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COVID-19; Immunosuppression; Inflammatory bowel disease COVID-19; Immunosupressió; Malaltia inflamatòria intestinal COVID-19; Inmunosupresión; Enfermedad inflamatoria intestinal (1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case−control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March−July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3−5.9), occupational risk (OR: 2.9; 95%CI: 1.8−4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2−2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09−0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution.

We present the case of an 82-year-old man with a medical history of hypertension, dyslipidemia, diabetes mellitus, chronic renal failure, ischemic heart disease and iron deficiency anemia. He was under therapy with hydralazine, furosemide, amlodipine, valsartan, nitroglycerin patches, bisoprolol, omeprazole, doxazosin, human insulin and oral iron. The patient presented at our Institution with melena. Initial gastroscopy showed fresh blood and a gastric angiodysplasia that was treated with argon plasma coagulation (APC). Three months later, he suffered from a new episode of bleeding and consequently, a small bowel capsule endoscopy (SBCE) was indicated. It was reported a gastric and duodenal mucosa with an intense speckled black pigmentation, compatible with pseudomelanosis.

Background Information on the use of fecal markers in microscopic colitis screening is limited. Aim To evaluate the risk variables associated with a diagnosis of microscopic colitis including fecal calprotectin. Methods Patients submitted for a colonoscopy due to chronic watery diarrhea fulfilling criteria of functional disease were evaluated. Colonic mucosa was normal but mild erythema and edema was allowed. Fecal calprotectin was analyzed. A logistic regression was used to evaluate variables associated with both raised fecal calprotectin and a diagnosis of microscopic colitis. Results 94 patients were included, 30 were diagnosed with microscopic colitis and 64 made up the control group. Median calprotectin levels were 175 (IQR, 59–325) for the microscopic colitis and 28 (IQR, 16–111) for the control group (p 100 μg/g (AUC, 0.73), with 67% sensitivity and 75% specificity. The number of drugs used ≥3 (OR, 3.9; CI, 1.4–10.4) and microscopic colitis diagnosis (OR, 6; CI, 2.2–16.3) were associated with raised calprotectin levels. Age >60 years (OR, 3.8; CI, 1.4–10.1) and calprotectin levels (OR, 5.3; CI, 2–14.1) were associated with a risk of microscopic colitis. Conclusions Elevated fecal calprotectin concentrations are often seen in microscopic colitis, and may be helpful in the diagnosis of women over 60 with chronic watery diarrhea.

1. Background: The long-term effect of a gluten-free diet (GFD) on functional bowel disorders (FBDs) has been scarcely studied. The aim was to assess the effect of a GFD on FBD patients, and to assess the role of both the low-grade coeliac score and coeliac lymphogram in the probability of response to a GFD. 2. Methods: 116 adult patients with either predominant diarrhoea or abdominal bloating, fulfilling Rome IV criteria of FBD, were treated with a GFD. Duodenum biopsies were performed for both pathology studies and intraepithelial lymphocyte subpopulation patterns. Coeliac lymphogram was defined as an increase in TCRγδ+ cells plus a decrease in CD3− cells. A low-grade coeliac score &gt, 10 was considered positive. 3. Results: Sustained response to GFD was observed in 72 patients (62%) after a median of 21 months of follow-up, who presented more often with coeliac lymphogram (37.5 vs. 11.4%, p = 0.02) and a score &gt, 10 (32 vs. 11.4%, p = 0.027) compared to non-responders. The frequency of low-grade coeliac enteropathy was 19.8%. 4. Conclusion: A GFD is effective in the long-term treatment of patients with previously unexplained chronic watery diarrhoea- or bloating-predominant symptoms fulfilling the criteria of FBD. The response rate was much higher in the subgroup of patients defined by the presence of both a positive low-grade coeliac score and coeliac lymphogram.

Background The exhaustive registry of COVID-19 cases in patients with IBD is a unique opportunity to learn how to deal with this infection, especially in reference to the management of immunosuppressive treatment, isolation measures or if the disease is more severe in IBD patients due to immunosuppression. With these premises, the aims of this study were to know the incidence and characteristics of COVID-19 in the ENEIDA cohort during the first wave of the pandemic; the outcomes among those under immunosuppressants/biologics for IBD; the risk factors for contracting the infection and poor outcomes; and the impact of the infection after three-month follow-up. Methods Prospective observational cohort study of all IBD patients with COVID-19 included in the ENEIDA registry (with 60.512 patients in that period) between March and July 2020, with at least 3 months of follow-up. Any patient with a confirmed (by PCR or SARS-CoV-2 serology) or probable (suggestive clinical picture) infection was considered as a case. Results A total of 484 patients with COVID-19 from 63 centres were included: 247 Crohn’s disease, 223 ulcerative colitis and 14 unclassified colitis; median age 52 years (IQR: 42–61), 48% women and 44% ≥1 comorbidity. Diagnosis was made by PCR: 63% and serology: 35%. The most frequent symptoms: fever (69%), followed by cough (63%) and asthenia (38%). During lockdown 78% followed strict isolation. 35% required hospital admission (ICU: 2.7%) and 12% fulfilled criteria for SIRS upon admission. 16 patients died from COVID-19 (mortality:3.3%). 12% stop IBD medication during COVID-19. At 3 months, taken into account all included cases, 76% were in remission of IBD. Male gender (OR 1.56; 95%CI:1–2.4, p=0.05), ≥40 years of age (OR 2.55; 95% CI:1.4–4.8; p=0.004), Charlson score ≥1 (OR 2.1; 95% CI:1.3–3.5; p=0.004), and systemic steroids Conclusion IBD does not seem to worsen the prognosis of COVID-19, even when immunosuppressants and biological drugs are used. Age and comorbidity are the most important prognostic factors for more severe COVID-19 in IBD patients. The use of aminosalicylates and the risk of a worse outcome deserves a deeper analysis. Funded by the Carlos III Health Institute (COV20 / 00227).

