Inflammatory Bowel Diseases (IBD) such as Crohn’s disease (CD) and ulcerative colitis (UC) are chronic immunological digestive diseases with a progressive character and associated with significant... Show moreInflammatory Bowel Diseases (IBD) such as Crohn’s disease (CD) and ulcerative colitis (UC) are chronic immunological digestive diseases with a progressive character and associated with significant healthcare costs. Different solutions have been proposed such as innovation in care monitoring or implementation of electronic health (eHealth). IBD is one of many chronic diseases that could benefit from eHealth, adding smartphone applications to the toolbox for care management has the potential improve disease understanding, enhance medication adherence, improve patient-physician communications, and for earlier interventions by medical professionals when problems arise. Furthermore, the accessibility to Big Data and increased computational resources have paved the way for Artificial Intelligence (AI) to provide potential solutions for the management of prototypical complex diseases with advanced heterogeneity and alternating disease states, like IBD. In this thesis we assessed the current economic and psychosocial impact of IBD by assessing its effect on indirect costs, productivity and caregiving. Furthermore, we observed if we can proactively identify IBD patients’ needs using eHealth and Artificial Intelligence. Lastly, we analyze the impact of monitoring IBD patients using eHealth interventions in order to facilitate the delivery of high-value care. Show less
Background: Liver transplantation remains the only effective evidence based treatment for advanced primary sclerosing cholangitis. However, recurrence of disease occurs in approximately 18%.Aims:... Show moreBackground: Liver transplantation remains the only effective evidence based treatment for advanced primary sclerosing cholangitis. However, recurrence of disease occurs in approximately 18%.Aims: This study aimed to assess risk factors of recurrence of primary sclerosing cholangitis.Methods: A retrospective cohort study was performed on patients undergoing transplantation for recurrence of primary sclerosing cholangitis in two academic centers (Leuven, Belgium and Leiden, The Netherlands). Besides other risk factors, the degree of mucosal inflammation was assessed as a potential risk factor using histological Geboes scores.Results: 81 patients were included, of which 62 (76.5%) were diagnosed with ulcerative colitis. Seventeen patients (21.0%) developed rPSC during a median follow-up time of 5.2 years. In a subset of 42 patients no association was found between the degree of mucosal inflammation and recurrence, using both original Geboes scores and multiple cut-off points. In the total cohort, cytomegaloviremia post-transplantation (HR: 4.576, 95%CI 1.688-12.403) and younger receiver age at time of liver transplantation (HR: 0.934, 95%CI 0.881-0.990) were independently associated with an increased risk of recurrence of disease.Conclusion: This study found no association between the degree of mucosal inflammation and recurrence of primary sclerosing cholangitis. An association with recurrence was found for cytomegaloviremia postliver transplantation and younger age at time of liver transplantation. (C) 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Show less
This thesis is focusing on cell-mediated induction of immune tolerance and consists of two parts. The studies described in Part I report the development of strategies for possible treatment of... Show moreThis thesis is focusing on cell-mediated induction of immune tolerance and consists of two parts. The studies described in Part I report the development of strategies for possible treatment of Inflammatory Bowel Diseases (IBD). Induction of immune tolerance, in IBD mouse model, with the use of regulatory T (Treg) cells generated in vitro by specific activation of naive T cells was achieved. Additionally Treg cells were also shown to be induced in vivo and restore intestinal immune tolerance with the use of adeno-associated virus (AAV) vector-based gene delivery. In relation to the use of AAV vector, Part II of this thesis is addressing the possibilities of tolerance induction to AAV capsid or transgene specific immune responses which can develop after AAV-based therapy Show less
Hematopoietic stem cell transplantation (HSCT) and mesenchymal stromal (MSC) cell therapy are currently under investigation as novel therapies for inflammatory bowel diseases (IBD). Hematopoietic... Show moreHematopoietic stem cell transplantation (HSCT) and mesenchymal stromal (MSC) cell therapy are currently under investigation as novel therapies for inflammatory bowel diseases (IBD). Hematopoietic stem cells are thought to repopulate the immune system and reset the immunological response to luminal antigens. MSCs have the capacity to differentiate into a wide variety of distinct cell lineages and to suppress immune responses in vitro and in vivo. The main goal of this thesis was to study the safety, feasibility, and applicability of stem cell therapy in IBD. Chapter 2 concludes that autologous HSCT appears to be safe and can be an alternative strategy for Crohn__s disease patients with severe and therapy resistant disease. Data from the phase I study described in Chapter 3 demonstrates that MSCs isolated from Crohn__s disease patients have similar characteristics compared to MSCs from healthy donors and that administration of autologous bone marrow derived MSCs appears to be safe and feasible in the treatment of refractory Crohn__s disease. Chapter 4 shows that MSC phenotype and function are not affected by therapeutic concentrations of drugs commonly used in the treatment of IBD. Chapter 5 demonstrates that IFN-_ activation of MSCs increases their immunosuppresive capacities and importantly, their therapeutic efficacy in vivo. Show less
