Induction and maintenance of mucosal healing in Crohn's disease with ustekinumab in clinical practice across all care levels in Germany (MUCUS).

The impact of ustekinumab (UST) on mucosal- and fistula healing and extraintestinal manifestations (EIM) in Crohn's disease (CD) were not fully elucidated in the registration trials. In this prospective, multicenter study (EudraCT number: 2017-005151-83) we evaluated the German label real-world-effectiveness of UST to achieve the primary endpoint of combined clinical and endoscopic response at week 52 and several secondary endpoints. Of 79 screened we enrolled 52 patients (female n = 28, bionaïve n = 13, biologic n = 39).

Clinical predictors for a complicated course of disease in an inception cohort of patients with ulcerative colitis: results from the prospective, observational EPICOL study.

Purpose: The clinical course of ulcerative colitis (UC) is highly heterogeneous, with 20 to 30% of patients experiencing chronic disease activity requiring immunosuppressive or biologic therapies. The aim of this study was to identify predictors for a complicated disease course in an inception cohort of patients with UC.

Methods: EPICOL was a prospective, observational, inception cohort (UC diagnosis, ≤ 6 months) study in 311 patients with UC who were naive to immunosuppressants (IS)/biologics.

Self-assessment of treatment targets in patients with inflammatory bowel disease using a survey.

Background: Physicians can improve their relationships with patients by understanding and meeting patients' treatment targets, leading to higher adherence to therapy and improved disease prognosis. In the current study, we performed a questionnaire-based survey to further understand treatment targets in patients with inflammatory bowel disease (IBD).

Methods: We created a questionnaire based on a point-allocation scale with 10 treatment target items.

Predictive parameters for the clinical course of Crohn's disease: development of a simple and reliable risk model.

Purpose: The aim of our study was to identify clinical parameters in recently diagnosed Crohn's disease (CD) patients for prediction of their disease course.

Methods: EPIC (Early Predictive parameters of Immunosuppressive therapy in Crohn's disease) is a prospective, observational study in 341 patients with a recent CD diagnosis (≤ 6 months), and naïve to immunosuppressants (IS) and anti-tumor necrosis factor α (TNF) agents. Patient characteristics were documented up to 2 years.

Syndecan-4 Modulates Epithelial Gut Barrier Function and Epithelial Regeneration in Experimental Colitis.

Background: The transmembrane heparan sulfate proteoglycan Syndecan-4 (Sdc4) plays an important role in the regulation of various inflammatory disorders. However, the involvement of Sdc4 in intestinal inflammation remains unknown. Therefore, we assessed the impact of Sdc4 deficiency on experimental colitis and epithelial wound healing in vitro and in vivo.

Detection and characterization of murine colitis and carcinogenesis by molecularly targeted contrast-enhanced ultrasound.

Aim: To study mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) and vascular endothelial growth factor (VEGF)-targeted contrast enhanced ultrasound (CEUS) for the assessment of murine colitis and carcinogenesis.

Methods: C57BL/6 mice were challenged with 3% dextran sodium-sulfate (DSS) for three, six or nine days to study the development of acute colitis. Ultrasound was performed with and without the addition of unspecific contrast agents.

The 5A apolipoprotein A-I (apoA-I) mimetic peptide ameliorates experimental colitis by regulating monocyte infiltration.

Background And Purpose: New therapies for inflammatory bowel disease (IBD) are highly desirable. As apolipoprotein (apo)A-I mimetic peptides are beneficial in several animal models of inflammation, we hypothesized that they might be effective at inhibiting murine colitis.

Experimental Approach: Daily injections of 5A peptide, a synthetic bihelical apoA-I mimetic dissolved in PBS, or PBS alone were administered to C57BL/6 mice fed 3% (w v(-1) ) dextran sodium sulfate (DSS) in drinking water or healthy controls.

Translational 18F-FDG PET/CT imaging to monitor lesion activity in intestinal inflammation.

