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Introduction: The impact of consensus, prescription choices and efficacy trends on clinical practice over time has not been studied in depth.Aims & Methods: International multicenter prospective non-intervention-al registry aimed to evaluate the decisions and outcomes of H. pyloriman-agement by European gastroenterologists. All infected adult patients were systematically registered at AEG-REDCap e-CRF from 2013 to December 2021. Variables included: previous eradication attempts, prescribed treatment, adverse events, and outcomes. Modified intention- to-treat (mITT) and time trend analyses were performed. Data were subject to quality review.Results: So far 49, 739 patients from 29 European countries have been in-cluded, and 35, 203 (71%) were first-line empirical prescriptions. Overall, the most common prescribed treatments in the 2013-21 period were triple therapies ; however, a shift in antibiotic regimens was identi-fied. Triple therapies decreased from over 50% of prescription in 2013/15 to less than 25% in 2020/21 ; likewise, non-bismuth concomitant therapy use decreased from 21% in 2013/14 to 13% in 2020/21, while three-in-one single- capsuleincreased from 0- 1% in 2014/2015 to 17% in 2020/21. An increase in the average duration of treatments from 9.8 days in 2013 to 13 days in 2021 was identified, as well as the daily high- dose of PPIs increasing from 16% in 2013 to 50% in 2021. Detailed description of most common treatments is shown in Table 1. Re-garding the effectiveness of each specific treatment, no trend was identi-fied (data now shown) ; however, there was a 10% overall improvement in first-line mITT overall effectiveness from 2013 to 2021. Conclusion: European gastroenterological practice is constantly adapting to the newest published evidence and recommendations (reducing the use of triple therapies and increasing both the duration of treatment and the dose of PPIs), with a subsequent progressive improvement in overall effectiveness.

Introduction: Introduction: Randomized clinical trials and meta-analyses, primarily from Asian countries, have reported good effectiveness with high-dose dual therapy (HDDT, i.e., PPIs plus high amoxicillin doses) when prescribed for H. pylorifirst-line or rescue treatment. However, combining amoxicillin with PPIs in the 1990s in several European countries yielded suboptimal results. The objective was to analyse the effectiveness, com-pliance and safety of HDDTin the European real clinical practice.Aims & Methods: Methods: International, multicenter, prospective non- interventional Registry aimed at evaluating the decisions and outcomes of H. pylori management by European gastroenterologists. All infected adult cases treated with HDDT were registered at AEG- REDCap e-CRF up to June 2021. Patients receiving HDDT (amoxicillin 1, 000 mg three times a day plus a PPI), with or without bismuth, in any treatment line and for at least 10 days, were selected for inclusion.Results: Sixty patients received HDDT (98% compliance), 19 of them as first-line and 41 as rescue treatment (2nd–6th line). Overall HDDT effec- tiveness was 52% (per-protocol) and 51% (modified intention-to- treat, mITT). First-line and rescue treatment lines were similarly effective. Cure rates were lower when patients had previously received metronidazole (mITT 32% vs. 70%, p

Resumen El tratamiento con farmacos anti-TNFα ha demostrado ser eficaz en las enfermedades inmunomediadas. Los primeros casos de linfoma diagnosticados tras la comercializacion de los anti-TNFα centraron el foco de atencion sobre el papel de estos farmacos en el riesgo de desarrollo de tumores. En los pacientes con enfermedad inflamatoria intestinal y otras enfermedades inmunomediadas, principalmente la artritis reumatoide, los farmacos anti-TNFα no parecen aumentar el riesgo de desarrollar neoplasias. Unicamente se observan resultados contradictorios en el caso del riesgo de linfoma y del cancer de piel. No obstante, en caso de que el tratamiento con farmacos anti-TNFα incrementara el riesgo de desarrollo de estas neoplasias, la magnitud del efecto y el numero absoluto de casos seria muy bajo, por lo que el beneficio de estos tratamientos supera claramente los potenciales riesgos. Finalmente, aun disponemos de pocos datos sobre el efecto de los anti-TNFα en los pacientes con antecedentes de neoplasia, pero la evidencia actual sugiere que no existe un mayor riesgo de recidiva tumoral en los pacientes expuestos a estos farmacos. No obstante, debido a que la informacion a este respecto es muy limitada, seria prudente evaluar cada caso de forma individualizada, teniendo en cuenta la historia oncologica y las alternativas disponibles para el control de la enfermedad inflamatoria intestinal.

