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BACKGROUND/OBJECTIVES Immune-mediated inflammatory diseases (IMIDs) are prevalent diseases. There is, however, a lack of understanding of the link between diet and IMIDs, how much dietary patterns vary between them and if there are food groups associated with a worsening of the disease. SUBJECTS/METHODS To answer these questions we analyzed a nation-wide cohort of n = 11,308 patients from six prevalent IMIDs and 2050 healthy controls. We compared their weekly intake of the major food categories, and used a Mendelian randomization approach to determine which dietary changes are caused by disease. Within each IMID, we analyzed the association between food frequency and disease severity. RESULTS After quality control, n = 11,230 recruited individuals were used in this study. We found that diet is profoundly altered in all IMIDs: at least three food categories are significantly altered in each disease (P

The production of antibodies to anti-tumor necrosis factor alpha (TNF) agents is one of the main causes of treatment failure in Crohn’s disease (CD). To date, however, the contribution of genetics to anti-TNF immunogenicity in CD is still unknown. The objective of the present study was to identify genetic variation associated with anti-TNF immunogenicity in CD. We performed a two-stage genome-wide association study in a cohort of 96 and 123 adalimumab-treated patients, respectively. In the discovery stage, we identified a genome-wide significant association between the CD96 locus and the production of antibodies to anti-TNF treatment (P = 1.88e–09). This association was validated in the replication stage (P

Background and aims: The aims of this study were to evaluate the frequency of entero-urinary fistulas in a cohort of Crohn’s disease (CD) patients and to analyse the outcomes of medical and surgical therapy. Methods: This multicentre retrospective study included all CD patients with entero-urinary fistulas diagnosed by the presence of clinical symptoms and confirmed at surgery or by radiological or endoscopic techniques. We evaluated outcomes of medical and surgical therapy. We defined remission as absence of clinical symptoms with a radiological confirmation of fistula closure. Cox regression analysis was performed to evaluate factors predictive of achieving remission without need for surgery. Results: Of 6081 CD patients screened, 97 had entero-urinary fistulas (frequency 1.6%). Seventy-five percent of fistulas occurred in men. After a median follow-up of 91 months, 96% of patients were in sustained remission. Thirty-three patients (35%) received anti-tumour necrosis factor (TNF) therapy. Of these, 45% achieved sustained remission (median follow-up 35 months) without needing surgery. More than 80% of patients required surgery, which induced remission (median follow-up 101 months) in 99% of them. Only the use of anti-TNF agents was associated with an increased rate of remission without need for surgery (hazard ratio 0.23, 95% confidence interval 0.12–0.44; p < 0.001). Conclusion: In this large cohort of CD patients, the frequency of entero-urinary fistulas was lower than previously described. More than 80% of patients required surgery, and in all but one of them surgery induced sustained remission. In a selected subgroup of patients, anti-TNF may induce long-term fistula remission and radiographic closure, making it possible to avoid surgery.

Infliximab (IFX) is a valid treatment for Crohn’s disease (CD), but a relevant percentage of patients do not benefit from this therapy. In the Japanese population, the response to IFX was associated with markers in the TNF receptor superfamily 1A ( TNFRSF1A ) and 1B ( TNFRSF1B ) genes. We aimed to replicate the association previously described in the Japanese population and to ascertain the role of TNF receptors as modulators of the response to IFX. We studied 297 white Spanish CD patients with a known response to IFX: 238 responders and 59 primary nonresponders. Four single nucleotide polymorphisms (SNPs) were analyzed: rs767455 in TNFRSF1A and rs1061622 , rs1061624 , and rs3397 in TNFRSF1B . Comparisons between groups were performed with chi-square tests or the Fisher’s exact test. Different features (sex, age, disease duration, smoking among others) were evaluated as possible confounding factors. No significant association was found between the studied TNFRSF1A polymorphisms and response to IFX. In the TNFRSF1B gene, the haplotype rs1061624_A-rs3397_T was significantly increased in nonresponders: p = 0.015, OR = 1.78, 95% CI 1.09–2.90; and an increased frequency of rs1061622_G carriers was observed in patients with remission: p = 0.033 vs nonresponders and p = 0.023 vs patients with a partial response. Our results support a role of TNFRSF1B gene variants in the response to IFX in CD patients.

Objective: to describe the experience at two tertiary centres during the first year of use of magnetic resonance enterography (MRE) for the management of Crohn's disease (CD): indications and influence of the technique in clinical decision making. Material and method: retrospective descriptive study in which patients who underwent MRE were included consecutively. Epidemiological and clinical data were collected from the patients, as well as the indication for the study and how it influenced clinical decision making in the 10 days following the radiological study. Results: 24 MREs were performed in suspected CD and 126 known CD; partial bowel obstruction in 53 patients (42%), monitoring of medical treatment in 34 (27%), due to incomplete ileocolonoscopy in 16 (13%), extension study of the small intestine in 15 (12%) and suspected complicated CD in 8 patients (6%). The MRE influenced in a change in treatment in 83 (55.3%) patients: 16 (10.7%) started with immunosuppressants, 41 (27.3%) with anti-TNFα were started on or switched, 15 (10%) were ordered surgery and in 3 (2%) changed from combined therapy to monotherapy. The MRE had less influence on clinical decision making in the group in which the indication was suspected CD (p < 0.05). Conclusions: the use of MRE helped on decision making in more than half of patients, especially with regards to decisions related to the use of biological therapies and the indication for surgery. MRE was less useful in suspected CD patients.

Methotrexate is an effective treatment for inflammatory bowel disease (IBD). However, long-term treatments have been associated with the development of liver fibrosis. FibroScan® is a noninvasive, safe, and effective technique to evaluate liver fibrosis.To evaluate the presence of significant liver fibrosis by transient elastography (FibroScan®) in IBD patients treated with methotrexate.Cross-sectional study including IBD patients treated with methotrexate from different hospitals. Clinical and analytical data, duration of treatment, and cumulative dose of methotrexate were obtained. Liver stiffness was assessed by FibroScan®. The cutoff value for significant liver fibrosis (according to METAVIR) was F ≥ 2: 7.1 kPa. Results. In the study, 46 patients were included, 30 women (65%), with a mean age of 43 ± 10 years. 31 patients had Crohn's disease (67.4%), 13 ulcerative colitis (28.3%), and 2 indeterminate colitis (4.3%). The mean cumulative dose of methotrexate was 1242 ± 1349 mg, with a mean treatment duration of 21 ± 24 months. The mean value of liver stiffness was 4.7 ± 6.9 kPa. There were 35 patients (76.1%) with F01, 8 patients (17.4%) with F = 2, and 3 patients with F ≥ 3 (6.5%). There were no differences in liver stiffness depending on sex, age, type of IBD, or cumulative dose of methotrexate.(1) Development of advanced liver fibrosis in IBD patients treated with methotrexate is exceptional. (2) There were no differences in liver stiffness depending on the type of IBD or the cumulative dose of methotrexate. (3) FibroScan® may be potentially useful for evaluation and follow-up of liver fibrosis in methotrexate-treated patients.

