Risk Factors of Cancer in Pediatric-Onset Inflammatory Bowel Disease in Denmark and Finland.

OBJECTIVES: Pediatric-onset inflammatory bowel disease (pIBD) increases the risk of developing several different cancer forms. In this case-control study, we aimed to assess the impact of medical treatment and disease activity on the risk of developing disease-associated cancer (DAC) and treatment-associated cancer (TAC). METHODS: In a previous study, we identified 27 cases of DAC (colorectal cancer, small bowel cancer, and cholangiocarcinoma) and 28 TAC (lymphoma and skin cancer) in 6689 patients with pIBD in Denmark and Finland during the period 1992-2015. In this study, the patient charts were reviewed manually. Cancer-free patients from another population-based pIBD cohort were included as controls. We recorded data on phenotype, medical treatment, surgery, and relapses. Logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) to estimate the relative risk. RESULTS: We included 16 cases with DAC, 21 with TAC, and 331 controls. For DAC, lower frequencies of IBD-relapses were associated with an increased risk of cancer (OR 0.2 [95% CI: 0.04-0.8]). For TAC, we found an increased risk in patients receiving thiopurines at any point during the follow-up period (aOR: 11.7 [95% CI: 2.1-116.2]) and an association with proportion of follow-up time being exposed to thiopurines (aOR 5.6 [95% CI: 1.1-31.5]). CONCLUSIONS: In this nation-wide study, covering all pIBD patients from Denmark and Finland, we found that pIBD patients treated with thiopurines had an increased risk of TAC.

Extraintestinal Manifestations Are Associated With Disease Severity in Pediatric Onset Inflammatory Bowel Disease.

OBJECTIVES: The aim of this study was to investigate a possible association between extraintestinal manifestations (EIM) and a more severe disease course in pediatric onset inflammatory bowel disease (pIBD). METHODS: This study compares the disease course of pIBD patients (IBD diagnosis <15 years of age) with and without EIM in a population-based cohort from Denmark. Patients diagnosed with pIBD between 1998 and 2008 were included in the study and followed until December 31, 2014. Data on phenotype, treatment, relapses, and the temporal relationship between IBD relapses and activity of EIM were collected at end of follow-up by manual revision of patient charts. RESULTS: Of 333 pIBD patients, 14 (4.2%) had EIM at time of diagnosis and 47 (14.1%) developed EIM during follow-up. Median follow-up time was 9.6 years for patients with EIM and 8.8 years for patients without. In ulcerative colitis, EIM were associated with an increased risk of biological treatment and surgery (hazard ratio: 2.6; 95% confidence interval [CI]: 1.3-5.5, P = 0.008 and 2.9 [95% CI: 1.1-7.7, P = 0.03], respectively). In Crohn disease, EIM were associated with an increased relapse rate (1.3 [95% CI: 1.1-1.5], P = 0.001). Lastly, we found a positive temporal relationship between relapse of IBD and EIM activity. CONCLUSION: The presence of EIM is associated with a more severe disease course in pIBD. This should be considered when deciding treatment options, as a more aggressive treatment approach could be warranted in patients with EIM. However, prospective studies are needed to fully evaluate this.

Plasma calprotectin is superior to serum calprotectin as a biomarker of intestinal inflammation in ulcerative Colitis.

Background and aims: Despite promising results, only a few studies have been published on serum calprotectin as a biomarker in IBD. Recently, plasma measurements of calprotectin have been shown to be more reliable than serum measurements. In this study, we aim to assess plasma and serum calprotectin measurements as biomarkers of disease activity in paediatric and adult ulcerative colitis.Methods: Paediatric (5-18 years) and adult (>18 years) patients scheduled for colonoscopy due to suspected or confirmed ulcerative colitis were included prospectively. Stool and blood samples were collected at time of colonoscopy and patient symptom scores were recorded. At colonoscopy the Ulcerative Colitis Endoscopic Index of Severity was recorded. Histology was graded according to the Geboes score.Results: 84 patients where included; 30 paediatric and 54 adult patients. Plasma calprotectin had a stronger correlation to all outcome variables than serum calprotectin. Plasma calprotectin correlated positively to disease extent (Rho = 0.53, p < .0001), symptoms scores (Rho = 0.54, p = .002, only in the paediatric cohort), endoscopic scores (Rho = 0.39, p = .0003), histological scores (Rho 0.28, p = .01) and, when using endoscopic assessment of severity as reference, could discriminate active disease from patients in remission (p = .03).Conclusions: While more studies are needed to assess if plasma calprotectin can discriminate healthy individuals from ulcerative colitis, this study indicates that plasma calprotectin can be used as a biomarker of disease activity, especially in cases where faecal calprotectin measurements are cumbersome either due to patient compliance or logistical requirements.

