182 results found
Alexander JL, Mullish BH, Danckert NP, et al., 2022, The gut microbiota and metabolome are associated with diminished COVID-19 vaccine-induced antibody responses in immunosuppressed inflammatory bowel disease patients, EBioMedicine, ISSN: 2352-3964
Alexander J, Liu Z, Munoz Sandoval D, et al., 2022, COVID-19 vaccine-induced antibody and T cell responses in immunosuppressed patients with inflammatory bowel disease after the third vaccine dose: a multicentre, prospective, case-control study, The Lancet Gastroenterology & Hepatology, Vol: 7, Pages: 1005-1015, ISSN: 2468-1253
Background:COVID-19 vaccine-induced antibody responses are reduced in patients with inflammatory bowel disease (IBD) taking anti-TNF or tofacitinib after two vaccine doses. We sought to determine whether immunosuppressive treatments were associated with reduced antibody and T cell responses after a third vaccine dose.Methods:352 adults (72 healthy controls and 280 IBD) were sampled 28-49 days after a third dose of SARS-CoV-2 vaccine. IBD medications studied included thiopurines (n=65), infliximab (n=46), thiopurine/infliximab combination therapy (n=49), ustekinumab (n=44), vedolizumab (n=50) or tofacitinib (n=26). SARS-CoV-2 spike antibody binding and T cell responses were measured. Findings:Geometric mean [geometric SD] anti-S1 RBD antibody concentrations increased in all groups following a third dose, but were significantly lower in patients treated with infliximab (2736.8 U/mL [4.3]; P<0.0001), infliximab and thiopurine combination (1818.3 U/mL [6.7]; P<0.0001) and tofacitinib (8071.5 U/mL [3.1]; P=0.0018) compared to controls (16774.2 U/ml [2.6]). There were no significant differences in anti-S1 RBD antibody concentrations between control subjects and thiopurine (12019.7 U/mL [2.2]; P=0.099), ustekinumab (11089.3 U/mL [2.8]; P=0.060), nor vedolizumab treated patients (13564.9 U/mL [2.4]; P=0.27). In multivariable modelling, lower anti-S1 RBD antibody concentrations were independently associated with infliximab (Geometric mean ratio 0.15, 95% CI 0.11-0.21, P<0.0001), tofacitinib (0.52, 95% CI 0.31-0.87, P=0.012) and thiopurine (0.69, 95% CI 0.51-0.95, P=0.021), but not with ustekinumab (0.64, 95% CI 0.39-1.06, P=0.083), or vedolizumab (0.84, 95% CI 0.54-1.30, P=0.43). Previous SARS-CoV-2 infection (1.58, 95% CI 1.22-2.05, P=0.00056) and older age (0.88, 95% CI 0.80-0.97, P=0.0073) were independently associated with higher and lower anti-S1 antibody concentrations respectively. Antigen specific T cell responses were similar in all groups, except for reci
Alexander J, Powell N, Ibraheim H, et al., 2022, Oral Beclomethasone Dipropionate is an effective treatment for immune checkpoint inhibitor induced colitis, Journal for ImmunoTherapy of Cancer, Vol: 10, Pages: 1-10, ISSN: 2051-1426
IntroductionSystemic corticosteroids are the mainstay of treatment for immune checkpoint inhibitor induced (CPI) colitis but are associated with complications including life-threatening infection. The topically-acting oral corticosteroid beclomethasone dipropionate (BD) is an effective treatment for mild to moderate flares of ulcerative colitis, and has fewer side effects than systemic corticosteroids. We hypothesised that BD would be an effective treatment for CPI-induced colitis.MethodsWe performed a retrospective analysis of all patients who started BD for CPI-induced colitis at three UK cancer centres between November 2017 and October 2020. All patients underwent endoscopic assessment and biopsy. The initial regimen of BD was 5mg once daily for 28 days. Data were collected from electronic patient records. Clinical outcomes were assessed at 28 days after initiation of treatment.ResultsTwenty-two patients (fourteen male) with a median age of 64 (range 45-84) with CPI-induced colitis were treated with BD. At baseline, the median number of loose stools in a 24-hour period was six (CTCAE grade diarrhoea = 2). Thirteen patients (59%) were dependent on systemic corticosteroids prior to starting BD. Baseline sigmoidoscopy showed moderate inflammation (Mayo endoscopic score [MES] = 2) in two patients (9%), mild inflammation (MES = 1) in nine patients (41%) and normal findings (MES = 0) in eleven patients (50%). Twenty patients (91%) had histopathological features of inflammation. All 22 patients (100%) had a clinical response to BD and 21 (95%) achieved clinical remission with a return to baseline stool frequency (CTCAE diarrhoea = 0). 10 patients (45%) had symptomatic relapse on cessation of BD, half within seven days of stopping. All patients recaptured response on restarting BD. No adverse events were reported in patients treated with BD.ConclusionsTopical BD represents an appealing alternative option to systemic immunosuppressive treatments to treat colonic inflamma
Alexander J, Mullish B, Danckert N, et al., 2022, COVID-19 VACCINATION RESPONSE IN IMMUNOSUPPRESSED PATIENTS WITH IBD IS ASSOCIATED WITH ALTERED GUT MICROBIOTA FUNCTION, Publisher: BMJ PUBLISHING GROUP, Pages: A36-A36, ISSN: 0017-5749
Alexander JL, Mullish BH, Danckert NP, et al., 2022, The gut microbiota and metabolome is associated with diminished COVID-19 vaccine-induced antibody responses in immunosuppressed inflammatory bowel disease patients
<jats:title>Abstract</jats:title> <jats:p>Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination. Forty-three infliximab-treated patients with IBD were recruited (30 Crohn’s disease, 12 ulcerative colitis, 1 IBD-unclassified; 26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.021). <jats:italic>Bilophila</jats:italic> abundance was associated with better serological response, while <jats:italic>Streptococcus</jats:italic> was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R<jats:sup>2</jats:sup>X 0.25, R&l
Aldhwayan MM, Al-Najim W, Ruban A, et al., 2022, Does bypass of the proximal small intestine impact food intake, preference, and taste function in humans? An experimental medicine study using the duodenal-jejunal bypass liner, Nutrients, Vol: 14, ISSN: 2072-6643
The duodenal-jejunal bypass liner (Endobarrier) is an endoscopic treatment for obesity and type 2 diabetes mellitus (T2DM). It creates exclusion of the proximal small intestine similar to that after Roux-en-Y Gastric Bypass (RYGB) surgery. The objective of this study was to employ a reductionist approach to determine whether bypass of the proximal intestine is the component conferring the effects of RYGB on food intake and sweet taste preference using the Endobarrier as a research tool. A nested mechanistic study within a large randomised controlled trial compared the impact of lifestyle modification with vs. without Endobarrier insertion in patients with obesity and T2DM. Forty-seven participants were randomised and assessed at several timepoints using direct and indirect assessments of food intake, food preference and taste function. Patients within the Endobarrier group lost numerically more weight compared to the control group. Using food diaries, our results demonstrated similar reductions of food intake in both groups. There were no significant differences in food preference and sensory, appetitive reward, or consummatory reward domain of sweet taste function between groups or changes within groups. In conclusion, the superior weight loss seen in patients with obesity and T2DM who underwent the Endobarrier insertion was not due to a reduction in energy intake or change in food preferences.
