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Jesús K Yamamoto-Furusho Inflammatory Bowel Disease Clinic, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico Abstract: Inflammatory bowel disease (IBD) is a chronic and heterogeneous disorder characterized by remitting and relapsing periods of activity. Pharmacogenetics refers to the study of the effect of inheritance on individual variation in drug responses. Several drug-related markers in IBD patients have been identified in order to predict the response to medical treatment including biological therapy as well as the reduction of adverse events. In the future, the treatment of IBD should be personalized in its specific profile to provide the most efficacious treatment with lack of adverse events. Keywords: individualized medicine, pharmacogenomics, genetic, serologic, profile, treatment, prognostic factors

Background/Objective : Ingestion of dietary fiber can influence in the remission of patients with ulcerative colitis (UC). There are no current recommendations for fiber intake in UC; therefore, we evaluate the association between dietary fiber and the activity of the disease. Methods : Ours is a cross-sectional study in patients with a confirmed diagnosis of UC to whom a 24 h recall was applied; this allowed for the estimation and classification of type of dietary fiber. The patients were divided into two groups: (1) remission and (2) active UC. We analyzed the quantity and type of fiber with the grades of disease activity through Spearman correlation and logistic regression. Results : A total of 152 patients were included; it was found that those with clinically active UC consumed less total fiber ( p = 0.016) and insoluble fiber ( p = 0.018). Meanwhile, in endoscopic grade, the difference was for insoluble fiber ( p = 0.038). Insoluble fiber had an inversely significant correlation with fecal calprotectin levels (r = -0.204; p = 0.018). Logistic regression showed that less than 11 g of insoluble fiber was a risk factor for clinical activity (OR = 2.37; 95% CI 1.107-5.019; p = 0.026). Conclusions : Consumption below the current recommendation of total and insoluble dietary fiber is associated with clinical activity of UC.

Background: Recruitment for randomized controlled trials [RCTs] in inflammatory bowel diseases [IBD] has substantially dropped over time. This study aimed to assess reasons why IBD patients are not included in sponsored multicentre phase IIb-III RCTs., Methods: All IOIBD members [n = 58] were invited to participate. We divided barriers to participation as follows: [1] reasons patients with active IBD were not deemed appropriate for an RCT; [2] reasons qualified patients did not wish to participate; and [3] reasons for screen failure [SF] in patients agreeing to participate. We assess these in a 4-week prospective study including, consecutively, all patients with symptomatic disease for whom a treatment change was required. In addition, we performed a 6-month retrospective study to further evaluate reasons for SF., Results: A total of 106 patients (60 male [56.6%], 63 Crohn's disease [CD] [59.4%]), from ten centres across the world, were included in the prospective study. An RCT has not been proposed to 65 of them [mainly due to eligibility criteria]. Of the 41 patients to whom an RCT was offered, eight refused [mainly due to reluctance to receive placebo] and 28 agreed to participate. Among these 28 patients, five failed their screening and 23 were finally included in an RCT. A total of 107 patients (61 male [57%], 67 CD [62.6%]), from 13 centres worldwide, were included in our retrospective study of SFs. The main reason was insufficient disease activity., Conclusion: This first multicentre study analysing reasons for non-enrolment in IBD RCTs shows that we lose patients at each step. Eligibility criteria, the risk of placebo assignment, and insufficient disease activity were part of the main barriers., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Crohn's disease (CD) is a subtype of chronic and incurable inflammatory bowel disease. It can affect the entire gastrointestinal tract and its etiology is unknown., Objective: The aim of this consensus was to establish the most relevant aspects related to definitions, diagnosis, follow-up, medical treatment, and surgical treatment of Crohn's disease in Mexico., Material and Methods: Mexican specialists in the areas of gastroenterology and inflammatory bowel disease were summoned. The consensus was divided into five modules, with 69 statements. Applying the Delphi panel method, the pre-meeting questions were sent to the participants, to be edited and weighted. At the face-to-face meeting, all the selected articles were shown, underlining their level of clinical evidence; all the statements were discussed, and a final vote was carried out, determining the percentage of agreement for each statement., Results: The first Mexican consensus on Crohn's disease was produced, in which recommendations for definitions, classifications, diagnostic aspects, follow-up, medical treatment, and surgical treatment were established., Conclusions: Updated recommendations are provided that focus on definitions, classifications, diagnostic criteria, follow-up, and guidelines for conventional medical treatment, biologic therapy, and small molecule treatment, as well as surgical management., (Copyright © 2024 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.)

TOB/BTG is a family of antiproliferative proteins that play an important role in the regulation of immune responses, acting as lymphocyte activators and macrophage-mediated cytotoxicity. No previous studies have explored their role in patients with psoriasis. The aim of this study was to characterize the expression of TOB/BTG family and their co-localization in skin from patients with psoriasis. This is an exploratory, observational, and cross-sectional study that included 24 plaque psoriasis patients and 15 controls. Gene expression of TOB/BTG family was determinate by RT-PCR. Protein products of TOB/BTG were evaluated by immunohistochemistry and compared with control skin tissues. Holm-Sidak's multiple comparisons test was performed. TOB/BTG family mRNA levels and protein expression were significantly decreased in psoriatic skin tissue compared to non-inflammatory control skin tissue. Double-positive cell TOB1/2, BTG1,2 and BTG4/CD16 expressions were found in normal control skin tissues through epidermis and dermis (p < 0.001) and lesser percentage in patients with mild, almost absent in moderate-severe plaque psoriasis. This is the first report of the TOB/BTG family gene and protein expression in skin tissues by a CD16 + subpopulation in plaque psoriasis. TOB/BTG family protein might represent a new therapeutic target among immune-mediated inflammatory diseases., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

