Acacia fiber or probiotic supplements to relieve gastrointestinal complaints in patients with constipation-predominant IBS: a 4-week randomized double-blinded placebo-controlled intervention trial.

PURPOSE: To date, no adequate treatment for irritable bowel syndrome with predominant constipation complaints (IBS-C) is available. Fibers with prebiotic properties and probiotic compounds have shown promise in relieving IBS-C-related complaints. We aimed to determine the effects of a 4-week intervention with either an Acacia fiber (AF) with prebiotic properties or a probiotic Bifidobacterium Lactis (BLa80) supplement, compared to a control supplement, on stool pattern, IBS symptoms and Quality of Life (QoL), in IBS-C individuals. METHODS: A parallel, double-blind, randomized controlled trial involving 180 subjects meeting the ROME IV criteria for IBS-C was conducted. Following a 4-week observation period, subjects received either AF (10 g), Probiotic BLa80 (4 g; 2 × 1011 CFU/g) or a maltodextrin placebo (10 g) daily for 4 weeks. Subjects reported daily information on stool pattern and gastrointestinal complaints. Before and after each 4-week period, questionnaires on symptom severity, constipation symptoms, anxiety and depression and QoL were completed. Stool mass was measured for 5-days before and after the intervention. RESULTS: Stool frequency significantly improved in the AF and Probiotic BLa80 groups compared to placebo (P < 0.001, P = 0.02, respectively). Probiotic BLa80 showed a significant reduction in IBS symptom severity (P = 0.03), for AF a trend towards decreased constipation symptoms (PAC-SYM, P = 0.10) was observed. No significant changes in stool consistency, stool mass or QoL measures were observed between the AF and Probiotic BLa80 compared to placebo. CONCLUSION: Daily dietary supplementation with Acacia fiber and probiotic supplements might help IBS-C patients by relieving IBS-related complaints compared to a placebo supplement. REGISTRATION NUMBER OF CLINICAL TRIAL: The trial is registered at ClinicalTrials.gov: NCT04798417: Study Details | Nutrition to Relieve IBS Constipation | ClinicalTrials.gov.

Two randomized crossover multicenter studies investigating gastrointestinal symptoms after bread consumption in individuals with noncoeliac wheat sensitivity: do wheat species and fermentation type matter?

BACKGROUND: Many individuals reduce their bread intake because they believe wheat causes their gastrointestinal (GI) symptoms. Different wheat species and processing methods may affect these responses. OBJECTIVES: We investigated the effects of 6 different bread types (prepared from 3 wheat species and 2 fermentation conditions) on GI symptoms in individuals with self-reported noncoeliac wheat sensitivity (NCWS). METHODS: Two parallel, randomized, double-blind, crossover, multicenter studies were conducted. NCWS individuals, in whom coeliac disease and wheat allergy were ruled out, received 5 slices of yeast fermented (YF) (study A, n = 20) or sourdough fermented (SF) (study B, n = 20) bread made of bread wheat, spelt, or emmer in a randomized order on 3 separate test days. Each test day was preceded by a run-in period of 3 d of a symptom-free diet and separated by a wash-out period of ≥7 d. GI symptoms were evaluated by change in symptom score (test day minus average of the 3-d run-in period) on a 0-100 mm visual analogue scale (ΔVAS), comparing medians using the Friedman test. Responders were defined as an increase in ΔVAS of ≥15 mm for overall GI symptoms, abdominal discomfort, abdominal pain, bloating, and/or flatulence. RESULTS: GI symptoms did not differ significantly between breads of different grains [YF bread wheat median ΔVAS 10.4 mm (IQR 0.0-17.8 mm), spelt 4.9 mm (-7.6 to 9.4 mm), emmer 11.0 mm (0.0-21.3 mm), P = 0.267; SF bread wheat 10.5 mm (-3.1 to 31.5 mm), spelt 11.3 mm (0.0-15.3 mm), emmer 4.0 mm (-2.9 to 9.3 mm), P = 0.144]. The number of responders was also comparable for both YF (6 to wheat, 5 to spelt, and 7 to emmer, P = 0.761) and SF breads (9 to wheat, 7 to spelt, and 8 to emmer, P = 0.761). CONCLUSIONS: The majority of NCWS individuals experienced some GI symptoms for ≥1 of the breads, but on a group level, no differences were found between different grains for either YF or SF breads. CLINICAL TRIAL REGISTRY: clinicaltrials.gov, NCT04084470 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT04084470).

Intraintestinal fermentation of fructo- and galacto-oligosaccharides and the fate of short-chain fatty acids in humans.

