bluuebunny/crossref_metadata_2025 huggingface dataset:
P779 Intestinal cancer associated with Crohn’s disease: difference between those with short duration and those with long duration
Authors: Shinozaki M , Takahashi R
Published: January 2020

Background

Patients with Crohn’s disease (CD) have increased risk of developing intestinal cancer (IC). In patients with ulcerative colitis, cancer risk is thought to increase around 10 years after the onset of colitis. However, in patients with CD, significant proportion of those was with shorter CD duration, and little has been known about the clinical management. The aim of this study was to clarify the clinicopathological characteristics of IC associated with Crohn’s disease with short duration.

Methods

We searched for IC cases associated with CD from a Japanese medical database (Ichushi). We picked up 272 cases, where we selected the two groups: those with short duration (5 years or less; S-group; n = 51) and those with long duration (15 years or more; L-group; n = 135). The median durations of the two groups were 0 year and 20 years, respectively.

Results

The age at cancer diagnosis was 51 years (interquartile (40–62)) and 45 (39–56) in S-group and L-group, respectively (p = 0.028). Patients in S-group were significantly older at the time of cancer diagnosis (p < 0.0001). The age at CD diagnosis was older in S-group than that in L-group (51 (38.5–62) years vs. 22 (9–68) years) with statistically significance (p < 0.0001). Relating to disease location of CD according to the Montreal classification, the proportion of L1 and L2 were significantly more in S-group than L-group (31% vs. 18%, and 49% vs. 10%, respectively; p < 0.0001). Penetrating type were significantly less in S group than that in L-group (28% vs. 59%; p = 0.003) in terms of disease behaviour according to the Montreal classification. In Japan, we found that majority of the colorectal cancer associated with CD is located at anorectum. However, in S-group, the proportion of anorectal cancer was only 26%, whereas that in L-group was 69%, and the difference reached statistical significance (p < 0.0001). Well to moderately differentiated adenocarcinoma accounts for 81% in S-group, while the ratio was 44% in L-group, and the difference was significant (p < 0.0001). Mucinous carcinoma was predominant in L-group (39%), and the proportion was significantly lower in S-group (12%; p = 0.0022). Clinical stage was similar in both groups, and the median was stage 2 (interquartile 1–3; p = 0.071). Median survivals were 21 and 26 months, and overall survival was also similar between the two groups (p = 0.51).

Conclusion

Some features were different between S-group and L-group, while the prognosis was not satisfactory in both groups despite relatively early clinical cancer stage. Older patients with short CD duration should be included as candidates of surveillance for neoplasia.
P785 Predictors of mortality in IBD patients treated for pneumonia
Authors: Ukashi O , Barash Y , Segel M J , Ungar B , Soffer S , Ben-Horin S , Klang E , Kopylov U
Published: January 2020

Background

Community-acquired pneumonia is among the most common infections affecting ulcerative colitis (UC) and Crohn’s disease (CD) patients. Data regarding epidemiology and outcomes of pneumonia in inflammatory bowel disease (IBD) patients is lacking. We aimed to investigate the epidemiology, natural history and predictors of adverse outcomes in IBD patients treated for pneumonia.

Methods

This was a retrospective cohort study that included consecutive adult patients that were admitted to Sheba Medical Center for pneumonia from an electronic repository of all emergency department admissions between 2012 and 2018. Data included tabular demographic and clinical variables and free-text physician records. Pneumonia cases were extracted using ICD10 coding. We compared the characteristics and outcomes of IBD and non-IBD patients, and CD and UC patients. We also examined the association of clinical and laboratory variables with thirty-day mortality.

Results

Of 16,732 admissions with pneumonia, 97 were IBD patients (45-CD; 52-UC). IBD patients were younger than non-IBD patients (66.8 years vs. 70.2 years, p-value = 0.077). Comorbidities such as diabetes (16.5% vs. 22.8%, p = 0.142), hypertension (30.9% vs. 41.4%, p = 0.037) and congestive heart failure (15.5% vs. 19.2%, p = 0.35) were more prevalent among non-IBD patients. Use of immunosuppressant and biological medications was more common among IBD patients (corticosteroids [19.6% vs. 9.7%, p = 0.001], azathioprine [5.2% vs. 0.4%, p < 0.001], vedolizumab [2.1% vs. 0%, p < 0.001], tumour necrosis factor-α inhibitors [6.2% vs. 0%, p < 0.001]). Thirty-day mortality rate was similar among IBD patients and non-IBD patients (12.1% vs. 11.3%, p = 0.824). We found increased hospitalisation rate among IBD patients (92.8% vs. 85.6%, p = 0.045), but similar length of stay in hospital (6.2 days vs. 6.2 days, p = 0.989). Thirty-day mortality rate (11.1% vs. 11.5%, p = 0.947) and hospitalisation rate (93.3% vs. 92.3%, p = 0.846) were similar in CD and UC patients. On the other hand, CD patients were younger (57.6 years vs. 74.8 years, p < 0.01) and had a shorter length of stay in hospital (4.8 days vs. 7.5 days, p = 0.046) compared with UC patients. Using regression analysis model, bronchiectasis (Adjusted odds ratio [AOR] 109.6, p = 0.008, opioid use (AOR 13.0, p = 0.03) and PPIs use (AOR 5.9, p = 0.05) were independently associated with the risk of 30-day mortality in IBD patients.

