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Background The immune response involved in the pathogenesis of Inflammatory Bowel Disease (IBD) may be present years before the diagnosis, but the characteristics of the disease during the preclinical period have been scarcely investigated. Aim To describe the microscopic findings of preclinical IBD and its relationship with the natural history of the disease. Methods Medical records from all patients with an incidental diagnosis of IBD during a screening colonoscopy were included in this multicentric and retrospective study. We assessed 15 histologic items in the biopsy samples at diagnosis, and the Geboes score was calculated in patients with Ulcerative Colitis (UC). The main outcome was the development of gastrointestinal symptoms during follow-up. Results We included 110 patients (79 UC, 24 Crohn's Disease (CD) and 7 with unclassified disease). In UC the most common histologic findings were acute or chronic inflammatory infiltrate and crypt epithelial polymorphs, while in CD we observed acute or chronic neutrophilic infiltrate and epithelial irregularity. Granuloma were only observed in 4% of CD patients. Crypt distortion and the infiltration of neutrophils in the epithelium were associated with a higher risk of developing symptomatic disease. Conclusions Preclinical IBD shows specific microscopic findings and they are associated with the progression to symptomatic disease.

Objective To evaluate the impact of magnetic resonance enterography (MRE) diagnosis on clinical decision-making regarding treatment choice and maintenance of treatment over time in patients with inflammatory bowel disease (IBD). Methods A cohort of patients who underwent MRE for IBD assessment between 2011 and 2014 was analyzed. From clinical records, we retrospectively retrieved their demographic data and clinical data on their IBD at the time of MRE, the results of MRE and the patient's clinical course. Medical management decisions made during the three months following MRE and at the 15-month follow-up were assessed. Results In total, 474 MREs were reviewed. In the first three-month period, MRE results led to changes in the medical management of 266 patients (56.1%). Of those, maintenance therapy was altered in 140 patients (68.3%) (90.7% step-up and 9.3% top-down strategy), 65 (24.4%) were prescribed a course of steroids and 61 (22.9%) underwent surgery. MRE confirmed a CD diagnosis in 14/41 patients (34.1%) previously diagnosed with indeterminate colitis or ulcerative colitis and in 4/18 patients (22.2%) with suspected IBD. At the 15-month follow-up, treatment remained unchanged in 289 patients (65.8%). Conclusions These results suggest that MRE is a diagnostic tool that provides valid information for the clinical-decision making process for patients with CD.

Background and aims Crohn’s disease [CD] can develop penetrating complications at any time during the disease course. Enterocutaneous fistulae [ECF] are disease-related complications with an important impact on quality of life. Our aim was to describe the outcomes of this complication, including its medical and/or surgical management and their temporal trends. The primary endpoint was fistula closure, defined as the absence of drainage, with no new abscess or surgery, over the preceding 6 months. Methods Clinical information from all adult patients with CD and at least one ECF—excluding perianal fistulae—were identified from the prospectively-maintained ENEIDA registry. All additional information regarding treatment for this complication was retrospectively reviewed. Results A total of 301 ECF in 286 patients [January 1970-September 2020] were analysed out of 30 088 records. These lesions were mostly located in the ileum [67%] and they had a median of one external opening [range 1-10]. After a median follow-up of 146 months (interquartile range [IQR], 69-233), 69% of patients underwent surgery. Fistula closure was achieved in 84%, mostly after surgery, and fistula recurrence was uncommon [13%]. Spontaneous and low-output fistulae were associated with higher closure rates (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.17-1.93, p = 0.001, and HR 1.49, 95% CI 1.07-2.06, p = 0.03, respectively); this was obtained more frequently with medical therapy since biologics have been available. Conclusions ECF complicating CD are rare but entail a high burden of medical and surgical resources. Closure rates are high, usually after surgery, and fistula recurrence is uncommon. A significant proportion of patients receiving medical therapy can achieve fistula closure.

[Objective] To evaluate the effectiveness and safety of the combination of granulocyte–monocyte apheresis (GMA) after loss of response (LOR) to anti-tumor necrosis factor (TNF) agents in ulcerative colitis (UC)., [Materials and methods] A retrospective, multicenter study was performed in 11 inflammatory bowel disease (IBD) Units. Clinical remission was defined as a partial Mayo score ≤2. The effectiveness of the treatment was evaluated by the partial Mayo score and the rate of anti-TNF intensification, switch, swap or colectomy., [Results] Forty-seven patients with ulcerative colitis were included (mean age 35 years, mean disease duration 52 months, 66% male and 59% extensive colitis). Twenty-three subjects were receiving infliximab, eighteen adalimumab and six golimumab. GMA was combined after a primary non-response (49%) or secondary loss of response (51%) to anti-TNF therapy. We observed a significant decrease in partial Mayo score and fecal calprotectin after GMA. Fifteen patients (32%) responded to the combination therapy without anti-TNF intensification, switch, swap or colectomy. Eight patients (17%) underwent colectomy. Two patients (4%) presented adverse events related to the technique., [Conclusions] Combination of GMA and anti-tumor necrosis factor is a safe and effective treatment after the loss of response to these biologic agents, with a significant decrease of the clinical disease activity and biomarkers, in a population with limited therapeutic alternatives.

Intestinal failure (IF) is defined as a reduction in intestinal function below the minimum necessary for the absorption of nutrients, requiring intravenous supplementation to maintain health and/or growth. The most common cause is short bowel syndrome (SBS). Approximately 50% of patients with SBS have IF and require parenteral support. Teduglutide is a human glucagon-like peptide-2 analogue (GLP-2) approved for the treatment of patients with SBS. Clinical trial results have proven its efficacy by reducing volume and days of administration of parenteral nutrition and fluid therapy. Few publications evaluate the effects on long-term bowel function in respondent patients after teduglutide suspension. A patient with type I SBS (terminal jejunostomy) due to multiple surgeries for Crohn's disease, who was treated with liraglutide for one year and sequential teduglutide for 21 months, is described. With the former, a reduction in the need for contribution and debit by jejunostomy was observed. The GLP-2 analogue achieved a greater reduction in the hydric disbalance that allowed the suspension of the nocturnal suerotherapy, with weight gain and maintenance of nutritional parameters; situation maintained two years after its suspension.El fallo intestinal se define como una reducción de la función intestinal por debajo del mínimo necesario para la absorción de nutrientes y que precisa suplementación intravenosa para mantener la salud y/o el crecimiento. La causa más frecuente es el síndrome de intestino corto. Aproximadamente el 50% de pacientes con SIC presenta FI y requiere soporte parenteral. Teduglutida es un análogo del péptido-2 similar al glucagón (GLP-2) humano aprobado para el tratamiento de pacientes con SIC. Los resultados de ensayos clínicos han probado su eficacia: se reducen el volumen y los días de administración de nutrición parenteral y fluidoterapia. Pocas publicaciones evalúan los efectos sobre la función intestinal a largo plazo en pacientes respondedores tras la suspensión de teduglutida. Se describe un paciente con SIC tipo I (yeyunostomía terminal) debido a múltiples intervenciones quirúrgicas por enfermedad de Crohn, que recibió tratamiento con liraglutida un año y teduglutida secuencial durante 21 meses. Con el primero, se objetivó una reducción en la necesidad de aporte y débito por yeyunostomía. El análogo del GLP-2 consiguió una mayor reducción del desequilibrio hídrico que permitió suspender sueroterapia nocturna, con ganancia ponderal y mantenimiento de parámetros nutricionales, situación mantenida dos años después de su suspensión.

