Ulcerative Colitis Activity Index Score Research Articles

A268 1 YEAR FOLLOW-UP OF PEDIATRIC ULCERATIVE COLITIS USING INTESTINAL ULTRASOUND

Abstract Background Intestinal ultrasound (IUS) is an emerging tool that offers a non-invasive method for monitoring inflammatory bowel disease in pediatric patients, with increasing popularity worldwide. Assessment of IUS for monitoring pediatric Ulcerative Colitis (UC) has been previously limited to small samples of patients with no long-term follow up. Aims This project aims to utilize intestinal ultrasound assessments obtained at routine time points to determine changes in IUS parameters within 12 months of study enrollment in newly diagnosed children with UC, and their relationship to biochemical markers, clinical assessments, and endoscopic findings. Methods Pediatric patients with suspected ulcerative colitis were prospectively enrolled through the Edmonton Pediatric IBD Clinic. Participants underwent IUS, clinical assessments, bloodwork for biomarkers, and fecal calprotectin (FCP) testing at baseline, 1-, 3-, 6-, and 12-month visits, as well as endoscopy at baseline and 6-12 months. In each IUS assessment, the bowel wall thickness (BWT), presence of hyperemia, abnormal haustrations, and fat wrapping was determined in 4 bowel segments (right, transverse, descending, and sigmoid colon). The Pediatric Ulcerative Colitis Activity Index (PUCAI) scores and Ulcerative Colitis Intestinal Ultrasound Scores (UC-IUS) were calculated at each visit. Results 42 patients (55% male) were included. Median UC-IUS total scores and BWT alone improved in all bowel segments over the study period. For the most affected bowel segment for all patients, median percent reduction of BWT was 39.6%, 34.2%, 33.7%, and 42.5%, at the 1-, 3-, 6-, and 12-month assessment respectively. The biggest decrease in UC-IUS scores and BWT occurred with the initiation of therapy between baseline and 1-month. UC-IUS scores significantly correlated with endoscopy at 12-months, clinical assessments at all time points, and biochemical markers of disease at all time points over the 12-month study period (pampersand:003C0.05). BWT measurement alone also had significant correlation with endoscopy at 12 months; clinical assessment at 1-, 3-, and 6-months; and with biochemical markers at every time point (pampersand:003C0.05). Patients with inflammatory bowel markers (indicated by elevated FCP (ampersand:003E250)) at 12-months were found to have significantly thicker BWT and UC-IUS scores at 3- and 6-months. Conclusions BWT and UC-IUS performed well in pediatric patients with newly-diagnosed UC, with UC-IUS scores and BWT measurements alone correlating significantly with endoscopic, clinical, and biochemical disease activity over the 12-month study period. BWT alone performed similarly to total UC-IUS scores. This data suggests that IUS can offer a non-invasive method to monitor long-term pediatric UC disease severity. Funding Agencies TRIANGLE, WCHRI, Stollery Children's Hospital Foundation.

BREASTFEEDING STATUS AND DISEASE SEVERITY IN PEDIATRIC PATIENTS WITH ULCERATIVE COLITIS: AN EXPLORATORY RETROSPECTIVE COHORT STUDY

Abstract OBJECTIVE While the protective effect of being breastfed on the development of ulcerative colitis has been well established, it is not known if being breastfed decreases colectomy rate and disease severity for pediatric patients. This work is designed to better understand the connection between breastfeeding status and disease severity of ulcerative colitis among pediatric patients. METHODS This exploratory retrospective cohort study analyzed the clinical and laboratory data of patients at Boston Children’s Hospital enrolled in a data registry and biorepository since 2012. Data was collected from charts and analyzed to determine if there is a significant difference in colectomy rate, pediatric ulcerative colitis activity index (PUCAI) score, ESR, or CRP, between not breastfed (n=56), breastfed (n=39), and mixed breastfed patients (n=31). Breastfed patients are defined as patients who were exclusively breastfed for greater than or equal to three months. Patients who were never breastfed were considered not breastfed. Patients who were exclusively breastfed for less than three months or received a mix of formula and breastfeeding were considered mixed breastfed. Statistical analysis of the groups was performed using a one-way ANOVA. RESULTS At disease diagnosis, the average PUCAI score of the not breastfed group (32.4) was significantly higher than the exclusively breastfed group (18.4) (p value = 0.0189). No significant difference was detected in the average PUCAI score of the mixed breastfed group (34.1) compared to the not breastfed group (32.4). Significant differences in the colectomy rate between all three groups were not detected, and likewise we did not find significant differences in markers of disease severity including ESR, CRP, and hemoglobin at diagnostic visit between groups. CONCLUSION These results suggest that children with ulcerative colitis who were exclusively breastfed have a lower average PUCAI score at the time of diagnosis than those who were not breastfed. Further investigation with larger data sets may be necessary to determine other benefits of exclusive breastfeeding in pediatric ulcerative colitis patients.

