Transoral Outlet Reduction (TORe) for the Treatment of Weight Regain and Dumping Syndrome after Roux-en-Y Gastric Bypass.

Obesity is a chronic relapsing disease of global pandemic proportions. In this context, an increasing number of patients are undergoing bariatric surgery, which is considered the most effective weight loss treatment for long-term improvement in obesity-related comorbidities. One of the most popular bariatric surgeries is the Roux-en-Y gastric bypass (RYGB). Despite its proven short- and long-term efficacy, progressive weight regain and dumping symptoms remain a challenge. Revisional bariatric surgery is indicated when dietary and lifestyle modification, pharmaceutical agents and/or psychological therapy fail to arrest weight regain or control dumping. However, these re-interventions present greater technical difficulty and are accompanied by an increased risk of peri- and postoperative complications with substantial morbidity and mortality. The endoscopic approach to gastrojejunal anastomotic revision, transoral outlet reduction (TORe), is used as a minimally invasive treatment that aims to reduce the diameter of the gastrojejunal anastomosis, delaying gastric emptying and increasing satiety. With substantial published data supporting its use, TORe is an effective and safe bariatric endoscopic technique for addressing weight regain and dumping syndrome after RYGB.

Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b/3 double-blind, randomised, placebo-controlled trial.

BACKGROUND: The global prevalence of ulcerative colitis is increasing, and induction and maintenance of remission is a crucial therapeutic goal. We assessed the efficacy and safety of filgotinib, a once-daily, oral Janus kinase 1 preferential inhibitor, for treatment of ulcerative colitis. METHODS: This phase 2b/3, double-blind, randomised, placebo-controlled trial including two induction studies and one maintenance study was done in 341 study centres in 40 countries. Eligible patients were aged 18-75 years with moderately to severely active ulcerative colitis for at least 6 months before enrolment (induction study A: inadequate clinical response, loss of response to or intolerance to corticosteroids or immunosuppressants, naive to tumour necrosis factor [TNF] antagonists and vedolizumab [biologic-naive]; induction study B: inadequate clinical response, loss of response to or intolerance to any TNF antagonist or vedolizumab, no TNF antagonist or vedolizumab use within 8 weeks before screening [biologic-experienced]). Patients were randomly assigned 2:2:1 to receive oral filgotinib 200 mg, filgotinib 100 mg, or placebo once per day for 11 weeks. Patients who had either clinical remission or a Mayo Clinic Score response at week 10 in either induction study entered the maintenance study. Patients who received induction filgotinib were rerandomised 2:1 to continue their induction filgotinib regimen or to placebo. Patients who received induction placebo continued receiving placebo. The primary endpoint was clinical remission by Mayo endoscopic, rectal bleeding, and stool frequency subscores at weeks 10 and 58. For the induction studies, efficacy was assessed in all randomised patients who received at least one dose of study drug or placebo within that study. For the maintenance study, efficacy was assessed in all patients randomised to any filgotinib treatment group in the induction studies who received at least one dose of study drug or placebo in the maintenance study. Patients who received placebo throughout the induction and maintenance study were not included in the full analysis set for the maintenance study. Safety was assessed in all patients who received at least one dose of the study drug or placebo within each study. This trial is registered with ClinicalTrials.gov, NCT02914522. FINDINGS: Between Nov 14, 2016, and March 31, 2020, we screened 2040 patients for eligibility. 659 patients enrolled in induction study A were randomly assigned to receive filgotinib 100 mg (n=277), filgotinib 200 mg (n=245), or placebo (n=137). 689 patients enrolled into induction study B were randomly assigned to receive filgotinib 100 mg (n=285), filgotinib 200 mg (n=262), or placebo (n=142). 34 patients in induction study A and 54 patients in induction study B discontinued the study drug before week 10. After efficacy assessment at week 10, 664 patients entered the maintenance study (391 from induction study A, 273 from induction study B). 93 patients continued to receive placebo. 270 patients who had received filgotinib 100 mg in the induction study were randomly assigned to receive filgotinib 100 mg (n=179) or placebo (n=91). 301 patients who had received filgotinib 200 mg in the induction study were randomly assigned to receive filgotinib 200 mg (n=202) or placebo (n=99). 263 patients discontinued treatment in the maintenance study. At week 10, a greater proportion of patients given filgotinib 200 mg had clinical remission than those given placebo (induction study A 26·1% vs 15·3%, difference 10·8%; 95% CI 2·1-19·5, p=0·0157; induction study B 11·5% vs 4·2%, 7·2%; 1·6-12·8, p=0·0103). At week 58, 37·2% of patients given filgotinib 200 mg had clinical remission versus 11·2% in the respective placebo group (difference 26·0%, 95% CI 16·0-35·9; p<0·0001). Clinical remission was not significantly different between filgotinib 100 mg and placebo at week 10, but was significant by week 58 (23·8% vs 13·5%, 10·4%; 0·0-20·7, p=0·0420). The incidence of serious adverse events and adverse events of interest was similar between treatment groups. In the induction studies, serious adverse events occurred in 28 (5·0%) of 562 patients given filgotinib 100 mg, 22 (4·3%) of 507 patients given filgotinib 200 mg, and 13 (4·7%) of 279 patients given placebo. In the maintenance study, serious adverse events were reported in eight (4·5%) of 179 patients given filgotinib 100 mg, seven (7·7%) of 91 patients in the respective placebo group, nine (4·5%) of 202 patients in the filgotinib 200 mg group, and no patients in the respective placebo group. No deaths were reported during either induction study. Two patients died during the maintenance study; neither was related to treatment. INTERPRETATION: Filgotinib 200 mg was well tolerated, and efficacious in inducing and maintaining clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. FUNDING: Gilead Sciences.

