Subgroup Of Inflammatory Bowel Disease Patients Research Articles

Increased Serum Apelin Levels in Patients with Inflammatory Bowel Disease

Apelin has been implicated in the pathogenesis of several chronic inflammatory diseases through mechanisms related to endothelial cells dysfunction. There is evidence of increased apelin levels in mesenteric adipose tissue and colonic epithelium in patients with inflammatory bowel disease (IBD), but their significance remains unclear. We aimed to measure serum apelin (SA) levels in patients with IBD and to evaluate an association with disease characteristics. SA levels of 104 IBD patients and age and sex matched healthy controls (HCs) in a 1:1 ratio were compared. SA-13 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Mean SA levels were increased in IBD patients compared to HCs (1996.29 ± 1592.96 pg/mL vs. 1552.99 ± 809.64 pg/mL, p = 0.012). Both patients without and with cardiovascular disease (CVD) had increased SA levels (2076.44 ± 1714.74 pg/mL vs. 1525.75 ± 818.74 pg/mL, p = 0.011 and 1743.01 ± 1116.26 pg/mL vs. 1283.92 ± 726.85 pg/mL, p = 0.035, respectively). An inverse association between mean SA levels and a history of musculoskeletal extraintestinal manifestations in the subgroup of IBD patients without CVD was found (p = 0.043). The present study—the first to evaluate SA levels in patients with IBD—showed that IBD patients have higher levels of SA compared to HCs. The potential role of SA in IBD merits further investigation in larger studies.

P898 Uncovering of tissue-associated risk factors that lead to different genetic risk profiles across Inflammatory Bowel Disease patients

Abstract Background Polygenic risk scores (PRSs) are emerging as a tool of choice to summarize the risk of disease in each individual. The calculation of PRSs is based on genetic variants and effect sizes obtained from large studies using many different cohorts of patients. In inflammatory bowel disease (IBD), GWAS meta-analysis based on over 75.000 IBD patients from different multi-ethnic cohorts has discovered around 300 independent associated variants. This information can be used to estimate genetic risk and detect individuals with several higher odds of developing the disease during their lifetime. However, PRSs usually do not incorporate functional information about causal variants, and the potential for heterogeneity in effect sizes among subgroups of individuals is disregarded entirely. Hence, PRSs might be ill-suited to capture subcomponents of genetic risk that may account for key differences among specific etiological profiles of patients. Fine mapping of GWAS causal variants show an enrichment in variants associated with changes in gene expression in specific tissues, suggesting that risk of complex diseases is led by an accumulation of variants that change the transcriptome towards a pathogenic profile. To explore the biological nature of IBD risk we propose a tissue transcriptional risk (t-TRS) score Methods We perform Transcription Wide Association studies (TWAS) based on gene expression prediction models in nine IBD relevant tissues and a meta-analysis of European IBD GWAS. We next estimated the t-TRS of people from UK biobank and compared its prediction performance against PRS measuring the area under the curve (AUC) Results We performed nine TWAS studies and obtained 636 genes that are genome wide significant in at least one tissue. Although eQTL weights are shared across tissues, we observe a high number of tissue specific signals, specifically in terminal ileum and lymphocytes. Pathway enrichment analysis on the 600-gene set showed enrichment of immune functions like “Signaling by interleukins” and “Antigen presentation”. We also show the predicting value of t-TRS is better than the PRS in all tissues. In addition, clustering of individuals according with t-TRS yield 3 subgroups of patients Conclusion Functionally informed genetic predictors allow not only to better stratify patients, but also to discover which are the biological pathways that accumulate risk variants in subgroups of IBD patients

P549 Oxidative stress and antioxidant capacity biomarkers in adults and children with IBD: current update from OxIBDiet trial

