Fucosyltransferase 2 Mutations Are Associated With a Favorable Clinical Course in Crohn's Disease.

BACKGROUND: Fucosyltransferase 2 (FUT2) participates in intestinal antigen secretion and bacterial adherence. FUT2 homozygous nonsense mutations (FUT2M) and subsequent nonsecretor status is associated with Crohn's disease (CD). The common null allele is rs601338. We assessed the relationship between FUT2M and disease course. METHODS: In consecutive adult CD outpatients, clinical, biochemical, and genetic data were collected at baseline visits. Patients were longitudinally followed over 5 years. The primary outcome analyzed the relationship between FUT2M and rates of CD patients in persistent steroid-free clinical remission requiring neither surgery, biologics, nor immunomodulators. RESULTS: Sixty-two CD patients were recruited. FUT2M homozygotes (rs601338 or any mutation in linkage disequilibrium) were detected in 27% of CD (17/62). Patients with rs601338 mutations had higher rates of the primary outcome (homozygous: 46.6%, heterozygous: 28.0%, wild-type: 5.3%, P=0.02). Similar findings existed for CD patients with homozygous mutations in any single-nucleotide polymorphism for FUT2 (homozygous: 41.2%, heterozygous: 25.9%, wild-type: 5.6%, P=0.04). On multivariable analysis, rs601338 mutation was associated with the primary outcome (odds ratio=3.4, 95% confidence interval: 1.3-8.7, P=0.01), while other parameters were not. Mutation of rs601338 was associated with lower rates of penetrating disease (homozygous: 13.3%, heterozygous: 28.0%, wild-type: 52.6%, P=0.05) and particularly in high-risk patients (homozygous: 0%, heterozygous: 37.5%, wild-type: 83.3%, P=0.01). CONCLUSIONS: FUT2 mutation status is associated with a favorable clinical course in CD. Further confirmatory studies are needed.

Diagnostic Delay Is Associated With Complicated Disease and Growth Impairment in Paediatric Crohn's Disease.

BACKGROUND: Paediatric data on the association between diagnostic delay and inflammatory bowel disease [IBD] complications are lacking. We aimed to determine the effect of diagnostic delay on stricturing/fistulising complications, surgery, and growth impairment in a large paediatric cohort, and to identify predictors of diagnostic delay. METHODS: We conducted a national, prospective, multicentre IBD inception cohort study including 1399 children. Diagnostic delay was defined as time from symptom onset to diagnosis >75th percentile. Multivariable proportional hazards [PH] regression was used to examine the association between diagnostic delay and stricturing/fistulising complications and surgery, and multivariable linear regression to examine the association between diagnostic delay and growth. Predictors of diagnostic delay were identified using Cox PH regression. RESULTS: Overall (64% Crohn's disease [CD]; 36% ulcerative colitis/IBD unclassified [UC/IBD-U]; 57% male]), median time to diagnosis was 4.2 (interquartile range [IQR] 2.0-9.2) months. For the overall cohort, diagnostic delay was >9.2 months; in CD, >10.8 months and in UC/IBD-U, >6.6 months. In CD, diagnostic delay was associated with a 2.5-fold higher rate of strictures/internal fistulae (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.41-4.56). Every additional month of diagnostic delay was associated with a decrease in height-for-age z-score of 0.013 standard deviations [95% CI 0.005-0.021]. Associations persisted after adjusting for disease location and therapy. No independent association was observed between diagnostic delay and surgery in CD or UC/IBD-U. Diagnostic delay was more common in CD, particularly small bowel CD. Abdominal pain, including isolated abdominal pain in CD, was associated with diagnostic delay. CONCLUSIONS: Diagnostic delay represents a risk factor for stricturing/internal fistulising complications and growth impairment in paediatric CD. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

No Change in Surgical and Hospitalization Trends Despite Higher Exposure to Anti-Tumor Necrosis Factor in Inflammatory Bowel Disease in the Québec Provincial Database From 1996 to 2015.

