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Background Patients with inflammatory bowel disease (IBD) are vulnerable to some psychological disorders. Here we describe the psychological impact of a COVID-19 pandemic lockdown in patients with IBD. Methods This multicenter prospective cohort study included 145 patients recently diagnosed with IBD. Data on clinical and demographic characteristics, anxiety and depression scales, and IBD activity were collected in two telephone surveys, during and after the first COVID-19 lockdown in Spain. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results During lockdown, 33.1% and 24.1% scored high on the anxiety and depression scales, respectively. Independent factors related to anxiety (all values ORs; 95% CIs) during lockdown were female sex (2; 1.2–5.4) and IBD activity (4.3; 1.8–10.4). Factors related to depression were comorbidity (3.3; 1.1–9.8), IBD activity (6; 1.9–18.1), use of biologics (2.9; 1.1–7.6), and living alone or with one person (3.1; 1.2–8.2). After lockdown, anxiety and depression symptoms showed significant improvement, with 24.8% and 15.2% having high scores for anxiety and depression, respectively. Factors related to post-lockdown anxiety were female sex (2.5; 1.01–6.3), Crohn's disease (3.3; 1.3–8.5), and active IBD (4.1; 1.2–13.7). Factors associated with depression were previous history of mood and/or anxiety disorders (6.3; 1.6–24.9), active IBD (7.5; 2.1–26.8), and steroid use (6.4; 1.4–29). Conclusions Lockdown during the COVID-19 pandemic had a significant psychological impact in patients with IBD. Disease activity was related to the presence of anxiety and depression symptoms during and after lockdown.

[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.

(1) Background: Stress, anxiety, and depression have been identified as factors that influence the development of inflammatory bowel disease (IBD). The main aim of this study was to test the effectiveness of group multicomponent cognitive-behavioral therapy at reducing stress, anxiety, and depression, and improving quality of life and the clinical course of the disease. (2) Methods: A total of 120 patients were evaluated using the General Perceived Stress Scale, Scale of Stress Perceived by the Disease, the anxiety and depression scale, and quality of life questionnaire for patients with IBD. Disease activity was measured using the Mayo Index for ulcerative colitis and CDAI for Crohn's disease, as well as the number of relapses self-reported by patients. Patients were randomized to receive group multicomponent cognitive-behavioral therapy or treatment as usual. (3) Results: The psychological intervention reduced stress (EAE: 45.7 ± 8.8 vs. 40.6 ± 8.4, p = 0.0001, PSS: 28.0 ± 7.3 vs. 25.1 ± 5.9, p = 0.001) and improved quality of life (164.2 ± 34.3 vs. 176.2 ± 28.0, p = 0.001). An improvement was found in the number of relapses self-reported by patients (0.2 relapses/patient vs. control 0.7 relapses/patient, p = 0.027). No differences were found in disease activity indexes. (4) Conclusions: Psychological therapy was associated with improved stress, quality of life and with a decrease in the number of relapses self-reported by patients. Clinical trial registration number: NCT02614014

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.

Resumen Objetivos Establecer recomendaciones para el manejo de los aspectos psicologicos de los pacientes con enfermedad inflamatoria intestinal (EII). Metodos Se llevo a cabo una reunion con un grupo de expertos en EII formado por medicos, psicologos, enfermeras y representantes de pacientes. Se presentaron resultados de: 1) un grupo focal previo, 2) encuestas a medicos y pacientes y 3) una revision sistematica sobre instrumentos de cribado de ansiedad y depresion. Se realizo una discusion guiada sobre los aspectos psicologicos y emocionales mas importantes en EII, los criterios de derivacion apropiados y situaciones a evitar. Se selecciono el instrumento validado mas aplicable a la practica clinica. Se diseno un documento con recomendaciones, asi como una encuesta Delphi. La encuesta fue enviada al grupo y a un comite cientifico seleccionado del grupo GETECCU, con el objetivo de establecer el grado de apoyo a las recomendaciones establecidas. Resultados Se establecieron 15 recomendaciones, pertenecientes a 3 procesos clave: 1) que pasos dar para identificar problemas psicologicos en consulta de EII, 2) criterios de derivacion a profesionales de la salud mental y 3) abordaje de los problemas psicologicos. Conclusiones Se deben facilitar recursos a los profesionales sanitarios para que puedan tratar estos aspectos en consulta, identificar los trastornos que puedan afectar el curso de la enfermedad o su impacto en la vida del paciente, para ser tratados y seguidos por el profesional mas adecuado. Estas recomendaciones pueden servir de base para el rediseno de los servicios o procesos de EII y como justificacion para la formacion del personal sanitario.

