Search

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.

Background and Aims: The majority of patients treated with anti-tumor necrosis factor (TNF) therapy develop anti-drug antibodies (ADAs), which might result in loss of treatment efficacy. Strict guidelines on measuring trough levels (TLs) and ADA in clinical routine do not exist. To provide real-world data, we took advantage of our tertiary inflammatory bowel disease (IBD) center patient cohort and determined indicators for therapeutic drug monitoring (TDM) and actual consequences in patient care. Methods: We retrospectively collected clinical data of 104 IBD patients treated with infliximab or adalimumab in our IBD clinic. Patients with TL and ADA measurements between June 2015 and February 2018 were included. Results: The main reason for determining TL was increased clinical disease. Subtherapeutic TLs were found in 33 patients, therapeutic TLs in 33 patients, and supratherapeutic TLs in 38 patients. Adjustments in anti-TNF therapy occurred more frequently (p = 0.01) in patients with subtherapeutic TL (24 of 33 patients; 73%) as compared to patients with therapeutic and supratherapeutic TLs (26 of 71 patients; 37%). No correlation could be found between TL and disease activity (p = 0.16). Presence of ADA was found in 16 patients, correlated with the development of infusion reactions (OR: 10.6, RR: 5.4, CI: 2.9–38.6), and was associated with subtherapeutic TL in 15 patients (93.8%). Treatment adaptations were based on TL and/or ADA presence in 36 of 63 patients. Conclusions: TDM showed significant treatment adaptations in patients with subtherapeutic TL. Conversely, in patients with therapeutic and supratherapeutic TLs, reasons for adaptations were based on considerations other than TL, such as clinical disease activity. Further studies should focus on decision-making in patients presenting with supratherapeutic TL in remission.

BACKGROUND AND AIMS BougieCap (Ovesco Endoscopy AG, Tübingen, Germany) is a new device that allows optical and tactile feedback during stricture dilation of the upper gastrointestinal tract. We evaluated the technical feasibility, clinical efficacy, and safety of a one-time esophageal stricture dilation using BougieCap in adults with eosinophilic esophagitis (EoE). METHODS EoE patients prospectively included in the Swiss EoE Cohort were dilated with BougieCap in case of the presence of esophageal strictures (esophageal diameter ≤14 mm) and stricture-related symptoms. Symptoms were assessed before and 2 weeks after a single dilation session using the validated Eosinophilic Esophagitis Activity Index Patient Reported Outcomes (EEsAI PRO)instrument (score ranges from 0-100 points). RESULTS Fifty patients (70% male, median age 41 years, median disease duration of 4 years, 50% treated with swallowed topical corticosteroids, 10% with proton pump inhibitors, 14% with combined swallowed topical corticosteroids plus proton pump inhibitors, 14% with elimination diet, 12% without anti-eosinophil therapy) were evaluated. Endoscopic bougienage was technically successful in 100%. Median esophageal diameter increased from 12 mm (IQR 12-13) to 16 mm (IQR 16-16, p

Zusammenfassung: Bei Patienten mit einer Proktitis - mit den Symptomen Tenesmen, anorektale Schmerzen, Diarrhö, Stuhldrang, Schleim- oder Blutabgang und Schmerzen im linken Unterbauch - sollte neben chronisch-entzündlichen Darmkrankheiten immer auch an die Möglichkeit einer infektiösen Ursache gedacht werden. Die Sexualanamnese, insbesondere der rezeptive anale Verkehr (dies muss auch bei heterosexuellen Frauen und auch bei Männern erhoben werden), spielt hier eine entscheidende Rolle. Patienten müssen über mögliche Risiken informiert und ggf. frühzeitig behandelt werden. Bei Nachweis einer Geschlechtskrankheit sollte dem Patienten ein weiterführendes Screening auf sexuell übertragbare Infektionen ("sexually transmitted diseases", STD) unter Einschluss eines HIV-Tests angeboten werden, da häufig mehrere Geschlechtskrankheiten gleichzeitig vorliegen können. Einer adäquaten und unverzüglichen Diagnostik sowie Therapie inklusive einer intensivierten Partnerbenachrichtigung und ggf. -therapie kommt hier eine besondere Bedeutung zu.

