Diagnosis Of Crohn's Disease Research Articles

P269 Spaciotemporal machine learning analysis of complete small bowel capsule endoscopy videos for prediction of outcomes in Crohn’s disease

Abstract Background Capsule endoscopy (CE) is a prime modality for diagnosis and monitoring of Crohn’s disease (CD). However utilization of CE for monitoring of CE is hampered by prolonged reading time and interobserver variability. Machine learning (ML) techniques such as convolutional neural networks (CNN) are capable of accurate detection and grading of inflammatory findings on isolated images from CE in CD patients, with accuracy above 95%. However, ML-based analysis of complete CE films have not yet been reported; moreover, the predictive utility of ML of CE in CD for disease outcomes has not been examined so far. Methods The study cohort included treatment-naïve CD patients that have performed CE (SBIII, Medtronic) within 6 months of diagnosis of CD and had a minimal follow-up of 6 months. Complete small bowel videos (first duodenal to first cecal image) were extracted using the RAPID reader software, V9.0. Prior to extraction, CE videos were scored using the Lewis score (LS). Clinical, endoscopic and laboratory data were extracted from the electronic medical records. All patients were classified as per start of biological therapy during follow-up. Machine learning analysis was performed by Intel Inc. using TimeSformer computer vision algorithm developed by Facebook. Timesformer algorithm utilizes spaciotemporal Results The patient cohort included 103 patients (54 (52%) female, median age- 25 years, interquartile ratio (IQR) 21–40). The median duration of follow-up was 941 (363–1644) days. The median LS was 450 (IQR-225–900). Biological therapy was initiated by 41(39.8%) of the patients (adalimumab -20 (48.7%), infliximab-14 (34,1%), vedolizumab- 7 (17%) patients, respectively). TimeSformer algorithm achieved training and testing accuracy of 91% and 79% respectively, with area under the curve (AUC) of 0.79 for prediction of the need for biologic therapy. In comparison, the AUC for LS was 0.69. The required time for analysis per complete video was 440ms on a single GPU. Conclusion Spaciotemporal analysis of complete small bowel CE videos of newly diagnosed CD patients achieved accurate prediction of the need for biological therapy. The accuracy was superior to that of human reader index. Following future validation, this approach will allow for fast and accurate personalization of treatment decisions in CD.

P643 Generalizability of Crohn’s disease randomized controlled trials compared to clinical practice

Abstract Background There are no curative medical therapies for Crohn’s disease (CD). However, multiple novel treatment options are currently being evaluated in randomized controlled trials (RCTs). Historically, CD populations enrolled in RCTs have not reflected the heterogeneity of patients observed in clinical practice due to strict inclusion/exclusion criteria and protocolized trial procedures do not reflect day-to-day care. These factors have raised concerns that results from pivotal RCTs required for drug approval are poorly generalizable. The aim of this study is to assess the generalizability of CD RCTs. We evaluated the proportion of CD patients initiating ustekinumab or vedolizumab in clinical care who would have been eligible for enrolment in the corresponding phase 3 registrational induction trial, and the factors impacting trial eligibility. Methods This is a retrospective cohort study using data from two ambulatory IBD clinics in Calgary, AB. Our study population included consecutive adult (>=18 years) patients with a confirmed diagnosis of CD, newly initiated on ustekinumab or vedolizumab between January 1, 2018 and January 1, 2020. We then applied the inclusion/exclusion criteria from the phase 3 GEMINI II/III and UNITI I/II induction trials to determine the proportion of patients who would have been trial-eligible. We then tabulated the indications for trial exclusion to determine the characteristics of patients who would not have been reflected in the trial population. Results A total of 50 patients were included. The results are outlined in Table 1. The median age was 42.5 years. Most patients had non-stricturing non-penetrating disease (44%, 22/50) and ileocolonic disease distribution (48%, 24/50). A total of 66% (33/50) would have been eligible for inclusion in GEMINI II/III and (30/50) 60% would be eligible for inclusion in UNITI I/II. The most common reasons for trial exclusion included extensive surgery (total colectomy/subtotal colectomy) with short bowel or ileostomy (n=12) and surgery within 6 months of enrolment (n=3), multiple previous resections (n=2). Four patients were excluded based on intra-abdominal abscess. A total of 13 patients (26%) were temporarily ineligible due to recent biologic switch and would have required an 8-week washout prior to trial enrolment. Only two patients were excluded based on age (>80 years). Conclusion Although most patients on ustekinumab or vedolizumab would have been eligible for the respective pivotal trials, patients who have complications of disease, extensive surgery, or altered anatomy are not reflected in current RCTs.