BACKGROUND: Crohn disease (CD) and ulcerative colitis (UC) have high health care expenditures because of medications, hospitalizations, and surgeries. We evaluated disease outcomes and treatment algorithms of patients with inflammatory bowel disease (IBD) in Québec, comparing periods before and after 2010. METHODS: The province of Québec's public health administrative database was used to identify newly diagnosed patients with IBD between 1996 and 2015. The primary and secondary outcomes included time to and probability of first and second IBD-related hospitalizations, first and second major surgery, and medication exposures. Medication prescriptions were collected from the public prescription database. RESULTS: We identified 34,644 newly diagnosed patients with IBD (CD = 59.5%). The probability of the first major surgery increased after 2010 in patients with CD (5 years postdiagnosis before and after 2010: 8% [SD = 0.2%] vs 15% [SD = 0.6%]; P < 0.0001) and patients with UC (6% [SD = 0.2%] vs 10% [SD = 0.6%] ;P < 0.0001). The probability of the second major surgery was unchanged in patients with CD. Hospitalization rates remained unchanged. Patients on anti-tumor necrosis factor (anti-TNF) medications had the lowest probability of hospitalizations (overall 5-year probability in patients with IBD stratified by maximal therapeutic step: 5-aminosalicylic acids 37% [SD = 0.6%]; anti-TNFs 31% [SD = 1.8%]; P < 0.0001). Anti-TNFs were more commonly prescribed for patients with CD after 2010 (4% [SD = 0.2%] vs 16% [SD = 0.6%]; P < 0.0001) in the public health insurance plan, especially younger patients. Corticosteroid exposure was unchanged before and after 2010. Immunosuppressant use was low but increased after 2010. The use of 5-ASAs was stable in patients with UC but decreased in patients with CD. CONCLUSIONS: The probability of first and second hospitalizations remained unchanged in Québec and the probability of major surgery was low overall but did increase despite the higher and earlier use of anti-TNFs.

Increased Intestinal Permeability Is Associated With Later Development of Crohn's Disease.

BACKGROUND & AIMS: Increased intestinal permeability has been associated with Crohn's disease (CD), but it is not clear whether it is a cause or result of the disease. We performed a prospective study to determine whether increased intestinal permeability is associated with future development of CD. METHODS: We assessed the intestinal permeability, measured by the urinary fractional excretion of lactulose-to-mannitol ratio (LMR) at recruitment in 1420 asymptomatic first-degree relatives (6-35 years old) of patients with CD (collected from 2008 through 2015). Participants were then followed up for a diagnosis of CD from 2008 to 2017, with a median follow-up time of 7.8 years. We analyzed data from 50 participants who developed CD after a median of 2.7 years during the study period, along with 1370 individuals who remained asymptomatic until October 2017. We used the Cox proportional hazards model to evaluate time-related risk of CD based on the baseline LMR. RESULTS: An abnormal LMR (>0.03) was associated with a diagnosis of CD during the follow-up period (hazard ratio, 3.03; 95% CI, 1.64-5.63; P = 3.97 × 10-4). This association remained significant even when the test was performed more than 3 years before the diagnosis of CD (hazard ratio, 1.62; 95% CI, 1.051-2.50; P = .029). CONCLUSIONS: Increased intestinal permeability is associated with later development of CD; these findings support a model in which altered intestinal barrier function contributes to pathogenesis. Abnormal gut barrier function might serve as a biomarker for risk of CD onset.

Benefits of implementing a rapid access clinic in a high-volume inflammatory bowel disease center: Access, resource utilization and outcomes.

