48 results on '"Tenckhoff, S."'
Search Results
2. Evaluation zur Infrastruktur für klinisch chirurgische Studien in Deutschland: Eine bundesweite Umfrage des chirurgischen Studiennetzwerks (CHIR-Net)
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Jakob, V., Neudecker, J., Tenckhoff, S., Seidel, D., and Neugebauer, E. A. M.
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- 2018
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3. Rekrutierende multizentrische chirurgische Studien in Deutschland: Laufende Studien
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Tenckhoff, S.
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- 2016
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4. Rekrutierende multizentrische chirurgische Studien in Deutschland: Laufende Studien
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Tenckhoff, S.
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- 2015
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5. Meta-analysis of reconstruction techniques after low anterior resection for rectal cancer
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Hüttner, F. J., Tenckhoff, S., Jensen, K., Uhlmann, L., Kulu, Y., Büchler, M. W., Diener, M. K., and Ulrich, A.
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- 2015
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6. Warum Schwestern fliegen und Ärzte rotieren: Das chirurgische Studiennetzwerk CHIR-Net
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Wyen, H., Jakob, V., Neudecker, J., Tenckhoff, S., Seidel, D., Affüpper-Fink, M., Knöll, P., Neugebauer, E.A.M., and und die ChirNet Studiengruppe
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- 2013
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7. 598P Influence of the early stoma closure after low rectal cancer resection on completeness of adjuvant chemotherapy (CoCStom): A randomized, controlled multicentre trial of the AIO (AIO KRK 0113)
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Sandra-Petrescu, F., Herrle, F., Reissfelder, C., Kienle, P., Suelberg, H., Hinke, A., Tenckhoff, S., and Hofheinz, R.D.
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- 2023
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8. Quality of life in patients with various liver diseases
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Tillmann, H. L., Wiese, M., Braun, Y., Wiegand, J., Tenckhoff, S., Mössner, J., Manns, M. P., and Weissenborn, K.
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- 2011
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9. Entwicklung und Evaluation eines Prüfstudierendenkurses für Medizinstudierende zur Qualifikation für prospektive Multizenterstudien im Sinne des research-based learning [Bericht über Entwicklungsprozess]
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Sliwinski, S, Rädeker, L, Schwab, M, Frey, P, Friedrich, M, Fink, C, Leuck, A, Ottawa, GB, Klose, C, Feißt, M, Tenckhoff, S, Dörr-Harim, C, Mihaljevic, A, and SIGMA Study Group
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Problemstellung/Ziele: Wissenschaftliche Kompetenzen in der Klinik bestehen aus der Anwendung Evidenzbasierter Medizin (EbM) sowie in der Generierung von neuer Evidenz durch klinische Studien. Klinische Forschung bedarf dabei einer Ausbildung in den nötigen Fertigkeiten zur Durchführung[zum vollständigen Text gelangen Sie über die oben angegebene URL], Jahrestagung der Gesellschaft für Medizinische Ausbildung (GMA)
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- 2018
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10. Rekrutierende multizentrische chirurgische Studien in Deutschland
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Diener Mk and Tenckhoff S
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Medical education ,business.industry ,Medicine ,Surgery ,Subject (documents) ,business - Published
- 2015
11. Rekrutierende multizentrische chirurgische Studien in Deutschland
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Tenckhoff S
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medicine.medical_specialty ,business.industry ,General surgery ,Medicine ,Surgery ,business - Published
- 2013
12. Rekonstruktionstechniken nach tiefer anteriorer Rektumresektion bei Rektumkarzinomen – eine systematische Übersichtsarbeit mit Meta-Analyse
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Hüttner, F, Tenckhoff, S, Kulu, Y, Ulrich, A, Diener, MK, and Büchler, MW
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Einleitung: Zur Rektumrekonstruktion nach tiefer anteriorer Resektion mit totaler mesorektaler Exzision stehen derzeit verschiedene Techniken zur Verfügung, deren Stellenwert nach wie vor kontrovers diskutiert wird. Ziel dieses Systematic Reviews mit Meta-Analyse ist es, die Wirksamkeit der direkten[for full text, please go to the a.m. URL], 131. Kongress der Deutschen Gesellschaft für Chirurgie
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- 2014
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13. Method-related bias in prevalence of oncogenic human papillomavirus (HPV) subtypes in head and neck squamous cell carcinoma
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Scharrer, U, Boehm, A, Mozet, C, Dietz, A, Reiche, A, Herrmann, K, Hentschel, N, Tenckhoff, S, Wichmann, G, Scharrer, U, Boehm, A, Mozet, C, Dietz, A, Reiche, A, Herrmann, K, Hentschel, N, Tenckhoff, S, and Wichmann, G
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- 2012
14. 1345 INTERACTION BETWEEN IL28B CCR5Δ32, AND HCV PERSISTENCE WITH GBV-C VIREMIA AND SYMPTOMS DURING ACUTE INFECTION
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Tenckhoff, S., primary, Wiegand, J., additional, Patel, K., additional, Wiese, M., additional, Tenckhoff, H., additional, Nischalke, H.D., additional, Kullig, U., additional, Gobel, U., additional, Capka, E., additional, Schiefte, I., additional, Güthoff, W., additional, Grüngreiff, K., additional, König, I., additional, Spengler, U., additional, McCarthy, J.J., additional, Thompson, A.J., additional, McHutchison, J.G., additional, Timm, J., additional, Viazov, S., additional, Nattermann, J., additional, and Tillmann, H., additional
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- 2011
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15. Quality of life in patients with various liver diseases
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Tillmann, H. L., primary, Wiese, M., additional, Braun, Y., additional, Wiegand, J., additional, Tenckhoff, S., additional, Mössner, J., additional, Manns, M. P., additional, and Weissenborn, K., additional
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- 2010
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16. Reaktive Gliose bei einem Modell der Netzhautablösung beim Schwein
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Iandiev, I, primary, Uckermann, O, additional, Pannicke, T, additional, Wurm, A, additional, Tenckhoff, S, additional, Pietsch, U, additional, Reichenbach, A, additional, Wiedemann, P, additional, Bringmann, A, additional, and Uhlmann, S, additional
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- 2006
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17. Changes in retinal gene expression in proliferative vitreoretinopathy: Glial cell expression of HB-EGF
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Hollborn, M., Tenckhoff, S., Jahn, K., Iandiev, I., Biedermann, B., Schnurrbusch, U. E. K., Gloria Astrid Limb, Reichenbach, A., Wolf, S., Wiedemann, P., Kohen, L., and Bringmann, A.
18. Cavitron ultrasonic surgical aspirator (CUSA) compared with conventional pancreatic transection in distal pancreatectomy: study protocol for the randomised controlled CUSA-1 pilot trial.
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Holze M, Loos M, Hüttner F, Tenckhoff S, Feisst M, Knebel P, Klotz R, Mehrabi A, Michalski C, and Pianka F
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- Humans, Pilot Projects, Pancreas diagnostic imaging, Pancreas surgery, Pancreatic Fistula etiology, Pancreatic Fistula prevention & control, Pancreatic Fistula epidemiology, Postoperative Complications epidemiology, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Pancreatectomy adverse effects, Pancreatectomy methods, Ultrasonics
- Abstract
Background: Postoperative pancreatic fistula (POPF) remains the most common and serious complication after distal pancreatectomy. Many attempts at lowering fistula rates have led to unrewarding insignificant results as still up to 30% of the patients suffer from clinically relevant POPF. Therefore, the development of new innovative methods and procedures is still a cornerstone of current surgical research.The cavitron ultrasonic surgical aspirator (CUSA) device is a well-known ultrasound-based parenchyma transection method, often used in liver and neurosurgery which has not yet been thoroughly investigated in pancreatic surgery, but the first results seem very promising., Methods: The CUSA-1 trial is a randomised controlled pilot trial with two parallel study groups. This single-centre trial is assessor and patient blinded. A total of 60 patients with an indication for open distal pancreatectomy will be intraoperatively randomised after informed consent. The patients will be randomly assigned to either the control group with conventional pancreas transection (scalpel or stapler) or the experimental group, with transection using the CUSA device. The primary safety endpoint of this trial will be postoperative complications ≥grade 3 according to the Clavien-Dindo classification. The primary endpoint to investigate the effect will be the rate of POPF within 30 days postoperatively according to the ISGPS definition. Further perioperative outcomes, including postpancreatectomy haemorrhage, length of hospital stay and mortality will be analysed as secondary endpoints., Discussion: Based on the available literature, CUSA may have a beneficial effect on POPF occurrence after distal pancreatectomy. The rationale of the CUSA-1 pilot trial is to investigate the safety and feasibility of the CUSA device in elective open distal pancreatectomy compared with conventional dissection methods and gather the first data on the effect on POPF occurrence. This data will lay the groundwork for a future confirmatory multicentre randomised controlled trial., Ethics and Dissemination: The CUSA-1 trial protocol was approved by the ethics committee of the University of Heidelberg (No. S-098/2022). Results will be published in an international peer-reviewed journal and summaries will be provided in lay language to study participants and their relatives., Trial Registration Number: DRKS00027474., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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19. Thoracic Epidural Analgesia Is Not Associated With Improved Survival After Pancreatic Surgery: Long-Term Follow-Up of the Randomized Controlled PAKMAN Trial.
