Inflammatory bowel disease (IBD) is associated with malnutrition, which can further impair disease course and quality of life. Therefore, guidelines advocate screening of patients in clinical practice. The prevalence of malnutrition in IBD-cohorts however, varies widely, mainly due to differences in parameters used. The primary aim of the present study was to assess the prevalence of malnutrition using single and a combined set of parameters (Global Leadership Initiative on Malnutrition (GLIM) criteria). Secondary aims were i) to evaluate the accuracy of screening recommendations given in current IBD guidelines and ii) to explore which patients have an increased risk of malnutrition. Malnutrition was defined by the GLIM criteria, based on the combination of a phenotypic (i.e. non-volitional weight loss, low body mass index (BMI), or reduced muscle mass) and an etiologic criterium (i.e. reduced food intake or assimilation, and disease burden or inflammation). Malnutrition was also determined using single parameters for impaired body composition, muscle strength or caloric intake (Table 1), and the combination of low BMI and unintentional weight loss as advised in current IBD guidelines. To screen for malnutrition, the Short Nutritional Assessment Questionnaire (SNAQ) and Malnutrition Universal Screening Tool (MUST) were completed. Independent risk factors (i.e. clinical and demographic factors) for malnutrition were analyzed by multivariable logistic regression. Of the 200 included patients (139 CD, 61 UC), 41 (20.5%) fulfilled the GLIM criteria, 95 (47.5%) had at least one parameter for malnutrition impaired (Figure 1). The fat free mass index was most often affected. When unintentional weight loss and/or low BMI was used as screening marker for nutritional status in line with current IBD guidelines, 29 (14.5%) patients would have been identified (Figure 2). Screening for malnutrition using the SNAQ and MUST detected 44 (22.0%) and 23 (12.9%) patients with a positive score. Only female sex was associated with malnutrition when at least one parameter was impaired (OR 2.47, 95% CI 1.35–4.51). Malnutrition prevalence among IBD outpatients according to the GLIM criteria was found to be 20.5%. Almost half of the IBD outpatients had malnutrition as defined by various single parameters and irrespective of disease characteristics. Screening instruments and/or markers according to current IBD guidelines, did not identify a substantial part of the patients. Therefore, screening for malnutrition is recommended for all IBD outpatients by multiple parameters, with special attention for assessing fat free mass and reduced intake.

Chronic abdominal pain is highly prevalent in IBD patients in remission. The aetiology is incompletely understood, although persistent histologic inflammation, post-inflammatory visceral hypersensitivity, and altered gut-brain interaction are believed to contribute. Data on the characteristics of IBD patients suffering from chronic abdominal pain are sparse, yet essential for the identification of treatment targets. We investigated clinical, lifestyle and psychosocial factors associated with chronic abdominal pain in a real-world cohort of IBD patients in remission. A prospective multicentre study was performed enrolling consecutive IBD patients, between Jan 1, 2020 and Jul 1, 2021, using myIBDcoach, an established remote monitoring platform for IBD. Patient reported outcome measures on disease activity, lifestyle and psychosocial factors (i.e. depressive symptoms, anxiety, stress, and life events) were assessed in three-monthly intervals. Chronic abdominal pain in IBD in remission (IBDremissionPain+) was defined as an abdominal pain score ≥3 (1–10 numeric rating scale (NRS)) at ≥1/3 of all assessments combined with faecal calprotectin <150 μg/g in 90 days around periodic assessments. Multivariable logistic regression, adjusting for relevant confounders, was performed to identify risk factors for IBDremissionPain+ compared to patients in remission without chronic abdominal pain (IBDremissionPain-). In total, 559 patients were followed prospectively, of which 429 (76.7%) were in biochemical remission. Of these, 198 (46.2%) fulfilled the criteria for chronic abdominal pain. IBDremissionPain+ patients were characterized by female sex, higher BMI, and shorter disease duration compared to IBDremissionPain- (Table 1). IBDremissionPain+ patients reported significantly higher levels of stress, fatigue, depressive and anxiety symptoms, and occurrence of life events (Table 2). On multivariable logistic regression, female sex (aOR 2.58), shorter disease duration (<10years, aOR 2.31), higher BMI (aOR 1.06), higher levels of stress (aOR 1.19), fatigue (aOR 4.73), and life events (aOR 1.65) were all significantly associated with chronic abdominal pain (Table 3). The univariable association between pain and anxiety and depressive symptoms was modulated by stress in the multivariable analysis. In this real-world population of IBD patients in remission, 46.2% experience chronic abdominal pain, characterized by female sex, shorter disease duration, higher BMI, fatigue and psychosocial factors. The gut-brain interaction in this population is represented by higher levels of depressive and anxiety symptoms, but the relation to abdominal pain is potentially modulated through increased levels of perceived stress.

