Outcome measures for clinical trials in paediatric IBD: an evidence-based, expert-driven practical statement paper of the paediatric ECCO committee
Conclusions It is crucial to perform paediatric trials early in the development of new drugs in order to reduce off-label use of IBD medication in children. The thoughtful choice of feasible and standardised outcome measures can help move us towards this goal. (Source: Gut)
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Ruemmele, F. M., Hyams, J. S., Otley, A., Griffiths, A., Kolho, K.-L., Dias, J. A., Levine, A., Escher, J. C., Taminiau, J., Veres, G., Colombel, J.-F., Vermeire, S., Wilson, D. C., Turner, D. Tags: Crohn's disease, Ulcerative colitis Inflammatory bowel disease Source Type: research

Diet-induced hypoxia responsive element demethylation increases CEACAM6 expression, favouring Crohn's disease-associated Escherichia coli colonisation
Conclusions HRE hypomethylation in CEACAM6 promoter correlates with high expression in IEC. Our findings suggest that abnormal DNA methylation leading to CEACAM6 increased expression and AIEC-mediated gut inflammation can be related to changes in nutritional habits, such as low intake in methyl donor molecules, leading to abnormal epigenetic marks in mouse model mimicking CD susceptibility. (Source: Gut)
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Denizot, J., Desrichard, A., Agus, A., Uhrhammer, N., Dreux, N., Vouret-Craviari, V., Hofman, P., Darfeuille-Michaud, A., Barnich, N. Tags: Crohn's disease Inflammatory bowel disease Source Type: research

Placebo analgesia in patients with functional and organic abdominal pain: a fMRI study in IBS, UC and healthy volunteers
Conclusions Patients with IBS failed to effectively engage neural downregulation of rectal distension-induced pain during placebo analgesia, indicating a specific deficit in cognitive pain inhibition, which may in part be mediated by depression. (Source: Gut)
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Schmid, J., Langhorst, J., Gass, F., Theysohn, N., Benson, S., Engler, H., Gizewski, E. R., Forsting, M., Elsenbruch, S. Tags: Neurogastroenterology Source Type: research

The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease
Conclusions The genotype of infants at family risk of developing CD, carrying the HLA-DQ2 haplotypes, influences the early gut microbiota composition. This finding suggests that a specific disease-biased host genotype may also select for the first gut colonisers and could contribute to determining disease risk. (Source: Gut)
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Olivares, M., Neef, A., Castillejo, G., Palma, G. D., Varea, V., Capilla, A., Palau, F., Nova, E., Marcos, A., Polanco, I., Ribes-Koninckx, C., Ortigosa, L., Izquierdo, L., Sanz, Y. Tags: Coeliac disease Source Type: research

Scheduled second-look endoscopy is not recommended after endoscopic submucosal dissection for gastric neoplasms (the SAFE trial): a multicentre prospective randomised controlled non-inferiority trial
Objective To clarify the effectiveness of second-look endoscopy (SLE) at preventing bleeding after gastric endoscopic submucosal dissection (ESD). Design A multicentre prospective randomised controlled non-inferiority trial was conducted at five referral institutions across Japan. Patients with a solitary gastric neoplasm were enrolled. Exclusion criteria were previous oesophagogastric surgery or radiation therapy; perforation and the administration of antithrombotics, steroids or non-steroidal anti-inflammatory drugs. Patients were assigned to the SLE group or the non-SLE group by a computer-generated random sequence aft...
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Mochizuki, S., Uedo, N., Oda, I., Kaneko, K., Yamamoto, Y., Yamashina, T., Suzuki, H., Kodashima, S., Yano, T., Yamamichi, N., Goto, O., Shimamoto, T., Fujishiro, M., Koike, K., Shinozaki, Yoshinaga, Nonaka, Abe, Ohno, Odagaki, Yagishita, Yoda, Kato, Ono, Tags: Pancreatic cancer Endoscopy Source Type: research

Demonstration of the usefulness of epigenetic cancer risk prediction by a multicentre prospective cohort study
Conclusions Assessment of the degree of an epigenetic field defect is a promising cancer risk marker that takes account of life history. (Source: Gut)
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Asada, K., Nakajima, T., Shimazu, T., Yamamichi, N., Maekita, T., Yokoi, C., Oda, I., Ando, T., Yoshida, T., Nanjo, S., Fujishiro, M., Gotoda, T., Ichinose, M., Ushijima, T., Yoshinaga, Suzuki Tags: Campylobacter, Salmonella, Shigella, Escherichia coli, Helicobacter pylori, Open access, Editor's choice, Pancreatic cancer Stomach Source Type: research

