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Non-steroidal antiinflammatory drugs (NSAIDs) are currently one of the most widely used drugs. The use of NSAIDs is associated with gastrointestinal toxicity, affecting both upper gastrointestinal tract (peptic ulcer disease) and lower gastrointestinal tract (NSAID-induced enteropathy). NSAIDs use has been associated with an increased risk of clinical relapse in inflammatory bowel disease patients. In this article, we review the upper and lower gastrointestinal toxicity of NSAIDs, with a focus on the risks and specific data of these drugs in inflammatory bowel disease patients, giving recommendations for its appropriate use in the clinical practice. Although evidence is scarce, short-term use of NSAIDs appears to be safe, and the data available suggest that selective COX-2 inhibitors are the safer option. NSAIDs should be avoided as long-term treatment or with high doses, especially in patients with active inflammation.

Non-steroidal antiinflammatory drugs (NSAIDs) are currently one of the most widely used drugs. The use of NSAIDs is associated with gastrointestinal toxicity, affecting both upper gastrointestinal tract (peptic ulcer disease) and lower gastrointestinal tract (NSAID-induced enteropathy). NSAIDs use has been associated with an increased risk of clinical relapse in inflammatory bowel disease patients. In this article, we review the upper and lower gastrointestinal toxicity of NSAIDs, with a focus on the risks and specific data of these drugs in inflammatory bowel disease patients, giving recommendations for its appropriate use in the clinical practice. Although evidence is scarce, short-term use of NSAIDs appears to be safe, and the data available suggest that selective COX-2 inhibitors are the safer option. NSAIDs should be avoided as long-term treatment or with high doses, especially in patients with active inflammation.

Background: Flexible endoscopy allows use of the vessel–tissue sealer Ligasure™ (Covidien, Massachusetts, USA) to perform diverticulotomy. Few studies have used this endoscopic approach in the uncommon disorder Zenker's diverticulum. The aim of the present study was to evaluate the effectiveness and safety of flexible endoscopy treatment assisted by Ligasure™. Methods: The single-center prospective and descriptive study included patients treated by flexible endoscopy using Ligasure™ for resection of Zenker’s diverticulum. Consecutive patients were included from March 2009 to April 2018. Patients were censored until the end of follow-up or death. Complications, symptoms before treatment, type of sedation, and number of interventions needed to resolve Zenker’s diverticulum were analyzed. Bleeding complications were considered when a case required a second endoscopy. Results: A total of 46 symptomatic patients with Zenker''s diverticulum were included in the final analysis (41.3% women, median age of 73.7 ± 11 years). The median follow-up period was 37.21 ± 28 months. Of all cases, 58.7% were considered small (< 3 cm). Solid or semi-solid food-related dysphagia was present in 55.6% of patients previously to the procedure. The technique was successful in a single procedure in 78.3% of cases. However, the success rate increased to 89.1% with a second procedure, and we had a complication rate of 4.3% with this technique. Most patients (79.66%) were managed as out-patients or with short (< 24 h) admission. Conclusion: In this large case series, treatment of Zenker''s diverticulum based on flexible endoscopy assisted by Ligasure™ was a safe and effective procedure with a high success rate in a few endoscopy sessions and low complication rate.

Helicobacter pylori (H. pylori) is a key agent in several upper gastrointestinal diseases. Treatment of H. pylori infection is the main strategy for resolving the associated gastroduodenal damage in infected patients and for the prevention of gastric cancer development. Infection management is becoming complex due to the increase in antibiotic resistance, which already represents a global healthcare problem. Resistance to clarithromycin, levofloxacin or metronidazole have forced the adaptation of eradication regimens in this new reality to reach the eradication rate target recommended in most international guidelines (>90%). In this challenging scenario, molecular methods are revolutionizing the diagnosis of antibiotic-resistant infections and the detection of antibiotic resistance and opening a path towards personalized treatments, although their use is not yet widespread. Moreover, the infection management by physicians is still not adequate, which contributes to aggravating the problem. Both gastroenterologists and mainly primary care physicians (PCPs), who currently routinely manage this infection, perform suboptimal management of the diagnosis and treatment of H. pylori infection by not following the current consensus recommendations. In order to improve H. pylori infection management and to increase PCPs’ compliance with guidelines, some strategies have been evaluated with satisfactory results, but it is still necessary to design and evaluate new different approaches.

Most colonoscopies performed to evaluate gastrointestinal symptoms detect only non-relevant pathologies. We aimed to evaluate the diagnostic accuracy of a qualitative point-of-care (POC) test combining four biomarkers (haemoglobin, transferrin, calprotectin, and lactoferrin), a quantitative faecal immunochemical test (FIT) for haemoglobin, and a quantitative faecal calprotectin (FC) test in symptomatic patients prospectively recruited. Colorectal cancer (CRC), adenoma requiring surveillance, inflammatory bowel disease (IBD), microscopic colitis, and angiodysplasia were considered significant pathologies. A total of 571 patients were included. Significant pathology was diagnosed in 118 (20.7%), including 30 CRC cases (5.3%). The POC test yielded the highest negative predictive values: 94.8% for a significant pathology and 100% for CRC or IBD if the four markers turned negative (36.8% of the patients). Negative predictive values of FIT, FC, and its combination for diagnosis of a significant pathology were 88.4%, 87.6%, and 90.8%, respectively. Moreover, the positive predictive value using the POC test was 82.3% for significant pathology when all biomarkers tested positive (6% of the patients), with 70.6% of these patients diagnosed with CRC or IBD. The AUC of the POC test was 0.801 (95%CI 0.754-0.848) for the diagnosis of a significant pathology. Therefore, this POC faecal test allows the avoidance of unnecessary colonoscopies and prioritizes high risk symptomatic patients.