P972 Short and long-term outcomes after acute severe ulcerative colitis in children: A Canadian single centre experience

Abstract Background The short and long-term course of ulcerative colitis (UC) following an episode of acute severe UC (ASUC) in children is insufficiently characterized. We aimed to assess contemporary outcomes in children hospitalized with ASUC. Methods This was a retrospective cohort study of children aged 2-17 years hospitalized with ASUC between 2010 and 2022 at a tertiary center in London, Ontario, Canada. All data were recorded using standardised Case Report Forms, de-identified, and entered into a central database registry using Research Electronic Data Capture (REDCap) Steroid non-response was defined as requirement of medical rescue therapy or colectomy. Results A total of 58 children hospitalized with ASUC were included (male: 55.2% [n =32], mean age at admission: 12.2 ± 3.5 years). The majority had extensive colitis (82.4% [n = 42]) at the time of diagnosis. 74% (n = 43) presented within one year of symptom onset and 31% (n = 18) had ASUC as their index presentation with UC. 15.5% (n = 9) of patients had prior purine analogues and 20.7% (n = 12) had received biologics prior to ASUC presentation. Median Pediatric Ulcerative Colitis Activity Index (PUCAI) score on admission was 65.0 (IQR: 60.0 – 75.0). After intravenous corticosteroid therapy 68.9% (n = 40) responded to steroids. Of the patients with steroid non-response (31% [n = 18]), 3.4% (2/58) underwent colectomy and 27.6% (16/58) patients received infliximab rescue therapy. Median PUCAI score was significantly lower on day 3 between steroid responders and steroid non-responders (37.5 vs 60, p <0.01). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 7.4% (4/54) and 8% (4/50) respectively. Short term and long-term hospitalization rates for UC exacerbation following discharge was 25.9% (14/54) and 16% (8/50) respectively. Similar rates of long-term colectomy and hospitalizations were observed between steroid responders and non-responders. On univariate analysis, no statistically significant factors associated with steroid non-response were identified. Conclusion 17% of patients hospitalized for ASUC required colectomy within 12 months of presentation. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates are still high. Future research should focus on earlier identification and treatment of children at high risk of exacerbation to prevent complications.

P417 1 year follow-up of pediatric ulcerative colitis using intestinal ultrasound

Abstract Background Intestinal ultrasound (IUS) is an emerging tool that offers a non-invasive method for monitoring inflammatory bowel disease in pediatric patients, with increasing popularity worldwide. Assessment of IUS for monitoring pediatric Ulcerative Colitis (UC) has been limited to small samples of patients with no long-term follow up. Our aim is to utilize intestinal ultrasound assessments obtained at routine time points to determine changes in IUS parameters within 12 months of study enrollment in newly diagnosed children with UC, and their relationship to biochemical markers, clinical assessments, and endoscopic findings. Methods Pediatric patients with suspected ulcerative colitis were prospectively enrolled through the Edmonton Pediatric IBD Clinic. Participants underwent IUS, clinical assessments, bloodwork for biomarkers, and fecal calprotectin (FCP) testing at baseline, 1-, 3-, 6-, and 12-month visits, as well as endoscopy at baseline and 6-12 months. In each IUS assessment, the bowel wall thickness (BWT), presence of hyperemia, abnormal haustrations, and fat wrapping was determined in 4 bowel segments (right, transverse, descending, and sigmoid colon). The Pediatric Ulcerative Colitis Activity Index (PUCAI) scores and Ulcerative Colitis Intestinal Ultrasound Scores (UC-IUS) were calculated at each visit. Results 42 patients (55% male) were included. Median UC-IUS total scores and BWT alone improved in all bowel segments over the study period. For the most affected bowel segment for all patients, median percent reduction of BWT was 39.6%, 34.2%, 33.7%, and 42.5%, at the 1-, 3-, 6-, and 12-month assessment respectively. The biggest decrease in UC-IUS scores and BWT occurred with the initiation of therapy between baseline and 1-month. UC-IUS scores significantly correlated with endoscopy at 12-months, clinical assessments at all time points, and biochemical markers of disease at all time points over the 12-month study period (p<0.05). BWT measurement alone also had significant correlation with endoscopy at 12 months; clinical assessment at 1-, 3-, and 6-months; and with biochemical markers at every time point (p<0.05). Patients with inflammatory bowel markers (indicated by elevated FCP (>250)) at 12-months were found to have significantly thicker BWT and UC-IUS scores at 3- and 6-months. Conclusion BWT and UC-IUS performed well in pediatric patients with newly-diagnosed UC, with UC-IUS scores and BWT measurements alone correlating significantly with endoscopic, clinical, and biochemical disease activity over the 12-month study period. BWT alone performed similarly to total UC-IUS scores. This data suggests that IUS can offer a non-invasive method to monitor long-term pediatric UC disease severity.

The Role of Tofacitinib in the Treatment of Acute Severe Colitis in Children.

