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1.
Safety and efficacy of intravenous iron isomaltoside for correction of anaemia in patients with inflammatory bowel disease in everyday clinical practice.
Stein, J, Walper, A, Klemm, W, Farrag, K, Aksan, A, Dignass, A
Scandinavian journal of gastroenterology. 2018;(9):1059-1065
Abstract
AIMS: Iron deficiency anaemia (IDA) is common in patients with inflammatory bowel disease (IBD), who are often treated with intravenous iron. This observational study aimed to investigate the effectiveness and safety of iron isomaltoside in routine practical care of IDA in IBD patients. METHODS The study included 197 IBD patients designated for treatment with iron isomaltoside. Treatment was administered according to routine practice. Data were recorded at baseline and after approximately 4, 8, and 16 weeks. Efficacy data included haemoglobin (Hb) levels and haematinics, while safety data included adverse drug reactions and safety laboratory variables. RESULTS Patients received a mean (range) cumulative dose of 1304 (100-3500) mg iron isomaltoside. Hb increased from 10.7(±1.6) g/dL at baseline to 13.1(±1.5) g/dL at the final visit. In addition, serum iron, ferritin and transferrin saturation increased and soluble transferrin receptor decreased. Calprotectin decreased, as did IBD symptom scores, Harvey-Bradshaw Index (Crohn's disease) and partial Mayo score (Ulcerative colitis). About 8% of patients reported transient adverse reactions, most commonly skin reactions, nausea and vomiting, and 2% SAEs, most frequently tachycardia. CONCLUSION Iron isomaltoside was demonstrated to be effective and had a good safety profile in IBD patients in everyday clinical practice in Germany.
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2.
Effect of diet and gut environment on the gastrointestinal formation of N-nitroso compounds: A review.
Kobayashi, J
Nitric oxide : biology and chemistry. 2018;:66-73
Abstract
Diet is associated with the development of cancer in the gastrointestinal (GI) tract, because dietary nitrate and nitrite are the main nitrosating agents that are responsible for the formation of carcinogenic N-nitroso compounds (NOCs) when nitrosatable substrates, such as amine and amide, are present in the GI tract. However, whether the nitroso compounds become beneficial S-nitroso compounds or carcinogenic NOCs might depend on dietary and environmental factors including food stuffs, gastric acidity, microbial flora, and the mean transit time of digesta. This review focused on GI NOC formation and environmental risk factors affecting its formation to provide appropriate nutritional strategies to prevent the development of GI cancer.
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Non-pharmacological therapies for inflammatory bowel disease: Recommendations for self-care and physician guidance.
Duff, W, Haskey, N, Potter, G, Alcorn, J, Hunter, P, Fowler, S
World journal of gastroenterology. 2018;(28):3055-3070
Abstract
We performed a scoping review on sought-after complementary therapies for patients with inflammatory bowel disease (IBD), specifically diet, physical activity and exercise (PA/E), and psychotherapy. We aim to update patients with IBD on therapies for self-care and provide physicians with guidance on how to direct their patients for the management of IBD. A search of MEDLINE, EMBASE, and PUBMED was completed in Sept 2016. Studies on diet, PA/E, or psychotherapy in patients with IBD were included. Medical Subject Heading terms and Boolean operators were used. The search was limited to full-text English articles describing an adult population. This review included 67 studies: Diet (n = 19); PA/E (n = 19); and psychotherapy (n = 29). We have made the following recommendations: (1) Diet: Consumption of diets rich in vegetables, fruit and soluble fiber may be beneficial in IBD. A trial of a low FODMAP diet can be considered in those patients with functional gastrointestinal symptoms. Restrictive diets are lacking in evidence and should be avoided; (2) PA/E: Regular low-moderate intensity activity, including cardiovascular and resistance exercise, has been shown to improve quality of life (QOL) and may improve inflammation; and (3) psychotherapy: Therapies such as cognitive-behavioural interventions, mindfulness, hypnosis, and stress management have been shown to improve QOL, but evidence is limited on their impact on anxiety, depression, and disease activity. Overall, these complementary therapies are promising and should be used to treat patients with IBD from a more holistic perspective.
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Inflammatory bowel disease and immunonutrition: novel therapeutic approaches through modulation of diet and the gut microbiome.
