The Molecular Mechanism of Polymer Formation of Farnesylated Human Guanylate-binding Protein 1 - Sistemich, Linda; Kutsch, Miriam; Hämisch, Benjamin; Zhang, Ping; Shydlovskyi, Sergii; Britzen-Laurent, Nathalie; Stürzl, Michael; Huber, Klaus; Herrmann, Christian (Journal of Molecular Biology, 2020)
The human guanylate-binding protein 1 (hGBP1) belongs to the dynamin superfamily proteins and represents a key player in the innate immune response. Farnesylation at the C-terminus is required for hGBP1’s activity against microbial pathogens, as well as for its antiproliferative and antitumor activity. The farnesylated hGBP1 (hGBP1fn) retains many characteristics of the extensively studied nonfarnesylated protein and gains additional abilities like binding to lipid membranes and formation of hGBP1fn polymers. These polymers are believed to serve as a protein depot, making the enzyme immediately available to fight the invasion of intracellular pathogens. Here we study the molecular mechanism of hGBP1 polymer formation as it is a crucial state of this enzyme, allowing for a rapid response demanded by the biological function. We employ Förster resonance energy transfer in order to trace intra and intermolecular distance changes of protein domains. Light scattering techniques yield deep insights into the changes in size and shape. The GTP hydrolysis driven cycling between a closed, farnesyl moiety hidden state and an opened, farnesyl moiety exposed state represents the first phase, preparing the molecule for polymerization. Within the second phase of polymer growth, opened hGBP1 molecules can be incorporated in the growing polymer where the opened structure is stabilized, similar to a surfactant molecule in a micelle, pointing the farnesyl moieties into the hydrophobic center and positioning the head groups at the periphery of the polymer. We contribute the molecular mechanism of polymer formation, paving the ground for a detailed understanding of hGBP1 function.
CRIS-Team Scopus Importer:2020-03-17
Keywords: dimer; GBPs; lag phase; large GTPase; polymerization

The Multifaceted Functionality of Plasmacytoid Dendritic Cells in Gastrointestinal Cancers: A Potential Therapeutic Target? - Hansen, Frederik; David, Paul; Weber, Georg (Cancers, 2024)
Gastrointestinal (GI) tumors pose a significant global health burden, necessitating the exploration of novel therapeutic approaches. Plasmacytoid dendritic cells (pDCs) play a crucial role in tumor immunity, exhibiting both anti-tumor and pro-tumor effects. This review aims to summarize the role of pDCs in different types of GI tumors and assess their potential as therapeutic targets. In gastric cancer, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma, increased infiltration of pDCs was associated with a worse outcome, whereas in esophageal cancer, pancreatic cancer, and colorectal cancer, pDC infiltration improved the outcome. Initial animal studies of gastric cancer and hepatocellular carcinoma showed that pDCs could be a successful therapeutic target. In conclusion, pDCs play a multifaceted role in GI tumors, influencing both anti-tumor immunity and tumor progression. Further research is needed to optimize their clinical application and explore combinatorial approaches.
CRIS-Team Scopus Importer:2024-07-12
Keywords: cholangiocarcinoma; colorectal cancer; esophageal cancer; gastric cancer; hepatocellular carcinoma; pancreatic cancer; pDCs; plasmacytoid dendritic cells

The novel allele, HLA-B*08:113, identified in a German cord blood donor and his mother - Strobel, Joachim; Ringwald, J.; Hauck-Dlimi, B.; Eckstein, Reinhold; Zingsem, Jürgen (Tissue Antigens, 2014)
The novel allele HLA-B*08:113 identified in two related individuals of Caucasian origin is described.
EVALuna2:15979

The Nuclear Receptor ROR-Alpha As a Key Checkpoint of Tissue Repair - Kagwiria, Rosebeth; Liang, Ruifang; Chen, Chih-Wei; Burris, Thomas; Schett, Georg; Distler, Jörg (2017)
EVALuna2:33434

The opportunistic pathogen Aspergillus fumigatus coats its infectious propagules with antimicrobial peptides - Duemig, Michaela; Binder, Johannes; Gaculenko, Anastasia; Daul, F.; Hasenberg, M.; Gunzer, M.; Krappmann, Sven (2018)
EVALuna2:213342

The outcome of patients with inflammatory bowel disease-associated colorectal cancer is not worse than that of patients with sporadic colorectal cancer-a matched-pair analysis of survival - Vitali, Francesco; Wein, Axel; Rath, Timo; Eckstein, Markus; Neufert, Clemens; Siebler, Jürgen; Atreya, Raja; Hartmann, Arndt; Hohenberger, Werner; Weber, Klaus; Neurath, Markus; Grützmann, Robert; et al. (International Journal of Colorectal Disease, 2021)
Purpose Patients with inflammatory bowel disease (IBD) have an increased risk for colorectal cancer (CRC). In IBD patients, cancer is often diagnosed in advanced stages and conflicting data on survival compared to sporadic CRC have been reported. The aim of this study was to directly compare clinical characteristics and prognosis of patients with IBD-CRC and sporadic CRC. Methods The clinical and pathological data of 63 patients with IBD-CRC and 3710 patients with sporadic CRC treated at the University Hospital of Erlangen between 1995 and 2015 were compared. Forty-seven M0 patients with IBD were matched with sporadic CRC patients after curative resection (R0) according to tumor localization, stage, sex, and year of treatment. Overall and disease-free survival were compared. Results Sixty-three patients presented IBD-CRC. Fifty were affected with ulcerative colitis (UC) and 13 with Crohn's disease (CD). CRC was diagnosed within 1.45 years since last endoscopic surveillance. Twelve patients (19%) had a diagnosis of primary sclerosing cholangitis. In matched analysis, IBD patients were diagnosed with CRC at younger age compared to sporadic CRC and were more likely to have right-sided CRC (40% versus 23.3%) and rare histological subtypes (19% versus 9.2%). No differences in 5-year overall (78.7 versus 80.9 months) and 5-year disease-free survival (74.5 versus 70.2 months) were noted. Conclusion IBD-CRC patients were younger and more frequently had right-sided carcinomas compared to sporadic CRC. CRC in IBD patients did not show survival difference compared to matched-pair sporadic CRC patients without distant metastases after curative resection. Surveillance might be important for early detection of CRC in IBD patients.
CRIS-Team WoS Importer:2021-12-17

The place of new oral anticoagulants in travel medicine - Ringwald, Juergen; Grauer, Martin; Eckstein, Reinhold; Jelinek, Tomas (Travel Medicine and Infectious Disease, 2014)
New oral anticoagulants are increasingly used instead of vitamin K antagonists or low molecular weight heparins. Hence, more individuals treated with new oral anticoagulants will seek travel medicine advice. Travel medicine experts should therefore become familiar with new oral anticoagulants and with their impact and role in travel medicine. This review summarizes pharmacological characteristics and approved indications of dabigatran, rivaroxaban and apixaban, and highlights their relevance for travellers on permanent oral anticoagulation and for the prophylaxis of travellers' thrombosis. Compared to vitamin K antagonists, the new oral anticoagulants have many advantages: they do not have interactions with food, they have lower potential for drug-drug interactions and do not require regularly performed laboratory tests. The oral administration, obviating the need to carry needles and syringes during travel may give the new oral anticoagulants a further advantage over low molecular weight heparins. Clinical experience with the new oral anticoagulants, however, is still rather limited and there is concern regarding the clinical management of patients treated with new oral anticoagulants who suffer from severe bleeding or who need urgent invasive procedures. Overall, it remains an individual decision based on a risk/benefit analysis as to whether or not patients on long-term treatment with vitamin K antagonists should be switched to new oral anticoagulants for intended travel. Further caution is also indicated so that the availability of orally administered new anticoagulants should not lead to undifferentiated and unjustified prescription of anticoagulants for the prophylaxis of traveller's thrombosis.
EVALuna2:15976

The predictive value of microperfusion assessments for the follow-up of tibial bypass grafts - Meyer, Alexander; Yagshyyev, Shatlyk; Lang, Werner; Rother, Ulrich (Journal of Vascular Surgery, 2021)
Objective: We conducted a prospective evaluation of microperfusion parameters after tibial bypass surgery was performed. Differences between grafts with occlusions during follow-up and patent grafts were analyzed in relation to the pedal arch quality. Methods: Patients receiving tibial bypass grafts for chronic limb-threatening ischemia from 2019 to 2020 were included. Assessment of microcirculation (parameters: hemoglobin oxygen saturation [sO2] and flow) was done by laser Doppler flowmetry and white light spectrometry (oxygen-to-see), supine and in elevation, whereas the macrocirculation was evaluated by the ankle-brachial index and duplex ultrasound examination. The quality of run-off was graded for each patient. Measurements were performed preoperatively, 1 day postoperatively, and after 6 months. Patients with graft occlusions during follow-up (OCCLUDED) and patients without occlusions (OPEN) were compared. Results: We included 42 patients (13 women, 29 men; mean age, 76.1 years; range, 60-89 years) were included. The patency of all grafts 1 day after the operation was confirmed by ultrasound examination. The overall analysis of the microcirculation showed significant changes in both the supine and elevated leg position between measurements taken preoperatively, 1 day after the operation, and after 6 months for the parameters sO2 and FLOW (sO2 supine, P = .001; sO2 elevated, P < .001; FLOW supine, P < .001; FLOW elevated, P < .001). The comparison of the values 1 day after the operation yielded significantly decreased microperfusion parameters (both O2 and FLOW) in the group that developed bypass occlusion in the later follow-up period (sO2 supine: OCCLUDED, 35.7% [7.3-65.0] and OPEN, 48.7% [25.0-72.3] P = .011; FLOW supine: OCCLUDED, 27.7 A.U. [12.7-52.7] and OPEN, 57.3 A.U. [16.0-106.7], P = .008). No significant differences in the severity of the arch impairment was found between the OPEN and OCCLUDED groups (P = .651). Absolute values of the parameters sO2 and flow showed no correlation with the pedal arch classification. Conclusions: Significantly poorer microperfusion was detected postoperatively in patients with later occurrence of graft occlusions despite patent grafts on the first postoperative day. Microperfusion measurements might be a possible tool for the prediction of graft failure.
CRIS-Team Scopus Importer:2021-10-29
Keywords: Bypass surgery; Chronic limb-threating ischemia; Graft occlusion; Microperfusion; O2C

The Probability of Incomplete or Hypoplastic Circle of Willis Reply - Rueffer, Andre; Tischer, Philipp; Cesnjevar, Robert; Juengert, Joerg (Annals of Thoracic Surgery, 2019)
CRIS-Team WoS Importer:2019-05-03

The prognostic value of the number of harvested negative lymph nodes in patients treated by esophagectomy with or without neoadjuvant chemoradiation - Brunner, Maximilian; Merkel, Susanne; Krautz, Christian; Kersting, Stephan; Grützmann, Robert; Weber, Georg (Anticancer Research, 2020)
Background/Aim: The prognostic value of the number of harvested negative lymph nodes (NLNs) in patients with node-negative esophageal carcinoma treated by esophagectomy with or without neoadjuvant chemoradiation is unclear. Patients and Methods: A total of 136 patients who underwent oncological esophagectomy with two-field lymphadenectomy from 1995 to 2014 were analyzed regarding the prognostic impact of NLNs. 86 patients received primary surgery (group 1) and 50 patients had preoperative chemoradiation followed by surgery (group 2). Results: The 5-year overall survival (OS) was 61.1%. Median lymph node harvest was significantly higher in group 1 (39 vs. 34 in group 2, p=0.007). In group 1, patients with a higher number of negative lymph nodes (>40) had a better OS [57.6% vs. 78.9%, HR=0.5 (0.3-0.9), p=0.026], whereas there was no significant difference in group 2 using the same cutoff (47.6% vs. 66.7%, p=0.476). Conclusion: The number of NLNs is an independent prognostic factor for patients with esophageal carcinoma treated by primary esophagectomy, but not in patients after neoadjuvant chemoradiation.
CRIS-Team Scopus Importer:2020-05-15
Keywords: Esophageal carcinoma; Lymphadenectomy; Neoadjuvant chemoradiation; Oncological esophagectomy; Prognosis; Survival

The Protein S Erlangen Mutation PROS1c.1904T>C (F635S) Suppresses Secretion. - Reißig, Julian; Cunningham, Sarah; Wandersee, Alexandra; Brox, Regine; Achenbach, Susanne; Strobel, Julian; Hackstein, Holger; Schneider, Sabine (Clinical Laboratory, 2024)
BACKGROUND: The recently identified PROS1 mutation Protein S Erlangen c.1904T>C, resulting in amino acid exchange F635S, is associated with severe quantitative protein S (PS) deficiency and clinical thrombosis. It was hypothesized that this deficiency is due to a secretion defect [1]. This report aims to further elucidate the potential secretion defect of PS Erlangen. METHODS: Coding sequences (CDS) of wild type (WT) PROS1 (encoding PS) and mutated PROS1c.1904T>C (encoding PSF635S) were cloned in front of the CDS of green fluorescent protein (GFP), and the respective plasmids were introduced into HEK293T cells. PROS1-GFP and PROS1c.1904T>C-GFP expressing HEK293T cell lines were analyzed by confocal laser scanning microscopy and western blot for cellular proteins and proteins secreted to the growth medium. RESULTS: Western blot analysis revealed a significantly reduced secretion of PSF635S compared to WT PS. This observation was confirmed by the detection of mutant PSF635S-GFP fusion exclusively in the endoplasmic reticulum (ER), while PS-GFP passed through the entire secretory pathway, as indicated by the localization within both the ER and Golgi apparatus. CONCLUSIONS: The Protein S Erlangen mutation results in type I PS deficiency caused by a secretion defect.
EVALuna2:562075
Keywords: point mutation; PROS1; secretion pathway; Protein S deficiency; secretion defect

The rate of cholangiocarcinoma in Caroli Disease A German multicenter study - Fard-Aghaie, Mohammad H.; Makridis, Georgios; Reese, Tim; Feyerabend, Bernd; Wagner, Kim C.; Schnitzbauer, Andreas; Bechstein, Wolf O.; Oldhafer, Felix; Kleine, Moritz; Klempnauer, Jürgen; Rolinger, Jens; Nadalin, Silvio; et al. (Hpb, 2021)
Background: Caroli Disease (CD) and Caroli Syndrome (CS) are rare disorders presenting with dilation of the intrahepatic bile ducts. CD/CS are associated with cholangiocarcinoma (CCA). However, the true incidence of CCA is still unclear, although it may serve as an indication for surgery. In this paper, we analyzed (I) the incidence of CCA in German centers, (II) reviewed our single center population together with its clinical presentation and (III) performed a thorough literature review. Methods: 17 large HPB-centers across Germany were contacted and their patients after surgical treatment due to CD/CS with histopathology were included. Medline search for all studies published in English or German literature was performed. Patients who underwent surgery at our department between 2012 and 2020 due to CD or CS were analyzed. Results: In the multicenter study, 79 patients suffered from CD and 119 patients from CS, with a total number of 198 patients. In 14 patients, CCA was found (Overall: 7,1%; CD: 6,3%, CS 7,6%). Between 2012 and 2020, 1661 liver resections were performed at our department. 14 patients underwent surgery due to CD or CS. Histological examination showed synchronous cholangiocarcinoma in one patient. The literature review revealed a CCA-rate of 7,3% in large series, whereas in case reports a rate of 6,8% was found. Conclusion: There is risk of malignant transformation and patients with CD might also benefit from resection due to improvement of symptoms. Therefore, resection is strongly advised. As certain patients with CS require transplantation, treatment should not be guided by the relatively low rate of CCA but by the concomitant diseases that come along with hepatic failure.
CRIS-Team Scopus Importer:2021-07-30
Keywords: Caroli disease; Caroli Syndrome; Intrahepatic bile duct dilation; Liver surgery

The rationale behind complete mesocolic excision (CME) and a central vascular ligation for colon cancer in open and laparoscopic surgery : proceedings of a consensus conference - Sondenaa, K.; Quirke, P.; Hohenberger, Werner; Sugihara, K.; Kobayashi, H.; Kessler, H.; Brown, G.; Tudyka, V.; D'Hoore, A.; Kennedy, R. H.; West, N. P.; Kim, S. H.; et al. (International Journal of Colorectal Disease, 2014)
It has been evident for a while that the result after resection for colon cancer may not have been optimal. Several years ago, this was showed by some leading surgeons in the USA but a concept of improving results was not consistently pursued. Later, surgeons in Europe and Japan have increasingly adopted the more radical principle of complete mesocolic excision (CME) as the optimal approach for colon cancer. The concept of CME is a similar philosophy to that of total mesorectal excision for rectal cancer and precise terminology and optimal surgery are key factors.There are three essential components to CME. The main component involves a dissection between the mesenteric plane and the parietal fascia and removal of the mesentery within a complete envelope of mesenteric fascia and visceral peritoneum that contains all lymph nodes draining the tumour area (Hohenberger et al., Colorectal Disease 11:354-365, 2009; West et al., J Clin Oncol 28:272-278, 2009). The second component is a central vascular tie to completely remove all lymph nodes in the central (vertical) direction. The third component is resection of an adequate length of bowel to remove involved pericolic lymph nodes in the longitudinal direction.The oncological rationale for CME and various technical aspects of the surgical management will be explored.The consensus conference agreed that there are sound oncological hypotheses for a more radical approach than has been common up to now. However, this may not necessarily apply in early stages of the tumour stage. Laparoscopic resection appears to be equally well suited for resection as open surgery.
EVALuna2:15165

The relevance of the "angiosome" concept for treatment of chronic limb-threatening ischemia - Rother, Ulrich; Günther, Josefine; Meyer, Alexander; Lang, Werner; Behrendt, C.; Gortz, H.; Rumenapf, G.; Uhl, C. (Gefässchirurgie, 2020)
Background The angiosome concept as a role model for decision making on revascularization in patients with chronic limb-threatening ischemia and the necessary lower leg revascularization has recently been the subject of controversial discussion in the literature. Methods A narrative literature search was conducted in PubMed (US National Library of Medicine). Results and conclusion There are a large number of retrospective studies showing the different relevance of this concept depending on the selected treatment procedure (open surgery vs. endovascular). Comorbidities also have an influence on the relevance. This article summarizes the current literature on the angiosome-oriented revascularization based on the selected treatment procedure and possible pre-existing comorbidities.
CRIS-Team WoS Importer:2021-01-08

The Role of Exosomes in Pancreatic Cancer - Lan, Bin; Zeng, Siyuan; Grützmann, Robert; Pilarsky, Christian (International Journal of Molecular Sciences, 2019)
Pancreatic cancer remains one of the deadliest cancers in the world, as a consequence of late diagnosis, early metastasis and limited response to chemotherapy, under which conditions the potential mechanism of pancreatic cancer progression requires further study. Exosomes are membrane vesicles which are important in the progression, metastasis and chemoresistance in pancreatic cancer. Additionally, they have been verified to be potential as biomarkers, targets and drug carriers for pancreatic cancer treatment. Thus, studying the role of exosomes in pancreatic cancer is significant. This paper focuses on the role of exosomes in the proliferation, metastasis and chemoresistance, as well as their potential applications for pancreatic cancer.
CRIS-Team Scopus Importer:2019-09-17
Keywords: biomarker; chemoresistance; exosomes; pancreatic cancer

The role of Foxp3 and Tbet co-expressing Treg cells in lung carcinoma - Kachler, Katerina; Holzinger, Corinna; Trufa, Denis; Sirbu, Horia; Finotto, Susetta (OncoImmunology, 2018)
Despite the opposite roles of Tbet and Foxp3 in the immune system as well as in tumour biology, recent studies have demonstrated the presence of of CD4+ T cells, expressing both, Tbet and Foxp3. Although Tbet+Foxp3+ T cells are currently a subject of intense research, less is known about their biological function especially in cancer. Here we found a considerable accumulation of Tbet+Foxp3+CD4+ T cells, mediated by the immunosuppressive cytokine TGFβ in the lungs of tumour bearing mice. This is in line with previous studies, demonstrating the important role of TGFβ for the immunopathogenesis of cancer. By gathering results both in murine model and in human disease, we demonstrate that, the conversion of IFNγ producing anti-tumoral T-bet+Th1 CD4+ T cells into immunosuppressive Tbet and Foxp3-PD1 co-expressing regulatory cells could represent an additional important mechanism of TGFβ-mediated blockade of anti-tumour immunity.
EVALuna2:35735