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Klotz R, Ahmed A, Tremmel A, Büsch C, Tenckhoff S, Doerr-Harim C, Lock JF, Brede EM, Köninger J, Schiff JH, Wittel UA, Hötzel A, Keck T, Nau C, Amati AL, Koch C, Diener MK, Weigand MA, Büchler MW, Knebel P, and Larmann J
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Background: Perioperative thoracic epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) are common forms of analgesia after pancreatic surgery. Current guidelines recommend EDA over PCIA, and evidence suggests that EDA may improve long-term survival after surgery, especially in cancer patients. The aim of this study was to determine whether perioperative EDA is associated with an improved patient prognosis compared to PCIA in pancreatic surgery., Methods: The PAKMAN trial was an adaptive, pragmatic, international, multicenter, randomized controlled superiority trial conducted from June 2015 to October 2017. Three to five years after index surgery a long-term follow-up was performed from October 2020 to April 2021., Results: For long-term follow-up of survival, 109 patients with EDA were compared to 111 patients with PCIA after partial pancreatoduodenectomy (PD). Long-term follow-up of quality of life (QoL) and pain assessment was available for 40 patients with EDA and 45 patients with PCIA (questionnaire response rate: 94%). Survival analysis revealed that EDA, when compared to PCIA, was not associated with improved overall survival (OS, HR, 1.176, 95% HR-CI, 0.809-1.710, P = .397, n = 220). Likewise, recurrence-free survival did not differ between groups (HR, 1.116, 95% HR-CI, 0.817-1.664, P = .397, n = 220). OS subgroup analysis including only patients with malignancies showed no significant difference between EDA and PCIA (HR, 1.369, 95% HR-CI, 0.932-2.011, P = .109, n = 179). Similar long-term effects on QoL and pain severity were observed in both groups (EDA: n = 40, PCIA: n = 45)., Conclusions: Results from this long-term follow-up of the PAKMAN randomized controlled trial do not support favoring EDA over PCIA in pancreatic surgery. Until further evidence is available, EDA and PCIA should be considered similar regarding long-term survival., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)
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- 2024
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20. Minimally invasivE versus open total GAstrectomy (MEGA): study protocol for a multicentre randomised controlled trial (DRKS00025765).
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Nickel F, Studier-Fischer A, Hausmann D, Klotz R, Vogel-Adigozalov SL, Tenckhoff S, Klose C, Feisst M, Zimmermann S, Babic B, Berlt F, Bruns C, Gockel I, Graf S, Grimminger P, Gutschow CA, Hoeppner J, Ludwig K, Mirow L, Mönig S, Reim D, Seyfried F, Stange D, Billeter A, Nienhüser H, Probst P, Schmidt T, and Müller-Stich BP
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- Humans, Adolescent, Young Adult, Adult, Middle Aged, Aged, Aged, 80 and over, Gastrectomy methods, Lymph Node Excision, Disease-Free Survival, Treatment Outcome, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Stomach Neoplasms pathology, Laparoscopy
- Abstract
Introduction: The only curative treatment for most gastric cancer is radical gastrectomy with D2 lymphadenectomy (LAD). Minimally invasive total gastrectomy (MIG) aims to reduce postoperative morbidity, but its use has not yet been widely established in Western countries. Minimally invasivE versus open total GAstrectomy is the first Western multicentre randomised controlled trial (RCT) to compare postoperative morbidity following MIG vs open total gastrectomy (OG)., Methods and Analysis: This superiority multicentre RCT compares MIG (intervention) to OG (control) for oncological total gastrectomy with D2 or D2+LAD. Recruitment is expected to last for 2 years. Inclusion criteria comprise age between 18 and 84 years and planned total gastrectomy after initial diagnosis of gastric carcinoma. Exclusion criteria include Eastern Co-operative Oncology Group (ECOG) performance status >2, tumours requiring extended gastrectomy or less than total gastrectomy, previous abdominal surgery or extensive adhesions seriously complicating MIG, other active oncological disease, advanced stages (T4 or M1), emergency setting and pregnancy.The sample size was calculated at 80 participants per group. The primary endpoint is 30-day postoperative morbidity as measured by the Comprehensive Complications Index. Secondary endpoints include postoperative morbidity and mortality, adherence to a fast-track protocol and patient-reported quality of life (QoL) scores (QoR-15, EUROQOL EuroQol-5 Dimensions-5 Levels (EQ-5D), EORTC QLQ-C30, EORTC QLQ-STO22, activities of daily living and Body Image Scale). Oncological endpoints include rate of R0 resection, lymph node yield, disease-free survival and overall survival at 60-month follow-up., Ethics and Dissemination: Ethical approval has been received by the independent Ethics Committee of the Medical Faculty, University of Heidelberg (S-816/2021) and will be received from each responsible ethics committee for each individual participating centre prior to recruitment. Results will be published open access., Trial Registration Number: DRKS00025765., Competing Interests: Competing interests: The authors declare that they have no conflicts of interest or relevant financial ties to disclose. FN reports support for courses and travel from Johnson & Johnson, Medtronic, Intuitive Surgical, Cambridge Medical Robotics and KARL STORZ as well as consultancy fees from KARL STORZ., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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21. Intraoperative visualisation of pancreatic leakage (ViP): study protocol for an IDEAL Stage I Post Market Clinical Study.
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Pausch TM, Holze M, Gesslein B, Rossion I, von Eisenhart Rothe F, Wagner M, Sander A, Tenckhoff S, Bartel M, Larmann J, Probst P, Pianka F, Hackert T, and Klotz R
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- Humans, Animals, Swine, Prospective Studies, Pancreatic Fistula etiology, Postoperative Complications prevention & control, Randomized Controlled Trials as Topic, Pancreas surgery, Pancreatectomy adverse effects
- Abstract
Introduction: Pancreatic resections are an important field of surgery worldwide to treat a variety of benign and malignant diseases. Postoperative pancreatic fistula (POPF) remains a frequent and critical complication after partial pancreatectomy and affects up to 50% of patients. POPF increases mortality, prolongs the postoperative hospital stay and is associated with a significant economic burden. Despite various scientific approaches and clinical strategies, it has not yet been possible to develop an effective preventive tool. The SmartPAN indicator is the first surgery-ready medical device for direct visualisation of pancreatic leakage already during the operation. Applied to the surface of pancreatic tissue, it detects sites of biochemical leak via colour reaction, thereby guiding effective closure and potentially mitigating POPF development., Methods and Analysis: The ViP trial is a prospective single-arm, single-centre first in human study to collect data on usability and confirm safety of SmartPAN. A total of 35 patients with planned partial pancreatectomy will be included in the trial with a follow-up of 30 days after the index surgery. Usability endpoints such as adherence to protocol and evaluation by the operating surgeon as well as safety parameters including major intraoperative and postoperative complications, especially POPF development, will be analysed., Ethics and Dissemination: Following the IDEAL-D (Idea, Development, Exploration, Assessment, and Long term study of Device development and surgical innovation) framework of medical device development preclinical in vitro, porcine in vivo, and human ex vivo studies have proven feasibility, efficacy and safety of SmartPAN. After market approval, the ViP trial is the IDEAL Stage I trial to investigate SmartPAN in a clinical setting. The study has been approved by the local ethics committee as the device is used exclusively within its intended purpose. Results will be published in a peer-reviewed journal. The study will provide a basis for a future randomised controlled interventional trial to confirm clinical efficacy of SmartPAN., Trial Registration Number: German Clinical Trial Register DRKS00027559, registered on 4 March 2022., Competing Interests: Competing interests: TMP reports financial support provided by Heidelberger Stiftung Chirurgie. BG reports a relationship with Magle Chemoswed that includes employment. TMP and TH have patent Body Fluid Leakage Detection Aqueous Composition (Pausch T, Hackert T, Johansson H, et al. European Patent Office, Germany. 2018) licensed to Magle Chemoswed Holding AB and University of Heidelberg., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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22. Efficacy of different spinal cord stimulation paradigms for the treatment of chronic neuropathic pain (PARS-trial): study protocol for a double-blinded, randomized, and placebo-controlled crossover trial.