Resumen Colitis microscopica es un termino generico que incluye 2 formas principales, colitis colagena y colitis linfocitica, que describe una forma de enfermedad inflamatoria intestinal con curso cronico y recidivante. La incidencia de colitis microscopica es entre 2 y 8 veces mas alta en mujeres que en hombres; sin embargo, la edad contribuye mas que el sexo en el riesgo de colitis colagena (OR 8,3 para edad ≥ 65 vs.

Background Vδ1+ and Vδ2+ are TCRγδ lymphocytes of the gut intraepithelial compartment that recognise proteins without help of antigen-presenting cells. Its relevance in inflammatory bowel disease (IBD) is unknown. Aim To measure Vδ1+ and Vδ2+ in T-cell subtypes [CD4+, CD8+, double positive (DP,CD4+CD8+), double negative (DN,CD4−CD8−) and CD103+] of healthy and IBD inflammed gut mucosa. Methods Twenty-six active IBD patients without immunosuppressants (n = 18 Crohn’s disease (CD), eight ulcerative colitis (UC)) and 10 healthy controls (paired biopsies of ileum, right and left colon) were included. Lymphocytes were analysed with LSRFortessa cytometer. Results expressed as % median (25–75%IQI). Results Healthy mucosa: reduction in ileum of total CD3+Vδ1+ due to CD3+CD8+Vδ1+ and CD3+DN_Vδ1+ Conclusion Reduction of Vδ1+ and Vδ2+, mainly of CD103+, may play a role in IBD pathophysiology by perpetuating inflammation. Increase of CD3+Vδ1+CD4+ in both Ileal CD and UC may compensate this decrease with a selective increase in ‘helper’ function.

Background and Aims There is controversy as to whether the risk of relevant infection in IBD is related to immunosuppressants or the disease itself. The aims of this study were to evaluate: [1] the life-long prevalence and types of relevant infections in patients with IBD related to immunosuppressive treatment, and [2] the relationship of both infection and patient comorbidity to mortality. Methods Observational multicentre retrospective study of IBD patients that presented a relevant infection. For each case, four periods of infection exposure were analysed: P1: pre-IBD diagnosis, P2: from IBD diagnosis to immunosuppressant initiation, P3: during immunosuppressant therapy, and P4: after treatment withdrawal. Results The life-long prevalence of relevant infection in the total cohort of patients [6914] was 3%, and 5% in immunosuppressed patients [4202]. 366 relevant infections were found in 212 patients [P1: 9, P2: 17, P3: 334, and P4: 6]. Differences between periods were significant [p < 0.0001]. The most frequent types of infection were respiratory, intestinal and urinary. The most frequent opportunistic infections were tuberculosis [prevalence: 2.6/1000] and herpes zoster [prevalence: 3.9/1000]. Herpes zoster infection was associated with thiopurines alone or in combination with anti-TNF in 75% of the cases, whereas tuberculosis was associated with anti-TNF in 94% of patients. The overall mortality was 4.2%. Infection-related mortality was 2.8% and it was not influenced by comorbidity. Conclusions Relevant infections in IBD patients are rare and appear to be related to immunosuppression. Relevant infection is a major cause of death in IBD.

Background and Aims: There is very limited information regarding region-specific immunological response in human intestine. We aimed to determine differences in immune compartmentalisation between ileum and colon in healthy and inflamed mucosa. Methods: T cell profile and its apoptosis were measured by flow cytometry, Th1, Th17, Treg [CD4+CD25+FOXP3+], double positive [DP, CD3+CD4+CD8+] and double negative T cells [DN, CD3+CD4-CD8-], immunohistochemistry \[FOXP3, caspase-3], and real-time polymerase chain reaction [PCR\] \[IFN-γ, IL-17-A, and FOXP3\] on biopsies from different regions of healthy intestine and of intestine in inflammatory bowel diseases. Results: Healthy colon showed higher percentages of Treg, Th17, and DN, and lower numbers of DP T cells compared with ileum [ p < 0.05]. Some but not all region-specific differences were lost in inflammatory conditions. Disease-specific patterns were found: a Th1/Th17 pattern and a Th17 pattern in Crohn’s disease and ulcerative colitis respectively, whereas a reduction in Th1/Th17 was found in microscopic colitis. In colonic Crohn’s disease and microscopic colitis, DN T cells had a pattern inverse to that of Th1/Th17 (increase in microscopic colitis [ p < 0.05] and decrease in Crohn’s disease [ p < 0.005]). Higher levels of lymphocyte apoptosis were found in healthy colon compared with the ileal counterparts [ p = 0.001]. All forms of colonic inflammation presented a dramatic decrease in apoptosis compared with healthy colon. By contrast ileal Crohn’s disease showed higher levels of cleaved-Caspase+ CD3+ cells. Conclusions: Immunological differences exist in healthy gastrointestinal tract. Inflammatory processes overwhelm some location-specific differences, whereas others are maintained. Care has to be taken when analysing immune response in intestinal inflammation, as location-specific differences may be relevant.

