@article{FlemmingHankirErnestusetal.2020,
  author    = {Flemming, S. and Hankir, M. and Ernestus, R.-I. and Seyfried, F. and Germer, C.-T. and Meybohm, P. and Wurmb, T. and Vogel, U. and Wiegering, A.},
  title     = {Surgery in times of COVID-19 — recommendations for hospital and patient management},
  series = {Langenbeck's Archives of Surgery},
  volume    = {405},
  journal   = {Langenbeck's Archives of Surgery},
  issn      = {1435-2443},
  doi       = {10.1007/s00423-020-01888-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231766},
  pages     = {359-364},
  year      = {2020},
  abstract  = {Background The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has escalated rapidly to a global pandemic stretching healthcare systems worldwide to their limits. Surgeonshave had to immediately react to this unprecedented clinical challenge by systematically repurposing surgical wards. Purpose To provide a detailed set of guidelines developed in a surgical ward at University Hospital Wuerzburg to safelyaccommodate the exponentially rising cases of SARS-CoV-2 infected patients without compromising the care of emergencysurgery and oncological patients or jeopardizing the well-being of hospital staff. Conclusions The dynamic prioritization of SARS-CoV-2 infected and surgical patient groups is key to preserving life whilemaintaining high surgical standards. Strictly segregating patient groups in emergency rooms, non-intensive care wards andoperating areas prevents viral spread while adequately training and carefully selecting hospital staff allow them to confidentlyand successfully undertake their respective clinical duties.},
  language  = {en}
}
@article{NotzSchmalzingWedekinketal.2020,
  author    = {Notz, Quirin and Schmalzing, Marc and Wedekink, Florian and Schlesinger, Tobias and Gernert, Michael and Herrmann, Johannes and Sorger, Lena and Weismann, Dirk and Schmid, Benedikt and Sitter, Magdalena and Schlegel, Nicolas and Kranke, Peter and Wischhusen, J{\"o}rg and Meybohm, Patrick and Lotz, Christopher},
  title     = {Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study},
  series = {Frontiers in Immunology},
  volume    = {11},
  journal   = {Frontiers in Immunology},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2020.581338},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212815},
  year      = {2020},
  abstract  = {Objectives The severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts and function. However, interactions of pro- and anti-inflammatory mechanisms remain elusive. In the current study we characterized the immune responses in patients suffering from severe COVID-19-induced acute respiratory distress syndrome (ARDS). Methods This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14th and May 28th 2020 (n = 39). Longitudinal data were collected within routine clinical care, including flow-cytometry of lymphocyte subsets, cytokine analysis and growth differentiation factor 15 (GDF-15). Antibody responses against the receptor binding domain (RBD) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein were analyzed. Results All patients suffered from severe ARDS, 30.8\% died. Interleukin (IL)-6 was massively elevated at every time-point. The anti-inflammatory cytokine IL-10 was concomitantly upregulated with IL-6. The cellular response was characterized by lymphocytopenia with low counts of CD8+ T cells, natural killer (NK) and na{\"i}ve T helper cells. CD8+ T and NK cells recovered after 8 to 14 days. The B cell system was largely unimpeded. This coincided with a slight increase in anti-SARS-CoV-2-Spike-RBD immunoglobulin (Ig) G and a decrease in anti-SARS-CoV-2-Spike-RBD IgM. GDF-15 levels were elevated throughout ICU treatment. Conclusions Massively elevated levels of IL-6 and a delayed cytotoxic immune defense characterized severe COVID-19-induced ARDS. The B cell response and antibody production were largely unimpeded. No obvious imbalance of pro- and anti-inflammatory mechanisms was observed, with elevated GDF-15 levels suggesting increased tissue resilience.},
  language  = {en}
}
@phdthesis{Knop2023,
  author    = {Knop, Juna-Lisa},
  title     = {Untersuchungen zur Bedeutung von Spaltprodukten des vaskul{\"a}r endothelialen (VE-) Cadherin als Ausl{\"o}ser f{\"u}r die Schrankenst{\"o}rung des Gef{\"a}ßendothels},
  doi       = {10.25972/OPUS-34468},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-344687},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {Ein Schl{\"u}sselereignis, welches dem prognosebestimmenden Organversagen bei systemi-schen Entz{\"u}ndungsprozessen und Sepsis vorangeht, ist die Entwicklung einer mikrovas-kul{\"a}ren endothelialen Schrankenst{\"o}rung. Das vaskul{\"a}re endotheliale (VE-) Cadherin als mechanischer Stabilisator der Endothelbarriere spielt dabei eine wichtige Rolle. In der Inflammation werden Spaltprodukte von VE-Cadherin (sVE-Cadherin) gebildet. Ge-genstand der vorliegenden Arbeit war die Untersuchung der Hypothese ob diese Spalt-produkte selbst an der St{\"o}rung der endothelialen Barrierefunktion beteiligt sind. Es wurde hierf{\"u}r humanes sVE-Cadherin bestehend aus den extrazellul{\"a}ren Dom{\"a}nen EC1-5 (sVE-CadherinEC1-5) generiert. In Messungen des transendothelialen elektrischen Widerstands (TER), mit Immunfluoreszenzf{\"a}rbungen und Western Blot Analysen wird gezeigt, dass sVE-Cadherin dosisabh{\"a}ngig die Barriere Integrit{\"a}t in prim{\"a}ren humanen dermalen Endothelzellen st{\"o}rt. Dies f{\"u}hrt zu einer Reduktion von VE-Cadherin und den assoziierten Proteinen α-, γ- und δ-Catenin und ZO-1, die nach der Applikation von sVE-Cadherin an den Zellgrenzen reduziert sind. Die Interaktion zwischen VE-PTP und VE-Cadherin wird durch sVE-CadherinEC1-5 reduziert. Durch pharmakologische Hem-mung der Phosphataseaktivit{\"a}t von VE-PTP mittels AKB9778 wird der durch sVE-CadherinEC1-5-induzierte Verlust der Endothelbarriere aufgehoben. Dagegen zeigt die direkte Aktivierung von Tie-2 mittels Angiopoetin-1 keinen protektiven Effekt auf die durch sVE-CadherinEC1-5 gest{\"o}rte Endothelbarriere. Weitere Analysen zeigen eine erh{\"o}h-te Expression von GEF-H1 durch sVE-CadherinEC1-5. Diese ist ebenfalls durch AKB9778 hemmbar. Zus{\"a}tzlich zu diesen Untersuchungen wurden die Konstrukte EC1-4 und EC3-5 in ver-schiedene Vektoren kloniert, um zu bestimmen, ob die extrazellul{\"a}re Dom{\"a}ne 5 von VE-Cadherin die dominante Rolle bei den sVE-Cadherin-vermittelten Effekten spielt. Zusammenfassend zeigen diese Untersuchungen zum ersten Mal, dass sVE-CadherinEC1-5 unabh{\"a}ngig von proinflammatorischen Ausl{\"o}sern {\"u}ber die Aktivierung des VE-PTP/RhoA-Signalweges den Zusammenbruch der Endothelbarriere mitversursacht. Dies stellt einen neuen pathophysiologischer Mechanismus dar, der zum Gesamtverst{\"a}ndnis der entz{\"u}ndungsinduzierten Barrierever{\"a}nderungen des Endothels beitr{\"a}gt.},
  subject      = {Endothel},
  language  = {de}
}
@article{GruschwitzHartungKleefeldtetal.2023,
  author    = {Gruschwitz, Philipp and Hartung, Viktor and Kleefeldt, Florian and Erg{\"u}n, S{\"u}leyman and Lichthardt, Sven and Huflage, Henner and Hendel, Robin and Kunz, Andreas Steven and Pannenbecker, Pauline and Kuhl, Philipp Josef and Augustin, Anne Marie and Bley, Thorsten Alexander and Petritsch, Bernhard and Grunz, Jan-Peter},
  title     = {Standardized assessment of vascular reconstruction kernels in photon-counting CT angiographies of the leg using a continuous extracorporeal perfusion model},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-39063-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357912},
  year      = {2023},
  abstract  = {This study evaluated the influence of different vascular reconstruction kernels on the image quality of CT angiographies of the lower extremity runoff using a 1st-generation photon-counting-detector CT (PCD-CT) compared with dose-matched examinations on a 3rd-generation energy-integrating-detector CT (EID-CT). Inducing continuous extracorporeal perfusion in a human cadaveric model, we performed CT angiographies of eight upper leg arterial runoffs with radiation dose-equivalent 120 kVp acquisition protocols (CTDIvol 5 mGy). Reconstructions were executed with different vascular kernels, matching the individual modulation transfer functions between scanners. Signal-to-noise-ratios (SNR) and contrast-to-noise-ratios (CNR) were computed to assess objective image quality. Six radiologists evaluated image quality subjectively using a forced-choice pairwise comparison tool. Interrater agreement was determined by calculating Kendall's concordance coefficient (W). The intraluminal attenuation of PCD-CT images was significantly higher than of EID-CT (414.7 ± 27.3 HU vs. 329.3 ± 24.5 HU; p < 0.001). Using comparable kernels, image noise with PCD-CT was significantly lower than with EID-CT (p ≤ 0.044). Correspondingly, SNR and CNR were approximately twofold higher for PCD-CT (p < 0.001). Increasing the spatial frequency for PCD-CT reconstructions by one level resulted in similar metrics compared to EID-CT (CNRfat; EID-CT Bv49: 21.7 ± 3.7 versus PCD-CT Bv60: 21.4 ± 3.5). Overall image quality of PCD-CTA achieved ratings superior to EID-CTA irrespective of the used reconstruction kernels (best: PCD-CT Bv60; worst: EID-CT Bv40; p < 0.001). Interrater agreement was good (W = 0.78). Concluding, PCD-CT offers superior intraluminal attenuation, SNR, and CNR compared to EID-CT in angiographies of the upper leg arterial runoff. Combined with improved subjective image quality, PCD-CT facilitates the use of sharper convolution kernels and ultimately bears the potential of improved vascular structure assessability.},
  language  = {en}
}
@phdthesis{Eichlinger2024,
  author    = {Eichlinger, Robin},
  title     = {Retrospektive monozentrische Analyse des Krankheitsverlaufs und Prognosefaktoren von Patient*innen mit Ileitis terminalis Crohn},
  doi       = {10.25972/OPUS-35255},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-352555},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Die Erkrankung MC z{\"a}hlt zusammen mit der Colitis Ulcerosa zu den CED. In Deutschland liegt die Pr{\"a}valenz bei ca. 100-200 Personen pro 100000 Einwohner und steigt stetig. {\"U}berwiegend sind Menschen im jungen Erwachsenenalter betroffen, die fest im Berufsleben stehen. Die Erkrankung f{\"u}hrt im Verlauf immer wieder zu Arbeitsausf{\"a}llen und verursacht neben den gesundheitlichen Kosten f{\"u}r Medikamente und Therapie auch wirtschaftliche Ausf{\"a}lle. Trotz der hohen sozio{\"o}konomischen Bedeutung und des Vorliegens gesicherter Erkenntnisse zu Risikofaktoren, anatomischen / histologischen Ver{\"a}nderungen, Symptomkomplexen und zahlreicher Hypothesen bez{\"u}glich der Entstehung, ist die Pathogenese nicht g{\"a}nzlich verstanden. Ebenso komplex wie das Erkrankungsbild selbst ist der Prozess der Diagnosefindung. Ein Goldstandard ist nicht etabliert. Die Diagnose MC ist meist eine klinische, in Zusammenschau mit endoskopischen, histologischen, laborchemischen und radiologischen Befunden. In dieser Arbeit wurde die Versorgungsrealit{\"a}t der MC Erkrankten {\"u}ber die letzten 15 Jahre betrachtet. Es konnte ein Wandel in der chirurgischen Operations- und Anastomosentechnik gezeigt werden. Die Zukunft ist eine minimalinvasive und darmsparende Chirurgie. Im retrospektiven Vergleich der Therapiealgorithmen erfolgte nach damaliger S3-Leitlinie in der Mehrzahl der MC F{\"a}lle initial eine medikament{\"o}se Therapie, alle untersuchten F{\"a}lle erhielten jedoch eine ICR. In der Subgruppenanalyse wurden F{\"a}lle mit isolierter Ileitis terminalis Crohn untersucht. Es konnte die Effektivit{\"a}t der chirurgischen Prim{\"a}rtherapie gegen{\"u}ber einer medikament{\"o}sen Prim{\"a}rtherapie gezeigt werden, was die Daten der aktuellen Literatur st{\"u}tzt. So bestand ein Vorteil hinsichtlich des verringerten Bedarfs an einer medikament{\"o}sen Therapie im postoperativen Verlauf von zwei Jahren und bez{\"u}glich der rezidiv- und medikamentenfreien Zeit. Die Ergebnisse zeigten zudem, dass eine pr{\"a}ventive, postoperative medikament{\"o}se Therapie bei pr{\"a}operativ vorliegenden Risikofaktoren f{\"u}r ein klinisches Rezidiv nicht zwingend notwendig ist und {\"u}berdacht werden sollte. Diese Arbeit konnte den Stellenwert der Chirurgie als wichtige S{\"a}ule der Therapie bei isolierter Ileitis terminalis Crohn untermauern.},
  subject      = {Crohn-Krankheit},
  language  = {de}
}
@article{BaurRamserKelleretal.2021,
  author    = {Baur, Johannes and Ramser, Michaela and Keller, Nicola and Muysoms, Filip and D{\"o}rfer, J{\"o}rg and Wiegering, Armin and Eisner, Lukas and Dietz, Ulrich A.},
  title     = {Robotische Hernienchirurgie II: Robotische prim{\"a}r ventrale und inzisionale Hernienversorgung (rv-TAPP und r-Rives/r-TARUP). Videobeitrag und Ergebnisse einer Kohortenstudie an 118 Patienten},
  series = {Der Chirurg},
  volume    = {92},
  journal   = {Der Chirurg},
  number    = {9},
  doi       = {10.1007/s00104-021-01450-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264912},
  pages     = {809-821},
  year      = {2021},
  abstract  = {Die endoskopische Versorgung von Umbilikal- und Inzisionalhernien hat sich in den vergangenen 30 Jahren an die Limitationen der konventionellen laparoskopischen Instrumente angepasst. Dazu geh{\"o}rt die Entwicklung von Netzen f{\"u}r die intraperitoneale Lage (intraperitoneales Onlay-Mesh, IPOM) mit antiadh{\"a}siven Beschichtungen; allerdings kommt es bei einem betr{\"a}chtlichen Teil dieser Patienten doch zu Adh{\"a}sionen. Minimal-invasive Verfahren f{\"u}hren zu weniger perioperativen Komplikationen, bei einer etwas h{\"o}heren Rezidivrate. Mit den ergonomischen Ressourcen der Robotik, die abgewinkelte Instrumente anbietet, besteht erstmals die M{\"o}glichkeit, Netze minimal-invasiv in unterschiedliche Bauchdeckenschichten zu implantieren und gleichzeitig eine morphologische und funktionelle Rekonstruktion der Bauchdecke zu erreichen. In diesem Videobeitrag wird die Versorgung von Ventral- und Inzisionalhernien mit Netzimplantation in den pr{\"a}peritonealen Raum (robotische ventrale transabdominelle pr{\"a}peritoneale Patchplastik, rv-TAPP) sowie in den retrorektalen Raum (r-Rives bzw. robotische transabdominelle retromuskul{\"a}re umbilikale Patchplastik [r-TARUP]) pr{\"a}sentiert. Es werden die Ergebnisse einer Kohortenstudie an 118 konsekutiven Patienten vorgestellt und im Hinblick auf den Mehrwert der robotischen Technik in der Extraperitonealisierung der Netze und in der Weiterbildung diskutiert.},
