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  • S. Karger AG  (20)
  • Rogler, Gerhard  (20)
  • 1
    Online Resource
    Online Resource
    The Clinical Relevance of the IBD-Associated Variation within the Risk Gene Locus Encoding Protein Tyrosine Phosphatase Non-Receptor Type 2 in Patients of the Swiss IBD Cohort
    S. Karger AG ; 2016
    In:  Digestion Vol. 93, No. 3 ( 2016), p. 182-192
    Details
    In: Digestion, S. Karger AG, Vol. 93, No. 3 ( 2016), p. 182-192
    Abstract: 〈 b 〉 〈 i 〉 Background/Aims: 〈 /i 〉 〈 /b 〉 The single nucleotide polymorphism (SNP) rs1893217 within the gene locus encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) results in a dysfunctional PTPN2 protein is associated with Crohn's disease (CD) and exists in perfect linkage disequilibrium with the CD- and ulcerative colitis (UC)-associated PTPN2 SNP rs2542151. We investigated associations of PTPN2 SNP rs1893217 and clinical characteristics of inflammatory bowel disease (IBD) patients. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 One thousand seventy three patients with CD and 734 patients with UC from the Swiss IBD Cohort Study (SIBDCS) were included. Epidemiologic, disease and treatment characteristics were analysed for an association with the presence of one of the rs1893217 genotypes ‘homozygous wild-type' (TT), ‘heterozygous' (CT) and ‘homozygous variant' (CC). 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 About 2.88% of IBD patients were identified with CC, 26.8% with CT and 70.4% with TT genotype. The CC-genotype was associated with the existence of gallstones in CD and pancolitis in UC patients. The presence of the C-allele (i.e. either CC or CT genotype) was associated with the onset of uveitis, but protected from aphthous oral ulcers in CD patients. UC patients carrying a C-allele were diagnosed at an older age but required intestinal surgery more often. The presence of the C-allele was associated with a successful treatment with anti-TNF antibodies in both CD and UC patients. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 IBD patients carrying the C-allele of PTPN2 SNP rs1893217 are at greater risk for developing a severe disease course but are more likely to respond to treatment with anti-TNF antibodies. These findings demonstrate a clinical relevance of this PTPN2 risk variant in IBD patients.
    Type of Medium: Online Resource
    ISSN: 0012-2823 , 1421-9867
    URL: Article
    DOI: 10.1159/000444479
    RVK:
    XA 40650
    RVK:
    XA 10000
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2016
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  • 2
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    Risk Factors for the Development of Fistulae and Stenoses in Crohn Disease Patients in the Swiss Inflammatory Bowel Disease Cohort
    S. Karger AG ; 2016
    In:  Inflammatory Intestinal Diseases Vol. 1, No. 4 ( 2016), p. 172-181
    Details
    In: Inflammatory Intestinal Diseases, S. Karger AG, Vol. 1, No. 4 ( 2016), p. 172-181
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Fistulae and stenoses represent frequent and severe complications in patients with Crohn disease (CD). Our study aimed to identify risk factors for fistula and stenosis formation in CD patients. 〈 b 〉 〈 i 〉 Summary: 〈 /i 〉 〈 /b 〉 We retrieved data of 1,600 CD patients from the nationwide Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). The risk for fistulae and stenoses in relation to gender, age at diagnosis, smoking status at diagnosis, and ileal involvement at diagnosis were analyzed. In the multivariate analysis, female gender showed a lower risk for developing perianal and any fistula (risk ratio [RR] 0.721, 95% confidence interval [CI] 0.582-0.893, 〈 i 〉 p 〈 /i 〉 = 0.003 and RR 0.717, 95% CI 0.580-0.888, 〈 i 〉 p 〈 /i 〉 = 0.002, respectively), and older age at diagnosis showed a lower risk for developing perianal fistula (RR 0.661, 95% CI 0.439-0.995, 〈 i 〉 p 〈 /i 〉 = 0.047). Furthermore, ileal involvement was associated with a lower risk for perianal fistula (RR 0.713, 95% CI 0.561-0.906, 〈 i 〉 p 〈 /i 〉 = 0.006), a lower risk for any fistula (RR 0.709, 95% CI 0.558-0.901, 〈 i 〉 p 〈 /i 〉 = 0.005), and a higher risk for stenosis (RR 2.170, 95% CI 1.728-2.725, 〈 i 〉 p 〈 /i 〉 〈 0.001). 〈 b 〉 〈 i 〉 Key Messages: 〈 /i 〉 〈 /b 〉 In the nationwide SIBDCS, younger age at diagnosis and male gender were risk factors for developing perianal and nonperianal fistulae. Additionally, ileal involvement was revealed to be a potent risk factor (RR 2.170) for developing a stenosis.