Biochemical Markers, Genotype, and Inflammation in Pediatric Inflammatory Bowel Disease: A Danish Population-Based Study.

BACKGROUND: Our aim was to characterize the biochemical markers at diagnosis in patients with inflammatory bowel disease (IBD), to assess the utility of these to predict disease course and investigate if genotype influences biochemical markers of inflammation. SUMMARY: Patients were included from a population-based pediatric IBD cohort from Eastern Denmark. Data on biochemical markers and medical as well as surgical treatment were registered at diagnosis, 30 days, 6 and 12 months after diagnosis. Fifty-two single nucleotide polymorphisms (SNPs) known to be associated with IBD were selected for genotyping based on previous genetic studies. Key messages: A total of 190 IBD patients (97 ulcerative colitis [UC], 87 Crohn's disease [CD], and 6 IBD unclassified) were included. UC patients with extensive disease had higher C-reactive protein, erythrocyte sedimentation rate, and platelet count at diagnosis compared to UC patients with less extensive disease. No similar differences between disease extent groups were found in CD. Low albumin at diagnosis was associated with an increased risk of surgery in both UC (OR 1.35; 95% CI: 1.05-1.75) and CD patients (OR 1.23; 95% CI: 1.01-1.48) and increased use of azathioprine and anti-tumor necrosis factor alpha use in the total IBD cohort (OR 1.15; 95% CI: 1.04-1.27 and OR 1.19 [1.08-1.34]). One SNP (rs4986791 in the TLR-4 locus) and 2 SNPs (rs6785049 in the Pregnane-x-receptor gene and rs10500264 in the SLCA10 gene) were associated with a change in albumin and hemoglobin over time respectively in our IBD cohort. Our study confirms albumin to be a marker of severe disease course. Furthermore, the patient's genotype possibly affects the inflammatory response. Future studies in larger pediatric cohorts are needed to confirm our findings.

Serum Calprotectin in Adolescents With Inflammatory Bowel Disease-A Pilot Investigation.

OBJECTIVES: Fecal calprotectin (FC) is a well-integrated parameter in the monitoring of adolescent patients with inflammatory bowel disease (IBD). However, measurement of FC is limited by day-to-day-variation and by the feces consistency. Furthermore, adolescents are often noncompliant to deliver fecal sampling leading to suboptimal monitoring. Consequently, we see the need of a substitute biomarker whenever measurement of FC fails and aimed to investigate serum calprotectin (SC) in adolescents with IBD. METHODS: In cross sectional data from 19 ulcerative colitis (UC) patients <18 years old, a Spearman correlation was used to analyze the correlation between SC, FC, C-reactive protein (CRP) and endoscopic and symptom scores. In longitudinal data collected from 20 UC and Crohn disease (CD) patients (10-17 years old), Mixed Effect Models (MEM) were used to analyze the association between SC, FC, CRP, and symptom scores. RESULTS: We found positive correlations between SC (19 samples) and the endoscopic score, symptom score, and CRP (r = 0.56, P = 0.01; r = 0.64, P = 0.003; r = 0.97, P < 0.0001). We found no significant correlation between SC and FC. In 27 samples from UC patients, the association of SC with FC and CRP were positive and significant (P = 0.004, estimate = 0.32; P = 0.0001, estimate = 0.002). The association between SC and symptom score was insignificant. In 49 samples from CD patients, the association between SC and CRP was significant (P = 0.02, estimate = 0.002) whereas associations between SC and FC and symptom score were insignificant. CONCLUSIONS: In the current pilot study, we found a correlation between SC and the endoscopically assessed inflammation in UC. SC may have the potential to improve disease monitoring of adolescent patients.