Alexander JL, Mullish BH, Danckert NP, et al., 2022, POOR RESPONSE TO ANTI-SARS-COV-2 VACCINATION IN IMMUNOSUPPRESSED INFLAMMATORY BOWEL DISEASE PATIENTS IS ASSOCIATED WITH ALTERED GUT MICROBIOTA FUNCTION, GASTROENTEROLOGY, Vol: 162, Pages: S653-S653, ISSN: 0016-5085
Alexander JL, Kennedy N, Ibraheim H, et al., 2022, COVID-19 VACCINE-INDUCED ANTIBODY RESPONSES ARE IMPAIRED IN IBD PATIENTS TREATED WITH INFLIXIMAB, USTEKINUMAB OR TOFACITINIB, BUT NOT THIOPURINES OR VEDOLIZUMAB, Publisher: W B SAUNDERS CO-ELSEVIER INC
Alexander JL, Kennedy NA, Ibraheim H, et al., 2022, COVID-19 vaccine-induced antibody responses in immunosuppressed patients with inflammatory bowel disease (VIP): a multicentre, prospective, case-control study, The Lancet Gastroenterology & Hepatology, Vol: 7, Pages: 342-352, ISSN: 2468-1253
BACKGROUND: The effects that therapies for inflammatory bowel disease (IBD) have on immune responses to SARS-CoV-2 vaccination are not yet fully known. Therefore, we sought to determine whether COVID-19 vaccine-induced antibody responses were altered in patients with IBD on commonly used immunosuppressive drugs. METHODS: In this multicentre, prospective, case-control study (VIP), we recruited adults with IBD treated with one of six different immunosuppressive treatment regimens (thiopurines, infliximab, a thiopurine plus infliximab, ustekinumab, vedolizumab, or tofacitinib) and healthy control participants from nine centres in the UK. Eligible participants were aged 18 years or older and had received two doses of COVID-19 vaccines (either ChAdOx1 nCoV-19 [Oxford-AstraZeneca], BNT162b2 [Pfizer-BioNTech], or mRNA1273 [Moderna]) 6-12 weeks apart (according to scheduling adopted in the UK). We measured antibody responses 53-92 days after a second vaccine dose using the Roche Elecsys Anti-SARS-CoV-2 spike electrochemiluminescence immunoassay. The primary outcome was anti-SARS-CoV-2 spike protein antibody concentrations in participants without previous SARS-CoV-2 infection, adjusted by age and vaccine type, and was analysed by use of multivariable linear regression models. This study is registered in the ISRCTN Registry, ISRCTN13495664, and is ongoing. FINDINGS: Between May 31 and Nov 24, 2021, we recruited 483 participants, including patients with IBD being treated with thiopurines (n=78), infliximab (n=63), a thiopurine plus infliximab (n=72), ustekinumab (n=57), vedolizumab (n=62), or tofacitinib (n=30), and 121 healthy controls. We included 370 participants without evidence of previous infection in our primary analysis. Geometric mean anti-SARS-CoV-2 spike protein antibody concentrations were significantly lower in patients treated with infliximab (156·8 U/mL [geometric SD 5·7]; p<0·0001), infliximab plus thiopurine (111·1 U/mL [5·
Ruban A, Miras AD, Glaysher MA, et al., 2022, Duodenal-Jejunal Bypass Liner for the management of Type 2 Diabetes Mellitus and Obesity, Annals of Surgery, Vol: 275, Pages: 440-447, ISSN: 0003-4932
Wei J, Nazarian S, Teare J, et al., 2022, A case for improved assessment of gut permeability: a meta-analysis quantifying the lactulose:mannitol ratio in coeliac and Crohn’s disease, BMC Gastroenterology, Vol: 22, ISSN: 1471-230X
Background:A widely used method in assessing small bowel permeability is the lactulose:mannitol test, where the lactulose:mannitol ratio (LMR) is measured. However, there is discrepancy in how the test is conducted and in the values of LMR obtained across studies. This meta-analysis aims to determine LMR in healthy subjects, coeliac and Crohn’s disease.Methods:A literature search was performed using PRISMA guidance to identify studies assessing LMR in coeliac or Crohn’s disease. 19 studies included in the meta-analysis measured gut permeability in coeliac disease, 17 studies in Crohn’s disease. Outcomes of interest were LMR values and comparisons of standard mean difference (SMD) and weighted mean difference (WMD) in healthy controls, inactive Crohn’s, active Crohn’s, treated coeliac and untreated coeliac. Pooled estimates of differences in LMR were calculated using the random effects model.Results:Pooled LMR in healthy controls was 0.014 (95% CI: 0.006–0.022) while pooled LMRs in untreated and treated coeliac were 0.133 (95% CI: 0.089–0.178) and 0.037 (95% CI: 0.019–0.055). In active and inactive Crohn’s disease, pooled LMRs were 0.093 (95% CI: 0.031–0.156) and 0.028 (95% CI: 0.015–0.041). Significant differences were observed in LMR between: (1) healthy controls and treated coeliacs (SMD = 0.409 95% CI 0.034 to 0.783, p = 0.032), (2) healthy controls and untreated coeliacs (SMD = 1.362 95% CI: 0.740 to 1.984, p < 0.001), (3) treated coeliacs and untreated coeliacs (SMD = 0.722 95% CI: 0.286 to 1.157, p = 0.001), (4) healthy controls and inactive Crohn’s (SMD = 1.265 95% CI: 0.845 to 1.686, p < 0.001), (5) healthy controls and active Crohn’s (SMD = 2.868 95% CI: 2.112 to 3.623, p < 0.001), and (6) active Crohn’s and inactive Crohn&rsquo