Helicobacter pylori infection (H. pylori) is mainly managed at the primary care level. Our group previously performed a study demonstrating that providing specific counselling (SC) to primary care practitioners (PCPs) who requested a urea breath test (UBT) improved treatment management but not indications for H. pylori tests. SC was given in the form of a personal letter addressed to PCPs with UBT results which contained information about accepted UBT indications and a Helicobacter pylori treatment algorithm. The purpose of the present study was to evaluate the effect of training sessions (TS) on UBT indications, antibiotic prescriptions and eradication rates. This was a quasi-experimental study performed at primary care centres (PCCs). Phase I included 399 patients diagnosed with H. pylori infection after providing SC to PCPs. Phase II included 400 H. pylori-positive patients after giving TS to PCPs who had already received SC (100 from PCCs with TS and 300 from PCCs without TS). An improved trend in the appropriate indication of H. pylori diagnosis was observed between Phase I and PCCs with TS in Phase II (57.5% vs. 67%; p = 0.06). TS improved appropriate prescriptions in PCCs with TS compared to PCCs that only received SC in Phase I and II (94% vs. 75.3%, p = 0.01; 94% vs. 85.6%, p = 0.04, respectively). Eradication rates showed no differences between groups. In conclusion, training sessions after specific counselling improved antibiotic prescription appropriateness but not eradication rates.

INTRODUCCIÓNLa bacteria Helicobacter pylori infecta aproximadamente a la mitad de la población mundial, y puede producir patología como dispepsia, úlcera gástrica y/o duodenal y cáncer gástrico, principales indicaciones de tratamiento. Existen métodos diagnósticos invasivos (basados en la gastroscopia) como es la histología, y otros métodos no invasivos como son el test de urea en aire espirado o la detección de antígeno en heces. El tratamiento se basa en un inhibidor de la bomba de protones (IBP) asociado a 2 o 3 antibióticos, tomados de 7 a 14 días. El aumento en la resistencia bacteriana en las últimas décadas ha conducido a un cambio constante en las recomendaciones terapéuticas por parte de los comités de expertos para poder mantener cifras aceptables de eficacia o incluso mejorarla. En Aragón apenas hay estudios recientes sobre eficacia y resistencia bacteriana, y el conocimiento de éstos a nivel local permite la elección del tratamiento más adecuado.OBJETIVOSDeterminar la eficacia de los distintos tratamientos en nuestra área sanitaria. Describir el manejo clínico de los pacientes infectados y analizar su adecuación a guías clínicas. Analizar la asociación e influencia de distintas variables sociodemográficas y clínicas sobre la eficacia. Evaluar la capacidad diagnóstica de distintos métodos diagnósticos y su concordancia. Evaluar las tasas de resistencia antibiótica.MÉTODOSSe realizó un estudio descriptivo retrospectivo de pacientes diagnosticados de infección por Helicobacter pylori y tratados por primera vez entre 2010 y 2019, ambos incluidos, en dos centros de Aragón (Hospital clínico universitario Lozano Blesa de Zaragoza y Hospital general Obispo Polanco de Teruel), que recogió la práctica clínica diaria: síntomas, métodos diagnósticos, tratamientos prescritos y su eficacia. Se hizo análisis descriptivo y estudio de asociación entre eficacia y otras variables con el estadístico Chi Cuadrado, y se obtuvo la influencia de dichas variables sobre la eficacia mediante Odds ratio tras análisis de regresión logística. Por otro lado, se realizó un estudio prospectivo de análisis de muestras obtenidas mediante gastroscopia para evaluar concordancia entre distintos métodos diagnósticos (mediante kappa de Cohen) y realizar antibiograma para evaluación de las resistencias.RESULTADOSSe evaluaron 1730 pacientes con una edad media de 50,5 años. El 59,8% fueron mujeres y el 58% menores de 55 años. La gastroscopia fue el método diagnóstico más utilizado (70,1%), seguido del test de aliento (28,8%).Los pacientes recibieron entre 1 y 5 líneas de tratamiento, aplicándose un total de 2260 tratamientos, el 58% de ellos indicados por dispepsia y el 16% por úlcera. A principios de la década se usaron más las pautas triples como ICA (IBP+claritromicina+amoxicilina) o ICL (IBP+claritromicina+levofloxacino) en alérgicos a penicilina, pero a partir de 2014 aumentó el uso de terapias cuádruples como ICAM (IBP+claritromicina+amoxicilina+metronidazol), y a partir de 2016 comenzó el uso de IPylera® (IBP+Pylera® (unicápsula 3en1 que contiene subcitrato de bismuto+metronidazol+tetraciclina).La eficacia global por intención de tratar tras una primera línea de tratamiento fue del 69,8%, siendo mayor con las terapias cuádruples ICAM e IPylera®, que alcanzaron el 84,5% al optimizar su prescripción (aumentando la duración del tratamiento y utilizando IBPs de nueva generación). La eficacia también fue mayor al utilizar tratamientos recomendados en las guías clínicas, si bien la adecuación de los tratamientos de primera línea a las guías en pacientes no alérgicos fue del 76,4%, usándose en ocasiones tratamientos no recomendados y tratando patologías sin indicación de tratamiento (como rosácea o corioretinopatía). No hubo diferencias de eficacia entre los dos centros ni entre los dos grupos de edad establecidos, salvo con la terapia ILA (IBP+levofloxacino+amoxicilina), que fue tanto en primera como en segunda línea más eficaz en menores de 55 años que en pacientes superando esa edad. La eficacia fue un 5% mayor en hombres que en mujeres no alérgicos a penicilina (p=0,021).La terapia de segunda línea más utilizada en no alérgicos a penicilina fue la triple con levofloxacino ILA hasta 2016 cuando comenzó a usarse IPylera®, con eficacia mayor del 70%. La edad influyó en la eficacia, siendo un 14% más alta en los pacientes menores de 55 años (p=0,006).Un 2,5% de los pacientes abandonaron en algún momento el seguimiento clínico, teniendo más probabilidad los hombres, los menores de 55 años, y los diagnosticados mediante test de aliento.En el segundo bloque, la parte prospectiva del estudio, se incluyeron finalmente a 66 pacientes. Los test diagnósticos con mayor concordancia y sensibilidad fueron la reacción en cadena de la polimerasa (PCR) de tejido gástrico y la histología. El cultivo tuvo una sensibilidad menor al 70% debido a sobrecrecimiento bacteriano. La resistencia primaria a claritromicina fue del 11,1% y a metronidazol del 44,4%, aunque un 31,7% de los casos presentaron sensibilidad a todos los antibióticos.CONCLUSIONESEl manejo de la infección es heterogéneo entre centros, y en ocasiones discrepante con las recomendaciones de las sociedades científicas. La mayor eficacia en nuestra muestra se ha alcanzado con ICAM y con IPylera®, confirmando así su alta eficacia en nuestro medio, si bien la eficacia de los tratamientos en práctica clínica real aún no alcanza el 90%. El uso de terapias triples debería abandonarse por influir negativamente en la eficacia. El tratamiento con la triple terapia de levofloxacino ha sido menos eficaz en mayores de 55 años que en menores, por lo que desaconsejamos su uso en este grupo de pacientes, al menos en primera y segunda línea de tratamiento. Debería prescribirse siguiendo las recomendaciones de las guías en cuanto a fármacos y duración para obtener mayor eficacia. La resistencia bacteriana antibiótica ha aumentado en la última década..