A new mutation in the C-terminal end of TTC37 leading to a mild form of syndromic diarrhea/tricho-hepato-enteric syndrome in seven patients from two families.

Syndromic diarrhea/tricho-hepato-enteric syndrome (SD/THE) is a rare congenital enteropathy with seven main clinical features: intractable diarrhea of infancy, hair abnormalities, intrauterine growth restriction (IUGR), facial dysmorphism, immune dysfunction, and liver and skin abnormalities. SD/THE is caused by mutations in TTC37 or SKIV2L, two genes encoding components of the human SKI complex. To date, approximately 50 SD/THE patients have been described with a wide spectrum of mutations, and only one recurrent mutation has been identified in independent families. We present a detailed description of seven patients of Turkish origin with the same new mutation in TTC37: c.4572 G>A p.(Trp1524X). All seven patients were homozygous for this mutation and presented the typical clinical features of SD/THE, but with a milder presentation than usual. All seven patients were alive at the last follow-up. Four out of seven patients had no IUGR, and four patients never required parenteral nutrition. All patients presented a better growth rate than previously described in patients with SD/THE, with 4/7 above the 3rd percentile. The mutation is localized only forty amino acids from the end of TTC37, and as TTC37 is longer than the yeast SKI3, it is possible that a truncated protein is expressed and plays a reduced role in the SKI complex.

F-calprotectin and Blood Markers Correlate to Quality of Life in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: Our aim was to investigate predictors of health-related quality of life (HRQoL) with respect to changes in disease parameters over time in children with inflammatory bowel disease. METHODS: This was a prospective longitudinal study examining the association between HRQoL (IMPACT III) and symptom scores (Pediatric Crohn Disease Activity Index, abbreviated Pediatric Ulcerative Colitis Activity Index), fecal calprotectin measures and blood analyses (C-reactive protein, erythrocyte sedimentation rate, orosomucoid, albumin, hemoglobin, and vitamin-D) in a cohort of 10- to 17-year-old patients with inflammatory bowel disease. Data were collected prospectively at 3-month intervals during a 2-year period. Associations were analyzed using linear mixed-effect models. Patients were divided into 2 groups, which received nonbiological oral treatment or biological parenteral treatment. RESULTS: From 79 patients (39 Crohn disease/40 ulcerative colitis), representing a total of 43,132 days of observation, 572 IMPACT measurements were paired with variables. A decrease in the IMPACT III score was significantly associated with increased ulcerative colitis-symptom score in the biological group (P = 0.005), and a similar inverse tendency was found in the nonbiological group and for Crohn disease symptoms in both groups. We found in both treatment groups overall a significant (P < 0.05) inverse association between the IMPACT III and the levels of fecal calprotectin, erythrocyte sedimentation rate, and orosomucoid, whereas albumin, hemoglobin, and vitamin-D were directly significantly associated. CONCLUSIONS: The IMPACT score, already known to correlate with disease activity, has now been shown to be associated with disease markers in feces and blood. This emphasizes that objective markers of disease activity indirectly can predict the patient's HRQoL.

Surgical Management of Crohn Disease in Children: Guidelines From the Paediatric IBD Porto Group of ESPGHAN.

The incidence of Crohn disease (CD) has been increasing and surgery needs to be contemplated in a substantial number of cases. The relevant advent of biological treatment has changed but not eliminated the need for surgery in many patients. Despite previous publications on the indications for surgery in CD, there was a need for a comprehensive review of existing evidence on the role of elective surgery and options in pediatric patients affected with CD. We present an expert opinion and critical review of the literature to provide evidence-based guidance to manage these patients. Indications, surgical options, risk factors, and medications in pre- and perioperative period are reviewed in the light of available evidence. Risks and benefits of surgical options are addressed. An algorithm is proposed for the management of postsurgery monitoring, timing for follow-up endoscopy, and treatment options.

Surgery and postoperative recurrence in children with Crohn disease.

