TY  - JOUR
A1  - Ulrichs, Karin
A1  - Eckstein, V.
A1  - Heiser, A.
A1  - Müller-Ruchholtz, W.
T1  - Die zellvermittelte Immunantwort des menschlichen Transplantat Empfängers gegen xenogenes Antigen (Schwein) ist abhängig vom Spenderkompartiment.
N2  - No abstract available.
KW  - Transplantation
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86978
ER  - 
TY  - JOUR
A1  - Breitkreuz, A.
A1  - Ulrichs, Karin
A1  - Eckstein, V.
A1  - Müller-Ruchholtz, W.
T1  - Induktion von Transplantat-Toleranz gegen Xenoantigen durch eine Pharmakon-Antigen-Kombinationsbehandlung
N2  - No abstract available.
KW  - Transplantat
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86969
ER  - 
TY  - JOUR
A1  - Heiser, A.
A1  - Ulrichs, Karin
A1  - Winoto-Morbach, S.
A1  - Vanucchi, A.
A1  - Jäger, H.
A1  - Müller-Ruchholtz, W.
T1  - Erste Kieler Erfahrungen mit 45 Isolierungen von Langerhansinseln aus Schweinepankreas
N2  - No abstract available.
KW  - Langerhans-Inseln
KW  - Bauchspeicheldrüse
KW  - Schwein
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-73205
ER  - 
TY  - JOUR
A1  - Ulrichs, Karin
A1  - Müller-Ruchholtz, W.
T1  - Pharmakologische Beeinflussung natürlicher Antikörper als Vorbedingung für die erfolgreiche Xenotransplantation
N2  - No abstract available.
KW  - Heterotransplantation
KW  - Antikörper
KW  - Pharmakologie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-73216
ER  - 
TY  - JOUR
A1  - Heiser, A.
A1  - Ulrichs, Karin
A1  - Gier, C.
A1  - Müller-Ruchholtz, W.
T1  - Isolierung Langerhans'scher Inseln aus dem Pankreas von Schweinen: Einfluss biologischer und technischer Parameter auf die Inselausbeite und -integrität
N2  - No abstract available.
KW  - Langerhans-Inseln
KW  - Isolierung <Mikrobiologie>
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-73223
ER  - 
TY  - JOUR
A1  - Ulrichs, Karin
A1  - Heiser, A.
A1  - Bosse, M.
A1  - Wacker, H. H.
A1  - Müller-Ruchholtz, W.
T1  - Histologische Untersuchungen des Schweinepankreas zur Verbesserung der Inselausbeute und -integrität nach Kollagenase-Verdauung
N2  - No abstract available.
KW  - Schwein
KW  - Bauchspeicheldrüse
KW  - Histologie
KW  - Kollagenase
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-73237
ER  - 
TY  - JOUR
A1  - Dickneite, G.
A1  - Schorlemmer, H. U.
A1  - Sedlacek, H. H.
A1  - Falk, W.
A1  - Ulrichs, Karin
A1  - Müller-Ruchholtz, W.
T1  - Suppression of macrophage function and prolongation of graft survival by the new guanidinic-like structure, 15-deoxyspergualin
N2  - No abstract available.
KW  - Makrophage
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86991
ER  - 
TY  - JOUR
A1  - Busch, Albert
A1  - Lorenz, Udo
A1  - Tiurbe, George Christian
A1  - Bühler, Christoph
A1  - Kellersmann, Richard
T1  - Femoral vein obturator bypass revascularization in groin infectious bleeding: two case reports and review of the literature
JF  - Journal of Medical Case Reports
N2  - Introduction

Groin infections resulting in arterial bleeding due to bacterial vessel destruction are a severe challenge in vascular surgery. Patients with them most often present as emergencies and therefore need individualized reconstruction solutions.

Case presentation

Case 1 is a 67-year-old man with infectious bleeding after an autologous reconstruction of the femoral bifurcation with greater saphenous vein due to infection of a bovine pericard patch after thrombendarterectomy. Case 2 is a 35-year-old male drug addict and had severe femoral bleeding and infection after repeated intravenous and intra-arterial substance abuse. Both patients were treated with an autologous obturator bypass of the superficial femoral vein. We review the current literature and highlight our therapeutic concept of this clinical entity.