IL-39 (Interleukin-39) is a heterodimeric cytokine composed of IL-23p19 and EBI3 (Epstein-Barr virus-induced gene 3) subunits. Despite the evidence that correlates the role of IL-39 in regulating inflammation, its expression in the intestinal microenvironment of IBD (inflammatory bowel disease) patients is still unknown. Thus, this work was focused on characterizing relative mRNA (messenger RNA) IL-39 expression and intestinal synthesis in IBD patients. This study includes 37 patients diagnosed with ulcerative colitis (UC), 15 with Chron's disease (CD), and 22 controls. Gene expression of IL-39 subunits (IL-23p19/EBI3) was measured by RT-PCR (real time polymerase chain reaction). Intestinal synthesis was evaluated by immunohistochemistry and serum levels by ELISA. Statistical analysis was done using Prism GraphPad V6. Relative mRNA IL-39 expression was increased in patients with active UC and active CD compared to the remission UC, remission CD, and control group. High levels of relative mRNA expression of IL-39 (IL-23p19 subunit) were associated with histological activity. IHQ analysis showed increased IL-39 production in mucosa, submucosa, muscular, and serosa layer of patients with active disease. IL-39 serum production was increased in patients with UC. IL-39 gene's upregulation was found in patients with active IBD and was associated with severe histological activity in UC. This is the first report regarding the role of IL-39 in patients with IBD. The findings suggest that IL-39 might play a role as an inflammatory mediator in active IBD and could be considered a new alternative in treating this condition., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To determine if anxiety and depression are associated with a lower QoL in patients with UC in remission., Patients and Methods: We included consecutive patients with a previously confirmed diagnosis of UC in remission for at least 12 months and who answered complete questionnaires: IBDQ-32, HAD. Clinical and sociodemographic characteristics were obtained. We performed non-parametric tests, and correlations between HADS and IBDQ-32 were analyzed using Spearman's correlation coefficient (r). A p-value of less than 0.05 was considered significant., Results: Among 124 patients, 65% were men, with a median evolution of UC of 10 years (IQR: 5-79 years). Prevalence for anxiety was 15.3% and 2.4% for depression. Global QoL was 192 (IQR: 175-208). Lower QoL was associated with anxiety (p=0.002) and depression (p=0.013). Depression represented lower QoL at the digestive level than no depression (p=0.04). Anxiety negatively correlated with QoL (r=-0.54; p<0.001)., Conclusions: Anxiety is frequent in patients with UC in remission; therefore, timely diagnosis and treatment must be implemented to improve QoL., (Copyright © 2023. Publicado por Elsevier España, S.L.U.)

Background & Aims: The evolving epidemiologic patterns of inflammatory bowel disease (IBD) throughout the world, in conjunction with advances in therapeutic treatments, may influence hospitalization rates of IBD. We performed a systematic review with temporal analysis of hospitalization rates for IBD across the world in the 21st century., Methods: We systematically reviewed Medline and Embase for population-based studies reporting hospitalization rates for IBD, Crohn's disease (CD), or ulcerative colitis (UC) in the 21st century. Log-linear models were used to calculate the average annual percentage change (AAPC) with associated 95% confidence intervals (95% CIs). Random-effects meta-analysis pooled country-level AAPCs. Data were stratified by the epidemiologic stage of a region: compounding prevalence (stage 3) in North America, Western Europe, and Oceania vs acceleration of incidence (stage 2) in Asia, Eastern Europe, and Latin America vs emergence (stage 1) in developing countries., Results: Hospitalization rates for a primary diagnosis of IBD were stable in countries in stage 3 (AAPC, -0.13%; 95% CI, -0.72 to 0.97), CD (AAPC, 0.20%; 95% CI, -1.78 to 2.17), and UC (AAPC, 0.02%; 95% CI, -0.91 to 0.94). In contrast, hospitalization rates for a primary diagnosis were increasing in countries in stage 2 for IBD (AAPC, 4.44%; 95% CI, 2.75 to 6.14), CD (AAPC, 8.34%; 95% CI, 4.38 to 12.29), and UC (AAPC, 3.90; 95% CI, 1.29 to 6.52). No population-based studies were available for developing regions in stage 1 (emergence)., Conclusions: Hospitalization rates for IBD are stabilizing in countries in stage 3, whereas newly industrialized countries in stage 2 have rapidly increasing hospitalization rates, contributing to an increasing burden on global health care systems., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There is a rapid increase in the incidence of inflammatory bowel diseases (IBD) in newly industrialized countries, yet epidemiological data is incomplete. We herein report the methodology adopted to study the incidence of IBD in newly industrialized countries and to evaluate the effect of environmental factors including diet on IBD development., Methods: Global IBD Visualization of Epidemiology Studies in the 21st Century (GIVES-21) is a population-based cohort of newly diagnosed persons with Crohn's disease and ulcerative colitis in Asia, Africa, and Latin America to be followed prospectively for 12 months. New cases were ascertained from multiple sources and were entered into a secured online system. Cases were confirmed using standard diagnostic criteria. In addition, endoscopy, pathology and pharmacy records from each local site were searched to ensure completeness of case capture. Validated environmental and dietary questionnaires were used to determine exposure in incident cases prior to diagnosis., Results: Through November 2022, 106 hospitals from 24 regions (16 Asia; 6 Latin America; 2 Africa) have joined the GIVES-21 Consortium. To date, over 290 incident cases have been reported. All patients have demographic data, clinical disease characteristics, and disease course data including healthcare utilization, medication history and environmental and dietary exposures data collected. We have established a comprehensive platform and infrastructure required to examine disease incidence, risk factors and disease course of IBD in the real-world setting., Conclusions: The GIVES-21 consortium offers a unique opportunity to investigate the epidemiology of IBD and explores new clinical research questions on the association between environmental and dietary factors and IBD development in newly industrialized countries., (© 2023. The Author(s).)

