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Crohn's disease genotypes of patients in remission vs relapses after infliximab discontinuation

World Journal of Gastroenterology 2012年第36期18卷 5058-5064页

作者： Cathy Lu Alistair Waugh Robert J Bailey Raeleen Cherry Levinus A Dieleman Leah Gramlich Kata Matic Mario Millan karen i kroeker Daniel Sadowski Christopher W Teshima Dennis Todoruk Clarence Wong karen Wong Richard N Fedorak Division of Gastroenterology Zeidler Ledcor CenterUniversity of AlbertaEdmontonAB T6G 2X8Canada Division of Gastroenterology Royal Alexandra HospitalEdmontonAB T5H 3V9Canada Division of Gastroenterology Grey Nuns HospitalEdmontonAB T6L 5X8Canada Division of Gastroenterology Misericordia HospitalEdmontonAB T5R 4H5Canada

AiM:To investigate genetic differences between Crohn's disease(CD) patients with a sustained remission vs relapsers after discontinuing infliximab while in corticosteroid-free remission.METHODS:Forty-eight CD patients received infliximab and were in full corticosteroid-free clinical remission but then discontinued infliximab for reasons other than a loss of response,were identified by review of an electronic database and charts.infliximab-associated remission was defined as corticosteroid-free plus normalization of clinical disease activity [CD activity index(CDAi) ing follow-up visits based on physician global assessments.A CD relapse(loss of infliximab-induced remission) was clinically defined as a physician visit for symptoms of disease activity(CDAi > 220) and a therapeutic intervention with CD medication(s),or a hospitalization with complications related to active CD.Genetic analyses were performed on samples from 14 patients(n = 6 who had a sustained long term remission after stopping infliximab,n = 8 who rapidly relapsed after stopping infliximab).Nucleotide-binding oligomerization domain 2(NOD2)/caspase activation recruitment domain 15(CARD15) polymorphisms(R702W,G908R and L1007fs) and the inflammatory bowel disease 5(iBD5) polymorphisms(iGR2060a1 and iGR3081a1) were analyzed in each group.RESULTS:Five single nucleotide polymorphisms of iBD5 and NOD2/CARD15 genes were successfully analyzed for all 14 subjects.There was no significant increase in frequency of the NOD2/CARD15 polymorphisms(R702W,G908R and L1007fs) and the iBD5 polymorphisms(iGR2060a1 and iGR3081a1) in either group of patients;those whose disease relapsed rapidly or those who remained in sustained long term remission following the discontinuation of infliximab.Nearly a third of patients in full clinical remission who stopped infliximab for reasons other than loss of response remained in sustained clinical remission,while two-thirds relapsed rapidly.There was a marked difference in the duration of clinical remission following discon

关键词：基因型单抗患者复发基因多态性房产管理信息系统糖皮质激素临床疾病

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Vitamin D improves inflammatory bowel disease outcomes:Basic science and clinical review

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World Journal of Gastroenterology 2014年第17期20卷 4934-4947页

作者： Krista M Reich Richard N Fedorak karen Madsen karen i kroeker Division of Gastroenterology University of AlbertaEdmontonAlberta T6G 2X8Canada

Vitamin D deficiency is commonly diagnosed among patients with inflammatory bowel disease(iBD).Patients with iBD are at risk of low bone density and increased fractures due to low vitamin D levels,long standing disease,and frequent steroid exposures;as a result,it is well established that vitamin D supplementation in this population is important.There is increasing support for the role of vitamin D in strengthening the innate immune system by acting as an immunomodulator and reducing inflammation in experimental and human iBD.The active form of vitamin D,1,25(OH)D3,acts on T cells to promote T helper(Th)2/regulatory T responses over Th1/Th17 responses;suppresses dendritic cell inflammatory activity;induces antibacterial activity;and regulates cytokine production in favor of an antiinflammatory response.Murine and human iBD studies support a therapeutic role of vitamin D in iBD.Risk factors for vitamin D deficiency in this population include decreased sunlight exposure,disease duration,smoking,and genetics.Vitamin D normalization is associated with reduced risk of relapse,reduced risk of iBD-related surgeries,and improvement in quality of life.Vitamin D is an inexpensive supplement which has been shown to improve iBD outcomes.However,further research is required to determine optimal serum vitamin D levels which will achieve beneficial immune effects,and stronger evidence is needed to support the role of vitamin D in inducing disease response and remission,as well as maintaining this improvement in patients’disease states.