Background & Aims Inflammatory bowel disease (IBD) is a chronic disease usually diagnosed after the appearance of gastrointestinal symptoms. Little is known about IBD progression during its early and even preclinical phases. We aimed to determine the number of new incidental diagnoses of IBD in an older population, and evaluate disease progression from its early stages. Methods We performed a retrospective analysis of 31,005 colonoscopies performed during colorectal cancer screening of patients with positive results from fecal immunochemical tests, at 11 centers in the Basque Country (Spain) from 2009 through 2014. We collected clinical and laboratory data from all asymptomatic individuals suspected to have IBD during screening colonoscopies, with histologic confirmation. Results Colonoscopy screening led to 79 new diagnoses of ulcerative colitis, 24 of Crohn's disease, and 7 of unclassified colitis (average patient age, 57 y; interquartile range, 52–62 y; 57% male). Eleven patients had symptoms before colonoscopy and were excluded from the analysis. Among those patients who were asymptomatic at diagnosis, 36% developed symptoms after a follow-up period of 25 months (interquartile range, 10.5–42 mo), mostly rectal bleeding and diarrhea. Treatment was prescribed for 81 patients (88%), and 2 cases required surgery. Conclusions We analyzed data from a large cohort of patients with IBD diagnosed at early or even preclinical stages, from an older population. New incidental diagnoses of IBD were made in 0.35% of individuals undergoing a population-based screening colonoscopy—most were classified as ulcerative colitis. Approximately one third of patients developed symptoms during the follow-up period.

Aim To assess the likelihood of detecting latent tuberculosis infection [LTBI] by the positive conversion of a serial tuberculin skin test [TST] at 1 year in inflammatory bowel disease [IBD] patients with negative baseline two-step TST. Methods In this multicentre prospective cohort study, we evaluated rate and predictors of conversion of TST at 1 year in patients with negative baseline TST. We also evaluated management of patients who had a positive TST at baseline or a conversion at 1 year. In all patients we assessed TB cases occurring during follow-up. Results Of the 192 IBD patients receiving anti-tumour necrosis factor [TNF] and 220 IBD controls not receiving anti-TNF, 35 [8.5%, 95% CI 5.7-11.3] had positive conversion (median TST induration 13 mm, interquartile range [IQR] 9-16). Ten anti-TNF cohort patients [5.2%, 95% CI 2.5-9.5] versus 25 controls [11.4%, 95% CI 7.5-16.3] had TST conversion [p = 0.029]. In multivariate analysis, conversion was associated with smoking habit (odds ratio [OR] 2.19, 95% CI 1.08-3.97; p = 0.028). Anti-TNF-treated patients had a lower conversion rate [OR 0.41, 95% CI 0.20-0.83; p = 0.013]. The likelihood of conversion correlates with fewer immunosuppressive therapies between baseline TST and TST at 1 year [p = 0.042]. One case of active TB [isoniazid-resistant strain] occurred in a patient with positive baseline TST receiving anti-TNF [0.05 events/100 patient-years]. Conclusions Serial TST at 1 year can detect LTBI in IBD patients receiving anti-TNF therapy with negative baseline TST. Serial TST seems to be advisable to reduce the risk of TB cases associated with inability to detect LTBI in pre-treatment screening.

[Background and Aims] Steroid-dependency occurs in up to 30% of patients with ulcerative colitis [UC]. In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim of this study was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis [GMA] to oral prednisone in patients with steroid-dependent UC., [Methods] This was a randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone [40 mg/day and tapering] with prednisone alone, in patients with active, steroid-dependent UC [Mayo score 4–10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation]. Patients were stratified by concomitant use of thiopurines at inclusion. A 9-week tapering schedule of prednisone was pre-established in both study groups. The primary endpoint was steroid-free remission [defined as a total Mayo score ≤2, with no subscore >1] at Week 24, with no re-introduction of corticosteroids. [Results] In all 123 patients were included [63 GMA group, 62 prednisone alone]. In the intention-to-treat analysis, steroid-free remission at Week 24 was achieved in 13% (95% confidence interval [CI] 6–24) in the GMA group and 7% [95% CI 2–16] in the control group [p = 0.11]. In the GMA group, time to relapse was significantly longer (hazard ratio [HR] 1.7 [1.16–2.48], P = 0.005) and steroid-related adverse events were significantly lower [6% vs 20%, P < 0.05]. [Conclusions] In a randomized trial, the addition of 7 weekly sessions of GMA to a conventional course of oral prednisone did not increase the proportion of steroid-free remissions in patients with active steroid-dependent UC, though it delayed clinical relapse., This work was supported by an unrestricted research grant from Otsuka Pharmaceuticals.

Aims The aims of this study were (a) to know the kinetics of antitumor necrosis factor (TNF) drug serum levels during the induction phase in patients with Crohn's disease; (b) to identify variables associated with these levels; and (c) to assess the relation between these levels and short-term effectiveness in Crohn's disease patients. Methods Patients with Crohn's disease naive to anti-TNF treatment were prospectively included. Remission was defined as a Crohn's disease activity index (CDAI) score 150 at study entry. At week 14, 52 out of 71 patients with CDAI > 150 at baseline (73%) had clinical remission. There were no differences in infliximab levels between patients with and without remission (8 vs. 9.1 mu g/mL, P > 0.05) or with and without response (7 vs. 11 mu g/mL, P > 0.05) at week 14. There was a trend to higher levels of adalimumab concentration in responders in comparison with nonresponders (13 vs. 6.7 mu g/mL, P = 0.05) and in patients who achieved remission in comparison with nonremitters (13.5 vs. 8.4 mu g/mL, P = 0.06). In the multivariate analysis, no variable was predictive of short-term remission, including infliximab and adalimumab serum levels. Conclusion Determining anti-TNF serum levels during the induction phase is not useful for predicting short-term remission in patients with Crohn's disease.

Introduction Aeromonas can cause several diseases in humans, with gastroenteritis accounting for most cases. The role of Aeromonas as a pathogen in human enterocolitis has been questioned in recent years. Objectives To determine the incidence of gastrointestinal infection caused by Aeromonas in our area and its possible relationship to inflammatory bowel disease. Patients and methods This was a retrospective observational study. All adult patients with a positive stool culture for Aeromonas were identified between January 2015 and December 2017 at Hospital Galdakao-Usansolo (Vizcaya, Spain). Results Ninety-eight patients were identified (median age 62 years; 51% women). Therefore, the incidence in our area was 32 cases per 105 inhabitants per year. Eleven per cent of them had been previously diagnosed with inflammatory bowel disease (four with ulcerative colitis and seven with Crohn's disease). Patients with inflammatory bowel disease more often received immunosuppressive therapy. Conversely, patients without inflammatory bowel disease suffered from more comorbidities. We also found comorbidity to be the risk factor most associated with Aeromonas infection. Conclusion Aeromonas infection is a common gastrointestinal infection that may occur in both immunocompetent and immunocompromised patients. Immunosuppression is a significant factor in inflammatory bowel disease patients, while comorbidity seems to confer a higher risk on patients without this disease.