Conclusions

Treatment should include systemic antibiotic medication, surgical control of the infectious site, revascularization and soft tissue repair. An extra-anatomical obturator bypass with autologous superficial femoral vein should be considered as the safest revascularization procedure in infections caused by highly pathogenic bacteria.
KW  - Obturator bypass
KW  - Groin infection
KW  - Autologous
KW  - Extra-anatomical
KW  - Femoral vein
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-95901
UR  - http://www.jmedicalcasereports.com/content/7/1/75
ER  - 
TY  - JOUR
A1  - Ulrichs, Karin
A1  - Eckstein, V.
A1  - Tibell, A.
A1  - Groth, C. G.
A1  - Korsgren, O.
A1  - Müller-Ruchholtz, W.
A1  - Thiede, A.
T1  - Natürliche und induzierte xenoreaktive Antikörper vor und nach klinischer Transplantation fötaler porziner Pankreasinselzellen
N2  - No abstract available.
KW  - Antikörper
KW  - Langerhans-Inseln
KW  - Schwein
KW  - Transplantation
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-72967
ER  - 
TY  - JOUR
A1  - Ulrichs, Karin
A1  - Eckstein, V.
A1  - Korsgren, O.
A1  - Tibell, A.
A1  - Groth, C. G.
A1  - Müller-Ruchholtz, W.
T1  - Characterization of natural and induced human xenophile antibodies before and after transplantation of the fetal porcine endocrine pancreas
N2  - No abstract available.
KW  - Bauspeicheldrüse
KW  - Antikörper
KW  - Transplantation
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86985
ER  - 
TY  - JOUR
A1  - Johanssen, Sarah
A1  - Hahner, Stefanie
A1  - Saeger, Wolfgang
A1  - Quinkler, Marcus
A1  - Beuschlein, Felix
A1  - Dralle, Henning
A1  - Haaf, Michaela
A1  - Kroiss, Matthias
A1  - Jurowich, Christian
A1  - Langer, Peter
A1  - Oelkers, Wolfgang
A1  - Spahn, Martin
A1  - Willenberg, Holger S.
A1  - Maeder, Uwe
A1  - Allolio, Bruno
A1  - Fassnacht, Martin
T1  - Deficits in the Management of Patients With Adrenocortical Carcinoma in Germany
N2  - Background: Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Often, the physicians who first treat patients with ACC have no prior experience with the disease. The aim of our study was to evaluate the quality of medical care for patients with ACC in Germany.
Methods: Data from the German ACC registry were analyzed with regard to the patients’ preoperative diagnostic evaluation, histopathological reporting, and clinical followup. The findings were compared with the recommendations of the European Network for the Study of Adrenal Tumors (ENSAT).
Results: Data were analyzed from 387 patients who had been given an initial diagnosis of ACC in the years 1998 to 2009. 21% of them underwent no hormonal evaluation before surgery, and 59% underwent an inadequate hormonal evaluation. This exposed the patients to unnecessary perioperative risks and impaired their follow-up. 48% did not undergo CT scanning of the chest, even though the lungs are the most frequent site of metastases of ACC. For 13% of the patients, the diagnosis of ACC was later revised by a reference pathologist. For 11% of the patients, the histopathology report contained no information about resection status, even though this is an important determinant of further treatment and prognosis. Optimal management requires re-staging at three-month intervals, yet some patients underwent re-staging only after a longer delay, or not at all.
Conclusion: We have identified significant deficits in the care of patients with ACC in Germany. We suspect that the situation is similar for other rare diseases. The prerequisite to better care is close and early cooperation of the treating physicians with specialized centers.
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85897
ER  - 
TY  - JOUR
A1  - Surat, Güzin
A1  - Meyer-Sautter, Pascal
A1  - Rüsch, Jan
A1  - Braun-Feldweg, Johannes
A1  - Markus, Christian Karl
A1  - Germer, Christoph-Thomas
A1  - Lock, Johan Friso
T1  - Cefazolin might be adequate for perioperative antibiotic prophylaxis in intra-abdominal infections without sepsis: a quality improvement study
JF  - Antibiotics
N2  - Background: The adequate choice of perioperative antibiotic prophylaxis (PAP) could influence the risk of surgical site infections (SSIs) in general surgery. A new local PAP guideline was implemented in May 2017 and set the first-generation cefazolin (CFZ) instead the second-generation cefuroxime (CXM) as the new standard prophylactic antibiotic. The aim of this study was to compare the risk of SSIs after this implementation in intra-abdominal infections (IAIs) without sepsis. Methods: We performed a single center-quality improvement study at a 1500 bed sized university hospital in Germany analyzing patients after emergency surgery during 2016 to 2019 (n = 985), of which patients receiving CXM or CFZ were selected (n = 587). Propensity score matching was performed to ensure a comparable risk of SSIs in both groups. None-inferiority margin for SSIs was defined as 8% vs. 4%. Results: Two matched cohorts with respectively 196 patients were compared. The rate of SSIs was higher in the CFZ group (7.1% vs. 3.6%, p = 0.117) below the non-inferiority margin. The rate of other postoperative infections was significantly higher in the CFZ group (2.0% vs. 8.7%, p = 0.004). No other differences including postoperative morbidity, mortality or length-of-stay were observed. Conclusion: Perioperative antibiotic prophylaxis might be safely maintained by CFZ even in the treatment of intra-abdominal infections.
KW  - antimicrobial stewardship
KW  - antibiotic prescribing quality
KW  - low-risk intra-abdominal infections
KW  - perioperative antibiotic prophylaxis
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270816
SN  - 2079-6382
VL  - 11
IS  - 4
ER  - 
TY  - THES
A1  - Jäger, Simon Ulrich
T1  - Surveillance des Barrett-Ösophagus – Vergleich konservative Therapie versus Anti-Reflux-Operation
T1  - Surveillance Strategies for Barrett's Esophagus - A Comparison between Medical and Surgical Therapy
N2  - Der Zusammenhang von Zylinder-Epithel ausgekleideten Abschnitten des Ösophagus mit der Entwicklung eines ösophagealen Adenokarzinoms ist nun schon seit fast 50 Jahren bekannt. Im Jahre 2008 geht man davon aus, dass jährlich etwa 0.5% der Patienten mit Barrett-Ösophagus ein Adenokarzinom entwickeln. Trotz verbesserter Operationstechnik und der zusätzlich angewandten neoadjuvanten Therapie bleibt die Prognose des Adenokarzinom infaust, nicht zuletzt weil sich die Patienten mangels eindrücklicher Frühsymptome oft erst in weit fortgeschrittenen Stadien präsentieren. Bei insgesamt kleinen Fallzahlen für das Adenokarzinom, der hohen Prävalenz der GERD-Symptomatik und des hohen Anteils der Patienten mit Barrett-Ösophagus die offensichtlich nie zu einem Adenokarzinom progredieren, erscheint ein weit angelegtes Screening durch Gastroskopien mit Biopsie-Entnahmen ineffektiv und unökonomisch. Aus dem Ende der Neunziger Jahre prospektiv angelegten Barrett-Register der chirurgischen Universitätsklinik Würzburg wurden 125 Patienten mit Barrett-Diagnose über 819 Patientenjahre verfolgt. Hier wurde lediglich ein Adenokarzinom mit begleitender high-grade Dysplasie beobachtet, das sich nach einem Intervall von 8 Jahren aus einem nicht-dysplastischen Barrett-Segment entwickelte. Weiterhin wurde in einer Patientin mit einem long-segment Barrett-Ösophagus die Rückbildung einer low-grade Dysplasie in ein nicht-dysplastisches Zylinderepithel beobachtet. Die um in etwa ein Drittel erniedrigte Inzidenz des Adenokarzinoms in dieser Studie (1,22 pro 1000 Patientenjahre) könnte sich durch ein längeres Follow-Up an die in der Literatur beschriebene Inzidenz durch das Auftreten weniger Fälle angleichen. Eine regelmäßige endoskopische Überwachung der Barrett-Schleimhaut bleibt, solange noch keine anderen Modalitäten zur sicheren Risikostratifizierung erhältlich sind, eine zwar belastende, im Einzelfall aber lebenswichtige Maßnahme.
N2  - In a population of 125 patients with histological confirmed non-dysplastic Barrett's esophagus progression to adenocarcinoma was a rare event (1 case in 819 patient years). 76,8% of patients underwent Nissen fundoplication in this population. The high percentage of surgically treated patients is explained by pre-selection, as the study population was recruited from a patient base in the surgical unit of an University Hospital.
KW  - Endobrachyösophagus
KW  - Adenokarzinom
KW  - GERD
KW  - Gastroösophageale Refluxkrankheit
KW  - Intestinale Metaplasie
KW  - Barrett's esophagus
KW  - adenocarcinoma
KW  - intestinal metaplasia
Y1  - 2009
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-39391
ER  - 
TY  - THES
A1  - Mueller, Nicolas
T1  - Langzeitergebnisse der intraoperativen iliakalen Angioplastie bei der Therapie der peripheren arteriellen Verschlusskrankheit vom Mehretagen-Typ durch Hybrideingriffe
T1  - Long-term results of iliac artery stenting and angioplasty combinded with peripheral reconstruction in the therapy of multi-level peripheral arterial disease
N2  - In den letzten Jahren hat sich die intraoperative Angioplastie (ITA) der Beckengefäße bei simultaner konventioneller peripherer Rekonstruktion als Behandlungsoption der Mehretagen-AVK entwickelt, ohne dass eine umfangreiche Datenlage bezüglich ihrer langfristigen Offenheitsraten vorliegt. Die Ergebnisse der weitaus häufiger durchgeführten perkutanen Angioplastie (PTA) im Iliakalbereich lassen sich nicht ohne weiteres auf die ITA übertragen. Daher soll es Ziel dieser Arbeit sein, die Langzeitergebnisse der intraoperativen iliakalen Angioplastie und Stentapplikation bei der kombinierten endovaskulären/ konventionellen gefäßchirurgischen Therapie der peripheren arteriellen Verschlusskrankheit vom Mehretagentyp darzustellen. Im Zeitraum von 11/98 bis 10/03 wurden bei insgesamt 63 Patienten (mittleres Alter: 65,5 Jahre) 66 Beckenetagen durch ITA behandelt. Es kamen insgesamt 76 Stents (12 x ballon-expandierend, 64 x selbst-expandierend) zum Einsatz. Simultan erfolgte bei allen Patienten eine periphere Gefäßrekonstruktion (Femoralis-TEA, poplitealer/cruraler Bypass, cross-over Bypass). Die Daten wurden anhand der Krankenakte, Hausarztanfragen sowie gezielter klinischer und sonographischer Nachuntersuchungen erhoben. Anhand der präoperativen Angiographien wurden sämtliche Beckenetagenläsionen nachträglich nach TASC-Kriterien klassifiziert. Von den 63 Patienten konnten von 55 (58 Beckenetagen) relevante Nachuntersuchungsdaten gewonnen werden (87%). Nach einem mittleren Beoachtungszeitraum von 5,5 Jahren ergab sich eine primäre Offenheitsrate der iliakalen Stents bezogen auf die behandelten Beckenetagen von 86%. Die kumulative Stentoffenheitsrate lag bei 73,9 % nach 9 Jahren. Es bestand kein signifikanter Unterschied der Stentoffenheitsrate zwischen TASC-A- (n=32) und Non-A- (n=26) Läsionen (p=0,82, log-Rang-Test). Ebenfalls fand sich kein signifikanter Unterschied in Abhängigkeit von der Art der peripheren Gefäßrekonstruktion. Im Verlauf des Untersuchungszeitraumes sind 16 Patienten verstorben (29%). Neunmal (15,5%) musste eine Major-Amputation der behandelten Extremität nach einer mittleren Zeitdauer von 2,7 Jahren erfolgen. Zusammenfassend lässt sich formulieren, dass ITA/Stent aufgrund ihrer guten Offenheitsrate auch im Langzeitverlauf eine sinnvolle Ergänzung des Behandlungsspektrums bei der pAVK vom Beckentyp darstellt. Unter Berücksichtigung der Morphologie der Gefäßläsionen eignet sich ihr gering-invasiver Charakter besonders für Patienten mit einem höheren perioperativen Risiko. Gerade bei komplexer Mehretagen-AVK bietet sie eine effiziente Möglichkeit der Einstromverbesserung für periphere Rekonstruktionen.
N2  - Between 11/98 and 10/03 63 patients (66legs) with multilevel-PAD were treated with iliac artery stenting and angioplasty. All in all, 76 stents were inserted (12x balloon-expandable, 64x self-expandable).A peripheral vessel reconstruction was performed simultaneously in every case. Data could be generated of 63 patients (58legs). After a mean period of 5,5 years the mean primary stent patency rate was 86%. The cumulative patency rate was 73,3% after 9 years. There was no significant difference between TASC-A and NonA-patients and no difference in patency rates among the several groups of peripheral revascularisation. Major-amputation had to be performed in 9 cases (15,5%), 16 patients died (29%).