Global incidence of oesophageal cancer by histological subtype in 2012
Conclusions These first global estimates of oesophageal cancer incidence by histology suggested a high concentration of AC in high-income countries with men being at much greater risk. This quantification of incidence will aid health policy makers to plan appropriate cancer control measures in the future. (Source: Gut)
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Arnold, M., Soerjomataram, I., Ferlay, J., Forman, D. Tags: Press releases, Oesophageal cancer Oesophagus Source Type: research

Pepsin in saliva for the diagnosis of gastro-oesophageal reflux disease
Conclusion In patients with symptoms suggestive of GORD, salivary pepsin testing may complement questionnaires to assist office-based diagnosis. This may lessen the use of unnecessary antireflux therapy and the need for further invasive and expensive diagnostic methods. (Source: Gut)
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Hayat, J. O., Gabieta-Somnez, S., Yazaki, E., Kang, J.-Y., Woodcock, A., Dettmar, P., Mabary, J., Knowles, C. H., Sifrim, D. Tags: Gastro-oesophageal reflux Oesophagus Source Type: research

ECM remodelling in IBD: innocent bystander or partner in crime? The emerging role of extracellular molecular events in sustaining intestinal inflammation
Introduction IBD, which primarily includes UC and Crohn's disease (CD), is a progressive, chronic and relapsing condition. This debilitating disease is steadily becoming a worldwide medical concern, with increasing prevalence and incidence in both industrialised and developing countries.1 While the exact aetiology of the disease remains unknown, genetic predisposition and various environmental and immunological causes have been identified as contributing factors.2 Generally, IBD is characterised by a dysregulated excessive immune response and tissue damage in the GI tract.3 4 This aberrant and sustained immune response is ...
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Shimshoni, E., Yablecovitch, D., Baram, L., Dotan, I., Sagi, I. Tags: Crohn's disease, Diarrhoea, Open access Leading article Source Type: research

Association between antiviral treatment and extrahepatic outcomes in patients with hepatitis C virus infection
Chronic infection with the hepatitis C virus (HCV) is a slow progressive disease. While fibrosis development may not be linear over time, it has been estimated that 15–20% of patients will establish cirrhosis within 20 years of HCV acquisition.1 Once cirrhosis is present, it is clear that the patient's prognosis is heavily affected, with a 3–5% annual risk of liver failure as well as hepatocellular carcinoma (HCC). Although liver transplantation may be lifesaving in selected cases, organ shortage remains an important limitation. As a result, cirrhosis-related complications are considered to be one of the m...
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: van der Meer, A. J. Tags: Commentary Source Type: research

Viral entry inhibition: too late for hepatitis C, but promising for other viral infections
In theory, any step of the hepatitis C virus (HCV) lifecycle can be a target for direct-acting antiviral (DAA) drugs (drugs that directly block a viral function), and/or host-targeted agents (HTA, drugs that block a cellular function essential to the viral lifecycle). Four classes of HCV DAAs and two classes of HTAs have reached late clinical development. The HCV DAAs include: inhibitors of the NS3/4A protease that block HCV polyprotein processing; inhibitors of the RNA-dependent RNA polymerase (RdRp), including nucleoside/nucleotide analogues and non-nucleoside inhibitors that block viral replication; and NS5A inhibitors ...
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Pawlotsky, J.-M. Tags: Commentary Source Type: research

Salivary pepsin to diagnose GORD?
GORD has been defined by international consensus based on symptoms of heartburn and regurgitation.1 While this definition is useful for patients with the typical reflux syndrome, these symptoms may not be present in patients with extra-oesophageal GORD. The limitations of pH testing and endoscopy were highlighted in a recent study that demonstrated that each failed to identify approximately 30% of patients with proven GORD.2 A test that establishes a diagnosis of GORD at low cost with minimal intervention would have great utility. The presence of pepsin in saliva or sputum has been proposed as a surrogate marker for reflux...
Source: Gut - February 3, 2015 Category: Gastroenterology Authors: Vakil, N. Tags: Commentary Source Type: research