BACKGROUND: Emergency situations in inflammatory bowel diseases (IBD) put significant burden on both the patient and the healthcare system. AIM: To prospectively measure Quality-of-Care indicators and resource utilization after the implementation of the new rapid access clinic service (RAC) at a tertiary IBD center. METHODS: Patient access, resource utilization and outcome parameters were collected from consecutive patients contacting the RAC between July 2017 and March 2019 in this observational study. For comparing resource utilization and healthcare costs, emergency department (ED) visits of IBD patients with no access to RAC services were evaluated between January 2018 and January 2019. Time to appointment, diagnostic methods, change in medical therapy, unplanned ED visits, hospitalizations and surgical admissions were calculated and compared. RESULTS: 488 patients (Crohn's disease: 68.4%/ulcerative colitis: 31.6%) contacted the RAC with a valid medical reason. Median time to visit with an IBD specialist following the index contact was 2 d. Patients had objective clinical and laboratory assessment (C-reactive protein and fecal calprotectin in 91% and 73%). Fast-track colonoscopy/sigmoidoscopy was performed in 24.6% of the patients, while computed tomography/magnetic resonance imaging in only 8.1%. Medical therapy was changed in 54.4%. ED visits within 30 d following the RAC visit occurred in 8.8% (unplanned ED visit rate: 5.9%). Diagnostic procedures and resource utilization at the ED (n = 135 patients) were substantially different compared to RAC users: Abdominal computed tomography was more frequent (65.7%, P < 0.001), coupled with multiple specialist consults, more frequent hospital admission (P < 0.001), higher steroid initiation (P < 0.001). Average medical cost estimates of diagnostic procedures and services per patient was $403 CAD vs $1885 CAD comparing all RAC and ED visits. CONCLUSION: Implementation of a RAC improved patient care by facilitating easier access to IBD specific medical care, optimized resource utilization and helped avoiding ED visits and subsequent hospitalizations.

Low Rate of Drug Discontinuation, Frequent Need for Dose Adjustment, and No Association with Development of New Arthralgia in Patients Treated with Vedolizumab: Results from a Tertiary Referral IBD Center.

BACKGROUND: Evaluating clinical data on the safety and efficacy of vedolizumab (VDZ) in 'real-world' setting is still desirable. Recent reports have raised concerns that arthralgia may be associated with VDZ. AIMS: The aim of this study is to present clinical experience with VDZ from a tertiary IBD center. METHODS: Retrospective chart reviews were performed of consecutive patients exposed to VDZ between 2015 and 2018. Clinical, biomarker, and endoscopic efficacy and safety data were evaluated. RESULTS: A total of 130 IBD (75CD, 55UC) patients were included. Median duration of VDZ therapy was 65 weeks. Probability of drug discontinuation was 4.9% and 9.4% at 1 and 2 years. Dose intensification was more frequent in CD compared to UC (at 1 and 2 years: 64.8/87.9% vs. 26.5/35.7%, p < 0.001). Clinical remission rates at 3-, 6- and 12 months were 44.4%, 71.4% and 77.1% in UC, and 9.1%, 26.7% and 29.2% in CD patients, respectively. Prior use of multiple biologic agents was associated with diminished efficacy of VDZ in CD. Three new cases of arthralgia were encountered during follow-up. CONCLUSION: Vedolizumab (VDZ) therapy displayed good drug sustainability and clinical efficacy in a population with severe disease phenotype and high rates of previous anti-TNF failure. Frequent dose intensification was required. The safety profile was good, and no association between newly onset arthralgia and VDZ therapy was observed.

