scholarly journals Noncanonical NF-κB Signaling Upregulation in Inflammatory Bowel Disease Patients is Associated With Loss of Response to Anti-TNF Agents

2021 ◽  
Vol 12 ◽  
Author(s):  
Vu Q. Nguyen ◽  
Kristin Eden ◽  
Holly A. Morrison ◽  
Megan B. Sammons ◽  
Kristin K. Knight ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Signaling Pathway ◽  
Bowel Disease ◽  
Target Genes ◽  
Preliminary Evidence ◽  
Lymphocyte Migration ◽  
Clinical Criteria ◽  
Number Of Patients ◽  
Effective Therapeutic Strategy ◽  
Inflammatory Bowel

Objectives: Targeting tumor necrosis factor (TNF) with biologic agents, such as infliximab and adalimumab, is a widely used and effective therapeutic strategy in inflammatory bowel disease (IBD). Unfortunately, a significant number of patients fail to respond or lose response over time to these agents. Previous studies have defined multiple complex roles for canonical NF-κB signaling in the pathogenesis of IBD. However, preliminary evidence suggests that the lesser defined noncanonical NF-κB signaling pathway also contributes to disease pathogenesis and response to anti-TNF agents. The objective of this study was to evaluate this hypothesis in Crohn’s disease (CD) and ulcerative colitis (UC) patients.Design: A total of 27 subjects with IBD (19 with CD and 8 with UC) and 15 control subjects were tested. Clinical criteria, patient history, and endoscopic disease activity were factors used to categorize patients and define therapeutic response. Biopsy specimens were collected during colonoscopy and expression was determined for 88 target genes known to be associated with noncanonical NF-κB signaling and IBD.Results: Noncanonical NF-κB signaling was significantly upregulated in IBD patients and was associated with increased gastrointestinal inflammation, epithelial cell death, lymphocyte migration, and Nod-like receptor signaling. Furthermore, noncanonical NF-κB signaling was further upregulated in patients unresponsive to anti-TNF agents and was suppressed in responsive patients. MAP3K14, NFKB2, CCL19, CXCL12, and CXCL13 were significantly dysregulated, as were genes that encode pathway regulators, such as CYLD, NLRP12, and BIRC2/3.Conclusion: Our study identifies a previously uncharacterized role for the understudied noncanonical NF-κB signaling pathway in the pathogenesis of IBD and anti-TNF therapy responsiveness. The genes and pathways identified may ultimately prove useful in IBD management and could potentially be used as biomarkers of drug response.

Very early onset inflammatory bowel disease: Investigation of the IL-10 signaling pathway in Iranian children

2017 ◽  
Vol 60 (12) ◽  
pp. 643-649 ◽  
Author(s):  
Shahram Nemati ◽  
Shahram Teimourian ◽  
Mina Tabrizi ◽  
Mehri Najafi ◽  
Naghi Dara ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Signaling Pathway ◽  
Bowel Disease ◽  
Early Onset ◽  
Inflammatory Bowel ◽  
Iranian Children

scholarly journals Diagnostic Radiation Exposure in Patients with Inflammatory Bowel Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Catherine Langevin ◽  
Lysanne Normandeau ◽  
Mickael Bouin
Keyword(s):  
Inflammatory Bowel Disease ◽  
Radiation Exposure ◽  
Bowel Disease ◽  
Indeterminate Colitis ◽  
Number Of Patients ◽  
Inflammatory Bowel ◽  
The Mean ◽  
Effects Of Radiation ◽  
And Control

