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The New Era of Nutraceuticals: Beneficial Effects of Polyphenols in Various Experimental and Clinical Settings.
Magrone, T, Jirillo, E
Current pharmaceutical design. 2018;(44):5229-5231
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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.
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The Relevance of Vitamin and Iron Deficiency in Patients with Inflammatory Bowel Diseases in Patients of the Swiss IBD Cohort.
Madanchi, M, Fagagnini, S, Fournier, N, Biedermann, L, Zeitz, J, Battegay, E, Zimmerli, L, Vavricka, SR, Rogler, G, Scharl, M, et al
Inflammatory bowel diseases. 2018;(8):1768-1779
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Abstract
BACKGROUND ANDAIMS Vitamin and iron deficiencies are common in patients with inflammatory bowel disease (IBD) as a result of chronic intestinal inflammation, increase in demand, or dietary restrictions. Here, we assessed the frequency of complications in relation to deficiency of iron, folate acid, and vitamin B12 in patients enrolled in the nationwide Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). METHODS A total of 2666 patients were included in the study, 1558 with Crohn's disease (CD) and 1108 with ulcerative colitis (UC). RESULTS Iron deficiency anemia was detected in 19.6% of CD patients and 21.6% of UC patients. In CD patients low BMI and nonsmoker status were positively associated with anemia. In both CD and UC, malabsorption syndrome, defined as failure of the GI tract to absorb 1 or more substances from the diet, was found to be significantly associated with anemia (6.2% and 3.8%, respectively) and current steroid use (40% CD, 52.7% UC). In CD patients with ileal (31.7% vs 20%) and colonic (29.9% vs 25%) disease location folate deficiency was significantly higher than in patients with ileocolonic CD or upper GI involvement. In CD patients, vitamin B12 deficiency was associated with the onset of stenosis and intestinal surgery (42.9% vs 32.8% and 46% vs 33% for patients with versus without B12 deficiency). CONCLUSION Our data indicate that due to frequent occurrence of deficiency states, regular monitoring and substitution of vitamins and iron are mandatory and may prevent long-term intestinal and extraintestinal complications in IBD patients.
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Nutritional Interventions in the Patient with Inflammatory Bowel Disease.
Limketkai, BN, Wolf, A, Parian, AM
Gastroenterology clinics of North America. 2018;(1):155-177
Abstract
Nutritional strategies have been explored as primary or adjunct therapies for inflammatory bowel disease (IBD). Exclusive enteral nutrition is effective for the induction of remission in Crohn disease and is recommended as a first-line therapy for children. Dietary strategies focus on adjusting the ratio of consumed nutrients that are proinflammatory or antiinflammatory. Treatments with dietary supplements focus on the antiinflammatory effects of the individual supplements (eg, curcumin, omega-3 fatty acids, vitamin D) or their positive effects on the intestinal microbiome (eg, prebiotics, probiotics). This article discusses the role of diets and dietary supplements in the treatment of IBD.
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IgG4-Related Disease Mimicking Crohn's Disease: A Case Report and Review of Literature.
Ciccone, F, Ciccone, A, Di Ruscio, M, Vernia, F, Cipolloni, G, Coletti, G, Calvisi, G, Frieri, G, Latella, G
Digestive diseases and sciences. 2018;(4):1072-1086
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Protective association of TNFSF15 polymorphisms with Crohn's disease and ulcerative colitis: A meta-analysis.
He, L, Chen, J, Sun, J, Peng, J, He, Q
Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association. 2018;(4):201-210
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Abstract
BACKGROUND/AIMS: Three extensively investigated polymorphisms (rs3810936, rs7848647, and rs6478108) in tumor necrosis factor super family member 15 (TNFSF15) gene have been implicated in risk for inflammatory bowel disease (IBD). We performed a quantitative synthesis of the evidence to clarify these associations of TNFSF15 polymorphisms with IBD. MATERIALS AND METHODS Data were extracted from PubMed and EMBASE, up to March 15, 2018. Meta-analysis was performed by critically reviewing five studies for rs3810936 polymorphism (2251 cases and 2442 controls), four studies for rs7848647 polymorphism (1503 cases and 1816 controls), and four studies for rs6478108 polymorphism (1502 cases and 1817 controls). RESULTS Our analysis suggested that rs3810936 polymorphism was significantly associated with decreased risk of Crohn's disease (CD) and ulcerative colitis (UC). For rs7848647 polymorphism, significantly protective association between this polymorphism and CD risk was also observed, but not in UC. For rs6478108 polymorphism, we also detected a significantly protective association with CD risk in all genetic model but not in UC. CONCLUSIONS This meta-analysis suggests that TNFSF15 polymorphisms may contribute to genetic susceptibility of IBD.
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The Association of Diet and Exercise With Body Composition in Pediatric Crohn's Disease.