  language  = {de}
}
@article{JurowichLichthardtKastneretal.2019,
  author    = {Jurowich, Christian and Lichthardt, Sven and Kastner, Caroline and Haubitz, Imme and Prock, Andre and Filser, J{\"o}rg and Germer, Christoph-Thomas and Wiegering, Armin},
  title     = {Laparoscopic versus open right hemicolectomy in colon carcinoma: A propensity score analysis of the DGAV StuDoQ|ColonCancer registry},
  series = {PLoS ONE},
  volume    = {14},
  journal   = {PLoS ONE},
  number    = {6},
  doi       = {10.1371/journal.pone.0218829},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202184},
  pages     = {e0218829},
  year      = {2019},
  abstract  = {Objective To assess whether laparoscopy has any advantages over open resection for right-sided colon cancer. Summary background data Right hemicolectomy can be performed using either a conventional open or a minimally invasive laparoscopic technique. It is not clear whether these different access routes differ with regard to short-term postoperative outcomes. Methods Patients documented in the German Society for General and Visceral Surgery StuDoQ|ColonCancer registry who underwent right hemicolectomy were analyzed regarding early postoperative complications according to Clavien-Dindo (primary endpoint), operation (OP) time, length of postoperative hospital stay (LOS), MTL30 and number of lymph nodes retrieved (secondary endpoints). Results A total of 4.997 patients were identified as undergoing oncological right hemicolectomy without additional interventions. Of these, 4.062 (81.3\%) underwent open, 935 (18.7\%) laparoscopic surgery. Propensity score analysis showed a significantly shorter LOS (OR: 0.55 CI 95\%0.47-.64) and a significantly longer OP time (OR2.32 CI 1.98-2.71) for the laparoscopic route. Risk factors for postoperative complications, anastomotic insufficiency, ileus, reoperation and positive MTL30 were higher ASA status, higher age and increasing BMI. The surgical access route (open / lap) had no influence on these factors, but the laparoscopic group did have markedly fewer lymph nodes retrieved. Conclusion The present registry-based analysis could detect no relevant advantages for the minimally invasive laparoscopic access route. Further oncological analyses are needed to clarify the extent to which the smaller lymph node harvest in the laparoscopic group is accompanied by a poorer oncological outcome.},
  language  = {en}
}
@article{BankogluStippGerberetal.2021,
  author    = {Bankoglu, Ezgi Eyluel and Stipp, Franzisca and Gerber, Johanna and Seyfried, Florian and Heidland, August and Bahner, Udo and Stopper, Helga},
  title     = {Effect of cryopreservation on DNA damage and DNA repair activity in human blood samples in the comet assay},
  series = {Archives of Toxicology},
  volume    = {95},
  journal   = {Archives of Toxicology},
  number    = {5},
  doi       = {10.1007/s00204-021-03012-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265326},
  pages     = {1831-1841},
  year      = {2021},
  abstract  = {The comet assay is a commonly used method to determine DNA damage and repair activity in many types of samples. In recent years, the use of the comet assay in human biomonitoring became highly attractive due to its various modified versions, which may be useful to determine individual susceptibility in blood samples. However, in human biomonitoring studies, working with large sample numbers that are acquired over an extended time period requires some additional considerations. One of the most important issues is the storage of samples and its effect on the outcome of the comet assay. Another important question is the suitability of different blood preparations. In this study, we analysed the effect of cryopreservation on DNA damage and repair activity in human blood samples. In addition, we investigated the suitability of different blood preparations. The alkaline and FPG as well as two different types of repair comet assay and an in vitro hydrogen peroxide challenge were applied. Our results confirmed that cryopreserved blood preparations are suitable for investigating DNA damage in the alkaline and FPG comet assay in whole blood, buffy coat and PBMCs. Ex vivo hydrogen peroxide challenge yielded its optimal effect in isolated PBMCs. The utilised repair comet assay with either UVC or hydrogen peroxide-induced lesions and an aphidicolin block worked well in fresh PBMCs. Cryopreserved PBMCs could not be used immediately after thawing. However, a 16-h recovery with or without mitotic stimulation enabled the application of the repair comet assay, albeit only in a surviving cell fraction.},
  language  = {en}
}
@article{SilwedelSpeerHaarmannetal.2019,
  author    = {Silwedel, Christine and Speer, Christian P. and Haarmann, Axel and Fehrholz, Markus and Claus, Heike and Schlegel, Nicolas and Glaser, Kirsten},
  title     = {Ureaplasma species modulate cytokine and chemokine responses in human brain microvascular endothelial cells},
  series = {International Journal of Molecular Science},
  volume    = {20},
  journal   = {International Journal of Molecular Science},
  number    = {14},
  issn      = {1422-0067},
  doi       = {10.3390/ijms20143583},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201848},
  year      = {2019},
  abstract  = {Ureaplasma species are common colonizers of the adult genitourinary tract and often considered as low-virulence commensals. Intraamniotic Ureaplasma infections, however, facilitate chorioamnionitis and preterm birth, and cases of Ureaplasma-induced neonatal sepsis, pneumonia, and meningitis raise a growing awareness of their clinical relevance. In vitro studies are scarce but demonstrate distinct Ureaplasma-driven impacts on immune mechanisms. The current study addressed cytokine and chemokine responses upon exposure of native or lipopolysaccharide (LPS) co-stimulated human brain microvascular endothelial cells (HBMEC) to Ureaplasma urealyticum or U. parvum, using qRT-PCR, RNA sequencing, multi-analyte immunoassay, and flow cytometry. Ureaplasma exposure in native HBMEC reduced monocyte chemoattractant protein (MCP)-3 mRNA expression (p < 0.01, vs. broth). In co-stimulated HBMEC, Ureaplasma spp. attenuated LPS-evoked mRNA responses for C-X-C chemokine ligand 5, MCP-1, and MCP-3 (p < 0.05, vs. LPS) and mitigated LPS-driven interleukin (IL)-1α protein secretion, as well as IL-8 mRNA and protein responses (p < 0.05). Furthermore, Ureaplasma isolates increased C-X-C chemokine receptor 4 mRNA levels in native and LPS co-stimulated HBMEC (p < 0.05). The presented results may imply immunomodulatory capacities of Ureaplasma spp. which may ultimately promote chronic colonization and long-term neuroinflammation.},
  language  = {en}
}
@article{DischingerHasingerKoenigsraineretal.2021,
  author    = {Dischinger, Ulrich and Hasinger, Julia and K{\"o}nigsrainer, Malina and Corteville, Carolin and Otto, Christoph and Fassnacht, Martin and Hankir, Mohamed and Seyfried, Florian Johannes David},
  title     = {Toward a Medical Gastric Bypass: Chronic Feeding Studies With Liraglutide + PYY\(_{3-36}\) Combination Therapy in Diet-Induced Obese Rats},
  series = {Frontiers in Endocrinology},
  volume    = {11},
  journal   = {Frontiers in Endocrinology},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2020.598843},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223113},
  year      = {2021},
  abstract  = {Background Combination therapies of anorectic gut hormones partially mimic the beneficial effects of bariatric surgery. Thus far, the effects of a combined chronic systemic administration of Glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) have not been directly compared to Roux-en-Y gastric bypass (RYGB) in a standardized experimental setting. Methods High-fat diet (HFD)-induced obese male Wistar rats were randomized into six treatment groups: (1) RYGB, (2) sham-operation (shams), (3) liraglutide, (4) PYY\(_{3-36}\), (5) PYY\(_{3-36}\)+liraglutide (6), saline. Animals were kept on a free choice high- and low-fat diet. Food intake, preference, and body weight were measured daily for 4 weeks. Open field (OP) and elevated plus maze (EPM) tests were performed. Results RYGB reduced food intake and achieved sustained weight loss. Combined PYY\(_{3-36}\)+liraglutide treatment led to similar and plateaued weight loss compared to RYGB. Combined PYY\(_{3-36}\)+liraglutide treatment was superior to PYY\(_{3-36}\) (p ≤ 0.0001) and liraglutide (p ≤ 0.05 or p ≤ 0.01) mono-therapy. PYY\(_{3-36}\)+liraglutide treatment and RYGB also reduced overall food intake and (less pronounced) high-fat preference compared to controls. The animals showed no signs of abnormal behavior in OF or EPM. Conclusions Liraglutide and PYY\(_{3-36}\) combination therapy vastly mimics reduced food intake, food choice and weight reducing benefits of RYGB.},
  language  = {en}
}
@article{LehmannKlingerDiersetal.2021,
  author    = {Lehmann, Kai S. and Klinger, Carsten and Diers, Johannes and Buhr, Heinz-Johannes and Germer, Christoph-Thomas and Wiegering, Armin},
  title     = {Safety of anastomoses in colorectal cancer surgery in octogenarians: a prospective cohort study with propensity score matching},
  series = {BJS Open},
  volume    = {5},
  journal   = {BJS Open},
  number    = {6},
  doi       = {10.1093/bjsopen/zrab102},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265044},
  year      = {2021},
  abstract  = {Background Up to 20 per cent of all operations for patients with colorectal cancer (CRC) are performed in octogenarians. Anastomotic leakage is a leading cause of morbidity and death after resection for CRC. The aim of this study was to assess the rate of anastomosis creation, the risk of anastomotic leakage and death in surgery for left-sided CRC in elderly patients. Methods This prospective cohort study compared patients less than 80 and 80 or more years with left-sided CRC resection performed between 2013 and 2019. Data were provided from a risk-adjusted surgical quality-assessment system with 219 participating centres in Germany. Outcome measures were the rate of anastomoses, anastomotic leakages, death at 30 days and 2-year overall survival (OS). Propensity score matching was used to control for selection bias and compare subgroups of patients of less than 80 and 80 or more years. Results Out of 18 959 patients, some 3169 (16.7 per cent) were octogenarians. Octogenarians were less likely to receive anastomoses (82.0 versus 92.9 per cent, P < 0.001; odds ratio 0.50 (95 per cent c.i. 0.44 to 0.58), P < 0.001). The rate of anastomotic leakages did not differ between age groups (8.6 versus 9.7 per cent, P = 0.084), but 30-day mortality rate after leakage was significantly higher in octogenarians (15.8 versus 3.5 per cent, P < 0.001). Overall, anastomotic leakage was the strongest predictor for death (odds ratio 4.95 (95 per cent c.i. 3.66 to 6.66), P < 0.001). In the subgroup with no leakage, octogenarians had a lower 2-year OS rate than younger patients (71 versus 87 per cent, P < 0.001), and in the population with anastomotic leakage, the 2-year OS was 80 per cent in younger and 43 per cent in elderly patients (P < 0.001). After propensity score matching, older age remained predictive for not receiving an anastomosis (odds ratio 0.54 (95 per cent c.i. 0.46 to 0.63), P < 0.001) and for death (odds ratio 2.60 (95 per cent c.i. 1.78 to 3.84), P < 0.001), but not for the occurrence of leakages (odds ratio 0.94 (95 per cent c.i. 0.76 to 1.15), P = 0.524). Conclusion Anastomotic leakage is not more common in octogenarians, but an age of 80 years or older is an independent factor for not receiving an anastomosis in surgery for left-sided CRC. The mortality rate in the case of leakage in octogenarians was reported to exceed 15 per cent.},
  language  = {en}
}
@article{WiegeringMatthesMuehlingetal.2017,
  author    = {Wiegering, Armin and Matthes, Niels and M{\"u}hling, Bettina and Koospal, Monika and Quenzer, Anne and Peter, Stephanie and Germer, Christoph-Thomas and Linnebacher, Michael and Otto, Christoph},
  title     = {Reactivating p53 and Inducing Tumor Apoptosis (RITA) Enhances the Response of RITA-Sensitive Colorectal Cancer Cells to Chemotherapeutic Agents 5-Fluorouracil and Oxaliplatin},
  series = {Neoplasia},
  volume    = {19},
  journal   = {Neoplasia},
  number    = {4},
  doi       = {10.1016/j.neo.2017.01.007},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171067},
  pages     = {301-309},
  year      = {2017},
  abstract  = {Colorectal carcinoma (CRC) is the most common cancer of the gastrointestinal tract with frequently dysregulated intracellular signaling pathways, including p53 signaling. The mainstay of chemotherapy treatment of CRC is 5-fluorouracil (5FU) and oxaliplatin. The two anticancer drugs mediate their therapeutic effect via DNA damage-triggered signaling. The small molecule reactivating p53 and inducing tumor apoptosis (RITA) is described as an activator of wild-type and reactivator of mutant p53 function, resulting in elevated levels of p53 protein, cell growth arrest, and cell death. Additionally, it has been shown that RITA can induce DNA damage signaling. It is expected that the therapeutic benefits of 5FU and oxaliplatin can be increased by enhancing DNA damage signaling pathways. Therefore, we highlighted the antiproliferative response of RITA alone and in combination with 5FU or oxaliplatin in human CRC cells. A panel of long-term established CRC cell lines (n = 9) including p53 wild-type, p53 mutant, and p53 null and primary patient-derived, low-passage cell lines (n = 5) with different p53 protein status were used for this study. A substantial number of CRC cells with pronounced sensitivity to RITA (IC\(_{50}\)< 3.0 μmol/l) were identified within established (4/9) and primary patient-derived (2/5) CRC cell lines harboring wild-type or mutant p53 protein. Sensitivity to RITA appeared independent of p53 status and was associated with an increase in antiproliferative response to 5FU and oxaliplatin, a transcriptional increase of p53 targets p21 and NOXA, and a decrease in MYC mRNA. The effect of RITA as an inducer of DNA damage was shown by a strong elevation of phosphorylated histone variant H2A.X, which was restricted to RITA-sensitive cells. Our data underline the primary effect of RITA, inducing DNA damage, and demonstrate the differential antiproliferative effect of RITA to CRC cells independent of p53 protein status. We found a substantial number of RITA-sensitive CRC cells within both panels of established CRC cell lines and primary patient-derived CRC cell lines (6/14) that provide a rationale for combining RITA with 5FU or oxaliplatin to enhance the antiproliferative response to both chemotherapeutic agents.},
