TY - JOUR A1 - Kredel, Markus A1 - Kunzmann, Steffen A1 - Schlegel, Paul-Gerhardt A1 - Wölfl, Matthias A1 - Nordbeck, Peter A1 - Bühler, Christoph A1 - Lotz, Christopher A1 - Lepper, Philipp M. A1 - Wirbelauer, Johannes A1 - Roewer, Norbert A1 - Muellenbach, Ralf M. T1 - Double Peripheral Venous and Arterial Cannulation for Extracorporeal Membrane Oxygenation in Combined Septic and Cardiogenic Shock JF - American Journal of Case Reports N2 - Background: The use of venoarterial extracorporeal membrane oxygenation (va-ECMO) via peripheral cannulation for septic shock is limited by blood flow and increased afterload for the left ventricle. Case Report: A 15-year-old girl with acute myelogenous leukemia, suffering from severe septic and cardiogenic shock, was treated by venoarterial extracorporeal membrane oxygenation (va-ECMO). Sufficient extracorporeal blood flow matching the required oxygen demand could only be achieved by peripheral cannulation of both femoral arteries. Venous drainage was performed with a bicaval cannula inserted via the left V. femoralis. To accomplish left ventricular unloading, an additional drainage cannula was placed in the left atrium via percutaneous atrioseptostomy (va-va-ECMO). Cardiac function recovered and the girl was weaned from the ECMO on day 6. Successful allogenic stem cell transplantation took place 2 months later. Conclusions: In patients with vasoplegic septic shock and impaired cardiac contractility, double peripheral venoarterial extracorporeal membrane oxygenation (va-va-ECMO) with transseptal left atrial venting can by a lifesaving option. KW - extracorporeal membrane oxygenation KW - myeloid KW - leukemia KW - acute KW - shock KW - cardiogenic KW - septic Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158193 VL - 18 ER - TY - THES A1 - Zeeb, Luisa T1 - Bedeutung der Expression von MMP-1 und MMP-13 beim Barrett assoziierten Adenokarzinom T1 - The role of MMP-1 and MMP-13 expression in Barrett associated adenocarcinoma N2 - Es wird vermutet, dass das ösophageale Adenokarzinom (EAC) durch gastroosophagealen Reflux auf dem Boden des Barrett-Ösophagus (BE) entsteht. Bei der Tumorprogression könnten Matrix-Metalloproteasen eine wichtige Rolle spielen. Die Expression von MMP-1 und MMP-13 wurde im Ösophaguskarziom (n=41 EAC mit BE, n=19 EAC ohne BE, n=10 Plattenepithelkarzinom, ESCC) sowie im nicht-dysplastischen BE (n=18) untersucht. Die Koexpression von MMP-1 und Cdx-2 (intestinale Metaplasie) und die Koexpression von MMP-1 und Ki-67 (Proliferation) wurde mittels Immunhistochemie und auf mRNA-Ebene untersucht. Die Ergebnisse wurde mit klinisch-pathologischen Eigenschaften korreliert. Im gesunden Plattenepithel wurde weder MMP-1 noch MMP-13 exprimiert. In allen EAC ohne BE wurde MMP-1 exprimiert (100%). Im EAC mit BE, war in 95% MMP-1 im EAC nachweisbar. Die Expression von MMP-1 im BE ohne IN lag bei 56%. Das ESCC exprimierte in 60% MMP-1. Bei der quantitativen Analyse zeigten sich 48% MMP-1 positive Zellen im EAC mit BE und 35% im angrenzendem BE (p<0,05). Mit 44% MMP-1 positiver Zellen im EAC ohne BE, lag die Expression signifikant über der im BE mit EAC (p<0,05). Im ESCC (32% MMP-1 positiv) lag eine im Vergleich zu allen EACs signifikant geringere Expression vor. Im BE ohne IN waren 4% der Zellen MMP-1 positiv. Die RT-PCR bestätigte die Ergebnisse der IHC auf mRNA-Ebene. Eine Präparate waren negativ für MMP-13. Die Untersuchung der Koexpression von MMP-1 in Ki-67 positiven Zellen zeigte eine starke direkte Korrelation (r=0,943 für BE und r= 0,811 für EAC). Eine hohe MMP-1 Expression war mit einem positiven Lymphknotenstatus assoziiert aber nicht mit einem schlechterem Überleben (p=0,307). Die Ergebnisse zeigen, dass MMP-1 eine wichtige Rolle bei der Invasion und Metastasierung des Barrett assoziierten EAC spielen könnte. Die Assoziation eines positiven Lymphknotenstatus mit hoher MMP-1-Expression spricht dafür, dass