The role of intraoperative swab during appendectomy in patients with uncomplicated and complicated appendicitis - Bancke Laverde, Bruno Leonardo; Maak, Matthias; Langheinrich, Melanie; Kersting, Stephan; Denz, Axel; Krautz, Christian; Weber, Georg; Grützmann, Robert; Brunner, Maximilian (International Journal of Colorectal Disease, 2023)
Introduction: Bacteria play an important role not only in pathogenesis of appendicitis but also in the postoperative course of patients. However, the usefulness of an intraoperative swab during appendectomy is controversial. The primary aim of this study was to investigate the impact of intraoperative swab during appendectomy on the postoperative outcome in patients with uncomplicated and complicated appendicitis. Methods: A retrospective analysis was conducted on a consecutive series of 1570 adult patients who underwent appendectomy for acute appendicitis at the University Hospital Erlangen between 2010 and 2020. Data regarding the intraoperative swab were collected and analyzed for the entire cohort as well as for patients with uncomplicated and complicated appendicitis. Results: An intraoperative swab was taken in 29% of the cohort. The bacterial isolation rate in the obtained intraoperative swabs was 51%, with a significantly higher rate observed in patients with complicated appendicitis compared to those with uncomplicated appendicitis (79% vs. 35%, p < 0.001). The presence of a positive swab was significantly associated with worse postoperative outcomes, including higher morbidity, increased need for re-surgery, and longer hospital stay, when compared to patients without a swab or with a negative swab. A positive swab was an independent risk factor for postoperative morbidity (OR 9.9 (95% CI 1.2–81.9), p = 0.034) and the need for adjustment of postoperative antibiotic therapy (OR 8.8 (95% CI 1.1–72.5), p = 0.043). However, a positive swab resulted in postoperative antibiotic therapy adjustment in only 8% of the patients with bacterial isolation in the swab. Conclusion: The analysis of swab samples obtained during appendectomy for acute appendicitis can help identify patients at a higher risk of a worse postoperative outcome. However, the frequency of antibiotic regime changes based on the swab analysis is low.
CRIS-Team Scopus Importer:2023-12-01
Keywords: Appendectomy; Bacterial isolation; Complicated appendicitis; Intraoperative swab; Uncomplicated appendicitis

The role of miR-200b/c in balancing EMT and proliferation revealed by an activity reporter - Gollavilli, Paradesi Naidu; Parma, Beatrice; Siddiqui, Aarif; Yang, Hai; Ramesh, Vignesh; Napoli, Francesca; Schwab, Annemarie; Natesan, Ramakrishnan; Mielenz, Dirk; Asangani, Irfan Ahmed; Brabletz, Thomas; Pilarsky, Christian; et al. (Oncogene, 2021)
Since their discovery, microRNAs (miRNAs) have been widely studied in almost every aspect of biology and medicine, leading to the identification of important gene regulation circuits and cellular mechanisms. However, investigations are generally focused on the analysis of their downstream targets and biological functions in overexpression and knockdown approaches, while miRNAs endogenous levels and activity remain poorly understood. Here, we used the cellular plasticity-regulating process of epithelial-to-mesenchymal transition (EMT) as a model to show the efficacy of a fluorescent sensor to separate cells with distinct EMT signatures, based on miR-200b/c activity. The system was further combined with a CRISPR-Cas9 screening platform to unbiasedly identify miR-200b/c upstream regulating genes. The sensor allows to infer miRNAs fundamental biological properties, as profiling of sorted cells indicated miR-200b/c as a molecular switch between EMT differentiation and proliferation, and suggested a role for metabolic enzymes in miR-200/EMT regulation. Analysis of miRNAs endogenous levels and activity for in vitro and in vivo applications could lead to a better understanding of their biological role in physiology and disease.
CRIS-Team Scopus Importer:2021-03-19

The role of plastic reconstructive surgery in surgical therapy of soft tissue sarcomas - Götzl, Rebekka; Sterzinger, Sebastian; Arkudas, Andreas; Boos, Anja; Semrau, Sabine; Vassos, Nikolaos; Grützmann, Robert; Agaimy, Abbas; Hohenberger, Werner; Horch, Raymund E.; Beier, Justus (Cancers, 2020)
Background: Soft tissue sarcoma (STS) treatment is an interdisciplinary challenge. Along with radio(chemo)therapy, surgery plays the central role in STS treatment. Little is known about the impact of reconstructive surgery on STS, particularly whether reconstructive surgery enhances STS resection success with the usage of flaps. Here, we analyzed the 10-year experience at a university hospital’s Comprehensive Cancer Center, focusing on the role of reconstructive surgery. Methods: We performed a retrospective analysis of STS-patients over 10 years. We investigated patient demographics, diagnosis, surgical management, tissue/function reconstruction, complication rates, resection status, local recurrence and survival. Results: Analysis of 290 patients showed an association between clear surgical margin (R0) resections and higher-grade sarcoma in patients with free flaps. Major complications were lower with primary wound closure than with flaps. Comparison of reconstruction techniques showed no significant differences in complication rates. Wound healing was impaired in STS recurrence. The local recurrence risk was over two times higher with primary wound closure than with flaps. Conclusion: Defect reconstructions in STS are reliable and safe. Plastic surgeons should have a permanent place in interdisciplinary surgical STS treatment, with the full armamentarium of reconstruction methods.
CRIS-Team Scopus Importer:2020-12-04
Keywords: Plastic surgery; Reconstruction; Reconstructive surgery; Soft tissue sarcoma; STS

The role of Signal Transducer and Activator of Transcription protein 5 (STAT5) in non-small cell lung cancer (NSCLC) - Friedrich, Juliane; Heim, Lisanne; Springel, Rebekka; Mittler, Susanne; Gafencu, Dumitrita; Hartmann, Arndt; Sirbu, Horia; Finotto, Susetta (2016)
EVALuna2:25983

The role of STAT3 (signal transducer and activator of transcription 3) in non-small cell lung cancer (NSCLC) - Heim, Lisanne; Andreev, Katerina; Balabko, Ljubov; Trufa, Denis; Sirbu, Horia; Hartmann, Arndt; Finotto, Susetta (2016)
EVALuna2:25984

The science behind programming algorithms for sacral neuromodulation - Knowles, Charles H.; De Wachter, Stefan; Engelberg, Stefan; Lehur, Paul; Matzel, Klaus E.; Zirpel, Lance (Colorectal Disease, 2020)
Aim Sacral neuromodulation (SNM) is a widely adopted treatment for overactive bladder, non-obstructive urinary retention and faecal incontinence. In the majority, it provides sustained clinical benefit. However, it is recognized that, even for these patients, stimulation parameters (such as amplitude, electrode configuration, frequency and pulse width) may vary at both initial device programming and at reprogramming, the latter often being required to optimize effectiveness. Although some recommendations exist for SNM programming, the scientific data to support them are understood by few clinicians.
CRIS-Team WoS Importer:2020-11-13

The significance of a concomitant clavicle fracture in flail chest patients: incidence, concomitant injuries, and outcome of 12,348 polytraumata from the TraumaRegister DGU® - Bakir, Mustafa Sinan; Langenbach, Andreas; Pinther, Melina; Lefering, Rolf; Krinner, Sebastian; Grosso, Marco; Ekkernkamp, Axel; Schulz-Drost, Stefan (European Journal of Trauma and Emergency Surgery, 2021)
Purpose: Isolated clavicle fractures (CF) rarely show complications, but their influence in the thorax trauma of the seriously injured still remains unclear. Some authors associate CF with a higher degree of chest injuries; therefore, the clavicle is meant to be a gatekeeper of the thorax. Methods: A retrospective analysis of the TraumaRegister DGU® (project 2017-10) was carried out involving the years 2009–2016 (ISS ≥ 16, primary admission to a trauma center). Cohort formation: unilateral and bilateral flail chest injuries (FC), respectively, with and without a concomitant CF. Results: 73,141 patients (26.5% female) met the inclusion criteria and 12,348 had flail chest injuries (FC; 20.0% CF; 67.7% monolateral FC), 25,425 other rib fractures (17.7% CF), and 35,368 had no rib fractures (6.5% CF). On average, monolateral FC patients were 56.0 ± 17.9 years old and bilateral FC patients were 57.7 ± 19 years old. The ISS in unilateral and bilateral FC were 29.1 ± 11.7 and 42.2 ± 12.9 points, respectively. FC with a CF occurred more frequently with bicycle and motorbike injuries in monolateral FC and pedestrians in bilateral FC injuries and less frequently due to falls. Patients with a CF in addition to a FC had longer hospital and ICU stays, underwent artificially respiration for longer periods, and died less often than patients without a CF. The effects were highly significant in bilateral FC. CF indicates more relevant concomitant injuries of the lung, scapula, and spinal column. Moreover, CF was associated with more injuries of the extremities in monolateral CF. Conclusion: Due to the relevance of a concomitant CF fracture in FC, diagnostics should focus on finding CFs or rule them out. Combined costoclavicular injuries are associated with a significantly higher degree of thoracic injuries and longer hospital stays.
CRIS-Team Scopus Importer:2021-11-19
Keywords: Clavicle fracture; Costoclavicular injury; Flail chest; Trauma registry

The Tat protein of human immunodeficiency virus type-1 promotes vascular cell growth and locomotion by engaging the alpha5beta1 and alphavbeta3 integrins and by mobilizing sequestered basic fibroblast growth factor. - Barillari, Giovanni; Sgadari, Cecilia; Fiorelli, V; Samaniego, F; Colombini, S; Manzari, Vittorio; Modesti, A; Nair, B. C.; Cafaro, Aurelio; Stürzl, Michael; Ensoli, Barbara (Blood, 1999)
The Tat protein of human immunodeficiency virus type-1 (HIV-1) has been shown to be released during acute infection of T cells by HIV-1 and to promote angiogenesis and Kaposi's sarcoma (KS) development in infected individuals. In this study, we investigated the molecular mechanisms responsible for the angiogenic effects of Tat. The results shown herein indicate that two different Tat domains cooperate to induce these effects by different pathways. The arginine-glycine-aspartic acid (RGD) sequence present at the carboxyterminal of Tat mediates vascular cell migration and invasion by binding to the alpha5beta1 and alphavbeta3 integrins. This interaction also provides endothelial cells with the adhesion signal they require to grow in response to mitogens. At the same time, the Tat basic sequence retrieves into a soluble form extracellular basic fibroblast growth factor (bFGF) bound to heparan sulfate proteoglycans by competing for heparin-binding sites. This soluble bFGF mediates Tat-induced vascular cell growth. These effects resemble those of extracellular matrix proteins, suggesting that Tat enhances angiogenesis and promotes KS progression by a molecular mimicry of these molecules.

The third dimension in perforator mapping—Comparison of Cinematic Rendering and maximum intensity projection in abdominal-based autologous breast reconstruction - Hauck, Theresa; Arkudas, Andreas; Horch, Raymund E.; Ströbel, Armin; May, Matthias; Binder, Johannes; Krautz, Christian; Ludolph, Ingo (Journal of Plastic Reconstructive and Aesthetic Surgery, 2022)
Background: Cinematic Rendering (CR) is a recently introduced post-processing three-dimensional (3D) visualization imaging tool. The aim of this study was to assess its clinical value in the preoperative planning of deep inferior epigastric artery perforator (DIEP) or muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM) flaps, and to compare it with maximum intensity projection (MIP) images. The study presents the first application of CR for perforator mapping prior to autologous breast reconstruction. Methods: Two senior surgeons independently analyzed CR and MIP images based on computed tomography angiography (CTA) datasets of 20 patients in terms of vascular pedicle characteristics, the possibility to harvest a DIEP or MS-TRAM flap, and the side of the flap harvest. We calculated inter- and intra-observer agreement in order to examine the accordance of both image techniques. Results: We observed a good inter- and intra-observer agreement concerning the type of flap and the side of the flap harvest. However, the agreement on the pedicle characteristics varies depending on the considered variable. Both investigators identified a significantly higher number of perforators with MIP compared with CR (observer 1, p<0.0001 and observer 2, p<0.0385). Conclusion: The current study serves as an explorative study, showing first experiences with CR in abdominal-based autologous breast reconstruction. In addition to MIP images, CR might improve the surgeon's understanding of the individual's anatomy. Future studies are required to compare CR with other 3D visualization tools and its possible effects on operative parameters.
CRIS-Team Scopus Importer:2022-03-11
Keywords: 3D visualization; Computed tomography angiography; DIEP; MS-TRAM

The TLR9 agonist cobitolimod induces IL10 producing wound healing macrophages and regulatory T cells in ulcerative colitis - Schmitt, Heike; Ulmschneider, Julia; Billmeier, Ulrike; Scarozza, Patrizio; Sonnewald, Sophia; Reid, Stephen; Atreya, Imke; Rath, Timo; Zundler, Sebastian; Langheinrich, Melanie; Schüttler, Jürgen; Hartmann, Arndt; et al. (Journal of Crohns & Colitis, 2020)
BACKGROUND AND AIMS: The topically applied Toll-like receptor 9 (TLR9) agonist cobitolimod is a first-in-class DNA-based oligonucleotide that demonstrated therapeutic efficacy in clinical trials with ulcerative colitis (UC) patients. We here characterized its anti-inflammatory mechanism in UC. METHODS: Luminal cobitolimod administration was evaluated in an experimental DSS-induced colitis model. Cultured blood and mucosal cells from UC patients were treated with cobitolimod and analyzed via microarray, qRT-PCR, ELISA and flow cytometry. Intestinal slides of cobitolimod treated UC patients were analyzed by immunohistochemistry. RESULTS: Cobitolimod administration markedly suppressed experimental colitis activity and microarrays analyses demonstrated mucosal IL10 upregulation and suppression of IL17 signaling pathways. Cobitolimod treatment was associated with significant induction of mucosal IL10+ Tr1 and Treg cells and suppression of Th17 cells. TLR9 knockout mice indicated that cobitolimod requires TLR9 signaling for IL10 induction. In UC patients, mucosal TLR9 levels correlated with severity of inflammation. Cobitolimod inhibited IL17A and IL17F, but increased IL10 and FoxP3 expression in cultured intestinal UC T cells. Cobitolimod-mediated suppression of intestinal IL17+ T cells was abrogated by IL10 blockade. Furthermore, cobitolimod led to heightened IL10 production by wound healing macrophages. Immunohistochemistry in intestinal biopsies of cobitolimod treated UC patients indicated increased presence of IL10+ mononuclear and regulatory T cells, as well as reduction of IL17+ cells. CONCLUSION: Our studies suggest that activation of TLR9 via cobitolimod might represent a novel therapeutic approach in UC, as it suppresses Th17 cells and induces anti-inflammatory IL10+ macrophages and regulatory T cells, thereby modifying the dysregulated intestinal cytokine balance.
EVALuna2:212910
Keywords: Ulcerative colitis; TLR9; cobitolimod

The transcription factor GLI2 as a downstream mediator of transforming growth factor-?-induced fibroblast activation in SSc - Liang, Ruifang; Sumova, Barbora; Cordazzo, Cinzia; Mallano, Tatjana; Zhang, Yun; Wohlfahrt, Thomas; Dees, Clara; Krasowska, Dorota; Michalska-Jakubus, Malgorzata; Distler, Oliver; Schett, Georg; Senolt, Ladislav; et al. (Annals of the Rheumatic Diseases, 2016)
Hedgehog signalling plays a critical role during the pathogenesis of fibrosis in systemic sclerosis (SSc). Besides canonical hedgehog signalling with smoothened (SMO)-dependent activation of GLI transcription factors, GLI can be activated independently of classical hedgehog ligands and receptors (so-called non-canonical pathways). Here, we aimed to evaluate the role of non-canonical hedgehog signalling in SSc and to test the efficacy of direct GLI inhibitors that target simultaneously canonical and non-canonical hedgehog pathways.The GLI inhibitor GANT-61 was used to inhibit canonical as well as non-canonical hedgehog signalling, while the SMO inhibitor vismodegib was used to selectively target canonical hedgehog signalling. Furthermore, GLI2 was selectively depleted in fibroblasts using the Cre-LoxP system. The effects of pharmacological or genetic of GLI2 on transforming growth factor-? (TGF-?) signalling were analysed in cultured fibroblasts, in bleomycin-induced pulmonary fibrosis and in mice with overexpression of a constitutively active TGF-? receptor I.TGF-? upregulated GLI2 in a Smad3-dependent manner and induced nuclear accumulation and DNA binding of GLI2. Fibroblast-specific knockout of GLI2 protected mice from TBR(act)-induced fibrosis. Combined targeting of canonical and non-canonical hedgehog signalling with direct GLI inhibitors exerted more potent antifibrotic effects than selective targeting of canonical hedgehog signalling with SMO inhibitors in experimental dermal and pulmonary fibrosis.Our data demonstrate that hedgehog pathways and TGF-? signalling both converge to GLI2 and that GLI2 integrates those signalling to promote tissue fibrosis. These findings may have translational implications as non-selective inhibitors of GLI2 are in clinical use and selective molecules are currently in development.
EVALuna2:13344

The use of single-stapling techniques reduces anastomotic complications in minimal-invasive rectal surgery - Brunner, Maximilian; Zu'bi, Alaa; Weber, Klaus; Denz, Axel; Langheinrich, Melanie; Kersting, Stephan; Grützmann, Robert; Krautz, Christian; Weber, Georg (International Journal of Colorectal Disease, 2022)
Background Leakage of rectal anastomoses is one of the most important and feared complications in colorectal surgery. Apart from patient-specific risk factors, technical aspects may influence the occurrence of anastomotic complications. This study investigated whether using single-stapling techniques (SST) instead of the double-stapling technique (DST) for minimal-invasive rectal anastomosis is associated with a lower rate of anastomotic complications. Methods A retrospective review of 272 patients who received a minimally invasive stapled rectal anastomosis (3-16 cm from the anal verge) at our institution from 2015 to 2020 was performed. In 131 patients, rectal anastomosis was created by SST (SST group), while 141 patients received a rectal anastomosis with crossing stapler lines (DST group). The impact of the anastomotic technique on patient outcomes was determined by uni- and multivariate analyses. Results Overall anastomotic leakage rate was 6%. Patients with SST anastomoses had a lower leakage rate than patients with DST anastomoses (3% vs. 9% in the DST group, p = 0.045). The rate of anastomotic stenosis was lower in the SST group than in the DST group (1% vs. 6%, p = 0.037). Overall morbidity and mortality did not differ between the two groups. Multivariate analysis showed that single-stapling techniques significantly reduce the risk of anastomotic leakage (OR 3.5 [1.0-11.5], p = 0.043). Conclusion The use of SST for rectal anastomosis may help to reduce anastomotic complications. This finding should be confirmed by a randomized controlled trial.
CRIS-Team WoS Importer:2022-07-01

The viral interferon-regulatory factor-3 is required for the survival of KSHV-infected primary effusion lymphoma cells. - Wies, Effi; Mori, Yasuko; Hahn, Alexander; Kremmer, Elisabeth; Stürzl, Michael; Fleckenstein, Bernhard; Neipel, Frank (Blood, 2008)
Human herpesvirus-8 (HHV-8), also known as Kaposi sarcoma-associated herpesvirus (KSHV), is etiologically linked to primary effusion lymphoma (PEL). At least 10 KSHV-encoded proteins with potential roles in KSHV-associated neoplasia have been identified. However, with few exceptions, these putative oncogenes were analyzed in heterologous systems only using overexpression of single genes. Thus, the pathogenetic relevance of most of these putative oncogenes remains essentially unclear. We used RNA interference (RNAi) to knock down the expression of several KSHV genes in cultured PEL cells carrying the KSHV genome. The viral interferon-regulatory factor-3 (vIRF-3) was found to be required for proliferation and survival of cultured PEL cells. Knock-down of vIRF-3 expression by various RNAi approaches unequivocally resulted in reduced proliferation and increased activity of caspase-3 and/or caspase-7. Thus, vIRF-3 can be seen as a bona fide oncogene of KSHV-associated lymphoma. Surprisingly, although the related Epstein-Barr virus (EBV) is usually sufficient to immortalize human B lymphocytes, silencing of vIRF-3 reduced the viability of both EBV(-) and EBV(+) PEL cells. This suggests that KSHV is the driving force in the pathogenesis of PEL.

