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| 1 | Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases显示文摘Anti-tumor necrosis factor(TNF) antibodies are successfully used in the therapy of inflammatory bowel diseases(IBD). However, the molecular mechanism of action of these agents is still a matter of debate. Apart from neutralization of TNF, influence on the intestinal barrier function, induction of apoptosis in mucosal immune cells, formation of regulatory macrophages as well as other immune modulating properties have been discussed as central features. Nevertheless, clinically effective anti-TNF antibodies were shown to differ in their mode-of-action in vivo and in vitro. Furthermore, the anti-TNF agent etanercept is effective in the treatment of rheumatoid arthritis but failed to induce clinical response in Crohn's disease patients, suggesting different contributions of TNF in the pathogenesis of these inflammatory diseases. In the following, we will review different aspects regarding the mechanism of action of anti-TNF agents in general and analyze comparatively different effects of each antiTNF agent such as TNF neutralization, modulation of the immune system, reverse signaling and induction of apoptosis. We discuss the relevance of the membranebound form of TNF compared to the soluble form for the immunopathogenesis of IBD. Furthermore, we review reports that could lead to personalized medicine approaches regarding treatment with antiTNF antibodies in chronic intestinal inflammation, by predicting response to therapy. | Ulrike Billmeier Walburga Dieterich Markus F Neurath Raja Atreya | 2016 | World Journal of Gastroenterology2016，22，42： | 19 |
| 2 | Colon cancer and the immune system:The role of tumor invading T cells显示文摘Colon cancer is still one of the leading causes of cancer death worldwide. Although the host immune system has been shown to react against tumor cells, mainly through tumor infi ltrating lymphocytes and NK cells, tumor cells may utilize different ways to escape anti-tumor immune response. Tumor infi ltration of CD8+ and CD4+ (T-bet+) effector T cells has been attributed to a beneficial outcome, and the enhancement of T cell activation through T cell receptor stimulation and co-stimulatory signals provides promising strategies for immunotherapy of colon cancer. Growing evidence supports a role for the Fas/FasL system in tumor immunology, although the mechanisms and consequences of FasL activation in colon cancer are not completely understood. In animal models, depletion of regulatory T cells (CD4+ CD25+ T cells) can enhance the anti-tumor immune response under certain conditions. Taken together, recent insights in the immune reaction against colon carcinoma have provided new approaches to immunotherapy, although much remains to be learned about the exact mechanisms. | Maximilian Waldner Carl C Schimanski Markus F Neurath | 2006 | World Journal of Gastroenterology2006，12，45： | 15 |
| 3 | Differential diagnosis in inflammatory bowel disease colitis:State of the art and future perspectives显示文摘Distinction between Crohn's disease of the colonrectum and ulcerative colitis or inflammatory bowel disease(IBD) type unclassified can be of pivotal importance for a tailored clinical management,as each entity often involves specific therapeutic strategies and prognosis.Nonetheless,no gold standard is available and the uncertainty of diagnosis may frequently lead to misclassification or repeated examinations.Hence,we have performed a literature search to address the problem of differential diagnosis in IBD colitis,revised current and emerging diagnostic tools and refined disease classification strategies.Nowadays,the differential diagnosis is an untangled issue,and the proper diagnosis cannot be reached in up to 10% of patients presenting with IBD colitis.This topic is receiving emerging attention,as medical therapies,surgical approaches and leading prognostic outcomes require more and more disease-specific strategies in IBD patients.The optimization of standard diagnostic approaches based on clinical features,biomarkers,radiology,endoscopy and histopathology appears to provide only marginal benefits.Conversely,emerging diagnostic techniques in the field of gastrointestinal endoscopy,molecular pathology,genetics,epigenetics,metabolomics and proteomics have already shown promising results.Novel advanced endoscopic imaging techniques and biomarkers can shed new light for the differential diagnosis of IBD,better reflecting diverse disease behaviors based on specific pathogenic pathways. | Gian Eugenio Tontini Maurizio Vecchi Luca Pastorelli Markus F Neurath Helmut Neumann | 2015 | World Journal of Gastroenterology2015，21，1： | 13 |
