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Background Safety of thioguanine in pregnant patients with inflammatory bowel disease [IBD] is sparsely recorded. This study was aimed to document the safety of thioguanine during pregnancy and birth. Methods In this multicentre case series, IBD patients treated with thioguanine during pregnancy were included. Data regarding disease and medication history, pregnancy course, obstetric complications, and neonatal outcomes were collected. Results Data on 117 thioguanine-exposed pregnancies in 99 women were collected. Most [78%] had Crohn’s disease and the mean age at delivery was 31 years. In 18 pregnancies [15%], IBD flared. Obstetric and infectious complications were seen in 15% [n = 17] and 7% [n = 8] of pregnancies, respectively. Ten pregnancies [8.5%] resulted in a first trimester miscarriage, one in a stillbirth at 22 weeks of gestational age and one in an induced abortion due to trisomy 21. In total, 109 neonates were born from 101 singleton pregnancies and four twin pregnancies. One child was born with a congenital abnormality [cleft palate]. In the singleton pregnancies, 10 children were born prematurely and 10 were born small for gestational age. Screening for myelosuppresion was performed in 16 neonates [14.7%]; two had anaemia in umbilical cord blood. All outcomes were comparable to either the general Dutch population or to data from three Dutch cohort studies on the use of conventional thiopurines in pregnant IBD patients. Conclusion In this large case series, the use of thioguanine during pregnancy is not associated in excess with adverse maternal or neonatal outcomes.

Capecitabine is a chemotherapeutic drug that is widely used as a monotherapy option in advanced cancer patients. After administration, it is converted into its active metabolite 5-fluorouracil (5-FU), a cytotoxic compound that may also induce adverse side effects in the gastrointestinal (GI) tract. Although these side effects can interfere with the continuation of the chemotherapy, diagnostic tools to detect early onset and prevention strategies are not available. In this explorative case study, we aim to identify differentially expressed genes (DEGs) that provide insight into the molecular mechanisms of toxicity induced by 5-FU in healthy colon tissue of breast cancer patients receiving capecitabine. Gene expression responses observed in patients were compared with those established in an in vitro model of healthy colon organoids. Colon biopsies from two patients with advanced breast cancer were collected before and after the treatment with capecitabine and used for RNA sequencing to determine transcriptomic responses. Differential expression analysis resulted in 31 affected genes, showing that the most affected pathways were transport of small molecules, cellular responses to stress, folate metabolism, NF-kB signalling pathway and immune system responses. The most biologically relevant genes were haemoglobin subunits encoding genes, involved in several processes; ATP12A, SLC26A3 and AQP8, involved in the transport of ions and water; TRIM31, a regulator of NF-kB signalling pathway; MST1P2 and MST1L, stimulators of macrophages. Comparison of human in vitro and in vivo responses showed that the gene expression of TRIM31 was similarly altered in the colon organoids exposed to 5-FU. Therefore, this gene constitutes a potential biomarker of colon toxicity that might be used in future in vitro drug safety design and screening.

BACKGROUND AND AIMS: Patients with COVID-19 infection presents with a broad clinical spectrum of symptoms and complications. As a consequence nutritional requirements are not met, resulting in weight- and muscle loss, and malnutrition. The aim of the present study is to delineate nutritional complaints, the (course of the) nutritional status and risk of sarcopenia of COVID-19 patients, during hospitalisation and after discharge.METHODS: In this prospective observational study in 407 hospital admitted COVID-19 patients in four university and peripheral hospitals, data were collected during dietetic consultations. Presence of nutrition related complaints (decreased appetite, loss of smell, changed taste, loss of taste, chewing and swallowing problems, nausea, vomiting, feeling of being full, stool frequency and consistency, gastric retention, need for help with food intake due to weakness and shortness of breath and nutritional status (weight loss, BMI, risk of sarcopenia with SARC-F ≥4 points) before, during hospital stay and after discharge were, where possible, collected.RESULTS: Included patients were most men (69%), median age of 64.8 ± 12.4 years, 60% were admitted to ICU at any time point during hospitalisation with a median LOS of 15 days and an in-hospital mortality rate of 21%. The most commonly reported complaints were: decreased appetite (58%), feeling of being full (49%) and shortness of breath (43%). One in three patients experienced changed taste, loss of taste and/or loss of smell. Prior to hospital admission, 67% of the patients was overweight (BMI >25 kg/m2), 35% of the patients was characterised as malnourished, mainly caused by considerable weight loss. Serious acute weight loss (>5 kg) was showed in 22% of the patents during the hospital stay; most of these patients (85%) were admitted to the ICU at any point in time. A high risk of sarcopenia (SARC-F ≥ 4 points) was scored in 73% of the patients during hospital admission.CONCLUSION: In conclusion, one in five hospital admitted COVID-19 patients suffered from serious acute weight loss and 73% had a high risk of sarcopenia. Moreover, almost all patients had one or more nutritional complaints. Of these complaints, decreased appetite, feeling of being full, shortness of breath and changed taste and loss of taste were the most predominant nutrition related complaints. These symptoms have serious repercussions on nutritional status. Although nutritional complaints persisted a long time after discharge, only a small group of patients received dietetic treatment after hospital discharge in recovery phase. Clinicians should consider the risks of acute malnutrition and sarcopenia in COVID-19 patients and investigate multidisciplinary treatment including dietetics during hospital stay and after discharge.