Three-Dimensional Cross-Sectional Light-Sheet Microscopy Imaging of the Inflamed Mouse Gut - Zundler, Sebastian; Klingberg, Anika; Schillinger, Daniela; Fischer, Sören; Neufert, Clemens; Atreya, Imke; Gunzer, Matthias; Neurath, Markus (Gastroenterology, 2017)
EVALuna2:33801

Thrombin Generation in Fresh and Frozen-Thawed Platelet Poor Plasma - Is there a Difference? - Kausche, Lea Elisabeth; Adler, Werner; Zimmermann, Robert; Hackstein, Holger; Strasser, Erwin (Clinical Laboratory, 2020)
Background: Applicability of thrombin generation tests to clinical routine has been sought for many years. The aim of this study was to compare thrombin generation measured in fresh platelet poor plasma (f-PPP) and frozen-thawed platelet poor plasma (ft-PPP) to prove the consistency of results.
CRIS-Team WoS Importer:2020-07-17

Thrombocyte apheresis cassettes as a novel source of viable peripheral blood mononuclear cells - Cunningham, Sarah; Buchele, Vera; Brox, Regine; Strasser, Erwin; Hackstein, Holger (Transfusion, 2020)
BACKGROUND: Traditionally, white blood cells (WBCs) are collected from buffy coats or freshly drawn blood. However, the increasing demand for peripheral blood mononuclear cells (PBMCs) in the research phases of immunological therapy development makes it necessary to identify alternative sources of these cells. STUDY DESIGN AND METHODS: Leukapheresis products are cost intensive and not offered by all blood banks. Therefore, thrombocyte apheresis cassettes (TACs), plateletpheresis waste products, were investigated as a possible low-cost and easily accessible blood source for research laboratories. The recovery rate, phenotype, and functionality of WBC subsets from TAC are unknown and were investigated in comparison to frequently used blood resources via flow cytometry. RESULTS: On average, TACs provide 30.3 × 106/mL PBMCs, situating themselves between peripheral whole blood (WB; 5.35 × 106/mL) and leukoreduction system chamber (LRSC; 163.9 × 106/mL) yields. Frequencies of CD14, CD3, CD4, CD8, CD56, CD19, and CD11c positive cells in TACs correlate with normal proportions of WBC populations. Stimulation of TAC-derived PBMCs by lipopolysaccharide (LPS) and resiquimod (R848) showed no significant differences in expression levels of human leukocyte antigen (HLA)-DR, DQ, DP, and CD86 or cytokine secretion compared to other blood source derived PBMC. Following stimulation with LPS or R848, comparable levels of tumor necrosis factor-α, interleukin-10, and interleukin-1β could be measured between TAC, LRSC, and WB. Additionally, TAC-derived T cells retained their proliferation capability and were able to produce interferon-γ following T-cell receptor stimulation. CONCLUSION: TACs provide a cost-effective source of viable and functional human blood cells that can readily be used for clinical and laboratory investigations after plateletpheresis preparation.
CRIS-Team Scopus Importer:2020-03-27

Time-extended local rtPA infiltration for acutely thrombosed hemodialysis fistulas - Regus, Susanne; Lang, Werner; Heinz, Marco; Rother, Ulrich; Meyer, Alexander; Almási-Sperling, Veronika; Uder, Michael; Schmid, Axel (Hemodialysis International, 2018)
This study describes results of a modified local thrombolysis technique for acutely thrombosed hemodialysis (HD) arteriovenous fistulas (AVF), which is characterized by prolonged recombinant tissue plasminogen activator (rtPA) local exposure times. Contrary to the standard lyse- and- wait (L&W) technique with local reaction times of 20-40 minutes, the modified protocol allows timing of challenging angioplasty maneuvers to the next regular working day.From February 2009 to April 2014, 84 patients on HD presented with 152 acutely thrombosed AVF. They proceeded to local thrombolysis including a single shot infiltration of rtPA, local reaction time up to 40 hours and finally percutaneous stenosis angioplasty. Success rates, major adverse events and need for temporary catheter placements (TCP) were retrospectively analyzed.The local thrombolysis time after single shot infiltration was 18.6 ± 6.2 (range 2-40) hours. Mean rtPA- dosage was 2.7 mg ± 1.2. The overall success rate was 89.5% and the major complication rate was 3.3%, whereas TCP was necessary in 12.5%. The PP/SP at 1, 3, 6, 12, 18, and 24 month were 86% ± 3%/95% ± 2%, 68% ± 4%/92% ± 2%, 43% ± 4%/90% ± 2%, 28% ± 4%/82% ± 3%, 12% ± 3%/82% ± 3%, 7% ± 2%/63% ± 4%, respectively.The modified L&W technique with prolonged local rtPA reaction times is a safe and effective declotting procedure. The need for TCP was not increased and therefore comparable to the standard technique.
EVALuna2:15322

Time to Surgery Does Not Affect Overall or Disease-Free Survival of Patients with Primary Resectable PDAC - Jacobsen, Anne; Hobbs, Mirianna; Merkel, Susanne; Mittelstädt, Anke; Czubayko, Franziska; Krautz, Christian; Grützmann, Robert; Brunner, Maximilian; Weber, Georg (Journal of Clinical Medicine, 2022)
(1) Background: Delay in therapy for pancreatic ductal adenocarcinoma (PDAC) may contribute to a worse outcome. The aim of this study was to investigate the prognostic value of time from diagnosis to surgery in patients undergoing upfront surgery for primarily resectable pancreatic carcinoma. (2) Methods: This retrospective single-center study included 214 patients who underwent primary resection of PDAC from January 2000 to December 2018 at University Hospital Erlangen. Using a minimum p-value approach, patients were stratified according to time to surgery (TtS) into two groups: TtS <= 23 days and TtS > 23 days. Postoperative outcome and long-term survival were compared. (3) Results: Median TtS was 25 days. The best cut-off for TtS was determined as 23 days. There were no differences regarding postoperative outcome or overall survival (OS) and disease-free survival (DFS) (OS: 23.8 vs. 20.4 months, p = 0.210, respectively, and DFS: 15.8 vs. 13.6 months, p = 0.187). Multivariate analysis revealed age, lymph node metastasis, tumor differentiation and resection status as significant independent prognostic predictors for OS and DFS. (4) Conclusions: A delay of surgery > 23 days after first diagnosis does not affect overall or disease-free survival of patients with primary resectable PDAC. However, the psychological impact of a delay to patients waiting for surgery should not be underestimated.
CRIS-Team WoS Importer:2022-08-26

Timing of first arteriovenous fistula cannulation in children on hemodialysis - Almási-Sperling, Veronika; Galiano, Matthias; Lang, Werner; Rother, Ulrich; Rascher, Wolfgang; Regus, Susanne (Pediatric Nephrology, 2016)
Due to lower complication rates in comparison to central venous catheter (CVC) arteriovenous fistulas (AVFs) are now the preferred hemodialysis access. Recommendations for the first access cannulation range from 6 to 12 weeks, which could lead to temporary or even permanent preference for CVC while awaiting the maturation of the newly created AVF. The aim of this study was to evaluate the influence of first cannulation of AVFs on primary (PP) and secondary (SP) patency rates in children on hemodialysis (HD).This was a retrospective cohort study of 42 pediatric patients with a median age of 14 (range 7-17) years. At the time of surgical AVF creation 21 patients (end-stage renal disease) were still on HD via CVC or peritoneal catheter, while 21 were pre-emptive with initiation of HD expected within a few weeks. All patients received an AVF by the same experienced surgeon between February 1993 and May 2014. Primary failure (PF) was defined as the inability to use the AVF even once due to absent maturation or occlusion within 4 weeks after creation. PP was defined as the interval from time of access placement to any intervention designed to maintain or reestablish patency, to access thrombosis or the time of measurement of patency, while SP was defined as the total lifespan from creation to access abandonment, end of follow-up or loss.Primary failure was observed in six (14.3 %) of 42 AVFs (all radiocephalic fistulas) within the first 10 days after cannulation. Excluding PF, the PP/SP rates at 1, 3, 6, 12, 18 and 24 months were 100/100, 91/99, 86/98, 76/95, 55/85 and 44/77 %, respectively. There was a significant decrease in PP when first cannulation was performed within the first 30 days after creation compared to first cannulation performed after 30 days (p = 0.004). In terms of PP/SP outcome and timing of the first cannulation, there was no significant difference in thee outcome of PP/SP between first cannulation within the first 45 days after creation and that after 45 days (p = 0.091/0.883).The findings suggest that cannulation of AVF within 30 days after surgical creation reduces PP, while SP may be influenced less by time until cannulation. We also found no significant differences in PP after maturing periods of >45 days.
EVALuna2:15275

TNF promotes DECTIN2 family C-type lectin receptor expression in human macrophages. - Haberkamp, Carl; Allabauer, Ida; Blaha, Niklas; Bodendorfer, Barbara; Cunningham, Sarah; Hörning, André; Lang, Roland (Journal of Leukocyte Biology, 2023)
TNF blockade constitutes an effective therapy for inflammatory bowel disease, yet increases the risk for infection, including active tuberculosis. The DECTIN2 family C-type lectin receptors MINCLE, MCL, and DECTIN2 sense mycobacterial ligands and activate myeloid cells. In mice, upregulation of DECTIN2 family C-type lectin receptor after stimulation with Mycobacterium bovis Bacille Calmette-Guérin requires TNF. Here, we investigated whether TNF controls inducible C-type lectin receptor expression in human myeloid cells. Monocyte-derived macrophages were stimulated with Bacille Calmette-Guérin and the TLR4 ligand lipopolysaccharide, and expression of C-type lectin receptor was analyzed. Bacille Calmette-Guérin and lipopolysaccharide strongly upregulated messenger RNA expression of DECTIN2 family C-type lectin receptor but not of DECTIN1. Bacille Calmette-Guérin and lipopolysaccharide also induced robust production of TNF. Recombinant TNF was sufficient to upregulate expression of DECTIN2 family C-type lectin receptor. Blocking TNF with the TNFR2-Fc fusion protein etanercept abrogated, as expected, the effect of recombinant TNF and impaired induction of DECTIN2 family C-type lectin receptor by Bacille Calmette-Guérin and lipopolysaccharide. Flow cytometry confirmed upregulation of MCL at the protein level by recombinant TNF and showed inhibition of Bacille Calmette-Guérin-induced MCL by etanercept. To investigate the impact of TNF on C-type lectin receptor expression in vivo, we analyzed peripheral blood mononuclear cells of patients with inflammatory bowel disease and observed downregulation of MINCLE and MCL expression after therapeutic TNF blockade. Together, TNF is sufficient to upregulate DECTIN2 family C-type lectin receptor in human myeloid cells and contributes to this process after encounter with Bacille Calmette-Guérin or lipopolysaccharide. Impaired C-type lectin receptor expression in patients receiving TNF blockade may dampen the sensing of microbes and defense against infection.
EVALuna2:531674
Keywords: MINCLE; MCL; DECTIN2; TNF blockade; mycobacteria; inflammatory bowel disease

To Surveil or Not To Surveil: That is (Still) the Question - Rother, Ulrich; Saratzis, Athanasios (European Journal of Vascular and Endovascular Surgery, 2024)
CRIS-Team Scopus Importer:2024-02-23

Total Pancreatectomy and Islet Autotransplantation in a Child with Recurrent Pancreatitis - Grützmann, Robert; Ludwig, B.; Weitz, J.; Ludwig, S. (Zentralblatt für Chirurgie, 2016)
Hereditary pancreatitis in children is rare. The indications for surgery in these children are complications and severe pain that cannot be managed by conservative treatment. Surgical treatment options are duodenum preserving resections as well as drainage procedures. Recurrences are common following theses surgical procedures, because usually the whole pancreas is affected. The majority of the children with symptomatic hereditary pancreatitis are free of pain after total pancreatectomy. When total pancreatectomy is combined with islet autotransplantation, pancreoprivic diabetes can be attenuated or even prevented. The principle of spleen-preserving total pancreatectomy combined with subsequent islet autotransplantation is shown in a case of a 10-year-old child with chronic recurrent pancreatitis in this video.Symptomatic chronic hereditary pancreatitis in children.Spleen-preserving total pancreatectomy, reconstruction with hepatico-jejunostomy and duodeno-jejunostomy, islet autotransplantation via portal vein.If the surgeon has appropriate experience, spleen-preserving total pancreatectomy is a safe procedure. In combination with islet autotransplantation, it may attenuate or prevent diabetes mellitus associated with total pancreatectomy. In highly selected pediatric patients, this surgical procedure has a major benefit compared to a purely symptomatic therapy.
EVALuna2:15256

Towards a better treatment of patients with vascular malformations: certified interdisciplinary centers are mandatory* - Cucuruz, Beatrix; Koller, Michael; Pfleiderer, Ronja; Geisthoff, Urban; Meyer, Lutz; Kapp, Friedrich; Lang, Werner; Schmitz-Rixen, Thomas; Wohlgemuth, Walter A. (Zeitschrift für Evidenz, Fortbildung und Qualitat im Gesundheitswesen, 2022)
Background: Vascular anomalies are orphan diseases that occur in all age groups and range from purely aesthetic to potentially life-threatening conditions. This thesis paper outlines the typical conferring problems in patient management and possible structural solutions for a better patient treatment in the future. Methods: A multi-perspective author panel consisting of key stakeholders from the German Interdisciplinary Society of Vascular Anomalies and the German Society for Surgery defined problem areas and possible solutions including quality indicators as criteria for certified interdisciplinary Vascular Anomalies Centers (VAC). Results: According to the literature available, clearly defined nomenclature and nosological entities often remain unused in this field, and consented diagnostic and therapeutic evidence is rare. Expert opinions dominate and in some cases lead to disparate recommendations. Typical patient problems arise from this situation, exemplified in patient vignettes. Centralized and standardized patient treatment in interdisciplinary VAC may be a solution to this problem. These centers should agree on a set of general principles and quality indicators with an additional minimum set of structural and procedural criteria. Discussion: The present position paper outlines perspectives for implementing certified interdisciplinary VAC. There is a need for a comprehensive nomenclature, access to interdisciplinary treatment centers, more scientific evidence, and further education in this rare group of diseases. Conclusion: Use of scientifically sound and patient-relevant criteria for certifying the interdisciplinary quality of VAC is expected to improve health care in Germany.
CRIS-Team WoS Importer:2022-06-24

To what extent is the low anterior resection syndrome (LARS) associated with quality of life as measured using the EORTC C30 and CR38 quality of life questionnaires? - Kupsch, Juliane; Kuhn, Matthias; Matzel, Klaus E.; Zimmer, Joerg; Radulova-Mauersberger, Olga; Sims, Anja; Witzigmann, Helmut; Stelzner, Sigmar (International Journal of Colorectal Disease, 2019)
Purpose: Treatment of rectal cancer often results in disturbed anorectal function, which can be quantified by the Low Anterior Resection Syndrome (LARS) score. This study investigates the association of impaired anorectal function as measured with the LARS score with quality of life (QoL) as measured with the EORTC-QLQ-C30 and CR38 questionnaires. Methods: All stoma-free patients who had undergone sphincter-preserving surgery for rectal cancer from 2000 to 2014 in our institution were retrieved from a prospective database. They were contacted by mail and asked to return the questionnaires. QoL was evaluated in relation to LARS and further patient- and treatment factors using univariate and multivariate analysis. Results: Of the eligible patients (n = 331), 261 (78.8%) responded with a complete LARS score. Mean score for global QoL according to the EORTC-QLQ-C30 questionnaire was 63 ± 21 for all patients. If major LARS was present, mean score decreased to 56 ± 19 in contrast to 67 ± 20 in patients with no/minor LARS (p < 0.001). In regression analysis, major LARS was furthermore associated with reduced physical, role, emotional, cognitive and social functioning as well as impaired body image, more micturition problems and poorer future perspective. It was not related to sexual function. The variance explained by major LARS in the differences of QoL was approximately 10%. Conclusion: The presence of major LARS after rectal resection for cancer is negatively associated with global health as well as many other aspects of QoL. Preserving anorectal function and treatment of LARS are potential measures to improve QoL in this patient group.
CRIS-Team Scopus Importer:2019-05-02
Keywords: Low anterior resection syndrome score; Quality of life; Rectal cancer; Sphincter-preserving surgery

Transcriptional activation of endogenous retroviral sequences in human epidermal keratinocytes by UVB irradiation. - Hohenadl, Christine; Germaier, Herbert; Walchner, Monika; Hagenhofer, Manuela; Herrmann, Martin; Stürzl, Michael; Kind, Peter; Hehlmann, Ruediger; Erfle, Volker; Leib-Mösch, Christine (Journal of Investigative Dermatology, 1999)
Ultraviolet radiation is a pathogenic factor in various diseases, e. g., autoimmune disorders such as lupus erythematosus. On the other hand, endogenous retroviruses are discussed as etiologic agents in lupus erythematosus. Therefore, we investigated the influence of ultraviolet irradiation on expression of human endogenous retroviral sequences and human endogenous retroviral sequence promoter-driven transcription of cellular genes using human epidermal keratinocytes as a model system. First, conserved sequences of endogenous retroviral pol genes were amplified from cellular mRNA by reverse transcriptase polymerase chain reaction with degenerate oligonucleotide primers. Polymerase chain reaction products were hybridized in a reverse dot blot hybridization assay to a representative number of distinct cloned human endogenous retroviral pol fragments. Using this method, we could show that irradiation with 30 mJ per cm2 ultraviolet B activates transcription of various endogenous retroviral pol sequences in primary epidermal keratinocytes as well as in a spontaneously immortalized keratinocyte cell line (HaCaT). Interestingly, some of these sequences were found to be closely related to pol sequences of human endogenous retroviral sequences which have been shown to be expressed in autoimmune patients. Analysis of human endogenous retroviral pol expression in vivo using skin biopsies of lupus erythematosus patients revealed similar activation patterns. In a second approach, ultraviolet B- induced chimeric transcripts were isolated which are initiated by human endogenous retroviral promoters and proceed into cellular sequences using a newly established modified differential display polymerase chain reaction technique. The activation of human endogenous retroviral sequence transcription by ultraviolet B may contribute to the pathogenesis of lupus erythematosus, where inappropriate antigenic presentation of ultraviolet B-induced viral and cellular proteins could stimulate autoantibody production.
Keywords: autoantigens; differential display polymerase chain reaction; lupus erythematosus; reverse dot blot hybridization

Transcription pattern of human herpesvirus 8 open reading frame K3 in primary effusion lymphoma and Kaposi's sarcoma. - Rimessi, Paola; Bonaccorsi, Angela; Stürzl, Michael; Fabris, Marina; Brocca-Cofano, Egidio; Caputo, Antonella; Melucci-Vigo, Gianna; Falchi, Mario; Cafaro, Aurelio; Cassai, Enzo; Ensoli, Barbara; Monini, Paolo (Journal of Virology, 2001)
Human herpesvirus 8 (HHV-8) is found in immunoblastic B cells of patients with multicentric Castleman's disease (MCD) and, predominantly in a latent form, in primary effusion lymphoma (PEL) cells and Kaposi's sarcoma (KS) spindle cells. Recent studies have shown that upon reactivation, HHV-8 expresses factors that downregulate major histocompatibility class I proteins and coactivation molecules and that may enable productively infected cells to escape cytotoxic T lymphocytes and natural killer cell responses. One of these viral factors is encoded by open reading frame (ORF) K3. Here we show that in PEL cells, ORF K3 is expressed through viral transcripts that are induced very early upon virus reactivation, including bicistronic RNA molecules containing coding sequences from viral ORFs K3 and 70. Specifically, we found that a bicistronic transcript was expressed in the absence of de novo protein synthesis, thereby identifying a novel HHV-8 immediate-early gene product. Several features of the RNA molecules encoding the K3 product, including multiple transcriptional start sites, multiple donor splicing sites, and potential alternative ATG usage, suggest that there exists a finely tuned modulation of ORF K3 expression. By contrast, ORF K3 transcripts are not detected in the majority of cells present in KS lesions that are latently infected by the virus, suggesting that there are other, as-yet-unknown mechanisms of immune evasion for infected KS spindle cells. Nevertheless, because HHV-8 viremia precedes the development of KS lesions and is associated with the recrudescence of MCD symptoms, the prompt expression of ORF K3 in productively infected circulating cells may be important for virus pathogenesis. Thus, molecules targeting host or viral factors that activate ORF K3 expression or inactivate the biological functions of the K3 product should be exploited for the prevention or treatment of HHV-8-associated diseases in at-risk individuals.