Iron deficiency (ID) and anaemia in Inflammatory Bowel Disease (IBD) are associated with reduced quality of life, worse disease outcomes, and an increase in healthcare costs. In the European guidelines, anaemia is listed as one of the treatment goals. The data on the prevalence of anaemia and ID are inconsistent. Therefore, we evaluated the prevalence of ID, anaemia, and potential risk factors in a large Dutch outpatient population. Between January and November 2021, consecutive adult outpatients with IBD, who did not have significant comorbidities associated with anaemia, were included in this study across 16 general, teaching, and academic hospitals within the Netherlands. Besides demographic and clinical data, relevant biochemical parameters such as haemoglobin (Hb), Mean Corpuscular Volume (MCV), iron indices, and inflammatory markers (e.g., C-reactive protein (CRP) and faecal calprotectin (FCP)) were extracted from medical records. Active IBD was defined by either CRP >5mg/L or FCP >150mg/g. ID was defined by ferritin <100µg/L in case of inflammation and <30µg/L in quiescent IBD, or transferrin saturation <20%. The Dutch national reference range was used to define anaemia: Hb <7.5mmol/L or <8.5mmol/L for females and males, respectively. The data were analysed by stratifying patients into Crohn’s Disease (CD) and Ulcerative Colitis (UC) groups, with the latter also including patients with IBD-unclassified (IBDU). In total, 2197 patients (1271 CD, 849 UC, and 77 IBDU) were included in the study. The overall prevalence of anaemia, iron-deficiency anaemia (IDA), and ID was: 18.0%, 12.2%, and 43.4%, respectively. The prevalence of all three conditions did not differ between the CD and UC groups (P>0.05). Severe anaemia (Hb<6.2 mmol/L) was observed only in 28 patients. ID was more frequently observed in biochemically active IBD compared with quiescent IBD (70.8% versus 23.9%; P<0.001). Female gender, younger age, low MCV, and a twofold increase in biochemical inflammation were associated with ID development in multivariable analysis: Log2FCP [OR 1.39; 95% CI: 1.29–1.50; P<0.001] and Log2platelets [OR 1.85; 95% CI: 1.16–2.95; P<0.01]. In multivariable analysis, low ferritin and MCV, inflammation, older age, and male gender were associated with a higher risk of anaemia; however, disease location or behaviour did not affect the risk of developing anaemia or ID. One in five ambulatory IBD patients presents with anaemia that is primarily caused by ID. Inflammation increases the risk of ID and anaemia regardless of IBD type or disease location. High ID prevalence suggests the need for screening and treatment optimisation.

EDITORS, We read with interest the study by Khan et al regarding the incidence and impact of IBD medications on risk of pneumonia and pneumoniarelated hospitalisation.1 We compliment the authors for their effort to address the paucity of data on infections such as pneumonia in the IBD population. Using the nationwide Veterans Affairs database, they found incidence rates of 6.47 and 2.52 per 1000 personyears (PY) for pneumonia and pneumoniarelated hospitalisations, respectively. The strict definition for pneumonia events in their study has ensured the inclusion of clinically relevant cases ( i.e., more severe cases) of pneumonia, but may have led to underreporting of milder infectious events. The choice to include a positive chest Xray in their definition might also have led to variable sensitivity rates.2 Although mildtomoderate lower respiratory tract infections (LRTIs) are generally associated with low morbidity and mortality rates, they can have negative effects on patients' quality of life and perceived health, lead to increased healthcare costs and decreased societal participation. Reporting differences in all infections is important when addressing the real burden of treatment options in IBD. To add further insight on the prevalence of these infections, we share our realworld multicentre experience with the IBD population in South Limburg based on data collected using myIBDcoach, an established telemedicine platform for IBD management, which contains several patientreported outcome measures and remote monitoring tools, including periodic assessment of infectious events.3 In 600 IBD patients (mean age at cohort entry 49.7 [SD 14.9]; n = 342 Crohn’s disease [59.9% female]; n = 258 ulcerative colitis [47.7% female]), included between 1 January 2020 and 1 January 2021, we observed 43 LRTIs during followup (including pneumonia, excluding COVID19). Of these, 16 were mild (i.e., either requiring no treatment or analgesics), 25 moderate (i.e., requiring oral antibiotics) and two severe ( i.e., hospitalisation or intravenous antibiotics), corresponding to incidence rates of 2.5, 4.0 and 0.3 per 100 PY, respectively (Table 1). All events were crosschecked with GP and pharmacy data, and no LRTIrelated deaths were observed. Representativeness of this subset of patients for the realworld situation was established by comparing demographics (age, sex, smoking) and clinical characteristics (Montreal classification) to the total IBD population in SouthLimburg.4 We acknowledge the smaller sample size when compared to the study of Khan et al and understand that their study design did not allow for capturing milder infections. However, the rates observed in our study, especially for moderate infections (requiring antibiotics), are substantially higher than those observed by Khan et al, which cannot only be explained by potential other causes of LRTIs in our cohort. Data on mild and moderate infections in medically treated IBD patients remain scarce and the most plausible explanation is that events treated by general practitioners are not systematically captured in surveillance registries. Our data particularly underscore that, in a realworld population of IBD patients, a substantial proportion of LRTIs follow a mildtomoderate course. Remote monitoring tools designed to periodically assess infectious events could overcome the paucity of data regarding mild and moderate infections.