    Type of Medium: Online Resource
    ISSN: 2296-9403 , 2296-9365
    URL: Article
    DOI: 10.1159/000458144
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2016
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  • 3
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    Malignancies in Patients with Inflammatory Bowel Disease: A Single-Centre Experience
    S. Karger AG ; 2016
    In:  Digestion Vol. 94, No. 1 ( 2016), p. 1-8
    Details
    In: Digestion, S. Karger AG, Vol. 94, No. 1 ( 2016), p. 1-8
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Gastrointestinal and extraintestinal malignancies are long-term complications in patients with inflammatory bowel disease (IBD), likely as a result of chronic inflammation and the use of immunosuppressive medications used to control inflammation. Here, we assessed the frequency of malignancies in a large tertiary IBD centre at the University Hospital Zurich. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We performed a retrospective analysis of data from 1,026 patients from our IBD clinic treated between 2007 and 2014. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Twenty two of the 1,026 patients developed 28 cases of malignancies, 14 patients were male and 8 patients female. The median latency between IBD diagnosis and first malignancy was 13 years (range 2-27 years). Most common malignancies were non-Hodgkin lymphoma, colorectal cancer (CRC), urothelial carcinoma, cholangiocellular carcinoma (CCC) and prostate cancer. The most common tumour type in Crohn's disease patients (13/22) was lymphoma (5 cases), in ulcerative colitis patients (9/22) CCC (2 cases) and CRC (2 cases). The observed incidence of lymphoma (32.5/100,000), bladder carcinoma (21.7/100,000) and CCC (10.8/100,000) was higher than expected and known from general population. All of the patients that developed a malignancy had received immunosuppressive therapy. Compared to a cohort of 927 IBD patients without malignancies there were no statistical differences regarding gender, antibodies targeting tumour necrosis factor and thiopurine use. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Our data support the assumption that a long-standing disease course and immunosuppressive therapy increase the risk for developing malignancies in IBD patients.
    Type of Medium: Online Resource
    ISSN: 0012-2823 , 1421-9867
    URL: Article
    DOI: 10.1159/000447259
    RVK:
    XA 40650
    RVK:
    XA 10000
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2016
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  • 4
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    Knock-Out of β-Glucosidase 2 Has No Influence on Dextran Sulfate Sodium-Induced Colitis
    S. Karger AG ; 2011
    In:  Digestion Vol. 84, No. 2 ( 2011), p. 156-167
    Details
    In: Digestion, S. Karger AG, Vol. 84, No. 2 ( 2011), p. 156-167
    Abstract: 〈 i 〉 Background/Aims: 〈 /i 〉 The non-lysosomal glucosylceramidase, β-glucosidase (Gba2), hydrolyzes glucosylceramide to glucose and ceramide (Cer). Cer is a potent second-messenger lipid that plays an important role in signaling cascades involved in apoptosis. The aim of this study was to investigate whether Gba2 knock-out (Gba2 〈 sup 〉 –/– 〈 /sup 〉 ) affects the extent of dextran sulfate sodium (DSS)-induced colitis in mice. 〈 i 〉 Methods: 〈 /i 〉 Acute colitis was induced in wild-type (WT) and Gba2 〈 sup 〉 –/– 〈 /sup 〉 mice by administration of 2% DSS in drinking water. After 7 days, mice underwent colonoscopy and were sacrificed. 〈 i 〉 Results: 〈 /i 〉 Both DSS-treated WT (n = 10) and Gba2 〈 sup 〉 –/– 〈 /sup 〉 (n = 12) mice showed elevated histological and endoscopic scores compared to respective H 〈 sub 〉 2 〈 /sub 〉 O controls (n = 9 each). However, no significant differences between the DSS groups were detected. Flow cytometric analysis of propidium iodide staining, cleavage of caspases-3 and -8, indicative for apoptosis, as well as Cer levels were not altered in DSS-treated WT or Gba2 〈 sup 〉 –/– 〈 /sup 〉 mice. Gba2 〈 sup 〉 –/– 〈 /sup 〉 resulted in slightly decreased expression of glucocerebrosidase (Gba1) as well as in upregulation of proteins being involved in cellular regeneration, such as STAT3 (signal transducer and activator of transcription), JNK and iNOS, upon DSS treatment. 〈 i 〉 Conclusion: 〈 /i 〉 We demonstrate that Gba2 〈 sup 〉 –/– 〈 /sup 〉 does not affect the extent of DSS-induced inflammation in mice, however, it might be involved in tissue regeneration in response to toxic agents.