Consumption of fructo- (FOS) and galacto-oligosaccharides (GOS) has health benefits which have been linked in part to short-chain fatty acids (SCFA) production by the gut microbiota. However, detailed knowledge of this process in the human intestine is lacking. We aimed to determine the acute fermentation kinetics of a FOS:GOS mixture in healthy males using a naso-intestinal catheter for sampling directly in the ileum or colon. We studied the fate of SCFA as substrates for glucose and lipid metabolism by the host after infusion of 13C-SCFA. In the human distal ileum, no fermentation of FOS:GOS, nor SCFA production, or bacterial cross-feeding was observed. The relative composition of intestinal microbiota changed rapidly during the test day, which demonstrates the relevance of postprandial intestinal sampling to track acute responses of the microbial community toward interventions. SCFA were vividly taken up and metabolized by the host as shown by incorporation of 13C in various host metabolites.

The impact of running on gastrointestinal symptoms in patients with irritable bowel syndrome.

INTRODUCTION: Physical activity has been suggested to alleviate gastrointestinal (GI) symptoms in patients with irritable bowel syndrome (IBS); however, evidence is scarce. Running has become increasingly popular and may be beneficial for patients with IBS. To obtain more insight in the potential application of running as therapy, we aimed to explore the impact of running and its intensity on GI symptoms in patients with IBS. METHODS: Data from a large observational study in runners were used for this nested case-control study, which included 153 runners with IBS and 153 controls. All participants had completed a questionnaire on personal characteristics, running characteristics and GI symptoms. Regarding GI symptoms, the severity of nine symptoms was asked, both at rest and during and/or shortly (up to 3 h) after running. Each symptom could be scored on a scale from 0 (not bothersome) to 100 (very bothersome), resulting in a maximum total score of 900 points. KEY RESULTS: The prevalence and total severity score of GI symptoms were higher in runners with IBS than in controls, both at rest and during running. Among runners with IBS, the median (25th-75th percentile) total severity score during/after running was significantly lower than at rest (118 [50-200] vs. 150 [90-217]), while in controls no significant difference between running and rest was observed. Analyses stratified for running intensity revealed that the beneficial effect in runners with IBS was present when their most intensive training session was moderately intensive or intensive but not very intensive. CONCLUSIONS & INFERENCES: Running, particularly on moderate intensity, could have a beneficial effect on GI symptoms in patients with IBS.

The effect of expectancy versus actual gluten intake on gastrointestinal and extra-intestinal symptoms in non-coeliac gluten sensitivity: a randomised, double-blind, placebo-controlled, international, multicentre study.

BACKGROUND: Many individuals without coeliac disease or wheat allergy reduce their gluten intake because they believe that gluten causes their gastrointestinal symptoms. Symptoms could be affected by negative expectancy. Therefore, we aimed to investigate the effects of expectancy versus actual gluten intake on symptoms in people with non-coeliac gluten sensitivity (NCGS). METHODS: This randomised, double-blind, placebo-controlled, international, multicentre study was done at the University of Leeds (Leeds, UK), Maastricht University (Maastricht, the Netherlands), and Wageningen University and Research (Wageningen, the Netherlands). People aged 18-70 years with self-reported NCGS (ie, gastrointestinal symptoms within 8 h of gluten consumption) without coeliac disease and wheat allergy were recruited. Participants had to follow a gluten-free or gluten-restricted diet for at least 1 week before (and throughout) study participation and had to be asymptomatic or mildly symptomatic (overall gastrointestinal symptom score ≤30 mm on the Visual Analogue Scale [VAS]) while on the diet. Participants were randomly assigned (1:1:1:1; blocks of eight; stratified by site and gender) to one of four groups based on the expectation to consume gluten-containing (E+) or gluten-free (E-) oat bread for breakfast and lunch (two slices each) and actual intake of gluten-containing (G+) or gluten-free (G-) oat bread. Participants, investigators, and those assessing outcomes were masked to the actual gluten assignment, and participants were also masked to the expectancy part of the study. The primary outcome was overall gastrointestinal symptom score on the VAS, which was measured at and corrected for baseline (before breakfast) and hourly for 8 h, with lunch served after 4 h, and analysed per-protocol. Safety analysis included all participants incorporated in the per-protocol analysis. The study is registered at ClinicalTrials.gov, NCT05779358, and has ended. FINDINGS: Between Oct 19, 2018, and Feb 14, 2022, 165 people were screened and 84 were randomly assigned to E+G+ (n=21), E+G- (n=21), E-G+ (n=20), or E-G- (n=22). One person in the E+G+ group was excluded due to not following test day instructions, leaving 83 participants in the per-protocol analysis. Median age was 27·0 years (IQR 21·0-45·0), 71 (86%) of 83 people were women, and 12 (14%) were men. Mean overall gastrointestinal symptom score was significantly higher for E+G+ (16·6 mm [95% CI 13·1 to 20·0]) than for E-G+ (6·9 mm [3·5 to 10·4]; difference 9·6 mm [95% CI 3·0 to 16·2], p=0·0010) and E-G- (7·4 mm [4·2 to 10·7]; difference 9·1 mm [2·7 to 15·6], p=0·0016), but not for E+G- (11·7 mm [8·3 to 15·1]; difference 4·9 mm [-1·7 to 11·5], p=0·28). There was no difference between E+G- and E-G+ (difference 4·7 mm [-1·8 to 11·3], p=0·33), E+G- and E-G- (difference 4·2 mm [-2·2 to 10·7], p=0·47), and E-G+ and E-G- (difference -0·5 mm [-7·0 to 5·9], p=1·0). Adverse events were reported by two participants in the E+G- group (itching jaw [n=1]; feeling lightheaded and stomach rumbling [n=1]) and one participant in the E-G+ group (vomiting). INTERPRETATION: The combination of expectancy and actual gluten intake had the largest effect on gastrointestinal symptoms, reflecting a nocebo effect, although an additional effect of gluten cannot be ruled out. Our results necessitate further research into the possible involvement of the gut-brain interaction in NCGS. FUNDING: Government of the Netherlands Topsector Agri & Food Top Consortium for Knowledge and Innovation, AB Mauri Global Bakery Ingredients, Baking Industry Research Trust, Borgesius-Albert Heijn, CSM Innovation Centre, the International Maize and Wheat Improvement Center (CIMMYT), DSM Food Specialties, Fazer, Healthgrain Forum, the International Association for Cereal Science and Technology, the International Wheat Gluten Association, Lantmännen, Mondelez International, Nederlands Bakkerij Centrum, Nutrition & Santé, Puratos, Rademaker, Sonneveld Group, and Zeelandia HJ Doeleman.

