Pan-intestinal capsule endoscopy as first-line procedure in patients with suspected mid or lower gastrointestinal bleeding.

BACKGROUND: Pan-intestinal capsule endoscopy (PCE) evaluates the small bowel and colon noninvasively. This study evaluated diagnostic accuracy and safety of PCE vs. colonoscopy as first-line examination in suspected mid-lower gastrointestinal bleeding (MLGIB). METHODS: In this prospective, single-center, single-blinded cohort study, consecutive patients with suspected MLGIB underwent PCE followed by same-day colonoscopy. Diagnostic accuracy for potentially hemorrhagic lesions (PHLs; combined diagnosis by PCE + colonoscopy) and incidence of adverse events were assessed. RESULTS: 100 patients were included (median age 70 [range 18-92] years; 65% female). PHLs were diagnosed in 46 patients, including small-bowel and/or colon angioectasias in 32. PCE correctly identified 54 individuals without PHLs, and 95.7% (44/46) of those with PHLs vs. 50.0% (23/46) for colonoscopy (P<0.01). PHLs were detected by PCE alone in 65.2% (30/46), both examinations in 28.3% (13/46), and colonoscopy alone in 6.5% (3/46). PHLs were diagnosed at the ileocolonic region in 28% of patients, with PCE diagnosing 25/28 cases (89.3%) and colonoscopy diagnosing 23/28 (82.1%; P=0.13). Interventional procedures were performed at colonoscopy in 13/81 patients with iron-deficiency anemia (16.0%) vs. 6/19 patients with overt bleeding (31.6%; P<0.01). No significant adverse events occurred with PCE vs. 2% with colonoscopy. CONCLUSIONS: In patients with MLGIB, PCE avoided further invasive procedures in >50% of patients. PCE was safe and more effective than colonoscopy in identifying PHL both in the small bowel and colon. These results support the potential use of PCE as first-line examination in patients with suspected MLGIB.

CC-CLEAR (Colon Capsule Cleansing Assessment and Report): the novel scale to evaluate the clinical impact of bowel preparation in capsule colonoscopy - a multicentric validation study.

BACKGROUND: Colon Capsule Cleansing Assessment and Report (CC-CLEAR) is a novel quantitative bowel preparation scale for colon capsule. AIM: The aim of this study is to validate the association between CC-CLEAR's classification and major CC outcomes: lesion detection rate, surveillance recommendations and post-CC endoscopic treatment. METHODS: Multicentric cohort of consecutive CCs. An expert's panel decided post-CC recommendations. Data included CC-CLEAR and Leighton-REX scales. Major CC outcomes were associated with the different cleansing grades. RESULTS: From 168 CC's included, findings were reported in 123 (73.2%), 67 (54.4%) of those being colorectal polyps. CC-CLEAR influenced CC's lesion detection (OR 1.25 95% IC [1.07-1.46], p-value .004) and polyp detection rate (OR 1.22 95% IC [1.04-1.43], p-value.014). Thirty-two (19%) post-CC colonoscopies were recommended, including 22 (68.75%) with at least one polypectomy. CC-CLEAR was associated with post-CC colonoscopy treatment (OR 1.40 95% IC [1.07-1.84], p-value .015). Regarding surveillance, CC-CLEAR influenced the decision for immediate CC repetition (OR 0.21 95% IC [0.12-0.36], p-value < .001) and the recommendation for CC in 3-5 years' time (OR 1.47 95% IC [1.50-1.86], p-value < .002). The Leighton-Rex scale was not correlated with major CC outcomes. CONCLUSION: CC-CLEAR impacts major CC outcomes: lesion detection, surveillance recommendations and post-CC endoscopic treatment.

Combination therapy in inflammatory bowel disease patients: do we need to maximize the dose of azathioprine?

