Fatigue Trajectory During the First Year of an Inflammatory Bowel Disease Diagnosis, Results from the IBSEN III study.

Background We currently lack sensitive and specific prognostic biomarkers of inflammatory bowel disease (IBD) onset and severity. In three large, population-scale cohorts, we investigated metabolomic biomarkers for predicting disease onset and course. Methods We measured 250 metabolomic biomarkers using nuclear magnetic resonance (NMR) in ~500,000 individuals from the UK Biobank [1]. 2036 individuals had prevalent Crohn’s disease (CD) and 4029 had ulcerative colitis (UC) at recruitment. 1242 participants developed incident CD and 2283 incident UC during 10-year follow-up, allowing us to study the pre-diagnostic metabolic profile of IBD. We investigated associations between individual metabolomic biomarkers with prevalent and incident IBD using logistic and proportional hazards regressions. Among the incident IBD cohort we used LASSO with five-fold cross-validation on 50% of the cohort to build predictive models of future IBD onset. The resulting predictive model was validated in the Estonian Biobank and the Finnish THL Biobank (N ~218,000), confirming its robustness in multiple cohorts. Finally, in the UK Biobank we identified individuals with prevalent IBD who had IBD-related emergency admission, surgery or death and used these to develop a disease course score. Results GlycA, a biomarker of systemic inflammation, was the strongest association for both incident and prevalent UC and CD. We also identified associations between non-inflammatory metabolomic markers and IBD, such as albumin, branched-chain amino acids, cardiovascular lipid factors, fatty acids and creatinine. Notably, the perturbation in metabolites was markedly greater in CD versus UC, showing that CD is a more systemic illness (Fig. 1). Metabolomics scores were predictive of CD (AUC=0.69) and UC (0.62) onset up to 10 years prior to diagnosis, with performance for CD improving closer to diagnosis (2y follow-up AUC: CD 0.76, UC 0.62). Patients in the highest decile of incident metabolomic score were substantially more likely to develop the disease, with this observation being consistent in other two biobanks (Fig. 2). Metabolite profiles were predictive of IBD complications in prevalent patients (AUC 0.68 for CD; 0.62 for UC), outperforming both genetic and blood biomarker scores. Conclusion Leveraging cohort-wide profiling of population-scale biobanks, we present the largest metabolomics study and the largest pre-diagnostic study of IBD to date. Pre-diagnostic metabolomic scores are predictive of disease onset. These results warrant further investigation of multi-omic prediction of the onset, comorbidities and disease course of IBD. References * A.S, K.S. contributed equally. # T.J., J.C.B., C.L. contributed equally. [1] Nightingale Health Biobank Collaborative Group, Barrett, J. C., Esko, T., Fischer, K., Jostins-Dean, L., Jousilahti, P., ... & Estonian Biobank Research Team. (2023). Metabolomic and genomic prediction of common diseases in 477,706 participants in three national biobanks. medRxiv, 2023-06. Figure 1: Associations between clinically validated biomarkers and prevalent IBD Figure 2: UK Biobank-derived score consistency across the three biobanks

: The objective of the present study was to quantify the national pediatric inpatient inflammatory bowel disease (IBD) burden in terms of the number of IBD-related hospitalizations, the number of days spent in the hospital, and hospitalization costs. : Hospitalizations for children and adolescents 20 years and younger with a primary diagnosis of either Crohn disease (CD) or ulcerative colitis (UC) were selected from the 2006 Kids' Inpatient Database (KID). Length of the hospital stay in days (LOS) and charges for the hospitalization were found directly in the Kids' Inpatient Database, and cost was calculated using the hospital's cost-to-charge ratio. Predictor variables included patient characteristics, such as age and severity of illness, and hospital characteristics. Ordinary-least-squares regressions were developed and estimated to explain hospitalization costs. : In 2006, there were 10,777 IBD-related hospitalizations. The total and mean costs for CD were $66.3 million and $10,176 (95% confidence interval [CI] $9647-$10,705), and for UC were $48.6 million and $11,836 (95% CI $10,760-$12,912). For CD, 0- to 5-year-old patients had the highest mean LOS (8.10, 95% CI 5.53-10.67, days) and mean cost ($13,894, 95% CI $9053-$18,735), whereas, for UC, 11- to 15-year-old patients had the highest mean LOS (7.49, 95% CI 6.88-8.10, 95% CI 5.53-10.67, days) and mean cost ($13,407, 95% CI $11,704-$15,110). : For a pediatric disease with a rather low prevalence rate, the estimated annual inpatient pediatric burden of IBD is a sizeable $152.4 million (2010 US$) and 64,985 days spent in the hospital. As medications and outpatient treatments improve for the treatment of IBD, there is an opportunity for significant reduction in inpatient burden.

