Claudia Ott

Circulating levels of chemerin and adiponectin are higher in ulcerative colitis and chemerin is elevated in Crohn's disease

Background: Chemerin is an adipokine that stimulates chemotaxis of cells of the innate immune system. Inflammatory bowel disease (IBD) is linked to an impaired immune response and, therefore, we hypothesized that systemic chemerin may be altered in IBD patients. Methods: Serum was collected from patients with Crohns disease (CD, 230 patients), ulcerative colitis (UC, 80 patients), and healthy controls (HC, 80 probands). Chemerin and adiponectin, which has already been measured in the serum of similar cohorts by others, were determined by enzyme‐linked immunosorbent assay (ELISA). Results: Chemerin was elevated in IBD compared to HC and was higher in male CD than UC patients. Female and male CD patients had lower adiponectin levels compared to UC, and adiponectin was lower in female CD patients compared to female HC. Adiponectin tended to be higher in female and male UC patients compared to HC and this difference became significant in the whole study group. Correlations with disease activity were only found in males. Here, chemerin was higher in CD patients on remission but was reduced in UC with nonactive disease. Adiponectin was higher in UC with inactive disease. Treatment with corticosteroids was linked to elevated adiponectin in male CD patients and higher chemerin in female UC patients. Unlike adiponectin, which was elevated in female serum in all cohorts, chemerin was only higher in female UC patients. Conclusions: These findings further indicate potential regulatory functions of adipokines in intestinal inflammation that are partly gender‐dependent and that may even be associated with the distinct immunopathogenesis of UC and CD. (Inflamm Bowel Dis 2009;)

The incidence of inflammatory bowel disease in a rural region of Southern Germany: a prospective population-based study.

Objective Although important advances in understanding the aetiology and pathogenesis of inflammatory bowel disease (IBD) have been made, many questions remain unanswered. As the most recent data available on the incidence of IBD in Germany were collected about 15 years ago, we set up a new population-based cohort to determine current incidence data for a defined region in Germany and to establish a basic cohort for prospective follow-up. Methods All patients living in the region of Oberpfalz newly diagnosed with IBD between 1 January 2004 and 31 December 2006 were included in this study by setting up a network of reporting clinicians and general practitioners in hospitals as well as in private practices. Demographic and clinical characteristics such as age at first diagnosis, localization of the disease, extraintestinal manifestations or family history on IBD were documented. Age-adjusted incidence rates are presented with 95% Poisson confidence intervals (CIs), based on the European standard population. Results In total, 286 newly diagnosed patients with IBD were reported in this region, 168 patients suffering from Crohns disease (CD), 105 patients with ulcerative colitis. Age-standardized incidence rates were 11.0/105 (95% CI: 9.1–11.6) for IBD, 6.6/105 (95% CI: 5.6–7.7) for CD and 3.9/105 (95% CI: 3.2–4.7) for ulcerative colitis. Peak incidences were found in the age interval of 16–24 years for both diseases, predominantly for CD. Age at first diagnosis was lower, extraintestinal manifestations and a positive family history on IBD were more common in patients with CD. Conclusion The incidence rate in IBD seems to be stable in Germany as compared with previously reported data, as is the remarkable predominance of CD. Prospective follow-up studies will be based on this incidence cohort.

Intraabdominal septic complications following bowel resection for Crohn’s disease: detrimental influence on long-term outcome

BackgroundA number of studies deal with factors affecting postoperative recurrence; however, they do not analyze the influence of postoperative morbidity on the long-term outcome. This was the aim of the present study.Materials and methodsTwo hundred eighty-two patients underwent 331 intestinal resections for primary or recurrent Crohn’s disease between 1992 and 2005. Closure of ileostomy or colostomy, isolated stricturoplasty, abdominoperineal resection for perianal disease, and reoperations for postoperative complications were excluded. “Surgical recurrence” was defined as a development of stricturing or perforating disease necessitating repeat surgical therapy.ResultsAnastomotic leak, intraabdominal abscess, enterocutaneous fistula (intraabdominal septic complications, IASC) occurred after 46 operations (16%). Four patients died (1.2%). By multivariate analysis, articular disease manifestation (p = 0.03), duration of symptoms leading to surgery (p = 0.009), and weight loss (p = 0.03) were associated with occurrence of postoperative complications. Surgical recurrence occurred following 86 bowel resections, and 36 occurred during the first postoperative year. The following factors were associated with an increased risk of surgical recurrence by multivariate analysis: postoperative IASC (p = 0.0002) and previous bowel resections (p = 0.002). Patients suffering IASC had statistically significantly higher 1-, 2-, 5-, and 10-year surgical recurrence rate (25%, 29%, 50%, and 57%) than patients without IASC (4%, 7%, 19%, and 38%, p = 0.0003).ConclusionThe incidence of the postoperative IASC is predominantly determined by preoperative disease severity. IASC have a detrimental influence on the long-term outcome following intestinal resections in patients with Crohn’s disease, leading to increased number of repeat resection surgery.