Abstract Background Oxidative stress takes part in the pathogenesis of inflammatory bowel disease (IBD). The OxIBDiet (NCT04513015) is a multicentre ongoing project designed to evaluate oxidative status of IBD children and adults and to estimate the effects of an antioxidant diet in a subgroup of IBD patients. Methods The total antioxidant capacity, measured through the ferric reducing ability of plasma (FRAP, µmol/equivalent FeSO4) and oxygen radical absorbance capacity (ORAC, plasma trolox equivalents), lipid peroxidation, as serum levels of the thiobarbituric acid reactive substances (TBARs, µmol MDA) and the degree of protein oxidation, as advanced Oxidation Protein Products (AOPP, µmol/g protein), were measured. Activities (nmol/min/mg of protein) of the main antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione S-Transferase (GST) and catalases (CAT) were evaluated in PMNs cells and plasma. Oxidative biomarkers were correlated with clinical parameters. Results Twenty-three adults (mean age: 33,7, IQR 20,5 years, 42% male, 63% in remission) and 41 children with IBD (mean age: 12, IQR 4 years, 52% male, 61% in remission) were enrolled and compared respectively to 29 adults and 23 children controls. FRAP was significantly reduced in IBD children compared to adults (202 vs 277 mcmol/eq FeSO4, p<0.0001) and was correlated with age (r=0.5718; p<0.0001). Plasmatic ORAC was significantly higher in IBD children compared to controls and adults with IBD (Figure 1). ORAC in IBD subjects resulted inversely correlated to age (r= -0.4417, p=0.0004) and use of biologics (r= -0.4246, p=0.0006). AOPP were elevated in paediatric IBD versus controls (p=0.0049) and correlated to the diagnosis of Crohn at the multiple regression analysis (r=-0.732; p=0.023). The main antioxidant enzymes plasmatic activities are shown in table 1. Conclusion The antioxidant system and therefore the antioxidant capacity is significantly different in IBD compared to controls and evolve from paediatric to adult age, maybe as an effort to compensate the persistent redox imbalance and inflammation. Involvement of antioxidant cascade in IBD pathogenesis and role in therapeutic approach will be better outlined by the final results.

Neuropathy and primary headaches affect different subgroups of inflammatory bowel disease patients.

Peripheral neuropathies (PN) and primary headaches (PH) are common comorbidities in inflammatory bowel disease (IBD) patients. We aimed to evaluate whether PN and PH affect the same subgroups of IBD patients. Since 2004, we established a cohort study to evaluate neurological diseases in IBD patients. Over 2years, all consecutive (N = 155) IBD patients (either Crohn's disease (CD) or ulcerative colitis (UC) were evaluated for the presence of PN and PH. PH were also evaluated in dyspeptic patients (N = 84) and IBD relatives (controls, N = 101). After neurological evaluation, symptomatic patients underwent skin wrinkling test to evaluate small fiber function and/or electromyography. Headaches and migraine were more prevalent in IBD than control patients: 52.3 and 34.2% vs. 40.6 and 20.8% (P < 0.05). Migraine was 2.6 times more common in CD patients than controls (CI = 1.34-5.129) and 8.6 times (13.3 times in the CD group) more common in men with IBD (P < 0.05). Headache and migraine were also more common in dyspeptic patients (P < 0.05). Chi-square, univariate, and multivariate regression analysis did not disclose any association between PN, headache, or PH (P > 0.05). Multivariate regression analysis disclosed that headaches were more prevalent in women, co-existing psychiatric disease, IBD, CD, and UC. After age, gender distribution, and prevalence of hypertension and psychiatric diseases were matched among the groups, there were still differences in the prevalence of headaches and migraine among IBD, CD, and UC versus control patients. In summary, PH and PN are common in IBD and do not affect the same subgroups of patients.

Diagnostic yield from colon biopsies in patients with inflammatory bowel disease and suspected cytomegalovirus infection: is it worth it?

BackgroundPatients with inflammatory bowel disease (IBD) are often immunosuppressed and are at risk for reactivation of latent cytomegalovirus (CMV) infection. We examined the diagnostic yield from colon biopsies in IBD patients with suspected CMV infection.MethodsPatients above 18 years of age who underwent testing for CMV on colon biopsies between January 1st, 2012, and December 31st, 2015, were identified from a pathology data base. A positive CMV result was included only if testing included both hematoxylin/eosin staining and immunohistochemistry from two or more biopsy samples.ResultsOne hundred twenty-five patients met the inclusion criteria. Of these, 99 had a diagnosis of IBD: 30 with Crohn’s disease, 63 with ulcerative colitis, and 6 with indeterminate colitis. As regards treatment, 21.2% of the patients had biologic therapy alone, 13.1% received immunomodulators, and 11.1% were treated with combined biologic and immunomodulator therapy within 3 months of the colon biopsy. In addition, 32.3% of the patients were on steroids. Of the 99 IBD patients, only 1 had biopsy-proven CMV colitis.ConclusionThe yield from colon biopsies with hematoxylin/eosin staining and immunohistochemistry to test for CMV in IBD flare is very low. Further multicenter studies with large numbers of patients are needed to compare all testing modalities in the same cohort of patients. This may help identify which subgroup of IBD patients are likely to benefit from specific modalities of CMV testing, with potential cost-saving implications.

Risk Factors for Rehospitalization Within 90 Days in Patients with Inflammatory Bowel Disease.