IgA Triggers Cell Death of Neutrophils When Primed by Inflammatory Mediators.

IVIG preparations consisting of pooled IgG are increasingly used for the treatment of autoimmune diseases. IVIG is known to regulate the viability of immune cells, including neutrophils. We report that plasma-derived IgA efficiently triggers death of neutrophils primed by cytokines or TLR agonists. IgA-mediated programmed neutrophil death was PI3K-, p38 MAPK-, and JNK-dependent and evoked anti-inflammatory cytokines in macrophage cocultures. Neutrophils from patients with acute Crohn's disease, rheumatoid arthritis, or sepsis were susceptible to both IgA- and IVIG-mediated death. In contrast to IVIG, IgA did not promote cell death of quiescent neutrophils. Our findings suggest that plasma-derived IgA might provide a therapeutic option for the treatment of neutrophil-associated inflammatory disorders.

Increasing Incidence of Microscopic Colitis in a Population-Based Cohort Study in Switzerland.

Microscopic colitis (MC) is a chronic inflammatory disease of the colon that presents with chronic, nonbloody watery diarrhea and only few or no endoscopic abnormalities. Histologic examination discriminates lymphocytic colitis (LyC; presence of ≥20 intraepithelial lymphocytes per 100 surface epithelial cells) and collagenous colitis (CC; colonic subepithelial collagen band >10 µm in diameter).1,2 MC not otherwise specified describes a subgroup of patients who do not fulfill the diagnostic criteria for either CC or LyC.1,2 Population-based epidemiologic data regarding MC are scarce. We aimed to evaluate the clinical presentation at diagnosis, incidence, and prevalence of MC in Cantons of Vaud and Fribourg, Switzerland.

Treatment Algorithms for Crohn's Disease.

BACKGROUND: Treatment of Crohn's disease (CD) patients is complex as therapy choices depend on a variety of factors, such as location and severity of inflammation, disease behavior (inflammatory, stricturing or penetrating) but also comorbidities, extra-intestinal manifestations, the patient's age, and previous therapies. Subsequently, the choice of treatment should be tailored to the individual patient. SUMMARY: This article gives the reader therapy algorithms as a guide through different CD scenarios to support the physician's decision making. New compounds introduced in CD therapy in recent years justify such an update on standard approaches. Ustekinumab and vedolizumab and their positions within the treatment options are discussed. Fistulizing perianal disease and postoperative medical prophylaxis are depicted in separate chapters with own algorithms. Key Messages: In recent years, a variety of new drugs became available to treat patients with CD - especially those who are antitumor necrosis factor (TNF) experienced with ongoing inflammation. The definitive role of vedolizumab and ustekinumab is not yet fully clarified. However, with the advantage of good safety profiles over TNF-inhibitors, these drugs will be more frequently used in the near future, also as first-line biologicals, compared to TNF-inhibitors. Concerning treatment of fistulizing disease, the knowledge of the exact anatomy of the fistula is of major importance. An interdisciplinary discussion involving gastroenterologists, surgeons, and in some cases gynecologists may help to optimize the treatment plan. Regarding the postsurgical setting in CD patients, according to the very recent Cochrane Network meta-analysis, mesalazine should be at least positioned equivalent to thiopurines and TNF-inhibitors, as shown in our algorithm.