Introduction: The world population is ageing, resulting in increased prevalence of age-related comorbidities and healthcare costs. Limited data are available on intestinal health in elderly populations. Structural and functional changes, including altered visceroperception, may lead to altered bowel habits and abdominal symptoms in healthy individuals and irritable bowel syndrome (IBS) patients. Our aim was to explore age-related changes in gastrointestinal symptoms and underlying mechanisms. Methods: In total, 780 subjects (IBS patients n = 463, healthy subjects n = 317) from two separate studies were included. Subjects were divided into different age groups ranging from young adult to elderly. Demographics and gastrointestinal symptom scores were collected from all participants using validated questionnaires. A subset of 233 IBS patients and 103 controls underwent a rectal barostat procedure to assess visceral hypersensitivity. Sigmoid biopsies were obtained from 10 healthy young adults and 10 healthy elderly. Expression of the visceral pain-associated receptors transient receptor potential (TRP) Ankyrin 1 (TRPA1) and Vanilloid 1 (TRPV1) genes were investigated by quantitative RT-PCR and immunofluorescence. Results: Both elderly IBS and healthy individuals showed significantly lower scores for abdominal pain (p < 0.001) and indigestion (p < 0.05) as compared to respective young adults. Visceral hypersensitivity was less common in elderly than young IBS patients (p < 0.001). Relative TRPA1 gene transcription, as well as TRPA1 and TRPV1 immunoreactivity were significantly lower in healthy elderly versus healthy young adults (p < 0.05). Conclusions: Our findings show an age-related decrease in abdominal pain perception. This may in part be related to decreased TRPA1 and/or TRPV1 receptor expression. Further studies are needed to reveal precise underlying mechanisms and the associations with intestinal health.

In current guidelines, thiopurines are still recommended as first-line maintenance therapy for patients with Crohn’s disease (CD). Due to their lack of immunogenicity, oral administration route and low costs, thiopurines are an attractive first-line treatment option. However, in recent studies the position of thiopurine monotherapy in CD has been questioned as a result of relatively lower overall effectiveness rates compared to ulcerative colitis. Real-world long-term effectiveness data substantiating the use and position of thiopurines in CD management remain sparse. We assessed long-term effectiveness of thiopurine monotherapy in CD using the population-based IBD South-Limburg (IBDSL) cohort. All CD patients in the IBDSL cohort starting thiopurine monotherapy as first-line maintenance therapy between 1991–2014 were included. Thiopurine monotherapy was defined effective if either: (1) no escalation to biological treatment, (2) no course of corticosteroids, (3) no resective surgery or, (4) no hospitalization for active disease was required whilst on thiopurine treatment. Patients with early treatment discontinuation (i.e. <3 months) were identified, including reason of discontinuation. Long-term effectiveness was assessed adjusting for differences in follow-up between patients using Kaplan-Meier analysis. Potential risk factors for therapy failure were identified using Cox regression. In total, 643/1162 (55.3%) CD patients (median follow-up: 8.5 years IQR 5.0–13.2) received first-line thiopurine monotherapy after a median of 9.7 months (IQR 3.2–31.3) after diagnosis. Therapy was discontinued within three months in 164 patients (25.5%), mainly due to adverse events [Figure 1]. Thiopurine monotherapy was effective for the duration of treatment in 229/479 (35.6%) patients, corresponding to estimated effectiveness rates of 62.9%, 43.9% and 31.2% after 1, 5 and 10 years, respectively [Figure 1–2]. No significant difference in effectiveness was observed after stratifying for era of thiopurine initiation (pre-biological (1991–1998) vs. biological (>1999) era, p=0.84). Factors associated with thiopurine failure were stricturing disease (aHR 1.41, 95%CI 1.01–1.96) and upper GI involvement (aHR 1.52, 95%CI 1.02–2.28) at diagnosis. During follow-up, 40/229 patients with a durable response discontinued treatment due to quiescent disease. Of these, 35 patients (87.5%) remained without treatment 24 months after discontinuation. Real-world data from this population-based study demonstrate that thiopurine monotherapy remains an effective and durable first-line treatment option for CD, even in the biological era. These results should be considered in the ongoing discussion regarding the position of thiopurine therapy.

