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Contains fulltext : 290620.pdf (Publisher’s version ) (Open Access) BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of treatment. AIM: The aim of this study was to assess the effectiveness and safety of 24 months of tofacitinib use in UC patients in the Netherlands. METHODS: Patients initiating tofacitinib treatment were included in the ICC Registry, a nationwide, observational registry. Patients were prospectively evaluated for up to 24 months. The primary outcome was corticosteroid-free clinical remission (CSFR, Simple Clinical Colitis Activity Index [SCCAI] ≤2) at week 104. Secondary outcomes included biochemical remission (C-reactive protein (CRP) ≤5 mg/L and faecal calprotectin (FC) ≤250 μg/g), safety, and discontinuation rate. RESULTS: We included 110 patients of whom 104 (94.5%) were anti-TNF experienced. After 104 weeks of tofacitinib, 31.8% (34/107) were in CSFR, 23.4% (25/107) in biochemical remission and 18.7% (20/107) in combined clinical and biochemical remission. Of the patients in CSFR at week 52, 76.5% (26/34) remained so after 104 weeks of treatment. Sixty-one patients (55.5%) discontinued tofacitinib after a median duration of 13 weeks (IQR 7-34). The main reasons for discontinuation were non-response (59%), loss of response (14.8%), and adverse events (18%). There were 33.9 possible tofacitinib-related adverse events per 100 patient-years during follow-up. Adverse events most probably related to tofacitinib were skin reactions and headaches. There were 6.4 herpes zoster infections per 100 patient-years. CONCLUSION: Tofacitinib was effective in 31.8% of patients after 24 months of treatment. 01 januari 2023

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: The LIR!C trial showed that laparoscopic ileocaecal resection is a cost-effective treatment that has similar quality-of-life outcomes to treatment with infliximab, an anti-tumour necrosis factor (TNF) drug. We aimed to compare long-term outcomes of both interventions and identify baseline factors associated with the duration of treatment effect in each group.METHODS: In this retrospective follow-up study, we collected data from patients who participated in the LIR!C trial, a multicentre randomised controlled trial that compared quality of life after surgical resection versus infliximab in adult patients with non-stricturing and immunomodulator-refractory ileocaecal Crohn's disease. From Jan 1 to May 1, 2018, we collected follow-up data from the time from enrolment in the LIR!C trial until the last visit at either the gastrointestinal surgeon or gastroenterologist. In this study, outcomes of interest were need for surgery or repeat surgery or anti-TNF therapy, duration of treatment effect, and identification of factors associated with the duration of treatment effect. Duration of treatment effect was defined as the time without need for additional Crohn's disease-related treatment (corticosteroids, immunomodulators, biologics, or surgery).FINDINGS: We collected long-term follow-up data for 134 (94%) of 143 patients included in the LIR!C trial, of whom 69 were in the resection group and 65 were in the infliximab group. Median follow-up was 63·5 months (IQR 39·0-94·5). In the resection group, 18 (26%) of 69 patients started anti-TNF therapy and none required a second resection. 29 (42%) patients in the resection group did not require additional Crohn's disease-related medication, although 14 (48%) of these patients were given prophylactic immunomodulator therapy. In the infliximab group, 31 (48%) of 65 patients had a Crohn's disease-related resection, and the remaining 34 patients maintained, switched, or escalated their anti-TNF therapy. Duration of treatment effect was similar in both groups, with a median time without additional Crohn's disease-related treatment of 33·0 months (95% CI 15·1-50·9) in the resection group and 34·0 months (0·0-69·3) in the infliximab group (log-rank p=0·52). In both groups, therapy with an immunomodulator, in addition to the allocated treatment, was associated with duration of treatment effect (hazard ratio for resection group 0·34 [95% CI 0·16-0·69] and for infliximab group 0·49 [0·26-0·93]).INTERPRETATION: These findings further support laparoscopic ileocaecal resection as a treatment option in patients with Crohn's disease with limited (affected segment ≤40 cm) and predominantly inflammatory terminal ileitis for whom conventional treatment is not successful.FUNDING: None.