Objectives: (a) To evaluate the diagnostic accuracy of anti-TNF trough levels to predict mucosal healing in inflammatory bowel disease (IBD); (b) to determine the best cut-off point to predict mucosal healing in IBD patients treated with anti-TNF. Methods: This is a multicenter, prospective study. IBD patients under anti-TNF treatment for at least 6 months that had to undergo an endoscopy were included. Mucosal healing was defined as: Simple endoscopic score for Crohn’s Disease < 3 for Crohn’s disease (CD), Rutgeerts score < i2 for CD in postoperative setting, or Mayo endoscopic score = 1 for ulcerative colitis (UC). Anti-TNF concentrations were measured using SMART ELISAs at trough. Results: A total of 182 patients were included. Anti-TNF trough levels were significantly higher among patients that had mucosal healing than among those who did not. The area under the curve of infliximab for mucosal healing was 0.63 (best cutoff value 3.4 µg/mL), and for adalimumab 0.60 (best cutoff value 7.2 µg/mL). In the multivariate analysis, having anti-TNF drug levels above the cutoff values [odds ratio (OR) 3.1]) and having UC instead of CD (OR 4) were associated with a higher probability of having mucosal healing. Additionally, the need for an escalated dosage (OR 0.2) and current smoking habit (OR 0.2) were also associated with a lower probability of mucosal healing. Conclusions: There was an association between anti-TNF trough levels and mucosal healing in IBD patients; however, the accuracy of the determination of infliximab and adalimumab concentrations able to predict mucosal healing was suboptimal.

Gastrointestinal (GI) symptoms can precede by many years the motor symptoms of Parkinson's disease (PD) and these patients can show some degree of inflammation associated with abnormal aggregates of alpha-synuclein in the GI tract. The abnormal accumulation of alpha-synuclein and the spreading of the aggregates from the gut to the brain might be promoted by inflammation, rising the hypothesis of a possible relationship between inflammatory bowel disease and PD. Many population-based studies have explored this association, but they have found conflicting results. It is essential to clarify this hypothesis and to try to elucidate the milestones of this relationship. There is no clear concordance between the results and the interpretation of different previous findings, probably due to many confounding factors such as drugs with anti-inflammatory activity, surgery, genetic predisposition and also selection bias. If there is a real association between both diseases, gastroenterologists and neurologists should be able to detect possible triggers of the disease or on the other hand, protective factors, that may be considered in clinical practice.

Objectives To assess the effectiveness and safety of combining granulocyte-monocyte apheresis (GMA) and vedolizumab (VDZ) in patients with refractory ulcerative colitis (UC). Methods This retrospective, multicentre pilot study included all UC patients receiving both GMA and VDZ. We recorded data on GMA sessions, demographic characteristics, and clinical response. Effectiveness was assessed 1 and 6 months after finishing the GMA using the partial Mayo score, C-reactive protein, and fecal calprotectin levels. Data were also compiled on VDZ intensification, use of new immunomodulators and colectomy during follow-up. Results Eight patients were included (mean age 46 years; 63% female; mean disease duration, 132 months; 50% E3). GMA was started after a loss of response to VDZ in all cases (25% primary nonresponse and 75% secondary loss of response). All had previously received anti-TNF agents. VDZ was prescribed as the second-, third-, or fourth-line biologic in 37%, 50%, and 13% of cases, respectively. Patients had a mean baseline partial Mayo score of 7.5 (SD 2.1) and received a median of 15 GMA sessions (range 5-38). After a median follow-up of 7.5 months (IQR 5-12), partial Mayo score decreased after 1 and 6 months (P = .01 and .06, respectively). Three patients (38%) achieved steroid-free clinical remission and five (63%) withdrew VDZ. Colectomy rate was 38%. No adverse events were observed during the combination therapy. Conclusions This small case series suggests that combining GMA with VDZ could be a treatment option in selected cases of UC with an inadequate response to this biologic agent.

Introduction Immunomodulators and biologics are two of the main drugs used for the treatment of inflammatory bowel disease (IBD). Some of these agents have been associated with certain infections and lymphoproliferative disorders, including Epstein–Barr virus (EBV) infection. Our aim was to determine the influence of immunosuppression in the EBV viral load in patients with IBD. Materials and methods We prospectively included naive patients with IBD who were starting immunosuppressive therapy in four IBD Units. All patients were assessed at baseline and four months after starting immunosuppression for clinical disease activity, biomarkers, EBV serology (IgM VCA, IgG VCA and IgG EBNA) and viral load. Results Thirty-two patients were included. At baseline, all patients showed positive results for IgG VCA or IgG EBNA with undetectable EBV viral load. No patient showed detectable EBV viral load after starting the immunosuppressive therapy. Conclusion Immunosuppression did not influence on EBV viral load in the short-term in naive IBD patients.

Nivolumab, a monoclonal antibody-targeting programmed cell death protein-1, is being increasingly used for the treatment of some advanced neoplasms. Several of its adverse effects are a result of the upregulation of T cells, with colitis as one of the most severe, and a challenging differential diagnosis with ulcerative colitis. However, few real-life clinical practice cases have been reported beyond trials. Our aim was to report a series of new cases, reviewing previously communicated endoscopic-proven nivolumab-induced colitis. All patients treated with nivolumab in three university centers were identified and those who developed immune-mediated colitis (defined as the presence of diarrhea and evidence of colitis demonstrated by colonoscopy) were described. Additionally, a review of case reports of nivolumab-induced colitis reported in the literature up to March 2018 was performed. Six new cases of nivolumab-induced colitis and 13 previously reported cases out of randomized clinical trials are described. Colonoscopy showed a mucosal pattern mimicking ulcerative colitis in a large proportion of patients. Clostridium difficile superinfection was observed in two out of 19 cases. All but three patients definitively discontinued nivolumab therapy. Most patients were initially managed with oral or intravenous corticosteroids, but five of them required rescue therapy with infliximab. Nivolumab-induced colitis may mimic ulcerative colitis. Steroid therapy (oral or intravenously) is often efficient, but one-fourth of patients need rescue therapy with anti-TNF. Intestinal superinfection with Clostridium difficile or cytomegalovirus should be ruled out before starting immunosuppressive therapy.

Epidemiological evidence suggests an association between psychological factors and functional dyspepsia (FD). Yet few randomized controlled trials (RCTs) of psychological interventions have been conducted for FD. We conducted an RCT to evaluate the efficacy of psychotherapy among chronic FD.One hundred fifty-eight consecutive patients with FD were randomized to medical therapy plus psychotherapy consisted in 8 group and 2 individual sessions focused on teaching techniques for coping with FD (intensive treatment (IT); n=76) or medical therapy alone (conventional treatment (CT); n=82). Patients completed validated self-reported questionnaires before and after the 10-week treatment and 6 months later. Linear mixed-effects models were used, in intention-to-treat analysis.At the end of treatment period, statistically significant improvements were observed for IT compared with CT for dyspepsia-related quality of life (DRQoL). DRQoL mean changes of 6.09 and 3.54 were obtained in IT and CT patients, respectively (p=0.0001); and SS mean changes of 11.55 and 4.57 were obtained in IT and CT patients, respectively (p=0.0013). Those improvements, measured by minimum clinically important difference (MCID), were clinically significant (DRQoL: 77% of the IT patients exceeded the MCID vs. the 45% of the CT; SS: 75% vs. 48%). Six months after treatment, those statistically significant improvements persisted for DRQoL (p=0.0067) and for SS (p=0.0405). Clinical improvements persisted for SS (63% vs. 41%).These findings suggest that adding psychotherapy to standard medical therapy improves short-term outcomes in patients with FD and may have long-term effects as well. The cost-effectiveness of intensive therapy needs to be evaluated. Registration number and name of trial registry: NCT01802710.