Resumen Las manifestaciones extraintestinales en general y, de entre ellas, las articulares en particular, suponen un problema frecuente en los pacientes con enfermedad inflamatoria intestinal. De hecho, la relacion entre ambas entidades parece estrecha y cada vez hay mas datos que indican que el intestino desempena un importante papel en la patogenia de las espondiloartritis. La asociacion de la enfermedad inflamatoria intestinal con algun tipo de espondiloartritis supone un escenario clinico complejo. Se hace necesario, por tanto, que gastroenterologos y reumatologos puedan trabajar juntos y establecer una comunicacion fluida que permita a cada paciente recibir el tratamiento mas adecuado para cada situacion concreta. El objetivo de esta revision es el de establecer unas recomendaciones sobre el tratamiento de los pacientes con enfermedad inflamatoria intestinal y espondiloartritis asociada, en cada uno de los distintos escenarios clinicos.

Background Anti-TNF and thiopurines are the only drugs that demonstrated efficacy in preventing postoperative recurrence (POR) in Crohn’s disease (CD). However, in some cases, these drugs are contraindicated or have previously failed. Vedolizumab was licensed for CD some years ago but scarce data on its efficacy for the prevention of POR is available. Methods All CD patients in whom vedolizumab was prescribed for primary prevention of POR within the first 3 months after ileocecal or ileocolonic resection with anastomosis were identified from the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD, GETECCU). We evaluated the rates of Endoscopic, clinical or surgical POR in the first 18 months. Endoscopic POR was defined by a Rutgeerts score >i1 and advanced endoscopic POR by >i2. Results Twenty-three patients were included; vedolizumab was started after a median time of 23 days (IIQ21-73). Concomitant immunosuppressants were used in 17%; 18% received an additional 3-month course of metronidazole after surgery. Regarding risk factors for POR: 13% were active smokers, 62% had prior resections, 33% had penetrating CD behaviour, and 22% had a history of perianal disease. Thirty-four per cent had been exposed to vedolizumab prior to the index surgery (26% within the last 6 months). The median time of follow-up on ustekinumab was 26 months (IQR 11–31). Eighty-three per cent of patients had at least one endoscopic assessment within 18 months after surgery: 40 % had endoscopic POR and 15% advanced endoscopic POR. Additionally, 22% presented clinical POR at the discretion of the treating physician and 9% developed surgical POR. Conclusion In a small clinical practice cohort, vedolizumab showed similar efficacy as that reported with anti-TNF in the prevention of endoscopic POR.

Background Intestinal dendritic cells (DCs) and macrophages govern the mechanisms of immune homeostasis having a role in inflammatory bowel disease (IBD) onset. However, the profile of their circulating precursors (DC and monocytes) in IBD has not been previously described in depth. Our aim was to characterise blood DC and monocyte subsets in healthy controls (HCs) and IBD patients in order to understand their potential implication in IBD pathogenesis. Methods 18 HC and 64 IBD patients were recruited. IBD patients were categorised into Crohn’s disease (CD) and ulcerative colitis (UC), either endoscopically active (aCD and aUC) or quiescent (qCD and qUC), based on the SES-CD or the Mayo index endoscopic subscore. Blood circulating type 1 conventional DC (cDC1), type 2 conventional DC (cDC2), plasmacytoid DC (pDC), classical monocytes, non-classical monocytes and intermediate monocytes were identified by flow cytometry and characterised for the expression of 18 homing and activation markers (β7, CCR1, CCR2, CCR3, CCR5, CCR6, CCR7, CCR9, CCRL1, CD40, CD86, CD137L, CD274 (PD-L1), CLA, CXCR1, CXCR3, ICOSL and HLA-DR). Association between markers and the presence, type or activity of IBD was tested by logistic regression. Discriminant canonical analysis was also performed to classify the patients on their own endoscopy category. Results All groups (HC, aCD, qCD, aUC and qUC) were separated from the others based on the discriminant canonical analyses of the 18 markers applied over all DC and monocytes subsets (Figure 1). Specifically, CCRL1, CCR3 and CCR5 expression on cDC1, CCRL1 on non-classical monocytes and CCR9 and b7 on classical monocytes were highly associated to IBD. CCR3 displayed an odds ratio (OR) of 2.29 along with its 95% confidential interval (CI) between 1.11 and 4.75, showing a strong association with activity in CD; whereas the other markers displayed an inverse association with IBD. Hence, expression of CCRL1 on cDC1 and non-classical monocytes from aUC showed an OR (95% CI) of 0.23 (0.08–0.66) and 0.52 (0.28–0.95), respectively. In the case of qUC, CCR5 on cDC1 and β7 on classical monocytes displayed an OR (95% CI) of 0.10 (0.01–0.83) and 0.56 (0.34–0.90), respectively. CCR9 was inversely associated to qCD with an OR (95% CI) of 0.64 (0.46–0.89) in the classical monocytes subset. Indeed, the same markers (excluding β7) were also associated with IBD when all DC and monocyte subsets were considered at the same time. Conclusion Differences on the expression of migration markers CCR3, CCR5, CCR9, b7 and decoy receptor CCRL1 on circulating DC and monocyte subsets from IBD groups suggest the presence of constitutive migratory differences underlying IBD pathogenesis in CD or UC and its condition (inflamed or non-inflamed).

