Endoscopic Balloon Dilatation in Pediatric Crohn Disease: An IBD Porto Group Study.

OBJECTIVE/BACKGROUND: Endoscopic balloon dilatation (EBD) has been shown to be effective and safe in adults with stricturing Crohn disease (CD) yet pediatric data is sparse. We aimed to assess efficacy and safety of EBD in stricturing pediatric CD. METHODS: International collaboration included 11 centers from Europe, Canada, and Israel. Recorded data included patient demographics, stricture features, clinical outcomes, procedural adverse events, and need for surgery. Primary outcome was surgery-free over 12 months and secondary outcomes were clinical response and adverse events. RESULTS: Eighty-eight dilatations were performed over 64 dilatation series in 53 patients. Mean age at CD diagnosis was 11.1 (±4.0) years, stricture length 4 cm [interquartile range (IQR) 2.8-5], and bowel wall thickness 7 mm (IQR 5.3-8). Twelve of 64 (19%) patients underwent surgery in the year following the dilatation series, at a median of 89 days (IQR 24-120; range 0-264) following EBD. Seven of 64 (11%) had subsequent unplanned EBD over the year, of whom two eventually underwent surgical resection. Two of 88 (2%) perforations were recorded, 1 of whom was managed surgically, and 5 patients had minor adverse events managed conservatively. There was a significant improvement in all clinical measures following EBD with weighted pediatric CD activity index-defined remission increasing from 13% at baseline to 44%, 46%, and 61%, and absence of obstructive symptoms in 55%, 53%, and 64% of patients at week 2, 8, and 24 respectively. CONCLUSIONS: In this largest study of EBD in pediatric stricturing CD to date, we demonstrated that EBD is effective in relieving symptoms and avoiding surgery. Adverse events rates were low and consistent with adult data.

Diagnostic Value of Quantitative Contrast-Enhanced Ultrasound in Comparison to Endoscopy in Children With Crohn's Disease.

OBJECTIVE: Quantitative contrast-enhanced US (CEUS) provides objective evaluation of bowel wall perfusion and has been reported as a useful method for evaluating Crohn's disease (CD) activity in children. We tested its' diagnostic accuracy in comparison to endoscopy and evaluated its' usefulness in comparison to Pediatric Crohn's Disease Activity Index (PCDAI) and fecal Calprotectin (FC). MATERIALS AND METHODS: Children with CD and thickened bowel wall on abdominal US were prospectively enrolled. Disease activity was evaluated with quantitative CEUS, PCDAI and FC and compared to a simple endoscopic score for Crohn's disease (SES-CD). Spearman's correlation and Cohen's kappa statistic between the SES-CD and other disease activity measures were performed and diagnostic accuracies calculated. RESULTS: 36 children 3.5-18 years old (mean age 14 years) were included. The quantitative CEUS had 78.57% sensitivity (95%CI 0.59-0.92), 100% specificity (95%CI 0.63-1.0) and 83.33% diagnostic accuracy (95% CI 0.67-0.94). The concordance remission agreement with endoscopy was substantial for quantitative CEUS and PCDAI (quantitative CEUS: κ = 0.62; 95% CI 0.363-0.877; PCDAI: κ = 0.615; 95% CI 0.311-0.920), but only fair for FC (κ = 0.389; 95% CI 0.006-0.783). Correlation between all measures and endoscopy was moderate and statistically significant (quantitative CEUS: rs  = 0.535, PCDAI: rs  = 0.543, FC: rs  = 0.497). CONCLUSIONS: Quantitative CEUS has a potential of becoming a complementary method for evaluation of CD activity in children due to its' high specificity in comparison to endoscopy. Lower sensitivity makes it deficient as a single measure and further management should be guided by PCDAI and FC results as well.

Clinical Features and Outcomes of Paediatric Patients With Isolated Colonic Crohn Disease.