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.

Background Inflammatory bowel disease (IBD) is a heterogeneous disorder. Both subtypes, i.e., Crohn’s disease (CD) and ulcerative colitis (UC), differ in disease behaviour and inflamed gastrointestinal segments. Despite this, randomized controlled trials stratify patients based on CD and UC. Molecular characterization could uncover subtype-specific differences that could guide treatment and thereby overcome current therapeutic limitations. Therefore, we aimed to examine differences in serum inflammatory protein profiles across the IBD spectrum. Methods This was a cross-sectional multicentre study of adult patients (≥18 years) with IBD from one Belgian and eight Swedish hospitals in the COLLIBRI consortium. IBD diagnosis and classification was based on international criteria, according to the Montreal classification. Relative serum protein levels were assessed using proximity extension assay technology (Olink Proteomics, Uppsala, Sweden; inflammation panel). We adopted smoothly clipped absolute deviation penalized logistic regression models to discriminate CD and UC patients. Using fitted CD vs UC logistic models, we estimated probability scores of CD vs UC for each patient based on their serum protein profiles. Scores ranged from 0 to 1, where lower scores indicated a higher molecular resemblance to UC. We evaluated the performance using leave-one-out cross-validation and the area under the curve (AUC). Results Relative levels of 86 serum inflammatory proteins were available from 1,551 patients with IBD (CD, N=883; UC, N=639 and IBD-U, N=29) (Table 1). CD vs UC probability scores based on protein estimates for patients with UC, IBDU and different CD phenotypes (ileal CD, L1; colonic CD, L2; ileocolonic CD L3) are shown in Figure 1A. We observed a spectrum of IBD patients based on their CD vs CD probability scores with most pronounced differences between ileal CD and UC. Probability scores also differed significantly between colonic CD and ileal CD, but not between ileal and ileocolonic CD. The model performance to discriminate CD and UC yielded an AUC of 0.75. Restricting the samples to only one CD phenotype vs UC respectively resulted in the highest AUC for ileal CD (0.81), followed by ileocolonic CD (0.75) and colonic CD (0.65). Key proteins in the CD vs. UC model with higher protein estimates in UC were IL-17A, MMP10, FGF19. Contrary, CSF1, and SLAMF1, were higher in CD (Figure 1B). Conclusion Our results on inflammation related serum proteins advocate for a more nuanced classification of CD into ileal-predominant and colonic-predominant subtypes. Such stratification could advance our understanding of IBD pathophysiology and may provide guidance for future therapeutic approaches.

The natural history of paediatric inflammatory bowel diseases (IBDs) is poorly understood. We aim to describe the disease course in this cohort and generate prognostic information for patients and clinicians. Patient records from 6 tertiary paediatric gastroenterology centres were reviewed to generate data concerning original diagnosis, change in diagnosis, family history, surgical interventions, growth, and presence of extragastrointestinal manifestations. Data were collected on 116 children with Crohn disease (CD), 74 with ulcerative colitis (UC), and 20 with indeterminate colitis (IC), followed for a mean period of 3.42, 3.3, and 2.9 years from date of diagnosis, respectively. A male predominance is demonstrated in CD. Revision of diagnosis in patients with IC is mainly to UC, with most children receiving a definitive diagnosis within 2 years of initial presentation. Of the children with UC, 17.6% underwent 1 or more major operations with a median time to surgery of 1.92 years. Of children with CD, 11.6% underwent 1 or more major intraabdominal procedures with a median time to surgery of 1.83 years. We recorded a positive family history in 2.7%, 8.2%, and 10% of cases for CD, UC, and IC, respectively. For both boys and girls with CD, but only for boys with UC, height standard deviation score became more negative over time. This retrospective study quantifies certain distinctions between IBDs diagnosed in paediatric and adult populations. We document a trend toward male predominance in children with CD. We also note impaired linear growth in children with CD, whereas it appears maintained in girls with UC. We also have recorded a low incidence of IBDs in the families of this cohort and suggest that environmental influences may be of greater importance. We document that major intraabdominal surgery may be required in about 15% of patients with either UC or CD within 2 years of diagnosis, and that the majority of those diagnosed initially with IC will be reclassified as either UC or CD within 2 years.