Analysis of Flagellin-Specific Adaptive Immunity Reveals Links to Dysbiosis in Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Bacterial flagellin is an important antigen in inflammatory bowel disease, but the role of flagellin-specific CD4+ T cells in disease pathogenesis remains unclear. Also unknown is how changes in intestinal microbiome intersect with those in microbiota-specific CD4+ T cells. We aimed to quantify and characterize flagellin-specific CD4+ T cells in Crohn's disease (CD) and ulcerative colitis (UC) patients and study their relationship with intestinal microbiome diversity. METHODS: Blood was collected from 3 cohorts that included CD patients, UC patients, and healthy controls. Flow cytometry analyzed CD4+ T cells specific for Lachnospiraceae-derived A4-Fla2 and Escherichia coli H18 FliC flagellins, or control vaccine antigens. Serum antiflagellin IgG and IgA antibodies were detected by enzyme-linked immunosorbent assay and stool samples were collected and subjected to 16S ribosomal DNA sequencing. RESULTS: Compared with healthy controls, CD and UC patients had lower frequencies of vaccine-antigen-specific CD4+ T cells and, as a proportion of vaccine-specific cells, higher frequencies of flagellin-specific CD4+ T cells. The proportion of flagellin-specific CD4+ T cells that were CXCR3negCCR4+CCR6+ Th17 cells was reduced in CD and UC patients, with increased proportions of CD39+, PD-1+, and integrin ß7+ cells. Microbiome analysis showed differentially abundant bacterial species in patient groups that correlated with immune responses to flagellin. CONCLUSIONS: Both CD and UC patients have relative increases in the proportion of circulating Fla2-specific CD4+ T cells, which may be associated with changes in the intestinal microbiome. Evidence that the phenotype of these cells strongly correlate with disease severity provides insight into the potential roles of flagellin-specific CD4+ T cells in inflammatory bowel disease.

Analysis of Genetic Association of Intestinal Permeability in Healthy First-degree Relatives of Patients with Crohn's Disease.

Excessive intestinal permeability or intestinal barrier dysfunction as measured by various assays has been observed in various diseases. However, little is known about the factors contributing to altered gut permeability in these diseases. Our objective was to determine the genetic determinants of altered gut permeability as measured by the lactulose mannitol fractional excretion ratio (LacMan ratio) in 1075 healthy first-degree relatives of patients with Crohn's disease (CD). In a targeted analysis of single nucleotide polymorphisms (SNPs) located in genes associated with intestinal barrier function related or not to inflammatory bowel disease, we did not find a significant association with intestinal permeability. In an untargeted genome-wide association analysis, the top 100 associations were located in 22 genomic loci, although they were not statistically significant after correction for multiple testing (raw P values [1.8 × 10-7 - 1.4 × 10-5]. The lowest P value was obtained for rs9616637 (22q13.33, C22orf34), for which the minor allele A was associated with a decreased LacMan ratio. These results suggest that host genetic background has limited contribution toward intestinal permeability. Despite this, our study is currently the largest of its kind assessing gut permeability in vivo. It remains possible that smaller genetic effect sizes on LacMan ratio are not detectable in this sized cohort. Larger studies are warranted to identify the potential genetic contribution to intestinal permeability.

High Adherence to Surveillance Guidelines in Inflammatory Bowel Disease Patients Results in Low Colorectal Cancer and Dysplasia Rates, While Rates of Dysplasia are Low Before the Suggested Onset of Surveillance.

BACKGROUND: Patients with Crohn's disease [CD] and ulcerative colitis [UC] are at increased risk for colorectal dysplasia [CRD] and colorectal cancer [CRC]. Adherence to CRC surveillance guidelines is reportedly low internationally. AIM: To evaluate surveillance practices at the tertiary IBD Center of the McGill University Health Center [MUHC] and to determine CRD/CRC incidence. METHODS: A representative inflammatory bowel disease cohort with at least 8 years of disease duration [or with primary sclerosing cholangitis] who visited the MUHC between July 1 and December 31, 2016 were included. Adherence to surveillance guidelines was compared to modified 2010 British Society of Gastroenterology guidelines. Incidence rates of CRC, high-grade dysplasia [HGD], low-grade dysplasia [LGD] and colorectal adenomas [CRA] were calculated based on pathology. RESULTS: In total, 1356 CD and UC patients (disease duration: 12 [interquartile range: 6-22) and 10 [interquartile range: 5-19] years) were identified. The surveillance cohort consisted of 680 patients [296 UC and 384 CD]. Adherence to surveillance guidelines was 76/82% in UC/colonic CD. An adequate number of biopsies were taken in 54/54% of UC/colonic CD patients. The incidence of CRC/HGD in UC and CD with colonic involvement was 19.5/58.5 and 25.1/37.6 per 100,000 patient-years, respectively. The incidence of dysplasia before 8 years of disease duration was low in both UC/CD [19.5 and 12.5/100,000 patient-years] with no CRC detected. The CRA rate was 30/38% in UC/colonic CD. CONCLUSION: High adherence to surveillance guidelines and low CRC and dysplasia, but not CRA rates were found, suggesting that adhering to updated, stratified, surveillance recommendations may result in low advanced neoplasia rates. The incidence of dysplasia before the start of surveillance was low.