Alexander J, Ibraheim H, Sheth B, et al., 2021, A MULTI-CENTRE STUDY OF INFLIXIMAB TREATMENT FOR CORTICOSTEROID-REFRACTORY CHECKPOINT INHIBITOR INDUCED ENTEROCOLITIS, Publisher: BMJ PUBLISHING GROUP, Pages: A22-A22, ISSN: 0017-5749
Alexander J, Ibraheim H, Richards C, et al., 2021, CLIPPER (BECLOMETHASONE DIPROPIONATE) AS A TREATMENT FOR CHECKPOINT INHIBITOR INDUCED ENTEROCOLITIS, Publisher: BMJ PUBLISHING GROUP, Pages: A101-A101, ISSN: 0017-5749
Glover B, Teare J, Patel N, 2021, Assessment of H. pylori status by examination of gastric mucosal patterns: diagnostic accuracy of white-light endoscopy and narrow-band imaging, BMJ Open Gastroenterology, Vol: 8, Pages: 1-9, ISSN: 2054-4774
ObjectivesHelicobacter pylori infection is a common cause of chronic gastritis worldwide and an established risk factor for developing gastric malignancy. The endoscopic appearances predicting H. pylori status are an ongoing area of research, as are their diagnostic accuracies. This study aimed to establish the diagnostic accuracy of several mucosal features predictive of H. pylori negative status and formulate a simple prediction model for use at the time of endoscopy.DesignPatients undergoing high-definition upper GI endoscopy without magnification were recruited prospectively. During endoscopy, the presence or absence of specific endoscopic findings was noted. Sydney protocol biopsies were used as the diagnostic reference standard, and urease test if taken. The results informed a logistic regression model used to produce a simple diagnostic approach. This model was subsequently validated using a further cohort of 30 patients.Results153 patients were recruited and completed the study protocol. The prevalence of active H. pylori infection was 18.3% (28/153). The overall diagnostic accuracy of the simple prediction model was 80.0%, and 100% of patients with active H. pylori infection were correctly classified. Presence of regular arrangement of collecting venules (RAC) showed a positive predictive value for H. pylori naïve status of 90.7%, rising to 93.6% for patients under the age of 60.ConclusionA simple endoscopic model may be accurate for predicting H. pylori status of a patient, and the need for biopsy-based tests. The presence of RAC in the stomach is an accurate predictor of H. pylori negative status, particularly in patients under the age of 60.
Nazarian S, Glover B, Ashrafian H, et al., 2021, Diagnostic Accuracy of Artificial Intelligence and Computer-Aided Diagnosis for the Detection and Characterization of Colorectal Polyps: Systematic Review and Meta-analysis, JOURNAL OF MEDICAL INTERNET RESEARCH, Vol: 23, ISSN: 1438-8871
Nazarian S, Glover B, Ashrafian H, et al., 2021, The diagnostic accuracy of artificial intelligence and computer-aided diagnosis for the detection and characterisation of colorectal polyps: A systematic review and meta-analysis., Journal of Medical Internet Research, Vol: 23, Pages: 1-18, ISSN: 1438-8871
AimsColonoscopy reduces the incidence of colorectal cancer by allowing detection and resection of neoplastic polyps. Evidence shows that many small polyps are missed on a single colonoscopy. There has been a successful adoption of AI technologies to tackle the issues around missed polyps and as a tool to increase adenoma detection rate (ADR). The aim of this review was to examine the diagnostic accuracy of AI-based technologies in assessing colorectal polyps.MethodA comprehensive literature search was undertaken using the databases of EMBASE, Medline and the Cochrane Library. PRISMA guidelines were followed. Studies reporting use of computer-aided diagnosis for polyp detection or characterisation during colonoscopy were included. Independent proportion and their differences were calculated and pooled through DerSimonian and Laird random-effects modelling. ResultsA total of 48 studies were included. The meta-analysis showed a significant increase in pooled PDR in patients with the use of AI for polyp detection during colonoscopy compared with patients who had standard colonoscopy (OR 1.75; 95% CI 1.56-1.96; p= 0.0005). When comparing patients undergoing colonoscopy with the use of AI to those without, there was also a significant increase in ADR (OR 1.53; 95% CI 1.32-1.77; p= 0005). ConclusionWith the aid of machine learning, there is potential to improve ADR and consequently reduce the incidence of CRC. The current generation of AI-based systems demonstrate impressive accuracy for the detection and characterisation of colorectal polyps. However, this is an evolving field and before its adoption into a clinical setting, AI systems must prove worthy to patients and clinicians.