P692 Clinical, therapeutic and evolutionary profile of fistulizing ano-perineal lesions in Crohn’s disease

Abstract Background Ano-perineal lesions (APLs) during Crohn’s disease (CD) are frequent and varied. Ano-perineal fistulas (APF) are the most common and severe manifestations. They are associated with increased morbidity and considerable impairment of quality of life. Their management is not always easy despite therapeutic advances, particularly anti-TNFα.The aim of our work was to describe the epidemiological profile, the therapeutic modalities and the evolutionary aspects of APF during CD. Methods This was a retrospective, descriptive, single-center study collecting records of patients followed for CD with APF between January 2010 and December 2020. The patients had a proctological examination and a perineal MRI. We recorded clinical, endoscopic, radiological data, therapeutic management and clinical response to the initial therapeutic regimen. Complete remission was defined as closure of all initially productive fistulas, partial response was defined as closure of more than 50% of fistulas. Therapeutic failure was defined as closure of less than 50% of the initially productive fistulas. Results 83 patients followed up for CD with APLs were collated of which 38 had APF (45.7%). The mean age was 42 years [26 - 73] with a sex ratio of 0.4. Active smoking was noted in six patients (15.8%). In 55.3% of cases, PAF was present at the time of diagnosis of CD (n=21).17 patients had developed one or more PAFs during the course of their disease with a mean delay of seven years [1 - 29]. APFs were associated with luminal involvement in 94.7% of cases, with ileal location in 10 patients (26.3%), colonic location in 13 patients (34.2%) and ileocolic location in 13 patients. The APFs were perianal in 34cases, vulvovaginal in five cases and gluteal in one case. There were complex fistulas in 92.1% of cases. The number of external orifices at the time of diagnosis was respectively: 1 orifice in 63.2% of cases, 2orifices in 26.3% of cases and more than two orifices in 10.5% of cases. A perineal abscess was associated in 44.7% of cases and anorectal stricture was observed in 7.9% of patients. Seton drainage was performed in 86.6% of patients. All patients with complex APF had received anti-TNFα after disappearance of collections if initially present (infliximab (92.1%), adalimumab (7.9%)) combined with thiopurines in 97.4% of cases. After a mean follow-up of 40 months, a complete remission was observed in 14 patients (36.8%), a partial response was noted in 13 patients (34.2%). 11 patients (28.9%) were in therapeutic failure. Conclusion In our study, APFs during CD account for almost half of all APLs.Thus, the development of local therapeutic means proves to be of necessity in order to increase the efficacy of biotherapies and to accelerate the healing of APFs.

P272 Psychological burden in newly diagnosed IBD patients: Differences between Crohn’s Disease and Ulcerative Colitis in early IBD

Abstract Background Psychological factors such as stress, anxiety and depression are frequently related to IBD. However, there are few studies of these factors in patients with a new diagnosis of IBD. The aim of the present study is to test the psychological burden in patients with a recent diagnosis of IBD and to check if there are differences between Crohn’s disease (CD) and Ulcerative Colitis (UC). Methods Prospective, multi-center, observational study in patients with a new diagnosis of IBD (<6 months). The patients were recruited from 4 different Spanish hospitals. Patients were evaluated using the Holmes and Rae social readjustment rating (SRRS), the hospital anxiety and depression scale (HAD), Scale of Stress Perceived by the Disease (EAE) and quality of life questionnaire for patients with inflammatory bowel disease (IBDQ). Results We included 156 patients, 69 (44.2%) women and 87 men (55.8%); 80 (51.3%) CD and 76 (48.7%) UC, mean age 42.3 (SD 16.21) years. The sample was homogeneous between groups in relation to socio-demographic variables. In the total sample a 60.9% of the patient associated the onset of the disease with a stressful life event. Patients with CD showed a greater psychological impact on measures of anxiety, CD 48.8% - UC 25%, OR 2.8, (95% CI 1.4–5.6), depression CD 25% - UC 9.2%, OR 3.2 (95%CI 1.2–8.3) and stressful life events CD 86.3% - UC 67.1%, OR 3 (95%CI 1.3–6.8). In terms of general quality of life, 82.9% of UC patients showed high scores compared to 57.5% of CD patients, OR 0.27 (95%CI 0.13–0.58). In the IBDQ domains, CD patients had lower scores than UC patients, except in the digestive domain, where scores were similar. In the scale of perceived stress due to the disease, both groups showed elevated values (CD 86.3% - UC 80.3%). Conclusion Patients with a recent diagnosis of CD are more emotionally affected and have a poorer quality of life at the beginning of the diagnosis when compared to patients with UC. Both have high scores in perceived stress due to the disease. They perceive the disease at diagnosis as a highly stressful life event, so this should be considered to promote interventions (perhaps disease-specific) aimed at alleviating that stress and preventing it from interfering with the course of the disease.