The PRSS1 c.623G>C (p.G208A) mutation is the most common PRSS1 mutation in Korean children with hereditary pancreatitis
We read the article by Schnúr et al1 and the letter by Atsushi et al2 reporting the functional aspects and Asian predominance of the p.G208A variant of the serine protease 1 gene (PRSS1) with great interest. Schnúr et al found that p.G208A is a rare variant of PRSS1 and suggested that, together with four other PRSS1 mutants, it is a mild pathogenic variant causing a moderate secretion defect and hereditary pancreatitis. Atsushi et al reported a relatively high prevalence of p.G208A variants in alcoholic and idiopathic Japanese patients with chronic pancreatitis (CP). We previously described two Korean childre...
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Lee, Y. J., Cheon, C. K., Kim, K., Oh, S. H., Park, J. H., Yoo, H. W. Tags: PostScript Source Type: research

Caecal intubation rates and colonoscopy competency
A recent study by Ward et al1 elegantly highlighted the steep and long learning curve for novice endoscopists to achieve competency in colonoscopy. In the study, they acquired data from the Joint Advisory Group (JAG) e-portfolio database which includes procedural outcomes from all training centres in the UK. The aim of the study was to establish the number of colonoscopies to be completed to achieve competency, defined as a caecal intubation rate (CIR) of ≥90%. They found that the endoscopy trainees obtained a CIR of ≥90% at 233 colonoscopies. The authors should be congratulated on a study that is by far the largest ...
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Benson, M., Lucey, M., Pfau, P. Tags: PostScript Source Type: research

Authors' response: impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia
We thank Prof Rodrigo and colleagues for their comments1 on our recent paper on increased permeability and low-grade inflammation in functional dyspepsia (FD).2 However, we disagree that our study is underpowered, which was confirmed by highly significant differences between the groups. As indicated in the manuscript, we calculated the minimum sample size and even included more subjects than statistically required. We also want to point out that our n-values are in the upper range for a study that combines functional and structural measurements of epithelial integrity. Questions were raised about the absence of Helicobacte...
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Vanheel, H., Vanuytsel, T., Farre, R., Tack, J. Tags: PostScript Source Type: research

Comments on 'Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia' by Vanheel et al
We note with great interest the finding by Vanheel et al of increased intestinal permeability in a series of patients with functional dyspepsia (FD). This represents an important contribution to the study of this disease.1 This has previously been observed in patients with IBS, which has led researchers to consider whether the two disorders, customarily considered to be functional, might have an underlying organic basis.2 Nevertheless, we find the information provided about the patient selection criteria to be insufficient, and we would like a complementary explanation of this matter. The 15 patients with FD included in th...
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Rodrigo, L., Lauret, E., Perez, I., Suarez, A. Tags: PostScript Source Type: research

Exome sequencing identifies MUTYH mutations in a family with colorectal cancer and an atypical phenotype
Ma et al1 comprehensively assessed the association of previously reported genetic variants with colorectal cancer (CRC) risk. The meta-analyses revealed strong evidence for association with rare MUTYH variants, even when excluding cases with MUTYH-associated polyposis. An article by Nieuwenhuis et al2 accurately defined the phenotypical features of MUTYH-associated polyposis. However, the study was performed on clinic-based series ascertained based on the inheritance model or the presence of polyps, which may miss additional phenotypes relevant to improve the disease characterisation and therefore, its genetic diagnosis. T...
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Segui, N., Navarro, M., Pineda, M., Koger, N., Bellido, F., Gonzalez, S., Campos, O., Iglesias, S., Valdes-Mas, R., Lopez-Doriga, A., Gut, M., Blanco, I., Lazaro, C., Capella, G., Puente, X. S., Plotz, G., Valle, L. Tags: PostScript Source Type: research

Paneth cell marker CD24 in NOD2 knockout organoids and in inflammatory bowel disease (IBD)
We read with great interest the article by Shanahan et al1 describing the roles of environmental conditions, notably co-housing with wild type (WT) littermates, and mouse genetic background in nucleotide-binding oligomerisation domain-containing protein 2 (NOD2)-dependent production of anti-microbial peptides in the mouse intestine. These authors demonstrate that expression, translation and anti-microbial activity of α-defensins are independent of NOD2.1 Robertson et al2 recently confirmed that housing conditions rather than NOD2 status influenced intestinal microbiota composition. Shanahan et al address the question...
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Van Limbergen, J., Geddes, K., Henderson, P., Russell, R. K., Drummond, H. E., Satsangi, J., Griffiths, A. M., Philpott, D. J., Wilson, D. C. Tags: PostScript Source Type: research

GI highlights from the literature
In this study, the authors investigate... (Source: Gut)
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