Alexander J, Ibraheim H, Sheth B, et al., 2021, Clinical outcomes of patients with corticosteroid refractory immune checkpoint inhibitor induced enterocolitis treated with infliximab, Journal for ImmunoTherapy of Cancer, Vol: 9, Pages: 1-9, ISSN: 2051-1426
IntroductionImmune Checkpoint Inhibitors (CPI) have changed the treatment landscape for many cancers, but also cause severe inflammatory side effects including enterocolitis. CPI-induced enterocolitis is treated empirically with corticosteroids, and infliximab (IFX) is used in corticosteroid-refractory cases. However, robust outcome data for these patients are scarce. MethodsWe conducted a multi-centre (six cancer centres), cohort study of outcomes in patients treated with IFX for corticosteroid-refractory CPI-induced enterocolitis between 2007 and 2020. The primary outcome was corticosteroid-free clinical remission (CFCR) with CTCAE grade 0 for diarrhoea at 12 weeks after IFX initiation. We also assessed cancer outcomes at one year using RECIST criteria.Results127 patients (73 male; median age 59 years) were treated with IFX for corticosteroid-refractory CPI-induced enterocolitis. Ninety-six (75.6%) patients had diarrhoea CTCAE grade >2 and 115 (90.6%) required hospitalisation for colitis. CFCR was 41.2% at 12 weeks and 50.9% at 26 weeks. In multivariable logistical regression, IFX-resistant enterocolitis was associated with rectal bleeding (OR 0.19; 95% CI 0.04-0.80; p=0.03) and absence of colonic crypt abscesses (OR 2.16; 95% CI 1.13-8.05; p=0.03). Cancer non-progression was significantly more common in patients with IFX-resistant enterocolitis (64.4%) as compared to patients with IFX-responsive enterocolitis (37.5%; p=0.013).ConclusionThis is the largest study to date reporting outcomes of IFX therapy in patients with corticosteroid-refractory CPI-induced enterocolitis. Utilizing pre-defined robust endpoints, we have demonstrated that fewer than half of patients achieved CFCR. Our data also indicate that cancer outcomes may be better in patients developing prolonged and severe inflammatory side effects of CPI-therapy.
Glaysher M, Ward J, Aldhwayan M, et al., 2021, The effect of a duodenal-jejunal bypass liner on lipid profile and blood concentrations of long chain polyunsaturated fatty acids, Clinical Nutrition, Vol: 40, Pages: 2343-2354, ISSN: 0261-5614
Background & aimsDuodenal-jejunal bypass liners (DJBLs) prevent absorption in the proximal small intestine, the site of fatty acid absorption. We sought to investigate the effects of a DJBL on blood concentrations of essential fatty acids (EFAs) and bioactive polyunsaturated fatty acids (PUFAs).MethodsSub-study of a multicentre, randomised, controlled trial with two treatment groups. Patients aged 18–65 years with type-2 diabetes mellitus and body mass index 30–50 kg/m2 were randomised to receive a DJBL for 12 months or best medical therapy, diet and exercise. Whole plasma PUFA concentrations were determined at baseline, 10 days, 6 and 11.5 months; data were available for n = 70 patients per group.ResultsWeight loss was significantly greater in the DJBL group compared to controls after 11.5 months: total body weight loss 11.3 ± 5.3% versus 6.0 ± 5.7% (mean difference [95% CI] = 5.27% [3.75, 6.80], p < 0.001). Absolute concentrations of both EFAs, linoleic acid and α-linolenic acid, and their bioactive derivatives, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, were significantly lower in the DJBL group than in the control group at 6 and 11.5 months follow-up. Total serum cholesterol, LDL-cholesterol and HDL-cholesterol were also significantly lower in the DJBL group.ConclusionOne year of DJBL therapy is associated with superior weight loss and greater reductions in total serum cholesterol and LDL-cholesterol, but also depletion of EFAs and their longer chain derivatives. DJBL therapy may need to be offset by maintaining an adequate dietary intake of PUFAs or by supplementation.