CROHN'S DISEASE AND ACUTE PANCREATITIS; ASSOCIATION, OUTCOMES, AND PREDICTORS OF 90-DAY READMISSION WITH ACUTE PANCREATITIS. INSIGHTS FROM THE NATIONWIDE READMISSION DATABASE

It’s a controversy if pancreatitis can be considered one of the extraintestinal manifestations of Crohn’s disease (CD). (Barthet et al AJG) CD patients have a fourfold increase in the risk of acute pancreatitis (AP) compared to the general population. (Rasmussen et al Scan J Gastroenterol) The annual incidence of AP in the general population ranges from 13 to 45/100,000 persons. (Dhiraj et al Gastroenterology) We collected data from the publicly available Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Databases (NRD) 2017-2018. We identified individuals discharged with a diagnosis of CD or one of its complications. The case selection process is summarized in Figure 1. We studied the burden of AP in patients with Crohn’s disease, hospitalization outcomes, and predictors of hospital readmissions with AP. Median and IQR were used to describe Continuous variables, and proportions were used with categorical variables. Comparison between groups was performed by Mann Whitney test for continuous variables and Chi-Square test for Categorical variables. We performed a binary logistic regression analysis for predictors of 90-day readmission with AP. Statistical analyses were performed using SPSS Version 25 (IBM Corporation, Armonk, NY, USA). We analyzed 147,501 index hospital discharges with Crohn’s disease or one of its complications, 0.9% had chronic pancreatitis, and 1.6% had a diagnosis of AP. Around 14% of AP was biliary, 13% was Alcohol-induced, 7% was drug-induced, while 66% was classified as idiopathic, other, or unspecified AP. Table 1 shows a Comparison between CD patients with AP and CD patients without AP. Having AP on index hospitalization wasn’t related to CD complication status as those without AP had a higher prevalence of complications (P values <0.001). After excluding those who died in index hospitalization, those with Chronic Pancreatitis, and those discharged in Oct-Dec, 0.3% of patients had 90-day readmission with AP. Characteristics of CD patients with 90-day readmission with AP are illustrated in Table 2. A binary logistic regression for predictors of 90-day readmission with AP is illustrated in Table 3. The chi-square test results indicate that our regression model is a significant improvement in fit relative to an intercept-only model (χ2 = 498.489, p<.001). AP is associated with higher morbidity and mortality in patients with CD. Age, number of comorbidities, and having AP in index hospitalization are significant predictors of 90-day readmission with AP. Further biochemical studies would be needed to investigate the association between AP and CD. The study was limited by the lack of a specific ICD-10 code for autoimmune pancreatitis and the inability to account for common CD drugs associated with Pancreatitis.Figure 2Table 1, 2 and 3View Large Image Figure ViewerDownload Hi-res image Download (PPT)

INCIDENTALLY DIAGNOSED ASYMPTOMATIC CROHN'S DISEASE: LONG-TERM CLINICAL OUTCOMES OF UNTREATED PATIENTS

Crohn's disease (CD) is occasionally diagnosed in asymptomatic patients undergoing colonoscopy for other reasons, but their clinical outcomes and optimal management remain poorly defined. A retrospective cohort study of asymptomatic patients with incidental diagnosis of CD. The primary outcome was defined as the occurrence of a clinical flare. Secondary outcomes included time to clinical flare, time to initiation of corticosteroids or immunomodulators/biologics, and rate of surgery. Of the 2558 patients in Sheba IBD registry, 53 asymptomatic patients with incidental diagnosis of CD were identified (median age 50 (41.75-57), 52% males, 32/53 with L1, 9/53 L2, 11/53 L3,1/53 L4, 41/53 B1, 10/53 B2, 2/53 B3, 1 with perianal disease). Most patients (48/53) did not receive any treatment after diagnosis. Of these untreated patients, 43/48 (89.5%) had not experienced a flare over a median follow-up of 4.5 years (IQR 2-8, range 1-15 years). None of the patients with over 8 years follow-up (n=14) experienced a flare. When comparing the group of patients with or without immediate post-diagnosis initiation of treatment (n=5, n=48, respectively), there was no difference in survival time without flare (p=0.3). Of the 48 patients without immediate treatment, immunomodulators/biologics were initiated in 4(8.3%) during follow-up. Surgery for CD occurred in 2 patients during the follow-up. None of the parameters examined, including age, CRP, ileal versus other locations, or having a complicated phenotype (B2/B3 versus B1) was found to predict a clinical flare later on. Many asymptomatic patients with an incidental diagnosis of Crohn's disease can probably be followed-up without immediate treatment. Although the majority remain asymptomatic and without complications during follow-up, close monitoring for disease progression is prudent.

Medication adherence in women with IBD of childbearing age likely associated with disease knowledge