Background Patients suffering from inflammatory bowel diseases (IBD) and treated with originator infliximab are increasingly being switched to biosimilars. Some patients, however, are “reverse switched” to treatment with the originator. Here we assess the prevalence of reverse switching, including its indication and outcomes. Methods In this retrospective multicenter cohort study, data on patients with IBD from 9 hospitals in the Netherlands were collected. All adult patients with IBD were included if they previously had been switched from originator infliximab to the biosimilar CT-P13 and had a follow-up time of at least 52 weeks after the initial switch. The reasons for reverse switching were categorized into worsening gastrointestinal symptoms, adverse effects, or loss of response to CT-P13. Drug persistence was analyzed through survival analyses. Results A total of 758 patients with IBD were identified. Reverse switching was observed in 75 patients (9.9%). Patients with reverse switching were predominantly female (70.7%). Gastrointestinal symptoms (25.5%) and dermatological symptoms (21.8%) were the most commonly reported reasons for reverse switching. In 9 patients (12.0%), loss of response to CT-P13 was the reason for reverse switching. Improvement of reported symptoms was seen in 73.3% of patients after reverse switching and 7 out of 9 patients (77.8%) with loss of response regained response. Infliximab persistence was equal between patients who were reverse-switched and those who were maintained on CT-P13. Conclusions Reverse switching occurred in 9.9% of patients, predominantly for biosimilar-attributed adverse effects. Switching back to originator infliximab seems effective in patients who experience adverse effects, worsening gastrointestinal symptoms, or loss of response after switching from originator infliximab to CT-P13.

Prehabilitation has been postulated as an effective preventive intervention to reduce postoperative complications, particularly for elderly patients with a relatively high risk of complications. To date, it remains to be determined whether prehabilitation increases physical capacity and reduces postoperative complications. The aim of this study was to assess the feasibility of a 4-week multimodal prehabilitation program consisting of a personalized, supervised training program and nutritional intervention with daily fresh protein-rich food for colorectal cancer patients aged over 64 years prior to surgery. The primary outcome was the feasibility of this prehabilitation program defined as ≥80% compliance with the exercise training program and nutritional intervention. The secondary outcomes were the organizational feasibility and acceptability of the prehabilitation program. A compliance rate of ≥80% to both the exercise and nutritional intervention was accomplished by 6 patients (66.7%). Attendance of ≥80% at all 12 training sessions was achieved by 7 patients (77.8%), all patients (100%) attended ≥80% of the available training sessions. Overall, compliance with the training was 91.7%. Six patients (66.7%) accomplished compliance of ≥80% with the nutritional program. The median protein intake was 1.2 (g/kg/d). No adverse events occurred. This multimodal prehabilitation program was feasible for the majority of patients.

Background and Aims Inflammatory bowel disease [IBD] is characterized by recurrent disease flares. The impact of psychosocial wellbeing on the occurrence of flares is unclear. In this prospective study, we aimed to evaluate the association between patient-reported psychosocial wellbeing and disease flares using continuous monitoring.Methods Consecutive IBD patients were recruited from the myIBDcoach telemedicine study cohort. Over 12 months, participants reported on disease activity together with anxiety, depression, fatigue, perceived stress and life events every 1-3 months. Flares were defined using a combination of clinical disease activity and additional measurements. Generalized estimating equation models were used to assess associations between psychosocial wellbeing and flares over time. The influences of both the presence of psychosocial symptoms in general as well as novel psychosocial symptoms were analysed.Results In total, 417 patients were included. Forty-nine patients [11.8%] experienced a flare during the study period. The occurrence of life events in the preceding 3 months was positively associated with flares (odds ratio [OR] = 1.81; 95% confidence interval [CI] = 1.04-3.17), while the presence of anxiety, depression, fatigue and perceived stress in general was not. However, novel perceived stress [OR = 2.92; 95% CI = 1.44-5.90] was associated with flares.Conclusions The occurrence of life events and novel perceived stress are associated with disease flares in the next 3 months, while the presence of perceived stress in general is not. These findings underline the importance of continuous personalized monitoring of IBD patients and may contribute to the prevention of disease flares.