Acute severe colitis (ASC) occurs in up to 15 percent of children with ulcerative colitis, with a high index of morbidity and mortality. Treatment includes high-dose steroids, infliximab, and salvage therapies. Unfortunately, up to 20 percent of patients may need an urgent colectomy due to treatment failure. We report our experience using tofacitinib for the treatment of six patients. A retrospective review of our medical electronic records was conducted. We included every patient with ASC and treatment failure, in whom tofacitinib was used as a salvage therapy. Response, complications, and disease course were noted. Six patients were included with Pediatric Ulcerative Colitis Activity Index (PUCAI) scores ranging from 65 to 85 on admission, and 35 to 85 before tofacitinib was started (P 0.07). Median response time was 72 h. A median decrease of 40 points in PUCAI was noted (P 0.00001). Mean length of stay was 18 days with discharge 9 days after tofacitinib introduction. Haemoglobin, albumin, fecal calprotectin, and CRP improved after tofacitinib (P 0.02, P 0.02, P 0.025, and P 0.01, respectively). The mean follow-up was 8.5 months, four patients achieved complete remission and only one had a recrudescence of symptoms (P 0.01). One patient had a systemic Epstein-Barr virus infection prior to tofacitinib therapy, which resolved with rituximab treatment. No other complications were noted. Tofacitinib response is rapid and impressive in children suffering from ASC, and the safety profile appears comparable to or better than other available treatments. In the future, tofacitinib should be integrated into pediatric protocols.

Outcomes of Tofacitinib Use in an Irish Pediatric Cohort.

Pediatric ulcerative colitis (UC) is typically more extensive and severe at diagnosis compared with adult disease. Tofacitinib, a Janus kinase inhibitor, has been used since 2018 to induce and maintain remission in UC. There are limited pediatric data regarding its use, either as a monotherapy or in combination with other treatments. To determine the real-world experience and outcomes of tofacitinib therapy in the Irish national cohort with pediatric UC. A retrospective study of tofacitinib outcomes was undertaken at Ireland's single national center for pediatric inflammatory bowel disease. All patients commenced on tofacitinib since its availability in 2019 were included. Baseline and follow-up clinical characteristics, phenotype, Pediatric Ulcerative Colitis Activity Index (PUCAI) scores, and treatments before and after tofacitinib commenced were recorded. The primary outcome was remission by 8 weeks, with other clinical outcomes being recorded to maximal available follow-up. Between November 1, 2019 and June 30, 2022, 15 children (M:F 1:2) were prescribed tofacitinib, 5 as monotherapy. Thirteen had baseline pancolitis at diagnosis and all patients had prior infliximab exposure. The mean time from diagnosis to starting tofacitinib was 381 days (±SD 265). Dual therapy included 5 with infliximab, 4 with vedolizumab, and 1 with adalimumab. The average length of treatment on tofacitinib was 232 days (±SD 170) with 2 patients transitioning to adult services while in remission on tofacitinib therapy. The mean PUCAI score was 48.7 (±SD 14.1) pre-tofacitinib, 16.7 (±SD 15.6) at week 8, and 22.5 (±SD 29.6) by week 16, with a significant reduction in PUCAI by week 16 (P = 0.0004). Eight patients (3 monotherapy) achieved clinical remission, with 4 of the 5 dual therapy patients on infliximab. There were no significant outcome differences between those on mono- or dual therapy. Three patients with combined vedolizumab therapy did not achieve remission, 2 of whom required colectomy by week 24. There were no malignancies, 1 patient developed shingles and another developed herpangina post-tofacitinib. Failure to achieve clinical remission by week 16 was seen in all children who progressed to colectomy (n = 4). Combining tofacitinib with other biologics is effective in select children with refractory UC. Early responders were more likely to achieve a sustained response at week 16. Failure to achieve remission by week 16 of tofacitinib therapy was strongly associated with progression to colectomy.

Utility of Intestinal Ultrasound in Clinical Decision-Making for Inflammatory Bowel Disease.

There is a clinical need to improve the monitoring of inflammatory bowel disease (IBD) activity. Despite being used regularly in European countries, intestinal ultrasound (IUS) has been implemented less in the United States for unclear reasons. The aim of this study is to illustrate how IUS can be used as a clinical decision-making tool in an American IBD cohort. This retrospective cohort analysis evaluated patients with IBD seen at our institution who underwent IUS as part of routine evaluation of their IBD from July 2020 to March 2022. To evaluate the clinical utility of IUS for different patient populations and against more frequently used measures of inflammation, we compared patient demographics, inflammatory markers, clinical scores, and medications between patients in remission and those with active inflammation. Treatment plans between the 2 groups were compared and we analyzed patients with follow-up IUS visits to validate treatment plan decisions at initial evaluation. Out of 148 total patients with IUS, we found that 62.1% (N = 92) of our patients had active disease and 37.9% (N = 56) were in remission. Ulcerative colitis activity index and Mayo scores were both significantly correlated with IUS findings. The treatment plan was significantly correlated with IUS findings (P = .004). At follow-up, we observed an overall decrease in intestinal thickening, improvements in vascular flow, and mural stratification. Clinical decisions incorporating IUS findings effectively reduced inflammation in our IBD patients. IUS should be strongly considered by IBD clinicians in the United States for monitoring disease activity in IBD.

