关键词： COLON cancer risk factors   INFLAMMATORY bowel diseases   PATIENTS   COLITIS diagnosis   CANCER treatment   DRUG efficacy  

摘要： Background Whether aminosalicylates or thiopurines reduce the risk of colorectal cancer (CRC) in inflammatory bowel (IBD) disease is controversial. Aim To assess simultaneously the chemopreventive effect of aminosalicylates or thiopurines in a case-control study nested in the CESAME observational cohort that enrolled consecutive patients with IBD between May 2004 and June 2005. Patients were followed up to December 2007. Methods Study population comprised 144 case patients who developed CRC from the diagnosis of IBD (65 and 79 cases diagnosed, respectively, before and from 2004, starting year of the prospective observational period of CESAME) and 286 controls matched for gender, age, IBD subtype and year of diagnosis, and cumulative extent of colitis. Exposure to aminosalicylates or thiopurines was defined by an exposure to the treatment during the year of the diagnosis of cancer. The propensity of receiving 5-ASA and thiopurines was quantified by a composite score taking into account patient and IBD characteristics. The role of aminosalicylates or thiopurines was assessed by multivariate analysis. Propensity scores and the history of primary sclerosing cholangitis were entered into the multivariate model for adjustment. Results By multivariate analysis adjusted for propensity, a significant protective effect of exposure to drugs during the year of cancer was found for aminosalicylates (OR = 0.587, 95% CI: 0.367-0.937, P = 0.0257), but not for thiopurines (OR = 0.762, 95% CI: 0.432-1.343, P = 0.3468). Conclusion In a case-control study nested in the CESAME cohort, a significant decrease in the risk of colorectal cancer in IBD was associated with exposure to aminosalicylates, not to thiopurines.

关键词： Crohn's Disease   Outcomes   Prognostic Factor   Ulcerative Colitis  

摘要： Crohn's disease and ulcerative colitis are heterogeneous inflammatory bowel diseases, and therapeutic requirements vary among patients. We have a limited capacity to predict disease progression for individual patients, therefore it is important that they are evaluated for the presence of active disease when symptoms are mild or even absent, when patients are more likely to respond to new treatment interventions. It then is important to monitor responses to treatment, to quickly identify those therapies that are ineffective, modify or change therapy, and avoid disease complications. Studies are underway to assess the effects of different monitoring strategies. Because of the heavy burden of severe inflammatory bowel disease on patients' health and quality of life, and the association between intestinal healing and disease progression in high-risk patients, a treat-to-target strategy (based on tissue healing) is likely to be optimal.

摘要： Thalidomide is an immunomodulatory drug (IMiD) with proven therapeutic action in several autoimmune/inflammatory diseases;however, its inherent high toxicity has led to the development of more powerful and safer thalidomide analogs, including lenalidomide and pomalidomide. These are new generation IMiDs that exhibit direct antitumor activity as well as anti-inflammatory/immunomodulatory properties, and are FDA-approved for the treatment of several hematological malignances. Here we investigated the potential therapeutic effects of lenalidomide and pomalidomide in several experimental murine models of autoimmune/inflammatory diseases: 2,4,6-trinitrobenzene sulfonic acid-and dextran sulfate sodium-induced inflammatory bowel disease and type IIcollagen-induced arthritis. Lenalidomide displayed a strong therapeutic effect in all these models of autoimmune/inflammatory diseases, while the effect of pomalidomide was less pronounced. In vitro experiments confirmed the immunosuppressive effect of both IMiDs on the proliferative response of stimulated human lymphocytes and on the balance of secreted cytokines toward an anti-inflammatory profile. We conclude that lenalidomide may offer a therapeutic opportunity against autoimmune/inflammatory diseases.

