Inflammatory Crohn Research Articles

Profiles of Lamina Propria T Helper Cell Subsets Discriminate Between Ulcerative Colitis and Crohnʼs Disease

Distinction between 2 forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), can be challenging. Aberrant mucosal immunity suggests that CD is a T helper type 1 cell (Th1)-driven disease, whereas UC as Th2-driven response. However, whether this paradigm truly distinguishes CD from UC is controversial. We aimed to clarify the discriminating potential of lamina propria Th subsets in patients with IBD. Biopsies from 79 patients with IBD and 20 healthy controls were collected for Th subsets analysis (Th1:interferon γ [IFN-γ], T-bet; Th2:interleukin 13 [IL-13], Gata3; Th17:IL-17, RORγt; Treg:FoxP3). The receiver-operating characteristic curves were constructed to assess the discriminating ability by calculating the area under the receiver-operating characteristic curve. The equation with the highest area under the receiver-operating characteristic curve was applied to newly diagnosed patients to evaluate discriminating ability. Patients with CD showed increased IFN-γ or T-bet cells and decreased IL-13 or Gata3 cells compared with UC. A discriminant equation composed of 4 markers (IFN-γ, T-bet, IL-13, and Gata3) yielded the highest area under the receiver-operating characteristic curve. In 36 established CD or UC, the sensitivity, specificity, positive and negative predictive probabilities were 92.6%, 55.6%, 86.2%, and 71.4% and in 14 newly diagnosed patients were 100.0%, 42.9%, 63.6%, and 100.0%. Furthermore, Gata3 cells were increased in tumor necrosis factor inhibitor therapy nonresponders compared with responders in CD. IFN-γ cells were directly and inversely proportional to disease activity in patients with CD and UC, respectively. The Th1/Th2 paradigm can distinguish CD from UC and may be further associated with response to tumor necrosis factor inhibitor in CD and disease activity in patients with IBD.

Beliefs about Medicines Questionnaire (BMQ) in inflammatory bowel disease patients in Greece. Ιs this useful?

Background and Aims: The aim of this study is the revalidation of the Beliefs about Medicine Questionnaire (BMQ) in outpatient gastroenterology clinic patients, in Greece. Methods: A cohort of 163 patients diagnosed with inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease (CD) was included in the study, with the majority of them being in the remission phase. Diagnosis of IBD was established using standard diagnostic criteria. Statistical analysis included descriptive statistics and frequency analysis, Pearson's correlation and analysis of variance (ANOVA). Results: Internal consistency of the BMQ validated with Cronbach's α, being 0.757 in overall and 0.795 and 0.691 for the specific and general parts, respectively. The data adequacy for factor analysis was determined with Kaiser-Meyer-Olkin (KMO) measure > 0.5, while inter-item correlations were found to be significant in all cases. Conclusions: The Greek version of BMQ presented satisfactory psychometric/measurement properties indicating its reliability for use in patients with IBD who receive care in an outpatient hospital clinic.

MRI characteristics of proctitis in Crohn's disease on perianal MRI.

Purpose Multiple features have been described for assessing inflammation in Crohn’s disease (CD) in MR enterography, but have not been validated in perianal magnetic resonance imaging (MRI). Retrospectively, we studied which MRI features are valuable in assessing proctitis.Materials and methodsCD patients (≥18 years) who underwent colonoscopy (reference standard) and perianal fistula MRI within 8 weeks were included. Seventeen MRI features were blindly scored by three observers and correlated to endoscopy (regression analysis). Reproducibility (multirater kappa, intraclass correlation coefficient) was determined for all three observer pairs. MRI features were considered relevant when significantly correlated to endoscopy for ≥2 observers, and reproducibility was ≥0.40 for ≥2 observer pairs.ResultsPerianal MRI of 58 CD patients were included. Wall thickness, rectal mural fat, creeping fat, and size of mesorectal lymph nodes showed a significant correlation with endoscopy for ≥2 observers (p = 0.000–0.023, p = 0.011–0.172, p = 0.007–0.011 and p = 0.000–0.005, respectively) with a kappa/intraclass correlation coefficient of ≥0.60 for ≥2 observer pairs. Perimural T2 signal and perimural enhancement significantly correlated to endoscopy (all p values ≤0.05) for all three observers and the reproducibility was ≥0.40 for ≥2 observer pairs. Mural T2 signal and degree and pattern of T1 enhancement showed significant correlation to endoscopy for two observers, but with poor to moderate reproducibility.Conclusion Wall thickness, mural fat, and mesorectal features (perimural T2 signal, perimural enhancement, creeping fat, and size of mesorectal lymph nodes) had significant correlation to endoscopy and were reproducible in diagnosing proctitis. Some established luminal features in MRE were considered not useful.