Background Granulocyte and monocyte apheresis is the main non-pharmacological treatment for inflammatory bowel disease (IBD), but we do not know how well accepted it is by patients in our setting. Aim To determine how granulocyte and monocyte apheresis is perceived by patients in clinical practice in Spain. Methods Outpatients treated with granulocyte and monocyte apheresis in five IBD Units in Spain were asked to fill in a 14-item questionnaire. Results Fifty-two patients completed the questionnaire (88% ulcerative colitis, 12% Crohn's disease; 44% female; age 35 years [IQR 23–51]). Granulocyte and monocyte apheresis was generally well tolerated and well accepted. Very few of the participants regarded the length of the sessions as a limitation. The gastrointestinal symptoms, however, were a frequent concern, both in terms of attending to receive treatment and during the sessions. Overall, 44% were satisfied with the treatment effectiveness. Sixty percent (60%) claimed to be satisfied with the therapy overall, but this was influenced by the patients’ clinical response to the therapy. Eighty-two percent (82%) of participants said they would agree to be treated with this technique again in the future, regardless of the response to the treatment. Conclusions Granulocyte and monocyte apheresis is well tolerated and accepted by patients with IBD. Although we found no significant differences according to type of IBD or apheresis regimen, patient perception was affected by clinical effectiveness.

Background: Data regarding the effectiveness of adalimumab (ADA) in the treatment of perianal fistula in patients with Crohn's disease (CD) naive to antitumor necrosis factor (TNF) therapy are scarce. Aim: To assess the effectiveness of ADA in the treatment of perianal fistulas in CD patients naive to anti-TNF therapy. Methods: A retrospective multicenter study was designed. The Fistula Drainage Assessment Index was used to assess the clinical response, and the Van Assche and Ng indexes to classify radiologic response (magnetic resonance imaging). Results: A total of 46 patients (83% women, 83% complex fistula) were included. At 6 months, 72% of patients responded to ADA (54% remission, 18% partial response) and at 12 months 49% responded (41% remission, 8% partial response). Among patients with complex fistula, the response rate was 66% at 6 months and 39% at 12 months. Nine patients escalated the ADA dose to 40mg weekly, 6 for partial response and 3 for absence of response. Thirty-three percent of these patients achieved remission after dose escalation. There was a good correlation between clinical and radiologic assessment of response (kappa = 0.68). In the multivariate analysis, complex fistula was the only predictor of a worse response (hazard ratio 0.083; 95% confidence interval, 0.0009-0.764; P = 0.028). Adverse effects were recorded in 11% of patients. Conclusions: ADA was effective for the treatment of perianal fistulas in CD patients naive to anti-TNF drugs. We found a good correlation between clinical and radiologic assessment of therapy response.

Background In conditions associated with inflammation, biochemical parameters alone could be inadequate for assessing iron status. We investigated the potential utility of mean reticulocyte hemoglobin content (MCHr) in the assessment of the erythropoiesis status in inflammatory bowel disease (IBD). Methods We recruited 124 anemic outpatients with IBD. Serum iron, transferrin and ferritin were tested. Complete blood counts were performed on a CELL-DYN Sapphire analyzer (Abbott Diagnostics). Differences among groups were assessed using analysis of variance, considering P Receiver operating characteristic analysis was used to assess the diagnostic performance of MCHr for detecting iron deficient erythropoiesis. The reference used as an indicator of insufficient iron availability was transferrin saturation Results Overall, 47.6% of the patients had iron deficiency anemia (IDA) and 31.5% anemia of chronic disease (ACD), while the others (20.9%) had mixed anemia. Patients with ACD or mixed anemia showed functional iron deficiency: normal or high ferritin and low MCHr. The area under curve was 0.858 (95% CI 0.742–0.942), considering a cut off 30.3 pg, the sensitivity was 82.2%, specificity 83.3%. Conclusions MCHr provides information on iron availability in IBD patients. It is a reliable test to assess iron supply for erythropoiesis.

Background Adalimumab is the second tumour necrosis factor antagonist (anti-TNF) adopted for the treatment of ulcerative colitis. Clinical data from naive patients are scarce. Aim Examine the response to adalimumab in TNF-antagonist-naive patients. Methods This multicentre, observational, prospective study was conducted using a cohort of consecutive patients with ulcerative colitis. Clinical remission, mucosal healing and deep remission were examined employing the Mayo Score and Mayo Endoscopic Score. Clinical response was assessed using the Partial Mayo Score. Results Of 53 individuals included in this study, 49.1% of patients were in clinical remission at week 8 and 60.3%, at week 52. Clinical response was observed in 84.9% and 69.8%, respectively. Mucosal healing was found in 62.3% and 67.9% of the patients, and 43.4% and 58.4% showed deep remission at week 8 and 52, respectively. After a year, 71.7% of the patients continued the adalimumab treatment. Adverse effects were observed in 28.3% of patients. Multivariate analysis showed that the long-term factor predictive of response at week 52 was the response in week 8 (expressed as Mayo Score; OR 0.66; 95% IC 0.1–0.67, p Conclusions Adalimumab treatment of ulcerative colitis is effective; the results are better in clinical practice and in patients naive to anti-TNF.

Background & aims: Disease outcome has been found to be poorer in familial inflammatory bowel disease (IBD) than in sporadic forms, but assessment of phenotypic concordance in familial IBD provided controversial results. We assessed the concordance for disease type and phenotypic features in IBD families. Methods: Patients with familial IBD were identified from the IBD Spanish database ENEIDA. Families in whom at least two members were in the database were selected for concordance analysis (K index). Concordance for type of IBD [Crohn's disease (CD) vs. ulcerative colitis (UC)], as well as for disease extent, localization and behaviour, perianal disease, extraintestinal manifestations, and indicators of severe disease (i.e., need for immunosuppressors, biological agents, and surgery) for those pairs concordant for IBD type, were analyzed. Results: 798 out of 11,905 IBD patients (7%) in ENEIDA had familial history of IBD. Complete data of 107 families (231 patients and 144 consanguineous pairs) were available for concordance analyses. The youngest members of the pairs were diagnosed with IBD at a significantly younger age (p < 0.001) than the oldest ones. Seventy-six percent of pairs matched up for the IBD type (kappa = 0.58; 95%CI: 0.42-0.73, moderate concordance). There was no relevant concordance for any of the phenotypic items assessed in both diseases. Conclusions: Familial IBD is associated with diagnostic anticipation in younger individuals. Familial history does not allow predicting any phenotypic feature other than IBD type. (C) 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Background and objective: There are no structural abnormalities in functional dyspepsia, therefore it is essential to have a viable questionnaire to measure treatment outcome according to patient perception. The aim of the study was to extensively document psychometric characteristics of the Glasgow Dyspepsia Severity Score and the Dyspepsia-Related Health Scale that are currently available in Spanish. Methods: Patients with functional dyspepsia (n = 158) were recruited from a randomized trial that assessed standard vs. standard and psychological treatment. Participants had completed the validation questionnaires and the Medical Outcome Study Short-form 36. Reliability (Cronbach's alpha), validity (Confirmatory Factor Analysis, convergent and known group validity) and responsiveness (minimal clinically important difference) were analyzed. Results: A Confirmatory Factor Analysis of the Glasgow Dyspepsia Severity Score showed a one-factor solution model, but a low Cronbach's alpha (0.61). With regard to the Dyspepsia-Related Health Scale, the Cronbach's alpha (0.80-0.97) and Confirmatory Factor Analysis supported a model with four inter-correlated dimensions and suggested a need to improve the "Satisfaction with dyspepsia-related health" dimension (Cronbach's alpha < 20). Finally, the global scores for both the Glasgow Dyspepsia Severity Score and the Dyspepsia-Related Health Scale were responsive at six months post-treatment, with a minimal clinically important difference of 4 and 6, respectively. Conclusions: Our findings support the continued application of the Dyspepsia-Related Health Scale and the need to improve the "Satisfaction with dyspepsia-related health" dimension. Although the Glasgow Dyspepsia Severity Score is a promising questionnaire, further review of the content is required to eliminate and add items in order to provide greater consistency to the evaluated construct.