    Type of Medium: Online Resource
    ISSN: 0012-2823 , 1421-9867
    URL: Article
    DOI: 10.1159/000327380
    RVK:
    XA 40650
    RVK:
    XA 10000
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2011
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  • 5
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    Probiotic 〈b〉〈i〉Escherichia coli〈/i〉〈/b〉 Nissle 1917 and Commensal 〈b〉〈i〉E. coli〈/i〉〈/b〉 K12 Differentially Affect the Inflammasome in Intestinal Epithelial Cells
    S. Karger AG ; 2014
    In:  Digestion Vol. 89, No. 2 ( 2014), p. 110-118
    Details
    In: Digestion, S. Karger AG, Vol. 89, No. 2 ( 2014), p. 110-118
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 The probiotic bacterial strain 〈 i 〉 Escherichia coli 〈 /i 〉 Nissle 1917 (EcN) is used for the treatment of ulcerative colitis (UC), diarrhea and constipation. Its beneficial effects in the treatment of UC have been demonstrated in several controlled clinical studies; however, the mechanism of action on the cellular level is still not completely clear. The intracellular pattern recognition receptor NLRP3 is expressed in intestinal epithelial cells (IEC), activates caspase-1 within the inflammasome complex and has been implicated to play a role in the etiology of inflammatory bowel diseases. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Probiotic EcN and commensal 〈 i 〉 E. coli 〈 /i 〉 K12 were applied to IEC in vitro. Inflammasome activation, interleukin (IL)-18 release and caspase-1 activation were determined by coimmunoprecipitation, Western blot and ELISA. Apoptosis was investigated by Western blot. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Incubation of Caco-2 cells with EcN resulted in lower inflammasome activation and subsequent secretion of mature IL-18 as compared to the commensal strain K12. Induction of apoptosis as determined by cleavage of caspase-3 and poly (ADP-ribose) polymerase were lower in EcN-stimulated cells. Autophagy was induced by both bacterial strains, but to a higher extent by K12. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 These findings indicate that genetically very similar 〈 i 〉 E. coli 〈 /i 〉 strains differ markedly in their ability to activate the inflammasome.
    Type of Medium: Online Resource
    ISSN: 0012-2823 , 1421-9867
    URL: Article
    DOI: 10.1159/000357521
    RVK:
    XA 40650
    RVK:
    XA 10000
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2014
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  • 6
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    Induction or Exacerbation of Psoriasis in Patients with Crohn's Disease under Treatment with Anti-TNF Antibodies
    S. Karger AG ; 2014
    In:  Digestion Vol. 89, No. 3 ( 2014), p. 209-215
    Details
    In: Digestion, S. Karger AG, Vol. 89, No. 3 ( 2014), p. 209-215
    Abstract: 〈 b 〉 〈 i 〉 Background and Aims: 〈 /i 〉 〈 /b 〉 Paradoxically, psoriasis or psoriasiform skin lesions induced or exacerbated by anti-TNF antibodies have been described. Here, we report a series of 13 novel cases featuring exacerbation or occurrence of psoriatic skin lesions induced by anti-TNF antibodies in patients with Crohn's disease (CD). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We performed a systematic analysis of exacerbation or occurrence of psoriasis or psoriasiform skin lesions induced by anti-TNF antibodies in an inflammatory bowel disease patient cohort at the University Hospital Zurich. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We identified 13 CD patients who developed psoriasis or psoriasiform lesions while receiving anti-TNF therapy. 10 of the 13 patients were female with an average age of 26.9 years at diagnosis. 11 of the 13 patients had a complicated disease. The mean time of clinical latency between diagnosis and onset of psoriasis was about 9.4 years, and the time between the beginning of all biological infusions and the onset of psoriasis was about 7 months. 7 of the 13 patients received infliximab, 3 adalimumab, and 3 certolizumab pegol at onset of psoriasis. In most of the cases, anti-TNF therapy was changed or discontinued and skin lesions improved. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Most of our described patients featured a complicated disease course of CD and had an improvement of the rash after changing the anti-TNF therapy.