Conclusion

This is the first study to identify predictors of mortality in IBD patients with pneumonia. The rate of mortality and duration of stay were similar between IBD and non-IBD patients. Use of PPIs, opioids and presence of bronchiectasis were associated with a higher risk of mortality in IBD patients with pneumonia.
P795 Risk of incident paradoxical immune-mediated inflammatory diseases in patients with inflammatory bowel diseases treated with anti-TNF therapies: a nationwide Danish cohort study
Authors: WARD D , Gørtz S , Nyboe Andersen N , Kirchgesner J , Jess T
Published: January 2020

Background

Tumour necrosis factor (TNF) has a central role in the pathophysiology of immune-mediated inflammatory diseases (IMIDs) including rheumatoid arthritis, psoriasis, hidradenitis suppurativa, and inflammatory bowel diseases (IBD). However, there have been case reports of patients receiving an anti-TNF therapy for one IMID subsequently developing a second IMID. We conducted a nationwide cohort study investigating the risk of incident IMID following anti-TNF exposure in patients with IBD in Denmark.

Methods

We followed patients with IBD from 1 January 2005 or date of IBD diagnosis (whichever occurred last) to an outcome event including incident diagnosis of hidradenitis suppurativa, arthropathic psoriasis, other forms of psoriasis, or rheumatoid arthritis; or emigration, death or 31 December 2018 (whichever occurred first). Patients were defined as exposed after a 3-month lag period from first anti-TNF infusion throughout follow-up, analogous to an intention-to-treat design. The lag period was censored from analyses to avoid including incipient IMIDs, unlikely to be caused by newly initiated anti-TNF treatment. We excluded patients initiating anti-TNF or with an outcome diagnosis before either 1 January 2005 or IBD diagnosis. We used Cox regression models with age as the underlying timescale, and sex, type of IBD (Crohn’s disease or ulcerative colitis), and calendar period of IBD diagnosis (in 5 year groups) as strata to estimate hazard ratios for each outcome, comparing anti-TNF users and non-users.

Results

Incidence rates (and 95% confidence intervals [CI]) as events per 100 000 person-years among anti-TNF users and non-users were, respectively, 138 (109–173) and 25.6 (22.0–29.7) for hidradenitis suppurativa, 26.3 (15.6–44.4) and 7.81 (5.95–10.2) for arthropathic psoriasis, 1177 (1085–1277) and 204 (121–189) for other forms of psoriasis, and 152 (121–189) and 95.6 (88.5–103) for rheumatoid arthritis. Hazard ratios (and 95% C.I.) were increased for hidradenitis suppurativa 2.91 (2.15–3.94), arthropathic psoriasis 2.62 (1.40–4.93), other forms of psoriasis 4.76 (4.27–5.31), and rheumatoid arthritis 2.35 (1.83–3.01).

Conclusion

The results indicate that patients with IBD receiving anti-TNF have an increased risk of IMIDs. An almost 5-fold increase in the risk of psoriasis is consistent with previous reports of psoriasiform skin lesions related to anti-TNF use. However, as more severe IBD is likely to be associated with both initiating anti-TNF and the incidence of other inflammatory diseases, the results are subject to confounding by indication. Thus, these results should be considered preliminary, and we plan to further address confounding by using propensity score methods.
P800 Treatment patterns for biologics in ulcerative colitis and Crohn’s disease: A Danish Nationwide Register Study from 2003 to 2015
Authors: Alulis S , Vadstrup K , Borsi A , Nielsen A , Rikke Jørgensen T , Qvist N , Munkholm P
Published: January 2020

Background

The choice of biological treatment for Crohn’s disease (CD) and Ulcerative Colitis (UC) depends on disease severity and possible other factors. Patients with moderate to severe disease should be prescribed biologic response modifiers (biologics), according to guidelines. This study aims to explore the treatment patterns of patients diagnosed with CD and UC.

Methods

This national register study included patients diagnosed between 2003 and 2015, identified in the Danish National Patient Registry (NPR). Biologic therapies available during the study period were infliximab, adalimumab, vedolizumab and golimumab. The share of patients initiating and receiving biologic treatment in each year was calculated. Additionally, the time from IBD diagnosis to first biologic treatment and time between treatments were calculated.

Results

Among 10,302 CD patients and 22,144 UC patients, 28.5% of CD patients and 11.3% of UC patients received treatment with biologics during the study period, with an increasing number of patients initiating treatment with biologics for each successive year. 46% of CD and 45% of UC patients in the study population received their first biologic treatment within the first year after IBD diagnosis. 57–68% of CD and UC patients started treatment with their second line biologic within two months of the last treatment with their first line.

Conclusion

The number of patients initiating biologic treatments after diagnosis increased throughout the study period. Approximately half of patients diagnosed with CD and UC are receiving biologic treatments within the first year after diagnosis.
P810 Geriatric impairments in older inflammatory bowel disease patients are associated with higher disease burden: results of a multicentre cohort study
Authors: Asscher V , Waars S , van der Meulen-de Jong A , Stuyt R , Brouwer S , van der Marel S , Haans J , van Deudekom F , Mooijaart S , Maljaars J
Published: January 2020

Background

The population of older patients with Inflammatory Bowel Diseases (IBD) is expanding. Knowledge on the prevalence and impact of geriatric impairments is scarce in this heterogenous group. In other fields of medicine, it has been established that geriatric impairments associate with adverse outcomes. Therefore, the aims of our study were to assess the prevalence of geriatric impairments in older IBD patients and to evaluate the association between geriatric impairments and disease burden of IBD through the short Inflammatory Bowel Disease Questionnaire (sIBDQ).