Introducción: La doble antiagregación plaquetaria (DAP) ha demostrado disminuir la incidencia de eventos cardiovasculares tras síndrome coronario agudo. Clásicamente se ha basado en ácido acetil salicílico (AAS) y clopidogrel, pero la variabilidad individual en la respuesta a clopidogrel ha favorecido el desarrollo de nuevos antiagregantes (NA), prasugrel y ticagrelor, que han demostrado ser más eficaces. Sin embargo, en los estudios de registro los NA se han asociado con un incremento del riesgo hemorrágico global, lo cuál ha limitado su uso a pacientes muy seleccionados y con menos comorbilidades y, por lo tanto, no utilizándolos en los pacientes con mayor riesgo que son los que más se beneficiarían. Destaca una gran variabilidad en el diseño y resultados de los estudios que pretenden evaluar el riesgo hemorrágico asociado a estos fármacos y no existe ningún estudio que compare el riesgo específico de hemorragia gastrointestinal (GI) de la DAP basada en los NA con respecto a clopidogrel. Hipótesis: la DAP basada en NA incrementa el riesgo de sangrado GI con respecto a clopidogrel, tras angioplastia coronaria percutáneaObjetivos: Primario: determinar y comparar la frecuencia de eventos GI mayores y menores durante 12 meses tras angioplastia coronaria en pacientes con DAP basada en prasugrel, ticagrelor o clopidogrel. Secundarios: comparar características demográficas entre grupos de tratamiento. Analizar tipo de hemorragia GI y origen. Determinar actitud con respecto a DAP tras evento GI. Analizar la utilización de inhibidores de la bomba de protones (IBP)Metodología: estudio de cohortes retrospectivo en el que se incluyeron pacientes que iniciaron DAP tras una angioplastia coronaria percutánea entre el 1 de enero de 2015 y el 31 de diciembre de 2016. A través de la historia clínica electrónica se recogieron datos demográficos y la aparición de eventos de interés: evento GI mayor (hemorragia GI), evento GI menor (anemia y/o ferropenia), eventos isquémicos, otros eventos hemorrágicos no GI y muerte. El seguimiento finalizó a los 12 meses de inicio del tratamiento, ante la aparición de un evento GI mayor, cuando la DAP se interrumpió de forma definitiva o si el paciente falleció.Resultados: Se incluyeron 1327 pacientes, 54% iniciaron DAP basada en clopidogrel y 45,9% basada en NA. En el grupo de pacientes tratados con AAS y clopidogrel hubo significativamente menor proporción de varones (73,5% vs 80,7%; p = 0,002), pacientes de mayor edad (edad media 71,4 vs 61,5; p < 0,001), así como más comorbilidad (media del índice de Charlson 4,2 vs 1,9; p Conclusión: Más de uno de cada cuatro pacientes tratados con DAP presenta un evento GI en el seguimiento, sin diferencias en la incidencia según pauta de tratamiento (DAP basada en NA vs clopidogrel), por lo que en base al riesgo GI la indicación de NA podría extenderse a población menos seleccionada