CT colonography: accuracy, acceptance, safety and position in organised population screening
Colorectal cancer (CRC) is the second most common cancer and second most common cause of cancer-related deaths in Europe. The introduction of CRC screening programmes using stool tests and flexible sigmoidoscopy, have been shown to reduce CRC-related mortality substantially. In several European countries, population-based CRC screening programmes are ongoing or being rolled out. Stool tests like faecal occult blood testing are non-invasive and simple to perform, but are primarily designed to detect early invasive cancer. More invasive tests like colonoscopy and CT colonography (CTC) aim at accurately detecting both CRC and...
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: de Haan, M. C., Pickhardt, P. J., Stoker, J. Tags: Endoscopy, GUT Recent advances in clinical practice, Colon cancer Source Type: research

Does the microbiota play a role in the pathogenesis of autoimmune diseases?
The microbiota of the human metaorganism is not a mere bystander. These microbes have coevolved with us and are pivotal to normal development and homoeostasis. Dysbiosis of the GI microbiota is associated with many disease susceptibilities, including obesity, malignancy, liver disease and GI pathology such as IBD. It is clear that there is direct and indirect crosstalk between this microbial community and host immune response. However, the precise mechanism of this microbial influence in disease pathogenesis remains elusive and is now a major research focus. There is emerging literature on the role of the microbiota in the...
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: McLean, M. H., Dieguez, D., Miller, L. M., Young, H. A. Tags: GUT Recent advances in basic science, Coeliac disease Source Type: research

Reliable prediction of clinical outcome in patients with chronic HCV infection and compensated advanced hepatic fibrosis: a validated model using objective and readily available clinical parameters
Objective Reliable tools to predict long-term outcome among patients with well compensated advanced liver disease due to chronic HCV infection are lacking. Design Risk scores for mortality and for cirrhosis-related complications were constructed with Cox regression analysis in a derivation cohort and evaluated in a validation cohort, both including patients with chronic HCV infection and advanced fibrosis. Results In the derivation cohort, 100/405 patients died during a median 8.1 (IQR 5.7–11.1) years of follow-up. Multivariate Cox analyses showed age (HR=1.06, 95% CI 1.04 to 1.09, p
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: van der Meer, A. J., Hansen, B. E., Fattovich, G., Feld, J. J., Wedemeyer, H., Dufour, J.-F., Lammert, F., Duarte-Rojo, A., Manns, M. P., Ieluzzi, D., Zeuzem, S., Hofmann, W. P., de Knegt, R. J., Veldt, B. J., Janssen, H. L. A. Tags: Cirrhosis Hepatology Source Type: research

Galectin-3 regulates hepatic progenitor cell expansion during liver injury
Conclusions We conclude that Gal-3 is required for the undifferentiated expansion of HPCs in their niche in injured liver. (Source: Gut)
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Hsieh, W.-C., Mackinnon, A. C., Lu, W.-Y., Jung, J., Boulter, L., Henderson, N. C., Simpson, K. J., Schotanus, B., Wojtacha, D., Bird, T. G., Medine, C. N., Hay, D. C., Sethi, T., Iredale, J. P., Forbes, S. J. Tags: Hepatology Source Type: research

Peginterferon alfa-2a with or without low-dose ribavirin for treatment-naive patients with hepatitis C virus genotype 2 receiving haemodialysis: a randomised trial
Objective Data comparing the efficacy and safety of combination therapy with peginterferon plus low-dose ribavirin and peginterferon monotherapy in treatment-naive haemodialysis patients with hepatitis C virus genotype 2 (HCV-2) infection are limited. Design In this randomised trial, 172 patients received 24 weeks of peginterferon alfa-2a 135 μg/week plus ribavirin 200 mg/day (n=86) or peginterferon alfa-2a 135 μg/week (n=86). The efficacy and safety endpoints were sustained virological response (SVR) rate and adverse event (AE)-related withdrawal rate. Results Compared with monotherapy, combina...
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Liu, C.-H., Liu, C.-J., Huang, C.-F., Lin, J.-W., Dai, C.-Y., Liang, C.-C., Huang, J.-F., Hung, P.-H., Tsai, H.-B., Tsai, M.-K., Lee, C.-Y., Chen, S.-I., Yang, S.-S., Su, T.-H., Yang, H.-C., Chen, P.-J., Chen, D.-S., Chuang, W.-L., Yu, M.-L., Kao, J.-H. Tags: Hepatology Source Type: research

