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Background: Over the last 20 years, diverse outcome measures have been used to evaluate the effectiveness of therapies for eosinophilic esophagitis (EoE). This systematic review aims to identify the readouts used in observational studies of topical corticosteroids, diet, and dilation in adult EoE patients. Methods: We searched MEDLINE and Embase for prospective and retrospective studies (cohorts/case series, randomized open-label, and case-control) evaluating the use of diets, dilation, and topical corticosteroids in adults with EoE. Two authors independently assessed the articles and extracted information about histologic, endoscopic, and patient-reported outcomes and tools used to assess treatment effects. Results: We included 69 studies that met inclusion criteria. EoE-associated endoscopic findings (assessed either as absence/presence or using Endoscopic Reference Score) were evaluated in 24/35, 11/17, and 9/17 studies of topical corticosteroids, diet, and dilation, respectively. Esophageal eosinophil density was recorded in 32/35, 17/17, and 11/17 studies of topical corticosteroids, diet, and dilation, respectively. Patient-reported outcomes were not uniformly used (only in 14, 8, and 3 studies of topical corticosteroids, diet, and dilation, respectively), and most tools were not validated for use in adults with EoE. Conclusions: Despite the lack of an agreed set of core outcomes that should be recorded and reported in studies in adult EoE patients, endoscopic EoE-associated findings and esophageal eosinophil density are commonly used to assess disease activity in observational studies. Standardization of outcomes and data supporting the use of outcomes are needed to facilitate interpretation of evidence, its synthesis, and comparisons of interventions in meta-analyses of therapeutic trials in adults with EoE. [ABSTRACT FROM AUTHOR]

Introduction: Rebleeding or emergency surgery in failed endoscopic therapy of peptic ulcer bleeding are associated with high rates of morbidity and mortality. The clinical benefit of an endoscopic Doppler (ED) examination prior to endoscopic injection therapy was evaluated in high risk ulcer patients for rebleeding episode. Standard injection therapy (non-Doppler (ND)) was compared with targeted injection therapy after examination of the supplying vessel in the ulcer base by the ED. Materials and methods: Sixty patients with peptic ulcer bleeding (Forrest Ia-IIa; Rockall score of 5 or higher) were included in the study. Patients were assigned to ED or ND group with conventional therapy by chance. In the ND group injection was directed by the visual aspect of the ulcer, whereas in ED therapy was directed by ED. Results: Thirty-five patients were allocated to the ED group, and 25 to the ND group, respectively. No significant differences in patient or ulcer characteristics were observed regarding ulcer size, localization, Forrest classification or endoscopic treatment. Recurrent bleeding was observed in 7/35 (20%) in the ED group and in 13/25 (52%) of patients in the ND group (p = .013). Fewer ED patients needed surgery for rebleeding (1/35 vs. 6/25; p = .017). Bleeding related, but not all-cause mortality was significantly lower in the ED group (1/35 vs. 6/25, p = .017). Discussion: In this comparative analysis, use of ED to guide hemostatic therapy was associated with a significant reduction in recurrence of bleeding, surgical intervention and bleeding associated mortality. [ABSTRACT FROM AUTHOR]

Background and aims: Eosinophilic esophagitis (EoE) is a mixed inflammatory and fibrostenotic disease. Unlike superficial inflammatory changes, subepithelial fibrosis is not routinely sampled in esophageal biopsies. This study aimed to evaluate the efficacy and safety of deep esophageal sampling with four different types of biopsy forceps. Patients and methods: In this cross-sectional study, esophageal biopsies were taken in 30 adult patients by one expert endoscopist. Biopsies sampled from distal esophagus using a static jaw forceps (Olympus, FB-11K-1) were compared with proximal biopsies sampled with static jaw (Olympus, FB-45Q-1), alligator jaw (Olympus, FB-210K), and large-capacity forceps (Boston Scientific, Radial Jaw 4). One pathologist calculated the surface area of epithelial and subepithelial layers in hematoxylin and eosin (H&E)-stained biopsies. Results: Subepithelial tissue was acquired in 97% (static jaw FB-11K-1), 93% (static jaw FB-45Q-1), 80% (alligator jaw), and 55% (large-capacity) of samples. Median (interquartile [IQR]) ratios of surface area of epithelial to subepithelial tissue were: static jaw FB-45Q-1, 1.07 (0.65-4.465); static jaw FB-11K-1, 1.184 (0.608-2.545); alligator jaw, 2.353 (1.312-4.465); and large-capacity, 2.71 (1.611-4.858). The static jaw models obtained a larger surface area of subepithelial tissue compared with the alligator jaw (P<0.001 and P= 0.037, for FB-11K-1 and FB-45Q-1, respectively) and the large-capacity forceps (P<0.001, for both static jaw models). No esophageal perforations occurred. Conclusions: The static jaw forceps models allowed sampling of subepithelial tissue in >90% of biopsies and appear to be superior to alligator or large-capacity forceps in sampling larger amounts of subepithelial tissue. [ABSTRACT FROM AUTHOR]

OBJECTIVES:There is no 'gold standard' for assessing disease activity in patients with eosinophilic esophagitis (EoE). We aimed to compare physicians' judgment of EoE activity with patients' judgment of symptom severity. We also aimed to examine the relative contribution of symptoms as well as endoscopic and histologic findings in shaping physicians' judgment of EoE activity.METHODS:Six gastroenterologists (all EoE experts) assessed EoE-associated symptoms in adult patients. Patients completed a symptom instrument and provided global assessment of EoE symptom severity (PatGA) (Likert scale: 0 (inactive) to 10 (most active)). Following esophagogastroduodenoscopy with biopsy sampling, gastroenterologists provided a global assessment of EoE activity (PhysGA) (Likert scale from 0 to 10) based on patient history and endoscopic and histologic findings. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms and endoscopic and histologic findings explain variations in PhysGA.RESULTS:A total of 149 EoE patients were prospectively included (71.8% male, median age at inclusion 38 years, 71.8% with concomitant allergies). A moderate positive correlation between PhysGA and PatGA (rho=0.442, P<0.001) was observed and the mean difference in the Bland-Altman plot was 1.77. Variations in severity of endoscopic findings, symptoms, and histologic findings alone explained 53%, 49%, and 30%, of the variability in PhysGA, respectively. Together, these findings explained 75% of variability in PhysGA.CONCLUSIONS:Gastroenterologists rate EoE activity mainly on the basis of endoscopic findings and symptoms and, to a lesser extent, on histologic findings. [ABSTRACT FROM AUTHOR]

