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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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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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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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Proinflammatory Properties of Peroxidized Fat May Contribute to the Etiology of Crohn's Disease.
Bhaskar, N, Narasimhulu, CA, Keewan, E, Rohr, M, Parthasarathy, S
Journal of medicinal food. 2019;(2):162-169
Abstract
Crohn's disease (CD) is a well-known subset of inflammatory bowel disease (IBD) that results in patchy inflammation through the entire thickness of the bowel wall, with the ability to target virtually any part of the gastrointestinal tract, but most commonly affecting the area between the ileum and the cecum. While a bacterial origin of Crohn's is well speculated, it is difficult to pinpoint what drives inflammation in these subjects, particularly the flare-ups or the sudden symptomatic intensification or recurrence. This review aims at tracing the etiology of CD back to diet, particularly fried foods, a known aggravator of symptoms. Based on the reactions that frying entails, the chemical composition of the food is altered in ways that can lead to maldigestion and inflammation. Current evidence suggests a direct dietary role in the inflammation underlying CD or the flare-ups. The presented review focuses on an underresearched, yet, very applicable topic. We suggest that emphasis should be put on dietary alteration as a means of treatment for patients with CD to supplement current therapy for optimal results. With the widespread popularity of fried foods, it is important to raise awareness about the potential negative outcomes that are prevalent worldwide.
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Endoscopy in Postoperative Patients with Crohn's Disease or Ulcerative Colitis. Does It Translate to Better Outcomes?
Bhattacharya, A, Shen, B, Regueiro, M
Gastrointestinal endoscopy clinics of North America. 2019;(3):487-514
Abstract
This article discusses the use of endoscopy in patients with Crohn disease and ulcerative colitis in the postoperative setting. Endoscopy is the most sensitive and validated tool available in the diagnosis of recurrence of Crohn disease in the postoperative setting. It is also the most effective diagnostic modality available for evaluating complications of pouch anatomy in patients with ulcerative colitis. In addition to diagnosis, management postoperatively can be determined through endoscopy.
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The pharmacotherapeutic management of pediatric Crohn's disease.
Zimmerman, L, Bousvaros, A
Expert opinion on pharmacotherapy. 2019;(17):2161-2168
Abstract
Introduction: Crohn's disease (CD) is a chronic inflammatory condition that can occur throughout the gastrointestinal tract. The aims of treatment of children with CD are to induce and maintain clinical remission of disease, optimize nutrition and growth, minimize adverse effects of therapies, and if possible, achieve mucosal healing.Areas covered: This review summarizes evidence for the various therapeutic options in the treatment of children with CD. Exclusive enteral nutrition, corticosteroids, and biologics may be used for induction of remission. Immunomodulators (thiopurines, methotrexate) and biologics (infliximab, adalimumab) may be employed for maintenance of remission to prevent flares of disease and avoid chronic steroid use. In cases of fibrotic disease, intestinal perforations, or medically refractory, surgery may be the best therapeutic option.Expert opinion: Exclusive enteral nutrition, corticosteroids, and biologics (including anti-TNF inhibitors) may be used for induction of remission in patients with active flare of their disease. Immunomodulators and TNF inhibitors may be used for maintenance of remission. Early use of anti-TNF inhibitors in patients with moderate to severe CD may improve efficacy and prevent penetrating complications of disease. While pediatric data is limited, newer biologics, such as vedolizumab and ustekinumab, are used off-label in anti-TNF refractory disease.
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9.
Current global trends in the incidence of pediatric-onset inflammatory bowel disease.
Sýkora, J, Pomahačová, R, Kreslová, M, Cvalínová, D, Štych, P, Schwarz, J
World journal of gastroenterology. 2018;(25):2741-2763
Abstract
AIM: To perform a comprehensive review and provide an up-to-date synopsis of the incidence and trends of inflammatory bowel disease (IBD). METHODS We systematically searched the MEDLINE (source PubMed), EMBASE and Cochrane Library databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (period: 1985-2018) to identify studies reporting population-based data on the incidence of pediatric-onset (< 19 years at diagnosis) IBD in full manuscripts. Two authors carried out screening and data extraction. Choropleth interactive maps and temporal trends were used to illustrate the international differences and incidences of and changes in IBD and subtypes. RESULTS In total, one hundred forty studies reporting data from 38 countries were considered in this review. The highest annual pediatric incidences of IBD were 23/100000 person-years in Europe, 15.2/100000 in North America, and 11.4/100000 in Asia/the Middle East and Oceania. The highest annual incidences of Crohn's disease (CD) were 13.9/100000 in North America and 12.3/100000 in Europe. The highest annual incidences of ulcerative colitis (UC) were 15.0/100000 in Europe and 10.6/100000 in North America. The highest annual incidences of IBD-unclassified (IBD-U) were 3.6/100000 in Europe and 2.1/100000 in North America. In the time-trend analyses, 67% of CD, 46% of UC and 11% of IBD-U studies reported an increasing incidence (P < 0.05). The risk of IBD is increasing among first-generation of migrant populations. CONCLUSION Globally, the incidence of IBD varies greatly by geographical areas. The steadily increasing incidence of pediatric IBD over time indicates its emergence as a global disease, suggesting that studies should investigate the environmental risk factors among pediatric cohorts.
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Enteral nutritional therapy for induction of remission in Crohn's disease.