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.

INTRODUCTION: Nodular regenerative hyperplasia (NRH) has been associated with thiopurine therapy in patients with inflammatory bowel disease (IBD), but prevalence and prognosis of NRH remain unclear. This study is a cross-sectional search for NRH in IBD patients with long-term azathioprine or 6-mercaptopurine treatment.MATERIAL AND METHODS: Thirty-three IBD patients with continuous azathioprine/6-mercaptopurine treatment for at least 5 years were included. Laboratory tests, thiopurine metabolite levels, liver histology, MRI were examined for NRH and signs of portal hypertension.RESULTS: NRH was not observed in this cohort of 33 patients. Nevertheless, some possibly related signs of vascular changes were found by MRI in three patients. Also, splenomegaly, which may be associated with portal hypertension, was found in one patient. No high thiopurine dose neither high metabolite levels were found in these patients.CONCLUSION: No NRH was found in this group of IBD patients with long-term azathioprine/6-mercaptopurine treatment. Larger multicenter studies are needed to determine the prevalence of NRH in thiopurine-treated IBD patients.

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: Inflammatory bowel disease (IBD) patients are at risk of an impaired nutritional status. The impact thereof on the IBD relapse risk is clinically relevant, though sparsely investigated.Aim: The aim was to explore the association between an impaired nutritional status risk and the occurrence of disease flares in IBD outpatients participating in a longitudinal telemedicine study.Methods: IBD outpatients were recruited from the myIBDcoach study cohort, with one year clinical follow-up. Through myIBDcoach, a telemedicine tool, patients reported on disease activity and risk of impaired nutritional status (i.e. Short Nutritional Assessment Questionnaire > 1 and/or BMI Results: In total, 417 patients were included. During follow-up, 49 patients (11.8%) flared after initial clinical remission and 53 patients (12.7%) showed an increased risk of impaired nutritional status. The risk of impaired nutritional status was associated with flare occurrence (OR 2.61 (95% CI 1.02-6.69)).Conclusions: The risk of an impaired nutritional status was associated with subsequent flares in IBD outpatients. This emphasizes the importance of monitoring disease activity in IBD patients at risk of impaired nutritional status. (C) 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Background: The authors aimed to conduct an extensive literature review and consensus meeting to identify unmet needs in ulcerative colitis (UC) and ways to overcome them. UC is a relapsing and remitting inflammatory bowel disease with varied, and changing, incidence rates worldwide. UC has an unpredictable disease course and is associated with a high health economic burden. During 2016 and 2017, a panel of experts was convened to identify, discuss and address areas of unmet need in UC. Methods: PubMed and Cochrane Library databases were searched for relevant articles describing studies performed in patients with UC. These findings were used to generate a set of statements relating to unmet needs in UC. Consensus on these statements was then sought from a panel of 9 expert gastroenterologists using a modified Delphi review process that consisted of anonymous surveys followed by live meetings. Results: In 2 literature reviews, over 5,000 unique records were identified and a total of 138 articles were fully reviewed. These were used to consider 26 areas of unmet need, which were explored in 2 face-to-face meetings, in which the statements were debated and amended, resulting in consensus on 30 final statements. The unmet needs identified were categorised into 7 areas: impact of UC on patients’ daily life; importance of early diagnosis and treatment; drawbacks of existing treatments; urgent need for new treatments; and disease-, practice- or patient-focused unmet needs. Conclusions: These expert group meetings found a number of areas of unmet needs in UC, which is an important first step in tackling them in the future. Future research and development should be focused in these areas for the management of patients with UC.

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.