Magnetic resonance enterography versus capsule endoscopy activity indices for quantification of small bowel inflammation in Crohn's disease.

Video capsule endoscopy (VCE) and magnetic resonance enterography (MRE) are the prime modalities for the evaluation of small bowel (SB) Crohn's disease (CD). Mucosal inflammation on VCE is quantified using the Lewis score (LS). Diffusion-weighted (DW) magnetic resonance imaging (MRI) allows for accurate assessment of SB inflammation without administration of intravenous contrast material. The Magnetic Resonance Index of Activity (MaRiA) and the Clermont index are quantitative activity indices validated for contrast-enhanced MRE and DW-MRE, respectively. The aim of this study was to compare the quantification of distal SB inflammation by VCE and MR-related activity indices. Patients with known quiescent SB CD were prospectively recruited and underwent MRE and VCE. LS, MaRIA and Clermont scores were calculated for the distal SB. Both MRI-based indices significantly correlated with the LS and the Clermont index (r = 0.50, p = 0.001 and r = 0.53, p = 0.001, respectively). Both MaRIA and Clermont scores were significantly lower in patients with mucosal healing (LS < 135). The area under the curve (AUC) with both MR scores was moderate for prediction of any mucosal inflammation (LS ⩾ 135) and excellent for prediction of moderate-to-severe inflammation (LS ⩾ 790) (0.71 and 0.74 versus 0.93 and 0.91 for MaRIA and Clermont score, respectively). Modest correlation between VCE- and MRE-based quantitative indices of inflammation in patients with quiescent SB CD was observed. Between-modality correlation was higher in patients with endoscopically severe disease. DW-MRE gauged by Clermont score was at least as accurate as contrast-enhanced MRE for quantification of SB inflammation.

Gut mucosal DAMPs in IBD: from mechanisms to therapeutic implications.

Endogenous damage-associated molecular patterns (DAMPs) are released during tissue damage and have increasingly recognized roles in the etiology of many human diseases. The inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), are immune-mediated conditions where high levels of DAMPs are observed. DAMPs such as calprotectin (S100A8/9) have an established clinical role as a biomarker in IBD. In this review, we use IBD as an archetypal common chronic inflammatory disease to focus on the conceptual and evidential importance of DAMPs in pathogenesis and why DAMPs represent an entirely new class of targets for clinical translation.

Tu1952 Serum Levels of 1,3-beta-D-Glucan Are Associated With Intestinal Inflammation in Crohn's Disease

Tu1952 Serum Levels of 1,3-beta-D-Glucan Are Associated With Intestinal Inflammation in Crohn's Disease

Su1832 Sacroiliitis is underrecognized in Inflammatory Bowel Disease and is Associated With Previous Arthritis and Inflammatory Crohn's Phenotype

Su1832 Sacroiliitis is underrecognized in Inflammatory Bowel Disease and is Associated With Previous Arthritis and Inflammatory Crohn's Phenotype

Diffusion-weighted Magnetic Resonance Enterography for Evaluating Bowel Inflammation in Crohn's Disease: A Systematic Review and Meta-analysis.

To systematically determine the performance of diffusion-weighted imaging magnetic resonance enterography (DWI-MRE) for evaluating bowel inflammation in Crohn's disease and sources of heterogeneity between reported results. We identified research studies that investigated DWI-MRE to diagnose bowel inflammation (present versus absent) or to assess bowel inflammatory severity in Crohn's disease by performing a systematic search of PubMed MEDLINE and EMBASE (until March 31, 2015). Study quality was assessed using QUADAS-2. For studies reporting dichotomous diagnosis of bowel inflammation, study heterogeneity and threshold effect were analyzed, summary sensitivity and specificity were estimated, and meta-regression analysis was performed to further explore study heterogeneity. For studies reporting assessment of inflammatory severity, a qualitative summary was performed. Of 159 articles screened, we found 12 studies (1515 bowel segments) reporting a diagnosis of bowel inflammation and 6 studies (1066 bowel segments) reporting assessment of inflammatory severity. The summary sensitivity and specificity were 92.9% (95% CI, 85.8%-96.6%; I = 87.9%) and 91% (95% CI, 79.7%-96.3%; I = 95.1%), respectively. Sensitivity and false-positive rate were inversely correlated (r = -0.650; P = 0.022). Lack of blinding to contrast-enhanced MRE when interpreting DWI-MRE (P = 0.01) and use of contrast-enhanced MRE as a reference standard (P < 0.01) in some studies were significant factors for study heterogeneity and likely caused overestimation of DWI-MRE accuracy. There was rather clear correlation between diffusion-related parameters and bowel inflammation severity, although the strengths were heterogeneous (correlation coefficient, 0.39-0.98). DWI-MRE accuracy was very heterogeneous between studies and was likely overestimated in some studies. Despite rather clear correlation between diffusion-related parameters and bowel inflammatory severity, its strength was variable.