Prospective multicentre study of indications for surgery in patients with idiopathic acute pancreatitis following endoscopic ultrasonography (PICUS).

BACKGROUND: Cholecystectomy in patients with idiopathic acute pancreatitis (IAP) is controversial. A randomized trial found cholecystectomy to reduce the recurrence rate of IAP but did not include preoperative endoscopic ultrasonography (EUS). As EUS is effective in detecting gallstone disease, cholecystectomy may be indicated only in patients with gallstone disease. This study aimed to determine the diagnostic value of EUS in patients with IAP, and the rate of recurrent pancreatitis in patients in whom EUS could not determine the aetiology (EUS-negative IAP). METHODS: This prospective multicentre cohort study included patients with a first episode of IAP who underwent outpatient EUS. The primary outcome was detection of aetiology by EUS. Secondary outcomes included adverse events after EUS, recurrence of pancreatitis, and quality of life during 1-year follow-up. RESULTS: After screening 957 consecutive patients with acute pancreatitis from 24 centres, 105 patients with IAP were included and underwent EUS. In 34 patients (32 per cent), EUS detected an aetiology: (micro)lithiasis and biliary sludge (23.8 per cent), chronic pancreatitis (6.7 per cent), and neoplasms (2.9 per cent); 2 of the latter patients underwent pancreatoduodenectomy. During 1-year follow-up, the pancreatitis recurrence rate was 17 per cent (12 of 71) among patients with EUS-negative IAP versus 6 per cent (2 of 34) among those with positive EUS. Recurrent pancreatitis was associated with poorer quality of life. CONCLUSION: EUS detected an aetiology in a one-third of patients with a first episode of IAP, requiring mostly cholecystectomy or pancreatoduodenectomy. The role of cholecystectomy in patients with EUS-negative IAP remains uncertain and warrants further study.

Some patients develop acute inflammation of the pancreas without a clear cause. These patients have a high risk of developing more episodes of acute inflammation of the pancreas. Potentially, such inflammation could be caused by tiny gallstones that physicians are not able to detect. If this is true, these patients may also benefit from surgical removal of the gallbladder. However, this is still controversial. Endoscopic ultrasonography is a diagnostic procedure during which a physician looks at the gallbladder and bile ducts in detail via a small ultrasound probe inserted through the mouth. This endoscopic ultrasonography may be able to detect gallstones better than physicians were able to previously. This study tested the value of endoscopic ultrasonography, and the number of patients who developed more episodes of acute inflammation after endoscopic ultrasonography was recorded. Some 106 patients with acute inflammation of the pancreas for the first time without a clear cause participated and were offered endoscopic ultrasonography. The number of times endoscopic ultrasonography found a cause for the acute inflammation was recorded, as well as safety parameters, number of patients who developed more episodes of acute inflammation, and quality of life. After screening 957 patients, 105 ultimately underwent endoscopic ultrasonography. A cause was found in one-third of patients. This was mostly (tiny) gallstones, but chronic inflammation and even tumours were found. These patients were mostly treated surgically for their gallstones and tumours. In the first year after the first acute episode of inflammation, the inflammation came back at least once in almost one in six patients in whom endoscopic ultrasonography did not find a cause. This occurred less in patients in whom a cause was found; the inflammation came back in 1 in 16 of these patients. It was also found that having inflammation coming back negatively affected quality of life. In this study, endoscopic ultrasonography was able to detect a cause in one-third of patients with first-time acute inflammation of the pancreas. In one in four patients, this cause could be treated by a surgical procedure. Whether surgical removal of the gallbladder can be helpful in patients in whom endoscopic ultrasonography is not able to detect an aetiology should be investigated in further studies.