Background and Aims: In the past decades, treatment options and strategies for ulcerative colitis [UC] have radically changed. Whether these developments have altered the disease outcome at population level is yet unknown. Therefore, we evaluated the disease outcome of UC over the past two decades in the South-Limburg area of The Netherlands. Methods: In the Dutch population-based IBDSL cohort, three time cohorts were defined: cohort 1991-1997 [cohort A], cohort 1998-2005 [cohort B], and cohort 2006-2010 [cohort C]. The colectomy and hospitalisation rates were compared between cohorts by Kaplan-Meier survival analyses. Hazard ratios [HR] for early colectomy [within 6 months after diagnosis], late colectomy [beyond 6 months after diagnosis], and hospitalisation were calculated using Cox regression models. Results: In total, 476 UC patients were included in cohort A, 587 patients in cohort B, and 598 patients in cohort C. Over time, an increase in the use of immunomodulators [8.1%, 22.8% and 21.7%, respectively, p

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

Introduction Vaginal (re)construction is essential for the psychological well‐being of biological women with a dysfunctional vagina and male‐to‐female transgender women. However, the preferred method for vagina (re)construction with respect to functional as well as aesthetic outcomes is debated. Regarding intestinal vaginoplasty, despite the asserted advantages, the need for intestinal surgery and subsequent risk of diversion colitis are often‐mentioned concerns. The outcomes of vaginal reconstructive surgery need to be appraised in order to improve understanding of pros and cons. Aims To review literature on surgical techniques and clinical outcomes of intestinal vaginoplasty. Methods Electronic databases and reference lists of published articles were searched for primary studies on intestinal vaginoplasty. Studies were included if these included at least five patients and had a minimal follow‐up period of 1 year. No constraints were imposed with regard to patient age, indication for vaginoplasty, or applied surgical technique. Outcome measures were extracted and analyzed. Main Outcome Measures Main outcome measures were surgical procedure, clinical outcomes, and outcomes concerning sexual health and quality of life. Results Twenty‐one studies on intestinal vaginoplasty were included (including 894 patients in total). All studies had a retrospective design and were of low quality. Prevalence and severity of procedure‐related complications were low. The main postoperative complication was introital stenosis, necessitating surgical correction in 4.1% of sigmoid‐derived and 1.2% of ileum‐derived vaginoplasties. Neither diversion colitis nor cancer was reported. Sexual satisfaction rate was high, but standardized questionnaires were rarely used. Quality of life was not reported. Conclusion Based on evidence presently available, it seems that intestinal vaginoplasty is associated with low complication rates. To substantiate these findings and to obtain information about functional outcomes and quality of life, prospective studies using standardized measures and questionnaires are warranted. Bouman M‐B, van Zeijl MCT, Buncamper ME, Meijerink WJHJ, van Bodegraven AA, and Mullender MG. Intestinal vaginoplasty revisited: A review of surgical techniques, complications, and sexual function. J Sex Med 2014;11:1835–1847.

Background Inflammatory bowel disease (IBD) is associated with high costs to society. Few data on the impact of IBD on work disability and potential predictive factors are available. Aim To assess the prevalence of and predictive factors for work disability in Crohn's disease (CD) and ulcerative colitis (UC). Methods A web-based questionnaire was sent out in seven university hospitals and seven general hospitals in the Netherlands. Initially, 3050 adult IBD patients were included in this prospective, nationwide cohort study, whereof 2629 patients were within the working-age (18–64 years). We used the baseline questionnaire to assess the prevalence rates of work disability in CD and UC patients within working-age. Prevalence rates were compared with the Dutch background population using age- and sex-matched data obtained from Statistics Netherlands. Multivariable logistic regression analyses were performed to identify independent demographic- and disease-specific risk factors for work disability. Results In CD, 18.3% of patients was fully disabled and 8.8% partially disabled, compared to 9.5% and 5.4% in UC patients (p Conclusion We report high work disability rates in a large sample of IBD patients in the Netherlands. CD patients suffer more frequently from work disability than UC patients. A combination of demographic and disease-related factors is predictive of work disability.

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.