Higher proportion of viral basal core promoter mutant increases the risk of liver cirrhosis in hepatitis B carriers
Background and objective Precore (PC) variant (G1896A) and basal core promoter (BCP) variant (A1762T/G1764A) of HBV are associated with risk of hepatocellular carcinoma in HBV carriers. However, little is known about their impact on the adverse outcomes of hepatitis B e antigen (HBeAg)-negative hepatitis and liver cirrhosis. Methods 251 spontaneous HBeAg seroconverters who had genotype B or C infection and received a long-term follow-up were enrolled. PC and BCP mutants were determined qualitatively and quantitatively to correlate with these adverse outcomes. The findings were validated by an independent case–contro...
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Tseng, T.-C., Liu, C.-J., Yang, H.-C., Chen, C.-L., Yang, W.-T., Tsai, C.-S., Kuo, S. F.-T., Verbree, F. C., Su, T.-H., Wang, C.-C., Liu, C.-H., Chen, P.-J., Chen, D.-S., Kao, J.-H. Tags: Cirrhosis, Hepatic cancer Hepatology Source Type: research

Colorectal cancer screening uptake over three biennial invitation rounds in the English bowel cancer screening programme
Conclusions Screening history is associated with overall gFOB uptake, inadequate gFOB screening and follow-up compliance. Socioeconomic deprivation is also consistently associated with lower gFOB uptake and inadequate gFOB screening. Improving regular screening among identified ‘at-risk’ groups is important for the effectiveness of CRC screening programmes. (Source: Gut)
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Lo, S. H., Halloran, S., Snowball, J., Seaman, H., Wardle, J., von Wagner, C. Tags: Endoscopy, Open access, Colon cancer Source Type: research

Colon capsule versus CT colonography in patients with incomplete colonoscopy: a prospective, comparative trial
Conclusions CCE and CTC were of comparable efficacy in completing colon evaluation after incomplete colonoscopy; the overall diagnostic yield of colon capsule was superior to CTC. Trial registration number NCT01525940. (Source: Gut)
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Spada, C., Hassan, C., Barbaro, B., Iafrate, F., Cesaro, P., Petruzziello, L., Minelli Grazioli, L., Senore, C., Brizi, G., Costamagna, I., Alvaro, G., Iannitti, M., Salsano, M., Ciolina, M., Laghi, A., Bonomo, L., Costamagna, G. Tags: Endoscopy, Colon cancer Source Type: research

Protective effects of Fc-fused PD-L1 on two different animal models of colitis
Conclusions Based on the protective effect of PD-L1-Fc against DSS-induced and T-cell-induced colitis, our results suggest that PD-1-mediated inhibitory signals have a crucial role in limiting the development of colonic inflammation. This implicates that PD-L1-Fc may provide a novel therapeutic approach to treat inflammatory bowel disease. (Source: Gut)
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Song, M.-Y., Hong, C.-P., Park, S. J., Kim, J.-H., Yang, B.-G., Park, Y., Kim, S. W., Kim, K. S., Lee, J. Y., Lee, S.-W., Jang, M. H., Sung, Y.-C. Tags: Experimental colitis Source Type: research

Generation of primary human intestinal T cell transcriptomes reveals differential expression at genetic risk loci for immune-mediated disease
Conclusions This is the first report of transcriptomes for minimally manipulated intestinal T lymphocyte subsets in humans. We have demonstrated that careful processing of mucosal biopsies allows the generation of transcriptomes from as few as 1000 highly purified cells with minimal interindividual variation. Bioinformatic integration of transcriptomic data with recent GWAS data identified specific candidate genes and cell types for inflammatory pathologies. (Source: Gut)
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Raine, T., Liu, J. Z., Anderson, C. A., Parkes, M., Kaser, A. Tags: Crohn's disease, Ulcerative colitis, Open access, Editor's choice, Coeliac disease Intestinal inflammation Source Type: research

Tralokinumab for moderate-to-severe UC: a randomised, double-blind, placebo-controlled, phase IIa study
Conclusions Add-on therapy with tralokinumab did not significantly improve clinical response. However, the higher clinical remission rate with tralokinumab than placebo suggests that tralokinumab may benefit some patients with UC. Tralokinumab was well tolerated. Trial registration number ClinicalTrials.gov number: NCT01482884. (Source: Gut)
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Danese, S., Rudzinski, J., Brandt, W., Dupas, J.-L., Peyrin-Biroulet, L., Bouhnik, Y., Kleczkowski, D., Uebel, P., Lukas, M., Knutsson, M., Erlandsson, F., Hansen, M. B., Keshav, S. Tags: Inflammatory bowel disease Source Type: research