OBJECTIVES:The impact of diagnostic delay (a period from appearance of first symptoms to diagnosis) on the clinical course of Crohn's disease (CD) is unknown. We examined whether length of diagnostic delay affects disease outcomes.METHODS:Data from the Swiss IBD cohort study were analyzed. Patients were recruited from university centers (68%), regional hospitals (14%), and private practices (18%). The frequencies of occurrence of bowel stenoses, internal fistulas, perianal fistulas, and CD-related surgery (intestinal and perianal) were analyzed.RESULTS:A total of 905 CD patients (53.4% female, median age at diagnosis 26 (20-36) years) were stratified into four groups according to the quartiles of diagnostic delay (0-3, 4-9, 10-24, and ≥25 months, respectively). Median diagnostic delay was 9 (3-24) months. The frequency of immunomodulator and/or antitumor necrosis factor drug use did not differ among the four groups. The length of diagnostic delay was positively correlated with the occurrence of bowel stenosis (odds ratio (OR) 1.76, P=0.011 for delay of ≥25 months) and intestinal surgery (OR 1.76, P=0.014 for delay of 10-24 months and OR 2.03, P=0.003 for delay of ≥25 months). Disease duration was positively associated and non-ileal disease location was negatively associated with bowel stenosis (OR 1.07, P<0.001, and OR 0.41, P=0.005, respectively) and intestinal surgery (OR 1.14, P<0.001, and OR 0.23, P<0.001, respectively).CONCLUSIONS:The length of diagnostic delay is correlated with an increased risk of bowel stenosis and CD-related intestinal surgery. Efforts should be undertaken to shorten the diagnostic delay. [ABSTRACT FROM AUTHOR]

The majority of Crohn's disease patients will develop a complicated disease course over time which is characterized by the occurrence of stricturing and penetrating disease. Penetrating disease comprises internal fistulas (e.g. enteroenteric) and perianal disease. A complicated disease course may be associated with considerable morbidity and professional and personal disabilities. Treatment options for fibrostenotic Crohn's disease comprise endoscopic balloon dilation, stricturoplasties and surgical resection. Treatment of symptomatic perianal fistulizing disease is based on antibiotics, immunomodulators and anti-TNF drugs. Surgical measures include fistula drainage by means of setons, temporary ileostomy or a proctectomy. The presence of internal fistulas often necessitates surgical measures. A close collaboration between the gastroenterologist and the surgeon is mandatory to solve these interdisciplinary challenges. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The majority of Crohn's disease patients will develop a complicated disease course over time which is characterized by the occurrence of stricturing and penetrating disease. Penetrating disease comprises internal fistulas (e.g. enteroenteric) and perianal disease. A complicated disease course may be associated with considerable morbidity and professional and personal disabilities. Treatment options for fibrostenotic Crohn's disease comprise endoscopic balloon dilation, stricturoplasties and surgical resection. Treatment of symptomatic perianal fistulizing disease is based on antibiotics, immunomodulators and anti-TNF drugs. Surgical measures include fistula drainage by means of setons, temporary ileostomy or a proctectomy. The presence of internal fistulas often necessitates surgical measures. A close collaboration between the gastroenterologist and the surgeon is mandatory to solve these interdisciplinary challenges. [ABSTRACT FROM AUTHOR]

Abstract: Background: There is increasing evidence for the clinical relevance of mucosal healing (MH) as therapeutic treatment goal in inflammatory bowel disease (IBD). We aimed to investigate by which method gastroenterologists monitor IBD activity in daily practice. Methods: A questionnaire was sent to all board-certified gastroenterologists in Switzerland to specifically address their strategy to monitor IBD between May 2009 and April 2010. Results: The response rate was 57% (153/270). Fifty-two percent of gastroenterologists worked in private practice and 48% worked in hospitals. Seventy-eight percent judged clinical activity to be the most relevant criterion for monitoring IBD activity, 15% chose endoscopic severity, and 7% chose biomarkers. Seventy percent of gastroenterologists based their therapeutic decisions on clinical activity, 24% on endoscopic severity, and 6% on biomarkers. The following biomarkers were used for IBD activity monitoring: CRP, 94%; differential blood count, 78%; fecal calprotectin (FC), 74%; iron status, 63%; blood sedimentation rate, 3%; protein electrophoresis, 0.7%; fecal neutrophils, 0.7%; and vitamin B12, 0.7%. Gastroenterologists in hospitals and those with ≤10years of professional experience used FC more frequently compared with colleagues in private practice (P =0.035) and those with >10years of experience (P <0.001). Conclusions: Clinical activity is judged to be more relevant for monitoring IBD activity and guiding therapeutic decisions than endoscopic severity and biomarkers. As such, the accumulating scientific evidence on the clinical impact of mucosal healing does not yet seem to influence the management of IBD in daily gastroenterologic practice. [Copyright &y& Elsevier]