Background. Because of the chronic and relapsing nature of inflammatory bowel disease (IBD), which often requires characterization with CT scan, IBD patients might be exposed to a large amount of radiation. As a cumulative effective dose (CED) ≥ 100 mSv is considered significant for stochastic risks of cancer, it is important to monitor and control the radiation exposure of the IBD patients. In the present work, we aimed to quantify the mean CED in IBD patients to assess any harmful effects of radiation. Methods. This study includes 200 IBD patients, identified retrospectively, from the outpatient clinics of the Centre Hospitalier de l’Université de Montréal between January 1, 2010, and February 15, 2017, from the gastroenterologists’ patients lists. The number and type of each radiology test performed were listed for each patient during the study period and the CED was calculated using our institution’s dose index when available and standardized tables. Results. Among the 200 IBD patients, 157 patients had Crohn’s disease (CD), 41 had ulcerative colitis (UC), and 2 had indeterminate colitis. The mean CED for IBD patients was 23.1 ± 45.2 mSv during a mean follow-up duration of 4.3 years. CED was higher among patients with CD than with UC (27.5 ± 49.5 versus 6.8 ± 14.8 mSv; p<0.01). Six patients were exposed to a high CED (>100 mSv) and all had CD. Conclusion. While potentially harmful levels of radiation exposure are of concern in only a small number of patients, strategies to limit such exposure are encouraged when clinically appropriate.

Management of Biological Therapy Before Elective Inflammatory Bowel Disease Surgeries

2019 ◽  
Vol 25 (10) ◽  
pp. 1613-1620 ◽  
Author(s):  
Tawnya M Hansen ◽  
Laura E Targownik ◽  
Ahmer Karimuddin ◽  
Yvette Leung
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Biologic Therapy ◽  
Preoperative Treatment ◽  
Necrosis Factor Alpha ◽  
Number Of Patients ◽  
Inflammatory Bowel ◽  
Factor Alpha ◽  
Alpha Therapy ◽  
Necrosis Factor

Abstract Increasing uptake of biologic therapy has contributed to declining surgical rates for inflammatory bowel disease (IBD). However, a significant number of patients on biologic therapy will go on to require surgery. The literature is conflicted with regard to the preoperative management of biologic therapy before urgent or elective IBD surgery. This article reviews the available data on postoperative complications following preoperative treatment with anti-tumor necrosis factor alpha therapy, anti-integrin therapy, and anti-interleukin therapy.

Application of Medical Information Support Platform based on Nursing Intervention on Inflammatory Bowel Disease (Preprint)

2020 ◽  
Author(s):  
Suyan Zhang ◽  
Xuemei Jiang ◽  
Aihua Liu ◽  
Jane Cansoni
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Medical Information ◽  
Immunoglobulin A ◽  
Nursing Intervention ◽  
Information Support ◽  
Blank Group ◽  
Number Of Patients ◽  
Improvement Effect ◽  
Inflammatory Bowel

BACKGROUND Background: Enteritis inflammatory disease is a common multiple disease in the intestine. And the number of patients with enteritis in China has increased year by year. OBJECTIVE Objective: In order to study the effect of information services on inflammatory bowel disease under medical information support platform, the patients with enteritis were selected as the research subject. METHODS Method: The effects of nursing intervention on inflammatory bowel disease based on information support platform were studied by experimental methods such as antidiarrheal time, elimination of flatulence time, Escherichia coli, lactobacillus, SlgA (secretory immunoglobulin A) content in stool samples and colonoscopy. RESULTS Results: The results showed that the nursing intervention based on the information support platform had a significant improvement effect on inflammatory bowel disease. The time of diarrhea and flatulence was significantly reduced compared with the blank group, and other indicators were also developing in a favorable direction. CONCLUSIONS Conclusion: Compared with the blank group, the patients in the experimental group had significant improvement in the recovery of a large number of indicators. Not only that, patients have improved physical or intellectual aspects, so information intervention can be promoted clinically.