Background: Lymphocytic (LC) and collagenous (CC) colitis are the two major forms of microscopic colitis (MC). The aim of this study was to identify similarities and differences in their mucosal immune characteristics. Methods: Colonic biopsies from 15 CC, 8 LC, and 10 healthy controls were collected. Mucosal lymphocytes were assessed by flow cytometry. Tissue gene expression and protein levels were determined by real-time PCR and ELISA, respectively. Results: LC patients had lower numbers of CD4+ and double-positive CD4+CD8+mucosal T lymphocytes, and higher numbers of CD8+ and CD4+TCRγδ+ mucosal T cells, compared with controls and CC patients. Regulatory Treg (CD4+CD25+FOXP3+) and double-negative (CD3+CD4-CD8-) T cell percentages were higher in both CC and LC compared with controls, coupled with higher levels of the anti-inflammatory IL-10, both at mRNA and protein levels. By contrast, Th1 and Th17 cells were lower in both CC and LC, although gene expression of Th1/Th17 cytokines was higher in both. Conclusion: CC and LC share some regulatory and effector mechanisms, but not others. Higher IL-10 levels and higher Treg and double-negative T cell percentages, found in both CC and LC, could be responsible for the lack of progression of structural damage and the blockade of proinflammatory cytokine production. However, CC and LC are revealed as separate, independent entities, as they show clearly different mucosal lymphocyte profiles, which could be caused by different luminal triggers of the two diseases. Hence, CC and LC are two closely related but independent intestinal disorders.

To evaluate the early and long-term efficacy of infliximab in ulcerative colitis and to determine predictors of response and colectomy. This is an ambidirectional cohort study in a tertiary referral center including patients who started infliximab within 2005 and 2008 and monitored until 2014. Efficacy was evaluated by partial Mayo scores at weeks 2, 4, 8, 30, and 54. Long-term treatment maintenance with infliximab and colectomy requirements were recorded. Fifty-three patients were included with a median follow-up of 69.5 months. Clinical remission at the time point assessments was 40.8, 47.2, 54.7, 54.7, and 49.1 %. At the time of maximal follow-up, the proportion of patients under infliximab maintenance was 24.5 %. A higher level of albumin (OR 1.4, CI 95 % 1.06–1.8; p = 0.017) was predictive of a higher remission rate at week 8. Concomitant immunomodulators beyond 6 months were predictive of infliximab’s long-term maintenance (OR 15.8, CI 95 % 1.8–135.4; p = 0.012). Colectomy was required in 41.5 %. Factors associated with a higher rate of colectomy at week 54 were previous treatment with cyclosporine (OR 3.4, CI 95 % 1.2–9.7; p = 0.012), absence of response at week 8 (OR 10.3, CI 95 % 3.3–31.7; p

Aims: (1) Assess the population-based incidence of severe olmesartan-associated enteropathy. (2) To describe patients of the Spanish registry. (3) Evaluate markers of potential coeliac disease and associated autoimmunity. Methods: Crude incidence rates in the area of Terrassa (Catalonia) were calculated. Clinical characteristics of patients in the Spanish registry were collected. Duodenal lymphocyte subpopulations and anti-TG2 IgA deposits were assessed in a subset of patients. Results: Annual incidence rates (2011-2014) ranged from 0 to 22 cases per 104 treated patients. Twenty patients were included in the Spanish registry. Nineteen (95%) exhibited villous atrophy and 16 (80%) had severe enteropathy. Lupus-like disease occurred during olmesartan treatment in 3 patients. HLA-DQ2/DQ8 was positive in 64%. Markers of potential coeliac disease were present in 4 out of 8 patients (positive anti-TG2 deposits and/or increased CD3+ gammadelta+ intraepithelial lymphocytes and reduced CD3-). Histopathological changes and clinical manifestations including autoimmune disorders improved after olmesartan discontinuation but not after gluten-free diet, irrespective of the presence or absence of coeliac markers. Conclusions: Incidence of severe olmesartan-associated enteropathy was low. Autoimmune phenomena were present in a subset of cases and reversed after olmesartan removal. A genetic coeliac disease background and the presence of potential coeliac markers might uncover predisposing factors. (C) 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Background CD161 is a type C lectin expressed in NKs cells and peripheral T cells (TCRγδ and αβ, NKTs), enriched in intestinal populations. Its expression can be modulated by infections and inflammation. MAIT cells are a subset of innate antimicrobial T-cells abundant in the mucosa but their role in immunological regulation is still unknown. Aim To measure CD161 levels in subtypes of T-lymphocytes of intestinal mucosa: CD4+, CD8+, double positive (DP,CD4+CD8+), double negative (DN,CD4−CD8−), MAIT cells (CD161+TCRVα7.2+) and intraepithelial cells (CD103+) Methods Twenty-six patients with active inflammatory bowel disease (IBD) without immunosuppressive treatment (n = 9 Crohn’s disease -CD- colon, 9 CD ileum, n = 8 ulcerative colitis -UC- and 10 healthy controls (paired biopsies of ileum, right and left colon) were included. Lymphocyte subpopulations were analysed with LSRFortessa cytometer. Non-parametric Kruskal–Wallis test was applied. Results are expressed as % of median (25–75%IQI). Results In healthy mucosa, we did not find differences related to location in any of CD161 subpopulations except for increase of CD3+CD161+CD103+ and decrease of CD3+CD161+CD103− in left colon compared with right colon and ileum. Regarding MAIT cells, a progressive decrease was observed in distal parts of intestine for CD3+MAIT+CD103+ while CD3+MAIT+CD103− subpopulation has a specular behaviour; CD3+CD8+MAIT+ was increased in ileum compared with colon (Table 1). Conclusion There is a regional specialisation for the subset CD103+ of both CD161+CD103+ and MAIT_CD103+ cells in healthy intestine. CD3+CD161+ T cells are reduced in IBD colonic inflammation and could serve as a marker of active IBD but not to sort between CD and UC.