Resumen Introduccion Los corticoides se consideran el tratamiento de eleccion para inducir la remision en pacientes con enfermedad de Crohn activa. Sin embargo, un numero significativo de pacientes presenta una respuesta inadecuada o efectos adversos a estos farmacos. Manejo terapeutico En esta situacion clinica, los inmunosupresores, tiopurinas y metotrexato, y los farmacos biologicos, fundamentalmente anti-TNF, pueden mantener la remision clinica libre de corticoides a largo plazo. Pronostico Ademas, el empleo precoz y combinado de estos farmacos se ha asociado a un mejor pronostico de la enfermedad, con menores tasas de recidivas, ingresos hospitalarios e intervenciones quirurgicas.

Basal metabolic rate (BMR) is an intensively topic studied in ecophysiology for the purpose of understanding energy budgets of the species, variations of energy expenditure during their diary activities and physiological acclimatization to the environment. Establishing how the metabolism is assembled to the environment can provide valuable data to improve conservation strategies of endangered species. In this sense, metabolic differences associated to habitats have been widely reported in the interspecific level, however little is known about the intraspecific view of BMR under an environmental gradient. In this study, we researched the effect of the habitat on metabolic rate of an Iberian endemic species: Iberomys cabrerae. Animals were captured in different subpopulations of its altitudinal range and their MR was studied over a thermal gradient. MR was analyzed through a Linear Mixed Model (LMM) in which, in addition to thermal effects, the bioclimatic zone and sex also influenced the metabolism of the species. The beginning of thermoneutrality zone was set on 26.5°C and RMR was 2.3ml O2g(-1)h(-1), intermediate between both bioclimatic zones. Supramediterranean subpopulations started the Tlc earlier (24.9°C) and had higher RMR than the mesomediterranean ones (26.9°C). The thermal environment together with primary productivity conditions could explain this difference in the metabolic behaviour of the Cabrera voles.

Resumen El uso de anticuerpos contra el factor de necrosis tumoral alfa (anti-TNF) aumenta el riesgo de tuberculosis (TB) en pacientes con enfermedad inflamatoria intestinal (EII). GETECCU publico las primeras guias de cribado de TB para pacientes con EII en 2003 y las reviso en 2006. Sin embargo, la implementacion en la practica clinica de nuevas pruebas diagnosticas como los test de liberacion de interferon gamma, el mayor conocimiento epidemiologico y clinico de la TB en el contexto de tratamiento anti-TNF y la evidencia de que las recomendaciones de cribado de infeccion tuberculosa latente en pacientes candidatos a terapia anti-TNF disminuye pero no erradica los casos de TB han motivado la revision de las recomendaciones de GETECCU al respecto.

Abstract Little is known about the breeding characteristics of the Lusitanian pine vole, Microtus lusitanicus, a Terricola representative from south-western Europe. The scarce information on this subject is surprising since, as with other arvicolines, in high population densities these animals can be agricultural pests. In this study we report on the reproduction of the species in a locality of El Bierzo (province of León, northwestern Spain), a zone where this vole frequently damages orchards, crops, and vegetable gardens. The sample analysed consisted of approximately 300 specimens, captured by farmers over several years, which were donated to us for study. Results revealed that reproduction in this population probably occurs all year round, although sexual activity could be slightly lower in winter. In males and females monthly mean of adult body mass did not vary significantly during the year. Sexual monomorphism in adult body size, the relatively small testes of mature males, and the balanced sex ratio observed both in non-mature and mature specimens suggest that in this population M. lusitanicus has a monogamous mating system. In general, mean litter size increased with body mass (age) and showed a seasonal variation, with significantly higher values in spring than in autumn. In comparison with other Microtus species, the mean litter size found in M. lusitanicus was low, indicative of a K-selection pattern.