Background & Aims: Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the Definition and endpoints for ulcerative PROCtitis in clinical TRIALs initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults., Methods: Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters., Results: The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity was proposed. Secondary endpoints that should be evaluated include endoscopic remission, histologic remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life., Conclusions: In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the Definition and end points for ulcerative PROCtitis in clinical TRIALs consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Ulcerative colitis (US) is a chronic disease of unknown etiology. It is incurable and its clinical course is intermittent, characterized by periods of remission and relapse. The prevalence and incidence of the disease has been increasing worldwide. The update presented herein includes the participation of healthcare professionals, decision-makers, and a representative of the patients, all of whom declared their conflicts of interest. Answerable clinical questions were formulated, and the outcomes were graded. The information search was conducted on the Medline/PubMed, Embase, Epistemonikos, and LILACS databases, and covered grey literature sources, as well. The search was updated on November 30, 2020, with no restrictions regarding date or language. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification system was implemented to establish the strength of the recommendation and quality of evidence. A formal consensus was developed, based on the RAND/UCLA methodology and the document was peer reviewed. The short version of the Clinical Practice Guidelines for the Treatment of Ulcerative Colitis in the Adult Population is presented herein, together with the supporting evidence and respective recommendations. In mild-to-moderate UC, budesonide MMX is an option when treatment with 5-ASA fails, and before using systemic steroids. In moderate-to-severe UC, infliximab, adalimumab, vedolizumab, ustekinumab, and tofacitinib can be used as first-line therapy. If there is anti-TNF therapy failure, ustekinumab and tofacitinib provide the best results. In patients with antibiotic-refractory pouchitis, anti-TNFs are the treatment of choice., (Copyright © 2022 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.)

Introduction and Aims: The 5-aminosalicylates, especially mesalazine, are the first option in the treatment of mild-to-moderate ulcerative colitis (UC). High rates of remission induction and maintenance have been observed with the new multimatrix (MMX) mesalazine formulation, mainly in patients with distal disease. Our aim was to describe the real-world experience with MMX mesalazine in patients with UC at two tertiary care centers., Materials and Methods: A retrospective cohort study was conducted that included 142 patients with confirmed UC diagnosis, analyzed in three study groups: 1) oral MMX mesalazine as monotherapy for remission induction, 2) oral MMX mesalazine as monotherapy for remission maintenance, and 3) oral MMX mesalazine plus topical therapy for remission induction., Results: The frequency of clinical remission induction in group 1 was 80.3%, with biochemical remission of 74.2%. Group 2 had 100% clinical and biochemical remission maintenance. The frequency of clinical remission induction in group 3 was 88.6%, biochemical remission was 85.7%, and topical therapy was suspended in 87.3% at the end of follow-up. No adverse events were documented., Conclusions: There were high percentages of clinical and biochemical remission in the two corresponding study groups and topical therapy was suspended in the majority of patients in ashort follow-up period., (Copyright © 2021 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.)

Abstract: The aim of the present study was to describe the epidemiological and clinical characteristics of inflammatory bowel disease (IBD), including medical and surgical treatments, in several countries in Latin America and the Caribbean.IBD is recognized as a global health problem because its incidence and prevalence have increased significantly over the last few years.This multicenter retrospective cohort study included 4714 patients with IBD diagnosed from 9 countries in Latin America and the Caribbean: Colombia, Cuba, Dominican Republic, Ecuador, Mexico, Peru, Puerto Rico, Uruguay, and Venezuela.Crohn disease (CD) was more frequent in Puerto Rico (71.9%), the Dominican Republic (61.0%), and Peru (53.1%). Ulcerative colitis was more frequent in Colombia (78.6%), Venezuela (78.2%), Mexico (75.5%), Cuba (69.9%), Ecuador (64.1%), and Uruguay (60.9%). The following clinical characteristics were more frequent in the Caribbean: penetrating behavior in CD, steroid dependence, steroid resistance, intolerance to thiopurines, extraintestinal manifestations, surgeries, hospitalizations due to IBD, and family history of IBD. The factors associated with the use of biological therapy were pancolitis in ulcerative colitis, penetrating behavior in CD, steroid resistance and dependence, presence of extraintestinal manifestations, and the need for surgery.This study from Latin America and the Caribbean demonstrated the different epidemiological and clinical characteristics of IBD., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Inflammatory bowel disease (IBD) is a chronic and incurable entity. The aim of the Pan American Crohn's and Colitis Organisation (PANCCO) is to create awareness of IBD, with special emphasis on Latin America, and the primary objective of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU, the Spanish acronym) is to obtain the accreditation of the clinical and therapeutic criteria for the diagnosis and treatment of IBD., Aim: To carry out a consensus for evaluating the approval criteria that a Comprehensive Care Clinic for Latin American IBD patients must meet, to be considered a center of excellence., Materials and Methods: Fourteen clinical experts participated in the consensus. They were made up of specialists in gastroenterology, with broad clinical experience, spanning several years, in managing the care of a large number of patients with IBD, as well as advanced specialists in IBD. Thirteen of the participants came from 11 Latin American countries (Argentina, Brazil, Colombia, Dominican Republic, Ecuador, Guatemala, Mexico, Peru, Puerto Rico, Uruguay, and Venezuela) that have IBD clinics. An expert from Spain, representing the GETECCU, provided the methodologic support. The consensus consisted of 52 statements divided into three sections: 1) Structure indicators, 2) Process indicators, and 3) Result indicators. The Delphi panel method was applied., Results: The present Latin American consensus describes the quality indicators that a Comprehensive Care Clinic for IBD patients must meet, to be considered a center of excellence, taking into account the needs of our region., Conclusions: This is the first Latin American consensus, jointly carried out by the PANCCO and GETECCU, to present accreditation standards for centers of excellence in the care of patients with IBD., (Copyright © 2021 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.)