BACKGROUND: The use of combination therapy of anti-TNFα and thiopurines in inflammatory bowel disease (IBD) is associated with greater efficacy and lower immunogenicity. However, the dose of thiopurine in this setting remains to be elucidated. AIM: To compare the trough levels, anti-TNFα antibodies and the inflammatory biomarkers between three groups in combotherapy: group 1 (dose of azathioprine <1 mg/kg); group 2 (dose of azathioprine ≥1 and <2 mg/kg), and group 3 (dose of azathioprine ≥2 mg/kg). METHODS: A retrospective study was performed, selecting all patients with established diagnosis of IBD who were on combined maintenance treatment. RESULTS: We included 99 patients, 52.5% female with median age 33 (17-61) years. Eighty patients (80.8%) were diagnosed with Crohn's disease and 19 (19.2%) with ulcerative colitis. Seventy-one (71.8%) patients were on infliximab (IFX) and 28 (28.3%) were on adalimumab (ADA). In patients treated with IFX, there were no differences in trough levels (p=.976) or formation of antibodies anti-IFX (p=.478) between groups. Moreover, there were no differences in inflammatory biomarkers: CRP (p=.385) and fecal calprotectin (p=.576) among the three groups. Regarding patients treated with ADA, there were no differences in trough levels of ADA (p=.249), formation of antibodies anti-ADA (p=.706) or in inflammatory biomarkers: CRP (p=.738) and fecal calprotectin (p=.269) among the three groups. CONCLUSION: In our cohort, there were no differences between anti-TNFα trough levels, formation of anti-TNFα antibodies or inflammatory biomarkers among patients in combotherapy with azathioprine, irrespective of its dosage. In conclusion, our study suggests that maintaining therapeutic levels of anti-TNFα drugs without antibodies formation is feasible with lower doses of azathioprine, minimizing its side effects.

Hepatic steatosis and patients with inflammatory bowel disease: when transient elastography makes the difference.

BACKGROUND: Recent studies suggest an increased prevalence of hepatic steatosis (HS) in patients with inflammatory bowel disease (IBD). Features such as chronic inflammation, previous surgeries, drug-induced hepatotoxicity, malnutrition, and intestinal dysbiosis seem to be involved in its pathogenesis. AIMS: The aim of this study was to assess the frequency of HS in patients with IBD quantified by controlled attenuation parameter (CAP) and by clinical-analytical scores: Hepatic Steatosis Index (HSI) and Fatty Liver Index (FLI). The secondary aim was to investigate risk factors associated with HS in patients with IBD. PATIENTS AND METHODS: A cross-sectional study was carried out including consecutive outpatients observed in our department between January and March 2017. HS was defined as HSI of at least 36 or FLI of at least 60 or CAP of greater than 248. RESULTS: A total of 161 patients were included, with a mean age of 40.6±12.8 years. There were 86 (53.4%) female patients. Overall, 62.7% had Crohn's disease and 37.1% had ulcerative colitis. Moreover, 73 (45.3%) patients had CAP greater than 248, 27 (16.8%) had FLI greater than 60, and 46 (28.6%) had HSI greater than 36.We found that patients with CAP of greater than 248 were more frequently obese (28.8 vs. 0.0% P<0.001), male (57.5 vs. 37.5% P=0.011), and presented more frequently with metabolic syndrome (23.9 vs. 4.5% P <0.001). With regard to IBD factors, patients with HS had a higher frequency of previous surgeries (31.5 vs. 12.5% P=0.003). In multivariate analysis, only male sex [odds ratio: 5.7 (95% confidence interval: 2.0-15.9); P=0.001] and previous surgeries [odds ratio: 5.9 (95% confidence interval: 1.5-22.9); P=0.011] were independent risk factors of HS. CONCLUSION: In our cohort, the frequency of HS varied between 16.8 and 45.3% defined by noninvasive methods. We found that male sex and previous history of surgery were the independent risk factors of HS when quantified by transient elastography.

Capsule Endoscopy: Diagnostic Accuracy of Lewis Score in Patients with Suspected Crohn's Disease.