Cardiovascular disease is the most important cause of morbidity and mortality in the world and low-dose aspirin is considered the cornerstone of the cardiovascular disease prevention. However, low-dose aspirin use is associated with gastrointestinal adverse effects in the whole gastrointestinal tract. In this setting, co-therapy with a proton pump inhibitor is the most accepted strategy to reduce aspirin related upper gastrointestinal damage. In addition, some adverse effects have been described with proton pump inhibitors long term use. Areas covered: Low-dose aspirin related beneficial and adverse effects in cardiovascular system and gastrointestinal tract are reviewed. In addition, this manuscript summarizes current data on upper gastrointestinal damage prevention and adverse events with proton pump inhibition. Finally, we discuss the benefit/risk ratio of proton pump inhibitor use in patients at risk of gastrointestinal damage taking low-dose aspirin. Expert commentary: Nowadays, with the current available evidence, the combination of low-dose aspirin with proton pump inhibitor is the most effective therapy for cardiovascular prevention in patients at high gastrointestinal risk. However, further studies are needed to discover new effective strategies with less related adverse events.

19 pags., 7 figs., 2 tabs. -- This article belongs to the Special Issue Gastrointestinal Cancers and Personalized Medicine, Background: Current efforts in the identification of new biomarkers are directed towards an accurate differentiation between benign and premalignant cysts. Thermal Liquid Biopsy (TLB) has been previously applied to inflammatory and tumor diseases and could offer an interesting point of view in this type of pathology. Methods: In this work, twenty patients (12 males and 8 females, average ages 62) diagnosed with a pancreatic cyst benign (10) and premalignant (10) cyst lesions were recruited, and biological samples were obtained during the endoscopic ultrasonography procedure. Results: Proteomic content of cyst liquid samples was studied and several common proteins in the different groups were identified. TLB cyst liquid profiles reflected protein content. Also, TLB serum score was able to discriminate between healthy and cysts patients (71% sensitivity and 98% specificity) and between benign and premalignant cysts (75% sensitivity and 67% specificity). Conclusions: TLB analysis of plasmatic serum sample, a quick, simple and non-invasive technique that can be easily implemented, reports valuable information on the observed pancreatic lesion. These preliminary results set the basis for a larger study to refine TLB serum score and move closer to the clinical application of TLB providing useful information to the gastroenterologist during patient diagnosis., This research was funded by the Spanish Ministry of Economy and Competitiveness and European ERDF Funds (MCIU/AEI/FEDER, EU) (BFU2016-78232-P to A.V.C.); Projects funded by Instituto de Salud Carlos III and co-funded by European Union (ESF, ”Investing in your future”): “PI15/00663 (FIS project to O.A)”, “PI18/00349 (FIS project to O.A. and Contract to LC)”, “FI19/00146 (PFIS contract for SHD)”, “CPII13/00017 (Miguel Servet Program to OA)”; Diputación General de Aragón (Protein Targets and Bioactive Compounds Group E45_17R to A.V.C. and Digestive Pathology Group B25_17R to O.A.); and the Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd).

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most numerous category of drugs sharing the same mechanism of action and therapeutic activities (anti-inflammatory, analgesic and anti-pyretic). Despite having similar efficacy for pain relieve, the different available NSAIDs show variability in its safety profile. The risk of gastrointestinal and cardiovascular complications varies depending on the dose of NSAID and also the presence of different risk factors. It is necessary, therefore, an individualized case assessment before establishing the indication of the best NSAID for each patient, taking account of the best gastroprotection strategy. Improved prescription and enhanced treatment adherence are central objectives to reduce NSAID-related complications. A recent consensus of the Spanish Association of Gastroenterology and the Spanish societies of Cardiology and Rheumatology intends to promote the rational use of NSAIDs according to new recent studies. This review provides additional aspects to facilitate the optimal decision-making process in the routine use of these drugs in clinical practice.