  language  = {en}
}
@article{MatthesDiersSchlegeletal.2020,
  author    = {Matthes, Niels and Diers, Johannes and Schlegel, Nicolas and Hankir, Mohammed and Haubitz, Imme and Germer, Christoph-Thomas and Wiegering, Armin},
  title     = {Validation of MTL30 as a quality indicator for colorectal surgery},
  series = {PLoS One},
  volume    = {15},
  journal   = {PLoS One},
  number    = {8},
  doi       = {10.1371/journal.pone.0238473},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230530},
  year      = {2020},
  abstract  = {Background Valid indicators are required to measure surgical quality. These ideally should be sensitive and selective while being easy to understand and adjust. We propose here the MTL30 quality indicator which takes into account 30-day mortality, transfer within 30 days, and a length of stay of 30 days as composite markers of an uneventful operative/postoperative course. Methods Patients documented in the StuDoQ|Colon and StuDoQ|Rectal carcinoma register of the German Society for General and Visceral Surgery (DGAV) were analyzed with regard to the effects of patient and tumor-related risk factors as well as postoperative complications on the MTL30. Results In univariate analysis, the MTL30 correlated significantly with patient and tumor-related risk factors such as ASA score (p<0.001), age (p<0.001), or UICC stage (p<0.001). There was a high sensitivity for the postoperative occurrence of complications such as re-operations (p<0.001) or subsequent bleeding (p<0.001), as well as a significant correlation with the CDC classification (p<0.001). In multivariate analysis, patient-related risk factors and postoperative complications significantly increased the odds ratio for a positive MTL30. A negative MTL30 showed a high specify for an uneventful operative and postoperative course. Conclusion The MTL30 is a valid indicator of colorectal surgical quality.},
  language  = {en}
}
@article{LockUngeheuerBorstetal.2020,
  author    = {Lock, J. F. and Ungeheuer, L. and Borst, P. and Swol, J. and L{\"o}b, S. and Brede, E. M. and R{\"o}der, D. and Lengenfelder, B. and Sauer, K. and Gremer, C. - T.},
  title     = {Markedly increased risk of postoperative bleeding complications during perioperative bridging anticoagulation in general and visceral surgery},
  series = {Perioperative Medicine},
  volume    = {9},
  journal   = {Perioperative Medicine},
  doi       = {10.1186/s13741-020-00170-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230690},
  year      = {2020},
  abstract  = {Background Increasing numbers of patients receiving oral anticoagulants are undergoing elective surgery. Low molecular weight heparin (LMWH) is frequently applied as bridging therapy during perioperative interruption of anticoagulation. The aim of this study was to explore the postoperative bleeding risk of patients receiving surgery under bridging anticoagulation. Methods We performed a monocentric retrospective two-arm matched cohort study. Patients that received perioperative bridging anticoagulation were compared to a matched control group with identical surgical procedure, age, and sex. Emergency and vascular operations were excluded. The primary endpoint was the incidence of major postoperative bleeding. Secondary endpoints were minor postoperative bleeding, thromboembolic events, length of stay, and in-hospital mortality. Multivariate analysis explored risk factors of major postoperative bleeding. Results A total of 263 patients in each study arm were analyzed. The patient cohort included the entire field of general and visceral surgery including a large proportion of major oncological resections. Bridging anticoagulation increased the postoperative incidence of major bleeding events (8\% vs. 1\%; p < 0.001) as well as minor bleeding events (14\% vs. 5\%; p < 0.001). Thromboembolic events were equally rare in both groups (1\% vs. 2\%; p = 0.45). No effect on mortality was observed (1.5\% vs. 1.9\%). Independent risk factors of major postoperative bleeding were full-therapeutic dose of LMWH, renal insufficiency, and the procedure-specific bleeding risk. Conclusion Perioperative bridging anticoagulation, especially full-therapeutic dose LMWH, markedly increases the risk of postoperative bleeding complications in general and visceral surgery. Surgeons should carefully consider the practice of routine bridging.},
  language  = {en}
}
@article{DiersWagnerBaumetal.2019,
  author    = {Diers, J. and Wagner, J. and Baum, P. and Lichthardt, S. and Kastner, C. and Matthes, N. and L{\"o}b, S. and Matthes, H. and Germer, C.-T. and Wiegering, A.},
  title     = {Nationwide in-hospital mortality following colonic cancer resection according to hospital volume in Germany},
  series = {BJS Open},
  volume    = {3},
  journal   = {BJS Open},
  number    = {5},
  doi       = {10.1002/bjs5.50173},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204385},
  pages     = {672-677},
  year      = {2019},
  abstract  = {Background: Colonic cancer is the most common cancer of the gastrointestinal tract. The aim of this study was to determine mortality rates following colonic cancer resection and the effect of hospital caseload on in-hospital mortality in Germany. Methods: Patients admitted with a diagnosis of colonic cancer undergoing colonic resection from 2012 to 2015 were identifed from a nationwide registry using procedure codes. The outcome measure was in-hospital mortality. Hospitals were ranked according to their caseload for colonic cancer resection, and patients were categorized into five subgroups on the basis of hospital volume. Results: Some 129 196 colonic cancer resections were reviewed. The overall in-house mortality rate was 5⋅8 per cent, ranging from 6⋅9 per cent (1775 of 25 657 patients) in very low-volume hospitals to 4⋅8 per cent (1239 of 25 825) in very high-volume centres (P < 0⋅001). In multivariable logistic regression analysis the risk-adjusted odds ratio for in-house mortality was 0⋅75 (95 per cent c.i. 0⋅66 to 0⋅84) in very high-volume hospitals performing a mean of 85⋅0 interventions per year, compared with that in very low-volume hospitals performing a mean of only 12⋅7 interventions annually, after adjustment for sex, age, co-morbidity, emergency procedures, prolonged mechanical ventilation and transfusion. Conclusion: In Germany, patients undergoing colonic cancer resections in high-volume hospitals had with improved outcomes compared with patients treated in low-volume hospitals},
  language  = {en}
}
@article{SchattonYangKleffeletal.2015,
  author    = {Schatton, Tobias and Yang, Jun and Kleffel, Sonja and Uehara, Mayuko and Barthel, Steven R. and Schlapbach, Christoph and Zhan, Qian and Dudeney, Stephen and Mueller, Hansgeorg and Lee, Nayoung and de Vries, Juliane C. and Meier, Barbara and Beken, Seppe Vander and Kluth, Mark A. and Ganss, Christoph and Sharpe, Arlene H. and Waaga-Gasser, Ana Maria and Sayegh, Mohamed H. and Abdi, Reza and Scharffetter-Kochanek, Karin and Murphy, George F. and Kupper, Thomas S. and Frank, Natasha Y. and Frank, Markus H.},
  title     = {ABCB5 Identifies Immunoregulatory Dermal Cells},
  series = {Cell Reports},
  volume    = {12},
  journal   = {Cell Reports},
  doi       = {10.1016/j.celrep.2015.08.010},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149989},
  pages     = {1564 -- 1574},
  year      = {2015},
  abstract  = {Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly defined immunomodulatory cell populations poses a barrier to this field. Here, we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1). Purified Abcb5\(^+\) DIRCs suppressed T cell proliferation, evaded immune rejection, homed to recipient immune tissues, and induced Tregs in vivo. In fully major-histocompatibility-complex-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of DIRCs on T cell activation, inhibited DIRC-dependent Treg induction, and attenuated DIRC-induced prolongation of cardiac allograft survival, indicating that DIRC immunoregulatory function is mediated, at least in part, through PD-1. Our results identify ABCB5\(^+\) DIRCs as a distinct immunoregulatory cell population and suggest promising roles of this expandable cell subset in cellular immunotherapy.},
  language  = {en}
}
@article{MuellerKoehlerHendricksetal.2021,
  author    = {M{\"u}ller, Sophie and K{\"o}hler, Franziska and Hendricks, Anne and Kastner, Carolin and B{\"o}rner, Kevin and Diers, Johannes and Lock, Johan F. and Petritsch, Bernhard and Germer, Christoph-Thomas and Wiegering, Armin},
  title     = {Brain metastases from colorectal cancer: a systematic review of the literature and meta-analysis to establish a guideline for daily treatment},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {4},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13040900},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228883},
  year      = {2021},
  abstract  = {Colorectal cancer (CRC) is the third most common malignancy worldwide. Most patients with metastatic CRC develop liver or lung metastases, while a minority suffer from brain metastases. There is little information available regarding the presentation, treatment, and overall survival of brain metastases (BM) from CRC. This systematic review and meta-analysis includes data collected from three major databases (PubMed, Cochrane, and Embase) based on the key words "brain", "metastas*", "tumor", "colorectal", "cancer", and "malignancy". In total, 1318 articles were identified in the search and 86 studies matched the inclusion criteria. The incidence of BM varied between 0.1\% and 11.5\%. Most patients developed metastases at other sites prior to developing BM. Lung metastases and KRAS mutations were described as risk factors for additional BM. Patients with BM suffered from various symptoms, but up to 96.8\% of BM patients were asymptomatic at the time of BM diagnosis. Median survival time ranged from 2 to 9.6 months, and overall survival (OS) increased up to 41.1 months in patients on a multimodal therapy regimen. Several factors including age, blood levels of carcinoembryonic antigen (CEA), multiple metastases sites, number of brain lesions, and presence of the KRAS mutation were predictors of OS. For BM diagnosis, MRI was considered to be state of the art. Treatment consisted of a combination of surgery, radiation, or systemic treatment.},
  language  = {en}
}
@article{NietzerBaurSieberetal.2016,
  author    = {Nietzer, Sarah and Baur, Florentin and Sieber, Stefan and Hansmann, Jan and Schwarz, Thomas and Stoffer, Carolin and H{\"a}fner, Heide and Gasser, Martin and Waaga-Gasser, Ana Maria and Walles, Heike and Dandekar, Gudrun},
  title     = {Mimicking metastases including tumor stroma: a new technique to generate a three-dimensional colorectal cancer model based on a biological decellularized intestinal scaffold},
  series = {Tissue Engineering Part C-Methods},
  volume    = {22},
  journal   = {Tissue Engineering Part C-Methods},
  number    = {7},
  doi       = {10.1089/ten.tec.2015.0557},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188202},
  pages     = {621-635},
  year      = {2016},
  abstract  = {Tumor models based on cancer cell lines cultured two-dimensionally (2D) on plastic lack histological complexity and functionality compared to the native microenvironment. Xenogenic mouse tumor models display higher complexity but often do not predict human drug responses accurately due to species-specific differences. We present here a three-dimensional (3D) in vitro colon cancer model based on a biological scaffold derived from decellularized porcine jejunum (small intestine submucosa+mucosa, SISmuc). Two different cell lines were used in monoculture or in coculture with primary fibroblasts. After 14 days of culture, we demonstrated a close contact of human Caco2 colon cancer cells with the preserved basement membrane on an ultrastructural level as well as morphological characteristics of a well-differentiated epithelium. To generate a tissue-engineered tumor model, we chose human SW480 colon cancer cells, a reportedly malignant cell line. Malignant characteristics were confirmed in 2D cell culture: SW480 cells showed higher vimentin and lower E-cadherin expression than Caco2 cells. In contrast to Caco2, SW480 cells displayed cancerous characteristics such as delocalized E-cadherin and nuclear location of beta-catenin in a subset of cells. One central drawback of 2D cultures-especially in consideration of drug testing-is their artificially high proliferation. In our 3D tissue-engineered tumor model, both cell lines showed decreased numbers of proliferating cells, thus correlating more precisely with observations of primary colon cancer in all stages (UICC I-IV). Moreover, vimentin decreased in SW480 colon cancer cells, indicating a mesenchymal to epithelial transition process, attributed to metastasis formation. Only SW480 cells cocultured with fibroblasts induced the formation of tumor-like aggregates surrounded by fibroblasts, whereas in Caco2 cocultures, a separate Caco2 cell layer was formed separated from the fibroblast compartment beneath. To foster tissue generation, a bioreactor was constructed for dynamic culture approaches. This induced a close tissue-like association of cultured tumor cells with fibroblasts reflecting tumor biopsies. Therapy with 5-fluorouracil (5-FU) was effective only in 3D coculture. In conclusion, our 3D tumor model reflects human tissue-related tumor characteristics, including lower tumor cell proliferation. It is now available for drug testing in metastatic context-especially for substances targeting tumor-stroma interactions.},
