Osteopenia and osteoporosis are common features in inflammatory bowel disease (IBD), comprising both Crohn's disease and ulcerative colitis. Moreover, Crohn's disease is associated with increased... Show moreOsteopenia and osteoporosis are common features in inflammatory bowel disease (IBD), comprising both Crohn's disease and ulcerative colitis. Moreover, Crohn's disease is associated with increased fracture risk. The etiology of bone loss in IBD is multifactorial. It includes insufficient intake or absorption of calcium, vitamin D, and potassium; smoking; a low peak bone mass; a low body mass index; and decreased physical activity. In several studies, it has been shown that elevated concentrations of systemic and local pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN gamma), interleukin (IL)-1 beta, IL-4, IL-5, IL-6, IL-13, and IL-17, present in IBD patients are potentially detrimental for bone metabolism and may be responsible for bone loss and increased fracture risk. This perspective aims to review the current literature on the role of inflammatory factors in the pathophysiology of skeletal problems in IBD and to suggest potential treatment to improve bone health, based on a combination of evidence and clinical and pathophysiological reasoning. Show less
Biemans, V.B.C.; Meulen-de Jong, A.E. van der; Woude, C.J. van der; Lowenberg, M.; Dijkstra, G.; Oldenburg, B.; ... ; Dutch Initiative Crohn Colitis ICC 2020
Background and Aims: Ustekinumab is approved for the treatment of Crohn's disease [CD]. Systematically registered prospective real-world data are scarce. We therefore aimed to study the... Show moreBackground and Aims: Ustekinumab is approved for the treatment of Crohn's disease [CD]. Systematically registered prospective real-world data are scarce. We therefore aimed to study the effectiveness, safety and usage of ustekinumab for CD in everyday practice.Methods: We prospectively enrolled CD patients initiating ustekinumab in regular care between December 2016 and January 2019. Clinical (Harvey Bradshaw Index [HBI]), biochemical (C-reactive protein [CRP] and faecal calprotectin [FCP]), extra-intestinal manifestations and, peri-anal fistula activity, ustekinumab dosage, concomitant medication use, and adverse events were documented at weeks 0, 12, 24, and 52.The primary outcome was corticosteroid-free clinical remission.Results: In total, 221 CD patients were included (98.6% anti-tumour necrosis factor [TNF] and 46.6% vedolizumab exposed) with a median follow-up of 52.0 weeks [interquartile range 49.3-58.4]. Corticosteroid-free clinical remission rates at weeks 24 and 52 were 38.2% and 37.1%, respectively. An initial dosing schedule of 8 weeks, compared to 12 weeks, correlated with a lower discontinuation rate [20.0% vs 42.6%, p = 0.01], but comparable corticosteroid-free clinical remission at week 52 (46.3% [q8w] vs 34.6% [q12w], p = 0.20). There was no clinical benefit of combination therapy after 52 weeks when compared to ustekinumab monotherapy [combi 40.6% vs mono 36.0%, p = 0.64]. At baseline, 28 patients had active peri-anal fistula, of whom 35.7% showed complete clinical resolution after 24 weeks. During follow-up we encountered six severe infections [3.5 per 100 patient-years], with all patients being on concomitant immunosuppressant therapies. Ustekinumab treatment discontinuation was observed in 75 [33.9%] patients mainly due to lack of response.Conclusion: Ustekinumab is a relatively safe and effective treatment option for CD patients with prior failure of anti-TNF and anti-integrin therapies. Show less
Barnhoorn, M.C.; Wasser, M.N.J.M.; Roelofs, H.; Maljaars, P.W.J.; Molendijk, I.; Bonsing, B.A.; ... ; Meulen-de Jong, A.E. van der 2020
Background and Aims: The long-term safety and efficacy of allogeneic bone marrow-derived mesenchymal stromal cell [bmMSC] therapy in perianal Crohn's disease [CD] fistulas is unknown. We aimed to... Show moreBackground and Aims: The long-term safety and efficacy of allogeneic bone marrow-derived mesenchymal stromal cell [bmMSC] therapy in perianal Crohn's disease [CD] fistulas is unknown. We aimed to provide a 4-year clinical evaluation of allogeneic bmMSC treatment of perianal CD fistulas.Methods: A double-blind dose-finding study for local bmMSC therapy in 21 patients with refractory perianal fistulising Crohn's disease was performed at the Leiden University Medical Center in 2012-2014. All patients treated with bmMSCs [1 x 10(7) bmMSCs cohort 1, n = 5; 3 x 10(7) bmMSCs cohort 2, n = 5; 9 x 10(7) bmMSCs cohort 3, n = 5] were invited for a 4-year evaluation. Clinical events were registered, fistula closure was evaluated, and anti-human leukocyte antigen [HLA] antibodies were assessed. Patients were also asked to undergo a pelvic magnetic resonance imaging [MRI] and rectoscopy.Results: Thirteen out of 15 patients [87%] treated with bmMSCs were available for long-term follow-up. Two non-MSC related malignancies were observed. No serious adverse events thought to be related to bmMSC therapy were found. In cohort 2 [n = 4], all fistulas were closed 4 years after bmMSC therapy. In cohort 1 [n = 4] 63%, and in cohort 3 [n = 5] 43%, of the fistulas were closed, respectively. In none of the patients anti-HLA antibodies could be detected 24 weeks and 4 years after therapy. Pelvic MRI showed significantly smaller fistula tracts after 4 years.Conclusions: Allogeneic bmMSC therapy for CD-associated perianal fistulas is also in the long-term a safe therapy. In bmMSC-treated patients, fistulas with closure at Week 24 were still closed after 4 years. Show less