Aliment Pharmacol Ther 2012; 35: 275–283 Summary Background Ciclosporin has proven to be effective in patients with corticosteroid-refractory ulcerative colitis (UC). When therapy with this drug fails, infliximab can be considered to avoid colectomy. The efficacy and safety of this sequential approach remain unknown. Aim To assess the efficacy and safety profile of treatment with infliximab after failure of ciclosporin in patients with a corticosteroid-refractory flare of UC. Methods Retrospective review of medical records of patients with a corticosteroid-refractory flare of UC who did not respond to ciclosporin and received salvage therapy with infliximab within a month of discontinuing ciclosporin. The severity of the flare and response to the treatment were graded using the Lichtiger index. Cumulative rates of colectomy were calculated using Kaplan–Meier analysis. Cox regression analysis was performed to identify predictors of colectomy. To evaluate the safety profile of this treatment strategy, any adverse event occurring after the first infusion of infliximab was considered. Results The study population comprised 47 patients with corticosteroid-refractory UC treated with infliximab after failure of ciclosporin. The median baseline Lichtiger index was 13. The mean time from the last ciclosporin dose to the first infliximab infusion was 6 days. After the first infliximab infusion, 13% of patients achieved remission, and 74% partial response. Of the 35 patients who received the third infliximab infusion, 60% achieved remission, and 37% partial response. Fourteen patients (30%) underwent colectomy. The rate of adverse events was 23%. One death occurred in a 40-year-old man who failed ciclosporin and infliximab and underwent surgery 10 days after the first infliximab infusion; he died of nosocomial pneumonia. Conclusions Treatment with infliximab makes it possible to avoid colectomy in two-thirds of corticosteroid-refractory UC patients in whom ciclosporin fails. However, the rates of adverse events and mortality mean that the decision to administer sequential therapy (ciclosporin–infliximab) should be taken on an individual basis.

Background Mucosal healing (MH) has emerged as a desirable treatment goal for patients with ulcerative colitis (UC). Currently little is known about the efficacy of using thiopurine immunosuppressants in monotherapy to achieve and maintain long-term MH in UC. This study analyzes the efficacy and the clinical impact of MH in patients with UC responded to thiopurine immunosuppressants in the long term. Methods An open, observational, cohort study in 20 patients with UC had been in clinical remission in monotherapy with thiopurine immunosuppressants for at least 1 year. MH was assessed by endoscopy. The patients according to the Mayo Endoscopic Score (0 vs 1 and 2), were followed until the end of the study or patient relapse. (according to Truelove and Witts criteria). Results Mean treatment time was 5.4 years. Twelve (60%) patients presented a Mayo Endoscopic Score of 0. A total of 18 patients were followed up for a median of 27.1 months. After endoscopy, 4 patients (22.2%) presented relapse, with a mean time of 27.5 months for a score ≥ 1 (95% CI; 18.2–36.8) versus 54.3 months for a score = 0 (95% CI 47.2–61.3) (p = 0.032). Conclusions This study shows the efficacy of thiopurine immunosuppressants in achieving mucosal healing in patients who respond to thiopurine immunosuppressants in the long term. We also observe the presence of endoscopy activity is not a rare event in this group of patients and is a predictor of early relapse.

Aliment Pharmacol Ther 2011; 34: 125–145 Summary Background Cross-sectional imaging techniques, including ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI), are increasingly used for evaluation of Crohn’s disease (CD). Aim To perform an assessment of the diagnostic accuracy of cross-sectional imaging techniques for diagnosis of CD, evaluation of disease extension and activity and diagnosis of complications, and to provide recommendations for their optimal use. Methods Relevant publications were identified by literature search and selected based on predefined quality parameters, including a prospective design, sample size and reference standard. A total of 68 publications were chosen. Results Ultrasonography is an accurate technique for diagnosis of suspected CD and for evaluation of disease activity (sensitivity 0.84, specificity 0.92), is widely available and non-invasive, but its accuracy is lower for disease proximal to the terminal ileum. MRI has a high diagnostic accuracy for the diagnosis of suspected CD and for evaluation of disease extension and activity (sensitivity 0.93, specificity 0.90), and is less dependent on the examiner and disease location compared with US. CT has a similar accuracy to MRI for assessment of disease extension and activity. The three techniques have a high accuracy for identification of fistulas, abscesses and stenosis (sensitivities and specificities >0.80), although US has false positive results for abscesses. As a result of the lack of radiation, US or MRI should be preferred over CT, particularly in young patients. Conclusions Cross-sectional imaging techniques have a high accuracy for evaluation of suspected and established CD, reliably measure disease severity and complications; they may offer the possibility to monitor disease progression.

Genome-wide association studies have reported the role of the interleukin (IL) 2-IL21 chromosomal region at 4q27 in several autoimmune conditions. Mice deficient in IL-2 develop a disease with clinical and histological similarity to ulcerative colitis (UC) in humans. Modest evidence of linkage with UC was tentatively proposed for the IL2 gene more than a decade ago. Therefore, we decide to investigate the association of polymorphisms in the IL-2 axis (IL2, IL2RA, and IL2RB genes) with inflammatory bowel diseases (IBDs).Seven hundred and twenty-eight white Spanish unrelated IBD patients (356 Crohn's disease (CD) and 372 UC) and 549 ethnically matched controls were included in a case-control study. In addition, a Spanish replication cohort with 562 CD and 430 UC patients and 1,310 controls were analyzed. Eight single-nucleotide polymorphisms previously associated with different autoimmune diseases were analyzed using TaqMan chemistry.The IL2-rs6822844 polymorphism modified CD predisposition (P=0.002; odds ratio, OR (95% confidence interval, CI)=0.61 (0.44-0.84)); this was replicated in the other Spanish cohort, resulting in a strong protective effect of the minor allele in the merged samples (P=0.0002; OR (95% CI)=0.70 (0.58-0.85)). A similar effect of rs6822844 was detected for UC. Another marker, rs11938795, also showed evidence of an association with CD (P=0.006; OR (95% CI)=0.73 (0.58-0.92)).Polymorphisms within the IL2-IL21 linkage disequilibrium (LD) block show a novel association with IBD, this is concordant with suggestive previous results of whole genome analyses in CD and type 1 diabetes. Our data agree with the effect previously observed for other conditions and delineate a shared underlying mechanism.