A Cross-Sectional Study on Malnutrition in Inflammatory Bowel Disease: Is There a Difference Based on Pediatric or Adult Age Grouping?

BACKGROUND: Malnutrition, commonly observed in inflammatory bowel disease (IBD), is associated with increased morbidity and mortality and is attributed to multiple causes. The added energy costs of growth in the child and adolescent with IBD are an additional risk factor. METHODS: The aim of the study was to perform a cross-sectional comparison of nutritional parameters in IBD between pediatric and adult cases. RESULTS: We found that prevalence of undernutrition (low body mass index) and hypoalbuminemia was not different in pediatric, compared with adult patients. Anemia and iron deficiency were more often observed in pediatric subjects, compared with adults (59.1% vs 36.9%, respectively, P < 0.0001; and 37.9% vs 25.3%, P < 0.002). Vitamin B12 deficiency was significantly less common in the pediatric than in the adult group (5.4% vs 19.4%, P < 0.0001). Elevated C-reactive protein was more frequent in pediatric compared with adult cases (49.8% vs 38.4%, P < 0.01). CONCLUSIONS: Patients with active Crohn's disease were more likely to be undernourished in both pediatric and adult populations. In both groups, predicators of undernutrition included low albumin levels (odds ratio [OR], 2.53; P < 0.006) and active disease (OR, 1.99; P < 0.03). Our results call for close surveillance of nutritional status for IBD patients, regardless of age.

Perceived Quality of Care is Associated with Disease Activity, Quality of Life, Work Productivity, and Gender, but not Disease Phenotype: A Prospective Study in a High-volume IBD Centre.

BACKGROUND AND AIMS: Measuring quality of care [QoC] in inflammatory bowel diseases [IBD] has become increasingly important, yet complex assessment of QoC from the patients' perspective is rare. We evaluated perceived QoC using the Quality of Care Through the Patient's Eyes-IBD [QUOTE-IBD] questionnaire, and investigated associations between QoC, disease phenotype, work productivity, and health-related quality of life [HRQoL] in a high-volume IBD centre. METHODS: Consecutive patients attending McGill University Health Centre [MUHC]-IBD Centre completed the QUOTE-IBD, Short Inflammatory Bowel Disease Questionnaire [SIBDQ], IBD-Control, and Work Productivity and Activity Impairment [WPAI] questionnaires. The QUOTE-IBD comprises 23 questions, each rated by a quality impact [QI] score. QI scores were calculated for the evaluation of IBD specialists, general practitioners [GPs], and hospital care. RESULTS: In all, 525 patients completed the questionnaire. Total QI scores for IBD specialists, GPs, and hospital care were 8.57, 8.70, and 8.33, respectively. The lowest QI scores were related to 'accessibility' for both IBD specialists and GPs. Female gender, current disease activity, poor HRQoL [SIBDQ score ≤50], and poor disease control [IBD-Control score <13] were associated with lower mean QI scores [p <0.001 for all]. Disease phenotype was not associated with QI scores in either Crohn's disease [CD] or ulcerative colitis [UC] [p = 0.69, p = 0.791, respectively]. An inverse correlation was found between total QI scores and work productivity loss [IBD specialist: p <0.001; GP: p = 0.004]. CONCLUSIONS: Overall patient satisfaction with QoC was good; however, improving patient accessibility to care is warranted. Disease phenotype was not associated with patient satisfaction, whereas female gender, current disease activity, HRQoL, and work productivity loss were associated with patients' quality assessment, underlining that perceived QoC could be partly subjective regarding disease control and quality of life.