  language  = {en}
}
@article{RamserBaurKelleretal.2021,
  author    = {Ramser, Michaela and Baur, Johannes and Keller, Nicola and Kukleta, Jan F. and D{\"o}rfer, J{\"o}rg and Wiegering, Armin and Eisner, Lukas and Dietz, Ulrich A.},
  title     = {Robotische Hernienchirurgie I: Robotische Leistenhernienversorgung (r‑TAPP). Videobeitrag und Ergebnisse einer Kohortenstudie an 302 operierten Hernien},
  series = {Der Chirurg},
  volume    = {92},
  journal   = {Der Chirurg},
  number    = {8},
  doi       = {10.1007/s00104-021-01425-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264883},
  pages     = {707-720},
  year      = {2021},
  abstract  = {Die Versorgung von Leistenhernien mit offenen und minimal-invasiven Verfahren hat in den vergangenen 30 Jahren einen vom Ergebnis her gesehen hohen Standard erreicht. Allerdings besteht noch Bedarf an einer weiteren Reduktion der postoperativen Serome, chronischen Schmerzen und des Rezidivs. In diesem Videobeitrag wird die endoskopische Anatomie der Leiste im Hinblick auf die robotische transabdominelle pr{\"a}peritoneale Patchplastik (r‑TAPP) dargestellt und die Operationsschritte der r‑TAPP als Video illustriert. Es werden die Ergebnisse einer Kohortenstudie an 302 konsekutiven Hernien, die mittels r‑TAPP operiert wurden, vorgestellt und hinsichtlich des Mehrwerts der robotischen Technik - auch in der Weiterbildung - diskutiert. Die r‑TAPP ist die nat{\"u}rliche Weiterentwicklung der konventionellen TAPP und hat das Potenzial, bei zunehmender Ger{\"a}teverf{\"u}gbarkeit und Reduktion der Materialkosten zu einem neuen Standard zu werden. K{\"u}nftige Studien werden den vielseitigen Mehrwert der r‑TAPP auch mit neuen Parametern verfeinern m{\"u}ssen.},
  language  = {de}
}
@article{AngerDoeringvanDametal.2021,
  author    = {Anger, Friedrich and D{\"o}ring, Anna and van Dam, Jacob and Lock, Johann Frisco and Klein, Ingo and Bittrich, Max and Germer, Christoph-Thomas and Wiegering, Armin and Kunzmann, Volker and van Eijck, Casper and L{\"o}b, Stefan},
  title     = {Impact of Borderline Resectability in Pancreatic Head Cancer on Patient Survival: Biology Matters According to the New International Consensus Criteria},
  series = {Annals of Surgical Oncology},
  volume    = {28},
  journal   = {Annals of Surgical Oncology},
  number    = {4},
  issn      = {1068-9265},
  doi       = {10.1245/s10434-020-09100-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235251},
  pages     = {2325-2336},
  year      = {2021},
  abstract  = {Background International consensus criteria (ICC) have redefined borderline resectability for pancreatic ductal adenocarcinoma (PDAC) according to three dimensions: anatomical (BR-A), biological (BR-B), and conditional (BR-C). The present definition acknowledges that resectability is not just about the anatomic relationship between the tumour and vessels but that biological and conditional dimensions also are important. Methods Patients' tumours were retrospectively defined borderline resectable according to ICC. The study cohort was grouped into either BR-A or BR-B and compared with patients considered primarily resectable (R). Differences in postoperative complications, pathological reports, overall (OS), and disease-free survival were assessed. Results A total of 345 patients underwent resection for PDAC. By applying ICC in routine preoperative assessment, 30 patients were classified as stage BR-A and 62 patients as stage BR-B. In total, 253 patients were considered R. The cohort did not contain BR-C patients. No differences in postoperative complications were detected. Median OS was significantly shorter in BR-A (15 months) and BR-B (12 months) compared with R (20 months) patients (BR-A vs. R: p = 0.09 and BR-B vs. R: p < 0.001). CA19-9, as the determining factor of BR-B patients, turned out to be an independent prognostic risk factor for OS. Conclusions Preoperative staging defining surgical resectability in PDAC according to ICC is crucial for patient survival. Patients with PDAC BR-B should be considered for multimodal neoadjuvant therapy even if considered anatomically resectable.},
  language  = {en}
}
@article{KoehlerHendricksKastneretal.2021,
  author    = {K{\"o}hler, Franziska and Hendricks, Anne and Kastner, Carolin and M{\"u}ller, Sophie and Boerner, Kevin and Wagner, Johanna C. and Lock, Johan F. and Wiegering, Armin},
  title     = {Laparoscopic appendectomy versus antibiotic treatment for acute appendicitis-a systematic review},
  series = {International Journal of Colorectal Disease},
  volume    = {36},
  journal   = {International Journal of Colorectal Disease},
  number    = {10},
  issn      = {1432-1262},
  doi       = {10.1007/s00384-021-03927-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266616},
  pages     = {2283-2286},
  year      = {2021},
  abstract  = {Background Over the last years, laparoscopic appendectomy has progressively replaced open appendectomy and become the current gold standard treatment for suspected, uncomplicated appendicitis. At the same time, though, it is an ongoing discussion that antibiotic therapy can be an equivalent treatment for patients with uncomplicated appendicitis. The aim of this systematic review was to determine the safety and efficacy of antibiotic therapy and compare it to the laparoscopic appendectomy for acute, uncomplicated appendicitis. Methods The PubMed database, Embase database, and Cochrane library were scanned for studies comparing laparoscopic appendectomy with antibiotic treatment. Two independent reviewers performed the study selection and data extraction. The primary endpoint was defined as successful treatment of appendicitis. Secondary endpoints were pain intensity, duration of hospitalization, absence from work, and incidence of complications. Results No studies were found that exclusively compared laparoscopic appendectomy with antibiotic treatment for acute, uncomplicated appendicitis. Conclusions To date, there are no studies comparing antibiotic treatment to laparoscopic appendectomy for patients with acute uncomplicated appendicitis, thus emphasizing the lack of evidence and need for further investigation.},
  language  = {en}
}
@article{KannapinSchmitzHansmannetal.2021,
  author    = {Kannapin, Felix and Schmitz, Tobias and Hansmann, Jan and Schlegel, Nicolas and Meir, Michael},
  title     = {Measurements of transepithelial electrical resistance (TEER) are affected by junctional length in immature epithelial monolayers},
  series = {Histochemistry and Cell Biology},
  volume    = {156},
  journal   = {Histochemistry and Cell Biology},
  number    = {6},
  issn      = {1432-119X},
  doi       = {10.1007/s00418-021-02026-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267465},
  pages     = {609-616},
  year      = {2021},
  abstract  = {The measurement of transepithelial electrical resistance (TEER) is a common technique to determine the barrier integrity of epithelial cell monolayers. However, it is remarkable that absolute TEER values of similar cell types cultured under comparable conditions show an immense heterogeneity. Based on previous observations, we hypothesized that the heterogeneity of absolute TEER measurements can not only be explained by maturation of junctional proteins but rather by dynamics in the absolute length of cell junctions within monolayers. Therefore, we analyzed TEER in epithelial cell monolayers of Caco2 cells during their differentiation, with special emphasis on both changes in the junctional complex and overall cell morphology within monolayers. We found that in epithelial Caco2 monolayers TEER increased until confluency, then decreased for some time, which was then followed by an additional increase during junctional differentiation. In contrast, permeability of macromolecules measured at different time points as 4 kDA fluorescein isothiocyanate (FITC)-dextran flux across monolayers steadily decreased during this time. Detailed analysis suggested that this observation could be explained by alterations of junctional length along the cell borders within monolayers during differentiation. In conclusion, these observations confirmed that changes in cell numbers and consecutive increase of junctional length have a critical impact on TEER values, especially at stages of early confluency when junctions are immature.},
  language  = {en}
}
@article{RullmannPreusserPoppitzetal.2019,
  author    = {Rullmann, Michael and Preusser, Sven and Poppitz, Sindy and Heba, Stefanie and Gousias, Konstantinos and Hoyer, Jana and Sch{\"u}tz, Tatjana and Dietrich, Arne and M{\"u}ller, Karsten and Hankir, Mohammed K. and Pleger, Burkhard},
  title     = {Adiposity Related Brain Plasticity Induced by Bariatric Surgery},
  series = {Froniers in Human Neuroscience},
  volume    = {13},
  journal   = {Froniers in Human Neuroscience},
  doi       = {10.3389/fnhum.2019.00290},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227168},
  pages     = {1-11},
  year      = {2019},
  abstract  = {Previous magnetic resonance imaging (MRI) studies revealed structural-functional brain reorganization 12 months after gastric-bypass surgery, encompassing cortical and subcortical regions of all brain lobes as well as the cerebellum. Changes in the mean of cluster-wise gray/white matter density (GMD/WMD) were correlated with the individual loss of body mass index (BMI), rendering the BMI a potential marker of widespread surgery-induced brain plasticity. Here, we investigated voxel-by-voxel associations between surgery-induced changes in adiposity, metabolism and inflammation and markers of functional and structural neural plasticity. We re-visited the data of patients who underwent functional and structural MRI, 6 months (n = 27) and 12 months after surgery (n = 22), and computed voxel-wise regression analyses. Only the surgery-induced weight loss was significantly associated with brain plasticity, and this only for GMD changes. After 6 months, weight loss overlapped with altered GMD in the hypothalamus, the brain's homeostatic control site, the lateral orbitofrontal cortex, assumed to host reward and gustatory processes, as well as abdominal representations in somatosensory cortex. After 12 months, weight loss scaled with GMD changes in right cerebellar lobule VII, involved in language-related/cognitive processes, and, by trend, with the striatum, assumed to underpin (food) reward. These findings suggest time-dependent and weight-loss related gray matter plasticity in brain regions involved in the control of eating, sensory processing and cognitive functioning.},
  language  = {en}
}
@article{ChenSchmidtSchuergeretal.2021,
  author    = {Chen, Jeremy Tsung-Chieh and Schmidt, Lea and Sch{\"u}rger, Christina and Hankir, Mohammed K. and Krug, Susanne M. and Rittner, Heike L.},
  title     = {Netrin-1 as a multitarget barrier stabilizer in the peripheral nerve after injury},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {18},
  issn      = {1422-0067},
  doi       = {10.3390/ijms221810090},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261695},
  year      = {2021},
  abstract  = {The blood-nerve barrier and myelin barrier normally shield peripheral nerves from potentially harmful insults. They are broken down during nerve injury, which contributes to neuronal damage. Netrin-1 is a neuronal guidance protein with various established functions in the peripheral and central nervous systems; however, its role in regulating barrier integrity and pain processing after nerve injury is poorly understood. Here, we show that chronic constriction injury (CCI) in Wistar rats reduced netrin-1 protein and the netrin-1 receptor neogenin-1 (Neo1) in the sciatic nerve. Replacement of netrin-1 via systemic or local administration of the recombinant protein rescued injury-induced nociceptive hypersensitivity. This was prevented by siRNA-mediated knockdown of Neo1 in the sciatic nerve. Mechanistically, netrin-1 restored endothelial and myelin, but not perineural, barrier function as measured by fluorescent dye or fibrinogen penetration. Netrin-1 also reversed the decline in the tight junction proteins claudin-5 and claudin-19 in the sciatic nerve caused by CCI. Our findings emphasize the role of the endothelial and myelin barriers in pain processing after nerve damage and reveal that exogenous netrin-1 restores their function to mitigate CCI-induced hypersensitivity via Neo1. The netrin-1-neogenin-1 signaling pathway may thus represent a multi-target barrier protector for the treatment of neuropathic pain.},
  language  = {en}
}
@phdthesis{Deckelmann2018,
  author    = {Deckelmann, Jana Verena},
