Publications
144 results found
Walker GJ, Harrison JW, Heap GA, et al., 2019, Association of genetic variants in NUDT15 with thiopurine-induced myelosuppression in patients with inflammatory bowel disease, JAMA: Journal of the American Medical Association, Vol: 321, Pages: 773-785, ISSN: 0098-7484
Importance Use of thiopurines may be limited by myelosuppression. TPMT pharmacogenetic testing identifies only 25% of at-risk patients of European ancestry. Among patients of East Asian ancestry, NUDT15 variants are associated with thiopurine-induced myelosuppression (TIM).Objective To identify genetic variants associated with TIM among patients of European ancestry with inflammatory bowel disease (IBD).Design, Setting, and Participants Case-control study of 491 patients affected by TIM and 679 thiopurine-tolerant unaffected patients who were recruited from 89 international sites between March 2012 and November 2015. Genome-wide association studies (GWAS) and exome-wide association studies (EWAS) were conducted in patients of European ancestry. The replication cohort comprised 73 patients affected by TIM and 840 thiopurine-tolerant unaffected patients.Exposures Genetic variants associated with TIM.Main Outcomes and Measures Thiopurine-induced myelosuppression, defined as a decline in absolute white blood cell count to 2.5 × 109/L or less or a decline in absolute neutrophil cell count to 1.0 × 109/L or less leading to a dose reduction or drug withdrawal.Results Among 1077 patients (398 affected and 679 unaffected; median age at IBD diagnosis, 31.0 years [interquartile range, 21.2 to 44.1 years]; 540 [50%] women; 602 [56%] diagnosed as having Crohn disease), 919 (311 affected and 608 unaffected) were included in the GWAS analysis and 961 (328 affected and 633 unaffected) in the EWAS analysis. The GWAS analysis confirmed association of TPMT (chromosome 6, rs11969064) with TIM (30.5% [95/311] affected vs 16.4% [100/608] unaffected patients; odds ratio [OR], 2.3 [95% CI, 1.7 to 3.1], P = 5.2 × 10−9). The EWAS analysis demonstrated an association with an in-frame deletion in NUDT15 (chromosome 13, rs746071566) and TIM (5.8% [19/328] affected vs 0.2% [1/633] unaffected patients; OR, 38.2
Koysombat K, Capanna MV, Stafford N, et al., 2018, Combination therapy for systemic sclerosis-associated pneumatosis intestinalis., BMJ Case Rep, Vol: 2018
We present a case of a patient with pneumatosis intestinalis and pneumoperitoneum secondary to gastrointestinal systemic sclerosis, who presented following recurrent accident and emergency attendances with abdominal pain. Pneumatosis intestinalis is a rare complication of systemic sclerosis; management approaches focus largely on exclusion of life-threatening surgical pathologies and subsequent symptom control. To date, there are still no established gold-standard treatment strategy and no large-scale trial data to support a specific management strategy. We describe a case of successful medical management with a combination of antimicrobial, elemental diet and high-flow inhalation oxygen therapy, with supporting evidence of CT image confirming resolution. This case therefore contributes to the literature, being the first to report both symptomatic and radiological improvement following combination therapy without the need for surgical intervention.
Powles ST, Chong LW, Cameron S, et al., 2018, THE USE OF RAPID EVAPORATIVE IONISATION MASS SPECTROMETRY (REIMS) IN FAECAL SAMPLES TO IDENTIFY INFLAMMATORY BOWEL DISEASE, Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy / Digestive Disease Week, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S396-S396, ISSN: 0016-5085
Williams HRT, Orchard TR, 2017, Volatile organic compounds in breath for monitoring IBD - longitudinal studies are essential, ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Vol: 46, Pages: 371-372, ISSN: 0269-2813
Hicks LC, Powles STR, Chong LWL, et al., 2017, EFFECTS OF TIME ON URINARY METABOLIC SIGNATURES IN INFLAMMATORY BOWEL DISEASE, Annual General Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A233-A234, ISSN: 0017-5749
McDonald J, Gordon H, Blad W, et al., 2017, FIRST ANALYSIS FROM UK IBD TWIN BIOBANK; 16S RRNA GENE SEQUENCING IDENTIFIES REDUCED DIVERSITY IN ACTIVE IBD AND TAXA ASSOCIATED WITH ACTIVE DISEASE PHENOTYPE TO LEVEL OF SPECIES, Annual General Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A249-A249, ISSN: 0017-5749
Chong LWL, Powles STR, Hicks LC, et al., 2017, ASSESSING THE INDIVIDUAL RISK OF ACUTE SEVERE COLITISAT DIAGNOSIS IN A SOUTH ASIAN POPULATION, Annual General Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A150-A151, ISSN: 0017-5749