Treatment Algorithm for Mild and Moderate-to-Severe Ulcerative Colitis: An Update.

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.

Therapeutic Drug Monitoring to Guide Clinical Decision Making in Inflammatory Bowel Disease Patients with Loss of Response to Anti-TNF: A Delphi Technique-Based Consensus.

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.

Alicaforsen, an Antisense Inhibitor of Intercellular Adhesion Molecule-1, in the Treatment for Left-Sided Ulcerative Colitis and Ulcerative Proctitis.

BACKGROUND: Data on the efficacy of intercellular adhesion molecule-1 antisense oligonucleotide alicaforsen in ulcerative colitis (UC) is inconsistent. METHODS: All patients, who had received at least one dose of alicaforsen, were analyzed retrospectively. Alicaforsen's efficacy was assessed in patients treated for left-sided UC and proctitis by comparing clinical and (if applicable) endoscopic disease activity before/after treatment. RESULTS: Twelve patients were treated for left-sided UC or proctitis. Eleven patients received a 6-week course of a once-daily 240 mg alicaforsen enema formulation. In 1 patient, treatment was discontinued, because it was found to be inefficient. Disease activity measured by the partial Mayo score and 6-point symptom score was significantly reduced after treatment (6.0 vs. 2.4, p = 0.011 and 3.7 vs. 1.4, p = 0.008). Faecal calprotectin showed a trend towards reduction (484.4 vs. 179.5 µg/g, p = 0.063). Clinical improvement was achieved in 10 patients (83.3%). In 7 patients, a relapse occurred (70%). Median duration of clinical improvement was 18.0 weeks (range 1-112). Three patients showed an ongoing improvement of >9 months. No adverse events were reported. CONCLUSIONS: A 6-week course of alicaforsen seemed to be safe and efficacious in inducing clinical improvement in patients with left-sided UC and proctitis. Prolonged clinical improvement was observed in many but not all patients.

Long-Term Efficacy and Safety of Certolizumab Pegol in an Unselected Crohn's Disease Population: The FACTS III Survey.

BACKGROUND: Long-term data of certolizumab pegol (CZP) in Crohn's disease (CD) from pivotal registry trials are limited. We therefore aimed to evaluate the long-term efficacy of CZP in clinical practice in Switzerland. METHODS: In the First Approved Certolizumab Therapeutic Experience in Switzerland-III phase IV multicenter cohort, patients receiving CZP were prospectively included all over Switzerland in (non-) academic hospitals and private practice. RESULTS: We included 104 CD patients (52 male; only 22.1% anti-tumor necrosis factor (TNF) naïve, CZP as third anti-TNF agent in 46.2%) with follow-up time between 6 weeks up to 5 years. During treatment with CZP, we observed a significant decrease of the Harvey Bradshaw Index from a median of 7 at baseline (interquartile range 4-11) to 4, 5, 4, 3, 3, and 2 at weeks 6, 26, 52, 78, 104, and 156, respectively. While anti-TNF naïve patients showed a significantly better response at the end of induction, during CZP maintenance therapy response was similar as compared to anti-TNF experienced patients as well as between patients with a short (0-5 years) vs. long duration of disease (>5 years). CONCLUSIONS: CZP is an effective long-term treatment option, including CD patients with long disease duration and prior treatment with 1 or 2 anti-TNF agents.

Development of psoriasis in IBD patients under TNF-antagonist therapy is associated neither with anti-TNF-antagonist antibodies nor trough levels.