Background Crohn’s disease (CD) affects young adults on reproductive age. They are likely to desire pregnancy and are often concerned about the potential effects of inflammatory bowel disease on fertility. Aims to investigate the effect of CD in fertility, studying the ovarian reserve in women by serum anti-Müllerian hormone (AMH) and Sertoli cell function in men measured by serum Inhibine (IB). Methods Cross-sectional, prospective, case-control study, including CD patients, aged 18–40 yr, and healthy controls(HC) matched by gender and age(ratio 2:1). Morning IB was measured using ELISA. Serum AMH was measured by ECLIA. Sociodemographic and phenotypic features of CD patients and controls were collected. We defined impaired fertility potential as IB level < 89 pg/mL and AMH Results A total of 122 subjects were included:73 men(48 CD, 25 HC) and 49 women(21 CD, 28 HC). No statistical difference was found between mean serum AMH levels in CD and HC women(2,23±1,8 vs 2,86±1,9 ug/L, p=0,5). The rate of abnormal serum AMH levels according to age did not differ between groups (19% CD vs 25% HC, p=0,4). When classified according to age(30 yr), the serum AMH levels remained comparable in 30 yr, 9 CD(90%)vs 4 in HC(40%)(p=0.02). Serum IB levels were significantly lower in CD men vs HC (175.4 ±62.3 vs 234.12±75.56 ug/L, p=0.002). We did not find abnormal IB( Conclusion Women with CD did not have severe ovarian reserve alterations compared to a control population. However higher proportion of CD women showed low AMH (< 2 ug/L), especially those > 30 years. These data could be helpful for female CD patients who want to have children. Inhibine levels, as biomarker of Sertoli cell function, were lower in CD men compared to healthy controls.

Background Patients with Crohn’s disease (CD) responding to anti–tumor necrosis factor (anti-TNF) show great variability in serum drug levels, even within the therapeutic range. We aimed at exploring the role of inflammatory, genetic, and bacterial variables in relation to anti-TNF through levels in CD patients. Methods Consecutive CD patients receiving stable doses of infliximab or adalimumab were included. Clinical and analytical parameters were recorded. Cytokine response, bacterial DNA translocation, and several immune-related genes’ genotypes were evaluated, along with serum through anti-TNF drug levels. A linear regression analysis controlled by weight and drug regimen was performed. Results One hundred nineteen patients were initially considered. Five patients on infliximab and 2 on adalimumab showed antidrug antibodies in serum and were excluded. One hundred twelve patients were finally included (62 on infliximab, 50 on adalimumab). Fourteen patients on infliximab and 15 on adalimumab (22.6% vs 30%, P = 0.37) were receiving an intensified drug regimen. C-reactive protein (CRP), fecal calprotectin, Crohn’s Disease Activity Index, leukocyte count, and albumin levels in plasma were not significantly associated with infliximab or adalimumab levels in the multivariate analysis. Serum interleukin-10 (IL-10) levels were directly related to infliximab (Beta = 0.097, P < 0.0001) and adalimumab levels (Beta = 0.069, P = 0.0241). The best multivariate regression model explaining the variability of serum infliximab and adalimumab levels included IL-10. Predicted drug levels by this model robustly fitted with actual drug levels (R2 = 0.841 for infliximab, R2 = 0.733 for adalimumab). Conclusion Serum IL-10 is significantly related to serum anti-TNF levels in CD patients, showing how the disposition of anti-TNF drugs is significantly influenced by the degree of immunological activation.

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.

Background and Aims Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies. Methods PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool. Results In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50–139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7–19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9–5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1–9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39–53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC. Conclusions PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival.