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: The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would facilitate the implementation of therapeutic drug monitoring in clinical decision-making. Our aim was to standardize the homogeneous mobility shift assay (HMSA) used in the measure of ATI levels. Methods: In this prospective longitudinal multicenter study, 50 IFX-treated Crohn's disease (CD) patients were followed up for 54 weeks. During this period 360 human serum samples were analysed. Monomeric ATI levels were measured by a quantitative HMSA-method using an anti-IFX calibrator. IFX trough levels measured by ELISA were correlated with ATI levels. Results: Using HMSA and a pure anti-idiotypic monoclonal antibody specific for IFX (anti-IFX calibrator), we measured the levels of monomeric ATI generated in Crohn's disease patients treated with IFX. AntiIFX calibrator allowed to quantify monomeric antibodies against IFX with a low limit of quantification (3 nM). The threshold level of ATI in order to classify the immunogenicity of the patients was 10 nM. We observed that 24% (12/50) of IFX-treated patients developed ATI (>10 nM) during the observation period (54 weeks). Serum concentration of ATI higher than 10 nM dramatically increased the probability (OR = 51.1; 95% CI: 20.4-128.0; p < 0.0001) of presenting low levels of IFX (

Biologic anti-tumor necrosis factor (TNF) drugs have demonstrated their efficacy for the treatment of ulcerative colitis. Nevertheless, some patients will not respond to this therapy or will develop loss of response. Leukapheresis is the main non-pharmacological therapy for some immune-mediated diseases. The aim of our study was to describe our experience with this therapy in ulcerative colitis patients after loss of response to anti-TNF treatment. Leukapheresis was indicated in four patients with left-sided or extensive colitis because of partial response to biological therapy or secondary loss of response to it. All patients received 8 to 10 sessions in an intensive regimen. Globally, a decrease in the Mayo score was observed. The overall response rate was 50% with one patient who displayed sustained response. No patients have required colectomy during follow-up. Adjuvant treatment with leukapheresis in patients with inadequate response to anti-TNF treatment showed some beneficial effect, although of limited duration, in patients with ulcerative colitis.

Several small, prospective, open studies suggest that leukocytapheresis might be efficient in patients with steroid-dependent ulcerative colitis (UC). To evaluate the short- and long-term effectiveness of leukocytapheresis for the management of steroid-dependent UC in clinical practice. A Web-based, nationwide database specifically designed to record the efficacy and safety data of leukocytapheresis therapy in UC was available from September 2007 in Spain. Clinical data were collected at treatment baseline, 1 month after the last apheresis session (initial efficacy), and 6 and 12 months thereafter (long-term efficacy). Remission was defined as a Mayo Clinic index ≤2 together with complete steroid withdrawal and response as a decrease of ≥3 from the baseline score. A total of 142 steroid-dependent UC patients were included in the registry, most of them treated with the Adacolumn™ system. In 69% of patients thiopurine therapy failed to achieve steroid-free clinical remission. Initial clinical remission was obtained in 37% of cases. The initial corticosteroid dose, the number and frequency of apheresis sessions, or the previous failure of thiopurines and/or infliximab did not influence the initial remission rate, but a greater decrease in CRP levels was associated with a higher probability to obtain initial remission. At 6 and 12 months, 41 and 36% of patients were in clinical remission, respectively. Only one serious adverse effect was recorded. In clinical practice, apheresis allows long-term steroid-free clinical remission in up to one third of steroid-dependent UC patients, even in those with prior failure of thiopurines.

There is a lack of prospective studies evaluating the natural history of colonic ischaemia (CI). We performed such a study to evaluate the clinical presentation, outcome, and mortality as well as clinical variables associated with poor prognosis.An open, prospective, and multicentre study was conducted in 24 Spanish hospitals serving a population of 3.5 million people. The study included only patients who met criteria for definitive or probable CI. A website (www.colitisisquemica.org) provided logistical support.A total of 364 patients met criteria for inclusion. CI was suspected clinically in only 24.2% of cases. The distribution of clinical patterns was as follows: reversible colopathy (26.1%), transient colitis (43.7%), gangrenous colitis (9.9%), fulminant pancolitis (2.5%), and chronic segmental colitis (17.9%). A total of 47 patients (12.9%) had an unfavorable outcome as defined by mortality and/or the need for surgery. Multivariate analysis identified the following signs as independent risk factors for an unfavorable outcome: abdominal pain without rectal bleeding [odds ratio (OR) 3.9; 95% confidence interval (CI) = 1.6-9.3], non-bloody diarrhoea (OR 10; 95% CI = 3.7-27.4), and peritoneal signs (OR 7.3; 95% CI = 2.7-19.6). Unfavorable outcomes also were more frequent in isolated right colon ischaemia (IRCI) compared with non-IRCI (40.9 vs. 10.3%, respectively; p0.0001). The overall mortality rate was 7.7%.The clinical presentation of CI is very heterogeneous, perhaps explaining why clinical suspicion of this disease is so low. The presence of IRCI, and occurrence of peritoneal signs or onset of CI as severe abdominal pain without bleeding, should alert the physician to a potentially unfavorable course.

Background Leukocytapheresis (LAP) could be an alternative treatment for steroid-dependent ulcerative colitis (UC). Aims To assess the duration of response at 1 year after this treatment. Patients and methods A prospective study in 18 patients with steroid-dependent UC treated with LAP plus steroids after failure or intolerance to immunomodulators. Clinical and endoscopic (Mayo Clinic index) examinations were performed at 1 month after the last apheresis and at 12 months. The clinical, endoscopic remission and the relapse during the 1-year follow-up were evaluated based on standard parameters. Results Induction of remission: clinical remission: 10/18 (55%). Partial response: 4. Endoscopic remission: 9 (50%), always accompanied by clinical remission. A significant correlation was observed between clinical remission and endoscopic remission (rs = 0.894; p ≤ 0.001). At 1 year: sustained steroid-free clinical remission in 9 (50%), all of whom presented initial endoscopic remission. Remission and relapse before 1 year in 17%. A tendency for sustained remission at 1 year was observed when initial endoscopic remission was achieved. Conclusions Initial remission can be maintained at 1 year in half of the patients without the need for additional steroids. Complete remission and endoscopic mucosal healing is proposed as an objective for achieving a lasting response.