Lee, D, Lewis, JD, Shults, J, Baldassano, RN, Long, J, Herskovitz, R, Zemel, B, Leonard, MB
Inflammatory bowel diseases. 2018;(6):1368-1375
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BACKGROUND In pediatric Crohn's disease, fat mass improves over time with treatment, but lean mass deficits persist. This observational study of the associations of physical activity and dietary intake with lean mass and muscle strength in children with Crohn's disease was ancillary to a previously reported randomized clinical trial of an intervention to improve bone health. METHODS In this study, 138 participants were followed at baseline and at 6, 12, and 24 months with evaluation of lean and fat mass using DXA, muscle strength (peak torque), Crohn's characteristics, dietary intake, time in moderate to vigorous physical activity (MVPA), and serum insulin-like growth factor-1 (IGF-1) and tumor necrosis factor-alpha (TNF-α). Race- and sex-specific Z-scores for leg lean mass and whole body fat mass were generated. Quasi least square regression evaluated determinants of changes in body composition and muscle strength. RESULTS Leg lean mass and muscle strength were positively associated with time in MVPA (P < 0.05) and negatively associated with increasing clinical disease activity (P < 0.05). Both leg lean mass and strength were positively associated with IGF-1 Z-score (P ≤ 0.03) but negatively associated with serum TNF-α (P ≤ 0.04). Neither lean mass nor muscle strength was associated with caloric or protein intake. CONCLUSIONS Persistence of lean mass deficits was related to ongoing Crohn's disease activity but improved with greater time spent in moderate to vigorous physical activity. Future trials are needed to evaluate the efficacy of physical activity in improving lean mass in pediatric Crohn's disease.
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Clinically Significant Small Bowel Crohn's Disease Might Only be Detected by Capsule Endoscopy.
Sorrentino, D, Nguyen, VQ
Inflammatory bowel diseases. 2018;(7):1566-1574
Abstract
BACKGROUND In Crohn's disease (CD) a small bowel study-in addition to colonoscopy-is considered necessary for diagnosis/staging. In this study we re-examined the role of capsule endoscopy (CE), colonoscopy, imaging tests [magnetic resonance enterography/computed tomographic enterography (MRE/CTE)], and inflammatory markers [fecal lactoferrin and C-reactive protein (FL/CRP)] in CD patients who had undergone intestinal resection and in those who never had surgery. METHODS In this retrospective study 43 consecutive patients underwent CE because of staging/symptoms unexplained by colonoscopy/imaging. We compared colonoscopy, imaging, and FL/CRP with CE and evaluated the impact of the latter on clinical management and outcomes. RESULTS In patients who never had surgery imaging was negative with a positive CE in 8/15 (53%) of cases. Colonoscopy was insufficient for disease staging in 10/20 (50%) cases. CRP and FL were normal with a positive CE in 35% and 28% of cases, respectively. CE findings changed the management in 6/20 (30%) of cases, with 83% showing clinical/biochemical improvement after up to 15 months of follow-up. In postoperative patients CE was positive with negative imaging in 6/8 (75%) cases. Colonoscopy was insufficient for disease staging in 13/22 (59%) cases. CRP and FL were normal in 42% and 31.8% of patients with positive CE. In these patients CE findings changed the management in 12/23 (52%) cases with 83% of them showing clinical/biochemical improvement after up to 18 months of follow-up. CONCLUSIONS Omitting CE from diagnostic/staging algorithms in CD tends to underdiagnose clinically significant small bowel lesions, thus impacting on patients' management and outcomes. 10.1093/ibd/izy048_video1izy048.video15794820403001.
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Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn's Disease.
Horneff, G, Seyger, MMB, Arikan, D, Kalabic, J, Anderson, JK, Lazar, A, Williams, DA, Wang, C, Tarzynski-Potempa, R, Hyams, JS
The Journal of pediatrics. 2018;:166-175.e3
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Abstract
OBJECTIVE To evaluate the safety of adalimumab in pediatric patients who participated in clinical trials of juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and pediatric enthesitis-related arthritis), psoriasis, and Crohn's disease. STUDY DESIGN This analysis included data from 7 global, randomized, and open-label AbbVie-sponsored clinical trials of adalimumab and their open-label extensions conducted between September 2002 and December 31, 2015 (cutoff date for ongoing studies). Patients who received ≥1 dose of adalimumab subcutaneously were included. Adverse events that occurred after the first dose of adalimumab and up to 70 days (5 half-lives) after the last dose were reported and events per 100 patient-years were calculated. RESULTS The analysis included 577 pediatric patients, representing 1440.7 patient-years of adalimumab exposure. Across indications, the most commonly reported adverse events (events/100 patient-years) were upper respiratory tract infections (24.3), nasopharyngitis (17.3), and headache (19.9). Serious infections (4.0 events/100 patient-years) were the most frequent serious adverse events across indications; the most commonly reported was pneumonia (0.6 events/100 patient-years). Serious infection rates were 2.7, 0.8, and 6.6 events/100 patient-years in patients with juvenile idiopathic arthritis, psoriasis, and Crohn's disease, respectively. No events of malignancies were reported. One death (accidental fall) occurred in a patient with psoriasis. CONCLUSIONS The safety profile of adalimumab in pediatric patients with polyarticular juvenile idiopathic arthritis, enthesitis-related arthritis, psoriasis, and Crohn's disease was generally similar across indications; no new safety signals were identified in the treatment of pediatric patients with adalimumab. TRIAL REGISTRATION Clinicaltrials.gov: NCT00048542, NCT00775437, NCT00690573, NCT01166282, NCT01251614, NCT00409682, and NCT00686374.