Transfusion-related alloimmune neutropenia with no pulmonary complications: one donor-five cases - Hauck-Dlimi, Barbara; Ruppel, Renate; Zimmermann, Robert; Strobel, Joachim; Reil, Angelika; Eckstein, Reinhold; Zingsem, Jürgen (Transfusion, 2016)
Neutrophil alloantibodies are well-known triggers of transfusion-related acute lung injury (TRALI) and also cause immune neutropenia. Alloimmune neutropenia due to transfusion is an isolated phenomenon that is only rarely identified. Its incidence is specified in the literature as being less than one in 10,000 transfused plasma-containing units. We expect that this phenomenon is underreported.We observed five cases of alloimmune neutropenia with no respiratory complications with only one case initially reported as a suspected transfusion reaction. The other four cases were detected in the course of the subsequent lookback investigation.The first case was reported as a potential transfusion reaction when a female patient showed a decrease in the white blood cell count after a platelet (PLT) transfusion. Examinations of the donor blood revealed an antibody against the human neutrophil antigen HNA-1b; the recipient was typed HNA-1b positive and HNA-1a negative. After examining the blood counts of other patients who previously received PLT concentrates from the same donor, we identified four other patients with an unreported decrease in the leukocyte and/or granulocyte count of more than approximately 50% after transfusion.HNA antibodies are generally regarded as potential triggers of TRALI. Here we describe an HNA antibody that reproducibly caused transfusion-related neutropenia only without pulmonary complications. Factors predisposing patients to TRALI development are widely discussed. Our case suggests that antibody characteristics are also relevant in the development of TRALI. Current measures to prevent TRALI should also prevent transfusion-related alloimmune neutropenia.
EVALuna2:15990

Transmural Placement of Endocardial Pacing Leads in Patients With Congenital Heart Disease - Sandrio, Stany; Purbojo, Ariawan; Toka, Okan; Dittrich, Sven; Cesnjevar, Robert; Rueffer, Andre (Annals of Thoracic Surgery, 2016)
This study evaluates the feasibility and outcomes of transmural placement of endocardial leads (TML) in patients with congenital heart disease.Between October 2009 and May 2015, 29 TML procedures were performed in 27 patients. Leads are grouped according to their pacing site: atrial (TML-A, n = 24) or ventricular (TML-V, n = 12). The TML-V includes transatrial and transventricular approaches. Clinical outcome, functional properties of TML, and Kaplan-Meier freedom from lead dysfunction were evaluated.Median age was 4 years (range, 29 days to 43 years). Median follow-up duration was 2 years (range, 1 day to 5.7 years). There was no early mortality. Three late deaths were observed (2 unrelated, 1 related to pacing). In group TML-A, no lead dysfunction was noted. In group TML-V, there were 3 lead dislodgements and 1 lead fracture. Kaplan-Meier freedom from lead dysfunction after 0.5, 1, and 5 years, respectively, was 100% in group TML-A and 82% ± 11%, 73% ± 13%, and 59% ± 17% in group TML-V (log rank p < 0.01). Mean acute (at implantation) and chronic (at last follow-up) sensing thresholds were 3.1 ± 2.3 mV and 3.5 ± 2.5 mV in group TML-A and 11.6 ± 4.9 mV and 7.5 ± 4.6 mV in group TML-V, respectively. Mean acute and chronic pacing thresholds at 0.5 ms were 1.1 ± 0.6 V and 0.6 ± 0.3 V in group TML-A and 1.0 ± 0.6 V and 0.9 ± 0.5 V in group TML-V, respectively.The transmural approach provides an alternative method in patients with congenital cardiac defects who cannot receive transvenous leads and who have extensive epicardial scarring. Subanalysis shows superior midterm performance for TML-A compared with TML-V.
EVALuna2:25118

Transplant Ureteral Stenosis after Renal Transplantation: Risk Factor Analysis - Apel, Hendrik; Rother, Ulrich; Wach, Sven; Schiffer, Mario; Kunath, Frank; Wullich, Bernd; Heller, Katharina M. (Urologia Internationalis, 2021)
Introduction: The results of kidney transplants have improved dramatically in recent years, leading to reduced morbidity and mortality. Despite continuous improvements, urological complications occur at a rate of 2.6%-15%. Ureteral stenosis of graft ureters is the most common complication, with a probability of 0.5%-6.3%. This study aimed to determine the incidence of ureteral stenosis after kidney transplantation and identify risk factors that distinguish transplant patients with and without ureteral stenosis. Methods: This study retrospectively analyzed patients who had undergone kidney transplantation at the Department of Urology of the Friedrich-Alexander University Erlangen-Nuremberg between 2001 and 2015. Forty-seven patients developed ureteral stenosis during the operation. Most of the ureteral stenosis cases occurred in the first 4 months after transplantation. Kaplan-Meier analysis and the log-rank test were used to calculate the cumulative risk, and the Mann-Whitney U test was used nonparametrically. The significance level was set at p < 0.05. Results: Statistical analysis showed that residual diuresis (p = 0.008), cold ischemia time (CIT) (p = 0.040), the body mass index (p = 0.027), and donor serum creatinine value (p = 0.039) showed a significantly different distribution between recipients with or without ureteral stenosis after kidney transplantation. In multivariate Cox's regression modeling, residual diuresis and the donor serum creatinine level were identified as the only independent predictors of patients' stenosis-free survival. Conclusion: Urological complications not diagnosed and treated in time endanger the success of kidney transplantation. After evaluating the kidney transplantation data of the patients at the Transplant Center Erlangen-Nuremberg from 2001 to 2015, residual diuresis, CIT, the body mass index, and donor serum creatinine value were found to influence the development of ureteral stenosis.
CRIS-Team WoS Importer:2021-12-03

Transrectal Absorber Guide Raster-Scanning Optoacoustic Mesoscopy for Label-Free In Vivo Assessment of Colitis - Bühler, Adrian; Brown, Emma; Paulus, Lars-Philip; Eckstein, Markus; Thoma, Oana-Maria; Oraiopoulou, Mariam-Eleni; Rother, Ulrich; Hörning, André; Hartmann, Arndt; Neurath, Markus; Wölfle, Joachim; Friedrich, Oliver; et al. (Advanced Science, 2023)
Optoacoustic imaging (OAI) enables microscale imaging of endogenous chromophores such as hemoglobin at significantly higher penetration depths compared to other optical imaging technologies. Raster-scanning optoacoustic mesoscopy (RSOM) has recently been shown to identify superficial microvascular changes associated with human skin pathologies. In animal models, the imaging depth afforded by RSOM can enable entirely new capabilities for noninvasive imaging of vascular structures in the gastrointestinal tract, but exact localization of intra-abdominal organs is still elusive. Herein the development and application of a novel transrectal absorber guide for RSOM (TAG-RSOM) is presented to enable accurate transabdominal localization and assessment of colonic vascular networks in vivo. The potential of TAG-RSOM is demonstrated through application during mild and severe acute colitis in mice. TAG-RSOM enables visualization of transmural vascular networks, with changes in colon wall thickness, blood volume, and OAI signal intensities corresponding to colitis-associated inflammatory changes. These findings suggest TAG-RSOM can provide a novel monitoring tool in preclinical IBD models, refining animal procedures and underlines the capabilities of such technologies to address inflammatory bowel diseases in humans.
CRIS-Team WoS Importer:2023-05-12

Transverse Incision for Pancreatoduodenectomy Reduces Wound Complications: A Single-Center Analysis of 399 Patients - Junker, Stefanie; Jacobsen, Anne; Merkel, Susanne; Denz, Axel; Krautz, Christian; Weber, Georg; Grützmann, Robert; Brunner, Maximilian (Journal of Clinical Medicine, 2023)
Background: Even if the minimally invasive approach is advancing in pancreatic surgery, the open approach is still the standard for a pancreatoduodenectomy. There are two types of incisions used: the midline incision (MI) and transverse incision (TI). The aim of this study was to compare these two incision types, especially regarding wound complications. Methods: A retrospective review of 399 patients who underwent a pancreatoduodenectomy at the University Hospital Erlangen between 2012 and 2021 was performed. A total of 169 patients with MIs were compared with 230 patients with TIs, with a focus on postoperative fascial dehiscence, postoperative superficial surgical site infection (SSSI) and the occurrence of incisional hernias during follow-up. Results: Postoperative fascial dehiscence, postoperative SSSI and incisional hernias occurred in 3%, 8% and 5% of patients, respectively. Postoperative SSSI and incisional hernias were significantly less frequent in the TI group (SSI: 5% vs. 12%, p = 0.024; incisional hernia: 2% vs. 8%, p = 0.041). A multivariate analysis confirmed the TI type as an independent protective factor for the occurrence of SSSI and incisional hernias (HR 0.45 (95% CI = 0.20–0.99), p = 0.046 and HR 0.18 (95% CI = 0.04–0.92), p = 0.039, respectively). Conclusion: Our data suggest that the transverse incision for pancreatoduodenectomy is associated with reduced wound complications. This finding should be confirmed by a randomized controlled trial.
CRIS-Team Scopus Importer:2023-05-12
Keywords: fascial dehiscence; incisional hernia; midline incision; pancreatoduodenectomy; surgical site infection; transverse incision

Traumatic Rupture of the Common Carotid Artery - Regus, Susanne; Lang, Werner (European Journal of Vascular and Endovascular Surgery, 2016)
EVALuna2:15279

Travel habits and complications in patients treated with vitamin K antagonists: A cross sectional analysis - Ringwald, Juergen; Lehmann, Marina; Niemeyer, Nicole; Seifert, Isabel; Daubmann, Anne; Wegscheider, Karl; Salzwedel, Annett; Luxembourg, Beate; Eckstein, Reinhold; Voeller, Heinz (Travel Medicine and Infectious Disease, 2014)
Travel-related conditions have impact on the quality of oral anticoagulation therapy (OAT) with vitamin K-antagonists. No predictors for travel activity and for travel-associated haemorrhage or thromboembolic complications of patients on OAT are known.A standardised questionnaire was sent to 2500 patients on long-term OAT in Austria, Switzerland and Germany. 997 questionnaires were received (responder rate 39.9%). Ordinal or logistic regression models with travel activity before and after onset of OAT or travel-associated haemorrhages and thromboembolic complications as outcome measures were applied.43.4% changed travel habits since onset of OAT with 24.9% and 18.5% reporting decreased or increased travel activity, respectively. Long-distance worldwide before OAT or having suffered from thromboembolic complications was associated with reduced travel activity. Increased travel activity was associated with more intensive travel experience, increased duration of OAT, higher education, or performing patient self-management (PSM). Travel-associated haemorrhages or thromboembolic complications were reported by 6.5% and 0.9% of the patients, respectively. Former thromboembolic complications, former bleedings and PSM were significant predictors of travel-associated complications.OAT also increases travel intensity. Specific medical advice prior travelling to prevent complications should be given especially to patients with former bleedings or thromboembolic complications and to those performing PSM.
EVALuna2:15980

Treatment and outcome of coronary artery perforations using a dual guiding catheter technique - Röther, Jens; Tröbs, Monique; Ludwig, Josef; Achenbach, Susanne; Schlundt, Christian (International Journal of Cardiology, 2015)
To evaluate the success rate and outcome of coronary artery perforation treatment using a dual guiding catheter technique.Coronary artery perforation is a rare but severe complication during percutaneous coronary intervention (PCI) with high mortality. The use of a second guiding catheter is a helpful technique to minimize hemorrhage through the perforation during interventional repair.We screened all patients between March 2004 and December 2014 who underwent PCI in our department for the occurrence of peri-interventional coronary perforation that was treated using a dual catheter technique. Patient and lesion characteristics as well as outcome were determined.We identified 8 patients who experienced coronary artery perforations (Ellis grade III) during coronary intervention and were treated using a dual guiding catheter approach. The procedure was technically successful (placement of covered stent and sealing of perforation) in 6 patients. Pericardiocentesis was required in 3 patients (38%). Total mortality was 12% (n=1). No coronary or peripheral vascular access complication occurred due to the use of a second guiding catheter.We suggest that the dual guiding catheter technique is a useful and alternative approach to treat severe Ellis grade III coronary artery perforations that occur in the context of percutaneous coronary interventions.
EVALuna2:12076

Treatment and Prognosis of the Oldest Old with Colorectal Cancer - Denz, Axel; Kohl, Valerie; Weber, Klaus; Langheinrich, Melanie; Schellerer, Vera; Merkel, Susanne; Grützmann, Robert (Zentralblatt für Chirurgie, 2018)
INTRODUCTION: The demographic trend will lead to an increase of elderly persons in Germany in the future. The population is becoming smaller and older because of the deficiency in childbirths. This results in demographic ageing of the population in Germany. Studies addressing patients ≥ 85 years, the oldest old, are becoming more and more important. MATERIALS AND METHODS: The prospectively collected data of 141 patients ≥ 85 years with colorectal carcinoma treated between 1995 and 2014 were analysed retrospectively. Treatment, complications and prognosis were compared with a historical group of patients ≥ 85 years treated previously between 1978 and 1994 (n = 57) and with a less old group of patients 75 - 84 years old treated between 1995 and 2014 (n = 726). RESULTS: The cohort consisted of 64 men and 77 women. 88 patients had colon carcinoma, 53 patients rectal carcinoma. 127 patients were treated with tumour resection; 112 were classified as R0. Compared with the historical cohort (1978 - 1994), the number of patients increased, and more patients were given tumour resection (74 vs. 90%, p = 0.003) and fewer patients had synchronous distant metastases (28 vs. 14%, p = 0.015). The 5-year locoregional recurrence rate after curative resection decreased from 11.5 to 1.4% (p = 0.027). Comparison with the younger age group (75 - 84 years) revealed more women (55 vs. 42.3%, p = 0.007), more emergencies (22 vs. 9.8%, p < 0.001) and less frequent neoadjuvant treatment (11 vs. 3%, p = 0.003). Morbidity (41 vs. 31.2%, p = 0.032) and mortality (16 vs. 5%, p < 0.001) were higher in the oldest old. After curative resection and exclusion of postoperative deaths, overall survival (2-year rate 66.4%, 5-year rate 32.9%) was found to be worse than for the less old group, whereas cancer-related survival (2-year rate 93.1%, 5-year rate 86.7%) was similar. CONCLUSION: The number of oldest old patients ≥ 85 years with colorectal carcinoma will further increase. These patients have a higher risk of postoperative complications. After recovering from the surgery cancer-related survival is not worse than for less old patients.
EVALuna2:210714

Treatment of aortic and peripheral prosthetic graft infections with bovine pericardium - Almási-Sperling, Veronika; Heger, Damaris; Meyer, Alexander; Lang, Werner; Rother, Ulrich (Journal of Vascular Surgery, 2019)
Objective: Graft infections are rare but serious complications of vascular operations. The aim of this study was to evaluate the results of in situ reconstruction with bovine pericardium in infected aortic and peripheral vessel fields. Methods: A retrospective cohort study was conducted with a focus on the treatment of infected grafts with bovine pericardium. We retrospectively reviewed 19 consecutive patients with prosthetic graft infections and in situ repair with bovine pericardium. All operations were done between March 2015 and January 2018. No other materials were used. Excision of the infected graft, radical débridement of the infected tissue, and in situ reconstruction with bovine pericardium were applied in all patients. Short-term outcomes including primary patency, freedom of reinfection, mortality, and complication rates were analyzed. Results: Bovine pericardium was used in 19 patients (84% male) with a median age of 70 years (range, 56-84 years) to reconstruct the descending aorta (n = 1), abdominal aorta (n = 5), iliac artery (n = 4), and femoral artery (n = 9). Graft infections were observed in all patients (one thoracic endovascular aneurysm repair, three infrarenal endovascular aneurysm repairs, two open aortic repairs, four iliac-femoral reconstructions, and nine femoral reconstructions including two closure device infections after coronary angiography). Ten patients (53%) had a complication perioperatively and postoperatively. The 30-day mortality was 10.5%; the total mortality rate after 1 year was 32%. There was no reinfection after bovine reconstruction observed in our cohort. Graft occlusions were detected in two cases during follow-up (median, 6 months; range, 1-47 months). Conclusions: Bovine pericardium reconstruction shows a good short-term outcome after aortic or peripheral graft infections. It is associated with good patency, low reinfection rate, and acceptably low early mortality rate. It can be a good therapeutic option in prosthetic graft infections when in situ repair with a prosthetic (even soaked) or autologous vein or homograft is not recommended or is not possible.
CRIS-Team Scopus Importer:2019-08-02
Keywords: Aortic repair; Infection; Pericardium; Vascular graft

Treatment of locoregional recurrent colon cancer - Handtrack, Claudia; Weber, Klaus; Merkel, Susanne; Grützmann, Robert; Denz, Axel (Coloproctology, 2022)
The local recurrence rate of colon cancer could be markedly reduced after complete mesocolic excision (CME) criteria were implemented in oncological surgery. Risk factors for local recurrence include incomplete resection as well as the site of the primary tumor and locally or lymph node advanced tumors (pT4/pN2). Further risk factors are emergency operations and postoperative complications, particularly anastomotic leakage. The outcome of local recurrent colon cancer is decisively influenced by the resectability. In cases of a curative R0 resection, possibly including neoadjuvant therapy or multivisceral resections, a 5-year survival rate of over 50% can be achieved.
CRIS-Team WoS Importer:2022-05-27
Keywords: Colorectal cancer; Local recurrence; R0 resection; Staging; Prognosis

Treatment of pediatric fistula-in-ano—Sphincter-sparing non-cutting seton placement as the future treatment of choice? - Besendörfer, Manuel; Langer, Laurin; Carbon, Roman; Weiss, Christel; Müller, Hanna; Diez, Sonja (Frontiers in Surgery, 2023)
Background: Therapeutic principles of fistula-in-ano (FIA) are lacking evidence-based consensus on treatment options. Non-cutting, sphincter-sparing options have not been published for infancy and childhood FIA. Patients and methods: We are presenting retrospective data on FIA treatment with non-cutting seton placement between 2011 and 2020. Data were collected based on medical records and complemented by patients’ contact for follow-up analyses between November 2021 and October 2022. Data were analyzed regarding the outcome variables of recurrent FIA and recurrent perianal abscess. Furthermore, outcomes in different age groups were compared (<1/1.5–12 years of age). Results: Treatment duration with non-cutting seton was at a median of 4.6 months and was not associated with recurrent FIA (p = 0.8893). Overall recurrence rate of FIA within an observation time of 9 months postsurgically was at 7% (n = 3/42) and was only seen in infancy, whereas recurrent perianal abscess was mainly observable in children (n = 2, p = 0.2132). Comparison of age groups revealed no significant differences. Of the 42 included patients, 37 responded in the follow-up analysis, resulting in a response rate of 88% with a median follow-up time of 4.9 years. Fecal incontinence was postsurgically only seen in two patients, who were diagnosed prior to surgery and symptoms remained unchanged. Conclusions: Non-cutting seton placement might be a promising option in the treatment of FIA in infancy and childhood. Perioperative settings like duration of placed seton and antibiotic treatment have to be discussed in further prospective, enlarged population-based studies.
CRIS-Team Scopus Importer:2023-05-05
Keywords: loose seton; pediatric fistula-in-ano; perianal abscess; placement of seton; sphincter sparing

Treatment of perforated colon carcinomas-outcomes of radical surgery - Daniels, Marc; Merkel, Susanne; Agaimy, Abbas; Hohenberger, Werner (International Journal of Colorectal Disease, 2015)
When patients present with a perforation of a colon cancer (CC), this situation increases the challenge to treat them properly. The question arises how to deal with these patients adequately, more restrictively or the same way as with elective cases.Between January 1995 and December 2009, 52 patients with perforated CC and 1206 nonperforated CC were documented in the Erlangen Registry of Colorectal Carcinomas (ERCRC). All these patients underwent radical resection of the primary including systematic lymph node dissection with CME. The median follow-up period was 68 months.The median age of the patients in the perforated CC group was significantly higher than in the nonperforated CC group (p = 0.010). Significantly, more patients with perforated CC were classified in ASA categories 3 and 4 (p = 0.014). Hartmann procedures were performed significantly more frequently with perforation than with the nonperforated ones (p < 0.001). If an anastomosis was performed, the leakage rate of primary anastomoses did not differ (p = 1.0). Cancer-related survival was significantly lower with perforated cancer (difference 12.8 percentage points) and by 9.6 percentage points for observed survival, if postoperative mortality was excluded.Perforated CC patients should be treated basically following the same oncologic demands, which are CME for colonic cancer including multivisceral resections, if needed. This strategy can only be performed if high-quality surgery is available, permanently.
EVALuna2:6709