BACKGROUND: The cause of anti-TNF-induced psoriasis is still unknown. OBJECTIVE: We aimed to evaluate if the appearance of psoriasis under anti-TNF therapy is associated with anti-TNF antibody levels and TNF-antagonist trough levels. METHODS: In this case-control study we identified 23 patients (21 with Crohn's disease [CD], two with ulcerative colitis [UC]) who developed psoriasis under infliximab (IFX, n = 20), adalimumab (ADA, n = 2), and certolizumab pegol (CZP, n= 1) and compared them regarding the anti-TNF-antagonist antibody levels with 85 IBD patients (72 with CD, 13 with UC) on anti-TNF therapy without psoriasis. RESULTS: Median disease duration was not different between the two groups (7 years in the group with psoriasis under TNF-antagonists vs. 10 years in the control group, p = 0.072). No patient from the psoriasis group had antibodies against TNF-antagonists compared to 10.6% in the control group (p = 0.103). No difference was found in IFX trough levels in the group of patients with psoriasis compared to the control group (2.6 µg/mL [IQR 0.9-5.5] vs. 3.4 µg/mL [IQR 1.4-8.1], p = 0.573). TNF-antagonist therapy could be continued in 91.3% of patients with TNF-antagonist related psoriasis and most patients responded to topical therapies. CONCLUSION: Anti-TNF-induced psoriasis seems to be independent of anti-TNF antibodies and trough levels. Interruption of Anti-TNF therapy is rarely necessary.

Crohn's disease-associated adherent invasive Escherichia coli modulate levels of microRNAs in intestinal epithelial cells to reduce autophagy.

BACKGROUND & AIMS: Levels of microRNAs are altered in intestinal tissues of patients with Crohn's disease (CD). The adherent-invasive Escherichia coli (AIEC), which colonize the ileal mucosa of patients with CD, adhere to and invade intestinal epithelial cells. We investigated the mechanism by which AIEC infection alters the expression of microRNAs and the host immune response. METHODS: Levels of microRNAs in human intestinal epithelial T84 cells and in mouse enterocytes were measured using quantitative reverse-transcription polymerase chain reaction. Luciferase assays were used to measure binding of microRNAs to the 3'-untranslated region of messenger RNA targets. Binding of nuclear factor-κB to promoters of genes encoding microRNAs was assessed by chromatin immunoprecipitation assays. Autophagy was measured by immunoblot analyses and immunofluorescent labeling of LC3. Anti-microRNAs were transferred to mice using ileal loops. Biopsy specimens from the terminal ileum of patients with ulcerative colitis (n = 20), CD (n = 20), or individuals without inflammatory bowel disease undergoing surveillance colonoscopies (controls, n = 13) were collected during endoscopic examination. RESULTS: AIEC infection up-regulated levels of microRNA (MIR) 30C and MIR130A in T84 cells and in mouse enterocytes by activating nuclear factor-κB. Up-regulation of these microRNAs reduced the levels of ATG5 and ATG16L1 and inhibited autophagy, leading to increased numbers of intracellular AIEC and an increased inflammatory response. In ileal biopsy samples of patients with CD, there was an inverse correlation between levels of MIR30C and MIR130A and those of ATG5 and ATG16L1, supporting in vitro findings. Inhibition of MIR30C and MIR130A in cultured intestinal epithelial cells and in mouse enterocytes blocked AIEC-induced inhibition of ATG5 and ATG16L1 expression and restored functional autophagy. This resulted in more effective clearance of intracellular AIEC and reduced AIEC-induced inflammation. CONCLUSIONS: Infection with AIEC up-regulates microRNAs to reduce expression of proteins required for autophagy and autophagy response in intestinal epithelial cells. Ileal samples from patients with CD have increased levels of these same microRNAs and reduced levels of ATG5 and ATG16L1.

Genetic and microbial factors modulating the ubiquitin proteasome system in inflammatory bowel disease.

OBJECTIVE: Altered microbiota composition, changes in immune responses and impaired intestinal barrier functions are observed in IBD. Most of these features are controlled by proteases and their inhibitors to maintain gut homeostasis. Unrestrained or excessive proteolysis can lead to pathological gastrointestinal conditions. The aim was to validate the identified protease IBD candidates from a previously performed systematic review through a genetic association study and functional follow-up. DESIGN: We performed a genetic association study in a large multicentre cohort of patients with Crohn's disease (CD) and UC from five European IBD referral centres in a total of 2320 CD patients, 2112 UC patients and 1796 healthy controls. Subsequently, we did an extensive functional assessment of the candidate genes to explore their causality in IBD pathogenesis. RESULTS: Ten single nucleotide polymorphisms (SNPs) in four genes were significantly associated with CD: CYLD, USP40, APEH and USP3. CYLD was the most significant gene with the intronically located rs12324931 the strongest associated SNP (p(FDR)=1.74e-17, OR=2.24 (1.83 to 2.74)). Five SNPs in four genes were significantly associated with UC: USP40, APEH, DAG1 and USP3. CYLD, as well as some of the other associated genes, is part of the ubiquitin proteasome system (UPS). We therefore determined if the IBD-associated adherent-invasive Escherichia coli (AIEC) can modulate the UPS functioning. Infection of intestinal epithelial cells with the AIEC LF82 reference strain modulated the UPS turnover by reducing poly-ubiquitin conjugate accumulation, increasing 26S proteasome activities and decreasing protein levels of the NF-κB regulator CYLD. This resulted in IκB-α degradation and NF-κB activation. This activity was very important for the pathogenicity of AIEC since decreased CYLD resulted in increased ability of AIEC LF82 to replicate intracellularly. CONCLUSIONS: Our results reveal the UPS, and CYLD specifically, as an important contributor to IBD pathogenesis, which is favoured by both genetic and microbial factors.