Background The Epi-IBD cohort is a prospective European population-based cohort of 1,508 patients diagnosed in 2010 and 2011 with inflammatory bowel disease (IBD) according to Copenhagen criteria in centres across 17 European countries. The study aims to describe treatment strategies, disease course and prognosis of IBD unclassified (IBDU) across Europe. Methods Patients with IBDU were defined as not fulfilling the Copenhagen diagnostic criteria of Crohn’s disease (CD) or ulcerative colitis (UC), but still required IBD related treatment and monitoring. They were followed prospectively from the time of diagnosis until December 31st, 2020, death, emigration or loss of follow-up. Clinical data on surgery, hospitalizations, and medical treatment were captured throughout the follow-up period and entered into a validated web-database, www.epi-ibd.org. Patients with IBDU were categorised as CD-like, UC-like or mixed CD-UC based on disease location and continuity of the affected bowel segments at diagnosis. Results In total, 129 IBDU patients aged ≥15 years from 22 centres were included. They comprised 8.5% (N=129/1,508) of the total cohort. The disease location was reported in Table 1 where 4 patients had unknown disease location at baseline. At diagnosis, 16% (N=25/129) were CD-like, 52% (N=62/129) were UC-like and 32% (N=42/129) were mixed CD-UC.During the 10-year follow-up, 32% (N=41/129) were re-classified as either CD (N=16) or UC (N=25). The crude 1-, 5-, and 10-year rates for re-classification of diagnosis were 19%, 26% and 32%. The time to initiation of therapies and the distribution of therapies according to re-classification of IBDU diagnosis at baseline are presented in Figure 1 A-B . Advanced therapies were used in 13% (N=17/129) of patients over the 10-year follow-up, and was initiated after a median period of 1.9 years (inter-quartile range 0.9-8.1). An intestinal resection was required in 7% (N=9/129). After 1, 5, and 10 years, 9%, 19% and 26% of the patients diagnosed with IBDU at baseline, respectively, required hospitalisation. Conclusion After 10 years of follow-up, a third of patients initially diagnosed with IBDU were re-classified as either CD or UC. The disease course was in general mild with a low number of patients requiring advanced therapy, intestinal resection, and hospitalization. However, patients who were re-classified as CD or UC were more frequently treated with medical therapies.

Background Psychiatric comorbidity might modify the disease course adversely in patients with inflammatory bowel disease (IBD). Treatment options include antidepressants, which, apart from improving mood, have anti-inflammatory properties that might modify the disease course. This nationwide study aimed to examine the influence of antidepressants on the disease course among patients with ulcerative colitis (UC) and Crohn's disease (CD). Methods Patients registered with an incident diagnosis of CD or UC in the Danish National Patient Register (2000-2017) were included. Information on antidepressant use and proxy measures of disease activity (health care and drug utilization) was extracted from national population registers. Poisson regression was performed to estimate disease activity rates by antidepressant use adjusted for confounders. Furthermore, the analyses were performed stratified by IBD subtype and type of antidepressants. Results A total of 42,890 patients were included (UC: 69.5%; CD: 30.5%). When adjusted for confounders, a lower incidence rate of disease activity was found among antidepressant users compared with nonusers in both CD (incidence rate ratio [IRR], 0.75; 95% confidence interval [CI], 0.68-0.82) and UC (IRR, 0.90; 95% CI, 0.84-0.95) patients. Further, markedly lower rates of disease activity were found among CD (IRR, 0.51; 95% CI, 0.43-0.62) and UC (IRR, 0.67; 95% CI, 0.59-0.75) patients with no use of antidepressants before IBD onset. Conclusions In this nationwide study, antidepressant use was found to be beneficial on the disease course among patients with UC and CD, particularly in patients with no use of antidepressants before IBD onset. Randomized controlled trials are warranted to investigate the potential of antidepressants being an adjunct treatment to conventional IBD therapy.