Background The prevalence of sexual dysfunction (SD) in general population has been estimated up to 30% in women and 5% in men, and 50% and 25% in IBD patients, respectively. We aimed to compare the rates of SD in young patients with Crohn’s disease (CD) with healthy controls (HC), as well as to identify SD associated factors in CD patients. Methods This was a cross-sectional, case-control, observational study, including CD out-patients, aged 18–40 years-old, and HC paired by gender and age. Sociodemographic and disease features were recorded. SD was measured by the Index of Female Sexual Function(IFSF) in women, and by International Index of Erectile Function(IIFE-15) in men. Psychological functioning was evaluated using the Hospital Anxiety and Depression Scale [HAD], and quality of life in IBD by SIBDQ-9. Differences between groups were statistically compared. Results A total of 122 subjects were included:73 men(48 CD, 25 HC) and 49 women(21 CD, 28 HC). Nineteen percent of CD women and 8.3% of men had active disease according to Harvey-Bradshaw Index. Nineteen percent of CD women and 6.3% of men were receiving steroids, 23.8% and 14.6% immunosuppressants, and 71.4% and 72.9% biologics, respectively. CD women had more sedentary lifestyle than HC(38.1% vs 3.6%, p=0.005). In women SD rates were 35% in CD vs 12% in HC(p < 0.08). Mean IFSF values were lower in CD women(27 CD vs 30 HC, p=0.02), as well as in the desire item(3.5 CD vs 4.3 HC, p=0.005). SD in men did not show significant difference between groups. Mean IIFE values differed between CD and HC(53.6 vs 67.2, p=0.001), as well as erectile disfunction, orgasm and global satisfaction(p< 0.05)(Table 1). Main factors associated with an abnormal SD in CD women were high fecal calprotectine, current use of steroids, lower SIBDQ score and higher depression score(p Conclusion In our serie SD was numerically higher in CD patients compared to HS. SD in CD women, but not in men, was driven by disease activity, current steroid treatment and depression.

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.

Interleukin IL26 supports killing of microbes and the innate sensing of bacterial-derived DNA (bactDNA). We evaluated the relationship between IL26 serum levels and bactDNA translocation in Crohn's disease (CD). We ran a prospective study on CD patients in remission. IL26 common polymorphisms, serum cytokines and complement protein, amplified-bactDNA, and anti-TNF-α were evaluated. In vitro PBMC analysis was performed. Three hundred and thirteen patients were included (mean CDAI: 83.6 ± 32.8; mean fecal calprotectin: 55.4 ± 35.3 μg/g). A total of 106 patients (33.8%) showed bactDNA and 223 patients (71%) had a varIL26 genotype. BactDNA significantly correlated with increased IL26 levels compared with bactDNA-negative patients. PBMCs from varIL26 patients significantly reduced E. coli killing capacity compared with wtIL26-genotyped patients. The stimulation with a recombinant IL26 protein reduced pro-inflammatory cytokines in response to E. coli in the varIL26 cell supernatants. Serum anti-TNF-α levels in varIL26 vs wtIL26-genotyped patients on biologics were significantly lower in the presence of bactDNA. Cells from varIL26 vs wtIL26-genotyped patients cultured with E. coli DNA and infliximab showed a significant decrease in free anti-TNF-α concentration. A varIL26 genotype was associated with the initiation of anti-TNF-α in CD patients during the 6-month follow-up. IL26 polymorphisms may prevent bactDNA clearance and identify CD patients with a worse inflammatory evolution and response to therapy.BactDNA translocation in CD is associated with an increased risk of relapse. IL26 is sensitive to bactDNA and modulates the inflammatory response in CD patients. The varIL26 genotype is associated with reduced PMN capacity to kill bacteria. A varIL26 genotype is associated with decreased levels of anti-TNF-α in CD patients. IL26 may help explain the role of bactDNA as a risk factor of flare in CD patients.

Anti-TNF-α therapies interact with the tolerogenic response in patients with Crohn’s disease, modulating inflammation. However, drug levels and the genetic background may affect this interaction. Patients with Crohn’s disease in remission on biologic monotherapy were enrolled in this study. FoxP3+ lymphocytes, NOD2 genotype, serum cytokine, anti-TNF-α levels, and anti-drug antibodies were evaluated. Regulatory T cell response to infliximab was evaluated in vitro. Fifty-seven patients were included. Thirty-nine patients (68.4 %) were receiving non-intensified biologic therapy whereas 18 patients (31.6 %) were under an intensified biologic schedule due to loss of response. Eleven intensified patients (61.1 %) showed a variant NOD2 genotype vs 9 on non-intensified biologics (23 %, p