Efficacy and Safety of Tacrolimus or Infliximab Therapy in Children and Young Adults With Acute Severe Colitis.

One-third of children and young adults admitted for management of acute severe colitis (ASC) fail intravenous corticosteroids. Infliximab (IFX) or tacrolimus (TAC) is often used to prevent urgent colectomy in these patients. However, no prior studies have reviewed the outcome of pediatric patients with ASC who were treated with either IFX or TAC. We retrospectively identified 170 pediatric patients with ASC admitted to our institution who did not respond to intravenous corticosteroids and were subsequently treated with either IFX or TAC. We compared 6-month colectomy rates, time to colectomy, improvement in disease activity indices, and adverse effects. The mean age of patients in the IFX (n = 84) and TAC (n = 86) groups were 14 and 13.8 years, respectively. The median study follow-up time was 23 months. The rate of colectomy 6 months from rescue therapy was similar whether patients received IFX or TAC (22.6% vs 26.7%, respectively, P = 0.53). The mean decline in Pediatric Ulcerative Colitis Activity Index scores from admission to discharge in those treated with IFX (31.9) or TAC (29.8) was similar (P = 0.63). Three patients treated with IFX experienced infusion reactions. Six patients treated with TAC experienced changes in renal function or electrolytes, and 4 patients reported neurologic symptoms. There were no significant differences in the likelihood of colectomy 6 months after initiating IFX or TAC rescue therapy. Efficacy of both agents was comparable. The types of adverse effects differed by therapy. These data support the use of either TAC or IFX in children with ASC refractory to intravenous corticosteroids.

Correlation Between the Nancy Histopathology Index and Markers of Disease Activity in Pediatric Ulcerative Colitis.

The Nancy Histological Index (NHI) was developed to assess histological disease activity in adult ulcerative colitis (UC) patients. However, data in pediatrics is limited. Our aim was to determine whether the NHI correlates with different indices of disease activity in pediatric UC patients. We retrospectively reviewed the NHI in rectal biopsies from 61 pediatric UC patients (median age 14.3 years), of whom 34 (55.7%) were newly diagnosed. The median Pediatric Ulcerative Colitis Activity Index (PUCAI) score among participants was 30 (interquartile range 5-55). Most patients exhibited an NHI of 3 (41/61, 67.2%) or 4 (8/61, 13.1%), reflecting moderate-severe histologic inflammation. A moderate positive correlation was identified between the NHI and PUCAI, fecal calprotectin, and Mayo endoscopic scores ( r = 0.60, 0.54, and 0.56 respectively, P ≤ 0.001), but not with CRP or albumin. These results indicate that the NHI has a modest correlation with clinical, laboratory and endoscopic indices of disease activity in pediatric UC patients.

P150 Identification of features associated with poor outcomes in pediatric patients with ulcerative proctitis: A Multicentre Study From the Paediatric IBD Porto Group of ESPGHAN

Abstract Background Ulcerative proctitis (UP) is an uncommon presentation in paediatric patients with ulcerative colitis, accounting for <10% of cases. Here we aimed to characterize the clinical features and natural history of paediatric patients with UP, and to identify predictors of poor outcomes. Methods A retrospective cohort study involving 37 sites affiliated with the IBD Interest group of ESPGHAN. Data were collected at different timepoints from patients diagnosed with UP aged <18 years between 01/01/2016-31/12/2020. Outcomes included time to initiation of systemic steroids, thiopurines or biologics, time to acute severe colitis (ASC), IBD-related admission and colectomy. Univariate cox regression was used to study the association between potential predictors and study outcomes. Results Two hundred and fifty patients with UP were included, with a median age at diagnosis of 14.5 (IQR 12.3-15.9) years, and a median follow-up of 2.7 (IQR 1.7-3.9) years. The most common presenting symptoms were bloody stools (94%), abdominal pain (59%) and diarrhea (53%). At diagnosis, the median pediatric ulcerative colitis activity index (PUCAI) score was 25 (IQR 20-35), and only 3 patients (1.3%) presented with ASC. Most children had normal inflammatory markers and albumin levels. the median fecal calprotectin level was 720 mcg/g (IQR 310-1800), while 16 patients (9.9%) had a calprotectin level <100mcg/g at diagnosis. Administration of oral or topical 5-ASA resulted in clinical remission rates of 52% and 48%, respectively, by the end of induction, while the combination of both led to remission in 73% of patients. The rates of treatment escalation to thiopurines and biologics at 1, 3 and 5 years were 11%, 27% and 45%, and 11%, 23% and 45%, respectively (Figure 1). Within 5 years from diagnosis, 20% of patients had presented with ASC. The PUCAI score at diagnosis of UP was highly associated with initiation of systemic steroids, thiopurines or biologics, as well as later ASC event and IBD admission, while a Mayo endoscopic score of 3 was associated with the initiation of biologics and subsequent ASC event and IBD admission (Table 1). Seven patients (4%) underwent colectomy by the end of follow-up. Among the 151/250 patients who had a repeat endoscopy, only 16% achieved mucosal healing and in 48% inflammation extended proximally. Cecal patch (P=0.009) and higher PUCAI score (P=0.009) at diagnosis, as well as higher PUCAI score (P=0.009) and lack of steroid-free clinical remission (P=0.005) by the end of induction were associated with proximal disease extension. Conclusion Disease burden is significant in paediatric patients that present with UP, with high rates of proximal disease extension and requirement for treatment escalation.