Resumen Objetivo Valorar la influencia de la erradicacion de Helicobacter pylori sobre las concentraciones basales de gastrina y pepsinogeno I y II en pacientes con ulcera gastrica, realizando un seguimiento de un ano, asi como estudiar la utilidad de estas determinaciones para confirmar la erradicacion de H. pylori tras el tratamiento. Metodos Se estudiaron prospectivamente 56 ulcerosos gastricos con infeccion por H. pylori . Al inicio se realizo endoscopia con biopsias para estudio histologico y test de ureasa, prueba del aliento con 13C-urea y extraccion de sangre para la determinacion de gastrina y pepsinogeno I y II (mediante radioinmunoanalisis) y serologia. La histologia, la prueba del aliento y las determinaciones analiticas se repitieron transcurridos 1, 6 y 12 meses de la finalizacion del tratamiento erradicador. Resultados La erradicacion se obtuvo en el 82,1% de los casos. En aquellos pacientes en los que se erradico H. pylori , el valor medio de gastrina al inicio fue de 75,5 ± 39,1 pg/ml, mientras que al mes de la finalizacion del tratamiento descendio hasta 49,2 ± 21 pg/ml (p Conclusiones a) la erradicacion de H. pylori se asocia con un descenso precoz en las concentraciones basales de gastrina y un descenso progresivo en las concentraciones basales de pepsinogeno I y II; b) en los pacientes con ulcera gastrica la comprobacion del descenso en las concentraciones basales de pepsinogeno II es un metodo util, precoz e indirecto para la confirmacion de la erradicacion, y c) los valores de gastrina y pepsinogeno I y II podrian ser utiles en la estimacion de la mejoria de la gastritis a los 6 meses de finalizar el tratamiento.

Objetivo . Estudiar en enfermos con ulcera gastrica la eficacia de cuatro metodos diagnosticos de la infeccion por Helicobacter pylori de amplio uso en la actualidad, utilizando para ello un «patron oro» que combina varias tecnicas diagnosticas. Material y metodos . Se estudiaron prospectivamente 73 ulcerosos gastricos consecutivos. En todos los pacientes se obtuvieron tres biopsias del antro y tres del cuerpo (dos para tincion de hematoxilina-eosina y una para la prueba rapida de la ureasa —Jatrox H.p. Test—). Asimismo se realizo una serologia ELISA IgG (Helico G) y una prueba del aliento con urea-C13. Segun el patron oro, un paciente estaba infectado cuando dos o mas tecnicas eran positivas; se considero ausencia de infeccion la negatividad de al menos tres de los metodos diagnosticos utilizados. Resultados . La prevalencia de la infeccion por H. pylori en los pacientes con ulcera gastrica tomando como referencia el patron oro fue del 87,6% (IC 95%: 78%-93%). La sensibilidad y especificidad de los metodos diagnosticos fueron las siguientes: histologia (antro), 96,8% (89%-99%) y 100% (66%-100%), respectivamente; histologia (cuerpo), 98,4% (91%-100%) y 100% (66%-100%); prueba de la ureasa (antro), 71,8% (60%-81%) y 100% (66%-100%); prueba de la ureasa (cuerpo), 96,8% (89%-99%) y 100% (66%-100%); prueba del aliento, 100% (94%-100%) y 100% (66%-100%), y serologia, 95,3% (87%-98%) y 100% (66%-100%). La sensibilidad de la prueba de la ureasa fue mayor en el cuerpo gastrico (McNemar: 15; p Conclusiones . Los metodos diagnosticos evaluados (histologia, prueba rapida de la ureasa, prueba del aliento con urea-C13 y serologia) tienen una elevada eficacia para el diagnostico de la infeccion por H. pylori en los pacientes con ulcera gastrica, con la excepcion de la prueba rapida de la ureasa realizada en muestras del antro, donde esta tecnica es menos sensible para la deteccion de la bacteria.

The urea breath test is a noninvasive and very accurate test for the diagnosis of Helicobacter pylori infection. However, false negative urea breath test results have been reported to occur in a considerable percentage of the individuals taking proton pump inhibitors; the interval needed to be completely confident that false negative tests had been excluded has varied among the different studies between 6 and 14 days. The impact of H(2)-receptor antagonists on the accuracy of urea breath test remains controversial, although, in contrast with proton pump inhibitors, the data suggest that H(2)-receptor antagonists, for the most part, have little effect on the result of the urea breath test. The urea breath test does not represent a suitable tool for estimating the density of H. pylori colonization. The only quantitative information to be obtained from the urea breath test is that the higher the delta value, the lower the probability of a false-positive urea breath test result. Although some authors have demonstrated a correlation between urea breath test values and histological lesions of the gastric mucosa, the practical utility of this relationship remains unclear. It has been suggested that the pretreatment urea breath test has the potential to identify patients who require modification of the standard therapeutic regimen (for example, prolonging the duration of treatment or increasing the pharmacological dose when bacterial density is high), but other studies could not confirm this relationship. Some studies have shown that the urea breath test is less accurate in patients who have undergone partial gastrectomy. Finally, in contrast with biopsy-based methods, which are responsible for a high number of false-negative results when used to diagnose H. pylori infection in patients with upper gastrointestinal bleeding, urea breath test seems not to be negatively influenced by the presence of this complication.