BACKGROUND & AIMS: Infliximab (IFX) and adalimumab (ADA) are thought to have equal efficacy for the treatment of Crohn's disease (CD), although no direct comparison has been performed. We compared the effectiveness and safety of IFX and ADA in carefully matched cohorts.METHODS: We performed a retrospective cohort study of 200 patients with CD (100 treated with IFX and 100 treated with ADA, starting in 2006 or later) who had not received anti-tumor necrosis factor alpha agents previously; the patients were identified from databases of 6 hospitals in The Netherlands. The groups were matched carefully for indication, duration of disease, age, and Montreal classification. The primary end point was the steroid-free clinical response, defined by a combination of multiple clinical parameters, after 1 year.RESULTS: Of the total patient population, 63.5% and 45% had a clinical response after 1 and 2 years, respectively. There were no significant differences between treatment groups: at 1 and 2 years, 62% and 41% of those receiving ADA vs 65% and 49% of those receiving IFX had responses, respectively. Kaplan-Meier curves showed identical decreases in response rates over time. Combining IFX or ADA with immunomodulator therapy was associated with a higher clinical response than monotherapy, although this was only significant among patients who received IFX (P = .03). There were no differences in numbers of side effects or opportunistic infections.CONCLUSIONS: The effectiveness of ADA or IFX treatment in anti-tumor necrosis factor alpha-naive patients with CD is comparable after 1 and 2 years of follow-up evaluation. The efficacies of IFX and ADA each seem to increase when given with immunomodulator therapy, although only significantly for IFX.

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.

ObjectiveImproving adherence is a challenge and multiple barriers are likely to explain non-adherence. These barriers differ per patient and over course of the regimen. Hence, personalized interventions tailored to the specific barriers are needed. In a theoretical and evidence-based Tailored Multimedia Intervention, technology (online preparatory assessment, text messaging) was used as an add-on to a tailored counseling session (learned during a communication skills training), with the expectation of synergistic effects.MethodsA cluster randomized controlled trial was conducted in six hospitals, eight nurses and 160 chronic patients. Patient satisfaction with communication, beliefs about medication, self-efficacy and medication adherence were assessed at initiation of the treatment and after six months.ResultsIntervention effects were found for patient satisfaction with nurses’ affective communication and self-efficacy at the initiation of treatment. The effect on self-efficacy remained after six months.ConclusionBy combining tailored counseling with technology, this intervention resulted in positive changes in important prerequisites of medication adherence.Practical implicationsTechnology can contribute significantly to health care providers’ ability to tailor information to the patients’ needs.

Thiopurines, such as azathioprine and mercaptopurine, are of pivotal importance in the treatment of inflammatory bowel disease. Although these drugs have been used for several decades, still many questions remain unanswered.To provide an overview of clinically and scientifically challenging topics concerning thiopurine therapy in inflammatory bowel disease treatment.The first meeting of the Thiopurine Task Force Interest Group was held during the 2009 United European Gastroenterology Week in London (GASTRO2009). The topics of this meeting were of particular clinical and scientific interest. Additional literature was identified by performing a Pubmed search using the search terms 'inflammatory bowel disease', 'azathioprine', '6-mercaptopurine' and 'thioguanine'.The following topics were discussed: therapeutic drug monitoring; the synergy of thiopurines with aminosalicylates and allopurinol; serious adverse events such as opportunistic infections, hepatotoxicity, carcinogenicity and pancreatitis; prolongation of thiopurines during clinical remission; indications for thiopurines in the postoperative setting; and the potential use of thioguanine. Specific interesting and clinically relevant topics for potential future research are provided.Thiopurines remain central to inflammatory bowel disease treatment, although future studies are required to substantiate a more personalised medicine approach to their use.

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.

Thiopurines such as azathioprine, 6-mercaptopurine and 6-thioguanine are antimetabolites that have been used for several decades in the treatment of several diseases including inflammatory bowel diseases. Additional anti-inflammatory properties of these thiopurines have been discovered in recent years. Thiopurine metabolism is complex due to the involvement of multiple enzymes, of which the activities are genetically determined and cell type dependent. Single nucleotide polymorphisms in the genes encoding these enzymes have been correlated with altered activities and drug intolerance. Detailed implications of these will be reviewed. Over the years several methods of therapeutic drug monitoring have been developed in an attempt to relate thiopurine drug availability with efficacy and intolerance. In this respect, monitoring pharmacologically active 6-thioguanine nucleotide concentrations is most widely used. So far, however, the clinical usefulness of these methods is hampered by methodological limitations. Some drug interactions may optimize the metabolization of thiopurines and consequently increase its efficacy and decrease drug intolerance. This review focuses on the clinical relevance and usefulness of therapeutic drug monitoring of thiopurines and provides suggestions to optimize thiopurine therapy in the treatment of inflammatory bowel diseases.