Neuropathic pain of various etiologies is a frequent symptom in HIV-infected patients that is underdiagnosed and inadequately treated. It requires a multidisciplinary pain approach based on psychosocial factors, diet and exercise, etiologic treatment whenever possible, symptomatic medical treatment, and sometimes, interventional techniques. Medical treatment should be individualized and introduced gradually, with a mind to potential drug interactions. Neuropathic pain responds poorly to conventional analgesics, such as nonsteroidal antiinflammatory drugs and opiates; tricyclic antidepressants and anticonvulsants are the drugs of choice. Before establishing an analgesic treatment, possible drug interactions should be ruled out, mainly those occurring with antiretroviral agents.

Efficacy of infliximab in Crohn's disease (CD) showed by randomized controlled trials must be confirmed in clinical practice. We aimed to evaluate efficacy and safety of infliximab in CD patients of the Madrid area, looking for clinical predictors of response.Multicenter retrospective survey of all CD patients treated with infliximab in 8 University hospitals of the Madrid area (Spain) with a minimum follow up of 14 wks.169 patients included (48%males, mean age 39 +/- 12 yrs). 64% of them had perianal disease. 82% were under immunosuppressants. 1,355 infliximab infusions administered (mean 8, range 1-30). 90% response rate and 48% remission rate were obtained with induction therapy. 73% followed maintenance treatment, and 78% of them maintained or improved the response after a mean follow up of 28 months (range 3.5-86). 24 patients lost response during the follow up, after a mean of 41 wks (range 6-248). Only the prescription of maintenance therapy was predictive factor for favourable response (p0.01). 17 infusion reactions were reported (10% of the patients, 1.2% of the infusions; only one case was severe) and were the cause of treatment withdrawal in 7 patients. Co-treatment with immunosuppressive drugs and maintenance infliximab therapy were protective factors for infusion reactions (p0.05). Other adverse events occurred in 26% of the patients, and were cause of treatment withdrawal in 7 patients.Infliximab is effective and safe for CD management but concomitant immunosuppressive drugs and maintenance treatment should be prescribed to obtain the best outcome. That confirms in a real life clinical setting the favourable results obtained in randomized clinical trials.

Background: To investigate the contribution of multidrug resistance 1 (MDR1) gene pharmacogenetics (G2677T/A and C3435T) to the efficacy of azathioprine in inducing remission in patients with Crohn's disease (CD). Methods: A cohort of 327 unrelated Spanish patients with CD recruited from a single center was studied. All patients were rigorously followed up for at least 2 years (mean time, 11.5 years). A case-control analysis of MDR1 G2677T/A and C3435T SNPs and 2 loci haplotypes in 112 steroid-dependent CD patients treated with azathioprine was performed. Patients were classified on the basis of response to azathioprine. Results: A total 76 patients treated with azathioprine for longer than 3 months were included. Remission was achieved in 42 CD patients (55.3%). A higher frequency of the 2677TT genotype was found in nonresponders than in responders (17.65% versus 7.14%; OR = 2.8; 95% CI; 0.6–12.1; P = 0.11). Nonresponders to azathioprine were found to have a higher frequency of the 3435TT genotype than did CD patients who had achieved clinical remission (17.64% versus 4.76%; OR = 4.3; 95% CI, 0.8–22.8; P = 0.06). The 2677T/3435T haplotype was also more abundant in nonresponders (29.4% versus 20.2%), whereas the 2677G/3435C haplotype was more frequent in responders (58.3% versus 47.1%). Lack of response to azathioprine therapy in CD patients was 1.8-fold greater in carriers of the 2677T/3435T haplotype than in carriers of the 2677G/3435C haplotype (OR = 1.8; 95% CI, 0.82–3.9; P = 0.14). Conclusions: The results of our study indicate higher frequencies of the 2677TT and 3435TT genotypes and the 2677T/3435T haplotype in CD patients who did not respond to azathioprine. Additional replications in independent populations would confirm the real impact of these polymorphisms in response to azathioprine therapy. (Inflamm Bowel Dis 2007)

The outcomes of infliximab dose escalation in ulcerative colitis (UC) have not been well evaluated. To assess the short- and long-term outcomes of infliximab dose escalation in a cohort of patients with UC. This was a multicenter, retrospective, cohort study. All consecutive UC patients who had lost response to infliximab maintenance infusions and who underwent infliximab dose escalation were included. Post-escalation short-term clinical response and remission were evaluated. In the long term, the cumulative probabilities of infliximab failure-free survival and colectomy-free survival were calculated. Predictors of short-term response and event-free survival were estimated using logistic regression analysis and Cox proportional hazard regression analysis. Seventy-nine patients were included. Fifty-four patients (68.4 %) achieved short-term clinical response and 41 patients (51.9 %) entered in clinical remission. After a median follow-up of 15 months [interquartile range (IQR) 8–26], 33 patients (41.8 %) had infliximab failure. Patients with short-term response had a significantly lower adjusted rate of infliximab failure [hazard ratio (HR) 0.24, 95 % confidence interval (CI) 0.12–0.49; p