    Type of Medium: Online Resource
    ISSN: 0012-2823 , 1421-9867
    URL: Article
    DOI: 10.1159/000358288
    RVK:
    XA 40650
    RVK:
    XA 10000
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2014
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  • 7
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    A Novel OGR1 (GPR68) Inhibitor Attenuates Inflammation in Murine Models of Colitis
    S. Karger AG ; 2021
    In:  Inflammatory Intestinal Diseases Vol. 6, No. 3 ( 2021), p. 140-153
    Details
    In: Inflammatory Intestinal Diseases, S. Karger AG, Vol. 6, No. 3 ( 2021), p. 140-153
    Abstract: 〈 b 〉 〈 i 〉 Background and Aims: 〈 /i 〉 〈 /b 〉 Local extracellular acidification is associated with several conditions, such as ischemia, cancer, metabolic disease, respiratory diseases, and inflammatory bowel disease (IBD). Several recent studies reported a link between IBD and a family of pH-sensing G protein-coupled receptors. Our previous studies point to an essential role for OGR1 (GPR68) in the modulation of intestinal inflammation and fibrosis. In the current study, we evaluated the effects of a novel OGR1 inhibitor in murine models of colitis. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 The effects of a novel small-molecule OGR1 inhibitor were assessed in the acute and chronic dextran sulfate sodium (DSS) murine models of colitis. Macroscopic disease indicators of intestinal inflammation were evaluated, and epithelial damage and immune cell infiltration and proliferation were assessed by immunohistochemistry. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 The OGR1 inhibitor ameliorated clinical parameters in acute and chronic DSS-induced colitis. In mice treated with the OGR1 inhibitor, endoscopy showed no thickening and normal vascularity, while fibrin was not detected. Histopathological findings revealed a decrease in severity of colonic inflammation in the OGR1 inhibitor group when compared to vehicle-DSS controls. In OGR1 inhibitor-treated mice, staining for the macrophage marker F4/80 and cellular proliferation marker Ki-67 revealed a reduction of infiltrating macrophages and slightly enhanced cell proliferation, respectively. This was accompanied by a reduction in pro-inflammatory cytokines, TNF and IL-6, and the fibrosis marker TGF-β1. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 This is the first report providing evidence that a pharmacological inhibition of OGR1 has a therapeutic effect in murine colitis models. Our data suggest that targeting proton-sensing OGR1 using specific small-molecule inhibitors may be a novel therapeutic approach for the treatment of IBD.
    Type of Medium: Online Resource
    ISSN: 2296-9403 , 2296-9365
    URL: Article
    DOI: 10.1159/000517474
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
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  • 8
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    Long-Term Efficacy and Safety of Certolizumab Pegol in an Unselected Crohn's Disease Population: The FACTS III Survey
    S. Karger AG ; 2017
    In:  Digestive Diseases Vol. 35, No. 5 ( 2017), p. 423-432
    Details
    In: Digestive Diseases, S. Karger AG, Vol. 35, No. 5 ( 2017), p. 423-432
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Long-term data of certolizumab pegol (CZP) in Crohn's disease (CD) from pivotal registry trials are limited. We therefore aimed to evaluate the long-term efficacy of CZP in clinical practice in Switzerland. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 In the First Approved Certolizumab Therapeutic Experience in Switzerland-III phase IV multicenter cohort, patients receiving CZP were prospectively included all over Switzerland in (non-) academic hospitals and private practice. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We included 104 CD patients (52 male; only 22.1% anti-tumor necrosis factor (TNF) naïve, CZP as third anti-TNF agent in 46.2%) with follow-up time between 6 weeks up to 5 years. During treatment with CZP, we observed a significant decrease of the Harvey Bradshaw Index from a median of 7 at baseline (interquartile range 4-11) to 4, 5, 4, 3, 3, and 2 at weeks 6, 26, 52, 78, 104, and 156, respectively. While anti-TNF naïve patients showed a significantly better response at the end of induction, during CZP maintenance therapy response was similar as compared to anti-TNF experienced patients as well as between patients with a short (0-5 years) vs. long duration of disease ( 〉 5 years). 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 CZP is an effective long-term treatment option, including CD patients with long disease duration and prior treatment with 1 or 2 anti-TNF agents.