Medication adherence in inflammatory bowel disease (IBD) is crucial, particularly during pregnancy. Unplanned pregnancies are common; therefore, efforts to maximise adherence should not be restricted to pregnant women. We aimed to assess medication adherence in women with IBD of childbearing age, regardless of their reproduction plans. We performed a multi-centre pilot questionnaire study of women with IBD age 18-45 years. Survey questions included patient demographics, disease history, and validated assessments of IBD and pregnancy knowledge, medication adherence and quality of life. The primary outcome was rates and predictors of medication adherence. In all, 72 women [58.3% Crohn's disease (CD) and 37.5% ulcerative colitis] completed the survey. The median patient age was 30 years [interquartile range (IQR): 24.8-36.0) and 37.5% had children. Medication adherence was high (84%; median Medication Adherence Report Scale: 19.0/20; IQR: 17.0-20.0). Knowledge scores were adequate for both the Crohn's and Colitis Knowledge (CCKnow; median: 15.5/30; IQR: 12.3-18.0) and Crohn's and Colitis Pregnancy Knowledge (CCPKnow; median: 8.0/17; IQR: 4.0-11.0). Disease knowledge was predictive of high medication adherence (CCPKnow: p = 0.02; CCKnow: p ⩽ 0.01). Higher adherence was significantly associated with a diagnosis of CD (p = 0.01), exposure to biological agents (p = 0.03) and immunomodulators (p = 0.04), childbearing after diagnosis with IBD (p = 0.03), and correctly understanding the importance of delivery modality (p = 0.02) and IBD activity in pregnancy (p = 0.01). Following dedicated education at the IBD clinic, medication adherence, disease-specific and pregnancy-specific knowledge in women with IBD of childbearing age tends to be high. Unplanned pregnancies are frequent; therefore, we should aim to maximise medication adherence in all women of childbearing age to optimise maternofoetal outcomes if unexpected pregnancies occur.

Initial Abdominal CT and Laboratory Findings Prior to Diagnosis of Crohn’s Disease in Children

PurposeTo identify initial abdominal computed tomography (CT) and laboratory findings prior to a diagnosis of Crohn’s disease (CD) in children.Materials and MethodsIn this retrospective study, patients (≤18 year-old) who were diagnosed with CD from 2004 to 2019 and had abdominal CT just prior to being diagnosed with CD were included in the CD group. Patients (≤18 years old) who were diagnosed with infectious enterocolitis from 2018 to 2019 and had undergone CT prior to being diagnosed with enterocolitis were included as a control group. We assessed the diagnostic performances of initial CT and laboratory findings for the diagnosis of CD using logistic regression and the area under the curve (AUC).ResultsIn total, 107 patients (50 CD patients, 57 control patients) were included, without an age difference between groups (median 13 years old vs. 11 years old, p=0.119). On univariate logistic regression analysis, multisegmental bowel involvement, mesenteric vessel engorgement, higher portal vein/aorta diameter ratio, longer liver longitudinal diameter, lower hemoglobin (≤12.5 g/dL), lower albumin (≤4 g/dL), and higher platelet (>320×103/µL) levels were significant factors for CD. On multivariate analysis, multisegmental bowel involvement [odds ratio (OR) 111.6, 95% confidence interval (CI) 4.778–2605.925] and lower albumin levels (OR 0.9, 95% CI 0.891–0.993) were significant factors. When these two features were combined, the AUC value was 0.985 with a sensitivity of 96% and specificity of 100% for differentiating CD.ConclusionMultisegmental bowel involvement on CT and decreased albumin levels can help differentiate CD from infectious enterocolitis in children prior to a definite diagnosis of CD.

Cross-scale Attention Guided Multi-instance Learning for Crohn's Disease Diagnosis with Pathological Images.

Multi-instance learning (MIL) is widely used in the computer-aided interpretation of pathological Whole Slide Images (WSIs) to solve the lack of pixel-wise or patch-wise annotations. Often, this approach directly applies "natural image driven" MIL algorithms which overlook the multi-scale (i.e. pyramidal) nature of WSIs. Off-the-shelf MIL algorithms are typically deployed on a single-scale of WSIs (e.g., 20× magnification), while human pathologists usually aggregate the global and local patterns in a multi-scale manner (e.g., by zooming in and out between different magnifications). In this study, we propose a novel cross-scale attention mechanism to explicitly aggregate inter-scale interactions into a single MIL network for Crohn's Disease (CD), which is a form of inflammatory bowel disease. The contribution of this paper is two-fold: (1) a cross-scale attention mechanism is proposed to aggregate features from different resolutions with multi-scale interaction; and (2) differential multi-scale attention visualizations are generated to localize explainable lesion patterns. By training ~250,000 H&E-stained Ascending Colon (AC) patches from 20 CD patient and 30 healthy control samples at different scales, our approach achieved a superior Area under the Curve (AUC) score of 0.8924 compared with baseline models. The official implementation is publicly available at https://github.com/hrlblab/CS-MIL.

Clinical Characteristics of Crohn's Disease in a Cohort from Saudi Arabia.