Unlabelled: In patients with inflammatory bowel disease (IBD) and in murine IBD models, mucosal disease activity is routinely assessed by endoscopy and histologic evaluation. This information is valuable for monitoring treatment response, with mucosal healing being a major treatment goal. The aim of this study was to evaluate the translational potential of noninvasive (18)F-FDG PET/CT for the assessment of mucosal damage in murine dextran sodium sulfate (DSS) colitis and human IBD.

Improving relapse prediction in inflammatory bowel disease by neutrophil-derived S100A12.

Background: Prediction of inflammatory bowel disease relapse has important implications for therapeutic strategies. Fecal S100A12 has been reported as a novel marker of intestinal inflammation. The objective was to investigate the utility of S100A12 as a marker for the confirmation of stable remission and prediction of relapses.

Green tea polyphenol epigallocatechin-3-gallate shows therapeutic antioxidative effects in a murine model of colitis.

Background And Aims: Leukocyte infiltration, up-regulation of proinflammatory cytokines and severe oxidative stress caused by increased amounts of reactive oxygen species are characteristics of inflammatory bowel disease. The catechin (2R,3R)-2-(3,4,5-Trihydroxyphenyl)-3,4-dihydro-1(2H)-benzopyran-3,5,7-triol-3-(3,4,5-trihydroxybenzoate), named epigallocatechin-3-gallate, EGCG, has been demonstrated to exert anti-inflammatory and antioxidative properties, reducing reactive oxygen species in the inflamed tissues. The aim of this study was to evaluate the therapeutic effects of EGCG in a murine model of colitis induced by oral administration of dextran sodium sulfate.

Cytomegalovirus (CMV)-Specific Perforin and Granzyme B ELISPOT Assays Detect Reactivation of CMV Infection in Inflammatory Bowel Disease.

The role of cytomegalovirus (CMV) infection in the pathogenesis and exacerbation of Inflammatory Bowel Disease (IBD) has been unresolved. Typically, the CMV genome remains dormant in infected cells, but a breakdown of immune surveillance can lead to re-activation of viral replication in the gut mucosa, which is not necessarily associated with viremia or changes in antibody titers. We hypothesized that the detection of CMV-specific CD8 effector T cells should permit the distinction between dormant and active CMV infection.

Collagen matrix-bound clotting factors (CMBCF) promote healing-associated events independent of factor XIII in an in vitro model.

We have previously explored in vitro as well as in vivo models of the biological effects of liquid fibrin glue (FG) containing factor XIII. The fixed combination of a collagen matrix and coagulation factors I and IIa (TachoSil(®) , Nycomed, Linz, Austria) is void of factor XIII. We aimed to determine whether (1) this preparation exerts similar effects to liquid FG on cells in an in vitro system, or (2) this effect is modulated by factor XIII.

The tripeptide KdPT protects from intestinal inflammation and maintains intestinal barrier function.

Treatment options for inflammatory bowel disease (IBD) are incompletely helpful, and surgery is often needed. One promising class of future therapeutic agents for IBD is melanocortin-related peptides, which exhibit potent immunomodulatory effects. We investigated KdPT, a tripeptide derivative of the C-terminus of α-melanocyte-stimulating hormone, as an anti-inflammatory small molecule in vivo and in vitro.

Course of a HBsAg positive liver transplantation in a hepatitis B and D virus coinfected recipient.

The increasing demand for transplantation has led to consideration of liver grafts from donors exposed to hepatitis B virus (HBV). Six transplantations of liver grafts from hepatitis B surface antigen (HBsAg) positive donors have been reported; two recipients suffered from HBV/HDV (hepatitis Delta virus) coinfection and were followed up for 10-12 months. Here, we report a 56 months follow-up of a HBV/HDV-coinfected recipient of a HBsAg positive liver graft.

The functional -374T/A polymorphism of the receptor for advanced glycation end products may modulate Crohn's disease.