Kohoutova D, Worku D, Aziz H, et al., 2021, Malignant melanoma of the gastrointestinal tract: symptoms, diagnosis, and current treatment options., Cells, Vol: 10, ISSN: 2073-4409
Malignant melanoma (MM) has become the fifth most frequent cancer in the UK. It is the most common carcinoma to metastasize to the gastrointestinal (GI) tract. MM particularly has an affinity to spread to the small bowel, which is followed by the involvement of the stomach and large intestine. Excellent endoscopic options including video capsule endoscopy and enteroscopy are available for a precise diagnosis of GI involvement by a metastatic MM. The complete surgical resection of GI metastatic MM in carefully selected patients not only provides symptom control, but has also been associated with an increase in overall survival. The approval of BRAF-targeted therapies and immune checkpoint inhibitors has transformed therapeutic approaches for patients with metastatic MM over the past decade. Currently, the overall survival of patients with advanced metastatic MM who have been treated with a combination of immunotherapeutic agents reaches 52% at five years. The role of surgery for patients with the metastatic involvement of the GI tract with MM is evolving in the era of effective systemic treatments.
Ruban A, Glaysher M, Miras A, et al., 2021, SAFETY PROFILE OF THE DUODENAL-JEJUNAL BYPASS LINER (ENDOBARRIER): A MULTICENTRE RANDOMISED CONTROL TRIAL, Publisher: BMJ PUBLISHING GROUP, Pages: A170-A170, ISSN: 0017-5749
Ruban A, Glaysher M, Ashrafian H, et al., 2021, DUODENAL-JEJUNAL BYPASS LINER THERAPY (ENDOBARRIER (R)) CAUSES REDUCTIONS IN PLASMA TRIMETHYLAMINE-N-OXIDE IN OBESE PATIENTS WITH DIABETES, Publisher: BMJ PUBLISHING GROUP, Pages: A19-A19, ISSN: 0017-5749
Awasthi A, Barbour J, Beggs A, et al., 2021, Enhanced neoplasia detection in chronic ulcerative colitis: the ENDCaP-C diagnostic accuracy study, Efficacy and Mechanism Evaluation, Vol: 8, Pages: 1-88, ISSN: 2050-4365
BackgroundChronic ulcerative colitis is a large bowel inflammatory condition associated with increased colorectal cancer risk over time, resulting in 1000 colectomies per year in the UK. Despite intensive colonoscopic surveillance, 50% of cases progress to invasive cancer before detection. Detecting early (precancer) molecular changes by analysing biopsies from routine colonoscopy should increase neoplasia detection.ObjectivesTo establish a deoxyribonucleic acid (DNA) marker panel associated with early neoplastic changes in ulcerative colitis patients. To develop the DNA methylation test for high-throughput analysis within the NHS. To prospectively evaluate the test within the existing colonoscopy surveillance programme.DesignModule 1 analysed 569 stored biopsies from neoplastic and non-neoplastic sites/patients using pyrosequencing for 11 genes that were previously reported to have altered promoter methylation associated with colitis-associated neoplasia. Classifiers were constructed to predict neoplasia based on gene combinations. Module 2 translated analysis to a NHS laboratory, assessing next-generation sequencing to increase speed and reduce cost. Module 3 applied the molecular classifiers within a prospective diagnostic accuracy study, in the existing ulcerative colitis surveillance programme. Comparisons were made between baseline and reference colonoscopies undertaken in a stratified patient sample 6–12 months later.SettingThirty-one UK hospitals.ParticipantsPatients with chronic ulcerative colitis, either for at least 10 years and extensive disease, or with primary sclerosing cholangitis.InterventionsAn optimised DNA methylation classifier tested on routine mucosal biopsies taken during colonoscopy.Main outcomeIdentifying ulcerative colitis patients with neoplasia.ResultsModule 1 selected five genes with specificity for neoplasia. The optimism-adjusted area under the receiver operating characteristic curve for neoplasia was 0.83 (95% confidence interv