Effective bowel management in spinal cord injury during inpatient rehabilitation: data from the Dutch spinal cord injury database.

STUDY DESIGN: Retrospective Observational Study. OBJECTIVES: To describe bowel management in individuals with a recently acquired spinal cord injury (SCI) both at admittance and discharge from first inpatient rehabilitation, and to determine factors that contribute to effective bowel management (EBM) at discharge. SETTING: Specialized rehabilitation centers in the Netherlands. METHODS: Data from the Dutch Spinal Cord Injury Database (DSCID) collected between 2015 and 2019 was used. EBM was defined by the variables of stool frequency and fecal incontinence. After univariate analysis, a multivariate regression analysis was conducted. RESULTS: Of 1,210 participants, 818 (68%) did not have EBM at admittance. At discharge, 308 (38%) did still not have EBM (in total 33% of all participants). The odds of having EBM at discharge was 2.82 times higher for participants with ASIA Impairment Scale (AIS) D compared to those with AIS-A (95% CI: 1.38-5.78). Participants with non-traumatic SCI had higher odds of having EBM than those with traumatic SCI (OR: 0.59, 95% CI 0.38-0.91). Use of suppositories, small enema, medication influencing bowel function, and oral laxatives at admittance did not influence EBM significantly at discharge. CONCLUSIONS: Bowel management improves during first inpatient rehabilitation. However, realizing EBM after a recently acquired SCI is a challenge. This endorses the importance of bowel management during inpatient rehabilitation, especially for people with AIS-A and non-traumatic etiology.

Exercise-related abdominal complaints in a large cohort of runners: a survey with a particular focus on nutrition.

Objectives: Abdominal complaints (AC) during exercise are a common problem in runners. Nutrition is known to play a role in exercise-related AC, but information on the role of habitual dietary intake is limited. We assessed the prevalence of AC in a large cohort of runners, and investigated its association with potential risk factors, with a particular focus on nutritional factors in the habitual diet. Methods: A total of 1993 runners completed two online questionnaires: a general questionnaire on, among others, running habits and exercise-related AC and a Food Frequency Questionnaire. Runners with and without either upper AC (UAC) or lower AC (LAC) were compared regarding personal characteristics, running characteristics and habitual dietary intake. Results: 1139 runners (57%) reported AC during and/or up to 3 hours after running: 302 runners (15%) reported UAC, 1115 (56%) LAC and 278 (14%) both. In about one-third of runners with AC, these complaints negatively affected their running. Exercise-related AC were positively associated with female gender, younger age and more intense running. Most associations with nutritional factors were observed only for LAC in men, with a higher intake of energy, all macronutrients and grain products in men with LAC. In both men and women, a higher intake of tea and unhealthy choices were associated with AC. Conclusion: Exercise-related AC were quite prevalent, and in about one-third of the cases, AC impacted their running. Being female, having a younger age and running at higher intensity were positively associated with AC. Some aspects of the habitual diet were associated with AC. Most notable were positive associations for intake of fat, tea and unhealthy choices.

Factors associated with lower limb tendinopathy in a large cohort of runners: a survey with a particular focus on nutrition.

Objectives: Lower limb tendinopathy (LLT) is highly prevalent in runners. Treatment can be challenging, and knowledge of risk factors may be valuable to develop preventive or treatment interventions for LLT. The aims of this study were (1) to assess the prevalence of three common LLTs (Achilles tendinopathy (AT), patellar tendinopathy and plantar fasciopathy) in a large cohort of Dutch and Belgian runners and (2) to investigate its association with potential risk factors, with a particular focus on nutritional factors in the habitual diet. Methods: A total of 1993 runners were included in the study. They completed two online questionnaires: a general questionnaire on running habits and injuries and a Food Frequency Questionnaire. Runners with and without LLT were compared regarding personal characteristics, running characteristics and nutritional factors. Results: The point prevalence for the three LLTs was 6%; 33% of the runners reported LLT in the past and 35% had either a current or past LLT. AT was the most prevalent type of LLT, and prevalence rates for all types of LLT were higher in men than women. Positive associations with LLT were observed for age and running years (men and women), running level and running distance (men). No associations between LLT and nutritional factors were observed. Conclusion: One-third of this population of runners had ever experienced an LLT. These tendinopathies were associated with gender, age and running load, but not with nutritional factors.