Objective:In Saudi Arabia, there are limited studies on the clinical characteristics of patients specifically with Crohn's disease (CD). This study was conducted to describe the clinical characteristics of CD at a tertiary care center in Jeddah, Saudi Arabia.Methods:This retrospective study included all patients aged >14 years who had a definitive diagnosis of CD and were managed at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, between 2012 and 2018. Data were collected for the following categories: clinical, laboratory, radiological, histological features at presentation, and disease-related complications.Results:The study included 245 newly diagnosed CD patients, aged 14–73 years (median: 26.3 years). All subjects presented with abdominal pain. Majority of the patients (59.7%) received a definitive diagnosis of CD >3 months after the onset of symptoms; 15.1% were initially suspected to have intestinal tuberculosis. Diarrhea and bleeding per rectum were reported in 60.8% and 49.7% of the patients, respectively. Sacroiliitis was the most frequent extraintestinal manifestations (11.4%). In terms of disease location, the terminal ileum (L1) was the most affected area (46.9%). Twenty-five patients had perianal disease, of which 40% had complex fistulae and 36% had perianal abscesses. The majority had hemoglobin levels >10 g/dl (74.1%), decreased serum iron (69.6%) and ferritin (50.5%) levels, and elevated erythrocyte sedimentation rate (68.2%) and C-reactive protein (82.2%).Conclusions:The majority of the patients in our cohort presented with the characteristic quartet of abdominal pain, weight loss, fever, and diarrhea. This study also found a significant number of patients with CD in Saudi Arabia experience diagnostic delay, which may contribute to disease morbidity and complications. These findings highlight the need for future studies to determine factors influencing this diagnostic delay.

Significance of granulomas in the outcomes of Crohn's disease patients.

BackgroundThe presence of granulomas in the gastrointestinal (GI) tract is one of the characteristic histologic features of Crohn’s disease (CD). The clinical significance of granulomas remains unclear. In this study, we aimed to determine whether the presence of granulomas on endoscopic pinch biopsy or surgical resection from the upper or lower GI tract is associated with worse outcomes among patients with CD.MethodsThis was a retrospective chart review of patients with CD evaluated at a tertiary care center between 1996 and 2019. Patients were divided into 2 groups based on the presence or absence of granulomas on GI histology. Clinical and laboratory data, and outcomes of interest, were obtained from the electronic medical records. Patients’ characteristics and outcomes were compared between the 2 groups.ResultsA total of 237 patients were included in our study; 41 (17.3%) had granulomas on their biopsy/resection specimen. The presence of granulomas in the GI tract was significantly associated with the development of intra-abdominal abscesses and/or fistulas (P=0.037), greater utilization of immunomodulators (P=0.029), and greater use of immunosuppressive medications (immunomodulator and/or biologic therapy) (P=0.015). No significant differences were found between the 2 groups in terms of number of hospitalizations, presence of perianal disease, intestinal resection, mean age, mean age at initial diagnosis of CD, duration of disease, sex, or smoking history.ConclusionsThe presence of granulomas in the GI tract of CD patients may serve as a prognostic biomarker of worse disease severity. Larger studies are needed to better validate this finding.

GBP4 is an immune-related biomarker for patients with ileocolonic Crohn’s disease by comprehensive analysis

Background: Extensive evidence has shown that immune cell infiltration is associated with the pathogenesis of Crohn’s disease (CD). Methods: Differentially expressed genes (DEGs) from the GSE179285 dataset in the intestinal mucosa of CD patients and healthy individuals were then identified. The infiltration pattern of 22 immune cell types was assessed using the CIBERSORT algorithm. The DEGs and 22 immune cell types were combined to find the key gene network using weighted gene co-expression network analysis (WGCNA). A linear regression model for the relationship between the expression of the hub genes in CD patients and infiltration of immune cells was also developed. The utility and accuracy of the hub genes for CD diagnosis were assessed using receiver operating characteristic (ROC) analysis. The accuracy of the model was validated using the GSE20881 dataset. Results: There were 1135 DEGs between the intestinal mucosal tissue of CD patients and healthy individuals. Of these DEGs, 711 genes were upregulated, whereas 424 of them were downregulated. There was also a significant difference in the infiltration of immune cells to the intestinal mucosal between the CD patients and healthy individuals. WGCNA revealed that the turquoise module genes were strongly correlated with the infiltration of M1 macrophages (cor =0.68, p = 10−16). Finally, the expression of GBP4, the identified hub gene, strongly correlated with the infiltration of M1 macrophages (adjusted r-squared =0.661, p &lt; 2×10−16), and is a relatively good marker for CD diagnostic prediction (AUC =0.736). The relationship between GBP4 expression and infiltration of M1 macrophages (adjusted r-squared =0.435, p &lt; 2×10−16) and diagnostic value of the gene (AUC =0.702) were verified using the GSE20881 validation dataset. Conclusion: The expression of GBP4 is associated with the infiltration of M1 macrophages to the intestinal mucosa of CD patients.

Intestinal strictures in Crohn's disease: a 2021 update.

Intestinal strictures remain one of the most intractable and common complications of Crohn’s disease (CD). Approximately 70% of CD patients will develop fibrotic strictures after 10 years of CD diagnosis. Since specific antifibrotic therapies are unavailable, endoscopic balloon dilation and surgery remain the mainstay treatments despite a high recurrence rate. Besides, there are no reliable methods for accurately evaluating intestinal fibrosis. This is largely due to the fact that the mechanisms of initiation and propagation of intestinal fibrosis are poorly understood. There is growing evidence implying that the pathogenesis of stricturing CD involves the intricate interplay of factors including aberrant immune and nonimmune responses, host-microbiome dysbiosis, and genetic susceptibility. Currently, the progress on intestinal strictures has been fueled by the advent of novel techniques, such as single-cell sequencing, multi-omics, and artificial intelligence. Here, we perform a timely and comprehensive review of the substantial advances in intestinal strictures in 2021, aiming to provide prompt information regarding fibrosis and set the stage for the improvement of diagnosis, treatment, and prognosis of intestinal strictures.