Tumor-associated fibroblasts isolated from colorectal cancer tissues exhibit increased ICAM-1 expression and affinity for monocytes - Schellerer, Vera; Langheinrich, Melanie; Hohenberger, Werner; Croner, Roland S.; Merkel, Susanne; Rau, Tilman; Stürzl, Michael; Naschberger, Elisabeth (Oncology Reports, 2014)
Progression of colorectal cancer (CRC) is strongly associated with inflammation and other desmoplastic reactions in the tumor cell-surrounding tissue. We successfully isolated fibroblasts from the desmoplastic stroma of human CRC specimens and uninvolved colon tissue of patients treated surgically for CRC and investigated potential functional capacities. All of the isolated fibroblasts were vimentin-positive and CK-20/CD45-negative confirming the fibroblast phenotype. Differential expression patterns were detected between tumor-associated fibroblasts (TAFs) and normal tissue-associated fibroblasts (NAFs) regarding intercellular adhesion molecule-1 (ICAM-1) expression. In 11 of 12 TAF cultures, basal ICAM-1 expression was increased as compared to corresponding NAF cultures (p=0.001). After stimulation of the cultures with interleukin-1?, 8 of the 12 TAF cultures presented higher ICAM-1 levels when compared with the level in the corresponding NAF cultures (p=0.001). Moreover, the adhesive capacity of these cultures for U937 was increased in 8 out of 10 unstimulated and in 10 out of 10 stimulated cultures when TAFs and NAFs were compared. In corresponding tumor tissue sections from the same patients, the amount of ICAM-1-positive fibroblasts was significantly higher than that in the corresponding normal colon mucosa, indicating a tumor-specific effect that was maintained in the isolated cultures. These results indicate that fibroblasts from CRC tissue exhibit an increased affinity for monocytic cells. This increased intercellular interaction may contribute to elongated residence times of monocytes in CRC tissue. Therefore, these isolated fibroblasts are a useful tool for further functional investigation of desmoplastic tissue reactions in CRC.
EVALuna2:6524

Tumor Infiltration with CD20+CD73+ B Cells Correlates with Better Outcome in Colorectal Cancer - Hansen, Frederik; Wu, Zhiyuan; David, Paul; Mittelstädt, Anke; Jacobsen, Anne; Podolska, Malgorzata; Ubieta Hernández, Kenia; Brunner, Maximilian; Kouhestani, Dina; Swierzy, Izabela; Roßdeutsch, Lotta; Klösch, Bettina; et al. (International Journal of Molecular Sciences, 2022)
Immunotherapy has become increasingly important in the treatment of colorectal cancer (CRC). Currently, CD73, also known as ecto-5′-nucleotidase (NT5E), has gained considerable interest as a potential therapeutic target. CD73 is one of the key enzymes catalyzing the conversion of extracellular ATP into adenosine, which in turn exerts potent immune suppressive effects. However, the role of CD73 expression on various cell types within the CRC tumor microenvironment remains unresolved. The expression of CD73 on various cell types has been described recently, but the role of CD73 on B-cells in CRC remains unclear. Therefore, we analyzed CD73 on B-cells, especially on tumor-infiltrating B-cells, in paired tumor and adjacent normal tissue samples from 62 eligible CRC patients. The highest expression of CD73 on tumor-infiltrating B-cells was identified on classswitched memory B-cells, followed by naive B-cells, whereas no CD73 expression was observed on plasmablasts. Clinicopathological correlation analysis revealed that higher CD73+ B-cells infiltration in the CRC tumors was associated with better overall survival. Moreover, metastasized patients showed a significantly decreased number of tumor-infiltrating CD73+ B-cells. Finally, neoadjuvant therapy correlated with reduced CD73+ B-cell numbers and CD73 expression on B-cells in the CRC tumors. As promising new immune therapies are being developed, the role of CD73+ B-cells and their subsets in the development of colorectal cancer should be further explored to find new therapeutic options.
CRIS-Team Scopus Importer:2022-05-20
Keywords: B-cells; CD20; CD73; colorectal cancer; neoadjuvant treatment

Tumor location determines tissue-specific recruitment of tumor-associated macrophages and antibody-dependent immunotherapy response - Lehmann, Birgit; Biburger, Markus; Brückner, Christin; Ipsen Escobedo, Andrea; Gordan, Sina; Lehmann, Christian; Vöhringer, David; Winkler, Thomas; Schaft, Niels; Dudziak, Diana; Sirbu, Horia; Nimmerjahn, Falk; et al. (Science immunology, 2017)
Despite recent advances in activating immune cells to target tumors, the presence of some immune cells, such as tumor-associated macrophages (TAMs) or tumor-associated neutrophils (TANs), may promote rather than inhibit tumor growth. However, it remains unclear how antibody-dependent tumor immunotherapies, such as cytotoxic or checkpoint control antibodies, affect different TAM or TAN populations, which abundantly express activating Fcγ receptors. In this study, we show that the tissue environment determines which cellular effector pathways are responsible for antibody-dependent tumor immunotherapy. Although TAMs derived from Ly6Chigh monocytes recruited by the CCL2-CCR2 axis were critical for tumor immunotherapy of skin tumors, the destruction of lung tumors was CCL2-independent and required the presence of colony-stimulating factor 2–dependent tissue-resident macrophages. Our findings suggest that TAMs may have a dual role not only in promoting tumor growth in certain tissue environments on the one hand but also in contributing to tumor cell destruction during antibody-mediated immunotherapy on the other hand.
EVALuna2:15237
Keywords: Cancer; Macrophages; Tumor associated macrophages; Antibodies; Tumor therapy; Immunotherapy

Tumor microenvironment-dependent epigenetic imprinting in the vasculature predicts colon cancer outcome - Naschberger, Elisabeth; Fuchs, Maximilian; Dickel, Nicholas; Kunz, Meik; Popp, Bernt; Anchang, Charles Gwellem; Demmler, Richard; Lyu, Yanmin; Uebe, Steffen; Ekici, Arif Bülent; Geppert, Carol-Immanuel; Hartmann, Arndt; et al. (Cancer Communications, 2023)
CRIS-Team Scopus Importer:2023-10-27

Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial - Fokas, Emmanouil; Liersch, Torsten; Fietkau, Rainer; Hohenberger, Werner; Beissbarth, Tim; Hess, Clemens; Becker, Heinz; Ghadimi, Michael; Mrak, Karl; Merkel, Susanne; Raab, Hans-Rudolf; Sauer, Rolf; et al. (Journal of Clinical Oncology, 2014)
We previously described the prognostic impact of tumor regression grading (TRG) on the outcome of patients with rectal carcinoma treated with preoperative chemoradiotherapy (CRT) in the CAO/ARO/AIO-94 trial. Here we report long-term results after a median follow-up of 132 months.TRG after preoperative CRT was determined in 386 surgical specimens by the amount of viable tumor cells versus fibrosis, ranging from TRG 4 (no viable tumor cells) to TRG 0 (no signs of regression). Clinicopathologic parameters and TRG were correlated to the cumulative incidence of local recurrence, distant metastasis, and disease-free survival (DFS).Ten-year cumulative incidence of distant metastasis and DFS were 10.5% and 89.5% for patients with TRG 4 (complete regression), 29.3% and 73.6% for TRG 2 and 3 (intermediate regression), and 39.6% and 63% for TRG 0 and 1 (poor regression), respectively (P = .005 and P = .008, respectively). On multivariable analysis, residual lymph node metastasis (ypN+) and TRG were the only independent prognostic factors for cumulative incidence of distant metastasis (P < .001 and P = .035, respectively) and DFS (P < .001 and P = .039, respectively), whereas local recurrence was significantly affected by ypN status (P < .001) and lymphatic invasion (P = .026).Complete and intermediate tumor regressions were associated with improved long-term outcome in patients with rectal carcinoma after preoperative CRT independent of clinicopathologic parameters. This classification system needs to be prospectively tested in multiple data sets to validate its reproducibility in a wider setting.
EVALuna2:15168

Tumor–Stroma Ratio in Colorectal Cancer—Comparison between Human Estimation and Automated Assessment - Firmbach, Daniel; Benz, Michaela; Kuritcyn, Petr; Bruns, Volker; Lang-Schwarz, Corinna; Stübs, Frederik; Merkel, Susanne; Leikauf, Leah-Sophie; Braunschweig, Anna Lea; Oldenburger, Angelika; Gloßner, Laura; Abele, Niklas; et al. (Cancers, 2023)
The tumor–stroma ratio (TSR) has been repeatedly shown to be a prognostic factor for survival prediction of different cancer types. However, an objective and reliable determination of the tumor–stroma ratio remains challenging. We present an easily adaptable deep learning model for accurately segmenting tumor regions in hematoxylin and eosin (H&E)-stained whole slide images (WSIs) of colon cancer patients into five distinct classes (tumor, stroma, necrosis, mucus, and background). The tumor–stroma ratio can be determined in the presence of necrotic or mucinous areas. We employ a few-shot model, eventually aiming for the easy adaptability of our approach to related segmentation tasks or other primaries, and compare the results to a well-established state-of-the art approach (U-Net). Both models achieve similar results with an overall accuracy of 86.5% and 86.7%, respectively, indicating that the adaptability does not lead to a significant decrease in accuracy. Moreover, we comprehensively compare with TSR estimates of human observers and examine in detail discrepancies and inter-rater reliability. Adding a second survey for segmentation quality on top of a first survey for TSR estimation, we found that TSR estimations of human observers are not as reliable a ground truth as previously thought.
CRIS-Team Scopus Importer:2023-06-09
Keywords: colorectal cancer; deep learning; few-shot learning; image analysis; segmentation; tumor–stroma ratio; U-Net

Tumour immune evasion mechanism in non-small cell lung cancer by inducing Blimp-1 in CD4+CD25+Foxp-3+T regulatory cells - Neurath-Finotto, Susetta; Tausche, Patrick; Hohenberger, Katja; Neurath, Laura; Trufa, Denis; Geppert, Carol-Immanuel; Rieker, Ralf; Sirbu, Horia (JOURNAL OF IMMUNOLOGY, 2021)
CRIS-Team WoS Importer:2021-12-03

Two successful pregnancies in a carrier of heterozygous factor V LEIDEN mutation with aplasia of the inferior vena cava and a history of proximal deep venous thrombosis - Hauck-Dlimi, Barbara; Zimmermann, Robert; Eckstein, Reinhold; Ringwald, Jürgen (Archives of Gynecology and Obstetrics, 2014)
EVALuna2:15978

Two Years of tranSMART in a University Hospital for Translational Research and Education - Christoph, Jan; Knell, Christian; Naschberger, Elisabeth; Stürzl, Michael; Maier, Christian; Prokosch, Hans-Ulrich; Sedlmayr, Martin (Studies in health technology and informatics, 2017)
For translational research, software platforms such as tranSMART with an integrated view of both clinical and omics data have gained more and more attention in the last years.We wanted to examine the success and failures of tranSMART in the fields of translational research and education by looking at the examples of six use cases at our hospital. We wanted to point out suitable scenarios and user groups as well as still existing challenges and limitations.We sum up the experience we made with our use cases with a focus on lessons learned.tranSMART was successfully established by a bottom-up approach at our university hospital and has been running for more than two years now. It has been used in four translational research projects as well as in education in the context of lectures and bachelor/master theses.tranSMART can be a very useful tool for translational research and education. But it should be used with both care and statistical knowledge to avoid wrong conclusions. Some technical constraints, especially for data modeling, still limit many applications. Version control and data provenance are remaining challenges.
EVALuna2:187

Two years of tranSMART in a university hospital for translational research and education - Christoph, Jan; Knell, Christian; Naschberger, Elisabeth; Stürzl, Michael; Maier, Christian; Prokosch, Hans-Ulrich; Sedlmayr, Martin (Health informatics meets eHealth: Digital insight information-driven health & care; proceedings of the 11th eHealth2017 Conference, 2017)
UnivIS-Import:2018-09-11:Pub.2017.tech.IMMD.infome.twoyea
Keywords: Biomedical research; Medical education; Research personnel; Translational medical research

Überblick über Subtypen und Therapien der akuten Mesenterialischämie - Eckhardt, Daniel; Schmid, Axel; Grützmann, Robert (Zentralblatt für Chirurgie, 2019)
CRIS-Team Scopus Importer:2019-06-28

Unique features of different members of the human guanylate-binding protein family - Tripal, Philipp; Bauer, Michael; Naschberger, Elisabeth; Mörtinger, Thomas; Hohenadl, Christine; Cornali, Emmanuelle; Thurau, Mathias; Stürzl, Michael (Journal of Interferon and Cytokine Research, 2007)
Guanylate-binding proteins (GBPs) are the most abundant cellular proteins expressed in response to interferon-γ (IFN-γ), with seven highly homologous members in humans, termed HuGBP-1 to HuGBP-7. To date, differential features that may indicate differential functions of these proteins have not been described. Here, we investigated the expression and subcellular localization of the different HuGBPs in endothelial cells (EC). IFN-γ, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) induced the expression of HuGBP-1, HuGBP-2, and HuGBP-3 at similar high levels. In contrast, expression of HuGBP-4 and HuGBP-5 was robustly induced only by IFN-γ and not by TNF-α and IL-1β. Expression of HuGBP-6 and HuGBP-7 was not detected in EC under the various conditions examined. Investigating subcellular localization of the EC-expressed HuGBPs, HuGBP-1, HuGBP-3, and HuGBP-5 were exclusively detected in the cytoplasm, whereas HuGBP-2 and HuGBP-4 displayed a nucleocytoplasmic distribution. Treatment of the cells with IFN-γ and aluminum fluoride caused rapid enrichment of HuGBP-1 and HuGBP-2 in the Golgi apparatus, as demonstrated by time-lapse microscopy and fluorescence analyses of GFP-tagged HuGBPs. HuGBP-3 and HuGBP-4 were never detected in the Golgi apparatus, whereas HuGBP-5 was constitutively enriched in this cytosolic compartment, irrespective of stimulation. These results assign a characteristic pattern of expression and subcellular localization to each of the HuGBPs, indicating for the first time that these proteins may have different cellular functions. © Mary Ann Liebert, Inc.
Created from Fastlane, Scopus look-up

Unusual Manifestation of Live Staphylococcus saprophyticus, Corynebacterium urinapleomorphum, and Helicobacter pylori in the Gallbladder with Cholecystitis - Backert, Steffen; Tegtmeyer, Nicole; Oyarzabal, Omar A.; Osman, Dana; Rohde, Manfred; Grützmann, Robert; Vieth, Michael (International Journal of Molecular Sciences, 2018)
Culture-independent studies have identified DNA of bacterial pathogens in the gallbladder under pathological conditions, yet reports on the isolation of corresponding live bacteria are rare. Thus, it is unclear which pathogens, or pathogen communities, can colonize the gallbladder and cause disease. Using light microscopy, scanning electron microscopy, culture techniques, phylogenetic analysis, urease assays and Western blotting, we investigated the presence of live bacterial communities in the gallbladder of a cholecystitis patient after cholecystectomy. 16S rRNA gene sequencing of isolated bacterial colonies revealed the presence of pathogens most closely resembling Corynebacterium urinapleomorphum nov. sp., Staphylococcus saprophyticus and Helicobacter pylori. The latter colonies were confirmed as H. pylori by immunohistochemistry and biochemical methods. H. pylori cultured from the gallbladder exhibited both the same DNA fingerprinting and Western cagA gene sequence with ABC-type EPIYA (Glu-Pro-Ile-Tyr-Ala) phosphorylation motifs as isolates recovered from the gastric mucus of the same patient, suggesting that gastric H. pylori can also colonize other organs in the human body. Taken together, here we report, for the first time, the identification and characterization of a community consisting of live S. saprophyticus; C. urinapleomorphum, and H. pylori in the gallbladder of a patient with acute cholecystitis. Their potential infection routes and roles in pathogenesis are discussed.
EVALuna2:210710

Update Curriculum Kardiale Computertomographie - Schmermund, A.; Achenbach, Susanne; Buß, S. J.; Hausleiter, J.; Korosoglou, G.; Leber, A.; Möhlenkamp, S.; Voigtländer, T. (Die Kardiologie, 2023)
CRIS-Team Scopus Importer:2023-06-16

Update on neuromodulation for fecal incontinence - Matzel, Klaus (Annals of Laparoscopic and Endoscopic Surgery, 2022)
Sacral neuromodulation (SNM) is an established surgical therapy for fecal incontinence (PI). The spectrum of indications has evolved over the last two decades. The role of SNM is the surgical treatment algorithm for FI is now central. Currently, the indications include a wide variety of pathophysiological and pathomorphological causes of FI, but also reach beyond FI to include complex conditions such as low anterior resection syndrome (LARS) and patients with concomitant evacuation disorders. The technique's minimal invasiveness, low risk and low comorbidity contributed to its success and increased acceptance, as did the option of a therapeutic test and a robust patient selection-patients are selected for chronic stimulation by a pragmatic approach, based on the clinical outcome of a highly predictive value of trial stimulation if positive-its sustained clinical efficacy, and reproducible outcomes. TO further improve the outcome of SNM, both for the test stimulation and the chronic stimulation, crucial elements of the therapy such as electrode placement, programming, and reprogramming have been revisited and standardized. This article addresses the scope of indications, highlights the reevaluation and standardization of the implant technique and updates on recent guidance for programming and troubleshooting. The standardization should lead to fewer side effects, more programming options, less battery consumption with increased battery longevity, and improved clinical outcome.
CRIS-Team WoS Importer:2022-06-10

Upper Extremity Ischemia as a "Warning Shot" of Cerebellar Infarction - Regus, Susanne; Lang, Werner (European Journal of Vascular and Endovascular Surgery, 2016)
EVALuna2:15274

Upregulation of CD20 positive B-cells and B-cell aggregates in the tumor infiltration zone is associated with better survival of patients with pancreatic ductal adenocarcinoma - Brunner, Maximilian; Maier, Katharina; Rümmele, Petra; Jacobsen, Anne; Merkel, Susanne; Benard, Alan; Krautz, Christian; Kersting, Stephan; Grützmann, Robert; Weber, Georg (International Journal of Molecular Sciences, 2020)
Patients with pancreatic ductal adenocarcinoma (PDAC) normally have a poor long-term prognosis. However, some rare cases of long-term survivors have been reported. The tumor microenvironment, consisting of cellular and stromal components, possibly plays an important role and might influence prognosis. In this context, the role of tumor-infiltrating B-cells and its impact on the survival in patients with PDAC remains controversial. We therefore aimed to assess the prognostic value of CD20-positive B-cells and CD20-positive B-cell aggregates as well as CD138, IgM, Pax5, and Ki67 on the survival of patients with PDAC using immunohistochemistry of FFPE pancreatectomy tissue sections from patients that underwent primary surgery for pT3-and R0-pancreatic adenocarcinoma between 1995 and 2016. Patients with PDAC were matched and grouped in 16 long-term-survivors (LTS, median overall survival (OS): 96 months [range: 61–177 months]) and 16 short-term-survivors (STS, median OS: 16 months [range: 7–32 months]). CD20-positive B-cells and B-cell aggregates in the tumor infiltration zone were significantly upregulated in the LTS-group compared to the STS-group (p = 0.0499 respectively p = 0.0432). Regarding the entire patient cohort (n = 32) CD20 positive B-cell aggregates in the tumor infiltration zone were an independent prognostic marker for overall survival in multivariate analysis (HR 9.2, CI 1.6–51.4, p = 0.012). These results underline the importance of tumor-associated B-cells for prognosis of patients with PDAC. The detailed role of B cells in the pathomechanism of PDAC should be further investigated for predicting outcome, identifying appropriate treatment regimens, and developing novel therapeutic options.
CRIS-Team Scopus Importer:2020-03-17
Keywords: B-cell aggregates; B-cells; CD20; Pancreatic ductal adenocarcinoma; Survival

