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Background The inflammatory process associated to ulcerative colitis (UC) and Crohn’s disease (CD) starts before the onset of symptoms and the diagnosis, but this period has not yet been well defined. Our aim was to determine if patients with an incidental diagnosis of UC or CD have an increase in healthcare utilization in the years preceding the symptomatic onset of the disease. Methods All asymptomatic patients with a diagnosis of UC or CD during the colorectal cancer screening program between October 2010-January 2021 were included in this multicentric retrospective case-control study. Cases were matched 1:3 with controls adjusted by sex, age and date, excluding subjects with any visit to Gastroenterology. The main outcomes were the number of outpatient or Emergency Rooms visits, admissions, radiological examinations (US, CT, MRI), sick-leaves, and drug prescriptions (antibiotics, systemic steroids) up to 5 years before the diagnosis. Descriptive statistics were used, with chi-square tests and a multivariable hurdle or negative binomial regression model, adjusted by smoking habits and Charlson index. Results A total of 124 patients were included (87 UC, 30 CD, 7 IBD-U; median 56 years (IQR, 53–62); 56% male), compared with 372 controls. Baseline characteristics including comorbidities were balanced between both cohorts. Patients demonstrated an increase in the number of visits to Primary Care physician during both 3 and 5 years before the diagnosis, but there were no differences in the remaining outcomes including hospital admissions, Emergency Room or outpatients visits, and sick-leaves (Figure 1 and 2). Systemic steroids were more frequently prescribed to patients in the preceding 3 to 5 years before diagnosis. Patients underwent US and/or CT scan less frequently in the preceding 5-year period. Conclusion Patients with IBD show an increased need of medical assistance in the years prior to the diagnosis, even during the presymptomatic phase of the disease. Tools focused on early identification of IBD may start on Primary Care facilities, but certain factors as steroids may alter the development of symptoms and the full spectrum of the disease.

Background The use of ustekinumab (UST) and vedolizumab (VDZ) as first line therapy for inflammatory bowel disease (IBD) is increasing due to safety reasons and contraindications of anti-TNFs. However, there are no studies evaluating their efficacy and safety in clinical practice under these circumstances. Thus, our aims were to describe bionaïve patients’ characteristics starting VDZ or UST and to evaluate treatment persistence of these drugs and their safety profile in this scenario. Methods Descriptive, retrospective and multicenter study based on the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD –GETECCU). All IBD patients never exposed to biological agents who started VDZ or UST as first-line biological treatment were identified. Results Out of 29,450 IBD patients ever exposed to biological drugs included in the ENEIDA registry, 924 patients met the inclusion criteria. Of these, 366 (40%) started UST and 558 (60%) VDZ as first line biological therapy. UST group: 48% women, 90% Crohn's disease (43% ileal; 13% colic; 43.5% ileocolic; 31% upper gastrointestinal involvement; 25% stricturing behaviour; 12% penetrating, 18% perianal disease), 10% ulcerative colitis (74% extensive, 17% left-sided, 9% proctitis), 27% had extraintestinal manifestations (EIM). Median age at the beginning of UST was 57 years (IQR 57-70), 17% patients had a past history of malignancy and, 34% had associated comorbidities. UST indication was luminal activity except in 2% for perianal disease and 5% for EIM. At the end of follow-up (median 14 months [IQR 6-30]), 12 patients (3.3%) developed adverse effects (AEs) that led to treatment discontinuation in the majority of them (92%). VDZ group: 44% women, 42% Crohn's disease (44% ileal; 18% colic; 38% ileocolic; 25% upper gastrointestinal involvement; 28% stricturing behaviour; 13% penetrating; 7% perianal disease), 58% ulcerative colitis (50% extensive, 42% left-sided, 8% proctitis), 17% had EIM. The median age at the beginning was 61 years (IQR 48-71), 24% had past history of malignancy and, 34% associated comorbidities. The indication was exclusively luminal activity. At the end of follow-up (median 21 months [IQR 8-36]), 36 patients (6.5%) had AEs, that lead to treatment withdrawal in 67% of them (24 patients). Cumulative treatment persistence rates were 78%, 60% and 50% for VDZ and 85%, 75% and 66% for UST at 12, 24 and 36 months, respectively (P Conclusion In clinical practice, VDZ and UST are used first-line particularly in elderly patients with comorbidities. Both treatments have a good safety profile and a high persistence of treatment, being superior for ustekinumab.