MMP-1 ein wichtiger Faktor bei der malignen Progression sein könnte. N2 - Background: Esophageal adenocarcinomas (EACs) arise due to gastroesophageal reflux, with Barrett’s esophagus (BE) regarded as precancerous lesion. Matrix metalloproteinases (MMPs) might play a role during the multistep carcinogenetic process. Methods: Expression of MMP-1 and -13 was analyzed in esophageal cancer (n = 41 EAC with BE, n = 19 EAC without BE, and n = 10 esophageal squamous-cell carcinomas, ESCC), furthermore in BE without intraepithelial neoplasia (IN) (n = 18), and the cell line OE-33. MMP-1 was co-labelled with Ki-67 (proliferation), Cdx-2 (marker for intestinal metaplasia, BE) and analyzed on mRNA level. MMP-1 staining results were correlated with clinicopatholocical parameters. Results: On protein level, MMP-1 expression was found in 39 of 41 (95%) EAC with BE, in 19 of 19 (100%) EAC without BE, in 6 of 10 (60%) ESCC, and in 10 of 18 (56%) BE without IN. No expression of MMP-13 was found in these specimens. Quantification showed 48% MMP-1 positive cells in EAC with BE, compared to 35% in adjacent BE (p < 0.05), 44% in EAC without BE, 32% in ESCC, and 4% in BE without IN. Immunofluorescence double staining experiments revealed increased MMP-1 expressing in proliferating cells (MMP-1+/Ki-67+) (r = 0.943 for BE and r = 0.811 for EAC). On mRNA-level, expression of MMP-1 was significantly higher in EAC compared to BE (p = 0.01) and confirmed immunohistochemical staining results. High MMP-1 levels were associated with lymph node metastases but not with poorer survival (p = 0.307). Conclusions: Our findings suggest that MMP-1 plays a role as preinvasive factor in BE-associated EAC. Expression of MMP-1 in proliferating BE and EAC cells suggest malignant proliferation following the clonal expansion model. MMP-13 seems to play no important role in the multistep carcinogenetic process. KW - Adenocarcinom KW - Speiseröhrenkrebs KW - Metalloproteinasen KW - Barrettösophagus Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-278723 ER - TY - JOUR A1 - Baur, Johannes A1 - Büntemeyer, Tjark-Ole A1 - Megerle, Felix A1 - Deutschbein, Timo A1 - Spitzweg, Christine A1 - Quinkler, Marcus A1 - Nawroth, Peter A1 - Kroiss, Matthias A1 - Germer, Christoph-Thomas A1 - Fassnacht, Martin A1 - Steger, Ulrich T1 - Outcome after resection of Adrenocortical Carcinoma liver metastases: a retrospective study JF - BMC Cancer N2 - Background: Metastatic Adrenocortical Carcinoma (ACC) is a rare malignancy with a poor 5-year-survival rate (<15%). A surgical approach is recommended in selected patients if complete resection of distant metastasis can be achieved. To date there are only limited data on the outcome after surgical resection of hepatic metastases of ACC. Methods: A retrospective analysis of the German Adrenocortical Carcinoma Registry was conducted. Patients with liver metastases of ACC but without extrahepatic metastases or incomplete tumour resection were included. Results: Seventy-seven patients fulfilled these criteria. Forty-three patients underwent resection of liver metastases of ACC. Complete tumour resection (R0) could be achieved in 30 (69.8%). Median overall survival after liver resection was 76.1 months in comparison to 10.1 months in the 34 remaining patients with unresected liver metastases (p < 0.001). However, disease free survival after liver resection was only 9.1 months. Neither resection status (R0/R1) nor extent of liver resection were significant predictive factors for overall survival. Patients with a time interval to the first metastasis/recurrence (TTFR) of greater than 12 months or solitary liver metastases showed significantly prolonged survival. Conclusions: Liver resection in the case of ACC liver metastases can achieve long term survival with a median overall survival of more than 5 years, but disease free survival is short despite metastasectomy. Time to recurrence