Background and Aims: Endoscopic outcomes have become important measures of eosinophilic esophagitis (EoE) disease activity, including as an endpoint in randomized controlled trials (RCTs). We evaluated the operating properties of endoscopic measures for use in EoE RCTs. Methods: Modified Research and Development/University of California Los Angeles appropriateness methods and a panel of 15 international EoE experts identified endoscopic items and definitions with face validity that were used in a 2-round voting process to define simplified (all items graded as absent or present) and expanded versions (additional grades for edema, furrows, and/or exudates) of the EoE Endoscopic Reference Score (EREFS). Inter- and intrarater reliability of these instruments (expressed as intraclass correlation coefficients [ICC]) were evaluated using paired endoscopy video assessments of 2 blinded central readers in patients before and after 8 weeks of proton pump inhibitors, swallowed topical corticosteroids, or dietary elimination. Responsiveness was measured using the standardized effect size (SES). Results: The appropriateness of 41 statements relevant to EoE endoscopic activity (endoscopic items, item definitions and grading, and other considerations relevant for endoscopy) was considered. The original and expanded EREFS demonstrated moderate-to-substantial inter-rater reliability (ICCs of.472-.736 and.469-.763, respectively) and moderate-to-almost perfect intrarater reliability (ICCs of.580-.828 and.581-.828, respectively). Strictures were least reliably assessed (ICC,.072-.385). The original EREFS was highly responsive (SES, 1.126 [95% confidence interval {CI},.757-1.534]), although both expanded versions of EREFS, scored based on worst affected area, were numerically most responsive to treatment (expanded furrows: SES, 1.229 [95% CI,.858-1.643]; all items expanded: SES, 1.252 [95% CI,.880-1.667]). The EREFS and its modifications were not more reliably scored by segment and also not more responsive when proximal and distal EREFSs were summed. Conclusions: EREFS and its modifications were reliable and responsive, and the original or expanded versions of the EREFS may be preferred in RCTs. Disease activity scored based on the worst affected area optimizes reliability and responsiveness.

The purpose of this study was to investigate the impact of obesity on disease activity and disease outcome in patients with inflammatory bowel disease.The impact of obesity on inflammatory bowel disease disease activity and outcome was retrospectively assessed in 3075 patients enrolled in the prospective nation-wide Swiss inflammatory bowel disease cohort between July 2006 and September 2018. Baseline characteristics, disease activity and disease course in 325 obese inflammatory bowel disease patients (body mass index ≥30 kg/mAmong 3075 patients in the prospective Swiss inflammatory bowel disease cohort, 325 patients (10.6%) were obese, namely, 194 Crohn's disease patients, 131 ulcerative colitis, and inflammatory bowel disease-unclassified patients. Disease activity scores were elevated in obese Crohn's disease (Crohn's Disease Activity Index 33 vs 20,Obesity is associated with decreased rates of disease remission and increased risk of complicated disease course in Crohn's disease over a six-year follow-up period. No effects were seen on disease progression and index treatment failure neither in Crohn's disease nor ulcerative colitis.

Hintergrund: Die Übernahme einer westlichen Lebensweise, insbesondere der damit verbundenen ernährungsbezogenen Veränderungen, gilt als einer der wichtigsten Faktoren, der zur steigenden Inzidenz entzündlicher Darmerkrankungen (IBD, inflammatory bowel disease), hauptsächlich Morbus Crohn und Colitis ulcerosa, beiträgt. Zusammenfassung: Die Ernährung stellt für Patienten mit IBD ein zentrales und intuitiv relevantes Thema dar. Auch wenn eine beträchtliche Zahl von Patienten geneigt ist, Ernährungsempfehlungen verschiedenster Anbieter, u.a. aus der Laienpresse, zu befolgen, lassen sich solche Anregungen nur selten durch wissenschaftliche Evidenzdaten untermauern. Dies kann dazu führen, dass Ärzte über verschiedene Aspekte der Ernährung unzureichend informiert sind, was wiederum eine fachgerechte Beratung ihrer Patienten mit IBD von vorne herein ausschließt. Zudem sind Patienten mit IBD gefährdet, Eisen-, Vitamin-B12-, und Folsäuremangel sowie einen Mangel an verschiedenen Mikronährstoffen zu entwickeln, der bei Patienten mit aktiver Erkrankung und solchen, die eine strikte Diät befolgen, besonders stark ausgeprägt sein kann. Ziel der vorliegenden Übersichtsarbeit ist es, die neuesten Daten aus klinischen und epidemiologischen Studien zur Untersuchung der Ernährungsweise und ihrer Auswirkungen auf den Krankheitsverlauf zusammenzufassen und die wichtigsten Nährstoffdefizite bei Patienten mit IBD zu umreißen. Wichtigste Aussagen: Eine westliche Ernährungsweise mit einem unausgewogenen Verhältnis zwischen den mehrfach ungesättigten Fettsäuren (PUFAs, polyunsaturated fatty acids) Omega-6 (n-6) und Omega-3 (n-3) zugunsten von n-6-PUFAs kann das Risiko für IBD erhöhen, während eine Ernährungsweise, die reich an Obst und Gemüse ist, das Risiko für IBD verringern kann. Es gibt eine Vielzahl von Ansätzen mit dem Ziel, den Krankheitsverlauf bei IBD durch Ernährungsmaßnahmen zu beeinflussen. Behandlungsstrategien zur Einleitung oder Aufrechterhaltung einer Remission entzündlicher Darmerkrankungen durch eine veränderte Ernährung stecken jedoch noch in den Kinderschuhen, und weitere Anstrengungen in der Ernährungsforschung sind erforderlich, bevor wir solche in der täglichen Praxis anwenden können. Patienten mit IBD, selbst solche in Remission, sind regelmäßig auf Mangelernährung zu untersuchen.