Background & Aims Two new classification systems for the severity of acute pancreatitis (AP) have been proposed, the determinant-based classification (DBC) and a revision of the Atlanta classification (RAC). Our aim was to validate and compare these classification systems. Methods We analyzed data from adult patients with AP (543 episodes of AP in 459 patients) who were admitted to Hospital General Universitario de Alicante from December 2007 to February 2013. Imaging results were reviewed, and the classification systems were validated and compared in terms of outcomes. Results Pancreatic necrosis was present in 66 of the patients (12%), peripancreatic necrosis in 109 (20%), walled-off necrosis in 61 (11%), acute peripancreatic fluid collections in 98 (18%), and pseudocysts in 19 (4%). Transient and persistent organ failures were present in 31 patients (6%) and 21 patients (4%), respectively. Sixteen patients (3%) died. On the basis of the DBC, 386 (71%), 131 (24%), 23 (4%), and 3 (0.6%) patients were determined to have mild, moderate, severe, or critical AP, respectively. On the basis of the RAC, 363 patients (67%), 160 patients (30%), and 20 patients (4%) were determined to have mild, moderately severe, or severe AP, respectively. The different categories of severity for each classification system were associated with statistically significant and clinically relevant differences in length of hospital stay, need for admission to the intensive care unit, nutritional support, invasive treatment, and in-hospital mortality. In comparing similar categories between the classification systems, no significant differences were found. Conclusion The DBC and the RAC accurately classify the severity of AP in subgroups of patients.

Hepatitis-B-seronegative patients with inflammatory bowel disease (IBD) should be vaccinated. However, response to vaccination in this population seems to be poorer than in healthy people. The aim of this study is to assess which clinical, analytical and immunosuppressive therapy parameters affect the response to hepatitis B vaccination in patients with IBD. A follow-up including monitoring of the immunosuppressive therapy of a cohort of 123 patients with IBD was carried out after each round of vaccination against hepatitis B virus. The recombinant HBsAg vaccine (20 μg) was administered using the standard regimen (0, 1 and 6 months). Anti-HBs values >10 IU/L after 1–3 months post-vaccination were considered as a successful response to vaccination. One hundred and five patients (85.5%) completed the programme and response to vaccination was observed in 50 (47.6%) patients. Multivariate analysis showed an independent relationship, with weaker response to vaccination, for IBD duration equal to or longer than 110 months [adjusted OR (95% CI): 0.282 (0.114–0.701)], serum albumin levels below 3.6 mg/dl at the beginning of vaccination [adjusted OR (95% CI): 0.336 (0.112–1.009)], and corticosteroid therapy in more than one vaccination dose [adjusted OR (95% CI): 0.333 (0.135–0.820)]. This study confirms the poor response to hepatitis B vaccination in patients with IBD, being particularly weak in individuals with long-term IBD progression, low serum albumin levels and those on corticosteroid therapy.

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 (

AIM To evaluate the real-world effectiveness of golimumab in ulcerative colitis (UC) and to identify predictors of response. METHODS We conducted an observational, prospective and multi-center study in UC patients treated with golimumab, from September 2014 to September 2015. Clinical activity was assessed at wk 0 and 14 with the physician' s global clinical assessment (PGA) and the partial Mayo score. Colonoscopies and blood tests were performed, following daily-practice clinical criteria, and the results were recorded in an SPSS database. RESULTS Thirty-three consecutive patients with moderately to severely active UC were included. Among them, 54.5% were female and 42 years was the average age. Thirty percent had left-sided UC (E2) and 70% had extensive UC (E3). All patients had an endoscopic Mayo score of 2 or 3 at baseline. Twenty-seven point three percent were anti-tumor necrosis factor (TNF) treatment naive, whereas 72.7% had previously received infliximab and/or adalimumab. Sixty-nine point seven percent showed clinical response and were steroid-free at wk 14 (a decrease from baseline in the partial Mayo score of at least 3 points). Based on PGA, the clinical remission and clinical response rates were 24% and 55% respectively. Withdrawal of corticosteroids was observed in 70.8% of steroid-dependent patients at the end of the study. Three out of 10 clinical non-responders needed a colectomy. Mean fecal calprotectin value at baseline was 300 mu g/g, and 170.5 mu g/g at wk 14. Being anti-TNF treatment naive was a protection factor, which was related to better chances of reaching clinical remission. Twenty-seven point three percent of the patients required treatment intensification at 14 wk of followup. Only three adverse effects (AEs) were observed during the study; all were mild and golimumab was not interrupted. CONCLUSION This real-life practice study endorses golimumab's promising results, demonstrating its short-term effectiveness and confirming it as a safe drug during the induction phase.