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

Thiopurines such as azathioprine (AZA) and 6-mercaptopurine are frequently used for the treatment of inflammatory bowel diseases. Patients with low or absent thiopurine S-methyltransferase (TPMT) activity, resulting in high 6-thioguanine nucleotide levels, have an increased risk of developing leukopenia. Alternatively, certain viral infections could induce leukopenia. We present the case of an adult Crohn’s disease patient with a parvovirusB19 infection and leukopenia during long-term AZA therapy. The uncomplicated long-term use of adequately-dosed AZA and stable non-toxic metabolite levels could not acknowledge TPMT deficiency as a primary cause of the leukopenia. ParvovirusB19 was assumed to induce the leukopenia by restraining myeloid proliferation. In addition, AZA probably potentiated susceptibility to this viral infection and may have inhibited adequate immunological defense. Leukopenia during thiopurine therapy not explained by TPMT deficiency could be induced by parvovirusB19 infection and compels temporal but not permanent cessation of thiopurine therapy.

Summary Background Most patients who have active Crohn's disease are treated initially with corticosteroids. Although this approach usually controls symptoms, many patients become resistant to or dependent on corticosteroids, and long exposure is associated with an increased risk of mortality. We aimed to compare the effectiveness of early use of combined immunosuppression with conventional management in patients with active Crohn's disease who had not previously received glucocorticoids, antimetabolites, or infliximab. Methods We did a 2-year open-label randomised trial at 18 centres in Belgium, Holland, and Germany between May, 2001, and January, 2004. We randomly assigned 133 patients to either early combined immunosuppression or conventional treatment. The 67 patients assigned to combined immunosuppression received three infusions of infliximab (5 mg/kg of bodyweight) at weeks 0, 2, and 6, with azathioprine. We gave additional treatment with infliximab and, if necessary, corticosteroids, to control disease activity. 66 patients assigned to conventional management received corticosteroids, followed, in sequence, by azathioprine and infliximab. The primary outcome measures were remission without corticosteroids and without bowel resection at weeks 26 and 52. Analysis was by modified intention to treat. This trial was registered with ClinicalTrials.gov, number NCT00554710. Findings Four patients (two in each group) did not receive treatment as per protocol. At week 26, 39 (60·0%) of 65 patients in the combined immunosuppression group were in remission without corticosteroids and without surgical resection, compared with 23 (35·9%) of 64 controls, for an absolute difference of 24·1% (95% CI 7·3–40·8, p=0·0062). Corresponding rates at week 52 were 40/65 (61·5%) and 27/64 (42·2%) (absolute difference 19·3%, 95% CI 2·4–36·3, p=0·0278). 20 of the 65 patients (30·8%) in the early combined immunosuppression group had serious adverse events, compared with 19 of 64 (25·3%) controls (p=1·0). Interpretation Combined immunosuppression was more effective than conventional management for induction of remission and reduction of corticosteroid use in patients who had been recently diagnosed with Crohn's disease. Initiation of more intensive treatment early in the course of the disease could result in better outcomes.