Azathioprine in the therapy of paediatric inflammatory bowel disease – part I: treatment indications, dosing and thiopurine-related adverse events

2021 ◽  
Vol 75 (6) ◽  
pp. 500-507
Author(s):  
Kristýna Pospíšilová ◽  
Jiří Bronský
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Bowel Disease ◽  
Maintenance Phase ◽  
Treatment Indications ◽  
Number Of Patients ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Keywords Crohn's Disease ◽  
Available Information

Background: Thiopurines (in Europe mainly azathioprine) are widely used in the treatment of inflammatory bowel diseases in children. Due to a prolonged time until the onset of therapeutic effect, those drugs are aimed to be used in the maintenance phase of the therapy rather than for induction of remission. Thiopurines are sometimes used in combination therapy (with aminosalicylates or biological treatment agents). The adverse events of these drugs occur as often as in 15–40% cases and may lead to treatment cessation in a significant number of patients. Aims: To overview available information on (mainly) children suffering from inflammatory bowel disease. Conclusion: Genetic examination accompanied with laboratory monitoring of blood count parameters (specifically at the beginning of therapy) and biochemistry can help prevent some of the severe adverse events. Keywords Crohn’s disease, ulcerative colitis, pediatrie, merkaptopurin, thiopuriny

Lactobacillus paracasei L9 improves colitis by expanding butyrate-producing bacteria that inhibits the IL-6/STAT3 signaling pathway

2021 ◽  
Author(s):  
Zhengquan Yu ◽  
Min Deng ◽  
Xi Wu ◽  
Xiaoyue Duan ◽  
Jiuzhi Xu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Signaling Pathway ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Lactobacillus Paracasei ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Inflammatory bowel disease (IBD) is a chronic intestinal inflammation that is currently incurable. Increasing evidences indicate that supplementation with probiotics could improve the symptoms of IBD. It is scientifically significant...

scholarly journals Metformin Ameliorates Inflammatory Bowel Disease by Suppression of the STAT3 Signaling Pathway and Regulation of the between Th17/Treg Balance

PLoS ONE ◽  
2015 ◽  
Vol 10 (9) ◽  
pp. e0135858 ◽  
Author(s):  
Seon-Yeong Lee ◽  
Seung Hoon Lee ◽  
Eun-Ji Yang ◽  
Eun-Kyung Kim ◽  
Jae-Kyung Kim ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Signaling Pathway ◽  
Bowel Disease ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Inflammatory Bowel

scholarly journals Designing fecal microbiota transplant trials that account for differences in donor stool efficacy

2017 ◽  
Vol 27 (10) ◽  
pp. 2906-2917 ◽  
Author(s):  
Scott W Olesen ◽  
Thomas Gurry ◽  
Eric J Alm
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Trials ◽  
Bowel Disease ◽  
Statistical Power ◽  
Fecal Microbiota Transplantation ◽  
Optimal Strategies ◽  
Fecal Microbiota ◽  
Fecal Microbiota Transplant ◽  
Number Of Patients ◽  
Inflammatory Bowel

Fecal microbiota transplantation is a highly effective intervention for patients suffering from recurrent Clostridium difficile, a common hospital-acquired infection. Fecal microbiota transplantation’s success as a therapy for C. difficile has inspired interest in performing clinical trials that experiment with fecal microbiota transplantation as a therapy for other conditions like inflammatory bowel disease, obesity, diabetes, and Parkinson’s disease. Results from clinical trials that use fecal microbiota transplantation to treat inflammatory bowel disease suggest that, for at least one condition beyond C. difficile, most fecal microbiota transplantation donors produce stool that is not efficacious. The optimal strategies for identifying and using efficacious donors have not been investigated. We therefore examined the optimal Bayesian response-adaptive strategy for allocating patients to donors and formulated a computationally tractable myopic heuristic. This heuristic computes the probability that a donor is efficacious by updating prior expectations about the efficacy of fecal microbiota transplantation, the placebo rate, and the fraction of donors that produce efficacious stool. In simulations designed to mimic a recent fecal microbiota transplantation clinical trial, for which traditional power calculations predict [Formula: see text] statistical power, we found that accounting for differences in donor stool efficacy reduced the predicted statistical power to [Formula: see text]. For these simulations, using the heuristic Bayesian allocation strategy more than quadrupled the statistical power to [Formula: see text]. We use the results of similar simulations to make recommendations about the number of patients, the number of donors, and the choice of clinical endpoint that clinical trials should use to optimize their ability to detect if fecal microbiota transplantation is effective for treating a condition.

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