Gut metabolomic profiles in paediatric ulcerative colitis patients prior to and after receiving faecal microbiota transplants.

Ulcerative colitis (UC) is an immune-mediated inflammation of the colonic mucosa. Gut microbiota dysbiosis may play a significant role in disease pathogenesis by causing shifts in metabolomic profiles within the gut. To identify differences and trends in the metabolomic profile of paediatric UC patients pre- and post-faecal microbiota transplants (FMT). Forty-six paediatric patients with mild-to-moderate UC and 30 healthy paediatric patients were enrolled in this study. Baseline stool samples were collected prior to FMT initiation and at months 1, 3, 6, and 12 post-FMT. Pediatric Ulcerative Colitis Activity Index (PUCAI) scores were calculated at baseline and months 1, 3, 6, and 12 after FMT. The average Bray-Curtis dissimilarities to healthy subjects decreased after FMT. In principal coordinate analysis plots, UC patients' centroids drew nearer to healthy individuals. The variance explained by phenotype (Healthy versus UC) reduced and remained significant. From 1 to 3 months after FMT, PUCAI trends were statistically significant and decreasing. PUCAI scores remain flat starting 6 months after FMT. This study concludes that paediatric UC patients have a significantly different baseline metabolite profile than healthy controls. Although being time limited, FMT significantly altered these metabolite profiles and shifted them towards that of healthy controls.

Epidemiological Trends of Pediatric Inflammatory Bowel Disease in Korea: A Multicenter Study of the Last 3 Years Including the COVID-19 Era.

BackgroundStudies on how the coronavirus pandemic has affected pediatric inflammatory bowel disease (PIBD) are lacking. We aimed to investigate the trends in epidemiology, characteristics, initial management, and short-term outcomes of PIBD in South Korea over the recent three years including the era of coronavirus disease 2019 (COVID-19).MethodsThis multicenter study retrospectively investigated temporal trends in the epidemiology of PIBD in Korea. Annual occurrences, disease phenotypes, and initial management at diagnosis were analyzed from January 2018 to June 2021.ResultsA total of 486 patients from 17 institutions were included in this epidemiological evaluation. Analysis of the occurrence trend confirmed a significant increase in PIBD, regardless of the COVID-19 pandemic. In Crohn’s disease, patients with post-coronavirus outbreaks had significantly higher fecal calprotectin levels than those with previous onset (1,339.4 ± 717.04 vs. 1,595.5 ± 703.94, P = 0.001). Patients with post-coronavirus-onset ulcerative colitis had significantly higher Pediatric Ulcerative Colitis Activity Index scores than those with previous outbreaks (48 ± 17 vs. 36 ± 15, P = 0.004). In the initial treatment of Crohn’s disease, the use of 5-aminosalicylic acid (5-ASA) and steroids significantly decreased (P = 0.006 and 0.001, respectively), and enteral nutrition and the use of infliximab increased significantly (P = 0.045 and 0.009, respectively). There was a significant increase in azathioprine use during the initial treatment of ulcerative colitis (P = 0.020).ConclusionRegardless of the COVID-19 pandemic, the number of patients with PIBD is increasing significantly annually in Korea. The initial management trends for PIBD have also changed. More research is needed to establish appropriate treatment guidelines considering the epidemiological and clinical characteristics of Korean PIBD.

Liver Pathology in Children with Diagnosed Inflammatory Bowel Disease-A Single Center Experience.