Identification of inflammatory mediators in patients with Crohn's disease unresponsive to anti-TNF{alpha} therapy
Conclusions Our results show that anti-TNFα therapy significantly downregulates a subset of inflammatory genes even in patients who fail to achieve endoscopic remission, suggesting that these genes may not be dominant in driving inflammation in non-responders. On the other hand, we identified IL1B and IL17A as genes that remained altered in non-responders, pointing to potentially more relevant targets for modulating mucosal damage in refractory patients. (Source: Gut)
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Leal, R. F., Planell, N., Kajekar, R., Lozano, J. J., Ordas, I., Dotti, I., Esteller, M., Masamunt, M. C., Parmar, H., Ricart, E., Panes, J., Salas, A. Tags: Crohn's disease Inflammatory bowel disease Source Type: research

Intestinal mucus affinity and biological activity of an orally administered antibacterial and anti-inflammatory peptide
Conclusions Our findings demonstrate the anti-inflammatory activity and mucus affinity of the synthetic AMP Pep19-2.5 and characterise the influence on microbiota composition and enteropathogen infection after oral administration. (Source: Gut)
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Dupont, A., Kaconis, Y., Yang, I., Albers, T., Woltemate, S., Heinbockel, L., Andersson, M., Suerbaum, S., Brandenburg, K., Hornef, M. W. Tags: Mucosal immunity Source Type: research

Risk of irritable bowel syndrome in first-degree, second-degree and thirddegree relatives of affected individuals: a nationwide family study in Sweden
Conclusions The increased IBS risk among first-degree relatives and also second-degree and third-degree relatives indicates a genetic component of the familial clustering of IBS. However, a non-genetic contribution is also suggested by the increased risk among spouses. (Source: Gut)
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Waehrens, R., Ohlsson, H., Sundquist, J., Sundquist, K., Zoller, B. Tags: Irritable bowel syndrome Neurogastroenterology Source Type: research

A rare cause of abdominal pain, diarrhoea and GI bleeding
Question A 62-year-old woman presented with abdominal pain and diarrhoea. She had a history of primary biliary cirrhosis and renal transplantation secondary to reflux nephropathy. Cross-sectional imaging and a colonoscopy demonstrated terminal ileal inflammation and ulceration, but histological biopsies were inconclusive and cytomegalovirus staining was negative. The patient subsequently developed spontaneous small bowel perforation due to deep ulceration, necessitating an emergency right hemicolectomy. Her postoperative period was complicated by several episodes of rectal bleeding. After a prolonged admission at her local...
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Laskaratos, F.-M., Hamilton, M., Novelli, M., Shepherd, N., Jones, G., Lawrence, C., Mitchison, M., Murray, C. D. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

MicroRNA-29c mediates initiation of gastric carcinogenesis by directly targeting ITGB1
Objective Gastric cancer (GC) remains difficult to cure due to heterogeneity in a clinical challenge and the molecular mechanisms underlying this disease are complex and not completely understood. Accumulating evidence suggests that microRNAs (miRNAs) play an important role in GC, but the role of specific miRNAs involved in this disease remains elusive. We performed next generation sequencing (NGS)-based whole-transcriptome profiling to discover GC-specific miRNAs, followed by functional validation of results. Design NGS-based miRNA profiles were generated in matched pairs of GCs and adjacent normal mucosa (NM). Quantitat...
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Han, T.-S., Hur, K., Xu, G., Choi, B., Okugawa, Y., Toiyama, Y., Oshima, H., Oshima, M., Lee, H.-J., Kim, V. N., Chang, A. N., Goel, A., Yang, H.-K. Tags: Pancreatic cancer Stomach Source Type: research

ER stress induces epithelial differentiation in the mouse oesophagus
Conclusions These results show that ER stress induces epithelial differentiation in precursor cells in the oesophageal epithelium. This UPR induced differentiation may serve as a quality control mechanism that protects against oesophageal cancer development. (Source: Gut)
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Rosekrans, S. L., Heijmans, J., Buller, N. V. J. A., Westerlund, J., Lee, A. S., Muncan, V., van den Brink, G. R. Tags: Oesophageal cancer Oesophagus Source Type: research

Prediction of clinical outcome in advanced hepatitis C-associated liver disease: identification of patients at the highest need for antiviral treatment and surveillance
Patients infected with HCV usually have a long period of mild disease of 15–25 years. After this period, a substantial number of patients develop liver-associated morbidity and mortality, including clinical complications of liver cirrhosis such as ascites, variceal haemorrhage, hepatic encephalopathy, hepatocellular carcinoma (HCC) or liver-related death. This natural course of disease has been best described in young and mostly healthy women who were infected by a contaminated anti-D immunoglobulin preparation in East Germany in 1978/1979. Less than 2% of women with chronic HCV infection developed liver cirrhos...
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Neumann-Haefelin, C., Thimme, R. Tags: Commentary Source Type: research