Resumen Introduccion y objetivo La adecuacion de las indicaciones de la colonoscopia a las recomendaciones vigentes es importante para optimizar los recursos disponibles. El objetivo fue valorar el grado de adecuacion de las indicaciones de colonoscopia en una unidad de endoscopia de acceso abierto utilizando los criterios EPAGE II. Metodos Se incluyeron de forma retrospectiva las colonoscopias realizadas entre el 1 de octubre y el 30 de noviembre de 2011. La adecuacion de la colonoscopia se establecio de acuerdo con los criterios EPAGE II. Se registraron datos demograficos, medicos solicitantes, indicaciones y hallazgos relevantes de estas exploraciones. Resultados Se incluyeron 440 colonoscopias (54% mujeres; edad, 60,8 ± 16,3 anos). La indicacion fue apropiada en 75,4% (IC: 71-79,3%), incierta en 13,1% (IC: 10,2-16,6%) e inapropiada en 11,4% (IC: 8,7-14,8%). En el analisis univariante la presencia de hallazgos relevantes se asocio a la edad, el sexo, la indicacion y EPAGE II. En el analisis de regresion logistica la edad ≥ 50 anos (OR: 1,84), el sexo masculino (OR: 2,7) y 2 indicaciones, control EII y vigilancia pospolipectomia (p Conclusiones El grado de inadecuacion de la colonoscopia es elevado, sobre todo en pacientes jovenes (

Ulcerative colitis (UC) treatment is focused to achieve mucosal healing, avoiding disease progression. The study aimed to evaluate the real-world effectiveness of adalimumab (ADA) in UC and to identify predictors of remission to ADA.This cohort study used data from the ENEIDA registry. Clinical response, clinical remission, endoscopic remission, adverse events (AE), colectomy, and hospitalisations were evaluated; baseline characteristics and biological parameters were compared to determine predictors of response.We included 263 patients (87 naïve and 176 previously exposed to anti-tumour necrosis factor alpha, TNF). After 12 weeks, clinical response, clinical remission, and endoscopic remission rates were 51, 26, and 14 %, respectively. The naïve group demonstrated better response to treatment than the anti-TNF-exposed group at short-term. Clinical and endoscopic remission within 1 year of treatment was better in the naïve group (65 vs. 49 and 50 vs. 35 %, respectively). The rates of AE, dose-escalation, hospitalisations, and colectomy during the first year were higher in anti-TNF-exposed patients (40, 43, and 27 % vs. 26, 21, and 11 %, respectively). Patients with primary failure and intolerance to the first anti-TNF and severe disease were associated with worse clinical response. Primary non-response to prior anti-TNF treatment and severe disease were predictive of poorer clinical remission. Low levels of C-reactive protein (CRP) and faecal calprotectin (FC) at baseline were predictors of clinical remission.In clinical practice, ADA was effective in UC, especially in anti-TNF naïve patients. FC and CRP could be predictors of treatment effectiveness.

Background and aims: Few studies have assessed the prevalence of microscopic colitis (MC) and the natural history of this disease is not well known. The aim of this study was to evaluate the prevalence rate of MC, the burden of disease in terms of loss of health and the long-term natural history of MC in a population-based cohort study. Methods: Cases were obtained from the pathology department registry Hospital Universitari Mutua Terrassa. Belonging to the catchment area, maintaining residence in that area, and being alive on August 31, 2014 were confirmed for each case. Adjusted prevalence rates were calculated. Current active drugs for MC and diarrhoea persistence in every patient were recorded. Results: The prevalence rate of MC was 107 per 105 inhabitants. The rate of patients with active disease, i.e. those representing the true burden of the disease in terms of loss of health, was 31 per 105 inhabitants. After a follow-up of 7.8±0.38 years from diagnosis, 75% of the patients experienced prolonged disease remission, defined as clinical remission without requiring drugs for 1 year or more. The only variable associated with prolonged MC remission was how clinical remission was achieved (spontaneous 93.3%, drug-induced, 60.5%; odds ratio 8.4, 95% confidence interval 2.7–26). Conclusions: The rate of patients with MC and active disease, which represents the true disease burden in terms of loss of health, is low. Most patients with MC experience prolonged disease remission, with key differences between spontaneous and drug-induced clinical remission.