Management of Paediatric Patients With Medically Refractory Crohn's Disease Using Ustekinumab: A Multi-Centred Cohort Study.

BACKGROUND: Ustekinumab [UST] is effective in the treatment of adults with moderate to severe Crohn's disease [CD]. There is a paucity of data on its use in children. AIM: To evaluate the response to UST in children with moderate to severe CD. METHODS: This multicentre retrospective cohort study identified children under 18 years old with CD, who received open-labelled subcutaneous UST. The primary outcome was changes in mean abbreviated Paediatric Crohn's Disease Activity Index [aPCDAI] between baseline and 3 and 12 months, and rate of clinical remission at 3 and 12 months. Secondary outcomes were clinical response at the same time points, changes in C-reactive protein [CRP] and albumin, improvement in growth parameters, and rate of adverse events. RESULTS: A total of 44 patients who failed at least one biological treatment were identified. Linear mixed model [LMM] analysis revealed a statistically significant effect of UST (χ2[1] = 42.7, p = 1.2 × 10-8) which lowered the aPCDAI scores by about 16 ± 2.7 at 3 months, and 19.6 ± 2.9 at 12 months. At 12 months, 38.6% of the patients achieved clinical remission and 47.8% achieved clinical response. There was a significant increase in mean weight z-score of 0.48 [±0.13] [p <0.001] and in mean body mass index [BMI] z score of 0.66 [±0.16] [p <0.001]. The probability of remaining on UST at 12 months was 76.9%. The rate of adverse events was 12.4 per 1000 patient-months. CONCLUSIONS: Subcutaneous UST should be considered a viable therapeutic option for paediatric patients who are refractory to other biological agents. Prospective randomised trials are needed.

Harmonization of quality of care in an IBD center impacts disease outcomes: Importance of structure, process indicators and rapid access clinic.

BACKGROUND AND AIMS: We aimed to evaluate the quality of care at a tertiary inflammatory bowel disease (IBD) center using quality of care indicators (QIs) including patient assessment strategy, monitoring, treatment decisions and outcomes. METHODS: We retrospectively reviewed the quality of care pre- and post-referral and during follow-up at the at the McGill University Health Center (MUHC) IBD center. Consecutive patients were included presenting with an outpatient visit ('index visit') between July and December 2016. Disease characteristics, biochemistry, imaging and endoscopy data, changes in medications, and vaccination profiles were captured. RESULTS: 1357 patients were included. At referral, a large proportion of patients were objectively re-evaluated (ileocolonoscopy: 79%, cross-sectional imaging: 39.3%, biomarkers: 89.9%, 81.9%). Therapeutic strategy was changed in 53.6% with 22.5% of patients starting biologics. Tight objective patient monitoring was applied during follow-up (colonoscopy: 79%, cross-sectional imaging: 61.8% were available at index visit; C-reactive protein: 78%, Faecal calprotectin: 37.6%, therapeutic drug monitoring: 16.3% were performed additionally). Maximum therapeutic step was biologicals in 48.8% of the patients, while only 6.6% of all patients were steroid dependent. Implementation of a rapid access clinic improved healthcare delivery. CONCLUSIONS: Our data support that tight monitoring was applied at the MUHC IBD center with a high emphasis on objective patient (re)evaluation, timely access and accelerated treatment strategy at referral and during follow-up.

