Applicability of the Barcelona scale to assess the quality of cleanliness of mucosa at esophagogastroduodenoscopy.

BACKGROUND AND OBJECTIVES: There are few scales with prospective validation for the assessment of the upper gastrointestinal mucosal cleanliness during an esophagogastroduodenoscopy (EGD). The aim of this study was to develop a valid and reproducible cleanliness scale for use during an EGD. METHODS: We developed a cleanliness scale (Barcelona scale) with a score (0-2 points) of five segments of the upper gastrointestinal tract with thorough cleaning techniques (esophagus, fundus, body, antrum, and duodenum). First, 125 photos (25 of each area) were assessed, and a score was assigned to each image by consensus among 7 experts endoscopists. Subsequently, 100 of the 125 images were selected and the inter- and intra-observer variability of 15 previously trained endoscopists was evaluated using the same images at two different times. RESULTS: In total, 1500 assessments were performed. In 1336/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.83 (0.45-0.96). In the second evaluation, in 1330/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.82 (0.45-0.93). The intra-observer variability was 0.89 (0.76-0.99). CONCLUSIONS: The Barcelona cleanliness scale is a valid measure and reproducible with minimal training. Its application in clinical practice is a significant step to standardize the quality of the EGD.

Gluten-induced RNA methylation changes regulate intestinal inflammation via allele-specific XPO1 translation in epithelial cells.

OBJECTIVES: Coeliac disease (CD) is a complex autoimmune disorder that develops in genetically susceptible individuals. Dietary gluten triggers an immune response for which the only available treatment so far is a strict, lifelong gluten free diet. Human leucocyte antigen (HLA) genes and several non-HLA regions have been associated with the genetic susceptibility to CD, but their role in the pathogenesis of the disease is still essentially unknown, making it complicated to develop much needed non-dietary treatments. Here, we describe the functional involvement of a CD-associated single-nucleotide polymorphism (SNP) located in the 5'UTR of XPO1 in the inflammatory environment characteristic of the coeliac intestinal epithelium. DESIGN: The function of the CD-associated SNP was investigated using an intestinal cell line heterozygous for the SNP, N6-methyladenosine (m6A)-related knock-out and HLA-DQ2 mice, and human samples from patients with CD. RESULTS: Individuals harbouring the risk allele had higher m6A methylation in the 5'UTR of XPO1 RNA, rendering greater XPO1 protein amounts that led to downstream nuclear factor kappa B (NFkB) activity and subsequent inflammation. Furthermore, gluten exposure increased overall m6A methylation in humans as well as in in vitro and in vivo models. CONCLUSION: We identify a novel m6A-XPO1-NFkB pathway that is activated in CD patients. The findings will prompt the development of new therapeutic approaches directed at m6A proteins and XPO1, a target under evaluation for the treatment of intestinal disorders.

The "diagnose and leave in" strategy for diminutive rectosigmoid polyps in Lynch syndrome: a post hoc analysis from a randomized controlled trial.

BACKGROUND: The "diagnose-and-leave-in" policy has been established to reduce the risks and costs related to unnecessary polypectomies in the average-risk population. In individuals with Lynch syndrome, owing to accelerated carcinogenesis, the general recommendation is to remove all polyps, irrespective of size, location, and appearance. We evaluated the feasibility and safety of the diagnose-and-leave-in strategy in individuals with Lynch syndrome. METHODS : We performed a post hoc analysis based on per-polyp data from a randomized, clinical trial conducted by 24 dedicated colonoscopists at 14 academic centers, in which 256 patients with confirmed Lynch syndrome underwent surveillance colonoscopy from July 2016 to January 2018. In vivo optical diagnosis with confidence level for all detected lesions was obtained before polypectomy using virtual chromoendoscopy alone or with dye-based chromoendoscopy. Primary outcome was the negative predictive value (NPV) for neoplasia of high-confidence optical diagnosis among diminutive (≤ 5 mm) rectosigmoid lesions. Histology was the reference standard. RESULTS: Of 147 rectosigmoid lesions, 128 were diminutive. In 103 of the 128 lesions (81 %), the optical diagnostic confidence was high and showed an NPV of 96.0 % (95 % confidence interval [CI] 88.9 %-98.6 %) and accuracy of 89.3 % (95 %CI 81.9 %-93.9 %). By following the diagnose-and-leave-in policy, we would have avoided 59 % (75/128) of polypectomies at the expense of two diminutive low grade dysplastic adenomas and one diminutive sessile serrated lesion that would have been left in situ. CONCLUSION: In patients with Lynch syndrome, the diagnose-and-leave-in strategy for diminutive rectosigmoid polyps would be feasible and safe.