OBJECTIVES:Esophageal dilation often leads to long-lasting relief of dysphagia in eosinophilic esophagitis (EoE). The aim of this study was to define the effectiveness, safety, and patient acceptance of esophageal dilation in EoE. In addition, we examined the influence of dilation on the underlying esophageal inflammation.METHODS:Two databases including 681 EoE patients were reviewed. Cohort 1 consisted of patients treated with dilation alone, whereas cohort 2 included patients treated with a combination of dilation and antieosinophilic medication. Patients from cohort 1 underwent a prospective histological reexamination and an evaluation using a questionnaire.RESULTS:In total, 207 EoE patients were treated with esophageal dilation, 63 in cohort 1 and 144 in cohort 2. Dilation led to a significant increase in esophageal diameter and to an improvement in dysphagia in both the cohorts (P<0.001). After dilation, dysphagia recurred after 23±22 months in cohort 1 and 20±14 months in cohort 2. No esophageal perforation or major bleeding occurred. Among the patients surveyed, 74% reported retrosternal pain after dilation; however, all were agreeable to repeated dilation if required. Eosinophil peak infiltration, eosinophil load, and EoE-associated histological signs were not significantly affected by esophageal dilation.CONCLUSIONS:Esophageal dilation is highly effective in providing long-lasting symptom relief and can be performed safely with a high degree of patient acceptance. However, dilation is associated with postprocedural pain in most patients and does not influence the underlying inflammatory process. Symptom improvement despite persistence of inflammation suggests that tissue remodeling contributes substantially to symptom generation in EoE. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Studies evaluating the correlation between the widely used Simple Endoscopic Score for Crohn's disease (SES-CD) and noninvasive markers are scarce. The aim of this study was to evaluate the correlation between the SES-CD and fecal calprotectin, C-reactive protein (CRP), blood leukocytes, and the Crohn's disease activity index (CDAI).METHODS:Crohn's disease patients undergoing complete ileocolonoscopy were prospectively enrolled and scored independently according to the SES-CD and the CDAI. SES-CD was defined as follows: inactive 0–3; mild 4–10; moderate 11–19; and high ≥20.RESULTS:Values in CD patients (n=140 ileocolonoscopies) compared with controls (n=43) are as follows: calprotectin, 334±322 vs. 18±5 μg/g; CRP, 26±29 vs. 3±2 mg/l; and blood leukocytes, 9.1±3.4 vs. 5.4±1.9 g/l (all P<0.001). The SES-CD correlated closest with calprotectin (Spearman's rank correlation coefficient r=0.75), followed by CRP (r=0.53), blood leukocytes (r=0.42), and the CDAI (r=0.38). Calprotectin was the only marker that could discriminate inactive endoscopic disease from mild activity (104±138 vs. 231±244 μg/g, P<0.001), mild from moderate activity (231±244 vs. 395±256 μg/g, P=0.008), and moderate from high activity (395±256 vs. 718±320 μg/g, P<0.001). The overall accuracy for the detection of endoscopically active disease was 87% for calprotectin (cutoff 70 μg/g), 66% for elevated CRP, 54% for blood leukocytosis, and 40% for the CDAI ≥150.CONCLUSIONS:Fecal calprotectin correlated closest with SES-CD, followed by CRP, blood leukocytes, and the CDAI. Furthermore, fecal calprotectin was the only marker that reliably discriminated inactive from mild, moderate, and highly active disease, which underlines its usefulness for activity monitoring. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Mannan-binding lectin (MBL) acts as a pattern-recognition molecule directed against oligomannan, which is part of the cell wall of yeasts and various bacteria. We have previously shown an association between MBL deficiency and anti-Saccharomyces cerevisiae mannan antibody (ASCA) positivity. This study aims at evaluating whether MBL deficiency is associated with distinct Crohn's disease (CD) phenotypes.METHODS:Serum concentrations of MBL and ASCA were measured using ELISA (enzyme-linked immunosorbent assay) in 427 patients with CD, 70 with ulcerative colitis, and 76 healthy controls. CD phenotypes were grouped according to the Montreal Classification as follows: non-stricturing, non-penetrating (B1, n=182), stricturing (B2, n=113), penetrating (B3, n=67), and perianal disease (p, n=65). MBL was classified as deficient (<100 ng/ml), low (100–500 ng/ml), and normal (500 ng/ml).RESULTS:Mean MBL was lower in B2 and B3 CD patients (1,503±1,358 ng/ml) compared with that in B1 phenotypes (1,909±1,392 ng/ml, P=0.013). B2 and B3 patients more frequently had low or deficient MBL and ASCA positivity compared with B1 patients (P=0.004 and P<0.001). Mean MBL was lower in ASCA-positive CD patients (1,562±1,319 ng/ml) compared with that in ASCA-negative CD patients (1,871±1,320 ng/ml, P=0.038). In multivariate logistic regression modeling, low or deficient MBL was associated significantly with B1 (negative association), complicated disease (B2+B3), and ASCA. MBL levels did not correlate with disease duration.CONCLUSIONS:Low or deficient MBL serum levels are significantly associated with complicated (stricturing and penetrating) CD phenotypes but are negatively associated with the non-stricturing, non-penetrating group. Furthermore, CD patients with low or deficient MBL are significantly more often ASCA positive, possibly reflecting delayed clearance of oligomannan-containing microorganisms by the innate immune system in the absence of MBL. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Reactivation of latent tuberculosis (TB) in inflammatory bowel disease (IBD) patients treated with antitumor necrosis factor-alpha medication is a serious problem. Currently, TB screening includes chest x-rays and a tuberculin skin test (TST). The interferon-gamma release assay (IGRA) QuantiFERON-TB Gold In-Tube (QFT-G-IT) shows better specificity for diagnosing TB than the skin test. This study evaluates the two test methods among IBD patients. METHODS: Both TST and IGRA were performed on 212 subjects (114 Crohn's disease, 44 ulcerative colitis, 10 indeterminate colitis, 44 controls). RESULTS: Eighty-one percent of IBD patients were under immunosuppressive therapy; 71% of all subjects were vaccinated with Bacille Calmette Guérin; 18% of IBD patients and 43% of controls tested positive with the skin test ( P < 0.0001). Vaccinated controls tested positive more often with the skin test (52%) than did vaccinated IBD patients (23%) ( P= 0.011). Significantly fewer immunosuppressed patients tested positive with the skin test than did patients not receiving therapy ( P= 0.007); 8% of patients tested positive with the QFT-G-IT test (14/168) compared to 9% (4/44) of controls. Test agreement was significantly higher in the controls ( P= 0.044) compared to the IBD group. CONCLUSIONS: Agreement between the two test methods is poor in IBD patients. In contrast to the QFT-G-IT test, the TST is negatively influenced by immunosuppressive medication and vaccination status, and should thus be replaced by the IGRA for TB screening in immunosuppressed patients having IBD. [ABSTRACT FROM AUTHOR]

Background/Aims: Herbal agents are popular and perceived as safe because they are supposedly ‘natural’. We report 10 cases of toxic hepatitis implicating Herbalife® products. Methods: To determine the prevalence and outcome of hepatotoxicity due to Herbalife® products. A questionnaire was sent to all public Swiss hospitals. Reported cases were subjected to causality assessment using the CIOMS criteria. Results: Twelve cases of toxic hepatitis implicating Herbalife® preparations (1998–2004) were retrieved, 10 sufficiently documented to permit causality analysis. Median age of patients was 51 years (range 30–69) and latency to onset was 5 months (0.5–144). Liver biopsy (7/10) showed hepatic necrosis, marked lymphocytic/eosinophilic infiltration and cholestasis in five patients. One patient with fulminant liver failure was successfully transplanted; the explant showed giant cell hepatitis. Sinusoidal obstruction syndrome was observed in one case. Three patients without liver biopsy presented with hepatocellular (2) or mixed (1) liver injury. Causality assessment of adverse drug reaction was classified as certain in two, probable in seven and possible in one case(s), respectively. Conclusions: We present a case series of toxic hepatitis implicating Herbalife® products. Liver toxicity may be severe. A more detailed declaration of components and pro-active role of regulatory agencies would be desirable. [Copyright &y& Elsevier]

Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease of increasing prevalence, characterized by symptoms of dysphagia and reduced quality of life. A dysregulated type 2 immune response to food and aeroallergen leads to barrier dysfunction, chronic esophageal inflammation, remodeling, and fibrosis. Patients with EoE have impaired quality of life because of dysphagia and other symptoms. They may also suffer social and psychological implications of food-related illness and expensive out-of-pocket costs associated with treatment. Disease burden in EoE is often compounded by the presence of comorbid type 2 inflammatory diseases. Current conventional treatments include elimination diet, proton pump inhibitors, and swallowed topical corticosteroids, as well as esophageal dilation in patients who have developed strictures. These treatments demonstrate variable response rates and may not always provide long-term disease control. There is an unmet need for long-term histologic, endoscopic, and symptomatic disease control; for targeted therapies that can normalize the immune response to triggers, reduce chronic inflammation, and limit or prevent remodeling and fibrosis; and for earlier diagnosis, defined treatment outcomes, and a greater understanding of patient perspectives on treatment. In addition, healthcare professionals need a better understanding of the patient perspective on disease burden, the disconnect between symptoms and disease activity, and the progressive nature of EoE and the need for continuous monitoring and maintenance treatment. In this review, we explore the progression of disease over the patient's lifespan, highlight the patient perspective on disease, and discuss the unmet need for effective long-term treatments. [ABSTRACT FROM AUTHOR]

Introduction: Given the lack of data, we aimed to explore which therapeutic endpoints pediatric patients with eosinophilic esophagitis (EoE) and their parents consider to be relevant. Methods: We created an educational brochure on EoE and a questionnaire, both of which were content-validated by pediatric patients and parents. Validated documents were sent to 112 patients and parents. They ranked the importance (5 levels) of short (during next 3 months) and long-term (≥1 year) treatment effect on symptoms, quality of life, endoscopic inflammation, stricture formation, histological inflammation, and fibrosis. Results: A total of 45 parents and 30 pediatric patients ≥11 years completed the questionnaires. Pediatric patients identified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (73% vs. 77%), QoL (53% vs. 57%), histologic inflammation (47% vs. 50%), histologic fibrosis (40% vs. 33%), endoscopic inflammation (47% vs. 40%), and strictures (33% vs. 40%). Parents of children ≥11 years old classified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (70% vs. 83%), QoL (63% vs. 80%), histologic inflammation (67% vs. 77%), histologic fibrosis (47% vs. 63%), endoscopic inflammation (77% vs. 80%), and strictures (40% vs. 53%). Agreement between caregiver and children on the short-term importance of treatment outcomes was as follows: symptoms (77%), QoL (40%), histologic inflammation and fibrosis (47% and 43%), endoscopic inflammation and strictures (50% and 40%). Conclusion: Pediatric patients and parents attributed most importance to improvement in symptoms and QoL. Agreement between parents and patients regarding therapy goals is limited. [ABSTRACT FROM AUTHOR]