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Ahmadi R, Campos B, Hajiabadi MM, Doerr-Harim C, Tenckhoff S, Rasche D, Unterberg A, Vesper J, Bruckner T, and Tronnier V
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- Adult, Chronic Pain diagnosis, Cross-Over Studies, Diagnostic Self Evaluation, Double-Blind Method, Female, Humans, Implantable Neurostimulators adverse effects, Male, Multicenter Studies as Topic, Neuralgia diagnosis, Pain Measurement, Quality of Life, Randomized Controlled Trials as Topic, Spinal Cord Stimulation adverse effects, Spinal Cord Stimulation instrumentation, Treatment Outcome, Wireless Technology instrumentation, Chronic Pain therapy, Neuralgia therapy, Spinal Cord Stimulation methods
- Abstract
Background: Spinal cord stimulation (SCS) is an effective method to treat neuropathic pain; however, it is challenging to compare different stimulation modalities in an individual patient, and thus, it is largely unknown which of the many available SCS modalities is most effective. Specifically, electrodes leading out through the skin would have to be consecutively connected to different, incompatible SCS devices and be tested over a time period of several weeks or even months. The risk of wound infections for such a study would be unacceptably high and blinding of the trial difficult. The PARS-trial seizes the capacity of a new type of wireless SCS device, which enables a blinded and systematic intra-patient comparison of different SCS modalities over extended time periods and without increasing wound infection rates., Methods: The PARS-trial is designed as a double-blinded, randomized, and placebo-controlled multi-center crossover study. It will compare the clinical effectiveness of the three most relevant SCS paradigms in individual patients. The trial will recruit 60 patients suffering from intractable neuropathic pain of the lower extremities, who have been considered for SCS therapy and were already implanted with a wireless SCS device prior to study participation. Over a time period of 35 days, patients will be treated consecutively with three different SCS paradigms ("burst," "1 kHz," and "1.499 kHz") and placebo stimulation. Each SCS paradigm will be applied for 5 days with a washout period of 70 h between stimulation cycles. The primary endpoint of the study is the level of pain self-assessment on the visual analogue scale after 5 days of SCS. Secondary, exploratory endpoints include self-assessment of pain quality (as determined by painDETECT questionnaire), quality of life (as determined by Quality of Life EQ-5D-5L questionnaire), anxiety perception (as determined by the Hospital Anxiety and Depression Scale), and physical restriction (as determined by the Oswestry Disability Index)., Discussion: Combining paresthesia-free SCS modalities with wireless SCS offers a unique opportunity for a blinded and systematic comparison of different SCS modalities in individual patients. This trial will advance our understanding of the clinical effectiveness of the most relevant SCS paradigms., Trial Registration: German Clinical Trials Register, DRKS00018929 . Registered on 14 January 2020.
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- 2021
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23. [Design and Evaluation of a Clinical Investigator Training for Student-lead Prospective Multicentre Clinical Trials: a CHIR-Net SIGMA Research-based Learning Project].
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Rädeker L, Schwab M, Frey PE, Friedrich M, Sliwinski S, Steinle J, Fink CA, Leuk A, Ganschow P, Ottawa GB, Klose C, Feißt M, Dörr-Harim C, Tenckhoff S, and Mihaljevic AL
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- Humans, Learning, Prospective Studies, Research, Clinical Trials as Topic, Curriculum, Education, Medical, Undergraduate, Research Personnel education, Students, Medical
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Background: Scientific skills are not sufficiently taught during medical training, neither in medical school nor during postgraduate education. This results in a lack of clinician scientists. In order to counter this problem, the surgical study network (CHIR -Net ) founded SIGMA (Student-initiated German Medical Audit). This paper describes the development, performance and evaluation of a Clinical Investigator Training (CIT) aiming to qualify students to autonomously conduct clinical trials., Material and Methods: Based on the Kern cycle, a curriculum was developed, composed of three parts: online tutorials, a workshop and a follow-up period. The educational objectives were defined according to Bloom's taxonomy of knowledge. The learning objectives were based on the requirements of the "Network of Coordinating Centers for Clinical Trials" and the German Medical Association as well as content relevant to clinical studies. A wide range of educational instruments and assessments were used. By including all relevant professional groups involved in clinical trials, an interconnected working environment for students was generated. The increase in knowledge was assessed by a multiple-choice pre/post exam. The satisfaction of participants was analysed by a 5-point Likert scale, on which 5 indicated full approval., Results: The first SIGMA CIT was realised in 2018; the workshop took place in Heidelberg in February. Thirty-two medical students from thirteen different centres participated. On average, 53.8 ± 8.3% of questions were answered correctly in the pre-test, compared with 71.2 ± 7.2% in the post-test (p < 0.0001). The maximal individual improvement was 30%; the lowest difference compared to the pre-test was 5%. Subjective evaluation results were positive with an average result of 4.63 ± 0.34 on a 5-point Likert scale., Conclusion: It is feasible to teach medical students the fundamentals of clinical trials. A compact Clinical Investigator Training using modern principles of teaching is able to prepare students for an autonomous performance of clinical trials., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)
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- 2020
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24. Rekrutierende multizentrische chirurgische Studien in Deutschland : Laufende Studien.
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Tenckhoff S
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- Germany, Longitudinal Studies
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- 2020
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25. Gastrointestinal Complications After Pancreatoduodenectomy With Epidural vs Patient-Controlled Intravenous Analgesia: A Randomized Clinical Trial.
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Klotz R, Larmann J, Klose C, Bruckner T, Benner L, Doerr-Harim C, Tenckhoff S, Lock JF, Brede EM, Salvia R, Polati E, Köninger J, Schiff JH, Wittel UA, Hötzel A, Keck T, Nau C, Amati AL, Koch C, Eberl T, Zink M, Tomazic A, Novak-Jankovic V, Hofer S, Diener MK, Weigand MA, Büchler MW, and Knebel P
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- Aged, Female, Gastrointestinal Diseases epidemiology, Humans, Male, Middle Aged, Postoperative Complications epidemiology, Analgesia, Epidural, Analgesia, Patient-Controlled, Gastrointestinal Diseases etiology, Pain, Postoperative prevention & control, Pancreaticoduodenectomy adverse effects, Postoperative Complications etiology
- Abstract
Importance: Morbidity is still high in pancreatic surgery, driven mainly by gastrointestinal complications such as pancreatic fistula. Perioperative thoracic epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) are frequently used for pain control after pancreatic surgery. Evidence from a post hoc analysis suggests that PCIA is associated with fewer gastrointestinal complications., Objective: To determine whether postoperative PCIA decreases the occurrence of gastrointestinal complications after pancreatic surgery compared with EDA., Design, Setting, and Participants: In this adaptive, pragmatic, international, multicenter, superiority randomized clinical trial conducted from June 30, 2015, to October 1, 2017, 371 patients at 9 European pancreatic surgery centers who were scheduled for elective pancreatoduodenectomy were randomized to receive PCIA (n = 185) or EDA (n = 186); 248 patients (124 in each group) were analyzed. Data were analyzed from February 22 to April 25, 2019, using modified intention to treat and per protocol., Interventions: Patients in the PCIA group received general anesthesia and postoperative PCIA with intravenous opioids with the help of a patient-controlled analgesia device. In the EDA group, patients received general anesthesia and intraoperative and postoperative EDA., Main Outcomes and Measures: The primary end point was a composite of pancreatic fistula, bile leakage, delayed gastric emptying, gastrointestinal bleeding, or postoperative ileus within 30 days after surgery. Secondary end points included 30-day mortality, other complications, postoperative pain levels, intraoperative or postoperative use of vasopressor therapy, and fluid substitution., Results: Among the 248 patients analyzed (147 men; mean [SD] age, 64.9 [10.7] years), the primary composite end point did not differ between the PCIA group (61 [49.2%]) and EDA group (57 [46.0%]) (odds ratio, 1.17; 95% CI, 0.71-1.95 P = .54). Neither individual components of the primary end point nor 30-day mortality, postoperative pain levels, or intraoperative and postoperative substitution of fluids differed significantly between groups. Patients receiving EDA gained more weight by postoperative day 4 than patients receiving PCIA (mean [SD], 4.6 [3.8] vs 3.4 [3.6] kg; P = .03) and received more vasopressors (46 [37.1%] vs 31 [25.0%]; P = .04). Failure of EDA occurred in 23 patients (18.5%)., Conclusions and Relevance: This study found that the choice between PCIA and EDA for pain control after pancreatic surgery should not be based on concerns regarding gastrointestinal complications because the 2 procedures are comparable with regard to effectiveness and safety. However, EDA was associated with several shortcomings., Trial Registration: German Clinical Trials Register: DRKS00007784.
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- 2020
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26. Postoperative complications and mobilisation following major abdominal surgery with vs. without fitness tracker-based feedback (EXPELLIARMUS): study protocol for a student-led multicentre randomised controlled trial (CHIR-Net SIGMA study group).