KW  - Arterielle Verschlusskrankheit
KW  - Mehretagen-AVK
KW  - Hybrideingriffe
KW  - Multilevel-PAD
Y1  - 2009
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-48514
ER  - 
TY  - THES
A1  - Stratmann, Robert Henrik
T1  - Ursachen und Therapie duodenaler Obstruktion im Kindesalter am Universitätsklinikum Würzburg – Analyse von Genese, assoziierten Fehlbildungen, Therapie und Outcome
T1  - Causes and therapy of duodenal obstruction in children at the university medical centre of Wuerzburg – An analysis of causes, associated malfornations, therapy and outcome
N2  - Eine retrospektive Analyse von kindlichen Patienten mit duodenaler Obstruktion, welche zwischen dem 01.01.2005 und dem 30.06.2020 im Universitätsklinikum Würzburg in der Abteilung für Kinderchirurgie operativ behandelt wurden. Analyse von Ursachen, Gestationsalter, Geburtsgewicht, Geburtsmodus, Begleitfehlbildungen, Diagnosestellung, operativer Versorgung und aufgetretener Komplikationen.
Duodenale Obstruktion wird meist von duodenalen Atresien und Stenosen verursacht. Es besteht eine Häufung von begleitenden Fehlbildungen wie z.B. einer Trisomie 21, urogenitalen- oder Herzfehlbildungen. Eine Mehrheit der Patienten ist frühgeboren, extreme Unreife ist jedoch selten. Es besteht eine leichte Linksverschiebung des Geburtsgewichtes zur Hypotrophie. Bei korrekter chirurgischer Therapie haben Duodenalatresien und -stenosen eine gute Prognose, welche zumeist von den Begleiterkrankungen limitiert wird.
N2  - A retrospective analysis of children with duodenal obstruction treated in the Department of pediatric surgery at the university medical centre Wuerzburg between Jan 1st 2005 and Jun 30st 2020. An analysis of causes, gestational age, weight at birth, way of childbirth, associated malformations, way and time of diagnosis, operative management and complications.
Duodenal obstruction in most cases is caused by duodenal aresia or stenosis. Trisomy 21, congenital heart diseases and genitourinary disorders among others can be accompanying malformations. Most patients are born premature. Severe prematurity is rare. The overall prognosis is good and mostly restricted by accompanying diseases.
KW  - Atresie
KW  - Duodenalatresie
KW  - duodenale Obstruktion
KW  - duodenal atresia
KW  - duodenal obstruction
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250552
ER  - 
TY  - THES
A1  - Christa [geb. Ludwig], Natalie Yvonne
T1  - Persistierender Urachus - häufiger als gedacht? Eine retrospektive Datenanalyse
T1  - Persistent urachus - more common than believed? A retrospective data analysis
N2  - Eine retrospektive Datenanalyse der Urachusoperationen von 2009- 2019 an der Kinderchirurgischen Klinik des Universitätsklinikums in Würzburg. Es zeigte sich, dass der Urachus häufiger als gedacht vorkommt und dies oft als intraoperativer Zufallsbefund.
N2  - A retrospective data analysis of urachus surgeries from 2009- 2019 at the Pediatric Surgical Clinic of the University Hospital in Würzburg. It was shown that the urachus occurs more frequently than thought and often as an intraoperative incidental finding.
KW  - Urachus
KW  - Kinderchirurgie
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287438
ER  - 
TY  - THES
A1  - Langseder, Theresa Christina
T1  - Charakterisierung intestinaler Barriereveränderungen bei Ratten nach Roux-en-Y Magenbypass
T1  - Characterization of intestinal barrier changes in rats after Roux-en-Y gastric bypass
N2  - Die bariatrische Chirurgie ist momentan die einzige Therapieoption der morbiden Adipositas mit der eine langfristige Gewichtsreduktion erreicht werden kann. Unter den Operationsmethoden gilt der RYGB als eine der wirksamsten Behandlungen bezogen auf den Gewichtsverlust und die Verbesserung von Begleiterkrankungen wie dem Diabetes mellitus Typ 2. Darüber hinaus belegt eine wachsende Zahl an Veröffentlichungen, dass der RYGB den Zustand chronischer Entzündung, wie er typischerweise mit Adipositas einhergeht, verringern kann. Diese sogenannte Endotoxämie geht unter anderem mit einer gestörten Integrität der intestinalen Epithelbarriere einher. Ziel der vorliegenden Arbeit war es eine Analyse der Veränderungen von für die Darmbarriere wichtigen Junktionsproteinen vorzunehmen, um eine Grundlage für künftige mechanistische Untersuchungen zu schaffen. Dafür wurden die Veränderungen von Barriereproteinen in Vollwandresektaten des Duodenums, des Jejunums, des Ileums sowie des Kolons von Ratten, die einen RYGB erhalten hatten, mittels Western Blot Untersuchungen quantifiziert. Als Kontrollgruppe dienten schein-operierte Ratten. Es kam zu tiefgreifenden Veränderungen der analysierten Barriereproteine in den Vollwandresektaten. Interessanterweise unterschieden sich die Verteilungsmuster der Veränderungen der Barriereproteinte deutlich zwischen den einzelnen Darmregionen. Um herauszufinden, ob diese Veränderungen durch regionale Veränderungen der Mikroumgebung nach RYGB- Operation induziert wurden, wurden im reduktionistischen Zellkultursystem Stuhl- Transferexperimente durchgeführt. Caco2-Zellkulturen dienten hierbei als Modell für die intestinale epitheliale Barriere. Es wurden funktionelle Messungen und quantitative Analysen der Veränderungen der Barriereproteine der Zellkultur durchgeführt. Die Funktionsmessungen zeigten, dass der Inhalt des Duodenums, des Jejunums sowie des Kolons deutliche barrierestabilisierende Effekte auf die Caco2-Zellmonolayer hatte. Zudem zeigten sich tiefgreifende Veränderungen der untersuchten Barriereproteine. Zusammenfassend wurde in der vorliegenden Arbeit erstmals eine regionenspezfische Regulation der intestinalen Barriereproteine in Korrelation mit funktionellen Messungen nach RYGB nachgewiesen.
N2  - Bariatric surgery is currently the only treatment option for morbid obesity that can achieve long-term weight loss. Among surgical methods, RYGB is considered one of the most effective treatments in terms of weight loss and improvement of associated diseases such as type 2 diabetes mellitus. In addition, a growing number of publications demonstrate that RYGB can reduce the state of chronic inflammation typically associated with obesity. This so-called endotoxemia is associated with impaired integrity of the intestinal epithelial barrier. The aim of the present work was to perform an analysis of changes in junctional proteins which are important for the intestinal barrier in order to provide a basis for future mechanistic studies. For this purpose, the changes of barrier proteins in whole-wall resections of the duodenum, jejunum, ileum, and colon of rats that had received an RYGB were quantified by Western blot studies. Sham-operated rats served as the control group. Profound changes in the analyzed barrier proteins occurred in the whole-wall resectates. Interestingly, the distribution patterns of barrier protein changes differed markedly between intestinal regions. To determine whether these changes were induced by regional changes in the microenvironment after RYGB- surgery, stool transfer experiments were performed in the reductionist cell culture system. Caco2 cell cultures served here as a model for the intestinal epithelial barrier. Functional measurements and quantitative analyses of the changes in the cell culture barrier proteins were performed. The functional measurements showed that the contents of the duodenum, jejunum, as well as the colon had significant barrier-stabilizing effects on the Caco2 cell monolayers. In addition, profound changes in the barrier proteins examined were evident. In summary, the present work was the first to demonstrate region-specific regulation of intestinal barrier proteins in correlation with functional measurements by RYGB.
KW  - Operation
KW  - Pathogenese
KW  - RYGB
KW  - terminal bar
KW  - Schlussleistenkomplex
KW  - intestinal epithelial barrier
KW  - bariatric surgery
KW  - Endotoxämie
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-305756
ER  - 
TY  - THES
A1  - Fink, Nicolas Robin
T1  - Hält doppelt besser? Retrospektiver Vergleich zweier operativer Therapiestrategien kindlicher Unterarmfrakturen
T1  - Is two better than one? Retrospective comparison of two surgical treatment strategies of pediatric forearm fractures
N2  - Die hier vorliegende Untersuchung beschäftigt sich mit dem Vergleich zweier minimalinvasiver operativer Therapiestrategien der distalen Unterarmfraktur als häufigster Fraktur im Kindesalter. 
Für die vorliegende Studie erfolgte eine umfassende retrospektive Auswertung von 122 Fällen distaler kindlicher Unterarmfrakturen aus einem Zeitraum von elf Jahren, die in der kinderchirurgischen Abteilung des Universitätsklinikums Würzburg osteosynthetisch versorgt wurden. Ziel der Untersuchung war die Betrachtung der Epidemiologie des Verletzungsbildes und des Therapieerfolges in Abhängigkeit von der gewählten Osteosynthesetechnik. Die Kinder wurden dabei entweder allein durch eine Kirschner-Draht-Osteosynthese des Radius oder durch eine zusätzliche Fixierung der Ulna mittels elastisch stabiler intramedullärer Nagelung versorgt.
Durch beide Operationsstrategien konnte für die meisten Patientinnen und Patienten ein gutes Therapieergebnis erreicht werden. Hinsichtlich der Operations- und Hospitalisierungsdauer zeigte sich ein Vorteil für Kinder, die osteosynthetisch lediglich durch Kirschner-Drähte versorgt wurden. In anderen Studien beobachtete Komplikationen in Form sekundärer Dislokationen der Fraktur auch nach Osteosynthese oder Infektionen im Bereich der Drahtenden konnten im hier untersuchten Kollektiv seltener festgestellt werden.
Die vorliegende Untersuchung zeigt, dass, sofern die Indikation zur operativen Versorgung besteht, die Fixierung des Radius allein mittels Kirschner-Drähten eine adäquate Therapie distaler Frakturen von Ulna und Radius im Kindesalter darstellt. Von einer kombinierten Osteosynthese mittels Kirschner-Drähten und ESIN könnten besonders Patientinnen und Patienten profitieren, bei denen initial große Dislokationen der Fraktur, Begleitverletzungen des Arms oder eine Lokalisation im Bereich des diametaphysären Übergangs bestehen. Um diese Beobachtungen auch in größeren Kollektiven und prospektiv sowie randomisiert zu untersuchen, sind weitere Studien wünschenswert.
N2  - The present study deals with the comparison of two minimally invasive surgical treatment strategies of the distal forearm fracture as the most frequent fracture in childhood. 
The study shows a comprehensive retrospective evaluation of 122 cases of distal pediatric forearm fractures from a period of eleven years, which were treated osteosynthetically in the pediatric surgery department of the University Hospital of Würzburg. The aim of the study was to examine the epidemiology of the injury pattern and the therapeutic success in relation to the selected osteosynthesis technique. The children were treated either by Kirschner wire osteosynthesis of the radius alone or by additional fixation of the ulna using elastic stable intramedullary nailing.
Both surgical strategies resulted in a good therapeutic outcome for most patients. With regard to the duration of surgery and hospitalization, there was an advantage for children who were treated osteosynthetically with Kirschner wires only. Complications observed in other studies in the form of secondary dislocation of the fracture even after osteosynthesis or infections in the area of the wire ends were found less frequently in the present collective.
The present study shows that, if surgical treatment is indicated, fixation of the radius using Kirschner wires alone is an adequate therapy for distal fractures of the ulna and radius in childhood. Patients who initially have large dislocations of the fracture, concomitant injuries of the arm, or a localization in the area of the diametaphyseal transition could particularly benefit from a combined osteosynthesis using Kirschner wires and ESIN. Further studies are desirable to investigate these observations also in larger collectives, prospectively and randomized.
KW  - Unterarmbruch
KW  - Unterarmfraktur
KW  - ESIN
KW  - Kirschner-Draht
KW  - K-wire