Methods

Consecutive IBD patients aged ≥65 years were included at outpatient departments and infusion centres of four hospitals in The Netherlands. Comorbidity, polypharmacy and malnutrition (somatic domain), cognitive impairment and depressive symptoms (mental domain), handgrip strength and gait speed (physical domain) and impairments in (instrumental) activities of daily living ((I)ADL) (functional domain) were assessed. Disease activity was assessed through Harvey Bradshaw Index (HBI) or partial Mayo Score (pMS) (remission: HBI<5 or pMS<2); The sIBDQ was used to assess IBD disease burden. Association between geriatric impairments and sIBDQ was assessed using multiple linear regression, including confounders age, sex, IBD type, disease duration and disease activity.

Results

In total, 336 patients were included: median age 70.0 (IQR 67.0–73.0); 161 CD (47.9%); 71 active disease (21.1%); mean sIBDQ 59.7 (SD 8.1). Prevalence of geriatric impairments is tabulated (Table 1). Both active disease and the presence of two or more impaired domains were statistically significantly and independently associated with a higher disease burden (lower sIBDQ) (Table 2).

Conclusion

In an older IBD patient population, geriatric impairments are frequently encountered and associate with a higher disease burden. These results are a call for more research on the relationship between geriatric impairments and IBD disease burden to improve patient care in older IBD patients.
P811 A watchful approach for newly diagnosed Crohn’s disease patients with an inflammatory phenotype
Authors: Yassin S , Fliss-Isakov N , Ron Y , Hirsch A , Cohen N A , Maharshak N
Published: January 2020

Background

Early treat-to-target approach in Crohn’s disease (CD) patients is recommended to avoid complications. However, CD may not progress in all patients, despite lack of treatment or 5-ASA medications use, exposing this group of patients to unnecessary side effects if treated according to guidelines. We aimed to examine whether newly diagnosed CD patients with an inflammatory phenotype can benefit from a watchful approach.

Methods

This was a retrospective cohort study following CD patients at a tertiary centre, who were diagnosed between 2010 and 2015 and were followed for at least 1 year. Only patients with an inflammatory phenotype (Montreal classification B1) were included. Epidemiologic, clinical and endoscopic data was retrieved from medical records. A watchful approach was defined as maintenance therapy with 5-ASA medication only or no treatment at all during first year of diagnosis or further. Disease complications were defined as surgery or change in disease phenotype.

Results

Thirty-seven patients, (35.1% males at a mean age of 41.4 ± 19.6 years) were included in the study. During the follow-up period of 54.9 ± 28.7 months, 31 patients (86.0%) did not develop disease complications. The patients were characterised by females predominance (83.3% vs. 25.8%, p = 0.007), less smokers (25.8% vs. 83.3%, p = 0.006), earlier diagnosis from symptom onset (9.6 ± 15.6 months vs. 49.8 ± 57.0 months, p = 0.001) and prednisone therapy at diagnosis (87.1% vs. 50.0%, p = 0.032), compared with the patients that developed complications. There was no difference in clinical disease severity (HBI score 2.9 ± 1.5 vs. 3.1 ± 0.9, p = 0.721) or endoscopic activity (SES-CD score 6.3 ± 4.8 vs. 5.0 ± 4.8, p = 0.528) at diagnosis. Only 22.6% (7/31) of the patients were eventually treated with thiopurines or biologics for disease exacerbation.

Conclusion

A watchful approach of newly diagnosed CD patients with an inflammatory phenotype can be considered, especially in non-smoking women. This sub-group should be further characterised.
P812 Inflammatory bowel disease and hepatopathies: Beyond primary sclerosing cholangitis
Authors: Sanchez M B , Etchevers M J , De Paula J A , Gonzalez Sueyro R , Daffra P , Ramirez Medinacelli J , Sobrero M J , Marcolongo M M
Published: January 2020

Background

Inflammatory bowel diseases (IBD) and primary sclerosing cholangitis (PSC) are closely related. IBD-PSC has clinical characteristics that distinguish it from IBD without autoimmune liver disease (ALD). The association between autoimmune hepatitis (AH), overlapping syndrome (OS), primary biliary cirrhosis (PBC) and IBD is less known.

Methods

Clinical records of patients with IBD and PSC, AH, OS and PBC in a reference centre were reviewed retrospectively. Primary objective: to estimate the prevalence of ALD in patients with IBD. Secondary objectives: to establish the temporal gap between diagnosis of IBD and hepatopathy, severity of IBD, transplant requirement, displasia/colorectal carcinoma (CRC), and correlation between symptoms and endoscopic findings. All variables were compared according to liver disease.

Results

Of 1895 patients with IBD, 108 (5.7% [CI95% 4.7–6.8%]) had concomitant ALD, 78 PSC, 27 AH, 3 OS; no patient had PBC. 96.3% were associated with ulcerative colitis (UC). The prevalence of ALD in patients with UC was 7.6% (CI95% 6.3–9.2) and 1% (CI95% 0.3–2.5%) in patients with Crohn’s Disease. In patients with PSC, 56.4% were men, IBD diagnosis was previous than hepatopathy in 54.3% (median time 8.0 years), subsequent in 10% (7.9 years) and simultaneous, less than 1 year, in 35.7%. Conversely, in patients with AH, 55.6% were women, IBD was first diagnosed in 16% (median time 6.5 years), subsequent in 40% (5.3 years) and simultaneous in 44.0%. The median age at diagnosis was 32.5 (IQR 19.5–50.1) years for PSC and 13.1 (IQR 5.6–16.0) years for AH. Of 77 patients with available data, 97% had extensive colitis, without difference between PSC and AH. Patients with AH had more severe phenotype than PSC (Graphic 1).