OBJECTIVES: Adult studies suggest that patients with isolated colonic Crohn disease (L2 CD) exhibit unique characteristics differentiating them from patients with ileo-caecal (L1) CD and ulcerative colitis (UC). We aimed to characterize clinical features and outcomes of paediatric patients with L2. METHODS: Retrospective data was collected through the Porto Inflammatory Bowel Disease group of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) on Paediatric patients with L2, L1 or UC at different time-points. Outcome measures included time to first flare, hospital admissions, initiation of anti-tumor necrosis factor-alpha (TNFα) drug, stricture and surgery. RESULTS: Three hundred patients were included: 102 L1, 94 L2 and 104 UC. Rates of hematochezia at presentation were 14.7%, 44.7% and 95.2%, while rates of fever were 12.7%, 26.6% and 2.9%, for patients with L1, L2 and UC, respectively (P < 0.001 for all comparisons). Skip lesions were identified in 65% of patients with L2, and granulomas in 36%, similar to L1 patients. Rates of anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic (pANCA) positivity significantly differed between the three groups: 25.4% and 16.7% for patients with L2, compared with 55.2% and 2.3%, and 1.8% and 52.9% for patients with L1 and UC, respectively. Response rates to exclusive enteral nutrition were comparable between L1 and L2 (78.3-82.4%), as was the response to oral steroids (70.4-76.5%) in the three groups. While times to first flare and admission were similar between groups, patients with L1 were commenced on anti-TNFα earlier. Moreover, stricturing phenotype and need for colectomy were very rare in patients with L2. CONCLUSIONS: Significant differences are observed in the clinical presentation and outcomes of Paediatric patients with L2, compared to patients with L1 and UC.

Contrast-enhanced ultrasonography in the evaluation of Crohn disease activity in children: comparison with histopathology.

BACKGROUND: Contrast-enhanced ultrasound (US) of the bowel wall has been suggested as an alternative imaging modality for the follow-up of children with Crohn disease. OBJECTIVE: To evaluate the diagnostic performance of contrast-enhanced US in the estimation of Crohn disease activity in children with histopathology as the reference standard. MATERIALS AND METHODS: In 24 children with Crohn disease confirmed on histopathology, disease activity was evaluated on 40 bowel segments using US score and subjective and quantitative contrast-enhanced US evaluation. Contrast-enhanced US evaluation included enhancement pattern analysis with a graphic representation of log time-intensity curve and calculation of kinetic parameters with the definition of thresholds for disease activity, as determined by receiver operating characteristics curve analysis. The diagnostic accuracy of US with colour Doppler imaging and subjective and quantitative contrast-enhanced US were calculated. RESULTS: Moderate or severe inflammation was identified in 18 segments and remission or mild inflammation was identified in 22 segments on histopathology. The quantitative contrast-enhanced US, namely the peak enhancement value, had 72.2% sensitivity (95% confidence interval [CI] 46.5-90.3), 100% specificity (95% CI 84.6-100.0) and 87.5% diagnostic accuracy (95% CI 73.2-95.8) in predicting moderate or severe grade inflammation at histopathology. The sensitivity, specificity and diagnostic accuracy of subjective contrast-enhanced US were 77.8% (95% CI 52.4-93.6), 77.3% (95% CI 54.6-92.2) and 77.5% (95% CI 61.6-89.2), respectively, and of US with colour Doppler imaging were 55.6% (95% CI 30.8-78.5), 86.4% (95% CI 65.1-79.1) and 72.5% (95% CI 56.1-85.4), respectively. CONCLUSION: Quantitative contrast-enhanced US has the potential of becoming a complementary method in the evaluation of Crohn disease activity in children. Fibrosis may affect peak enhancement results and underestimate inflammatory activity.

Partial enteral nutrition induces clinical and endoscopic remission in active pediatric Crohn's disease: results of a prospective cohort study.

The aim of this study was to evaluate rates of clinical remission, endoscopic remission, and mucosal healing after a 6-week treatment period with partial enteral nutrition (PEN) and to compare them to those obtained by standard exclusive enteral nutrition (EEN) treatment in children with active Crohn's disease (CD). Twenty-five patients with active CD (median age 13.6 years, range 3.6-18.0) were recruited to either PEN (n = 12) or EEN (n = 13) treatment groups. The PEN group received 75% of their dietary needs from a polymeric formula plus one meal per day from an anti-inflammatory diet (AID). Patients were assessed at weeks 0, 1, 3, and 6 using clinical and laboratory parameters. Endoscopic assessment was performed at induction and week 6. On intention to treat analysis, clinical remission (Pediatric CD Activity Index < 10) was achieved in 69.2% and 75.0% of EEN and PEN patients, respectively (p = 0.999). The endoscopic remission (Simple Endoscopic Score for CD (SES-CD) ≤ 2) rates were 45.5% in both groups, while mucosal healing rates (SES-CD = 0) were 45.5% with EEN and 27.3% with PEN (p = 0.659).Conclusion: The results of our prospective pilot study suggest that PEN, allowing one meal from AID, could be as effective as EEN in inducing clinical and endoscopic remission in children with active CD. However, larger randomized controlled studies are warranted to confirm our findings.Trial registration: This clinical trial was registered under the number ClinicalTrials.govidentifier: NCT03176875.What is Known:• Exclusive enteral nutrition is a first-line treatment in active pediatric Crohn's disease; however, patients often find it difficult to adhere to.• Exclusive enteral nutrition is more effective than corticosteroids in achieving mucosal healing.What is New:• This is the first prospective study on partial enteral nutrition in active pediatric Crohn's disease, evaluating not only clinical, but also endoscopic remission.• A novel approach of partial enteral nutrition that allows one meal per day from an anti-inflammatory diet was as effective as exclusive enteral nutrition in inducing clinical and endoscopic remission in active Crohn's disease.