Celiberto, LS, Graef, FA, Healey, GR, Bosman, ES, Jacobson, K, Sly, LM, Vallance, BA
Immunology. 2018;(1):36-52
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Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, thought to at least in part reflect an aberrant immune response to gut bacteria. IBD is increasing in incidence, particularly in populations that have recently immigrated to western countries. This suggests that environmental factors are involved in its pathogenesis. We hypothesize that the increase in IBD rates might reflect the consumption of an unhealthy Western diet, containing excess calories and lacking in key nutritional factors, such as fibre and vitamin D. Several recent studies have determined that dietary factors can dramatically influence the activation of immune cells and the mediators they release through a process called immunonutrition. Moreover, dietary changes can profoundly affect the balance of beneficial versus pathogenic bacteria in the gut. This microbial imbalance can alter levels of microbiota-derived metabolites that in turn can influence innate and adaptive intestinal immune responses. If the diet-gut microbiome disease axis does indeed underpin much of the 'western' influence on the onset and progression of IBD, then tremendous opportunity exists for therapeutic changes in lifestyle, to modulate the gut microbiome and to correct immune imbalances in individuals with IBD. This review highlights four such therapeutic strategies - probiotics, prebiotics, vitamin D and caloric restriction - that have the potential to improve and add to current IBD treatment regimens.
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Combining Biologics in Inflammatory Bowel Disease and Other Immune Mediated Inflammatory Disorders.
Hirten, RP, Iacucci, M, Shah, S, Ghosh, S, Colombel, JF
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2018;(9):1374-1384
Abstract
Current therapies used in the treatment of inflammatory bowel disease (IBD) are not effective in all patients. Biologic agents result in approximately 40% remission rates at 1 year in selected populations, prompting a growing interest in combining biologic therapy to improve outcomes. There are limited published data regarding the efficacy and safety of combination targeted therapy in IBD specifically, which include only 1 exploratory randomized control trial and 3 case reports or series. This review evaluates the published literature regarding this therapeutic paradigm in IBD and its extensive utilization in the treatment of other immune-mediated inflammatory disorders. The combination of biologic therapies demonstrates variable degrees of efficacy and highlights some safety concerns, depending upon the agents used and the disease state treated. A trial (Clinical Trials.gov Identifier: NCT02764762) combining vedolizumab and adalimumab is currently underway evaluating the effectiveness and safety of this approach in patients with Crohn's disease, which should provide further insight into this treatment concept. While combination biologic therapy is an attractive strategy, the lack of consistent superior efficacy as well as safety concerns militates the need for further trials prior to its general application in IBD.
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Escherichia coli B2 strains prevalent in inflammatory bowel disease patients have distinct metabolic capabilities that enable colonization of intestinal mucosa.
Fang, X, Monk, JM, Mih, N, Du, B, Sastry, AV, Kavvas, E, Seif, Y, Smarr, L, Palsson, BO
BMC systems biology. 2018;(1):66
Abstract
BACKGROUND Escherichia coli is considered a leading bacterial trigger of inflammatory bowel disease (IBD). E. coli isolates from IBD patients primarily belong to phylogroup B2. Previous studies have focused on broad comparative genomic analysis of E. coli B2 isolates, and identified virulence factors that allow B2 strains to reside within human intestinal mucosa. Metabolic capabilities of E. coli strains have been shown to be related to their colonization site, but remain unexplored in IBD-associated strains. RESULTS In this study, we utilized pan-genome analysis and genome-scale models (GEMs) of metabolism to study metabolic capabilities of IBD-associated E. coli B2 strains. The study yielded three results: i) Pan-genome analysis of 110 E. coli strains (including 53 isolates from IBD studies) revealed discriminating metabolic genes between B2 strains and other strains; ii) Both comparative genomic analysis and GEMs suggested that B2 strains have an advantage in degrading and utilizing sugars derived from mucus glycan, and iii) GEMs revealed distinct metabolic features in B2 strains that potentially allow them to utilize energy more efficiently. For example, B2 strains lack the enzymes to degrade amadori products, but instead rely on neighboring bacteria to convert these substrates into a more readily usable and potentially less sought after product. CONCLUSIONS Taken together, these results suggest that the metabolic capabilities of B2 strains vary significantly from those of other strains, enabling B2 strains to colonize intestinal mucosa.The results from this study motivate a broad experimental assessment of the nutritional effects on E. coli B2 pathophysiology in IBD patients.
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Prolyl Hydroxylase Inhibitors: A Breakthrough in the Therapy of Anemia Associated with Chronic Diseases.
Joharapurkar, AA, Pandya, VB, Patel, VJ, Desai, RC, Jain, MR
Journal of medicinal chemistry. 2018;(16):6964-6982
Abstract
Chronic kidney disease, cancer, chronic inflammatory disorders, nutritional, and genetic deficiency can cause anemia. Hypoxia causes induction of hypoxia-inducible factor (HIF), which stimulates erythropoietin (EPO) synthesis. Prolyl hydroxylase domain (PHD) enzyme inhibition can stabilize hypoxia-inducible factor (HIF). HIF stabilization also decreases hepcidin, a hormone of hepatic origin, which regulates iron homeostasis. PHD inhibitors represent a novel pharmacological treatment of anemia associated with chronic diseases. Many orally active PHD inhibitors like roxadustat, molidustat, vadadustat, and desidustat are in late phase clinical trials. This review discusses the role of PHD inhibitors in the treatment of anemia associated with chronic diseases.