and single versus multiple metastases are predictive factors for the outcome. KW - Adrenocortical Carcinoma KW - liver resection KW - retrospective study KW - prognosis KW - survival analysis Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159409 VL - 17 IS - 522 ER - TY - JOUR A1 - Kress, Sebastian A1 - Baur, Johannes A1 - Otto, Christoph A1 - Burkard, Natalie A1 - Braspenning, Joris A1 - Walles, Heike A1 - Nickel, Joachim A1 - Metzger, Marco T1 - Evaluation of a miniaturized biologically vascularized scaffold in vitro and in vivo JF - Scientific Reports N2 - In tissue engineering, the generation and functional maintenance of dense voluminous tissues is mainly restricted due to insufficient nutrient supply. Larger three-dimensional constructs, which exceed the nutrient diffusion limit become necrotic and/or apoptotic in long-term culture if not provided with an appropriate vascularization. Here, we established protocols for the generation of a pre-vascularized biological scaffold with intact arterio-venous capillary loops from rat intestine, which is decellularized under preservation of the feeding and draining vascular tree. Vessel integrity was proven by marker expression, media/blood reflow and endothelial LDL uptake. In vitro maintenance persisted up to 7 weeks in a bioreactor system allowing a stepwise reconstruction of fully vascularized human tissues and successful in vivo implantation for up to 4 weeks, although with time-dependent decrease of cell viability. The vascularization of the construct lead to a 1.5× increase in cellular drug release compared to a conventional static culture in vitro. For the first time, we performed proof-of-concept studies demonstrating that 3D tissues can be maintained within a miniaturized vascularized scaffold in vitro and successfully implanted after re-anastomosis to the intrinsic blood circulation in vivo. We hypothesize that this technology could serve as a powerful platform technology in tissue engineering and regenerative medicine. KW - biological models KW - translational research Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176343 VL - 8 IS - 4719 ER - TY - JOUR A1 - Wallstabe, Julia A1 - Bussemer, Lydia A1 - Groeber-Becker, Florian A1 - Freund, Lukas A1 - Alb, Mirian A1 - Dragan, Mariola A1 - Waaga-Gasser, Ana Maria A1 - Jakubietz, Rafael A1 - Kneitz, Hermann A1 - Rosenwald, Andreas A1 - Rebhan, Silke A1 - Walles, Heike A1 - Mielke, Stephan T1 - Inflammation-Induced Tissue Damage Mimicking GvHD in Human Skin Models as Test Platform for Immunotherapeutics JF - ALTEX N2 - Due to the rapidly increasing development and use of cellular products, there is a rising demand for non-animal-based test platforms to predict, study and treat undesired immunity. Here, we generated human organotypic skin models from human biopsies by isolating and expanding keratinocytes, fibroblasts and microvascular endothelial cells and seeding these components on a collagen matrix or a biological vascularized scaffold matrix in a bioreactor. We then were able to induce inflammation-mediated tissue damage by adding pre-stimulated, mismatched allogeneic lymphocytes and/or inflammatory cytokine-containing supernatants histomorphologically mimicking severe graft versus host disease (GvHD) of the skin. This could be prevented by the addition of immunosuppressants to the models. Consequently, these models harbor a promising potential to serve as a test platform for the prediction, prevention and treatment of GvHD. They also allow functional studies of immune effectors and suppressors including but not limited to allodepleted lymphocytes, gamma-delta T cells, regulatory T cells and mesenchymal stromal cells, which would otherwise be limited to animal models. Thus, the current test platform, developed with the limitation that no professional antigen presenting cells are in place, could greatly reduce animal testing for investigation