IntroductionCrohn’s disease (CD) is a chronic inflammatory bowel disease with a heterogeneous clinical presentation, relapse rate and treatment response. At present, no markers are available to adequately predict disease course at diagnosis. To prevent overtreatment of patients with a relative mild disease course, a step-up approach starting with corticosteroids is usually applied. Timely introduction of potentially disease modifying drugs and tight control of mucosal inflammation are crucial to prevent disease-related complications in patients with a complex disease course. We hypothesise that episodic treatment with adalimumab monotherapy in combination with close monitoring after drug discontinuation improves long-term outcome and reduces drug-related side effects, while preventing overtreatment.Methods and analysisIn this pragmatic multicentre randomised controlled trial, newly diagnosed CD patients or CD patients with a flare, naïve to thiopurines and biologicals, will be included and randomised 1:1 to open-label episodic (ie, 24 weeks) adalimumab monotherapy or step-up care starting with corticosteroids. The primary outcome is the number of yearly quarters of corticosteroid free clinical (Monitor Inflammatory Bowel Disease At Home score ≤3) and biochemical (C reactive protein within normal range and faecal calprotectin ≤200 µg/g) remission at week 96. Secondary outcomes are total healthcare costs, cumulative corticosteroid dose, proportion of patients with endoscopic remission at week 24, corticosteroid-free clinical remission, time to remission and patient-reported outcome measures on quality of life, (work) disability and treatment adherence. Safety outcomes are drug-related and disease-related adverse events and disease progression on MRI-enterography at week 96.Ethics and disseminationThis study is approved by the Medical Research Ethics Committee of azM/UM in Maastricht dated 21 August 2019 (METC18-076) and is monitored by the Clinical Trial Centre Maastricht according to Good Clinical Practice guidelines. Written informed consent will be obtained from all patients. Study results will be published in international peer-reviewed medical journals.Trial registration numberNCT03917303.

Objective Data on the course of severe COVID-19 in inflammatory bowel disease (IBD) patients remains limited. We aimed to determine the incidence rate and clinical course of severe COVID-19 in the heavily affected South-Limburg region in the Netherlands. Methods All COVID-19 patients admitted to the only two hospitals covering the whole South-Limburg region between February 27, 2020 and January 4, 2021 were included. Incidence rates for hospitalization due to COVID-19 were determined for the IBD (n = 4980) and general population (n = 597,184) in South-Limburg. Results During a follow-up of 4254 and 510,120 person-years, 20 IBD patients (0.40%; 11 ulcerative colitis (UC), 9 Crohn’s disease (CD)) and 1425 (0.24%) patients from the general population were hospitalized due to proven COVID-19 corresponding to an incidence rate of 4.7 (95% Confidence interval (CI) 3.0–7.1) and 2.8 (95% CI 2.6–2.9) per 1000 patient years, respectively (Incidence rate ratio: 1.68, 95% CI 1.08–2.62, p = 0.019). Median age (IBD: 63.0 (IQR 58.0–75.8) years vs. general population: 72.0 (IQR 62.0–80.0) years, p = 0.10) and mean BMI (IBD: 24.4 (SD 3.3) kg/m2 vs. general population 24.1 (SD 4.9) kg/m2, p = 0.79) at admission were comparable in both populations. As for course of severe COVID-19, similar rates of ICU admission (IBD: 12.5% vs. general population: 15.7%, p = 1.00), mechanical ventilation (6.3% vs. 11.2%, p = 1.00) and death were observed (6.3% vs. 21.8%, p = 0.22). Conclusion We found a statistically significant higher rate of hospitalization due to COVID-19 in IBD patients in a population-based setting in a heavily impacted Dutch region. This finding reflects previous research that showed IBD patients using systemic medication were at an increased risk of serious infection. However, although at an increased risk of hospitalization, clinical course of severe COVID-19 was comparable to hospitalized patients without IBD.

BACKGROUND & AIMS: Telemedicine can be used to monitor determinants and outcomes of patients with chronic diseases, possibly increasing the quality and value of care. Telemedicine was found to reduce outpatient visits and hospital admissions for patients with inflammatory bowel diseases (IBD). We performed a full economic evaluation of telemedicine interventions in patients with IBD, comparing the cost-utility of telemedicine vs standard care.METHODS: We performed a randomized trial of 909 patients with IBD at 2 academic and 2 non-academic hospitals in The Netherlands. Patients were randomly assigned to groups that received telemedicine (myIBDcoach; n = 465) or standard outpatient care (n = 444) and followed for 12 months. Costs were measured from a societal perspective. Direct healthcare costs were based on actual resource use. Indirect costs comprised self-reported hours sick leave from work, intervention costs (annual license fee of €40 per patient [$45]), and utility costs (assessed using EQ5D). Cost-utility and uncertainty were estimated using the non-parametric bootstrapping method.RESULTS: Telemedicine resulted in lower mean annual costs of €547/patient [$612] (95% CI, €1029-2143 [$1150-2393]; mean costs of €9481 [$10,587] for standard care and €8924 [$9965] for telemedicine) without changing quality adjusted life years. At the Dutch threshold of €80,000 [$89,335] per quality adjusted life year, the intervention had increased incremental cost-effectiveness over standard care in 83% of replications and an incremental net monetary benefit of €707/patient [$790] (95% CI, €1241-2544 [$1386-2841]).CONCLUSIONS: Telemedicine with myIBDcoach is cost saving and has a high probability of being cost effective for patients with IBD. This self-management tool enables continuous registration of quality indicators and (patient-reported) outcomes and might help reorganize IBD care toward value-based healthcare. ClinicalTrials.gov no: NCT02173002.