High grade dysplasia/CRC was detected in 5 patients (9.6%) all with PSC. Liver transplantation was required in 38.5% of PSC-UC patients and in 20% of AH-UC patients. Regarding endoscopic-clinical concordance, 52% of patients with moderate-severe endoscopic score were asymptomatic with similar behaviour in both hepatopathies.

Conclusion

PSC and AH were the most frequent ALD associated with IBD, mostly extensive UC. In contrast to PSC, AH tended to be diagnosed before intestinal disease and at an earlier age with higher biological and hospital admissions requirement. More than a half of our cohort had an important clinical-endoscopic dissociation, so we emphasise the relevance of the objective measurement of inflammation with colonoscopy in this particular group of patients
P815 Are hospitalised patients with inflammatory bowel disease at increased risk of invasive bacterial infections? Results from POLIBD 2-year cohort study
Authors: Filip R , Gruszecka J
Published: January 2020

Background

The disease itself as well as immunomodulatory and biological therapy are risk factors for invasive bacterial infections in patients with inflammatory bowel disease (IBD). However, there are limited data on risk factors for bacteraemia in the general population of hospitalised patients with inflammatory bowel disease.

The aim of the study was to assess the rate of bacteraemia in hospitalised patients with Inflammatory Bowel Disease and risk factors.

Methods

An observational cohort of hospitalised patients with Inflammatory Bowel Disease, aged 23–65 years, from 2017 to 2019 in a large tertiary hospital localised in Rzeszow (south-eastern Poland). Patients with one or more positive blood culture were reviewed. Those with Carlson comorbidity index of 2 or greater were excluded. Basic descriptive statistic and logistic regression to evaluate risk factors for bacteraemia were used.

Results

Of 727 admitted patients, only 1.24% had bacteraemia (9/727) (8, Crohn’s Disease; 1, Ulcerative Colitis). The most common pathogens were Staphylococcus epidermidis (MRCNS - methicillin-resistant coagulase-negative Staphylococcus - strain resistant to all beta-lactam antibiotics: penicillins, penicillins with a B-lactamase inhibitor, cephalosporin and carbapenem) (4/9 patients) and Escherichia coli (3/9 patients). The mortality rate at 30 days of patients with bacteraemia was 0% (no deaths in IBD patients with bacteraemia observed). Longer hospitalisation (mean length of stay for patients with CD was 42 ± 33 vs. 7.95 ± 17.3, p <0.001; mean length of stay for a patient with UC 15 ± 23 vs. 6.25 ± 15.4, p = 0.004) was associated with an increased risk of bacteraemia. Older age was not associated with an increased risk of bacteraemia (P>0.05). In multivariate analysis, treatment with either anti-tumour necrosis factor α, purine analogues, steroids or amino salicylates was not associated with an increased risk of bacteraemia.

Conclusion

Prolonged hospitalisation, but not Inflammatory Bowel Disease-related treatment, is associated with an increased risk of bacteraemia in hospitalised patients with Inflammatory Bowel Disease.
P818 Venous thromboembolism is rare among hospitalised patients with an inflammatory bowel disease flare: a multicentre retrospective cross-sectional study
Authors: Khoury T , Shafrir A , Kalisky I , Safadi M , Mari A , Mahamid M , H Katz L , Kadah A , Sbeit W
Published: January 2020

Background

Inflammatory bowel disease (IBD) patients have twice the risk of venous thromboembolism (VTE) compared with healthy controls. VTE can occur at both hospitalisation and after discharge. We aimed to assess the prevalence of VTE among IBD patients who were hospitalised with disease flare at three Israeli Hospitals.

Methods

A retrospective cross-sectional analysis including all IBD patients who were admitted with disease flare at Galilee Medical Center, EMMS Nazareth Hospital and Hadassah Medical Center. Exclusion criteria were patients with confirmed diagnosis of hypercoagulable state or patients on drugs with pro-coagulable potential.

Results

Eighty-one patients with overall 114 admissions were included in the study. The average age was 42.2 ± 18.5 years. Sixty-six patients (57.9%) were males. Forty-five admissions (39.5%) were due to ulcerative colitis (UC) flare and 69 admissions (60.5%) were secondary to Crohn’s disease (CD) flare. Twenty-eight patients (24.6%) were smokers. Twenty-five patients (21.9%) and 39 patients (34.2%) were on recent biological and steroid treatment (within 3 months). The mean C-reactive protein and albumin levels at the day of discharge were 4.2 ± 4.6 mg/dl (normal range 0–0.5) and 3.5 ± 0.7 g/dl (normal values above 3.2), respectively. During hospitalisation, 57 (50%), 55 (48.2%), 29 (25.4%), 19 (16.7%) and 8 (7%) patients were treated with intravenous steroids, antibiotics, amino-salicylates, surgery and immunomodulators, respectively. Only four patients (3.5 %) were on prophylactic subcutaneous anticoagulation (enoxaparin) throughout their hospital stay and only 1 patient (0.9%) who have not been on anticoagulation developed in-hospital symptomatic VTE episode. Notably, this patient suffering from CD with ileo-colonic involvement developed subclavian vein thrombosis two day after PICC line insertion for total parenteral nutrition to optimise his nutritional state before performing surgery. The mean hospitalisation length was 6.5 ± 6.6 days.