High prevalence but insufficient treatment of iron-deficiency anemia in patients with inflammatory bowel disease: results of a population-based cohort.

Background. Iron-deficiency anemia is described to be a common problem in patients with inflammatory bowel disease (IBD), which is frequently associated with a reduced quality of life. Therefore, the aim of this study is to assess the prevalence of iron deficiency anemia in a population-based cohort at time of first diagnosis and during the early course of the disease. Methods. As far as available, lab values of patients registered in the population-based “Oberpfalz cohort” were screened. In anemic patients, we further investigated all laboratory results to differentiate between iron deficiency and other reasons for anemia. All patients with any kind of anemia were interviewed separately according to symptoms of iron-deficiency anemia and administration of iron. Results. In total, we evaluated hemoglobin values of 279 patients (183 Crohns disease, 90 ulcerative colitis, and 6 indeterminate colitis). Lab data which allowed further differentiation of the type of anemia were available in 70% of anemic patients, in 34.4% values of iron, ferritin and transferrin saturation had been measured. At time of first diagnosis, an iron-deficiency anemia was diagnosed in 26 of 68 patients with anemia (38.2%, 20 CD, 4 UC, and 2 IC patients), but only 9 patients (34.6%) received subsequent iron therapy. After one year, 27 patients were identified to have an iron-deficiency anemia (19 CD, 8 UC), 20 of them were treated with iron (71.4%). Of 9 patients with proven iron-deficiency anemia at time of first diagnosis and subsequent administration of iron, 5 (55.5%) had iron-deficiency anemia despite permanent treatment after one year. In total, 38 patients (54.3%) did not receive any iron substitution at all despite of proven iron-deficiency anemia, and only 13 patients of 74 patients were treated with intravenous iron (17.6%). Conclusion. We found a high prevalence of iron-deficiency anemia at different points during the early course of disease in this population-based cohort of IBD patients. Surprisingly, only in one-third of patients with proven anemia, further diagnostic approach was undertaken. Even patients with diagnosed iron-deficiency anemia were infrequently and inconsequently treated with iron preparations, despite the high impact on quality of life.

Determinants of female sexual function in inflammatory bowel disease: a survey based cross-sectional analysis

BackgroundSexual function is impaired in women with inflammatory bowel disease (IBD) as compared to normal controls. We examined disease specific determinants of different aspects of low sexual function.MethodsWomen with IBD aged 18 to 65 presenting to the university departments of internal medicine and surgery were included. In addition, a random sample from the national patients organization was used (separate analyses). Sexual function was assessed by the Brief Index of Sexual Function in Women, comprising seven different domains of sexuality. Function was considered impaired if subscores were < -1 on a z-normalized scale. Results are presented as age adjusted odds ratios with 95% CI based on multiple logistic regression.Results336 questionnaires were included (219 Crohns disease, 117 ulcerative colitis). Most women reported low sexual activity (63%; 17% none at all, 20% moderate or high activity). Partnership satisfaction was high in spite of low sexual interest in this group. Depressed mood was the strongest predictor of low sexual function scores in all domains. Urban residency and higher socioecomic status had a protective effect. Disease activity was moderately associated with low desire (OR 1.8, 95% CI 1.0 to 3.2). Severity of the disease course impacted most on intercourse frequency (OR 2.3, 95% CI 1.4 to 4.7). Lubrication problems were more common in smokers (OR 2.5, 95% CI 1.3 to 5.1).ConclusionMood disturbances and social environment impacted more on sexual function in women with IBD than disease specific factors. Smoking is associated with lubrication problems.