BACKGROUND: Mucosal healing is presently considered one of the primary goals in treatment of Crohn's disease (CD), but this can only be confirmed by endoscopy. We aimed to design and validate a new disease activity index based on a combination of clinical characteristics and readily available laboratory parameters, which reliably predicts the presence and severity of endoscopic disease activity in patients with CD. METHODS: Thirteen clinical characteristics and laboratory variables were selected for analysis. Endoscopic disease activity was assessed by the Crohn's disease Endoscopic Index of Severity. A linear regression model was based on 93 ileocolonoscopies performed in 82 patients with CD and internally validated by bootstrap resampling. Subsequently, the newly developed model was validated in a cohort of 99 patients. RESULTS: The number of liquid stools during 1 day × 0.25 + C-reactive protein (in milligrams per liter) × 0.1 + platelet count (× 10(9)/L) × 0.01 + fecal calprotectin (in milligrams per liter) × 0.001 - mean platelet volume (in femtoliters) × 0.2 optimally predicted the severity of endoscopic disease activity (bootstrap adjusted R2 = 0.50). The model demonstrated good agreement in the external validation (r = 0.7), especially for (ileo)colonic CD (r = 0.8). Using receiver operator characteristic statistics, a cutoff point of 3 on the new index indicated endoscopic disease activity with a sensitivity of 80% and a specificity of 92%. CONCLUSIONS: This newly developed, noninvasive, index was found to reliably predict endoscopic disease activity in patients with CD. This tool can facilitate clinical decision making and might prove valuable in clinical trials.

Objective: The aim of the study was to evaluate postoperative recovery after hand-assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis and familial adenomatous polyposis in a randomized controlled trial. Methods: Sixty patients were randomized for hand-assisted laparoscopic (n = 30) or open surgery (n = 30). Primary outcome parameter was postoperative recovery in the 3 months after surgery, measured by quality of life questionnaires (SF-36 and GIQLI). Secondary parameters were postoperative morphine requirement and surgical parameters, viz. operating time, morbidity, hospital stay, and costs. Results: There was no difference between the 2 procedures in quality of life assessment in the 3 months after surgery. There was a significant decline in quality of life on all scales of the SF-36 (P < 0.001) and total GIQLI score (P < 0.001) in the first 2 weeks in both groups (no significant difference between the groups). Quality of life returned to baseline levels after 4 weeks. Operating times were longer in the laparoscopic group compared with the open group (210 and 133 minutes, respectively; P < 0.001). No significant differences were found in morphine requirement. Neither morbidity nor postoperative hospital stay differed between the laparoscopic and open group (20% versus 17%, in 10 versus 11 days, respectively). Median overall costs were? 16.728 for the hand-assisted laparoscopic procedure and? 13.406 for the open procedure (P = 0.095). Conclusions: Recovery measured using quality of life questionnaires is comparable for hand-assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis. The laparoscopic approach is as safe, but more costly than the open procedure.

The human gastric pathogen Helicobacter pylori spontaneously switches lipopolysaccharide (LPS) Lewis (Le) antigens on and off (phase-variable expression), but the biological significance of this is unclear. Here, we report that Le+ H. pylori variants are able to bind to the C-type lectin DC-SIGN and present on gastric dendritic cells (DCs), and demonstrate that this interaction blocks T helper cell (Th)1 development. In contrast, Le− variants escape binding to DCs and induce a strong Th1 cell response. In addition, in gastric biopsies challenged ex vivo with Le+ variants that bind DC-SIGN, interleukin 6 production is decreased, indicative of increased immune suppression. Our data indicate a role for LPS phase variation and Le antigen expression by H. pylori in suppressing immune responses through DC-SIGN.

Massive haemorrhage in ulcerative colitis mainly occurs as a result of exacerbated disease, usually acute or even fulminant colitis. Emergency proctocolectomy is currently advocated as the only reliable treatment of this patient group. However, this type of surgical intervention has a high rate of morbidity and mortality. Recently, several promising studies have been published that describe transcatheter embolization for the treatment of massive lower gastrointestinal bleeding in cases of bleeding colonic diverticular disease and angiodysplasia. Success rates of 48-88% have been reported. To avoid the high risk associated with emergency colectomy, this modern procedure was performed in an ulcerative colitis patient with intractable lower gastrointestinal bleeding. To our knowledge, this is the first patient with ulcerative colitis presenting with massive lower gastrointestinal blood loss to be successfully treated by highly selective transcatheter embolization. This interventional procedure is suggested as an alternative therapeutic approach to haematochezia in selected ulcerative colitis patients.