Effects of multidomain lifestyle interventions on cognitive decline and Alzheimer's disease prevention: A literature review and future recommendations.

Alzheimer's disease (AD) is a neurodegenerative disorder with an increasing incidence and currently without a cure. It is speculated that targeting multiple modifiable risk factors (MRFs) could be a beneficial strategy for the prevention of cognitive decline and AD. This study provides an overview and discusses the existing literature on multidomain lifestyle interventions in relation to cognitive decline and the prevention of AD. A literature search was performed in PubMed and Scopus, for studies published in English up to 31 May 2021. We identified nine relevant studies on the effect of multidomain lifestyle interventions on cognition (n = 8) and/or AD incidence or risk scores (n = 4). The studies included a combination of the separate intervention components diet (n = 8), physical activity (n = 9), cognitive activity (n = 6), metabolic or cardiovascular risk factor reduction strategies (n = 8), social activity (n = 2), medication (n = 2), and/or supplementation (n = 1). Global cognition was improved significantly in four of the eight studies that had global cognition as the outcome. Moreover, significant improvements were shown for cognitive domains in two of the three studies with specific cognitive domains as an outcome. No effect on AD incidence was observed, although positive results were shown for AD risk scores. The results suggest that multidomain lifestyle intervention studies may be partially effective in preventing cognitive decline. However, studies were heterogeneous and limited in follow-up. Future research on the effect of multidomain lifestyle interventions on cognitive decline and AD incidence must be conducted with a longer follow-up period.

Patient selection for urgent endoscopic retrograde cholangio-pancreatography by endoscopic ultrasound in predicted severe acute biliary pancreatitis (APEC-2): a multicentre prospective study.

OBJECTIVE: Routine urgent endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic biliary sphincterotomy (ES) does not improve outcome in patients with predicted severe acute biliary pancreatitis. Improved patient selection for ERCP by means of endoscopic ultrasonography (EUS) for stone/sludge detection may challenge these findings. DESIGN: A multicentre, prospective cohort study included patients with predicted severe acute biliary pancreatitis without cholangitis. Patients underwent urgent EUS, followed by ERCP with ES in case of common bile duct stones/sludge, within 24 hours after hospital presentation and within 72 hours after symptom onset. The primary endpoint was a composite of major complications or mortality within 6 months after inclusion. The historical control group was the conservative treatment arm (n=113) of the randomised APEC trial (Acute biliary Pancreatitis: urgent ERCP with sphincterotomy versus conservative treatment, patient inclusion 2013-2017) applying the same study design. RESULTS: Overall, 83 patients underwent urgent EUS at a median of 21 hours (IQR 17-23) after hospital presentation and at a median of 29 hours (IQR 23-41) after start of symptoms. Gallstones/sludge in the bile ducts were detected by EUS in 48/83 patients (58%), all of whom underwent immediate ERCP with ES. The primary endpoint occurred in 34/83 patients (41%) in the urgent EUS-guided ERCP group. This was not different from the 44% rate (50/113 patients) in the historical conservative treatment group (risk ratio (RR) 0.93, 95% CI 0.67 to 1.29; p=0.65). Sensitivity analysis to correct for baseline differences using a logistic regression model also showed no significant beneficial effect of the intervention on the primary outcome (adjusted OR 1.03, 95% CI 0.56 to 1.90, p=0.92). CONCLUSION: In patients with predicted severe acute biliary pancreatitis without cholangitis, urgent EUS-guided ERCP with ES did not reduce the composite endpoint of major complications or mortality, as compared with conservative treatment in a historical control group. TRIAL REGISTRATION NUMBER: ISRCTN15545919.

Short-term and Long-term Outcomes of a Disruption and Disconnection of the Pancreatic Duct in Necrotizing Pancreatitis: A Multicenter Cohort Study in 896 Patients.