Hicks LC, Powles STR, Chong LWL, et al., 2017, ASSESSING THE EFFECT OF ETHNICITY ON URINARY METABOLIC PROFILES IN INFLAMMATORY BOWEL DISEASE, Annual General Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A261-A262, ISSN: 0017-5749
Hicks L, Powles S, Swann J, et al., 2017, Assessing the effect of ethnicity on urinary metabolic profiles in inflammatory bowel disease, JOURNAL OF CROHNS & COLITIS, Vol: 11, Pages: S168-S168, ISSN: 1873-9946
Hicks L, Powles S, Swann J, et al., 2017, Effects of time on urinary metabolic signatures in inflammatory bowel disease, JOURNAL OF CROHNS & COLITIS, Vol: 11, Pages: S207-S207, ISSN: 1873-9946
McDonald J, Gordon H, Blad W, et al., 2017, First analysis from UK IBD Twin Biobank; 16S rRNA gene sequencing identifies reduced diversity in IBD and bacterial taxa associated with disease, Journal of Crohns & Colitis, Vol: 11, Pages: S474-S475, ISSN: 1873-9946
Russo E, Khan S, Janisch R, et al., 2016, Role of 18F-fluorodeoxyglucose Positron Emission Tomography in the Monitoring of Inflammatory Activity in Crohn's Disease., Inflammatory Bowel Diseases, ISSN: 1536-4844
Background: 18Fluorine-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has recently attracted interest for the measurement ofdisease activity in Crohn’s disease (CD). The aim of this study was to assess the utility of FDG-PET as a marker of progression of inflammatory activityand its response to treatment in patients with CD.Methods: Twenty-two patients with active CD were recruited prospectively to undergo FDG-PET scanning at 2 time points. All 22 index scans were used toassess sensitivity and specificity against a reference standard magnetic resonance imaging measure. Correlations with clinicopathological markers of severity(Harvey-Bradshaw Index, C-reactive protein, and calprotectin) were also performed. Of note, 17/22 patients participated in the longitudinal component andunderwent scanning before and 12 weeks after the initiation of anti–tumor necrosis factor alpha therapy. Patients were subcategorized on the basis ofa clinically significant response, and responsiveness of the PET measures was assessed using previously described indices. Of note, 5/22 patients took partin the test–retest component of the study and underwent scanning twice within a target interval of 1 week, to assess the reproducibility of the PET measures.Results: The sensitivity and specificity of 18F-FDG PET were 88% and 70%, respectively. Standardized uptake value (SUV)-related PET measurescorrelated significantly both with C-reactive protein and Harvey-Bradshaw Index in cross-sectional and longitudinal analyses. (G)SUVMAX and (G)SUVMEANdemonstrated favorable responsiveness and reliability characteristics (responsiveness ratio of Guyatt .0.80 and % variability ,20%) compared with volumedependentFDG-PET measures. A proportion of the FDG signal (10%–30%) was found to originate from the lumen of diseased segments.Conclusions: 18F-FDG PET may be useful for longitudinal monitoring of inflammatory activity in CD.
Orchard T, 2016, UK guidance opens new therapeutic avenues for patients with moderate-severe ulcerative colitis, EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY, Vol: 10, Pages: 281-282, ISSN: 1747-4124
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- Citations: 1
Harbord M, Annese V, Vavricka SR, et al., 2016, The First European Evidence-based Consensus on Extra-intestinal Manifestations in Inflammatory Bowel Disease, JOURNAL OF CROHNS & COLITIS, Vol: 10, Pages: 239-254, ISSN: 1873-9946
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- Citations: 443
Heap GA, So K, Weedon M, et al., 2016, Clinical Features and HLA Association of 5-Aminosalicylate (5-ASA)-induced Nephrotoxicity in Inflammatory Bowel Disease, JOURNAL OF CROHNS & COLITIS, Vol: 10, Pages: 149-158, ISSN: 1873-9946
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- Citations: 70
Hicks LC, Huang J, Kumar S, et al., 2015, Analysis of Exhaled Breath Volatile Organic Compounds in Inflammatory Bowel Disease: A Pilot Study, JOURNAL OF CROHNS & COLITIS, Vol: 9, Pages: 731-737, ISSN: 1873-9946
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- Citations: 46
Liu JZ, van Sommeren S, Huang H, et al., 2015, Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations, NATURE GENETICS, Vol: 47, Pages: 979-+, ISSN: 1061-4036
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- Citations: 1405
Plumb AA, Menys A, Russo E, et al., 2015, Magnetic resonance imaging-quantified small bowel motility is a sensitive marker of response to medical therapy in Crohn's disease, ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Vol: 42, Pages: 343-355, ISSN: 0269-2813
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- Citations: 35