BACKGROUND: Tight and personalised control of inflammatory bowel disease in a traditional setting is challenging because of the disease complexity, high pressure on outpatient clinics, and rising incidence. We compared the effects of self-management with a telemedicine system, which was developed for all subtypes of inflammatory bowel disease, on health-care utilisation and patient-reported quality of care versus standard care.METHODS: We did this pragmatic, randomised trial in two academic and two non-academic hospitals in the Netherlands. Outpatients aged 18-75 years with inflammatory bowel disease and without an ileoanal or ileorectal pouch anastomosis, who had internet access and Dutch proficiency, were randomly assigned (1:1) to care via a telemedicine system (myIBDcoach) that monitors and registers disease activity or standard care and followed up for 12 months. Randomisation was done with a computer-generated sequence and used the minimisation method. Participants, health-care providers, and staff who assessed outcome measures were not masked to treatment allocation. Primary outcomes were the number of outpatient visits and patient-reported quality of care (assessed by visual analogue scale score 0-10). Safety endpoints were the numbers of flares, corticosteroid courses, hospital admissions, emergency visits, and surgeries. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02173002.FINDINGS: Between Sept 9, 2014, and May 18, 2015, 909 patients were randomly assigned to telemedicine (n=465) or standard care (n=444). At 12 months, the mean number of outpatient visits to the gastroenterologist or nurse was significantly lower in the telemedicine group (1·55 [SD 1·50]) than in the standard care group (2·34 [1·64]; difference -0·79 [95% CI -0·98 to -0·59]; pINTERPRETATION: Telemedicine was safe and reduced outpatient visits and hospital admissions compared with standard care. This self-management tool might be useful for reorganising care of inflammatory bowel disease towards personalised and value-based health care.FUNDING: Maastricht University Medical Centre and Ferring.

Background Treatment of patients with ileocaecal Crohn's disease who have not responded to conventional therapy is commonly scaled up to biological agents, but surgery can also offer excellent short-term and long-term results. We compared laparoscopic ileocaecal resection with infliximab to assess how they affect health-related quality of life. Methods In this randomised controlled, open-label trial, in 29 teaching hospitals and tertiary care centres in the Netherlands and the UK, adults with non-stricturing, ileocaecal Crohn's disease, in whom conventional therapy has failed were randomly allocated (1:1) by an internet randomisation module with biased-coin minimisation for participating centres and perianal fistula to receive laparoscopic ileocaecal resection or infliximab. Eligible patients were aged 18–80 years, had active Crohn's disease of the terminal ileum, and had not responded to at least 3 months of conventional therapy with glucocorticosteroids, thiopurines, or methotrexate. Patients with diseased terminal ileum longer than 40 cm or abdominal abscesses were excluded. The primary outcome was quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) at 12 months. Secondary outcomes were general quality of life, measured by the Short Form-36 (SF-36) health survey and its physical and mental component subscales, days unable to participate in social life, days on sick leave, morbidity (additional procedures and hospital admissions), and body image and cosmesis. Analyses of the primary outcome were done in the intention-to-treat population, and safety analyses were done in the per-protocol population. This trial is registered at the Dutch Trial Registry (NTR1150). Findings Between May 2, 2008, and October 14, 2015, 73 patients were allocated to have resection and 70 to receive infliximab. Corrected for baseline differences, the mean IBDQ score at 12 months was 178·1 (95% CI 171·1–185·0) in the resection group versus 172·0 (164·3–179·6) in the infliximab group (mean difference 6·1 points, 95% CI −4·2 to 16·4; p=0·25). At 12 months, the mean SF-36 total score was 112·1 (95% CI 108·0–116·2) in the resection group versus 106·5 (102·1–110·9) in the infliximab group (mean difference 5·6, 95% CI −0·4 to 11·6), the mean physical component score was 47·7 (45·7–49·7) versus 44·6 (42·5–46·8; mean difference 3·1, 4·2 to 6·0), and the mean mental component score was 49·5 (47·0–52·1) versus 46·1 (43·3–48·9; mean difference 3·5, −0·3 to 7·3). Mean numbers of days of sick leave were 3·4 days (SD 7·1) in the resection group versus 1·4 days (4·7) in the infliximab group (p