Background: Inflammatory bowel disease (IBD) in children is frequently associated with liver pathology manifested as transient elevation of liver enzymes or specified liver diseases. The aim of the study was to evaluate the prevalence and the type of liver pathology in children with IBD within 2 years’ follow-up after the IBD diagnosis. Methods: We retrospectively reviewed records of children with IBD. Liver pathology was defined as elevated activity of liver enzymes (alanine transaminase (ALT) and/or gamma-glutamyl transpeptidase (GGT)) and bilirubin concentration in serum and/or as pathological changes of the organ on imaging tests (abdominal ultrasound and/or magnetic resonance cholangiopancreatography) or on liver histology performed when indicated. Results: Liver pathology was detected in 21 from 119 children (18%), including 7 (17%) with Crohn’s disease (CD) and 14 (18%) with ulcerative colitis (UC). Specified diagnosis for liver abnormality was found in 14 of 21 children (67%), including primary sclerosing cholangitis (PSC, 19%), non-alcoholic fatty liver disease (NAFLD, 19%), autoimmune sclerosing cholangitis (ASC, 5%), autoimmune hepatitis (AIH, 5%), cholelithiasis (5%), drug-induced liver disease (9%) and viral infection (herpes simplex virus, 5%). Most patients manifested mild IBD or were in clinical remission at the time of liver pathology diagnosis. 14% of patients with liver disease (including only cases with PSC) were diagnosed before IBD, 33% at the same time, and 52% in the later period. Patients with the specified diagnosis of liver pathology were younger, had higher ALT activity and more often demonstrated liver abnormalities on imaging tests. UC patients with idiopathic elevation of liver enzymes had higher pediatric ulcerative colitis activity index scores compared to children with specified liver disease. Conclusions: Liver pathology was observed in a significant percentage of children with IBD in our study. The majority of cases of hepatobiliary abnormalities were detected after diagnosis of IBD; therefore, children with IBD should undergo routine monitoring of liver enzymes.

Familial Mediterranean Fever Mutation Analysis in Pediatric Patients With İnflammatory Bowel Disease: A Multicenter Study.

The aim of the study was to evaluate familial Mediterranean fever (FMF) mutation analysis in pediatric patients with inflammatory bowel disease (IBD). The relation between MEFV mutations and chronic inflammatory diseases has been reported previously. Children with IBD (334 ulcerative colitis (UC), 224 Crohn's disease (CD), 39 indeterminate colitis (IC)) were tested for FMF mutations in this multicenter study. The distribution of mutations according to disease type, histopathological findings, and disease activity indexes was determined. A total of 597 children (mean age: 10.8 ± 4.6 years, M/F: 1.05) with IBD were included in the study. In this study, 41.9% of the patients had FMF mutations. E148Q was the most common mutation in UC and CD, and M694V in IC (30.5%, 34.5%, 47.1%, respectively). There was a significant difference in terms of endoscopic and histopathological findings according to mutation types (homozygous/ heterozygous) in patients with UC (P < .05). There was a statistically significant difference between colonoscopy findings in patients with or without mutations (P = .031, P = .045, respectively). The patients with UC who had mutations had lower Pediatric Ulcerative Colitis Activity Index (PUCAI) scores than the patients without mutations (P = .007). Although FMF mutations are unrelated to CD patients, but observed in UC patients with low PUCAI scores, it was established that mutations do not have a high impact on inflammatory response and clinical outcome of the disease.

Diagnosis and prognosis of epidemic inflammatory bowel disease under convolutional neural network algorithm and nonlinear equation model

this study was to analyze the effect of optimization algorithm based on convolutional neural network (CNN) on the image quality of magnetic resonance enterography (MRE) for small intestine, and explore the diagnosis and prognosis of epidemic inflammation bowel disease (IBD) with the MRE under the optimization algorithm and nonlinear equation model. The residual network structure (RNS) was incorporated into the CNN algorithm to establish an optimization algorithm, which was compared with other algorithms in terms of the peak signal to noise ratio (PSNR), structural similarity (SSIM), and high frequency error norm (HFEN). 392 patients suspected as IBD in the Gastroenterology Department were selected as the research objects. They were divided into a Crohn’s disease (CD) group (243 cases), an ulcerative colitis (UC) group (78 cases), an indeterminate enteritis (IDE) group (49 cases), and a non-IBD group (22 cases). The intestinal manifestations, clinical manifestations, MRE imaging manifestations, and gastrointestinal lesion distribution of patients in different groups were compared to analyze the diagnostic value of MRE for epidemic IBD. It was found that the optimized CNN algorithm showed better PSNR, SSIM, and HFEN than other algorithms. The percentages of patients with diarrhea in the CD group and UC group were 67.90% and 100%, respectively. The pediatric ulcerative colitis activity index (PUCAI) score of patients in the UC group showed that the number of patients with mild activity was at most 40 (51.28%). The Crohn’s disease activity index (CDAI) score showed that there were 197 of patients in the CD group (81.07%) with severe activity. In the CD group, the numbers of patients suffered with lesions in proximal colon, terminal ileum, and upper gastrointestinal tract were 125 (51.44%), 127 (52.26%), and 132 (54.32%), respectively. In the UC group, there were 32 (41.03%), 51 (65.38%), and 25 (32.05%) patients with lesions in the rectum, distal colon, and proximal colon, respectively. The diagnostic sensitivity and specificity of MRE for epidemic IBD was 95.18% and 46.7%, respectively. It indicated that the image quality of the optimization algorithm based on the CNN algorithm was improved greatly. Under the nonlinear equation model, the image characteristics of MRE in patients with different diseases were various, and the diseased parts were greatly different. MRE showed high sensitivity and specificity in the diagnosis of epidemic IBD. This study could provide a reference basis for the clinical diagnosis and prognosis of patients with epidemic IBD.