  title     = {Einfluss bariatrischer Operationen auf das Geruchsempfinden morbid adip{\"o}ser Patienten},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157076},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Weltweit steigt die Anzahl der morbid adip{\"o}sen Menschen stetig an. Dies f{\"u}hrt zu einer Zunahme der medizinischen und psychosozialen Komplikationen des Einzelnen und der gesundheits{\"o}konomischen Belastung der Gesellschaft. Kosteneffektive und langfristige Therapiekonzepte sind dringend notwendig. Die bariatrische Chirurgie stellt die einzige Therapieoption der morbiden Adipositas dar, mit der eine langfristige Gewichtsreduktion und damit eine signifikante Verbesserung der adipositasassoziierten Begleiterkrankungen erreicht werden kann. Die Mechanismen der Gewichtsabnahme im Rahmen einer bariatrischen Operation sind noch nicht ausreichend erforscht und verstanden. Hinweise Das Geruchsempfinden, als wichtiger Bestandteil der Nahrungsauswahl, k{\"o}nnte durch eine Ver{\"a}nderung in Folge einer bariatrischen Operation einen Einfluss auf die Gewichtsreduktion haben. In der vorliegenden Arbeit wurde mittels der Sniffin´sticks das Geruchsempfinden morbid adip{\"o}ser Menschen in Zusammenhang mit einer bariatrischen Operation (RYGB, n=15 vs. SG, n=15) untersucht (0-1-6-12-24 Wochen). Als Kontrollgruppe dienten morbid adip{\"o}se Probanden unter konservativer Therapie (n=12). Der Ausgangs-BMI der SG-Gruppe (56,04 ± 7,09 kg/m2) war im Vergleich zur RYGB- Gruppe (48,71 ± 6,49 kg/m2) und der konservativ behandelten Gruppe (50,35 ± 6,78 kg/m2) signifikant h{\"o}her (p= 0,011*). Das Ausmaß der Gewichtsabnahme der beiden operierten Gruppen zeigte keine signifikanten Unterschiede (p=0,87). Die konservativ behandelte Gruppe nahm praktisch kein Gewicht ab. Der Ausgangs-SDI-Wert der SG-Gruppe (27,09 ± 3,93) war im Vergleich zur RYGB- Gruppe (32,61 ± 3,64) und zur konservativ behandelten Gruppe (32,15 ± 5,32) signifikant niedriger. Die SG-Gruppe erreichte nach 6 Monaten SDI-Werte von 31,06 ± 3,49, was einen signifikanten Anstieg darstellt (p=0,040*). Die SG-Gruppe hatte anfangs signifikant niedrigere Schwellenwerte als die RYGB- Gruppe (p=0,0050**). Auch im Vergleich zu den Patienten der konservativ behandelten Gruppe erzielte die SG-Gruppe pr{\"a}operativ signifikant niedrigere Schwellenwerte (p=0,0026). Ein signifikanter Anstieg der Schwellenwerte innerhalb von 6 Monaten zeigte sich nur in der SG-Gruppe (p=0,00061***). Die Mittelwerte lagen pr{\"a}operativ bei 4,71 ± 1,31 und nach sechs Monaten bei 7,29 ± 2,11. Die RYGB-Gruppe erzielte pr{\"a}operativ Mittelwerte von 6,82 ± 1,85 und nach sechs Monaten von 7,8 ± 1,41, was ein knapp nicht signifikanter Anstieg ist (p=0,054). Im Vergleich der Diskriminationswerte zeigte sich lediglich ein knapp signifikanter Anstieg der konservativ behandelten Gruppe (p=0,035*). Alle weiteren Werte waren nicht signifikant. Bez{\"u}glich der Identifikationswerte konnten keine signifikanten Ver{\"a}nderungen beobachtet werden. Mit abnehmendem BMI nahm der SDI-Wert der SG-Gruppe signifikant zu (p=0,0074**), was bei der RYGB-Gruppe nicht zutraf (p=0,20). Die Ergebnisse dieser Arbeit zeigen, dass das Geruchsempfinden durch einen wesentlichen Gewichtsverlust an sich nicht beeinflusst wird. Die Daten deuten darauf hin, dass sich die Riechfunktion nach einer Sleeve Gastrectomy im Vergleich zu einer Roux-Y gastric bypass verbessert. Es scheint folglich Mechanismen zu geben, die von der Operationsmethode abh{\"a}ngen. In der Zukunft sind weitere Forschungsanstrengungen n{\"o}tig, um die Mechanismen der Gewichtsabnahme nach bariatrischer Operation und insbesondere die Ver{\"a}nderungen des Geruchsempfindens in Abh{\"a}ngigkeit des Operationsverfahrens besser verstehen zu k{\"o}nnen.},
  subject      = {Adipositas},
  language  = {de}
}
@article{KelmAnger2022,
  author    = {Kelm, Matthias and Anger, Friedrich},
  title     = {Mucosa and microbiota - the role of intrinsic parameters on intestinal wound healing},
  series = {Frontiers in Surgery},
  volume    = {9},
  journal   = {Frontiers in Surgery},
  issn      = {2296-875X},
  doi       = {10.3389/fsurg.2022.905049},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282096},
  year      = {2022},
  abstract  = {Mucosal healing in the gut is an essential process when it comes to chronic inflammatory disorders such as inflammatory bowel diseases (IBD) but also to the creation of intestinal anastomosis. Despite an improvement of surgical techniques, the rates of anastomotic leakage remain substantial and represent a significant health-care and socio-economic burden. Recent research has focused on intrinsic factors such as mucosal linings and differences in the intestinal microbiota and identified specific endoluminal bacteria and epithelial proteins which influence intestinal wound healing and re-establishment of mucosal homeostasis. Despite the lack of large clinical studies, previous data indicate that the identified bacteria such as aerotolerant lactobacilli or wound-associated Akkermansia muciniphila as well as epithelial-expressed sialyl Lewis glycans or CD47 might be critical for wound and anastomotic healing in the gut, thus, providing a potential novel approach for future treatment strategies in colorectal surgery and IBD therapy. Since microbiota and mucosa are interacting closely, we outline the current discoveries about both subsets in this review together to demonstrate the significant interplay},
  language  = {en}
}
@phdthesis{Buentemeyer2017,
  author    = {B{\"u}ntemeyer, Tjark-Ole},
  title     = {Wertigkeit der Leberresektion bei Metastasen des Nebennierenkarzinoms - Analyse anhand des Deutschen Nebennierenkarzinom-Registers},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155743},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Patienten mit einem hepatisch metastasierten Nebennierenkarzinom und ohne Hinweise auf extrahepatische Tumormanifestationen profitieren von einer Operation im Hinblick auf das Gesamt{\"u}berleben. Dies gilt sowohl f{\"u}r synchron- als auch f{\"u}r metachron metastasierte Patienten.},
  subject      = {Nebenniere},
  language  = {de}
}
@article{GlaserGradzkaLuczewskaSzymankiewiczBreborowiczetal.2019,
  author    = {Glaser, Kirsten and Gradzka-Luczewska, Anna and Szymankiewicz-Breborowicz, Marta and Kawczynska-Leda, Natalia and Henrich, Birgit and Waaga-Gasser, Ana Maria and Speer, Christian P.},
  title     = {Perinatal ureaplasma exposure is associated with increased risk of late onset sepsis and imbalanced inflammation in preterm infants and may add to lung injury},
  series = {Frontiers in Cellular and Infection Microbiology},
  volume    = {9},
  journal   = {Frontiers in Cellular and Infection Microbiology},
  number    = {68},
  doi       = {10.3389/fcimb.2019.00068},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201270},
  year      = {2019},
  abstract  = {Background: Controversy remains concerning the impact of Ureaplasma on preterm neonatal morbidity. Methods: Prospective single-center study in very low birth weight infants <30 weeks' gestation. Cord blood and initial nasopharyngeal swabs were screened for Ureaplasma parvum and U. urealyticum using culture technique and polymerase chain reaction. Neonatal outcomes were followed until death or discharge. Multi-analyte immunoassay provided cord blood levels of inflammatory markers. Using multivariate regression analyses, perinatal Ureaplasma exposure was evaluated as risk factor for the development of bronchopulmonary dysplasia (BPD), other neonatal morbidities until discharge and systemic inflammation at admission. Results: 40/103 (39\%) infants were positive for Ureaplasma in one or both specimens, with U. parvum being the predominant species. While exposure to Ureaplasma alone was not associated with BPD, we found an increased risk of BPD in Ureaplasma-positive infants ventilated ≥5 days (OR 1.64; 95\% CI 0.12-22.98; p = 0.009). Presence of Ureaplasma was associated with a 7-fold risk of late onset sepsis (LOS) (95\% CI 1.80-27.39; p = 0.014). Moreover, Ureaplasma-positive infants had higher I/T ratios (b 0.39; 95\% CI 0.08-0.71; p = 0.014), increased levels of interleukin (IL)-17 (b 0.16; 95\% CI 0.02-0.30; p = 0.025) and matrix metalloproteinase 8 (b 0.77; 95\% CI 0.10-1.44; p = 0.020), decreased levels of IL-10 (b -0.77; 95\% CI -1.58 to -0.01; p = 0.043) and increased ratios of Tumor necrosis factor-α, IL-8, and IL-17 to anti-inflammatory IL-10 (p = 0.003, p = 0.012, p < 0.001). Conclusions: Positive Ureaplasma screening was not associated with BPD. However, exposure contributed to BPD in infants ventilated ≥5 days and conferred an increased risk of LOS and imbalanced inflammatory cytokine responses.},
  language  = {en}
}
@phdthesis{Fehrmann2018,
  author    = {Fehrmann, Marion Valerie},
  title     = {Inzidenz und Outcome von Teratomen des Ovars - eine retrospektive Datenanalyse},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168988},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {In der vorliegenden Arbeit " Inzidenz und Outcome von Teratomen des Ovars - eine retrospektive Datenanalyse " werden die Ergebnisse einer retrospektiven Datenanalyse f{\"u}r ein Zeitfenster von 10 Jahren diskutiert. Gegenstand war die Auswertung der Patientenakten aller ovariellen Neubildungen, welche in den Jahren 2005-2015 in der Abteilung f{\"u}r Kinderchirurgie der chirurgischen Universit{\"a}tsklinik W{\"u}rzburg (Chirurgische Klinik I) behandelt wurden. Die Filterung der Datenbanken nach den erforderlichen Kriterien ergab einen Patientenstamm von 28 F{\"a}llen. Zentrale Untersuchungsparameter stellten das Patientenalter zum Erkrankungszeitpunkt, die diagnoseweisenden Symptome, die pr{\"a}operative Diagnostik, die Wahl der Operationsmethode, der postoperative Verlauf der Krankengeschichte, das Nachsorgeprogramm sowie die Untersuchung auf rezidivierende Prozesse dar. Die gewonnenen Ergebnisse des betrachteten Patientenstamms wurden objektiv zusammengefasst, auf m{\"o}gliche Gesetzm{\"a}ßigkeiten untersucht, pr{\"a}sentiert und durch Grafiken bildlich veranschaulicht. In der Diskussion erfolgte die Einordnung in die aktuelle wissenschaftliche Studienlage und der Vergleich mit themenspezifischen bekannten Erkenntnissen und Literatur.},
  subject      = {Teratom},
  language  = {de}
}
@phdthesis{Schmitt2021,
  author    = {Schmitt, Johannes Christian},
  title     = {{\"U}ber das Expressionsverhalten von Reparatur- und ABC- Transporter-Genen sowie inflammatorischen Signalwegen im Kolon- und Pankreaskarzinom},
  doi       = {10.25972/OPUS-24988},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-249884},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Das Mikromilieu solider Tumor (tumor mircoenvironment, TME) weist verschiedene Besonderheiten auf, von denen bekannt ist, dass sie zu Chemotherapieresistenz und Tumorprogression beitragen k{\"o}nnen. Neben der Extrazellul{\"a}ren Matrix (ECM), den cancer associated cells (CAC) und diversen Entz{\"u}ndungszellen tragen auch chemische und physikalische Besonderheiten (Hypoxie, Azidose, erh{\"o}hter Gewebedruck, oxidativer Stress und N{\"a}hrstoffmangel) zu Tumorprogression und Chemotherapieresistenz bei. Zudem wissen wir, dass Hitzeschock-Proteine (HSPs), Toll-like Rezeptoren (TLRs) und ABC-Transporter mit erh{\"o}hter Chemotherapieresistenz und Tumorprogression im Pankreas- und Kolonkarzinom einhergehen. Hier wurde untersucht, ob ein in vitro induzierter N{\"a}hrstoffmangel im HT29 Kolonkarzinom, im Panc-1 Pankreaskarzinom und im MIA PaCa-2 Pankreaskarzinom zu einer gesteigerten Expression von HSP70, HSP90, MDR1, ABCB5 und TLR1 bis TLR10 auf mRNA und Proteinebene f{\"u}hrt. Zudem wurde unter allen Versuchsbedingungen die Stoffwechselaktivit{\"a}t {\"u}ber einen MTS-Test gemessen. Der N{\"a}hrstoffmangel wurde {\"u}ber die Kultivierung in einem Hybridomamedium, welches als proteinfreies Medium gilt und {\"u}ber die Kultivierung in einem serumfreien Medium induziert. Es zeigte sich, dass insbesondere die entdifferenzierte Panc-1 Pankreaskarzinomzelllinie eine erh{\"o}hte Resistenz gegen{\"u}ber dem induzierten N{\"a}hrstoffmangel aufwies. Auf mRNA-Ebene zeigten sich bei allen drei Tumorzelllinien deutliche Expressionssteigerungen. Diese waren insbesondere im Hybridomamedium nachweisbar und traten beim HT29-Kolonkarzinom nach 48h und im Panc-1 Pankreaskarzinom bereits nach 24h auf. Besonders intensive Expressionssteigerungen konnten im HT29 Kolonkarzinom bei ABCB5, TLR7 und TLR9 nachgewiesen werden. Die Expression von MDR1 war insbesondere im MIA PaCa-2 Pankreaskarzinom gesteigert. Auf Proteinebene konnte im HT29 Kolonkarzinom eine Expressionssteigerung bei HSP90 und TLR6 nachgewiesen werden. Die Ergebnisse lassen zwei Interpretationen zu. Zum einen k{\"o}nnte {\"u}ber den N{\"a}hrstoffmangel eine aggressivere Subpopulation selektioniert worden sein. In diesem Zusammenhang konnten die Expressionsdaten des Tumorstammzellmarkers CD133 leider nicht ausgewertet werden. Alternativ kann angenommen werden, dass die untersuchten Tumorzelllinien ihren aggressiven Ph{\"a}notyp erst unter N{\"a}hrstoffmangelbedingungen, wie wir sie regelm{\"a}ßig in soliden Tumoren finden, zur Expression bringen.},
  subject      = {International Conference on Tumor Microenvironment (4 : 2007 : Florenz)},
  language  = {de}
}
@article{RadevaWalterStachetal.2019,
  author    = {Radeva, Mariya Y. and Walter, Elias and Stach, Ramona Alexandra and Yazdi, Amir S. and Schlegel, Nicolas and Sarig, Ofer and Sprecher, Eli and Waschke, Jens},
  title     = {ST18 Enhances PV-IgG-Induced Loss of Keratinocyte Cohesion in Parallel to Increased ERK Activation},
  series = {Frontiers in Immunology},
  volume    = {10},
  journal   = {Frontiers in Immunology},
  doi       = {10.3389/fimmu.2019.00770},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224910},
  pages     = {770, 1-11},
  year      = {2019},
  abstract  = {Pemphigus is an autoimmune blistering disease targeting the desmosomal proteins desmoglein (Dsg) 1 and Dsg3. Recently, a genetic variant of the Suppression of tumorigenicity 18 (ST18) promoter was reported to cause ST18 up-regulation, associated with pemphigus vulgaris (PV)-IgG-mediated increase in cytokine secretion and more prominent loss of keratinocyte cohesion. Here we tested the effects of PV-IgG and the pathogenic pemphigus mouse anti-Dsg3 antibody AK23 on cytokine secretion and ERK activity in human keratinocytes dependent on ST18 expression. Without ST18 overexpression, both PV-IgG and AK23 induced loss of keratinocyte cohesion which was accompanied by prominent fragmentation of Dsg3 immunostaining along cell borders. In contrast, release of pro-inflammatory cytokines such as IL-1 alpha, IL-6, TNF alpha, and IFN-gamma was not altered significantly in both HaCaT and primary NHEK cells. These experiments indicate that cytokine expression is not strictly required for loss of keratinocyte cohesion. Upon ST18 overexpression, fragmentation of cell monolayers increased significantly in response to autoantibody incubation. Furthermore, production of IL-1 alpha and IL-6 was enhanced in some experiments but not in others whereas release of TNF-alpha dropped significantly upon PV-IgG application in both EV- and ST18-transfected HaCaT cells. Additionally, in NHEK, application of PV-IgG but not of AK23 significantly increased ERK activity. In contrast, ST18 overexpression in HaCaT cells augmented ERK activation in response to both c-IgG and AK23 but not PV-IgG. Because inhibition of ERK by U0126 abolished PV-IgG- and AK23-induced loss of cell cohesion in ST18-expressing cells, we conclude that autoantibody-induced ERK activation was relevant in this scenario. In summary, similar to the situation in PV patients carrying ST18 polymorphism, overexpression of ST18 enhanced keratinocyte susceptibility to autoantibody-induced loss of cell adhesion, which may be caused in part by enhanced ERK signaling.},