Magnetic resonance enterography with and without biphasic contrast agent enema compared to conventional ileocolonoscopy in patients with Crohn's disease

Background: Magnetic resonance imaging (MRI) of the bowel is a valuable diagnostic tool for assessing disease activity in patients with inflammatory bowel disease (IBD). We compared magnetic resonance enterography (MRE) with and without water enema to conventional ileocolonoscopy to evaluate the advantage of a water enema for MRI diagnostics of Crohns disease (CD). Methods: We prospectively evaluated 50 patients with known CD. MRE with enema was performed in 23 cases, whereas 27 patients received an MRE without enema. All patients underwent conventional ileocolonoscopy. We assessed the degree of inflammation in both modalities, evaluating up to seven bowel segments in each patient. We compared MRE with and without rectal enema to each other and to conventional ileocolonoscopy. Results: MRE achieved a sensitivity and specificity of 100% and 74%, respectively, for detection of inflammation in the terminal ileum with enema and a sensitivity and specificity of 72% and 87%, respectively, without enema. Considering the colon, MRE with enema had a sensitivity of 79% (specificity 96%), while the examination without enema showed a sensitivity of 38% (specificity 99%). MRE with enema proved statistically superior to MRE without enema in detecting inflammation in the terminal ileum, ascending colon, and rectum (P < 0.05). Conclusions: MRE with enema is a valuable diagnostic tool for assessing inflammation in CD patients. Water enema is well tolerated and significantly improves detection of inflammation in the terminal ileum. Water enema should therefore be included in MRE protocols for CD patients. (Inflamm Bowel Dis 2012)

A randomised, double-blind, placebo-controlled trial of trichuris suis ova in active crohn's disease

Abstract Background and Aims: To investigate the efficacy and safety of three different dosages of embryonated, viable eggs of Trichuris suis [TSO] versus placebo for induction of remission in mildly-to-moderately active ileocolonic, uncomplicated Crohn’s disease [CD]. Methods: Adults with active CD [n = 252] randomly received six fortnightly doses of 250, 2500, or 7500 TSO/15 ml suspension/day [TSO 250, TSO 2500, TSO 7500], or 15 ml placebo solution/day, in a double-blind fashion, with 4 weeks’ follow-up. Primary endpoint was the rate of clinical remission [Crohn’s Disease Activity Index [CDAI] < 150] at end of treatment, ie at Week 12 or withdrawal. Secondary endpoints included the course of clinical remission, rate of clinical response, change in CDAI, change in markers of inflammation, mucosal healing, and Physician’s Global Assessment. Results: Clinical remission at Week 12 occurred in 38.5%, 35.2%, and 47.2% of TSO 250, TSO 2500, and TSO 7500 patients, respectively, and in 42.9% of placebo recipients. TSO induced a dose-dependent immunological response. There was no response regarding laboratory markers of inflammation. Other secondary efficacy variables also showed no advantage of TSO over placebo for treatment of active CD. Administration of TSO did not result in any serious adverse drug reaction. Review of non-serious suspected adverse drug reactions following TSO did not reveal any safety concerns. Conclusions: Administration of 250–7500 TSO fortnightly over 12 weeks was safe and showed a dose-dependent immunological response, but no TSO dose showed a clinically relevant effect over placebo for induction of clinical remission or response in mildly-to-moderately active, ileocolonic CD.

The role of domestic hygiene in inflammatory bowel diseases: hepatitis A and worm infestations.

Background Environmental factors are likely to be involved in the pathogenesis of inflammatory bowel disease (IBD), as the incidence of both Crohns disease (CD) and ulcerative colitis (UC) increased with improved living standards in Europe after World War II. On the basis of earlier reports suggesting that hygienic standards may also play a role in the pathogenesis of IBD, we investigated the influence of hepatitis A seroprevalence as an indicator for poorer hygienic conditions and worm infestations in IBD. Methods Hepatitis A seroprevalence was examined in patients with UC and CD. Patients with minor endocrinological disorders served as controls. All patients were questioned about immunizations, parasitic infections (worms), contact with animals, living on a farm, and ever traveling abroad. Patients were excluded for active hepatitis A immunization or recent passive immunization. Results are presented as Mantel–Haenszel odds ratios with 95% confidence interval, adjusted for age group. Results The sample included 307 patients (73 CD, 48 UC, and 186 controls). Hepatitis A seroprevalence was strongly associated with age older than 50 years. Age adjusted Mantel–Haenszel odds ratios were 0.25 (0.09–0.71) for UC and 0.75 (0.38–1.46) for CD versus controls. For parasitic infections, the odds ratios were 1.15 (0.52–2.53) for UC and 0.34 (0.13–0.89) for CD. Conclusion We were able to demonstrate a negative association of hepatitis A infection with UC only. In contrast, a novel finding was a strong protective effect of worm infestations for the occurrence of CD, but not UC.