OBJECTIVES: We aimed at evaluating bacterial DNA (bactDNA) presence in blood of Crohn's disease (CD) patients in remission as an independent risk factor of flare at 6 months. METHODS: This is a prospective, multicenter study on CD patients with Crohn's disease activity index (CDAI)150 in the following 6 months. BactDNA in blood, the nucleotide-binding oligomerization domain containing 2 (NOD2) genotype, and serum cytokine levels were determined at baseline. RESULTS: A total of 288 patients were included. BactDNA was detected in 98 patients (34.0%). A variantNOD2 genotype was identified in 114 patients (39.6%). Forty patients (14%) relapsed during follow-up. Multivariate survival analysis identified bactDNA as an independent risk factor of flare (hazard ratio (HR) 8.75 (4.02-19.06) 95% confidence interval (CI)). Hospitalization, surgery, switch of treatment, initiation and escalation of anti-tumor necrosis factor (TNF) therapy, steroids initiation, and increased fecal calprotectin levels at 6 months were associated with bactDNA at baseline. A logistic regression analysis showed bactDNA as an independent and significant predictive factor of hospitalization (odds ratio (OR) 11.9 (3.4-42.3); P

Although aggressive fluid therapy during the first days of hospitalization is recommended by most guidelines and reviews on acute pancreatitis (AP), this recommendation is not supported by any direct evidence. We aimed to evaluate the association between the amount of fluid administered during the initial 24 h of hospitalization and the incidence of organ failure (OF), local complications, and mortality.This was a prospective cohort study. We included consecutive adult patients admitted with AP. Local complications and OF were defined according to the Atlanta Classification. Persistent OF was defined as OF of48-h duration. Patients were divided into three groups according to the amount of fluid administered during the initial 24 h: group A:3.1 l (less than the first quartile), group B: 3.1-4.1 l (between the first and third quartiles), and group C:4.1 l (more than the third quartile).A total of 247 patients were analyzed. Administration of4.1 l during the initial 24 h was significantly and independently associated with persistent OF, acute collections, respiratory insufficiency, and renal insufficiency. Administration of3.1 l during the initial 24 h was not associated with OF, local complications, or mortality. Patients who received between 3.1 and 4.1 l during the initial 24 h had an excellent outcome.In our study, administration of a small amount of fluid during the initial 24 h was not associated with a poor outcome. The need for a great amount of fluid during the initial 24 h was associated with a poor outcome; therefore, this group of patients must be carefully monitored.

Persistent and multiple organ failure (POF and MOF) are predictive of death in acute pancreatitis (AP). Local complications without organ failure are associated with morbidity but a low risk of mortality.To design a three-category classification of AP severity and to compare it with the Atlanta Classification (AC) in terms of morbidity and mortality.Severe AP was defined as death, POF (48 h) or MOF. Moderate AP was defined as the presence of acute collections and/or pancreatic necrosis. Mild AP was defined by exclusion. We compared this classification with AC in 144 episodes of AP.In the three-category classification, severe AP was associated with significantly more frequent intensive care unit admission, invasive treatment and mortality than moderate and mild AP (p0.01). Severe AP patients required longer hospital stay and more nutritional support than mild AP patients (p0.01). Patients with moderate AP had significantly longer hospital stay and more need for nutritional support than patients with mild AP (p0.01). Five patients died, all of them with MOF and/or POF.A three-category classification distinguishes three homogeneous groups of severity.

In the last few years, major advances have been produced in knowledge of the pathogenesis of colorectal cancer, which have led to the development of new drugs for the treatment of this disease. Likewise, molecular markers have been identified that are useful in prognosis. However, decisions on adjuvant therapy in colorectal cancer continue to be based exclusively on histological stage. Distinct markers that can be detected in tumoral tissue may be useful in predicting response to antineoplastic drugs. The present article reviews the possible clinical utility of these markers and their role in decision-making in the treatment of patients with colorectal cancer.