Ruban A, Glaysher MA, Miras AD, et al., 2020, A duodenal sleeve bypass device added to intensive medical therapy for obesity with type 2 diabetes: a RCT, Efficacy and Mechanism Evaluation, Vol: 7, Pages: 1-130, ISSN: 2050-4365
BackgroundThe EndoBarrier® (GI Dynamics Inc., Boston, MA, USA) is an endoluminal duodenal–jejunal bypass liner developed for the treatment of patients with obesity and type 2 diabetes mellitus. Meta-analyses of its effects on glycaemia and weight have called for larger randomised controlled trials with longer follow-up.ObjectivesThe primary objective was to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level reduction of ≥ 20%. The secondary objectives were to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level of < 42 mmol/mol, blood pressure of < 135/85 mmHg, and the effectiveness on total body weight loss. Additional secondary outcomes were to investigate the cost-effectiveness and mechanism of action of the effect of a duodenal–jejunal bypass liner on brain reward system responses, insulin sensitivity, eating behaviour and metabonomics.DesignA multicentre, open-label, randomised controlled trial.SettingImperial College Healthcare NHS Trust and University Hospital Southampton NHS Foundation Trust.ParticipantsPatients aged 18–65 years with a body mass index of 30–50 kg/m2 and with inadequately controlled type 2 diabetes mellitus who were on oral glucose-lowering medications.InterventionsParticipants were randomised equally to receive intensive medical therapy alongside a duodenal–jejunal bypass liner device (n = 85) or intensive medical therapy alone for 12 months (n = 85), and were followed up
Glover B, Teare J, Patel N, 2020, The endoscopic predictors of H. pylori status: a meta-analysis of diagnostic performance., Therapeutic Advances in Gastrointestinal Endoscopy, Vol: 13, Pages: 1-19, ISSN: 1179-5522
ObjectiveThe endoscopic findings associated with H. pylori naïve status, current infection or past infection is an area of ongoing interest. Previous studies have investigated parameters with potential diagnostic value. The aim of this study was to perform meta-analysis of the available literature to validate the diagnostic accuracy of mucosal features proposed in the Kyoto classification.Data SourcesThe databases of Medline and Embase, clinicaltrials.gov and the Cochrane library were systematically searched for relevant studies from October 1999 to October 2019.MethodsA bivariate random effects model was used to produce pooled diagnostic accuracy calculations for each of the studied endoscopic findings. Diagnostic odds ratios and sensitivity and specificity characteristics were calculated to identify significant predictors of H. pylori status.ResultsMeta-analysis included 4,380 patients in 15 studies. The most significant predictor of an H. pylori naïve status was a regular arrangement of collecting venules (RAC). (DOR 55.0, Sensitivity 78.3%, Specificity 93.8%) Predictors of active H. pylori infection were mucosal oedema (18.1, 63.7%, 91.1%) and diffuse redness (14.4, 66.5%, 89.0%). Map-like redness had high specificity for previous H. pylori eradication (99.0%), but poor specificity (13.0%).ConclusionsThe RAC, mucosal oedema, diffuse redness and map-like redness are important endoscopic findings for determining H. pylori status. This meta-analysis provides a tentative basis for developing future endoscopic classification systems.
