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1.
Enteral Nutrition in Adult Crohn's Disease: Toward a Paradigm Shift.
Di Caro, S, Fragkos, KC, Keetarut, K, Koo, HF, Sebepos-Rogers, G, Saravanapavan, H, Barragry, J, Rogers, J, Mehta, SJ, Rahman, F
Nutrients. 2019;(9)
Abstract
Medical and surgical treatments for Crohn's disease are associated with toxic effects. Medical therapy aims for mucosal healing and is achievable with biologics, immunosuppressive therapy, and specialised enteral nutrition, but not with corticosteroids. Sustained remission remains a therapeutic challenge. Enteral nutrition, containing macro- and micro-nutrients, is nutritionally complete, and is provided in powder or liquid form. Enteral nutrition is a low-risk and minimally invasive therapy. It is well-established and recommended as first line induction therapy in paediatric Crohn's disease with remission rates of up to 80%. Other than in Japan, enteral nutrition is not routinely used in the adult population among Western countries, mainly due to unpalatable formulations which lead to poor compliance. This study aims to offer a comprehensive review of available enteral nutrition formulations and the literature supporting the use and mechanisms of action of enteral nutrition in adult Crohn's disease patients, in order to support clinicians in real world decision-making when offering/accepting treatment. The mechanisms of actions of enteral feed, including their impact on the gut microbiome, were explored. Barriers to the use of enteral nutrition, such as compliance and the route of administration, were considered. All available enteral preparations have been comprehensively described as a practical guide for clinical use. Likewise, guidelines are reported and discussed.
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2.
Exclusive enteral nutrition in Crohn's disease: Evidence and practicalities.
Ashton, JJ, Gavin, J, Beattie, RM
Clinical nutrition (Edinburgh, Scotland). 2019;(1):80-89
Abstract
Exclusive enteral nutrition (EEN) is the first line therapy for paediatric Crohn's disease, providing a complete nutritional feed whilst simultaneously inducing remission in up to 80% of cases. The effect of EEN on systemic/local intestinal immune function and subsequent inflammation (including barrier permeability, direct anti-inflammatory effects and cytokine signalling pathways), alongside changes in the microbiome (specific species and broad taxonomic shifts, functional changes) are becoming clearer, however the exact mechanism for induction of remission in Crohn's disease remains uncertain. The evidence of efficacy in paediatric Crohn's disease is strong, with selected adult populations also benefiting from EEN. However despite recommendations from all major societies (ECCO, ESPGHAN, NASPGHAN and ESPEN) first-line use of EEN is varied and Europe/Australasia/Canada show significantly more routine use than other parts of North America. Growth and nutritional status are significantly improved with EEN compared to corticosteroids but long-term outcomes are sparse. This review discusses the evidence underlying the use of EEN, highlighting the mechanisms thought to underlie how EEN induces remission in Crohn's disease, when and how to use EEN, including practical issues in both paediatric and adult practice (formulation, compliance, volumes and administration), and summarises the ongoing research priorities.
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3.
Exclusive enteral nutrition versus corticosteroids for treatment of pediatric Crohn's disease: a meta-analysis.
Yu, Y, Chen, KC, Chen, J
World journal of pediatrics : WJP. 2019;(1):26-36
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Abstract
BACKGROUND Many studies have examined the effects of exclusive enteral nutrition (EEN) in children with Crohn's disease (CD), but corticosteroids are considered a superior therapy and are frequently used in China. This meta-analysis aims to compare the efficacy of EEN with corticosteroids in treating pediatric CD. METHODS A comprehensive retrieval from medical databases, including PubMed, EMBASE, MEDLINE, Web of Science, Wanfang data, VIP and CNKI, was performed using the search terms "diet therapy", "exclusive enteral nutrition", "Crohn's disease", "inflammatory bowel diseases", "child" and "pediatrics" from January 1990 to April 2017. RESULTS We included 18 studies from 1329 identified sources in this meta-analysis. EEN was as effective as corticosteroids in inducing remission rate of children suffering from CD (OR = 1.35; 95% CI 0.90, 2.10; P = 0.14). Nevertheless, patients who received EEN were more likely to achieve both endoscopic mucosal healing (OR = 5.24; 95% CI 2.06, 13.37; P = 0.0005) and histological mucosal healing (OR = 4.78; 95% CI 1.89, 12.08; P = 0.0009) than those who received corticosteroids; the Pediatric Crohn's Disease Activity Index was lower [mean difference (MD) = - 3.67; 95% CI - 4.91, - 2.43] and weight gain was higher (MD = 1.92; 95% CI 0.02, 3.83; P = 0.05) in those patients who received EEN than in those who received corticosteroids. No difference was found in relapse rate (OR = 0.57; 95% CI 0.25, 1.29; P = 0.18), height for age or body mass index between the patients treated with EEN and corticosteroids at the 1-year end point. CONCLUSIONS This meta-analysis reveals that there is no significant difference between EEN and corticosteroids in the efficacy of inducing remission rate of CD in a pediatric population, but EEN is superior to corticosteroids in improving short-term mucosal inflammation and reducing the PCDAI index.