set enrichment analysis (GSEA) and informatics database consultation (PubMed). Results: Macroscopically healthy intestinal tissue of patients with early PSR showed 16 up-regulated (DNAH3, GOLGA1, etc.) and 6 down-regulated genes (MAML2, CABYR, etc.) as compared to patients without PSR. These differently expressed genes are related to ciliar motility, extracellular matrix activity and, particularly, to the Notch pathway. This biological activity was also found in the profile obtained from inflamed ileal tissue (like SAMD4 and NFIC), but was not outstanding probably because the high inflammatory background. Conclusions: Transcriptomic exploration of macroscopically healthy ileal tissue identified the ciliar motility/Notch pathway axis as a mechanism possibly related to early PSR in CD. Alterations of this biological activity have been recently shown in the development of spontaneous colitis of murine models [Obata, et al, J Immunol, 2012].

these experiments have been conducted with drug induced models, such as 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Considering that drug induced models are artificial and affect large bowel rather than small intestine, it is not suitable for studies on CD. A senescence-accelerated mouse (SAM) P1/Yit is a strain that develop spontaneous ileitis with 100% penetrance until 30 weeks of age, while losing its senescence accelerated phenotype. In this study, we investigated that whether exposure to SJ eggs prevent spontaneous ileitis. Methods: Specific pathogen-free SAMP1/Yit mice were donated by the Yakult Central Institute for Microbiological Research (Tokyo, Japan). AKR/NSLc mice were used as control mice. SJ eggs were collected from the liver of Schistosome-infected mice. The eggs were washed in phosphate buffered saline (PBS). Mice were injected with freeze-killed 5,000 eggs intraperitoneally once a week from 12 to 29 weeks of age. Control mice received PBS with the same volume. The effects of SJ eggs were quantified as follows: 1) body weight loss, 2) histological score of microscopic inflammation of ileum, 3) cytokines profiles of T-lymphocytes which are isolated from mesenteric lymph nodes (MLN). Statistical analyses were performed using Student’s t test. P< 0.05 was considered to be statistically significant. Results: 1) SAMP1/Yit mice treatment with SJ eggs showed tendency to gain weight. 2) Histological score of ileitis was not modulated. 3) In the treatment group, the concentration of Interleukin (IL) 4 was increased significantly, however interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha were not decreased and IL-10 was not increased compared to the control group. Conclusions: This is the first report that investigated the effects of SJ eggs antigen on spontaneous ileitis model of CD. These findings suggest that treatment with SJ eggs did not attenuate ileitis, but increased body weight and the upregulation of IL-4 suggest the therapeutic potentials of the parasite antigen for CD.

analyzed by gene array, immunofluorescence, flow cytometry and thymidine incorporation. Results Anti-TNF induced regulatory macrophages displayed increased numbers of autophagosomes as well as an increased expression of autophagy related transcripts including atg5, atg7, atg9 and atg16l2, suggesting induction of autophagy by IFX treatment. Of all donors, 7 were homozygously carrying the CD associated risk allele, 14 were heterozygous and 7 were homozygous for the WT allele. The number of CD14+ regulatory macrophages correlated significantly with the number of WT alleles present in each individual culture, with the largest number of macrophages found in cultures containing 3 or 4 WT alleles (2 WT donors or 1 WT and 1 heterozygous). Similarly, expression of CD206, which is associated with the immunosuppressive function of macrophages, positively correlated with the number of WT alleles present. To confirm the functional consequences of these findings, IFX mediated suppression of T cell proliferation was determined. Again, the level of suppression correlated significantly with the number of WT alleles present in the respective donor combinations. Conclusion Induction of regulatory macrophages by IFX is associated with induction of autophagy. In vitro, the number and function of IFX induced macrophages correlated with the number of WT alleles for the autophagy related gene ATG16L1. This suggests that an intact autophagy pathway is important for effectiveness of anti-TNF therapy.