White-Light Endoscopy Is Adequate for Lynch Syndrome Surveillance in a Randomized and Noninferiority Study.

BACKGROUND & AIMS: Dye-based pancolonic chromoendoscopy is recommended for colorectal cancer surveillance in patients with Lynch syndrome. However, there is scarce evidence to support its superiority to high-definition white-light endoscopy. We performed a prospective study assess whether in the hands of high detecting colonoscopists, high-definition, white-light endoscopy is noninferior to pancolonic chromoendoscopy for detection of adenomas in patients with Lynch syndrome. METHODS: We conducted a parallel controlled study, from July 2016 through January 2018 at 14 centers in Spain of adults with pathogenic germline variants in mismatch repair genes (60% women; mean age, 47 ± 14 years) under surveillance. Patients were randomly assigned to groups that underwent high-definition white-light endoscopy (n = 128) or pancolonic chromoendoscopy (n = 128) evaluations by 24 colonoscopists who specialized in detection of colorectal lesions in high-risk patients for colorectal cancer. Adenoma detection rates (defined as the proportion of patients with at least 1 adenoma) were compared between groups, with a noninferiority margin (relative difference) of 15%. RESULTS: We found an important overlap of confidence intervals (CIs) and no significant difference in adenoma detection rates by pancolonic chromoendoscopy (34.4%; 95% CI 26.4%-43.3%) vs white-light endoscopy (28.1%; 95% CI 21.1%-36.4%; P = .28). However, pancolonic chromoendoscopy detected serrated lesions in a significantly higher proportion of patients (37.5%; 95% CI 29.5-46.1) than white-light endoscopy (23.4%; 95% CI 16.9-31.4; P = .01). However, there were no significant differences between groups in proportions of patients found to have serrated lesions of 5 mm or larger (9.4% vs 7.0%; P = .49), of proximal location (11.7% vs 10.2%; P = .68), or sessile serrated lesions (3.9% vs 5.5%; P = .55), respectively. Total procedure and withdrawal times with pancolonic chromoendoscopy (30.7 ± 12.8 minutes and 18.3 ± 7.6 minutes, respectively) were significantly longer than with white-light endoscopy (22.4 ± 8.7 minutes and 13.5 ± 5.6 minutes; P < .001). CONCLUSIONS: In a randomized parallel trial, we found that for Lynch syndrome surveillance, high-definition white-light endoscopy is not inferior to pancolonic chromoendoscopy if performed by experienced and dedicated endoscopists. ClinicalTrials.gov no: NCT02951390.

Clinical validation of risk scoring systems to predict risk of delayed bleeding after EMR of large colorectal lesions.