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Schwab M, Brindl N, Studier-Fischer A, Tu T, Gsenger J, Pilgrim M, Friedrich M, Frey PE, Achilles C, Leuck A, Bürgel T, Feisst M, Klose C, Tenckhoff S, Dörr-Harim C, and Mihaljevic AL
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- Adult, Cost-Benefit Analysis, Elective Surgical Procedures adverse effects, Feedback, Germany epidemiology, Humans, Length of Stay, Postoperative Complications epidemiology, Recovery of Function, Safety, Time Factors, Treatment Outcome, Abdomen surgery, Early Ambulation instrumentation, Fitness Trackers statistics & numerical data, Postoperative Complications prevention & control
- Abstract
Background: Postoperative complications following major abdominal surgery are frequent despite progress in surgical technique and perioperative care. Early and enhanced postoperative mobilisation has been advocated to reduce postoperative complications, but it is still unknown whether it can independently improve outcomes after major surgery. Fitness trackers (FTs) are a promising tool to improve postoperative mobilisation, but their effect on postoperative complications and recovery has not been investigated in clinical trials., Methods: This is a multicentre randomised controlled trial with two parallel study groups evaluating the efficacy of an enhanced and early mobilisation protocol in combination with FT-based feedback in patients undergoing elective major abdominal surgery. Participants are randomly assigned (1:1) to either the experimental group, which receives daily step goals and a FT giving feedback about daily steps, or the control group, which is mobilised according to hospital standards. The control group also receives a FT, however with a blackened screen; thus no FT-based feedback is possible. Randomisation will be stratified by type of surgery (laparoscopic vs. open). The primary endpoint of the study is postoperative morbidity within 30 days measured via the Comprehensive Complication Index. Secondary endpoints include number of steps as well as a set of functional, morbidity and safety parameters. A total of 348 patients will be recruited in 15 German centres. The study will be conducted and organised by the student-led German Clinical Trial Network SIGMA., Discussion: Our study aims at investigating whether the implementation of a simple mobilisation protocol in combination with FT-based feedback can reduce postoperative morbidity in patients undergoing major abdominal surgery. If so, FTs would offer a cost-effective intervention to enhance postoperative mobilisation and improve patient outcomes., Trial Registration: Deutsches Register Klinischer Studien (DRKS, German Clinical Trials Register): DRKS00016755, UTN U1111-1228-3320. Registered on 06.03.2019.
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- 2020
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27. Hernia reduction following laparotomy using small stitch abdominal wall closure with and without mesh augmentation (the HULC trial): study protocol for a randomized controlled trial.
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Heger P, Feißt M, Krisam J, Klose C, Dörr-Harim C, Tenckhoff S, Büchler MW, Diener MK, and Mihaljevic AL
- Subjects
- Abdominal Wound Closure Techniques adverse effects, Double-Blind Method, Germany, Hernia, Abdominal diagnosis, Hernia, Abdominal etiology, Humans, Incisional Hernia diagnosis, Incisional Hernia etiology, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Suture Techniques adverse effects, Time Factors, Treatment Outcome, Abdominal Wound Closure Techniques instrumentation, Hernia, Abdominal prevention & control, Incisional Hernia prevention & control, Surgical Mesh, Suture Techniques instrumentation
- Abstract
Background: Incisional hernias are among the most frequent complications following abdominal surgery and cause substantial morbidity, impaired health-related quality of life and costs. Despite improvements in abdominal wall closure techniques, the risk for developing an incisional hernia is reported to be between 10 and 30% following midline laparotomies. There have been two recent innovations with promising results to reduce hernia risks, namely the small stitches technique and the placement of a prophylactic mesh. So far, these two techniques have not been evaluated in combination., Methods: The HULC trial is a multicentre, randomized controlled, observer- and patient-blinded surgical effectiveness trial with two parallel study groups. A total of 812 patients scheduled for elective abdominal surgery via a midline laparotomy will be randomized in 12 centres after informed consent. Patients will be randomly assigned to the control group receiving closure of the midline incision with a slowly absorbable monofilament suture in the small stitches technique or to the intervention group, who will receive a small stitches closure followed by augmentation with a light-weight polypropylene mesh in the onlay technique. The primary endpoint will be the occurrence of incisional hernias, as defined by the European Hernia Society, within 24 months after surgery. Further perioperative parameters, as well as patient-reported outcomes, will be analysed as secondary outcomes., Discussion: The HULC trial will address the yet unanswered question of whether a combination of small stitched fascial closure and onlay mesh augmentation after elective midline laparotomies reduces the risk of incisional hernias. The HULC trial marks the logical and innovative next step in the development of a safe abdominal closure technique., Trial Registration: German Clinical Trials Register, DRKS00017517. Registered on 24th June 2019.
- Published
- 2019
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28. Prospective multicentre cohort study of patient-reported outcomes and complications following major abdominal neoplastic surgery (PATRONUS) - study protocol for a CHIR-Net student-initiated German medical audit study (CHIR-Net SIGMA study).
- Author
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Fink CA, Friedrich M, Frey PE, Rädeker L, Leuck A, Bruckner T, Feisst M, Tenckhoff S, Klose C, Dörr-Harim C, Neudecker J, and Mihaljevic AL
- Subjects
- Cohort Studies, Elective Surgical Procedures methods, Humans, Medical Audit, Postoperative Complications mortality, Prospective Studies, Students, Medical, Abdomen surgery, Patient Reported Outcome Measures, Postoperative Complications epidemiology, Quality of Life
- Abstract
Background: One of the most important aspects of designing a clinical trial is selecting appropriate outcomes. Patient-reported outcomes (PROs) can provide a personal assessment of the burden and impact of a malignant disease and its treatment. PROs comprise a wide range of outcomes including basic clinical symptom scores and complex metrics such as health-related quality of life (HRQoL). There is limited data on how postoperative complications following cancer surgery affect symptoms and HRQoL. For this reason the primary aim of the PATRONUS study is to investigate how perioperative complications affect cancer-related symptoms and HRQoL in patients undergoing abdominal cancer surgery. The PATRONUS study is designed and will be initiated and conducted by medical students under the direct supervision of clinician scientists based on the concept of inquiry-based learning., Methods: PATRONUS is a non-interventional prospective multicentre cohort study. Patients undergoing elective oncological abdominal surgery will be recruited at regional centres of the clinical network of the German Surgical Society (CHIR-Net) and associated hospitals. A core set of 12 cancer associated symptoms will be assessed via the PRO version of the Common Terminology Criteria for Adverse Events. The cancer-specific HRQoL will be measured via the computerised adaptive testing version of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. PROs will be measured eight times over a period of six months. The short-term clinical outcome measure is the rate of postoperative complications (grade II to V) within 30 days according to the Clavien-Dindo classification. The long-term clinical outcome is overall survival within six months postoperative., Discussion: PATRONUS will provide essential insights into the patients' assessment of their well-being and quality of life in direct relation to clinical outcome parameters following abdominal cancer surgery. Furthermore, PATRONUS will investigate the feasibility of multicentre student-led clinical research., Trial Registration: German Clinical Trials Register: DRKS00013035 (registered on October 26, 2017). Universal Trial Number (UTN): U1111-1202-8863.
- Published
- 2018
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29. Optimal literature search for systematic reviews in surgery.
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Goossen K, Tenckhoff S, Probst P, Grummich K, Mihaljevic AL, Büchler MW, and Diener MK
- Subjects
- Humans, Databases, Factual, Knowledge Discovery, Review Literature as Topic
- Abstract
Background: The aim of the present study was to determine empirically which electronic databases contribute best to a literature search in surgical systematic reviews., Methods: For ten published systematic reviews, the systematic literature searches were repeated in the databases MEDLINE, Web of Science, CENTRAL, and EMBASE. On the basis of these reviews, a gold standard set of eligible articles was created. Recall (%), precision (%), unique contribution (%), and numbers needed to read (NNR) were calculated for each database, as well as for searches of citing references and of the reference lists of related systematic reviews (hand search)., Results: CENTRAL yielded the highest recall (88.4%) and precision (8.3%) for randomized controlled trials (RCT), MEDLINE for non-randomized studies (NRS; recall 92.6%, precision 5.2%). The most effective combination of two databases plus hand searching for RCT was MEDLINE/CENTRAL (98.6% recall, NNR 97). Adding EMBASE marginally increased the recall to 99.3%, but with an NNR of 152. For NRS, the most effective combination was MEDLINE/Web of Science (99.5% recall, NNR 60)., Conclusions: For surgical systematic reviews, the optimal literature search for RCT employs MEDLINE and CENTRAL. For surgical systematic reviews of NRS, Web of Science instead of CENTRAL should be searched. EMBASE does not contribute substantially to reviews with a surgical intervention.