Introduction: Dietary fiber intake helps in the remission of ulcerative colitis (UC)., Objective: To evaluate if there is an association between the amount of fiber in usual diet and disease activity in patients with UC., Methods: Cross-sectional study of a cohort of patients with UC. Dietary fiber intake was calculated and compared with the recommended amount (14 g/1000 kcal) with Mann-Whitney's U-test. Using Spearman's correlation coefficient, the number of relapses and the amount of consumed fiber were analyzed, and the relationship of dietary fiber consumption with disease activity was established by logistic regression., Results: The group without ongoing UC activity consumed a higher amount of dietary fiber (20 g, IQR = 18-26, p = 0.062), and 47% consumed more than the recommended amount; the logistic regression analysis showed that compliance with recommended fiber consumption was associated as a protective factor against UC current activity (OR = 0.227, p = 0.032). As for dietary fiber intake and the number of relapses within previous year, an inversely proportional correlation was observed (r = -0.399, p = 0.011)., Conclusions: Consumption of the recommended dietary fiber amount in the general population had a protective effect against UC activity in Mexican patients., (Copyright: © 2022 Permanyer.)

Inflammatory bowel disease (IBD) is a chronic disease that requires chronic treatment throughout the evolution of the disease, with a complex physiopathology that entails great challenges for the development of new and specific treatments for ulcerative colitis and Crohn´s disease. The anti-tumor necrosis factor alpha therapy has impacted the clinical course of IBD in those patients who do not respond to conventional treatment, so there is a need to develop new therapies and markers of treatment response. Various pathways involved in the development of the disease are known and the new therapies have focused on blocking the inflammatory process at the gastrointestinal level by oral, intravenous, subcutaneous, and topical route. All these new therapies can lead to more personalized treatments with higher success rates and fewer relapses. These treatments have not only focused on clinical remission, but also on achieving macroscopic changes at the endoscopic level and microscopic changes by achieving mucosal healing. These treatments are mainly based on modifying signaling pathways, by blocking receptors or ligands, reducing cell migration and maintaining the integrity of the epithelial barrier. Therefore, this review presents the efficacy and safety of the new treatments that are currently under study and the advances that have been made in this area in recent years., Competing Interests: Conflict-of-interest statement: Yamamoto-Furusho JK is a member of the advisory board, an opinion leader and speaker for Abbvie Laboratories de México, Abbvie (international), Takeda México, Pfizer (international and regional), and Janssen Cilag (international and Mexico). He is an opinion leader and speaker for Farmasa, Ferring, and Farmasa Schwabe and a research advisor for UCB México. He has received funds for research studies from the Shire, Bristol Myers Squib, Pfizer, Takeda, and Celgene laboratories. Parra-Holguín NN declares no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn's disease (CD) characterized by a fluctuating course with periods of clinical activity and remission. No previous studies have demonstrated the frequency of delay at diagnosis and its associated factors in Mexico and Latin America. The aim of this study was to evaluate diagnostic delay of IBD in the last 4 decades in 2 different health care systems (public vs. private) and its associated factors., Methods: This is a cohort study that included 1,056 patients with a confirmed diagnosis of IBD from public and private health care systems. The diagnostic delay was defined as time >1 year from the onset of symptoms to the confirmed diagnosis for patients with UC and 2 years for patients with CD. Statistical analysis was performed with the SPSS v.24 program. A value of p ≤ 0.05 was taken as significant., Results: The delay at diagnosis decreased significantly by 24.9% in the last 4 decades. The factors associated with the diagnostic delay were proctitis in UC, clinical course >2 relapses per year and IBD surgeries for CD. We found a delay at diagnosis in 35.2% of IBD patients in the public versus 16.9% in the private health care system ( p = 0.00001)., Conclusions: We found a significant diagnosis delay of IBD in 35.2% from the public health care system versus 16.9% in the private health care system., (Copyright © 2021 by The Author(s). Published by S. Karger AG, Basel.)

Background: Inflammatory bowel disease comprises two conditions: ulcerative colitis and Crohn's disease. Inflammatory Bowel Disease Questionnaire 32 (IBDQ-32) is a specific questionnaire which has been translated from English into Spanish and validated. In the Spanish-speaking countries of America it has not been validated. The aim was to determine the psychometric properties, validity and reliability of the Mexican version of the IBDQ-32 questionnaire., Methods: A total of 316 patients with inflammatory bowel disease and 100 healthy controls participated in the study. The questionnaires IBDQ-32 and SF-36 were issued on two occasions (separated by 15 days). The psychometric properties of the Mexican version of the IBDQ-32 questionnaire were determined., Results: Patients with inflammatory bowel disease had an impaired quality of life compared to healthy controls. There were no differences between ulcerative colitis and Crohn's disease in the total scores of IBDQ-32 and its domains. The internal consistency reliability was good. The intraclass coefficient showed good reliability (repeated measurement) for total scale and all four subscales. Factor analysis explained variance is higher than 50% therefore is considered adequate/acceptable. The correlation between IBDQ-32 and SF-36 showed a satisfactory association. The social domain is the only one that presented a ceiling effect., Conclusions: The Mexican version of the IBDQ-32 quality of life questionnaire is valid and reliable. This sample included the entire spectrum of inflammatory disease (remission and activity) and was comparable when assessing quality of life with the SF-36 generic questionnaire., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