OBJECTIVES: The aim of this study was to describe surgery rates, complications, and risk of disease recurrence after surgery in paediatric Crohn disease (CD). METHODS: Children <18 years with a diagnosis of CD and a least 1 intestinal resection from the period January 1, 1978 to December 31, 2007 were identified using the Danish National Patient Registry. Patient charts were used to extract data. RESULTS: A total of 115 of 422 children with CD, who had surgery in 2 referral centres, were further studied. Disease extension according to the Montreal classification at the time of operation was available in 106/115 patients: B1, 39/106 (37%); B2, 59/106 (56%); and B3, 8/106 (7%). Before/after surgery 89%/36% of the patients received corticosteroids, 26%/61% azathioprine, and 15%/34% infliximab. Ileocoecal resection was performed in 54 (47%); 17 (15%) underwent ileal resection, 21 (18%) colectomy, 13 (11%) hemicolectomy, and 10 (9%) a combined colonic and ileal resection. Median time from diagnosis to surgery was 23 months (range 0-147). The median follow-up time after surgery was 121 months (16-226), and median time to disease recurrence was 12 months (3-160). The cumulative clinical recurrence rates at 1, 5, and 10 years were 50%, 73%, and 77%, respectively. More than 1 bowel resection was needed in 39%. Postoperative azathioprine treatment did not affect rate of recurrence after surgery. CONCLUSIONS: In this large cohort of children with CD studied for >10 years postoperatively, we found a high postoperative recurrence rate of disease and a frequent need for >1 intestinal resection.

Does infliximab prevent colectomy in acute and chronic active ulcerative colitis?

OBJECTIVES: The aim of the study was to evaluate clinical response, use of colectomy, and adverse events related to infliximab (IFX) treatment in acute and chronic active ulcerative colitis (UC) in children. METHODS: Children from 3 centers, who had received IFX for UC, were identified, and patient charts were reviewed retrospectively. Data concerning symptoms, biochemistry, concomitant medical treatment, colectomy, and adverse events were registered. RESULTS: A total of 45 patients with UC (median age at diagnosis 12 years, interquartile range 10-14) were included, and studied for a median of 15 months (interquartile range 4.5-29) after first IFX infusion. The cumulative 1- and 2-year risks of colectomy were 21% and 26%, respectively. The cumulative 1- and 2-year risks of receiving a new course of systemic corticosteroids were 32% and 48%, respectively. Twenty-one patients (46%) experienced adverse events. Most common were mild infusion reactions, but 3 (7%) had serious adverse events. CONCLUSIONS: IFX was efficient in preventing colectomy in children with UC. The risk of receiving systemic corticosteroids was lower than that reported in other studies. Most adverse events were mild to moderate and self-limiting.

ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents.

BACKGROUND: The diagnosis of pediatric-onset inflammatory bowel disease (PIBD) can be challenging in choosing the most informative diagnostic tests and correctly classifying PIBD into its different subtypes. Recent advances in our understanding of the natural history and phenotype of PIBD, increasing availability of serological and fecal biomarkers, and the emergence of novel endoscopic and imaging technologies taken together have made the previous Porto criteria for the diagnosis of PIBD obsolete. METHODS: We aimed to revise the original Porto criteria using an evidence-based approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD. These revised criteria are based on the Paris classification of PIBD and the original Porto criteria while incorporating novel data, such as for serum and fecal biomarkers. A consensus of at least 80% of participants was achieved for all recommendations and the summary algorithm. RESULTS: The revised criteria depart from existing criteria by defining 2 categories of ulcerative colitis (UC, typical and atypical); atypical phenotypes of UC should be treated as UC. A novel approach based on multiple criteria for diagnosing IBD-unclassified (IBD-U) is proposed. Specifically, these revised criteria recommend upper gastrointestinal endoscopy and ileocolonscopy for all suspected patients with PIBD, with small bowel imaging (unless typical UC after endoscopy and histology) by magnetic resonance enterography or wireless capsule endoscopy. CONCLUSIONS: These revised Porto criteria for the diagnosis of PIBD have been developed to meet present challenges and developments in PIBD and provide up-to-date guidelines for the definition and diagnosis of the IBD spectrum.

Diagnostic workup of paediatric patients with inflammatory bowel disease in Europe: results of a 5-year audit of the EUROKIDS registry.