Associations of Inflammatory Bowel Disease and Subsequent Cancers in a Population-Based Study of Older Adults in the United States.

Cancer risk is elevated in patients with inflammatory bowel disease (IBD). A comprehensive investigation of cancer risk in older patients (≥66 years of age) is needed, because this understudied population is at high risk. We performed a case-control study using Surveillance Epidemiology and End Results-Medicare data including 1 986 735 incident cancer cases (aged 66-99 years; diagnosed 1992-2015) and 200 000 controls matched by sex, age, race and ethnicity, and selection year. IBD was identified by ulcerative colitis (UC) or Crohn's disease (CD) diagnosis codes. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with logistic regression, adjusting for potential confounders. For colorectal cancers, we further adjusted for screening rates. We assessed confounding by medication exposure among patients with prescription drug coverage. IBD, CD, and UC were present in 0.8%, 0.3%, and 0.5% in both cancer cases and non-cancer controls. Of 51 cancers examined, IBD was statistically significantly associated with cancers of the small intestine (OR = 2.55, 95% CI = 2.15 to 3.01), intrahepatic (OR = 1.92, 95% CI = 1.47 to 2.51) and extrahepatic bile ducts (OR = 1.75, 95% CI = 1.38 to 2.22), rectum (OR = 1.61, 95% CI = 1.36 to 1.90), and colon (OR = 1.21, 95% CI = 1.10 to 1.33). CD was associated with cancers of the small intestine (OR = 4.55, 95% CI = 3.65 to 5.67), and UC was associated with cancers of the intrahepatic bile ducts (OR = 1.87, 95% CI = 1.34 to 2.61), rectum (OR = 1.80, 95% CI = 1.47 to 2.20), and colon (OR = 1.28, 95% CI = 1.14 to 1.43). After adjusting for medication exposure, IBD was not statistically significantly associated with lung cancer, melanoma, diffuse large B-cell lymphoma, and myelodysplastic syndrome. In this large study among older adults (≥66 years of age), IBD was positively associated with gastrointestinal cancers. Associations with extraintestinal cancers may reflect the effect of immunosuppressive medications.

ПОРАЖЕНИЕ РЕСПИРАТОРНОГО ТРАКТА ПРИ БОЛЕЗНИ КРОНА У РЕБЕНКА 6 ЛЕТ

The article is devoted to rare extraintestinal manifestations of Crohn's disease (CD) in children, primarily to the respiratory tract. A review of the literature on this problem in children's practice is presented. On the example of clinical case, data on the classification, pathogenesis, clinical picture, diagnosis, differential diagnosis and treatment of CD with respiratory tract damage in a young child are summarized.

БОЛЕЗНЬ КРОНА У ДЕТЕЙ: СОВРЕМЕННОЕ СОСТОЯНИЕ ПРОБЛЕМЫ

Crohn's disease (CD) is chronic recurrent bowel disease of unknown etiology, characterized by segmental transmural granulomatous inflammation, mainly with the development of local and systemic complications. Despite the active development of conservative therapy methods, the number of drug-resistant forms of CD and complications of the disease requiring surgical treatment continues to increase. The article reflects modern scientific ideas about the methods of diagnosis, conservative and surgical treatment of CD in children.

MicroRNAs expression influence in ulcerative colitis and Crohn's disease: A pilot study for the identification of diagnostic biomarkers.

BACKGROUNDInflammatory bowel disease (IBD) comprises two distinct diseases, Crohn’s disease (CD) and ulcerative colitis (UC), both of which are chronic, relapsing inflammatory disorders of the gastrointestinal tract with a mostly unknown etiology. The incidence and prevalence of IBD are continually increasing, indicating the need for further studies to investigate the genetic determinants of these diseases. Since microRNAs (miRNAs) regulate protein translation via complementary binding to mRNA, discovering differentially expressed miRNAs (DE) in UC or CD patients could be important for diagnostic biomarker identification, assisting in the appropriate disease differentiation progressing the understanding of IBD pathogenesis.AIMTo determine the miRNA expression profile in UC and CD patients and the potential pathophysiological contributions of differentially expressed miRNA. METHODSA total of 20 formalin-fixed paraffin-embedded colonic samples were collected from the Pathology Department of Botucatu Medical School at São Paulo State University (Unesp). The diagnosis of UC or CD was based on clinical, endoscopic, radiologic, and histological criteria and confirmed by histopathological analysis at the time of selection. The TaqMan™ Array Human MicroRNA A+B Cards Set v3.0 (Applied Biosystems™) platform was used to analyze 754 miRNAs. Targets of DE-miRNAs were predicted using miRNA Data Integration Portal (mirDIP) and the miRNA Target Interaction database (MiRTarBase). All statistical analyses were conducted using GraphPad Prism software. Parametric and nonparametric data were analyzed using t-tests and Mann-Whitney U tests, respectively.RESULTSThe results showed that of the 754 miRNAs that were initially evaluated, 643 miRNAs were found to be expressed in at least five of the patients who were diagnosed with either CD or UC; the remaining 111 miRNAs were not considered to be expressed in these patients. The expression levels of 28 miRNAs were significantly different between the CD and UC patients (P ≤ 0.05); 13 miRNAs demonstrated a fold-change in expression level greater than 1. Five miRNAs with a downregulated expression were selected for enrichment analysis. The miRNAs whose expression levels were significantly lower in UC patients than in CD patients were enriched in certain signaling pathways that were mostly correlated with cancer-related processes and respective biomarkers. CONCLUSIONMiRNAs could be used to differentiate UC from CD, and differently expressed miRNAs could help explain the distinct pathophysiology of each disease.