- Published
- 2018
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30. Encouraging student-driven clinical research in Germany: the CHIR- Net SIGMA network.
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Frey PE, Friedrich M, Rädeker L, Fink CA, Leuck A, Tenckhoff S, Neudecker J, and Mihaljevic AL
- Abstract
Evidence should define and guide modern clinical care, yet many relevant questions in surgical practice remain unconfirmed by substantial data. Evidence-based medicine requires both the implementation of its principles in day-to-day work and the acquisition of new evidence preferably by randomized controlled trials and systematic reviews. Meaningful clinical research, however, is challenging to conduct, and its overall infrastructure in Germany was, until recently, considered poor compared to other leading countries. Although this has been significantly improved after the establishment of the Study Center of the German Surgical Society (SDGC) and the surgical clinical trial network CHIR- Net , limited focus has been put on the training, teaching, and recruitment of medical students to become competent clinical researchers and clinician scientists. To ensure continuing comprehensive clinical research in surgery, CHIR- Net aims to establish a student-driven multicenter research network in Germany, which is embedded in both the national CHIR- Net and the pan-European and international frameworks. Student-Initiated German Medical Audits (SIGMA) is a product of the strong collaboration between clinical scientists and medical trainees, enabling students to contribute to high-quality clinical trials. Additionally, participants are offered extensive training to support the next generation of research-active clinicians. Starting on 2018, SIGMA will perform its first multicenter observational study in Germany., (©2017 Frey P.-E., et al., published by De Gruyter, Berlin/Boston.)
- Published
- 2017
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31. A systematic review and meta-analysis of the utility of repeated versus single hepatic resection for colorectal cancer liver metastases.
- Author
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Wurster EF, Tenckhoff S, Probst P, Jensen K, Dölger E, Knebel P, Diener MK, Büchler MW, and Ulrich A
- Subjects
- Chi-Square Distribution, Colorectal Neoplasms mortality, Hepatectomy adverse effects, Hepatectomy mortality, Humans, Kaplan-Meier Estimate, Liver Neoplasms mortality, Metastasectomy adverse effects, Metastasectomy mortality, Odds Ratio, Postoperative Complications etiology, Reoperation, Risk Factors, Time Factors, Treatment Outcome, Colorectal Neoplasms pathology, Hepatectomy methods, Liver Neoplasms secondary, Liver Neoplasms surgery, Metastasectomy methods
- Abstract
Background: Recurrence of colorectal liver metastases after a first hepatectomy is common (4-48% of patients). This review investigates the utility of repeated hepatic resection of colorectal liver metastases., Methods: A systematic search of the literature was performed in the Cochrane Library, MEDLINE, EMBASE, and trial registers. All studies comparing repeated hepatic resection for colorectal liver metastases with patients who underwent only one hepatectomy were eligible. Outcome criteria were safety parameters and survival rates. Data were analyzed using the random-effects model., Results: In eight observational clinical studies, 450 patients with repeated hepatic resection were compared with 2669 single hepatic resections. Morbidity such as hepatic insufficiency (OR [95% CI] 1.46 [0.69; 3.08], p = 0.32) and biliary leakage and fistula (OR [95% CI] 1.22 [0.80; 1.85], p = 0.35) was comparable between the two groups. Mortality (OR [95% CI] 1.13 [0.46; 2.74], p = 0.79) and overall survival (HR [95% CI] 1.00 [0.63; 1.60], p = 0.99) were not significantly different between the two groups., Discussion: Repeated hepatic resection for colorectal liver metastases is safe in selected patients. A prospective, multicenter high-quality trial or register study of repeated hepatic resection will be required to clarify patient-oriented outcomes such as overall survival and quality of life., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2017
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32. Industry Bias in Randomized Controlled Trials in General and Abdominal Surgery: An Empirical Study.
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Probst P, Knebel P, Grummich K, Tenckhoff S, Ulrich A, Büchler MW, and Diener MK
- Subjects
- Conflict of Interest economics, Digestive System Surgical Procedures economics, General Surgery methods, Humans, Randomized Controlled Trials as Topic, United States, Abdomen surgery, Bias, General Surgery economics, Industry
- Abstract
Background: Industry sponsorship has been identified as a source of bias in several fields of medical science. To date, the influence of industry sponsorship in the field of general and abdominal surgery has not been evaluated., Methods: A systematic literature search (1985-2014) was performed in the Cochrane Library, MEDLINE, and EMBASE to identify randomized controlled trials in general and abdominal surgery. Information on funding source, outcome, and methodological quality was extracted. Association of industry sponsorship and positive outcome was expressed as odds ratio (OR) with 95% confidence interval (CI). A χ test and a multivariate logistic regression analysis with study characteristics and known sources of bias were performed., Results: A total of 7934 articles were screened and 165 randomized controlled trials were included. No difference in methodological quality was found. Industry-funded trials more often presented statistically significant results for the primary endpoint (OR, 2.44; CI, 1.04-5.71; P = 0.04). Eighty-eight of 115 (76.5%) industry-funded trials and 19 of 50 (38.0%) non-industry-funded trials reported a positive outcome (OR, 5.32; CI, 2.60-10.88; P < 0.001). Industry-funded trials more often reported a positive outcome without statistical justification (OR, 5.79; CI, 2.13-15.68; P < 0.001). In a multivariate analysis, funding source remained significantly associated with reporting of positive outcome (P < 0.001)., Conclusions: Industry funding of surgical trials leads to exaggerated positive reporting of outcomes. This study emphasizes the necessity for declaration of funding source. Industry involvement in surgical research has to ensure scientific integrity and independence and has to be based on full transparency.
- Published
- 2016
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33. Intravenous versus epidural analgesia to reduce the incidence of gastrointestinal complications after elective pancreatoduodenectomy (the PAKMAN trial, DRKS 00007784): study protocol for a randomized controlled trial.
- Author
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Klotz R, Hofer S, Schellhaaß A, Dörr-Harim C, Tenckhoff S, Bruckner T, Klose C, Diener MK, Weigand MA, Büchler MW, and Knebel P
- Subjects
- Administration, Intravenous, Analgesia, Epidural adverse effects, Analgesia, Patient-Controlled adverse effects, Clinical Protocols, Elective Surgical Procedures, Gastrointestinal Diseases etiology, Gastrointestinal Diseases physiopathology, Germany, Humans, Pain, Postoperative etiology, Research Design, Risk Factors, Time Factors, Treatment Outcome, Analgesia, Epidural methods, Analgesia, Patient-Controlled methods, Gastrointestinal Diseases prevention & control, Pain, Postoperative prevention & control, Pancreaticoduodenectomy adverse effects
- Abstract
Background: Despite substantial improvements in surgical and anesthesiological practices leading to decreased mortality of less than 5 % at high-volume centers, pancreatic surgery is still associated with high morbidity rates of up to 50 %. Attention is increasingly directed toward the optimization of perioperative management to reduce complications and enhance postoperative recovery. Currently, two different strategies for postoperative pain management after pancreatoduodenectomy are being routinely used: patient-controlled intravenous analgesia and thoracic epidural analgesia. Evidence is lacking to assess which strategy entails fewer postoperative complications., Methods/design: The PAKMAN trial is designed as an adaptive, pragmatic, randomized, controlled, multicenter, open-label, superiority trial with two parallel study groups. A total of 370 patients scheduled for elective pancreatoduodenectomy will be randomized after giving written informed consent, and 278 patients are needed for analysis. Patients with chronic pancreatitis, severe chronic obstructive pulmonary disease (COPD), American Society of Anesthesiologists (ASA) physical status classification ≥ IV, or chronic pain syndrome will be excluded. The group A intervention includes intraoperative general anesthesia and postoperative patient-controlled intravenous analgesia; the group B intervention comprises combined intraoperative general anesthesia and epidural analgesia with postoperative epidural analgesia. The primary endpoint of this trial is a composite of the gastrointestinal complications (delayed gastric emptying, pancreatic fistula, biliary leak, gastrointestinal bleeding, and postoperative ileus) up to postoperative day 30. The aim is to investigate whether the frequency of gastrointestinal complications following pancreatoduodenectomy can be reduced by 15 % using postoperative, patient-controlled intravenous analgesia compared with epidural analgesia., Discussion: Several previous studies investigating the two different strategies for postoperative pain management have mainly focused on their effectiveness in pain control. However, the PAKMAN trial is the first to compare them with regard to their impact on the surgical endpoint "postoperative gastrointestinal complications" after pancreatoduodenectomy., Trial Registration: German Clinical Trials Register, DRKS00007784.
- Published
- 2016
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34. [In Process Citation].