Background Diagnostic delay (DD) is defined as the time between the onset of the first symptoms and the definitive diagnosis of IBD. It is highly heterogeneous and it has a negative impact on the disease course. Our objective was to describe the main clinical and histological characteristics at diagnosis of UC according to the DD and its influence on clinical course. Methods A retrospective study compiled information from consecutive patients diagnosed with UC between January 2015 and December 2019 and included in the ENEIDA registry in our hospital. Patient and disease characteristics at diagnosis such as age, DD, disease extent, partial Mayo Score (PMS), extraintestinal manifestations (EIM), fecal calprotectin (FC), and histological characteristics at diagnosis were compiled. The role of DD was evaluated as both quantitative and dichotomous variable using Spearman correlation, chi-square and Mann-Whitney tests. Results A total of 146 patients (53% male; 47% former smokers; median age 46 years [IQR, 34-56]; 27% E2 and 35% E3; median FC of 289 mg/kg (IQR, 105-586) with a median DD of 2 months (IQR, 1 -4) were included. The median PMS at diagnosis was 2 points (IQR, 2-5), with higher scores in patients with shorter DD (≤2 months, median 3 points [IQR, 2-5] vs >2 months, median 2 points [IQR, 2-4]; p=0.002). Among them, 7% of patients presented at least one EIM, reported more frequently in patients with a DD >2 months (1.4% with DD≤2 vs 13.4% with DD>2 months; p=0.007; Figure A). During follow-up, 9% developed proximal disease extension. The most frequent histological findings were cryptic abscesses (71%), with a predominantly chronic infiltrate with basal plasmacytosis (97%), epithelial irregularity (83%), decreased mucosecretion (46%), erosions (21%), and ulceration (12%). The presence of eosinophils was more frequent as DD increases (5.6% if DD≤2 vs 18% if DD>2 months; p=0.029; Figure B), whereas the degree of chronic infiltration is more severe in patients with shorter DD (94% if DD≤2 vs 82% if DD>2 months; p=0.029; Figure C). Conclusion DD in UC influences the severity of clinical disease activity and the rate of EIM at diagnosis. In addition, eosinophils are more frequent as DD increases, while the degree of chronic infiltrate was more pronounced in patients with shorter disease duration.

Background Previous data have shown that the inflammatory process underlying ulcerative colitis (UC) and Crohn’s disease (CD) can start years before the diagnosis, but the role of triggering factors and environmental exposures is still unknown. Hair element analysis is a valuable and inexpensive screen for physiological excess or deficiency of certain elements. Our aim was to determine if patients with an incidental diagnosis of UC or CD demonstrate exposure of minerals or toxic metals in the years preceding the symptomatic onset of the disease. Methods We performed a prospective single-center study including all asymptomatic subjects with a diagnosis of UC or CD during the colorectal cancer screening program between January 2021 – June 2022 in Vizcaya (Basque Country, Spain). The diagnosis of IBD was established by a combination of clinical data, endoscopic findings suggestive of UC or CD, and after histologic confirmation. Cases were compared with a healthy non-IBD control population. An approximate hair sample of 0.25 g was obtained up to 3 months since diagnosis. We used a commercial kit that allows the investigation of 17 metals (Al, Sb, As, Ba, Be, Bi, Cd, Pb, Hg, Pt, Tl, Th, U, Ni, Ag, Sn, Ti) and 22 minerals (Ca, Mg, Na, K, Cu, Zn, Mn, Cr, V, Mo, B, I, Li, P, Se, Sr, S, Co, Fe, Ge, Rb, Zr). Descriptive statistics and non-parametric tests were used for comparisons between both groups. Results Three patients with preclinical IBD were included (median age 53 years; 67% male; all former smokers). Two of them had a diagnosis of UC (one left-sided colitis and one extensive colitis) and one with ileal CD. Extraintestinal manifestations were observed in one patient (33%). No family history of IBD was reported. Thirteen healthy controls with no relevant environmental exposures (median age 34 years; 69% female; 92% non-smokers). We found that cases demonstrated statistically significant higher concentrations of bismuth, sodium and boron compared to controls (Figure). In contrast, there was a lower exposure to uranium, zinc and germanium, with a trend towards lower copper levels among cases. Conclusion A range of environmental exposures can be identified during the preclinical phase of IBD. However, their relationship with the symptomatic onset and disease progression should be further explored.