BACKGROUND & AIMSIntestinal microbiota is considered to play a crucial role in the aetiology of inflammatory bowel disease (IBD). We aimed to describe faecal microbiota composition and dynamics in a large cohort of children with de novo (naïve) IBD, in comparison to healthy paediatric controls (HC).METHODSIn this prospective study, performed at two tertiary centres, faecal samples from newly diagnosed, treatment-naïve paediatric IBD patients were collected prior to bowel cleansing for colonoscopy (t0) and 1, 3 and 6 weeks and 3 months after initiation of therapy. The microbial profiles of Crohn’s disease (CD) and Ulcerative colitis (UC) patients were compared with HC and linked to therapeutic response. Microbiota composition was analysed by IS-pro technology.RESULTSMicrobial profiles of 104 new IBD-patients (63 CD, 41 UC, median age 14.0 years) were compared to 61 HC (median 7.8 years). IBD was mainly characterised by decreased abundance of Alistipes finegoldi and Alistipes putredinis, which characterize a healthy state microbial core. The classifier including these core species as predictors achieved an AUC of the ROC curve of .87. Core bacteria tended to regain abundance during treatment, but did not reach healthy levels.CONCLUSIONFaecal microbiota profiles of children with de novo CD and UC can be discriminated from HC with high accuracy, mainly driven by a decreased abundance of species shaping the microbial core in the healthy state. Paediatric IBD can therefore be characterized by decreased abundance of certain bacterial species reflecting the healthy state rather than by the introduction of pathogens.

In this review the risk of breast, ovarian, and endometrial cancer and cervical and vulvovaginal (pre)malignant abnormalities in patients with inflammatory bowel disease (IBD) with or without immune suppressive treatment will be discussed. So far, this has not been studied thoroughly and large studies taking into account diverse potential confounding factors are lacking. IBD per se has not been associated with development of cervical cancer, yet patients with Crohn's disease who smoke, have a younger age at diagnosis or who use(d) thiopurines might be more at risk. Other immunosuppressive medication seems not to increase this risk, however, as evidence at this point is incomplete, physician awareness and prevention by lifestyle counseling, HPV vaccination and (intensified) screening are warranted. The risk for breast, endometrial, ovarian, and vulvovaginal cancer in IBD patients appears to be comparable to the background population, although for breast cancer this may even be decreasedin Crohn's disease specifically. Immunosuppressive medication in general does not seem to alter this risk. Earlier and more frequent screening for breast cancer than currently conducted in general nationwide screening programs is not recommended at this moment. Current literature suggests a much lower overall malignancy recurrence rate in IBD patients than has been observed previously. More importantly, immune suppressive medication does not appear to increase the recurrence risk. Robust epidemiologic data on female genital tract cancer are needed.

Job HC Peters,1 Nicolette J Wierdsma,2,3 Albertus Beishuizen,4,5 Tom Teerlink,6 Ad A van Bodegraven,3,7 1Department of Gastroenterology and Hepatology, Red Cross Hospital, Beverwijk, 2Department of Nutrition and Dietetics, VU University Medical Center, Amsterdam, 3Department of Gastroenterology, Small Bowel Disease Unit, VU University Medical Center, Amsterdam, 4Department of Intensive Care, VU University Medical Center, Amsterdam, 5Department of Intensive Care, Intensive Care Center,Medisch Spectrum Twente, Enschede, 6Department of Clinical Chemistry, Metabolic Laboratory, VU University Medical Center, Amsterdam, 7Department of Gastroenterology, Geriatrics, Intensive Care and InternalMedicin (Co-MIK), Zuyderland MC, Heerlen-Sittard-Geleen, the Netherlands Background: Assessment of a quantifiable small intestinal function test is cumbersome. Fasting citrulline concentrations have been proposed as a measure of enterocyte function and elaborated into a citrulline generation test (CGT), which is applicable only when glutamine is administered orally. CGT is an oral test, limiting its use, for example, in critically ill patients.Objective: Assessment of normative values and feasibility of an intravenously performed CGT in intensive care unit (ICU) patients with presumed gastrointestinal motility disturbances, especially when performed intravenously.Design: CGT reference values were determined in 16 stable ICU patients using two different CGT methods, namely following either enteral or intravenous glutamine administration and both with simultaneous arterial and venous plasma citrulline sampling at six time-points. Plasma amino acid analysis was performed using reverse-phase high-performance liquid chromatography.Results: The median total generation of citrulline in 90 min (CGT iAUCT90) was markedly higher with arterial citrulline sampling compared with venous citrulline sampling, being 724±585 and 556±418 µmol/L/min for enteral glutamine, respectively (p=0.02) and 977±283 and 769±231 µmol/L/min for intravenous glutamine, respectively (p=0.0004). The median slope (time-dependent increase) for plasma arterial and venous citrulline during the CGT was 0.20±0.16 and 0.18±0.12 µmol/L/min for enteral glutamine, respectively (p=0.004) and 0.22±0.16 and 0.19±0.05 µmol/L/min for intravenous glutamine, respectively (p=0.02). Conclusion: Intravenous glutamine administration combined with arterial plasma citrulline sampling yielded the least variation in CGT characteristics in stable ICU patients. A 2-point measurement test had comparable test characteristics as a 6-point measurement CGT and seems promising. Keywords: citrulline, citrulline generation test, critical illness, enterocyte, intestinal function, intensive care, ICU, glutamine, HPLC