Pancreatic Enzyme Supplementation in Patients with Atopic Dermatitis and Food Allergies: An Open-Label Pilot Study.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects both patients and their families. Current therapies often alleviate symptoms but do not prevent or eradicate the disease. OBJECTIVES: Our objective was to determine whether pancreatic enzyme supplementation is an effective and safe treatment in refractory pediatric AD associated with food allergies. METHODS: We conducted an open-label pilot study using a case-control design. Patients with severe AD and known food allergies refractory to conventional therapies and exclusion diets were recruited and treated for 6 weeks with oral supplementation of pancreatic enzymes. The primary endpoint was the severity of AD, using the Scoring Atopic Dermatitis (SCORAD) index. Secondary measures included markers of intestinal permeability (urinary sucrose and lactulose/mannitol excretion). RESULTS: A total of 11 patients met all eligibility criteria and completed the trial. Significant improvement in AD was observed after 6 weeks of pancreatic enzyme supplementation (SCORAD index 52.3 ± 5.5 vs. 34.6 ± 7.6; p = 0.0008). Beneficial effect was observed in 9 of 11 patients, without adverse events. Fractional urinary sucrose excretion improved to a level comparable to that of age-matched controls (p < 0.05). However, urinary lactulose:mannitol ratios remained abnormally high compared with those of controls (p = 0.01). CONCLUSIONS: Pancreatic enzyme supplementation was associated with improved AD and gastroduodenal permeability. Additional randomized placebo-controlled studies are required before this treatment can be recommended in this clinical setting.

Clinical Parameters Correlate With Endoscopic Activity of Ulcerative Colitis: A Systematic Review.

BACKGROUND & AIMS: Optimal management of patients with ulcerative colitis (UC) requires assessment of disease activity-usually by endoscopy, which is invasive, costly, and not risk free. We performed a systematic review to determine whether clinical symptoms correlate with findings from endoscopy assessments of patients with UC. METHODS: We performed a systematic review of publication databases from January 1980 through July 2018 to identify clinical trials and observational studies reporting correlations among symptoms, disease activity index scores and/or patient reported outcomes (rectal bleeding and/or stool frequency), and endoscopic disease activity. Correlations were ascertained in patients with active vs inactive disease and by disease extent and treatment type. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Because of significant heterogeneity, meta-analysis was not possible. Results were synthesized qualitatively and systematically. RESULTS: Our final analysis included 23 studies (1 randomized trial, 22 observational studies) comprising 3320 patients with UC. The studies used a variety of measures to assess clinical activity, endoscopic activity, and measures of correlation (sensitivity, specificity, correlation coefficients, area under the receiver operator curve). Overall, studies were at moderate-high risk of bias. Composite clinical measures, including rectal bleeding and stool frequency, had moderate to strong correlations with endoscopic disease activity; the absence of rectal bleeding identified patients with inactive disease with higher levels of sensitivity than normalization of stool frequency. In general, symptoms correlated more strongly with endoscopic activity in patients with left-sided colitis than extensive colitis. The effect of different medications on the correlation between clinical and endoscopic activity has not been well studied. CONCLUSIONS: In a systematic review, we found a moderate to strong correlation between clinical activity, particularly the combination of rectal bleeding and stool frequency, and endoscopic activity in patients with UC. Although these clinical assessments could help prioritize patients for endoscopic evaluation in resource-limited settings, challenges associated with treating patients based on symptoms alone preclude adaptation of current management algorithms.

A Study of Optimal Screening for Latent Tuberculosis in Patients with Inflammatory Bowel Disease.

BACKGROUND: Reactivation of LTBI in patients with IBD on anti-TNF-α agents can lead to serious life-threatening illness. No gold standard exists for the detection of LTBI. We examined whether a dual testing strategy with TST and IGRA would improve the detection of LTBI. METHODS: Consecutive IBD patients being considered for anti-TNF-α treatment underwent testing with a TST, IGRA and CXR. All patients completed a self-administered questionnaire. The association of both tests with demographic factors, LTBI risk factors, BCG vaccination, IS therapy and agreement between the TST and IGRA were evaluated. RESULTS: One-hundred and fifty-five IBD patients were included, 6% were TST positive and 5% were IGRA positive. Concordance between TST and IGRA was fair (κ = 0.21, 95% CI - 0.081-0.498). Neither test was affected by age, gender or BCG vaccination. The presence of risk factors for LTBI was found to be positively associated with TST (OR 19.8, 95% CI 3.9-102.1), but not IGRA. IGRA was negatively associated with IS therapy (OR 0.06, 95% CI 0.007-0.5), but not TST. Four patients who were IGRA positive but TST negative were treated for LTBI by a respirologist. CONCLUSION: An IGRA result was negatively associated with IS therapy, while the presence of risk factors for LTBI was found to be positively associated with TST results. There was fair agreement between positive TST and IGRA results. The addition of IGRA to the standard practice of TST and CXR increased the number of cases that were initiated on LTBI therapy.

