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INTRODUCTION Given the lack of data, we aimed to assess the impact of the length of diagnostic delay on the natural history of ulcerative colitis (UC) in pediatric (diagnosed <18 years) and adult patients (diagnosed ≥18 years). METHODS Data from the Swiss Inflammatory Bowel Disease Cohort Study were analyzed. Diagnostic delay was defined as the interval between the first appearance of UC-related symptoms until diagnosis. Logistic regression modeling evaluated the appearance of the following complications in the long term according to the length of diagnostic delay: colonic dysplasia, colorectal cancer, UC-related hospitalization, colectomy, and extraintestinal manifestations (EIMs). RESULTS A total of 184 pediatric and 846 adult patients were included. The median diagnostic delay was 4 [IQR 2-7.5] months for the pediatric-onset group and 3 [IQR 2-10] months for the adult-onset group (p = 0.873). In both, pediatric- and adult-onset groups, the length of diagnostic delay at UC diagnosis was not associated with colectomy, UC-related hospitalization, colon dysplasia, and colorectal cancer. EIMs were significantly more prevalent at UC diagnosis in the adult-onset group with long diagnostic delay than in the adult-onset group with short diagnostic delay (p = 0.022). In the long term, the length of diagnostic delay was associated in the adult-onset group with colorectal dysplasia (p = 0.023), EIMs (p < 0.001), and more specifically arthritis/arthralgias (p < 0.001) and ankylosing spondylitis/sacroiliitis (p < 0.001). In the pediatric-onset UC group, the length of diagnostic delay in the long term was associated with arthritis/arthralgias (p = 0.017); however, it was not predictive for colectomy and UC-related hospitalization. CONCLUSIONS As colorectal cancer and EIMs are associated with considerable morbidity and costs, every effort should be made to reduce diagnostic delay in UC patients.

Background: Tumor necrosis factor (TNF) inhibitors have improved treatment of ulcerative colitis (UC), but loss of response remains a frequent problem. The anti-TNF agent, golimumab, was approved in Switzerland for the treatment of UC in 2014. This study aims to summarize the experience of golimumab in a real-world setting in Switzerland. Methods: We analyzed real-world data from 1769 UC patients from the Swiss Inflammatory Bowel Disease Cohort (SIBDC) study and performed a chart review of golimumab-treated patients. We extracted the partial Mayo score at t0 (baseline), t1 (2-16 weeks), t2 (17-35 weeks), and t3 (36-89 weeks). The primary endpoint was clinical response at t1, defined as marked improvement in partial Mayo score and objective parameters. Clinical remission was defined as resolution of symptoms and normalization of objective parameters. Results: Our chart review included 103 UC patients with golimumab treatment (5.8% of all SIBDC UC patients); only 16 (15.5%) were anti-TNF naïve. Sixty-three patients remained on golimumab (61.2%) after 180 days, 51 (44.7%) after 365 days, and 34 (33%) after 630 days after the start of treatment. Upon golimumab treatment, the partial Mayo score decreased from 4 [interquartile range (IQR): 2-6] at t0 to 2 (IQR: 0-4) at t1, 1 (IQR: 0-3.5) at t2, and 1 (IQR: 0-3) at t3 (p < 0.001 for all comparisons with t0). The primary endpoint, clinical response at t1, could be evaluated in 52 patients and was met in 15 individuals (28.8%). Clinical remission at t1 was observed in 8 out of 52 patients (15.4%). Golimumab was generally well tolerated, one patient developed meningitis. The most frequent reasons to stop treatment were primary and secondary non-response. Conclusion: Golimumab was used in 5.8% of Swiss UC patients, mainly in biologic-experienced individuals. Golimumab treatment was associated with a sustained reduction of symptoms and clinical response in approximately 30% of patients.[ClinicalTrials.gov identifier: NCT0048863

Intestinal fibrosis, characterized by excessive deposition of extracellular matrix proteins, is a common and severe clinical complication of inflammatory bowel disease (IBD). However, the mechanisms underlying fibrosis remain elusive, and currently, there are limited effective pharmacologic treatments that target the development of fibrosis. Hypoxia is one of the key microenvironmental factors influencing intestinal inflammation and has been linked to fibrosis. In the present study, we sought to elucidate the impact of hypoxia on fibrotic gene expression in the intestinal mucosa. Methods:Human volunteers, IBD patients, and dextran sulphate sodium-treated mice were exposed to hypoxia, and colonic biopsies were collected. The human intestinal epithelial cell line Caco-2, human THP-1 macrophages, and primary human gut fibroblasts were subjected to hypoxia, and changes in fibrotic gene expression were assessed. Results:Human volunteers subjected to hypoxia presented reduced transcriptional levels of fibrotic and epithelial-mesenchymal transition markers in the intestinal mucosa. IBD patients showed a trend towards a decrease in tissue inhibitor of metalloproteinase 1 protein expression. In mice, hypoxic conditions reduced the colonic expression of several collagens and matrix metalloproteinases. Hypoxic Caco-2 cells, THP-1 cells, and primary gut fibroblasts showed a significant downregulation in the expression of fibrotic and tissue remodelling factors. Conclusions:Stabilization of hypoxia-inducible factors might represent a novel therapeutic approach for the treatment of IBD-associated fibrosis.