S0810 Dual Biologic Therapy for the Treatment of Severe/Refractory Inflammatory Bowel Disease: Intravenous Immunoglobulin in Combination With Standard Biologic Agents

INTRODUCTION: Despite improved therapeutic options, a subgroup of Inflammatory Bowel Disease (IBD) patients follow a severe/refractory disease trajectory. Intravenous immunoglobulin (IVIG) is a biologic agent, derived from pooled human plasma, used to treat severe inflammation (i.e. vasculitis, dermatomyositis, etc.) which has been explored as a potential therapy for refractory IBD. However, the use of dual biologic therapy, with IVIG and a second standard biologic agent for IBD treatment has not been described. We report our institutional experience with dual biologic therapy; IVIG treatment with standard biologic therapy in refractory IBD. METHODS: We analyzed a prospective registry of consented IBD patients followed at a tertiary-center to identify Crohn’s disease (CD) or Ulcerative Colitis (UC) patients that received IVIG therapy for refractory disease. Patients that received IVIG for other conditions were excluded. Clinic visits, endoscopic reports and medication exposure before and after IVIG were collected. Harvey-Bradshaw index (HBI) for CD and Ulcerative Colitis Activity Index (UCAI) for UC were utilized to assess the disease course. Quality of life was characterized using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). RESULTS: Among 25 IBD patients (median age 43 yrs, median disease duration 14 yrs, CD 20, females 21), 14 received a combination of IVIG with a 2nd biologic agent (Table 1). Among 19 patients who had active disease before IVIG initiation, 6 (31.6%) achieved remission, 5 of them in combination with second biologic agent. The median improvement in HBI score was 2 (0–3) and in UCAI was 6 (2–10), while the median SIBDQ improvement was 2.5 (1–13). In 6 patients, CRP levels normalized. Furthermore, among 17 patients who were on systemic steroids before IVIG, 3 transitioned to topical steroids, 3 reduced the dosage and 2 patients completely tapered off steroids. In addition, 15 patients reported that IVIG therapy was helpful while 9 patients demonstrated marked improvement endoscopically. Finally, regarding side effects, 7 patients reported headache, 2 nausea, 1 emesis, 1 abdominal pain while 1 patient required hospitalization because of hives and shortness of breath after IVIG infusion. CONCLUSION: Dual biologic therapy using IVIG in combination with standard biologic agents is safe and effective in IBD patients with refractory disease. Further investigation is warranted to define the optimal use of IVIG alone or in combination with biologic agents in refractory IBD.Table 1Figure 1.: The effect of IVIG therapy in averages HBI and UCAI scores when used as monotherapy or in combination with another biologic agent.

Predicting Outcomes in Pediatric Ulcerative Colitis for Management Optimization: Systematic Review and Consensus Statements From the Pediatric Inflammatory Bowel Disease–Ahead Program

A better understanding of prognostic factors in ulcerative colitis (UC) could improve patient management and reduce complications. We aimed to identify evidence-based predictors for outcomes in pediatric UC, which may be used to optimize treatment algorithms. Potential outcomes worthy of prediction in UC were determined by surveying 202 experts in pediatric UC. A systematic review of the literature, with selected meta-analysis, was performed to identify studies that investigated predictors for these outcomes. Multiple national and international meetings were held to reach consensus on evidence-based statements. Consensus was reached on 31 statements regarding predictors of colectomy, acute severe colitis (ASC), chronically active pediatric UC, cancer and mortality. At diagnosis, disease extent (6 studies, N= 627; P= .035), Pediatric Ulcerative Colitis Activity Index score (4 studies, n= 318; P < .001), hemoglobin, hematocrit, and albumin may predict colectomy. In addition, family history of UC (2 studies, n= 557; P= .0004), extraintestinal manifestations (4 studies, n= 526; P= .048), and disease extension over time may predict colectomy, whereas primary sclerosing cholangitis (PSC) may be protective. Acute severe colitis may be predicted by disease severity at onset and hypoalbuminemia. Higher Pediatric Ulcerative Colitis Activity Index score and C-reactive protein on days 3 and 5 of hospital admission predict failure of intravenous steroids. Risk factors for malignancy included concomitant diagnosis of primary sclerosing cholangitis, longstanding colitis(>10 years), male sex, and younger age at diagnosis. These evidence-based consensus statements offer predictions to be considered for a personalized medicine approach in treating pediatric UC.