P291. Sacroiliitis is under-recognised in inflammatory bowel disease and is associated with previous arthritis and inflammatory Crohn’s phenotype

P291. Sacroiliitis is under-recognised in inflammatory bowel disease and is associated with previous arthritis and inflammatory Crohn’s phenotype

Inflammatory bowel disease in pregnancy: a population‐based study of prevalence and pregnancy outcomes

To determine the prevalence of the inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), in pregnant women and determine pregnancy and fetal/neonatal outcomes. Population-based cohort study. New South Wales, Australia, 2001-11. A total of 630742 women who delivered at ≥20weeks of gestation. Descriptive and multivariate regression analyses of perinatal data linked to hospital admission data. We compared birth outcomes of women with and without a documented diagnosis of IBD. Caesarean section, severe maternal morbidity, preterm birth <37weeks of gestation, planned preterm birth, small-for-gestational-age (birthweight <10th centile), perinatal mortality (stillbirth/neonatal death ≤28days). In all, 1960 women (0.31%) with IBD, who had 2781 births (1183 UC, 1287 CD and 311 IBD-indeterminate). Women with IBD were more likely than women without IBD to have a caesarean section [41.5 versus 28.2%, adjusted risk ratio (aRR) 1.38, 95% CI 1.31-1.45], severe maternal morbidity (2.6 versus 1.6%, aRR 1.54, 95% CI 1.17-2.03), preterm birth (9.7 versus 6.6%, aRR 1.47, 95% CI 1.30-1.66), planned preterm birth (5.3 versus 2.9%, aRR 1.74, 95% CI 1.47-2.07), and their infants to be small-for-gestational-age (9.7 versus 9.5%, aRR 1.19, 95% CI 1.04-1.36). There was no evidence of a difference in perinatal mortality. Pregnancy-associated IBD is more common than previously reported. Pregnancies complicated by IBD at or near the time of birth have significantly higher rates of adverse pregnancy outcomes than pregnancies of women without IBD. Increased rates preterm birth and caesarean section in women with inflammatory bowel disease.

Exploring and Enhancing the Anti-Inflammatory Properties of Polymeric Formula.

Exclusive enteral nutrition (EEN) therapy using a polymeric formula (PF) can substantially attenuate intestinal inflammation in Crohn's disease (CD) patients. However, the mechanism(s) by which EEN suppresses inflammation are not yet fully understood. The aims were to examine cellular mechanism(s) through which EEN may suppress inflammation and investigate potential pathways to enhance anti-inflammatory properties of EEN. Glutamine, arginine, vitamin D3, and α linolenic acid (ALA), present in PF, along with curcumin, were identified as immunoactive nutrient therapies. Tumor necrosis factor (TNF)-α-exposed HT-29 colonic epithelial cells were used to investigate the immunosuppressive activity of the nutrients by assessing their effect on cell viability, cell activity, chemokine response (interleukin-8 [IL-8]), nuclear factor (NF)-κB, P38 mitogen-activated protein kinase, IκB kinase (Iκκ), and nitric oxide (NO). Cellular viability and activity were maintained with all nutrient treatments. Glutamine, arginine, and vitamin D3, but not ALA, significantly attenuated IL-8 production. Glutamine and arginine led to phosphorylation blockade of the signaling components in NF-κB and P38 pathways, reduction in kinase activity, and enhancement in NO production. Combining glutamine, arginine, and curcumin at optimal concentrations completely abolished the IL-8 response. These data indicate that glutamine, arginine, and vitamin D3 can suppress inflammation at concentrations equivalent to those used in PF. The mechanisms of this action were mediated through influencing the NF-κB and P38 cascades. Glutamine and arginine-fortified PF with curcumin might be a promising option to enhance the effectiveness and expand the scope of EEN therapy in CD treatment.