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Treatments for Crohn's Disease-Associated Bowel Damage: A Systematic Review.
Pariente, B, Hu, S, Bettenworth, D, Speca, S, Desreumaux, P, Meuwis, MA, Danese, S, Rieder, F, Louis, E
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2019;(5):847-856
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BACKGROUND & AIMS Despite significant advances in the treatment of Crohn's disease (CD), most patients still develop stricturing or penetrating complications that require surgical resections. We performed a systematic review of mechanisms and potential treatments for tissue damage lesions in CD patients. METHODS We searched the PubMed, MBASE, and Cochrane databases from January 1960 to July 2017 for full-length articles on CD, fibrosis, damage lesions, mesenchymal stem cells, and/or treatment. We also searched published conference abstracts and performed manual searches of all reference lists of relevant articles. RESULTS Mechanisms of intestinal damage in patients with CD include fibroblast proliferation and migration, activation of stellate cells, recruitment of intestinal or extra-intestinal fibroblast, and cell trans-differentiation. An altered balance of metalloproteinases and tissue inhibitors of metalloproteinases might contribute to fistula formation. Treatment approaches that reduce excessive transforming growth factor beta (TGFB) activation might be effective in treating established intestinal damage. Stem cell therapies have been effective in tissue damage lesions in CD. Particularly, randomized controlled trials have shown local injections of mesenchymal stem cells to heal perianal fistulas. CONCLUSION In a systematic review of mechanisms and treatments of bowel wall damage in patients with CD, we found a need to test drugs that reduce TGFB and increase healing of transmural damage lesions and to pursue research on local injection of mesenchymal stem cells.
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Thiopurine Therapy in Patients With Inflammatory Bowel Disease: A Focus on Metabolism and Pharmacogenetics.
Chang, JY, Cheon, JH
Digestive diseases and sciences. 2019;(9):2395-2403
Abstract
Thiopurines have been widely used for the maintenance of remission or steroid sparing in patients with inflammatory bowel disease. However, potential drug-related adverse events frequently interfere with their use. Indeed, drug withdrawals associated with adverse reactions have been reported in approximately 25% of patients. To balance the efficacy, safety, and tolerability of thiopurines, regular monitoring of biomarkers (complete blood cell count, liver function test, and metabolic profiles), steady dose escalation, and pretreatment thiopurine S-methyltransferase (TPMT) genotype screening have been routinely recommended. However, the complex thiopurine metabolic pathway and individual differences attributed to pharmacogenetic diversity limit the effectiveness of these strategies in the optimization of thiopurine therapy. Recently, in an effort to facilitate more accurate and personalized prediction of thiopurine response or toxicity, novel genetic markers including NUDT15 and FTO genes were discovered. These discoveries are remarkable because TPMT screening has minimal efficacy for predicting myelosuppression especially in Asian populations, despite the fact that thee populations have a higher frequency of myelosuppression than Western populations. This review focuses on the current understanding of the metabolic pathway and the pharmacogenetics of thiopurines and suggests a personalized preventive strategy against potential adverse drug reactions to optimize their therapeutic application.
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Treatment-Specific Composition of the Gut Microbiota Is Associated With Disease Remission in a Pediatric Crohn's Disease Cohort.