BACKGROUND AND AIMS: The Endoscopic Resection Group of the Spanish Society of Endoscopy (GSEED-RE) model and the Australian Colonic Endoscopic Resection (ACER) model were proposed to predict delayed bleeding (DB) after EMR of large superficial colorectal lesions, but neither has been validated. We validated and updated these models. METHODS: A multicenter cohort study was performed in patients with nonpedunculated lesions ≥20 mm removed by EMR. We assessed the discrimination and calibration of the GSEED-RE and ACER models. Difficulty performing EMR was subjectively categorized as low, medium, or high. We created a new model, including factors associated with DB in 3 cohort studies. RESULTS: DB occurred in 45 of 1034 EMRs (4.5%); it was associated with proximal location (odds ratio [OR], 2.84; 95% confidence interval [CI], 1.31-6.16), antiplatelet agents (OR, 2.51; 95% CI, .99-6.34) or anticoagulants (OR, 4.54; 95% CI, 2.14-9.63), difficulty of EMR (OR, 3.23; 95% CI, 1.41-7.40), and comorbidity (OR, 2.11; 95% CI, .99-4.47). The GSEED-RE and ACER models did not accurately predict DB. Re-estimation and recalibration yielded acceptable results (GSEED-RE area under the curve [AUC], .64 [95% CI, .54-.74]; ACER AUC, .65 [95% CI, .57-.73]). We used lesion size, proximal location, comorbidity, and antiplatelet or anticoagulant therapy to generate a new model, the GSEED-RE2, which achieved higher AUC values (.69-.73; 95% CI, .59-.80) and exhibited lower susceptibility to changes among datasets. CONCLUSIONS: The updated GSEED-RE and ACER models achieved acceptable prediction levels of DB. The GSEED-RE2 model may achieve better prediction results and could be used to guide the management of patients after validation by other external groups. (Clinical trial registration number: NCT03050333.).

European Registry on Helicobacter pylori Management: Effectiveness of First and Second-Line Treatment in Spain.

The management of Helicobacter pylori infection has to rely on previous local effectiveness due to the geographical variability of antibiotic resistance. The aim of this study was to evaluate the effectiveness of first and second-line H. pylori treatment in Spain, where the empirical prescription is recommended. A multicentre prospective non-interventional registry of the clinical practice of European gastroenterologists concerning H. pylori infection (Hp-EuReg) was developed, including patients from 2013 until June 2019. Effectiveness was evaluated descriptively and through a multivariate analysis concerning age, gender, presence of ulcer, proton-pump inhibitor (PPI) dose, therapy duration and compliance. Overall, 53 Spanish hospitals were included, and 10,267 patients received a first-line therapy. The best results were obtained with the 10-day bismuth single-capsule therapy (95% cure rate by intention-to-treat) and with both the 14-day bismuth-clarithromycin quadruple (PPI-bismuth-clarithromycin-amoxicillin, 91%) and the 14-day non-bismuth quadruple concomitant (PPI-clarithromycin-amoxicillin-metronidazole, 92%) therapies. Second-line therapies were prescribed to 2448 patients, with most-effective therapies being the triple quinolone (PPI-amoxicillin-levofloxacin/moxifloxacin) and the bismuth-levofloxacin quadruple schemes (PPI-bismuth-levofloxacin-amoxicillin) prescribed for 14 days (92%, 89% and 90% effectiveness, respectively), and the bismuth single-capsule (10 days, 88.5%). Compliance, longer duration and higher acid inhibition were associated with higher effectiveness. "Optimized" H. pylori therapies achieve over 90% success in Spain.

Open-label infliximab therapy in Crohn's disease: a long-term multicenter study of efficacy, safety and predictors of response.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (p < 0.01). 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 (p < 0.05). Other adverse events occurred in 26% of the patients, and were cause of treatment withdrawal in 7 patients. CONCLUSIONS: 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.

Screening for latent tuberculosis infection in patients with inflammatory bowel disease: Can interferon-gamma release assays replace the tuberculin skin test?