Background: Cow's milk protein allergy (CMPA) is the most prevalent food allergy in children, and its pathogenesis remains poorly understood. It has been shown that the combination of genetic predisposition, perinatal factors, and intestinal imbalance of the immune response mediated by cytokines may play an essential role in CMPA pathogenesis., Aim: To characterize the gene expression of Th1, Th2, and Th17 cytokines in the duodenum and rectum in patients with CMPA., Methods: This is an observational, descriptive, cross-sectional, prospective study. We used specific IgE (ImmunoCAP ® ) in serum and biopsies from the rectum and duodenum for the detection of cytokine messenger RNA levels by real-time PCR in patients with a positive oral food challenge for CMPA. We analyzed the relative quantification of the gene expression of cytokines by real-time PCR, and we used the housekeeping gene GAPDH for normalization purposes., Results: Thirty children (13 male and 17 female) were evaluated. All patients had an open challenge for CMPA. IgE specific to casein, alfa-lactalbumin, and beta-lactoglobulin was negative in all patients. In terms of cytokine levels, the levels of TNFα, IL-6, IL-12 (Th1), IL-4, IL-10, IL-13 (Th2), and IL-17 were found to be higher in the rectum than in the duodenum (p < 0.05). IL-15 was found to be higher in the duodenum than in the rectum (p < 0.05)., Conclusions: In the present study we observed that the immune response in CMPA seems to be mediated by a Th1, Th2, and Th17 cytokine profile, with the rectum being the main affected site., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Anxiety and depression have a negative influence in the quality of life. The aim of the study was to determinate the levels of sensitivity and specificity of the Anxiety and Hospital Depression Scale (HADS) and compare the quality of life in patients with inflammatory bowel disease (IBD) and depression or anxiety., Methods: This study included 104 patients with diagnosis of IBD. Each patient received psychiatric intervention with SCID-I (Structured Clinical Interview for DSMIV Axis I Disorders) instrument as a gold standard to stablish the cut-off points of HADS. Quality of life was also evaluated with IBDQ-32. Demographic and clinical variables were collected., Results: Most of the patients reported a high quality of life (73.1%, n = 76), while 25.0% ( n = 26) express a moderate quality of life. The ROC curves for both psychiatric entities showed an adequate discriminative capacity of the HADS-anxiety dimension (AUC = 0.84, 95%CI = 0.76-0.92) with a limited discriminability of the HADS-depression dimension (AUC = 0.58, 95%CI = 0.46-0.70) using the proposed scoring of 8 as a cut-off point., Conclusions: Anxiety and depression impact negatively in the quality of life in Mexican patients with IBD. The Mexican version of HADS had acceptable internal consistency and external validity, with moderate sensitivity and specificity for clearly identifying clinical cases of anxiety and depression in patients with IBD., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Jesús K. Yamamoto-Furusho et al.)

The gene of A-kinase anchor protein 12 (AKAP12) regulates cell cycle progression, cell motility, and morphology through its multiple scaffolding domains. However, the role of AKAP12 expression in ulcerative colitis (UC) patients has not been yet described. The aim of the study was to describe the gene and protein of AKAP12 expression in patients with UC and its association regarding the disease severity. We included a total of 40 patients with confirmed diagnosis of UC and 25 controls without endoscopic evidence of colitis or neoplasia. The relative quantification of the gene expression was performed by real-time PCR for AKAP12. Kruskal-Wallis was used to test differences among groups, and Spearman correlation to assess the relationship between AKAP12 gene and clinical outcomes. The extent of disease was evaluated using total colonoscopy, and biopsies were taken from rectum segments. The AKAP12 gene expression was increased in colonic mucosa from patients with active UC when compared with UC remission and control group. The overexpression of AKAP12 in patients with UC was associated with the presence of extensive colitis (p = 0.04, RM = 12, IC = 1.29-186.37). AKAP12/CD16 double positive cells were higher in submucosa (p = 0.04), muscular (p < 0.001), and cells from serosa (p < 0.001) in patients affected by UC in comparison to controls. The overexpression of AKAP12 was associated with the extent of disease. This is the first report about the role of AKAP12 in patients with UC suggesting that this gene and its protein could be involved in the modulation of the disease., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Inflammatory bowel disease includes ulcerative colitis (UC) and Crohn's disease (CD) of unknown etiology. The expression of ATP-binding cassette (ABC) family proteins has been associated with drug resistance and development of UC. The cystic fibrosis transmembrane conductance regulator (CFTR) or also known as ABCC7 is involved in the inflammatory chronic response. The aim of this study was to evaluate the role of ABCC7/CFTR in UC patients and normal controls without inflammation. This is an exploratory, observational, and cross-sectional study that included a total of 62 patients with UC and normal controls. Gene expression of CFTR was measured by RT-PCR, and protein expression of CFTR was determined by western blot analysis. We found a significant downregulation of the CFTR gene expression in patients with active UC compared to normal controls without inflammation ( P < 0.004); even the gene expression of CFTR was decreased in remission UC patients compared to normal controls without inflammation ( P = 0.04). The CFTR gene expression was associated with the clinical course of UC and the protein expression of CFTR was decreased in active UC patients compared to normal controls without inflammation suggesting that this molecule might play a role in the inflammation in UC patients., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Marco A. Villeda-Ramírez et al.)