Introduction: It is still unknown whether eosinophilic esophagitis (EoE) patients with localized disease are different from those with extended disease. Methods: We evaluated prospectively included patients in the Swiss EoE cohort. Data on all patients with active disease at baseline, no concomitant gastroesophageal reflux disease, no strictures at baseline, and at least one follow-up visit were analyzed. We compared patients with histologically localized proximal versus distal versus extended (=proximal and distal) disease with regard to patient, disease characteristics, disease presentation, and development of complications. Results: We included 124 patients with a median of 2.5 years of follow-up (73.4% males, median age 35.0 years). Ten patients had proximal (8.1%), 46 patients had distal (37.1%), and 68 patients had extended disease (54.8%). Patients with proximal disease were significantly more often females (80%) compared with patients with distal (26.1%, p = 0.002) or extended disease (19.1%, p < 0.001) and reported less severe symptoms (VAS 0 vs. VAS 1, p = 0.001). Endoscopic and histological disease was less pronounced in the proximal esophagus of proximal EoE compared to extended disease (EREFS 1.0 vs. 3.0, p = 0.001; 27.0 eos/hpf vs. 52.5 eos/hpf, p = 0.008). Patients with proximal disease were less likely to undergo dilation compared to patients with distal disease in the follow-up (3.3% vs. 23.3%, p = 0.010). In a multivariate Cox regression model, proximal eosinophilia was less likely to be associated with treatment failure compared to distal eosinophilia. Conclusion: Although isolated proximal EoE is infrequent, it is associated with less severe disease and better disease outcome. Proximal disease appears to present a unique EoE phenotype. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We investigated whether dilation modifies the association between symptoms and esophageal eosinophilia (peak esophageal eosinophils/high-power field [eos/hpf]) in patients with eosinophilic esophagitis enrolled into a randomized trial comparing the efficacy of budesonide and fluticasone. METHODS: Baseline Dysphagia Symptom Questionnaire and Eosinophilic Esophagitis Activity Index were available in 102 and 73 patients, respectively, of whom 56 and 39 underwent dilation at screening endoscopy before symptom assessment. The pair-wise relationship between Dysphagia Symptom Questionnaire, Eosinophilic Esophagitis Activity Index, and eos/hpf was analyzed with nonparametric correlations. RESULTS: In nondilated patients, the association between baseline eos/hpf and symptoms was moderate and significant, although it was abolished in dilated patients. DISCUSSION: Dilation modifies association between symptoms and eos/hpf (clinicaltrials.gov NCT02019758). [ABSTRACT FROM AUTHOR]

Background: Patient care in ulcerative colitis (UC) remains challenging despite an array of established treatment options and emerging new therapies. The management of UC therapy should be guided by the endoscopic extent of inflammation, disease severity, and prognostic factors of poor outcome. Complete remission, defined as durable symptomatic and endoscopic remission without corticosteroid therapy, is the desired treatment goal. Summary: This review focuses on treatment recommendations for different clinical scenarios in moderate-to-severe UC: Active UC of any extent not responding to aminosalicylates, steroid-dependent UC, steroid-refractory UC, immunomodulator-refractory UC, and acute severe UC. Comprehensive treatment algorithms for daily clinical practice were developed based on published guidelines and current literature. Key Messages: While current treatment options including a number of biologicals and small molecules have evolved UC treatment to achieve sustained remission in a majority of patients, upcoming treatment options with different molecular pathways and different modes of actions will further increase the need for personalized medicine. [ABSTRACT FROM AUTHOR]

Having long been considered the mainstay in eosinophilic esophagitis (EoE) diagnosis and pathogenesis, the role of eosinophils has been questioned and might be less important than previously thought. It is well known now that EoE is a Th2-mediated disease with many more disease features than eosinophilic infiltration. With more knowledge on EoE, less pronounced phenotypes or nuances of the disease have become apparent. In fact, EoE might be only the tip of the iceberg (and the most extreme phenotype) with several variant forms, at least three, lying on a disease spectrum. Although a common (food induced) pathogenesis has yet to be confirmed, gastroenterologists and allergologists should be aware of these new phenomena in order to further characterize these patients. In the following review, we discuss the pathogenesis of EoE, particularly those mechanisms beyond eosinophilic infiltration of the esophageal mucosa, non-eosinophilic inflammatory cell populations, the new disease entity EoE-like disease, variant forms of EoE, and the recently coined term mast cell esophagitis. [ABSTRACT FROM AUTHOR]

Background: Real-life data on inflammatory bowel disease (IBD) prevalence and costs are scarce. The aims of this study were to provide an overview of the prevalence, mortality, health care utilization and costs of IBD patients in Switzerland in the years 2010, 2012, and 2014.Methods: Based on claims data of the Helsana-Group, prevalence of IBD was assessed for 2010, 2012 and 2014. Mortality rates, costs (inpatient, outpatient, medication costs) and utilization (visits, hospitalizations) were compared between patients with and without IBD, and between IBD patients treated with and without biologics. Results were extrapolated to the Swiss general population using national census data. Multivariate linear regression was used to identify socio-demographic and regional factors influencing total costs.Results: The overall extrapolated prevalence rates of IBD were 0.32% in 2010, 0.38% in 2012, and 0.41% in 2014. Mortality rate didn't differ between the IBD and non-IBD population. Costs increased annually by 6% in IBD versus 2.4% in non-IBD subjects, which was solely due to increased outpatient costs. Almost one-fourth of IBD patients were hospitalized at least once a year. Costs were higher in IBD patients treated with biologics (OR = 3.98, CI: 3.72-4.27, p < 0.001) when compared to IBD patients without biologic therapies. Over 70% of the total costs in IBD patients treated with biologics were due to drug costs, compared with 28% in patients without use of biologic therapies, whereas inpatient costs didn't differ.Conclusions: The prevalence of IBD seems to be increasing in Switzerland. Outpatient costs increased substantially, while no decrease in inpatient costs was found. Treatment of IBD is more and more based on biologic therapies. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic progressive disease. Diagnostic delay (DD) is associated with increased risk of esophageal strictures and food impactions. We aimed to assess the evolution of DD since the first description of EoE in 1993 until 2021. METHODS: We analyzed data from patients prospectively included in the Swiss EoE database. DD was calculated as the time interval between the first occurrence of EoE symptoms and the confirmed diagnosis. DD was analyzed annually over time (1989–2021) and according to milestone publications in the field (1993: first description; 2007: first consensus recommendations; and 2011: updated consensus recommendations). In addition, a Cox proportional hazards model has been used to describe the relation between DD and covariates. RESULTS: Complete data of 1,152 patients (857 male [74%]; median age at diagnosis: 38 years, interquartile range: 28–49, range: 1–86) were analyzed. Overall, median DD was 4 years (interquartile range: 1–11, range, 0–56), with DD ≥ 10 years in 32% of the population. Over time, DD did not significantly change, neither annually nor according to release dates of milestone publications with a persistently stable fraction of roughly one-third of all patients with a DD of ≥10 years. Both ages at diagnosis (P < 0.001, with an increase in DD up to the age of 31–40 years) and at symptom onset (younger patients had a longer DD; P < 0.001) were significantly associated with DD. DISCUSSION: DD has not changed since the first description of EoE almost 30 years ago and remains substantial. Even today, one-third of patients have a persistently high DD of ≥10 years. Substantial efforts are warranted to increase awareness for EoE and its hallmark symptom, solid food dysphagia, as an age-independent red-flag symptom among healthcare professionals and presumably the general population alike to lower risk of long-term complications. [ABSTRACT FROM AUTHOR]