P032 Clinical Usefulness of Double Balloon Enteroscopy in Patients With Established or Suspected Small Bowel Crohn's Disease.

The diagnosis of isolated small bowel Crohn's disease (CD) can be challenging. Symptoms are non-specific and both imaging and capsule endoscopy (CE) may be misleading as several diseases may mimic CD. Double balloon enteroscopy (DBE) allows a more extensive endoscopic and histologic evaluation of the small bowel. Our aim was to describe the diagnostic utility and impact of DBE on management of patients with known CD and in patients with suspected/rule-out CD. Retrospective review of our institution's DBE database from February 2009 to May 2013. Adult patients referred for DBE for further evaluation of known or suspected CD (due to symptoms, abnormal imaging and/or CE) were included. Patient demographics, clinical characteristics, imaging and CE results, prior DBE, indication for DBE, DBE findings, DBE adverse events, pathology findings, final diagnosis, treatment prior and post DBE and follow-up DBE were abstracted from the electronic medical record. A total of 108 patients were included, 61 (56%) females, mean age 52 years (range 20-83). Indications for DBE included: disease activity assessment/therapeutic in 10 patients with established diagnosis of CD and for diagnostic purposes in 98 patients with suspected CD (31 patients due to abnormal imaging, 29 due to abnormal CE and 26 due to both abnormal imaging and CE). Upper, lower, bidirectional upper and lower, and stomal DBE were performed in 21, 24, 62 and 1 patients, respectively. DBE revealed active disease in 8/10 patients with known CD with one patient undergoing dilation of a stricture. Changes in management were recommended for all patients with active disease - start thiopurine (2), optimize thiopurine dose (1), start biologics (3) change biologics (1), systemic steroids (1) and budesonide (1). The patient who underwent stricture dilation ultimately required surgery. A definitive diagnosis of CD (both endoscopic and histologic) was reached in only 39/98 (40%) patients who were referred for suspected CD. Changes in management were recommended in 32/39 (82%) patients. Interestingly, 24/98 patients had been diagnosed with CD at outside institutions and were recommended to initiate therapy for CD. Of these, CD was confirmed in only 15/24 (63%) patients. Adverse events included perforation in 1 patient (1%) who required surgical management and mouth swelling/abrasion in 3 patients (3%). Follow-up DBE to re-assess disease activity was performed in 10/49 (20%) patients with definitive diagnosis of CD, average time between procedures 4.5 years (range 0.7-11.6). One patient with CD was diagnosed with lymphoma 2.4 years after initial DBE. Changes in management were recommended in 6 patients: de-escalation of therapy (3, two underwent surgery), start thiopurine and/or biologic (2) and switch biologics (1). No complications were seen at follow-up DBE. DBE is a useful technique to confirm a diagnosis in patients who have suspected CD and can help establish a diagnosis of several diseases that may mimic CD on CT scan or CE. Additionally, DBE in patients with established diagnosis of small bowel CD is an effective tool to assess disease activity and guide therapy. Serious complications are infrequent.

P042 Early Versus Later Use of Vedolizumab In IBD: Patient Characteristics And Treatment Patterns In The Real World (RALEE).