Monitoring disease activity and progression in Crohn's disease. A Swiss perspective on the IBD ahead 'optimised monitoring' recommendations.

BACKGROUND AND AIMS: The structured IBD Ahead 'Optimised Monitoring' programme was designed to obtain the opinion, insight and advice of gastroenterologists on optimising the monitoring of Crohn's disease activity in four settings: (1) assessment at diagnosis, (2) monitoring in symptomatic patients, (3) monitoring in asymptomatic patients, and (4) the postoperative follow-up. For each of these settings, four monitoring methods were discussed: (a) symptom assessment, (b) endoscopy, (c) laboratory markers, and (d) imaging. Based on literature search and expert opinion compiled during an international consensus meeting, recommendations were given to answer the question 'which diagnostic method, when, and how often'. The International IBD Ahead Expert Panel advised to tailor this guidance to the healthcare system and the special prerequisites of each country. The IBD Ahead Swiss National Steering Committee proposes best-practice recommendations adapted for Switzerland. METHODS: The IBD Ahead Steering Committee identified key questions and provided the Swiss Expert Panel with a structured literature research. The expert panel agreed on a set of statements. During an international expert meeting the consolidated outcome of the national meetings was merged into final statements agreed by the participating International and National Steering Committee members - the IBD Ahead 'Optimized Monitoring' Consensus. RESULTS: A systematic assessment of symptoms, endoscopy findings, and laboratory markers with special emphasis on faecal calprotectin is deemed necessary even in symptom-free patients. The choice of recommended imaging methods is adapted to the specific situation in Switzerland and highlights the importance of ultrasonography and magnetic resonance imaging besides endoscopy. CONCLUSION: The recommendations stress the importance of monitoring disease activity on a regular basis and by objective parameters, such as faecal calprotectin and endoscopy with detailed documentation of findings. Physicians should not rely on symptoms only and adapt the monitoring schedule and choice of options to individual situations.

Bone health in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are prone to reduced bone mineral density and elevated overall fracture risk. Osteopenia affects up to 40% of patients with IBD (high regional variability). Besides disease activity, IBD specialists must consider possible side effects of medication and the presence of associated diseases and extraintestinal manifestations. Osteopenia and osteoporosis remain frequent problems in patients with IBD and are often underestimated because of widely differing screening and treatment practices. Malnutrition, chronic intestinal inflammation and corticosteroid intake are the major pathophysiological factors contributing to osteoporosis. Patients with IBD are screened for osteoporosis using dual-energy X-ray absorptiometry (DXA), which is recommended for all patients with a prolonged disease course of more than three months, with repeated corticosteroid administration, aged >40 years with a high FRAX risk score or aged <40 years with multiple risk factors. From a therapeutic perspective, besides good disease control, vitamin D supplementation and glucocorticoid sparing, several specific osteological options are available: bisphosphonates, receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors (denosumab), parathyroid hormone (PTH) analogues and selective estrogen receptor modulators. This review provides an overview of the pathophysiology, diagnosis, prevention and treatment of IBD-associated bone loss.

SARS-CoV-2 vaccination in inflammatory bowel disease patients is not associated with flares: a retrospective single-centre Swiss study.