Objective To assess whether a combination of adalimumab and ciprofloxacin is superior to adalimumab alone in the treatment of perianal fistulising Crohn's disease (CD).Design Randomised, double-blind, placebo controlled trial in eight Dutch hospitals. In total, 76 CD patients with active perianal fistulising disease were enrolled. After adalimumab induction therapy (160/80mg week 0, 2), patients received 40mg every other week together with ciprofloxacin 500mg or placebo twice daily for 12weeks. After 12weeks, adalimumab was continued. Follow-up was 24weeks. Primary endpoint (clinical response) was defined as 50% reduction of fistulas from baseline to week 12. Secondary endpoints included remission (closure of all fistulas), Perianal Crohn's Disease Activity Index, Crohn's Disease Activity Index (CDAI) and Inflammatory Bowel Disease Questionnaire (IBDQ).Results Clinical response was observed in 71% of patients treated with adalimumab plus ciprofloxacin and in 47% treated with adalimumab plus placebo (p=0.047). Likewise, remission rate at week 12 was significantly higher (p=0.009) in the combination group (65%) compared with adalimumab plus placebo (33%). Combination treatment was associated with a higher mean CDAI change and mean IBDQ change at week 12 (p=0.005 and p=0.009, respectively). At week 24, no difference in clinical response between the two treatment groups was observed (p=0.22). No difference in safety issues was observed.Conclusions Combination therapy of adalimumab and ciprofloxacin is more effective than adalimumab monotherapy to achieve fistula closure in CD. However, after discontinuation of antibiotic therapy, the beneficial effect of initial coadministration is not maintained.Trial registration ClinicalTrials.gov Identifier: NCT00736983.

Item does not contain fulltext BACKGROUND: Nodular regenerative hyperplasia (NRH) of the liver is associated with inflammatory-mediated diseases and certain drugs. There is conflicting data on the prevalence of NRH and its clinical implications in inflammatory bowel disease (IBD) patients treated with thioguanine. METHODS: A retrospective cohort study involving 7 Dutch centers comprised all IBD patients who were being treated with thioguanine and underwent a liver biopsy as part of the standard toxicity screening. Liver biopsy specimens were reviewed by 2 experienced liver pathologists. Clinical data as well as liver chemistry, blood counts, and abdominal imaging were collected. RESULTS: One hundred eleven IBD patients who submitted to liver biopsy were treated with thioguanine in a daily dose of 0.3 mg/kg for a median duration of 20 (4-64) months. NRH was detected in 6% of patients (7; 95% confidence interval, 3-14 patients). Older age (P = 0.02), elevated gamma-glutamyl transferase (P = 0.01) and alkaline phosphatase (P = 0.01) levels, a higher mean corpuscular volume (P = 0.02), and a lower platelet or leukocyte count (P < 0.01 and P = 0.02, respectively) were associated with NRH. Three of the 7 patients with NRH did not have any associated clinical symptoms or signs. The other 4 had minor biochemical abnormalities only. Ultrasonography revealed splenomegaly in 3 of the 78 patients (4%; 95% confidence interval, 0%-9%), only one of whom had NRH. There was no clinically overt portal hypertension. CONCLUSIONS: The prevalence of NRH was 6% in liver biopsies obtained from IBD patients treated with thioguanine. Histopathological irregularities including NRH were not associated with clinically significant findings over the period of observation.

Lucia Snoei1, Ad van Bodegraven2, Bas Oldenburg3, Theo Stijnen4, Ad A Kaptein11Unit of Psychology, Leiden University Medical Center, Leiden, The Netherlands; 2Department of Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands; 3Department of Gastroenterology, University Medical Center Utrecht, The Netherlands; 4Department of Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The NetherlandsObjective: To evaluate content, navigation, usability, and impact measurability of a prototype Internet-based self-management intervention for patients with ulcerative colitis.Material and methods: Analysis of 52 Internet diaries that were used in a six-month test trial. Analysis was done using an evaluation framework for eHealth applications that incorporates goals from theory and empirical studies on living with chronic illness, the software design industry, and health services research.Results: Content of the diary covered the intended functions of the Internet-based self-management intervention. The evaluation led to several refinement suggestions concerning navigation, usability, and impact measurability of the Internet diary.Conclusion: Psychosocial, medical, and scientific content as well as interface and design are equally important in the development of effective eHealth interventions. Keywords: self-management, Internet diary, ulcerative colitis, eHealth, prototype&nbsp