Ureterovesical Anastomosis Complications in Kidney Transplantation: Definition, Risk Factor Analysis, and Prediction by Quantitative Fluorescence Angiography with Indocyanine Green - Gerken, Andreas L. H.; Nowak, Kai; Meyer, Alexander; Kriegmair, Maximilian C.; Weiss, Christel; Kraemer, Bernhard K.; Glossner, Pauline; Heller, Katharina M.; Karampinis, Ioannis; Kunath, Frank; Rahbari, Nuh N.; Schwenke, Kay; et al. (Journal of Clinical Medicine, 2022)
Ureteral stenosis and urinary leakage are relevant problems after kidney transplantation. A standardized definition of ureterovesical anastomosis complications after kidney transplantation has not yet been established. This study was designed to demonstrate the predictive power of quantitative indocyanine green (ICG) fluorescence angiography. This bicentric historic cohort study, conducted between November 2015 and December 2019, included 196 kidney transplantations. The associations between quantitative perfusion parameters of near-infrared fluorescence angiography with ICG and the occurrence of different grades of ureterovesical anastomosis complications in the context of donor, recipient, periprocedural, and postoperative characteristics were evaluated. Post-transplant ureterovesical anastomosis complications occurred in 18%. Complications were defined and graded into three categories. They were associated with the time on dialysis (p = 0.0025), the type of donation (p = 0.0404), and the number of postoperative dialysis sessions (p = 0.0173). Median ICG ingress at the proximal ureteral third was 14.00 (5.00–33.00) AU in patients with and 23.50 (4.00–117.00) AU in patients without complications (p = 0.0001, cutoff: 16 AU, sensitivity 70%, specificity 70%, AUC = 0.725, p = 0.0011). The proposed definition and grading of post-transplant ureterovesical anastomosis complications is intended to enable valid comparisons between studies. ICG Fluorescence angiography allows intraoperative quantitative assessment of ureteral microperfusion during kidney transplantation and is able to predict the incidence of ureterovesical anastomosis complications. Registration number: NCT-02775838.
CRIS-Team Scopus Importer:2022-11-25
Keywords: near-infrared; NIR; perfusion assessment; renal transplantation

Usability and Suitability of the Omics-Integrating Analysis Platform tranSMART for Translational Research and Education - Christoph, Jan; Knell, Christian; Boßerhoff, Anja Katrin; Naschberger, Elisabeth; Stürzl, Michael; Rübner, Matthias; Seuß, Hannes; Ruh, Manuel; Prokosch, Hans-Ulrich; Sedlmayr, Brita (Applied Clinical Informatics, 2017)
Platforms like tranSMART assist researchers in analyzing clinical and corresponding omics data. Usability is an important, yet often overlooked, factor affecting the adoption and meaningful use. Analyses on the specific needs of translational researchers and considerations about the application of such platforms for education are rare. The aim of this study was to test whether tranSMART can be used in education and how well medical students and professional researchers can handle it; to identify which kind of translational researchers-in terms of skills, experienced limitations, and available data-can take advantage of tranSMART; and to evaluate the usability and to generate recommendations for improvements. An online-based test has been done by medical students (N = 109) and researchers (N = 26). The test comprised 13 tasks in the context of four typical research scenarios based on experimental and clinical data. A web questionnaire was provided to identify both the needs and the conditions of research as well as to evaluate the system's usability based on the "System Usability Scale" (SUS). Students and researchers were able to handle tranSMART well and coped with most scenarios: cohort identification, data exploration, hypothesis generation, and hypothesis validation were answered with a rate of correctness between 82 and 100%. Of the total, 72.2% of the teaching researchers considered tranSMART suitable for their lessons and 84.6% of the researchers considered the platform useful for their daily work; 65.4% of the researchers named the nonavailability of a platform like tranSMART as a restriction on their research. The usability was rated "acceptable" with a SUS of 70.8. tranSMART is potentially suitable for education purposes and fits most of the needs of translational researchers. Improvements are needed on the presentation of analysis results and on the guidance of users through the analysis, especially to ensure the compliance of the analysis with the requirements of statistical testing.
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Use of negative pressure wound therapy on surgical incisions (prevena(TM)) after surgery of pectus deformities reduces wound complications - Simon, Kirsten; Schulz-Drost, M.; Besendörfer, Manuel; Carbon, R. T.; Schulz-Drost, S. (Zentralblatt für Chirurgie, 2015)
Pectus surgery can lead to postoperative wound complications in some cases. The purpose of this study is to determine whether preventive negative pressure wound therapy (NPWT) could reduce wound complications after open pectus surgery.100 patients after open procedure for the treatment of pectus excavatum or pectus carinatum in the years 2010 to 2012 were retrospectively analysed. 50 patients treated with Prevena(TM) (KCI Medical Products GmbH, Wiesbaden, Germany) were compared with 50 patients whose wounds were covered with OPSITE® film (Smith & Nephew, Hamburg, Germany). Wound closure was performed following a standard procedure as well as the placement of subcutaneous drains. Therefore two comparable groups of patients were formed and analysed by standardised parameters. The wound dressing was placed epicutaneously immediately after wound closure in the operating room and removed after 5 days in each case. Follow-ups were performed immediately after removal of the wound dressing, at the time of discharge from hospital as well as 6 and 12 weeks after operation. The wounds were checked for tenderness, pain, secretion, redness and fistulas.The Prevena group showed 10 % wound complications which needed operative treatment, whereas the OPSITE group showed complications in 24 %. Some patients who were treated with Prevena showed superficial skin lesions at the rim of the foam and the film. All of these lesions healed well.Treating wounds postoperatively with preventive measures (NPWT) showed a remarkable reduction of wound complications following open pectus surgery whereas statistically the difference was not significant (p = 0.074).
EVALuna2:15835

Use of Preoperative Magnetic Resonance Imaging to Select Patients with Rectal Cancer for Neoadjuvant Chemoradiation-Interim Analysis of the German OCUM Trial (NCT01325649) - Kreis, Martin E.; Ruppert, R.; Ptok, H.; Strassburg, J.; Brosi, P.; Lewin, A.; Schoen, M. R.; Sauer, J.; Junginger, T.; Merkel, Susanne; Hermanek, Peter (Journal of Gastrointestinal Surgery, 2016)
Introduction of total mesorectal excision (TME) surgery for rectal cancer decreased local recurrence dramatically. Additional neoadjuvant chemoradiation (nCR) is frequently given in UICC II and III tumors based on TNM staging which is of limited accuracy. We aimed to evaluate determination of circumferential margin by magnetic resonance imaging (mrCRM) as an alternative criterium for nCR.Multicenter prospective cohort study which enrolled 642 patients in 13 centers with non-metastasized rectal adenocarcinoma. Patients with T4 tumors or patients with a mrCRM of 1 mm or less were treated by neoadjuvant chemoradiation. All others proceeded directly to surgery when inclusion criteria and no exclusion criteria were met. Quality of TME and accuracy of mrCRM determination were assessed during pathology workup.TME was complete in 381 of 389 patients after surgery without nCR (97.9 %) and in 245 of 253 patients (96.8 %) after nCR. Negative pathology circumferential margins (pCRM) were seen in 97.4 % without nCR and in 89 % of patients after nCR. Negative pCRM was predicted by negative mrCRM in 98.3 % of rectal cancers. NCR was given to 253 of 642 patients (39.5 %). Lymph node count was 23 (range 7-79; median/range) for surgery without nCR and 19 (range 2-56) for surgery after nCR.Surgical quality determined by pathology workup of specimen was very good in this study. Magnetic resonance imaging guided indication for nCR allows to achieve superb results concerning surrogate parameters for good oncological outcome. Thus, use of neoadjuvant chemoradiation with its potential detrimental side effects may be substantially reduced in selected patients.
EVALuna2:15216

Utilization of Interdisciplinary Tumor Boards for Sarcoma Care in Germany: Results from the PROSa Study - Eichler, Martin; Andreou, Dimosthenis; Golcher, Henriette; Hentschel, Leopold; Richter, Stephan; Hohenberger, Peter; Kasper, Bernd; Pink, Daniel; Jakob, Jens; Ashmawy, Hany; Hettmer, Simone; Tuchscherer, Armin; et al. (Oncology Research and Treatment, 2021)
Background: Data on institutional structures of sarcoma care in Germany are scarce. The utilization of an interdisciplinary tumor board (IDTB) is an essential part of modern cancer care. We investigated to which extent and when IDTB are used in sarcoma care. We hypothesized that IDTB before treatment initiation were used more often at certified cancer centers and at high-volume centers and that IDTB utilization increased over time. Methods: From 2017 to 2020 we conducted a prospective cohort study, undertaking major efforts to include the whole spectrum of sarcoma treatment facilities. To analyze potential predictors of IDTB utilization, we calculated multivariable logistic regressions. Results: Patients and survivors (n = 1,309) from 39 study centers (22 tertiary referral hospitals, 9 other hospitals, and 8 office-based practices) participated; 88.3% of the patients were discussed at some stage of their disease in an IDTB (56.1% before treatment, 78% after therapy, and 85.9% in metastatic disease). Hypotheses were confirmed regarding the utilization of IDTB in certified cancer centers (vs. all others: OR = 5.39; 95% CI 3.28-8.85) and the time of diagnosis (2018/2019 vs. until 2013: OR = 4.95; 95% CI 2.67-9.21). Conclusion:Our study adds to the evidence regarding the institutional structures of sarcoma care in Germany. Utilization of a tumor board before therapy seems to be in an implementation process that is making progress but is far from complete. Certification is a possible tool to accelerate this development.
CRIS-Team WoS Importer:2021-05-14

Validation of a Parvovirus B19 NAT Assay for Screening of Umbilical Cord Blood for Allogenic Hematopoietic Stem Cell Donation - Steininger, Philipp; Korn, Klaus; Hackstein, Holger; Strasser, Erwin F. (Transfusion Medicine and Hemotherapy, 2023)
Introduction: Parvovirus B19 transmitted by umbilical cord blood (UCB) products may cause severe disease in allogenic hematopoietic stem cell transplant recipients. Thus, commercially available nucleic acid test (NAT) assays for highly sensitive detection of parvovirus B19 DNA validated for the specimen cord blood plasma (CBP) are required to avoid parvovirus B19 transmission by umbilical hematopoietic stem cell preparations. Methods: The multiplex cobas DPX NAT assay was validated for detection of parvovirus B19 DNA in CBP derived from citrate anticoagulated UCB units which have been processed by the Rubinstein method. In total, 363 retained CBP samples pretested negative for parvovirus B19 DNA were prepared for analyzing sensitivity, specificity, and interference of that NAT assay. The 3rd WHO International Standard for parvovirus B19 DNA was used for determining the 95% limit of detection (LOD95) by probit analysis. Results: The validation of the parvovirus B19 NAT assay for CBP demonstrated high sensitivity, specificity, intra- and inter-assay precision. Dilution series and replicate analyses showed a high linearity of the assay with a coefficient of determination above 0.99 and revealed a LOD95 of 17 International Units (IU)/mL (95% confidence interval, 14-44 IU/mL) for parvovirus B19 DNA in CBP samples. Conclusion: The validation of a commercially available parvovirus B19 NAT assay for the specimen CBP demonstrated a high assay performance fulfilling German guidelines and international regulations.
CRIS-Team Scopus Importer:2023-10-20
Keywords: Allogenic hematopoietic stem cell donation; Nucleic acid test screening; Parvovirus B19; Umbilical cord blood

Validation of a SARS-CoV-2 RNA RT-PCR assay for high-throughput testing in blood of COVID-19 convalescent plasma donors and patients - Strasser, Erwin; Steininger, Philipp; Korn, Klaus; Achenbach, Susanne; Tenbusch, Matthias; Cunningham, Sarah; Zimmermann, Robert; Überla, Klaus; Hackstein, Holger (Transfusion, 2020)
Background The frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNAemia in blood donors is uncertain. Thus, assays for SARS-CoV-2 RNA detection in blood, validated on commercially available polymerase chain reaction (PCR) systems, are required to allow a good comparability of data.
CRIS-Team WoS Importer:2020-11-27

Validation of the reliability of computational O-GlcNAc prediction - Jochmann, Ramona; Holz, Patrick; Sticht, Heinrich; Stürzl, Michael (Biochimica Et Biophysica Acta-Proteins and Proteomics, 2014)
O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. Based on this information, computational prediction tools of O-GlcNAc sites have been developed. Here, we retrospectively assessed the performance of two available O-GlcNAc prediction programs YinOYang 1.2 server and OGlcNAcScan by comparing their predictions for recently discovered experimentally validated O-GlcNAc sites. Both prediction programs efficiently identified O-GlcNAc sites situated in an environment resembling the consensus sequence P-P-V-[ST]-T-A. However, both prediction programs revealed numerous false negative O-GlcNAc predictions when the site of modification was located in an amino acid sequence differing from the known consensus sequence. By searching for a common sequence motif, we found that O-GlcNAcylation of nucleocytoplasmic proteins preferably occurs at serine and threonine residues flanked downstream by proline and valine and upstream by one to two alanines followed by a stretch of serine and threonine residues. However, O-GlcNAcylation of proteins located in the mitochondria or in the secretory lumen occurs at different sites and does not follow a distinct consensus sequence. Thus, our study indicates the limitations of the presently available computational prediction methods for O-GlcNAc sites and suggests that experimental validation is mandatory. Continuously update and further development of available databases will be the key to improve the performance of O-GlcNAc site prediction.
EVALuna2:15154

Variation in Bile Microbiome by the Etiology of Cholestatic Liver Disease - Tyc, Olaf; Jansen, Christian; Schierwagen, Robert; Uschner, Frank Erhard; Israelsen, Mads; Klein, Sabine; Ortiz, Cristina; Strassburg, Christian P.; Zeuzem, Stefan; Gu, Wenyi; Torres, Sandra; Praktiknjo, Michael; et al. (Liver Transplantation, 2020)
CRIS-Team Scopus Importer:2020-10-16

Variations in the Vascular Anatomy of the Right Colon and Implications for Right-Sided Colon Surgery - Kuzu, Mehmet Ayhan; Ismail, Erkin; Celik, Safa; Sahin, Muhammed Feyzi; Guner, Mehmet Ali; Hohenberger, Werner; Acar, Halil Ibrahim (Diseases of the colon & rectum, 2017)
Knowledge of the normal pattern and variations of the blood supply of the right colon is crucial for better outcomes after colon surgery.The purpose of this study was to describe the precise vascular anatomy of the right colon according to surgical perspective.Adult fresh cadavers were dissected between January 2013 and October 2015, focusing on the venous and arterial anatomy of the right side of the colon.Macroscopic anatomical dissections were performed on 111 adult fresh cadavers with emphasis on the vascular anatomy of the right colon. The colic tributaries of the superior mesenteric artery and vein were documented in writing. Furthermore, the dissections were recorded with a video camera.The incidence of colic arteries arising from the superior mesenteric artery included ileocolic artery, 100%; right colic artery, 33.3%; middle colic artery, 100%; and accessory middle colic artery, 11,7%. All 111 cadavers had a single ileocolic vein, which drained into the superior mesenteric vein in 103 cases (92.8%), into the gastro-pancreatico-colic trunk in 7 cases (6.3%), and into the jejunal trunk in 1 case (0.9%). The drainage site of the ileocolic vein to the superior mesenteric vein varied, and in 9% of cases the ileocolic vein did not accompany the ileocolic artery. The gastro-pancreatico-colic trunk was detected in 87 cases (78.4%); with several forms of the origin of the respective branches, the gastropancreatic trunk was detected in 24 cases (21.6), and the classic gastrocolic trunk of Henle was not detected. Variations were found in the formation and drainage routes of other venous colic tributaries of the superior mesenteric vein.This study is limited by its use of cadavers in that it is impossible to trace each vessel to its origin in live surgery.Surgeons must watch, observe, and bear in mind that vascular variations can occur. Awareness of these complex variations may improve the quality of surgery and may prevent devastating complications during right-sided colon resections.
EVALuna2:15296

Vascular diseases in triathletes - Regus, Susanne (Gefässchirurgie, 2019)
The vast majority of triathletes do not have any cardiovascular risk factors; however, there are increasing numbers of reports of arterial complications in these unusual patients for vascular surgeons. In the literature three types of complications have been reported: iliac artery endofibrosis, femoral adductor canal syndrome and popliteal artery entrapment syndrome. All three disease entities have in common an exogenic compression-related vascular wall damage. The correct diagnosis is not uncommonly made after a delay of several years. This can be explained by the mostly unspecific symptoms, easily palpable foot pulses and a resting ankle-brachial index (ABI) within normal ranges. The most important diagnostic tool is a reduction of the ABI after maximum effort. Magnetic resonance angiography (MRA) is often preferred to computed tomography angiography (CTA) to reduce radiation exposure. Digital subtraction angiography (DSA) should first be used following cross-sectional imaging methods and only in combination with interventional treatment measures. The exogenic vascular affection can only be eliminated by operative repair, which is why surgical treatment shows the best long-term results.
CRIS-Team WoS Importer:2019-02-21

Vascular occlusion by neutrophil extracellular traps in COVID-19 - Leppkes, Moritz; Knopf, Jasmin; Naschberger, Elisabeth; Lindemann, Aylin; Singh, Jeeshan; Herrmann, Irmgard; Stürzl, Michael; Staats, Léonie; Mahajan, Aparna; Kremer, Anita; Amann, Kerstin Ute; Evert, Katja; et al. (EBioMedicine, 2020)
Background: Coronavirus induced disease 2019 (COVID-19) can be complicated by severe organ damage leading to dysfunction of the lungs and other organs. The processes that trigger organ damage in COVID-19 are incompletely understood. Methods: Samples were donated from hospitalized patients. Sera, plasma, and autopsy-derived tissue sections were examined employing flow cytometry, enzyme-linked immunosorbent assays, and immunohistochemistry. Patient findings: Here, we show that severe COVID-19 is characterized by a highly pronounced formation of neutrophil extracellular traps (NETs) inside the micro-vessels. Intravascular aggregation of NETs leads to rapid occlusion of the affected vessels, disturbed microcirculation, and organ damage. In severe COVID-19, neutrophil granulocytes are strongly activated and adopt a so-called low-density phenotype, prone to spontaneously form NETs. In accordance, markers indicating NET turnover are consistently increased in COVID-19 and linked to disease severity. Histopathology of the lungs and other organs from COVID-19 patients showed congestions of numerous micro-vessels by aggregated NETs associated with endothelial damage. Interpretation: These data suggest that organ dysfunction in severe COVID-19 is associated with excessive NET formation and vascular damage. Funding: Deutsche Forschungsgemeinschaft (DFG), EU, Volkswagen-Stiftung
CRIS-Team Scopus Importer:2020-08-14
Keywords: Aggregated neutrophil extracellular traps; Coagulopathy; Endothelialitis; Immunothrombosis; SARS-CoV-2

VEGFR2 Signaling Prevents Colorectal Cancer Cell Senescence to Promote Tumorigenesis in Mice With Colitis - Försch, Sebastian; Sperka, Tobias; Lindner, Christina; Taut, Astrid; Rudolph, Karl L.; Breier, Georg; Boxberger, Frank; Rau, Tilman; Hartmann, Arndt; Stürzl, Michael; Wittkopf, Nadine; Haep, Lisa; et al. (Gastroenterology, 2015)
Senescence prevents cellular transformation. We investigated whether vascular endothelial growth factor (VEGF) signaling via its receptor, VEGFR2, regulates senescence and proliferation of tumor cells in mice with colitis-associated cancer (CAC).CAC was induced in VEGFR2(?IEC) mice, which do not express VEGFR2 in the intestinal epithelium, and VEGFR2(fl/fl) mice (controls) by administration of azoxymethane followed by dextran sodium sulfate. Tumor development and inflammation were determined by endoscopy. Colorectal tissues were collected for immunoblot, immunohistochemical, and quantitative polymerase chain reaction analyses. Findings from mouse tissues were confirmed in human HCT116 colorectal cancer cells. We analyzed colorectal tumor samples from patients before and after treatment with bevacizumab.After colitis induction, VEGFR2(?IEC) mice developed significantly fewer tumors than control mice. A greater number of intestinal tumor cells from VEGFR2(?IEC) mice were in senescence than tumor cells from control mice. We found VEGFR2 to activate phosphatidylinositol-4,5-bisphosphate-3-kinase and AKT, resulting in inactivation of p21 in HCT116 cells. Inhibitors of VEGFR2 and AKT induced senescence in HCT116 cells. Tumor cell senescence promoted an anti-tumor immune response by CD8(+) T cells in mice. Patients whose tumor samples showed an increase in the proportion of senescent cells after treatment with bevacizumab had longer progression-free survival than patients in which the proportion of senescent tumor cells did not change before and after treatment.Inhibition of VEGFR2 signaling leads to senescence of human and mouse colorectal cancer cells. VEGFR2 interacts with phosphatidylinositol-4,5-bisphosphate-3-kinase and AKT to inactivate p21. Colorectal tumor senescence and p21 level correlate with patient survival during treatment with bevacizumab.
EVALuna2:1356