Fundamento y objetivo La prevalencia de las manifestaciones extraintestinales (MEI) en la enfermedad inflamatoria intestinal (EII) varia en funcion de las areas geograficas, el tipo de EII, la localizacion, la duracion de la enfermedad y el tratamiento y la rapidez en el diagnostico. El objetivo de este trabajo ha sido determinar la prevalencia de las principales MEI en la EII y las diferencias existentes entre la enfermedad de Crohn (EC) y la colitis ulcerosa (CU). Pacientes y metodo Estudio prospectivo en el que se incluyo a 566 pacientes con EII (295 con EC y seguimiento medio de 11,6 anos [extremos: 2-32 anos] y 271 con CU y seguimiento medio de 10,4 anos [extremos: 2-36 anos]. Los datos referidos a las MEI y tests de laboratorio se obtuvieron en el momento del diagnostico y durante las visitas posteriores. Resultados La aparicion de al menos una MEI se observo en el 46,6% de los pacientes. Las MEI fueron frecuentes tanto en la CU (51,5%) como en la EC (42,2%). Las manifestaciones hepatobiliares (odds ratio [OR] = 1,91; intervalo de confianza [IC] del 95%, 1,15-3,16), la enfermedad tromboembolica venosa (OR = 4,26; IC del 95%, 1,3-15,4) y las artralgias (OR = 1,59; IC del 95%, 1,01-2,5) fueron mas frecuentes en la CU que en la EC. El eritema nodoso (OR = 2,35; IC del 95%, 1,13-5,0) y las artritis perifericas (OR = 1,95; IC del 95%, 1,02- 3,74) fueron mas frecuentes en la EC. La prevalencia de las manifestaciones oculares y del resto de manifestaciones articulares no difirio entre la CU y la EC. Conclusiones La prevalencia de las MEI en los pacientes con EII espanoles es una de las mas altas publicadas. La frecuencia del tipo de MEI es diferente entre los pacientes con EC y CU, un aspecto que es importante conocer para realizar un diagnostico adecuado de la EII y de sus complicaciones.

Background: Inflammatory bowel disease (IBD) is considered a heterogeneous, complex polygenic disease where both genetic and environmental factors are involved in the development of the disease. Interleukin-10 (IL-10) is a regulatory cytokine that might play an important role in disease pathogenesis. IL-10 contains single nucleotide polymorphisms and 2 polymorphic microsatellites in the 5′-flanking region. Our aim was to ascertain if any of these polymorphic markers is associated with IBD among Spanish patients. Methods: We genotyped 470 patients with IBD, 242 with ulcerative colitis and 228 with Crohn's disease (CD), and 572 ethnically matched controls for microsatellites IL-10R and IL-10G and 2 single nucleotide polymorphisms at positions -1082 and -819 in the proximal promoter of the gene. Results: IL-10G14 microsatellite allele as well as -1082G allele were significantly increased in patients with CD. The combined presence of both alleles in 1 individual notably increased the risk to develop CD (P = 0.00006, odds ratio = 3.18). Conclusion: IL-10 polymorphisms contribute to susceptibility to CD in Spanish population.

Magnetic resonance enterography in Crohn disease management has been rapidly growing in importance during recent years. Being familiar to this technique is essential for radiologists and also, to some extent, for gastroenterologists. Our aim is to study and describe the imaging findings in magnetic resonance enterography in Crohn disease to develop a comprehensive and useful review article and imaging atlas.

Fundamento El beneficio de la terapia antirretroviral de gran actividad (TARGA) puede verse limitado por la aparicion de hepatotoxicidad. La frecuencia de esta complicacion con las distintas combinaciones de farmacos y los factores que propician su aparicion no se conocen bien. Pacientes y metodo Estudio retrospectivo de todos los pacientes sin experiencia previa a los antirretrovirales que iniciaron TARGA entre enero de 1997 y enero de 2000 en un hospital de Madrid. La hepatotoxicidad se definio por una elevacion de la cifra de transaminasas. Resultados Se incluyo a un total de 91 pacientes. De ellos, 36 (40%) eran ex-adictos a drogas por via parenteral, 35 (38%) homosexuales y 20 (22%) heterosexuales. Un total de 43 (47%) estaban coinfectados por algun virus hepatotropo (42% virus de la hepatitis C [VHC], 8% virus de la hepatitis B [VHB]). El tratamiento consistio en dos nucleosidos mas un inhibidor de la proteasa (IP) en 48 sujetos o bien un no nucleosido en 50. Tres pacientes recibieron dos nucleosidos, un IP y un no nucleosido. Las caracteristicas basales de los pacientes eran similares en los diferentes grupos de tratamiento. En 30 individuos (31%) se produjo hepatotoxicidad. Aunque fue transitoria en el 80%, ocurrieron formas graves en 10 (11%). La hepatotoxicidad grave fue mas frecuente en las personas coinfectadas por VHC y/o VHB (riesgo relativo [RR], 10,36; intervalo de confianza [IC] del 95%, 1,38–77,56; p = 0,03). La ingestion elevada de alcohol tambien se asocio con una mayor frecuencia de hepatotoxicidad (RR, 3,35; IC del 95%, 2,43–4,62; p = 0,01). No se objetivaron diferencias en cuanto al tipo de medicacion antirretroviral. La hiperbilirrubinemia aislada (27%) se asocio al uso de indinavir (RR, 3,61; IC del 95%, 1,81–7,21; p Conclusiones Un tercio de los pacientes que inician TARGA desarrollan hepatotoxicidad, sin diferencias apreciables en frecuencia o gravedad al comparar las distintas combinaciones de antirretrovirales. La coinfeccion por VHB y/o VHC, asi como la ingestion elevada de alcohol representan los principales factores predictivos de hepatotoxicidad.

Fundamento La promocion y el fomento de la investigacion es actualmente una de las estrategias fundamentales sobre la que se asienta el desarrollo de nuestra sociedad moderna. Los parses estan invirtiendo grandes recursos destinados a este fin, y por ello se hace necesario un proceso serio y riguroso de evaluacion de la investigacion, asi como el analisis de los resultados obtenidos en los numerosos proyectos de investigacion subvencionados tanto en convocatorias publicas como privadas, para asegurar el buen fin de las inversiones realizadas. Material y metodo Se ha analizado una muestra de 431 proyectos pertenecientes a la convocatoria FIS de 1998. Las evaluaciones FIS y ANEP (Agencia Nacional de Evaluacion y Prospectiva) fueron analizadas y puntuadas (calidad de evaluacion) en sus principales contenidos por tres evaluadores independientes; asimismo, los resultados fueron sometidos a comparaciones intraagencia e interagencia Resultados En la evaluacion FIS intervinieron 20 comisiones, y el analisis intraFIS detecto que la calidad de la evaluacion era dependiente de la comision correspondiente responsable de la evaluacion (F = 3,71; p Conclusiones Los resultados obtenidos aconsejan una modificacion de la estructura evaluativa y de la composicion de las comisiones cientifico-tecnicas del FIS que tenga como finalidad una mejora del proceso de evaluacion de los proyectos de investigacion presentados en convocatoria publica al FIS.