| 4 | Double-balloon-enteroscopy-based endoscopic retrograde cholangiopancreatography in post-surgical patients显示文摘AIM: To evaluate double balloon enteroscopy (DBE) in post-surgical patients to perform endoscopic retrograde cholangiopancreatography (ERCP) and interventions. METHODS: In 37 post-surgical patients, a stepwise approach was performed to reach normal papilla or enteral anastomoses of the biliary tract/pancreas. When conventional endoscopy failed, DBE-based ERCP was performed and standard parameters for DBE, ERCP and interventions were recorded. RESULTS: Push-enteroscopy (overall, 16 procedures) reached enteral anastomoses only in six out of 37 post-surgical patients (16.2%). DBE achieved a high rate of luminal access to the biliary tract in 23 of the remaining 31 patients (74.1%) and to the pancreatic duct (three patients). Among all DBE-based ERCPs (86 procedures), 21/23 patients (91.3%) were successfully treated. Interventions included ostium incision or papillotomy in 6/23 (26%) and 7/23 patients (30.4%), respectively. Biliary endoprosthesis insertion and regular exchange was achieved in 17/23 (73.9%) and 7/23 patients (30.4%), respectively. Furthermore, bile duct stone extraction as well as ostium and papillary dilation were performed in 5/23 (21.7%) and 3/23 patients (13.0%), respectively. Complications during DBE-based procedures were bleeding (1.1%), perforation (2.3%) and pancreatitis (2.3%), and minor complications occurred in up to 19.1%. CONCLUSION: The appropriate use of DBE yields a high rate of luminal access to papilla or enteral anastomoses in more than two-thirds of post-surgical patients, allowing important successful endoscopic therapeutic interventions. | Martin Raithel Harald Dormann Andreas Naegel Frank Boxberger Eckhart G Hahn Markus F Neurath Juergen Maiss | 2011 | World Journal of Gastroenterology2011，17，18： | 9 |
| 5 | Advances in hepatitis C therapy: What is the current state-what come's next?显示文摘Chronic hepatitis C virus(HCV) infection affects 80-160 million people worldwide and is one of the leading causes of chronic liver disease.It is only a few years ago that standard treatment regimes were based on pegylated interferon alpha and ribavirin.However,treatment of HCV has undergone a revolutionary change in recent years.The admission of the nucleotide polymerase inhibitor Sofosbuvir enabled an interferon-free regimen with direct antiviral agents(DAA).Meanwhile seven DAAs are available and can be applied in several combinations for 8 to 24 wk depending on HCV genotype and patient characteristics such as cirrhosis and chronic renal failure.High rates of sustained virological response(SVR) rates can be achieved with these novel drugs.Even in difficult to treat populations such as patients with liver cirrhosis,HCV-human immunodeficiency virus co-infections,after liver transplantion,or with chronic kidney disease comparable high rates of SVR can be achieved.The anticipated 2nd generation DAAs are strikingly effective in patients so far classified as difficult to treat including decompensated liver cirrhosis or posttransplant patients.These 2nd generations DAAs will have higher resistance barriers,higher antiviral effects and a pan-genotypic spectrum.This review highlights the current state of the art of antiviral treatment in hepatitis Cand gives an outlook for upcoming therapies. | Steffen Zopf Andreas E Kremer Markus F Neurath Juergen Siebler | 2016 | World Journal of Hepatology2016，8，3： | 7 |