Success and safety of high infliximab trough levels in inflammatory bowel disease.

OBJECTIVE: A prospective trial suggests target infliximab trough levels of 3-7 µg/mL, yet data on additional therapeutic benefits and safety of higher trough levels are scarce. AIM: To explore whether high infliximab trough levels (≥7 µg/mL) are more effective and still safe. MATERIAL AND METHODS: In this cohort study of 183 patients (109 Crohn's disease and 74 ulcerative colitis) on infliximab maintenance treatment at a tertiary referral center we correlated fecal calprotectin and C-reactive protein to trough levels (426 samples) at different time points during treatment. Rates of infections were compared in quadrimesters (four-month periods) with high trough levels to quadrimesters with trough levels <7 µg/mL during 420 patient-years. RESULTS: Fecal calprotectin and C-reactive protein (median [interquartile range]) were lower in patients with high trough levels (fecal calprotectin 66 mg/kg [30-257]; C-reactive protein 3 mg/L [3-3]) compared to trough levels below 7 µg/mL (fecal calprotectin 155 mg/kg [72-474]; C-reactive protein 3 mg/L [3-14.5]) (p < .001). High trough levels were superior also after excluding samples with trough levels <3 µg/mL from analysis. No differences in rates of infections were observed in quadrimesters with high trough levels (16/129 [12.4%]) compared to quadrimesters with trough levels <7 µg/mL (32/344 [9.3%]) (p = .32). Maintaining high trough levels resulted in 32% (interquartile range: 2-54%) increase of infliximab consumption. CONCLUSION: High infliximab trough levels provide better control of inflammation in inflammatory bowel disease without increasing the risk of infection.

Dynamic contrast-enhanced ultrasound of the bowel wall with quantitative assessment of Crohn's disease activity in childhood.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) has become an established non-invasive, patient-friendly imaging technique which improves the characterization of lesions. In addition, dynamic contrast-enhanced ultrasound (DCE-US) provides valuable information concerning perfusion of examined organs. This review addresses current applications of CEUS in children, focused on DCE-US of the bowel wall in patients with Crohn disease, which enables realtime assessment of the bowel wall vascularity with semi-quantitative and quantitative assessment of disease activity and response to medical treatment. CONCLUSIONS: Crohn's disease is a chronic inflammatory relapsing disease. Frequent imaging re-evaluation is necessary. Therefore, imaging should be as little invasive as possible, children friendly with high diagnostic accuracy. US with wide varieties of techniques, including CEUS/DCE-US, can provide an important contribution for diagnosing and monitoring a disease activity. Even if the use of US contrast agent is off-label in children, it is welcome and widely accepted for intravesical use, and a little less for intravenous use, manly in evaluation of parenchymal lesions. To our knowledge this is the first time that the use of DCE-US in the evaluation of activity of small bowel Crohn disease with quantitative assessment of kinetic parameters is being described in children. Even if the results of the value and accuracy of different quantitative kinetic parameters in published studies in adult population often contradict one another there is a great potential of DCE-US to become a part of the entire sonographic evaluation not only in adults, but also in children. Further control studies should be performed.

Incidence and phenotypic characteristics of pediatric IBD in northeastern Slovenia, 2002-2010.