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 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.

Zusammenfassung. Bei chronisch entzündlichen Darmerkrankungen (Inflammatory Bowel Diseases, IBD) können nicht-entzündliche Gelenkschmerzen und entzündliche Gelenkmanifestationen auftreten. Letztere gehören zur Gruppe der Spondyloarthritiden. Sie werden am Achsenskelett als entzündlicher Rückenschmerz mit nächtlichen Schmerzen, Morgensteifigkeit und Besserung unter Aktivität manifest. Einschränkungen der Gelenkfunktion sind ebenfalls möglich. Bei anderen Patienten stehen periphere Gelenkbeschwerden im Vordergrund. Als Schmerzmedikamente werden COX-2-selektive, nicht-steroidale Antirheumatika (NSAR) empfohlen, da unselektive NSAR die zugrundeliegende IBD verschlimmern können. Am Achsenskelett werden Physiotherapie und Tumornekrosefaktor(TNF)-Inhibitoren eingesetzt, während bei peripherem Gelenkbefall Steroidinjektionen, Sulfasalazin und TNF-Inhibitoren wirksam sind. Entzündung, Malabsorption und Steroide führen bei IBD-Patienten zu Osteopenie und Osteoporose. Bei langdauernder Krankheitsaktivität bzw. langer Steroidgabe ist ein Screening mit DXA-Scan indiziert. Therapeutisch sollten ausreichend Kalzium und Vitamin D sowie gegebenenfalls Bisphosphonate gegeben werden.

Background and Aims The optimal timing of treatment escalation in Crohn’s disease [CD] remains a challenging issue, and very little is known about its long-term development following early versus late administration of anti-TNF antibodies. The long-term outcome of Swiss CD patients was comparatively assessed in an up to 10-year follow-up, using patients participating in the Swiss Inflammatory Bowel Disease Cohort Study [SIBDCS]. Methods Prospectively collected SIBDCS patient data, including disease history, baseline characteristics at enrolment, and course of disease, were analysed in patients with early versus late [ Results A reduced risk of developing bowel stenosis was found in patients who received early anti-TNF treatment. This association was seen in patients overall and also in the subgroups of CD patients without pre-existing complications [Log-rank test: p < 0.001]. Furthermore, osteoporosis and anaemia were observed significantly less frequently in patients who received early anti-TNF treatment, compared with either patients who received treatment late [p < 0.001 and p = 0.046, respectively] or were never [p < 0.001 for both] treated with anti-TNF antibodies. Patients with early anti-TNF administration sought medical consultations significantly less often, including gastroenterologists in private practice [p = 0.017], ambulatory [outpatient] hospital visits [p = 0.038], and a composite of any medical visits [p = 0.001]. The percentage of patients unable to work was lowest for early-anti-TNF–treated patients, in comparison with patients who were treated late or never [3.6% vs 8.8% vs 3.7%, p = 0.016]. Conclusions In CD patients within the SIBDCS, early anti-TNF administration was found to be associated with several indicators of a more favourable long-term outcome.

Eosinophilic esophagitis has a strong male predominance that appears at least partially due to genetic susceptibility. However, data regarding sex-related differences in patients with EoE are scarce.We analyzed prospectively collected data from adults enrolled into the Swiss Eosinophilic Esophagitis Cohort Study. Patients with and without dilation in the past 12 months completed patient-reported Eosinophilic Esophagitis Activity Index (EEsAI) and EoE-specific quality of life in adults (EoE-QoL-A) and underwent endoscopy with biopsies. We used linear regression with EEsAI or EoE-QoL-A as the outcome, eosinophils per high power field, rings and strictures, current therapy use, and disease duration as predictors.A total of 266 patients (77% male, median age at diagnosis 35.8 years, median disease duration 10.4 years) were seen during 408 visits. Men had a longer diagnostic delay (62 months vs 36 months; P = .022), higher endoscopic disease activity (median endoscopic reference score 3.0 [interquartile range, 1.0-6.0] vs 2.0 [interquartile range, 0.0-4.0]; P = .010), more microabscesses (25% vs 13%; P = .025), and more often fibrosis of the lamina propria (mild/moderate 74.7% vs 61.5%, severe 9.1% vs 5.8%; P = .047) than women. When adjusting for objective measures of disease activity, disease duration, and current therapy use, we did not observe differences in EEsAI or EoE-QoL-A between women and men.Male EoE patients had higher endoscopic and histologic disease activity than female patients. When adjusting for biologic activity and therapy use, we did not identify differences in symptom severity or EoE-QoL between male and female eosinophilic esophagitis patients.