KW  - ESIN
KW  - Forearm fracture
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-302604
ER  - 
TY  - JOUR
A1  - Lenschow, Christina
A1  - Fuss, Carmina Teresa
A1  - Kircher, Stefan
A1  - Buck, Andreas
A1  - Kickuth, Ralph
A1  - Reibetanz, Joachim
A1  - Wiegering, Armin
A1  - Stenzinger, Albrecht
A1  - Hübschmann, Daniel
A1  - Germer, Christoph Thomas
A1  - Fassnacht, Martin
A1  - Fröhling, Stefan
A1  - Schlegel, Nicolas
A1  - Kroiss, Matthias
T1  - Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management
JF  - Frontiers in Endocrinology
N2  - Parathyroid carcinoma (PC) is an orphan malignancy accounting for only ~1% of all cases with primary hyperparathyroidism. The localization of recurrent PC is of critical importance and can be exceedingly difficult to diagnose and sometimes futile when common sites of recurrence in the neck and chest cannot be confirmed. Here, we present the diagnostic workup, molecular analysis and multimodal therapy of a 46-year old woman with the extraordinary manifestation of abdominal lymph node metastases 12 years after primary diagnosis of PC. The patient was referred to our endocrine tumor center in 2016 with the aim to localize the tumor causative of symptomatic biochemical recurrence. In view of the extensive previous workup we decided to perform [18F]FDG-PET-CT. A pathological lymph node in the liver hilus showed slightly increased FDG-uptake and hence was suspected as site of recurrence. Selective venous sampling confirmed increased parathyroid hormone concentration in liver veins. Abdominal lymph node metastasis was resected and histopathological examination confirmed PC. Within four months, the patient experienced biochemical recurrence and based on high tumor mutational burden detected in the surgical specimen by whole exome sequencing the patient received immunotherapy with pembrolizumab that led to a biochemical response. Subsequent to disease progression repeated abdominal lymph node resection was performed in 10/2018, 01/2019 and in 01/2020. Up to now (12/2020) the patient is biochemically free of disease. In conclusion, a multimodal diagnostic approach and therapy in an interdisciplinary setting is needed for patients with rare endocrine tumors. Molecular analyses may inform additional treatment options including checkpoint inhibitors such as pembrolizumab.
KW  - parathyroid carcinoma
KW  - abdominal lymph node metastases
KW  - molecular diagnostics
KW  - repeated surgery
KW  - [18F]FDG-PET-CT
KW  - immune check inhibitor
KW  - pembrolizumab
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233362
SN  - 1664-2392
VL  - 12
ER  - 
TY  - JOUR
A1  - Hendricks, Anne
A1  - Lenschow, Christina
A1  - Kroiss, Matthias
A1  - Buck, Andreas
A1  - Kickuth, Ralph
A1  - Germer, Christoph-Thomas
A1  - Schlegel, Nicolas
T1  - Evaluation of diagnostic efficacy for localization of parathyroid adenoma in patients with primary hyperparathyroidism undergoing repeat surgery
JF  - Langenbeck's Archives of Surgery
N2  - Purpose
Repeat surgery in patients with primary hyperparathyroidism (pHPT) is associated with an increased risk of complications and failure. This stresses the need for optimized strategies to accurately localize a parathyroid adenoma before repeat surgery is performed. However, evidence on the extent of required diagnostics for a structured approach is sparse.
Methods
A retrospective single-center evaluation of 28 patients with an indication for surgery due to pHPT and previous thyroid or parathyroid surgery was performed. Diagnostic workup, surgical approach, and outcome in terms of complications and successful removement of parathyroid adenoma with biochemical cure were evaluated.
Results
Neck ultrasound, sestamibi scintigraphy, C11-methionine PET-CT, and selective parathyroid hormone venous sampling, but not MRI imaging, effectively detected the presence of a parathyroid adenoma with high positive predictive values. Biochemical cure was revealed by normalization of calcium and parathormone levels 24-48h after surgery and was achieved in 26/28 patients (92.9%) with an overall low rate of complications. Concordant localization by at least two diagnostic modalities enabled focused surgery with success rates of 100%, whereas inconclusive localization significantly increased the rate of bilateral explorations and significantly reduced the rate of biochemical cure to 80%.
Conclusion
These findings suggest that two concordant diagnostic modalities are sufficient to accurately localize parathyroid adenoma before repeat surgery for pHPT. In cases of poor localization, extended diagnostic procedures are warranted to enhance surgical success rates. We suggest an algorithm for better orientation when repeat surgery is intended in patients with pHPT.
KW  - Primary hyperparathyroidism (pHPT)
KW  - preoperative localization
KW  - repeat surgery
KW  - diagnostics
KW  - imaging
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-267520
SN  - 1435-2451
VL  - 406
IS  - 5
ER  - 
TY  - JOUR
A1  - Surat, Güzin
A1  - Vogel, Ulrich
A1  - Wiegering, Armin
A1  - Germer, Christoph-Thomas
A1  - Lock, Johan Friso
T1  - Defining the scope of antimicrobial stewardship interventions on the prescription quality of antibiotics for surgical intra-abdominal infections
JF  - Antibiotics
N2  - Background: The aim of this study was to assess the impact of antimicrobial stewardship interventions on surgical antibiotic prescription behavior in the management of non-elective surgical intra-abdominal infections, focusing on postoperative antibiotic use, including the appropriateness of indications. Methods: A single-center quality improvement study with retrospective evaluation of the impact of antimicrobial stewardship measures on optimizing antibacterial use in intra-abdominal infections requiring emergency surgery was performed. The study was conducted in a tertiary hospital in Germany from January 1, 2016, to January 30, 2020, three years after putting a set of antimicrobial stewardship standards into effect. Results: 767 patients were analyzed (n = 495 in 2016 and 2017, the baseline period; n = 272 in 2018, the antimicrobial stewardship period). The total days of therapy per 100 patient days declined from 47.0 to 42.2 days (p = 0.035). The rate of patients receiving postoperative therapy decreased from 56.8% to 45.2% (p = 0.002), comparing both periods. There was a significant decline in the rate of inappropriate indications (17.4% to 8.1 %, p = 0.015) as well as a significant change from broad-spectrum to narrow-spectrum antibiotic use (28.8% to 6.5%, p ≤ 0.001) for postoperative therapy. The significant decline in antibiotic use did not affect either clinical outcomes or the rate of postoperative wound complications. Conclusions: Postoperative antibiotic use for intra-abdominal infections could be significantly reduced by antimicrobial stewardship interventions. The identification of inappropriate indications remains a key target for antimicrobial stewardship programs.
KW  - antimicrobial stewardship
KW  - antibiotic prescription behavior
KW  - surgical intra-abdominal infections
KW  - post-operative antibiotic treatment
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223034
SN  - 2079-6382
VL  - 10
IS  - 1
ER  - 
TY  - JOUR
A1  - Dietz, Ulrich A.
A1  - Kudsi, O. Yusef
A1  - Garcia-Ureña, Miguel
A1  - Baur, Johannes
A1  - Ramser, Michaela
A1  - Maksimovic, Sladjana
A1  - Keller, Nicola
A1  - Dörfer, Jörg
A1  - Eisner, Lukas
A1  - Wiegering, Armin
T1  - Robotische Hernienchirurgie III: Robotische Inzisionalhernienversorgung mit „transversus abdominis release“ (r-TAR). Videobeitrag und Ergebnisse einer Kohortenstudie
JF  - Der Chirurg
N2  - Das Prinzip der gezielten Trennung bzw. Schwächung einzelner Komponenten der Bauchdecke zur Spannungsentlastung der Medianlinie bei großen abdominellen Rekonstruktionen ist seit über 30 Jahren als anteriore Komponentenseparation (aKS) bekannt und ein etabliertes Verfahren. Auf der Suche nach Alternativen mit geringerer Komplikationsrate wurde die posteriore Komponentenseparation (pKS) entwickelt; der „transversus abdominis release“ (TAR) ist eine nervenschonende Modifikation der pKS. Mit den ergonomischen Ressourcen der Robotik (z. B. abgewinkelte Instrumente) kann der TAR minimal-invasiv durchgeführt werden (r-TAR): Bruchlücken von bis zu 14 cm lassen sich verschließen und ein großes extraperitoneales Netz implantieren. In diesem Videobeitrag wird die Versorgung großer Inzisionalhernien in der r‑TAR-Technik präsentiert. Exemplarisch werden die Ergebnisse einer Kohortenstudie an 13 konsekutiven Patienten vorgestellt. Der Eingriff ist anspruchsvoll, die eigenen Ergebnisse sind – wie auch die Berichte aus der Literatur – ermutigend. Der r‑TAR entwickelt sich zur Königsdisziplin der Bauchdeckenrekonstruktion.
KW  - posteriore Komponentenseparation
KW  - Robotik
KW  - inzisionale Hernie
KW  - ventrale Hernie
KW  - retromuskuläres Netz
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265172
VL  - 92
IS  - 10
ER  - 
TY  - JOUR
A1  - Lauruschkat, Chris D.
A1  - Page, Lukas
A1  - White, P. Lewis
A1  - Etter, Sonja
A1  - Davies, Helen E.
A1  - Duckers, Jamie
A1  - Ebel, Frank
A1  - Schnack, Elisabeth
A1  - Backx, Matthijs
A1  - Dragan, Mariola
A1  - Schlegel, Nicolas
A1  - Kniemeyer, Olaf
A1  - Brakhage, Axel A.
A1  - Einsele, Hermann
A1  - Loeffler, Juergen
A1  - Wurster, Sebastian
T1  - Development of a simple and robust whole blood assay with dual co-stimulation to quantify the release of T-cellular signature cytokines in response to Aspergillus fumigatus antigens
JF  - Journal of Fungi
N2  - Deeper understanding of mold-induced cytokine signatures could promote advances in the diagnosis and treatment of invasive mycoses and mold-associated hypersensitivity syndromes. Currently, most T-cellular immunoassays in medical mycology require the isolation of mononuclear cells and have limited robustness and practicability, hampering their broader applicability in clinical practice. Therefore, we developed a simple, cost-efficient whole blood (WB) assay with dual α-CD28 and α-CD49d co-stimulation to quantify cytokine secretion in response to Aspergillus fumigatus antigens. Dual co-stimulation strongly enhanced A. fumigatus-induced release of T-cellular signature cytokines detectable by enzyme-linked immunosorbent assay (ELISA) or a multiplex cytokine assay. Furthermore, T-cell-dependent activation and cytokine response of innate immune cells was captured by the assay. The protocol consistently showed little technical variation and high robustness to pre-analytic delays of up to 8 h. Stimulation with an A. fumigatus lysate elicited at least 7-fold greater median concentrations of key T-helper cell signature cytokines, including IL-17 and the type 2 T-helper cell cytokines IL-4 and IL-5 in WB samples from patients with Aspergillus-associated lung pathologies versus patients with non-mold-related lung diseases, suggesting high discriminatory power of the assay. These results position WB-ELISA with dual co-stimulation as a simple, accurate, and robust immunoassay for translational applications, encouraging further evaluation as a platform to monitor host immunity to opportunistic pathogens.
KW  - immunoassay
KW  - biomarker
KW  - Aspergillus
KW  - cytokines
KW  - inflammation
KW  - adaptive immunity
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241025
SN  - 2309-608X
VL  - 7
IS  - 6
ER  - 
TY  - JOUR
A1  - Gerhard-Hartmann, Elena
A1  - Wiegering, Verena
A1  - Benoit, Clemens
A1  - Meyer, Thomas
A1  - Rosenwald, Andreas
A1  - Maurus, Katja
A1  - Ernestus, Karen
T1  - A large retroperitoneal lipoblastoma as an incidental finding: a case report
JF  - BMC Pediatrics
N2  - Background
Lipoblastoma is a rare benign mesenchymal neoplasm of infancy that most commonly occurs on the extremities and trunk but can arise at variable sites of the body. Retroperitoneal lipoblastomas are particularly rare but can grow to enormous size, and preoperative diagnosis is difficult with diverse, mostly malignant differential diagnoses that would lead to aggressive therapy. Since lipoblastoma is a benign tumor that has an excellent prognosis after resection, correct diagnosis is crucial.