of novel immune therapies. KW - inflammation-induced tissue demage KW - immunotherapeutics Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229974 VL - 37 IS - 3 ER - TY - JOUR A1 - Kippnich, Maximilian A1 - Schorscher, Nora A1 - Kredel, Markus A1 - Markus, Christian A1 - Eden, Lars A1 - Gassenmaier, Tobias A1 - Lock, Johann A1 - Wurmb, Thomas T1 - Dual‑room twin‑CT scanner in multiple trauma care: first results after implementation in a level one trauma centre JF - European Journal of Trauma and Emergency Surgery N2 - Purpose The trauma centre of the Wuerzburg University Hospital has integrated a pioneering dual-room twin-CT scanner in a multiple trauma pathway. For concurrent treatment of two trauma patients, two carbon CT examination and intervention tables are positioned head to head with one sliding CT-Gantry in the middle. The focus of this study is the process of trauma care with the time to CT (tCT) and the time to operation (tOR) as quality indicator. Methods All patients with suspected multiple trauma, who required emergency surgery and who were initially diagnosed by the CT trauma protocol between 05/2018 and 12/2018 were included. Data relating to time spans (tCT and tOR), severity of injury and outcome was obtained. Results 110 of the 589 screened trauma patients had surgery immediately after finishing primary assessment in the ER. The ISS was 17 (9–34) (median and interquartile range, IQR). tCT was 15 (11–19) minutes (median and IQR) and tOR was 96.5 (75–119) minutes (median and IQR). In the first 30 days, seven patients died (6.4%) including two within the first 24 h (2%). There were two ICU days (1–6) (median and IQR) and one (0–1) (median and IQR) ventilator day. Conclusion The twin-CT technology is a fascinating tool to organize high-quality trauma care for two multiple trauma patients simultaneously KW - trauma centre KW - trauma management KW - resuscitation time KW - dual-room whole-body CT Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232390 SN - 1863-9933 ER - TY - JOUR A1 - Bachmann, Julia A1 - Ehlert, Elias A1 - Becker, Matthias A1 - Otto, Christoph A1 - Radeloff, Katrin A1 - Blunk, Torsten A1 - Bauer-Kreisel, Petra T1 - Ischemia-like stress conditions stimulate trophic activities of adipose-derived stromal/stem cells JF - Cells N2 - Adipose-derived stromal/stem cells (ASCs) have been shown to exert regenerative functions, which are mainly attributed to the secretion of trophic factors. Upon transplantation, ASCs are facing an ischemic environment characterized by oxygen and nutrient deprivation. However, current knowledge on the secretion capacity of ASCs under such conditions is limited. Thus, the present study focused on the secretory function of ASCs under glucose and oxygen deprivation as major components of ischemia. After exposure to glucose/oxygen deprivation, ASCs maintained distinct viability, but the metabolic activity was greatly reduced by glucose limitation. ASCs were able to secrete a broad panel of factors under glucose/oxygen deprivation as revealed by a cytokine antibody array. Quantification of selected factors by ELISA demonstrated that glucose deprivation in combination with hypoxia led to markedly higher secretion levels of the angiogenic and anti-apoptotic factors IL-6, VEGF, and stanniocalcin-1 as compared to the hypoxic condition alone. A conditioned medium of glucose/oxygen-deprived ASCs promoted the viability and tube formation of endothelial cells, and the proliferation and migration of fibroblasts. These findings indicate that ASCs are stimulated by ischemia-like stress conditions to secrete trophic factors and would be able to exert their beneficial function in an ischemic environment. KW - adipose-derived stromal/stem cells (ASCs) KW - regenerative medicine KW - secretion KW - trophic factors KW - ischemia KW - glucose starvation KW - hypoxia Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211233 