OBJECTIVE: In 2005, the Inflammatory Bowel Disease (IBD) Working Group of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition published consensus guidelines on the diagnostic workup of paediatric IBD, the Porto criteria. According to these guidelines, children suspected of having IBD should undergo an oesophagogastroduodenoscopy (OGD), ileocolonoscopy, and (except in cases of definitive ulcerative colitis) adequate imaging of the small bowel. To audit and evaluate the diagnostic workup of paediatric patients with IBD in Europe, the Working Group created EUROKIDS, a prospective, Web-based registry of newly diagnosed paediatric patients with IBD. METHODS: Patients with IBD (ages 0-18 years) were registered in 44 centres in 18 countries. Data on diagnostic workup were analysed according to the year of diagnosis, type of IBD, and centre size. Diagnostic yield of OGD and ileal intubation were evaluated. RESULTS: Between 2004 and 2009, 2087 newly diagnosed patients were correctly registered. Both OGD and ileocolonoscopy had been performed in 64% of all of the patients and increased significantly from year 1 (52 %) to 5 (71%, P  <  0.001). Small-bowel follow-through use decreased during the years (year 1 n = 213, year 5 n = 108; P < 0.001), whereas magnetic resonance imaging use increased (year 1 n  = 25, year 5 n  = 171; P < 0.001). Patients diagnosed as having Crohn disease (CD, 59%) and ulcerative colitis (58%) were more likely to have had a complete diagnostic workup than patients diagnosed as having IBD unclassified (45%). In CD, the diagnostic yield of OGD was 7.5% and the yield of ileal intubation was 13%. CONCLUSIONS: The quality of diagnostic workup in paediatric patients with IBD increased steadily between 2004 and 2009. Small-bowel imaging by magnetic resonance imaging superseded the use of small-bowel follow-through. OGD and ileal intubation contributed to a definitive diagnosis of CD.

Management of pediatric ulcerative colitis: joint ECCO and ESPGHAN evidence-based consensus guidelines.

BACKGROUND AND AIMS: Pediatric ulcerative colitis (UC) shares many features with adult-onset disease but there are some unique considerations; therefore, therapeutic approaches have to be adapted to these particular needs. We aimed to formulate guidelines for managing UC in children based on a systematic review (SR) of the literature and a robust consensus process. The present article is a product of a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). METHODS: A group of 27 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to ESPGHAN and ECCO members. A list of 23 predefined questions were addressed by working subgroups based on a SR of the literature. RESULTS: A total of 40 formal recommendations and 68 practice points were endorsed with a consensus rate of at least 89% regarding initial evaluation, how to monitor disease activity, the role of endoscopic evaluation, medical and surgical therapy, timing and choice of each medication, the role of combined therapy, and when to stop medications. A management flowchart, based on the Pediatric Ulcerative Colitis Activity Index (PUCAI), is presented. CONCLUSIONS: These guidelines provide clinically useful points to guide the management of UC in children. Taken together, the recommendations offer a standardized protocol that allows effective, timely management and monitoring of the disease course, while acknowledging that each patient is unique.

Changes in Incidence and Management of Acute Appendicitis in Children-A Population-Based Study in the Period 2000-2015.

INTRODUCTION: Recent studies suggest that the epidemiology and management of appendicitis have changed during the last decades. The purpose of this population-based study was to examine this in the pediatric population in Denmark. MATERIALS AND METHODS: Data were retrieved from the Danish National Patient Registry, the Danish Civil Registration System, and the Statbank Denmark. Patients aged 0 to 17 years diagnosed with appendicitis and appendectomized during the period 2000 to 2015 were included. The primary outcome was the annual incidences of appendicitis. Secondary outcomes were the annual percent of patients with appendicitis having a laparoscopic appendectomy, delay from admission to surgery, length of postoperative hospital stay, and 30-day postoperative mortality. RESULTS: A total of 24,046 pediatric cases of appendicitis were identified. The annual incidence steadily declined until 2008 (-29%, all ages) and then remained stable. The surgical approach of choice changed from being open appendectomy in 2000 (97%) to laparoscopic appendectomy in 2015 (94%). Simultaneously, the duration of postoperative hospital stay declined from 41 hours (median) to 17 hours. Delay from admission until surgery did not change during the period. Only one child died within the 30-day postoperative period. CONCLUSION: In accordance with other recent studies from Western countries, we found significant changes in the incidence of acute appendicitis including a decline in all age groups except those below 5 years of age, a shift toward laparoscopic appendectomy, and decreasing time spent in the hospital during the years 2000 to 2015.