The ability to maintain or enhance quality of care in an increasingly cost-conscious environment may depend on the ability to determine the appropriateness of care. By definition, a procedure is considered appropriate if its health benefit exceeds its health risk by a sufficiently wide margin, thus making the procedure worth performing.1 Applying this definition to clinical care requires determining what constitutes appropriate indications for a given procedure. A method that combines expert opinion with available scientific evidence to create explicit appropriateness criteria was developed by investigators at the RAND Corporation and the University of California at Los Angeles.2 Cholecystectomy is a commonly performed procedure. Although its use is still increasing in most developed countries,3 surgical rates vary moderately across regions and countries,4,5 a finding not explained solely by differences in the prevalence of gallbladder disease. Variations in clinical decision-making likely contribute to this variation. Previous RAND methodology-based studies of this procedure were performed in the early 1980s in the United States6 and in the late 1980s in Israel7 and the United Kingdom.8 The criteria developed by those studies are no longer useful since they did not include new variables such as the use of endoscopic retrograde cholangiopancreatography (ERCP) or new imaging tests such as echography. To update the explicit appropriateness criteria for cholecystectomy, a new panel of experts was formed in 2000.9 Although partial validation of the new criteria has been published,9 an important issue was to validate those criteria against relevant outcomes. Greater importance is now being given to measuring the HRQoL when evaluating the outcome of medical interventions, particularly with regard to chronic diseases.10 The measurement of HRQoL is increasingly being used in the field of gastroenterology and digestive surgery to evaluate the evolution of certain digestive diseases and to ascertain the effectiveness of medical or surgical treatments. It is also being applied not only to chronic diseases such as inflammatory bowel disease or liver diseases but also to digestive surgery, transplants, or oncological problems.11,12 We conducted a prospective observational study to validate the newly developed explicit appropriateness criteria for cholecystectomy by looking at the relationship between appropriateness evaluation and outcomes measured by 2 HRQoL instruments, the SF-36 Health Survey (SF-36) and the Gastrointestinal Quality of Life Index (GIQLI). We hypothesized that patients considered appropriate for cholecystectomy would have higher HRQoL improvement on some domains of these instruments. We also wanted to determine if there were subclasses of patients with lower HRQoL improvements who might not benefit from cholecystectomy.

Ultrasonography (US) is currently the reference technique for evaluating gallbladder pathology. The aim of this study was to prospectively determine the diagnostic efficacy of magnetic resonance cholangiography (MRCP) in evaluating the gallbladder, as compared with US. The study included 80 patients (mean age, 69.3 years; male-to-female ration, 1.3:1) who underwent prospective US and MRCP; 5 patients in whom MRCP was contraindicated were excluded. In all cases, US was performed before MRCP. Ultrasound was the reference technique for evaluating MRCP sensitivity and specificity. Magnetic resonance cholangiopancreatography provided good image quality in 65 patients (81.2%) and poor image quality in 15 (mostly because of poor patient cooperation). Artefacts did not influence visualization of the gallbladder or evaluation of the background pathology. The sensitivity of MRCP in diagnosing gallbladder stones (43 patients; 97.7%) was comparable to US (44 patients). In contrast, MRCP diagnosed biliary sludge or microlithiasis in 13 patients, versus 5 in the case of US. Magnetic resonance cholangiopancreatography is a good technique for diagnosing cholelithiasis and biliary sludge. However, its high cost, contraindications, and the need for patient cooperation limit the use of the technique in routine clinical gallbladder studies. Magnetic resonance cholangiopancreatography could contribute to the diagnosis of microlithiasis, provided that future studies confirm its greater sensitivity versus US.

Double-blind study comparing efficacy and safety of the topically acting corticosteroid beclomethasone dipropionate (BDP) to prednisone (PD) in patients with active, mild-to-moderate ulcerative colitis (UC).Overall, 282 patients were randomized to receive BDP-prolonged release tablets 5 mg once daily for 4 weeks and then every other day for an additional 4 weeks or oral PD 40 mg once daily for the initial 2 weeks tapered of 10 mg every 2 weeks during the 8-week study period. Efficacy end point was the non-inferiority of BDP vs. PD in terms of Disease Activity Index (DAI) score3 or reduction by at least 3 points for patients with a baseline DAI ≥7 at week 4. Safety end point was the proportion of patients with steroid-related adverse events (AEs) and cortisol150 nmol/l at week 4.DAI response rates at week 4 were 64.6% and 66.2% with BDP and PD, respectively, demonstrating non-inferiority of BDP vs. PD (delta: -1.56; 95% confidence interval (CI) -13.00-9.88, P=0.78). Patients with steroid-related AEs and cortisol150 nmol/l at week 4 were 38.7% in the BDP group and 46.9% in the PD group (P=0.17 between groups). No safety signals were observed in both the groups.BDP was non-inferior to PD in the treatment of active UC, with a good safety profile in both the groups.

Background To evaluate the safety of thiopurines in patients with inflammatory bowel disease. To identify predictive factors associated with the development of thiopurine-induced adverse events. Methods Long-term incidence of adverse events was estimated in patients from a prospectively maintained Spanish nationwide database using Kaplan-Meier analysis. Cox regression analysis was performed to identify potential predictive factors of adverse events. Results Three thousand nine hundred and thirty-one patients were included. Ninety-five percent of patients were on azathioprine. The median follow-up with thiopurines was 44 months (range, 0-420). Adverse events occurred at a median of 1 month after starting treatment. The cumulative incidence of adverse events was 26%, with an annual risk of 7% per patient-year of treatment. Most frequent adverse events were nausea (8%), hepatotoxicity (4%), myelotoxicity (4%), and pancreatitis (4%). Four patients had lymphoma. Female and Crohn's disease increased the risk of having nausea. The risk of hepatotoxicity was lower in females and higher in Crohn's disease. The risk of myelotoxicity was significantly higher in patients treated with mercaptopurine and in females. The risk of pancreatitis was higher in Crohn's disease. Overall, 17% of patients discontinued thiopurine treatment due to adverse events. Thirty-seven percent of these patients started thiopurines again and 40% of them had adverse events again. Conclusions As many as 1 of 4 patients on thiopurine therapy had adverse events during follow-up. A relatively high proportion of patients (17%) had to discontinue the treatment with thiopurines due to adverse events. However, more than half of patients that restarted thiopurine treatment after its discontinuation due to adverse events tolerated it. Several predictive factors for some adverse events have been identified.