Conclusion

In-hospital VTE was rare among our IBD patients admitted with disease flare. In fact, the only one VTE event reported in our cohort is probably related to the PICC line insertion and not related to IBD flare. Notably undergoing surgery in our cohort was not correlated with VTE episodes. Further studies are warranted to characterise IBD patients at risk for VTE, to assess the risk factors for in-hospital VTE development and to address further the role of prophylactic anticoagulation among hospitalised IBD patients, mainly those with bloody diarrhoea.
P819 Seroprevalence of Borrelia burgdorferi antibodies in patients with ulcerative colitis
Authors: Dulger A C
Published: January 2020

Background

Lyme disease is a significant zoonotic tick-borne disease with an increasing prevalence in northern hemisphere. The infected tick of the genus Ixodes is responsible for spreading of the disease. Erythema migrans lesions, cranial-nerve (particularlyfacial-nerve) palsy and meningitis, carditis and arthritis are the main manifestations of the disease. Diagnosis of Lyme disease mainly depends on medical history, compatible clinical signs in connection with laboratory findings including more than two IgM bands or more than 5 IgG bands on immunoblot. Ulcerative colitis (UC) is a immun-mediated large bowel disease that is characterised by abdominal pain, bloody diarrhoea and tenesmus due to lymphoplasmocyter infiltration of the mucosal crypts. There have been many studies describing a wide range of genetic, immunologic and environmental risk factors in patients with UC. However, there is no report whether Borrelia burgdorferi antibodies are protective in patients with UC.

Methods

This was a single centre retrospective observational study of patients with UC vs. age and -matched healthy controls. The medical records of gastroenterology clinic patients with UC between July 2018 and May 2019 were reviewed. At total, 51 (15 female; the mean age 46 years; 35 of them were using anti-TNF agents) UC patients have tested for Borrelia antibodies. On the other hand, 66 age-matched otherwise healthy control subjects (36 female; mean age was 54 years) were selected as comparator group.

Results

While, only 2 patients (3%) were tested positive for Borrelia bugdorferi (BB) Ig G antibody, 15 subjects (22.7%) had a positive result for BB Ig G antibody in control group. There was a significant difference between groups in terms of BB Ig G seropositivity (p < 0.001). found significantly low rates of BB Ig g seroprevalance in patients with UC. The reason of this phenomenon is unclear.

Conclusion

The low rate of BB Ig G in patients with UC may have been related to presence of aberrant NK T cells in colonic mucosa. Evidence suggests a inverse link between Lyme arthritis and elevated levels of NK T cells, therefore we hypothesise that UC-related T cells regulates Borrelia trafficking. On the other hand, it has been a well known fact that UC is also related to improvement in sociodemographic development in developing world. Lyme disease is mostly driven by tick exposure in rural areas and mostly seen in forestal areas of the world rather than city centres. This phenomenon may also compatible with real life prevalence models of the inflammatory bowel diseases. In conclusion, these data indicate, for the first time, the inverse association between UC and seropositivity of BB antibodies could lead to design new diagnostic and prognostic tools.
P827 The clinical phenotype of collagenous colitis is associated with T-cell-related genetic variants
Authors: Roda G , Piovani D , Prantesh J , Gordon I , Asselta R , Duga S , Vetrano S , Bonovas S , Harpaz N , Danese S , Peter I , Colombel J F , Rieder F
Published: January 2020

Background

Collagenous colitis (CC) is a common cause of chronic diarrhoea and highly associated with immune-mediated diseases. The aetiology of CC may involve a dysregulated immune response in genetically predisposed individuals. Our preliminary data identified ancestral HLA haplotype 8.1 and non-HLA CC risk loci being associated with CC. We here carried out the first genotype/clinical phenotype association study in a large cohort of CC patients.

Methods

This study combined Immunochip data from 300 patients with centrally read histologically confirmed CC with retrospectively collected clinical data in a quarternary care centre. We tested 21 SNPs previously associated with CC (Roda et al. submitted) for their genetic association with selected phenotypic variables (histology, autoimmune diseases, relapse rate, concomitant medications, number of bowel movements at diagnosis, sex and response to therapy). We performed univariable linear, logistic and Poisson regression analyses for associations with the outcome variables.

Results

300 CC patients [median age 63 (IQR: 54–63); 80% female] were included after quality control. The genetic variants associated with clinical phenotypes can be found in Table 1. We identified a link of several genes involved in T cell function with CC phenotypes. IL2A was associated with risk of additional autoimmune disorders reinforcing the possible role of T cells in both diseases. RUNX3 involved in Th17 cells and TGF-beta pathways was a risk factor for IEL infiltrates. Notably, we identified two protective factors: one near C5orf30, previously implicated in rheumatoid arthritis and collagen-induced arthritis, was linked with a reduced rate of flares; ZNF365, involved in uric acid excretion and associated with ileal Crohn’s disease, was found protective in relation to collagen band thickness. When assessing non-genetic variables, number of bowel movements correlated with collagen band thickness (p < 0.01); concomitant use of sertraline was protective for relapse rates (p = 0.021), and current smoking (p = 0.022) was linked with relapse rates.

Conclusion

We found a significant association of T-cell-related genes and CC clinical phenotypes. Additionally, our study identified current smoking and increased collagen band thickness as risk factors for disease severity.
P829 Methylation patterns in dysplasia in inflammatory bowel disease patients
Authors: da Luz Rosa I A , Silva P , Mata S , Magro F , Carneiro F , Peixoto A , Silva M , Sousa H , Roseira J , Parra J , Barosa R , Vieira A , Brito M J , Lago P , Coelho A , Moleiro J , Silva J , Fonseca R , Albuquerque C , Pereira A D
Published: January 2020

Background

Inflammatory Bowel Disease (IBD) with colonic involvement increases colorectal cancer risk. However, the distinction between IBD related and sporadic dysplasia in IBD patients is difficult. Some data favours the importance of abnormal DNA methylation in IBD-related carcinogenesis. Our study aimed to define methylation patterns in patients with a colonic cancer or dysplasia diagnosis following an IBD diagnosis.