Sprockett, D, Fischer, N, Boneh, RS, Turner, D, Kierkus, J, Sladek, M, Escher, JC, Wine, E, Yerushalmi, B, Dias, JA, et al
Inflammatory bowel diseases. 2019;(12):1927-1938
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BACKGROUND The beneficial effects of antibiotics in Crohn's disease (CD) depend in part on the gut microbiota but are inadequately understood. We investigated the impact of metronidazole (MET) and metronidazole plus azithromycin (MET+AZ) on the microbiota in pediatric CD and the use of microbiota features as classifiers or predictors of disease remission. METHODS 16S rRNA-based microbiota profiling was performed on stool samples from 67 patients in a multinational, randomized, controlled, longitudinal, 12-week trial of MET vs MET+AZ in children with mild to moderate CD. Profiles were analyzed together with disease activity, and then used to construct random forest models to classify remission or predict treatment response. RESULTS Both MET and MET+AZ significantly decreased diversity of the microbiota and caused large treatment-specific shifts in microbiota structure at week 4. Disease remission was associated with a treatment-specific microbiota configuration. Random forest models constructed from microbiota profiles before and during antibiotic treatment with metronidazole accurately classified disease remission in this treatment group (area under the curve [AUC], 0.879; 95% confidence interval, 0.683-0.9877; sensitivity, 0.7778; specificity, 1.000; P < 0.001). A random forest model trained on pre-antibiotic microbiota profiles predicted disease remission at week 4 with modest accuracy (AUC, 0.8; P = 0.24). CONCLUSIONS MET and MET+AZ antibiotic regimens in pediatric CD lead to distinct gut microbiota structures at remission. It may be possible to classify and predict remission based in part on microbiota profiles, but larger cohorts will be needed to realize this goal.
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Early Predictors of the Long-term Response to Therapy in Patients With Crohn Disease Derived From a Time-Intensity Curve Analysis After Microbubble Contrast Agent Injection.
Quaia, E, Gennari, AG, Cova, MA
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine. 2019;(4):947-958
Abstract
OBJECTIVES The aim of this study was to identify early predictors of the long-term response to therapy in patients with Crohn disease (CD) from time-intensity curves obtained after microbubble injection. METHODS One hundred fifteen consecutive patients with a proven diagnosis of CD involving the terminal ileal loop who were scheduled to begin pharmacologic therapy with biologics (infliximab or adalimumab) were scanned after sulfur hexafluoride-filled microbubble injection before the beginning and at the end of the sixth week of treatment. The absolute value and percentage change of each semiquantitative kinetic parameter (peak enhancement, time to peak enhancement, rise time, mean transit time, wash-in and wash-out rates, area under the curve [AUC] for the whole time-intensity curve, AUC during wash-in, AUC during wash-out, and wash-in perfusion index) as measured on the terminal ileal tract and adjacent reactive mesenteric fat were calculated from time-intensity curves. Patients were followed for at least 24 months with redetermination of the Crohn Disease Activity Index and with at least 1 endoscopy within 18 weeks after the beginning of pharmacologic treatment. The absolute values and percentage changes of kinetic parameters were assessed as potential predictors of the therapeutic outcome by a logistic regression analysis. RESULTS The study group included 66 male and 49 female patients (mean age ± SD, 45.76 ± 11 years). The pretreatment values and percentage changes of the peak enhancement, AUC, AUC during wash-in, and AUC during wash-out were found to be predictors (P < .05) of the long-term therapeutic outcome. CONCLUSIONS The analysis of time-intensity curves obtained after microbubble contrast agent injection provides early predictors of the long-term therapeutic outcome in patients with CD.
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Mucosal Healing and Bacterial Composition in Response to Enteral Nutrition Vs Steroid-based Induction Therapy-A Randomised Prospective Clinical Trial in Children With Crohn's Disease.
Pigneur, B, Lepage, P, Mondot, S, Schmitz, J, Goulet, O, Doré, J, Ruemmele, FM
Journal of Crohn's & colitis. 2019;(7):846-855
Abstract
AIMS: Exclusive enteral nutrition [EEN] is as efficacious as corticosteroids [CS] to induce remission in Crohn's disease [CD], without their adverse effects. EEN seems to be more efficient than steroids to induce mucosal healing, but the underlying molecular mechanisms are only sparsely understood. We aimed in the present work to study the anti-inflammatory effects of EEN with Modulen IBD® vs CS in active paediatric CD, and to assess its modulatory effects on the intestinal microbiota as compared with steroids. MATERIALS AND METHODS Nineteen patients with new-onset active CD (Harvey-Bradshaw index [HBI] >5), aged from 6 to 17 years, were included in this prospective randomised induction trial with CS [n = 6] or EEN [n = 13]. Patients were assessed at Weeks 0 and 8 using clinical parameters HBI, endoscopic findings (Crohn's Disease Endoscopic Index of Severity [CDEIS] score) and analysis of faecal microbiota composition. RESULTS At 8 weeks, clinical remission [HBI <5] was achieved in 13/13 patients on EEN and 5/6 patients on steroids; the mucosal healing rate was significantly higher in the EEN [89%] compared with steroid group [17%]. There were no significant differences between groups regarding biological markers, but the intestinal microbiota profiles shifted upon EEN-induced remission to a higher proportion of Ruminococcus bacteria compared with steroid-induced remission [p = 0.049], and with higher proportions of bacteria belonging to Clostridium in EEN-treated patients. CONCLUSIONS Both steroid and EEN induced clinical remission. However, patients with EEN-induced remission showed a higher rate of mucosal healing and this was associated with a different gut microbiota compositional shift in these children.
