Advances In Inflammatory Bowel Diseases

The annual clinical and research conference of the Crohn’s and Colitis Foundation of America, Advances in Inflammatory Bowel Diseases, provided a comprehensive overview of the year’s newest developments regarding inflammatory bowel diseases (IBD). The program was again successful. Attracting a wide range of participants including leaders in the field from around the world, the program offered a unique opportunity to review and debate the most important clinical studies, current controversies in the management of IBD, and the most recent perspectives on current research in the investigation of IBD.     

Recent Advances in Gastrointestinal Endoscopy

Since 1970 considerable advances have been made in the field of fiber-optical endoscopy. One essential factor is that a greater variety and more efficient instruments became available. The development moved first in the direction of a more precise diagnosis and second in the direction of therapeutic or operative endoscopy.     

Complementary Therapies in Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBDs) often take a chronic debilitating course. Given the chronicity of IBD, the limitations of the available medications, their potential side effects, and the impact of the disease on patients’ quality of life, it is not surprising IBD patients are ranked among the highest users of complementary and alternative medicine (CAM). Since CAM has become very popular in real-life practice of Western Communities, caregivers must gain more knowledge about these therapies, their mechanism of action, benefits, and risks. This article reviews and discusses up-to-date scientific and clinical data regarding the most prevalent herbal CAM therapies.     

Inflammatory Bowel Disease and Cardiovascular Diseases

BackgroundEmerging data showed patients with chronic inflammatory disorders, including inflammatory bowel disease, are more likely to develop atherosclerotic cardiovascular diseases, heart failure, and atrial fibrillation. This article aims to review the evidence of those associations.MethodsPubMed was searched from inception to January 2022 using the keywords, including inflammatory bowel diseases, Crohn disease, ulcerative colitis, atherosclerotic cardiovascular disease, coronary artery disease, cardiovascular disease, atrial fibrillation, heart failure, and premature coronary artery disease. Relevant literature, including retrospective/prospective cohort studies, clinical trials, meta-analyses, and guidelines, were reviewed and summarized.ResultsBoth ulcerative colitis and Crohn disease are associated with an increased risk of atherosclerotic cardiovascular diseases, cerebrovascular accidents, premature coronary artery disease, and atrial fibrillation. Ulcerative colitis is associated with an increased risk of heart failure. The increased atrial fibrillation occurred during inflammatory bowel disease flares and persistent activity but not during periods of remission. Hypotheses for the mechanism underlying the association of inflammatory bowel disease and atherosclerotic cardiovascular diseases include shared risk factors (ie, obesity, diabetes, smoking, diet) and pathophysiology (gut microbiome dysfunction) or adverse effects from inflammatory bowel disease itself or its treatment (ie, chronic inflammation, dyslipidemia, thrombocytosis, steroids).ConclusionInflammatory bowel disease is associated with an increased risk of atherosclerotic cardiovascular diseases, heart failure, and atrial fibrillation. A multidisciplinary team with gastroenterologists and cardiologists is needed to optimize the care for patients with inflammatory bowel disease and associated cardiac diseases.     

Metabolic Syndrome Frequency in Inflammatory Bowel Diseases

Background/Aim:

Metabolic syndrome (MetS) is a clinical condition characterized by central obesity, elevated triglycerides, low–high density lipoproteins, impaired fasting glucose, and hypertension. There is insufficient data on the prevalence of MetS in patients with inflammatory bowel disease (IBD). This study sought to determine the prevalence of MetS in a Turkish cohort of patients with IBD and the association between insulin resistance (IR) and the MetS parameters, in this population.

Patients and Methods:

A total of 177 patients over 18 years of age (62 with Crohn''s disease (CD) and 115 with ulcerative colitis (UC)) were enrolled in the study. The presence of at least three criteria of the International Diabetes Federation (IDF) was accepted for the diagnosis of MetS. The Homeostasis Model Assessment (HOMA) was used to determine IR. HOMA values < 1 were considered normal and values > 2.5 indicated a high probability of IR.

Results:

MetS frequency was higher in patients n=34 (29.5%) with UC than in patients n=11 (17.7%) with CD (P < 0.01). MetS was detected in 12 of the 117 patients (10.3%) with IBD, under 45 years of age, and in 33 of 60 patients (55%) over 45 years of age. HOMA value in n=31 patients (27%) with UC was > 2.5. Body mass index, insulin (P < 0.001), waist circumference, fasting plasma glucose, leukocyte count (P < 0.01), triglycerides, C-reactive protein, and uric acid values (P < 0.05) were significantly higher in UC patients with IR than those without IR.