Resumen Los antiinflamatorios no esteroideos (AINE) configuran la familia mas numerosa de farmacos que comparten los mismos mecanismos de accion y actividades terapeuticas (antiinflamatoria, analgesica y antipiretica). A pesar de tener una eficacia similar para controlar el dolor, los diferentes AINE disponibles presentan variabilidad en su perfil de seguridad. El riesgo de complicaciones gastrointestinales y cardiovasculares varia en funcion del AINE y de la dosis que utilicemos, ademas de la presencia de factores de riesgo. Es necesaria una evaluacion individualizada de cada caso antes de sentar tanto la indicacion del AINE «ideal» como la estrategia de prevencion gastrointestinal si fuera necesaria. Una correcta prescripcion y una adecuada adherencia al tratamiento gastroprotector son los objetivos que hay que plantearse para conseguir reducir las complicaciones secundarias al tratamiento con AINE. Recientemente se han publicado unas recomendaciones de prescripcion adecuada fruto de la colaboracion de la Asociacion Espanola de Gastroenterologia y las sociedades espanolas de Reumatologia y Cardiologia que tiene por objeto impulsar un uso racional de los AINE en funcion de los ultimos estudios publicados. Esta revision completa aspectos adicionales necesarios para facilitar la toma de decisiones optima en el uso habitual de estos farmacos en la practica clinica diaria.

Background Patients with gastrointestinal bleeding during anticoagulant and/or antiplatelet therapy represent a clinical challenge. Aim To determine the risk/rates of rebleeding, vascular events and death in patients treated with antiplatelet or anticoagulant agents who developed major gastrointestinal bleeding METHODS: This was an observational cohort study of patients who developed gastrointestinal bleeding while on antiplatelet and/or anticoagulant therapy. Drug use information was collected prospectively during bleeding events. Cox proportional hazards models were used to evaluate rebleeding, vascular events and death. Results Among 871 patients (mean age 78.9 ± 8.6 years), 38.9% used an anticoagulant, 52.5% used an antiplatelet and 8.6% used both; 93.1% interrupted treatment after gastrointestinal bleeding and 80.5% restarted therapy within 7.6 ± 36.4 days; 38.7% had upper gastrointestinal bleeds, 46.7% lower gastrointestinal bleeds and 14.6% gastrointestinal bleeds of unknown origin. Median follow-up was 24.9 months (IQR: 7.0-38.0). Resumption of both therapies was associated with a higher risk of rebleeding, lower risk of ischaemic events or death and a similar risk for upper and lower gastrointestinal events. Resumption of therapy ≤ 7 days after bleeding showed a similar pattern with no differences in death. Rebleeding rates were higher in anticoagulant vs antiplatelet patients (138.0 vs 99.0 events per 1000 patient-years), and the bleeding location was identical in 61.8% of cases. Conclusions Resumption of anticoagulant or antiplatelet therapy after a gastrointestinal bleeding event was associated with a lower risk of vascular events and death and a higher rebleeding risk. The benefits of early reinstitution of anticoagulant/antiplatelet therapy outweigh the gastrointestinal-related risks.

No abstract available Keywords: Dyspepsia; Helicobacter pylori; Peptic ulcer; Stomach diseases.

T1 colorectal polyps with at least 1 risk factor for metastasis to lymph node should be treated surgically and are considered endoscopically unresectable. Optical analysis, based on the Narrow-Band Imaging International Colorectal Endoscopic (NICE) classification system, is used to identify neoplasias with invasion of the submucosa that require endoscopic treatment. We assessed the accuracy of the NICE classification, along with other morphologic characteristics, in identifying invasive polyps that are endoscopically unresectable (have at least 1 risk factor for metastasis to lymph node).We performed a multicenter, prospective study of data collected by 58 endoscopists, from 1634 consecutive patients (examining 2123 lesions) at 17 university and community hospitals in Spain from July 2014 through June 2016. All consecutive lesions10 mm assessed with narrow-band imaging were included. The primary end point was the accuracy of the NICE classification for identifying lesions with deep invasion, using findings from histology analysis as the reference standard. Conditional inference trees were fitted for the analysis of diagnostic accuracy.Of the 2123 lesions analyzed, 89 (4.2%) had features of deep invasion and 91 (4.3%) were endoscopically unresectable. The NICE classification system identified lesions with deep invasion with 58.4% sensitivity (95% CI, 47.5-68.8), 96.4% specificity (95% CI, 95.5-97.2), a positive-predictive value of 41.6% (95% CI, 32.9-50.8), and a negative-predictive value of 98.1% (95% CI, 97.5-98.7). A conditional inference tree that included all variables found the NICE classification to most accurately identify lesions with deep invasion (P.001). However, pedunculated morphology (P.007), ulceration (P = .026), depressed areas (P.001), or nodular mixed type (P.001) affected accuracy of identification. Results were comparable for identifying lesions that were endoscopically unresectable.In an analysis of 2123 colon lesions10 mm, we found the NICE classification and morphologic features identify those with deep lesions with96% specificity-even in non-expert hands and without magnification. ClinicalTrials.gov number NCT02328066.