    Type of Medium: Online Resource
    ISSN: 0257-2753 , 1421-9875
    URL: Article
    DOI: 10.1159/000475494
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2017
    detail.hit.zdb_id: 1482221-0
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  • 9
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    The Efficacy and Safety of Golimumab as Third- or Fourth-Line Anti-TNF Therapy in Patients with Refractory Crohn's Disease: A Case Series
    S. Karger AG ; 2017
    In:  Inflammatory Intestinal Diseases Vol. 2, No. 2 ( 2017), p. 131-138
    Details
    In: Inflammatory Intestinal Diseases, S. Karger AG, Vol. 2, No. 2 ( 2017), p. 131-138
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 The TNF-α antagonist golimumab is approved for the treatment of ulcerative colitis but not for Crohn's disease (CD). We herein report a case series of 8 difficult-to-treat patients with severe and refractory CD receiving golimumab as an off-label rescue medication and fourth-line anti-TNF agent in our tertiary referral inflammatory bowel disease center. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We performed a retrospective analysis of clinical, biochemical, and radiological as well as endoscopic parameters. The patients all suffered from severe refractory CD with ongoing symptoms. Moreover, all 8 patients had previously been treated with all 3 other TNF-α antagonists approved for CD in Switzerland (infliximab, adalimumab, and certolizumab pegol) without durable clinical response. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Three out of 8 patients showed a primary nonresponse. Among the 5 patients responding after induction, 1 patient showed a loss of response, and in 1 patient, treatment was terminated due to side effects. Three patients have a continuous clinical response under golimumab. We did not observe any severe adverse events during golimumab administration. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 A considerable fraction of this highly selected subgroup of difficult-to-treat CD patients responded to golimumab, indicating a promising potential for refractory CD patients, including those with multiple previous anti-TNF exposures.
    Type of Medium: Online Resource
    ISSN: 2296-9403 , 2296-9365
    URL: Article
    DOI: 10.1159/000481400
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2017
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  • 10
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    The Influence of Breastfeeding, Cesarean Section, Pet Animals, and Urbanization on the Development of Inflammatory Bowel Disease: Data from the Swiss IBD Cohort Study
    S. Karger AG ; 2020
    In:  Inflammatory Intestinal Diseases Vol. 5, No. 4 ( 2020), p. 170-179
    Details
    In: Inflammatory Intestinal Diseases, S. Karger AG, Vol. 5, No. 4 ( 2020), p. 170-179
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 The pathophysiology of inflammatory bowel disease (IBD) is incompletely understood. Current concepts imply that environmental factors (EFs) trigger disease onset as well as flares in genetically susceptible individuals. 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 The objective of this study is to analyze the association between IBD and various EFs, which may influence the pathogenesis of the disease. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 2,294 patients from the Swiss IBD Cohort Study (SIBDCS) received a questionnaire regarding EF including mode of delivery, breastfeeding, animals in household, and place of residence. The control group comprised patients’ childhood friends, who grew up in a similar environment (“friends cohort”). 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 A total of 1,111 questionnaires were returned from SIBDCS patients (response rate: 48.4%). Breastfeeding for & #x3c;6 months was associated with a decreased risk for ulcerative colitis/indeterminate colitis (UC/IC) (OR: 0.473, 〈 i 〉 p 〈 /i 〉 = 0.006). IBD patients reported less pet animals in the household than the control group ( 〈 i 〉 p 〈 /i 〉 = 0.004). The presence of cats or dogs (OR: 0.688, 〈 i 〉 p 〈 /i 〉 = 0.015) and pet rodents (OR: 0.598, 〈 i 〉 p 〈 /i 〉 = 0.001) in the household before the age of 20 was inversely associated with the risk for UC/IC. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 The present study underlines the importance of EFs in the pathogenesis of IBD. Overall, the development of UC/IC seems to be more affected from environmental influences than from Crohn’s disease. Our results imply a protective effect of possessing pet animals in household and short breastfeeding regarding the onset of UC/IC.
    Type of Medium: Online Resource
    ISSN: 2296-9403 , 2296-9365
    URL: Article
    DOI: 10.1159/000509058
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2020
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