Background Recently, the notion that smoking may adversely affect Crohn's disease (CD) outcomes has been challenged by the suggestion that the widespread use of immunosuppressants and anti-TNF drugs might offset the adverse effects of tobacco. Aim To reassess the influence of tobacco smoking on disease phenotype and complications on a time-dependent analysis, taking into account the different therapeutic interventions. Methods We designed a retrospective cohort study of 3224 patients with Crohn's disease. The data were collected from the Spanish national inflammatory bowel disease registry (ENEIDA), including information regarding demographics, clinical characteristics, disease complications, therapeutic interventions and smoking status. Patients were classified as nonsmokers, smokers and former smokers, according to their present and past smoking habits. Results In the univariate analysis, smokers had more strictures (22.6% vs. 19.3%, P < 0.05) and less colonic involvement (7.2% vs. 10.9%, P < 0.05), and were more frequently under treatment with steroids (91.6% vs. 85.8%, P < 0.05), immunosuppressants (73.5% vs. 63.6% P < 0.05) or anti-TNF drugs (31.4% vs. 25.1%, P < 0.05) than nonsmokers. In the time-dependent multivariate analysis, smokers were found to have a significantly decreased survival free of stricturing disease (HR: 1.5, CI 95% 1.18-1.90) or perianal complications (HR: 1.50, CI 95% 1.01-1.46), and had a higher risk for requiring thiopurine therapy (HR: 1.20, CI 95% 1.05-1.30). Conclusion These results suggest that, despite the widespread use of immunosuppressants and anti-TNF drugs, smokers with Crohn's disease still have a more severe disease course, with increased therapeutic requirements when compared with nonsmokers.

Summary Background In some cases, Helicobacter pylori infection persists even after three eradication treatments. Aim To evaluate the efficacy of an empirical fourth-line rescue regimen with rifabutin in patients with three eradication failures. Methods Design: Multicentre, prospective study. Patients: In whom the following three treatments had consecutively failed: first (PPI + clarithromycin + amoxicillin); second (PPI + bismuth + tetracycline + metronidazole); third (PPI + amoxicillin + levofloxacin). Intervention: A fourth regimen with rifabutin (150 mg b.d.), amoxicillin (1 g b.d.) and a PPI (standard dose b.d.) was prescribed for 10 days. Outcome: Eradication was confirmed by 13C-urea breath test 4–8 weeks after therapy. Compliance and tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated using a questionnaire. Results One-hundred patients (mean age 50 years, 39% men, 31% peptic ulcer/69% functional dyspepsia) were included. Eight patients did not take the medication correctly (in six cases due to adverse effects). Per-protocol and intention-to-treat eradication rates were 52% (95% CI = 41–63%) and 50% (40–60%). Adverse effects were reported in 30 (30%) patients: nausea/vomiting (13 patients), asthenia/anorexia (8), abdominal pain (7), diarrhoea (5), fever (4), metallic taste (4), myalgia (4), hypertransaminasemia (2), leucopenia (

Background: Adalimumab is an effective treatment for Crohn's disease (CD), but may also be associated with loss of response. Few reports provide insight into the durability of treatment of CD with adalimumab for periods longer than 12 months in clinical practice. Aims: To evaluate the long-term durability of adalimumab maintenance treatment and to identify predictive factors associated with loss of response. Methods: CD patients who initially responded to adalimumab were evaluated in a historical cohort study. Maintenance of long-term response was estimated using Kaplan–Meier analysis. Cox regression analysis was performed to identify potential predictive factors for loss of efficacy. Results: In all, 380 CD patients were included (mean age, 38 years; 52% female). Of these, 43% had ileocolic CD, 50% inflammatory CD, and 41% perianal CD. Median follow-up with adalimumab was 8 months (range, 4–75 months). The annual risk of loss of response to adalimumab was 18% per patient-year of follow-up. Twenty-eight percent of patients were anti-TNF-naive and 72% anti-TNF-experienced. The loss of efficacy was 8% per patient-year of follow-up in the anti-TNF-naive patients and 22% in the anti-TNF-experienced group (P < 0.01). In the multivariate analysis, the presence of extraintestinal manifestations (hazard ratio [HR] = 1.7; 95% confidence interval [CI] = 1.02–2.9) and previous experience with other anti-TNF agents (HR = 2.5,95% CI = 1.2–5.3) were associated with higher risk of loss of efficacy. Conclusions: A relevant proportion of CD patients on long-term adalimumab lost response. The risk of loss of response was higher (more than 2-fold) in anti-TNF-experienced than in anti-TNF-naive patients (22% vs. 8% per patient-year of treatment). Having extraintestinal manifestations seems to increase the risk of loss of efficacy. (Inflamm Bowel Dis 2011;)

Leukocyte apheresis works by purifying distinct populations of active leukocytes and by modifying inflammatory mediators. Based on their theoretical immunomodulatory effect, these techniques have begun to be used in inflammatory bowel disease. There are two types of devices: granulocytapheresis, which performs selective granulocyte and monocyte absorption, and leukocytapheresis, which carries out non-selective filtration. Conventional treatment regimens consist of between 5 and 10 sessions, normally one session per week, to induce remission. Although the indications for apheresis have not been clearly defined, this technique can be considered a valid option in selected patients with ulcerative colitis, mainly those with corticosteroid-dependent or corticosteroid-refractory disease when other, better-established immunosuppressive or biological treatments have failed. In addition to avoiding the use of corticosteroids, due to its excellent safety profile, apheresis is an attractive option to avoid the risks of immunosuppressive and biological treatments and for use in the pediatric population. The present reviews analyzes the data on the safety and efficacy of apheresis in those patients with inflammatory bowel diseases who could benefit from this technique.

The efficacy of infliximab therapy in patients with Crohn's disease (CD) is unknown beyond 12 months. For patients who lose their initial response, consideration can be given to dose "escalation" to regain therapeutic benefit.Our primary goal was to evaluate the long-term durability of maintenance infliximab treatment. The secondary goals were to identify potential predictors of loss of infliximab efficacy, to evaluate the response to infliximab escalation, and the safety of the treatment with infliximab with and without escalation of dose.CD patients treated with infliximab with response to an induction regimen were evaluated. Maintenance of long-term response was estimated using Kaplan-Meier analysis. The effect of specific variables was calculated using logistic regression analysis. Efficacy of dose escalation in patients who lose response to infliximab was analyzed.Three hundred and nine CD patients were included. The mean follow-up time with infliximab treatment was 41 months, and the majority (95%) were on concomitant immunosuppressive therapy. The annual risk of loss of response to infliximab was 12% per patient-year of treatment. After loss of response, 41% of patients were managed with infliximab therapy escalation. After the first intensified dose, 56% of patients achieved remission and 40% partial response. Concurrent immunomodulators enhanced and smoking decreased the proportion of patients who maintained response (P0.05).A relevant proportion of CD patients on long-term infliximab treatment loss response. After loss of response, a high proportion of these patients initially respond to infliximab dose escalation. Concurrent immunomodulators may increase and smoking may decrease maintenance of response.

Endoscopic biliary stenting is a well-established palliative treatment in patients with unresectable malignant biliary strictures. Obstruction of uncovered self-expanding metal stent (SEMS) due to tumor ingrowth is the most frequent complication. Partially covered SEMS might increase stent patency but could favor complications related to stent covering, such as pancreatitis, cholecystitis, and migration. The aim of this study was to evaluate the efficacy and safety of partially covered SEMS in patients with an unresectable malignant biliary stricture. Patients with malignant extrahepatic biliary obstruction treated endoscopically with partially covered SEMS were included in this multicenter, prospective, nonrandomized study. One hundred ninety-nine patients were endoscopically treated with partially covered SEMS in 32 Spanish hospitals. Clinical success after deep cannulation was 96%. Early complications occurred in 4% (3 pancreatitis, 2 cholangitis, 1 hemorrhage, 1 perforation, and 1 cholecystitis). Late complications occurred in 19.5% (18 obstructions, 10 migrations, 6 cholangitis without obstruction, 3 acute cholecystitis, and 2 pancreatitis), with no tumor ingrowth in any case. Median stent patency was 138.9 ± 112.6 days. One-year actuarial probability of stent patency was 70% and that of nonmigration was 86%. Multivariate analysis showed adjuvant radio- or chemotherapy as the only independent predictive factor of stent patency and previous insertion of a biliary stent was the only predictive factor of migration. The partially covered SEMS was easily inserted, had a high clinical success rate, and prevented tumor ingrowth. The incidence of possible complications related to stent coverage, namely, migration, pancreatitis, and cholecystitis, was lower than in previously published series.