Ruban A, Glaysher M, Miras A, et al., 2020, ONE YEAR OF DUODENAL-JEJUNAL BYPASS LINER THERAPY (ENDOBARRIER (R)) LEADS TO SIGNIFICANT CHANGES IN LIVER BIOCHEMISTRY ASSOCIATED WITH NON-ALCOHOLIC FATTY LIVER DISEASE, GI Fellows Sessions at Digestive Disease Week / 61st Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract, Publisher: MOSBY-ELSEVIER, Pages: AB225-AB226, ISSN: 0016-5107
Glaysher M, Ward J, Aldhwayan M, et al., 2020, The effect of a duodenal-jejunal bypass liner device (Endobarrier (R)) on lipid profile and blood concentrations of long chain polyunsaturated fatty acids, 11th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S16-S17, ISSN: 0960-8923
Ruban A, Liu Z, Glaysher M, et al., 2020, One year of duodenal-jejunal bypass liner therapy (Endobarrier (R)) leads to perturbations in the metabolic profile of urine, plasma and stool of obese diabetic patients., 11th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S10-S10, ISSN: 0960-8923
Glaysher M, Miras A, Ruban A, et al., 2020, The effect of a duodenal-jejunal bypass liner device (Endobarrier (R)) on insulin sensitivity, 11th Annual Scientific Meeting of the British-Obesity-and-Metabolic-Surgery-Society (BOMSS), Publisher: SPRINGER, Pages: S25-S26, ISSN: 0960-8923
Glover B, Teare J, Patel N, 2020, The status of advanced imaging techniques for ‘optical biopsy’ of colonic polyps, Clinical and Translational Gastroenterology, Vol: 11, Pages: 1-11, ISSN: 2155-384X
Introduction: The progressive miniaturisation of photonics components presents the opportunity to obtain unprecedented microscopic images of colonic polyps in real-time, during endoscopy. This information has the potential to act as an ‘optical biopsy’ to aid clinical decision making, including the possibility of adopting new paradigms such as a ‘resect and discard’ approach for low-risk lesions. The technologies discussed in this review include Confocal Laser Endomicroscopy, Optical Coherence Tomography, Multiphoton Microscopy, Raman Spectroscopy and Hyperspectral Imaging. These are in different stages of development and clinical readiness, but all show the potential to produce reliable in-vivo discrimination of different tissue types.Methods:A structured literature search of the imaging techniques for colorectal polyps has been conducted. The significant developments in endoscopic imaging was identified for each modality, and the status of current development was discussed.Conclusions:Of the advanced imaging techniques discussed, Confocal Laser Endomicroscopy is in clinical use, and under optimal conditions with an experienced operator, can provide accurate histological assessment of tissue. The remaining techniques show potential for incorporation into endoscopic equipment and practice, although further component development is needed, followed by robust prospective validation of accuracy. Optical Coherence Tomography illustrates tissue ‘texture’ well and gives good assessment of mucosal thickness and layers. Multiphoton Microscopy produces high resolution images at a subcellular resolution. Raman Spectroscopy and Hyperspectral Imaging are less developed endoscopically but provide a tissue ‘fingerprint’ which can distinguish between tissue types. Molecular Imaging may become a powerful adjunct to other techniques, with its ability to precisely label specific molecules within tissue and thereby enhance imaging.
Glover B, Teare J, Patel N, 2020, A systematic review of the role of non-magnified endoscopy for the assessment of H. pylori infection., Endoscopy International Open, Vol: 8, Pages: E105-E114, ISSN: 2196-9736
BackgroundThere is growing interest in the endoscopic recognition of H. pylori infection, and application to routine practice. We present a systematic review of the current literature regarding diagnosis of H. pylori during standard (non-magnified) endoscopy, including adjuncts such as image enhancement and computer-aided diagnosis.MethodThe Medline and Cochrane databases were searched for studies investigating the performance of non-magnified optical diagnosis for H. pylori, or those which characterised mucosal features associated with H. pylori infection. Studies were preferred with a validated reference test as the comparator, although were included if at least one validated reference test was used.Results20 suitable studies were identified and included for analysis. In total, 4,703 patients underwent investigation including white light endoscopy, narrow band imaging, i-scan, blue-laser imaging, and computer-aided diagnostic techniques. The endoscopic features of H. pylori infection observed using each modality are discussed and diagnostic accuracies reported. The Regular Arrangement of Collecting Venules (RAC) is an important predictor of the H. pylori naïve stomach. ‘Mosaic’ and ‘Mottled’ patterns have a positive association with H. pylori infection. The ‘Cracked’ pattern may be a predictor of an H. pylori negative stomach following eradication.ConclusionsThis review summarises the current progress made in endoscopic diagnosis of H. pylori infection. At present there is no single diagnostic approach that provides validated diagnostic accuracy. Further prospective studies are required, as is the development of a validated classification system. Early studies in Computer-Aided Diagnosis suggest potential for a high level of accuracy but real-time results are awaited.
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