- Author
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Tenckhoff S
- Subjects
- Germany, Humans, Controlled Clinical Trials as Topic, Multicenter Studies as Topic, Patient Selection, Surgical Procedures, Operative
- Published
- 2016
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35. [Research subject recruiting multicenter surgical studies in Germany].
- Author
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Diener MK and Tenckhoff S
- Subjects
- Germany, Humans, Digestive System Surgical Procedures, Multicenter Studies as Topic, Patient Selection
- Published
- 2015
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36. [Patient-oriented multicentre research in surgery: the Surgical Trial Network (CHIR-Net)].
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Neudecker J, Tenckhoff S, and Mihaljevic AL
- Subjects
- Germany, Health Plan Implementation, Humans, Quality Assurance, Health Care, Evidence-Based Medicine, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Surgical Procedures, Operative
- Abstract
Background: Patient-oriented clinical research in surgery requires prospective randomised multicentre trials (mRCTs) to generate valid evidence. In order to conduct high quality mRCTs, a network of surgical clinical trial centres is necessary., Methods: The Surgical Trial Network (CHIR-Net), which is funded by the German Federal Ministry of Education and Research (BMBF), was established as a structure of surgical regional centres. Currently, the CHIR-Net comprises 12 regional surgical centres with their associated clinical partner hospitals. The major aim of this network is to generate patient-relevant surgical questions of high clinical impact and to answer these questions in high-quality prospective randomised multicentre trials with well-trained study personnel., Results: Since 2006 32 mRCTs have been initiated in the CHIR-Net. Twelve surgical regional centres - in cooperation with 333 German and European hospitals - have recruited more than 7,500 patients. More than 80 surgeons have successfully completed the CHIR-Net educational curriculum for young surgeons., Conclusions: The CHIR-Net has successfully established a national clinical trial network to investigate surgical questions in randomised multicentre clinical trials. A nationwide research infrastructure, including university and non-university hospitals as well as the associated clinical coordination centres (KKS), was created to ensure patient-oriented surgical clinical research in a network at the highest methodological level thus implementing evidence-based medicine in daily surgical practice., (Copyright © 2015. Published by Elsevier GmbH.)
- Published
- 2015
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37. Study methods in evidence-based surgery: methodological impediments and suggested approaches for the creation and transfer of knowledge in surgery.
- Author
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Hüttner FJ, Doerr-Harim C, Probst P, Tenckhoff S, Knebel P, and Diener MK
- Subjects
- Knowledge Management, Research Design, Clinical Trials as Topic, Evidence-Based Medicine, General Surgery
- Abstract
Background: Since its introduction more than 20 years ago, evidence-based medicine has become an important principle in the daily routine of clinicians around the globe. Nevertheless, many surgical interventions are still not based on high-quality evidence from clinical trials. This is partially due to the fact that surgical trials pose some specific obstacles, which have to be overcome during the planning and conduct of such a trial., Objective: In this study, we will highlight specific challenges and discuss explicit obstacles of surgical clinical research. Moreover, potential solutions will be substantiated by the experience of the Study Centre of the German Surgical Society (SDGC) in surgical clinical research., Conclusions: Surgical researchers should be equipped with a basic knowledge of research methodology to be able to overcome the common impediments posed by surgical trials. Collaborations between surgeons and methodologists as well as trial networks have proven to be useful in accomplishing high-quality surgical research in various randomized controlled trials. By maintaining and refining this work and with sufficient and prompt translation of investigational knowledge into daily practice, the treatment of surgical patients should result in an improved outcome in the future.
- Published
- 2014
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38. [Recruiting for multicenter surgical studies in Germany].
- Author
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Tenckhoff S
- Subjects
- Germany, Humans, Multicenter Studies as Topic, Patient Selection, Surgical Procedures, Operative
- Published
- 2013
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39. Role of GB virus C in HIV-1-infected and hepatitis C virus-infected hemophiliac children and adolescents.
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Tenckhoff S, Kaiser T, Bredeek F, Donfield S, Menius E, Lail A, Mössner J, Daar ES, and Tillmann HL
- Subjects
- Adolescent, Child, Cohort Studies, Female, HIV Infections pathology, Hepatitis, Viral, Human virology, Humans, Male, Prevalence, RNA, Viral blood, Real-Time Polymerase Chain Reaction, Young Adult, GB virus C isolation & purification, HIV Infections complications, Hemophilia A complications, Hepatitis C, Chronic complications, Hepatitis, Viral, Human epidemiology
- Abstract
Background: GB Virus C (GBV-C) has been associated with a better prognosis of HIV-1 disease in adults. Little is known about prevalence and interaction between GBV-C, HIV-1, and/or hepatitis C virus (HCV) in hemophiliac children and adolescents., Methods: A well-characterized cohort of HIV-1-infected and HIV-1-uninfected hemophiliac children and adolescents followed in the Hemophilia Growth and Development Study (HGDS) were evaluated using quantitative reverse transcription polymerase chain reaction to detect GBV-C RNA in samples from baseline and last follow-up visit., Results: HIV-1-infected (n = 202) and HIV-1-uninfected (n = 119) patients had a low prevalence of GBV-C infection at baseline (0.9 and 0%), which increased at time of last follow-up visit to 25.2% and 26.3%, respectively. In addition, at the time of the follow-up GBV-C measurement, those GBV-C infected had been followed longer and had higher CD4(+) cell counts and lower HIV-1 viral loads than those GBV-C uninfected. These beneficial effects of GBV-C were no longer significant after controlling for CD4(+) cell count and HIV-1 RNA at baseline. HCV RNA clearance was more common amongst those who were not GBV-C infected than those who became GBV-C viremic., Conclusions: This study confirms a positive association of GBV-C with milder course of HIV-1 infection. GBV-C infection was associated with a higher likelihood of persistent HCV infection.
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- 2012
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40. Diagnostic value of anti-GBV-C antibodies in HIV-infected patients.
- Author
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Gómara MJ, Fernández L, Pérez T, Tenckhoff S, Casanovas A, Tillmann HL, and Haro I
- Subjects
- Biomarkers blood, Enzyme-Linked Immunosorbent Assay, HIV Infections diagnosis, Hepatitis, Viral, Human blood, Hepatitis, Viral, Human diagnosis, Humans, Antibodies, Viral blood, GB virus C immunology, HIV Infections complications, Hepatitis, Viral, Human complications
- Abstract
The beneficial effect of co-infection by GB virus C (GBV-C) in the course of the disease in human immunodeficiency virus (HIV)-infected patients has been described, although its mechanism of action is yet to be determined. The role of anti-GBV-C antibodies in HIV-infected patients also remains unknown. At present, there are no commercial systems to detect specific markers of GBV-C infection. The research presented follows our previous work from which we obtained chimeric molecules formed by two domains of different GBV-C proteins with good sensitivity/specificity balances in the detection of anti-GBV-C antibodies in hemodialyzed and chronic hepatitis patient samples. It has been investigated the ability of the synthetic peptides to recognize specific anti-GBV-C antibodies in HIV and HCV/HIV co-infected patients by a peptide-based ELISA immunoassay. The results showed that human immunodeficiency virus-infected patients have a significantly higher frequency of anti-GBV-C antibodies than healthy controls. A comparison between HCV(+) /HIV(+) and HCV(-) /HIV(+) was analyzed. Although a higher percentage of HCV/HIV-positive sera were positive for antibodies against GBV-C peptides, the difference was not significant. The presence of anti-GBV-C antibodies could represent a good marker of exposure to GBV-C in HIV-infected patients to facilitate a further analysis of the effect of this exposure in the progression of illness caused by HIV infection., (© 2011 John Wiley & Sons A/S.)
- Published
- 2011
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41. Effect of synthetic peptides belonging to E2 envelope protein of GB virus C on human immunodeficiency virus type 1 infection.
- Author
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Herrera E, Tenckhoff S, Gómara MJ, Galatola R, Bleda MJ, Gil C, Ercilla G, Gatell JM, Tillmann HL, and Haro I
- Subjects
- Amino Acid Sequence, Anti-HIV Agents pharmacology, Cell Line, HIV Envelope Protein gp41 chemistry, HIV-1 pathogenicity, HIV-1 physiology, Humans, Membrane Fusion drug effects, Molecular Sequence Data, Oligopeptides pharmacology, Protein Structure, Tertiary, Structure-Activity Relationship, Anti-HIV Agents chemistry, HIV-1 drug effects, Oligopeptides chemistry, Viral Envelope Proteins chemistry
- Abstract
The use of synthetic peptides as HIV-1 inhibitors has been subject to research over recent years. Although the initial therapeutic attempts focused on HIV-coded enzymes, structural HIV proteins and, more specifically, the mechanisms that the virus uses to infect and replicate are now also considered therapeutic targets. The interest for viral fusion and entry inhibitors is growing significantly, given that they are applicable in combined therapies or when resistance to other antiretroviral drugs is seen and that they act before the virus enters the cell. The 124 synthetic sequences of the GBV-C E2 envelope protein have been obtained by SPPS. The interaction of certain GBV-C peptide sequences with the HIV-1 fusion peptide has been proven through the use of biophysical techniques. We also show how GBV-C E2 domains notably decrease cellular membrane fusion and interfere with the HIV-1 infectivity in a dose-dependent manner, highlighting their potential utility in future anti-HIV-1 therapies.