Case presentation
A case of a large retroperitoneal tumor of a 24-month old infant that was clinically suspicious of a malignant tumor is presented. Due to proximity to the right kidney, clinically most probably a nephroblastoma or clear cell sarcoma of the kidney was suspected. Radiological findings were ambiguous. Therefore, the mass was biopsied, and histology revealed an adipocytic lesion. Although mostly composed of mature adipocytes, in view of the age of the patient, the differential diagnosis of a (maturing) lipoblastoma was raised, which was supported by molecular analysis demonstrating a HAS2-PLAG1 fusion. The tumor was completely resected, and further histopathological workup led to the final diagnosis of a 13 cm large retroperitoneal maturing lipoblastoma. The child recovered promptly from surgery and showed no evidence of recurrence so far.

Conclusion
Although rare, lipoblastoma should be included in the differential diagnoses of retroperitoneal tumors in infants and children, and molecular diagnostic approaches could be a helpful diagnostic adjunct in challenging cases.
KW  - retroperitoneal tumor
KW  - pediatric
KW  - lipoblastoma
KW  - PLAG1 rearrangement
KW  - case report
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260173
VL  - 21
ER  - 
TY  - JOUR
A1  - Kayisoglu, Özge
A1  - Schlegel, Nicolas
A1  - Bartfeld, Sina
T1  - Gastrointestinal epithelial innate immunity-regionalization and organoids as new model
JF  - Journal of Molecular Medicine
N2  - The human gastrointestinal tract is in constant contact with microbial stimuli. Its barriers have to ensure co-existence with the commensal bacteria, while enabling surveillance of intruding pathogens. At the centre of the interaction lies the epithelial layer, which marks the boundaries of the body. It is equipped with a multitude of different innate immune sensors, such as Toll-like receptors, to mount inflammatory responses to microbes. Dysfunction of this intricate system results in inflammation-associated pathologies, such as inflammatory bowel disease. However, the complexity of the cellular interactions, their molecular basis and their development remains poorly understood. In recent years, stem cell-derived organoids have gained increasing attention as promising models for both development and a broad range of pathologies, including infectious diseases. In addition, organoids enable the study of epithelial innate immunity in vitro. In this review, we focus on the gastrointestinal epithelial barrier and its regional organization to discuss innate immune sensing and development.
KW  - regionalization and organoids
KW  - immunity
KW  - gastrointestinal tract
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265220
VL  - 99
IS  - 4
ER  - 
TY  - THES
A1  - Kettler, Julia
T1  - Der antiproliferative Effekt des epigenetischen BRD4- Inhibitors JQ1 auf den proliferativen Phänotyp humaner kolorektaler Karzinomzellen
T1  - The antiproliferative effect of epigenetic BRD4 inhibitor JQ1 on the proliferative phenotype of human colorectal cancer cells
N2  - Der niedermolekulare Inhibitor JQ1 bindet an der Bromodomäne von BRD4, ein auf epigenetischer Ebene agierendes Protein. Der antiproliferative Effekt von JQ1 wurde bisher bei verschiedenen Tumorentitäten vor allem des lymphatischen und blutbildenden Systems gezeigt. In dieser Arbeit wurde der antiproliferative Effekt von JQ1 an fünf humanen kolorektalen Karzinomzelllinien im Vergleich zu nicht transformierten Kontrollzellen (Fibroblasten) in Normoxie, Hypoxie und in der Langzeitkultur nachgewiesen. Außerdem verringerte JQ1 die Expression von MYC auf Protein- und mRNA-Ebene und steigerte die Transkription des durch MYC negativ regulierten Zielegens p21. Diese Steigerung korrelierte mit einem Zellzyklusarrest in der G0/G1-Phase in vier von fünf kolorektalen Karzinomzelllinien.
N2  - The small molecule inhibitor JQ1 binds to the bromodomain of BRD4, a protein acting on the epigenetic level. The antiproliferative effect of JQ1 has been shown in various tumor entities, especially in lymphatic and hematopoietic systems. In this study, the antiproliferative effect of JQ1 was demonstrated in five human colorectal carcinoma cell lines compared to non-transformed control cells (fibroblasts) in normoxia, hypoxia and long-term culture. In addition, JQ1 reduced expression of MYC at the protein and mRNA levels and increased transcription of MYC-negatively regulated target p21. This increase correlated with a cell cycle arrest in the G0/G1 phase in four of five colorectal carcinoma cell lines.
KW  - MYC
KW  - JQ1
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176418
ER  - 
TY  - THES
A1  - Fuhr, Sebastian
T1  - Behandlungsoptionen Offene Abdomen Therapie - Entwicklung und Validierung eines multizentrischen Registers
T1  - Treatment options Open Abdomen Therapy - Development and validation of a multicenter registry
N2  - Die Offene Abdomen Therapie (OAT) stellt eine der größten Herausforderungen im Bereich der Chirurgie dar. Ziel war es ein offenes, kostenloses und internationales Register zu entwickeln, um eine Basis für zukünftige Therapien und den Weg zu einer evidenzbasierten Leitlinie zu legen. 
Es wurden 630 Fälle identifiziert welche mittels OAT behandelt wurden und im Rahmen einer gemischt retrospektiven als auch prospektiven Datenauswertung in das von uns entwickelte Register eingetragen. Schwerpunkte waren dabei einerseits die Praktikabilität des Registers zu testen als auch Einflussfaktoren für eine erfolgreiche OAT zu finden. 
Es konnte gezeigt werden, dass das Register in seiner Konzeption funktioniert und in der ersten Auswertungen Einflussfaktoren für eine erhöhte Faszienverschlussrate gefunden werden konnten. Der verbesserte Faszienverschluss am Ende der Therapie mit zeitgleich reduzierter Komplikationsrate ist möglich.
Aus diesem Grund besitzt die konsequente Nutzung des Registers von behandelnden Einrichtungen, die wo immer mögliche lückenlose Dokumentation, sowie die multizentrische Auswertung der Daten einen hohen Stellenwert in Hinsicht auf Prävention, Therapie und Nachsorge der OAT.
N2  - Open abdomen therapy (OAT) represents one of the greatest challenges in the field of surgery. The aim was to develop an open, free and international registry to provide a basis for future therapies and to pave the way for an evidence-based guideline. 
We identified 630 cases treated with OAT and entered them into the registry in a mixed retrospective and prospective data analysis. The main focus was to test the practicability of the registry as well as to find influencing factors for a successful OAT. 
It could be shown that the register works in its conception and in the first evaluations influencing factors for an increased fascial closure rate could be found. Improved fascial closure at the end of therapy with a simultaneously reduced complication rate is possible.
For this reason, the consistent use of the registry by treating institutions, the complete documentation wherever possible, as well as the multicenter evaluation of the data is of high importance with regard to prevention, therapy and follow-up of OAT.
KW  - Chirurgie
KW  - Laparostomie
KW  - Laparotomie
KW  - Offene Abdomen Therapie
KW  - Open abdomen therapy
KW  - Registerstudie
KW  - Multizentrisches Register
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257080
ER  - 
TY  - THES
A1  - Dörries, Luise
T1  - Einfluss der präoperativen Konditionierung mittels Magenballon vor bariatrischer Operation auf den Therapieerfolg bei extremer Adipositas –  Eine retrospektive Vergleichsstudie
T1  - Impact of preoperative weight loss achieved by gastric balloon on peri‑ and postoperative outcomes of bariatric surgery in super‑obese patients - a retrospective matched‑pair analysis
N2  - Die Adipositaschirurgie ist die effektivste Methode in der Behandlung der Adipositas. Bei extrem adipösen Patientin ist eine primäre Operation oftmals riskant. Die Anlage eines Magenballons als erster Schritt von Mehrstufenkonzepten kann die Operabilität gewährleisten und die perioperative Sicherheit erhöhen. Durch den Magenballon wird ein signifikanter Gewichtsverlust erreicht. Der postoperative Gewichtsverlust fällt allerdings schwächer aus. Es ist wichtig, den Patienten realistische Therapieergebnisse zu vermitteln, um überhöhte Erwartungen und Unzufriedenheit zu vermeiden. Die Sleevegastrektomie eignet sich besonders für extrem adipöse Patienten, da diese eine geringere Komplikationsrate aufweist und einfach in einen Roux-en-Y Bypass umzuwandeln ist.
N2  - Bariatric surgery is currently the most effective method in the treatment of obesity. In extreme obese patients, primary surgery is often challenging and risky. A treatment with gastric balloon as first of more-stage concepts can make surgery possible and increase the perioperative safety. As a result of the gastric balloon a significant weight loss can be achieved. However, postoperative weight loss is reduced. It is important to convey patients realistic results in order to avoid excessive expectations and dissatification. Laparoscopic sleeve gastrectomy is favourable for extrem obese patient because of its lower complication rate and good technical feasibility of conversion to roux-en-y gastric bypass.
KW  - Sleeve-Resektion
KW  - Magenbypass
KW  - Magenballon
KW  - extreme Adipositas
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-272945
ER  - 
TY  - JOUR
A1  - Reimer, Stanislaus
A1  - Lock, Johan F.
A1  - Flemming, Sven
A1  - Weich, Alexander
A1  - Widder, Anna
A1  - Plaßmeier, Lars
A1  - Döring, Anna
A1  - Hering, Ilona
A1  - Hankir, Mohammed K.
A1  - Meining, Alexander
A1  - Germer, Christoph-Thomas
A1  - Groneberg, Kaja
A1  - Seyfried, Florian
T1  - Endoscopic management of large leakages after upper gastrointestinal surgery
JF  - Frontiers in Surgery
N2  - Background
Endoscopic vacuum therapy (EVT) is an evidence-based option to treat anastomotic leakages of the upper gastrointestinal (GI) tract, but the technical challenges and clinical outcomes of patients with large defects remain poorly described.

Methods
All patients with leakages of the upper GI tract that were treated with endoscopic negative pressure therapy at our institution from 2012–2021 were analyzed. Patients with large defects (>30 mm) as an indicator of complex treatment were compared to patients with smaller defects (control group).

Results
Ninety-two patients with postoperative anastomotic or staplerline leakages were identified, of whom 20 (21.7%) had large defects. Compared to the control group, these patients required prolonged therapy (42 vs. 14 days, p < 0.001) and hospital stay (63 vs. 26 days, p < 0.001) and developed significantly more septic complications (40 vs. 17.6%, p = 0.027.) which often necessitated additional endoscopic and/or surgical/interventional treatments (45 vs. 17.4%, p = 0.007.) Nevertheless, a resolution of leakages was achieved in 80% of patients with large defects, which was similar compared to the control group (p = 0.42). Multiple leakages, especially on the opposite side, along with other local unfavorable conditions, such as foreign material mass, limited access to the defect or extensive necrosis occurred significantly more often in cases with large defects (p < 0.001).