SN - 2073-4409 VL - 9 IS - 9 ER - TY - THES A1 - Deckelmann, Jana Verena T1 - Einfluss bariatrischer Operationen auf das Geruchsempfinden morbid adipöser Patienten T1 - Influence of bariatric surgery on olfactory function of morbidly obese patients N2 - Weltweit steigt die Anzahl der morbid adipösen Menschen stetig an. Dies führt zu einer Zunahme der medizinischen und psychosozialen Komplikationen des Einzelnen und der gesundheitsökonomischen Belastung der Gesellschaft. Kosteneffektive und langfristige Therapiekonzepte sind dringend notwendig. Die bariatrische Chirurgie stellt die einzige Therapieoption der morbiden Adipositas dar, mit der eine langfristige Gewichtsreduktion und damit eine signifikante Verbesserung der adipositasassoziierten Begleiterkrankungen erreicht werden kann. Die Mechanismen der Gewichtsabnahme im Rahmen einer bariatrischen Operation sind noch nicht ausreichend erforscht und verstanden. Hinweise Das Geruchsempfinden, als wichtiger Bestandteil der Nahrungsauswahl, könnte durch eine Veränderung in Folge einer bariatrischen Operation einen Einfluss auf die Gewichtsreduktion haben. In der vorliegenden Arbeit wurde mittels der Sniffin´sticks das Geruchsempfinden morbid adipöser Menschen in Zusammenhang mit einer bariatrischen Operation (RYGB, n=15 vs. SG, n=15) untersucht (0-1-6-12-24 Wochen). Als Kontrollgruppe dienten morbid adipöse Probanden unter konservativer Therapie (n=12). Der Ausgangs-BMI der SG-Gruppe (56,04 ± 7,09 kg/m2) war im Vergleich zur RYGB- Gruppe (48,71 ± 6,49 kg/m2) und der konservativ behandelten Gruppe (50,35 ± 6,78 kg/m2) signifikant höher (p= 0,011*). Das Ausmaß der Gewichtsabnahme der beiden operierten Gruppen zeigte keine signifikanten Unterschiede (p=0,87). Die konservativ behandelte Gruppe nahm praktisch kein Gewicht ab. Der Ausgangs-SDI-Wert der SG-Gruppe (27,09 ± 3,93) war im Vergleich zur RYGB- Gruppe (32,61 ± 3,64) und zur konservativ behandelten Gruppe (32,15 ± 5,32) signifikant niedriger. Die SG-Gruppe erreichte nach 6 Monaten SDI-Werte von 31,06 ± 3,49, was einen signifikanten Anstieg darstellt (p=0,040*). Die SG-Gruppe hatte anfangs signifikant niedrigere Schwellenwerte als die RYGB- Gruppe (p=0,0050**). Auch im Vergleich zu den Patienten der konservativ behandelten Gruppe erzielte die SG-Gruppe präoperativ signifikant niedrigere Schwellenwerte (p=0,0026). Ein signifikanter Anstieg der Schwellenwerte innerhalb von 6 Monaten zeigte sich nur in der SG-Gruppe (p=0,00061***). Die Mittelwerte lagen präoperativ bei 4,71 ± 1,31 und nach sechs Monaten bei 7,29 ± 2,11. Die RYGB-Gruppe erzielte präoperativ Mittelwerte von 6,82 ± 1,85 und nach sechs Monaten von 7,8 ± 1,41, was ein knapp nicht signifikanter Anstieg ist (p=0,054). Im Vergleich der Diskriminationswerte zeigte sich lediglich ein knapp signifikanter Anstieg der konservativ behandelten Gruppe (p=0,035*). Alle weiteren Werte waren nicht signifikant. Bezüglich der Identifikationswerte konnten keine signifikanten Veränderungen beobachtet werden. Mit abnehmendem BMI nahm der SDI-Wert der SG-Gruppe signifikant zu (p=0,0074**), was bei der RYGB-Gruppe nicht zutraf (p=0,20). Die Ergebnisse dieser Arbeit zeigen, dass das Geruchsempfinden durch einen wesentlichen Gewichtsverlust an sich nicht beeinflusst wird. Die Daten deuten darauf hin, dass sich die Riechfunktion nach einer Sleeve Gastrectomy im Vergleich zu einer Roux-Y gastric bypass verbessert. Es scheint folglich Mechanismen zu geben, die von der Operationsmethode abhängen. In der Zukunft sind weitere Forschungsanstrengungen nötig, um die Mechanismen der Gewichtsabnahme nach bariatrischer Operation und insbesondere die Veränderungen des Geruchsempfindens in Abhängigkeit des Operationsverfahrens besser verstehen zu können. N2 - Changes of food preference toward foods with low caloric density have been demonstrated after bariatric surgery and may contribute to sustained body weight loss. It has been