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  • 1
    Online Resource
    Online Resource
    The Role of Anti(myco)bacterial Interventions in the Management of IBD: Is There Evidence at All?
    S. Karger AG ; 2012
    In:  Digestive Diseases Vol. 30, No. 4 ( 2012), p. 358-367
    Details
    In: Digestive Diseases, S. Karger AG, Vol. 30, No. 4 ( 2012), p. 358-367
    Abstract: 〈 b 〉 〈 i 〉 Background/Aims: 〈 /i 〉 〈 /b 〉 The etiology of IBD is unknown but may relate to an unidentified bacterial pathogen or an immunological reaction to gut microbiota. Antibiotics have therefore been proposed as a therapy for Crohn’s disease (CD) and ulcerative colitis (UC). The aim of this review was to compel the evidence for the use of antibiotics in the treatment of IBD. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We performed a systematic review of the literature regarding the use of antibiotics for inducing or maintaining remission in IBD. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Current data are conflicting, but a recent systematic review of randomized controlled trials has shown a statistically significant effect of antibiotics being superior to placebo for active, perianal and quiescent CD and for active UC. These data have been poorly translated in clinical practice and the place of antibiotics is restricted to certain specific situations in the international guidelines. This is first linked to the difficulties in interpreting clinical trials because of their heterogeneity in study design, endpoints, type of antibiotic and concomitant therapies. The exception to this is the use of either ciprofloxacin or metronidazole for treating CD perianal fistulas. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 The pathology of CD, the likely primary and known secondary pathogens in this disease and the successful responses in animal models all plead for new trials of antibiotics in IBD. This is a call to select patients more carefully, and to continue antibiotics for longer than is customary. Beside antibiotics, new therapeutic approaches that can balance gut dysbiosis should be tested.
    Type of Medium: Online Resource
    ISSN: 0257-2753 , 1421-9875
    URL: Article
    DOI: 10.1159/000338126
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2012
    detail.hit.zdb_id: 1482221-0
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  • 2
    Online Resource
    Online Resource
    Previous Cancer/Lymphoma and Refractory Inflammatory Bowel Disease
    S. Karger AG ; 2015
    In:  Digestive Diseases Vol. 33, No. Suppl. 1 ( 2015), p. 44-49
    Details
    In: Digestive Diseases, S. Karger AG, Vol. 33, No. Suppl. 1 ( 2015), p. 44-49
    Abstract: Immunomodulators and biologic agents are effective in treating inflammatory bowel diseases (IBDs), and recent evidence supports their introduction earlier in the disease course. An important concern to both patients and physicians considering immunosuppression (IS) for the treatment of IBD is the potential associated cancer risk. Several important clinical questions deserve attention with respect to IBD therapy and cancer. First, does medical therapy for IBD predispose to developing cancer? Second, in an IBD patient with a history of cancer, does IBD therapy impact cancer recurrence? Third, once cancer develops in an IBD patient, is the cancer outcome different? Finally, in an IBD patient with current cancer, does the cancer therapy affect IBD outcomes? In a recent multicentric study, patients were identified based on a diagnosis of IBD and cancer with subsequent exposure to anti-tumor necrosis factor α (anti-TNFα arm), thiopurines or methotrexate (antimetabolite arm) or without subsequent IS exposure (control arm). Two hundred and fifty-five patients met the inclusion criteria. Prior cancers included 121 solid, 62 gastrointestinal, 55 dermatologic and 17 hematologic malignancies. During the follow-up period, 75 (29.4%) patients developed incident cancer: 36 (14.1%) a new cancer, 33 (12.9%) a recurrent cancer and 6 (2.4%) a new and recurrent cancer. Incident cancer rate per 100 person-years for patients exposed to anti-TNFα, anti-metabolites and controls was 2.6 with 795 person-years of follow-up, 14.8 with 122 person-years of follow-up and 8.52 with 422 person-years of follow-up, respectively. In this series of IBD patients with a history of cancer, exposure to IS following a cancer diagnosis was not associated with an increased risk of incident cancer compared to patients who did not receive these agents. Prospective data are needed to confirm these findings.