Fundamento y objetivo: El estrenimiento afecta mucho la calidad de vida, pero apenas hay cuestionarios especificos que evaluen en que medida. El objetivo de este trabajo ha sido desarrollar y validar un cuestionario capaz de medir la calidad de vida en pacientes con estrenimiento. Pacientes y metodo: Se ha realizado un estudio multicentrico espanol en 2 fases: a) desarrollo del cuestionario (entrevista a pacientes con estrenimiento, obtencion del cuestionario piloto, analisis cuantitativo y factorial, analisis de Rasch y diseno del cuestionario especifico) y b) validacion del cuestionario en 136 pacientes con estrenimiento (segun criterios de Roma II). Se dividio a estos pacientes en 2 grupos: a) grupo de fiabilidad (n = 55; pacientes que no precisaban iniciar o cambiar el tratamiento actual; retest a los 15 dias), y b) grupo de sensibilidad al cambio (n = 81; requerian iniciar o cambiar el tratamiento; retest a los 3 meses). Se recogieron las variables sociodemograficas y clinicas, y se evaluo la calidad de vida mediante el cuestionario general EuroQoL-5D (EQ-5D) y el especifico disenado en la fase anterior (25 items). Se analizaron la factibilidad, fiabilidad y validez (de constructo, convergente y longitudinal). Resultados: En la fase de desarrollo se obtuvo un cuestionario piloto de 51 items, que se redujeron a 25 en la fase de validacion; lo completaron correctamente 126 pacientes. El tiempo medio de respuesta fue de 12 min. La validez de constructo redujo el cuestionario a 20 items (CVE-20) con 4 dimensiones: emocional, fisica general, fisica rectal y social. La fiabilidad fue alta para la puntuacion global (alfa de Cronbach = 0,87), siendo para las diferentes dimensiones de 0,79; 0,73; 0,75, y 0,60, respectivamente. Las puntuaciones del CVE-20 se relacionaron con los cambios en el EQ-5D. La fiabilidad test-retest fue buena, con un coeficiente de correlacion intraclase de 0,89 (extremos: 0,80-0,88 en las diferentes dimensiones). La diferencia minima clinicamente importante fue de 17 puntos (intervalo de confianza del 95%,11-23). La validez de constructo demostro una correlacion elevada entre el CVE-20 y la gravedad del estrenimiento. Conclusiones: El CVE-20 es el primer cuestionario especifico en castellano para pacientes con estrenimiento; es valido, fiable, sensible a los cambios y cumple con los criterios psicometricos requeridos para la utilizacion en la practica diaria y estudios clinicos.

Background/Aims: Surveillance programmes (SPs) for hepatocellular carcinoma (HCC) in patients with cirrhosis intend to diagnose the tumour in its early stages when an effective therapy can be applied. The aims of this study have been to compare the survival of patients with HCC being diagnosed or not in SPs, and to establish a more accurate profile of the best target population. Methods: From January 1996 to June 2005, 290 patients with HCC were included. The relationship between being diagnosed or not in an SP and survival has been analysed in a univariate analysis. Pretreatment variables found to be significant predictors of survival in univariate analysis were included in a multivariate analysis. Results: The mean survival for patients diagnosed in SPs (27 months, 16.6–37.4) was significantly longer than in patients being diagnosed out of these programmes (6 months, 2.6–9.4) (P=0.001). Child–Pugh class A [β 1.4, 95% confidence interval (CI) 1.14–1.78; P=0.0002] and being diagnosed in SPs (β 0.4, 95% CI 0.3–0.6; P=0.0003) became the only independent predictive factors of longer survival. Conclusions: SPs for HCC allow the detection of small tumours and the application of intention-to-cure therapies, which improves survival. However, these programmes do not improve prognosis in patients with advanced cirrhosis.

Purpose: Some new staging systems in hepatocellular carcinoma (HCC) have been described in the last years. The aim of this study was to compare the survival-predicting capacity of some variables and the prognostic classifications. Methods: Demographic, clinical, analytical variables and tumour characteristics were collected in a study including 115 patients with HCC. Predictors of survival were identified using the Kaplan–Meier test and the Cox model. Comparison between different staging systems was carried out. Results: The 1-, 2- and 3-year estimated survival was 65%, 45% and 30%, respectively. Child–Pugh score and α-fetoprotein level greater than 400 UI/l were independent predictors of survival in the Cox model. Although all systems correctly differentiated between patients regarding survival (Kaplan–Meier, log rank