Background Previous data have shown that the inflammatory process underlying ulcerative colitis (UC) and Crohn’s disease (CD) can start years before the diagnosis. Serum proteomic and serologic markers have been identified during this period, providing the opportunity for early detection of the initial immune disturbances. Our aim was to determine if patients with an incidental diagnosis of UC or CD demonstrate a serologic response based on antimicrobial antibodies, therefore preceding the symptomatic onset of the disease. Methods We performed a prospective single-center study including all asymptomatic subjects with a diagnosis of UC or CD during the colorectal cancer screening program and available data on antimicrobial antibodies between 01/10/2013 – 29/02/2022. The diagnosis of IBD was established by a combination of clinical data, endoscopic findings suggestive of UC or CD, and after histologic confirmation. ASCA IgA, ASCA IgG (EliA ASCA IgA/IgG, ThermoFisher) and ANCA (EUROPattern, PerkinElmer; EliA IgG, ThermoFisher) antibodies were determined. Positive results were considered above 10 U/mL for ASCA, 3.5 for ANCA-MPO and 2.00 for ANCA-PR3. Descriptive statistics were used. Results A total of 26 incidentally-diagnosed patients were included, 19 with UC (21% left-sided, 32% extensive; 53% former smokers), and 7 with CD (57% ileal, 29% colonic; 14% active smokers), with a median age of 51 years (IQR, 51-57). Three patients showed at least one positive test (12%). One patient (5%) with extensive UC showed positive ANCA results, and he developed symptoms 2 months after diagnosis. Two patients (28%) with CD (L2B2 and L1B1, according to Montreal classification) showed positivity to ASCA IgA/IgG at diagnosis, and both have remained asymptomatic after a median of 23 months. After a median follow-up of the whole cohort of 54 months (IQR, 26-67), 12 patients (46%) developed symptomatic disease. Conclusion A low proportion of patients with an incidental diagnosis of IBD demonstrate a serological response based on antimicrobial antibodies, suggesting that this situation corresponds to the initial phases of IBD when systemic immune disturbances might not be detectable yet.

Background It has been reported that familial aggregation occurs in 10–20% of inflammatory bowel disease (IBD) patients1. Familial IBD has been associated with disease anticipation2 and with an increased need for immunosuppressants3 and surgery4. However, most studies were performed before the widespread use of biological agents and this may impact on the need for surgery. We aimed to compare the clinical outcomes of IBD (by means of the need for biological therapy and abdominal surgery) between familial and sporadic forms of IBD in the era of biological therapies. Methods Data were extracted from the ENEIDA registry by GETECCU, a Spanish, prospectively-maintained, IBD database in which more than 80 centers are participating. Only adult patients diagnosed with IBD since 2005 and prospectively followed in the registry since diagnosis were included. Familial IBD was defined as those cases with at least one first-degree relative diagnosed with IBD. Sporadic IBD was defined as those cases with no familial relative (of any degree) with IBD. Kaplan-Meier survival curves were performed to evaluate the cumulative probabilities of remaining biologic-free and surgery-free. Log-rank test was performed to compare them between familial and sporadic IBD forms. Chi-square test was performed for the rest of variables. Results A total of 5,263 patients (2,627 Crohn’s disease [CD]; 2,636 ulcerative colitis [UC]) were included. Of them, 507 (10%) were familial cases (274 CD, 233 UC; P=0.05). The median follow-up was 38,4 and 35.5 months, respectively (P=0.086). Familial cases were younger (P=0.022) and had a higher proportion of females among UC cases (P=0.048). No differences were observed in the need for biological therapy in both CD and UC between familial and sporadic IBD. Regarding surgery, no differences were observed in the cumulative probabilities of a first intestinal resection for CD and colectomy for UC. Similar results were obtained when all the analyses were restricted to those subgroups at high-risk for surgery (i.e. CD with ileal involvement and extensive UC). Conclusion In patients diagnosed with IBD in the era of biological therapies, familial forms have the same requirements for biological agents and resectional surgery as sporadic forms. Therefore, familial aggregation does not seem to be a factor for a more aggressive disease.