BACKGROUND: The Lewis Score (LS) aims to standardize the method of quantification of small bowel inflammatory activity detected by the small bowel capsule endoscopy (SBCE). The aim of this study was to evaluate the diagnostic accuracy of the LS in patients with suspected CD undergoing SBCE. METHODS: We performed a retrospective study including patients who underwent SBCE for suspected CD between September 2006 and February 2013. Patients were grouped according to the criteria of the International Conference on Capsule Endoscopy for the definition of suspected CD. Inflammatory activity on SBCE was objectively assessed by determining the LS. RESULTS: Ninety-five patients were included. Group 1: 37 patients not fulfilling International Conference on Capsule Endoscopy criteria; Group 2: 58 patients with ≥ 2 International Conference on Capsule Endoscopy criteria. The diagnosis of CD was established in 38 patients (40%): 8 (21.6%) from group 1 and 30 from group 2 (51.7%) (P = 0.003). Among those patients, 34 had LS ≥ 135 (73.9%) and 4 had LS <135 (8.2%) at SBCE (P < 0.001). The LS ≥ 135 had an overall diagnostic accuracy of 83.2% with a sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of CD of 89.5%, 78.9%, 73.9%, and 91.8%, respectively. CONCLUSIONS: The application of LS ≥ 135 as the cutoff value for the presence of significant inflammatory activity in patients undergoing SBCE for suspected CD may be useful to establish the diagnosis of CD. In patients with LS < 135, the probability of having CD confirmed on follow-up is low.

Phenotype-genotype profiles in Crohn's disease predicted by genetic markers in autophagy-related genes (GOIA study II).

BACKGROUND: About 70 loci are associated with susceptibility to Crohn's disease (CD), particularly in pathways of innate immunity, autophagy, and pathogen recognition. Phenotype-genotype associations are inconsistent. METHODS: CD susceptibility polymorphisms ATG16L1 rs2241880, ICAM1 rs5498, IL4 rs2070874, IL17F rs763780, IRGM rs13361189, ITLN1 rs2274910, LRRK2 rs11175593, and TLR4 rs4986790 were genotyped in a Portuguese population (511 CD patients, 626 controls) and assessed for association with CD clinical characteristics. RESULTS: There is a significant association of CD with the single nucleotide polymorphisms (SNPs) in ATG16L1 (odds ratio [OR] 1.36 [1.15-1.60], P = 2.7 × 10(-6) for allele G), IRGM (OR 1.56 [1.21-1.93], P = 3.9 × 10(-4) for allele C), and ITLN1 (OR 1.55 [1.28-1.88], P = 4.9 × 10(-4) for allele C). These SNPs are associated with ileal location (OR, respectively, 1.49, 1.52, and 1.70), ileocolonic location (OR, respectively, 1.31, 1.57, and 1.68), and involvement of the upper digestive tract (OR, respectively for ATG16L1 and IRGM, 1.96 and 1.95). The risk genotype GG in ATG16L1 is associated with patients who respond to steroids (OR 1.89), respond to immunosuppressants (OR 1.77), and to biologic therapy (OR 1.89). The SNPs in ITLN1 and IRGM are both associated with a positive response to biologic therapy. The risk for ileal, ileocolonic, and upper digestive tract locations increases with the number of risk alleles (OR for three alleles, respectively, 7.10, 3.54, and 12.07); the OR for positive response to biologic therapy is 3.66. CONCLUSIONS: A multilocus approach using autophagy-related genes provides insight into CD phenotype-genotype associations and genetic markers for predicting therapeutic responses.

Kinetic studies for sorption of amino acids using a strong anion-exchange resin. Effect of ionic strength.

This work deals with the influence of the ionic strength on the sorption of L-phenylalanine and L-tyrosine by a strong basic anion-exchange resin, converted to the hydroxide form with sodium hydroxide. Equilibrium uptake isotherms were obtained for phenylalanine and tyrosine by carrying out batch experiments at different ionic strength values of the solution. The model used to correlate these results is the modified Langmuir equation which has been applied with success to biological systems. Batch kinetic experiments were performed using a packed bed of differential length inserted in a liquid circulation loop and in which the ionic strength of the solution was varied. Moreover, an experiment at variable pH for tyrosine was also performed. Experimental transient concentration profiles were compared to those predicted by the pore diffusion model and enabled the estimation of the intraparticle diffusivities for phenylalanine and tyrosine.