The receptor for advanced glycation end products (RAGE) is involved in innate immune mechanisms. Polymorphisms of the RAGE gene have been described as a factor amplifying inflammation in susceptible patients, but the association with Crohn's disease (CD) is not known. The coding RAGE polymorphism G82S (rs2070600) and two promoter polymorphisms, -374T/A (rs1800624) and -429T/C (rs1800625), were studied in two samples from Germany and the United States consisting of 421 and 317 CD patients and 549 and 218 controls, respectively.

Terminal signal: anti-inflammatory effects of α-melanocyte-stimulating hormone related peptides beyond the pharmacophore.

During the last two decades a significant number of investigations has established the fact that α-Melanocyte-stimulating hormone (α-MSH) is a potent anti-inflammatory mediator. The anti-inflammatory effects of α-MSH can be elicited via melanocortin receptors (MC-Rs) broadly expressed in a number of tissues ranging from the central nervous system to cells of the immune system and on resident somatic cells of peripheral tissues. α-MSH affects various pathways regulating inflammatory responses such as NF-κB activation, expression of adhesion molecules, inflammatory cytokines, chemokine receptors, T-cell proliferation and activity and inflammatory cell migration.

Long-term efficacy and safety of double balloon enteroscopy--prospective and retrospective data from a single center study.

Objective: Double balloon enteroscopy (DBE) has evolved as one of the most innovative and fast spreading endoscopic procedures in the last decade. With increasing experience of performing endoscopic procedures in the mid gut outside the operating room it is necessary to investigate the effectiveness of DBE regarding therapeutic consequences, long-term efficacy as well as safety.

Material And Methods: To address this we retrospectively analyzed all DBE performed over a period of 2 years at our department.

Resistance of chemokine receptor 6-deficient mice to Yersinia enterocolitica infection: evidence of defective M-cell formation in vivo.

M cells, specialized cells within Peyer's patches (PPs), are reduced in number in chemokine receptor 6 (CCR6)-deficient mice. The pathogenic microorganism Yersinia enterocolitica exploits M cells for the purpose of mucosal tissue invasion exclusively through PPs. The aim of this study was to evaluate the course of yersiniosis in CCR6-deficient mice and to investigate whether these mice might be used as an in vivo model to determine M-cell function.

Recent understanding of IBD pathogenesis: implications for future therapies.

The inflammatory bowel diseases (IBD) are comprised of two major phenotypes, Crohn's disease (CD) and ulcerative colitis (UC). Research over the last couple of years has led to great advances in understanding the inflammatory bowel diseases and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses to a subset of luminal bacteria.

Induction of intestinal lymphoid tissue: the role of cryptopatches.

The intestinal immune system includes several organized structures, such as Peyer's patches, isolated lymphoid follicles (ILFs), cryptopatches (CPs) as well as mesenteric lymph nodes (MLNs) that constitute an extensive network with other nonorganized parts, such as intraepithelial and lamina propria lymphocytes. CPs are small clusters of lymphoid cells with an immature lymphocyte phenotype and dendritic cells. Initial observations in transfer experiments suggested that the immature lymphocytes are T cell precursors and CPs are a potential site of extrathymic intraepithelial lymphocyte (IEL) differentiation.

Apoptosis as a therapeutic tool in IBD?

Defective apoptosis of mucosal cell populations seems to be a relevant pathogenetic mechanism in inflammatory bowel disease (IBD). It has been suggested that the induction of apoptosis in various effector cells may be a relevant therapeutic mechanism in IBD. Indeed, it was shown that different drugs used for treatment of IBD have the capacity to induce apoptosis in T cells or monocytes in vitro and in vivo.

Gastric epithelial expression of macrophage migration inhibitory factor is not altered by Helicobacter pylori infection in humans.

Background: Recent reports have shown an upregulation of macrophage migration inhibitory factor (MIF) during gastric ulcer development in a rat model and elevated counts of MIF-positive cells in biopsies from Helicobacter pylori-infected patients. H. pylori infection is a proven cofactor in humans causing gastritis and gastric ulcers.