Goals: The aim of this study was to describe mental health factors associated with the development of fatigue in inflammatory bowel disease (IBD) patients., Background: IBD includes ulcerative colitis and Crohn's disease. Patients with chronic diseases can present fatigue differently and qualitatively more severely than those typically represented by healthy populations., Study: This was a cross-sectional study in which 200 Mexican patients were attending the Inflammatory Bowel Disease Clinic at the National Institute of Medical Sciences and Nutrition. All patients answered 3 instruments: the first IBD-fatigue, HADS (Hospital Anxiety and Depression Scale), and PSQI (Pittsburgh Sleep Quality Index). The statistical analysis was carried out in the statistical program SPSS v 24., Results: The percentage of fatigue in our patients was 55.5% (n=111) for mild-moderate fatigue, 31.5% (n=63) for severe fatigue, and only 13% (n=26) had no fatigue. Sleep disturbance and sleep latency were the most important predictors of fatigue in IBD patients., Conclusions: Sleep quality and depression have an impact on fatigue in Mexican patients with IBD. It is important for multidisciplinary management to reduce these symptoms and improve the quality of life of patients with IBD., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction and Aims: The 5-aminosalicylates, especially mesalazine, are the first option in the treatment of mild-to-moderate ulcerative colitis (UC). High rates of remission induction and maintenance have been observed with the new multimatrix (MMX) mesalazine formulation, mainly in patients with distal disease. Our aim was to describe the real-world experience with MMX mesalazine in patients with UC at two tertiary care centers., Materials and Methods: A retrospective cohort study was conducted that included 142 patients with confirmed UC diagnosis, analyzed in three study groups: 1) oral MMX mesalazine as monotherapy for remission induction, 2) oral MMX mesalazine as monotherapy for remission maintenance, and 3) oral MMX mesalazine plus topical therapy for remission induction., Results: The frequency of clinical remission induction in group 1 was 80.3%, with biochemical remission of 74.2%. Group 2 had 100% clinical and biochemical remission maintenance. The frequency of clinical remission induction in group 3 was 88.6%, biochemical remission was 85.7%, and topical therapy was suspended in 87.3% at the end of follow-up. No adverse events were documented., Conclusions: There were high percentages of clinical and biochemical remission in the two corresponding study groups and topical therapy was suspended in the majority of patients in a short follow-up period., (Copyright © 2021 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.)

Background and Aims: Persons with inflammatory bowel disease (IBD) may be particularly vulnerable to COVID-19 either because of their underlying disease or its management. Guidance has been presented on the management of persons with IBD in the time of this pandemic by different groups. We aimed to determine how gastroenterologists around the world were approaching the management of IBD., Methods: Members of the World Gastroenterology Organization (WGO) IBD Task Force contacted colleagues in countries largely beyond North America and Europe, inviting them to review the WGO website for IBD and COVID-19 introduction, with links to guideline documents, and then to respond to 9 ancillary open-ended management questions., Results: Fifty-two gastroenterologists from 33 countries across 6 continents completed the survey (April 14 to May 16, 2020). They were all adhering for the most part to published guidelines on IBD management in the COVID-19 era. Some differences and reductions in services related to access, and some related to approach within their communities in terms of limiting virus spread. In particular, most gastroenterologists reduced in-person clinics (43 of 52), limited steroid use (47 of 51), limited elective endoscopy (45 of 52), and limited elective surgeries (48 of 51). If a patient was diagnosed with COVID-19, immunomodulatory therapy was mostly held., Conclusions: In most countries, the COVID-19 pandemic significantly altered the approach to persons with IBD. The few exceptions were mostly based on low burden of COVID-19 in individual communities. Regardless of resources or health care systems, gastroenterologists around the world took a similar approach to the management of IBD., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The clinical endoscopic phenotypes of gastroesophageal reflux disease (GERD) are classified as Barrett's esophagus (BE), erosive esophagitis (EE) and non-erosive gastroesophageal reflux disease (NERD). NERD is subclassified as abnormal acid exposure (AAE) and normal acid exposure (NAE) based on pH monitoring study results. The aim of this study was to characterize genes involved in the pathophysiology and immune response of GERD., Methods: This is an observational and cross-sectional study. All patients with BE, EE, AAE, and NAE and a control group were subjected to superior endoscopy (with biopsies of esophageal mucosa). Relative mRNA quantification of cytokine and target genes was conducted by quantitative Polymerase Chain Reaction (RT-qPCR). Changes in the expression of genes associated with inflammation were assessed for each disease phenotype. Statistical analysis of differential gene expression was performed using the Mann-Whitney U non-parametric test. A p value < 0.05 was considered significant., Results: A total of 82 patients were included and were divided into the following groups: Group BE, 16 (19.51%); Group EE, 23 (28.04%); Group AAE, 13 (15.86%); NAE 13 (15.86%); and Control Group, 17 (20.73%). Compared with the control group, patients with BE exhibited increased IL-8 expression (p < 0.05) and increased levels of IL-10, MMP-3, and MMP-9. Patients with EE exhibited increased levels of IL-1B, IL-6 and IL-10 (p < 0.05), and patients with AAE exhibited increased expression of IL-1B, IL-6, IFN-γ and TNF-α (p < 0.05). AAE exhibited increased IL-1B and TNF-α expression compared with NAE (p < 0.05)., Conclusion: This study demonstrates the differential expression of mediators of inflammation in the esophageal mucosa of patients with different GERD endoscopic phenotypes. IL-1B and TNF-α could be useful to differentially diagnose AAE and NAE in the non-erosive phenotype using endoscopic biopsies.

