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1.
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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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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The efficacy of curcuminoids in improvement of ulcerative colitis symptoms and patients' self-reported well-being: A randomized double-blind controlled trial.
Masoodi, M, Mahdiabadi, MA, Mokhtare, M, Agah, S, Kashani, AHF, Rezadoost, AM, Sabzikarian, M, Talebi, A, Sahebkar, A
Journal of cellular biochemistry. 2018;(11):9552-9559
Abstract
BACKGROUND Curcuminoids are polyphenols with documented anti-inflammatory activity and has been shown to improve the symptoms of several inflammatory diseases. We aimed to evaluate the effectiveness of a nanoformulation of curcuminoids in the treatment of ulcerative colitis. METHODS This randomized double-blinded controlled trial was conducted on 56 patients aged 18 years or older with the final diagnosis of mild to moderate ulcerative colitis according to the Simple Clinical Colitis Activity Index (SCCAI). The patients were randomly assigned (using a computerized random sampling table) to receive curcuminoids nanomicelles (80 mg, three times daily, orally) plus mesalamine (3 g/24 hours, orally) as the treatment group and placebo plus mesalamine (3 g/24 hours, orally) as the control group for a period of four weeks. The severity of disease was assessed at baseline and at the end of the second and fourth weeks of the treatment according to the SCCAI. RESULTS The score for urgency of defecation reduced significantly more in case group as compared with control group at four weeks after beginning the treatment. The patients in case group experienced better general condition than the control ones after 4 weeks of treatment. Overall, the mean SCCAI score was significantly lower in the patients received curcuminoids nanomicelles plus mesalamine as compared with the group received placebo plus mesalamine at fourth week after the treatment (1.71 ± 1.84 vs 2.68 ± 2.09, p = 0.050). CONCLUSION Adding curcuminoids nanomicelles to routine treatment of patients with ulcerative colitis is associated with a significant improvement of symptoms, including reduced frequency of urgent defecation, improved patients' self-reported well-being and reduced clinical activity of ulcerative colitis. ClinicalTrials. "IRCT2017052634142N1".
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Joint involvement in Mexican patients with ulcerative colitis: a hospital-based retrospective study.
Yamamoto-Furusho, JK, Sarmiento-Aguilar, A
Clinical rheumatology. 2018;(3):677-682
Abstract
The most frequent extra-intestinal manifestation in ulcerative colitis (UC) around the world is joint involvement. There are no previous data in Latin America that is about this aspect of disease; hence, the aim of this study was to determine the frequency and factors associated to joint involvement in Mexican patients with UC. A total of 295 patients with histological diagnosis of UC were studied, divided into two groups: (1) 154 cases with at least one joint affection (arthralgia, peripheral, or axial arthropathy (sacroilitis (SI) or ankylosing spondylitis (AS))) and (2) 141 controls that had never presented any joint involvement during the clinical course of UC. Demographic, clinical, and laboratory variables were collected from the clinical records, at the time of presentation of the joint involvement for the cases and with the last information available for controls. A total of 52.2% of the patients had joint involvement, which was also the most frequent extra-intestinal manifestation (EIM). The frequency of peripheral arthralgia was 46.8% and of axial arthropathy was 5.4% (2.7% AS, 2.4% SI, and 0.3% both). The female gender (P = 0.01, OR = 3.061 95% CI: 1.311-7.15), elevated erythrocyte sedimentation rate (ESR) (P = 0.07, OR = 8.04 95% CI: 1.759-36.764), and moderate disease activity by Truelove and Witts criteria (P = 0.024, OR = 4.37 95% CI: 1.211-15.78) were factors associated at the time of presentation of the joint affection. Joint involvement is the most frequent EIM in Mexican patients with UC. The female gender, elevated ESR, and disease activity are factors associated with its presentation.
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Use of Curcumin in Achieving Clinical and Endoscopic Remission in Ulcerative Colitis: A Systematic Review and Meta-analysis.