Fundamento y objetivo: La enfermedad inflamatoria intestinal (EII) es una enfermedad poligenica compleja. Tanto la expresion de PAR1 y PAR2 como su presencia en biopsias de pacientes con EII apuntan a un posible papel de estos genes en la susceptibilidad genetica a presentar EII. Este es el primer estudio de asociacion genetica que se realiza con estos genes en la EII. Pacientes y metodo: Se analizaron mediante sondas TaqMan dos polimorfismos en el gen F2R/PAR1 y otro mas en el gen F2RL1/PAR2 en 778 controles sanos y 943 afectados de EII (pacientes con enfermedad de Crohn y colitis ulcerosa de Madrid y Granada). Resultados: No se encontraron diferencias significativas en la distribucion de alelos entre pacientes y controles. Conclusiones: No hay evidencia de asociacion de los polimorfismos analizados en F2R/PAR1 y F2RL1/PAR2 con modificaciones del riesgo de presentar EII.

Achalasia is a motor disorder of the esophagus resulting in functional obstruction. The cause of the lesion is unknown although genetic and immunologic factors have been suggested. An association with serological HLA epitopes has been previously reported. In this study, we have further examined this HLA class II association with susceptibility to achalasia by DNA based methods. Achalasia patients (n=40) and healthy controls (n=275), all Caucasians and unrelated, were included in the analysis. The strongest associations were with HLA-DQA1*0101 and two HLA-DQ alphabeta heterodimers having their alpha chain encoded by this allele. Moreover, relative risk was significantly higher in DQA1*0101 homozygotes as compared to heterozygotes and results suggested that DQB1*02 may have a protective role.

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;)

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.

2 páginas.-- Póster presentado al 5º European Workshop on Immune-Mediated Inflammatory Diseases celebrado en Sitges (Barcelona) dxel 1 al 3 de Diciembre de 2010.-- et al., The PTPN22 gene is an important risk factor for human autoimmunity. Two PTPN22 missense-SNPs, both with functional influence, the R620W (1858C>T, rs2476601) in exon 14 and the R263Q (788G>A, rs33996649) in exon 10 have been associated with autoimmune diseases [1-4].

The Faculty of Management, at the Rosario University (Colombia) has been developing since 2004 studies aimed at understanding the dynamics of different sectors of the Colombian economy, with the aim of identifying elements contribute to achieving the sustainability of enterprises. One of the methodologies implemented for this purpose, structural analysis is called strategic sectors, which to identify levels of market consolidation, structural analysis market forces and an assessment of competitors. The information obtained in tests, allows decision makers to take steps to achieve business improvement. On this occasion, an analysis of the sector passenger and freight transport. Unlike previous studies, the analysis seeks to place a focus on improvement track.

Background: The mechanisms responsible for the pathogenesis of peripheral arthropathies (PA) in Crohn's disease (CD) are largely unknown, although many studies indicate that genetic and environmental factors are likely to contribute to risk. Methods: Because variants in the Fc receptor-like 3 (FcRL3) gene have recently been associated with rheumatoid arthritis and several other autoimmune diseases, we tested 2 FcRL3 promoter variants (−169 C>T and −110 G>A) for association with PA in Spanish CD patients that were recruited from a single center and followed for at least 4 years (mean follow-up time, 11 years). Results: Among the 342 CD patients evaluated, there were 88 cases of peripheral arthropathy; 31 were classified as arthritis and 57 were classified as arthralgia. We used contingency tables and logistic regression to test for association between PA or either subtype and FcRL3 and other factors that have previously been associated with extraintestinal manifestations in CD. Conclusions: We found that female sex, colonic involvement, and the AA genotype at −110 G>A were associated with increased risk of both subtypes of PA, although the association appears to be stronger for arthritis than for arthralgia. (Inflamm Bowel Dis 2009)

Objective The STAT4 gene encodes a transcription factor involved in the signaling pathways of several cytokines, including interleukin-12 (IL-12), the type I interferons, and IL-23. Recently, the association of a STAT4 haplotype marked by rs7574865 with rheumatoid arthritis (RA) and systemic lupus erythematosus was reported. The aim of this study was to investigate the role of this STAT4 tagging polymorphism in other immune-mediated diseases. Methods The study group comprised 2,776 consecutively recruited Spanish individuals: 575 with RA, 440 with multiple sclerosis, 700 with inflammatory bowel disease, 311 with type 1 diabetes, and 723 ethnically matched healthy control subjects. The STAT4 polymorphism rs7574865 was genotyped using a predesigned TaqMan assay. Allele and genotype frequencies in patients and control subjects were compared by chi-square test. Results The association of STAT4 polymorphism rs7574865 with RA was validated in patients of Spanish origin (for T versus G, P = 1.2 × 10−6, odds ratio [OR] 1.59, 95% confidence interval [95% CI] 1.31–1.92), and the association was described for the first time in both clinical forms of inflammatory bowel disease, Crohn's disease and ulcerative colitis (for T versus G, P = 0.006, OR 1.29, 95% CI 1.07–1.55), and in type 1 diabetes mellitus (for T versus G, P = 0.008, OR 1.36, 95% CI 1.07–1.71). In contrast, the genotypic distribution of this polymorphism showed no difference between patients with multiple sclerosis and healthy control subjects (for T versus G, P = 0.83, OR 1.02, 95% CI 0.82–1.28). Conclusion The STAT4 gene is emerging as a novel common risk factor for diverse complex diseases.