Helicobacter pylori (H. pylori) infection and NSAID/low-dose aspirin (ASA) use are associated with peptic ulcer disease. The risk of peptic ulcer bleeding (PUB) associated with the interaction of these factors remains unclear. The objective of this study was to determine the risk of PUB associated with the interaction between H. pylori infection and current nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose ASA use.This was a case-control study of consecutive patients hospitalized because of PUB. Controls were matched by age, sex, and month of admission. H. pylori infection status was determined in all cases and controls by serology. Drug use was determined by structured questionnaire. Adjusted relative risk (RR) associated with different factors, and the interaction between NSAID/ASA and H. pylori infection was estimated by logistic regression analysis.The study included 666 cases of PUB and 666 controls; 74.3% cases and 54.8% controls (RR: 2.6; 95% confidence interval (CI): 2.0-3.3) tested positive for H. pylori infection; 34.5% of cases had current NSAID use compared with 13.4% of controls (RR: 4.0; 95% CI: 3.0-5.4). Respective proportions for low-dose ASA use were 15.8 and 12%, respectively (RR: 1.9; 95% CI: 1.3-2.7). The RR of PUB for concomitant NSAID use and H. pylori infection suggested an additive effect (RR: 8.0; 95% CI: 5.0-12.8), whereas no interaction was observed with ASA use (RR: 3.5; 95% CI: 2.0-6.1).NSAID, low-dose ASA use, and H. pylori infection are three independent risk factors for the development of PUB, but there were differences in the interaction effect between low-dose ASA (no interaction) or NSAID (addition) use and H. pylori infection, which may have implications for clinical practice in prevention strategies.

Nonsteroidal anti-inflammatory drug (NSAID) treatment will be necessary as part of our therapeutic armamentarium for many years to come. Therefore, safe prescription is mandatory in order to prevent adverse events. In the last two decades, new strategies and new drugs have been developed to reduce NSAID-associated upper gastrointestinal (GI) adverse events. Although the implementation of guidelines into clinical practice takes time, several studies have shown a recent and profound decrease in hospitalizations due to upper GI complications, which has been linked to widespread use of proton pump inhibitors (PPIs), better NSAID prescription, and decreased prevalence of Helicobacter pylori infection. This is encouraging. Safe NSAID prescription should be straightforward since the most relevant aspects are clinical in nature. Before issuing any prescription, three key questions should be considered: 1) Is NSAID treatment necessary for this patient? 2) What cardiovascular (CV) and GI risk factors does this patient have? 3) What is the most suitable NSAID for this patient? GI and CV risk are easy to estimate, and we know that these risks are not the same for all NSAIDs. Selective cyclooxygenase (COX)-2 inhibitors, like celecoxib at usual doses, carry the lowest GI risk and are the best option in patients with moderate/high GI risk without high CV risk. Gastroprotective therapy (PPI as the drug of choice) should be considered if a non-selective NSAID is prescribed. For those at the highest risk, a combination of PPI plus a coxib is the best option. Also, eradication of H. pylori infection in patients with previous peptic ulcer or in NSAID-naive users must be considered. Naproxen is the best option in patients with high CV risk and low/moderate GI risk. Patients taking aspirin represent a real challenge for treatment, since interaction with frequently prescribed NSAIDs (e.g. ibuprofen/naproxen) may alter its antiplatelet effect, representing a potential clinical problem. Switching treatment (e.g. taking aspirin before NSAID dosing) may not be an alternative since interaction may persist, especially when taking enteric-coated aspirin. Changing NSAID treatment to diclofenac/celecoxib/etoricoxib may also not be an option in patients with high or previous CV event history. Under these circumstances, careful prescription should be considered at the individual patient level. When dyspepsia develops in an NSAID user, PPI co-therapy plus reduction of the NSAID dose or a change in the type of NSAID are valid alternatives, but clinical experience shows that, for some patients, stopping NSAID therapy may be the only option. After a bleeding episode, most patients can be managed with alternative therapy to NSAIDs, but if needed, a coxib plus a PPI and H. pylori eradication is a safe alternative.

BACKGROUND Management of Helicobacter pylori infection has been expanded from the gastroenterology specialist (GS) to primary care physicians (PCPs), with a large increase in requests for urea breath tests (UBT). Due to the lack of evidence at this level, we evaluated the appropriateness of UBT indications and treatment for H pylori infections between PCPs and GSs and the effect of introducing specific counseling to PCPs. MATERIALS AND METHODS This was a quasi-experimental study. Phase I included 650 consecutive UBT requested by PCPs (400) and GSs (250). Indications and treatments were classified as appropriate or inappropriate based on national guidelines. Data on eradication rates were also collected. In phase II, 240 UBT and patients' treatment outcomes were analyzed after individually counseling PCPs on both aspects. RESULTS Of 1049 UBT, inappropriate indications in phase I were significantly higher in tests requested by PCP compared with GS (35.9% vs 7.2%; P

The availability of fully functional human hepatocytes is critical for progress in human hepatocyte transplantation and the development of bioartificial livers and in vitro liver systems. However, the cell isolation process impairs the hepatocyte status and determines the number of viable cells that can be obtained. This study aimed to evaluate the effects of using dimethyl sulfoxide (DMSO) and melatonin in the human hepatocyte isolation protocol. Human hepatocytes were isolated from liver pieces resected from 10 patients undergoing partial hepatectomy. Each piece was dissected into 2 equally sized pieces and randomized, in 5 of 10 isolations, to perfusion with 1% DMSO-containing perfusion buffer or buffer also containing 5 mM melatonin using the 2-step collagenase perfusion technique (experiment 1), and in the other 5 isolations to standard perfusion or perfusion including 1% DMSO (experiment 2). Tissues perfused with DMSO yielded 70.6% more viable hepatocytes per gram of tissue (p = 0.076), with a 26.1% greater albumin production (p < 0.05) than those perfused with control buffer. Melatonin did not significantly affect (p > 0.05) any of the studied parameters, but cell viability, dehydrogenase activity, albumin production, urea secretion, and 7-ethoxycoumarin O-deethylase activity were slightly higher in cells isolated with melatonin-containing perfusion buffer compared to those isolated with DMSO. In conclusion, addition of 1% DMSO to the hepatocyte isolation protocol could improve the availability and functionality of hepatocytes for transplantation, but further studies are needed to clarify the mechanisms involved.