Psychosocial and functional outcomes after intestinal resection in pediatric Crohn's disease (CD) are lacking. Therefore, we (I) assessed health-related quality of life (HRQOL), colorectal function... Show morePsychosocial and functional outcomes after intestinal resection in pediatric Crohn's disease (CD) are lacking. Therefore, we (I) assessed health-related quality of life (HRQOL), colorectal function, and satisfaction with surgery and (II) investigated their relationship with surgical outcomes, after ileocecal resection for CD. Crohn's patients that underwent ileocecal resection during childhood were included. HRQOL and colorectal function were assessed using SF-36 and COREFO, respectively, and compared with reference values. Satisfaction was scored on a 5-point Likert scale. In total, 80 patients (50% male, median age 23.0 years) were included. Physical HRQOL was impaired (SF-36 [mean]: CD, 47 vs. general, 54; p < 0.001), while mental HRQOL was similar to that in the general population. Overall colorectal function was impaired (COREFO [mean]: CD, 12.6 vs. normal, 7.2; p < 0.001). Worse colorectal function was associated with increasing clinical disease activity and longer interval since resection. Majority of patients was satisfied with surgery (81% satisfied/very satisfied, 11% neither satisfied nor dissatisfied, 8% dissatisfied/very dissatisfied). Decreased satisfaction with surgery was associated with increased clinical disease activity but not related to colorectal function. Conclusions: Physical HRQOL and colorectal function in CD patients who underwent ileocecal resection during childhood seem impaired and related to adverse surgical outcomes. This emphasizes the need for post-operative monitoring and prophylactic therapies.What is Known:center dot Up to 25% of pediatric-onset Crohn's disease (CD) patients undergo an intestinal resection within 5 years from diagnosis.center dot Many children and adults with CD experience disruption of their daily activities and health-related quality of life (HRQOL).What is New:center dot Physical HRQOL and colorectal function are impaired in patient with CD that underwent ileocecal resection during childhood.center dot Increasing clinical disease activity, a longer interval since surgery, severe complications related to surgery, and recurrent surgeries are all associated with worse colorectal function. Show less
Barnhoorn, M.C.; Halteren, A.G.S. van; Pel, M. van; Molendijk, I.; Struijk, A.C.; Jansen, P.M.; ... ; Meulen-de Jong, A.E. van der 2019
It is increasingly recognized that in order to gain further insights into human disorders and develop new therapeutic strategies and diagnostic tools, it is critical to have a comprehensive... Show moreIt is increasingly recognized that in order to gain further insights into human disorders and develop new therapeutic strategies and diagnostic tools, it is critical to have a comprehensive overview of immune cell subsets resident in tissues under physiological and pathological conditions. Flow cytometry has been the golden standard for analyzing immune cell subsets, and with a typical experiment, dozens of immune subsets can be discriminated. Due to the lack of spectrally-resolvable fluorochromes, mass cytometry utilizing metal-conjugated antibodies has shown to be a powerful tool for dissecting the immune landscape even further. Inflammatory intestinal diseases can only be understood by studying specialized cell types within the tissue niche itself. In this thesis, we applied mass cytometry and data-driven, automated analysis approaches to investigate the complex compositions of heterogeneous cell subsets, such as those encountered in intestinal biopsies. These types of data have the potential to greatly improve our understanding of human disease. In concert with clinical data, mass cytometry could enable a finer classification of patients and might aid in the development of improved diagnostics, prognostics and personalized therapeutic regimens. Show less
![A Simple Endoscopic Score Modified for the Upper Gastrointestinal Tract in Crohn's Disease [UGI-SES-CD]: A Report From the ImageKids Study](/sites/all/modules/custom/islandora_solr_search/images/defaultimg.png?solr_nav%5Bid%5D=ab503f9caf509eb3415b&solr_nav%5Bpage%5D=1&solr_nav%5Boffset%5D=11)