The use of magnetic resonance imaging (MRI) for assessment of Crohn's disease (CD) is expanding. The aim of this study is to define and provide an external validation of the MRI predictors of active CD, severe CD, and a quantitative Magnetic Resonance Index of Activity (MaRIA).In all, 48 patients with clinically active (n = 29) or inactive (n = 19) CD underwent ileocolonoscopy (reference standard) and MRI. T2-weighted and pre- and postcontrast-enhanced T1-weighted sequences were acquired. Endoscopic activity was evaluated by the Crohn's Disease Endoscopic Index of Severity (CDEIS), and also classified as absent, mild (inflammation without ulcers), or severe (presence of ulceration).In complete agreement with a previous derivation study, independent predictors of disease severity using CDEIS as a reference were wall thickness, relative contrast enhancement (RCE), presence of edema, and ulcers on MRI. Estimation of activity in each segment using this regression model, or another with simplified coefficients (MaRIA(S) = 1.5*wall thickness + 0.02*RCE + 5*edema + 10*ulceration) correlated with CDEIS (r = 0.798, P0.001; r = 0.80 P0.001, respectively). In the validation cohort both indexes had a high and equal accuracy for diagnosis of active disease: receiver operator characteristic (ROC) area 0.93, sensitivity 0.87, specificity 0.87 using a cutoff point ≥ 7, and for diagnosis of severe disease: ROC area 0.96, sensitivity 0.92, specificity 0.92 using a cutoff point ≥ 11. The total of segment values (MaRIA(T)) correlated with global CDEIS (r = 0.83, P0.001).The MRI variables that should be evaluated in clinical practice to diagnose active CD and severe CD are validated, as well as the quantitative index of activity for use in research studies.

Microscopic colitis is a generic term that includes 2 main forms, collagenous colitis and lymphocytic colitis, and describes a form of inflammatory bowel disease with a chronic and relapsing course. The incidence of microscopic colitis is between 2 and 8 times higher in women than in men, although age, more than sex, increases the risk of collagenous colitis (odds ratio [OR] 8.3 for age ≥65 vs.

Background: The aim of this study was to determine the accuracy of advanced endoscopy for prediction of relapse in ulcerative colitis, in comparison with serum and fecal biomarkers. Methods: Patients with ulcerative colitis with sustained clinical remission defined as absence of blood in stool for a minimum of 3 months and Mayo endoscopic subscore of 0 were included. High-resolution rectosigmoidoscopy was performed at baseline and at the end of study (week 52 or relapse), assessing mucosal pit pattern by chromoendoscopy and narrow band imaging as well as vascular pattern by narrow band imaging. Histology was evaluated at baseline and at the end of the study. Follow-up for 1 year or until relapse with clinical evaluations and serum and fecal biomarkers every 3 months was established. Relapse was defined as presence of blood in stool and a Mayo endoscopic subscore $1 with histologic confirmation. Results: Seventeen out of 64 patients (27%) relapsed during the follow-up period. Baseline clinical characteristics in patients who relapsed and those who did not were similar. Neither pit or vascular pattern nor histology was significantly different between relapsers and nonrelapsers. Among serum biomarkers, high platelet count was significantly associated with higher relapse rates. Fecal calprotectin was predictor of relapse within 3- and 12-month period with high specificity but low sensitivity. Conclusions: Advanced endoscopy and histology do not predict relapse over 1-year period in patients with ulcerative colitis. Fecal calprotectin can predict relapse in 3- and 12-month period with low accuracy. (Inflamm Bowel Dis 2014;20:1187–1193)

The suitability of indications for colonoscopy is important to optimize the available resources. The aim of this study was to assess the appropriateness of colonoscopy indications in an open access endoscopy unit using the EPAGE II criteria.Colonoscopies performed between October 1 and November 30, 2011 were retrospectively included. The appropriateness of the colonoscopy was established according to the EPAGE II criteria. Demographics, medical applicants, indications and relevant findings from these examinations were recorded.We included 440 colonoscopies (60.8 ± 016.3 years, 54% women). The indication was appropriate in 75.4% (CI, 71-79.3%), uncertain in 13.1% (CI, 10.2-16.6%) and inappropriate in 11.4% (CI, 8.7-14.8%). In the univariate analysis, the relevant findings in the colonoscopy were associated with age, sex, colonoscopy indications and EPAGE II. In the logistic regression analysis, factors independently associated with the presence of relevant findings were age (≥ 50 years) (OR, 1.84), male sex (OR, 2.7) and two indications, inflammatory bowel disease and post-polypectomy surveillance (P.03). The diagnostic yield of EPAGE II criteria was 37.3% for appropriate colonoscopies and 28.3% for inappropriate colonoscopies (P = .09).The rate of unnecessary colonoscopy is high, especially in young patients (50 years) and some colonoscopy indications. Age (≥ 50 years) and male sex are independently associated with the presence of relevant findings in colonoscopy. The diagnostic yield of EPAGE II criteria does not differ between appropriate and inappropriate examinations.