Barrett's esophagus (BE) is the main recognized risk factor for the development of esophageal adenocarcinoma (EAC). The incidence of this cancer and its associated mortality has increased in developed countries during the last few years. Detection of EAC at earlier stages could potentially improve survival dramatically in these patients, which is especially important as mortality from EAC remains high despite the available treatments. Therefore, endoscopic surveillance is an attractive option for patients with Barrett's esophagus. Consequently, periodic endoscopic surveillance is recommended by all the International Gastroenterology Societies in an attempt to detect EAC at an early and potentially curable stage. Currently, the frequency of endoscopic surveillance and its need in Barrett's esophagus with low-grade dysplasia or without dysplasia are under discussion. This review presents the available evidence in order to assist clinicians in the decision-making process.

This article describes the mechanism of action, pharmacokinetics, and pharmacodynamics of aspirin at doses used for cardiovascular prevention and provides specific management recommendations for optimal use in clinical practice. The paper highlights practical aspects related to antiplatelet therapy, including the optimal dose of aspirin, concomitant treatment with other NSAIDs, and strategies for the prevention of gastrointestinal toxicity. Specifically, we revise the benefits and hazards in different clinical settings to help the clinician in the decision-making process for individuals who have different risks for cardiovascular and gastrointestinal bleeding events.

The mechanism of action of low-dose aspirin in the prevention of colorectal cancer (CRC) remains largely hypothetical. We aimed to compare the effects of low-dose aspirin (100 mg/day for 7 days) given to 40 individuals undergoing CRC screening on the extent of cyclooxygenase (COX)-1 acetylation at serine-529 (AceCOX-1), in blood platelets vs. colorectal mucosa, at 7 (group 1) and 24 h (group 2) after dosing. A significantly (P < 0.01) lower %AceCOX-1 was detected in colonic and rectal mucosa (average 64%) vs. platelets (average 75%) in both groups. This effect was associated with an average 46% (P < 0.01) and 35% (P < 0.05) reduction in prostaglandin (PG) E2 levels and phosphorylated S6 (p-S6) levels, respectively. Rectal mucosal levels of p-S6/S6 significantly (P < 0.01) correlated with PGE2 . These findings demonstrate that low-dose aspirin produces long-lasting acetylation of COX-1 and downregulation of p-S6 in human colorectal mucosa, an effect that may interfere with early colorectal carcinogenesis.

Background: The best available evidence regarding non-steroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) bleeding comes from randomized controlled trials including patients who use NSAIDs to manage chronic rheumatic diseases; however, patients with varying background profiles commonly take NSAIDs for many other reasons, often without prescription, and such usage has not been well studied. Objectives and methods: To define the characteristics of patients hospitalized for upper GI bleeding in clinical practice, we conducted a case–control study among patients with endoscopy-proven major upper GI bleeding due to gastroduodenal peptic lesions and control subjects. We used adjusted logistic regression models to estimate bleeding risks. Data analysis was performed using SPSS 22.0. Results: Our analysis included 3785 cases and 6540 controls, including 1270 cases (33.55%) and 834 controls (12.75%) reporting recent use (Conclusions: The majority of patients hospitalized due to NSAID-related upper GI bleeding reported short-term NSAID use for reasons other than chronic rheumatic disease. These findings suggest that current prevention strategies may not reach a wide population of short-term NSAID users.

Helicobacter pylori eradication has become the recognized standard and widely adopted therapy to cure peptic ulcer disease. Other H. pylori associated conditions with potential benefit from eradication therapy are still subject to clinical investigations. The current state of evidence for these indications is summarized in this article. For NSAID associated peptic ulcer disease the current evidence needs to be grouped in three subsets of clinical conditions: a) H. pylori eradication for prevention of ulcers before starting NSAIDs therapy is advisable; b) eradication during PPI treatment for NSAID associated active ulcer shows no advantage on healing; and c) eradication alone is not sufficient for secondary prevention of ulcer complications induced by NSAID, however it appears to protect from further episodes of aspirin induced bleeding. In nonulcer dyspepsia the latest Cochrane collaboration review supports a small benefit in favour of H. pylori eradication. New insight in the relationship of H. pylori with GERD is provided from clinical trials which show that H. pylori eradication does not influence the clinical course of patients with reflux esophagitis. Finally important new data are presented regarding the management of dyspepsia at the primary care level with the confirmation that the H. pylori 'test and treat' strategy in the appropriate setting is more cost-effective than endoscopy.