Relevance. Defects of innate and acquired immunity, intestinal microflora disorders, environmental factors against the background of genetic predisposition play a role in the development of ulcerative colitis and Crohn's disease. The question of the influence of genetic factors on the appearance of these diseases remains open. The purpose of the study. To develop approaches to assessing the course of ulcerative colitis and Crohn's disease, taking into account mutations of genes regulating tumor necrosis factor (TNF-a), vascular endothelial growth factor (VEGFA), interleukin-6 (IL-6) and polymorphic variants of the CARD15/NOD2 gene (Gly908Arg, Leu3020insC). Materials and methods. Polymorphic gene variants were studied in 50 patients with ulcerative colitis aged 18 to 79 years, 28 men (56%) and 22 women (44%). Age: under 35 years (38%), from 36 to 50 years (30%), over 51 years (32%). According to the extent of the pathological process, patients with total colitis prevailed (84%). Patients with left-sided colitis (14%) or proctitis (2%) were less common. In 28 patients (56%), chronic continuous course was observed, in 14 (28%) — chronic recurrent, in 8 (16%) — acute course. According to the severity of the attack: moderate (42%), light (28%) and heavy (32%) attacks were observed less frequently. Among the examined patients, surgical intervention was performed in 8 patients (16%), the remaining patients (84%) were treated conservatively. The diagnosis of ulcerative colitis was made on the basis of clinic data, ultrasound, colonoscopy, visual assessment of the pathological process during surgery and histological examination of the surgical material. The frequency of two polymorphic variants of the CARD15/NOD2 gene (Gly908Arg, Leu3020insC) was studied in 40 patients with Crohn's disease. All patients were admitted to the surgical hospital in an emergency. The diagnosis of Crohn's disease was made on the basis of clinic data, ultrasound examination, visual assessment of the pathological process during surgery and histological examination of the surgical material. The studies were conducted within a period of 1 to 10 years from the moment of discharge from the hospital. Results. In ulcerative colitis, mutations of the gene encoding IL-6 for the homozygous variant G174G occurred in 24%, mutations of the gene encoding VEGFA for the homozygous variant C634C occurred with a frequency of 12%. Mutations in the gene encoding tumor necrosis factor (TNF-α) were not detected in the study group. IL-6 gene mutation is almost equally found among groups of patients who underwent surgery and patients after conservative treatment, namely in 25% and 23.8%, respectively. However, mutations of the VEGFA gene were significantly more common (p=0.03) among patients with a history of surgical treatment (37.5%). Genetic testing in patients with ulcerative colitis makes it possible to predict the effectiveness of therapeutic measures, the likelihood of an increased risk of surgical treatment and can act as one of the criteria for the implementation of a personalized approach in this contingent of patients. In patients with Crohn's disease, polymorphisms of the CARD15/NOD2 gene according to the heterozygous variant occurred with a frequency of 35%, polymorphic variant Leu3020insC in 30% of patients, Gly908Arg in 2.5% of cases. Both polymorphic variants were observed in 2.5% of patients. The polymorphic variant Leu3020insC is associated with the localization of a pathological focus and dominates inflammation in the area of the ileocecal angle. Conclusions. In ulcerative colitis, the frequency of IL-6 gene mutations reaches 24%. Mutations of the VEGFA gene were 2 times less common (12%). Mutations in the TNF-α gene were not detected. It was found that mutations in the IL-6 gene are more common among male patients older than 51 years. According to the length of the process, IL-6 gene mutations are associated with left-sided colitis, and EGFR mutations with total intestinal damage. Mutation of the VEGFA gene to a certain extent may indicate the likelihood of an increased risk of surgical treatment. In Crohn's disease, the frequency of gene polymorphism reaches 35%. The polymorphic variant Leu3020insC is associated with the localization of a pathological focus and dominates inflammation in the area of the ileocecal angle. The appearance of a polymorphic variant of Gly908Arg to a certain extent may indicate a possible relapse of the disease.