Viral factors and predicting disease outcomes in chronic hepatitis B
One of the conundrums of chronic infection with the hepatitis B virus (HBV) is identifying those individual patients who are at risk for the development of the serious sequelae of cirrhosis and hepatocellular carcinoma (HCC). It has been estimated that 25–40% of patients with chronic hepatitis B (CHB) who acquire the virus early in life (perinatal or early horizontal transmission from an HBeAg-positive source) will eventually develop these serious and disastrous consequences.1 Viral factors associated with the outcome of CHB include hepatitis B e antigen (HBeAg) status, HBV DNA and HBsAg levels (>2000 IU/mL) ...
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Revill, P., Locarnini, S. Tags: Commentary Source Type: research

Ribavirin with interferon for hepatitis C in dialysis patients: efficacious and safe in the right patients in good hands
Hepatitis C virus infection, with both hepatic and extrahepatic manifestations, is an important issue for patients requiring renal replacement therapy (RRT) and for those who receive kidney transplants (KT). Registry studies show a clear adverse impact of HCV-positivity on RRT patient survival and on KT graft and patient survival.1 In pretransplant and post-transplant settings, HCV-positivity (vs uninfected patients) is clearly associated with a relatively increased liver-related mortality and morbidity. However, reflecting the frequent comorbid cardiovascular disease that is observed in these settings, the absolute risk f...
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Mutimer, D. Tags: Commentary Source Type: research

A multi-journal partnership to highlight joint first-authors of manuscripts
Our journals came together to put forth a plan that highlights joint first-authors in citations that are part of the references section of original articles. This has already been implemented by some of us (Gastroenterology,1 2 Hepatology3) but is now part of the Instructions to Authors in all five partnering journals (Gastroenterology, Gastrointestinal Endoscopy, Gut, Hepatology, and Journal of Hepatology). Prior to this, we and most, if not all, other journals highlighted joint first-authors of articles they published on the first page of the article (though such acknowledgment is sometimes difficult to note in some jour...
Source: Gut - January 8, 2015 Category: Gastroenterology Authors: Omary, M. B., Wallace, M. B., El-Omar, E. M., Jalan, R., Nathanson, M. H. Tags: Commentary Source Type: research

Authors' response: surgery rates in IBD
To the Editor, We thank Dr Tøttrup and colleagues for their comments1 on our recent paper on decreasing risk of surgery over time among Danish patients with IBD.2 We agree with the authors that it is not certain the observed decrease in surgery is explained by the parallel changes in medication use. However, results do not reflect the fact that outpatients were included in later cohorts. This was tested thoroughly and—as described in the paper—restricting analyses to inpatients only, we obtained nearly identical results. In other words, even among inpatients, a statistically significant decrease in surge...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Rungoe, C., Jess, T. Tags: PostScript Source Type: research

Surgery rates in IBD
With great interest we have read the paper by Rungoe et al1 describing a possible decrease rate in surgery in patients with IBD. The authors have identified all Danish patients with IBD by their first IBD diagnosis registered in the time period from 1979 to 2011. Data were extracted from the Danish National Patient Register, which contains information about all inpatient hospital contacts including diagnoses and surgical interventions, and outpatient diagnoses were not registered before 1995. Accordingly, Cohorts 1 and 2 represent only patients, who have had conditions requiring first time admissions, whereas Cohorts 3 and...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Tottrup, A., Norgard, B. M., Qvist, N. Tags: PostScript Source Type: research

Author's response: Hepatitis B virus seromarkers clearance and risk of hepatocellular carcinoma: serious risks of misinterpretation
We would like to respond to Dr Pariente's letter, which addresses our recently reported results regarding the seroclearance of HBV seromarkers and subsequent risk for hepatocellular carcinoma (HCC).1 2 Unfortunately, his comments are based on serious misunderstandings of our findings. First, he suggests that there may be underestimation of the protective roles of marker seroclearance, since incidence rates of HCC were measured from baseline, and that the duration of seromarkers’ positivity would be a better indicator of HCC risk. In order to truly measure the effect of HBV DNA and Hepatitis B surface Antigen (HBsAg) ...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Liu, J., Yang, H.-I., Chen, C.-J. Tags: PostScript Source Type: research