Ventral rectopexy with biological mesh for recurrent disorders of the posterior pelvic organ compartment - Brunner, Michaela; Roth, H.; Günther, K.; Grützmann, Robert; Matzel, Klaus E. (International Journal of Colorectal Disease, 2019)
PURPOSE: Recurrent prolapse of the posterior pelvic organ compartment presents a management challenge, with the best surgical procedure remaining unclear. We present functional outcome and patient satisfaction after laparoscopic and robotic ventral mesh rectopexy (VMR) with biological mesh in patients with recurrence. METHODS: We analyzed data from 30 patients with recurrent posterior pelvic organ prolapse who underwent VMR with biological mesh from August 2012 to January 2018. Data included patient demographics and intra- and postoperative findings; functional outcome as assessed by Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Score Longo (ODS), and Cleveland Clinic Incontinence Score (CCIS); and patient satisfaction. RESULTS: CCCS, CCIS, and ODS were significantly improved at 6-12 months postoperatively and at last follow-up. Patient satisfaction (visual analog scale [VAS] 6.7 [0 to 10]), subjective symptoms (+ 3.4 [scale - 5 to + 5]), and quality of life improvement (+ 3.0 [scale from - 5 to + 5]) were high at last follow-up. The rates of morbidity and major complications were 13% and 3%, respectively. There were no mesh-related complications or deaths. Difference in type of previous surgery (abdominal or transanal/perineal) had no significant effect on results. CONCLUSIONS: VMR with biological mesh is a safe and effective option for patients with recurrent posterior pelvic organ prolapse. It reduces functional symptoms, has a low complication rate, and promotes patient satisfaction.
CRIS-Team Scopus Importer:2019-10-01
Keywords: Biological mesh; Functional outcome; Laparoscopic ventral rectopexy; Recurrent posterior compartment prolapse; Recurrent rectal prolapse

Ventral rectopexy with biological mesh: short-term functional results - Brunner, Michaela; Roth, H.; Guenther, K.; Grützmann, Robert; Matzel, K. E. (International Journal of Colorectal Disease, 2018)
PURPOSE: Ventral mesh rectopexy (VMR) is an established, minimally invasive, nerve-sparing procedure for the treatment of various symptomatic morphological changes in the posterior pelvic compartment. We present the short-term functional outcome and patient satisfaction after laparoscopic and robotic VMR with biological mesh. METHODS: We analyzed data from 123 patients who underwent laparoscopic ventral mesh rectopexy (LVMR) or robotic ventral mesh rectopexy (RVMR) from August 2012 to January 2017. Included in these data were patient demographics, intra- and postoperative findings, Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Score Longo (ODS), Cleveland Clinic Incontinence Score (CCIS), and patient satisfaction as measured by visual analog scale (0-10). RESULTS: Improvements in CCCS, CCIS, and ODS were statistically significant at 6 and 12 months (p < 0.001). Patient satisfaction was excellent at 6 and 12 months (8.2/10 and 8.3/10, respectively). The overall complication rate was 14%, with a major complication rate of 2%. No mesh-related complications were observed. The need for surgical re-intervention because of relapse, symptom persistence or recurrence, or new symptoms was 3%. Outcome appears to be similar between LVMR and RVMR. CONCLUSIONS: Both LVMR and RVMR with biological mesh are safe and effective in reducing symptoms, as measured by CCCS, CCIS, and ODS, and patient satisfaction is high.
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Vertebral Penetration of an Inferior Vena Cava Filter - Regus, Susanne; Lang, Werner (European Journal of Vascular and Endovascular Surgery, 2017)
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Video double-lumen tube for one lung ventilation: implementation and experience in 343 cases of routine clinical use during the first 20 months of the SARS-CoV-2 pandemic - Irouschek, Andrea; Schmidt, Joachim; Birkholz, Torsten; Sirbu, Horia; Moritz, Andreas (Journal of Cardiothoracic Surgery, 2024)
Background: Double-lumen tubes (DLTs) are the preferred device for lung isolation. Conventional DLTs (cDLT) need a bronchoscopic position control. Visualisation of correct DLT positioning could be facilitated by the use of a video double-lumen tube (vDLT). During the SARS-CoV-2-pandemic, avoiding aerosol-generation was suggesting using this device. In a large retrospective series, we report both general and pandemic related experiences with the device. Methods: All anesthesia records from patients aged 18 years or older undergoing surgery from April 1st, 2020 to December 31st, 2021 in the department of thoracic surgery requiring intraoperative lung isolation were analyzed retrospectively. Results: During the investigation period 343 left-sided vDLTs (77.4%) and 100 left-sided cDLTs (22.6%) were used for one lung ventilation. In the vDLT group bronchoscopy could be reduced by 85.4% related to the cDLT group. Additional bronchoscopy to reach or maintain correct position was needed in 11% of the cases. Other bronchoscopy indications occured in 3.6% of the cases. With cDLT, in 1% bronchoscopy for other indications than conforming position was observed. Conclusions: The Ambu® VivaSight™ vDLT is an efficient, easy-to-use and safe airway device for the generation of one lung ventilation in patients undergoing thoracic surgery. The vDLT implementation was achieved easily with full interchangeability to the left-sided cDLT. Using the vDLT can reduce the need for aerosol-generating bronchoscopic interventions by 85.4%. Continuous video view to the carina enabling position monitoring of the DLT without need for bronchoscopy might be beneficial for both employee’s and patient’s safety.
CRIS-Team Scopus Importer:2024-05-03
Keywords: Double-lumen tube; One lung ventilation; SARS-CoV-2; Thoracic surgery; Video double-lumen tube

Videothoracoscopic Sympathetic Clipping in a Patient With Azygos Lobe. Intraoperative Management to Avoid Potential Complications - Schreiner, Waldemar; Mykoliuk, Iurii; Dudek, Wojciech; Sirbu, Horia (Zentralblatt für Chirurgie, 2018)
INTRODUCTION: Sympathetic clipping in the presence of an azygos lobe is a rare combination. Anatomical relations between the sympathetic trunk and the mesoazygos impede surgical handling and can be associated with potential complications. INDICATION: We report the case of a 25-year old woman with grade III palmoplantar and axillary hyperhidrosis with azygos lobe incidentally found on preoperative chest X-ray. METHOD: Our intraoperative video shows a step-by-step approach to the sympathetic trunk in the presence of the azygos lobe, involving thoracoscopic looping and precise clip application onto the sympathetic trunk. Video-assisted reposition and expansion of the accessory lobe to avoid potential complications have been demonstrated. CONCLUSION: Videothoracoscopic sympathetic clipping in patients with lobus azygos is technically challenging. Potential complications can be avoided by coordinated surgical management.
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Viral FLIP blocks Caspase-8 driven apoptosis in the gut in vivo - Ruder, Barbara; Günther, Claudia; Stürzl, Michael; Neurath, Markus; Cesarman, Ethel; Ballon, Gianna; Becker, Christoph (PLoS ONE, 2020)
A strict cell death control in the intestinal epithelium is indispensable to maintain barrier integrity and homeostasis. In order to achieve a balance between cell proliferation and cell death, a tight regulation of Caspase-8, which is a key player in controlling apoptosis, is required. Caspase-8 activity is regulated by cellular FLIP proteins. These proteins are expressed in different isoforms (cFLIPlong and cFLIPshort) which determine cell death and survival. Interestingly, several viruses encode FLIP proteins, homologous to cFLIPshort, which are described to regulate Caspase-8 and the host cell death machinery. In the current study a mouse model was generated to show the impact of viral FLIP (vFLIP) from Kaposi's Sarcoma-associated Herpesvirus (KSHV)/ Human Herpesvirus-8 (HHV-8) on cell death regulation in the gut. Our results demonstrate that expression of vFlip in intestinal epithelial cells suppressed cFlip expression, but protected mice from lethality, tissue damage and excessive apoptotic cell death induced by genetic cFlip deletion. Finally, our model shows that vFlip expression decreases cFlip mediated Caspase-8 activation in intestinal epithelial cells. In conclusion, our data suggests that viral FLIP neutralizes and compensates for cellular FLIP, efficiently counteracting host cell death induction and facilitating further propagation in the host organism.
CRIS-Team Scopus Importer:2020-02-11

Viral inhibitor of apoptosis vFLIP/K13 protects endothelial cells against superoxide-induced cell death - Thurau, Mathias; Marquardt, Gaby; Britzen-Laurent, Nathalie; Weinlaender, Kristina; Naschberger, Elisabeth; Jochmann, Ramona; Alkharsah, Khaled R.; Schulz, Thomas F.; Thome, Margot; Neipel, Frank; Stürzl, Michael (Journal of Virology, 2009)
Human herpesvirus 8 (HHV-8) is the etiological agent of Kaposi's sarcoma (KS). HHV-8 encodes an antiapoptotic viral Fas-associated death domain-like interleukin-1β-converting enzyme-inhibitory protein (vFLIP/K13). The antiapoptotic activity of vFLIP/K13 has been attributed to an inhibition of caspase 8 activation and more recently to its capability to induce the expression of antiapoptotic proteins via activation of NF-κB. Our study provides the first proteome-wide analysis of the effect of vFLIP/K13 on cellular-protein expression. Using comparative proteome analysis, we identified manganese superoxide dismutase (MnSOD), a mitochondrial antioxidant and an important antiapoptotic enzyme, as the protein most strongly upregulated by vFLIP/K13 in endothelial cells. MnSOD expression was also upregulated in endothelial cells upon infection with HHV-8. Microarray analysis confirmed that MnSOD is also upregulated at the RNA level, though the differential expression at the RNA level was much lower (5.6-fold) than at the protein level (25.1-fold). The induction of MnSOD expression was dependent on vFLIP/K13-mediated activation of NF-κB, occurred in a cell-intrinsic manner, and was correlated with decreased intracellular superoxide accumulation and increased resistance of endothelial cells to superoxide-induced death. The upregulation of MnSOD expression by vFLIP/K13 may support the survival of HHV-8-infected cells in the inflammatory microenvironment in KS. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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Virus-reactive T cells expanded in aplastic anemia eliminate hematopoietic progenitor cells by molecular mimicry - Ben Hamza, Amin; Welters, Carlotta; Stadler, Serena; Brüggemann, Monika; Dietze, Kerstin; Brauns, Olaf; Brümmendorf, Tim H.; Winkler, Thomas; Bullinger, Lars; Blankenstein, Thomas; Rosenberger, Leonie; Leisegang, Matthias; et al. (Blood, 2024)
Acquired aplastic anemia is a bone marrow failure syndrome characterized by hypocellular bone marrow and peripheral blood pancytopenia. Frequent clinical responses to calcineurin inhibition and antithymocyte globulin strongly suggest critical roles for hematopoietic stem/progenitor cell–reactive T-cell clones in disease pathophysiology; however, their exact contribution and antigen specificities remain unclear. We determined differentiation states and targets of dominant T-cell clones along with their potential to eliminate hematopoietic progenitor cells in the bone marrow of 15 patients with acquired aplastic anemia. Single-cell sequencing and immunophenotyping revealed oligoclonal expansion and effector differentiation of CD8+ T-cell compartments. We reexpressed 28 dominant T-cell receptors (TCRs) of 9 patients in reporter cell lines to determine reactivity with (1) in vitro–expanded CD34+ bone marrow, (2) CD34− bone marrow, or (3) peptide pools covering immunodominant epitopes of highly prevalent viruses. Besides 5 cytomegalovirus-reactive TCRs, we identified 3 TCRs that recognized antigen presented on hematopoietic progenitor cells. T cells transduced with these TCRs eliminated hematopoietic progenitor cells of the respective patients in vitro. One progenitor cell–reactive TCR (11A5) also recognized an epitope of the Epstein-Barr virus–derived latent membrane protein 1 (LMP1) presented on HLA-A∗02:01. We identified 2 LMP1-related mimotopes within the human proteome as activating targets of TCR 11A5, providing proof of concept that molecular mimicry of viral and self-epitopes can drive T cell–mediated elimination of hematopoietic progenitor cells in aplastic anemia.
CRIS-Team Scopus Importer:2024-03-08

Voice- and health-related quality of life in the elderly - Plank, Christian Georg; Schneider, Sabine; Eysholdt, Ulrich; Schützenberger, Anne; Rosanowski, Frank (Journal of Voice, 2011)
Objective: Restrictions of verbal communication and high prevalence of voice disorders in the elderly are suspected to influence the quality of life. For assessment, both voice-specific and unspecific methods are already established and fundamental components of clinical diagnostics, but the question of correlation between voice-related and general health-related quality of life is still open in this subpopulation. Methods: One hundred and seven socially active persons aged 65+ years were recruited and asked to complete Voice-Related Quality of Life (V-RQOL) and Short Form (SF)-36 questionnaires. Results: There was a mild correlation between V-RQOL score and both of the SF-36 subscores (rs = 0.28 for the physical subscore and rs = 0.27 for the mental subscore). Conclusion: As correlation of voice- and health-related quality of life in elderly persons is only mild, both voice-specific and unspecific assessment methods are required for clinical diagnostics. © 2011 The Voice Foundation.
CRIS-Team Scopus Importer:2022-09-20
Keywords: Elderly; Quality of life; Voice

Von der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie konsentierte Operationsindikationen beim duktalen Pankreasadenokarzinom - Belyaev, Orlin; Bösch, Florian; Brunner, Maximilian; Müller-Debus, Charlotte Friederieke; Radulova-Mauersberger, Olga; Wellner, Ulrich Friedrich; Grützmann, Robert; Keck, Tobias; Werner, Jens; Witzigmann, Helmut; Uhl, Waldemar (Zentralblatt für Chirurgie, 2020)
Background Surgery for pancreatic cancer in Germany is increasing due to the climbing incidence of this cancer in the population. This review presents a summary of modern evidence-based indications for surgery in patients with pancreatic ductal adenocarcinoma (PDAC). Methods The German Society for General and Visceral Surgery (DGAV) authorised a task force to define evidence based indications for surgery in patients with PDAC. A systematic literature search in Medline and Cochrane Library databases (1989-2019) was performed. Recommendations were summarised on the basis of the most relevant and recent guidelines and clinical studies and then voted by members of the Working Group on Hepato-Biliary and Pancreatic Diseases (CALGP) in a Delphi procedure. Results Indications for surgery in patients with PDAC should be set by experienced pancreatic surgeons within a tumour board. Decisions should consider the guidelines as well as the individual patient characteristics. Large vessel infiltration, metastatic disease and severe comorbidities are the most common contraindications for surgery. Borderline-resectable, primary resectable oligometastatic and secondary resectable PDAC should be preferably managed at high-volume centres as a part of clinical studies. Centralisation of pancreatic surgery reduces mortality and improves survival. Palliative bypass surgery as well as staging laparoscopy are still indicated in a large proportion of patients with PDAC. Conclusion Irrespective of the recent development of multimodal therapeutic concepts, surgical resection remains the sole chance of long-term cure for patients with PDAC. Due to the significant proportion of patients in advanced stages of the disease, palliative surgery still plays an important role in the complex management of this cancer.
CRIS-Team Scopus Importer:2020-07-24
Keywords: German Society for General and Visceral Surgery; guideline; indications for surgery; pancreatic ductal adenocarcinoma; surgery

von Willebrand factor, clotting factors, and clotting inhibitors in apheresis platelet concentrates - Weiss, Dominik R.; Franke, D.; Strasser, Erwin F.; Ringwald, Juergen; Zimmermann, Robert; Eckstein, Reinhold (Transfusion, 2014)
Apheresis platelet concentrates (APCs) are usually stored in citrated plasma at 22°C. The stability of coagulation proteins-von Willebrand factor (vWF), clotting factors (CFs), and their inhibitors-has often been described in association with the storage of thawed plasma. However, fewer data are available regarding changes in APCs.We measured CF activities and inhibitors in APCs on the day of manufacture (Day 0) and on Days 4, 5, and 7. vWF was determined by measuring vWF antigen (vWF:Ag) and vWF ristocetin cofactor (vWF:RCo) and by multimer analysis.Twenty-one PCs obtained by plateletpheresis were studied. Major changes were observed for Factor (F)VIII (37% loss of activity within 4 days), FV (20% within 4 days), and protein S (76% within 4 days). All other CF activities remained higher than 80% over the 7 days. Fibrinogen and the inhibitors antithrombin and protein C remained quite stable. FXI, FXII, and FXIII actually increased during storage (8, 11, and 12% within 4 days). vWF:Ag increased during storage of APCs by 2% per day, with a relative loss of vWF:RCo and high-molecular-weight multimers.Even after 7 days of storage at 22°C, the hemostatic potential of the plasma content in APCs was roughly preserved. The increase in FXII antigen indicates that this CF may also be stored in platelets; however, this has not yet been described.
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Von Willebrand factor multimer structure is neither acutely nor chronically affected by plateletpheresis - Weiss, Dominik R; Dankerl, Helen; Martin, Alexander; Strasser, Erwin F; Ringwald, Jürgen; Eckstein, Reinhold; Zimmermann, Robert (Clinical Laboratory, 2014)
Plateletpheresis (PltPh) exposes the donor's blood to artificial surfaces and mechanical forces such as shear stress and centrifugation. In terms of the donor's safety and the quality of the apheresis platelet concentrate (APC), possible impairment of platelet function due to PltPh should be excluded. Von Willebrand factor (VWF) plays a pivotal role in platelet adhesion and aggregation. VWF is a multimeric protein and can be damaged by adsorption or shear stresses. It is unclear whether VWF structure could be damaged during PltPh, leading to platelet dysfunction.We analyzed VWF antigen (VWF:Ag), ristocetin cofactor (VWF:RCo), and VWF multimer structure immediately before and after apheresis in the donor and in the APC. These parameters and factor VIII activity (FVIII:C) and closure time using PFA-100 (CT) were also analyzed in blood samples taken from new donors before the first and before subsequent donations and from long-term donors.During apheresis, VWF:Ag falls by about 15% but the VWF multimer structure remains unchanged. In samples taken before subsequent donations, there was a tendency of VWF:Ag and FVIII:C to increase throughout the initial donations, but no alteration of multimer structure. Long-term donors, however, show a normal VWF multimer structure and normal concentrations of VWF:Ag, VWF:RCo, and FVIII:C. In some donors with low-normal VWF:Ag and VWF:RCo, PFA-100 CT was prolonged.VWF multimer structure is neither acutely nor chronically affected by plateletpheresis. A decrease in VWF:Ag with no functional damage only occurs acutely and can be explained by the withdrawal of plasma and dilution with the anticoagulant ACD-A due to apheresis.
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Waiting ("Watch and Wait") for complete clinical remission after neoadjuvant radiochemotherapy of rectal carcinomas: influence of salvage-therapy on local tumor control - Hohenberger, Werner (Strahlentherapie und Onkologie, 2014)
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„Watchful Waiting“ als Alternative zur Rektumexstirpation nach kompletter Tumorremission infolge neoadjuvant intendierter Radiochemotherapie? - Hohenberger, Werner; Sauer, Rolf (Strahlentherapie und Onkologie, 2016)
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What is Changing in Indications and Treatment of Focal Nodular Hyperplasia of the Liver. Is There Any Place for Surgery? - Perrakis, Aristotelis; Vassos, Nikolaos; Grützmann, Robert; Croner, Roland S. (Annals of Hepatology, 2017)
Focal nodular hyperplasia (FNH) is a common benign liver tumor, which occurs in the vast majority of the cases in young women. FNH represents a polyclonal lesion characterized by local vascular abnormalities and is a truly benign lesion without any potential for malignant transformation. A retrospective single institution analysis of 227 FNH patients, treated from 1990 to 2016 and a review of studies reporting surgical therapy of overall 293 patients with FNH was performed. Indications for resection with a focus on diagnostic workup, patient selection, surgical mode and operative mortality and morbidity have been analysed. Ninety three patients underwent elective hepatectomy and 134 patients observation alone, where median follow-up was 107 months. Postoperative complications were recorded in 14 patients, 92% of patients reported an improvement with respect to their symptoms. Overall among 293 patients underwent surgery in the series, included to this review, there was a morbidity of 13%, where median follow-up was 53 months. Systematic follow-up remains the gold standard in asymptomatic patients with FNH. However elective surgery should be considered in symptomatic patients, in those with marked enlargement and in case of uncertainty of diagnosis. Surgery for FNH is a safe procedure with low morbidity and very good long term results as far as quality of life after surgery is concerned and surely an integral part of the modern management of FNH.
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What rheumatologists can learn from gastroenterologists - Fischer, Sören; Beyer, Christian; Neurath, Markus (Zeitschrift für Rheumatologie, 2018)
BACKGROUND: Chronic inflammatory diseases are complex disorders, which due to their multitude of manifestations require interdisciplinary treatment. OBJECTIVE: The aim of this article is to provide a brief overview of current strategies and innovations for chronic inflammatory bowel diseases. METHODS: A literature search was carried out in PubMed. RESULTS: Shared pathophysiological pathways in chronic inflammatory diseases sometimes lead to common targets in treatment; however, there are also relevant specific differences with respect to treatment. CONCLUSION: Due to the many extraintestinal organ manifestations, chronic inflammatory bowel diseases require interdisciplinary treatment.
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WNT4 overexpression and secretion in thymic epithelial tumors drive an autocrine loop in tumor cells in vitro - Zhang, Xiaonan; Schalke, Berthold; Kvell, Krisztian; Kriegsmann, Katharina; Kriegsmann, Mark; Graeter, Thomas; Preissler, Gerhard; Ott, German; Kurz, Katrin; Bulut, Elena; Stroebel, Philipp; Marx, Alexander; et al. (Frontiers in Oncology, 2022)
Background: WNT4-driven non-canonical signaling is crucial for homeostasis and age-related involution of the thymus. Abnormal WNT signaling is important in many cancers, but the role of WNT signaling in thymic tumors is largely unknown. Materials & Methods: Expression and function of WNT4 and FZD6 were analyzed using qRT-PCR, Western blot, ELISA, in biopsies of non-neoplastic thymi (NT), thymoma and thymic carcinomas. ShRNA techniques and functional assays were used in primary thymic epithelial cells (pTECs) and TC cell line 1889c. Cells were conventionally (2D) grown and in three-dimensional (3D) spheroids. Results: In biopsy, WHO classified B3 thymomas and TCs showed increased WNT4 expression compared with NTs. During short-term 2D culture, WNT4 expression and secretion declined in neoplastic pTECs but not in 3D spheroids or medium supplemented with recombinant WNT4 cultures. Under the latter condition, the growth of pTECs was accompanied by increased expression of non-canonical targets RAC1 and JNK. Down-regulation of WNT4 by shRNA induced cell death in pTECs derived from B3 thymomas and led to decreased RAC1, but not JNK protein phosphorylation. Pharmacological inhibition of NF-kappa B decreased both RAC1 and JNK phosphorylation in neoplastic pTECs. Conclusions: Lack of the age-related decline of non-canonical WNT4 expression in TETs and restoration of declining WNT4 expression through exogeneous WNT4 or 3D culture of pTECs hints at an oncogenic role of WNT4 in TETs and is compatible with the WNT4 autocrine loop model. Crosstalk between WNT4 and NF-kappa B signaling may present a promising target for combined interventions in TETs.
CRIS-Team WoS Importer:2022-10-14