关键词： antisense therapy   biologics   Crohn’s disease   leukocyte trafficking   small molecules   ulcerative colitis  

摘要： Our growing understanding of the immunopathogenesis of inflammatory bowel disease (IBD) has opened new avenues for developing targeted therapies. These advances in treatment options targeting different mechanisms of action offer new hope for personalized management. In this review we highlight emerging novel and easily administered therapeutics that may be viable candidates for the management of IBD, such as antibodies against interleukin 6 (IL-6) and IL-12/23, small molecules including Janus kinase inhibitors, antisense oligonucleotide against SMAD7 mRNA, and inhibitors of leukocyte trafficking to intestinal sites of inflammation (e.g., sphingosine 1-phosphate receptor modulators). We also provide an update on the current status in clinical development of these new classes of therapeutics.

关键词： inflammatory bowel disease   marijuana   young adults  

摘要： Objectives: Recent studies in adults report symptom relief with marijuana use in patients with inflammatory bowel disease (IBD). We assessed the prevalence, pattern, effects, and adverse effects of marijuana use in young adults with IBD. Methods: We conducted a prospective questionnaire survey study at a pediatric IBD clinic. All patients (18-21 years of age) answered anonymous questionnaires about demographics, IBD, medications, and marijuana use. Results: Fifty-three patients (mean age 18.7 years, 32 boys) were enrolled. Thirty-seven patients (70%) reported using marijuana currently or in the past. There was no statistically significant difference between the users and nonusers of marijuana regarding demographics, disease activity, or medications. Despite prolonged use of marijuana, 70% of patients did not discuss it with their gastroenterologists. Twenty-four patients used marijuana medicinally for IBD symptoms in addition to medical therapy. Although majority found marijuana to be moderately/very helpful, complete relief of symptoms such as abdominal pain, poor appetite, nausea, and diarrhea was seen in 29%, 37%, 14%, and 10% of patients, respectively. Only half of patients reported knowledge of possible adverse effects of marijuana and 19% of patients reported mild neuropsychiatric adverse effects. Overall, 98% of patients supported legalization of marijuana and 85% were interested in using medical marijuana if it became legally available. Conclusions: We found a high rate of marijuana use in our cohort of young adults with IBD. Majority of users report symptom improvement but do not inform physicians. Future well-controlled studies are necessary to assess role of marijuana in IBD therapy.

关键词： INFLAMMATORY bowel disease treatment   INFLIXIMAB   ANTINEOPLASTIC agents   TUMOR necrosis factor   MEDICAL care costs   SYSTEMATIC reviews (Medical research)   THERAPEUTIC use  

摘要： Background Biological therapies represent a fundamental innovation for the management of inflammatory bowel diseases (IBD). However, many biological originators have reached, or are about to reach, patent expiry and long-term therapy costs have become progressively unsustainable. CT-P13, a biosimilar of the anti-tumor necrosis factor (anti-TNF) monoclonal antibody infliximab, might represent a significant alternative to its originator, with the potential to decrease medical care costs and, therefore, become available to a large number of patients. Objectives In this systematic review, we analyzed the data from available clinical trials that recently investigated the validity of indication extrapolation of CT-P13 for the treatment of IBD in naive patients and in patients who switched from its originator infliximab, focusing on clinical efficacy, safety and immunogenicity. Methods A detailed literature search was developed a priori to identify articles that investigated the validity of indication extrapolation of CT-P13 for the treatment of IBD in TNF inhibitor treatment-naive patients and in patients who switched from the originator infliximab. This was applied to Ovid MEDLINE, In-Process and Other Non-Indexed Citations, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus for content from 2012 to September 2016. Results We based our review on the available data from 11 studies that included a total of 1007 IBD patients: 570 patients suffering from Crohn's disease (294 switched and 276 nave), 435 patients suffering from ulcerative colitis (127 switched and 308 naive), and two IBD unclassified patients (switched). Overall, no significant difference in efficacy and safety between the originator infliximab and its biosimilar CT-P13 was observed. When assessing the safety of CT-P13, we found that 9.2% of patients experienced adverse effects (4.1% infusion-related reactions and 4.3% infections). Conclusion The analyzed studies did not report a significant di

关键词： INFLAMMATORY bowel disease treatment   ULCERATIVE colitis treatment   AZATHIOPRINE   DRUG side effects   MEDICAL care   THERAPEUTIC use  