    Type of Medium: Online Resource
    ISSN: 0257-2753 , 1421-9875
    URL: Article
    DOI: 10.1159/000437064
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2015
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  • 3
    Online Resource
    Online Resource
    Immune Cell Therapy in IBD
    S. Karger AG ; 2014
    In:  Digestive Diseases Vol. 32, No. Suppl. 1 ( 2014), p. 61-66
    Details
    In: Digestive Diseases, S. Karger AG, Vol. 32, No. Suppl. 1 ( 2014), p. 61-66
    Abstract: The therapeutic landscape of IBD has undergone a dramatic transformation since the advent of biologic therapies, especially TNF inhibitors. However, 30% of patients are primary nonresponders to biologic therapy and secondary failures are frequent. Due to substantial progress in our understanding of the biology of regulatory T cells (Tregs) and in the pathways of homing to the gastrointestinal tract, novel cell-based therapies for IBD have become possible. For example, although a reductionist view, one could envisage IBD as an imbalance between the proinflammatory effectors (such as Th17 cells) and the anti-inflammatory regulators (like Tregs). Here we focus on the development of ex vivo and in vivo approaches to enhance Tregs in the gastrointestinal tract. Specifically, herein we highlight a recently concluded phase 1/2a clinical trial that investigated the safety and efficacy of a single injection of escalating doses of autologous ovalbumin-specific Tregs in patients with active Crohn's disease refractory to conventional therapy. This therapy was well tolerated and demonstrated dose-related efficacy. We also discuss the potential of directing Tregs derived through intranasal as well as epicutaneous immunization to the gastrointestinal tract by enhancing their gut homing signature and their potential to decrease gastrointestinal inflammation. Finally, the strengths and pitfalls of these new therapeutic approaches are discussed as we move forward in this largely uncharted territory.
    Type of Medium: Online Resource
    ISSN: 0257-2753 , 1421-9875
    URL: Article
    DOI: 10.1159/000367827
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2014
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  • 4
    Online Resource
    Online Resource
    What Are the Most Challenging Aspects of Inflammatory Bowel Disease? An International Survey of Gastroenterologists Comparing Developed and Developing Countries
    S. Karger AG ; 2021
    In:  Inflammatory Intestinal Diseases Vol. 6, No. 2 ( 2021), p. 78-86
    Details
    In: Inflammatory Intestinal Diseases, S. Karger AG, Vol. 6, No. 2 ( 2021), p. 78-86
    Abstract: 〈 b 〉 〈 i 〉 Background and Aims: 〈 /i 〉 〈 /b 〉 As inflammatory bowel disease (IBD) becomes more prevalent, the challenges that gastroenterologists face in managing these patients evolve. We aimed to describe the most important challenges facing gastroenterologists from around the world and compare these between those working in developed and developing countries. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 An online questionnaire was developed, and a link distributed to gastroenterologists. Data were analyzed descriptively using Friedman and Wilcoxon matched-pair signed rank tests to compare rankings for responses. Mann-Whitney 〈 i 〉 U 〈 /i 〉 tests were used to compare rankings between responses from gastroenterologists from developed and developing countries. Lower scores reflected greater challenges. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Of 872 who started, 397 gastroenterologists (45.5%) completed the survey. Respondents represented 65 countries (226 [56.9%] from developed countries). Overall, the challenge ranked most important (smallest number) was increasing IBD prevalence (13.6%). There were significant differences in mean ranking scores for many simple aspects of care for those from developing countries compared to providers from developed countries, such as access to simple IBD treatments (5.52 vs. 6.02, 〈 i 〉 p 〈 /i 〉 = 0.01), access to anti-TNF drugs including dose escalation (3.33 vs. 3.93, 〈 i 〉 p 〈 /i 〉 & #x3c; 0.01), access to good stoma care (2.57 vs. 3.03, 〈 i 〉 p 〈 /i 〉 & #x3c; 0.001), access to therapeutic drug monitoring (1.47 vs. 1.84, 〈 i 〉 p 〈 /i 〉 & #x3c; 0.001), and access to care for people from low socioeconomic status (2.77 vs. 3.37, 〈 i 〉 p 〈 /i 〉 & #x3c; 0.001). 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Increasing IBD prevalence is seen by gastroenterologists as the greatest challenge facing them. There are significant differences between the IBD challenges facing gastroenterologists from developed and developing countries that reflect inequities in access to health care.
    Type of Medium: Online Resource
    ISSN: 2296-9403 , 2296-9365
    URL: Article
    DOI: 10.1159/000512310
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 2817967-5
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  • 5
    Online Resource
    Online Resource
    Deep Remission: A New Concept?