BACKGROUND Inflammatory bowel disease (IBD) can be exacerbated by stress and depression. Type D personality, characterised by high negative affectivity and social inhibition, represents a vulnerability towards stressors and is associated with adverse outcomes in coronary heart disease. AIMS To assess the prevalence of Type D personality in IBD patients and investigate potential associations with disease course. METHODS We tested for associations between Type D (Type D Scale-14), depressive symptoms (Hospital Anxiety and Depression Scale's depression subscore ≥11) and recurrent IBD amongst Swiss IBD cohort patients. We built regression models for cross-sectional and Cox proportional hazards models for time-to-event analyses. IBD disease course was assessed by the future occurrence of active disease (Crohn's Disease Activity Index ≥150/Modified Truelove & Witts activity index ≥10) and several IBD-relevant endpoints. RESULTS Amongst 2275 patients (1005 ulcerative colitis, 1270 Crohn's disease), 672 (29.5%) had Type D. Type D was a significant risk factor for future active disease (adjusted hazard ratio, aHR: 1.60, corrected P value, q = 0.007) and predicted the future presence of depressive symptoms (aHR: 3.30, P

Immune checkpoint inhibitors have revolutionized the treatment of various cancers but are notorious for their potential to cause severe side effects. While most side effects occur during ongoing therapy, an increasing number of reports of late onset have emerged. It is also not yet clear how long side effects can last. Resolution is achieved under symptomatic therapy, but the side effects may persist latently. We present a patient case with recurrence of colitis after closure of an ileostomy over 1 year after discontinuation of immune checkpoint inhibitor therapy with nivolumab and ipilimumab. To the best of our knowledge, no other case with severe colitis still lasting after more than a year of suspension of therapy has yet been reported.Lay abstract Checkpoint inhibitors have revolutionized therapy for suitable cancers. However, they can cause side effects that are reminiscent of autoimmune diseases. While most adverse effects occur during ongoing therapy, there are increasing reports of late-onset adverse effects after discontinuation of therapy and of long-lasting adverse effects after discontinuation of treatment, which may remain latent even if symptom relief could be achieved by immunosuppression. We present a patient case with reappearance of a severe inflammation of the large bowel (colitis) after closure of an ostomy over 1 year after withdrawal of immune checkpoint inhibitor therapy. To the best of our knowledge, no other case with severe colitis still lasting after more than a year of suspension of therapy has yet been reported.

Background Inflammatory bowel disease (IBD) patients are at high risk for depression, and depression has been shown to affect disease course. We examined interrelations between depression, genetic risk factors for depression, and IBD flares. Method In 1973 patients (1137 Crohn’s disease, 836 ulcerative colitis) of the Swiss IBD Cohort Study (SIBDCS), depressive status (hospital anxiety and depression subscale for depression, HADS-D ≥11) was assessed on a yearly basis. We investigated the impact of depression on IBD-relevant clinical outcomes in Cox proportional hazards models. We used active disease (CDAI ≥150 or MTWAI ≥10) and 2 published composite flare definitions—FNCE (physician-reported flare, nonresponse to therapy, new complication, or extraintestinal manifestation) and AFFSST (active disease, physician-reported flare, fistula, stenosis, and new systemic therapy)—as clinical end points. Additionally, 62 preselected single nucleotide polymorphisms (SNPs) were screened for cross-sectional associations with depression, and if present, their predictive value for future depression and clinical deterioration was assessed. Results Depression was a strong risk factor for disease-related end points, including active disease (adjusted hazard ratio [aHR], 3.55; P < 0.001), AFFSST (aHR, 1.62; P < 0.001), and FNCE (aHR, 1.35; P = 0.019). The SNP rs2522833 was significantly associated with depression at enrollment (q = 0.059). The TC allele of rs588765 was negatively associated with the presence of depression at enrollment (q = 0.050) and after enrollment (aHR, 0.67; P = 0.035) and with fewer active disease states (aHR, 0.72; P = 0.045) during follow-up. Conclusion In IBD, depressive symptoms and inflammatory activity are intimately related. Depressive symptoms were a strong predictor of clinical deterioration, and genetic markers may play a role in this relationship.

