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世界核心医学期刊文摘（胃肠病学分册） 2006年第9期2卷 57-58页

作者： Florin T.H.J. Paterson E.W.J. Fowler E.V. radford-smith g.l. 成虹 Mater Adult Hospital South BrisbaneQLD 4101Australia

*** interest in C-reactive protein(CRP)-a component of the innate immune system-has focused mainly on its worth as an indicator of disease *** has been a resurgence of interest in CRP in the Crohn’s disease(CD)literature because several trials of new treatments for active CD have been characterized by both a large proportion of patients with low CRP(g.l.at entry to the trials and by a negative therapeutic *** is therefore of interest to study the clinical characteristics of patients who are thought to have at the same time both active CD and a low *** and *** were prospectively recruited as part of the Brisbane IBD clinical and research *** were included in the low CRP group only if there were complete datasets for CRP on all occasions of active CD,and CRP was g/*** disease was defined as CD activity index(CDAI)> *** low CRP group was compared with patients in the raised CRP group for a range of clinical variables as well as the major NOD2 *** were data sets for 223 CD patients,with a mean disease duration of 12 *** these,22 patients fulfilled the criteria for low *** low CRP group(group 1)showed significant differences for disease site(p group(group 2).Specifically,group 1 had a predominance of pure ileal disease(95%versus 53%)and lack of pure colonic disease(0%versus 24%)compared to group 2,and their BMI was significantly lower(20.3 kg/m2 versus 25.0 kg/m2).groups 1 and 2 did not differ with respect to Vienna behaviour at diagnosis,smoking,appendicectomy,extra-intestinal manifestations of CD,or NOD2 SNP *** was a trend for low CRP patients with previous ileal resection to evolve to a stricturing *** wrapping was noted in 11/13(85%)of low CRP patients undergoing ileal *** with CD and a persistently low CRP in the face of active disease were char

关键词：疾病活动性 C反应蛋白临床试验克罗恩病低水平 NOD2基因天然免疫系统治疗方法

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Associations between NOD2/CARD15 genotype andphenotype in Crohn’s disease-Are we there yet?

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World Journal of gastroenterology 2006年第44期12卷 7097-7103页

作者： graham radford-smith Nirmala Pandeya IBD Unit Department of Gastroenter-ology Royal Brisbane and Womens Hospital Brisbane Queensland 4029 Australia Cancer and Population studies group Queensland Institute of Medical Research Brisbane Australia

There have been multiple NOD2/CARD15 genotype- phenotype analyses undertaken in patients with Crohn’s disease since the gene’s discovery in 2001. This review focuses on the major published series based upon their size and on the presence of specific clinical and genetic information provided in the published material from 2001 to 2005. Twelve studies provided raw data to carry out comparisons of disease location while ten studies included analysis of NOD2/CARD15 genotypes. NOD2/CARD15 variant frequency in ileal disease did not differ significantly among studies, whereas a comparison of disease location demonstrated hig.l. significant differences among studies. Meta-analysis confirmed significant associations between NOD2/CARD15 variants and both ileal and ileocolonic disease locations, and with both stricturing and penetrating forms of disease behavior. This review underlines the significant phenotypic differences that exist among populations, including similar ethnic groups, and has demonstrated the need for further studies of patients with long-term “inflammatory” Crohn’s disease.

关键词： Crohn's disease Phenotypic heterogeneity genotype Inter-observer agreement Disease location Disease behavior

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Hygiene hypothesis in inflammatory bowel disease: A criticalreview of the literature

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World Journal of gastroenterology 2008年第2期14卷 165-173页

作者： Natasha A Koloski laurel Bret graham radford-smith Department of gastroenterology Royal Brisbane & Women'sHospital Herston Queensland 4072Australia Department of gastroenterology Royal Brisbane & Women’sHospitalHerston Queensland 4072Australia

The hygiene hypothesis is thought to be a significant contributor to the growing incidence of inflammatory bowel disease (IBD) around the world, although the evidence for specific factors that underlie the hygiene hypothesis in IBD is unclear. We aimed to systematically review the literature to determine which hygiene-related factors are associated with the development of IBD. Publications identified from a broad based MEDlINE and Current Contents search between 1966 and 2007 on key terms relevant to the 'hygiene hypothesis' and IBD including H pylori exposure, helminths, cold chain hypothesis, measles infection and vaccination, antibiotic use, breastfeeding, family size, sibship, urban upbringing, day care attendance and domestic hygiene were reviewed. The literature suggests that the hygiene hypothesis and its association with decreased microbial exposure in childhood probably plays an important role in the development of IBD, although the strength of the supporting data for each of the factors varies considerably. The most promising factors that may potentially be associated with development of IBD include H pylori exposure, helminths, breastfeeding and sibship. However, the vast majority of studies in this area are plagued by serious methodological shortcomings, particularly the reliance on retrospective recall of information making it difficult to truly ascertain the importance of a 'hygiene hypothesis' in IBD. The 'hygiene hypothesis' in IBD is an important area of research that may give clues to the aetiology of this disease. Directions for future research are recommended.