    S. Karger AG ; 2012
    In:  Digestive Diseases Vol. 30, No. Suppl. 3 ( 2012), p. 107-111
    Details
    In: Digestive Diseases, S. Karger AG, Vol. 30, No. Suppl. 3 ( 2012), p. 107-111
    Abstract: Crohn’s disease (CD) is a chronic inflammatory disorder characterized by periods of clinical remission alternating with periods of relapse defined by recurrent clinical symptoms. Persistent inflammation is believed to lead to progressive bowel damage over time, which manifests with the development of strictures, fistulae and abscesses. These disease complications frequently lead to a need for surgical resection, which in turn leads to disability. So CD can be characterized as a chronic, progressive, destructive and disabling disease. In rheumatoid arthritis, treatment paradigms have evolved beyond partial symptom control alone toward the induction and maintenance of sustained biological remission, also known as a ‘treat to target’ strategy, with the goal of improving long-term disease outcomes. In CD, there is currently no accepted, well-defined, comprehensive treatment goal that entails the treatment of both clinical symptoms and biologic inflammation. It is important that such a treatment concept begins to evolve for CD. A treatment strategy that delays or halts the progression of CD to increasing damage and disability is a priority. As a starting point, a working definition of sustained deep remission (that includes long-term biological remission and symptom control) with defined patient outcomes (including no disease progression) has been proposed. The concept of sustained deep remission represents a goal for CD management that may still evolve. It is not clear if the concept also applies to ulcerative colitis. Clinical trials are needed to evaluate whether treatment algorithms that tailor therapy to achieve deep remission in patients with CD can prevent disease progression and disability.
    Type of Medium: Online Resource
    ISSN: 0257-2753 , 1421-9875
    URL: Article
    DOI: 10.1159/000342732
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2012
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  • 6
    Online Resource
    Online Resource
    Yeasts: Neglected Pathogens
    S. Karger AG ; 2009
    In:  Digestive Diseases Vol. 27, No. Suppl. 1 ( 2009), p. 104-110
    Details
    In: Digestive Diseases, S. Karger AG, Vol. 27, No. Suppl. 1 ( 2009), p. 104-110
    Abstract: 〈 i 〉 Background: 〈 /i 〉 Current research on Crohn’s disease (CD) concerns molecular events related to loss of tolerance to microbes that could trigger or maintain inflammation in genetically susceptible individuals. CD is also associated with antimicrobial antibodies, including the antibodies we described against yeast oligomannosides (ASCA). This prompted us to investigate a role for another yeast, 〈 i 〉 Candida albicans, 〈 /i 〉 a very common commensal of the human digestive tract and an important opportunistic pathogen. 〈 i 〉 Clinical and Experimental Data: 〈 /i 〉 It has been revealed that the major oligomannose epitopes supporting ASCA are expressed by 〈 i 〉 C. albicans 〈 /i 〉 in human tissues, suggesting that 〈 i 〉 C. albicans 〈 /i 〉 is the immunogen for ASCA. This link has been reinforced by the demonstration that novel serological markers of CD (ALCA and ACCA), consisting of antibodies against chitin and glucan (two components of the 〈 i 〉 C. albicans 〈 /i 〉 cell wall), are also generated during 〈 i 〉 C. albicans 〈 /i 〉 infection. Mycological investigation of families with multiple cases of CD shows that patients with CD and their healthy relatives are colonized with 〈 i 〉 C. albicans 〈 /i 〉 more commonly than control families. In healthy relatives, 〈 i 〉 C. albicans 〈 /i 〉 colonization correlates with ASCA levels, whereas the onset of CD is associated with ASCA stability and is independent of the 〈 i 〉 C. albicans 〈 /i 〉 intestinal load. Experimental studies show that chemically-induced colitis promotes 〈 i 〉 C. albicans 〈 /i 〉 colonization in mice. In turn, 〈 i 〉 C. albicans 〈 /i 〉 colonization generates ASCA, increases inflammation, histological scores and pro-inflammatory cytokine expression. 〈 i 〉 Perspectives: 〈 /i 〉 Current investigations focus on interactions of TLRs and lectins with yeast epitopes that differently polarize the immune response to 〈 i 〉 C. albicans 〈 /i 〉 cell wall glycans, which are the targets of an ‘excessive’ adaptive response associated with CD.
    Type of Medium: Online Resource
    ISSN: 0257-2753 , 1421-9875
    URL: Article
    DOI: 10.1159/000268129
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2009
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  • 7
    Online Resource
    Online Resource
    Preface
    S. Karger AG ; 2009
    In:  Digestive Diseases Vol. 27, No. 1 ( 2009), p. 1-2
    Details
    In: Digestive Diseases, S. Karger AG, Vol. 27, No. 1 ( 2009), p. 1-2
    Type of Medium: Online Resource
    ISSN: 1421-9875 , 0257-2753
    URL: Article
    DOI: 10.1159/000268114
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2009
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  • 8
    Online Resource
    Online Resource
    Anti-TNF Withdrawal in Inflammatory Bowel Disease
    S. Karger AG ; 2016
    In:  GE Portuguese Journal of Gastroenterology Vol. 23, No. 3 ( 2016-05), p. 153-161
    Details
    In: GE Portuguese Journal of Gastroenterology, S. Karger AG, Vol. 23, No. 3 ( 2016-05), p. 153-161
    Type of Medium: Online Resource
    ISSN: 2341-4545
    URL: Article
    DOI: 10.1016/j.jpge.2015.11.004
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2016
    detail.hit.zdb_id: 2835774-7
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