Background: Vedolizumab (VDZ) drug monitoring strategies in inflammatory bowel disease (IBD) patients have not been systematically investigated so far. We evaluated the correlation between VDZ trough levels (VTL) and the treatment response in IBD.Methods: Fifty-one patients with active IBD on or starting a therapy with VDZ were enrolled in this prospective and observational single centre study. Disease activity indices, blood tests, and anthropometric parameters were assessed over a time period of 6 months. One hundred and fifty-five VDZ serum trough levels were measured directly before the next scheduled application using liquid chromatography mass spectrometry (LC-MS/MS).Results: VDZ treatment was found to be clinically effective (Harvey Bradshaw Index (HBI) dropping from 10 to 5.5 points (p<.0005) in Crohn's disease (CD) patients; partial Mayo score (pMS) from 4.4 to 2.1 points (p<.0005) in ulcerative colitis patients (UC). CRP levels tended to decrease and haemoglobin levels to increase under VDZ therapy. CD patients with a serum CRP level lower than 5mg/l exhibited significantly higher VTL than those with elevated CRP levels (34.9 versus 21.7 mu g/ml, p=.00153). UC patients with haemoglobin levels higher 12g/dl at the time of VTL measurement had significantly higher VTL compared to patients with lower haemoglobin levels (35.4 versus 15.6 mu g/ml, p<.0005).Conclusions: Our data suggest a significant correlation between VTL and response to therapy in IBD patients (higher VTL associated with better response).

Einleitung: Erhöhte Calprotectin-Konzentrationen in Stuhl sind ein Hinweis auf eine Mukosaentzündung oder Zellschädigung. Das fäkale Calprotectin ist ein etablierter Marker zum Nachweis inflammatorischer Läsionen im Kolon. Zur Calprotectin-Bestimmung steht eine Reihe quantitativer, qualitativer und semiquantitativer Verfahren zur Verfügung. Vergleichende Studien zur diagnostischen Performance gibt es kaum.

BACKGROUND & AIMS:Early detection of neoplastic lesions is essential in patients with long-standing ulcerative colitis but the best technique of colonoscopy still is controversial. METHODS:We performed a prospective multicenter study in patients with long-standing ulcerative colitis. Two colonoscopies were performed in each patient within 3 weeks to 3 months. In white-light (WL) colonoscopy, stepwise random biopsy specimens (4 biopsy specimens every 10 cm), segmental random biopsies (2 biopsy specimens in 5 segments), and targeted biopsy specimens were taken. In NBI colonoscopy, segmental and targeted biopsy specimens were taken. The sequence of WL and NBI colonoscopy was randomized. RESULTS:In 36 of 159 patients enrolled (22.6%), 54 lesions with intraepithelial neoplasia (IN) were found (51 low-grade, 3 high-grade). In WL colonoscopy we found 11 IN in stepwise biopsy specimens, 4 in segmental biopsy specimens, and 15 in targeted biopsy specimens. In NBI colonoscopy 7 IN were detected in segmental biopsy specimens and 24 IN were detected in targeted biopsy specimens. Almost all IN were found with one technique alone (κ value of WL vs NBI, -0.86; P < .001). Statistically equivalent numbers of IN were found in NBI colonoscopy with targeted and segmental biopsy specimens as in WL colonoscopy with targeted and stepwise biopsy specimens, but with fewer biopsy specimens (11.9 vs 38.6 biopsy specimens, respectively; P < .001), and less withdrawal time was necessary (23 vs 13 min, respectively; P < .001). CONCLUSIONS:Stepwise biopsy specimens are indispensable in WL colonoscopy. The combination of targeted and segmental biopsy specimens in the NBI technique is as sensitive as targeted together with stepwise biopsy specimens in WL colonoscopy, but requires fewer biopsy specimens and less time. The highest sensitivity should be reached by combining the WL and NBI techniques by switching between the modes.