Interobserver Agreement in MR Enterography for Diagnostic Assessment in Patients with Crohn's Disease

PURPOSE To evaluate the extent to which MRE can be used as an observer-independent, objective imaging method for the diagnosis and evaluation of CD with respect to the detection of inflammatory changes of the small bowel and lymphadenopathy as diagnostic criterion and bowel distension as a quality criterion. MATERIALS AND METHODS MRE scans of 84 patients (42 female, median age 37 years) were evaluated independently by 4 experienced radiologists. Analysis of inflammatory changes of the bowel wall, lymphadenopathy and adequate bowel distension was conducted separately for the jejunum, ileum and terminal ileum. The Kendalls W-test was used for the statistical comparison of concordance. RESULTS In a total of 55 patients, inflammatory activity of the bowel wall was detected and MRE was found to have a high interobserver reproducibility concerning inflammatory changes of the intestinal wall (Kendalls W 0.527 - 0.823). Concerning lymphadenopathy (31 cases, 36.9 %), a low to moderate consensus could be shown with a Kendalls W value of 0.402 - 0.505. For the assessment of adequate bowel distension, a moderate concordance between the operators could be found (Kendalls W 0.497 - 0.581). CONCLUSION MRE has proven high interobserver agreement with respect to the diagnosis of inflammatory disease activity of the bowel as a diagnostic criterion in patients with CD. Concerning adequate bowel distension as a quality criterion of the examination itself and lymphadenopathy as a diagnostic criterion, moderate interobserver agreement could be found. This is thought to have a rather small effect on the diagnostic significance and conclusiveness of the method in the daily routine. KEY POINTS ▶ MR enterography as observer independent diagnostic procedure in patients with Chrons Disease. ▶ Highest interobserver concordance for the criterion of inflammatory bowel wall affection. ▶ Moderate interobserver concordance for lymphadenopathy and bowel distension.

Low Risk of Clostridium difficile Infections in Hospitalized Patients with Inflammatory Bowel Disease in a German Tertiary Referral Center

Introduction: Many reports, mainly from the US and Canada but also a recent report from a center in Europe, have documented the increasing impact of Clostridium difficile infections in patients with inflammatory bowel disease (IBD) during the last years. To determine the prevalence of C. difficile infections in hospitalized IBD patients in a tertiary referral center in Germany, we conducted this retrospective analysis. Methods: Data of all IBD in-patients treated due to an acute flare of their IBD at the Department of Internal Medicine I of the University of Regensburg between January 1, 2001, and June 30, 2008, were analyzed. In patients with a concomitant diagnosis of C. difficile infection, further variables such as IBD-related treatment at the time of infection or outcome were examined. Results: In total, 995 in-patients with IBD were treated in this hospital [638 patients with Crohn’s disease (CD), 357 with ulcerative colitis (UC)] during the study period. Of these, 279 patients with CD and 242 patients with UC were admitted with an acute flare and suffering from diarrhea and abdominal pain. Only 10 of those were diagnosed as having a concomitant infection with C. difficile. Six patients were female and the median age was 49 years (range: 15–80). Six patients with C. difficile infections suffered from UC and 4 patients from CD, all with previous colonic involvement. Eight patients used immunosuppressive therapies; only 2 patients were treated with antibiotics before infection. Conclusion: In contrast to recent reports from other countries, only a low percentage of hospitalized patients with acute flares of their IBD were identified as having an underlying C. difficile infection in this German tertiary referral center. However, in IBD patients with an acute flare, a concomitant C. difficile infection should be excluded, especially in patients with immunosuppressive treatment and colonic involvement of their disease. Further research is needed to evaluate if regions with different risks of C. difficile infections exist and to find out more about potential reasons for this observation.