关键词： metaproteomics   SILAM   activity-based probes   microbiome   MudPIT   quantitative proteomics   ComPIL   GO term enrichment  

摘要： Tandem mass spectrometry based shotgun proteomics of distal gut microbiomes is exceedingly difficult due to the inherent complexity and taxonomic diversity of the samples. We introduce two new methodologies to improve metaproteomic studies of microbiome samples. These methods include the stable isotope labeling in mammals to permit protein quantitation across two mouse cohorts as well as the application of activity-based probes to enrich and analyze both host and microbial proteins with specific functionalities. We used these technologies to study the microbiota from the adoptive T cell transfer mouse model of inflammatory bowel disease (IBD) and compare these samples to an isogenic control, thereby limiting genetic and environmental variables that influence microbiome composition. The data generated highlight quantitative alterations in both host and microbial proteins due to intestinal inflammation and corroborates the observed phylogenetic changes in bacteria that accompany IBD in humans and mouse models. The combination of isotope labeling with shotgun proteomics resulted in the total identification of 4434 protein clusters expressed in the microbial proteomic environment, 276 of which demonstrated differential abundance between control and IBD mice. Notably, application of a novel cysteine-reactive probe uncovered several microbial proteases and hydrolases overrepresented in the IBD mice. Implementation of these methods demonstrated that substantial insights into the identity and dysregulation of host and microbial proteins altered in IBD can be accomplished and can be used in the interrogation of other microbiome-related diseases.

关键词： cannabidiol   cannabis   inflammatory bowel disease   marijuana   pediatric   tetrahydrocannabinol  

摘要： The trend toward decriminalization of cannabis (marijuana) continues sweeping across the United States. Colorado has been a leader of legalization of medical and recreational cannabis use. The growing public interest in the medicinal properties of cannabis and its use by patients with a variety of illnesses including inflammatory bowel disease (IBD) makes it important for pediatric gastroenterologists to understand this movement and its potential effect on patients. This article describes the path to legalization and "medicalization" of cannabis in Colorado and the public perception of safety despite the known adverse health effects of use. We delineate the mammalian endocannabinoid system and our experience of caring for children and adolescents with IBD in an environment of increasing awareness and acceptance of its use. We then summarize the rationale for considering that cannabis may have beneficial and harmful effects for patients with IBD. Finally, we highlight the challenges federal laws impose on conducting research on cannabis in IBD. The intent of this article is to inform health care providers about the issues around cannabis use and research in adolescents and young adults with IBD.

关键词： Inflammatory bowel disease   Abstracts   Conferences  

摘要： Numerous abstracts related to inflammatory bowel disease (IBD) are presented at national conferences in the USA. The overall rate of publication of these abstracts as complete manuscripts is unknown . Abstracts submitted to the 2010 American College of Gastroenterology (ACG), Advances in Inflammatory Bowel Diseases (AIBD), and the American Gastroenterological Association abstracts at Digestive Disease Week (DDW) were reviewed. Each abstract was reviewed manually by two authors for type of research, study design, patient population, and outcome. Both PubMed and Google were then searched to determine whether the abstract was published as a full manuscript within five years of the conference. Univariate and multivariate logistic regression analysis was carried out using Stata 14.1. In total, 872 abstracts were reviewed. 49% (426/872) were published as complete manuscripts within five years of the conference. The average length of time to publication was 1.87 years (range 0-5). 42% of abstracts from ACG, 58% from AIBD, and 23% from DDW were eventually published (p < 0.0001). However, abstracts presented at DDW had the shortest time to publication compared to the other conferences (p = 0.002). Factors predictive of eventual publication include: number of authors (mean 7.5 for published vs 6.4 for unpublished p = 0.0001), clinical research compared to basic and translational (p = 0.026), and studies assessing drug safety with no adverse effects reported (p = 0.006). Nearly 50% of the abstracts presented at major gastroenterology conferences in the USA are published as full manuscripts 5 years after the conference. Further studies are needed to assess why so many abstracts are not published.