Immunomodulators and biologicals are cornerstones in the current management of Inflammatory Bowel Disease (IBD), but are associated with increased risk of infections. Post-marketing surveillance studies are important to assess the risk for infectious side effects in real-world populations, yet mainly focus on severe infections. Data on mild and moderate infections in IBD patients are scarce, primarily since self-limiting infections and infections treated by the general practitioner are not systematically captured in surveillance registries. Mild and moderate infections take longer to clear in immunosuppressed patients, have a large impact on (work) disability and quality of life, and potentially precede severe infections. In the current study, we aimed to develop and implement a remote monitoring tool for real-world assessment of infections in IBD patients. Through a structured iterative process with input from IBD specialists, nurse practitioners, and a comprehensive literature review, a 7-item Questionnaire comprising 15 different types of infections (covering e.g. upper/lower respiratory tract; urinary tract; eye; and skin infections) was developed to measure Patient-Reported Infections (PRIQ) with a recall period of 3 months. Infection severity was defined as either mild (self-limiting or requiring topical/local treatment), moderate (requiring oral antibiotic, antiviral or antifungal drugs) or severe (requiring hospitalization and/or IV treatment). To ascertain comprehensiveness and comprehensibility in the intended study population prior to implementation, in three rounds a total of 36 randomly selected IBD patients visiting the outpatient clinic were interviewed individually until saturation was reached. Overall, patient understanding of the PRIQ was good and cognitive interviews did not result in reduction of questionnaire-items. Analysis of feedback from interviews resulted in addition of definitions to certain response options (e.g. definition for antivirals) and minor linguistic adjustments to further improve patient understanding. A total of three patients (8.3%) raised concerns on the recall period of 3 months, which after expert consensus, did not result in alteration of the recall period. Next, the PRIQ was digitized and implemented in myIBDcoach, an established telemedicine platform for management of IBD. We developed a remote monitoring tool (PRIQ) to assess patient-reported infections in IBD and ascertained patient understanding through cognitive interviewing. A prospective multicentre study using the myIBDcoach platform is ongoing to validate the PRIQ and subsequently report the risk of mild and moderate infections across different treatment regimens in IBD patients (NCT04151420).

Self‐rating scales are frequently used to screen for anxiety and depression in patients with irritable bowel syndrome (IBS). Different cutoff values are recommended in literature, and guidelines have suggested the use of other screening instruments over time. The aim of this study was to assess the correlation between the most commonly used psychological screening instruments for anxiety and depression in IBS and to compare custom cutoff scores for these instruments.

Abstract Background and study aims There are no reliable data to predict which patients with gastroparesis (GP) would benefit the most from gastric peroral endoscopic pyloromyotomy (G-POEM). The aim of the present study was to assess whether antro-duodenal motility patterns and pyloric distensibility can predict the outcome of G-POEM in patients with decompensated GP. Patients and methods In an open-label study, patients with GP and refractory symptoms were eligible for treatment with G-POEM if treatment attempts according to a standardized stepwise protocol had failed. Baseline assessment included Gastroparesis Cardinal Symptom Index (GCSI), C13-octanoic gastric emptying breath test and high-resolution antro-duodenal manometry. Pyloric distensibility using EndoFlip measurements was assessed at baseline and 3 months after the procedure. Explorative analyses were performed on potential predictors of response using logistic regression analyses. Results Twenty-four patients with decompensated GP underwent G-POEM. At baseline, 78.3 % and 61.9 % of patients showed antral hypomotility and neuropathic motor patterns, respectively. The technical success rate was 100 % (24/24). Mean GCSI improved significantly at 3, 6, and 12 months after G-POEM (P = 0.01). Median distensibility index (DI) improved significantly as compared with baseline (7.5 [6.9;11.7] vs. 5.3[3.1;8.1], P = 0.004). A significant correlation was found between clinical response at 6 months and pyloric DI improvement (P = 0.003). No potential predictors of clinical response after G-POEM could be identified in an explorative analysis. Conclusions G-POEM improved pyloric distensibility patterns in patients with decompensated GP. Clinical response at 6 months after G-POEM was associated with pyloric distensibility improvement. However, no potential predictors of response could be identified from either antro-duodenal motility patterns or pyloric distensibility.