关键词： Inflammatory bowel disease Hygiene hypothesis Microbial exposure Cold chain hypothesis H pylori Helminths Measles Antibiotic Breastfeeding Child care

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Dysreg.l.tion of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy

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World Journal of gastroenterology 2016年第41期22卷 9104-9116页

作者： Ang.l. C Baird Dominic Mallon graham radford-smith Julien Boyer Thierry Piche Susan l Prescott Ian C lawrance Meri K Tulic Faculty of Medicine and Dentistry School of Medicine and Pharmacology University of Western Australia Perth WA 6009 Australia Department of Immunology Fremantle Hospital Royal Brisbane and Women’s Hospital Perth WA 6160 Australia Royal Brisbane Queensland 4006 Australia University of Nice Sophia-Antipolis EA6302 06202 Nice France Department of gastroenterology and Nutrition l’Archet Hospital 2 06202 Nice France School of Paediatrics and Child Health University of Western Australia Subiaco WA 6008 Australia International Inflammation network (in-FlAME) of the World Universities Network University of Western Australia Subiaco WA 6008 Australia Centre for Inflammatory Bowel Diseases St John of God Subiaco Hospital Perth WA 6009 Australia Mediterranean Center for Molecular Medicine (C3M)-INSERM U1065 Team 12 06204 Nice France

AIM To study the innate immune function in ulcerative colitis(UC) patients who fail to respond to anti-tumor necrosis factor(TNF) *** Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell(PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor(TlR) expression and cytokine production post TlR stimulation was assessed in UC "responders"(n = 12) and "non-responders"(n = 12) and compared to healthy controls(n = 12). Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory(TNF, Il-1β, Il-6), immuno-reg.l.tory(Il-10), Th1(Il-12, IFNγ) and Th2(Il-9, Il-13, Il-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TlR cellular composition and intracellular signalling was assessed with *** Prior to anti-TNF therapy, responders and nonresponders had similar level of disease severity and activity. PBMC's ability to respond to TlR stimulation was not affected by TNF therapy, patient's severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders(P llowing TlR stimulation, nonresponders had consistently reduced innate cytokine responses to all TlRs compared to healthy controls(P l-1β(P lating plasmacytoid dendritic cells(p DCs)(P g.l.tory T cells(Tregs)(P = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TlR-2,-4 and-7 activation(P lUSION Reduced innate immunity in non-responders may explain reduced efficacy

关键词： Ulcerative colitis Innate immunity Antitumor necrosis factor therapy Toll-like receptor IRAK4 Inflammatory bowel disease

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人肿瘤坏死因子α单克隆抗体(CDP571)治疗中重度克罗恩病:一项随机双盲安慰剂对照试验

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世界核心医学期刊文摘（胃肠病学分册） 2005年第2期1卷 35-36页

作者： Sandborn W.J. Feagan B.g. radford-smith g. 翟惠虹 Mayo Cl inic 200 First Street SW Rochester MN 55905 United StatesDr.

Background: Targeting tumour necrosis factor α(TNF-α) has demonstrated effi cacy in Crohn’s disease. Aim: To evaluate CDP571, a humanised antibody to TNF- α, for treating active Crohn’s disease. Patients: A total of 396 patients with moderate to severe Crohn’s disease. Methods: In a 28 week, randomised, double blind, placebo controlled trial, patients received intravenous CDP571 (10 mg/kg) or placebo every eight weeks to week 24. The primary outcome measure was clinic al response (a decrease in the Crohn’s disease activity index (CDAI) to ≥100 p oints or remission (CDAI score ≤150 points)) at week 28. A secondary outcome me asure was clinical response (using the same definition) at week 2. Results: Clin ical response occurred at week 28 in 80/263 (30.4%) CDP571 patients and 31/132 (23.5%) placebo patients (p = 0.102). Clinical response at week 2 occurred in 9 0/263 (34.2%) CDP571 patients and 28/132 (21.2%) placebo patients (p = 0.011). Post hoc exploratory subgroup analysis of 159 patients with baseline C reactive protein (CRP) ≥10 mg.l.demonstrated significant differences between CDP571 and placebo in clinical response rates at weeks 2 (CDP571, 50/101 (49.5%); placebo , 9/58 (15.5%); placebo, 7/58 (12.1% ); p = 0.018). Adverse events occurred at similar frequencies in both treatment groups. Conclusions: CDP571 is modestly effective for short but not long term tr eatment of unselected patients with moderate to severe Crohn’s disease. The cli nical relevance of this short term effect is unclear. Post hoc analysis suggests both short and long term efficacy of CDP571 in patients with elevated baseline CRP (≥10 mg.l.. CDP571 is well tolerated.