Objective: Physicians are increasingly confronted with patients presenting with symptoms of esophageal dysfunction resembling eosinophilic esophagitis (EoE), but absence of significant esophageal eosinophilia. The purpose of this study was to characterize and classify this group of EoE variants. Design: Patients from six EoE‐centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <60/mm2 (<15/hpf) in esophageal biopsies and absence of gastro‐esophageal reflux disease (GERD) were included. Clinical, endoscopic, (immuno)‐histological, and molecular features were determined and compared with EoE, GERD, and healthy controls. Results: We included 69 patients with EoE variants. Endoscopic abnormalities were found in 53.6%. We identified three histological subtypes: EoE‐like esophagitis (36/69, 52.2%), lymphocytic esophagitis (14/69, 20.3%), and non‐specific esophagitis (19/69, 27.5%). Immunohistochemistry revealed—in contrast to EoE—no significant increase in inflammatory cell infiltrates compared with GERD and healthy controls, except for lymphocytes in lymphocytic esophagitis. EoE‐typical Th2‐response was absent in all EoE variants. However, considerable structural changes were detected based on histology and protein expression. Using next generation mRNA sequencing, we found the three EoE variants to have distinct molecular fingerprints partially sharing pronounced traits of EoE. Hierarchical sample clustering of RNA sequencing data confirmed the presence of an EoE‐like (characterized by eotaxin‐3 expression), non‐specific, and lymphocytic variant cluster (characterized by CD3 cells and TSLP expression). Conclusion: All EoE variants are clinically and histologically active conditions despite the absence of esophageal eosinophilia. EoE variants appear to be part of a disease spectrum, where classical EoE represents the most common and apparent phenotype. [ABSTRACT FROM AUTHOR]

Abstract: Background: Anaemia represents a common complication of inflammatory bowel disease (IBD). Most studies on anaemia in IBD patients have been performed in tertiary referral centres (RC) and data from gastroenterologic practices (GP) are lacking. We investigated the frequency and severity of anaemia in IBD patients from tertiary referral centres and gastroenterologic practices compared to the general population. Methods: Data were acquired from patients included in the Swiss IBD Cohort Study. IBD activity was evaluated by CDAI and modified Truelove and Witts severity index (MTWSI). Anaemia was defined as haemoglobin ≤120g/L in women and ≤130g/L in men. Results: 125 patients from RC (66 with Crohn''s disease (CD) and 59 with ulcerative colitis (UC)) and 116 patients from GP (71 CD and 45 UC) were included and compared to 6074 blood donors. Anaemia was found in 21.2% (51/241) of the IBD patients and more frequently in patients from RC as compared to GP and healthy controls (28.8% vs. 12.9% vs. 3.4%; P <0.01). IBD patients from RC suffered more frequently from active disease compared to IBD patients in GP (36% vs. 23%, P =0.032). Supplementation therapy (iron, vitamine B12, folic acid) was performed in 40% of anaemic IBD patients in GP as compared to 43% in RC. Conclusions: Anaemia is a common complication in patients with IBD and significantly more prevalent in patients from referral centres as compared to patients from gastroenterologic practices. Physicians treating IBD patients should pay attention to the presence of anaemia and ensure sufficient supplementation therapy. [Copyright &y& Elsevier]

Inflammatory bowel disease (IBD) is increasingly diagnosed among elderly persons (older than 60 years). Epidemiological studies show that late-onset IBD is characterized by predominance of colonic disease, milder disease course, and less frequent occurrence of extraintestinal manifestations. However, due to comorbidities, polypharmacy and reduced resistance to severe disease course elderly patients have an increased risk of mortality. Drug treatment generally follows the same algorithms as in the younger IBD patients. This is challenging for the treating physician as this population is usually underrepresented in clinical trials and treatment outcomes as well as safety data on the elderly population are scarce. Choice of drugs should consider risk of infections, skin cancer, lymphoma, and metabolic as well as cardiovascular side effects. Considering comorbidities, surgical interventions such as colectomy with ileo-anal pouch anastomosis for refractory ulcerative colitis can be performed safely provided that the anal sphincter function is adequately maintained. Special attention should be given in this age group to general health issues, including nutrition, vaccination, bone, muscle, and mental health as well as colorectal and skin cancer screening. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) affects patients during their peak reproductive years. This raises important questions, in both patients and healthcare providers, regarding conception, pregnancy, and breastfeeding. Lack of information and insufficient communication among healthcare providers can leave patients with limited information and even contradictory advice. Given the fact that pregnant and/or breastfeeding IBD patients are excluded from clinical studies the evidence on many questions related to pregnancy and postpartum period is limited. However, there exists increasing data from case series and cohort studies that allows to provide clinical guidance. The overarching concept is that optimizing the mother's health is critical for optimizing the health of the unborn child and benefit of continuing medical therapy in IBD during pregnancy outweighs possible risks in most instances. This paper provides an up-to-date systematic review of the literature on IBD in pregnancy and proposes guidance to questions frequently encountered by healthcare professionals. [ABSTRACT FROM AUTHOR]

Background: While the long-term evolution of disease behavior in Crohn's disease has been well described in the pre-anti-TNF era, our knowledge thereon remains scarce after the introduction of anti-TNF.Aims: Our investigation examined the long-term evolution of disease concerning Montreal classification's B-stages over time in patients enrolled into the Swiss IBD Cohort Study between 2006 and 2017.Methods: We analyzed prospectively collected SIBDCS data using a Markov model and multivariate testing for effects of treatment and other confounders on B-stage migration over time. The primary outcome was a transition in disease behavior from B1 to either B2 or pB3, or from B2 to pB3, respectively.Results: The 10- and 15-year probability of remaining in B1 was 0.61 and 0.48, as opposed to a probability to migrate to B2 or B3 of 0.25 or 0.14, and 0.32 or 0.2, after 10 and 15 years, respectively. In multivariate testing, the hazard ratio for migrating from B1 to pB3 (HR 0.27) and from B2 to pB3 (HR 0.12) was lower in patients > 40 years compared to patients < 17 years. We found that immunosuppression (HR 0.38) and treatment with anti-TNF for > 1 year (HR 0.30) were associated with a decreased likelihood of transitioning from stage B1 to pB3.Conclusions: While in the anti-TNF era most patients with Crohn's disease will eventually develop stricturing and/or penetrating complications, our data indicate that immunosuppressive and anti-TNF treatment for more than 1 year reduce the risk of transitioning from stage B1 to pB3 in the long-term run. [ABSTRACT FROM AUTHOR]