OBJECTIVES: The purpose of the present study was to determine the incidence of inflammatory bowel disease (IBD) and its subgroups in children in northeastern Slovenia (NE Slovenia) during the period 2002-2010, and to assess the phenotypic characteristics at the diagnosis and during the follow-up. METHODS: A retrospective investigation was conducted on a cohort of newly diagnosed children and adolescents with IBD ages 0 to 18 years between 2002 and 2010 and residing in NE Slovenia. The phenotypic characteristics were determined at presentation and during follow-up. The location of Crohn disease (CD) and ulcerative colitis (UC) was assessed according to the Paris classification at diagnosis, and later in patients who had a follow-up period >2 years. The type of therapy at diagnosis and during follow-up, and the need for surgery were determined. The study covered approximately one-third of the total pediatric population (0-18 years). RESULTS: In total, 107 cases of IBD were diagnosed during the study period. The mean annual incidence (per 100,000) was 7.6 (95% confidence interval [CI] 6.3-9.2) for all IBD, 4.6 (95% CI 3.6-5.9) for CD, and 2.8 (95% CI 1.9-3.8) for UC. The incidences of total IBD, CD, and UC increased from 5.7 (3.8-8.2), 3.9 (2.3-6.1), and 1.8 (0.8-3.5) in the period 2002-2004, respectively, to 8.9 (6.3-12.2), 5.0 (3.1-7.6), and 3.4 (1.9-5.6) in the period 2008-2010, respectively. During the follow-up, the proportion of complicated CD disease behavior (stricturing/penetrating) had doubled. A total of 18.5% of patients with CD underwent bowel surgery. CONCLUSIONS: The incidence of childhood IBD in the northeastern part of the country is high and comparable with that reported from the developed western countries of Europe, and is probably still increasing. This increase may be the result of changes in the lifestyle, especially in dietary habits during the last 20 years.

Effectiveness and Safety of Ustekinumab in Pediatric Ulcerative Colitis: A Multi-center Retrospective Study from the Pediatric IBD Porto Group of ESPGHAN.

BACKGROUND AND OBJECTIVES: Current data on ustekinumab therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBDU) are limited. We aimed to evaluate the effectiveness and safety of ustekinumab in pediatric UC and IBDU. METHODS: This multicenter retrospective study included 16 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. Children with UC or IBDU treated with ustekinumab were enrolled. Demographic, clinical, laboratory, endoscopic, and imaging data as well as adverse events were recorded. Analyses were all based on the intention-to-treat principle. RESULTS: Fifty-eight children (39 UC and 19 IBDU, median age 14.5 [IQR 11.5-16.5] years) were included. All had failed biologic therapies, and 38 (66%) had failed two or more biologics. Corticosteroid-free clinical remission (CFR) was observed in 27 (47%), 33 (57%), and 37 (64%) children at 16, 26, and 52 weeks, respectively. Normalization of C-reactive protein and calprotectin < 150 µg/g were achieved in 60% and 52%, respectively, by 52 weeks. Endoscopic and radiologic remissions were reached in 8% and 23%, respectively. The main predictors of CFR were diagnosis of UC compared with IBDU (hazard ratio [HR] 2.2, 95% CI 1.03-4.85; p = 0.041) and no prior vedolizumab therapy (HR 2.1, 95% CI 1.11-4.27; p = 0.023). Ustekinumab serum levels were not associated with disease activity. Adverse events were recorded in six (10%) children, leading to discontinuation of the drug in three. CONCLUSION: Based on these findings, ustekinumab appears as an effective therapy for pediatric refractory UC and IBDU. The potential efficacy should be weighed against the risks of serious adverse events.

Treatment of Active Crohn's Disease in Children Using Partial Enteral Nutrition Combined with a Modified Crohn's Disease Exclusion Diet: A Pilot Prospective Cohort Trial on Clinical and Endoscopic Outcomes.