hypothesized that olfactory perception as an integral part of food selection might be altered after bariatric surgery. Sniffin' Sticks® were used to investigate the olfactory perception of morbidly obese patients undergoing either Roux-en-Y gastric bypass (RYGB, n = 15) or sleeve gastrectomy (SG, n = 15) before 1, 6, 12, and 24 weeks after surgery. Obese patients without surgical intervention served as controls (CG, n = 15). Results are presented using the testing odor threshold, discrimination, and identification score (TDI; higher scores indicate better olfactory perception). Body weight loss was recorded. Initial BMI of the SG group (56.04 ± 7.096 kg m(-2)) was higher compared to the BMI of the RYGB (48.71 ± 6.49 kg m(-2)) and CG (50.35 ± 6.78 kg m(-2)); p = 0.011. Body weight loss among the surgical groups was not different (p = 0.011) while controls did not lose weight. Mean baseline TDI scores were significantly lower in the SG group 27.1 ± 3.9 vs. 32.6 ± 3.6 (RYGB) and 32.1 ±  5.3 (CG), respectively, whereas there were after 24 weeks no changes in RYGB and CG patients; the TDI score in the SG group increased significantly to 31.1 ± 3.5 (p < 0.01). Our data suggest that a substantial body weight loss per se does not affect olfactory perception. However, our results point after sleeve gastrectomy but not Roux-en-Y gastric bypass. KW - Adipositas KW - Geruchsmpfinden KW - bariatrische Operation Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157076 ER - TY - JOUR A1 - Kelm, Matthias A1 - Anger, Friedrich T1 - Mucosa and microbiota – the role of intrinsic parameters on intestinal wound healing JF - Frontiers in Surgery N2 - Mucosal healing in the gut is an essential process when it comes to chronic inflammatory disorders such as inflammatory bowel diseases (IBD) but also to the creation of intestinal anastomosis. Despite an improvement of surgical techniques, the rates of anastomotic leakage remain substantial and represent a significant health-care and socio-economic burden. Recent research has focused on intrinsic factors such as mucosal linings and differences in the intestinal microbiota and identified specific endoluminal bacteria and epithelial proteins which influence intestinal wound healing and re-establishment of mucosal homeostasis. Despite the lack of large clinical studies, previous data indicate that the identified bacteria such as aerotolerant lactobacilli or wound-associated Akkermansia muciniphila as well as epithelial-expressed sialyl Lewis glycans or CD47 might be critical for wound and anastomotic healing in the gut, thus, providing a potential novel approach for future treatment strategies in colorectal surgery and IBD therapy. Since microbiota and mucosa are interacting closely, we outline the current discoveries about both subsets in this review together to demonstrate the significant interplay KW - epithelial cells KW - mucosal healing (MH) KW - microbiota KW - inflammatory bowel disease KW - anastomotic leakage Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-282096 SN - 2296-875X VL - 9 ER - TY - THES A1 - Büntemeyer, Tjark-Ole T1 - Wertigkeit der Leberresektion bei Metastasen des Nebennierenkarzinoms - Analyse anhand des Deutschen Nebennierenkarzinom-Registers T1 - Role of Liverresection in adrenocortical carcinoma liver metastases N2 - Patienten mit einem hepatisch metastasierten Nebennierenkarzinom und ohne Hinweise auf extrahepatische Tumormanifestationen profitieren von einer Operation im Hinblick auf das Gesamtüberleben. Dies gilt sowohl für synchron- als auch für metachron metastasierte Patienten. N2 - Liver resection in case of ACC liver metastases can achieve long term survival, but disease free survival is short despite metastasectomy. Time to recurrence is a predictive factor for the outcome. KW - Nebenniere KW - Leberresektion KW - Nebennierenkarzinom Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-155743 ER -