Conclusions
Overall, our study confirms that EVT for leakages even from large defects of the upper GI tract is feasible in most cases but comes with significant technical challenges.
KW  - anastomotic leakage
KW  - endoluminal
KW  - vacuum-assisted closure
KW  - negative pressure
KW  - endoscopic
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-274044
SN  - 2296-875X
VL  - 9
ER  - 
TY  - JOUR
A1  - Widder, Anna
A1  - Kelm, Matthias
A1  - Reibetanz, Joachim
A1  - Wiegering, Armin
A1  - Matthes, Niels
A1  - Germer, Christoph-Thomas
A1  - Seyfried, Florian
A1  - Flemming, Sven
T1  - Robotic-assisted versus laparoscopic left hemicolectomy — postoperative inflammation status, short-term outcome and cost effectiveness
JF  - International Journal of Environmental Research and Public Health
N2  - Robotic-assisted colon surgery may contain advantages over the laparoscopic approach, but clear evidence is sparse. This study aimed to analyze postoperative inflammation status, short-term outcome and cost-effectiveness of robotic-assisted versus laparoscopic left hemicolectomy. All consecutive patients who received minimal-invasive left hemicolectomy at the Department of Surgery I at the University Hospital of Wuerzburg in 2021 were prospectively included. Importantly, no patient selection for either procedure was carried out. The robotic-assisted versus laparoscopic approaches were compared head to head for postoperative short-term outcomes as well as cost-effectiveness. A total of 61 patients were included, with 26 patients having received a robotic-assisted approach. Baseline characteristics did not differ among the groups. Patients receiving a robotic-assisted approach had a significantly decreased length of hospital stay as well as lower rates of complications in comparison to patients who received laparoscopic surgery (n = 35). In addition, C-reactive protein as a marker of systemic stress response was significantly reduced postoperatively in patients who were operated on in a robotic-assisted manner. Consequently, robotic-assisted surgery could be performed in a cost-effective manner. Thus, robotic-assisted left hemicolectomy represents a safe and cost-effective procedure and might improve patient outcomes in comparison to laparoscopic surgery.
KW  - robotic surgery
KW  - colon resection
KW  - postoperative inflammation
KW  - cost-effectiveness
KW  - left hemicolectomy
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286203
SN  - 1660-4601
VL  - 19
IS  - 17
ER  - 
TY  - THES
A1  - Osterholt [geb. Callies], Simone Caroline
T1  - Die Bedeutung von tumorzellassoziierter CD137L-Aktivierung für das Proliferationsverhalten und das Proteinexpressions- und -sekretionsprofil von humanen Kolonkarzinomzellen
T1  - Effects of CD137L-mediated reverse signaling on protein expression and secretion in human colon cancer cells
N2  - CD137 und CD137L stellen ein Rezeptor-Liganden-Paar dar, welches auf vielen Immunzellen exprimiert wird und eine wichtige Rolle im Rahmen der Immunstimulation spielt. CD137L fungiert jedoch nicht nur als Ligand sondern auch als Rezeptor und vermittelt als ein solcher Signale in die ihn exprimierende Zelle. Neben seinem Vorkommen auf Immunzellen wird CD137L auch von einigen Tumorzellen exprimiert, unter anderem auch auf denen des Kolonkarzinoms. In dieser Tumorentität korreliert eine hohe CD137L-Expression mit dem Auftreten von Fernmetastasen und einer insgesamt schlechteren Prognose. Die genaue Rolle von CD137L im Kolonkarzinom ist bislang kaum erforscht. Im Rahmen dieser Arbeit wurden daher die Auswirkungen einer CD137L-Aktivierung auf die Proliferation sowie die Proteinexpression und -sekretion von Kolonkarzinomzellen untersucht. 
Die Ergebnisse deuten erstmals darauf hin, dass die CD137L-Stimulation in vitro die Proliferation der entarteten Zellen reduziert und die Expression bzw. Sekretion der Proteine Vimentin, TLR7, VEGF und PDGF steigert. 
Hieraus wird geschlossen, dass eine Stimulation des von den Kolonkarzinomzellen exprimierten CD137L dazu führt, dass sich der Phänotyp der Tumorzellen von einem epithelialen in Richtung eines mesenchymalen Zelltyps verändert. Darüber hinaus werden vermehrt Proteine exprimiert und sezerniert, welche über unterschiedliche Signalwege an der Invasion und Migration der entarteten Zellen beteiligt sind. 
Folglich lässt sich annehmen, dass CD137L eine entscheidende Rolle im Metastasierungsprozess von humanen Kolonkarzinomzellen spielt. Sollte sich dies in weiterführenden Untersuchungen bestätigen, könnte eine pharmazeutische Beeinflussung der beteiligten Signalwege möglicherweise die Prognose von an Kolonkarzinomen erkrankten Patient:innen deutlich verbessern.
N2  - CD137 and CD137L represent a receptor/ligand-pair expressed on a variety of immune cells which exerts an important immunostimulatory effect. Besides its function as a ligand to CD137, CD137L also acts as a receptor itself, thereby transmitting signals into the cell via reverse signaling. Apart from being expressed on immune cells CD137L is also found on many tumor cells, including colon carcinoma cells. In this tumor entity the expression is positively correlated with distant metastases and poor prognosis, nevertheless little is known about the function of CD137L in the progression of colon cancer. The aim of this study was to investigate the effects of CD137L-mediated reverse signaling on protein expression and secretion in human colon cancer cells in vitro. 
The results indicate for the first time that a stimulation of the cells via CD137L induces a decreased proliferation and an increased expression or secretion of the proteins vimentin, TLR7, VEGF and PDGF.
Reverse signaling via CD137L proposedly leads to a transition of the cancer cells from an epithelial to a mesenchymal phenotype. In addition, the increasingly expressed and secreted proteins presumably activate signaling pathways which are involved in the invasion and migration of the tumor cells. 
Hence it is suggested, that CD137L plays a crucial role in the process of metastasis of human colon cancer cells. Should this be confirmed by further studies, impairing this pathway could represent a promising new therapeutic approach which could improve the prognosis of patients suffering from colon cancer.
KW  - Colonkrebs
KW  - Metastase
KW  - Immun-Checkpoint
KW  - CD137
KW  - CD137L
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-293382
ER  - 
TY  - THES
A1  - Nagel, Kathrin
T1  - Definition und Diagnostik des postoperativen Hypoparathyreoidismus nach Thyreoidektomie - ein systematischer Review und Metaanalyse
T1  - Definition and diagnosis of postsurgical hypoparathyroidism after thyroid surgery: systematic review and meta-analysis
N2  - Der postoperative Hypoparathyreoidismus (PH) stellt eine der häufigsten Komplikationen nach Schilddrüsenoperationen dar. Ziel dieses systematischen Reviews und Metaanalyse ist die Erarbeitung einer einheitlichen Definition sowie die Ermittlung des bestmöglichen Ansatzes für eine frühzeitige Detektion des PH. 

Nach Durchführung einer systematischen Literaturrecherche gemäß der PICo-Systematik unter Verwendung der Datenbanken Embase, Pubmed und der Cochrane Library, erfolgte die themenbezogene Aufarbeitung der eingeschlossenen Studien, sowie eine Bias-Bewertung und Metaanalyse geeigneter Arbeiten. 

Von 13.704 Artikeln konnten 188 in die weitere Analyse eingeschlossen werden. In diesen fanden sich sehr heterogene Definitionen des PH. Sowohl in der systematischen Analyse als auch in der Metaanalyse zeigte sich eine genauere Vorhersagekraft des PH durch eine postoperative im Vergleich zu einer intraoperativen PTH-Messung. Keiner der analysierten Zeiträume innerhalb des ersten postoperativen Tages (POD1) zeigte eine signifikante Überlegenheit in der Vorhersage eines PH. Die PTH- Schwellenwerte 10 bzw. 15 pg/ml können einen PH zuverlässig detektieren. Als Entscheidungsgrundlage zwischen den beiden Werten kann die untere Normwertgrenze des angewendeten Testverfahrens herangezogen werden. Bei präoperativer PTH-Abnahme nach Anästhesieeinleitung ist ein relativer PTH-Abfall von prä- nach postoperativ von 73 ± 11% prädiktiv für die Entwicklung eines PH. Die Bestimmung des Calciumspiegels an POD1 ist obligat und optimiert insbesondere die Erkennung einer biochemischen Hypokalzämie. 

Ein nicht nachweisbarer oder inadäquat niedriger postoperativer PTH-Spiegel im Zusammenhang mit einer biochemischen oder symptomatischen Hypokalzämie kann als einheitliche Definition des postoperativen Hypoparathyreoidismus vorgeschlagen werden. Die Messung des Parathormons sollte zwischen einer und sechs Stunden postoperativ, spätestens aber innerhalb von 24 Stunden erfolgen. Sowohl der Schwellenwert ≤ 15 pg/ml als auch ein relativer PTH-Abfall von prä- nach postoperativ sind zuverlässig in der Detektion gefährdeter Patienten.
N2  - Background: Postsurgical hypoparathyroidism (PH) is the most frequent complication after
thyroid surgery. The aim of this systematic review and meta-analysis is to summarize a
unifying definition of PH and to elucidate the best possible approach for early detection of
PH.

Methods: A systematic review of the literature according to the PICO framework using
Embase, PUBMED and the Cochrane library was carried out on 1 December 2021 followed
by analysis for risk of bias, data extraction and meta-analysis. All studies addressing the
definition of postoperative hypoparathyroidism and/or diagnostic approaches for early
detection and diagnosis were included. Case reports, commentaries, non-English articles,
book chapters and pilot studies and reviews were excluded.

Results: From 13 704 articles, 188 articles were eligible for inclusion and further analysis.
These articles provided heterogeneous definitions of PH. Meta-analysis revealed that
postoperative measurements of parathormone (PTH) levels have a higher sensitivity and
specificity than intraoperative PTH measurements to predict PH after thyroid surgery. None
of the timeframes analysed after surgery within the first postoperative day (POD1) was
superior to predict the onset of PH. PTH levels of less than 15 pg/ml and less than 10 pg/ml
are both reliable threshold levels to predict the postoperative onset of PH. A relative
reduction of mean (s.d.) PTH levels from pre- to postoperative values of 73 (+/- 11) per cent
may also be predictive for the development of PH. The estimation of calcium levels on POD1
are recommended.

Conclusion: PH is best defined as an undetectable or inappropriately low postoperative
PTH level in the context of hypocalcaemia with or without hypocalcaemic symptoms. PTH
levels should be measured after surgery within 24 h. Both threshold levels below 10 and 15
pg/ml or relative loss of PTH before/after thyroid surgery are reliable to predict the onset of
PH.
KW  - Hypoparathyreoidismus
KW  - Thyreoidektomie
KW  - postoperative Komplikationen
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300083
ER  - 
TY  - JOUR
A1  - Diers, Johannes
A1  - Baum, Philip
A1  - Lehmann, Kai
A1  - Uttinger, Konstatin
A1  - Baumann, Nikolas
A1  - Pietryga, Sebastian
A1  - Hankir, Mohammed
A1  - Matthes, Niels
A1  - Lock, Johann F.
A1  - Germer, Christoph-Thomas
A1  - Wiegering, Armin
T1  - Disproportionately high failure to rescue rates after resection for colorectal cancer in the geriatric patient population - A nationwide study
JF  - Cancer Medicine
N2  - Background
Colorectal cancer incidence increases with patient age. The aim of this study was to assess, at the nationwide level, in-hospital mortality, and failure to rescue in geriatric patients (≥ 80 years old) with colorectal cancer arising from postoperative complications.

Methods
All patients receiving surgery for colorectal cancer in Germany between 2012 and 2018 were identified in a nationwide database. Association between age and in-hospital mortality following surgery and failure to rescue, defined as death after complication, were determined in univariate and multivariate analyses.

Results
Three lakh twenty-eight thousands two hundred and ninety patients with colorectal cancer were included of whom 77,287 were 80 years or older. With increasing age, a significant relative increase in right hemicolectomy was observed. In general, these patients had more comorbid conditions and higher frailty. In-hospital mortality following colorectal cancer surgery was 4.9% but geriatric patients displayed a significantly higher postoperative in-hospital mortality of 10.6%. The overall postoperative complication rate as well as failure to rescue increased with age. In contrast, surgical site infection (SSI) and anastomotic leakage (AL) did not increase in geriatric patients, whereas the associated mortality increased disproportionately (13.3% for SSI and 29.9% mortality for patients with AI, both p < 0.001). Logistic regression analysis adjusting for confounders showed that geriatric patients had almost five-times higher odds for death after surgery than the baseline age group below 60 (OR 4.86; 95%CI [4.45–5.53], p < 0.001).