BACKGROUND: Partial enteral nutrition (PEN) coupled with the Crohn's disease (CD) exclusion diet (CDED) was shown to be effective in inducing clinical remission in paediatric CD. There are currently no robust data on the endoscopic outcomes of PEN. The aim of this study was to evaluate the clinical and endoscopic rates of remission after PEN combined with a modified CDED (mCDED) adjusted to the local cuisine in comparison with exclusive enteral nutrition (EEN) for the induction of remission. METHODS: Between June 2017 and February 2021, a prospective cohort study on children with active CD, treated with PEN + mCDED or EEN, was performed at a single tertiary centre. RESULTS: During the study period, 54 patients were screened and 15 were excluded according to the exclusion criteria, with six patients excluded in the first two days due to intolerance of the enteral formula. Fourteen patients were included in the PEN and 19 in the EEN group. They were assessed at Weeks 0, 1, 3 and 6, using clinical and laboratory parameters. Endoscopy was performed at Weeks 0 and 6. Clinical remission rates per protocol analysis were 84.6% in the PEN group and 81.3% in the EEN group (p = 0.99). At Week 6, an endoscopic response (a decline in the Simple Endoscopic Score for CD (SES-CD) > 50%) was observed in 84.6% of patients on PEN and in 68.8% on EEN treatment (p = 0.41). Endoscopic remission (SES-CD ≤ 2) was achieved in 53.8% of patients in the PEN group and in 50.0% in the EEN group (p = 0.99), while the mucosal healing rates (SES-CD = 0) were 38.5% with PEN and 43.8% with EEN (p = 0.99). A significant decline in the clinical and endoscopic activity scores was observed in both groups. CONCLUSION: Our study suggests that PEN + mCDED could be effective in inducing endoscopic remission and mucosal healing in active paediatric CD patients. Here, we present an analysis of the data from our cohort of patients and our real-world experience with PEN + mCDED.

Non-alcoholic fatty liver disease in a pediatric patient with heterozygous familial hypobetalipoproteinemia due to a novel APOB variant: a case report and systematic literature review.

Background: Familial hypobetalipoproteinemia (FHBL) is an autosomal semi-dominant disorder usually caused by variants in the APOB gene that frequently interferes with protein length. Clinical manifestations include malabsorption, non-alcoholic fatty liver disease, low levels of lipid-soluble vitamins, and neurological, endocrine, and hematological dysfunction. Methods: Genomic DNA was isolated from the blood samples of the pediatric patient with hypocholesterolemia and his parents and brother. Next-generation sequencing (NGS) was performed, and an expanded dyslipidemia panel was employed for genetic analysis. In addition, a systematic review of the literature on FHBL heterozygous patients was performed. Case report: Genetic investigation revealed the presence of a heterozygous variant in the APOB (NM_000384.3) gene c.6624dup[=], which changes the open reading frame and leads to early termination of translation into the p.Leu2209IlefsTer5 protein (NP_000375.3). The identified variant was not previously reported. Familial segregation analysis confirmed the variant in the mother of the subject, who also has a low level of low-density lipoprotein and non-alcoholic fatty liver disease. We have introduced therapy that includes limiting fats in the diet and adding lipid-soluble vitamins E, A, K, and D and calcium carbonate. We reported 35 individuals with APOB gene variations linked to FHBL in the systematic review. Conclusion: We have identified a novel pathogenic variant in the APOB gene causing FHBL in pediatric patients with hypocholesterolemia and fatty liver disease. This case illustrates the importance of genetic testing for dyslipidemias in patients with significant decreases in plasma cholesterol as we can avoid damaging neurological and ophthalmological effects by sufficient vitamin supplementation and regular follow-ups.

Outcomes, dosing, and predictors of vedolizumab treatment in children with inflammatory bowel disease (VEDOKIDS): a prospective, multicentre cohort study.