Pouchitis is the most frequent complication following total proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Up to 15% of patients with pouchitis experience a chronic course, which can be resistant to antibiotic therapy and may lead to surgical excision of the pouch. Further therapeutic options are therefore needed. Oral budesonide, a corticosteroid with topical activity in the terminal ileum (controlled ileal release [CIR] capsules), may be an alternative.We performed a prospective, open study of five patients with chronic refractory pouchitis. Patients were treated with 9 mg of budesonide capsules after other causes of the lack of treatment response were excluded. Assessments included clinical, endoscopic and histological evaluation at baseline and after 8 weeks of treatment. Efficacy was evaluated using the pouchitis disease activity index (PDAI) global scores as well as the clinical, endoscopic and histological subscores at baseline and 8 weeks. Remission was defined as a global score7. Variations in laboratory parameters and tolerance were also assessed.Four out of five patients went into remission at 8 weeks and a significant decrease was observed in the median total PDAI score from 14 (range, 12-15) to 4 (range, 4-11) (p = 0.0422) and in the three subscores: clinical from 4 (range, 4-5) to 1 (range, 0-4) (p = 0.0394), endoscopic from 5 (range, 4-6) to 2 (range, 1-5) (p = 0.0394), and histologic from 4 (range, 4-5) to 2 (range, 2-2) (p = 0.0339). No significant adverse effects were reported.Oral budesonide CIR capsules may be an option to induce remission in active chronic refractory pouchitis. Because tolerance is good, the use of enemas may be avoided.

Background: Preventive actions are advised since the use of anti-tumor necrosis factor (TNF) agents is known to increase the risk of tuberculosis (TB). No data related to the effectiveness and safety of the preventive chemoprophylaxis (ChP) for TB in inflammatory bowel disease (IBD) patients are available. The goal was to evaluate the requirements, effectiveness, and safety profile of ChP in IBD patient candidates for anti-TNF therapy. Methods: All IBD patients diagnosed with latent TB while evaluated for anti-TNF therapy from the IBD database of 9 Spanish centers were included. Epidemiological and clinical data, risk factors for hepatotoxicity, ChP regimens, and side effects were registered. Results: Sixty-three out of 497 IBD evaluated patients (12.5%) had latent TB. Sixty-eight percent were on immunomodulators and 42% on systemic corticosteroids when a TB skin test (TST) was performed. The detection of a positive TST was done in 86% after a single exposure, but 14% needed a booster. All but 1 were treated with isoniazid alone for 6 or 9 months, and only 1 case required ChP discontinuation because of hepatotoxicity. No risk factors for hepatotoxicity were found. No cases of active TB were noticed in the 67 patients further treated with anti-TNF therapy. Conclusions: More than 10% of Spanish IBD patients who are candidates for anti-TNF therapy have latent TB. TST retest is required to identify at least 14% of such patients; therefore, it should be considered if the initial TST is negative. ChP is safe in IBD patients even in those taking concomitant, potentially hepatotoxic drugs. (Inflamm Bowel Dis 2008)

The use of immunomodulators for the treatment of inflammatory bowel disease is increasing. One of the most common adverse effects associated with this kind of drugs are infectious complications. In recent years, special attention has been paid to certain latent infections which, in patients under immunomodulatory therapy, can be reactivated and prove lethal. Consequently, preventive actions have been adopted, such as screening for hepatitis B virus and tuberculosis infection before starting these treatments. Primary infection with the Epstein-Barr herpesvirus is usually asymptomatic. However, this virus can have an aggressive course and even lead to the development of lymphoma. We report two cases of atypical infectious mononucleosis in patients with inflammatory bowel disease under azathioprine therapy and review the available evidence on the most appropriate therapeutic approach in this subset of patients.

Background: Cholecystectomy use varies moderately across regions and countries. The purpose of this study was to evaluate the appropriateness of the use of cholecystectomy in patients with nonmalignant diseases in different hospitals using explicit criteria developed by an expert panel. Methods: Patients on waiting lists to undergo a cholecystectomy for nonmalignant diseases in six public hospitals in Spain were included in this prospective observational study over a 1-year period. Appropriateness criteria were first developed by a panel of experts using the RAND appropriateness method. The appropriateness of the indication was judged by applying explicit criteria developed previously. Complications were recorded 3 months after surgery. Results: After evaluation of 960 patients, 7 (0.7%) were considered to have undergone inappropriate procedures and 76 (7.9%) were judged to be uncertain. Differences were found in the rate of appropriateness among some centres (inappropriateness rate ranging from to 0 to 2.6%). No differences were found among the appropriateness categories for length of stay or complications, mortality, or readmission up to the third month after discharge. Conclusions: This study identified a low percentage of inappropriately performed cholecystectomies in our area. Even so, appropriateness differences among hospitals were found.

Postoperative biliary tract lesions are becoming increasingly common. The diagnosis is made by direct cholangiography via endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC). The present comparative study evaluates the diagnostic efficacy of magnetic resonance cholangiopancreatography (MRCP) in application to iatrogenic bile duct injury. A prospective blind study was performed, contrasting MRCP and ERCP in 10 patients with suspected postoperative biliary tract lesions. MRCP was performed less than 72 h before ERCP. Final diagnosis was made on the basis of findings at surgery and ERCP. The presence of biliary dilatation, excision injury, stricture, fluid collection and free fluid was analyzed. The mean patient age was 66.5 years. There were three males and seven females. The type of postoperative lesion (Bergman classification) are five patients type C, three type D, one type B and one type A. Diagnostic failure was recorded in two cases with ERCP, while in five patients it was unable to define a therapeutic approach. In contrast, MRCP correctly diagnosed all patients. MRCP is effective in diagnosing postoperative biliary tract lesions, and can help decide the best therapeutic approach.

Background Few studies have assessed health-related quality of life (HRQoL) among patients undergoing cholecystectomy. This study aimed to determine clinical variables that predict changes in HRQoL following cholecystectomy. Methods This was a prospective study of consecutive patients undergoing elective cholecystectomy for gallstones in six hospitals. Patients were asked to complete two questionnaires—the Short Form 36 (SF-36) and the Gastrointestinal Quality of Life Index (GIQLI)—before and 3 months after cholecystectomy. Multivariate linear regression models were used to examine factors potentially contributing to changes in HRQoL. Results Patients with symptomatic cholelithiasis and low surgical risk experienced the highest HRQoL gains in several SF-36 and GIQLI domains, with significant improvements in physical function detected by both instruments, compared with asymptomatic individuals at high surgical risk. Patients with asymptomatic cholelithiasis or high surgical risk experienced least improvement. Conclusion These data indicate that cholecystectomy is appropriate for patients with symptomatic cholelithiasis and low surgical risk. In terms of HRQoL, the risk to benefit ratio seems poor for patients with asymptomatic gallstones.