INTRODUCTION: Vaccination hesitancy is an important barrier to vaccination among IBD patients. The development of adverse events is the main concern reported. The purpose of this monocentric study was to assess SARS-CoV-2 vaccination safety in IBD patients by evaluating the postvaccination flare risk and incidence of overall adverse events. METHODS: Surveys were handed out on three consecutive months to each patient presenting at the Crohn-Colitis Centre, where they documented their vaccination status and any side effects experienced after vaccination.Dates of flares occurring in 2021 were recorded from their electronic medical records. Baseline and IBD characteristics and flare incidence were compared between the vaccinated and unvaccinated patients, and among the vaccinated population before and after their vaccination doses. The characteristics of patients who developed side effects and of those who did not were compared. RESULTS: We enrolled 396 IBD patients, of whom 91% were vaccinated. The proportion of patients who experienced flares was statistically not different between the vaccinated and the unvaccinated population (1.8 vs 2.6 flares per 100 person-months (p = 0.28)). Among vaccinated patients, there was no difference across the prevaccination, 1 month post any vaccination, and more than 1 month after any vaccination periods, and between the Spikevax and Cominarty subgroups. Overall, 46% of patients reported vaccination side effects, mostly mild flu-like symptoms. CONCLUSION: SARS-CoV-2 vaccination with mRNA vaccines seems safe, with mostly mild side effects. The IBD flare risk is not increased in the month following any vaccination.

Fecal urgency and incontinence in inflammatory bowel disease perceived by physician and patient: Results from the Swiss fecal urgency survey.

INTRODUCTION: Although increasingly appreciated, little is known about the prevalence of fecal urgency, fecal incontinence and differences between patients' and physicians' perception in inflammatory bowel disease (IBD). METHODS: We performed an online patient and physician survey to evaluate the assessment, prevalence and impact of fecal urgency and incontinence in IBD. RESULTS: A total of 593 patients (44.0% ulcerative colitis (UC), 53.5% Crohn's disease (CD), 2.2% indeterminate colitis, 2 not specified) completed the survey (65.8% females, mean age 47.1 years). Fecal urgency was often reported (UC: 98.5%, CD: 96.2%) and was prevalent even during remission (UC: 65.9%, CD: 68.5%). Fecal urgency considerably impacted daily activities (visual analog scale [VAS] 5, IQR 3-8). Yet, 22.8% of patients have never discussed fecal urgency with their physicians. Fecal incontinence was experienced by 44.7% of patients and 7.9% on a weekly basis. Diapers/pads were required at least once a month in 20.4% of patients. However, 29.7% of patients never talked with their physician about fecal incontinence. UC was an independent predictor for the presence of moderate-severe fecal urgency (OR 1.65, 95% CI 1.13-2.41) and fecal incontinence (OR 1.77, 95% CI 1.22-2.59). All physicians claimed to regularly inquire about fecal urgency and incontinence. However, the impact of these symptoms on daily activities was overestimated compared with the patient feedback (median VAS 8 vs. 5, p = 0.0113, and 9 vs. 5, p = 0.0187). CONCLUSIONS: Fecal urgency and incontinence are burdensome symptoms in IBD, with a similar prevalence in UC and CD. A mismatch was found between the physician and patient perception. These symptoms should be addressed during outpatient visits.

Swiss expert opinion: current approaches in faecal microbiota transplantation in daily practice.

INTRODUCTION: Faecal microbiota transplantation (FMT) is an established therapy for recurrent C. difficile infection, and recent studies have reported encouraging results of FMT in patients with ulcerative colitis. Few international consensus guidelines exist for this therapy, and thus FMT policies and practices differ among European countries. As of 2019, stool transplants are considered a non-standardised medicinal product in Switzerland, and a standardised production process requires authorisation by the Swiss Agency for Therapeutic Products. This authorisation leads to prolonged administrative procedures and increasing costs, which reduces treatment accessibility. In particular, patients with ulcerative colitis in Switzerland can only benefit from FMT off-label, even though it is a valid therapeutic option. Therefore, this study summarised the available data on FMT and established a framework for the standardised use of FMT. METHODS: A panel of Swiss gastroenterologists with a special interest in inflammatory bowel disease was established to identify the current key issues of FMT. After a comprehensive review of the literature, statements were formulated about FMT indications, donor screening, stool transplant preparation and administration, and safety aspects. The panel then voted on the statements following the Delphi process; the statements were reformulated and revoted until a consensus was reached. The manuscript was then reviewed by an infectiologist (the head of Lausanne's FMT centre). RESULTS: The established statements are summarised in the supplementary tables in the appendix to this paper. The working group hopes these will help standardise FMT practice in Switzerland and contribute to making faecal microbiota transplantation a safe and accessible treatment for patients with recurrent C. difficile infections and selected patients with ulcerative colitis, as well as other indications in the future.