| 6 | Cancer risk in IBD: How to diagnose and how to manage DALM and ALM显示文摘The risk of developing neoplasia leading to colorectal cancer is significantly increased in ulcerative colitis (UC) and most likely in Crohn's disease. Several endoscopic surveillance strategies have been implemented to identify these lesions. The main issue is that colitisassociated neoplasms often occurs in flat mucosa, often being detected on taking random biopsies rather than by identification of these lesions via endoscopic imaging. The standard diagnostic procedure in long lasting UC is to take four biopsies every 10 cm. Image enhancement methods, such as chromoendoscopy and virtual histology using endomicroscopy, have greatly im- proved neoplasia detection rates and may contribute toreduced random biopsies by taking targeted 'smart' biopsies. Chromoendoscopy may effectively be performed by experienced endoscopists for routine screening of UC patients. By contrast, endomicroscopy is often only available in selected specialized endoscopic centers. Importantly, advanced endoscopic imaging has the poten- tial to increase the detection rate of neoplasia whereas the interplay between endoscopic experience and interpretation of histological biopsy evaluation allows the physician to make a proper diagnosis and to find the appropriate therapeutic approach. Colitis-associated intraepithelial neoplasms may occur in flat mucosa of endoscopically normal appearance or may arise as dysplasia-associated lesion or mass (DALM), which may be indistinguishable from sporadic adenomas in healthy or non-colitis mucosa [adenoma-like mass (ALM)]. The aim of this review was to summarize endoscopic and histological characteristics of DALM and ALM in the context of therapeutic procedures. | Helmut Neumann Michael Vieth Cord Langner Markus F Neurath Jonas Mudter | 2011 | World Journal of Gastroenterology2011，17，27： | 6 |
| 7 | In vivo subsurface morphological and functional cellular and subcellular imaging of the gastrointestinal tract with confocal mini-microscopy显示文摘瞄准:为在活体内评估一根最新发达的手持的共焦的探针在啮齿类动物的完全的胃肠道的显微镜的成像。方法:一根新奇僵硬共焦的探针(直径 7 公里) 为 fluorophore 刺激用 488 nm 单身者线激光在人为使用与类似于灵活 endomicroscopy 系统的光特征被设计。轻排放在 505 ~ 750 nm 被检测。看法的地多样地是 475 妈妈 475 妈妈。光片厚度是有 0.7 妈妈的侧面的分辨率的 7 妈妈。在不同深度(到 250 妈妈的表面) 的表面下的连续图象多样地在 1024 点在实时被产生由在轻轻的、稳定的接触把探查放到织物上的 1024 个象素(0.8 frames/s ) 。织物标本为组织病理学说的关联被取样。结果:食管,胃,小并且大肠和中央,肝,胰和胆囊是在在 n = 的高分辨率的视觉 ised 在活体内 48 个鼠标。有共焦的微型显微镜学探查的实时显微镜的成像是容易的完成。不同染色协议(荧光黄,吖啶黄,标记 FITC 的葡聚糖和 L。可食用嗯植物凝血素) 织物的每个加亮的特定的方面,和在活体内成像与常规组织学最优地相关。在活体内血流监视把功能的质量加到词法成像。结论:共焦的显微镜学是在甚至表面下的织物结构的高分辨率允许完全的官方补给的道的可视化的可行在活体内。在这研究评估的新共焦的探查设计与腹腔镜检查兼容并且显著地扩展可能的应用的地到 intra 腹的机关。它允许新在活体内染色和申请选择的立即的测试因此在病人从动物研究允许快速的转移到临床的使用。 | Martin Goetz Beena Memadathil Stefan Biesterfeld Constantin Schneider Sebastian Gregor Peter R Galle Markus F Neurath Ralf Kiesslich | 2007 | World Journal of Gastroenterology2007，13，15： | 6 |
| 8 | New endoscopic approaches in IBD显示文摘Recent advances in endoscopic imaging techniques have revolutionized the diagnostic approach of patients with inflammatory bowel disease(IBD).New,emerging endoscopic imaging techniques visualized a plethora of new mucosal details even at the cellular and subcellular level.This review offers an overview about new endoscopic techniques,including chromoendoscopy,magnification endoscopy,spectroscopy,confocal laser endomicroscopy and endocytoscopy in the face of IBD. | Helmut Neumann Markus F Neurath Jonas Mudter | 2011 | World Journal of Gastroenterology2011，17，1： | 6 |
| 9 | First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy显示文摘We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies(infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6(IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody(tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN-γ. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may leadto aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling. | Raja Atreya Ulrike Billmeier Timo Rath Jonas Mudter Michael Vieth Helmut Neumann Markus F Neurath | 2015 | World Journal of Gastroenterology2015，21，45： | 5 |