  language  = {en}
}
@article{DischingerHeckelBischleretal.2021,
  author    = {Dischinger, Ulrich and Heckel, Tobias and Bischler, Thorsten and Hasinger, Julia and K{\"o}nigsrainer, Malina and Schmitt-B{\"o}hrer, Angelika and Otto, Christoph and Fassnacht, Martin and Seyfried, Florian and Hankir, Mohammed Khair},
  title     = {Roux-en-Y gastric bypass and caloric restriction but not gut hormone-based treatments profoundly impact the hypothalamic transcriptome in obese rats},
  series = {Nutrients},
  volume    = {14},
  journal   = {Nutrients},
  number    = {1},
  issn      = {2072-6643},
  doi       = {10.3390/nu14010116},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252392},
  year      = {2021},
  abstract  = {Background: The hypothalamus is an important brain region for the regulation of energy balance. Roux-en-Y gastric bypass (RYGB) surgery and gut hormone-based treatments are known to reduce body weight, but their effects on hypothalamic gene expression and signaling pathways are poorly studied. Methods: Diet-induced obese male Wistar rats were randomized into the following groups: RYGB, sham operation, sham + body weight-matched (BWM) to the RYGB group, osmotic minipump delivering PYY3-36 (0.1 mg/kg/day), liraglutide s.c. (0.4 mg/kg/day), PYY3-36 + liraglutide, and saline. All groups (except BWM) were kept on a free choice of high- and low-fat diets. Four weeks after interventions, hypothalami were collected for RNA sequencing. Results: While rats in the RYGB, BWM, and PYY3-36 + liraglutide groups had comparable reductions in body weight, only RYGB and BWM treatment had a major impact on hypothalamic gene expression. In these groups, hypothalamic leptin receptor expression as well as the JAK-STAT, PI3K-Akt, and AMPK signaling pathways were upregulated. No significant changes could be detected in PYY3-36 + liraglutide-, liraglutide-, and PYY-treated groups. Conclusions: Despite causing similar body weight changes compared to RYGB and BWM, PYY3-36 + liraglutide treatment does not impact hypothalamic gene expression. Whether this striking difference is favorable or unfavorable to metabolic health in the long term requires further investigation.},
  language  = {en}
}
@phdthesis{Bergauer2017,
  author    = {Bergauer, Lisa},
  title     = {Die Bedeutung des neurotrophen Faktors Glial cell line-derived neurotrophic factor (GDNF) f{\"u}r die Integrit{\"a}t der intestinalen Epithelbarriere},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155259},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {In der vorliegenden Arbeit wurden die Effekte des neurotrophen Faktors GDNF auf die Struktur und Funktion der intestinalen Epithelbarriere untersucht. Zellkulturen mit Caco2 beziehungsweise HT29B6 dienten als Modellsysteme f{\"u}r die Epithelschicht der Darmschleimhaut. Transwellsassays und TER-Messungen mittels ECIS-Ger{\"a}t fungierten als zentrale Untersuchungsmethoden zur Evaluation der funktionellen Barriereeigenschaft der Zellmonolayer. Die morphologischen und quantitativen Ver{\"a}nderungen von Zelljunktionsproteinen wurden mittels indirekter Immunfluoreszenzf{\"a}rbungen beziehungsweise Western Blot-Untersuchungen dargestellt. Um Migration- und Proliferationsverhalten nach Verletzung des Zellmonolayers zu untersuchen, f{\"u}hrten wir in vitro-Scratch-Assays durch. Zun{\"a}chst wurde best{\"a}tigt, dass intestinale Epithelzellen die GDNF-Rezeptoren GFRα1, GFRα2 und RET exprimieren. Es zeigte sich sowohl in Immunf{\"a}rbungen gegen Junktionsproteine als auch in Permeabilit{\"a}tsmessungen, dass GDNF zu einer verst{\"a}rkten Differenzierung der intestinalen Epithelbarriere f{\"u}hrt. In Inhibitions- und Aktivierungsexperimenten mit verschiedenen Mediatoren wurde als zugrunde liegender Mechanismus die Inaktiverung der p38 MAPK durch GDNF identifiziert. Weiterhin zeigten Versuche mit epithelialen Wundheilungsassays, dass GDNF, {\"u}ber eine cAMP/PKA-abh{\"a}ngige Induktion der Proliferation, zu einer Verbesserung der Wundheilung f{\"u}hrt. In Immunf{\"a}rbungen und Western Blot-Analysen wurde beobachtet, dass auch intestinale Epithelzelllinien in der Lage sind GDNF zu synthetisieren. Zusammenfassend konnte in der vorliegenden Arbeit erstmals gezeigt werden, dass der neurotrophe Faktor GDNF direkt auf die Differenzierung und Proliferation von kultivierten Enterozyten Einfluss nehmen kann. Die Tatsache, dass intestinale Epithelzellen selbst GDNF synthetisieren und sezernieren k{\"o}nnen, weist auf einen neuen autokrinen- oder parakrinen Wirkmechanismus des neurotrophen Faktors hin.},
  subject      = {Epithel},
  language  = {de}
}
@phdthesis{Wennmann2021,
  author    = {Wennmann, Andreas},
  title     = {Retrospektiver Vergleich der pr{\"a}operativen Lokalisationsdiagnostik mit der intraoperativen Detektion von Nebenschilddr{\"u}sen-Adenomen sowie dem perioperativen Verlauf bei Patienten/Patientinnen mit prim{\"a}rem Hyperparathyreoidismus},
  doi       = {10.25972/OPUS-24989},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-249895},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Die Exstirpation erkrankter Nebenschilddr{\"u}sen (NSD) ist die einzige kurative Therapie des prim{\"a}ren Hyperparathyreoidismus (pHPT). Die pr{\"a}operative Detektion der dem pHPT zugrunde liegenden NSD-Adenome durch eine ad{\"a}quate Lokalisationsdiagnostik stellt eine wichtige S{\"a}ule bei der Operationsplanung dar. Angesichts der umfangreichen diagnostischen M{\"o}glichkeiten ist noch nicht abschließend beantwortet, wie viel und welche Diagnostik mit hoher Wahrscheinlichkeit zur erfolgreichen Lokalisation von NSD-Adenomen f{\"u}hrt und ob/wie diese den perioperativen Verlauf beeinflusst. Die Beantwortung dieser Fragen war das Hauptziel der vorliegenden Arbeit. Es handelt sich um eine monozentrische, retrospektive Datenanalyse anhand des Kollektivs des Universit{\"a}tsklinikums W{\"u}rzburg (UKW) der Jahre 2005 bis 2017. Nach Datenextraktion aller Patienten/Patientinnen mit Hyperparathyreoidismus aus dem Dokumentationssystem des UKW erfolgten die deskriptiven und statistischen Auswertungen mittels Excel und SPSS. Insgesamt wurden im untersuchten Zeitraum 467 Patienten/Patientinnen aufgrund eines pHPT operiert. NSD-Sono und NSD-Szinti waren die am h{\"a}ufigsten durchgef{\"u}hrten Lokalisationsdiagnostika mit Sensitivit{\"a}ten von 61,5 \% bzw. 66,3 \% f{\"u}r die Seite. Bei der Etagen-Blutentnahme lag die Sensitivit{\"a}t bei 100 \%; bei der MRT bei 47,4 \% und bei der 11Kohlenstoff-Methionin-Positronenemissionstomographie/Computertomographie (11C-Methionin-PET/CT) bei 58,8 \%. Durch zus{\"a}tzliche Diagnostik konnte nicht grunds{\"a}tzlich eine Erh{\"o}hung der Treffsicherheit erreicht werden. Die Analyse der perioperativen Parameter zeigte, dass das Alter der Operierten positiv mit der Operationsdauer, der Krankenhausaufenthaltsdauer und dem Auftreten postoperativer Hypocalc{\"a}mien korrelierte. Die Einnahme eines Thrombozytenaggregationshemmers f{\"u}hrte zu einer verl{\"a}ngerten Krankenhausaufenthaltsdauer. Die therapeutische Antikoagulation war ein Risikofaktor in Bezug auf l{\"a}ngere OP-Dauern und das Auftreten von Nachblutungen. Eine zus{\"a}tzlich zur Parathyreoidektomie durchgef{\"u}hrte Sanierung der Schilddr{\"u}se war mit einer erh{\"o}hten Rate an postoperativen Hypocalc{\"a}mien vergesellschaftet. Zusammenfassend zeigen die vorliegenden Daten, dass nach initial vermeintlich erfolgreicher Detektion eines NSD-Adenoms mit NSD-Sono oder NSD-Szinti eine weiterf{\"u}hrende Lokalisationsdiagnostik nicht sinnvoll ist. Nach initial erfolgloser NSD-Sono oder NSD-Szinti dagegen ist die Durchf{\"u}hrung einer 11C-Methionin-PET/CT zu erw{\"a}gen.},
  subject      = {Prim{\"a}rer Hyperparathyreoidismus},
  language  = {de}
}
@article{SchmitzStormsKochetal.2023,
  author    = {Schmitz, Sophia M. and Storms, Sebastian and Koch, Alexander and Stier, Christine and Kroh, Andreas and Rheinwalt, Karl P. and Schipper, Sandra and Hamesch, Karim and Ulmer, Tom F. and Neumann, Ulf P. and Alizai, Patrick H.},
  title     = {Insulin resistance is the main characteristic of metabolically unhealthy obesity (MUO) associated with NASH in patients undergoing bariatric surgery},
  series = {Biomedicines},
  volume    = {11},
  journal   = {Biomedicines},
  number    = {6},
  issn      = {2227-9059},
  doi       = {10.3390/biomedicines11061595},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319213},
  year      = {2023},
  abstract  = {(1) Background: Metabolically healthy obesity (MHO) is a concept that applies to obese patients without any elements of metabolic syndrome (metS). In turn, metabolically unhealthy obesity (MUO) defines the presence of elements of metS in obese patients. The components of MUO can be divided into subgroups regarding the elements of inflammation, lipid and glucose metabolism and cardiovascular disease. MUO patients appear to be at greater risk of developing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) compared to MHO patients. The aim of this study was to evaluate the influence of different MUO components on NAFLD and NASH in patients with morbid obesity undergoing bariatric surgery. (2) Methods: 141 patients undergoing bariatric surgery from September 2015 and October 2021 at RWTH Aachen university hospital (Germany) were included. Patients were evaluated pre-operatively for characteristics of metS and MUO (HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension). Intraoperatively, a liver biopsy was taken from the left liver lobe and evaluated for the presence of NAFLD or NASH. In ordinal regression analyses, different factors were evaluated for their influence on NAFLD and NASH. (3) Results: Mean BMI of the patients was 52.3 kg/m\(^2\) (36-74.8, SD 8.4). Together, the parameters HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension accounted for a significant amount of variance in the outcome, with a likelihood ratio of χ\(^2\) (9) = 41.547, p < 0.001, for predicting the presence of NASH. Only HOMA was an independent predictor of NASH (B = 0.102, SE = 0.0373, p = 0.007). Evaluation of steatosis showed a similar trend (likelihood ratio χ\(^2\) (9) = 40.272, p < 0.001). Independent predictors of steatosis were HbA1c (B = 0.833, SE = 0.343, p = 0.015) and HOMA (B = 0.136, SE = 0.039, p < 0.001). (4) Conclusions: The above-mentioned model, including components of MUO, was significant for diagnosing NASH in patients with morbid obesity undergoing bariatric surgery. Out of the different subitems, HOMA independently predicted the presence of NASH and steatosis, while HbA1c independently predicted steatosis and fibrosis. Taken together, the parameter of glucose metabolism appears to be more accurate for the prediction of NASH than the parameters of lipid metabolism, inflammation or the presence of cardiovascular disease.},
  language  = {en}
}
@article{ReschkeSalvadorSchlegeletal.2022,
  author    = {Reschke, Moritz and Salvador, Ellaine and Schlegel, Nicolas and Burek, Malgorzata and Karnati, Srikanth and Wunder, Christian and F{\"o}rster, Carola Y.},
  title     = {Isosteviol sodium (STVNA) reduces pro-inflammatory cytokine IL-6 and GM-CSF in an in vitro murine stroke model of the blood-brain barrier (BBB)},
  series = {Pharmaceutics},
  volume    = {14},
  journal   = {Pharmaceutics},
  number    = {9},
  issn      = {1999-4923},
  doi       = {10.3390/pharmaceutics14091753},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286275},
  year      = {2022},
  abstract  = {Early treatment with glucocorticoids could help reduce both cytotoxic and vasogenic edema, leading to improved clinical outcome after stroke. In our previous study, isosteviol sodium (STVNA) demonstrated neuroprotective effects in an in vitro stroke model, which utilizes oxygen-glucose deprivation (OGD). Herein, we tested the hypothesis that STVNA can activate glucocorticoid receptor (GR) transcriptional activity in brain microvascular endothelial cells (BMECs) as previously published for T cells. STVNA exhibited no effects on transcriptional activation of the glucocorticoid receptor, contrary to previous reports in Jurkat cells. However, similar to dexamethasone, STVNA inhibited inflammatory marker IL-6 as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion. Based on these results, STVNA proves to be beneficial as a possible prevention and treatment modality for brain ischemia-reperfusion injury-induced blood-brain barrier (BBB) dysfunction.},
  language  = {en}
}
@phdthesis{MeyerSautter2024,
  author    = {Meyer-Sautter, Pascal Willy},
  title     = {Evaluation der postoperativen empirischen antibiotischen Therapie intraabdomineller Infektionen aus Sicht des Antimicrobical Stewardships (AMS)},