Background: Iron deficiency anemia (IDA) is commonly measured by multiple indicators. Choice of a single iron biomarker for IDA screening at population level is controversial. Zinc protoporphyrin (ZPP) has proved a sensitive and specific marker for functional iron deficiency. Our study evaluated for the first time the diagnostic value of ZPP in IDA and differential diagnosis of IDA/anemia of chronic disease (ACD). Methods: The study included 136 patients with IBD (age, 36.40 ± 13.14 years, 41 % male), who consecutively attended the Crohn Colitis Centre Frankfurt for routine evaluation between Jan 2009 and Oct 2012. Blood count, transferrin saturation (TSAT), serum ferritin (SF), C-reactive protein and ZPP were determined by routine assay. Anemia was defined in accordance with WHO criteria as hemoglobin (Hb) concentration of < 13 g/dl/12 g/dl (m/f). For the multiple-criteria model, ID was considered present when ≥2 values from SF (<30 μg/l), TSAT (<20%), and ZPP (<40 μmol/mol Hb)1 were abnormal. Anemia was classified as IDA, ACD or a mixed form (IDA/ACD)2. Results: Unlike SF, ZPP significantly correlated with Hb. Receiver operating characteristic (ROC) curves for the multiple markers used to diagnose IDA indicated a superior diagnostic accuracy of ZPP. Crucially ZPP is elevated even in ACD, indicating irondeficient erythropoiesis (fig. 1). Conclusion: ZPP is not a simple ID parameter but a marker of iron-deficient erythropoiesis. Our results confirm the utility of ZPP in detection of ID in IBD patients with inflammation and anemia, even in ACD. 1Grant KE et al. Comparison of indicators of iron deficiency in Kenyan children. Am J Clin Nutr 2012;95:1231-7 2Weiss G, Goodnough LT. Anemia of chronic disease. N EnglJ Med 2005;352:1011-23

P380 Safety and efficacy of bolus administered ferric carboxymaltose (500mg) in the treatment of iron deficiency anaemia in IBD patients D. Jakobsen1 *, M. Wiesenthal2, F. Hartmann3, A. Dignass4, S. Weber-Mangal5, J. Stein2. 11Krankenhaus Sachsenhausen, Crohn Colitis Center, Frankfurt, Germany, 2Crohn Colitis Zentrum Rhein-Main, Frankfurt, Germany, 3Marien Krankenhaus, Frankfurt, Germany, 4Apaglesion Markus Krankenhaus, Frankfurt, Germany, 5Vifor Pharma Germany, Munich, Germany

The treatment of ulcerative colitis is based on systemic corticosteroids, immunomodulators such as cyclosporine and azathioprine and TNF-α antagonists. Patients undergoing such immunosuppressive treatment are more susceptible for infectious pathogens. Here, we report the case of a patient with a 13-year history of ulcerative colitis, treated initially with systemic corticosteroids in combination with immunomodulators, and subsequently with infliximab. The patient presented with severe watery diarrhoea, abdominal cramps, weight loss and low-grade fever. Stool examinations for cytomegalovirus, bacteria and parasites were negative. Following detection of numerous oocytes of Isospora belli (IB) in direct smear preparations of the diarrhoeic stool samples, the patient was successfully treated with trimethoprim-sulfamethoxazole (co-trimoxazole).

AbstractDie Pathogenese der chronisch‐entzündlichen Darmerkrankungen Morbus Crohn und Colitis ulcerosa ist trotz erheblicher Fortschritte in der Ätiopathogenese‐Forschung weiterhin ungeklärt. Verschiedene Faktoren, wie z.B. eine genetische Prädisposition oder Umweltfaktoren (u.a. bakterielle oder virale Infekte, Ernährungsbestandteile, Rauchen) führen vermutlich zu einer Barrierestörung und konsekutiver Fehlregulation des mukosalen Immunsystems, die in der Entwicklung einer chronisch‐entzündlichen Darmerkrankung (CED) resultiert.