Powles STR, Hicks LC, Jimenez B, et al., 2015, Effect of co-morbidities on urinary metabolic profiling in the characterisation of patients with inflammatory bowel disease, 2nd Digestive Disorders Federation Conference, Publisher: BMJ Publishing Group, Pages: A436-A437, ISSN: 0017-5749
Hicks L, Huang J, Kumar S, et al., 2015, EXHALED VOLATILE ORGANIC COMPOUND BREATH ANALYSIS IN INFLAMMATORY BOWEL DISEASE, 2nd Digestive-Disorders-Federation Conference, Publisher: BMJ PUBLISHING GROUP, Pages: A6-A6, ISSN: 0017-5749
Hicks L, Huang J, Kumar S, et al., 2015, Exhaled volatile organic compound breath analysis in Inflammatory Bowel Disease, JOURNAL OF CROHNS & COLITIS, Vol: 9, Pages: S161-S161, ISSN: 1873-9946
Nolan JD, Johnston IM, Pattni SS, et al., 2014, Diarrhea in Crohn's Disease: investigating the role of the ileal hormone Fibroblast Growth Factor 19., Journal of Crohns & Colitis, Vol: 9, Pages: 125-131, ISSN: 1873-9946
Background: Bile acids (BA) are usually reabsorbed by the terminal ileum, but this is frequently abnormal in Crohn's disease (CD). BA malabsorption occurs and excess colonic BA cause secretory diarrhea. Furthermore, the hormone Fibroblast Growth Factor 19 (FGF19) is synthesized in the ileum in response to BA absorption and regulates BA synthesis. We hypothesized that reduced serum FGF19 levels will be associated with diarrheal symptoms and disease activity in both ileal-resected (IR-CD) and non-resected CD (NR-CD) patients. Methods: Fasting serum FGF19 levels were measured in 58 patients (23 IR-CD patients and 35 NR-CD patients). Disease activity was assessed using the Harvey Bradshaw Index and CRP. Stool frequency, Bristol stool form scale and length of previous ileal resection were recorded. FGF19 levels were also compared to healthy and diarrhea control patients. Results: FGF19 levels were inversely correlated with ileal resection length in IR-CD patients (r=-0.54, p=0.02). In NR-CD patients, median FGF19 levels were significantly lower in patients with active disease compared to inactive disease (103 vs 158 pg/ml, p=0.04) and in those with symptoms of diarrhea compared to those without (86 vs 145 pg/ml, p=0.035). FGF19 levels were inversely correlated (r =-0.52, P=0.02) with stool frequency, Bristol stool form and CRP in NR-CD patients with ileal disease. Conclusions: Reduced FGF19 levels are associated with diarrhea and disease activity. FGF19 may have utility as a biomarker for functioning ileum in CD. This study supports a potential role of FGF19 in guiding treatments for diarrhea in Crohn's disease.
Heap GA, Weedon MN, Bewshea CM, et al., 2014, <i>HLA</i>-<i>DQA1</i>-<i>HLA</i>-<i>DRB1</i> variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants, NATURE GENETICS, Vol: 46, Pages: 1131-1134, ISSN: 1061-4036
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- Citations: 146
Russo E, Hackett R, Campbell S, et al., 2014, EFFICACY OF INFLIXIMAB AS SECOND- LINE BIOLOGIC IN CROHN'S DISEASE, GUT, Vol: 63, Pages: A154-A155, ISSN: 0017-5749
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- Citations: 1
Russo E, Khan S, Brown AP, et al., 2014, CORRELATION OF FDG PET SCANNING WITH ENDOSCOPIC FINDINGS IN PATIENTS WITH CROHN'S DISEASE, GUT, Vol: 63, Pages: A74-A74, ISSN: 0017-5749
Heap GA, Singh A, Bewshea C, et al., 2014, THIOPURINE INDUCED PANCREATITIS IN INFLAMMATORY BOWEL DISEASE: CLINICAL FEATURES AND GENETIC DETERMINANTS, GUT, Vol: 63, Pages: A2-A3, ISSN: 0017-5749
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- Citations: 2
Russo E, Khan S, Brown A, et al., 2014, Correlation of FDG PET scanning with clinical and laboratory markers of activity in patients with Crohn's disease, JOURNAL OF CROHNS & COLITIS, Vol: 8, Pages: S167-S168, ISSN: 1873-9946
Heap G, Bewshea C, Singh A, et al., 2014, A genome wide association study identifying association of the MHC region with 5-aminosalicylate (5-ASA) induced nephrotoxicity in inflammatory bowel disease, JOURNAL OF CROHNS & COLITIS, Vol: 8, Pages: S19-S20, ISSN: 1873-9946
Walker DG, Williams HRT, Bancil AS, et al., 2013, Ethnicity Differences in Genetic Susceptibility to Ulcerative Colitis: A Comparison of Indian Asians and White Northern Europeans, INFLAMMATORY BOWEL DISEASES, Vol: 19, Pages: 2888-2894, ISSN: 1078-0998
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- Citations: 10
Lindsay JO, Chipperfield R, Giles A, et al., 2013, A UK retrospective observational study of clinical outcomes and healthcare resource utilisation of infliximab treatment in Crohn's disease, ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Vol: 38, Pages: 52-61, ISSN: 0269-2813
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- Citations: 16
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