关键词：克罗恩病 CDP571 肿瘤坏死因子α 随机双盲安慰剂对照短期疗效统计学结果临床因素活动指数基线水平

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Vedolizumab for ulcerative colitis: Real world outcomes from a multicenter observational cohort of Australia and Oxford

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World Journal of gastroenterology 2020年第30期26卷 4428-4441页

作者： Samba Siva Reddy Pulusu Ashish Srinivasan Krupa Krishnaprasad Daniel Cheng Jakob Begun CharlotteKeung Daniel Van langenberg.l.na Thin Tamara Mog.l.vski Peter De Cruz graham radford-smith Emma Flanagan Sally Bell Soleiman Kashkooli Miles Sparrow Simon ghaly Peter Bampton Elise Sawyer Susan Connor Quart-ul-ain Rizvi Jane M Andrews g.l.ian Mahy Paola Chivers Simon Travis Ian Craig.l.wrance Centre for Inflammatory Bowel Diseases St John of God HospitalSubiaco 6008Western AustraliaAustralia Translational gastroenterology Unit NIHR Oxford Biomedical Research CentreOxford University Hospitals NHS Foundation TrustJohn Radcliffe HospitalOxford OX39DUUnited Kingdom Inflammatory Bowel Disease Research group Queensland institute of Medical ResearchHerston 4006QueenslandAustralia Department of gastroenterology Mater HospitalBrisbane 4101QueenslandAustralia Department of gastroenterology Mater HospitalSouth Brisbane 4101QueenslandAustralia of gastroenterology Eastern HealthBox Hill 3128VictoriaAustralia Department of gastroenterology Fiona Stanley HospitalMurdoch 6150Western AustraliaAustralia Department of gastroenterology Austin HealthHeidelberg 3084VictoriaAustralia Department of gastroenterology St Vincent’s HospitalFitzroy 3065VictoriaAustralia Department of gastroenterology Northern HealthEpping 3076VictoriaAustralia Department of gastroenterology The Alfred HospitalMelbourne 3004VictoriaAustralia Department of gastroenterology St Vincent’s HospitalDarlinghurst 2010New South WalesAustralia Department of gastroenterology Flinders Medical CentreBedford Park 5042South AustraliaAustralia Department of gastroenterology Liverpool HospitalSydney 2170New South WalesAustralia Department of gastroenterology Royal Adelaide Hospital&University of AdelaideAdelaide 5000South AustraliaAustralia Department of gastroenterology Townsville HospitalDouglas 4814QueenslandAustralia Institute for Health Research University of Notre DameFremantle 6160Western AustraliaAustralia School of Medicine and Pharmacology University of Western AustraliaCrawley 6009Western AustraliaAustralia

BACKgROUND Vedolizumab(VDZ),a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis(UC)*** To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving *** A retrospective review of Australian and Oxford,United Kingdom data for UC *** response at 3 mo,endoscopic remission at 6 mo and clinical remission at 3,6 and 12 mo were *** regression models and Kaplan Meier curves were performed to assess the time to remission,time to failure and the covariates influencing *** outcomes were *** Three hundred and three UC patients from 14 centres in Australia and United Kingdom,[60%n=182,anti-TNF naïve]were *** clinical response was 79%at 3 mo with more Australian patients achieving clinical response compared to Oxford(83%vs 70%P=0.01).Clinical remission for all patients was 56%,62%and 60%at 3,6 and 12 mo ***-TNF naive patients were more likely to achieve remission than exposed patients at all the time points(3 mo 66%vs 40%Plian patients achieved endoscopic remission at 6 mo compared to Oxford(69%vs 43%P=0.01).On multi-variate analysis,anti-TNF naïve patients were 1.8(95%CI:1.3-2.3)times more likely to achieve remission than anti-TNF exposed(Plectomy by 12 *** VDZ was safe and effective with 60%of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.

关键词： Vedolizumab Ulcerative colitis Outcomes

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