BACKGROUND/AIMS: Screening for latent tuberculosis infection is mandatory before starting anti-tumor necrosis factor therapy. New assays based on interferon-γ (IFN-γ) release have recently become available and may be more accurate. The aim of this study was to compare QuantiFERON-TB and tuberculin skin test in screening for latent infection in patients with inflammatory bowel disease. MATERIALS AND METHODS: We prospectively screened 138 patients with inflammatory bowel disease for latent tuberculosis infection with chest X-ray, tuberculin skin test, and a third-generation QuantiFERON-TB test. The association of the results in both tests with immunosuppression or inflammatory activity was determined by logistic regression. RESULTS: The tuberculin skin test and QuantiFERON-TB were positive in 21.7% and 24.6% of the patients, respectively. Overall, 71% patients were receiving immunosuppressants. Concordance between the two tests was moderate (κ=0.59; 95% confidence interval (CI), 0.43-0.75) and was higher in immunosuppressant-naïve patients (κ=0.75; 95% CI, 0.52-0.97) than in immunosuppressed patients (κ=0.51; 95% CI, 0.30-0.72). In both the tests, disease activity and receiving immunosuppression were not associated with the test results. Nevertheless, QuantiFERON-TB was negatively influenced with two or more immunosuppressive drugs. CONCLUSION: Concordance between the two tests was moderate, and it appears lower with immunosuppression. QuantiFERON-TB alone may be appropriate in immunosuppressant-naïve patients. Both tests should be considered in immunosuppressed patients.

Applicability of the Barcelona scale to assess the quality of cleanliness of mucosa at esophagogastroduodenoscopy / Aplicabilidad de la escala Barcelona para valorar la calidad de la limpieza de la mucosa en la esofagogastroduodenoscopia

Background and objectives There are few scales with prospective validation for the assessment of the upper gastrointestinal mucosal cleanliness during an esophagogastroduodenoscopy (EGD). The aim of this study was to develop a valid and reproducible cleanliness scale for use during an EGD. Methods We developed a cleanliness scale (Barcelona scale) with a score (0–2 points) of five segments of the upper gastrointestinal tract with thorough cleaning techniques (esophagus, fundus, body, antrum, and duodenum). First, 125 photos (25 of each area) were assessed, and a score was assigned to each image by consensus among 7 experts endoscopists. Subsequently, 100 of the 125 images were selected and the inter- and intra-observer variability of 15 previously trained endoscopists was evaluated using the same images at two different times. Results In total, 1500 assessments were performed. In 1336/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.83 (0.45–0.96). In the second evaluation, in 1330/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.82 (0.45–0.93). The intra-observer variability was 0.89 (0.76–0.99). Conclusions The Barcelona cleanliness scale is a valid measure and reproducible with minimal training. Its application in clinical practice is a significant step to standardize the quality of the EGD. (AU)

Introducción Existen pocas escalas validadas prospectivamente para evaluar la limpieza de la mucosa esofagogastroduodenal durante la endoscopia digestiva alta (EDA). El objetivo de este estudio fue desarrollar una escala válida y reproducible para su uso en la realización de una EDA. Métodos Desarrollamos una escala de limpieza (escala Barcelona) en la que se aplicó una puntuación de 0 a 2 a cinco áreas del tracto digestivo superior (esófago, fundus, cuerpo, antro y duodeno) después de haber realizado todas las maniobras de lavado necesarias. Inicialmente, se evaluaron 125 fotos (25 de cada área) y se asignó una puntuación (de 0 a 2) a cada una por consenso entre siete endoscopistas. Posteriormente, se seleccionaron 100 de las 125 fotografías y se evaluó la variabilidad inter e intraobservador de 15 endoscopistas previamente formados utilizando las mismas imágenes en dos momentos diferentes. Resultados Se efectuaron un total de 1.500 observaciones. En 1.336/1.500 de ellas (89%) hubo coincidencia con la puntuación del consenso, siendo el valor medio de kappa de 0,83 (0,45-0,96). En la segunda evaluación, en 1.330/1.500 observaciones (89%) hubo coincidencia con la puntuación del consenso, siendo el valor medio de kappa de 0,82 (mínimo 0,45 y máximo 0,93). La variabilidad intraobservador fue de 0,89 (0,76-0,99). Conclusiones La escala de limpieza Barcelona es una medida válida y reproducible con un mínimo entrenamiento. Su uso en la práctica clínica podría ser un paso significativo para estandarizar la calidad de la EDA. (AU)