Sleep Quality in Adolescents with Inflammatory Bowel Disease

Background: The incidence and prevalence of Inflammatory BowelDisease (IBD) in the U.S. is increasing. Because adequate sleep quality and duration play a role in the mental and physical wellbeingof children, this study aimed to determine the prevalence of sleep difficulties in our urban pediatric IBD cohort and evaluateassociations between sleep quality and disease severity. Methods: Patients completed the Pittsburgh Sleep Quality Index(PSQI) questionnaire during an office visit. Chart review provided demographic information, and Pediatric Crohn’s Disease ActivityIndex (PCDAI) and Pediatric Ulcerative Colitis Activity Index (PUCAI) scores were calculated from the day of the visit. Results: The prevalence of sleep problems was 33.54% (95%CI: 26.24% to 41.48%; p-value=0.02). PUCAI scores in children with sleep problems (PSQI mean 19.17 ± 20.43) were significantlyhigher than PUCAI scores in children without sleep problems. There was no association between total PSQI scores, classification of IBD,age, gender, ethnicity, steroid use, or disease duration. Conclusion: Our IBD cohort reported a 33% prevalence ofsleep disturbance symptoms. In the small group of patients withUlcerative Colitis (UC), there was a trend toward a greater degree ofsleep disturbances and a higher PUCAI score. Further investigationinto sleep disorders among children with IBD is warranted toprovide further insight into this issue. Additional evaluation of the differences between Crohn’s disease (CD) and ulcerative colitis asthey relate to sleep quality as well as studies implementing objectivesleep assessments, such as polysomnography or actigraphy, arewarranted as they may offer better understanding of the relationshipbetween pediatric IBD and sleep quality.

Pulmonary Manifestations in Adolescents With Inflammatory Bowel Disease.

Objectives. The available literature on pulmonary disease in pediatric inflammatory bowel disease is limited. We evaluated the prevalence of pulmonary manifestations in pediatric inflammatory bowel disease and their association with disease severity. Methods. Patients completed the St. George's Respiratory Questionnaire (SGRQ), a self-reported measure of quality of life in patients with pulmonary disease. Chart review provided demographic information and Pediatric Crohn's Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index scores. Regression models were utilized to evaluate associations between SGRQ score and clinical risk factors. Results. The prevalence of pulmonary manifestations was 9.62% (95% confidence interval = 5.48% to -15.36%). PCDAI scores in Crohn's disease patients with pulmonary symptoms were significantly higher (SGRQ mean = 10.71 ± 10.94) than in patients without such symptoms. SGRQ score was also higher in patients with indeterminate colitis (8.64, 95% confidence interval = 0.72-16.57, P = .03), when compared with Crohn's disease. Conclusions. Additional investigations including pulmonary function tests and imaging could provide further insight into this issue.

P416 Results of the first paediatric randomised controlled trial of faecal microbiota transplant for ulcerative colitis

Abstract Background The role of faecal microbiota transplant (FMT) for the treatment of ulcerative colitis (UC) has been reported across 4 randomised-controlled trials (RCT) in adults. Promising data have emerged from small, open-label paediatric case series and case reports but a proper blinded, placebo-controlled RCT has not been described in children. We report results from the first multicentre RCT of FMT in paediatric UC patients, conducted over 36 months in Ontario and Quebec, Canada. Methods We enrolled 25 children, ages 4–17 years old with active UC across two tertiary IBD clinics. Patients had active inflammation and remained on stable doses of medication at entry. Blinded participants received enemas containing healthy donor stool (active) or normal saline (placebo), 2×/week for 6 weeks. Faecal calprotectin (fCal), C-reactive protein (CRP), and paediatric ulcerative colitis activity index (PUCAI) scores were compared between groups during intervention, and at four follow-up time points over 30 weeks. Donor and recipient stools were measured for 16s rRNA and metagenomics analyses. Results In intention-to-treat (ITT) analysis, FMT (n = 13) at 6 weeks was more likely to improve clinical response (OR 9.3, 95% CI [0.7, 122.6]), CRP (OR 4.7, 95% CI [0.8, 28.4]), and fCal (OR 13.3, 95% CI [1.1, 166.4]) from baseline compared with placebo (n = 12). FMT at 30 weeks was also more likely than placebo to improve clinical response, CRP, and fCal (Table 1). In ITT analysis of the open-label arm (n = 7), FMT at 6 weeks and 30 weeks decreased CRP (−42.9%, −28.6%), fCal (−28.6%, −42.9%), and PUCAI score (−14.3%, −42.9%) from baseline. Conclusion Serial FMT enemas containing healthy donor microbiota led to greater improvements in serum and stool inflammatory markers, and rates of clinical response, in paediatric patients with active UC compared with placebo. These improvements largely persisted beyond 6 months after final FMT treatment. This study offers the strongest preliminary evidence, from a blinded, placebo-controlled multicentre RCT for the role of FMT in the management of paediatric UC.