Methods

Multicentric cross-sectional study- 91 samples from colonic mucosa with/without dysplasia from 9 patients with IBD-related dysplasia/cancer and 26 patients with IBD and sporadic dysplasia/cancer were included. Methylation patterns of CpG islands in the promoter regions of 67 genes were studied by Methylation-specific Multiplex Ligation-dependent Probe Amplification.

Results

Mean age at IBD diagnosis: 42±16 years; at dysplasia diagnosis: 56± ± 14 years. Twenty-nine patients had ulcerative colitis. Twenty-five patients had at least 1 lesion endoscopically described as adenoma-like, 4 at least 1 non-adenoma like, 3 had cancer and 3 had dysplasia in flat mucosa. No patient had both adenoma-like and non-adenoma-like lesions. Patients with an IBD-related lesion were significantly younger at IBD diagnosis (p = 0.003) and at dysplasia/cancer diagnosis (p = 0.039). Promoter methylation of IGF2, RARB, ESR1, CHFR, CDH13, WT1, GATA5, WIF1 genes was significantly associated to dysplasia/cancer; methylation of MSH6, TIMP3 was significantly associated to IBD-related dysplasia/cancer. Promoter methylation of MSH6, MSH3, RUNX3, CRABP1, TP73, RARB, CDH13, PAX5, WT1, THBS1, TP53, SFRP1, WIF1, APAF1, BCL2 genes was significantly associated to active IBD.

Conclusion

Methylation analysis, namely of MSH6, may contribute to the classification of dysplastic lesions in IBD– to be further tested in prospective studies.
P836 Biomarkers response to anti-TNF treatment in Crohn’s disease through the intestinal microbiota
Authors: Sanchis L , Manresa S , Martínez J F , Valls M , Iborra M , Paredes J M , Boscá M , Huguet J M , Gil R , Maroto N , Rodriguez J , Cortés X
Published: January 2020

Background

The alteration of the intestinal microbiota is a necessary requirement for the development of Crohn’s disease (CD). The anti-TNF alfa (TNF) treatment has radically changed the prognosis of the disease, modifying the therapeutic objective which is the induction and subsequent maintenance of mucosal healing. It is unknown, if this cure/improvement correlates with changes in the microbiota. The objectives of the study were: evaluate the changes in the microbiota in CD pre and after six months with TNF, determine the changes in the microbiota based on the clinical-biological response to TNF and calculate the F. prausnitzii/E. coli (F/E) ratio as an indicator of therapeutic response.

Methods

This was a prospective observational multicentre study that included 27 patients with CD who started treatment with TNF. 16 healthy individuals were included to establish the local healthy microbiota. The existence of disease activity was determined using the Harvey-Bradshaw index (HBI), analytical parameters such as C-reactive protein and faecal calprotectin measured at the beginning of the study, 3 and 6 months; classifying patients as responders (R) and non-responders (NR). The composition of the microbiota (the alpha and beta diversity), as well as the F/E ratio as indicators of dysbiosis, were evaluated by massive genomic sequencing, at the date of inclusion and 6 months after starting TNF through faecal samples.

Results

Prior to TNF, the loss of Clostridia class genera, producers of short chain fatty acids, as well as the significant increase (p <0.01) of Proteobacteria, highlighting the Escherichia/Shigella genus with respect to healthy controls. The microbiota varied according to response to the TNF: the Proteobacteria phylum affected in NR with respect to healthy and R group (p <0.005). Although, R group (13/27) significantly increase Clostridia class bacteria (such as Faecalibacterium) as well as alpha diversity with respect to NR group (p <0.01), with a tendency towards a microbiota similar to controls. There is a significant association (p <0.001) in the F/E relationship between the R group and NR group The F/E ratio was the most accurate (area under a curve of 0.87), when, we compare this value with HBI and CF as biomarkers of response to TNF.

Conclusion

The anti-TNF treatment allows partial restoration of the intestinal microbiota in responders with a tendency towards eubiosis, with respect to non-responders. The determination of F. prausnitzii/E. coli ratio can provide a reliable indicator of response to anti-TNF treatment in Crohn’s disease.
P843 Intestinal microbiota changes according to disease activity in patients with ulcerative colitis
Authors: Barberio B , Bertazzo E , Marinelli C , Massimi D , Ghisa M , Gubbiotti A , Casadei C , Lorenzon G , Zingone F , D’Incà R , Savarino E V
Published: January 2020

Background

Intestinal dysbiosis has been consistently described in patients with inflammatory bowel disease (IBD), particularly about changes in gut microbiota’s composition and reduction of biodiversity. The identification of a characteristic microbiota could bring to a better understanding of ulcerative colitis (UC) pathogenesis and to find possible microbial markers of disease activity in UC. The primary purpose of our study has been to evaluate the different compositions of gut microbiota between subjects with UC and healthy controls and between patients in remission and patients with severe colitis.

Methods

A total of 64 subjects were enrolled: 18 with severe colitis (sUC), 22 UC patients in remission (rUC) and 24 healthy controls (HC). Faecal samples were analysed using the Illumina technique (16S NGS). Statistical analyses were performed with Kruskal–Wallis test. Shannon index and equipartition index were calculated to evaluate α-diversity between the samples and then were compared trough Student’s t-test.