Hepatitis B virus seromarkers clearance and risk of hepatocellular carcinoma: serious risks of misinterpretation
Liu et al1 have to be commended for their recent report concerning the predictive value of hepatitis B virus (HBV) seromarkers clearance for hepatocellular carcinoma (HCC) risk in the REVEAL study. There are, however, some limits and interrogations:The incidence rates of HCC are measured from baseline (as the characteristics of the patients) and not from the first occurrence of seromarkers clearance, causing probably an underestimation of the protective roles of the clearances of HBsAg and HBV DNA against HCC occurrence. In other words, the predictive value of the duration of seromarkers positivity could be a better indica...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Pariente, A. Tags: PostScript Source Type: research

Authors' response: the role of risedronate in osteopenia in Crohn's disease
We read with interest the comments of Buchan and Manuel concerning our risedronate intervention trial in osteopenic patients with Crohn's disease.1 2 They stipulated that exclusion of patients with vitamin D deficiency limited the significance of the performed study, as this deficiency is frequently observed in Crohn's disease. It is however well known that replenishment of vitamin D (and calcium) in patients with vitamin D deficiency would lead to a rapid improvement of bone density, irrespective of any effect of risedronate. As assessment of a therapeutic effect of the latter was our primary study aim, we decided to excl...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: van Bodegraven, A. A., Witte, B. I., Lips, P., for the Crohn and Bone Study Group of the Dutch Initiative on Crohn and Colitis (ICC) Tags: PostScript Source Type: research

The role of risedronate in osteopenia in Crohn's disease
We read with great interest van Bodegraven et al's1 paper about the treatment of osteopenia in patients with Crohn's disease. They have identified an evidence gap, as many studies of interventions to treat osteoporosis and prevent bone loss have been conducted on older and primarily female patients. In contrast, both male and female patients with Crohn's disease may develop osteopenia and osteoporosis at a younger age. The authors found that use of risedronate can improve bone density in the lumbar spine of patients with Crohn's disease. One of the exclusion criteria for patients in this study was vitamin D deficiency. Vit...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Buchan, A., Manuel, A. Tags: PostScript Source Type: research

The learning curve for detection of non-polypoid (flat and depressed) colorectal neoplasms
We read with interest the two excellent studies on interval colorectal cancers (CRC) following colonoscopy and wish to present important data relevant to the prevention of interval CRC. In a pooled multicohort analysis, Robertson and coauthors found that invasive cancer was diagnosed in 0.6% of patients after clearing colonoscopy among eight large North American trials, and concluded that half of these were likely missed lesions.1 In a population-based study, le Clercq and coauthors reported that CRC found following colonoscopy were more likely to have non-polypoid morphology than prevalent cancers.2 We previously describe...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: McGill, S. K., Kaltenbach, T., Friedland, S., Soetikno, R. Tags: PostScript Source Type: research

GI highlights from the literature
In this study, bacteria from several foreign environments were used to colonise germ-free mice, and their ability to metabolise dietary and host carbohydrates and bile acids were measured. The findings demonstrate that the mouse intestinal tract, while highly selective, shows unanticipated patterns of ecological succession. Nonetheless, cohousing the various colonised mice revealed that most bacterial phylotypes, including those from... (Source: Gut)
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Endoscopic submucosal dissection of an unusual flat rectal neoplasm
Clinical presentation A 63-year-old woman was admitted to our gastroenterology unit to undergo a screening colonoscopy, scheduled for faecal occult blood test positivity. During the procedure, a flat, rectal granular lesion was found. With the use of magnification and narrow band image (NBI) technology, the lesion was diagnosed as a laterally spreading tumour (LST), granular mixed type, 30 mm in maximum diameter (figure 1). The pit pattern was unclassifiable and vascular pattern was similar to the type IV of the classification proposed by Inoue regarding the microvasculature pattern of the oesophagus for diagnosis and...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Azzolini, F., Cecinato, P., Iori, V., De Marco, L., Zecchini, R., Fodero, C., Tioli, C., Sassatelli, R. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Therapeutic targeting of GSK3{beta} enhances the Nrf2 antioxidant response and confers hepatic cytoprotection in hepatitis C
Conclusions Inhibition of GSK3β exerts hepatoprotection in CHC possibly through its direct regulation of Nrf2 antioxidant response. (Source: Gut)
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Jiang, Y., Bao, H., Ge, Y., Tang, W., Cheng, D., Luo, K., Gong, G., Gong, R. Tags: Hepatology Source Type: research