BACKGROUND AND AIMS Extraintestinal manifestations are reported to occur in up to 45% of inflammatory bowel disease (IBD) patients during the course of disease. It is unknown whether colectomy reduces the rate of de novo extraintestinal manifestations (EIMs) or impacts on severity of EIMs following a parallel versus independent disease course from underlying IBD. METHODS Using data from the Swiss Inflammatory Bowel Disease Cohort Study we aimed to analyse the course of EIMs in ulcerative colitis (UC) and Crohn's disease (CD) patients undergoing colectomy during the cohort's prospective follow-up. RESULTS One hundred and twenty-one IBD patients (33 CD, 81 UC and seven unclassified) underwent colectomy during prospective follow-up in the Swiss Inflammatory Bowel Disease Cohort Study. Within the 114 patients with UC or CD any EIM was reported in 40 (nine CD and 31 UC) patients. Activity of EIMs ceased entirely after colectomy in 21 patients (52.5%). Complete cessation of EIM after colectomy was higher in patients with UC versus CD with 58.1% versus 33.3%. After colectomy, 29 out of the 114 patients (25.4%) experienced any EIM. Two thirds of these (19 patients) represented persisting EIMs, while in one third (10 patients) EIM represented a de-novo event after colectomy. Overall, 13.5% of IBD patients developed a de-novo EIM after colectomy. CONCLUSIONS In IBD patients undergoing colectomy, EIMs present prior to surgery will persist in about half of patients. Complete cessation of EIM after colectomy may be less common in CD than in UC. In patients who never experienced EIMs prior to colectomy de-novo manifestations thereafter should be expected in up to one in seven patients.

We report the case of a 63-year-old female patient with liver cirrhosis who presented with symptoms of severe hypoalbuminaemia and diarrhoea. After ruling out other causes of hypoalbuminaemia and confirmation of an elevated faecal α-1 antitrypsin clearance, the diagnosis of protein-losing enteropathy (PLE) could be established. Since PLE is a syndrome caused by various diseases, classified into erosive and non-erosive gastrointestinal diseases or lymphatic obstruction, an extensive work-up was necessary, establishing the final diagnosis of Crohn’s disease.

Infancy is a period of marked development, entailing many maturation processes that lay the foundation for later health. Two crucial health factors in infancy are the establishment of a sleep-wake rhythm and the growth of gut bacterial diversity - both have been linked to later cognitive and physiological outcomes. In adults and animal models, evidence is emerging that sleep and gut bacteria are bidirectionally linked. However, it is yet unclear when and how the sleep-gut link in early life evolves. Here we demonstrate that a sleep-gut link develops in infancy, undergoes transitional dynamics, and involves an early sensitive period. Specifically, infants' daytime sleep is linked to markers of bacterial diversity, and nighttime awakenings are associated with gut bacterial maturity and bacterial enterotype. Furthermore, both sleep and gut bacteria are associated with behavioral developmental outcomes, with the strongest connections at 3 months of age. Our results demonstrate the dynamic interplay of sleep and gut bacteria within healthy human development. As both sleep and gut bacteria are modifiable, they are promising targets for early intervention in clinical groups.

BACKGROUND: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. CONCLUSIONS: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:149 issue:2 pages:659-670 ispartof: location:United States status: published

BACKGROUND Dysphagia is the main symptom of adult eosinophilic esophagitis (EoE). We describe a novel syndrome, referred to as "food-induced immediate response of the esophagus" (FIRE), observed in EoE patients. METHODS Food-induced immediate response of the esophagus is an unpleasant/painful sensation, unrelated to dysphagia, occurring immediately after esophageal contact with specific foods. Eosinophilic esophagitis experts were surveyed to estimate the prevalence of FIRE, characterize symptoms, and identify food triggers. We also surveyed a large group of EoE patients enrolled in the Swiss EoE Cohort Study for FIRE. RESULTS Response rates were 82% (47/57) for the expert and 65% (239/368) for the patient survey, respectively. Almost, 90% of EoE experts had observed the FIRE symptom complex in their patients. Forty percent of EoE patients reported experiencing FIRE, more commonly in patients who developed EoE symptoms at a younger age (mean age of 46.4 years vs 54.1 years without FIRE; P

Many patients suffering from inflammatory bowel disease (IBD) follow restrictive diets, as many respective recommendations circulate. Efforts are made to evaluate and summarize the published information, for example, in a recent consensus manuscript by the International Organization for the Study of IBD (IOIBD). However, the standards that should be applied to make claims about dietary effects are poorly defined. In this manuscript, the scientific basis of recommendations for nutritional interventions in IBD is analyzed. Epidemiological evidence on diet in IBD is always biased by numerous factors, and the number of robust dietary intervention studies is limited due to methodological difficulties. Therefore, animal models are used to test hypotheses with respect to dietary factors and intestinal inflammation. Naturally, animal models have limitations, and knowledge of key characteristics of colitis animal models is crucial to understand their advantages and disadvantages. In recent years the important role of the microbiota for IBD and dietary factors has been discovered. Microbiota data are added to many publications on IBD and nutrition. The quality of those data varies largely. Subsequently, quality standards for microbiota analyses also are discussed. Finally, quality requirements to be applied on recommendations for dietary changes in patients with IBD are suggested.