  doi       = {10.25972/OPUS-35920},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-359201},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Ziele: Das Ziel dieser Dissertation ist es, die empirischen antibiotische Therapien (PAT) bei komplizierten intraabdominellen Infektionen (cIAI) in den Jahren 2016 - 2018 in einem großen deutschen Maximalversorger zu evaluieren. Aktuelle Studien legen nahe, dass viele Patienten keine Nachteile durch k{\"u}rzere Therapien mit schmaler wirksamen Antibiotika oder das vermeiden einer nicht notwendigen antibiotischen Therapie haben. Methoden: Es wurde eine retrospektive Kohortenstudie durch Analyse von elektronischen Patientenakten an einem 1500-Betten-Universit{\"a}tsklinikum in Deutschland durchgef{\"u}hrt, bei der die Dauer der Antibiotikatherapie nach Notfalloperationen erhoben und mit antibiotischen Leitlinien durch die hausinterne Antibiotic-Stewardship-Abteilung (AMS) verglichen. Ergebnisse: 767 Patienten konnten eingeschlossen werden, davon erhielten 404 (52.7\%) eine PAT. Die Gesamtanzahl der Therapietage pro 100 Patiententagen ging von 47,0 auf 42,2 Tage zur{\"u}ck (p = 0,035) ohne einen Anstieg an Komplikationen. Patienten ohne Sepsis, bei denen eine initiale chirurgischer Fokuskontrolle m{\"o}glich war profitierten nicht von einer Therapiedauer {\"u}ber 4 Tage (160 vs 100 Patienten). Bei Patienten, bei denen diese Bedingungen nicht gegeben waren, zeigte sich ebenfalls kein Vorteil bei l{\"a}ngeren Behandlungen ({\"u}ber >7 Tage, 74 lang vs. 32 kurz behandelte Patienten). Es zeigte sich ebenfalls kein Vorteil von empirischen Therapien mit Carbapenem statt mit Piperacillin-Tazobactam (n=51 C vs n=40 vs Pip/Taz). Schlussfolgerung: Die Reduktion unn{\"o}tiger, zu breiter und zu langer antibiotischer Therapien bei cIAI ist ohne einen Anstieg der postoperativen Komplikationen m{\"o}glich. Weitere RCTs sind notwendig, um das Wissen um sichere Behandlungen zu vergr{\"o}ßern.},
  subject      = {Bakterielle Infektion},
  language  = {de}
}
@phdthesis{Kusan2024,
  author    = {Kusan, Simon Ferdinand},
  title     = {Keimspektrum und antibiotische Therapie bei Morbus Crohn-assoziierten Abszessen : Eine retrospektive monozentrische Analyse},
  doi       = {10.25972/OPUS-35946},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-359467},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {In dieser monozentrischen retrospektiven Analyse wurde das Keimspektrum und die antibiotische Therapie bei Morbus Crohn- assoziierten Abszessen untersucht.},
  subject      = {Antibiotikum},
  language  = {de}
}
@article{DenkSchmidtSchurretal.2021,
  author    = {Denk, S. and Schmidt, S. and Schurr, Y. and Schwarz, G. and Schote, F. and Diefenbacher, M. and Armendariz, C. and Dejure, F. and Eilers, M. and Wiegering, Armin},
  title     = {CIP2A regulates MYC translation (via its 5′UTR) in colorectal cancer},
  series = {International Journal of Colorectal Disease},
  volume    = {36},
  journal   = {International Journal of Colorectal Disease},
  number    = {5},
  doi       = {10.1007/s00384-020-03772-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280092},
  pages     = {911-918},
  year      = {2021},
  abstract  = {Background Deregulated expression of MYC is a driver of colorectal carcinogenesis, suggesting that decreasing MYC expression may have significant therapeutic value. CIP2A is an oncogenic factor that regulates MYC expression. CIP2A is overexpressed in colorectal cancer (CRC), and its expression levels are an independent marker for long-term outcome of CRC. Previous studies suggested that CIP2A controls MYC protein expression on a post-transcriptional level. Methods To determine the mechanism by which CIP2A regulates MYC in CRC, we dissected MYC translation and stability dependent on CIP2A in CRC cell lines. Results Knockdown of CIP2A reduced MYC protein levels without influencing MYC stability in CRC cell lines. Interfering with proteasomal degradation of MYC by usage of FBXW7-deficient cells or treatment with the proteasome inhibitor MG132 did not rescue the effect of CIP2A depletion on MYC protein levels. Whereas CIP2A knockdown had marginal influence on global protein synthesis, we could demonstrate that, by using different reporter constructs and cells expressing MYC mRNA with or without flanking UTR, CIP2A regulates MYC translation. This interaction is mainly conducted by the MYC 5′UTR. Conclusions Thus, instead of targeting MYC protein stability as reported for other tissue types before, CIP2A specifically regulates MYC mRNA translation in CRC but has only slight effects on global mRNA translation. In conclusion, we propose as novel mechanism that CIP2A regulates MYC on a translational level rather than affecting MYC protein stability in CRC.},
  language  = {en}
}
@misc{BaurRamserKelleretal.2021,
  author    = {Baur, Johannes and Ramser, Michaela and Keller, Nicola and Muysoms, Filip and D{\"o}rfer, J{\"o}rg and Wiegering, Armin and Eisner, Lukas and Dietz, Ulrich A.},
  title     = {Erratum to: Robotic hernia repair II. English version Robotic primary ventral and incisional hernia repair (rv-TAPP and r-Rives or r-TARUP). Video report and results of a series of 118 patients},
  series = {Der Chirurg},
  volume    = {92},
  journal   = {Der Chirurg},
  number    = {SUPPL 1},
  doi       = {10.1007/s00104-021-01563-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-326357},
  pages     = {S27},
  year      = {2021},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{RiedmeierDecarolisHaubitzetal.2021,
  author    = {Riedmeier, Maria and Decarolis, Boris and Haubitz, Imme and M{\"u}ller, Sophie and Uttinger, Konstantin and B{\"o}rner, Kevin and Reibetanz, Joachim and Wiegering, Armin and H{\"a}rtel, Christoph and Schlegel, Paul-Gerhardt and Fassnacht, Martin and Wiegering, Verena},
  title     = {Adrenocortical carcinoma in childhood: a systematic review},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {21},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13215266},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248507},
  year      = {2021},
  abstract  = {Adrenocortical tumors are rare in children. This systematic review summarizes the published evidence on pediatric adrenocortical carcinoma (ACC) to provide a basis for a better understanding of the disease, investigate new molecular biomarkers and therapeutic targets, and define which patients may benefit from a more aggressive therapeutic approach. We included 137 studies with 3680 ACC patients (~65\% female) in our analysis. We found no randomized controlled trials, so this review mainly reflects retrospective data. Due to a specific mutation in the TP53 gene in ~80\% of Brazilian patients, that cohort was analyzed separately from series from other countries. Hormone analysis was described in 2569 of the 2874 patients (89\%). Most patients were diagnosed with localized disease, whereas 23\% had metastasis at primary diagnosis. Only 72\% of the patients achieved complete resection. In 334 children (23\%), recurrent disease was reported: 81\% — local recurrence, 19\% (n = 65) — distant metastases at relapse. Patients < 4 years old had a different distribution of tumor stages and hormone activity and better overall survival (p < 0.001). Although therapeutic approaches are typically multimodal, no consensus is available on effective standard treatments for advanced ACC. Thus, knowledge regarding pediatric ACC is still scarce and international prospective studies are needed to implement standardized clinical stratifications and risk-adapted therapeutic strategies.},
  language  = {en}
}
@article{BauerOpitzFilseretal.2019,
  author    = {Bauer, Maria and Opitz, Anne and Filser, J{\"o}rg and Jansen, Hendrik and Meffert, Rainer H. and Germer, Christoph T. and Roewer, Norbert and Muellenbach, Ralf M. and Kredel, Markus},
  title     = {Perioperative redistribution of regional ventilation and pulmonary function: a prospective observational study in two cohorts of patients at risk for postoperative pulmonary complications},
  series = {BMC Anesthesiology},
  volume    = {19},
  journal   = {BMC Anesthesiology},
  doi       = {10.1186/s12871-019-0805-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200730},
  pages     = {132},
  year      = {2019},
  abstract  = {Background Postoperative pulmonary complications (PPCs) increase morbidity and mortality of surgical patients, duration of hospital stay and costs. Postoperative atelectasis of dorsal lung regions as a common PPC has been described before, but its clinical relevance is insufficiently examined. Pulmonary electrical impedance tomography (EIT) enables the bedside visualization of regional ventilation in real-time within a transversal section of the lung. Dorsal atelectasis or effusions might cause a ventral redistribution of ventilation. We hypothesized the existence of ventral redistribution in spontaneously breathing patients during their recovery from abdominal and peripheral surgery and that vital capacity is reduced if regional ventilation shifts to ventral lung regions. Methods This prospective observational study included 69 adult patients undergoing elective surgery with an expected intermediate or high risk for PPCs. Patients undergoing abdominal and peripheral surgery were recruited to obtain groups of equal size. Patients received general anesthesia with and without additional regional anesthesia. On the preoperative, the first and the third postoperative day, EIT was performed at rest and during spirometry (forced breathing). The center of ventilation in dorso-ventral direction (COVy) was calculated. Results Both groups received intraoperative low tidal volume ventilation. Postoperative ventral redistribution of ventilation (forced breathing COVy; preoperative: 16.5 (16.0-17.3); first day: 17.8 (16.9-18.2), p < 0.004; third day: 17.4 (16.2-18.2), p = 0.020) and decreased forced vital capacity in percentage of predicted values (FVC\%predicted) (median: 93, 58, 64\%, respectively) persisted after abdominal surgery. In addition, dorsal to ventral shift was associated with a decrease of the FVC\%predicted on the third postoperative day (r = - 0.66; p < 0.001). A redistribution of pulmonary ventilation was not observed after peripheral surgery. FVC\%predicted was only decreased on the first postoperative day (median FVC\%predicted on the preoperative, first and third day: 85, 81 and 88\%, respectively). In ten patients occurred pulmonary complications after abdominal surgery also in two patients after peripheral surgery. Conclusions After abdominal surgery ventral redistribution of ventilation persisted up to the third postoperative day and was associated with decreased vital capacity. The peripheral surgery group showed only minor changes in vital capacity, suggesting a role of the location of surgery for postoperative redistribution of pulmonary ventilation.},
  language  = {en}
}
@article{GilbertSchneemannScholzetal.2018,
  author    = {Gilbert, F. and Schneemann, C. and Scholz, C. J. and Kickuth, R. and Meffert, R. H. and Wildenauer, R. and Lorenz, U. and Kellersmann, R. and Busch, A.},
  title     = {Clinical implications of fracture-associated vascular damage in extremity and pelvic trauma},
  series = {BMC Muscuskeletal Disorders},
  volume    = {19},
  journal   = {BMC Muscuskeletal Disorders},
  number    = {404},
  doi       = {10.1186/s12891-018-2333-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176252},
  year      = {2018},
  abstract  = {Background: Vascular damage in polytrauma patients is associated with high mortality and morbidity. Therefore, specific clinical implications of vascular damage with fractures in major trauma patients are reassessed. Methods: This comprehensive nine-year retrospective single center cohort study analyzed demography, laboratory, treatment and outcome data from 3689 patients, 64 patients with fracture-associated vascular injuries were identified and were compared to a control group. Results: Vascular damage occurred in 7\% of patients with upper and lower limb and pelvic fractures admitted to the trauma room. Overall survival was 80\% in pelvic fracture and 97\% in extremity fracture patients and comparable to non-vascular trauma patients. Additional arterial damage required substantial fluid administration and was visible as significantly anemia and disturbed coagulation tests upon admission. Open procedures were done in over 80\% of peripheral extremity vascular damage. Endovascular procedures were predominant (87\%) in pelvic injury. Conclusion: Vascular damage is associated with high mortality rates especially in combination with pelvic fractures. Initial anemia, disturbed coagulation tests and the need for extensive pre-clinical fluid substitution were observed in the cohort with vascular damage. Therefore, fast diagnosis and early interventional and surgical procedures are necessary to optimize patient-specific outcome.},
  language  = {en}
}
@article{WagnerEikenHaubitzetal.2019,
  author    = {Wagner, Johanna and Eiken, Barbara and Haubitz, Imme and Lichthardt, Sven and Matthes, Niels and L{\"o}b, Stefan and Klein, Ingo and Germer, Christoph-Thomas and Wiegering, Armin},
  title     = {Suprapubic bladder drainage and epidural catheters following abdominal surgery—a risk for urinary tract infections?},
  series = {PLoS ONE},
  volume    = {14},
  journal   = {PLoS ONE},
  number    = {1},
  doi       = {10.1371/journal.pone.0209825},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177731},
  pages     = {e0209825},
  year      = {2019},
  abstract  = {Background Epidural catheters are state of the art for postoperative analgesic in abdominal surgery. Due to neurolysis it can lead to postoperative urinary tract retention (POUR), which leads to prolonged bladder catheterization, which has an increased risk for urinary tract infections (UTI). Our aim was to identify the current perioperative management of urinary catheters and, second, to identify the optimal time of suprapubic bladder catheter removal in regard to the removal of the epidural catheter. Methods We sent a questionnaire to 102 German hospitals and analyzed the 83 received answers to evaluate the current handling of bladder drainage and epidural catheters. Then, we conducted a retrospective study including 501 patients, who received an epidural and suprapubic catheter after abdominal surgery at the University Hospital W{\"u}rzburg. We divided the patients into three groups according to the point in time of suprapubic bladder drainage removal in regard to the removal of the epidural catheter and analyzed the onset of a UTI. Results Our survey showed that in almost all hospitals (98.8\%), patients received an epidural catheter and a bladder drainage after abdominal surgery. The point in time of urinary catheter removal was equally distributed between before, simultaneously and after the removal of the epidural catheter (respectively: ~28-29\%). The retrospective study showed a catheter-associated UTI in 6.7\%. Women were affected significantly more often than men (10,7\% versus 2,5\%, p<0.001). There was a non-significant trend to more UTIs when the suprapubic catheter was removed after the epidural catheter (before: 5.7\%, after: 8.4\%). Conclusion The point in time of suprapubic bladder drainage removal in relation to the removal of the epidural catheter does not seem to correlate with the rate of UTIs. The current handling in Germany is inhomogeneous, so further studies to standardize treatment are recommended.},