Narula, N, Dhillon, A, Zhang, D, Sherlock, ME, Tondeur, M, Zachos, M
The Cochrane database of systematic reviews. 2018;(4):CD000542
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Abstract
BACKGROUND Corticosteroids are often preferred over enteral nutrition (EN) as induction therapy for Crohn's disease (CD). Prior meta-analyses suggest that corticosteroids are superior to EN for induction of remission in CD. Treatment failures in EN trials are often due to poor compliance, with dropouts frequently due to poor acceptance of a nasogastric tube and unpalatable formulations. This systematic review is an update of a previously published Cochrane review. OBJECTIVES To evaluate the effectiveness and safety of exclusive EN as primary therapy to induce remission in CD and to examine the importance of formula composition on effectiveness. SEARCH METHODS We searched MEDLINE, Embase and CENTRAL from inception to 5 July 2017. We also searched references of retrieved articles and conference abstracts. SELECTION CRITERIA Randomized controlled trials involving patients with active CD were considered for inclusion. Studies comparing one type of EN to another type of EN or conventional corticosteroids were selected for review. DATA COLLECTION AND ANALYSIS Data were extracted independently by at least two authors. The primary outcome was clinical remission. Secondary outcomes included adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI). A random-effects model was used to pool data. We performed intention-to-treat and per-protocol analyses for the primary outcome. Heterogeneity was explored using the Chi2 and I2 statistics. The studies were separated into two comparisons: one EN formulation compared to another EN formulation and EN compared to corticosteroids. Subgroup analyses were based on formula composition and age. Sensitivity analyses included abstract publications and poor quality studies. We used the Cochrane risk of bias tool to assess study quality. We used the GRADE criteria to assess the overall quality of the evidence supporting the primary outcome and selected secondary outcomes. MAIN RESULTS Twenty-seven studies (1,011 participants) were included. Three studies were rated as low risk of bias. Seven studies were rated as high risk of bias and 17 were rated as unclear risk of bias due to insufficient information. Seventeen trials compared different formulations of EN, 13 studies compared one or more elemental formulas to a non-elemental formula, three studies compared EN diets of similar protein composition but different fat composition, and one study compared non-elemental diets differing in glutamine enrichment. Meta-analysis of 11 trials (378 participants) demonstrated no difference in remission rates. Sixty-four per cent (134/210) of patients in the elemental group achieved remission compared to 62% (105/168) of patients in the non-elemental group (RR 1.02, 95% CI 0.88 to 1.18; GRADE very low quality). A per-protocol analysis (346 participants) produced similar results (RR 1.04, 95% CI 0.91 to 1.18). Subgroup analyses performed to evaluate the different types of elemental and non-elemental diets (elemental, semi-elemental and polymeric) showed no differences in remission rates. An analysis of 7 trials including 209 patients treated with EN formulas of differing fat content (low fat: < 20 g/1000 kCal versus high fat: > 20 g/1000 kCal) demonstrated no difference in remission rates (RR 1.03; 95% CI 0.85 to 1.26). Very low fat content (< 3 g/1000 kCal) and very low long chain triglycerides demonstrated higher remission rates than higher content EN formulas. There was no difference between elemental and non-elemental diets in adverse event rates (RR 1.00, 95% CI 0.63 to 1.60; GRADE very low quality), or withdrawals due to adverse events (RR 1.29, 95% CI 0.80 to 2.09; GRADE very low quality). Common adverse events included nausea, vomiting, diarrhea and bloating.Ten trials compared EN to steroid therapy. Meta-analysis of eight trials (223 participants) demonstrated no difference in remission rates between EN and steroids. Fifty per cent (111/223) of patients in the EN group achieved remission compared to 72% (133/186) of patients in the steroid group (RR 0.77, 95% CI 0.58 to 1.03; GRADE very low quality). Subgroup analysis by age showed a difference in remission rates for adults but not for children. In adults 45% (87/194) of EN patients achieved remission compared to 73% (116/158) of steroid patients (RR 0.65, 95% CI 0.52 to 0.82; GRADE very low quality). In children, 83% (24/29) of EN patients achieved remission compared to 61% (17/28) of steroid patients (RR 1.35, 95% CI 0.92 to 1.97; GRADE very low quality). A per-protocol analysis produced similar results (RR 0.93, 95% CI 0.75 to 1.14). The per-protocol subgroup analysis showed a difference in remission rates for both adults (RR 0.82, 95% CI 0.70 to 0.95) and children (RR 1.43, 95% CI 1.03 to 1.97). There was no difference in adverse event rates (RR 1.39, 95% CI 0.62 to 3.11; GRADE very low quality). However, patients on EN were more likely to withdraw due to adverse events than those on steroid therapy (RR 2.95, 95% CI 1.02 to 8.48; GRADE very low quality). Common adverse events reported in the EN group included heartburn, flatulence, diarrhea and vomiting, and for steroid therapy acne, moon facies, hyperglycemia, muscle weakness and hypoglycemia. The most common reason for withdrawal was inability to tolerate the EN diet. AUTHORS' CONCLUSIONS Very low quality evidence suggests that corticosteroid therapy may be more effective than EN for induction of clinical remission in adults with active CD. Very low quality evidence also suggests that EN may be more effective than steroids for induction of remission in children with active CD. Protein composition does not appear to influence the effectiveness of EN for the treatment of active CD. EN should be considered in pediatric CD patients or in adult patients who can comply with nasogastric tube feeding or perceive the formulations to be palatable, or when steroid side effects are not tolerated or better avoided. Further research is required to confirm the superiority of corticosteroids over EN in adults. Further research is required to confirm the benefit of EN in children. More effort from industry should be taken to develop palatable polymeric formulations that can be delivered without use of a nasogastric tube as this may lead to increased patient adherence with this therapy.