Summary Background Eosinophilic esophagitis is a chronic inflammatory gastrointestinal disease with a high prevalence in younger, atopic males. In our clinical practice, we observed a striking preponderance of patients having a high educational background. The purposes of this study were first to assess the level of education of eosinophilic esophagitis patients and second to compare the findings to patients with inflammatory bowel disease, another chronic immune-mediated condition of the gastrointestinal tract, and with the Swiss general population. Methods Using a questionnaire, we assessed the educational level of adult patients who have attended Swiss Eosinophilic Esophagitis Clinics in the past. In addition, the educational level of the parents was assessed as well. We calculated the proportions of patients and parents who have obtained a higher educational level. Data from the Swiss Inflammatory Bowel Disease Cohort Study and from the Swiss general population served as confirmation and as comparison, respectively. Results A total of 277 successfully contacted patients (response rate 69.1%; mean age 51.1 years, 73% male) participated. A significantly higher proportion of surveyed eosinophilic esophagitis patients had a high International Standard Classification of Education level (66.8%, P Conclusion Our analysis confirms the clinical observation that eosinophilic esophagitis patients have a significantly higher educational level compared with the general population and to patients with other chronic inflammatory diseases of the gastrointestinal tract. As a limitation, this impressive finding remains on a purely descriptive level.

Background: Crohn’s disease (CD) may progress from an inflammatory to a stricturing or penetrating disease phenotype. The aim of our study was to identify single nucleotide polymorphisms (SNPs) that predict disease progression in patients of the Swiss IBD Cohort Study (SIBDCS). Methods: We applied a multi-state Markov model for progression behavior of CD with three behavioral states according to the Montreal classification. The model considered transition from B1 to B2/B3 or from B2 to B3 stage. Model dynamics were summarized with transition intensities by including the effect of SNPs and calculating transition intensities for each SNP. Results: We included 1276 CD patients [669 (52.4%) B1, 248 (19.4%) B2, 359 (28.1%) B3 patients] with a median follow-up of 6.8 (interquartile range = 3.6–9.1; range 0–11.6) years. Probability for a B1 patient to develop a stenosis (B1 to B2, q = 0.033) was twice as much as compared to developing a penetrating complication (B3) during the disease course. In contrast, the probability of entering B3 stage was similar regardless of whether antecedent stricture was present (B2 to B3, q = 0.016) or not (B1 to B3, q = 0.016). We identified SNPs within the gene loci encoding ZMIZ1, LOC105373831 and KSR1 as carrying the highest risk for progression to B3, while the presence of SNPs within gene loci TNFSF15 and CEBPB-PTPN1 protected from progression to B2 or B3. Conclusion: We identified new genetic risk factors that can predict disease course in CD patients. A closer understanding on the functional impact of these genetic variations might improve our treatment options finally to prevent disease progression in CD patients.

Summary As the awareness among gastroenterologists regarding endoscopic features suggesting eosinophilic esophagitis is increasing, individuals without symptoms of esophageal dysfunction are increasingly being found to have esophageal eosinophilia on biopsies performed during upper gastrointestinal endoscopies. However, the course of disease and the management of these asymptomatic individuals with esophageal eosinophilia remain elusive. In this review, we propose a definition of asymptomatic individuals with esophageal eosinophilia and discuss the prevalence, risk factors, and course of disease of this specific patient group. Furthermore, we have established a diagnostic and therapeutic pathway based on the most recent available data.

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.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.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.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.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.

Background and Aims Inflammatory bowel disease (IBD) patients are at high risk for depression. We examined interrelations between genetic risk factors for depression, depressive symptoms and IBD flares. Methods In 1973 patients (1137 Crohn's disease, 836 ulcerative colitis) of the Swiss IBD cohort study (SIBDC), 62 single nucleotide polymorphisms (SNPs) preselected for associations with depression, stress, pain and smoking were screened for cross-sectional associations with depression (hospital anxiety and depression subscale for depression, HADS-D≥11). Logistic regression and Cox proportional hazards models were built to test for effects of depressive symptoms on disease course and genetic risk factors on depression and disease course. As endpoints we used active disease (CDAI≥150 or MTWAI≥10) and two published composite flare definitions: FNCE: physician reported flare, non-response to therapy, new complication or extraintestinal manifestation and AFFSST: active disease, physician reported flare, fistula, stenosis and new systemic therapy. Results Depressive symptoms were a strong risk factor for disease related endpoints including active disease (adjusted hazard ratio, aHR: 3.25, p

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P, Adult forms of inflammatory bowel disease (IBD) are of a polygenic nature, but paediatric and very early onset (VEO) IBD also occur as monogenic forms. Here, using whole exome sequencing, the authors explore both the monogenic and polygenic contribution to VEO-IBD and characterize a rare somatic mosaic VEO-IBD patient.

Primary varicella zoster virus [VZV] infection results in varicella [chickenpox] and its reactivation results in herpes zoster [HZ; shingles]. Patients with inflammatory bowel disease [IBD] are susceptible to complications of primary VZV infection and have an increased risk of HZ. Concerns of VZV and HZ infection in the IBD population have been highlighted by the emergence of JAK inhibitors and their safety profile in this patient population, as with tofacitinib for the treatment of ulcerative colitis [UC]. The current pipeline of emerging therapies includes novel molecules targeting multiple pathways, including JAK/signal transducer and cytokine signalling pathways, such as JAK/STAT. Hence VZV and HZ will be increasingly relevant for gastroenterologists treating IBD patients in light of these emerging therapies. This review will focus on the epidemiology, disease course, prevention, and management of these two distinct infections in patients with IBD.