Care of patients with inflammatory bowel disease (IBD) poses a significant burden to the health-care system. Repeat hospitalization in subgroups of IBD patients seems to be a large part of this issue; however, there are limited data examining the characteristics of these patients. The aim of this study was to characterize admission patterns in patients with IBD at a tertiary-care center and to identify preventable risk factors of 90-day readmission after an index IBD admission. Retrospective analysis was performed extracting data from an electronic medical record over a 2-year period. Three hundred fifty-six patients were admitted at least once during the 2-year study period for an unplanned IBD-related reason. Of these, 48.9% were admitted once, 38.2% were admitted 2 to 4 times, and 12.9% were admitted 5 or more times during the study period. Patients with any admission within 90 days before index were excluded; n = 33. One hundred two patients had experienced a readmission by 90 days after index admission. Numerous demographic and medical factors were examined for association with readmission. The final Cox model included 3 variables: depression (HR = 1.99, 1.33-3.00), chronic pain (HR = 1.88, 1.14-3.10), and steroid use in the previous 6 months (HR = 1.33, 0.92-2.04). Our findings suggest that patients with depression and chronic pain are at greatest risk for a readmission within 90 days after an initial IBD admission. Disease activity, represented by steroid use in the previous 6 months, was not related to readmission. Addressing these problems in the outpatient setting may reduce future hospitalizations.

Sa1247 Risk Factors for Re-Hospitalization Within 90 Days in Patients With Inflammatory Bowel Disease Are Not Related to Disease Activity

Background: Previous studies have demonstrated that the care of inflammatory bowel disease (IBD) patients poses a significant burden to the healthcare system. More than one and a half million people in the United States suffer from ulcerative colitis (UC) and Crohn's disease (CD) and these patients require more frequent hospital admissions than non-IBD patients, and have an increased average length of stay. Moreover, hospital care for IBD patients has been shown to be twice as expensive as that for non-IBD controls. Repeat hospitalization in subgroups of IBD patients appears to be a large part of this issue, however there is only limited literature examining the characteristics of IBD patients that are associated frequent hospital use. Aims: To characterize admission patterns in patients with IBD at a tertiary care referral center, and identify preventable causes of 90-day readmission after an index IBD admission. Methods: Data was gathered retrospectively from a tertiary-care IBD referral center. Study subjects included all patients age 18 or older with a known diagnosis of IBD, who were admitted at least once between January 1st, 2011 and December 31st, 2012 for a non-elective, IBD-related reason. Hospital billing records were searched using the Research Patient Data Registry. Univariate analysis was performed. A cox proportional hazards model was developed with covariates felt a priori to be related to readmission. Forward selection was performed. Results: 356 patients were admitted at least once during the 2-year study period for an unplanned, IBD-related reason. 208 (58.4%) had CD and 148 (41.6%) had UC. The mean age at time of index admission was 41.7 years (SD +/17). Women accounted for 62% (n = 220). 125 patients had experienced a re-admission by 90 days and no patients were censored prior to 90 days. The initial model contained 19 covariates. Depression and steroid use in the prior 6 months (a marker of active disease) were forced in. After forward selection the final model included four variables, depression (HR=2.06, 1.42-2.98), chronic pain (HR=1.87,1.19-2.94) etoh use (HR=2.43, 1.21-5.29) and Remicade use (HR=1.15, 0.76-1.72).The proportional hazard assumption was then tested on using Martingale residuals for each of the four variables in the final model and all resulted in non-significant p-value. Conclusions: These findings suggests that patients with depression, chronic pain, and who drink alcohol are at greatest risk for a re-admission within 90 days after an initial IBD admission. Disease activity, represented by steroid use in the prior 6 months, was not related to re-admission. Our study identified that comorbid psychiatric disease, chronic pain, and substance abuse are associated with repeat hospitalization. Addressing these problems in the outpatient setting may reduce future hospitalizations in IBD patients. Table 1: Cox Proportional Hazard Model for 90-day Readmission

Discriminatory Ability of Calcaneal Quantitative Ultrasound in the Assessment of Bone Status in Patients With Inflammatory Bowel Disease