Results

Significant statistical differences in relative frequencies of phyla exist between UC patients and HC: frequencies of the phyla Firmicutes (with a median of 48.10% in UC and of 34.31% in HC, p < 0.001) and Actinobacteria (0.67% in UC and 0.17% in HC, p = 0.006) were higher in UC, while frequencies of the phyla Bacteroidetes (48.82% in UC and 54.97% in HC, p = 0.005), Cyanobacteria (0% in UC and 1.28 in HC, p < 0.001) and Verrucomicrobia (0% in UC and 2.58% in HC, p < 0.001) were lower in UC. Significant statistical differences in relative frequencies of phyla were found between patients with rUC and sUC: Fusobacteria (median 0.005% for sUC, 0% for rU, p = 0.05) and Proteobacteria (7.88% in sUC, 3.22% for rUC, p = 0.015) were higher in patients with sUC. There was no difference between the relative frequencies of the other phyla (Firmicutes, Bacteroidetes, Actinobacteria, Cyanobacteria and Verruccomicrobia). The gut microbiota biodiversity has been evaluated through Shannon index and equipartition index. Biodiversity was increased in UC patients respect to HC, while it was similar between rUC and sUC patients.

Conclusion

The difference between the gut microbiota of rUC and sUC patients is mainly the relative frequency of the phylum Proteobacteria, increased in sUC patients. The α-diversity is similar in these two groups, suggesting a limited role in the influence of the course of the disease.
P844 Higher proportions of genera and species in the Firmicutes phylum are associated with a healthy pouch compared with patients with chronic pouchitis
Authors: Segal J , Mullish B , Clark S , Marchesi J , Hart A
Published: January 2020

Background

Studies highlighting changes in bacterial composition in the ileoanal pouch are limited by heterogeneity in analysis techniques and sampling strategies Therefore, caution must be used when interpreting microbiota data. Similar to findings in IBD, a decrease in bacterial diversity and ‘dysbiosis’ are associated with acute and chronic inflammation in the pouch. Changes in Clostridium spp. and E. coli are associated with inflamed pouches and treatment response. This study aimed to compare the bacterial microbiota composition in patients with chronic pouchitis who responded to antibiotics vs. those who did not.

Methods

Patients with confirmed chronic pouchitis defined by a pouch disease activity score ≥ 7 were treated with antibiotics. If patients were already on antibiotics, they were offered the opportunity to stop. Follow up was at 4 weeks to check clinical status. Patients who came off antibiotics who flared were given the opportunity to restart the antibiotics to prevent deterioration. Patients were analysed as either on antibiotics if they received antibiotics 2 weeks prior to the clinic or off antibiotics if they had stopped all antibiotics 2 weeks prior to follow-up. Stool was collected from patients on follow-up and DNA was extracted from this stool. Sequencing was performed on an Illumina platform. Statistical analysis was performed using STAMP 2.1.3 software with Welch’s two-sided t-test for comparing two groups with false discovery rate correction.

Results

There were 28 patients in the cohort; 23 patients with chronic pouchitis and 5 healthy controls who had never had pouchitis. Ten patients were female. The median age of the cohort was 47 years (range 26–74 years). A total of 12 samples on antibiotics and 11 off antibiotics. There were 10 responders and 13 non-responders. There were no differences between responders and non-responders and no differences in those taking antibiotics vs. those not taking antibiotics with chronic pouchitis. Healthy controls had significantly higher proportions of clostridium genera (p = 0.01) when compared with patients who fail to respond to antibiotics. Healthy controls had significantly higher proportions of lachnospiraceae species (p = 0.03) when compared with those that responded to antibiotic treatment for chronic pouchitis.

Conclusion

In a small cohort with chronic pouchitis we were unable to detect any bacterial differences between those that responded to antibiotics vs. those that did not. Despite this a healthy pouch had significantly higher proportions of Firmicutes species and genera which has been supported in other literature.
P853 Amoebic colitis mimicking inflammatory bowel disease: a report of four cases
Authors: Tufail Q , O’Meara D , Thi A , Lim F , Richards C
Published: January 2020

Background

Amoebic colitis, caused by Entamoeba histolytica is an emerging diagnostic challenge for gastroenterologists in developed countries. Due to the similarity of symptoms and endoscopic findings, it can be easily misdiagnosed as inflammatory bowel disease (IBD) with a potentially devastating outcome especially if patient receives immunosuppression. The aim of this study is to look into the misdiagnosed cases to identify the challenges in differentiating amoebic colitis from IBD and to outline strategies to avoid this

Methods

Clinical and electronic case notes for the 4 patients, who were misdiagnosed as IBD between September 2015 to February 2019 at University Hospitals of Leicester U.K. were reviewed. The histology of resected colon specimens and endoscopic colonic biopsies were re-reviewed specifically for amoebic trophozoites.

Results

Three were male and 1 female. 1 patient was Caucasian while 3 patients were British Asian. Their mean age was 47.75 years (range 28–71). 3 cases were new IBD presentations while 1 patient was misdiagnosed as IBD since 2015. Two patients had a travel history to India and travelled to South East Asia 12 months prior to presentation. The travel history for 1 patient was not available. All 4 cases presented with bloody diarrhoea and had an endoscopic examination around the time of diagnosis which suggested acute inflammation likely IBD. Three were treated as ulcerative colitis while 1 patient was treated as Crohn’s disease. One patient required rescue therapy with cyclosporin while on intravenous steroids. As clinical symptoms worsened with rescue therapy, the patient required a subtotal colectomy. Similarly the patient who was treated for Crohn’s disease with Azathioprine and intravenous steroids, required subtotal colectomy due to recurrent flare ups. The other two cases were successfully treated with antimicrobial after the diagnosis of amoebic colitis although one of them received adalimumab prior to the correct diagnosis. The diagnosis of amoebic colitis was made through histological examination of the resected colon in 2 patients, colonic biopsy in 1 patient and stool E. histolytica DNA polymerase chain reaction (PCR) in 1 patient.