Efficient cryopreservation of human hepatocytes is essential for their use in cell therapy. This study investigated the effects of adding melatonin and/or dimethyl sulfoxide (DMSO) to pre-incubation and/or freezing solutions on the viability and function of thawed human hepatocytes.Isolated human hepatocytes were pre-incubated for 90 min at 4°C in Williams' Medium E (WEM), WEM containing 5 mM melatonin dissolved in DMSO, or WEM containing the equivalent amount of DMSO (1%). The hepatocytes were frozen in University of Wisconsin solution (UW) and 10% DMSO, with or without 5 mM melatonin. After thawing, viability, plating efficiency, mitochondrial dehydrogenase activity (MTT), and albumin and urea production were analyzed.Viability and plating efficiency were not affected by melatonin or DMSO in pre-incubation media. Unexpectedly, hepatocytes pre-incubated with DMSO had significantly higher MTT (29.7% vs. control, p0.01), albumin (82.8% vs. control, p0.05), and urea amounts (26.2% vs. control, p=0.06) than those incubated only with WEM. Hepatocytes pre-incubated in media containing melatonin had amounts between those of cells incubated with DMSO or only with WEM (p0.05 for MTT and p0.05 for albumin and urea values). Also, the addition of melatonin to the freezing media did not significantly improve any of the studied parameters (p0.05).Adding 1% DMSO to pre-incubation media prior to the cryopreservation of human hepatocytes preserves hepatocyte function after thawing. These findings could be considered in current hepatocyte cryopreservation protocols.

Aspirin is being used as an effective analgesic and anti-inflammatory agent at doses >325 mg daily. At low doses (75-325 mg daily), aspirin is the key antiplatelet drug in the pharmacological prevention of cardiovascular diseases. Topical and systemic effects of aspirin in the gastrointestinal mucosa are associated with mucosal damage in the upper and lower gastrointestinal tract. The risk of upper gastrointestinal bleeding with aspirin is increased with old age, male sex, ulcer history and concomitant medication with NSAIDs, cyclooxygenase 2 selective inhibitors, corticosteroids or other antithrombotic agents. In some patients, the cardiovascular benefits of low-dose aspirin might be overcome by the risk of gastrointestinal complications, but withdrawal of aspirin therapy can precipitate a cardiovascular event. These patients will need concomitant therapy with antisecretory agents, especially PPIs, to reduce the gastrointestinal risk. Eradication of Helicobacter pylori infection might be an additional option in patients with a history of ulcer. Furthermore, there is growing evidence that long-term use of aspirin decreases the risk of colorectal cancer, even at low doses. As aspirin is one of the most prescribed drugs worldwide and its clinical impact is huge, physicians need to consider the benefits and harms for each individual patient in order to maximize the benefits of aspirin.

Celsior solution (CS) is a high-sodium, low-potassium, low-viscosity extracellular solution that has been used for liver graft preservation in recent years, although experience with it is still limited. We performed an open-label randomized active-controlled trial comparing CS with the University of Wisconsin solution (UW) for liver transplantation (LT), with a follow-up period of 5 years. Adult transplant recipients (n = 102) were prospectively randomized to receive either CS (n = 51) or UW (n = 51). The two groups were comparable with respect to donor and recipient characteristics. The primary outcome measure was the incidence of postreperfusion syndrome (PRS). Secondary outcome measures included primary nonfunction (PNF) or primary dysfunction (PDF), liver retransplantation, and graft and patient survival. Other secondary outcome measures were days in the intensive care unit (ICU) and the rates of acute rejection, chronic rejection, infectious complications, postoperative reoperations, and vascular and biliary complications. In all, 14 posttransplant variables revealed no significant differences between the groups. There were no cases of PNF or PDF. The incidence of PRS was 5.9% in the CS group and 21.6% in the UW group (P = 0.041). After reperfusion, CS revealed greater control of serum potassium (P = 0.015), magnesium levels (P = 0.005), and plasma glucose (P = 0.042) than UW. Respective patient survivals at 3, 12, and 60 months were 95.7, 87.2, and 82.0% for the CS group and 95.7, 83.3, and 66.6% for the UW group (P = 0.123). While retaining the same degree of safety and effectiveness as UW for LT, CS may yield postliver graft reperfusion benefits, as shown in this study by a significant reduction in the incidence of PRS and greater metabolic control.

A new study suggests that co-prescription of low-dose aspirin and PPIs increases the incidence of small-bowel mucosal breaks. Should we be concerned about the potential negative interactions of these drugs? Or is the balance of evidence still substantially tipped towards the need for PPIs to protect against aspirin-induced upper gastrointestinal damage?

Drug use increases with age and the elderly is at increased risk of adverse drug reactions. Gastrointestinal adverse effects are one of the most often reported. Serious event are mostly caused by NSAIDs and/or aspirin which are the most widely prescribed medications in the world. NSAIDs and/or aspirin use are associated with complications from both the upper and the lower gastrointestinal tract. The risk of these complications depends on presence of risk factors, and age is the most frequent and relevant one. At-risk patients should be on prevention strategies including the use of the lowest effective dose, co-therapy with a gastroprotective agents or use of a COX-2 selective agent. Treatment of Helicobacter pylori infection is beneficial in patients starting therapy with these agents, especially in the presence of ulcer history. The best strategy to prevent lower GI complications has yet to be defined.