BACKGROUND:Despite the use of prophylactic antibiotics, peristomal infection is the most common complication of percutaneous endoscopic gastrostomy (PEG). A new glycerin hydrogel (GHG) wound dressing has been proposed to possess more effective antimicrobial properties but has not been tested in a larger trial. The aim of the study was therefore to assess the superiority of GHG regarding the incidence of peristomal wound infections during a 30-day postprocedure follow-up.METHODS:Sixty-eight patients with cancer undergoing PEG were recruited from 1 university and 2 general hospitals between January 2007 and December 2008. Patients were randomized to group 1 (34 patients), which received GHG, or group 2 (34 patients), which received a traditional wound dressing. Dressing changes were done at day 1 and weeks 1, 2, and 4 (group 1) vs daily changes during week 1 and at weeks 2 and 4 (group 2). The PEG site was assessed by using 2 different infection scores.RESULTS:At the end of the first and second weeks, a statistically significant reduction of the mean infection scores was seen in patients with GHG wound dressings (first week: 1.64 ± 1.6 vs 3.12 ± 2.69, P < .008; second week: 1.37 ± 1.11 vs 2.53 ± 2.37, P < .02). After 7 days, wound reactions occurred in 14.7% in the GHG group vs 47.05% in the traditional group (p <0.005). The GHG wound dressing required 5 times less frequent dressing changes.CONCLUSION:The GHG wound dressing significantly reduces peristomal wound infections and is a convenient, cost-effective alternative for wound management following PEG.

Introduction: This study was aimed to evaluate the diagnostic accuracy of fecal S100A12, and fecal calprotectin in adult patients with irritable bowel syndrome (IBS) and active or inactive inflammatory bowel disease (IBD). As some authors suppose the use of higher cutoff levels for an improved discrimination of active from inactive IBD, different cutoff-levels were compared with endoscopic disease activity.

AIM: Growth failure in children and adolescents, weight loss and catabolism in adults, are well known features of active Crohn's disease (CD).Increasing evidence shows that these features may be due to growth hormone (GH) resistance caused by persistent chronic inflammation.Aim of this study was to evaluate, in CD patients, a possible peripheral GHresistance (intestinal mucosa), and eventual modifications following anti TNF-α treatment.MATERIALS AND METHODS: 9 patients (5 F, median age 42.2 years, range 19-67) with moderate-severe active CD (CDAI>220), consecutively scheduled to receive three infliximab infusions at a dose of 5 mg/kg for induction of remission, were studied.Biopsy specimens from normal appearing duodenal mucosa were collected, in the 2 weeks prior to the first and after the third infusion.Confocal and real time PCR analysis of insulin-like growth factor 1 (IGF-1), activated signal transducer and activator of transcription protein 5 (phospho-STAT5) and suppressor of cytokine signalling protein 3 (SOCS-3) were carried out and normalised to GAP, 18S and H3 referring genes.Four dyspeptic patients (2 F, median age 39 years, range 24-57), who underwent upper endoscopy with duodenal biopsy sampling, represented our control group.Differences between CD patients and controls were analysed by one-way ANOVA and REST-coupled ANOVA analysis.RESULTS: In CD patients, a significant inverse correlation was found when comparing phospho-STAT5 levels with CDAI (r=-0.71;p=0.003).Confocal analysis showed a significant decrease in phospho-STAT5 immunoreactivity in sections from CD patients, compared to controls (p<0.001).After treatment, phospho-STAT5 levels significantly increased (p<0.001).Molecular data for phospho-STAT5 were in keeping with biochemical findings.At baseline, compared with controls, in CD patients, the PCR analysis of IGF-1, showed a trend towards a decrease, while SOCS-3 showed a trend towards an increase.Following treatment, SOCS-3 and IGF-1 target genes showed a trend toward a decrease and an increase, respectively.Nevertheless, following infliximab induction treatment, IGF-1, phospho-STAT5 and SOCS-3 levels did not reach those of the control group.CONCLUSION: The present study underline the effect of inflammation on the growth hormone axis not only at the level of hepatic metabolism, but also in the intestinal mucosa, since biologic agents able to inhibit pro-inflammatory cytokines, in particular TNF-α, the main inflammatory mediator, reverse growth hormone resistance.These therapeutic approaches could prevent the onset of those clinical conditions with a negative impact on child growth and quality of life of adults.

Aims: Anemia in patients with inflammatory bowel disease (IBD) is multifactorial, however the two most common causes of anemia in IBD are iron deficiency and anemia of inflammation (ACI). Although the exact pathogenesis of ACI is unknown, one hypothesis suggests that-caused by the effects of inflammatory cytokines-ACI arises in part as a result of an impaired intestinal Iron absorption. Recently it has been shown, that the acute phase protein hepcidin impairs intestinal iron uptake. We therefore hypothesized that iron absorption is impaired in patients with active IBD at least in part as an increased hepcidin release by the liver.