Iqbal, U, Anwar, H, Quadri, AA
The American journal of the medical sciences. 2018;(4):350-356
Abstract
BACKGROUND Ulcerative Colitis (UC) is characterized by chronic inflammation of the mucosal layers of the colon. Treatment of refractory UC is challenging and has a huge healthcare burden. Although there have been advancements in immunomodulatory therapies, these require a step-up financially, and these medications are also associated with significant adverse events. Curcumin, an active ingredient of turmeric, has been studied in the past and found to be useful in the treatment of UC when used as an adjuvant along with mesalamine. We did a systematic review and meta-analysis to explore the role curcumin plays in clinical and endoscopic remission in patients with UC. MATERIALS AND METHODS A comprehensive literature review was conducted by first searching the MEDLINE, Pubmed, and Embase databases through December 2017 to identify all studies that compared the use of curcumin when used along with mesalamine with placebo for clinical and endoscopic improvement and remission. RESULTS Three randomized controlled trials including 142 patients were included in the study. Use of curcumin along with mesalamine was associated with increased odds of clinical remission (pooled odds ratio of 6.78, 95% CI: 2.39-19.23, P = 0.042). Clinical improvement, endoscopic remission and improvement rate also trended higher in the curcumin group compared to placebo. CONCLUSIONS This study demonstrates higher clinical remission rates when curcumin was used in combination with mesalamine to achieve remission in patients with UC. Curcumin, due to its cost effectiveness and safer side effect profile, can decrease the healthcare burden and morbidity associated with this relapsing and remitting disease.
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Cannabis for the treatment of ulcerative colitis.
Kafil, TS, Nguyen, TM, MacDonald, JK, Chande, N
The Cochrane database of systematic reviews. 2018;(11):CD012954
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Abstract
BACKGROUND Cannabis and cannabinoids are often promoted as treatment for many illnesses and are widely used among patients with ulcerative colitis (UC). Few studies have evaluated the use of these agents in UC. Further, cannabis has potential for adverse events and the long-term consequences of cannabis and cannabinoid use in UC are unknown. OBJECTIVES To assess the efficacy and safety of cannabis and cannabinoids for the treatment of patients with UC. SEARCH METHODS We searched MEDLINE, Embase, WHO ICTRP, AMED, PsychINFO, the Cochrane IBD Group Specialized Register, CENTRAL, ClinicalTrials.Gov and the European Clinical Trials Register from inception to 2 January 2018. Conference abstracts and references were searched to identify additional studies. SELECTION CRITERIA Randomized controlled trials (RCTs) comparing any form or dose of cannabis or its cannabinoid derivatives (natural or synthetic) to placebo or an active therapy for adults (> 18 years) with UC were included. DATA COLLECTION AND ANALYSIS Two authors independently screened search results, extracted data and assessed bias using the Cochrane risk of bias tool. The primary outcomes were clinical remission and relapse (as defined by the primary studies). Secondary outcomes included clinical response, endoscopic remission, endoscopic response, histological response, quality of life, C-reactive protein (CRP) and fecal calprotectin measurements, symptom improvement, adverse events, serious adverse events, withdrawal due to adverse events, psychotropic adverse events, and cannabis dependence and withdrawal effects. We calculated the risk ratio (RR) and corresponding 95% confidence interval for dichotomous outcomes. For continuous outcomes, we calculated the mean difference (MD) and corresponding 95% CI. Data were pooled for analysis when the interventions, patient groups and outcomes were sufficiently similar (determined by consensus). Data were analyzed on an intention-to-treat basis. GRADE was used to evaluate the overall certainty of evidence. MAIN RESULTS Two RCTs (92 participants) met the inclusion criteria. One study (N = 60) compared 10 weeks of cannabidiol capsules with up to 4.7% D9-tetrahydrocannabinol (THC) with placebo capsules in participants with mild to moderate UC. The starting dose of cannabidiol was 50 mg twice daily increasing to 250 mg twice daily if tolerated. Another study (N = 32) compared 8 weeks of therapy with two cannabis cigarettes per day containing 0.5 g of cannabis, corresponding to 23 mg THC/day to placebo cigarettes in participants with UC who did not respond to conventional medical treatment. No studies were identified that assessed cannabis therapy in quiescent UC. The first study was rated as low risk of bias and the second study (published as an abstract) was rated as high risk of bias for blinding of participants and personnel. The studies were not pooled due to differences in the interventional drug.The effect of cannabidiol capsules (100 mg to 500 mg daily) compared to placebo on clinical remission and response is uncertain. Clinical remission at 10 weeks was achieved by 24% (7/29) of the cannabidiol group compared to 26% (8/31) in the placebo group (RR 0.94, 95% CI 0.39 to 2.25; low certainty evidence). Clinical response at 10 weeks was achieved in 31% (9/29) of cannabidiol participants