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.

BACKGROUND AND AIMS Crohn's disease (CD) can involve any part of the gastrointestinal tract. We aimed to characterize clinical, endoscopic, histologic features and treatment outcomes of CD patients with oesophageal involvement. METHODS We collected cases through a retrospective multicentre European Crohn's and Colitis Organisation CONFER [COllaborative Network For Exceptionally Rare case reports] project. Clinical data were recorded in a standardized case report form. RESULTS A total of 40 patients were reported [22 males, mean (±SD, range) age at oesophageal CD diagnosis: 25 (±13.3, 10-71) years and mean time of follow-up: 67 (±68.1, 3-240) months]. Oesophageal involvement was established at CD diagnosis in 26 patients (65%) and during follow-up in 14. CD was exclusively located in the oesophagus in 2 patients. Thirteen patients (32.2%) were asymptomatic at oesophageal disease diagnosis. Oesophageal strictures were present in 5 patients and fistulizing oesophageal disease in one. Eight patients exhibited granulomas on biopsies. Proton-pump inhibitors (PPIs) were administered in 37 patients (92.5%). Three patients underwent endoscopic dilation for symptomatic strictures and none oesophageal-related surgery. Diagnosis in pre-established CD resulted in treatment modifications in 9/14 patients. Clinical remission of oesophageal disease was seen in 33/40 patients (82.5%) after a mean time of 7 (±5.6, 1-18) months. Follow-up endoscopy was performed in 29/40 patients and 26/29 (89.7%) achieved mucosal healing. CONCLUSION In this case series the endoscopic and histologic characteristics of isolated oesophageal CD were similar to those reported in other sites of involvement. Treatment was primarily conservative, with PPIs administered in the majority of patients and modifications in pre-existing IBD-related therapy occurring in two thirds of them. Clinical and endoscopic remission was achieved in more than 80% of the patients.

Background: Postoperative recurrence is frequently observed after ileocecal resection in Crohn's disease (CD) patients. Since 2010, endoscopy within 1 year is considered the gold standard for its diagnosis. However, if and how frequent such endoscopies are performed in clinical practice remains unknown. Methods: We analyzed 1-year follow-up data on CD patients who underwent ileocecal resection between 2012 and 2014 and compared them with hospitalized, non-resected CD controls. Data were extracted from the Helsana database. Helsana is one of the largest Swiss health insurance companies providing coverage for 1.2 million individuals. Results: A total of 645 CD patients were identified with ≥1 hospitalization between 2012 and 2014 and a follow-up of 1 year. Of these, 79 (12.2%) underwent ileocecal resection. Although endoscopy rates increased over time and were higher in patients with resection versus controls (p = 0.029), in only 54.4% a 1-year follow-up ileocolonoscopy was performed. Postoperative prophylaxis with anti-tumor necrosis factor or azathioprine was prescribed in 63.3%. Female sex and age >60 years were independent predictors for not receiving prophylaxis (odds ratio [OR] 0.36, p = 0.048, and OR 0.2, p = 0.022). Patients with resection had significantly lower numbers of rehospitalizations (1.2 vs. 1.8, p = 0.021), with resection being an independent negative predictor for number of rehospitalizations in a Poisson regression model (incident risk ratio 0.64, p = 0.029). However, disease-related surgery was more often the cause for rehospitalization after resection versus controls (47.6 vs. 22.1%, p = 0.015). Total and inpatient health-care costs were higher in these patients. Conclusion: Endoscopies are underused after ileocecal resection. This contrasts current guidelines. Physicians should be aware of this underuse and perform follow-up examinations more often.

Extra-intestinal manifestations (EIMs) of inflammatory bowel disease (IBD) occur frequently and contribute to morbidity and reduced quality of life. The musculoskeletal, ocular and cutaneous organ systems are frequently involved in IBD-related EIMs. By focusing on manifestations involving the joints, skin and eyes, this review will discuss the most common clinically relevant and burdensome EIMs that affect IBD patients, and strives for early recognition, adequate treatment and timely referral. For this purpose, we aimed to create a comprehensive overview on this topic, with the main focus on the treatment of reactive and associated EIMs, including spondyloarthropathies, pyoderma gangrenosum, erythema nodosum, psoriasis and anterior uveitis. The recently developed biologicals enable simultaneous treatment of inflammatory disorders. This review can be used as a helpful guide in daily clinical practice for physicians who are involved in the treatment of IBD patients.