ABSTRACT Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) show a large overlap in clinical presentation, which presents diagnostic challenges. As a consequence, invasive and burdensome endoscopies are often used to distinguish between IBD and IBS. Here, we aimed to develop a noninvasive fecal test that can distinguish between IBD and IBS and reduce the number of endoscopies. We used shotgun metagenomic sequencing to analyze the composition and function of gut microbiota of 169 IBS patients, 447 IBD patients and 1044 population controls and measured fecal Calprotectin (FCal), human beta defensin 2 (HBD2), and chromogranin A (CgA) in these samples. These measurements were used to construct training sets (75% of data) for logistic regression and machine learning models to differentiate IBS from IBD and inactive from active IBD. The results were replicated on test sets (remaining 25% of the data) and microbiome data obtained using 16S sequencing. Fecal HBD2 showed high sensitivity and specificity for differentiating between IBD and IBS (sensitivity = 0.89, specificity = 0.76), while the inclusion of microbiome data with biomarkers (HBD2 and FCal) showed a potential for improvement in predictive power (optimal sensitivity = 0.87, specificity = 0.93). Shotgun sequencing–based models produced comparable results using 16S-sequencing data. HBD2 and FCal were found to have predictive power for IBD disease activity (AUC ≈ 0.7). HBD2 is a novel biomarker for IBD in patients with gastro-intestinal complaints, especially when used in combination with FCal and potentially in combination with gut microbiome data.

A 31-year-old woman with hepatocellular carcinoma suffered from recurrent oesophageal variceal bleeding due to portal hypertension, which was caused by severe compression of the portal vein by metastatic lymph nodes. Endoscopic band ligation and pharmacological treatment did not suffice to prevent recurrence of variceal bleeding. Eventually, after the fifth variceal bleeding within 6 months, the patient was admitted to the intensive care unit in a haemodynamic shock. A Sengstaken-Blakemore tube was inserted and all treatment options were discussed, but only percutaneous transhepatic recanalisation of the portal vein with stent placement to reduce portal vein pressure was thought to be feasible with any chance to relieve portal vein pressure. After successful portal vein stenting, our patient did not have any recurrent bleeding in the remaining year of her life. We suggest that percutaneous transhepatic portal vein stenting may be a feasible and adequate last line treatment for complications of portal hypertension.

INTRODUCTION: Gastrointestinal symptoms in irritable bowel syndrome (IBS) have been correlated with psychological factors using retrospective symptom assessment. However, real-time symptom assessment might reveal the interplay between abdominal and affective symptoms more reliably in a longitudinal perspective. The aim was to evaluate the association between stress and abdominal pain, using the Experience Sampling Method (ESM) as a real-time, repeated measurement method. METHODS: Thirty-seven patients with IBS (26 women; mean age 36.7 years) and 36 healthy controls (HC; 24 women; mean age 31.1 years) completed an electronic ESM during 7 consecutive days. Abdominal pain and stress were scored on an 11-point Numeric Rating Scale at a maximum of 10 random moments each day. RESULTS: Abdominal pain scores were 2.21 points higher in patients with IBS compared with those in HC (P < 0.001), whereas stress levels did not differ significantly (B: 0.250, P = 0.406). In IBS, a 1-point increase in stress was associated with, on average, 0.10 points increase in abdominal pain (P = 0.017). In HC, this was only 0.02 (P = 0.002). Stress levels at t = −1 were not a significant predictor for abdominal pain at t = 0 in both groups, and vice versa. DISCUSSION: Our results demonstrate a positive association between real-time stress and abdominal pain scores and indicate a difference in response to stress and not a difference in experienced stress per se. Furthermore, an in-the-moment rather than a longitudinal association is suggested. This study underlines the importance of considering the individual flow of daily life and supports the use of real-time measurement when interpreting potential influencers of abdominal symptoms in IBS.