Background: Ulcerative colitis (UC) is an inflammatory disease of the intestine. The genetics factors play an important role in the pathogenesis of UC. SPARC exacerbates colonic inflammatory symptoms in dextran sodium sulphate-induced murine colitis. The aim of the study was to measure the gene expression and intestinal production of SPARC in patients with UC and controls as well as, to determine its correlation with histological activity., Methods: We included 40 patients with confirmed diagnosis of UC, and 20 controls without endoscopic evidence of any type of colitis or neoplasia. The relative quantification of the gene expression was performed by real time PCR. GAPDH was used as housekeeping gene for normalization purposes and quality controls. Protein expression was determined by immunohistochemistry., Results: The gene expression of SPARC was increased in patients with active UC vs in remission UC and vs. controls (P = 0.005). There was no significant difference between patients with remission UC and controls. The overexpression of SPARC in patients with active UC correlated significantly with mild histological activity (P = 0.06, OR = 7.77, IC = 0.77-77.9) moderate (P = 0.06, OR = 8.1, IC 95%=0.79-82.73), and severe (P = 0.03, OR = 6.5, IC 95%=1.09-38.6). Double positive SPARC+/CD16+ cells were localized mainly in submucosa, muscular layer, and adventitia, and in perivascular inflammatory infiltrates in patients with active UC., Conclusion: The gene and protein expression of SPARC is increased in active UC. SPARC could be a marker of intestinal inflammation and its expression correlates with histological activity., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

In recent years, the role of anti-proliferative TOB proteins in the regulation of immune response by inhibiting T cell activation has been demonstrated. Nevertheless, no previous studies have explored their expression in patients with IBD. The aim of the study was to characterize the gene and protein expression of the TOB/BTG family in intestinal tissue of patients with IBD. This is an observational and cross-sectional study that included 63 IBD patients. Gene expression of TOB/BTG family was measured by RT-PCR. Protein expression of TOB/CD16 and BTG/Ki-67 was evaluated by immunohistochemistry. TOB/BTG family mRNAs were detected and quantitated by RT-qPCR in rectal and ileum biopsies from UC patients and CD patients, respectively, and non-inflammatory control tissues. Results showed that TOB1 and BTG1 gene expression was decreased in the colonic mucosa from patients with UC compared with the control group. The TOB2 and BTG2 genes were over-expressed in the colonic mucosa of patients with UC in remission compared with the active UC and control group. The high TOB2 gene expression was associated with histological remission (P = .01). TOB1/CD16, TOB2/CD16, BTG1/Ki-67, BTG2/Ki-67 and BTG4/Ki-67 single and double positive cells were mostly NK, macrophages, epithelial cells, connective tissue cells and perivascular inflammatory infiltrates in tissues from patients with UC and CD. This is the first depiction of the TOB/BTG family gene and protein expression in rectal and ileum tissues by a CD16 + subpopulation in IBD., (© 2020 The Scandinavian Foundation for Immunology.)

Introduction: Different studies have described psychiatric comorbidities in inflammatory bowel disease (IBD) patients, but most of them focus mainly on depression and anxiety. Even though major mental disorders are considered one of the main factors that decrease quality of life (QoL), its role in IBD patients remains unclear. We sought to identify the prevalence of different mental disorders as well as its relationship with QoL., Patients and Methods: Subjects were recruited from the IBD Clinic. IBD Questionnaire 32 and structured clinical interview (SCID) for DMS-IV Text Revision were applied. Demographic and clinical data were collected via self-report questionnaires and medical records. The correlation between mental disorders and QoL (IBDQ-32 score) was evaluated using the Spearman correlation test., Results: In all, 104 patients were recruited, 12 with Crohn's disease, and 92 with ulcerative colitis. The prevalence of any major mental disorder was 56.7%: anxiety (44.2%), mood (27.9%), substance use (12.2%), and other psychiatric diagnoses (17.3%), and 29.8% of the patients presented three or more comorbid diagnoses. Mental Disorder (p=0.005), mood disorder (p=0.004), anxiety disorder (p=0.009), were found to be significantly associated with lower QoL. Substance use disorder was associated with lower Digestive QoL (p=0.01). Major depressive disorder (p=0.004), social phobia (p=0.03), PTSD (p=0.02), and Generalized Anxiety Disorder (p<0.001), were found to be significantly associated with lower QoL., Conclusions: IBD patients had important psychiatric comorbidity that significantly affects their QoL. These results warrant a systematic evaluation of psychiatric conditions in IBD patients., (Copyright © 2020 Elsevier España, S.L.U. All rights reserved.)

Introduction: Fatigue is an extra-intestinal manifestation of inflammatory bowel disease (IBD)., Objective: To determine the construct validity, discriminant validity and reliability of an instrument for evaluating the Fatigue Scale for IBD in Mexican patients., Methods: Two hundred patients with an IBD confirmed diagnosis were included. Current demographic and clinical characteristics of the condition were evaluated. Each patient answered the IBD Fatigue Scale (IBD-F) and the Pittsburgh Sleep Quality Index (PSQI), which was used to determine IBD-F discriminant validity. A factor analysis of each IBD-F section was performed, independent sample Student's t-tests were used to contrast the PSQI, and reliability was evaluated using Cronbach's alpha., Results: The items in both IBD-F sections showed high factor loadings, which explained 68.3 and 38.4% of variance, respectively. Cronbach's alpha was > 0.80 in both, which discriminated patients with greater sleep disturbances., Conclusions: IBD-F is a valid and reliable scale for Mexican patients with IBD. Fatigue objective evaluation will allow timely interventions in order to reduce its impact on patients with IBD., (Copyright: © 2021 Permanyer.)

Introduction and Aim: The Revista de Gastroenterología de México (RGM), founded in 1935, is one of the most influential journals of scientific dissemination in Mexico and Latin America. The aim of the present review was to characterize the RGM's most frequently cited original articles, review articles, and consensuses., Methods: The most cited original articles, review articles, and consensuses of the RGM were identified using the Scopus, PubMed, and Google Scholar databases. Their designs and topics, as well as their authors and participating institutions, were analyzed., Results: The most highly cited articles of the RGM corresponded to the period from 1996 to 2018, with a mean of 16.5 citations per article. Fifty-eight percent (n = 29) of the articles belonged to the area of gastroenterology and 20% (n = 10) to surgery. The most frequent topics were functional gastrointestinal disorders, hepatitis virus, and gastric cancer. Thirty-six percent of the articles had a nonrandomized prospective design, followed by cross-sectional studies (26%) and randomized prospective studies (18%)., Conclusion: The 50 most-cited articles included a total of 826 citations and the 10 most-cited consensuses and review articles had a total of 208 citations. Those studies encompass a diversity of disciplines related to gastroenterology that have impacted the scientific community and correspond to the work of different active research groups in Mexico and other countries., (Copyright © 2020 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.)