| 10 | Comparison of Hemospray~? and Endoclot? for the treatment of gastrointestinal bleeding显示文摘BACKGROUND Gastrointestinal(GI) bleeding is a common indication for endoscopy. For refractory cases, hemostatic powders(HP) represent 'touch-free' agents.AIM To analyze short term(ST-within 72 h-) and long-term(LT-within 30 d-) success for achieving hemostasis with HP and to directly compare the two agents Hemospray(HS) and Endoclot(EC).METHODS HP was applied in 154 consecutive patients(mean age 67 years) with GI bleeding.Patients were followed up for 1 mo(mean follow-up: 3.2 mo).RESULTS Majority of applications were in upper GI tract(89%) with following bleeding sources: peptic ulcer disease(35%), esophageal varices(7%), tumor bleeding(11.7%), reflux esophagitis(8.7%), diffuse bleeding and erosions(15.3%). Overall ST success was achieved in 125 patients(81%) and LT success in 81 patients(67%). Re-bleeding occurred in 27% of all patients. In 72 patients(47%), HP was applied as a salvage hemostatic therapy, here ST and LT success were 81% and64%, with re-bleeding in 32%. As a primary hemostatic therapy, ST and LT success were 82% and 69%, with re-bleeding occurring in 22%. HS was more frequently applied for upper GI bleeding(P = 0.04)CONCLUSION Both HP allow for effective hemostasis with no differences in ST, LT success and re-bleeding. | Francesco Vitali Andreas Naegel Raja Atreya Steffen Zopf Clemens Neufert Juergen Siebler Markus F Neurath Timo Rath | 2019 | World Journal of Gastroenterology2019，25，13： | 2 |
| 11 | 显示文摘 | Finotto S Markus F Neurath MF | 2002 | Science2002，295，： | 1 |
| 12 | Retrograde inspection vs standard forward view for the detection of colorectal adenomas during colonoscopy: A back-to-back randomized clinical trial显示文摘BACKGROUND The adenoma detection rate(ADR)is inversely associated with the incidence of interval colorectal cancer and serves as a benchmark quality criterion during screening colonoscopy.However,adenoma miss rates reach up to 26%and studies have shown that a second inspection of the right colon in retroflected view(RFV)can increase ADR.AIM To assess whether inspection of the whole colon in RFV compared to standard forward view(SFV)can increase ADR.METHODS Patients presenting for screening or surveillance colonoscopy were invited to participate in this randomized controlled trial and randomized into two arms.In RFV arm colonoscopy was initially performed with SFV,followed by a second inspection of the whole colon in RFV.In the SFV arm first withdrawal was performed with SFV,followed by a second inspection of the whole colon again with SFV.Number,size and morphology of polyps found during first and second inspection in each colonic segment were recorded and all polyps were removed and sent for histopathology in separate containers.RESULTS Two hundred and five patients were randomly assigned to the RFV(n=101)and SFV(n=104)arm.In the RFV arm,both polyp detection rate(PDR)and ADR were increased under second inspection in RFV(PDR 1st SFV:39.8%,PDR 2nd RFV:46.6%;ADR 1st SFV:35.2%,ADR 2nd RFV:42%).Likewise,in the SFV arm,PDR and ADR were increased under second inspection(PDR 1st SFV:37.5%,PDR 2nd SFV:46.6%;ADR 1st SFV:34.1%,ADR 2nd SFV:44.3%)with no significant differences in ADR and PDR between the SFV and RFV arm.Mean number of adenomas per patient(APP)was increased in the RFV and SFV(APP RFV arm:1st SFV:1.71;2nd RFV:2.38;APP SFV arm:1st SFV:1.83,2nd SFV:2.2).The majority of adenomas additionally found during second inspection in RFV or in SFV were located in the transverse and left-sided colon and were>5 mm in size.CONCLUSION Second inspection of the whole colon leads to increased adenoma detection with no differences between SFV and RFV.Hence,increased detection is most likely a feature of the second inspection itself but not of the inspection mode. | Timo Rath Lukas Pfeifer Clemens Neufert Andreas Kremer Moritz Leppkes Arthur Hoffman Markus F Neurath Steffen Zopf | 2020 | World Journal of Gastroenterology2020，26，16： | 1 |
| 13 | RAGE Mediates a Novel Proinflammatory Axis显示文摘 | Marion A Hofmann Steven Drury Caifeng Fu Wu Qu Akihiko Taguchi Yan Lu Cecilia Avila Neeraja Kambham Angelika Bierhaus Peter Nawroth Markus F Neurath Timothy Slattery Dale Beach John McClary Mariko Nagashima John Morser David Stern Ann Marie Schmidt | 1999 | Cell1999，，7： | 1 |