INTRODUCTION: Necrotizing pancreatitis may result in a disrupted or disconnected pancreatic duct (DPD) with the potential for long-lasting negative impact on a patient's clinical outcome. There is a lack of detailed data on the full clinical spectrum of DPD, which is critical for the development of better diagnostic and treatment strategies. METHODS: We performed a long-term post hoc analysis of a prospectively collected nationwide cohort of 896 patients with necrotizing pancreatitis (2005-2015). The median follow-up after hospital admission was 75 months (P25-P75: 41-151). Clinical outcomes of patients with and without DPD were compared using regression analyses, adjusted for potential confounders. Predictive features for DPD were explored. RESULTS: DPD was confirmed in 243 (27%) of the 896 patients and resulted in worse clinical outcomes during both the patient's initial admission and follow-up. During hospital admission, DPD was associated with an increased rate of new-onset intensive care unit admission (adjusted odds ratio [aOR] 2.52; 95% confidence interval [CI] 1.62-3.93), new-onset organ failure (aOR 2.26; 95% CI 1.45-3.55), infected necrosis (aOR 4.63; 95% CI 2.87-7.64), and pancreatic interventions (aOR 7.55; 95% CI 4.23-13.96). During long-term follow-up, DPD increased the risk of pancreatic intervention (aOR 9.71; 95% CI 5.37-18.30), recurrent pancreatitis (aOR 2.08; 95% CI 1.32-3.29), chronic pancreatitis (aOR 2.73; 95% CI 1.47-5.15), and endocrine pancreatic insufficiency (aOR 1.63; 95% CI 1.05-2.53). Central or subtotal pancreatic necrosis on computed tomography (OR 9.49; 95% CI 6.31-14.29) and a high level of serum C-reactive protein in the first 48 hours after admission (per 10-point increase, OR 1.02; 95% CI 1.00-1.03) were identified as independent predictors for developing DPD. DISCUSSION: At least 1 of every 4 patients with necrotizing pancreatitis experience DPD, which is associated with detrimental, short-term and long-term interventions, and complications. Central and subtotal pancreatic necrosis and high levels of serum C-reactive protein in the first 48 hours are independent predictors for DPD.

Suspected common bile duct stones: reduction of unnecessary ERCP by pre-procedural imaging and timing of ERCP.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is the procedure of choice to remove sludge/stones from the common bile duct (CBD). In a small but clinically important proportion of patients with suspected choledocholithiasis ERCP is negative. This is undesirable because of ERCP associated morbidity. We aimed to map the diagnostic pathway leading up to ERCP and evaluate ERCP outcome. METHODS: We established a prospective multicenter cohort of patients with suspected CBD stones. We assessed the determinants that were associated with CBD sludge or stone detection upon ERCP. RESULTS: We established a cohort of 707 patients with suspected CBD sludge or stones (62% female, median age 59 years). ERCP was negative for CBD sludge or stones in 155 patients (22%). Patients with positive ERCPs frequently had pre-procedural endoscopic ultrasonography (EUS) or magnetic resonance cholangiopancreatography (MRCP) imaging (44% vs. 35%; P = 0.045). The likelihood of ERCP sludge and stones detection was higher when the time interval between EUS or MRCP and ERCP was less than 2 days (odds ratio 2.35; 95% CI 1.25-4.44; P = 0.008; number needed to harm 7.7). CONCLUSIONS: Even in the current era of society guidelines and use of advanced imaging CBD sludge or stones are absent in one out of five ERCPs performed for suspected CBD stones. The proportion of unnecessary ERCPs is lower in case of pre-procedural EUS or MRCP. A shorter time interval between EUS or MRCP increases the yield of ERCP for suspected CBD stones and should, therefore, preferably be performed within 2 days before ERCP.

Comparison of lumen-apposing metal stents versus double-pigtail plastic stents for infected necrotising pancreatitis.

OBJECTIVE: Lumen-apposing metal stents (LAMS) are believed to clinically improve endoscopic transluminal drainage of infected necrosis when compared with double-pigtail plastic stents. However, comparative data from prospective studies are very limited. DESIGN: Patients with infected necrotising pancreatitis, who underwent an endoscopic step-up approach with LAMS within a multicentre prospective cohort study were compared with the data of 51 patients in the randomised TENSION trial who had been assigned to the endoscopic step-up approach with double-pigtail plastic stents. The clinical study protocol was otherwise identical for both groups. Primary end point was the need for endoscopic transluminal necrosectomy. Secondary end points included mortality, major complications, hospital stay and healthcare costs. RESULTS: A total of 53 patients were treated with LAMS in 16 hospitals during 27 months. The need for endoscopic transluminal necrosectomy was 64% (n=34) and was not different from the previous trial using plastic stents (53%, n=27)), also after correction for baseline characteristics (OR 1.21 (95% CI 0.45 to 3.23)). Secondary end points did not differ between groups either, which also included bleeding requiring intervention-5 patients (9%) after LAMS placement vs 11 patients (22%) after placement of plastic stents (relative risk 0.44; 95% CI 0.16 to 1.17). Total healthcare costs were also comparable (mean difference -€6348, bias-corrected and accelerated 95% CI -€26 386 to €10 121). CONCLUSION: Our comparison of two patient groups from two multicentre prospective studies with a similar design suggests that LAMS do not reduce the need for endoscopic transluminal necrosectomy when compared with double-pigtail plastic stents in patients with infected necrotising pancreatitis. Also, the rate of bleeding complications was comparable.