The treatment of severe ulcerative colitis remains a challenge for gastroenterologists. A not inconsiderable number of patients will experience severe flares throughout their lives and will require hospitalization. Mortality in severe ulcerative colitis is still high and consequently treatment must be aggressive, avoiding delays in rescue therapies or even surgery. The aim of this review was to describe the medical treatment of severe ulcerative colitis, highlighting recent therapeutic advances.

Background: Clinical trials in ulcerative colitis (UC) rely on certain parameters to evaluate responses that are highly subjective or of low sensitivity. Here, using a select group of genes, we tested the accuracy of gene expression analysis as a biomarker of clinical, endoscopic, and histologic improvements. Methods: Intestinal biopsies were obtained from UC patients included in two cohorts. Cohort 1 was used to select for genes whose expression was modulated in active (vs. inactive) UC. Cohort 2 included patients recruited in a phase II study receiving placebo, mesalazine, or dersalazine sodium for 4 weeks. The expression of 44 genes identified in Cohort 1 was assessed at weeks 0 and 4, and was then correlated with biomarkers, as well as with clinical, endoscopic, and histologic scores. Results: Significant changes in the expression of 31 of the 44 genes tested were detected in Cohort 2 at week 4. Gene expression (ΔCt) significantly correlated with the total Mayo score, C-reactive protein (CRP), and fecal calprotectin. The number of genes significantly regulated at week 4 was highly associated with histologic and endoscopic responses. Logistic regression analysis identified four separate genes (IFITM1, ITGB2, IL1R2, IL2RA) whose relative change was independently associated with endoscopic remission with high specificity and sensitivity. Conclusions: Change in the expression of a select set of genes can serve as an early biomarker, one with high specificity and sensitivity to clinical, endoscopic, and histologic responses. This could represent a new tool for identifying early response to treatment in mild to moderately active UC patients. (Inflamm Bowel Dis 2012;)

Experimental experience and the technological evolution of minimally invasive surgical devices have allowed initial reports describing the clinical applicability of natural orifice translumenal endoscopic surgery (NOTES). Colorectal resections are an interesting target for the NOTES platform. Theoretically, the transrectal approach could overcome the proposed limitations of transvaginal access, increasing NOTES clinical applicability. Hybrid procedures such as minilaparoscopy-assisted natural orifice surgery (MA-NOS) are the safe progression to pure NOTES. This report describes the first clinical case of a transrectal MA-NOS total colectomy.The patient was a 36-year-old man with severe ulcerative colitis (UC) who experienced failure of immunosuppressive therapy. The standard steps of laparoscopic total colectomy were respected, with basic triangulation maintained throughout the case. A transrectal endoscopic device was used for optic assistance, colon dissection, ileum section, and specimen retrieval. Transrectal MA-NOS total colectomy was assisted by three laparoscopic ports: a 12-mm port used as the terminal ileostomy site, a 2-mm needle epigastric port, and a 5-mm umbilical port used as a drain site at the final intervention. No intraoperative complications occurred.The total operative time was 240 min. Oral intake was initiated on postoperative day 2. Because of UC rectal activity, a course with azathioprine was completed, and the patient was discharged receiving 1 g of rectal mesalazine for maintenance. The final pathology demonstrated pancolonic inflammatory bowel disease in the form of UC with severe activity.Transrectal MA-NOS total colectomy was feasible and safe in the reported case. Improvement in NOTES instrumentation and selective clinical applications are mandatory before clinical trials.

Narrow-band imaging (NBI) is a novel technique that may represent an alternative method to chromoendoscopy (CE) for the detection of colitis-associated intraepithelial neoplasia (IN) in patients with long-standing inflammatory bowel disease (IBD).To compare NBI with CE for the detection of IN.Prospective, randomized, crossover study.Academic hospital.Patients with clinically inactive colonic IBD (≥8 years).Patients underwent both CE and NBI in randomized order. Targeted biopsy specimens from abnormal areas were obtained. Pathological examination was regarded as the reference standard.Number of false-positive and true-positive lesions in patients undergoing CE and NBI were compared as well as the proportion of patients with missed IN lesions.Eighty patients were screened, of whom 20 were excluded. Mean ± standard deviation withdrawal time for CE was significantly longer than that for NBI (26.87 ± 9.89 minutes vs 15.74 ± 5.62 minutes, P.01). Thirteen patients had at least 1 IN lesion on 1 of the examinations. In the per-lesion analysis, NBI resulted in a significantly inferior false-positive biopsy rate (P = .001) and a similar true-positive rate. The percentage of missed IN lesions and patients was superior with NBI, albeit without reaching statistical significance.Lesions were sampled immediately after detection, which precluded the possibility of paired analysis.NBI appears to be a less time-consuming and equally effective alternative to CE for the detection of IN. However, given the NBI lesion and patient miss rates, it cannot be recommended as the standard technique.