Pivotal trials in inflammatory bowel disease (IBD) demonstrate that earlier use of biologics is associated with greater likelihood of response/remission, but multiple studies have identified that in the real world, biologic treatment is often delayed, thereby limiting optimal effectiveness and increasing likelihood of adverse outcomes. Further assessment of patient, provider, and payor factors that contribute to therapy choice is needed. We assessed utilization of vedolizumab (VDZ) and performed a real-world assessment using administrative datasets. Here, we describe the different treatment patterns and demographics of patients who received VDZ. We identified VDZ-treated patients (aged ≥18 years) with Crohn's disease (CD) or ulcerative colitis (UC) in the MarketScan commercial and Medicare claims databases from 2017 to 2019 and included those who had continuous enrollment in the same health plan for ≥12 months prior to their initial IBD diagnostic claim, ≥1 VDZ claim after the initial IBD diagnosis, and continuous enrollment for ≥12 months prior to and after their initial UC or CD diagnosis. Patients exposed to VDZ, anti-TNF, or other biologic therapy in the 12-month pre-index period were excluded. We pre-defined 5 treatment pathways: (1) EARLY VDZ - VDZ within 30 days of first IBD diagnostic claim; (2) DELAYED VDZ 1 - immunomodulators and then switch to VDZ; (3) DELAYED VDZ 2 - corticosteroids with immunomodulators prior to VDZ; (4) DELAYED VDZ 3 - 5-ASA with corticosteroids prior to VDZ; or (5) DELAYED VDZ 4 - 5-ASA with corticosteroids and immunomodulators prior to VDZ. Differences in patient baseline characteristics among these treatment pathways were analyzed descriptively. We identified 136,315 patients with UC and 103,591 with CD, from which 1,342 patients with UC (median age 43 years; 51.0% male; 96.4% commercially insured; 86.4% diagnosed in 2017) and 964 with CD (median age 45 years; 43.6% male; 94.6% commercially insured; 88.6% diagnosed in 2017) received VDZ and met criteria. The proportions of patients by treatment pathway were (UC|CD): EARLY VDZ (6.6%|9.6%); DELAYED VDZ 1 (7.5%|19.0%); DELAYED VDZ 2 (14.8%|36.8%); DELAYED VDZ 3 (37.6%|19.0%); DELAYED VDZ 4 (33.4%|15.6%). Among patients with UC, EARLY VDZ vs DELAYED VDZ cohorts had median age of 40 vs 44 years and proportion of men of 46.1% vs 51.4%. Among patients with CD, EARLY VDZ vs DELAYED VDZ had median age of 43 vs 45 years and proportion of men of 39.8%% vs 43.9%. For both indications, no meaningful differences among treatment groups by geographic region, payor type (i.e., commercial vs Medicare), and year of diagnosis were observed. In this administrative real-world dataset, fewer than 10% of patients with IBD were treated with VDZ within 30 days of diagnosis, and these patients were more likely to be younger and women. These findings are distinct from guidelines suggesting VDZ may be used earlier, or due to its safety profile, preferentially in older patients at higher risk for infection. Further analyses of safety and effectiveness outcomes are underway.

P043 Resource Utilization and Productivity Loss among Patients with Inflammatory Bowel Disease in Sweden: A Longitudinal Nationwide Population-based Study.

Crohn's disease (CD) and ulcerative colitis (UC) are the two most prevalent forms of inflammatory bowel disease (IBD) causing frequent diarrhea, rectal bleeding, fatigue, and abdominal pain. IBD may result in complications requiring hospitalizations and surgical procedure, hence IBD can negatively impact patients' quality of life, work productivity, and increase societal economic burden. Limited data exists assessing epidemiologic trends and population-level health outcomes among patients with IBD in Sweden. This study assessed the trends in annual incidence and prevalence of CD, annual inpatient and outpatient visits, employment status and sickness absence among adults with IBD in Sweden from 2001 to 2017. Data were acquired from four nationwide registers provided by the National Board of Health and Welfare in Sweden and linked through the unique personal identity number. Individuals aged ≥18 years with ≥2 primary diagnoses of CD (ICD-10 K50) or ≥2 primary diagnoses of UC (ICD-10 K51) from 01/01/2001 to 12/30/2017 were selected. Date of the first CD or UC diagnosis was designated as index date. All individuals were followed until death, lost to follow up or end of study. A total of 30,895 patients with CD and 50,415 with UC were included in the analysis, respectively. The mean follow-up for patients was 10.1 (±5.33) and 10.4 (±5.21) years for CD and UC. The mean (±SD) age among CD patients was 40.4 (±18.4) years and 42.6 (±18.2) years for UC. The most frequently observed comorbid condition was noninfective enteritis and colitis for patients with CD (24.2%) and UC (15.7%). The annual incidence of CD was 10 per 100,000 person-years in 2017, while the incidence of UC was 3 per 100,000 in 2017. 40.6% of CD patients and 30.8% of UC patients had ≥ 1 inpatient admission during 1-year post-index period, of which 53.5% and 51.2% had inpatient care lasting more than 1 week. Among patients with ≥ 1 outpatient services (CD: n = 30,675; UC: n = 50,183), 41.7% and 29.2% of patients had more than 5 visits during 1-year post-index period. Among patients who were eligible for employment and disability benefit analyses who had at least 1-year follow-up (CD: n = 23,731; UC: n = 39,391), 27.9% of CD patients and 23.1% of UC patients were not in employment; among those who were in employment (CD: n = 17,039; UC: n=30,302), 30% and 24.6% reported sickness absence within the calendar year after the index date, respectively. Findings from this study of a large national cohort of patients followed for many years demonstrates the significant epidemiological, clinical, and socioeconomic impact of patients with CD and UC. Further research is needed to understand underlying factors driving inpatient admissions among patients with IBD. With an increasing annual prevalence, IBD continues to impose a substantial public health burden to patients, their families and health care services.