Summary Background Pancreatitis is a potentially severe condition. Patients with inflammatory bowel disease (IBD) seem to be at increased risk for acute pancreatitis. Aim To describe the incidence, main causes and possible predictive factors of acute pancreatitis in inflammatory bowel disease. Methods Information was retrospectively extracted from the clinical records of patients followed in the IBD Units of nine hospitals in Madrid (n = 5073). Results A total of 82 acute pancreatitis episodes were diagnosed (cumulative incidence, 1.6%); 98% of them were mild. Recurrent acute pancreatitis developed in 13% of patients. Most cases of acute pancreatitis (63.4%) were attributed to drug exposure [azathioprine/mercaptopurine (AZA/MP) n = 46, mesalazine (mesalamine) n = 6]; 20.7% were idiopathic, and 12.2% were biliary. Incidence of acute pancreatitis in patients treated with AZA/MP was 3.1%. In patients with acute pancreatitis, female gender (OR 3.4 95% CI: 1.3–9.3; P = 0.012) and Crohn’s disease (CD) (OR 5.8 95% CI: 1.6–20.6; P = 0.007) were risk factors for AZA/MP-associated acute pancreatitis, the latter also when analysed only in patients treated with AZA/MP (n = 1477) (OR 5.2 95% CI: 1.8–14; P = 0.002). Conclusions The incidence of acute pancreatitis in our IBD patients (1.6%) is similar to that previously described. Drugs, mainly AZA/MP, are the leading cause. AZA-induced acute pancreatitis is always mild. Patients with CD are at a higher risk for AZA/MP-associated acute pancreatitis. The frequency of idiopathic acute pancreatitis is higher than expected, suggesting that part of these cases could be extraintestinal manifestations of IBD.

Background: Recent genomic surveys have identified IL23R and IL12B as susceptibility loci for inflammatory bowel disease (IBD). Our aim in the present study was to ascertain whether the IL23R and IL12B associations with IBD are also observed in our population, and to analyze possible genetic interactions between polymorphisms at IL12B and IL23R, ligand and receptor, respectively. Methods: In all, 707 IBD patients (344 with Crohn's disease and 363 with ulcerative colitis) and 547 healthy controls from the same ethnic origin (Caucasian Spaniards) were included in the present study. Two single nucleotide polymorphisms (SNPs) in IL23R (rs7517847 and rs11209026) and 2 in IL12B (rs3212227 and rs6887695) genes were analyzed by TaqMan technology. Genetic frequencies were compared with a chi-square test. Interaction between genes was analyzed by case-only comparisons. Results: The data show an association of both IL23R SNPs with overall IBD (statistically stronger, rs7517847; odds ratio [OR] = 0.79, 95% confidence interval [CI]: 0.67–0.94, minor allele frequencies: 0.355 in IBD patients versus 0.410 in controls; P = 0.005), somewhat stronger in Crohn's disease (OR = 0.74, 95% CI: 0.61–0.91) than in ulcerative colitis (OR = 0.84, 95% CI: 0.69–1.03). IL12B rs6887695 showed a weak association with IBD (OR = 1.24, 95% CI: 1.04–1.47, minor allele frequencies: 0.375 in IBD patients versus 0.326 in controls, P = 0.012), stronger in UC (OR = 1.31, 95% CI: 1.07–1.60, P = 0.007). No statistically significant differences were apparent when patients were stratified according to clinical characteristics. No interaction was observed between any of the polymorphisms studied at IL12B and IL23R. Conclusions: Our study confirms the association of IL23R and IL12B with IBD in the Spanish population, but no interaction between either loci could be detected. (Inflamm Bowel Dis 2008)

Introducción: el adalimumab ha demostrado, en ensayos clínicos controlados con placebo y en estudios no controlados, ser efectivo en la EC luminal y fistulosa perianal. Objetivo: evaluar la eficacia y seguridad del adalimumab como tratamiento de inducción y mantenimiento en la EC. Metodología: se incluyeron 22 pacientes con EC tratados con adalimumab (16 por enfermedad luminal y 6 por enfermedad fistulosa perianal activa). Veintiún pacientes habían recibido previamente IFX. Se realizó tratamiento de inducción con 160 mg s.c. en la semana 0 y 80 mg s.c. a las 2 semanas. Los respondedores recibieron 40 mg s.c. cada 14 días como tratamiento de mantenimiento. Se valoró la respuesta a las 4 semanas de la dosis inicial, y se clasificó la respuesta como remisión, respuesta parcial o ausencia de respuesta. Resultados: tras la inducción, el 25% de los pacientes con enfermedad luminal tuvieron remisión completa y el 56,3% respuesta parcial. La respuesta clínica se mantuvo al año en el 71,6% de los pacientes, a los 18 meses en el 53,7% y a los 48 meses en el 35,8%. No se objetivaron diferencias en la respuesta entre pacientes que presentaron reacciones de hipersensibilidad o pérdida de respuesta a IFX. Todos los pacientes con enfermedad fistulosa perianal (n = 6) habían recibido previamente tratamiento con IFX. Tras la inducción un 16,7% entran en remisión y un 66,7% presentan respuesta parcial. Todos los pacientes mantienen remisión o respuesta en el tiempo con una mediana de seguimiento de 15 meses. Conclusiones: el adalimumab es un tratamiento eficaz y seguro en la inducción y mantenimiento de la respuesta en la EC luminal y fistulosa perianal. Estos resultados confirman que los hallazgos obtenidos en los ensayos clínicos controlados son reproducibles en la práctica clínica diaria.

OBJECTIVES: Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon. Major histocompatibility complex (MHC) on the short arm of human chromosome 6 has been thoroughly studied as a susceptibility locus. However, one of the strongest MHC associations found, that of HLA-DR3 with UC protection, has not been observed in all populations. Our aim in the present study was to evaluate this negative association in a large cohort of Spanish UC patients and controls, and to try to elucidate which, if any, of the diverse DR3 haplotypes (identified by TNFa and b microsatellites, located in the MHC class III region) is most tightly associated (negatively) with the disease. METHODS: A total of 537 UC patients and 748 healthy controls from Spain were included in the present study. Low-resolution DR genotyping was performed by PCR and hybridization with allele-specific oligonucleotide probes. TNFa and b microsatellites were studied in a subset of samples (279 UC patients and 503 healthy controls) by PCR followed by capillary electrophoresis. DR-TNFa-TNFb haplotypes were estimated by the expectation-maximization algorithm and comparisons were performed by a Χ 2 test. RESULTS: After a stepwise procedure, the only DR alleles significantly associated with the disease were DR3 (very strongly, protection) and DR4 (weakly, protection). The strong protective effect of DR3 was evenly distributed among the haplotypes DR3-TNFa1b5, DR3-TNFa2b3, and DR3-TNFother. CONCLUSIONS: Our results confirm the strong protective effect of DR3 in our population, and suggest that the relevant protective gene is located centromeric to TNFa and TNFb markers in the MHC region.