Background: Loss of response is frequently encountered in patients with inflammatory bowel disease (IBD) treated with antitumor necrosis factor (TNF) agents. Therapeutic drug monitoring (TDM) and antidrug antibody measurement are increasingly used in this setting. Methods: To establish a consensus on the use of TDM in the context of loss of response to anti-TNFs, we performed a vote using a Delphi-style process followed by an expert panel discussion among 8 IBD specialists practicing in Switzerland, Europe. Statements were rated on an even Likert-scale ranging from 1 (strong disagreement) to 4 (strong agreement), based on expert opinion and the available literature. Results: The experts agreed on the following statements: (i) loss of response is associated with inadequate drug levels in both Crohn's disease and ulcerative colitis; (ii) best timepoint for measuring drug levels is prior to the next application (= trough levels) with different thresholds for anti-TNF agents (infliximab 5 μg/mL, adalimumab 8 μg/mL, certolizumab pegol 10 μg/mL); (iii) antidrug antibodies are predictive for loss of response; and (iv) antidrug-antibody titers and drug trough levels are key determinants in the treatment algorithm. Data about non-anti-TNF biologics were considered too limited to propose recommendations. Conclusion: A Delphi-style consensus among 8 IBD experts shows that TDM and measurement of antidrug-antibody titers are useful in the context of loss of response to anti-TNF. Optimal cutoff levels depend on the type of anti-TNF. These values are critical in the decision making process. More studies are needed to address the value of such measurements for non-anti-TNF biologics. [ABSTRACT FROM AUTHOR]

Background and Aims: The treatment options for eosinophilic esophagitis (EoE) patients include drugs (proton pump inhibitors [PPIs], swallowed topical corticosteroids [STCs]), elimination diets, and dilation. Given the lack of data, we aimed to assess adult EoE patients' satisfaction with different EoE-specific treatment modalities. Patients and Methods: We evaluated therapy satisfaction recalled over a 12-month period using the validated Treatment Satisfaction Questionnaire for Medication that assesses effectiveness, side effects, convenience, and overall satisfaction. The score for each scale ranges from 0 (dissatisfied) to 100 (satisfied). To evaluate satisfaction with nonpharmacologic therapies, the questionnaire was modified and debriefed into three focus groups. The final questionnaire was sent to 147 patients. Results: The patient response rate was 74%. In the last 12 months, 24, 75, 19, and 9% were treated with PPIs, STCs, elimination diet, and dilation, respectively. Patients identified the following considerations as important for therapy choice: effect on symptoms (89%), effect on esophageal inflammation (76%), side effects (69%), and ease of use (58%). Patients found STCs to be effective (83 points), convenient (83 points), and experienced no side effects when using this therapy. When using STCs alone (43%), overall patient satisfaction was high (86 points). Patients judged PPIs to be most convenient (89 points), STCs to be a bit less convenient (83 points), and diet to be most inconvenient (46 points) of the three therapies examined. Conclusions: Adult EoE patients consider both therapy effect on symptoms and esophageal inflammation as important criteria when choosing EoE therapy and appear to be satisfied with STC use. [ABSTRACT FROM AUTHOR]

BACKGROUND: Malignancy may occur as long-term complication of inflammatory bowel disease (IBD) due to different risk factors. We assessed prevalence and incidence of malignancy, and predictive factors in the Swiss IBD Cohort Study (SIBDCS). METHODS: All IBD patients in the SIBDCS were analyzed from a cross-sectional and longitudinal perspective. Patients with malignancies were compared to controls. Standardized incidence ratios (SIR) were calculated based on age-specific and sex-specific background rates. RESULTS: Malignancies were identified in 122 of 3119 patients (3.9%). In a logistic regression model, age (OR 1.04 per year), intestinal surgery (OR 3.34), and treatment with steroids (OR 2.10) were the main predictors for the presence of malignancy, while treatment with 5-ASA (OR 0.57) and biologics (OR 0.38) were protective. From a longitudinal perspective, 67 out of 2580 patients (2.6%) were newly diagnosed with malignancy during a follow-up of 12,420.8 years (median 4.9 years). While there was no increased risk for malignancy overall (SIR 0.93, 95% CI 0.72–1.18) and colorectal cancer (SIR 1.55, 95% CI 0.71–2.95), IBD patients had an increased risk for lymphoma (SIR 2.98, 95% CI 1.36–5.66) and biliary cancer (SIR 6.3, 95% CI 1.27–18.41). In a Cox regression model, age and recent use of immunomodulators were the main predictors for development of malignancies, while 5-ASA, biologics were protective. CONCLUSIONS: IBD patients showed increased risk for lymphoma and biliary cancer, but not colorectal cancer and cancer overall. Age and recent use of immunomodulators were the main risk factors for malignancy, while aminosalicylates and biologics appear to be protective. [ABSTRACT FROM AUTHOR]

Summary: Background: Well informed patients who are in cohesive partnership with physicians and who have realistic expectations towards therapy are more likely to be adherent, which results in better disease control. Aim: To assess which therapy goals adults with eosinophilic oesophagitis consider relevant. Methods: Following refinement during three focus groups, a study brochure and questionnaire were sent to 148 patients. Patients ranked the importance (five levels) of short‐term (in the next 3 months) and long‐term (≥1 year) treatment effect on symptoms, quality of life (QoL), histologically‐detected inflammation and fibrosis, endoscopically‐detected inflammation, and stricture formation as well as achieving histological remission while asymptomatic. Patients' characteristics associated with treatment goals were identified using logistic regression. Results: Of 109 respondents (mean age 43 years), 85 were men. Over 90% chose symptoms and QoL improvement as important short‐ and long‐term therapy goals. A greater proportion attributed more importance to long‐term reduction in endoscopic (90% vs 73%, P < 0.001) and histological (81% vs 62%, P = 0.002) inflammation, and histologically‐detected fibrosis (79% vs 64%, P = 0.018) when compared to short‐term reduction in these features. Patients (88%) ranked achieving histological remission while being asymptomatic as important. Gender, therapy use, education level, QoL, symptom severity, and history of dilation were associated with patients' choice of treatment goals. Conclusions: Patients attributed most importance to improvement in symptoms and QoL. Reduction in biological activity was judged less important, but more relevant in the long‐ compared to the short‐term. [ABSTRACT FROM AUTHOR]