BACKGROUND: Scarce data are available on the use of vedolizumab in children with inflammatory bowel disease (IBD). We aimed to evaluate the safety, effectiveness, and dosing of vedolizumab to induce remission of IBD. METHODS: VEDOKIDS was a paediatric, multicentre, prospective cohort study done in 17 centres in six countries. We report the 14-week outcomes as the first analyses of the planned 3-year follow-up of the VEDOKIDS cohort. Children (aged 0-18 years) with IBD who had commenced vedolizumab were followed up at baseline and at 2, 6, and 14 weeks. Children were managed according to local prescribing practices without standardisation of dosing or criteria for escalation, but the study protocol suggested dosing of 177 mg/m2 body surface area (up to 300 mg maximum). The primary outcome was steroid-free and exclusive enteral nutrition-free remission at 14 weeks, analysed according to the intention-to-treat principle. Serum samples were taken for analysis of drug concentration and faecal calprotectin at baseline, and at 2, 6, and 14 weeks. Adverse events were recorded in real time and classified as severe or non-severe and related or unrelated to vedolizumab. This study is registered with ClinicalTrials.gov, NCT02862132. FINDINGS: Between May 19, 2016, and April 1, 2022, 142 children (76 [54%] girls and 66 [46%] boys; mean age 13·6 years [SD 3·6]) were enrolled. 65 (46%) children had Crohn's disease, 68 (48%) had ulcerative colitis, and nine (6%) had unclassified IBD (those with unclassified IBD were analysed with the ulcerative colitis group). 32 (42% [95% CI 30-54]) of 77 children with ulcerative colitis and 21 (32% [23-45]) of 65 children with Crohn's disease were in steroid-free and exclusive enteral nutrition-free remission at 14 weeks. Median drug concentrations at week 14 were higher in children with ulcerative colitis than in those with Crohn's disease (11·5 µg/mL [IQR 5·5-18·1] vs 5·9 µg/mL [3·0-12·7]; p=0·006). In children who weighed less than 30 kg, the optimal drug concentration associated with steroid-free and exclusive enteral nutrition-free clinical remission was 7 µg/mL at week 14 (area under the curve 0·69 [95% CI 0·41-0·98]), corresponding to a dose of 200 mg/m2 body surface area or 10 mg/kg. 32 (23%) of 142 children reported at least one adverse event, the most common were headache (five [4%]), myalgia (four [3%]), and fever (three [2%]). None of the adverse events were classified as severe, and only two (1%) patients discontinued treatment due to adverse events. INTERPRETATION: Vedolizumab showed good safety and effectiveness at inducing remission in children with IBD at 14 weeks, especially those with ulcerative colitis. Vedolizumab should be considered in children when other approved drug interventions for IBD are unsuccessful. In children who weigh less than 30 kg, vedolizumab should be dosed by the child's body surface area (200 mg/m2) or weight (10 mg/kg). FUNDING: The European Crohn's and Colitis Organization, the European Society for Paediatric Gastroenterology Hepatology and Nutrition, and Takeda.

Clinical Features and Natural History of Paediatric Patients with Ulcerative Proctitis: A Multicentre Study from the Paediatric IBD Porto Group of ESPGHAN.

BACKGROUND AND AIMS: Ulcerative proctitis [UP] is an uncommon presentation in paediatric patients with ulcerative colitis. We aimed to characterize the clinical features and natural history of UP in children, and to identify predictors of poor outcomes. METHODS: This was a retrospective study involving 37 sites affiliated with the IBD Porto Group of ESPGHAN. Data were collected from patients aged <18 years diagnosed with UP between January 1, 2016 and December 31, 2020. RESULTS: We identified 196 patients with UP (median age at diagnosis 14.6 years [interquartile range, IQR 12.5-16.0]), with a median follow-up of 2.7 years [IQR 1.7-3.8]. The most common presenting symptoms were bloody stools [95%], abdominal pain [61%] and diarrhoea [47%]. At diagnosis, the median paediatric ulcerative colitis activity index [PUCAI] score was 25 [IQR 20-35], but most patients exhibited moderate-severe endoscopic inflammation. By the end of induction, 5-aminosalicylic acid administration orally, topically or both resulted in clinical remission rates of 48%, 48%, and 73%, respectively. The rates of treatment escalation to biologics at 1, 3, and 5 years were 10%, 22%, and 43%, respectively. In multivariate analysis, the PUCAI score at diagnosis was significantly associated with initiation of systemic steroids, or biologics, and subsequent acute severe colitis events and inflammatory bowel disease-associated admission, with a score ≥35 providing an increased risk for poor outcomes. By the end of follow-up, 3.1% of patients underwent colectomy. Patients with UP that experienced proximal disease progression during follow-up [48%] had significantly higher rates of a caecal patch at diagnosis and higher PUCAI score by the end of induction, compared to those without progression. CONCLUSION: Paediatric patients with UP exhibit high rates of treatment escalation and proximal disease extension.

Long-term Outcomes of Paediatric Patients Admitted With Acute Severe Colitis- A Multicentre Study From the Paediatric IBD Porto Group of ESPGHAN.