  language  = {en}
}
@article{BartmannJanakiRamanFloeteretal.2018,
  author    = {Bartmann, Catharina and Janaki Raman, Sudha R. and Fl{\"o}ter, Jessica and Schulze, Almut and Bahlke, Katrin and Willingstorfer, Jana and Strunz, Maria and W{\"o}ckel, Achim and Klement, Rainer J. and Kapp, Michaela and Djuzenova, Cholpon S. and Otto, Christoph and K{\"a}mmerer, Ulrike},
  title     = {Beta-hydroxybutyrate (3-OHB) can influence the energetic phenotype of breast cancer cells, but does not impact their proliferation and the response to chemotherapy or radiation},
  series = {Cancer \& Metabolism},
  volume    = {6},
  journal   = {Cancer \& Metabolism},
  number    = {8},
  doi       = {10.1186/s40170-018-0180-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175607},
  year      = {2018},
  abstract  = {Background: Ketogenic diets (KDs) or short-term fasting are popular trends amongst supportive approaches for cancer patients. Beta-hydroxybutyrate (3-OHB) is the main physiological ketone body, whose concentration can reach plasma levels of 2-6 mM during KDs or fasting. The impact of 3-OHB on the biology of tumor cells described so far is contradictory. Therefore, we investigated the effect of a physiological concentration of 3 mM 3-OHB on metabolism, proliferation, and viability of breast cancer (BC) cells in vitro. Methods: Seven different human BC cell lines (BT20, BT474, HBL100, MCF-7, MDA-MB 231, MDA-MB 468, and T47D) were cultured in medium with 5 mM glucose in the presence of 3 mM 3-OHB at mild hypoxia (5\% oxygen) or normoxia (21\% oxygen). Metabolic profiling was performed by quantification of the turnover of glucose, lactate, and 3-OHB and by Seahorse metabolic flux analysis. Expression of key enzymes of ketolysis as well as the main monocarboxylic acid transporter MCT2 and the glucose-transporter GLUT1 was analyzed by RT-qPCR and Western blotting. The effect of 3-OHB on short- and long-term cell proliferation as well as chemo- and radiosensitivity were also analyzed. Results: 3-OHB significantly changed the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in BT20 cells resulting in a more oxidative energetic phenotype. MCF-7 and MDA-MB 468 cells had increased ECAR only in response to 3-OHB, while the other three cell types remained uninfluenced. All cells expressed MCT2 and GLUT1, thus being able to uptake the metabolites. The consumption of 3-OHB was not strongly linked to mRNA overexpression of key enzymes of ketolysis and did not correlate with lactate production and glucose consumption. Neither 3-OHB nor acetoacetate did interfere with proliferation. Further, 3-OHB incubation did not modify the response of the tested BC cell lines to chemotherapy or radiation. Conclusions: We found that a physiological level of 3-OHB can change the energetic profile of some BC cell lines. However, 3-OHB failed to influence different biologic processes in these cells, e.g., cell proliferation and the response to common breast cancer chemotherapy and radiotherapy. Thus, we have no evidence that 3-OHB generally influences the biology of breast cancer cells in vitro.},
  language  = {en}
}
@article{BurkardMeirKannapinetal.2021,
  author    = {Burkard, Natalie and Meir, Michael and Kannapin, Felix and Otto, Christoph and Petzke, Maximilian and Germer, Christoph-Thomas and Waschke, Jens and Schlegel, Nicolas},
  title     = {Desmoglein2 Regulates Claudin2 Expression by Sequestering PI-3-Kinase in Intestinal Epithelial Cells},
  series = {Frontiers in Immunology},
  volume    = {12},
  journal   = {Frontiers in Immunology},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2021.756321},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-247059},
  year      = {2021},
  abstract  = {Inflammation-induced reduction of intestinal desmosomal cadherin Desmoglein 2 (Dsg2) is linked to changes of tight junctions (TJ) leading to impaired intestinal epithelial barrier (IEB) function by undefined mechanisms. We characterized the interplay between loss of Dsg2 and upregulation of pore-forming TJ protein Claudin2. Intraperitoneal application of Dsg2-stablising Tandem peptide (TP) attenuated impaired IEB function, reduction of Dsg2 and increased Claudin2 in DSS-induced colitis in C57Bl/6 mice. TP blocked loss of Dsg2-mediated adhesion and upregulation of Claudin2 in Caco2 cells challenged with TNFα. In Dsg2-deficient Caco2 cells basal expression of Claudin2 was increased which was paralleled by reduced transepithelial electrical resistance and by augmented phosphorylation of AKT\(^{Ser473}\) under basal conditions. Inhibition of phosphoinositid-3-kinase proved that PI-3-kinase/AKT-signaling is critical to upregulate Claudin2. In immunostaining PI-3-kinase dissociated from Dsg2 under inflammatory conditions. Immunoprecipitations and proximity ligation assays confirmed a direct interaction of Dsg2 and PI-3-kinase which was abrogated following TNFα application. In summary, Dsg2 regulates Claudin2 expression by sequestering PI-3-kinase to the cell borders in intestinal epithelium.},
  language  = {en}
}
@article{DiersWagnerBaumetal.2020,
  author    = {Diers, J. and Wagner, J. and Baum, P. and Lichthardt, S. and Kastner, C. and Matthes, N. and Matthes, H. and Germer, C.-T. and L{\"o}b, S. and Wiegering, A.},
  title     = {Nationwide in-hospital mortality rate following rectal resection for rectal cancer according to annual hospital volume in Germany},
  series = {BJS Open},
  volume    = {4},
  journal   = {BJS Open},
  number    = {2},
  doi       = {10.1002/bjs5.50254},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212878},
  pages     = {310 -- 319},
  year      = {2020},
  abstract  = {Background The impact of hospital volume after rectal cancer surgery is seldom investigated. This study aimed to analyse the impact of annual rectal cancer surgery cases per hospital on postoperative mortality and failure to rescue. Methods All patients diagnosed with rectal cancer and who had a rectal resection procedure code from 2012 to 2015 were identified from nationwide administrative hospital data. Hospitals were grouped into five quintiles according to caseload. The absolute number of patients, postoperative deaths and failure to rescue (defined as in-hospital mortality after a documented postoperative complication) for severe postoperative complications were determined. Results Some 64 349 patients were identified. The overall in-house mortality rate was 3·9 per cent. The crude in-hospital mortality rate ranged from 5·3 per cent in very low-volume hospitals to 2·6 per cent in very high-volume centres, with a distinct trend between volume categories (P < 0·001). In multivariable logistic regression analysis using hospital volume as random effect, very high-volume hospitals (53 interventions/year) had a risk-adjusted odds ratio of 0·58 (95 per cent c.i. 0·47 to 0·73), compared with the baseline in-house mortality rate in very low-volume hospitals (6 interventions per year) (P < 0·001). The overall postoperative complication rate was comparable between different volume quintiles, but failure to rescue decreased significantly with increasing caseload (15·6 per cent after pulmonary embolism in the highest volume quintile versus 38 per cent in the lowest quintile; P = 0·010). Conclusion Patients who had rectal cancer surgery in high-volume hospitals showed better outcomes and reduced failure to rescue rates for severe complications than those treated in low-volume hospitals.},
  language  = {en}
}
@article{ZaitsevaHoffmannOttoetal.2022,
  author    = {Zaitseva, Olena and Hoffmann, Annett and Otto, Christoph and Wajant, Harald},
  title     = {Targeting fibroblast growth factor (FGF)-inducible 14 (Fn14) for tumor therapy},
  series = {Frontiers in Pharmacology},
  volume    = {13},
  journal   = {Frontiers in Pharmacology},
  issn      = {1663-9812},
  doi       = {10.3389/fphar.2022.935086},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290238},
  year      = {2022},
  abstract  = {Fibroblast growth factor-inducible 14 (Fn14) is a member of the tumor necrosis factor (TNF) receptor superfamily (TNFRSF) and is activated by its ligand TNF-like weak inducer of apoptosis (TWEAK). The latter occurs as a homotrimeric molecule in a soluble and a membrane-bound form. Soluble TWEAK (sTWEAK) activates the weakly inflammatory alternative NF-κB pathway and sensitizes for TNF-induced cell death while membrane TWEAK (memTWEAK) triggers additionally robust activation of the classical NF-κB pathway and various MAP kinase cascades. Fn14 expression is limited in adult organisms but becomes strongly induced in non-hematopoietic cells by a variety of growth factors, cytokines and physical stressors (e.g., hypoxia, irradiation). Since all these Fn14-inducing factors are frequently also present in the tumor microenvironment, Fn14 is regularly found to be expressed by non-hematopoietic cells of the tumor microenvironment and most solid tumor cells. In general, there are three possibilities how the tumor-Fn14 linkage could be taken into consideration for tumor therapy. First, by exploitation of the cancer associated expression of Fn14 to direct cytotoxic activities (antibody-dependent cell-mediated cytotoxicity (ADCC), cytotoxic payloads, CAR T-cells) to the tumor, second by blockade of potential protumoral activities of the TWEAK/Fn14 system, and third, by stimulation of Fn14 which not only triggers proinflammtory activities but also sensitizes cells for apoptotic and necroptotic cell death. Based on a brief description of the biology of the TWEAK/Fn14 system and Fn14 signaling, we discuss the features of the most relevant Fn14-targeting biologicals and review the preclinical data obtained with these reagents. In particular, we address problems and limitations which became evident in the preclinical studies with Fn14-targeting biologicals and debate possibilities how they could be overcome.},
  language  = {en}
}
@article{SchmidtDenkWiegering2020,
  author    = {Schmidt, Stefanie and Denk, Sarah and Wiegering, Armin},
  title     = {Targeting protein synthesis in colorectal cancer},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {5},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12051298},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206014},
  year      = {2020},
  abstract  = {Under physiological conditions, protein synthesis controls cell growth and survival and is strictly regulated. Deregulation of protein synthesis is a frequent event in cancer. The majority of mutations found in colorectal cancer (CRC), including alterations in the WNT pathway as well as activation of RAS/MAPK and PI3K/AKT and, subsequently, mTOR signaling, lead to deregulation of the translational machinery. Besides mutations in upstream signaling pathways, deregulation of global protein synthesis occurs through additional mechanisms including altered expression or activity of initiation and elongation factors (e.g., eIF4F, eIF2α/eIF2B, eEF2) as well as upregulation of components involved in ribosome biogenesis and factors that control the adaptation of translation in response to stress (e.g., GCN2). Therefore, influencing mechanisms that control mRNA translation may open a therapeutic window for CRC. Over the last decade, several potential therapeutic strategies targeting these alterations have been investigated and have shown promising results in cell lines, intestinal organoids, and mouse models. Despite these encouraging in vitro results, patients have not clinically benefited from those advances so far. In this review, we outline the mechanisms that lead to deregulated mRNA translation in CRC and highlight recent progress that has been made in developing therapeutic strategies that target these mechanisms for tumor therapy.},
  language  = {en}
}
@article{HankirSeyfriedSchellingeretal.2021,
  author    = {Hankir, Mohammed K. and Seyfried, Florian and Schellinger, Isabel N. and Schlegel, Nicolas and Arora, Tulika},
  title     = {Leaky gut as a potential culprit for the paradoxical dysglycemic response to gastric bypass-associated ileal microbiota},
  series = {Metabolites},
  volume    = {11},
  journal   = {Metabolites},
  number    = {3},
  issn      = {2218-1989},
  doi       = {10.3390/metabo11030153},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234085},
  year      = {2021},
  abstract  = {Altered host-intestinal microbiota interactions are increasingly implicated in the metabolic benefits of Roux-en-Y gastric bypass (RYGB) surgery. We previously found, however, that RYGB-associated ileal microbiota can paradoxically impair host glycemic control when transferred to germ-free mice. Here we present complementary evidence suggesting that this could be due to the heightened development of systemic endotoxemia. Consistently, application of ileal content from RYGB-treated compared with sham-operated rats onto Caco-2 cell monolayers compromised barrier function and decreased expression of the barrier-stabilizing proteins claudin-4 and desmoglein-2. Our findings raise the possibility that RYGB-associated ileal microbiota produce and release soluble metabolites which locally increase intestinal permeability to promote systemic endotoxemia-induced insulin resistance, with potential implications for the treatment of RYGB patients who eventually relapse onto type 2 diabetes.},
  language  = {en}
}