Background: Both the Swedish National Patient Register (NPR) and the Swedish Quality Register for inflammatory bowel disease (IBD, SWIBREG) are important sources of research data and information. However, the validity of a diagnosis of IBD in these registers is unknown.Methods: Medical charts of 129 randomly selected patients from the NPR and 165 patients registered both in SWIBREG and the NPR were reviewed. Patients were classified according to standardized criteria for ulcerative colitis (UC), Crohn’s disease (CD), or IBD unclassified (IBD-U). Positive predictive values (PPVs) for UC, CD, IBD-U (only SWIBREG), or having any form of IBD were then calculated.Results: For cases with ≥2 diagnoses of IBD in the NPR (hospitalizations or non-primary care outpatient visits), the PPV was 93% (95% CI: 87–97) for any IBD, 79% (66–88) for UC and 72% (60–82) for CD. In UC patients with ≥2 UC diagnoses but never a CD diagnosis, the PPV increased to 90% (77–97). The PPV for CD in patients with ≥2 CD diagnoses but never a UC diagnosis was 81% (67–91)). Combining data from SWIBREG (≥1 record) and the NPR (≥1 record), the PPV was 99% for any IBD (97–100), 96% (89–99) for UC, and 90% (82–96) for CD.Conclusion: The validity of the UC, CD, and IBD diagnoses is high in the NPR but even higher when cases were identified both in SWIBREG and the NPR. These results underline the need for a well-functioning Swedish Quality Register for IBD as a complement to the NPR.

P-049: Reproducibility of serologic antibody activity at diagnosis and after treatment in pediatric ulcerative colitis and Crohn’s disease

Background Inflammatory bowel disease(IBD),including Crohn's Disease(CD) and ulcerative colitis (UC), is closely linked with altered gut microbiota.Roles of bacteria in IBD have been widely investigated, whereas other microbial kingdoms, fungi, archaea, virus, are less explored. Here, we aim to investigate the multi-kingdom microbial alterations and their capabilities for IBD diagnosis. Methods A total of 968 stool samples (292 CD, 305 UC and 371 controls) of untreated patients from iHMP were collected. Differential microorganisms were identified via wilcoxon test followed by adjustment for confounders. Inter-kingdom co-occurrence interactions analysis was performed by SparCC then microorganism modules were clustered by “MCODE”. Subsequently, neural networks algorithm was used to build diagnostic models for CD or UC with single- or multi-kingdom microbial features and the best panel of biomarkers was further identified by recursive feature elimination. Moreover, diagnostic models were validated in additional independent cohorts. Differential microbial pathways were analyzed to further explore functional alterations in CD and UC. Results In CD and UC, the microbial compositional change was identified in different kingdoms. Compared to controls, we identified 41 bacteria, 37 fungi, 40 archaea and 50 viruses with differential abundance in CD. Similarly, 63 bacteria, 52 fungi, 58 archaea and 39 viruses with differential abundance were detected in UC. Moreover, inter-kingdom interactions were more complex in IBD than controls, especially the interactions between fungal Aspergillusand BeAn 58058 virus. Notably, the diagnostic models constructed with multi-kingdom microbial features performed better (AUC of 0.90 in CD and 0.91 in UC) than that with single kingdom microbial features. The diagnostic models also showed reliable accuracy in independent cohorts with an average AUC of 0.93 (CD) and 0.74 (UC), respectively. Among these biomarkers, bacterial Bacteroidesand fungalAspergillusare the main contributors to the distinguishing ability in both CD and UC diagnostic models. In addition, pathways related to lipid and terpenoids metabolism and immune response were altered in CD and UC, such as glycosphingolipid biosynthesis, carotenoid biosynthesis and IL-17 signaling pathway. Conclusions Our study investigated comprehensivepathogenic microbiota of IBD, which encompasses bacteria, fungi, virus and archaea. And the combination of multi-kingdom microbial biomarkers may serve as effective tools for CD and UC diagnosis, which outperforms single kingdom biomarkers. The alterations of microbial inter-kingdom interactions and cross-kingdom functional changes provide new insight in understanding pathological mechanisms of IBD.