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Evaluation of a 12-week targeted vitamin D supplementation regimen in patients with active inflammatory bowel disease.
Garg, M, Rosella, O, Rosella, G, Wu, Y, Lubel, JS, Gibson, PR
Clinical nutrition (Edinburgh, Scotland). 2018;(4):1375-1382
Abstract
BACKGROUND & AIMS Vitamin D at serum 25(OH)D concentrations above 100 nmol/L is associated with disease remission in patients with IBD, suggesting targeted dosing might be anti-inflammatory. This study aimed to assess the effectiveness, safety and predictors of a 12-week regimen of vitamin D supplementation to achieve such a target in patients with active disease. METHODS In a pilot study, patients with active colitis and a serum 25(OH)D concentration <75 nmol/L were prescribed oral liquid vitamin D supplementation over 12 weeks using a specific protocol with dose adjusted 4-weekly to aim for a target level of 100-125 nmol/L. RESULTS Five patients each with Crohn's colitis or ulcerative colitis (UC) had mean 25(OH)D concentration 52 (range 27-73 nmol/L). Five reached the targeted level and four 89-95 nmol/L. One withdrew after 4 weeks (88 nmol/L). Target dose was met only in those with BMI <30 kg/m2 and total dose inversely correlated with initial serum 25(OH)D. One patient had developed a high level at 8 weeks (146 nmol/L) and another new hypercalciuria. There were no serious adverse events attributable to the therapy. Clinical disease activity consistently declined, but faecal calprotectin and circulating markers of inflammation did not. CONCLUSIONS A specified oral vitamin D regimen successfully and safely achieved target or near-target levels, improved symptom-based activity scores, but did not alter objective measures of intestinal or systemic inflammation. A modified version of this dose-escalating regimen would be suitable for a randomised placebo-controlled trial, but does require regular safety monitoring.
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Vitamin D receptor FokI polymorphism and the risks of colorectal cancer, inflammatory bowel disease, and colorectal adenoma.
Cho, YA, Lee, J, Oh, JH, Chang, HJ, Sohn, DK, Shin, A, Kim, J
Scientific reports. 2018;(1):12899
Abstract
Based on an inverse association between vitamin D levels and the risks of colorectal diseases, a functional start codon polymorphism in the vitamin D receptor (VDR) gene is speculated to affect the risks for these diseases. To validate this hypothesis, we first conducted a case-control study of 695 colorectal cancer patients and 1,397 controls. The association of VDR FokI polymorphism with colorectal cancer risk was analyzed using a logistic regression model. In the present case-control study, compared to the F allele, the f allele seemed to be associated with lower risks of colon cancer and advanced colorectal cancer. Additionally, a meta-analysis of 27 studies was conducted to combine findings from previous studies investigating the association of FokI polymorphism with colorectal disease using a random effects model. In the present meta-analysis, the f allele was positively associated with the risk of inflammatory bowel disease, including Crohn's disease and ulcerative colitis. However, this allele was inversely associated with colon cancer and was not associated with the risk of rectal cancer or colorectal adenoma. In conclusion, the findings from this study imply that the role of VDR FokI polymorphism may differ based on the type and severity of colorectal disease.
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10.
Fecal calprotectin: beyond intestinal organic diseases.
Caviglia, GP, Ribaldone, DG, Rosso, C, Saracco, GM, Astegiano, M, Pellicano, R
Panminerva medica. 2018;(1):29-34
Abstract
Fecal calprotectin (FC) is a calcium-binding protein with antimicrobic, imunomodulatory and antiproliferative properties that is mainly found in the cytoplasm of neutrophil granulocytes. During the last decades, FC became an increasingly useful tool both for gastroenterologists and for general practitioners for distinguishing inflammatory bowel disease (IBD) from irritable bowel syndrome. FC correlates with clinical scoring systems and endoscopic lesions in IBD and is considered a reliable biomarker for the prediction of clinical relapse or remission. However, FC elevation could be observed also in other gastrointestinal pathological conditions including infective colitis, microscopic colitis, eosinophilic colitis, adenomas and colorectal cancer. In addition, there are several non-pathological conditions that can lead to altered FC values. In this review, we aimed to point out individual, environmental and method-related factors that can affect FC measurement and thus its clinical interpretation.