De ziekte van Crohn (CD) en colitis ulcerosa (UC) zijn chronisch inflammatoire darmziekten (IBD). Ondanks dat er de laatste jaren significante stappen zijn gezet in de medicamenteuze behandeling... Show moreDe ziekte van Crohn (CD) en colitis ulcerosa (UC) zijn chronisch inflammatoire darmziekten (IBD). Ondanks dat er de laatste jaren significante stappen zijn gezet in de medicamenteuze behandeling van IBD, ervaart een groot deel van de IBD patiënten klachten van aanhoudende ontsteking en bijwerkingen van de behandeling, wat de noodzaak voor het zoeken naar nieuwe behandelingsopties onderstreept. Door ons te richten op zowel de ontsteking die de klachten van IBD veroorzaakt, als op de onderliggende pathogenese die deze ontsteking aanstuurt middels het introduceren van een gezond microbioom en een gebalanceerde leefstijl, hopen we een (kleine) stap voorwaarts gezet te hebben richting een toekomst met een betere kwaliteit van leven voor patiënten met IBD. Show less
Background: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch... Show moreBackground: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch outpatients with IBD and compared routine ID(A) management among medical professionals to the European Crohn's and Colitis Organisation (ECCO) treatment guidelines. Methods: Between January and November 2021, consecutive adult outpatients with IBD were included in this study across 16 Dutch hospitals. Clinical and biochemical data were extracted from medical records. Additionally, medical professionals filled out questionnaires regarding routine ID(A) management. Results: In total, 2197 patients (1271 Crohn's Disease, 849 Ulcerative Colitis, and 77 IBD-unclassified) were included. Iron parameters were available in 59.3% of cases. The overall prevalence of anemia, ID, and IDA was: 18.0%, 43.4%, and 12.2%, respectively. The prevalence of all three conditions did not differ between IBD subtypes. ID(A) was observed more frequently in patients with biochemically active IBD than in quiescent IBD (ID: 70.8% versus 23.9%; p < 0.001). Contrary to the guidelines, most respondents prescribed standard doses of intravenous or oral iron regardless of biochemical parameters or inflammation. Lastly, 25% of respondents reported not treating non-anemic ID. Conclusions: One in five patients with IBD suffers from anemia that-despite inconsistently measured iron parameters-is primarily caused by ID. Most medical professionals treat IDA with oral iron or standard doses of intravenous iron regardless of biochemical inflammation; however, non-anemic ID is often overlooked. Raising awareness about the management of ID(A) is needed to optimize and personalize routine care. Show less
Background: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch... Show moreBackground: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch outpatients with IBD and compared routine ID(A) management among medical professionals to the European Crohn’s and Colitis Organisation (ECCO) treatment guidelines. Methods: Between January and November 2021, consecutive adult outpatients with IBD were included in this study across 16 Dutch hospitals. Clinical and biochemical data were extracted from medical records. Additionally, medical professionals filled out questionnaires regarding routine ID(A) management. Results: In total, 2197 patients (1271 Crohn’s Disease, 849 Ulcerative Colitis, and 77 IBD-unclassified) were included. Iron parameters were available in 59.3% of cases. The overall prevalence of anemia, ID, and IDA was: 18.0%, 43.4%, and 12.2%, respectively. The prevalence of all three conditions did not differ between IBD subtypes. ID(A) was observed more frequently in patients with biochemically active IBD than in quiescent IBD (ID: 70.8% versus 23.9%; p < 0.001). Contrary to the guidelines, most respondents prescribed standard doses of intravenous or oral iron regardless of biochemical parameters or inflammation. Lastly, 25% of respondents reported not treating non-anemic ID. Conclusions: One in five patients with IBD suffers from anemia that—despite inconsistently measured iron parameters—is primarily caused by ID. Most medical professionals treat IDA with oral iron or standard doses of intravenous iron regardless of biochemical inflammation; however, non-anemic ID is often overlooked. Raising awareness about the management of ID(A) is needed to optimize and personalize routine care. Show less