Conclusion
Geriatric patients have higher mortality after colorectal cancer surgery. This may be partly due to higher frailty and disproportionately higher rates of failure to rescue arising from postoperative complications.
KW  - colorectal cancer
KW  - geriatric
KW  - octogenerians
KW  - surgery
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312858
VL  - 11
IS  - 22
ER  - 
TY  - JOUR
A1  - Uttinger, Konstantin L.
A1  - Riedmeier, Maria
A1  - Reibetanz, Joachim
A1  - Meyer, Thomas
A1  - Germer, Christoph Thomas
A1  - Fassnacht, Martin
A1  - Wiegering, Armin
A1  - Wiegering, Verena
T1  - Adrenalectomies in children and adolescents in Germany – a diagnose related groups based analysis from 2009-2017
JF  - Frontiers in Endocrinology
N2  - Background
Adrenalectomies are rare procedures especially in childhood. So far, no large cohort study on this topic has been published with data on to age distribution, operative procedures, hospital volume and operative outcome.


Methods
This is a retrospective analysis of anonymized nationwide hospital billing data (DRG data, 2009-2017). All adrenal surgeries (defined by OPS codes) of patients between the age 0 and 21 years in Germany were included.


Results
A total of 523 patient records were identified. The mean age was 8.6 ± 7.7 years and 262 patients were female (50.1%). The majority of patients were between 0 and 5 years old (52% overall), while 11.1% were between 6 and 11 and 38.8% older than 12 years. The most common diagnoses were malignant neoplasms of the adrenal gland (56%, mostly neuroblastoma) with the majority being younger than 5 years. Benign neoplasms in the adrenal gland (D350) account for 29% of all cases with the majority of affected patients being 12 years or older. 15% were not defined regarding tumor behavior. Overall complication rate was 27% with a clear higher complication rate in resection for malignant neoplasia of the adrenal gland. Bleeding occurrence and transfusions are the main complications, followed by the necessary of relaparotomy. There was an uneven patient distribution between hospital tertiles (low volume, medium and high volume tertile). While 164 patients received surgery in 85 different “low volume” hospitals (0.2 cases per hospital per year), 205 patients received surgery in 8 different “high volume” hospitals (2.8 cases per hospital per year; p<0.001). Patients in high volume centers were significant younger, had more extended resections and more often malignant neoplasia. In multivariable analysis younger age, extended resections and open procedures were independent predictors for occurrence of postoperative complications.