Conclusion

All 4 cases who were misdiagnosed as IBD had the diagnostic challenge of differentiating IBD from amoebic colitis due to similarity of symptoms and the endoscopic findings. Travel history is an important clue and should be considered for any patient presenting with colitis. New local guidelines were introduced to screen all patient with colitis for E. histolytica with serology and stool PCR. Patients requiring immunosuppression for suspected IBD are commenced on antimicrobial cover until E. histolytica results are available.
N01 Factors related to self-medication with corticosteroids, aminosalicylates or analgesics and reasons given by patients with ulcerative colitis from Spain
Authors: Cañas M , Mesonero F , Rodriguez-Lago I , Savini C , Saldaña R , Feo-Luca L , FERNANDEZ S , Cea-Calvo L , Juliá B
Published: January 2020

Background

Self-medication, when agreed with the treating physician, is an essential component of self-care. We describe the associated factors and the reasons related to the practice of self-medication with steroids, aminosalcylates (AS) or analgesics in patients with ulcerative colitis (UC) in Spain.

Methods

Information was anonymoulsy provided by patients through a web-based cross-sectional survey developed by 3 inflammatory bowel disease (IBD) experts from the Spanish working group on IBD (GETECCU), one nurse from the Spanish nursing working group on IBD (GETEII) and two patients from the Spanish confederation of associations of patients with IBD (ACCU). Participants voluntarily answered to the survey based on their own experiences from February to April 2019. Reasons for self-medication are described as frequencies and associated factors through logistic regression models.

Results

A total of 546 patients (61% women, mean age 40 years old) responded. Of these, 36 (7%) patients self-medicated with corticosteroids, and was associated with higher number of UC self-reported flares during the past year [OR 7 (95% CI: 1–32), p < 0.001] and follow-up by a general gastroenterologist instead of in an IBD unit [OR 0.08 (0.01–0.5), p = 0.007]. Self-medication with AS was reported by 90 patients (16%) [oral 20 (22%) and topic 70 (78%)], and was associated with treatment with topical AS [OR 3 (95% CI: 2–4), p < 0.001]. Finally, 320 patients (59%) self-medicated with analgesics and this was associated with female gender [OR 2 (95% CI: 1–3), p < 0.001], need of intravenous (IV) biological therapy [OR 3 (95% CI: 2–5) p < 0.001] and emergency room visits within the past year [OR 3 (95% CI: 2–4), p < 0.001]. The main reasons for self-medication were ‘need for quick relief of symptoms’, ‘fear of worsening’ and, for AS, ‘agreed with the doctor’ (Table 1).

Conclusion

Self-medication in UC is not a common practice, but most of the times it is not agreed with the treating physician. Self-medication with analgesics was more frequent, probably reflecting a need of self-care. Female sex, number of flares, IV treatment, and need of emergency room care were factors associated to self-medication.

This project was endorsed by GETECCU, GETEII, ACCU and funded by MSD Spain.
N03 Disease burden of patients with inflammatory bowel disease from the viewpoint of QOL and depression
Authors: Takahashi M , Aoyama N , Nunotani M
Published: January 2020

Background

Inflammatory bowel disease (IBD) can lead to a decreased quality of life (QOL), and mental care is necessary for patients with IBD. Disease burden (patient burden caused by a disease) attracts attention from the viewpoint of QOL and mental care. However, the relationship between QOL and depression in patients with IBD has not yet been adequately researched. Therefore, we aimed to examine disease burden and the relationship between QOL and depression in Japanese patients with IBD.

Methods

The present study enrolled 200 patients with ulcerative colitis (UC) and 31 patients with Crohn’s disease (CD) who were treated in Aoyama Clinic between July 2018 and September 2018. We evaluated QOL using a 24-item questionnaire which we made originally based on previous studies. Next, we evaluated depression according to the Patient Health Questionnaire-9 (PHQ-9). Partial Mayo score of less than 2 points indicated UC remission, whereas the CDAI score of less than 150 points denoted CD remission. We analysed the difference in QOL and depression scores between UC and CD, the age or sex, the disease activity, and the time since diagnosis using chi-square test. The association between QOL and depression scores was analysed using Spearman’s rank correlation coefficient. This study was approved by the Aoyama Clinic Ethical Review Board (2018-1).

Results

Decrease in QOL (scale ≥ 7) and depression (PHQ-9 score ≥ 10) in active phase were higher than those in remission phase (decrease in QOL among UC in active phase: 6.3 ± 4.8, among UC remission phase: 2.2 ± 3.4; p < 0.05, among CD in active phase: 3.8 ± 3.3, among CD remission phase: 2.3 ± 2.7, depression score among UC in active phase: 4.9 ± 4.8, among UC remission phase: 3.1 ± 3.8; p < 0.05, among CD in active phase: 3.8 ± 3.3, among CD remission phase: 2.3 ± 2.7), but no difference was noted in the age or sex and disease duration. Meanwhile, the QOL decrease and depression score in UC as a whole (r = 0.397, p = 0.000) positively correlated. In remission, the correlation in women (r = 0.385, p = 0.000) was considerably higher than that in men (r = 0.290, p = 0.007). Factors regarding QOL decrease in remission were carcinogenesis, defecation frequency, surgery, economic matters, relapse, lavatory, and heredity.

Conclusion

Even in UC remission and when QOL decrease is mild, women strongly feel a mental burden; thus, they should be given the appropriate care. Disease burden including QOL and mental care is an important point that medical staff and physicians should deal with together.