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- 2010
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42. Kinetics of hepatitis C viral RNA and HCV-antigen during dialysis sessions: evidence for differential viral load reduction on dialysis.
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Kaiser T, Damerow HC, Tenckhoff S, Finger A, Böttcher I, Hafer C, Schwarz A, Lüth JB, Schmidt Gürtler H, Colucci G, Manns MP, Wedemeyer H, and Tillmann HL
- Subjects
- Hepacivirus genetics, Hepatitis C Antigens isolation & purification, Humans, Kinetics, Viral Load, Hepacivirus isolation & purification, Hepatitis C virology, Hepatitis C Antigens blood, RNA, Viral isolation & purification, Renal Dialysis
- Abstract
Hepatitis C infection is a common problem in dialysis units. The prevalence ranges from 3% to more than 50%. Several reports have described a variable reduction of HCV-RNA during hemodialysis treatment sessions. But so far nothing is known about the HCV antigenemia or the kinetics of the reduction of HCV-RNA and HCV antigenemia during these sessions. HCV-RNA was monitored using the VERSANT HCV bDNA assay 3.0 (Bayer Healthcare Diagnostics, Leverkusen, Germany) or the HCV-Monitor TaqMan (Roche Diagnostics). HCV antigenemia was tested by using Ortho-trac-C assay (Ortho Clinical Diagnostics, Neckargemünd, Germany). Kinetics of HCV-RNA were available in 15 dialysis sessions measured by bDNA assay and in 5 dialysis sessions measured by rt-PCR. Quantitative HCV-antigenemia was available in fourteen dialysis sessions. Not only HCV-RNA but as expected also the HCV-antigenemia fell during the dialysis session. However, while the average reduction of HCV-antigen appears steady and linear, the level of HCV-RNA seems to be stable during the first 3 hr of dialysis, and decreases rapidly during the last 2 hr. The results seem to be independent of the HCV-RNA detection method. The different kinetics of HCV RNA and HCV antigen load suggest that there are different mechanisms responsible for the reduction of the HCV antigen and HCV-RNA, respectively. Reduction of viral load during dialysis session indicates a potential benefit of dialysis in case of HCV associated antiviral therapy.
- Published
- 2008
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43. Human retinal epithelium produces and responds to placenta growth factor.
- Author
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Hollborn M, Tenckhoff S, Seifert M, Köhler S, Wiedemann P, Bringmann A, and Kohen L
- Subjects
- Blotting, Western, Cells, Cultured, Chemotaxis, Cytokines pharmacology, DNA biosynthesis, Enzyme-Linked Immunosorbent Assay, Humans, Intercellular Signaling Peptides and Proteins pharmacology, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Neuropilin-1 genetics, Neuropilin-2 genetics, Phosphorylation, Pigment Epithelium of Eye cytology, Placenta Growth Factor, Pregnancy Proteins pharmacology, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Vascular Endothelial Growth Factor A biosynthesis, Vascular Endothelial Growth Factor Receptor-1 genetics, Vascular Endothelial Growth Factor Receptor-2 genetics, Gene Expression Regulation physiology, Pigment Epithelium of Eye drug effects, Pigment Epithelium of Eye metabolism, Pregnancy Proteins genetics
- Abstract
Background: Placenta growth factor (PlGF) is an important co-factor in retinal neovascularization. To examine whether retinal pigment epithelial (RPE) cells may represent a source for PlGF during retinopathy, we determined whether human RPE cells in vitro produce and respond to PlGF. In addition, we determined whether the cells express receptors for PlGF, i.e. flt-1 and neuropilins., Methods: Cultured human RPE cells of passages 3-5 were used. The regulation of the PlGF gene and protein expression by growth factors and cytokines was evaluated by quantitative PCR and ELISA. Proliferation rates and chemotaxis were determined by a bromodeoxyuridine and a Boyden chamber assay., Results: Human RPE cells express mRNAs for various members of the vascular endothelial growth factor family and for their receptors, including mRNAs for PlGF, flt-1, KDR, and neuropilins-1 and -2. The expression levels of the mRNAs for neuropilins-1 and -2 were significantly higher than those for flt-1 and KDR. Members of the transforming growth factor (TGF)-beta superfamily of growth factors (BMP-4, TGF-beta1, and beta2) were strong inducers of PlGF gene expression, and evoked secretion of PlGF-2 protein by RPE cells. Exogenous PlGF-2 induced chemotaxis in RPE cells and reduced slightly the cell proliferation at high concentrations., Conclusion: The findings that RPE cells produce and respond to PlGF indicate that the factor exerts an autocrine/paracrine action on these cells. It is suggested that increased expression of TGF-beta-related growth factors during diabetic retinopathy may cause PlGF secretion by RPE cells contributing to the stimulation of cell migration as a critical component of the progression of fibrovascular membranes.
- Published
- 2006
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44. Glial cell reactivity in a porcine model of retinal detachment.
- Author
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Iandiev I, Uckermann O, Pannicke T, Wurm A, Tenckhoff S, Pietsch UC, Reichenbach A, Wiedemann P, Bringmann A, and Uhlmann S
- Subjects
- Animals, Aquaporin 4 metabolism, Blotting, Western, Calcium metabolism, Cell Count, Female, Fluorescent Antibody Technique, Indirect, Glial Fibrillary Acidic Protein metabolism, Male, Membrane Potentials physiology, Patch-Clamp Techniques, Potassium Channels metabolism, Potassium Channels, Inwardly Rectifying genetics, Potassium Channels, Inwardly Rectifying metabolism, Receptors, Purinergic P2 metabolism, Reverse Transcriptase Polymerase Chain Reaction, Swine, Disease Models, Animal, Gliosis metabolism, Neuroglia physiology, Retina metabolism, Retinal Detachment metabolism
- Abstract
Purpose: Detachment of the neural retina from the pigment epithelium causes, in addition to photoreceptor deconstruction and neuronal cell remodeling, an activation of glial cells. It has been suggested that gliosis contributes to the impaired recovery of vision after reattachment surgery that may involve both formerly detached and nondetached retinal areas. Müller and microglial cell reactivity was monitored in a porcine model of rhegmatogenous retinal detachment, to determine whether gliosis is present in detached and nondetached retinal areas., Methods: Local detachment was created in the eyes of adult pigs by subretinal application of hyaluronate. Retinal slices were immunostained against glial intermediate filaments and K+ and water channel proteins (aquaporin-4, Kir4.1, Kir2.1), and P2Y receptor proteins. In retinal wholemounts, adenosine 5'-triphosphate (ATP)-induced intracellular Ca2+ responses of Müller cells were recorded, and microglial and immune cells were labeled with Griffonia simplicifolia agglutinin isolectin I-B4. K+ currents were recorded from isolated Müller cells., Results: At 3 and 7 days after surgery, Müller cells in detached retinas showed a pronounced gliosis, as revealed by the increased expression of the intermediate filaments glial fibrillary acidic protein and vimentin, by the decrease of Kir4.1 immunoreactivity and of the whole-cell K+ currents, and by the increased incidence of cells that showed Ca2+ responses on stimulation of purinergic (P)2 receptors by ATP. By contrast, the immunohistochemical expression of Kir2.1 and aquaporin-4 were not altered after detachment. The increase in the expression of intermediate filaments, the decrease of the whole-cell K+ currents and of the Kir4.1 immunolabeling, and the increase in the Ca2+ responsiveness of Müller cells were also observed in attached retinal areas surrounding the focal detachment. The density of microglial-immune cells at the inner surface of the retinas increased in both detached and nondetached retinal areas. The immunoreactivities for P2Y1 and P2Y2 receptor proteins apparently increased only in detached areas., Conclusions: Reactive responses of Müller and microglial cells are not restricted to detached retinal areas but are also observed in nondetached regions of the porcine retina. The gliosis in the nondetached retina may reflect, or may contribute to, neuronal degeneration that may explain the impaired recovery of vision observed in human subjects after retinal reattachment surgery.
- Published
- 2006
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45. Differential regulation of Kir4.1 and Kir2.1 expression in the ischemic rat retina.