Survey of dietary beliefs and habits of inflammatory bowel disease patients.

BACKGROUND & AIMS: It is presumed that diet plays a role in the prevention and pathogenesis of inflammatory bowel disease (IBD). Patients with Crohn's disease (CD) and ulcerative colitis (UC) often report a link between their disease and diet. However, studies evaluating patient perceptions on diet in IBD are lacking. This study aimed to assess patient beliefs on the role of diet in IBD and the adequacy of dietary advice they received. METHODS: A self-administered questionnaire was offered to consecutive patients attending two IBD centers in Switzerland. Data were collected regarding patient dietary beliefs and behaviors and whether they received medical advice on their diet. RESULTS: Of 210 questionnaires distributed, 171 were completed. Participants were mainly female (53%), young (median age 38 years) with either CD (66%) or UC (34%). Most patients believed that diet plays a role in their disease (74%), whereas only 15% believed that diet could be the trigger of their disease. Since their IBD diagnosis, more than half of patients (56%) modified their diet, and 39% did not receive dietary advice from their physicians or a dietician. Most patients (91-95%) ingested gluten, lactose, red and white meat. 20% of patients practiced intermittent fasting and only a minority had previously tried a low-FODMAP (9%) diet or probiotics supplementation (16%). CONCLUSION: The majority of IBD patients believe that diet plays a role in their disease but have never received dietary advice from their doctor or a dietician. This highlights a need for more information for IBD patients on dietary advice from the medical profession.

Pregnancy and breastfeeding in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is frequent in women during their peak reproductive years. Accordingly, a significant number of questions and uncertainties arise from this population regarding the risk of transmission of IBD to the offspring, the impact of the disease and therapies on the fertility, the role of the disease on the course of the pregnancy and the mode of delivery, the impact of the therapy on the pregnancy and fetal development as well as breastfeeding. The safety of medical therapy during pregnancy and lactation is a major concern for both pregnant women and their partners as well as for physicians. As a general rule, it can be stated that the benefit of continuing medical therapy in IBD during pregnancy outweighs the potential risks in the vast majority of instances. This article will review recent developments on this topic consistent with the European Crohn's and Colitis Organization guidelines.

Mannan-binding lectin deficiency results in unusual antibody production and excessive experimental colitis in response to mannose-expressing mild gut pathogens.

BACKGROUND: In Crohn's disease (CD) the deficiency of mannan-binding lectin (MBL) is associated with an increased prevalence of anti-Saccharomyces cerevisiae antibodies (ASCA) and with complicated phenotypes of the disease. However, the role of MBL in intestinal inflammation is currently unclear. A study was undertaken to analyse local MBL expression in human intestine and the consequences of MBL deficiency in experimental colitis and yeast infection. METHODS: ASCA were measured by ELISA. MBL was assessed by ELISA and quantitative PCR. Wild type and MBL-deficient mice were administered dextran sulfate sodium (DSS) in the presence or absence of viable Candida albicans or adhesive invasive Escherichia coli (AIEC). Mice were infected with C albicans to assess generation of anti-yeast mannan antibodies. RESULTS: MBL expression was virtually undetectable in the intestinal mucosa of both healthy controls and patients with CD, irrespective of macroscopic inflammation, indicating that systemic MBL must be responsible for the reduced risk of complicated disease in MBL-competent patients with CD. MBL-deficient mice showed enhanced DSS colitis upon oral challenge with C albicans or AIEC. C albicans could be recovered from the kidneys of colitic/C albicans-fed MBL-deficient, but not wild type mice. Infection with C albicans induced high titres of anti-C albicans mannan IgM and IgG in MBL-deficient mice but only a modest and transient IgM response with no class switch to IgG in wild type mice. Cross-reactive ASCA IgM continuously increased in MBL-deficient mice but rapidly declined after transient induction in wild type mice. In MBL-deficient mice, increased C albicans dissemination correlated with reduced early retention in the circulation. CONCLUSIONS: These results suggest that systemic MBL helps to prevent excessive inflammation upon access of normally mild pathogens across the damaged intestinal epithelium. Lack of this innate defence promotes antibody responses with cross-reactive potential against common mannan epitopes. These interpretations are compatible with the increased prevalence of ASCA and complicated disease phenotypes in MBL-deficient patients with CD.