Ex vivo response to mucosal bacteria and muramyl dipeptide in inflammatory bowel disease.

AIMTo evaluate how mucosal bacteria impact on the spontaneous and muramyl dipeptide (MDP)-induced inflammation in Crohn’s disease (CD) and ulcerative colitis (UC).METHODSColonic mucosal biopsies were collected from children with active or remissive CD, UC and controls. Two tissue samples were taken from inflamed mucosal segments (in patients with active disease) or from non-inflamed mucosa [in patients in remission or in healthy controls (HC)]. Experiments were performed in the presence or absence of antibiotics, to assess whether the disease-associated microbiota can modulate the cytokine response ex vivo. For this purpose, each specimen was half-cut to compare spontaneous and MDP-induced inflammation in the presence of live bacteria (LB) or antibiotics. After 24 h of culture, an array of 17 cytokines was assessed in supernatants. Statistical analyses were performed to find significant differences in single cytokines or in patterns of cytokine response in the different groups.RESULTSWe demonstrated that subjects with CD display a spontaneous production of inflammatory cytokines including granulocyte-colony stimulating factor (G-CSF), interleukin (IL) 6, IL8, IL10 and IL12, that was not significantly influenced by the addition of antibiotics. UC specimens also displayed a trend of increased spontaneous secretion of several cytokines, which however was not significant due to broader variability among patients. After the addition of antibiotics, spontaneous IL8 secretion was significantly higher in UC than in controls. In HC, a trend towards the weakening of spontaneous IL8 production was observed in the presence of live mucosal bacteria with respect to the presence of antibiotics. In contrast, in the presence of LB UC showed an increasing trend of spontaneous IL8 production, while MDP stimulation resulted in lower IL8 production in the presence of antibiotics. We also showed that subjects with CD seem to have a lowered production of IL8 in response to MDP in the presence of LB. Only with the addition of antibiotics, likely reducing the contribution of LB, multivariate statistical analysis could identify the combination of measures of G-CSF, tumor necrosis factor alpha, IL4 and IL17 as a good discriminator between CD and UC.CONCLUSIONWe showed that the presence of LB or antibiotics can significantly influence the inflammatory response ex vivo in inflammatory bowel diseases.

Current status of Mycobacterium avium subspecies paratuberculosis infection in animals & humans in India: What needs to be done?

Mycobacterium avium subspecies paratuberculosis (MAP) has emerged as a major health problem for domestic livestock and human beings. Reduced per animal productivity of domestic livestock seriously impacts the economics of dairy farming globally. High to very high bioload of MAP in domestic livestock and also in the human population has been reported from north India. Presence of live MAP bacilli in commercial supplies of raw and pasteurized milk and milk products indicates its public health significance. MAP is not inactivated during pasteurization, therefore, entering into human food chain daily. Recovery of MAP from patients with inflammatory bowel disease or Crohn's disease and animal healthcare workers suffering with chronic gastrointestinal problems indicate a close association of MAP with a number of chronic and other diseases affecting human health. Higher bioload of MAP in the animals increases the risk of exposure to the human population with MAP. This review summarizes the current status of MAP infection in animals as well as in human beings and also highlights the prospects of effective management and control of disease in animals to reduce the risk of exposure to human population.

(1)H-NMR based metabolomics study for the detection of the human urine metabolic profile effects of Origanum dictamnus tea ingestion.

(1)H NMR spectroscopy was employed to investigate the repercussion of Origanum dictamnus tea ingestion in several volunteers' urine metabolic profiles, among them two with chronic inflammatory bowel diseases (IBD), mild IBD and Crohn's disease. Herein, we demonstrate that the concentrations of a lot of urinary metabolites such as hippurate, trimethylamine oxide (TMAO), citrate, and creatinine are altered, which prompts the intestinal microflora function/content perturbation as well as kidney function regulation by dictamnus tea. Interestingly, our preliminary results showed that a high dose of dictamnus tea intake appeared to be toxic for a person with Crohn's disease, since it caused high endogenous ethanol excretion in urine. All subjects' metabolic effects caused by the dictamnus tea appeared to be reversible, when all volunteers stopped its consumption. Finally, we highlight that individuals' metabolic phenotype is reflected in their urine biofluid before and after the dictamnus tea effect while all individuals have some common and different metabolic responses to this tea, implying that each phenotype has a quite different response to this tea consumption.

TREATMENT OF ANEMIA AND IMPROVEMENT OF QUALITY OF LIFE AMONG PATIENTS WITH CROHN'S DISEASE: experience using ferric carboxymaltose.