Background & Aims Patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC, termed PSC-IBD) are at increased risk for colorectal cancer, but their risk following a diagnosis of low-grade dysplasia (LGD) is not well described. We aimed to determine the rate of advanced colorectal neoplasia (aCRN), defined as high-grade dysplasia and/or colorectal cancer, following a diagnosis of indefinite dysplasia or LGD in this population. Methods We performed a retrospective, longitudinal study of 1911 patients with colonic IBD (293 with PSC and 1618 without PSC) who underwent more than 2 surveillance colonoscopies from 2000 through 2015 in The Netherlands or the United States (9265 patient-years of follow-up evaluation). We collected data on clinical and demographic features of patients, as well as data from each surveillance colonoscopy and histologic report. For each surveillance colonoscopy, the severity of active inflammation was documented. The primary outcome was a diagnosis of aCRN during follow-up evaluation. We also investigated factors associated with aCRN in patients with or without a prior diagnosis of indefinite dysplasia or LGD. Results Patients with PSC-IBD had a 2-fold higher risk of developing aCRN than patients with non-PSC IBD. Mean inflammation scores did not differ significantly between patients with PSC-IBD (0.55) vs patients with non-PSC IBD (0.56) (P = .89), nor did proportions of patients with LGD (21% of patients with PSC-IBD vs 18% of patients with non-PSC IBD) differ significantly (P = .37). However, the rate of aCRN following a diagnosis of LGD was significantly higher in patients with PSC-IBD (8.4 per 100 patient-years) than patients with non-PSC IBD (3.0 per 100 patient-years; P = .01). PSC (adjusted hazard ratio [aHR], 2.01; 95% CI, 1.09–3.71), increasing age (aHR 1.03; 95% CI, 1.01–1.05), and active inflammation (aHR, 2.39; 95% CI, 1.63–3.49) were independent risk factors for aCRN. Dysplasia was more often endoscopically invisible in patients with PSC-IBD than in patients with non-PSC IBD. Conclusions In a longitudinal study of almost 2000 patients with colonic IBD, PSC remained a strong independent risk factor for aCRN. Once LGD is detected, aCRN develops at a higher rate in patients with PSC and is more often endoscopically invisible than in patients with only IBD. Our findings support recommendations for careful annual colonoscopic surveillance for patients with IBD and PSC, and consideration of colectomy once LGD is detected.

Annemiek J Linn,1 Julia CM van Weert,1 Barbara C Schouten,1 Edith G Smit,1 Ad A van Bodegraven,2 Liset van Dijk31Amsterdam School of Communication Research (ASCoR), University of Amsterdam, Amsterdam, The Netherlands; 2VU University Medical Center, Amsterdam, The Netherlands; 3Netherlands Institute for Health Services Research, Utrecht, The NetherlandsPurpose: The barriers to patients’ successful medication intake behavior could be reduced through tailored communication about these barriers. The aim of this study is therefore (1) to develop a new communication typology to address these barriers to successful medication intake behavior, and (2) to examine the relationship between the use of the typology and the reduction of the barriers to successful medication intake behavior.Patients and methods: Based on a literature review, the practical and perceptual barriers to successful medication intake behavior typology (PPB-typology) was developed. The PPB-typology addresses four potential types of barriers that can be either practical (memory and daily routine barriers) or perceptual (concern and necessity barriers). The typology describes tailored communication strategies that are organized according to barriers and communication strategies that are organized according to provider and patient roles. Eighty consultations concerning first-time medication use between nurses and inflammatory bowel disease patients were videotaped. The verbal content of the consultations was analyzed using a coding system based on the PPB-typology. The Medication Understanding and Use Self-efficacy Scale and the Beliefs about Medicine Questionnaire Scale were used as indicators of patients’ barriers and correlated with PPB-related scores.Results: The results showed that nurses generally did not communicate with patients according to the typology. However, when they did, fewer barriers to successful medication intake behavior were identified. A significant association was found between nurses who encouraged question-asking behavior and memory barriers (r = −0.228, P = 0.042) and between nurses who summarized information (r = −0.254, P = 0.023) or used cartoons or pictures (r = −0.249, P = 0.026) and concern barriers. Moreover, a significant relationship between patients’ emotional cues about side effects and perceived concern barriers (r = 0.244, P = 0.029) was found as well.Conclusion: The PPB-typology provides communication recommendations that are designed to meet patients’ needs and assist providers in the promotion of successful medication intake behavior, and it can be a useful tool for developing effective communication skills training programs.Keywords: interpersonal communication, tailoring, adherence, coding provider-patient interaction, beliefs, self-efficacy