Objective The aetiology of Crohn9s disease (CD) has been related to nucleotide-binding oligomerisation domain containing 2 (NOD2) and ATG16L1 gene variants. The observation of bacterial DNA translocation in patients with CD led us to hypothesise that this process may be facilitated in patients with NOD2/ATG16L1-variant genotypes, affecting the efficacy of anti-tumour necrosis factor (TNF) therapies. Design 179 patients with Crohn9s disease were included. CD-related NOD2 and ATG16L1 variants were genotyped. Phagocytic and bactericidal activities were evaluated in blood neutrophils. Bacterial DNA, TNFα, IFNγ, IL-12p40, free serum infliximab/adalimumab levels and antidrug antibodies were measured. Results Bacterial DNA was found in 44% of patients with active disease versus 23% of patients with remitting disease (p=0.01). A NOD2-variant or ATG16L1-variant genotype was associated with bacterial DNA presence (OR 4.8; 95% CI 1.1 to 13.2; p=0.001; and OR 2.4; 95% CI 1.4 to 4.7; p=0.01, respectively). This OR was 12.6 (95% CI 4.2 to 37.8; p=0.001) for patients with a double-variant genotype. Bacterial DNA was associated with disease activity (OR 2.6; 95% CI 1.3 to 5.4; p=0.005). Single and double-gene variants were not associated with disease activity (p=0.19). Patients with a NOD2-variant genotype showed decreased phagocytic and bactericidal activities in blood neutrophils, increased TNFα levels in response to bacterial DNA and decreased trough levels of free anti-TNFα. The proportion of patients on an intensified biological therapy was significantly higher in the NOD2-variant groups. Conclusions Our results characterise a subgroup of patients with CD who may require a more aggressive therapy to reduce the extent of inflammation and the risk of relapse.

Linitis plastica of the rectum is an uncommon entity that is difficult to diagnose due to the lack of mucosal lesions on endoscopy, the low diagnostic yield of biopsy and non-specific findings of barium radiology and computerized tomography. Rectal endoscopic ultrasonography has had a radical impact on the differential diagnosis of stenosing lesions of the rectum, among them linitis plastica, allowing diagnosis of this lesion even in patients with negative results of biopsy.

Prophylactic treatment of variceal bleeding in cirrhotic patients with beta-blockers is effective in only some patients. Our aim was to determine whether the response of the hepatic venous pressure gradient (HVPG) to the intravenous administration of propranolol predicts the response after chronic oral propranolol treatment.We included prospectively cirrhotic patients with esophageal varices under primary prophylaxis (PP) and secondary prophylaxis (SP). The HVPG was measured at baseline and after a propranolol bolus (0.15 mg/kg intravenous). A patient was considered a good-responder if HVPG decreased to 12 mmHg or 20% from baseline. Patients then received oral propranolol (heart rate titrated). Poor-responders under SP were also included in a variceal band ligation program. After at least 3 months, a second hemodynamic study was conducted.Fifty-six patients were included (36 SP and 20 PP). Response rate was similar (32.1 and 41.9%, P=0.7) and the Pearson's correlation coefficient was 0.61 (P=0.001). In 81.4% patients, the first study predicted the response status of the second. Six patients rebled on follow-up between the studies, all of them were poor responders to intravenous propranolol.A single hemodynamic study using intravenous propranolol seems to predict chronic response to propranolol.

Objetivo: evaluar la eficacia de los diferentes indicadores pronósticos de supervivencia a corto y largo plazo en pacientes con cirrosis y hemorragia digestiva alta por hipertensión portal (HTP). Material y métodos: calculamos los indicadores pronósticos en una cohorte de 201 pacientes con cirrosis y hemorragia digestiva por HTP ingresados en el Hospital General Universitario de Alicante. Las variables a estudio fueron: edad, sexo, etiología de la cirrosis, hallazgos endoscópicos, episodios previos de hemorragia digestiva por HTP. Infección por el virus de la inmunodeficiencia humana (VIH), hepatocarcinoma (HCC), infección bacteriana durante el episodio de hemorragia digestiva y clasificación de Child-Turcotte-Pugh (CTP) y el modelo para enfermedades terminales del hígado (MELD score) calculados dentro de las primeras 24 horas del inicio de la hemorragia. Los pacientes fueron seguidos al menos 6 meses hasta su muerte, trasplante hepático o final del seguimiento. Resultados: la mediana de seguimiento fue de 66,85 semanas (rango 0-432,4). La mortalidad a las 6 semanas, 3 meses, 12 meses y 36 meses fue de 22,9, 24,9, 34,3 39,8%, respectivamente. La edad ≥ 65 años, la presencia de HCC, una clasificación de CTP ≥ 10 y un MELD score ≥ 18 fueron las variables asociadas a la mortalidad en el estudio multivariante. La precisión del MELD score como predictor de mortalidad a las 6 semanas, 3 meses, 12 meses y 36 meses fue superior a la de la clasificación de CTP (valor c-estadístico: 6 semanas MELD 0,804, CTP 0,762; 3 meses MELD 0,794, CTP 0,760; 12 meses MELD 0,766, CTP 0,741; 36 meses MELD 0,737, CTP 0,717). Conclusión: el MELD score y la clasificación de CTP, junto con la edad y la presencia de HCC, son marcadores útiles en la valoración pronóstica de supervivencia a corto y largo plazo de los paciente con cirrosis y hemorragia digestiva por HTP.

