Incidentally Diagnosed Asymptomatic Crohn's Disease: A Retrospective Cohort Study of Long-Term Clinical Outcomes.

Background: Crohn's disease (CD) is occasionally diagnosed in asymptomatic patients who have undergone colonoscopy or imaging for other reasons. The clinical outcome and optimal management of these patients remain poorly defined. Methods: This was a retrospective cohort study of asymptomatic patients with incidental diagnosis of CD from the electronic patient registry of the IBD Unit of Sheba Medical Center in Israel. The primary outcome was defined as the occurrence of a clinical flare. Results: Of the 2700 CD patients in Sheba IBD registry, 60 asymptomatic patients with incidental diagnosis of CD were identified (31/60 males, median age 50.5, 25%-75% interquartile range [IQR] 43.5-57.25 years, median follow-up 4.5 years, 25-75% IQR 2.5-6.75, range 1-15 years). Most of the patients did not receive any treatment after diagnosis (53/60-88.33%). Of these, 5 patients (9.43%) experienced a flare during follow-up (median 4.5 years, IQR 2.5-6.75, range 1-15 years). Patients with subsequent flare had numerically higher CRP at diagnosis than patients who did not flare (2.2, IQR 2.0-3.0 vs 1.04, IQR 1.0-2.2, P = .09). When comparing the group of patients who received treatment immediately after diagnosis (n = 7) with the group who did not receive treatment (n = 53), there was no difference with respect to the survival time without a flare (P = .3). For other secondary outcomes, 3/40 progressed from B1 phenotype to B2, and 3/53 (6%) patients underwent surgery during the follow-up. Conclusions: The majority of patients with an incidental diagnosis of asymptomatic CD can probably be followed-up without immediate treatment. Although most remain asymptomatic and without complications during follow-up, close monitoring for disease progression is prudent.

Automated Detection of Crohn's Disease Intestinal Strictures on Capsule Endoscopy Images Using Deep Neural Networks.

BACKGROUND AND AIMS: Passable intestinal strictures are frequently detected on capsule endoscopy [CE]. Such strictures are a major component of inflammatory scores. Deep neural network technology for CE is emerging. However, the ability of deep neural networks to identify intestinal strictures on CE images of Crohn's disease [CD] patients has not yet been evaluated. METHODS: We tested a state-of-the-art deep learning network for detecting CE images of strictures. Images of normal mucosa, mucosal ulcers, and strictures of Crohn's disease patients were retrieved from our previously described CE image bank. Ulcers were classified as per degree of severity. We performed 10 cross-validation experiments. A clear patient-level separation was maintained between training and testing sets. RESULTS: Overall, the entire dataset included 27 892 CE images: 1942 stricture images, 14 266 normal mucosa images, and 11 684 ulcer images [mild: 7075, moderate: 2386, severe: 2223]. For classifying strictures versus non-strictures, the network exhibited an average accuracy of 93.5% [±6.7%]. The network achieved excellent differentiation between strictures and normal mucosa (area under the curve [AUC] 0.989), strictures and all ulcers [AUC 0.942], and between strictures and different grades of ulcers [for mild, moderate, and severe ulcers-AUCs 0.992, 0.975, and 0.889, respectively]. CONCLUSIONS: Deep neural networks are highly accurate in the detection of strictures on CE images in Crohn's disease. The network can accurately separate strictures from ulcers across the severity range. The current accuracy for the detection of ulcers and strictures by deep neural networks may allow for automated detection and grading of Crohn's disease-related findings on CE.

Clinical and laboratory markers associated with anti-TNF-alpha trough levels and anti-drug antibodies in patients with inflammatory bowel diseases.

Monitoring anti-TNF agents in inflammatory bowel disease (IBD) patients may be helpful in optimizing outcomes. We aimed to evaluate potential correlations among demographic, clinical, laboratory, or imaging parameters, as well as serum levels of infliximab (IFX) and adalimumab (ADA) and their respective antibodies, in the clinical management of IBD patients.A cross-sectional study of 95 patients with Crohn's disease (CD) or ulcerative colitis (UC) in maintenance therapy with infliximab or adalimumab was performed. Drug trough levels and anti-drug levels were determined using ELISA-based assays.Regarding the serum IFX dosage, patients with higher relative C-reactive protein (CRP) levels had significantly lower relative serum IFX levels (<3 µg/mL) (P = .028). In contrast, higher concentrations of anti-IFX antibodies were found in patients who were not on concomitant immunomodulators (P = .022) and who had more biological-related adverse events (P = .001) and higher levels of CRP (P = .042). Serum CRP levels were also negatively correlated with IFX (CC = -0.315; P = .033) but positively correlated with the presence of IFX antibodies (CC = 0.327; P = .027). Serum albumin dosage showed a positive correlation with levels of both IFX (CC = 0.379; P = .004) and ADA (CC = 0.699; P = .003).Although anti-TNF-α trough levels and immunogenicity do not show a significant correlation with disease outcome, our results reinforce the use of combination therapy for patients treated with infliximab. Moreover, we confirmed the presence of significant associations between anti-TNF-α trough levels and immunogenicity with body mass index (BMI), the concomitant use of immunomodulators, the rates of side effects, and laboratory markers, including serum albumin and CRP.

Multidrug resistance 1 gene polymorphisms may determine Crohn's disease behavior in patients from Rio de Janeiro.