Background: The main objective was to identify risk factors for extent progression in distal ulcerative colitis. The secondary objective was to determine clinical characteristics of disease at the time of progression. Methods: Data were obtained from a prospective database. Distal colitis was defined as disease limited to rectum and sigmoid colon (n = 178), extensive colitis as involvement of at least the descending colon (n = 179), and colitis with progression when there was a change of category from distal to extensive (n = 63). To study clinical characteristics at the time of progression, a nested case–control study was performed. Results: Compared to distal colitis, colitis with progression was associated to significantly higher prevalence of extraintestinal manifestations (42.9% versus 15.5%) steroid-refractory course (28.0% versus 2.2%), requirement of thiopurines (44.3% versus 17.3%), cyclosporine (25.4% versus 1.9%), infliximab (9.5% versus 1.2%), surgery (20.6% versus 0.6%), and incidence of neoplasia (6.3% versus 0%). However, these differences appeared after disease progression. Regression analysis demonstrated that preexisting independent predictive factors for progression were younger age at diagnosis (hazard ratio [HR] 0.979 95% confidence interval [CI] 0.959–0.999) and presence of sclerosing cholangitis (HR 12.83, 95% CI 1.36–121.10). The nested case–control study showed that at the time of progression the flare was more severe in cases than in matched controls, with significant differences in markers of disease severity, therapeutic requirements, hospitalizations, and surgery. Conclusions: Patients with distal ulcerative colitis diagnosed at a younger age or with associated sclerosing cholangitis are at higher risk for progression. Disease flare associated with progression follows a severe course with high therapeutic requirements. (Inflamm Bowel Dis 2009)

Assessment of disease extension and activity is crucial to guide treatment in Crohn's disease. The objective of the current cross-sectional study was to determine the accuracy of MR for this assessment.50 patients with clinically active (n = 35) or inactive (n = 15) Crohn's disease underwent ileocolonoscopy (reference standard) and MR. T2-weighted and precontrast and postcontrast-enhanced T1-weighted sequences were acquired. Endoscopic activity was evaluated by CDEIS (Crohn's Disease Endoscopic Index of Severity); in addition endoscopic lesions were classified as absent, mild (inflammation without ulcers) or severe (presence of ulceration).The comparison of intestinal segments with absent, mild and severe inflammation demonstrated a progressive and significant (p0.001) increase in the following MR parameters: wall thickness, postcontrast wall signal intensity, relative contrast enhancement, presence of oedema, ulcers, pseudopolyps and lymph node enlargement. Independent predictors for CDEIS in a segment were wall thickness (p = 0.007), relative contrast enhancement (p = 0.01), presence of oedema (p = 0.02) and presence of ulcers at MR (p = 0.003). There was a significant correlation (r = 0.82, p0.001) between the CDEIS of the segment and the MR index calculated according to the logistic regression analysis coefficients. The MR index had a high accuracy for the detection of disease activity (area under the receiver operating characteristic (ROC) curve 0.891, sensitivity 0.81, specificity 0.89) and for the detection of ulcerative lesions (area under the ROC curve 0.978, sensitivity 0.95, specificity 0.91) in the colon and terminal ileum.The accuracy of MR for detecting disease activity and assessing severity brings about the possibility of using MR as an alternative to endoscopy in the evaluation of ileocolonic Crohn's disease.

Background: One-third of patients with steroid-refractory ulcerative colitis (UC) do not respond to cyclosporine and require colectomy. Since alternative pharmacological treatments for this condition are available, it is pertinent to identify factors that predict response. The objective of this study was to determine predictive factors of response prior to cyclosporine administration, with validation in an independent cohort. Methods: The 2 cohorts of patients were identified from prospectively established databases. All patients had received 1 mg/kg/day prednisolone or equivalent for at least 5 days before cyclosporine. The efficacy measure was need of early surgery (within 3 months). Results: From 1998 to 2005, 34 patients were treated in 1 institution (derivation cohort) and 38 patients in the second institution (validation cohort). Eleven patients in the derivation cohort and 9 patients in the validation cohort underwent early colectomy. Univariate analysis in the derivation cohort demonstrated a significant association of colectomy with C-reactive protein (P = 0.012) and the Ho index before initiation of cyclosporine (P = 0.013). Regression analysis showed that only the Ho index (P = 0.011) had an independent predictive value. The Ho index predicted need of colectomy, with an area under the characteristic receiver operating curve of 0.79 (95% confidence interval [CI], 0.59–0.99) in the derivation cohort and 0.74 (95% CI, 0.53–0.96) in the validation cohort. The cutoff point with the best sensitivity and specificity ratio was ≥5. Conclusions: The Ho-based predictive score is a good predictor of response to cyclosporine and avoidance of colectomy, and may aid in the indication of this treatment for management of steroid-resistant UC. (Inflamm Bowel Dis 2007)