Complete Endoscopic Healing Is Associated With Lower Relapse Risk After Anti-TNF Withdrawal in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Discontinuation of anti-tumor necrosis factor-α treatment (anti-TNF) (infliximab and adalimumab) in patients with inflammatory bowel disease (IBD) is associated with a high relapse risk that may be influenced by endoscopic activity at the time of stopping. We assessed the relapse rate after anti-TNF withdrawal in patients with endoscopic healing and studied predictors of relapse including the depth of endoscopic healing. METHODS: This was a multicenter, prospective study in adult patients with Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU), with ≥6 months of corticosteroid-free clinical remission (confirmed at baseline) and endoscopic healing (Mayo <2/SES-CD <5 without large ulcers), who discontinued anti-TNF between 2018 and 2020 in the Netherlands. We performed Kaplan-Meier and Cox regression analyses to assess the relapse rate and evaluate potential predictors: partial (Mayo 1/SES-CD 3-4) versus complete (Mayo 0/SES-CD 0-2) endoscopic healing, anti-TNF trough levels, and immunomodulator and/or mesalamine use. RESULTS: Among 81 patients (CD: n = 41, 51%) with a median follow-up of 2.0 years (interquartile range, 1.6-2.1), 40 patients (49%) relapsed. Relapse rates in CD and UC/IBDU patients were comparable. At 12 months, 70% versus 35% of patients with partial versus complete endoscopic healing relapsed, respectively (adjusted hazard rate [aHR], 3.28; 95% confidence interval [CI], 1.43-7.50). Mesalamine use was associated with fewer relapses in UC/IBDU patients (aHR, 0.08; 95% CI, 0.01-0.67). Thirty patients restarted anti-TNF, and clinical remission was regained in 73% at 3 months. CONCLUSIONS: The relapse risk was high after anti-TNF withdrawal in IBD patients with endoscopic healing, but remission was regained in most cases after anti-TNF reintroduction. Complete endoscopic healing and mesalamine treatment in UC/IBDU patients decreased the risk of relapse.

Methanogen Levels Are Significantly Associated with Fecal Microbiota Composition and Alpha Diversity in Healthy Adults and Irritable Bowel Syndrome Patients.

Hydrogenotrophic microbes, primarily including the three functional groups methanogens, sulfate-reducing bacteria, and reductive acetogens, use hydrogen as an energy source and play an important role in maintaining the hydrogen balance in gut ecosystems. A distorted hydrogen balance has been associated with irritable bowel syndrome (IBS). However, the role of hydrogenotrophic microbes in overall microbiota composition and function remains largely unknown. This study aims to assess the distribution and stability of hydrogenotrophic functional groups in healthy adults (HAs) and IBS patients and their association with overall microbiota composition and IBS symptoms. A two-time-point study with 4 weeks in between was performed with 27 HAs and 55 IBS patients included. Our observations revealed that methanogens showed a bimodal distribution across samples. A high-level methanogen microbiota was consistently associated with higher alpha diversity, and its composition was significantly different from that of individuals with a low-level methanogen microbiota. In general, these associations were more pronounced in IBS patients than in HAs. The differences in the copy numbers of genes indicative of total bacteria and acetogens between HAs and IBS patients and their correlations with IBS symptom severity, anxiety, depression, and quality of life (QoL) were sampling time dependent. Hydrogenotrophic functional groups did not show negative abundance correlations with each other in HAs and IBS patients. These findings suggest that methanogen levels in the gut have a pronounced association with microbiota alpha diversity and composition, and the interactions between hydrogenotrophic functional groups are complex in gut ecosystems. IMPORTANCE Hydrogenotrophic microbes play an essential role in the disposal of hydrogen and the maintenance of the hydrogen balance in gut ecosystems. Their abundances vary between individuals and have been reported to be associated with human gut disorders such as irritable bowel disease. This study confirms that methanogen levels show a bimodal distribution. Moreover, a high-level methanogen microbiota was associated with higher alpha diversity, and its composition was different from that of individuals with a low-level methanogen microbiota. These associations are more pronounced in IBS patients than in healthy subjects. In addition, associations between hydrogenotrophic microbes and IBS symptom scores vary over time, which argues for the use of longitudinal study designs. Last but not least, this study suggests that the different hydrogenotrophic microbes coexist with each other and do not necessarily compete for hydrogen in the gut. The findings in this study highlight the impact of methanogens on overall microbiota composition and function.

Patient Education Regarding Fasting Recommendations to Shorten Fasting Times in Patients Undergoing Esophagogastroduodenoscopy: A Controlled Pilot Study.