ObjectivesVitamin D deficiency predicts unfavorable disease outcomes in inflammatory bowel disease. Endogenous vitamin D synthesis is affected by seasonal factors including sunlight exposure, raising the question whether seasonality determines the risk of vitamin D deficiency and may mask other clinical risk factors.MethodsUnivariable and multiple regression analyses were performed in a retrospective cohort of 384 patients to determine risk factors for vitamin D deficiency. Since the observed 25-hydroxyvitamin D [25(OH)D] concentrations followed a sinusoidal pattern over the year, all 25(OH)D concentrations were normalized for the predicted variability of the respective day of analysis based on a sinusoidal regression analysis of 25(OH)D test results obtained in more than 86,000 control serum samples.ResultsVitamin D deficiency was highly prevalent in patients with Crohn’s disease or ulcerative colitis (63% and 55%, respectively) and associated with winter/spring seasons. After normalization of 25(OH)D concentrations for the day of analysis, vitamin D deficiency was associated with histories of complications related to inflammatory bowel disease, surgery, smoking and ongoing diarrhea while initial disease manifestation during adulthood, ongoing vitamin D supplementation and diagnosis of ulcerative colitis vs. Crohn’s disease appeared to be protective. Multiple regression analyses revealed that vitamin D deficiency was associated with disease activity in Crohn’s disease and anemia in ulcerative colitis patients. Only few deficient patients achieved sufficient 25(OH)D concentrations over time. However, increasing 25(OH)D concentrations correlated with improved Crohn’s disease activity.ConclusionsVitamin D deficiency was highly prevalent in patients with Crohn’s disease and ulcerative colitis and dependent on the season of the year. Following normalization for seasonality by sinusoidal regression analysis, vitamin D deficiency was found to be associated with parameters of complicated disease course while increasing 25(OH)D concentrations over time correlated with reduced activity of Crohn’s disease.

Introduction/Objective A subset of patients with an established diagnosis of UC develops signs of CD (de novo CD) following IPAA. While the etiology and risk factors of de novo CD remain largely unknown, preliminary studies have shown controversial results regarding family history of inflammatory bowel disease (IBD) and smoking history. Methods Patients that underwent IPAA for UC, with at least 1 year of follow-up, were identified (n=161; 1996 to 2018). We retrospectively reviewed the electronic medical records. Patients that were diagnosed with de novo CD during the follow-up period were further identified. Smoking history and family history of IBD were evaluated. Chi square test was performed to compare the frequencies. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated by logistic regression model. P<0.05 was considered statistically significant. Results 29 de novo CD were identified. At the time of proctocolectomy, the family history of IBD and smoking history was documented in 152 UC patients including 27 that subsequently developed de novo CD. 23 of 152 had a family history of IBD (12 UC, 9 CD and 2 IBD, NOS). 19/129 (14.7%) UC patients without a family history of any type of IBD, 4/9 (44.4%) with a family history of CD, and 4/12 (33.3%) with a family history of UC developed de novo CD. Patients with a family history of CD were more likely to develop de novo CD post IPAA than those without a family history of any type of IBD (OR 4.63, 95% CI 1.14-18.82, p=0.03). Family history of UC did not correlate with development of de novo CD (OR 2.90; 95% CI 0.79-10.57, p=0.108). At the time of proctocoletomy, 11 were current smokers, 25 were former smokers, and 116 never smoked. In de novo CD group, there were 4/27 (14.8 %) former smokers and 23/27 (85.2 %) never smokers. No de novo CD patient was current smoker. In the UC group that remained as UC following IPAA, 11/125 (8.8%) were current smokers, 21/125 (16.8 %) former smokers, and 93/125 (74.4 %) were never smokers. Current smoking status was not associated with development of de novo CD (p = 0.214). Conclusion Family history of CD may be a risk factor for developing de novo CD following IPAA for UC. Current smoking status was not associated with development of de novo CD following IPAA for UC.