Checkpoint inhibitor-induced side effects such as diarrhea and colitis occur in up to 30% of patients. We present a case of recurrent episodes of checkpoint inhibitor-induced colitis and subsequent Fournier gangrene that resolved after ileostomy formation. Once the Fournier gangrene and colitis had resolved, the ileostomy was reversed. However, within only 4 days, another serious flare-up of colitis occurred, necessitating emergent re-formation of the ileostomy. Expertise in the management of side effects of immune checkpoint inhibitor therapy is currently limited. Although most side effects are mild to moderate and transient, a minority of patients suffer from life-threatening complications, such as colitis. The creation of an ileostomy might be a valid treatment option in severe or recurrent colitis due to immune checkpoint inhibitor therapy. Intestinal diversion surgery may be useful if conservative treatment has failed, similar to other forms of immune-mediated intestinal inflammation.

Background Pathogenesis of cutaneous extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) remains elusive. Efficacy of anti-TNF agents suggests TNF-dependent mechanisms. The role of other biologics such as anti-integrins or JAK-inhibitors is not yet clear. Methods We performed immunohistochemistry for TNFα, NFκB, STAT1/STAT3, MAdCAM1, CD20/68, caspase 3/9, IFNγ, Hsp-27/70 on 240 intestinal (55 controls, 185 IBD) and 64 skin biopsies (11 controls, 18 Erythema nodosum (EN), 13 Pyoderma gangenosum (PG), 22 psoriasis). A semiquantitative score (0-100%) was used for evaluation. Results TNFα was upregulated in intestinal biopsies from active Crohn`s disease (CD) vs. controls (36.2 vs. 12.1, p

Here we report the case of a patient with psoriasis who developed ulcerative colitis most likely caused by adalimumab. After cessation of adalimumab, colitis improved significantly. However, as psoriasis worsened, the patient was switched to ustekinumab, which resulted in complete cessation of colitis. During the 2-year follow-up under ustekinumab therapy, no further gastrointestinal complaints occurred. Paradoxical psoriasis manifestations in inflammatory bowel disease (IBD) under tumour necrosis factor (TNF)-inhibitor therapy have been reported and paradoxical IBD occurred rarely (mostly Crohn disease) in patients with rheumatological conditions treated with infliximab or etanercept. Due to the highly probable association of adalimumab with the onset of colitis in this case, we would like to suggest the term 'paradoxical ulcerative colitis' (PUC) for this as yet extremely rarely reported phenomenon. To the best of our knowledge this is the first description of PUC in a patient with psoriasis and in adalimumab treatment. Our observation suggests that ustekinumab is an effective treatment option in patients with paradoxical anti-TNF-driven inflammatory reactions like psoriasis or IBD.

An acute sigmoid volvulus is due to the torsion of the sigmoid colon around its mesenteric axis. It mainly occurs in elderly patients and represents an abdominal emergency requiring urgent treatment. A 53-year-old male patient with severe craniocerebral injury and traumatic subarachnoidal bleeding 3 weeks prior presented on the ward with distended abdomen without abdominal pain, muscular defense, or resistances. He featured large volume diarrhea within the last few hours without signs of bleeding. A plain abdominal X-ray demonstrated a coffee bean sign indicating a sigmoid volvulus. A consequent CT scan of the abdomen revealed a deep outlet obstruction with massively dilated, elongated and twisted loop of the sigmoid colon and no signs of perforation. We performed emergency colonoscopy under the assumption of an acute sigmoid volvulus. After careful insertion of the endoscope completely refraining from insufflation of air or CO2, endoscopic reposition of the sigma could be achieved and a colonic drainage was placed over an inserted guide wire up to the proximal transverse colon. No relapse occurred and a diagnostic colonoscopy after 4 weeks revealed no tumor or polyps. Our report describes a classic case of acute sigmoid volvulus and undermines the potential of colonoscopy as conservative primary treatment of choice.

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.