Conclusion:

Frequent occurrence of MS with increasing age in IBD, particularly in UC, showed the importance of early diagnosis and treatment of cardiovascular disease risk factors in the long-term follow-up of these diseases.     

Proinflammatory Progranulin Antibodies in Inflammatory Bowel Diseases

Background

Recently, we identified neutralizing autoantibodies against progranulin (PGRN) in a wide spectrum of rheumatic diseases including cases with enteropathic spondylarthritis. PGRN is a secreted protein with strong anti-inflammatory effects, believed to be mediated by the direct inhibition of TNF receptors 1&2. Given the central role of TNF-α as proinflammatory cytokine, a neutralizing antibody directed against its physiologic antagonist PGRN might entertain a proinflammatory environment.

Objective

The aim of the present study was to investigate a possible occurrence of PGRN-antibodies (PGRN-Abs) in inflammatory bowel disease (IBD), and to investigate a possible pathogenic effect.

Materials and Methods

Sera samples of 141 patients with Crohn’s disease (CD) and of 71 patients with ulcerative colitis (UC) were tested for PGRN-Abs by ELISA. PGRN plasma levels were detected by ELISA. Proinflammatory effects of progranulin-antibodies were analyzed by TNF-α-mediated cytotoxicity assays using HT29 cells and by examination of possible effects of PGRN and of PGRN-antibodies on TNF-α-induced downmodulation of FOXP3 expression in CD4⁺CD25^hi Tregs.

Results

PGRN-Abs were found in sera of 23/141 (16.31 %) patients with CD, and 15/71 (21.13 %) patients with UC. PGRN-Abs were more frequent than anti-neutrophil cytoplasmic autoantibodies (ANCAs) in UC, but less frequent than anti-Saccharomyces cerevisiae antibodies (ASCAs) in CD. PGRN-Abs belonged mostly to IgG1 (71.1 %) and IgA (26.3 %). They occurred in relevant titres and had significant neutralizing effects on PGRN plasma levels. Cytotoxicity assays comparing PGRN-antibody-positive sera with negative sera from matched patients with IBD showed a proinflammatory effect of PGRN-Abs on HT29 cells. Moreover, PGRN-antibodies led to an increase of TNF-α-induced downmodulation of FOXP3 in CD4⁺CD25^hi Tregs.

Conclusion

The results suggest that PGRN-Abs occur frequently in CD and UC, and have a proinflammatory effect.     

胶囊内镜在小肠疾病中的应用进展

胶囊内镜（CE）技术发展迅速,已成为一线小肠无创检查技术之一,目前已广泛用于不明原因消化道出血（OGIB）、炎症性肠病、小肠肿瘤、乳糜泻和腹痛等的诊断,其与双气囊小肠镜（DBE）联合应用可提高小肠疾病的诊疗水平。本文就CE在小肠疾病中的应用进展作一综述。     

Evolution of Clinical Trials in Inflammatory Bowel Diseases

Purpose of Review

Since the first clinical trial of cortisone in ulcerative colitis in 1955, remarkable progress has been made in the design and conduct of clinical trials in inflammatory bowel diseases (IBD). In this review article, we will discuss evolution of clinical trials in IBD over the last 3–5 years.

Recent Findings

Recognizing limitations intrinsic to clinical disease activity indices in IBD, regulatory authorities have recommended evaluating co-primary endpoints of patient-reported outcomes and endoscopic disease activity in clinical trials. Biomarker-enriched trial enrolment and central endoscopy reading have emerged as critical events in trial recruitment and outcome assessment and have driven placebo response rates down. While trials of novel biologic therapies and advanced small molecules continue at an accelerated pace, pragmatic comparative efficacy trials of treatment strategy aimed at optimizing current therapies (such as early combined immunosuppression [REACT], tight disease control [CALM], therapeutic drug monitoring [TAXIT, TAILORIX]) have directly informed clinical practice. With emphasis on value-based care and population health management, multi-pronged remote monitoring, self-management, and telemedicine approaches in the era of smartphones have re-emerged with promise. Non-conventional therapies such as fecal microbiota transplantation, though still experimental, have provided insight into disease pathogenesis and offered hope for microbial manipulation strategies for treating these complex diseases.

Summary

Clinical trials have rapidly evolved over the last 5 years not only focusing on novel therapies but also optimizing existing treatment approaches and population health management. Over the next decade, these trials will continue to advance the field, and be readily translatable into clinical practice.