Wound closure by means of free flap and arteriovenous loop: Development of flap autonomy in the long-term follow-up - Rother, Ulrich; Müller-Mohnssen, Helena; Lang, Werner; Ludolph, Ingo; Arkudas, Andreas; Horch, Raymund E.; Regus, Susanne; Meyer, Alexander (International Wound Journal, 2019)
Free flaps in combination with arterial reconstruction by means of arteriovenous loops or bypass have, meanwhile, been established as a therapeutic option in defect reconstruction for areas without recipient vessels. Our aim was to analyse the long-term performance, flap autonomy, and the flap perfusion. Patients receiving this combined reconstruction at a single-centre institution were included. During follow-up examination, the patency of arterial reconstruction was investigated by duplex ultrasound. Flap micro-circulation was assessed by laser Doppler flowmetry and white light tissue spectrometry (O2C) as well as by indocyanine green fluorescence angiography. Twenty-three patients could be clinically followed up. Duplex ultrasound showed, in four cases, arterial pedicle occlusion in spite of vital flap. Comparison of the O2C perfusion parameters between flaps with occluded pedicles and those with intact inflow showed no significant difference (parameters sO2: P =.82; Flow: P =.31). Similar results were obtained by fluorescence angiography; no significant difference could be detected between both groups (parameters Ingress P =.13; Ingressrate P =.54). Combined vascular reconstruction with free tissue transfer is associated with a good long-term outcome and wound closure. Even after flap transplantation to areas with critical tissue perfusion, the flap can develop autonomy and thus survive after pedicle occlusion.
CRIS-Team Scopus Importer:2019-11-19
Keywords: arteriovenous loop; flap autonomy; flap perfusion; indocyanine green; laser Doppler

XCR1 expression distinguishes human conventional dendritic cell type 1 with full effector functions from their immediate precursors - Heger, Lukas; Hatscher, Lukas; Liang, Chunguang; Lehmann, Christian; Amon, Lukas; Lühr, Jennifer J.; Kaszubowski, Tomasz; Nzirorera, Rayk; Schaft, Niels; Dörrie, Jan; Irrgang, Pascal; Tenbusch, Matthias; et al. (Proceedings of the National Academy of Sciences of the United States of America, 2023)
Dendritic cells (DCs) are major regulators of innate and adaptive immune responses. DCs can be classified into plasmacytoid DCs and conventional DCs (cDCs) type 1 and 2. Murine and human cDC1 share the mRNA expression of XCR1. Murine studies indicated a specific role of the XCR1-XCL1 axis in the induction of immune responses. Here, we describe that human cDC1 can be distinguished into XCR1- and XCR1+ cDC1 in lymphoid as well as nonlymphoid tissues. Steady-state XCR1+ cDC1 display a preactivated phenotype compared to XCR1- cDC1. Upon stimulation, XCR1+ cDC1, but not XCR1- cDC1, secreted high levels of inflammatory cytokines as well as chemokines. This was associated with enhanced activation of NK cells mediated by XCR1+ cDC1. Moreover, XCR1+ cDC1 excelled in inhibiting replication of Influenza A virus. Further, under DC differentiation conditions, XCR1- cDC1 developed into XCR1+ cDC1. After acquisition of XCR1 expression, XCR1- cDC1 secreted comparable level of inflammatory cytokines. Thus, XCR1 is a marker of terminally differentiated cDC1 that licenses the antiviral effector functions of human cDC1, while XCR1- cDC1 seem to represent a late immediate precursor of cDC1.
CRIS-Team Scopus Importer:2023-08-25
Keywords: antiviral immunity; cDC1; DC differentiation; IL-12; XCR1

ypN0 nodal status after neoadjuvant chemoradiotherapy for rectal carcinoma is not associated with adverse prognosis as compared with pN0 after primary surgery - Erlenbach-Wuensch, Katharina; Semrau, Sabine; Fietkau, Rainer; Weber, Klaus; Hohenberger, Werner; Rau, Tilman; Hartmann, Arndt; Merkel, Susanne; Agaimy, Abbas (International Journal of Colorectal Disease, 2014)
Neoadjuvant chemoradiotherapy (nCRT) has been established as standard treatment for locally advanced rectal cancer (cT3/4 or cN+ cM0, distance from circumferential resection margin <=1 mm) to enhance local disease control and minimize the rate of locoregional recurrence. As a consequence of downstaging, a significant proportion of patients show non-viable tumor deposits within regional lymph nodes that qualify as ypN0 according to the current TNM classification irrespective of the actual pre-treatment status. Accordingly, the prognostic relevance of ypN0 status as compared with true pN0 without preceding nCRT is not known.We retrospectively analyzed 132 patients who underwent standard total mesorectal excision (TME) surgery after nCRT for rectal carcinoma and were classified as ypN0, and compared their prognoses with those of 341 patients with pN0 without nCRT.Re-evaluation of regional lymph nodes after nCRT showed no evidence of previous metastasis in 91 cases (ypN0(-)), sure but non-viable metastasis in 14 patients (ypN0(+)), and unsure status in 27 patients (ypN0(X)). The local recurrence rate, distant metastases, and disease-free, observed, and cancer-related survival were similar in all subgroups (p = 0.447, 0.695, 0.759, 0.655, and 0.354, respectively).Our results showed a similar outcome in patients with ypN0 and in the control group with pN0 regarding local recurrence rate, distant metastases, and disease-free, observed, and cancer-related survival. Validation of these results is necessary to clarify the questions regarding postoperative adjuvant chemotherapy for patients with ypN0(+).
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Zusammenfassung des ESC Positionsdokuments „Krebsbehandlung und kardiovaskuläre Toxizität“ - Achenbach, Susanne (Best Practice Onkologie, 2017)
The numbers of survivors of cancer have increased as a consequence of advances in chemotherapy; however, the side effects of cancer treatment have become increasingly more important. The most frequent side effects include cardiovascular complications, which can lead to acute and delayed morbidity and mortality, often many years later. The discipline of cardio-oncology deals with the prevention, diagnostics and treatment of cardiovascular diseases caused by cancer therapy. The most important cardiovascular side effects of cytostatic therapy are heart failure due to myocardial dysfunction (cardiotoxicity), coronary artery disease, valvular disease and ventricular arrhythmia as a result of QT extension. In addition, arterial hypertension, thromboembolic events, pulmonary hypertension, vasculopathy and pericardial complications can also occur. Fundamentally, a strict limitation of risk factors is necessary to minimize the cardiovascular side effects of potentially cardiotoxic therapeutic procedures. Patients with impaired left ventricular function should be identified by echocardiographic examination prior to cardiotoxic chemotherapy. Treatment with beta blockers and angiotensin-converting enzyme (ACE) inhibitors can also be indicated in asymptomatic patients in order to minimize the effects of chemotherapy on myocardial dysfunction. Prophylactic administration of ACE inhibitors and beta blockers during anthracycline chemotherapy can be considered in patients free of cardiac disease.
CRIS-Team Scopus Importer:2023-03-08
Keywords: Cardiac arrhythmias; Cardio-oncology; Cardiotoxicity; Hypertension; Left ventricular dysfunction

β6-integrin serves as a novel serum tumor marker for colorectal carcinoma - Bengs, Susan; Becker, Eugenia; Busenhart, Philipp; Spalinger, Marianne R.; Raselli, Tina; Kasper, Stephanie; Lang, Silvia; Atrott, Kirstin; Mamie, Celine; Vavricka, Stephan R.; von Boehmer, Lotta; Knuth, Alexander; et al. (International Journal of Cancer, 2019)
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide and the need for novel biomarkers and therapeutic strategies to improve diagnosis and surveillance is obvious. This study aims to identify β6-integrin (ITGB6) as a novel serum tumor marker for diagnosis, prognosis, and surveillance of CRC. ITGB6 serum levels were validated in retro- and prospective CRC patient cohorts. ITGB6 serum levels were analyzed by ELISA. Using an initial cohort of 60 CRC patients, we found that ITGB6 is present in the serum of CRC, but not in non-CRC control patients. A cut-off of ≥2 ng/mL ITGB6 reveals 100% specificity for the presence of metastatic CRC. In an enlarged study cohort of 269 CRC patients, ITGB6 predicted the onset of metastatic disease and was associated with poor prognosis. Those data were confirmed in an independent, prospective cohort consisting of 40 CRC patients. To investigate whether ITGB6 can also be used for tumor surveillance, serum ITGB6-levels were assessed in 26 CRC patients, pre- and post-surgery, as well as during follow-up visits. After complete tumor resection, ITGB6 serum levels declined completely. During follow-up, a new rise in ITGB6 serum levels indicated tumor recurrence or the onset of new metastasis as confirmed by CT scan. ITGB6 was more accurate for prognosis of advanced CRC and for tumor surveillance as the established marker carcinoembryonic antigen (CEA). Our findings identify ITGB6 as a novel serum marker for diagnosis, prognosis, and surveillance of advanced CRC. This might essentially contribute to an optimized patient care.
CRIS-Team Scopus Importer:2019-06-18
Keywords: colorectal cancer; ITGB6; metastasis; serum tumor marker; surveillance; therapy response

β8 Integrin Mediates Pancreatic Cancer Cell Radiochemoresistance - Jin, Sha; Lee, Wei Chun; Aust, Daniela; Pilarsky, Christian; Cordes, Nils (Molecular Cancer Research, 2019)
Pancreatic ductal adenocarcinoma (PDAC) stroma, composed of extracellular matrix (ECM) proteins, promotes therapy resistance and poor survival rate. Integrin-mediated cell/ECM interactions are well known to control cancer cell survival, proliferation, and therapy resistance. Here, we identified β8 integrin in a high-throughput knockdown screen in three-dimensional (3D), ECM-based cell cultures for novel focal adhesion protein targets as a critical determinant of PDAC cell radiochemoresistance. Intriguingly, β8 integrin localizes with the golgi apparatus perinuclearly in PDAC cells and resection specimen from PDAC patients. Upon radiogenic genotoxic injury, β8 integrin shows a microtubule-dependent perinuclear-to-cytoplasmic shift as well as strong changes in its proteomic interactome regarding the cell functions transport, catalysis, and binding. Parts of this interactome link β8 integrin to autophagy, which is diminished in the absence of β8 integrin. Collectively, our data reveal β8 integrin to critically coregulate PDAC cell radiochemoresistance, intracellular vesicle trafficking, and autophagy upon irradiation. IMPLICATIONS: This study identified β8 integrin as an essential determinant of PDAC cell radiochemosensitivity and as a novel potential cancer target.
CRIS-Team Scopus Importer:2019-10-11

Effects of regional anesthesia techniques on local anesthetic plasma levels and complications in carotid surgery: A randomized controlled pilot trial - Roessel, Thomas; Uhlig, Christopher; Pietsch, Joerg; Ludwig, Stefan; Koch, Thea; Richter, Torsten; Spieth, Peter Markus; Kersting, Stephan (BMC Anesthesiology, 2019)
Background: The ultrasound guided intermediate cervical plexus block with perivascular infiltration of the internal carotid artery (PVB) is a new technique for regional anesthesia in carotid endarterectomy (CEA). We conducted a pilot study investigating the effects of deep cervical block (DCB), intermediate cervical block alone (ICB) and PVB on perioperative complications in patients undergoing elective CEA. We hypothesized, that the ropivacaine plasma concentration is higher in patients receiving DCB compared to PVB and ICB. Methods: In a randomized controlled pilot study thirty patients scheduled for elective CEA were randomly assigned into three groups: DCB receiving 20 mL ropivacaine 0.5% (n = 10), ICB receiving 20 mL ropivacaine 0.5% (n = 10) and PVB receiving 20 mL ropivacaine 0.5% and 10 mL ropivacaine 0,3% (n = 10). As primary outcome, plasma levels of ropivacaine were measured with high performance liquid chromatography before, 5, 10, 20, 60, and 180 min after the injection of ropivacaine. Secondary outcomes were vascular and neurological complications as well as patients' and surgeons' satisfaction. All analyses were performed on an intention-to-treat basis. Statistical significance was accepted at p < 0.05. Results: No conversion to general anesthesia was necessary and we observed no signs of local anesthetic intoxication or accidental vascular puncture. Plasma concentration of ropivacaine was significantly higher in the DCB group compared to PVB and ICB (p < 0.001) and in the PVB group compared to ICB (p = 0.008). Surgeons' satisfaction was higher in the PVB group compared to ICB (p = 0.003) and patients' satisfaction was higher in the PVB group compared to ICB (p = 0.010) and DCB group (p = 0.029). Phrenic nerve paralysis was observed frequently in the DCB group (p < 0.05). None of these patients with hemi-diaphragmatic paralysis showed signs of respiratory distress. Conclusion: The ultrasound guided PVB is a safe and effective technique for CEA which is associated with lower plasma levels of local anesthetic than the standard DCB. Considering the low rate of complications in all types of regional anesthesia for CEA, larger randomized controlled trials are warranted to assess potential side effects among the blocks.
CRIS-Team Scopus Importer:2019-12-10
Keywords: Carotid endarterectomy; Cervical plexus block; Local anesthetic; Plasma concentration; Regional anesthesia; Ropivacaine

International continence society best practice statement for use of sacral neuromodulation - Goldman, Howard B.; Lloyd, Jessica C.; Noblett, Karen L.; Carey, Marcus P.; Castano-Botero, Juan Carlos; Gajewski, Jerzy B.; Lehur, Paul A.; Hassouna, Magdy M.; Matzel, Klaus E.; Paquette, Ian M.; De Wachter, Stefan G.; Ehlert, Michael J.; et al. (Neurourology and Urodynamics, 2018)
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Risk stratification for postoperative pancreatic fistula using the pancreatic surgery registry StuDoQ|Pancreas of the German Society for General and Visceral Surgery - Petrova, Ekaterina; Lapshyn, Hryhoriy; Bausch, Dirk; D'Haese, Jan; Werner, Jens; Klier, Thomas; Nuessler, Natascha C.; Gaedcke, Jochen; Ghadimi, Michael; Uhl, Waldemar; Belyaev, Orlin; Kantor, Olga; et al. (Pancreatology, 2019)
Background: Postoperative pancreatic fistula (POPF) is a major factor for morbidity and mortality after pancreatic resection. Risk stratification for POPF is important for adjustment of treatment, selection of target groups in trials and quality assessment in pancreatic surgery. In this study, we built a risk-prediction model for POPF based on a large number of predictor variables from the German pancreatic surgery registry StuDoQ|Pancreas. Methods: StuDoQ|Pancreas was searched for patients, who underwent pancreatoduodenectomy from 2014 to 2016. A multivariable logistic regression model with elastic net regularization was built including 66 preoperative und intraoperative parameters. Cross-validation was used to select the optimal model. The model was assessed via area under the ROC curve (AUC) and calibration slope and intercept. Results: A total of N = 2488 patients were included. In the optimal model the predictors selected were texture of the pancreatic parenchyma (soft versus hard), body mass index, histological diagnosis pancreatic ductal adenocarcinoma and operation time. The AUC was 0.70 (95% CI 0.69–0.70), the calibration slope 1.67 and intercept 1.12. In the validation set the AUC was 0.65 (95% CI 0.64–0.66), calibration slope and intercept were 1.22 and 0.42, respectively. Conclusion: The model we present is a valid measurement instrument for POPF risk based on four predictor variables. It can be applied in clinical practice as well as for risk-adjustment in research studies and quality assurance in surgery.
CRIS-Team Scopus Importer:2019-05-02

Targeting nNOS ameliorates the severe neuropathic pain due to chronic pancreatitis - Demir, Ihsan Ekin; Heinrich, Tobias; Carty, Dominique G.; Saricaoglu, Ömer Cemil; Klauss, Sarah; Teller, Steffen; Kehl, Timo; Mota Reyes, Carmen; Tieftrunk, Elke; Lazarou, Maria; Bahceci, Dorukhan H.; Gökcek, Betül; et al. (EBioMedicine, 2019)
Background: Pain due to pancreatic cancer/PCa or chronic pancreatitis/CP, is notoriously resistant to the strongest pain medications. Here, we aimed at deciphering the specific molecular mediators of pain at surgical-stage pancreatic disease and to discover novel translational targets. Methods: We performed a systematic, quantitative analysis of the neurotransmitter/neuroenzmye profile within intrapancreatic nerves of CP and PCa patients. Ex vivo neuronal cultures treated with human pancreatic extracts, conditional genetically engineered knockout mouse models of PCa and CP, and the cerulein-induced CP model were employed to explore the therapeutic potential of the identified targets. Findings: We identified a unique enrichment of neuronal nitric-oxide-synthase (nNOS) in the pancreatic nerves of CP patients with increasing pain severity. Employment of ex vivo neuronal cultures treated with pancreatic tissue extracts of CP patients, and brain-derived-neurotrophic-factor-deficient (BDNF+/−) mice revealed neuronal enrichment of nNOS to be a consequence of BDNF loss in the progressively destroyed pancreatic tissue. Mechanistically, nNOS upregulation in sensory neurons was induced by tryptase secreted from perineural mast cells. In a head-to-head comparison of several genetically induced, painless mouse models of PCa (KPC, KC mice) or CP (Ptf1a-Cre;Atg5fl/fl) against the hypersecretion/cerulein-induced, painful CP mouse model, we show that a similar nNOS enrichment is present in the painful cerulein-CP model, but absent in painless genetic models. Consequently, mice afflicted with painful cerulein-induced CP could be significantly relieved upon treatment with the specific nNOS inhibitor NPLA. Interpretation: We propose nNOS inhibition as a novel strategy to treat the unbearable pain in CP. Fund: Deutsche Forschungsgemeinschaft/DFG (DE2428/3-1 and 3-2).
CRIS-Team Scopus Importer:2019-08-13
Keywords: Atg5; Chronic pancreatitis; Genetically engineered mice; Neurology of the digestive tract; Nitrergic; nNOS; Pain; Pancreatic cancer