Complicated Disease and Response to Initial Therapy Predicts Early Surgery in Paediatric Crohn's Disease: Results From the Porto Group GROWTH Study.

INTRODUCTION: The ability to predict risk for poor outcomes in Crohn's disease [CD] would enable early treatment intensification. We aimed to identify children with CD with complications at baseline and throughout the study period who are at risk for surgery 2 years from diagnosis. METHODS: Newly diagnosed children with CD were enrolled into a prospective, multicentre inception cohort. Disease characteristics and serological markers were obtained at baseline and week 12 thereafter. Outcome data including disease activity, therapies, complications and need for surgery were collected until the end of 104 weeks. A chi-square automatic interaction detection [CHAID] algorithm was used to develop a prediction model for early surgery. RESULTS: Of 285 children enrolled, 31 [10.9%] required surgery within 2 years. Multivariate analysis identified stricturing disease at baseline (odds ratio [OR] 5.26, 95% confidence interval [CI] 2.02-13.67 [p = 0.001]), and Paediatric Crohn's Disease Activity Index [PCDAI] >10 at week 12 (OR 1.06, 95% CI 1.02-1.10 [p = 0.005]) as key predictors for early surgery. CHAID demonstrated that absence of strictures at diagnosis [7.6%], corticosteroid-free remission at week 12 [4.1%] and early immunomodulator therapy [0.8%] were associated with the lowest risk of surgery, while stricturing disease at diagnosis [27.1%, p < 0.001] or elevated PCDAI at week 12 [16.7%, p = 0.014] had an increased risk of surgery at follow-up. Anti-OmpC status further stratified high-risk patients. DISCUSSION: A risk algorithm using clinical and serological variables at diagnosis and week 12 can categorize patients into high- and low-risk groups from diagnosis.

The incidence of cancer and mortality in paediatric onset inflammatory bowel disease in Denmark and Finland during a 23-year period: a population-based study.

BACKGROUND: Recent studies report increased risks of both cancer and mortality in paediatric onset inflammatory bowel disease (pIBD) but the reproducibility of this is unknown. AIM: To estimate the risk of cancer and mortality in the Danish and Finnish pIBD population in a 23-year period compared to the general population. METHODS: The pIBD population was defined as individuals registered in the national patient registries with a diagnosis of Crohn's disease (CD), ulcerative colitis (UC) or IBD-unclassified before their 18th birthday from 1992 to 2014. This cohort was cross referenced with the national cancer and mortality registries identifying all pIBD patients who subsequently developed cancer and/ or died and followed up to the end of 2014. Risk estimates are presented as standardised incidence ratios calculated based on incidence figures from the populations. RESULTS: Six thousand six hundred and eight-nine patients with pIBD were identified (median age at follow-up 22.3 years; median follow-up: 9.6 years [interquartile range: 4.8-16.0]). Seventy-two subsequently developed cancer and 65 died. The standardised incidence ratio of cancer in general was 2.6 (95% CI: 1.8-3.7) and 2.5 (95% CI: 1.8-3.4) in CD and UC, respectively. The standardised mortality ratios were 2.2 (95% CI: 1.4-3.4) and 3.7 (95% CI: 2.7-5.0) in CD and UC, respectively. The leading causes for mortality were cancer, suicide and infections. CONCLUSIONS: We found an increased risk of cancer and mortality in pIBD. This underlines the importance of cancer surveillance programs and assessment of mental health in the standard of care in adolescent pIBD patients.

Response to treatment is more important than disease severity at diagnosis for prediction of early relapse in new-onset paediatric Crohn's disease.