Enterococcus faecium SF68® (SF68) is a licensed pharmaceutical for treatment and prevention of diarrhea in Austria, Italy and Switzerland. However, as for other probiotics, evidence for its efficacy is based on small to medium-sized studies. Four unpublished studies on the treatment of acute diarrhea and the prevention of antibiotic-associated diarrhea were analyzed: one randomized, double blind, placebo-controlled trial (RCT) for treatment (n = 1,143), one open-label study for treatment (n = 5,093), one RCT for prevention (n = 1,397) and one open-label study for prevention (n = 4,340). Patients in the treatment-arm and the open-label studies received SF68 (b.i.d. for the prevention studies, t.i.d. for the treatment trials) for 7 days. Primary end points were time to resolution of diarrhea (treatment) and percentage of development of diarrhea (prevention). The primary endpoint of the treatment study was met with a decreased time to resolution of diarrhea in SF68-treated patients compared to controls (median 3 vs. 4 days, p < 0.001). Time to resolution of secondary symptoms was also significantly reduced. Preventive treatment with SF68 was more effective than placebo with development of diarrhea in 8.6 vs. 16.2% (p < 0.001). Results from the open-label studies were consistent with the RCTs. The incidence of adverse events were low (1.1 and 1.4% in the RCT and 4.7 and 7.4% in the open-label studies). SF68 is effective and safe in the treatment of acute diarrhea and prevention of antibiotic-associated diarrhea.

Extraintestinal manifestations (EIM) have become an important source of morbidity and disability as well as an identified risk factor for an unfavorably course of disease in inflammatory bowel diseases (IBD). Therefore, efforts have been put into a more global and interdisciplinary management of IBD patients in collaboration with rheumatologists, dermatologists, and ophthalmologists. A real therapeutic success has also been obtained with a more "systemic" IBD treatment associated with the development of monoclonal antibodies against TNF alpha and biological agents derived from the treatment of rheumatological disease (also called biological Disease-Modifying Antirheumatic Drugs). The prevalence of these EIM remains too low to undergo randomized controlled trials with this specific focus and therefore the evidence relies on case series and experts' opinions, which lowers the level of evidence. After a careful review of the most recent literature, this paper aims to update the reader on the latest therapeutic management of IBD patients with EIM.

BACKGROUND Westernization, above all associated changes in diet, has been postulated to be one of the most important factors contributing to the increasing incidence in inflammatory bowel disease (IBD), consisting mainly of Crohn's disease and ulcerative colitis. SUMMARY Diet represents a crucially important and intuitively relevant topic for IBD patients. Although a substantial number of patients are prone to follow dietary advice from a variety of sources, including the lay press, there is intriguingly little scientific evidence for such an incitement. This may result in physicians being insufficiently informed about various aspects of nutrition, precluding adequate guidance of their patients with IBD. Importantly, IBD patients are at risk to develop deficiencies in iron, vitamin B12, folic acid, and several micronutrients, which may even be more pronounced in patients with active disease and those following a restrictive diet. This review aims to summarize the latest data from clinical and epidemiological studies investigating diet and its effect on the course of the disease and to outline the most important nutrient deficiencies in IBD patients. Key Messages: A western diet with an imbalance between omega-6 (n-6)/omega-3 (n-3) polyunsaturated fatty acids (PUFAs), in favor of n-6 PUFAs, may increase the risk of IBD, whereas a diet high in fruits and vegetables may decrease the risk of IBD. Many approaches to influence the course of IBD with dietary intervention exist. However, to induce or maintain remission in IBD with a change of diet is still in its infancy, and more dietary research is needed before we can apply it in daily practice. Patients with IBD, even in remission, have to be screened regularly for malnutrition.

Background: Inflammatory bowel disease (IBD) needs early interventions and an individual specialist-patient relationship. Distance from a tertiary IBD center might affect patient's disease course and outcome. We investigated whether the patient-to-specialist distance has an impact on the disease course using the well-defined patient collective of the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). Methods: Patient's home address at diagnosis (postal zip code) was extracted from the SIBDCS database. Distance between each zip code and the nearest located IBD specialist center was calculated and classified into the following three sections based on proximity: <10 km (group 1); 10-35 km (group 2); >35 km (group 3). Results: Our study included in total 408 IBD patients [234 Crohn's disease (CD), 154 ulcerative colitis (UC), 20 IBD unclassified (IBDU)]. Median age was lowest in group 2 at diagnosis (G1: 28 years; G2: 21 years, G3: 26 years, p < 0.01). The diagnostic delay did not differ between groups. CD patients in group 1 were treated more often with anti-tumor necrosis factor (TNF) agents (72% versus 56%, p = 0.04) and 5-aminosalicylates (44% versus 28%, p = 0.04) than in group 3. UC/IBDU patients in group 1 were treated more often with corticosteroids than patients in group 3 (83% versus 58%, p < 0.01). The occurrence of IBD-related surgeries did not differ between groups. Conclusions: Patient-to-specialist distance might affect drug treatment. However, disease course and the need for IBD-related surgery does not seem to be associated with a longer distance to specialist care in Switzerland.