| 14 | Novel cytokine-targeted therapies and intestinal inflammation显示文摘 | Maximilian J Waldner Markus F Neurath | 2009 | Current Opinion in Pharmacology2009，，6： | 1 |
| 15 | Targeting the VEGF signaling pathway in cancer therapy显示文摘 | Maximilian J Waldner Markus F Neurath | 2012 | Expert Opinion on Therapeutic Targets2012，，1： | 1 |
| 16 | Treatment of patients with Crohn’s disease and concomitant chronic hepatitis C with a chimeric monoclonal antibody to TNF显示文摘 | Martin H Holtmann Peter R Galle Markus F Neurath | 2003 | The American Journal of Gastroenterology2003，，2： | 1 |
| 17 | From the surface to the single cell: Novel endoscopic approaches in inflammatory bowel disease显示文摘Inflammatory bowel diseases(IBD) comprise the two major entities Crohn's disease and ulcerative colitis and endoscopic imaging of the gastrointestinal tract has always been an integral and central part in the management of IBD patients. Within the recent years,mucosal healing emerged as a key treatment goal in IBD that substantially decides about the clinical outcome of IBD patients,thereby demanding for a precise,timely and detailed endoscopic assessment of the mucosal inflammation associated with IBD. Further,molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy,now encompassing not only diagnosis,surveillance,and treatment but also the prediction of individual therapy response. Within this review we describe novel endoscopic approaches and advanced endoscopic imaging methods for the diagnosis,treatment and surveillance of IBD patients. We begin by providing an overview over novel and advanced imaging techniques such as magnification endoscopy and dye-based and dye-less chromoendoscopy,endomicroscopy and endocytoscopy. We then describe how these techniques can be utilized for the precise and ultrastructural assessment of mucosal inflammation and dysplasia development associated with IBD and outline how they have enabled the endoscopist to gain insight onto the cellular level in real-time. Finally,we provide an outlook on how molecular imaging has rapidly evolved in the recent past and can be used to make individual predictions about the therapeutic response towards biological treatment. | Timo Rath Gian Eugenio Tontini Markus F Neurath Helmut Neumann | 2015 | World Journal of Gastroenterology2015，21，40： | 0 |
| 18 | In vivo detection of mucosal healing-involved histiocytes by confocal laser endomicroscopy显示文摘Histiocytes have a pivotal role in wound repair and intestinal epithelial recovery-the most important goal to sustain gut functionality.Yet,an in vivo description of colonic histiocytes by confocal laser endomicroscopy(CLE) is missing.Here,we report the case of a 45-yearsold male patient who was referred to our clinic with weight loss and a history of two consecutive Clostridium difficile colitis episodes,the latter cured 3 wk before present admission.Stool microbiology was negative.Conventional colonoscopy showed atrophy and a light mucosal oedema in the distal colon.During on-going endoscopy,we performed a fluorescein-aided CLE which revealed large polygonal(histiocytes-like) cells with copious cytoplasm and large nuclei in the lamina propria of the sigmoid colon as well as regenerative epithelial changes.Histopathological assessment of biopsies from the same areas confirmed the endomicroscopical findings:Periodic acid-Schiff-and CD68-positive foamy histiocytes in the colonic lamina propria and an advanced epithelial recovery.Since stool microbiology was repeatedly negative and polymerase chain reaction-analysis from colonic biopsies could not detect any mRNA for Thropheryma whippleii and common pathogens,we interpreted this particular setting as a mucosal healing process after consecutive Clostridium difficile infections.In conclusion,by describing these colonic histiocytes,we highlight the clinical usefulness of CLE in describing the entity of histiocytes in vivo and in real-time during the process of post-infectious mucosal healing in the colon. | Gheorghe Hundorfean Abbas Agaimy Mircea T Chiriac Walter GeiBdrfer Jochen Wacker Markus F Neurath Jonas Mudter | 2012 | World Journal of Gastroenterology2012，18，32： | 0 |
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