- Author
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Iandiev I, Tenckhoff S, Pannicke T, Biedermann B, Hollborn M, Wiedemann P, Reichenbach A, and Bringmann A
- Subjects
- Animals, Cells, Cultured, Gene Expression Regulation, Optic Neuropathy, Ischemic, Rats, Rats, Long-Evans, Retinal Vessels metabolism, Tissue Distribution, Ischemia metabolism, Neuroglia metabolism, Potassium Channels, Inwardly Rectifying metabolism, Retina metabolism
- Abstract
Ischemia-reperfusion of the rat retina causes gliosis of Müller cells that is associated with a decrease of their K+ conductance. By using quantitative PCR and immunohistochemical staining of retinal slices, we investigated the effect of transient ischemia-reperfusion on retinal expression of two inward-rectifying K+ (Kir) channels, Kir4.1 and Kir2.1. In control retinas, Müller cells prominently expressed both Kir4.1 and Kir2.1 proteins. At 7 days after reperfusion, the expression of Kir4.1 protein was strongly downregulated, while the Kir2.1 protein expression remained unaltered. The expression of Kir4.1 mRNA was reduced by 55% after ischemia while the expression of Kir2.1 mRNA was not altered. The data suggest that the glial expression of distinct Kir channels is differentially regulated after retinal ischemia, with deletarious consequences for K+ ion and water homeostasis.
- Published
- 2006
- Full Text
- View/download PDF
46. Changes in retinal gene expression in proliferative vitreoretinopathy: glial cell expression of HB-EGF.
- Author
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Hollborn M, Tenckhoff S, Jahn K, Iandiev I, Biedermann B, Schnurrbusch UE, Limb GA, Reichenbach A, Wolf S, Wiedemann P, Kohen L, and Bringmann A
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Blotting, Western, Cell Culture Techniques, Cell Proliferation, Chemotaxis, DNA biosynthesis, Enzyme-Linked Immunosorbent Assay, Epidermal Growth Factor pharmacology, Epiretinal Membrane metabolism, Epiretinal Membrane pathology, Expressed Sequence Tags, Female, Glial Fibrillary Acidic Protein metabolism, Heparin-binding EGF-like Growth Factor, Hepatocyte Growth Factor genetics, Humans, Intercellular Signaling Peptides and Proteins, Male, Microscopy, Confocal, Middle Aged, Neuroglia drug effects, Neuroglia pathology, Oligonucleotide Array Sequence Analysis, RNA, Messenger metabolism, Retina pathology, Reverse Transcriptase Polymerase Chain Reaction, Up-Regulation, Vascular Endothelial Growth Factor A metabolism, Vitreoretinopathy, Proliferative pathology, Epidermal Growth Factor genetics, Gene Expression Regulation physiology, Neuroglia metabolism, Retina metabolism, Vitreoretinopathy, Proliferative metabolism
- Abstract
Purpose: To compare the gene expression pattern of control postmortem retinas with retinas from patients with proliferative vitreoretinopathy (PVR), to determine the expression of the heparin binding epidermal growth factor-like growth factor (HB-EGF) by glial cells in fibroproliferative membranes, and to examine whether cells of the human Müller cell line, MIO-M1, respond to HB-EGF with proliferation, migration, and secretion of the vascular endothelial growth factor (VEGF)., Methods: To identify genes that were differently expressed in PVR and control retinas, the RNA from the neural retinas of seven postmortem donors and of two patients with PVR were analyzed for differential gene expression, by hybridization of labeled cRNA probes to an Affymetrix human genome microarray set. The results were validated by real time PCR experiments investigating RNA from 6 postmortem retinas and 4 PVR retinas. Epiretinal PVR membranes were immunohistochemically stained for colocalization of HB-EGF and the glial cell marker, glial fibrillary acidic protein (GFAP). The HB-EGF evoked proliferation of cultured Müller cells was investigated by a bromodeoxyuridine immunoassay, chemotaxis was assessed with a migration assay, and the release of VEGF was evaluated by ELISA., Results: Out of the 12,600 genes and expressed sequence tags investigated, the levels of 80 showed an increased expression, and 21 were expressed at decreased levels, in the retinas of PVR patients compared to the control retinas. The upregulated signals include genes for nuclear and cell cycle related proteins, extracellular secretory proteins, cytosolic signaling proteins, and proteins of the membrane and the extracellular matrix. The genes of the hepatocyte growth factor and of HB-EGF were found to be expressed in PVR retinas but not in control retinas. In epiretinal membranes of patients with PVR, HB-EGF immunoreactivity partially colocalized with GFAP. In cultured Müller cells, HB-EGF stimulated both proliferation and chemotaxis, and the secretion of VEGF, via activation of the extracellular signal regulated kinases 1 and 2 and of the phosphatidylinositol-3 kinase., Conclusions: The development of PVR is accompanied by complex changes of the gene expression in the neural retina, with an upregulation of genes that support cell proliferation, cell signaling, cell motility, and extracellular matrix remodeling. HB-EGF is one of the factors that are significantly upregulated in PVR retinas. HB-EGF expression in fibroproliferative tissue and its stimulatory effect on glial cell proliferation, chemotaxis, and VEGF secretion suggest that HB-EGF may be a factor mediating glial cell responses during PVR.
- Published
- 2005
47. Diversity of aquaporin mRNA expressed by rat and human retinas.
- Author
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Tenckhoff S, Hollborn M, Kohen L, Wolf S, Wiedemann P, and Bringmann A
- Subjects
- Animals, Base Sequence, DNA Primers, Humans, Polymerase Chain Reaction, Potassium Channels, Rats, Transcription, Genetic, Aquaporins genetics, RNA, Messenger genetics, Retina physiology
- Abstract
Muller glial cells of the sensory retina mediate K+ and water fluxes that are facilitated by aquaporin-4 (AQP4) water channels and by Kir4.1-K+ channels. However, it is not known which subtypes of aquaporins are expressed in the mammalian retina. Using RT-PCR, we found that both human and rat retinas express mRNA for a diversity of water channel proteins. The human retina expresses mRNAs for AQP0 to AQP12 proteins. Using real-time PCR, we found that the mRNAs for AQP4 and Kir4.1 are downregulated in retinas that were obtained from patients with proliferative retinopathy compared with post-mortem controls. The data suggest that the development of proliferative gliosis is accompanied by disturbed transglial water and ion movements.
- Published
- 2005
- Full Text
- View/download PDF
48. Glial cell expression of hepatocyte growth factor in vitreoretinal proliferative disease.
- Author
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Hollborn M, Krausse C, Iandiev I, Yafai Y, Tenckhoff S, Bigl M, Schnurrbusch UE, Limb GA, Reichenbach A, Kohen L, Wolf S, Wiedemann P, and Bringmann A
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Base Sequence, Case-Control Studies, Cell Line, Cell Movement, DNA Primers genetics, Female, Gene Expression, Hepatocyte Growth Factor genetics, Humans, Immunohistochemistry, Male, Middle Aged, Neuroglia pathology, Proto-Oncogene Proteins c-met genetics, Proto-Oncogene Proteins c-met metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Retina metabolism, Retina pathology, Vascular Endothelial Growth Factor A metabolism, Vitreoretinopathy, Proliferative genetics, Vitreoretinopathy, Proliferative pathology, Vitreoretinopathy, Proliferative physiopathology, Hepatocyte Growth Factor metabolism, Neuroglia metabolism, Vitreoretinopathy, Proliferative metabolism
- Abstract
The hepatocyte growth factor (HGF) has been crucially implicated in the development of proliferative retinal diseases; however, it is unclear whether retinal glial cells express or respond to HGF. Therefore, we examined the expression of HGF and of the receptor for HGF, c-Met, by immunohistochemical costaining with glial fibrillary acidic protein (GFAP) in epiretinal membranes of patients with proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), respectively. Furthermore, it was determined whether cells of the human retinal glial cell line, MIO-M1, secrete HGF protein, and whether HGF stimulates proliferation and chemotaxis, and secretion of the vascular endothelial growth factor (VEGF). Neuroretinas of patients with PVR express elevated mRNA level for HGF in comparison to control retinas. In epiretinal membranes of patients with PVR or PDR, immunoreactivity for HGF and for c-Met, respectively, partially colocalized with immunoreactivity for GFAP. Fetal bovine serum and basic fibroblast growth factor, but not heparin-binding epidermal or platelet-derived growth factors, evoked HGF secretion by cultured retinal glial cells. HGF displayed only a marginal effect on cell proliferation while it stimulated chemotaxis. HGF promoted the secretion of VEGF, via activation of the phosphatidylinositol-3 kinase. It is concluded that glial cells in epiretinal membranes express both HGF protein and c-Met receptors. The results suggest an autocrine/paracrine role of HGF in glial cell responses during proliferative vitreoretinal disorders as well as in retinal neovascularization, by stimulating of VEGF release.
- Published
- 2004
- Full Text
- View/download PDF
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