关键词： Vitamin D inflammatory bowel disease immune respon

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Systematic review of nutrition screening and assessment in inflammatory bowel disease

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World Journal of Gastroenterology 2019年第28期25卷 3823-3837页

作者： Suqing Li Michael Ney Tannaz Eslamparast Ben Vandermeer Kathleen P ismond karen kroeker Brendan Halloran Maitreyi Raman Puneeta Tandon Division of internal Medicine Department of Medicine Faculty of Medicine and Dentistry University of Alberta Edmonton Alberta T6G 2G3 Canada Division of Gastroenterology and Hepatology Department of Medicine University of Calgary Calgary Alberta T2N 2T9 Canada Cirrhosis Care Clinic Division of Gastroenterology Department of Medicine Faculty of Medicine and Dentistry University of Alberta Edmonton Alberta T6G 2X8 Canada Alberta Research Centre for Health Evidence Biostatistician Faculty of Medicine and Dentistry University of Alberta Edmonton Alberta T6G 1C9 Canada

BACKGROUND Malnutrition is prevalent in inflammatory bowel disease (iBD). Multiple nutrition screening (NST) and assessment tools (NAT) have been developed for general populations, but the evidence in patients with iBD remains unclear. AiM To systematically review the prevalence of abnormalities on NSTs and NATs, whether NSTs are associated with NATs, and whether they predict clinical outcomes in patients with iBD. METHODS Comprehensive searches performed in Medline, CiNAHL Plus and PubMed. included: English language studies correlating NSTs with NATs or NSTs/NATs with clinical outcomes in iBD. Excluded: Review articles/case studies;use of body mass index/laboratory values as sole NST/NAT;ageies and 1618 patients were included, 72% Crohn’s disease and 28% ulcerative colitis. Four NSTs (the Malnutrition Universal Screening Tool, Malnutrition inflammation Risk Tool (MiRT), Saskatchewan inflammatory Bowel Disease Nutrition Risk Tool (SaskiBD-NRT) and Nutrition Risk Screening 2002 (NRS-2002) were significantly associated with nutritional assessment measures of sarcopenia and the Subjective Global Assessment (SGA). Three NSTs (MiRT, NRS-2002 and Nutritional Risk index) were associated with clinical outcomes including hospitalizations, need for surgery, disease flares, and length of stay (LOS). Sarcopenia was the most commonly evaluated NAT associated with outcomes including the need for surgery and post-operative complications. The SGA was not associated with clinical outcomes aside from LOS. CONCLUSiON There is limited evidence correlating NSTs, NATs and clinical outcomes in iBD. Although studies support the association of NSTs/NATs with relevant outcomes, the heterogeneity calls for further studies before an optimal tool can be recommended. The NRS-2002, measures of sarcopenia and developments of novel NSTs/NATs, such as the MiRT, represent key, clinically-relevant areas for future exploration.

关键词： Nutrition inflammatory bowel disease Ulcerative colitis Crohn’s disease Screening Outcomes research

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Dietary and metabolomic determinants of relapse in ulcerative colitis patients: A pilot prospective cohort study

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World Journal of Gastroenterology 2017年第21期23卷 3890-3899页

作者： Ammar Hassanzadeh Keshtel iFloris F van den Brand karen L Madsen Rupasri Mandal Rosica Valchevakaren i kroeker Beomsoo Han Rhonda C Bell Janis Cole Thomas Hoevers David S Wishart Richard N Fedorak Levinus A Dieleman Department of Medicine Division of Gastroenterology and CEGIIRUniversity of Alberta Department of Biological Sciences University of Alberta Department of Agricultural Food and Nutritional ScienceFaculty of AgriculturalLife and Environmental SciencesUniversity of Alberta Department of Computing Science University of Alberta

AiM To identify demographic, clinical, metabolomic, and lifestyle related predictors of relapse in adult ulcerative colitis(UC) patients.METHODS in this prospective pilot study, UC patients in clinical remission were recruited and followed-up at 12 mo to assess a clinical relapse, or not. At baseline information on demographic and clinical parameters was collected. Serum and urine samples were collected for analysis of metabolomic assays using a combined direct infusion/liquid chromatography tandem mass spectrometry and nuclear magnetic resolution spectroscopy. Stool samples were also collected to measure fecal calprotectin(FCP). Dietary assessment was performed using a validated self-administered food frequency questionnaire. RESULTS Twenty patients were included(mean age: 42.7 ± 14.8 years, females: 55%). Seven patients(35%) experienced a clinical relapse during the follow-up period. While 6 patients(66.7%) with normal body weight developed a clinical relapse, 1 UC patient(9.1%) who was overweight/obese relapsed during the follow-up(P = 0.02). At baseline, poultry intake was significantly higher in patients who were still in remission during follow-up(0.9 oz vs 0.2 oz, P = 0.002). Five patients(71.4%) with FCP > 150 μg/g and 2 patients(15.4%) with normal FCP(≤ 150 μg/g) at baseline relapsed during the follow-up(P = 0.02). interestingly, baseline urinary and serum metabolomic profiling of UC patients with or without clinical relapse within 12 mo showed a significant difference. The most important metabolites that were responsible for this discrimination were trans-aconitate, cystine and acetamide in urine, and 3-hydroxybutyrate, acetoacetate and acetone in serum. CONCLUSiON A combination of baseline dietary intake, fecal calprotectin, and metabolomic factors are associated with risk of UC clinical relapse within 12 mo.

关键词： Ulcerative 大肠炎恶化 Metabolomics 饮食烘便的 calprotectin

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