Background and Study Aims: The recommended minimum withdrawal time for screening colonoscopy is 6 minutes. Adenoma detection rates (ADRs) increase with longer withdrawal times. We aimed to compare withdrawal times and ADRs of endoscopists unaware of being monitored vs. aware. Patients and Methods: Seven experienced gastroenterologists prospectively performed 558 screening colonoscopies during a 9-month period in a Swiss University hospital. Colonoscopy withdrawal times were first measured without the gastroenterologists’ knowledge of being monitored (n = 355 colonoscopies) and then with their knowledge (n = 203 colonoscopies). Results: The median withdrawal time when gastroenterologists were unaware of being monitored was 4.5 minutes (interquartile range [IQR] 4 – 5.5 minutes) without intervention and 6 minutes (IQR 4 – 9 minutes) with intervention, increasing significantly to 7.3 minutes (IQR 6.5 – 9 minutes) and 8 minutes (IQR 7 – 11 minutes), respectively, when they were aware of being monitored (P < 0.001 both for colonoscopies with and without intervention). The ADR increased from 21.4 % when the gastroenterologists were unaware of being monitored to 36.0 % when they were aware (P < 0.001). In the multivariate regression model, the endoscopists knowing they were being monitored was the strongest factor associated with ADR (odds ratio 4.417; 95 % confidence interval [CI] 2.241 – 8.705; P < 0.001). Conclusions: Colonoscopy withdrawal time in unmonitored gastroenterologists is shorter than recommended and increases with awareness of monitoring. ADR significantly increases when gastroenterologists are aware of being monitored. Implementation of systematic monitoring, and analysis of withdrawal time and ADR for each endoscopist may help to increase the ADR. [ABSTRACT FROM AUTHOR]

Background and aims. Limited data from large cohorts are available on tumor necrosis factor (TNF) antagonists (infliximab, adalimumab, certolizumab pegol) switch over time. We aimed to evaluate the prevalence of switching from one TNF antagonist to another and to identify associated risk factors. Methods. Data from the Swiss Inflammatory Bowel Diseases Cohort Study (SIBDCS) were analyzed. Results. Of 1731 patients included into the SIBDCS (956 with Crohn's disease [CD] and 775 with ulcerative colitis [UC]), 347 CD patients (36.3%) and 129 UC patients (16.6%) were treated with at least one TNF antagonist. A total of 53/347 (15.3%) CD patients (median disease duration 9 years) and 20/129 (15.5%) of UC patients (median disease duration 7 years) needed to switch to a second and/or a third TNF antagonist, respectively. Median treatment duration was longest for the first TNF antagonist used (CD 25 months; UC 14 months), followed by the second (CD 13 months; UC 4 months) and third TNF antagonist (CD 11 months; UC 15 months). Primary nonresponse, loss of response and side effects were the major reasons to stop and/or switch TNF antagonist therapy. A low body mass index, a short diagnostic delay and extraintestinal manifestations at inclusion were identified as risk factors for a switch of the first used TNF antagonist within 24 months of its use in CD patients. Conclusion. Switching of the TNF antagonist over time is a common issue. The median treatment duration with a specific TNF antagonist is diminishing with an increasing number of TNF antagonists being used. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Mannan-binding lectin (MBL) and ficolins are microbial pattern recognition molecules that activate the lectin pathway of complement. We previously reported the association of MBL deficiency with anti-Saccharomyces cerevisiae antibodies (ASCA) in patients with Crohn''s disease (CD). However, ASCA are also frequently found in MBL-proficient CD patients. Here we addressed expression/function of ficolins and MBL-associated serine protease-2 (MASP-2) regarding potential association with ASCA. Methods: ASCA titers and MBL, ficolin and MASP-2 concentrations were determined by ELISA in the serum of patients with CD, ulcerative colitis (UC), and in healthy controls. MASP-2 activity was determined by measuring complement C4b-fixation. Anti-MBL autoantibodies were detected by ELISA. Results: In CD and UC patients, L-ficolin concentrations were significantly higher compared to healthy controls (p<0.001 and p=0.029). In contrast, H-ficolin concentrations were slightly reduced in CD and UC compared to healthy controls (p=0.037 for UC vs. hc). CD patients with high ASCA titers had significantly lower H-ficolin concentrations compared to ASCA-low/negative CD patients (p=0.009). However, MASP-2 activity was not different in ASCA-negative and ASCA-positive CD patients upon both, ficolin- or MBL-mediated MASP-2 activation. Finally, anti-MBL autoantibodies were not over-represented in MBL-proficient ASCA-positive CD patients. Conclusions: Our results suggest that low expression of H-ficolin may promote elevated ASCA titers in the ASCA-positive subgroup of CD patients. However, unlike MBL deficiency, we found no evidence for low expression of serum ficolins or reduced MASP-2 activity that may predispose to ASCA development. [Copyright &y& Elsevier]

Background and Aims: Medical therapy of inflammatory bowel disease (IBD) is becoming more complex, given the increasing choice of drugs to treat Crohn's disease (CD) and ulcerative colitis (UC). We aimed to summarize the current guidelines for first-line treatments in IBD. Methods: An extensive literature search with focus on the guidelines of the European Crohn's and Colitis Organisation for the diagnosis and treatment of CD and UC was performed. First-line treatments were defined as the following drug categories: 5-aminosalicylates, budesonide, systemic steroids, azathioprine, 6-mercaptopurine, methotrexate, infliximab, adalimumab and certolizumab pegol. The following drug categories were not included: cyclosporine and tacrolimus (not yet approved by Swissmedic for IBD treatment). Results: Treatment recommendations for the following clinically frequent situations are presented according to disease severity: ileocecal CD, colonic CD, proximal small bowel CD and perianal CD. For UC the following situations are presented: ulcerative proctitis, left-sided colitis and pancolitis. Conclusions: We provide a summary on the use of first-line therapies for clinically frequent situations in patients with CD and UC. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Aims: Although systemic corticosteroids are successfully administered for the induction of clinical response and remission in the majority of patients with inflammatory bowel disease (IBD) presenting with a flare, a proportion of these patients demonstrate a primary nonresponse to steroids or in the case of an initial response, they develop a resistance or a steroid dependence. Long-term therapy with corticosteroids for treatment of IBD should be avoided, given the high frequency of adverse treatment effects. Knowledge about treatment strategies in case of steroid nonresponse is therefore highly relevant. Methods: A systematic literature research was performed using Medline and Embase to summarize the currently recommended treatment strategies for steroid-resistant IBD. Results: Treatment of steroid-resistant Crohn's disease is based on the introduction of immunomodulators such as azathioprine, 6-mercaptopurine or methotrexate, the anti-TNF drugs infliximab, adalimumab and certolizumab pegol. In the case of steroid resistance in ulcerative colitis, aminosalicylates, the above-mentioned immunomodulators, infliximab, adalimumab or calcineurin inhibitors such as ciclosporin or tacrolimus may be administered. Conclusion: This review summarizes the current evidence for treating steroid-resistant IBD. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Aims: Although systemic corticosteroids are successfully administered for the induction of clinical response and remission in the majority of patients with inflammatory bowel disease (IBD) presenting with a flare, a proportion of these patients demonstrate a primary nonresponse to steroids or in the case of an initial response, they develop a resistance or a steroid dependence. Long-term therapy with corticosteroids for treatment of IBD should be avoided, given the high frequency of adverse treatment effects. Knowledge about treatment strategies in case of steroid nonresponse is therefore highly relevant. Methods: A systematic literature research was performed using Medline and Embase to summarize the currently recommended treatment strategies for steroid-resistant IBD. Results: Treatment of steroid-resistant Crohn's disease is based on the introduction of immunomodulators such as azathioprine, 6-mercaptopurine or methotrexate, the anti-TNF drugs infliximab, adalimumab and certolizumab pegol. In the case of steroid resistance in ulcerative colitis, aminosalicylates, the above-mentioned irnmunomodulators, infliximab, adalimumab or calcineurin inhibitors such as ciclosporin or tacrolimus may be administered. Conclusion: This review summarizes the current evidence for treating steroid-resistant IBD. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: The clinical course of Crohn''s disease (CD) is highly variable with a subgroup of patients developing a progressive disease course necessitating immunosuppressive therapy (IT). However, reliable, stable and non-invasive individual clinical parameters in order to identify patients at risk for undergoing subsequent IT have not been sufficiently established. We therefore aimed to identify such clinical parameters. Methods: A retrospective, multicenter analysis of CD patients from 6 German tertiary IBD centers was performed. Patients were classified into two groups depending on requiring IT or not. Personal data, clinical and laboratory parameters during the first 3months after CD diagnosis and effects of initial medical therapy were compared between these two groups. Results: In 218 (61.8%) of the 353 patients the CD course necessitated IT. Those patients were significantly younger at symptom onset and diagnosis, and required significantly more often a systemic corticosteroid therapy. Furthermore, significant differences in serological markers of inflammation were observed. Age, gender and the effect of initial steroid therapy were used to develop a prognostic model predicting the individual probability of necessitating IT. Conclusions: The simple clinical items age at diagnosis, gender, and need for systemic steroid therapy can predict a progressive disease course in early CD. Our model based on these parameters allows an individualized estimation of each patient''s risk to develop a progressive disease course. Thereby, our model can help in deciding if patients will need immunosuppressive drugs early in the disease course or if a careful watch and wait strategy is justified. [Copyright &y& Elsevier]