CFTR Deletion Confers Mitochondrial Dysfunction and Disrupts Lipid Homeostasis in Intestinal Epithelial Cells.

BACKGROUND: Cystic Fibrosis (CF) is a genetic disease in which the intestine exhibits oxidative and inflammatory markers. As mitochondria are the central source and the main target of reactive oxygen species, we hypothesized that cystic fibrosis transmembrane conductance regulator (CFTR) defect leads to the disruption of cellular lipid homeostasis, which contributes to mitochondrial dysfunction. METHODS: Mitochondrial functions and lipid metabolism were investigated in Caco-2/15 cells with CFTR knockout (CFTR-/-) engineered by the zinc finger nuclease technique. Experiments were performed under basal conditions and after the addition of the pro-oxidant iron-ascorbate (Fe/Asc) complex. RESULTS: Mitochondria of intestinal cells with CFTR-/-, spontaneously showed an altered redox homeostasis characterised by a significant decrease in the expression of PPARα and nuclear factor like 2. Consistent with these observations, 8-oxoguanine-DNA glycosylase, responsible for repair of ROS-induced DNA lesion, was weakly expressed in CFTR-/- cells. Moreover, disturbed fatty acid β-oxidation process was evidenced by the reduced expression of CPT1 and acyl-CoA dehydrogenase long-chain in CFTR-/- cells. The decline of mitochondrial cytochrome c and B-cell lymphoma 2 expression pointing to magnified apoptosis. Mitochondrial respiration was also affected as demonstrated by the low expression of respiratory oxidative phosphorylation (OXPHOS) complexes and a high adenosine diphosphate/adenosine triphosphate ratio. In contrast, the FAS and ACC enzymes were markedly increased, thereby indicating lipogenesis stimulation. This was associated with an augmented secretion of lipids, lipoproteins and apolipoproteins in CFTR-/- cells. The addition of Fe/Asc worsened while butylated hydroxy toluene partially improved these processes. CONCLUSIONS: CFTR silencing results in lipid homeostasis disruption and mitochondrial dysfunction in intestinal epithelial cells. Further investigation is needed to elucidate the mechanisms underlying the marked abnormalities in response to CFTR deletion.

Unsuspected Small-Bowel Crohn's Disease in Elderly Patients Diagnosed by Video Capsule Endoscopy.

BACKGROUND: Video capsule endoscopy (VCE) is increasingly performed among the elderly for obscure bleeding. Our aim was to report on the utility of VCE to uncover unsuspected Crohn's disease (CD) in elderly patients. METHODS: Retrospective review of VCE performed in elderly patients (≥70 y) at a tertiary hospital (2010-2015). All underwent prior negative bidirectional endoscopies. CD diagnosis was based on consistent endoscopic findings, exclusion of other causes, and a Lewis endoscopic score (LS) > 790 (moderate-to-severe inflammation). Those with lower LS (350-790) required histological confirmation. Known IBD cases were excluded. RESULTS: 197 VCE were performed (mean age 78; range 70-93). Main indications were iron deficiency anemia (IDA), occult GI bleeding (OGIB), chronic abdominal pain, or diarrhea. Eight (4.1%) were diagnosed as CD based on the aforementioned criteria. Fecal calprotectin (FCP) was elevated in 7/8 (mean 580 µg/g). Mean LS was 1824. Small-bowel CD detected by VCE led to a change in management in 4/8. One patient had capsule retention secondary to NSAID induced stricture, requiring surgical retrieval. CONCLUSIONS: VCE can be safely performed in the elderly. A proportion of cases may have unsuspected small-bowel CD despite negative endoscopies. FCP was the best screening test. Diagnosis frequently changed management.