Background & Aims: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder. Swallowed topical-acting corticosteroids are effective in bringing active EoE into remission. However, it is not clear whether these drugs are effective for long-term maintenance of remission. Methods: We performed a double-blind trial to compare the efficacy and safety of 2 dosages of a budesonide orodispersible tablet (BOT) vs placebo in maintaining remission of EoE. Maintenance of remission was defined as absence of clinical and histologic relapse and no premature withdrawal for any reason. Two hundred and four adults with EoE in clinical and histologic remission, from 29 European study sites, were randomly assigned to groups given BOT 0.5 mg twice daily (n = 68), BOT 1.0 mg twice daily (n = 68), or placebo twice daily (n = 68) for up to 48 weeks. Results: At end of treatment, 73.5% of patients receiving BOT 0.5 mg twice daily and 75% receiving BOT 1.0 mg twice daily were in persistent remission compared with 4.4% of patients in the placebo group (P < .001 for both comparisons of BOT with placebo). Median time to relapse in the placebo group was 87 days. The frequency of adverse events was similar in the BOT and placebo groups. Morning serum levels of cortisol were in the normal range at baseline and did not significantly change during treatment. Four patients receiving BOT developed asymptomatic, low serum levels of cortisol. Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5 mg group and in 11.8% of patients in the BOT 1.0 mg group; all infections resolved with treatment. Conclusions: In a phase 3 trial, up to 48 weeks of treatment with BOT (0.5 mg or 1.0 mg twice daily) was superior to placebo in maintaining remission of EoE. Both dosages were equally effective and well tolerated. EudraCT number; 2014-001485-99; ClinicalTrials.gov number, NCT02434029.

Introduction: The pathophysiology of inflammatory bowel disease (IBD) is incompletely understood. Current concepts imply that environmental factors (EFs) trigger disease onset as well as flares in genetically susceptible individuals. Objective: The objective of this study is to analyze the association between IBD and various EFs, which may influence the pathogenesis of the disease. Methods: 2,294 patients from the Swiss IBD Cohort Study (SIBDCS) received a questionnaire regarding EF including mode of delivery, breastfeeding, animals in household, and place of residence. The control group comprised patients’ childhood friends, who grew up in a similar environment (“friends cohort”). Results: A total of 1,111 questionnaires were returned from SIBDCS patients (response rate: 48.4%). Breastfeeding for p = 0.006). IBD patients reported less pet animals in the household than the control group (p = 0.004). The presence of cats or dogs (OR: 0.688, p = 0.015) and pet rodents (OR: 0.598, p = 0.001) in the household before the age of 20 was inversely associated with the risk for UC/IC. Conclusion: The present study underlines the importance of EFs in the pathogenesis of IBD. Overall, the development of UC/IC seems to be more affected from environmental influences than from Crohn’s disease. Our results imply a protective effect of possessing pet animals in household and short breastfeeding regarding the onset of UC/IC.

Background/Aims: Among the severe immune-related adverse events (irAEs) that occur with immune checkpoint inhibitor (ICI) therapy, colitis is the most frequent one. This study aimed at describing the experience from the largest gastroenterology unit in Switzerland with immune checkpoint inhibitor-associated colitis (ICIAC), its clinical presentation, management, and outcomes. Methods: We performed a retrospective review of patients who were referred for the evaluation of ICIAC between January 2011 and October 2018 to the Division of Gastroenterology and Hepatology, University Hospital Zurich. Results: Thirty-three patients with immune-related colitis grade 3 or 4 met the inclusion criteria and were analyzed in detail: All patients had diarrhea, 64% had abdominal pain, 42% had bloody stool, 27% had emesis, and 18% developed fever. In total, 33% were successfully treated with corticosteroids alone; 66% were steroid-refractory and treated with infliximab or vedolizumab. Two of these patients developed severe complications requiring surgery. All patients reached complete remission of ICIAC and its symptoms. At colonoscopy, ulcerations were seen in 37% of steroid-refractory versus 63% of steroid-responsive cases. Deep histological ulcerations invading the submucosa were only present in steroid-refractory cases. Conclusion: ICIAC is a severe irAE which frequently requires high-dose steroids and a close follow-up due to deleterious complications. The detection of histologically diagnosed deep ulcerations may predict a steroid-refractory course and may warrant early application of infliximab. However, larger studies are required to confirm our findings.

Klassifikationen und Aktivitatsindizes bei Colitis ulcerosa und Morbus Crohn konnen klinische Hilfsmittel zur Aktivitatsbeurteilung chronisch-entzundlicher Darmerkrankungen (CED) darstellen. Viele der Indizes sind jedoch recht kompliziert und werden daher haufig nur fur klinische Studien gebraucht, um den Effekt einer therapeutischen Intervention moglichst klar quantifizieren zu konnen. Die therapeutischen Fortschritte, die bei der Behandlung von CED in den letzten Jahren gemacht wurden, und die wachsende Zahl der Optionen, die zur Verfugung stehen, haben die Bedeutung der Beurteilung der Krankheitsaktivitat deutlich gesteigert und fur den klinischen Alltag relevanter gemacht.

Blutige Diarrho oft mit Schleimbeimengungen ist das Leitsymptom der Colitis ulcerosa (CU). Seltener als beim Morbus Crohn (MC) sind Abdominalschmerzen und systemische Symptome vorhanden. Beides jedoch kommt vor, besonders bei schwerer Krankheitsaktivitat. Im Falle einer starker aktiven Erkrankung findet sich auch Fieber und Gewichtsverlust.