Background: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch... Show moreBackground: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch outpatients with IBD and compared routine ID(A) management among medical professionals to the European Crohn’s and Colitis Organisation (ECCO) treatment guidelines. Methods: Between January and November 2021, consecutive adult outpatients with IBD were included in this study across 16 Dutch hospitals. Clinical and biochemical data were extracted from medical records. Additionally, medical professionals filled out questionnaires regarding routine ID(A) management. Results: In total, 2197 patients (1271 Crohn’s Disease, 849 Ulcerative Colitis, and 77 IBD-unclassified) were included. Iron parameters were available in 59.3% of cases. The overall prevalence of anemia, ID, and IDA was: 18.0%, 43.4%, and 12.2%, respectively. The prevalence of all three conditions did not differ between IBD subtypes. ID(A) was observed more frequently in patients with biochemically active IBD than in quiescent IBD (ID: 70.8% versus 23.9%; p < 0.001). Contrary to the guidelines, most respondents prescribed standard doses of intravenous or oral iron regardless of biochemical parameters or inflammation. Lastly, 25% of respondents reported not treating non-anemic ID. Conclusions: One in five patients with IBD suffers from anemia that—despite inconsistently measured iron parameters—is primarily caused by ID. Most medical professionals treat IDA with oral iron or standard doses of intravenous iron regardless of biochemical inflammation; however, non-anemic ID is often overlooked. Raising awareness about the management of ID(A) is needed to optimize and personalize routine care. 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
Crohn__s disease (CD) is characterized by chronic, patchy, transmural inflammation of the entire gastrointestinal tract, while ulcerative colitis (UC) is manifested by chronic, continuous,... Show moreCrohn__s disease (CD) is characterized by chronic, patchy, transmural inflammation of the entire gastrointestinal tract, while ulcerative colitis (UC) is manifested by chronic, continuous, superficial inflammation of the colon. Matrix metalloproteinases (MMPs) constitute a family of matrix degrading zinc and calcium-activated neutral endoproteinases, implicated in a wide range of biological processes. We found a marked upregulation of MMP-1, -2, -3 and -9 relative to their natural inhibitors, i.e., tissue inhibitors of metalloproteinases (TIMP) -1 and/or -2, in inflamed mucosa of IBD patients, paralleled by an increase in net MMP activity. Administration of TNF-alpha neutralizing antibody infliximab_ decreased MMP-1, -3 and -9 expression by cultured intestinal IBD explants and serum MMP-9 levels in CD patients, while MMP-2 levels remained almost the same. These observations suggest diverse regulator y pathways for the MMPs examined and a mechanistic pathway for infliximab_ in the treatment of CD. The T allele at TIMP-1 SNP locus +372 T/C, downregulating TIMP-1, appeared to enhance CD susceptibility and worsen prognosis of these patients. Ultimately, these studies might give rationale for the development of novel therapeutic drugs in IBD, based on the inhibition or activation of one or more members of the matrix metalloproteinases family. Show less
Inflammatory bowel disease (IBD), i.e. Crohn__s disease and ulcerative colitis are characterized by a chronic inflammation of the gastrointestinal tract. Neuropeptides are involved in the... Show moreInflammatory bowel disease (IBD), i.e. Crohn__s disease and ulcerative colitis are characterized by a chronic inflammation of the gastrointestinal tract. Neuropeptides are involved in the regulation of intestinal motility, chloride secretion and inflammatory response, three processes that are disturbed in patients with IBD. This has led to the suggestion that neuropeptides are involved in the pathology of IBD. Neuropeptides exert their effects by binding to specific cell surface receptors, a better understanding of these receptor expression patterns in normal and diseased intestine may lead to new diagnostic and therapeutic approaches. In this thesis the receptor expression of the neuropeptides substance P, neurotensin, gastrin-releasing peptide and motilin was studied. In IBD patients, an increased mucosal substance P receptor expression and a decreased muscular neurotensin receptor-1 and -3 expression was found. No neurotensin receptor-2 was detected in the human intestine. The expression of the gastrin-releasing peptide receptor in the smooth muscle was decreased in Crohn__s disease and not in ulcerative colitis. For the first time motilin receptor expression was demonstrated in human intestinal mucosa, but no differences were observed between IBD and controls. Overall this thesis contributes to a better understanding of neuropeptide receptor expression in control and IBD human tissue. Show less