Introduction: Malabsorption, which is frequently underdiagnosed in critically ill patients, is clinically relevant with regard to nutritional balance and nutritional management. We aimed to validate the diagnostic accuracy of fecal weight as a biomarker for fecal loss and additionally to assess fecal macronutrient contents and intestinal absorption capacity in ICU patients. Methods: This was an observational pilot study in a tertiary mixed medical-surgical ICU in hemodynamically stable adult ICU patients, without clinically evident gastrointestinal malfunction. Fecal weight (grams/day), fecal energy (by bomb calorimetry in kcal/day), and macronutrient content (fat, protein, and carbohydrate in grams/day) were measured. Diagnostic accuracy expressed in terms of test sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and receiver operator curves (ROCs) were calculated for fecal weight as a marker for energy malabsorption. Malabsorption was a priori defined as 350 g/day (that is, diarrhea) was linked to the optimal ROC (0.879), showing a sensitivity and PPV of 80%, respectively. Specificity and NPV were both 96%. Fecal weight (grams/day) and intestinal energy-absorption capacity were inversely correlated (r = -0.69; P 350 g feces/day had a significantly morenegative energy balance compared with patients with 350 g/day in ICU patients is a biomarker applicable in daily practice, which can act as a surrogate for fecal energy loss and intestinal energy absorption. Daily measurement of fecal weight is a feasible means of monitoring the nutritional status of critically ill patients and, in those identified as having malabsorption, can monitor responses to changes in dietary management.

Background: Dectin-1 is a pattern recognition receptor (PRR) expressed by myeloid cells that specifically recognizes b-1,3 glucan, a polysaccharide and major component of the fungal cell wall. Upon activation, dectin-1 signaling converges, similar to NOD2, on the adaptor molecule CARD9 which is associated with inflammatory bowel disease (IBD). An early stop codon polymorphism (c.714T.G) in DECTIN-1 results in a loss-of-function (p.Y238X) and impaired cytokine responses, including TNF-a, interleukin (IL)-1b and IL-17 upon in vitro stimulation with Candida albicans or b-glucan. The aim of the present study was to test the hypothesis that the DECTIN-1 c.714T.G (p.Y238X) polymorphism is associated with lower disease susceptibility or severity in IBD and to investigate the level of dectin-1 expression in inflamed and non-inflamed colon tissue of IBD patients. Methodology: Paraffin embedded tissue samples from non-inflamed and inflamed colon of IBD patients and from diverticulitis patients were immunohistochemically stained for dectin-1 and related to CD68 macrophage staining. Genomic DNA of IBD patients (778 patients with Crohn’s disease and 759 patients with ulcerative colitis) and healthy controls (n=772) was genotyped for the c.714T.G polymorphism and genotype-phenotype interactions were investigated. Principal Findings: Increased expression of dectin-1 was observed in actively inflamed colon tissue, as compared to noninflamed tissue of the same patients. Also an increase in dectin-1 expression was apparent in diverticulitis tissue. No statistically significant difference in DECTIN-1 c.714T.G allele frequencies was observed between IBD patients and healthy controls. Furthermore, no differences in clinical characteristics could be observed related to DECTIN-1 genotype, neither alone, nor stratified for NOD2 genotype. Conclusions: Our data demonstrate that dectin-1 expression is elevated on macrophages, neutrophils, and other immune cells involved in the inflammatory reaction in IBD. The DECTIN-1 c.714T.G polymorphism however, is not a major susceptibility factor for developing IBD. Citation: de Vries HS, Plantinga TS, van Krieken JH, Stienstra R, van Bodegraven AA, et al. (2009) Genetic Association Analysis of the Functional c.714T.G

OBJECTIVES: Our aim was to explore the diagnostic value of fasting citrulline concentrations to detect decreased intestinal energy absorption in patients with recently diagnosed celiac disease (CeD), refractory celiac disease (RCeD), and short bowel syndrome (SBS). Decreased intestinal energy absorption is regarded a marker of intestinal failure. METHODS: Fasting plasma citrulline concentrations were determined by high performance liquid chromatography (HPLC) in a prospective study of 30 consecutive adult patients (15 CeD, 9 RCeD, and 16 SBS) and 21 healthy subjects. Intestinal energy absorption capacity using bomb calorimetry was determined in all patients and healthy subjects and was regarded as the gold standard for intestinal energy absorption function. RESULTS: The mean fasting plasma citrulline concentration was lower in RCeD patients than in healthy subjects (28.5 ± 9.9 vs 38.1 ± 8.0 μmol/L, P < 0.05) and CeD patients (28.5 ± 9.9 vs 38.1 ± 6.4 μmol/L, P < 0.05), however, clearly within reference values. The mean intestinal energy absorption capcity was lower in SBS patients than in healthy subjects (64.3 ± 18.2 vs 90.3 ± 3.5%, P < 0.001), CeD patients (64.3 ± 18.2 vs 89.2 ± 3.4%, P < 0.001), and the RCeD group (64.3 ± 18.2 vs 82.3 ± 11.7%, P < 0.01). No relation was observed between fasting plasma citrulline concentration and intestinal energy absorption capacity (Pearson r = 0.09, P = 0.56). The area under the ROC curve for fasting plasma citrulline to detect decreased intestinal energy absorption capcity (i.e., < 85%) was 0.50. CONCLUSION: Fasting plasma citrulline concentrations have poor test characteristics for detection of decreased intestinal energy absorption capacity in patients with enterocyte damage.