The circumstances that determine how acute pancreatitis (AP) becomes severe are unknown. Differences in cytokine genetic encoding may determine the severity or influence the etiology of AP. This article investigates the relationship between different polymorphisms of tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), IL-1 receptor antagonist, IL-6, and IL-10 with the severity and etiology of AP and the serum levels of the cytokine encoded.Patients with AP were included prospectively. Severity of the disease was determined according to Atlanta classification. Serum levels of these cytokines were determined within the first 72 hours after the onset of symptoms. The following polymorphisms were determined by polymerase chain reaction: IL-1a -889, IL-1b +3954, IL-1b -511, variable number tandem repeats, IL-6 -174, IL-6 -597, IL-10 -592, TNF-alpha 308, TNF-alpha 238, and TNF-B250.Eighty-four patients were included. The GA genotype of the TNF-alpha 238 polymorphism was associated with more frequent respiratory failure and shock than the GG genotype. Gallstone pancreatitis was associated with the CC genotype of the IL-6 -174 CC polymorphism.AG genotype of the TNF-alpha 238 polymorphism is associated with organic failure in patients with AP. The CC genotype of the IL-6 174 polymorphism is associated with biliary etiology of acute pancreatitis.

The aim of this study is to evaluate if mismatch repair (MMR) defective colorectal cancer has a different response to adjuvant 5-fluorouracil (5-FU) chemotherapy in a cohort of patients prospectively followed during 5 years.The cohort included 754 surgically treated patients with colorectal cancer. MMR status was diagnosed by MLH1 and MSH2 immunohistochemistry and microsatellite instability analysis. Median follow-up was 49.2 months (range 1-73). At inclusion, 505 patients were diagnosed as TNM II or III stage, analysis of the efficacy of adjuvant chemotherapy was made on this population. Adjuvant chemotherapy was applied to 248 patients (98.2% 5-FU based).MMR deficiency was found in 76 patients (10.1%). No differences were found in overall survival (log-rank p=0.3) or disease-free survival (log-rank p=0.3) regarding MMR status. Adjuvant chemotherapy improves survival in patients in the II or III stage, but this improvement is only evident in patients with MMR-competent tumours (log-rank p=0.00001). Survival of patients with MMR-defective tumours does not improve with adjuvant chemotherapy (log-rank p=0.7). A multivariate analysis showed an independent effect of the interaction between MMR status and adjuvant chemotherapy (Hazard ratio 2.04; 95% confidence interval: 1.42-2.93).In a cohort of colorectal cancer patients, those with MMR-deficient tumours seem not to benefit from 5-FU-based chemotherapy.

Acute pancreatitis (AP) is a systemic inflammatory disease. It is already known that obesity and central fat distribution are related to the severity of AP, but the intimate mechanism of this relationship remains unknown. Obesity and central fat distribution are associated with an inflammatory state that could amplify the systemic inflammatory response (SIR) in AP. The aim of this study was to investigate how obesity and body fat distribution correlate with the SIR and severity of AP.85 consecutive patients with AP were studied. Body mass index, body fat distribution and previous comorbidity were obtained at admission. The SIR was assessed by the serum levels of interleukin (IL)-1beta, IL-1ra, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein. Serum concentrations of the previously mentioned cytokines were also determined in a control group of 40 healthy volunteers.63 patients (74%) had mild AP and 22 patients (26%) had severe AP. All the cytokines except IL-12p70 and TNF-alpha were increased in the AP group in comparison with the control group. The SIR was significantly increased in patients with severe AP. Obese patients and patients with central fat distribution had significantly more comorbidity, a higher proportion of severe AP and more intense SIR. Patients with comorbidity had a significantly higher proportion of severe AP and more SIR.The severity of AP in obese patients and in patients with central fat distribution seems to be related to the comorbidity and the amplification of SIR. and IAP.