OBJECTIVES:Data on the frequency of extraintestinal manifestations (EIMs) in Crohn's disease (CD) and ulcerative colitis (UC) and analyses of their risk factors are scarce. We evaluated their prevalence and risk factors in a large nationwide cohort of inflammatory bowel disease (IBD) patients.METHODS:IBD patients from an adult clinical cohort in Switzerland (Swiss IBD cohort study) were prospectively included. Data from validated physician enrolment questionnaires were analyzed.RESULTS:A total of 950 patients were included, 580 (61%) with CD (mean age 41 years) and 370 (39%) with UC (mean age 42 years). Of these, 249 (43%) of CD and 113 (31%) of UC patients had one to five EIMs. The following EIMs were found: arthritis (CD 33%, UC 21%), aphthous stomatitis (CD 10%, UC 4%), uveitis (CD 6%, UC 4%), erythema nodosum (CD 6%, UC 3%), ankylosing spondylitis (CD 6%, UC 2%), psoriasis (CD 2%, UC 1%), pyoderma gangrenosum (CD and UC each 2%), and primary sclerosing cholangitis (CD 1%, UC 4%). Multiple logistic regression identified the following risk factors for ongoing EIM in CD: active disease (odds ratio (OR)=1.95, 95% confidence interval (CI)=1.17-3.23, P=0.01), and positive IBD family history (OR=1.77, 95% CI=1.07-2.92, P=0.025). No risk factors were identified in UC patients.CONCLUSIONS:EIMs are a frequent problem in CD and UC patients. Active disease and positive IBD family history are associated with ongoing EIM in CD patients. Identification of EIM prevalence and associated risk factors may result in increased awareness for this problem and thereby facilitating their diagnosis and therapeutic management. [ABSTRACT FROM AUTHOR]

Background: Enquiries among patients on the one hand and experimental and observational studies on the other suggest an influence of stress on inflammatory bowel diseases (IBD). However, since this influence remains hypothetical, further research is essential. We aimed to devise recommendations for future investigations in IBD by means of scrutinizing previously applied methodology. Methods: We critically reviewed prospective clinical studies on the effect of psychological stress on IBD. Eligible studies were searched by means of the PubMed electronic library and through checking the bibliographies of located sources. Results: We identified 20 publications resulting from 18 different studies. Sample sizes ranged between 10 and 155 participants. Study designs in terms of patient assessment, control variables, and applied psychometric instruments varied substantially across studies. Methodological strengths and weaknesses were irregularly dispersed. Thirteen studies reported significant relationships between stress and adverse outcomes. Conclusions: Study designs, including accuracy of outcome assessment and repeated sampling of outcomes (i.e. symptoms, clinical, and endoscopic), depended upon conditions like sample size, participants’ compliance, and available resources. Meeting additional criteria of sound methodology, like taking into account covariates of the disease and its course, is strongly recommended to possibly improve study designs in future IBD research. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: The incidence of duodenal diverticula (DD) found at autopsy may be as high as 22%. Perforation is the least frequent but also the most serious complication. This case series gives an overview of the management of this rare entity.Methods: This study is a case series of eight patients treated for symptomatic DD.Results: Two patients had a perforated DD. One perforation was in segments III-IV, which to our knowledge is the first published case; the other perforation was in segment II. A segmental duodenectomy was performed in the first patient and a pylorus-preserving duodeno-pancreatectomy (pp-Whipple) in the second. A third patient with chronic complaints and recurring episodes of fever required an excision of the DD. In a fourth patient with biliary and pancreatic obstruction, a pp-Whipple was carried out, and a DD was discovered as the underlying cause. Four patients (one small perforation, one hemorrhage, and two recurrent cholangitis/pancreatitis caused by a DD) were treated conservatively.Conclusions: Symptomatic DD and, in particular, perforations are rare, encompass diagnostic challenges, and may require technically demanding surgical or endoscopic interventions. The diagnostic value of forward-looking gastroduodenoscopy in this setting seems limited. If duodenoscopy is performed at all, the use of a side-viewing endoscope is mandatory. [ABSTRACT FROM AUTHOR]

Background: Zinc deficiency (ZD) in Crohn's disease (CD) is considered a frequent finding and may exacerbate CD activity. ZD is associated with depression in non-CD patients. We aimed to assess the prevalence of ZD in CD patients in clinical remission, its association with mood disturbances and to analyze a potential impact on future disease course. Methods: Zinc levels from CD patients in clinical remission at baseline and an uncomplicated disease course within the next 3 years (n = 47) were compared with those from patients developing complications (n = 50). Baseline symptoms of depression and anxiety were measured with the Hospital Anxiety and Depression scale. Results: Mean zinc level in the 97 patients (40.4 ± 15.7 years, 44.3% males) was 18.0 ± 4.7 μmol/l. While no ZD (<11 μmol/l) was observed, we found low zinc levels (<15.1 μmol/l) in 28 patients (28.9%). Males had higher zinc levels compared with females (19.4 ± 5.7 versus 16.8 ± 3.3, p = 0.006). Patients with low zinc levels more often reported depression symptoms compared with patients with higher levels (27.3 versus 9.4%, p = 0.047). In a multivariate analysis, zinc levels were an independent negative predictor for depression symptoms [odds ratio (OR) 0.727, 95% confidence interval (CI) 0.532–0.993, p = 0.045]. Zinc levels of patients with a complicated disease course were not different from those of patients without (17.7 ± 4.3 versus 18.3 ± 5.1, n.s.). Baseline zinc levels did not predict disease outcome regardless of ATG16L1 genotype. Conclusion: Low–normal zinc levels were an independent predictor for the presence of depression symptoms in CD patients. Zinc levels at baseline did not predict a complicated disease course, neither in CD patients overall, nor ATG16L1T300A carriers. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Variant alleles of the mannose binding lectin 2 gene (MBL2) confer heterozygote advantage within Crohn's families," in the January 9, 2010 issue.