Conclusion
Overall complication rate of adrenalectomies in the pediatric population in Germany is low, demonstrating good therapeutic quality. Our analysis revealed a very uneven distribution of patient volume among hospitals.
KW  - pediatric
KW  - neuroblastoma – diagnosis
KW  - therapy
KW  - adrenocortical adenocarcinoma
KW  - outcome
KW  - volume
KW  - adrenalectomia
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-282280
SN  - 1664-2392
VL  - 13
ER  - 
TY  - JOUR
A1  - Leikam, C
A1  - Hufnagel, AL
A1  - Otto, C
A1  - Murphy, DJ
A1  - Mühling, B
A1  - Kneitz, S
A1  - Nanda, I
A1  - Schmid, M
A1  - Wagner, TU
A1  - Haferkamp, S
A1  - Bröcker, E-B
A1  - Schartl, M
A1  - Meierjohann, S
T1  - In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells
JF  - Cell Death and Disease
N2  - Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi-or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS\(^{61K}\) in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation.
KW  - reactive oxygen
KW  - human melanoma
KW  - MITF
KW  - cancer
KW  - skin
KW  - DNA damage
KW  - kappa-B
KW  - oncogene-induced senescence
KW  - cellular senescence
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148718
VL  - 6
IS  - e1711
ER  - 
TY  - JOUR
A1  - Diers, Johannes
A1  - Acar, Laura
A1  - Wagner, Johanna C.
A1  - Baum, Philip
A1  - Hankir, Mohammed
A1  - Flemming, Sven
A1  - Kastner, Carolin
A1  - Germer, Christoph-Thomas
A1  - L’hoest, Helmut
A1  - Marschall, Ursula
A1  - Lock, Johan Friso
A1  - Wiegering, Armin
T1  - Cancer diagnosis is one quarter lower than the expected cancer incidence in the first year of COVID-19 pandemic in Germany: A retrospective register-based cohort study
JF  - Cancer Communications
N2  - No abstract available.
KW  - cancer diagnosis
KW  - COVID-19 pandemic
KW  - Germany
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312862
VL  - 42
IS  - 7
ER  - 
TY  - JOUR
A1  - Radeva, Mariya Y.
A1  - Walter, Elias
A1  - Stach, Ramona Alexandra
A1  - Yazdi, Amir S.
A1  - Schlegel, Nicolas
A1  - Sarig, Ofer
A1  - Sprecher, Eli
A1  - Waschke, Jens
T1  - ST18 Enhances PV-IgG-Induced Loss of Keratinocyte Cohesion in Parallel to Increased ERK Activation
JF  - Frontiers in Immunology
N2  - 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.
KW  - pemphigus
KW  - desmosome
KW  - desmoglein
KW  - ST18
KW  - ERK
KW  - cytokines
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224910
VL  - 10
ER  - 
TY  - JOUR
A1  - Dischinger, Ulrich
A1  - Heckel, Tobias
A1  - Bischler, Thorsten
A1  - Hasinger, Julia
A1  - Königsrainer, Malina
A1  - Schmitt-Böhrer, Angelika
A1  - Otto, Christoph
A1  - Fassnacht, Martin
A1  - Seyfried, Florian
A1  - Hankir, Mohammed Khair
T1  - Roux-en-Y gastric bypass and caloric restriction but not gut hormone-based treatments profoundly impact the hypothalamic transcriptome in obese rats
JF  - Nutrients
N2  - 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.
KW  - obesity
KW  - Roux-en-Y gastric bypass surgery
KW  - liraglutide
KW  - PYY3-36
KW  - hypothalamic gene expression
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252392
SN  - 2072-6643
VL  - 14
IS  - 1
ER  - 
TY  - THES
A1  - Bergauer, Lisa
T1  - Die Bedeutung des neurotrophen Faktors Glial cell line-derived neurotrophic factor (GDNF) für die Integrität der intestinalen Epithelbarriere
T1  - The importance of Glial cell line-derived neurotrophic factor (GDNF) for the integrity of the intestinal epithelial barrier
N2  - 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 für die Epithelschicht der Darmschleimhaut. Transwellsassays und TER-Messungen mittels ECIS-Gerät fungierten als zentrale Untersuchungsmethoden zur Evaluation der funktionellen Barriereeigenschaft der Zellmonolayer. Die morphologischen und quantitativen Veränderungen von Zelljunktionsproteinen wurden mittels indirekter Immunfluoreszenzfärbungen beziehungsweise Western Blot-Untersuchungen dargestellt. Um Migration- und Proliferationsverhalten nach Verletzung des Zellmonolayers zu untersuchen, führten wir in vitro-Scratch-Assays durch.
Zunächst wurde bestätigt, dass intestinale Epithelzellen die GDNF-Rezeptoren GFRα1, GFRα2 und RET exprimieren. Es zeigte sich sowohl in Immunfärbungen gegen Junktionsproteine als auch in Permeabilitätsmessungen, dass GDNF zu einer verstärkten Differenzierung der intestinalen Epithelbarriere führt. 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, über eine cAMP/PKA-abhängige Induktion der Proliferation, zu einer Verbesserung der Wundheilung führt. In Immunfärbungen 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 können, weist auf einen neuen autokrinen- oder parakrinen Wirkmechanismus des neurotrophen Faktors hin.
N2  - Recent data suggest that neurotrophic factors that derive from the enteric nervous system are involved in intestinal epithelial barrier regulation. In this context the glial cell line-derived neurotrophic factor (GDNF) was shown to affect gut barrier properties in vivo directly or indirectly by largely undefined processes in a model of inflammatory bowel disease (IBD). Here, we further investigated the potential role and mechanisms of GDNF in the regulation of intestinal epithelial barrier functions.
In Western blot analyses of serum-starved intestinal epithelial cell lines Caco2 and HT29B6 significant amounts of GDNF were detected suggesting that enterocytes may represent an additional source of GDNF secretion.  Application of recombinant GDNF on Caco2 monolayers for 24h resulted in significant epithelial barrier stabilisation in Caco2 and HT29B6 monolayers with immature barrier functions. Wound healing assays in cell monolayers showed a significantly faster closure of the wounded areas after GDNF application. GDNF augmented cAMP levels and led to significant inactivation of p38MAPK in immature epithelial cells. While inactivation of p38MAPK signalling by SB202190 mimicked GDNF-induced barrier maturation, coincubation of GDNF with p38MAPK activator anisomycin blocked GDNF effects. Increasing cAMP levels by forskolin and rolipram had adverse effects on barrier maturation as revealed by permeability measurements. However, increased cAMP augmented the proliferation rate in Caco2 cells and GDNF-induced proliferation of epithelial cells was abrogated by PKA-inhibitor H89.   
In summary, our data show that enterocytes represent an additional source of GDNF synthesis. GDNF contributes to wound healing in a cAMP/PKA-dependent manner and promotes barrier maturation in immature enterocytes cells by inactivation of p38MAPK signalling.
KW  - Epithel
KW  - Epithelgewebe
KW  - epithelial
KW  - Darmchirurgie
KW  - GDNF
KW  - Intestinale Epithelbarriere
KW  - Glia
KW  - Stabilität
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-155259
ER  - 
TY  - THES
A1  - Wennmann, Andreas
T1  - Retrospektiver Vergleich der präoperativen Lokalisationsdiagnostik mit der intraoperativen Detektion von Nebenschilddrüsen-Adenomen sowie dem perioperativen Verlauf bei Patienten/Patientinnen mit primärem Hyperparathyreoidismus
T1  - Retrospective comparison of preoperative localization diagnostics with intraoperative detection of parythyroid adenomas as well as perioperative course in patients with primary hyperparathyroidism
N2  - Die Exstirpation erkrankter Nebenschilddrüsen (NSD) ist die einzige kurative Therapie des primären Hyperparathyreoidismus (pHPT). Die präoperative Detektion der dem pHPT zugrunde liegenden NSD-Adenome durch eine adäquate Lokalisationsdiagnostik stellt eine wichtige Säule bei der Operationsplanung dar. Angesichts der umfangreichen diagnostischen Möglichkeiten ist noch nicht abschließend beantwortet, wie viel und welche Diagnostik mit hoher Wahrscheinlichkeit zur erfolgreichen Lokalisation von NSD-Adenomen führt 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 Universitätsklinikums Würzburg (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 häufigsten durchgeführten Lokalisationsdiagnostika mit Sensitivitäten von 61,5 % bzw. 66,3 % für die Seite. Bei der Etagen-Blutentnahme lag die Sensitivität bei 100 %; bei der MRT bei 47,4 % und bei der 11Kohlenstoff-Methionin-Positronenemissionstomographie/Computertomographie (11C-Methionin-PET/CT) bei 58,8 %. Durch zusätzliche Diagnostik konnte nicht grundsätzlich eine Erhöhung 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 Hypocalcämien korrelierte. Die Einnahme eines Thrombozytenaggregationshemmers führte zu einer verlängerten Krankenhausaufenthaltsdauer. Die therapeutische Antikoagulation war ein Risikofaktor in Bezug auf längere OP-Dauern und das Auftreten von Nachblutungen. Eine zusätzlich zur Parathyreoidektomie durchgeführte Sanierung der Schilddrüse war mit einer erhöhten Rate an postoperativen Hypocalcämien vergesellschaftet.
Zusammenfassend zeigen die vorliegenden Daten, dass nach initial vermeintlich erfolgreicher Detektion eines NSD-Adenoms mit NSD-Sono oder NSD-Szinti eine weiterführende Lokalisationsdiagnostik nicht sinnvoll ist. Nach initial erfolgloser NSD-Sono oder NSD-Szinti dagegen ist die Durchführung einer 11C-Methionin-PET/CT zu erwägen.
N2  - Extirpation of diseased parathyroid glands is the only curative therapy for primary hyperparathyroidism (pHPT). Preoperative localization of parathyroid adenomas underlying pHPT by appropriate localization diagnostics is important for planning surgery. Considering extensive diagnostic possibilities, it is not completely clear yet how much and which diagnostics with high probability will detect parathyroid adenomas correctly and if/how it influences perioperative course. Answering these questions was main aim of the present work.
It is a monocentric, retrospective data analysis of the collective of Universitätsklinikum Würzburg (UKW) from 2005 - 2017. After data extraction of all patients with hyperparathyroidism out of documentation system of UKW, descriptive and statistic evaluations were made by Excel and SPSS.
All in all, 467 patients underwent surgery for pHPT during the investigated timespace. Parathyroid-ultrasound and parathyroid-scintigraphy were the localization techniques used most frequently with sensitivities of 61,5 % and 66,3 % respectively for correct localization of the side. Sensitivity of selective venous sampling was 100 %, of MRI was 47,4 % and of 11carbon methionine positron emission tomography/computed tomography (11C methionine PET/CT) was 58,8 %. Using additional diagnostics, the detection rate could not necessarily be increased.
Analysis of perioperative parameters showed that age was positively correlated with duration of surgery, length of stay at the hospital and postoperative hypocalcaemias. Inhibitors of platelet aggregation led to longer duration of hospitalisation stay. Therapeutic anticoagulation was risk factor for longer duration of surgery and appearance of postoperative bleedings. Additional to parathyroid gland performed thyroid surgery was associated with postoperative hypocalcaemias.
In summary the present data show that after supposedly successful parathyroid ultrasound or parathyroid scintigraphy, no further localization diagnostics is indicated. After initially unsuccessful parathyroid ultrasound or parathyroid scintigraphy however, 11C methionine PET/CT should be considered.
KW  - Primärer Hyperparathyreoidismus
KW  - Epithelkörperchen
KW  - Lokalisation
KW  - Operation
KW  - Verlauf
KW  - primary hyperparathyroidism
KW  - parathyroid glands
KW  - localization
KW  - surgery
KW  - course
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-249895
ER  - 
TY  - JOUR
A1  - Riedmeier, Maria
A1  - Decarolis, Boris
A1  - Haubitz, Imme
A1  - Müller, Sophie
A1  - Uttinger, Konstantin
A1  - Börner, Kevin
A1  - Reibetanz, Joachim
A1  - Wiegering, Armin
A1  - Härtel, Christoph
A1  - Schlegel, Paul-Gerhardt
A1  - Fassnacht, Martin
A1  - Wiegering, Verena
T1  - Adrenocortical carcinoma in childhood: a systematic review
JF  - Cancers
N2  - 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.
KW  - pediatric adrenocortical cancer
KW  - pediatric adrenocortical adenoma
KW  - pediatric adrenocortical tumor
KW  - prognostic factors
KW  - therapy
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248507
SN  - 2072-6694
VL  - 13
IS  - 21
ER  - 
TY  - JOUR
A1  - Bauer, Maria
A1  - Opitz, Anne
A1  - Filser, Jörg
A1  - Jansen, Hendrik
A1  - Meffert, Rainer H.
A1  - Germer, Christoph T.
A1  - Roewer, Norbert
A1  - Muellenbach, Ralf M.
A1  - Kredel, Markus
T1  - Perioperative redistribution of regional ventilation and pulmonary function: a prospective observational study in two cohorts of patients at risk for postoperative pulmonary complications
JF  - BMC Anesthesiology
N2  - 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.
KW  - Electrical impedance tomography
KW  - General anaesthesia
KW  - Postoperative complications
KW  - Pulmonary function tests
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200730
VL  - 19
ER  - 
TY  - JOUR
A1  - Gilbert, F.
A1  - Schneemann, C.
A1  - Scholz, C. J.
A1  - Kickuth, R.
A1  - Meffert, R. H.
A1  - Wildenauer, R.
A1  - Lorenz, U.
A1  - Kellersmann, R.
A1  - Busch, A.
T1  - Clinical implications of fracture-associated vascular damage in extremity and pelvic trauma
JF  - BMC Muscuskeletal Disorders
N2  - 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.
KW  - endovascular repair
KW  - extremity trauma
KW  - fracture-associated vascular damage
KW  - level of evidence: IV
KW  - surgical trauma room
KW  - pelvic trauma
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176252
VL  - 19
IS  - 404
ER  - 
TY  - JOUR
A1  - Wagner, Johanna
A1  - Eiken, Barbara
A1  - Haubitz, Imme
A1  - Lichthardt, Sven
A1  - Matthes, Niels
A1  - Löb, Stefan
A1  - Klein, Ingo
A1  - Germer, Christoph-Thomas
A1  - Wiegering, Armin
T1  - Suprapubic bladder drainage and epidural catheters following abdominal surgery—a risk for urinary tract infections?
JF  - PLoS ONE
N2  - 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 Würzburg. 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.
KW  - catheters
KW  - epidural block
KW  - bladder
KW  - urinary tract infections
KW  - abdominal surgery
KW  - catheterization
KW  - surgical and invasive medical procedures
KW  - rectum
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177731
VL  - 14
IS  - 1
ER  - 
TY  - JOUR
A1  - Bartmann, Catharina
A1  - Janaki Raman, Sudha R.
A1  - Flöter, Jessica
A1  - Schulze, Almut
A1  - Bahlke, Katrin
A1  - Willingstorfer, Jana
A1  - Strunz, Maria
A1  - Wöckel, Achim
A1  - Klement, Rainer J.
A1  - Kapp, Michaela
A1  - Djuzenova, Cholpon S.
A1  - Otto, Christoph
A1  - Kämmerer, Ulrike
T1  - 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
JF  - Cancer & Metabolism
N2  - 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.
KW  - ketogenic diet
KW  - β-Hydroxybutyrate
KW  - ketone bodies
KW  - breast cancer
KW  - seahorse
KW  - metabolic profile
KW  - chemotherapy
KW  - ionizing radiation
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175607
VL  - 6
IS  - 8
ER  - 
TY  - JOUR
A1  - Burkard, Natalie
A1  - Meir, Michael
A1  - Kannapin, Felix
A1  - Otto, Christoph
A1  - Petzke, Maximilian
A1  - Germer, Christoph-Thomas
A1  - Waschke, Jens
A1  - Schlegel, Nicolas
T1  - Desmoglein2 Regulates Claudin2 Expression by Sequestering PI-3-Kinase in Intestinal Epithelial Cells
JF  - Frontiers in Immunology
N2  - 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.
KW  - Claudin2
KW  - Dsg2
KW  - inflammation
KW  - intestinal barrier
KW  - PI-3-kinase
KW  - inflammatory bowel disease
KW  - desmosome
KW  - tight junction
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-247059
SN  - 1664-3224
VL  - 12
ER  - 
TY  - JOUR
A1  - Diers, J.
A1  - Wagner, J.
A1  - Baum, P.
A1  - Lichthardt, S.
A1  - Kastner, C.
A1  - Matthes, N.
A1  - Matthes, H.
A1  - Germer, C.‐T.
A1  - Löb, S.
A1  - Wiegering, A.
T1  - Nationwide in‐hospital mortality rate following rectal resection for rectal cancer according to annual hospital volume in Germany
JF  - BJS Open
N2  - 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.
KW  - rectal resection
KW  - rectal cancer
KW  - mortality rate
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212878
VL  - 4
IS  - 2
SP  - 310
EP  - 319
ER  - 
TY  - JOUR
A1  - Zaitseva, Olena
A1  - Hoffmann, Annett
A1  - Otto, Christoph
A1  - Wajant, Harald
T1  - Targeting fibroblast growth factor (FGF)-inducible 14 (Fn14) for tumor therapy
JF  - Frontiers in Pharmacology
N2  - 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.
KW  - agonistic antibodies
KW  - cell death
KW  - Fn14
KW  - NFκB
KW  - TNF
KW  - TWEAK
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290238
SN  - 1663-9812
VL  - 13
ER  - 
TY  - JOUR
A1  - Schmidt, Stefanie
A1  - Denk, Sarah
A1  - Wiegering, Armin
T1  - Targeting protein synthesis in colorectal cancer
JF  - Cancers
N2  - 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.
KW  - colorectal cancer
KW  - protein synthesis
KW  - translation initiation
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-206014
SN  - 2072-6694
VL  - 12
IS  - 5
ER  - 
TY  - JOUR
A1  - Hankir, Mohammed K.
A1  - Seyfried, Florian
A1  - Schellinger, Isabel N.
A1  - Schlegel, Nicolas
A1  - Arora, Tulika
T1  - Leaky gut as a potential culprit for the paradoxical dysglycemic response to gastric bypass-associated ileal microbiota
JF  - Metabolites
N2  - 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.
KW  - Roux-en-Y gastric bypass surgery
KW  - intestinal microbiota
KW  - intestinal epithelial barrier
KW  - systemic endotoxemia
KW  - type 2 diabetes
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234085
SN  - 2218-1989
VL  - 11
IS  - 3
ER  -