PURPOSE: Infliximab has been reported to improve fistulizing Crohn’s disease. Moreover, prompt healing of mucosal ulcers has been described. Whether fistulas disappear or remainders of fistulas persist is unknown. This study documents fistulous tracts before and after infliximab therapy by means of hydrogen peroxide-enhanced endosonography METHODS: Eight patients with perianal, vaginal, or perineal fistulas were treated with a triplet of infliximab 5 mg/kg infusions. At baseline, and at Week 4 after the last infusion, fistulas were documented by local inspection, digital examination, and hydrogen peroxide-enhanced anal or vaginal endosonography. RESULTS: Patients with vaginal or perineal fistulas did not respond clinically to therapy, whereas patients with perianal fistulas improved considerably. However, in all patents remainders of fistulous tracts were demonstrated by endosonographic techniques. CONCLUSIONS: Short-term treatment of Crohn’s disease-associated fistulas with infliximab does not induce disappearance of fistulous tracts, irrespective of therapeutic response.

Natural killer T (NKT) cells have been implicated as playing an important role in regulating immune responses. Defects in the NKT cell population were reported in animal autoimmune disease models and in distinct human autoimmune diseases. Here, we report that circulating V(alpha24+) Vbeta11+ NKT cell numbers are decreased in a broad variety of disorders with (auto)immune-mediated pathology, affecting the skin, bowel, central nervous system, and joints, regardless of disease duration or activity. Remarkably, normal circulating V(alpha24+) Vbeta11+ NKT cell numbers were found in Graves disease and coeliac disease. Since earlier studies noted a rise in NKT cells in myasthenia gravis, the picture emerges in which a defective NKT cell population is associated with autoreactive tissue damage rather than with the propensity to develop autoimmune disease. The present data support the idea that therapies aiming at the in vivo expansion of regulatory NKT cells might help to control immune-mediated damage in autoimmune disease.

Inflammatory bowel disorders are characterized by an accumulation of eosinophilic granulocytes, mast cells, lymphocytes and neutrophilic granulocytes in the intestinal mucosa. The aim of this study was to examine the concentration of eosinophilic granulocytes in the blood of patients during active ulcerative colitis in comparison with patients during remission and apparently healthy control subjects. Besides counting, the activity grade of eosinophilic granulocytes has been studied by estimation of their degranulation product eosinophil cationic protein.Subjects with active ulcerative colitis could be distinguished from patients with quiescent ulcerative colitis by establishment of the eosinophil cationic protein concentration, neutrophilic granulocyte count, erythrocyte sedimentation rate, C-reactive protein and albumin concentration.After two weeks of corticosteroid treatment, serum eosinophil cationic protein concentrations and eosinophil counts in blood were significantly decreased. A decrease in blood eosinophil count was accompanied by a decrease in eosinophil cationic protein concentrations in serum in most subjects with ulcerative colitis. After twelve weeks of corticosteroid administration, serum albumin concentrations were significantly increased, whereas serum concentrations of C-reactive protein were significantly decreased.During treatment with corticosteroids, serum eosinophil cationic protein concentrations and blood eosinophil counts are appropriate laboratory markers to detect the effect of medication in the course of ulcerative colitis.

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

Where health care is concerned, the introduction of biologicals has greatly improved the treatment of chronic inflammatory disorders. This class of drugs is not only noticeably effective, but is also well tolerated. The cost effectiveness of these drugs means that there are limits to their use. This is the other face of success. The Dutch Ministry of Health, Welfare and Sport recently announced measures intended to limit the growth of costs while at the same time requiring that savings should be made on the current budget. Recently the Canadian Agency for Drugs and Technologies in Health (CADTH) produced a report on the effects and costs of biologicals for adults with rheumatoid arthritis (www.cadth.ca). Here we discuss their findings. Organizations for medical specialists should be societal aware and be able to deal with these drugs in a cost-conscious manner, including the development of dynamic guidelines and quality visitations.

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.