Objectives: Expression of major histocompatibility complex (MHC) class II genes is almost exclusively regulated by the class II transactivator. A promoter polymorphism (−168A/G, rs3087456) in the MHC2TA gene was associated with increased susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction in a northern European population. However, no evidence of association of this MHC2TA variant with the two autoimmune diseases could be subsequently detected in independent cohorts. Aim: To test the aforementioned single nucleotide polymorphism and another G→C change (nt1614 from coding sequence, rs4774) to analyse the haplotype pattern in this MHC2TA gene. Methods: A case–control study was performed with 350 patients with rheumatoid arthritis, 396 patients with multiple sclerosis, 663 patients with inflammatory bowel disease (IBD) and 519 healthy controls from Madrid. Genotyping was ascertained by using TaqMan assays-on-demand on a 7900HT analyser, following the manufacturer’s suggestions (Applied Biosystems, Foster City, California, USA). Haplotypes were inferred with the expectation–maximisation algorithm implemented by the Arlequin software. Results: No independent association with these autoimmune diseases was found for either polymorphism in the Spanish cohorts tested. However, when haplotypes were compared between patients with rheumatoid arthritis and controls, a significant difference in their overall frequency distribution was observed, evidencing a protective haplotype (−168A/1614C, p = 0.006; odds ratio (OR) 0.7) and a risk haplotype (−168G/1614C, p = 0.019; OR 1.6). Patients with multiple sclerosis mirrored these results, but no effect on IBD was identified. Conclusions: The MHC2TA gene influences predisposition to rheumatoid arthritis and multiple sclerosis, but not to IBD. The −168G allele is not an aetiological variant in itself, but a genetic marker of susceptibility/protection haplotypes.

BACKGROUND AND OBJECTIVES Interleukin-10 (IL-10) has a key role in regulating mucosal inflammation in inflammatory bowel disease. In our population of Spanish ulcerative colitis (UC) patients, we have previously demonstrated that two polymorphisms (IL-10.G14 microsatellite allele and homozygous for the -1082G allele (guanine at position -1082)) in the IL-10 gene were susceptibility markers for disease. No data exist regarding the relationship of these IL-10 polymorphisms with phenotypic subpopulations in UC. Therefore, this study sought to examine the contribution of IL-10 polymorphisms to phenotypical variability in UC. MATERIAL AND METHODS A cohort of 215 Spanish unrelated patients with UC recruited in a single center was studied. All patients were rigorously phenotyped and followed for at least 3 years (mean time: 11.8 years). The clinical phenotype was established before genotyping. Genotyping was performed using polymerase chain reaction (PCR) assays. RESULTS Patients with UC included 129 (60%) men and 89 (40%) women. Mean age at diagnosis was 38 years, with a range of 8-83. Disease extent included 127 (59.1%) left-side patients and 88 (40.9%) extensive patients. Neither UC phenotype variable was associated with the presence of susceptibility polymorphisms (10G14 microsatellite and -1082G allele). CONCLUSIONS In Madrid's Spanish population of UC patients, the carrying of the ILG14 microsatellite or -1082G polymorphism in the IL-10 gene was not associated with phenotype of disease.

Background: The multidrug resistance MDR1 gene codes for a membrane transporter associated with inflammatory bowel disease. The polymorphism Ala893Ser/Thr (G2677T/A) previously showed significant association with Crohn's disease (CD) and the Ile1145Ile (C3435T) with ulcerative colitis (UC). We studied the association of both polymorphisms in an independent population to reveal the impact of the MDR1 gene on predisposition to inflammatory bowel disease. Methods: Case-control study with 321 CD and 330 UC white Spanish patients recruited from the same center, and 352 healthy ethnically matched controls. Results: A significant association of MDR1 C3435T with CD was observed (CC vs (CT + TT): P = 0.007; OR [95% CI] = 1.58 [1.12-2.23]). A CD susceptibility haplotype 2677T/C3435 was identified. No difference between UC patients as a whole and controls could be detected. Conclusions: New evidence supports the role of the MDR1 gene on CD susceptibility. Therefore, considering our results and those from others, the MDR1 gene behaves as a common risk factor for both CD and UC. We discovered that the C3435 allele conferring susceptibility to CD is different from the described 3435T UC risk allele.

Ulcerative colitis is often accompanied by the development of extraintestinal, mainly articular, manifestations. Genetic differences could be underlying that clinical heterogeneity. We performed a case-control study to determine whether TNFab microsatellites or HLA-DR alleles were associated with the development of articular manifestations in patients with ulcerative colitis. With that aim, a total of 84 ulcerative colitis patients with articular manifestations and 172 without them were genotyped for TNFab microsatellites and HLA-DR. A healthy control sample (n = 595) was also included for comparative purposes. Haplotypes were inferred with the Arlequin software. The influence of HLA-DRB1*0103 and HLA-B27, factors previously known to be associated with extraintestinal manifestations, was specifically addressed. We observed that TNFa6b5 minihaplotype increases the susceptibility to developing articular manifestations in ulcerative colitis patients (p = 0.003, OR = 2.39). The locus HLA-DR does not appear to be involved in these extraintestinal manifestations by itself; however, the frequency of subjects carrying TNFa6b5 in combination with DR1, DR7, or DR11 is very significantly increased in patients with articular manifestations (p = 3.9 x 10(-8)). The associations found were independent of DRB1*0103 and HLA-B27. Thus, it seems that the development of articular manifestations in ulcerative colitis patients appears to be influenced by some genetic factor(s) present in some major histocompatibility complex haplotypes.

Treatment of perianal fistulas in Crohn's disease should be defined on an individual basis. A combined medical and surgical approach is the optimal treatment. Adequate management of perianal fistula disease is based on the presence or absence of active proctitis, anatomic location, and fistula type. Furthermore, the presence of perianal abscesses must be ruled out. This evaluation includes digital rectal examination, endoscopy, and examination under anesthesia combined with pelvic magnetic resonance imaging or anorectal endoscopy ultrasonography findings.

interest that goes to the emergency department coming from the dentist s consultation. During the endodontic treatment she has ingested accidentally one of the metallic instruments (dental screwdriver) with which the intervention was being made. She refers sharp body sensation at epigastrium. Abdominal radiograph is made in which is appraised in the gastric camera a metallic object of great size with a sharp edge (Fig. 1). Before the perforation risk, emergent endoscopic removal is made without complications in spite of the size of this object (Fig. 2). The ingestion of foreign bodies supposes a frequent consultation in the emergency department and it is the second cause of accomplishment of emergency upper flexible (1). The most frequent location is in the esophagus and although until 90% of the foreign bodies they are eliminated spontaneously recommends its precocious endoscopic removal once identified to avoid complications (perforation, hemorrhage, aspiration, pneumomediastinum, mediastinitis). When the foreign bodies are in the stomach is possible to be had an expectant attitude except the characteristics of the object are susceptible to cause complications, as it is our case when being a metallic instrument with a sharp edge that can produce a perforation in its progression by digestive tract (2). The flexible fibroendoscopy has demonstrated to be a safe and effective technique for the removal of foreign bodies, reason why it is exceptional to resort to the use of rigid endoscopy or surgery (3,4).