Open-label infliximab therapy in Crohn’s disease: a long-term multicenter study of efficacy, safety and predictors of response

OBJETIVO: La eficacia de infliximab en la enfermedad deCrohn (EC), demostrada por los diferentes ensayos clínicos,ha de ser confirmada en la práctica clínica. Nuestro objetivofue evaluar la eficacia y la seguridad del infliximab en pacientescon EC del área de Madrid, buscando predictores derespuesta.MÉTODOS: Estudio retrospectivo y multicéntrico que incluyelos pacientes con EC tratados con infliximab en 8 hospitalesde la Comunidad de Madrid, con un seguimiento mínimo de14 semanas.RESULTADOS: Se incluyó a un total de 169 pacientes (un 48%varones, con una edad de 39 ± 12 años), un 64% con enfermedadperianal y un 82% bajo tratamiento inmunosupresor.Se administraron un total de 1.355 perfusiones de infliximab(media, 8; rango, 1-30): un 90% de los pacientesrespondió, un 48% alcanzó la remisión clínica, un 73% siguiótratamiento de mantenimiento, y un 78% mantuvo omejoró su respuesta tras un seguimiento medio de 28 meses(rango, 3,5-86). Se perdió la respuesta durante el seguimientode 24 pacientes, tras una media de 41 semanas (rango, 6-248). Sólo la prescripción de tratamiento de mantenimientofue un predictor favorable de respuesta (p < 0,01); se contabilizaron 17 reacciones infusionales (en el 10% de los pacientes,el 1,2% de las perfusiones; sólo se constató un casograve) y fueron causa de la suspensión del tratamiento en 7pacientes. El cotratamiento con los inmunosupresores y eltratamiento de mantenimiento con infliximab fueron los factoresprotectores para sufrir reacciones infusionales (p <0,05). Otros efectos adversos se produjeron en el 26% de lospacientes, y fueron causa de suspensión del tratamiento en 7pacientes.CONCLUSIONES: Infliximab es eficaz y seguro en el tratamientode la EC, pero deberían prescribirse el tratamientode mantenimiento y el concomitante con inmunosupresorespara obtener los mejores resultados. Esto confirma en un escenariode práctica clínica real los resultados obtenidos enensayos clínicos

BACKGROUND: Efficacy of infliximab in Crohn’s disease(CD) showed by randomized controlled trials must beconfirmed in clinical practice. We aimed to evaluate efficacyand safety of infliximab in CD patients of the Madrid area,looking for clinical predictors of response.METHODS: Multicenter retrospective survey of all CD patientstreated with infliximab in 8 University hospitals of theMadrid area (Spain) with a minimum follow up of 14wks.RESULTS: 169 patients included (48%males, mean age 39 ±12 yrs). 64% of them had perianal disease. 82% were underimmunosuppressants. 1355 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 maintainedor improved the response after a mean follow up of 28months (range 3.5-86). 24 patients lost response during thefollow up, after a mean of 41wks (range 6-248). Only theprescription of maintenance therapy was predictive factorfor favourable response (p < 0.01). 17 infusion reactionswere reported (10% of the patients, 1.2% of the infusions;only one case was severe) and were the cause of treatmentwithdrawal in 7 patients. Co-treatment with immunosuppressivedrugs and maintenance infliximab therapy wereprotective factors for infusion reactions (p < 0.05). Other adverseevents occurred in 26% of the patients, and were causeof treatment withdrawal in 7 patients.CONCLUSIONS: Infliximab is effective and safe for CD managementbut concomitant immunosuppressive drugs andmaintenance treatment should be prescribed to obtain thebest outcome. That confirms in a real life clinical setting the favourable results obtained in randomized clinical trials (AU)