Inflammatory bowel disease (IBD) encompasses ulcerative colitis (UC) and Crohn’s disease (CD). Both conditions cause chronic relapsing inflammation in the gastrointestinal (GI) tract, but have different characteristics. UC causes diffuse mucosal inflammation limited to the colon, extending proximally from the anal verge, with the rectum involved in 95% of patients. UC is described in terms of the disease extent: proctitis (confined to the rectum), proctosigmoiditis (disease confined to the recto-sigmoid colon), distal disease (distal to the splenic flexure), and pan-colitis (the entire large intestine). The extent of disease can change, with proximal extension seen in approximately a third of patients with proctitis, although there is great variation between studies. CD causes inflammation that can affect the entire thickness of the wall of the intestine, and is not confined to the mucosa. CD can affect any part of the GI tract. The terminal ileum is affected in approximately 80% of cases, the colon in approximately 60% of cases, and the rectum and perianal region in approximately 40% of cases. CD is classified by location (ileal, colonic, ileocolonic, upper GI tract), by the presence of stricturing or penetrating disease, and by the age of onset (before or after the age of 40). Penetrating disease refers to the development of fistulae, which can lead to complications such as abscesses or perforations. An earlier age at onset is associated with more complicated disease. The diagnosis of UC or CD is established through a combination of clinical, endoscopic, radiological, and histological criteria rather than by any single modality. Occasionally, it is not possible to establish an unequivocal diagnosis of CD or UC in IBD, and a third category, accounting for nearly 10% of cases, is used, termed IBD unclassified.

Although inflammatory bowel diseases (IBD) are known for a long time, it is still difficult to distinguish between Crohn's disease (CD) and ulcerative colitis (UC). Since the therapeutic treatment vary extremely the differentiation is very important. To facilitate and accelerate the diagnostic procedures a simple diagnostic test is required. Neither the question whether IBD-patients who show autoantibodies (AAB) stay positive for them all their lives is sufficiently studied nor if patients develop autoantibodies during their course of disease. The aim of this study was to evaluate the (differential) diagnostic value of antibodies (AB) to human neutrophils (pANCA) and AB to mannan of Saccharomyces cerevisiae (ASCA) combined with AB to antigens of exocrine pancreas (PAB) and AB to intestinal goblet cells (GAB). On the other hand the aim was to investigate whether patients have constant antibody titers. Sera from 444 patients (261 CD, 131 UC, 27 IC, 25 healthy people) were tested for the autoantibodies by indirect immunofluorescence. IgA and IgG were determined for pANCA, PAB and GAB and IgA, IgG and IgM for ASCA. Sensitivity, specificity, positive and negative predictive values of single AAB and special combinations were determined regarding the diagnosis of CD and UC. As shown in Table 1 ASCA and PAB are specific for CD and pANCA for UC, while GAB shows indifferent results. The defined profiles even reach higher incidences for the specific diseases. Incidences of autoantibodies in patients with IBD. CD-profile:= ASCA and/or PAB positive, UC-profile:= pANCA and/or GAB positive, healthy-profile:= all tested antibodies are negative. Incidences of autoantibodies in patients with IBD. CD-profile:= ASCA and/or PAB positive, UC-profile:= pANCA and/or GAB positive, healthy-profile:= all tested antibodies are negative. About one third of the patients with IBD doesn't have these autoantibodies. To investigate the change of AAB during the lifetime of an IBD-patient we studied the results of 178 patients, who had several antibody testings. The observing period reached from zero to twelve years. 78 patients changed their autoantibody results during this period. ASCA and pANCA could help in indeterminate cases to differentiate between CD and UC. PAB rises the diagnostic and predictive value of ASCA. The endoscopy as a first line method cannot be replaced by the AAB. As one third of the patients is negative for the antibodies they aren't qualified as screeningmarkers. Besides a positive antibody result without clinical symptoms or endoscopic findings doesn't diagnose an IBD. On the other hand a negative AB-test result can't exclude the diagnosis of an IBD. During their course of disease about 40% of the patients change their antibody profile. So in indeterminate cases without a positive antibody test it is recommendable to repeat the testing after some months. (2924 Zeichen)