Objective: to describe our experience with granulocyte apheresis to induce remission in patients with active Crohn's disease refractory to conventional treatment. We summarize the results previously obtained with this technique. Conclusions: granulocyte apheresis is a safe and well tolerated therapeutic modality that can be a valid therapeutic alternative in the induction of remission in inflammatory bowel disease, although controlled clinical trials must be conducted to define long-term efficacy, as well as to establish “optimal patient” selection, re-treatment interval, and number of sessions.

Background: Crohn's disease is a heterogeneous disease from both genetic and clinical points of view. Aims: To look for associations between distinct genetic polymorphisms and clinical subgroups of the disease. Subjects: A total of 210 patients and 343 healthy control subjects, all adult, unrelated, white, Spanish individuals. Methods: DNA was purified from peripheral blood samples and was typed by sequence-specific oligonucleotide polymerase chain reaction (PCR) method for human leukocyte antigen (HLA)-DRB1 alleles (IBD3) and by allele-specific PCR for NOD2/CARD15 (IBD1) polymorphisms. Results: NOD2/CARD15 mutations and HLA-DRB1*07 confer susceptibility only to the ileal location of the disease, whereas HLA-DRB1*0103 is associated only with the colonic location of the disease. The IBD3 effect was overshadowed by IBD1 mutations when present. Conclusion: The studied genetic polymorphisms of Crohn's disease basically determine the location of the disease and, only secondarily, the clinical form of the disease. This appears to be true for both inflammatory bowel diseases as HLA-DRB1*0103 is associated both with colonic Crohn's disease and ulcerative colitis.

La enfermedad inflamatoria intestinal (EII) es un procesocronico que puede afectar al colon (colitis ulcerosa) o a cual -quier parte del aparato gastrointestinal (enfermedad de Crohn)y no tiene un tratamiento curativo en la actualidad. En su evo -lucion natural se intercalan episodios de reactivacion sintoma -ticos con periodos de inactividad. Su curso cronico recidivan -te se debe a la perdida de la tolerancia, funcionamientoanomalo o a una curacion defectuosa en la barrera mucosa.Los diferentes tratamientos intentan: obtener la remision clini -ca en el brote agudo, mantenerla posteriormente el maximotiempo posible con los menores efectos secundarios, conser -var un estado nutricional adecuado y mejorar la calidad devida de los pacientes.El mejor conocimiento de los mecanismos por los que seproduce la inflamacion y los efectos secundarios asociados aluso continuado de los corticoides, que ademas no son utiles enel mantenimiento de la remision, han llevado a la busqueda denuevos tratamientos para aplicarlos a grupos de pacientes con -cretos. En el tratamiento farmacologico sintetico de la EII lasaportaciones mas importantes son: modificaciones quimicasque aumentan la efectividad disminuyendo los efectos secun -darios (la evolucion desde la hidrocortisona a la budesonida ydesde la sulfazalacina a los diferentes 5-aminosalicilatos) y lamejora en los parametros farmacocineticos (como ocurre conla azatioprina y la 6-mercaptopurina). Mediante la determina -cion de la actividad de la tiopurinmetiltransferasa (TPMT)podemos mejorar la efectividad y disminuir los efectos secun -darios de la azatioprina y de la 6-mercaptopurina. A pesar deestos avances, una de las principales razones para continuarcon el desarrollo de nuevos tratamientos es que los actualesnecesitan semanas para ser efectivos y cuando lo consiguen,lo son solo parcialmente. La mayoria de las veces, sobre todoen la enfermedad de Crohn (EC), no hay remision histopatolo -gica y en general no se previene la cirugia a largo plazo ni ladegeneracion maligna. Todos estos factores, junto con la importancia de losmecanismos inmunologicos que regulan la inflamacion, hanhecho que se desarrollen agentes biologicos en el tratamien-to. Estos nuevos farmacos tratan de forma simultanea dedisminuir los niveles de antigenos bacterianos intralumina-les y/o bloquear de forma selectiva la respuesta inmunedanina en la mucosa, como los anticuerpos monoclonalesanti-TNF o los nuevos tratamientos que inhiben la respuestaTh1. El uso de estos tratamientos biologicos es mas costosoy, al igual que los tratamientos tradicionales, tampoco soncurativos. Sus complicaciones a largo plazo aun estan porver y no solo se trata de inducir la remision sino de mante-nerla. Ademas, en general, han sido mas eficaces en la EC,concretamente en la forma fistulizante, descrita por primeravez en 1932 por Crohn y cols., que es la que tiene unamayor morbilidad.Por tanto, debido a que los avances mas importantes en eltratamiento farmacologico de la EII han sido en la EC fistu-lizante, aunque todos ellos son aplicables en alguna medidao momento a las restantes formas complicadas de la enfer-medad, como son la corticodependencia o la corticoresisten-cia, es en la primera de estas complicaciones donde nos cen-traremos, para ver si realmente se ha optimizado eltratamiento con los farmacos “tradicionales” antes deemplear los nuevos.

Acute pancreatitis due to ascaris lumbricoides infestation is extraordinarily uncommon in Europe. The diagnosis can be difficult because of the low index of suspicion in our area, and this may lead to death. The case of a Columbian patient living in Spain who developed an acute pancreatitis is discussed. He had no history of alcohol abuse, gallstones, or drug abuse. The sonography showed a longitudinal structure with inner parallel linear bands and undulant movements inside the gallbladder and a hypoechogenic pancreas. These features are compatible with acute pancreatitis secondary to Ascaris lumbricoides infestation. The patient was treated with mebendazole and his evolution was excellent. Sonography was useful as an assessment modality during follow-up. We conclude that Ascaris lumbricoides should be recalled as a rare cause of acute pancreatitis in Western countries. Sonography allows early diagnosis and prompt treatment.