OBJECTIVES: Conflicting data from studies on the potential role of multidrug resistance 1 gene polymorphisms in inflammatory bowel disease may result from the analysis of genetically and geographically distinct populations. Here, we investigated whether multidrug resistance 1 gene polymorphisms are associated with inflammatory bowel diseases in patients from Rio de Janeiro. METHODS: We analyzed 123 Crohn's disease patients and 83 ulcerative colitis patients to determine the presence of the multidrug resistance 1 gene polymorphisms C1236T, G2677T and C3435T. In particular, the genotype frequencies of Crohn's disease and ulcerative colitis patients were analyzed. Genotype-phenotype associations with major clinical characteristics were established, and estimated risks were calculated for the mutations. RESULTS: No significant difference was observed in the genotype frequencies of the multidrug resistance 1 G2677T/A and C3435T polymorphisms between Crohn's disease and ulcerative colitis patients. In contrast, the C1236T polymorphism was significantly more common in Crohn's disease than in ulcerative colitis (p = 0.047). A significant association was also found between the multidrug resistance 1 C3435T polymorphism and the stricturing form of Crohn's disease (OR: 4.13; p = 0.009), whereas no association was found with penetrating behavior (OR: 0.33; p = 0.094). In Crohn's disease, a positive association was also found between the C3435T polymorphism and corticosteroid resistance/refractoriness (OR: 4.14; p = 0.010). However, no significant association was found between multidrug resistance 1 gene polymorphisms and UC subphenotypic categories. CONCLUSION: The multidrug resistance 1 gene polymorphism C3435T is associated with the stricturing phenotype and an inappropriate response to therapy in Crohn's disease. This association with Crohn's disease may support additional pathogenic roles for the multidrug resistance 1 gene in regulating gut-microbiota interactions and in mediating fibrosis. Understanding the effects of several drugs associated with multidrug resistance 1 gene variants may aid in the selection of customized therapeutic regimens.

Thiopurine-methyltransferase variants in inflammatory bowel disease: prevalence and toxicity in Brazilian patients.

AIM: To analyze the prevalence of thiopurine-methyltransferase (TPMT) genotypes and their association with drug toxicity in inflammatory bowel disease (IBD) patients from southeastern Brazil. METHODS: A total of 219 consecutive patients with IBD, of which 146 had Crohn's disease and 73 had ulcerative colitis, regularly seen at the outpatient unit of the Division of Gastroenterology at the University Hospital Pedro Ernesto of the State University of Rio de Janeiro, a tertiary referral center, were enrolled in this study from February 2009 to January 2011. We analyzed the presence of major TPMT genetic variants (TPMT 2, 3A, 3C) in IBD patients by means of a specific allele and RFLP-PCR. Genomic DNA was isolated from peripheral blood leukocytes by proteinase-K/Sodium Dodecyl Sulfate digestion and phenol-chloroform extraction. TPMT 2 (C238G), TPMT 3A (G460A/A719G), and TPMT 3C (A719G) genotypes were detected by real-time polymerase chain reaction followed by direct sequencing with specific primers. Clinical data were systematically recorded, and correlated with the genotype results. RESULTS: The distribution of the selected TPMT gene polymorphism TPMT 2 (C238G), TPMT 3A (G460A/A719G), and TPMT 3C (A719G) genotypes was 3.6%, 5.4%, and 7.7% of the patients, respectively. Among the side effects recorded from patients taking azathioprine, 14 patients presented with pancreatitis and/or an elevation of pancreatic enzymes, while 6 patients had liver toxicity, and 2 patients exhibited myelosuppression/neutropenia. TPMT polymorphisms were detected in 37/219 patients (8 heterozygous for 2, 11 heterozygous for 3A, and 18 heterozygous for 3C). No homozygotic polymorphisms were found. Despite the prevalence of the TPMT 3C genotype, no differences among the genotype frequencies were significant. Although no association was detected regarding myelotoxicity or hepatotoxicity, a trend towards the elevation of pancreatic enzymes was observed for TPMT 2 and TPMT 3C genotypes. CONCLUSION: The prevalence of TPMT genotypes was high among Brazilian patients. Variants genes 2 and 3C may be associated with azathioprine pancreatic toxicity in a IBD southeastern Brazilian population.

Multidrug resistance 1 gene polymorphisms may determine Crohn's disease behavior in patients from Rio de Janeiro

OBJECTIVES: Conflicting data from studies on the potential role of multidrug resistance 1 gene polymorphisms in inflammatory bowel disease may result from the analysis of genetically and geographically distinct populations. Here, we investigated whether multidrug resistance 1 gene polymorphisms are associated with inflammatory bowel diseases in patients from Rio de Janeiro. METHODS: We analyzed 123 Crohn's disease patients and 83 ulcerative colitis patients to determine the presence of the multidrug resistance 1 gene polymorphisms C1236T, G2677T and C3435T. In particular, the genotype frequencies of Crohn's disease and ulcerative colitis patients were analyzed. Genotype-phenotype associations with major clinical characteristics were established, and estimated risks were calculated for the mutations. RESULTS: No significant difference was observed in the genotype frequencies of the multidrug resistance 1 G2677T/A and C3435T polymorphisms between Crohn's disease and ulcerative colitis patients. In contrast, the C1236T polymorphism was significantly more common in Crohn's disease than in ulcerative colitis (p = 0.047). A significant association was also found between the multidrug resistance 1 C3435T polymorphism and the stricturing form of Crohn's disease (OR: 4.13; p = 0.009), whereas no association was found with penetrating behavior (OR: 0.33; p = 0.094). In Crohn's disease, a positive association was also found between the C3435T polymorphism and corticosteroid resistance/refractoriness (OR: 4.14; p = 0.010). However, no significant association was found between multidrug resistance 1 gene polymorphisms and UC subphenotypic categories. CONCLUSION: The multidrug resistance 1 gene polymorphism C3435T is associated with the stricturing phenotype and an inappropriate response to therapy in Crohn's disease. This association with Crohn's disease may support additional pathogenic roles ...