Modulation of adhesion molecule expression or function is regarded as a promising therapy for inflammatory conditions. This study evaluates the effects of an inhibitor of adhesion molecule expression (GI270384X) in two experimental models of colitis. Colitis of different severity was induced in C57BL/6J mice by administering 1, 2, or 3% dextran sulfate sodium (DSS). GI270384X (3, 10, or 25 mg·kg-1·day-1) was administered as pretreatment or started 3 days after colitis induction. In IL-10-deficient mice, the highest dose was given for 2 wk. The clinical course of colitis, pathological changes, serum inflammatory biomarkers, expression of adhesion molecules, and leukocyte-endothelial cell interactions in colonic venules were measured in mice treated with vehicle or with active drug. In the most severe forms of colitis (2% and 3% DSS and IL-10-deficient mice), the magnitude of colonic inflammation was not modified by treatment with GI270384X. In a less severe form of colitis (1% DSS), GI270384X treatment dose dependently ameliorated the clinical signs of colitis, colonic pathological changes, and serum levels of biomarkers (IL-6 and serum amyloid A). Administration of 25 mg·kg-1·day-1 GI270384X abrogated upregulation of ICAM-1 in the inflamed colon but had no effect on VCAM-1 or E-selectin expression. This was associated with a significant reduction in number of rolling and firmly adherent leukocytes in colonic venules. These results indicate that GI270384X is effective in the treatment of experimental colitis of moderate severity. Reduced adhesion molecule expression and leukocyte recruitment to the inflamed intestine contribute to this beneficial effect. Copyright © 2007 the American Physiological Society., This work was supported by Grant SAF 2005-03755 and SAF 2006-03074 from Ministerio de Educación y Ciencia, and a Grant from GlaxoSmithKline R&D Ltd. (Harlow, UK).

short (=12 weeks) and long (=52 weeks) term. Adverse events were registered as well. Results: Thirty patients were recruited (age 34.5±15 yrs) 17 females, 43.3% smokers & ex-smokers. Median follow-up was 36 months (range 3 84 weeks). Mayo scores at the beginning of infliximab was 8±2 and after induction therapy, within a period of 12 weeks the score decreased to 3±2. Twenty one patients (70%) had short term complete response. Sixteen of the initial responders (55.7%) maintained long term complete clinical remission without steroids, while 4 of them (13.8%) had partial response. Dose intensification was required in 8 patients (26.7%), 5 patients (17.3%) did not respond and therapy was changed. Five adverse events were detected in 4 patients: serum sickness (1), and infectious complications (4). Only one event was serious. No infusion reactions were experienced in this group. Short and long term response in active smokers and ex-smokers was 83.3% (10 patients) and 58.3% (7 patients), respectively. Endoscopic evaluation performed at two time points demonstrated mucosal healing in five patients (16.7%), and partial endoscopic improvement in 10 patients (33.3%) Mucosal healing correlated with clinical response. Infliximab average trough levels detected during maintenance were 2.41mg/ml. Correlation between trough levels and clinical response existed in 16 patients (53.3%). Conclusions: Infliximab is an effective and safe treatment for moderate to severe, steroid refractory/dependent UC. Smoking is a positive predictive factor for initial response to infliximab in UC patients. Significant correlation was found between clinical response, endoscopic parameters and serum infliximab levels.

Methods: The study included 15 patients with CD (3 men, 12 women, mean age 43.1±11, 22 59 years) in clinical remission (CDAI 0.05). However after the probiotic intake in CD we found a positive correlation between the ratios IL-10/IL-12 and IL-13/IL-8 (R = 0.571; p = 0.028) and it was different than the correlations found in controls IL-10/IL-12 and IL-13/IFN-gamma (R = 0.525; p = 0.044); IL-13/IL-12 and IL-10/IL-8 (R = 0.575; p = 0.025). Conclusions: Cytokine ratios are a novel marker of immune reactivity in CD. Our results raise the question whether the differences in cytokine ratios after the probiotic intake may be a result of altered immune reactivity in CD clinical remission.

Background: There is scarce information concerning T lymphocyte subpopulations in the normal intestine and their phenotypic and functional differences related to anatomic location. This knowledge is important in studies comparing normal and inflamed intestine in diseases involving different parts of the gastrointestinal tract. Aim: To asses if there are location related differences in T cell subpopulation and apoptosis in healthy intestine. Methods: Ileocolonoscopy for colon cancer prevention was performed to 7 healthy subjects (age 48.6±7) and 10 biopsies were collected from terminal ileum, right and left colon. Flow cytometric analysis was performed to asses cell phenotype (CD3, CD4, CD8), Treg cells (CD25FoxP3), intracellular cytokines (IFNg, IL-17-A), apoptosis (AnnexinV). Results were compared by using paired Friedman test. Results: A significant decrease in the total cell count was observed in colon compared to ileum. Intracellular IFNg+CD4+ were significantly increased, whereas CD8 apoptosis was significantly decreased in ileum as compared with colonic mucosa. An increase of Double Positive CD4+CD8+ T Cells, whereas Double negative CD4 CD8 T Cells were reduced in ileum compared to colon. There were no significant differences for the remaining lymphocyte subpopulations. The most remarkable results are shown in the table.