BACKGROUND AND AIM: Acute severe colitis [ASC] is associated with significant morbidity in paediatric patients with ulcerative colitis [UC]. Most outcome studies in ASC since tumour necrosis factor alpha [TNFα] antagonists became available have focused on the first year after admission. The aim of this study was to characterise the longer-term outcomes of paediatric patients admitted with ASC. METHODS: This retrospective study was conducted in 25 centres across Europe and North America. Data on patients with UC aged <18 years, admitted with ASC (defined as paediatric ulcerative colitis activity index [PUCAI] score ≥65) between 2009 and 2011, were collected at discharge and 1, 3 and 5 years after admission. The primary outcome was colectomy-free rates at each time point. RESULTS: Of the 141 patients admitted with ASC, 137 [97.1%] were treated with intravenous corticosteroids. Thirty-one [22.6%] patients were escalated to second-line therapy, mainly to infliximab. Sixteen patients [11.3%] underwent colectomy before discharge. Long-term follow-up showed colectomy-free rates were 71.3%, 66.4% and 63.6% at 1, 3 and 5 years after initial ASC admission, respectively, and were similar across different age groups. Sub-analysis of colectomy rates in patients with new-onset disease [42.5% of the cohort] yielded similar results. In a multivariate analysis, use of oral steroids in the 3 months before admission, erythrocyte sedimentation rate >70 mm/h, and albumin <2.5 g/dL, were significantly associated with 5-year colectomy risk. CONCLUSIONS: High colectomy rates were demonstrated in paediatric UC patients admitted with ASC. Additional studies are required to determine whether intensification of anti-TNFα treatment, close therapeutic drug monitoring, and use of new drugs alter this outcome.

Incidence Trends and Geographical Variability of Pediatric Inflammatory Bowel Disease in Slovenia: A Nationwide Study.

BACKGROUND: The aims of the study were to determine the incidence rate of pediatric inflammatory bowel disease (PIBD) and its trends for the period of 2002-2010 and to assess the geographical distribution of PIBD in Slovenia. MATERIALS AND METHODS: Medical records of patients (0-18 years) with newly diagnosed IBD during the study period were retrospectively reviewed. RESULTS: The mean incidence rate for IBD in 2002-2010 was 7.6 per 100,000 children and adolescents per year, 4.5 for Crohn's disease (CD), 2.9 for ulcerative colitis (UC), and 0.2 for IBD-unclassified, respectively. The incidence rate increased from 5.8 per 100,000 per year in 2002-2004 to 8.6 in 2005-2007 and remained stable afterwards. Statistically significant difference in the incidence rate between the Northeastern and Southwestern parts of the country was observed (p = 0.025). CONCLUSION: This nationwide study demonstrates that Slovenia is among the European countries with the highest PIBD incidence. During the study period a substantial rise of PIBD incidence was observed during the first half of the study and it seems to have stabilized in the second half. The significant difference in PIBD incidence between Northeastern and Southwestern parts of the country merits further exploration of the possible environmental factors.

The prevalence of celiac disease among family members of celiac disease patients.

INTRODUCTION: Celiac disease (CD) is more common in certain risk groups. Family members of known celiac patients represent the most important group. Serological screening enables us to detect patients before they develop serious complications. HLA typing has also proven to be a valuable diagnostic tool, especially in excluding the disease. METHODS: To assess the prevalence of CD among family members, we screened 106 first-degree relatives (73 parents, 33 siblings; mean age 27.9 years) of 45 celiac patients in NE Slovenia. We analysed antigliadin (AGA) and antiendomysium (EMA) antibodies. Levels of IgG and IgAAGA were determined using the ELISA method, and EMA using indirect immunofluorescence. Serologically positive patients were recalled for intestinal biopsy and were HLA typed. Intestinal biopsy was performed by peroral aspiration capsule or during upper GI endoscopy. Biopsy specimens were examined histologically. RESULTS: Six family members (5.67%) were both AGA IgG and EMA positive, and one (0.94%) was only EMA positive. All were either HLA DQ2 or DQ8 positive. Nine family members (8.49%) were only AGA IgG positive, two of them lacked the HLA DQ susceptibility alleles. Intestinal biopsy was performed in six family members, and the diagnosis of CD confirmed in five. All were both AGA IgG and EMA positive. They were either symptom-free or had only mild gastrointestinal symptoms, and carried the known HLA DQ risk alleles. The minimum prevalence of CD among family members in NE Slovenia can therefore be estimated at 4.72%. DISCUSSION: The prevalence of CD among first-degree relatives is much higher than the prevalence of the disease in the general population. Most of these patients have an atypical form of the disease and would therefore be overlooked without an active search. Serological testing is recommended for all first-degree relatives of CD patients; they should also undergo HLA typing to detect those whose HLA phenotype is consistent with CD. This approach can also help in excluding individuals who do not need further diagnostic procedures for CD.