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  • S. Karger AG  (5)
  • Zeitz, Jonas  (5)
  • 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
    detail.hit.zdb_id: 1482218-0
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  • 2
    Online Resource
    Online Resource
    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
    detail.hit.zdb_id: 2817967-5
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  • 3
    Online Resource
    Online Resource
    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
    detail.hit.zdb_id: 1482218-0
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    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
    detail.hit.zdb_id: 1482218-0
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  • 5
    Online Resource
    Online Resource
    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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