A high incidence of bone disease in patients with inflammatory bowel disease (IBD) requires frequent monitoring of skeletal status and, for that reason, evaluation of radiation-free technology is an issue of interest. Our objective was to appraise the parameters of calcaneal quantitative ultrasound (QUS): broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (QUI), and establish their t-score values to investigate discriminatory ability of QUS in IBD patients with metabolic bone disease. The study included 126 patients (Crohn’s disease [ n = 94] and ulcerative colitis [ n = 32]), and 228 age- and sex-matched healthy volunteers. Bone status was evaluated on the same day by calcaneal QUS and dual-energy x-ray absorptiometry (DXA) at spine (L1–L4) and total hip. All QUS measurements were lower in patients compared with healthy controls (BUA p < 0.001; SOS p < 0.001; QUI p < 0.001) and correlated significantly but inversely with disease duration (r = –0.3, p = 0.002). There was no difference with respect to type of disease (Crohn’s disease or ulcerative colitis) or corticosteroid therapy. All three QUS t-scores were significantly lower in patients who had previously sustained fragile fractures ( n = 28) than in those without fracture in their history ( n = 98) (t-scores: BUA –2.0 vs. –1.3, p = 0.008; SOS –2.1 vs. –1.4, p = 0.02: QUI –2.3 vs. –1.5, p = 0.009). Axial DXA was not significantly different between the fracture and nonfracture patients (–1.7 vs. –1.2, p = 0.1), whereas total hip DXA showed a discriminatory power between the two (–1.6 vs. –0.7, p = 0.001). Patients with t-score < –1.0 scanned by DXA were classified as bone disease. The sensitivity of QUS to identify bone disease was 93% and specificity 63%. The sensitivity of QUS to detect osteopenia was 84% and 72% for osteoporosis. Alternatively, lower negative QUS t-score cutoff ≤ –1.8 identified 83% of osteoporosis at lumbar spine and 100% at total hip. All three QUS variables had t-scores less than –1.8 when osteoporosis was detected at both spine and hip. However, the subgroup of IBD patients with QUI t-score cutoff ≤ –1.8 still included 26% of individuals with normal bone status. Calcaneal QUS measurements may identify patients with IBD who are at a higher risk of fracture independently of DXA measurements. However, QUS showed poor agreement with bone status scanned by DXA and a low discriminatory power between osteopenia and osteoporosis. (E-mail: niksa_turk@net.hr)

Screening for dysplasia and TP53 mutations in closed rectal stumps of patients with ulcerative colitis or Crohn disease

Background: Patients who undergo colectomy due to intractable chronic inflammatory bowel disease (IBD) may keep a closed rectal stump for several years, which may be at increased risk of malignant transformation owing to residual inflammatory activity. We examined a hospital series of patients with ulcerative colitis or Crohn colitis to describe the clinical, endoscopical and histological features of the closed rectal stump and to screen for dysplasia and mutations in the TP53 tumour suppressor gene. Methods: During rigid proctoscopy, rectal mucosal biopsy specimens and rectal lavage fluid were collected from 42 patients. Biopsy specimens were examined histologically, and genomic DNA extracted from frozen biopsies and lavage fluid was analysed for mutations in TP53 exons 4–9. Results: The median disease duration was 8.5 years (range 1.3–34 years). No endoscopic or histological signs of dysplasia or carcinoma were seen and no mutations in the TP53 gene were detected in any biopsy or lavage fluid specimens. Histological moderate to severe mucosal inflammation was present in 78% (33/42) of the patients, however, and rectal stump involution was noted in 43% (18/42). Conclusion: No signs of malignancy or premalignant degeneration were detected in this prospective series of IBD patients with a closed rectal stump. Although this is reassuring for patients, the presence of moderate to severe inflammation in the majority of rectal stumps indicates a role for adjuvant molecular markers to improve colorectal cancer surveillance on this subgroup of IBD patients.

Prevalence of factor V Leiden and the G20210A prothrombin-gene mutation in inflammatory bowel disease.

A hypercoagulable state has been hypothesized as a contributing factor in the pathogenesis of inflammatory bowel disease (IBD); moreover, such patients have an increased risk of thrombotic complications. The aim of the present paper was to study the prevalence of the two most important causes of inherited thrombophilia: factor V Leiden and the G20210A prothrombin-gene mutation in patients with Crohn's disease (CD) and ulcerative colitis (UC). Fifty-two patients affected by IBD (33 UC and 19 CD, 16 female and 36 male; mean age, 42 years) and 156 healthy controls (48 female and 108 male; mean age, 37 years) were studied. Seven out of 52 patients (13%) had previous thrombotic events. High molecular weight DNA was analysed for the presence of factor V Leiden and the G20210A prothrombin-gene mutation. One out of 52 IBD patients (1.9%) and three out of 156 control subjects (1.9%) were heterozygous for factor V Leiden. One IBD patient (1.9%) and four healthy controls (2.6%) were heterozygous for the prothrombin-gene mutation. The prevalence of the two mutations was similar in patients and controls. In the subgroup of IBD patients with previous thrombotic events, only one patient was heterozygous for the prothrombin-gene mutation. Factor V Leiden and the G20210A prothrombin-gene mutation do not seem to play a major role in the pathogenesis of IBD or be associated with an increased incidence of thrombotic complications, but with limited data.