluating an expanded panel of potential biomarkers are needed to optimally stratify anti-PD-1 first-line cHL treatment. KW - fluorescence in situ hybridisation KW - major histocompatibility complex KW - immune checkpoint blockade KW - classical Hodgkin lymphoma KW - CD274 Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258358 VL - 196 IS - 1 ER - TY - JOUR A1 - Gabel, Judith A1 - Pickem, Matthias A1 - Scheiderer, Philipp A1 - Dudy, Lenart A1 - Leikert, Berengar A1 - Fuchs, Marius A1 - Stübinger, Martin A1 - Schmitt, Matthias A1 - Küspert, Julia A1 - Sangiovanni, Giorgio A1 - Tomczak, Jan M. A1 - Held, Karsten A1 - Lee, Tien–Lin A1 - Claessen, Ralph A1 - Sing, Michael T1 - Toward Functionalized Ultrathin Oxide Films: The Impact of Surface Apical Oxygen JF - Advanced Electronic Materials N2 - Thin films of transition metal oxides open up a gateway to nanoscale electronic devices beyond silicon characterized by novel electronic functionalities. While such films are commonly prepared in an oxygen atmosphere, they are typically considered to be ideally terminated with the stoichiometric composition. Using the prototypical correlated metal SrVO\(_{3}\) as an example, it is demonstrated that this idealized description overlooks an essential ingredient: oxygen adsorbing at the surface apical sites. The oxygen adatoms, which are present even if the films are kept in an ultrahigh vacuum environment and not explicitly exposed to air, are shown to severely affect the intrinsic electronic structure of a transition metal oxide film. Their presence leads to the formation of an electronically dead surface layer but also alters the band filling and the electron correlations in the thin films. These findings highlight that it is important to take into account surface apical oxygen or—mutatis mutandis—the specific oxygen configuration imposed by a capping layer to predict the behavior of ultrathin films of transition metal oxides near the single unit-cell limit. KW - transition metal oxides KW - correlated oxides KW - electronic phase transitions KW - photoelectron spectroscopy KW - thin films Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318914 SN - 2199-160X VL - 8 IS - 4 ER -