Anemia is the most common hematological alteration in patients with Crohn's disease, and is frequently related to intestinal inflammatory activity. Its cause is multifactorial and mostly associated with absolute iron deficiency (iron deficiency anemia) and/or functional iron deficiency (inflammation anemia or anemia of chronic disease). It may also be identified through other causes, such as folic acid or vitamin B12 deficiency and secondary to adverse effects from medications (salicylic derivatives and immunosuppressive drugs). In the present study, patients with active Crohn's disease and anemia were evaluated and treated with intravenous ferric carboxymaltose. We discuss the therapeutic schemes (doses), safety, results and improvement of quality of life. In the present prospective study, 10 consecutive patients with Crohn's disease, with moderate to severe activity, with anemia (Hb: 6.7 to 10 g/dL), who were attended between March 2014 and March 2015, were evaluated. Six (60%) were men and four were women, all with moderate or severe anemia (hemoglobin <10 g/dL). They were treated with a maximum of three intravenous infusions of 1000 mg of ferric carboxymaltose, of at least 15 minutes in duration. It was also sought to correlate the inflammatory Crohn's disease activity degree (measured using the Crohn's Disease Activity Index, CDAI) and C-reactive protein level with the severity of anemia. The primary outcome was an increase in Hb of ≥2 g/dL and the secondary outcome was the normalization of anemia (Hb ≥12 g/dL for women and ≥13 g/dL for men) and the improvement in quality of life seen 12 weeks after the last application of carboxymaltose. Among the 10 patients studied, parenteral iron supplementation was administered in three cases during hospitalization and the others received this on an outpatient basis. The total iron dose ranged from 1,000 to 2,000 mg, with an average of 1,650 mg. Crohn's disease activity measured using CDAI and C-reactive protein correlated with the intensity of anemia. An increase of 2 g/dL occurred in eight (80%) patients after 12 weeks and normalization of anemia was found in seven (70%) patients. Improvements in quality-of-life scores were found for all (100%) patients after 12 weeks. Carboxymaltose was well tolerated. Three patients presented adverse reactions (two with nausea and one with headache) of mild intensity. Anemia is a frequent complication for Crohn's disease patients. Intravenous iron therapy has been recommended for Crohn's disease patients, because for these patients, oral iron absorption is very limited. This is because of the inflammatory state and "blocking" of iron entry into enterocytes through hepcidin action on ferroportin, along with the elevated rates of gastrointestinal adverse events that compromise adherence to treatment and possibly aggravate the intestinal inflammatory state. The degree of Crohn's disease activity, as measured using CDAI and C-reactive protein, correlates with the severity of anemia. Carboxymaltose is a safe drug, which can be administrated in high doses (up to 1,000 mg per application per week) and corrects anemia and iron stocks over a short period of time, with consequent improvement in quality of life.

JAK inhibition using tofacitinib for inflammatory bowel disease treatment: a hub for multiple inflammatory cytokines.

The inflammatory diseases ulcerative colitis and Crohn's disease constitute the two main forms of inflammatory bowel disease (IBD). They are characterized by chronic, relapsing inflammation of the gastrointestinal tract, significantly impacting on patient quality of life and often requiring prolonged treatment. Existing therapies for IBD are not effective for all patients, and an unmet need exists for additional therapies to induce and maintain remission. Here we describe the mechanism of action of the Janus kinase (JAK) inhibitor, tofacitinib, for the treatment of IBD and the effect of JAK inhibition on the chronic cycle of inflammation that is characteristic of the disease. The pathogenesis of IBD involves a dysfunctional response from the innate and adaptive immune system, resulting in overexpression of multiple inflammatory cytokines, many of which signal through JAKs. Thus JAK inhibition allows multiple cytokine signaling pathways to be targeted and is expected to modulate the innate and adaptive immune response in IBD, thereby interrupting the cycle of inflammation. Tofacitinib is an oral, small molecule JAK inhibitor that is being investigated as a targeted immunomodulator for IBD. Clinical development of tofacitinib and other JAK inhibitors is ongoing, with the aspiration of providing new treatment options for IBD that have the potential to deliver prolonged efficacy and clinically meaningful patient benefits.

Bugs, genes, fatty acids, and serotonin: Unraveling inflammatory bowel disease?