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Curcuminoids from Curcuma Longa: New adjuvants for the treatment of crohn's disease and ulcerative colitis?
Cunha Neto, F, Marton, LT, de Marqui, SV, Lima, TA, Barbalho, SM
Critical reviews in food science and nutrition. 2019;(13):2136-2143
Abstract
Crohn's Disease (CD) and Ulcerative Colitis (UC) result from an overreaction of the bowel to multifactorial stimuli leading to discomfort, pain, and it is associated with high morbidity and lethality. The medications commonly used are expensive and associated with multiple side effects. Curcuma longa exerts anti-inflammatory and antioxidant actions and has shown positive effects on CD and UC treatment, possibly due to the presence of curcuminoids. The objective of this review was to evaluate the role of curcuminoids in the treatment of IBD. A search for articles associating curcuminoids and CD and UC was performed using MEDLINE-PubMed. It has been found that curcumin can reduce oxidative stress and inhibit the migration of neutrophils and inducible nitric oxide synthase in the intestine. It may also improve micro and macroscopic lesions, prevent apoptosis of intestinal cells and also induce the restoration of the mitogen-activated protein kinase immune reaction. As the incidence of CD and UC is growing in many populations, there is an urgency to find an appropriate and accessible therapeutic approach to improve quality of life of patients. The use of curcumin is cheap, efficient and associated with no side effects, and may become an alternative to the IBD treatment.
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Ethnic differences in inflammatory bowel disease: Results from the United Kingdom inception cohort epidemiology study.
Misra, R, Limdi, J, Cooney, R, Sakuma, S, Brookes, M, Fogden, E, Pattni, S, Sharma, N, Iqbal, T, Munkholm, P, et al
World journal of gastroenterology. 2019;(40):6145-6157
Abstract
BACKGROUND The current epidemiology of inflammatory bowel disease (IBD) in the multi-ethnic United Kingdom is unknown. The last incidence study in the United Kingdom was carried out over 20 years ago. AIM: To describe the incidence and phenotype of IBD and distribution within ethnic groups. METHODS Adult patients (> 16 years) with newly diagnosed IBD (fulfilling Copenhagen diagnostic criteria) were prospectively recruited over one year in 5 urban catchment areas with high South Asian population. Patient demographics, ethnic codes, disease phenotype (Montreal classification), disease activity and treatment within 3 months of diagnosis were recorded onto the Epicom database. RESULTS Across a population of 2271406 adults, 339 adult patients were diagnosed with IBD over one year: 218 with ulcerative colitis (UC, 64.3%), 115 with Crohn's disease (CD, 33.9%) and 6 with IBD unclassified (1.8%). The crude incidence of IBD, UC and CD was 17.0/100000, 11.3/100000 and 5.3/100000 respectively. The age adjusted incidence of IBD and UC were significantly higher in the Indian group (25.2/100000 and 20.5/100000) compared to White European (14.9/100000, P = 0.009 and 8.2/100000, P < 0.001) and Pakistani groups (14.9/100000, P = 0.001 and 11.2/100000, P = 0.007). The Indian group were significantly more likely to have extensive disease than White Europeans (52.7% vs 41.7%, P = 0.031). There was no significant difference in time to diagnosis, disease activity and treatment. CONCLUSION This is the only prospective study to report the incidence of IBD in an ethnically diverse United Kingdom population. The Indian ethnic group showed the highest age-adjusted incidence of UC (20.5/100000). Further studies on dietary, microbial and metabolic factors that might explain these findings in UC are underway.