BACKGROUND: Paediatric Crohn's disease is characteried by frequently relapsing disease which may lead to hospitalisations and complications. AIM: To develop predictive models for early relapse following first remission. METHODS: The GROWTH CD prospective inception cohort was designed to predict risk for early disease relapse and poor outcomes. Newly diagnosed children underwent endoscopies and imaging. They were phenotyped and followed at scheduled visits through 78 weeks for relapses. Twenty-eight dichotomous and continuous variables were assessed at baseline and week 12, including phenotype, inflammatory markers, disease activity (PCDAI) and other markers. Clinical relapses defined as PCDAI >10 after remission were recorded using a relapse form. Logistic regression & risk modelling was performed. RESULTS: We enrolled 282 eligible patients of whom 178 (63.6%) patients achieved steroid free remission by week 12. Disease complications developed in 22/76(29%) of patients with relapse compared to 20/206 (9.7%) without relapse (P = 0.01). Multivariable analysis demonstrated that while variables from age/gender at diagnosis were not predictive, week 12 variables including PCDAI >5 (P = 0.02), CRP >20 mg/L (P = 0.02), and faecal calprotectin >400 µg/g (P = 0.03) as optimal cut-offs were associated with increased risk of relapse. A prediction model for patients in remission including gender, age, week 12 PCDAI, calprotectin and CRP had sensitivity 43%, specificity 92%, PPV 78%, NPV 71% for relapse. CONCLUSIONS: Early relapses were associated with a higher risk for disease complications at followup. Relapse prediction based on week 12 disease activity or inflammation is superior to prediction using data from diagnosis.

Differences in Outcomes Over Time With Exclusive Enteral Nutrition Compared With Steroids in Children With Mild to Moderate Crohn's Disease: Results From the GROWTH CD Study.

BACKGROUND: Exclusive enteral nutrition [EEN] and corticosteroids [CS] induce similar rates of remission in mild to moderate paediatric Crohn's disease [CD], but differ with regard to mucosal healing. Our goal was to evaluate if EEN at diagnosis was superior to CS for improving long-term outcomes. METHODS: We prospectively followed newly diagnosed children aged < 17 years, with mild to moderate CD at baseline, for 2 years in the GROWTH CD study. Patients were evaluated at baseline and at 8, 12, 78, and 104 weeks. Remission, relapses, complications [fibrostenotic disease, penetrating disease, and active perianal disease] and growth were recorded throughout the study. A propensity score analysis was performed. RESULTS: A total of 147 children [mean age 12.9 ± 3.2 years], treated by EEN [n = 60] or CS [n = 87] were included. New complications developed in 13.7% of CS [12/87] versus 11.6% of EEN [7/60], p = 0.29. Remission was achieved in 41/87 [47%] in CS and 38/60 [63%] EEN, p = 0.036. Median time to relapse did not differ [14.4 ± 1 months with CS, 16.05 ± 1.1 EEN, p = 0.28]. Mean height Z scores decreased from Week 0 to Week 78 with CS [-0.34 ± 1.1 to -0.51 ± 1.2, p = 0.01], but not with EEN [-0.32 ± 1.1 to -0.22 ± 0.9, p = 0.56]. In a propensity score analysis, EEN was superior to CS for inducing remission [p = 0.05] and trended to superiority for height Z score [p = 0.055]. CONCLUSIONS: Use of EEN was associated with higher remission rates and a trend toward better growth but with similar relapse and complication rates in new-onset mild to moderate paediatric CD.

[Lactose malabsorption and -intolerance - who will benefit from a lactose-reduced diet?]

During the last decade, lactose-free diets have become increasingly popular in the general population, either isolated or as a part of a cow's milk-free diet. However, health-related benefits from a lactose-free diet are only documented for individuals with clinical lactose intolerance due to decreased intestinal lactase activity and subsequent lactose malabsorption. In this paper we summarize the current knowledge of lactose intolerance regarding diagnostic procedures and treatment.

[Gluten-free diet is for some a necessity, for others a lifestyle].

This review provides a brief overview of the gluten-related conditions coeliac disease (CD), wheat allergy (WA), and non-coeliac gluten sensitivity (NCGS). NCGS is a new entity which includes individuals who report symptoms when exposed to gluten and benefit from gluten-free diet, but do not have CD or WA. The concept NCGS is still controversial and a subject of considerable overdiagnosis, and consensus regarding diagnostic criteria is lacking. Furthermore, the overlap with irritable bowel syndrome is unsettled.