The annual incidence of the inflammatory bowel diseases (IBDs) ulcerative colitis and Crohn’s disease has increased at an alarming rate. Although the specific pathophysiology underlying IBD continues to be elusive, it is hypothesized that IBD results from an aberrant and persistent immune response directed against microbes or their products in the gut, facilitated by the genetic susceptibility of the host and intrinsic alterations in mucosal barrier function. In this review, we will describe advances in the understanding of how the interaction of host genetics and the intestinal microbiome contribute to the pathogenesis of IBD, with a focus on bacterial metabolites such as short chain fatty acids (SCFAs) as possible key signaling molecules. In particular, we will describe alterations of the intestinal microbiota in IBD, focusing on how genetic loci affect the gut microbial phylogenetic distribution and the production of their major microbial metabolic product, SCFAs. We then describe how enteroendocrine cells and myenteric nerves express SCFA receptors that integrate networks such as the cholinergic and serotonergic neural systems and the glucagon-like peptide hormonal pathway, to modulate gut inflammation, permeability, and growth as part of an integrated model of IBD pathogenesis. Through this integrative approach, we hope that novel hypotheses will emerge that will be tested in reductionist, hypothesis-driven studies in order to examine the interrelationship of these systems in the hope of better understanding IBD pathogenesis and to inform novel therapies.

Linkage between genotype and immunological phenotype in Crohn's disease.

Understanding the mechanisms that drive uncontrolled inflammation in Crohn's disease (CD) remains one of the most pressing challenges in contemporary experimental medicine. Recently, a three-phased view on the pathogenesis of CD was proposed in which following the breakdown of intestinal epithelial barrier function, CD patients fail to clear the resulting infectious debris, provoking subsequent immune responses. This view on CD is attractive in that it is testable and allows better diagnosis of disease if proven correct, apart from opening a window on new therapeutic horizons. Here we shall argue, however, that this scheme may be an oversimplification in that it ignores the genetic diversity of CD and thus does not fully take into account the nature of the intestinal epithelium, which appears a non-passive actor in this disease.

Increased catabolism and decreased unsaturation of ganglioside in patients with inflammatory bowel disease.

To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease (n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps (n = 6) and colorectal cancer (n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine (PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A (HEXA) and sialidase-3 (NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. Relative GM3 ganglioside content was 2-fold higher (P < 0.05) in intestine from patients with inflammatory bowel disease (IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue (P < 0.05). Control intestine exhibited 3-fold higher (P < 0.01) relative GD1a ganglioside content than IBD intestine. GD3 and GD1a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine (P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold (P < 0.05) and NEU3 was increased 8.3-fold (P < 0.01) compared to normal intestine. Intestinal mucosa in IBD is characterized by increased GM3 content, decreased GD1a, and a reduction in polyunsaturated fatty acid constituents in GD3, GD1a and PC. This study suggests a new paradigm by proposing that IBD occurs as a consequence of increased metabolism of specific gangliosides.

Lewis Score – Prognostic Value in Patients with Isolated Small Bowel Crohn’s Disease

Small bowel capsule endoscopy (SBCE) allows mapping of small bowel inflammation in Crohn's disease (CD). We aimed to assess the prognostic value of the severity of inflammatory lesions, quantified by the Lewis score (LS), in patients with isolated small bowel CD. A retrospective study was performed in which 53 patients with isolated small bowel CD were submitted to SBCE at the time of diagnosis. The Lewis score was calculated and patients had at least 12 months of follow-up after diagnosis. As adverse events we defined disease flare requiring systemic corticosteroid therapy, hospitalization and/or surgery during follow-up. We compared the incidence of adverse events in 2 patient subgroups, i.e. those with moderate or severe inflammatory activity (LS ≥790) and those with mild inflammatory activity (135 ≤ LS < 790). The LS was ≥790 in 22 patients (41.5%), while 58.5% presented with LS between 135 and 790. Patients with a higher LS were more frequently smokers (p = 0.01), males (p = 0017) and under immunosuppressive therapy (p = 0.004). In multivariate analysis, moderate to severe disease at SBCE was independently associated with corticosteroid therapy during follow-up, with a relative risk (RR) of 5 (p = 0.011; 95% confidence interval [CI] 1.5-17.8), and for hospitalization, with an RR of 13.7 (p = 0 .028; 95% CI 1.3-141.9). In patients with moderate to severe inflammatory activity there were higher prevalences of corticosteroid therapy demand and hospitalization during follow-up. Thus, stratifying the degree of small bowel inflammatory activity with SBCE and LS calculation at the time of diagnosis provided relevant prognostic value in patients with isolated small bowel CD.