This study evaluated the applicability and efficacy of patient education regarding fasting recommendations to shorten fasting times in patients undergoing esophagogastroduodenoscopy (EGD). A prospective nonrandomized controlled pilot study was performed. The intervention group (IG) was educated by nurses to eat until 6 hours and drink until 2 hours before EGD. The control group (CG) received usual care. Outcomes were applicability as perceived by patients, adherence to fasting recommendations, gastric visibility, and patients' comfort. A total of 109 patients were included of whom 42 were IG patients (37%). Patients' perspectives on fasting, their experienced discomfort, professional support, and circadian rhythm influenced application of fasting recommendations. Adherence to length of fasting from foods improved with 3:14 hours ( p < .001) and from liquids with 5:22 hours ( p < .001) in the IG compared with the CG. Gastric visibility during EGD was better in the IG than in the CG. The IG patients experienced significant less thirst, hunger, headache, and anxiety. To successfully reduce fasting times, fasting education should include positive, individual instructions, which help patients apply the fasting recommendations within their biorhythm. Positive, concrete instructions by nurses shortened fasting times before EGD, which improved gastric visibility and reduced patient discomfort.

The Experiences of Female IBS Patients Concerning Physical Activity as Treatment Modality: A Qualitative Study.

The purpose of this study is to investigate the patient's perspective on physical activity as treatment modality for irritable bowel syndrome (IBS). An interpretive phenomenological analysis (IPA) approach was used to examine the experiences of IBS patients with physical activity, through in-depth interviews with 11 female IBS patients. Experiences with physical activity varied substantially among patients. Patients attributed negative experiences with physical activity to embarrassment, anxiety, inability, and symptom deterioration. Positive experiences with physical activity were attributed to symptom relief and improvements in overall health. Accordingly, patients discussed how they considered the application of physical activity in respect of IBS. Disease activity and the timing, type, and intensity of physical activities all could alter a patient's response to physical activity. Physical activity seems to relieve complaints in most scenarios; however, a personal approach is required to tailor physical activity to the needs of each patient.

Endoscopic Versus Surgical Step-Up Approach for Infected Necrotizing Pancreatitis (ExTENSION): Long-term Follow-up of a Randomized Trial.

BACKGROUND & AIMS: Previous randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis (TENSION) trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years. METHODS: In this long-term follow-up study, we reevaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-month follow-up. The primary end point, similar to the TENSION trial, was a composite of death and major complications. Secondary end points included individual major complications, pancreaticocutaneous fistula, reinterventions, pancreatic insufficiency, and quality of life. RESULTS: After a mean follow-up period of 7 years, the primary end point occurred in 27 patients (53%) in the endoscopy group and in 27 patients (57%) in the surgery group (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.65-1.32; P = .688). Fewer pancreaticocutaneous fistulas were identified in the endoscopy group (8% vs 34%; RR, 0.23; 95% CI, 0.08-0.83). After the initial 6-month follow-up, the endoscopy group needed fewer reinterventions than the surgery group (7% vs 24%; RR, 0.29; 95% CI, 0.09-0.99). Pancreatic insufficiency and quality of life did not differ between groups. CONCLUSIONS: At long-term follow-up, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing death or major complications in patients with infected necrotizing pancreatitis. However, patients assigned to the endoscopic approach developed overall fewer pancreaticocutaneous fistulas and needed fewer reinterventions after the initial 6-month follow-up. Netherlands Trial Register no: NL8571.

A high-fibre personalised dietary advice given via a web tool reduces constipation complaints in adults.

Constipation can greatly impact the quality of life (QoL), which can be relieved by dietary fibres; however, preserving a higher fibre intake remains a challenge. We investigated the effects of a personalised dietary advice (PDA) on fibre intake and mild constipation complaints. A total number of twenty-five adults with mild constipation complaints were included in a 4-week observation period followed by a 4-week personalised intervention. The PDA provided high-fibre alternatives via a web tool. In weeks 1, 4 and 8, dietary intake, constipation complaints and QoL were assessed. Furthermore, participants collected a faecal sample at weeks 1, 4 and 8 to determine microbiota diversity and composition, and short-chain fatty acids (SCFA). Participants completed questions daily for 8 weeks regarding abdominal complaints, stool frequency and stool consistency. Fibre intake in week 8 was significantly higher compared to week 1 (Δ = 5·7 ± 6·7 g, P < 0·001) and week 4 (Δ = 5·2 ± 6·4 g, P < 0·001). Constipation severity and QoL significantly improved at week 8 compared to the observation period (P < 0·001). A higher fibre intake significantly reduced constipation severity (ß = -0·031 (-0·05; -0·01), P = 0·001) and the QoL (ß = -0·022 (-0·04; -0·01), P = 0·009). Stool consistency (P = 0·040) and abdominal pain (P = 0·030) improved significantly during the intervention period (P = 0·040), but stool frequency did not. Average microbial alpha diversity and composition and SCFA concentrations did not change over time, but indicated individual-specific dynamics. Several SCFAs were associated with constipation complaints. To conclude, a PDA effectively increased fibre intake and subsequently reduced constipation complaints, indicating that guided dietary adjustments are important and feasible in the treatment of mild constipation complaints.