compared to 22% (7/31) of placebo patients (RR 1.37, 95% CI 0.59 to 3.21; low certainty evidence). Serum CRP levels were similar in both groups after 10 weeks of therapy. The mean CRP in the cannabidiol group was 9.428 mg/L compared to 7.638 mg/L in the placebo group (MD 1.79, 95% CI -5.67 to 9.25; moderate certainty evidence). There may be a clinically meaningful improvement in quality of life at 10 weeks, measured with the IBDQ scale (MD 17.4, 95% CI -3.45 to 38.25; moderate certainty evidence). Adverse events were more frequent in cannabidiol participants compared to placebo. One hundred per cent (29/29) of cannabidiol participants had an adverse event, compared to 77% (24/31) of placebo participants (RR 1.28, 95% CI 1.05 to1.56; moderate certainty evidence). However, these adverse events were considered to be mild or moderate in severity. Common adverse events included dizziness, disturbance in attention, headache, nausea and fatigue. None (0/29) of the cannabidiol participants had a serious adverse event compared to 13% (4/31) of placebo participants (RR 0.12, 95% CI 0.01 to 2.11; low certainty evidence). Serious adverse events in the placebo group included worsening of UC and one complicated pregnancy. These serious adverse events were thought to be unrelated to the study drug. More participants in the cannabidiol group withdrew due to an adverse event than placebo participants. Thirty-four per cent (10/29) of cannabidiol participants withdrew due to an adverse event compared to 16% (5/31) of placebo participants (RR 2.14, 95% CI 0.83 to 5.51; low certainty evidence). Withdrawls in the cannabidiol group were mostly due to dizziness. Withdrawals in the placebo group were due to worsening UC.The effect of cannabis cigarettes (23 mg THC/day) compared to placebo on mean disease activity, CRP levels and mean fecal calprotectin levels is uncertain. After 8 weeks, the mean disease activity index score in cannabis participants was 4 compared with 8 in placebo participants (MD -4.00, 95% CI -5.98 to -2.02). After 8 weeks, the mean change in CRP levels was similar in both groups (MD -0.30, 95% CI -1.35 to 0.75; low certainty evidence). The mean fecal calprotectin level in cannabis participants was 115 mg/dl compared to 229 mg/dl in placebo participants (MD -114.00, 95% CI -246.01 to 18.01). No serious adverse events were observed. This study did not report on clinical remission, clinical response, quality of life, adverse events or withdrawal due to adverse events. AUTHORS' CONCLUSIONS The effects of cannabis and cannabidiol on UC are uncertain, thus no firm conclusions regarding the efficacy and safety of cannabis or cannabidiol in adults with active UC can be drawn.There is no evidence for cannabis or cannabinoid use for maintenance of remission in UC. Further studies with a larger number of patients are required to assess the effects of cannabis in UC patients with active and quiescent disease. Different doses of cannabis and routes of administration should be investigated. Lastly, follow-up is needed to assess the long term safety outcomes of frequent cannabis use.
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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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Higher serum vitamin D levels are associated with protective serum cytokine profiles in patients with ulcerative colitis.
Gubatan, J, Mitsuhashi, S, Longhi, MS, Zenlea, T, Rosenberg, L, Robson, S, Moss, AC
Cytokine. 2018;:38-45
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Abstract
BACKGROUND & AIMS Vitamin D has immune modulating effects on cytokines. Serum vitamin D levels are associated with the risk of relapse in patients with ulcerative colitis (UC), through unknown mechanisms. We tested the hypothesis that this beneficial role of vitamin D on UC is mediated through anti-inflammatory serum cytokine profiles. METHODS Serum samples from a prospective cohort of seventy UC patients in clinical remission were collected and baseline histological and endoscopic scores were recorded at enrollment. Clinical relapse events were recorded over the 12-month follow-up period. Serum vitamin D and cytokines levels (IL-6, IL-8, IL-17A, TNF-α, IFN-γ, IL-4, IL-10) were quantified using ELISA. Linear regression was used to determine correlation between vitamin D and cytokine profiles. Logistic regression models were used to determine the association between serum cytokine profiles and baseline histologic mucosal healing and clinical relapse. RESULTS Higher serum vitamin D levels positively correlated with higher ratios of IL-4 + IL-10/IL-17A + TNF-α (r = 0.37, P < .01), and IL-4 + IL-10/IL-6 + TNF-α (r = 0.32, P < .01). In multivariate analysis, IL-4 + IL-10/IL-17A + TNF-α ratios at baseline were associated with the presence of histologic mucosal healing (O.R. 1.29, 95% CI 1.02-1.62, P = .03). A higher ratio of serum IL-4 + IL-10 to IL-6 + TNF-α was associated with a reduced risk of clinical relapse (O.R. 0.72, 95% CI 0.58-0.89, P = .003), and longer time to relapse (p = .03), over the 12-month follow-up period. This ratio during remission had an AUC of 0.7 in predicting later clinical relapse. CONCLUSIONS Vitamin D is associated with anti-inflammatory serum cytokine profiles. Anti-inflammatory cytokine patterns may mediate the protective effects of higher serum vitamin D levels in patients with ulcerative colitis.