Background: Chronic idiopathic ulcerative colitis (CIUC) is a disease with multifactorial chronic inflammation of the colonic mucosa. Its prevalence ranges from 37.5-250/100,000 in North America to 10-500/100,000 in Europe. In Mexico, there are studies that show an increase in the frequency of new cases. The purpose of this work was to identify possible changes in CIUC behavior in a referral hospital., Methods: New ulcerative colitis (UC) cases confirmed by histopathology from January 2007 to December 2014 were included. Clinical and demographic data were collected through the review of medical records and direct interview in order to compare them with a previous study conducted at the same institution from January 1986 to December 2006., Results: A total of 189 patients were included. Mean number of UC annual new cases was 23.6. The study included 95 male patients (50 %) and 94 female patients (50 %), with an average age of 44.6 years at diagnosis. The frequency of pancolitis was 77 %, in comparison with 59 % in the previous period. Extra-intestinal manifestations (EIM) were present in 55.8 % and colectomies in 5.2 %., Conclusion: There is a lower mean of annual new cases; however, some characteristics of the disease have changed over time: there is an increased frequency of pancolitis and EIM, as well as a decrease in the rate of colectomies., (Copyright: © 2021 Permanyer.)

It has been reported that EMMPRIN is involved in the regulation of immune response and the induction of MMPs production by fibroblasts. The aim of this study was to describe the intestinal gene expression and protein production of EMMPRIN, MMP23 and MMP10 in patients with ulcerative colitis (UC) and Crohn's disease (CD) and compared them with a control group. Gene expression of EMMPRIN, MMP10 and MMP23B was measured by RT-PCR. In order to determine EMMPRIN and MMP protein expression, colonic tissues were immunostained. The results of the study showed EMMPRIN gene expression was upregulated in rectal mucosa from active (a)UC versus aCD patients (P = .045), remission (r)CD group (P = .0009) and controls (P < .0001). We detected differences between rUC and aCD (P = .004), rCD (P < .0001) or control group (P < .0001). EMMPRIN showed a higher expression in mucosa (intraepithelial lymphocytes), submucosa and adventitia (endothelial cells) from aCD patients. MMP23 levels were increased in aUC and aCD compared to rUC and rCD and the control group (P = .0001). EMMPRIN+/MMP23+─expressing cells were localized mainly in mucosa, muscular and adventitia from active UC patients. MMP10 gene expression was increased in aUC versus CD patients and the control group (P = .0001). MMP10 gene expression is associated with inflammation in UC patients (P = .0001, r 2  = .585). EMMPRIN+/MMP10+─producing cells were found mainly in all intestinal layers and perivascular inflammatory infiltrates from aUC patients. In conclusion, EMMPRIN, MMP23 and MMP10 were upregulated in patients with active UC versus remission UC , CD and control groups suggesting that, they are involved in the inflammatory process., (© 2020 The Scandinavian Foundation for Immunology.)

Background: Currently, the treatment goal in ulcerative colitis (UC) is to achieve clinical and endoscopic remission; nevertheless, histologic remission is a potential new treatment goal since it is associated with favorable long-term clinical outcome lower rates of hospitalization, complications, and colectomies., Aim: Evaluate clinical and histopathologic characteristics at diagnosis as potential predictors of histologic remission in patients with ulcerative colitis., Methods: This is a retrospective cohort study from 2007 to 2014, including 260 patients. Clinical and demographic information and Mayo endoscopic and Riley histologic grade were obtained accordingly with the follow-up. Histological evaluation was made for all 260 patients; fifty-six patients with histologic remission at the follow-up underwent separate evaluation of mucosal biopsy at the moment of diagnosis. Univariate and multivariate analyses were applied to data from these 56 patients to identify histologic features at diagnosis associated with histologic remission during follow-up. The odds ratio (OR) was determined as a measure for the strength of association. A P value of less than 0.05 was taken as a level of significance., Results: The frequency of histologic remission according to the Riley index in our study group was 21.5%. Factors associated with histologic remission were treatment with steroids ( P = 0.01, OR = 0.38, CI 95% = 0.16-0.90), reduced mucin production ( P = 0.02, OR = 0.23, CI 95% = 0.06-0.86), and less than 10 eosinophils per high power field ( P = 0.001, OR = 6.66, CI 95% = 2.03-21.84)., Conclusion: Factors that impair histologic remission in patients with ulcerative colitis were treatment with steroids and reduced mucin production; meanwhile, less than 10 eosinophils per high power showed a predictive value for histologic remission., Competing Interests: The authors declare they have no competing interests., (Copyright © 2020 Jesús K. Yamamoto-Furusho et al.)

Background and Aim: Ulcerative colitis (UC) is a subtype of inflammatory bowel disease that can develop extraintestinal manifestations (EIMs) in a subgroup of patients. The aim of this work was to study the frequency and clinical factors associated with the development of EIMs., Methods: We evaluated a total of 260 Mexican patients with confirmed UC who were followed retrospectively in order to identify the factors associated with the presence of EIMs., Results: The frequency of EIM was 55.8%. The factors associated with the development of EIM were pancolitis ( p = 0.003, OR = 2.44, 95% CI = 1.34-4.56) and previous colectomy ( p = 0.024, OR = 7.54, 95% CI = 1.20-60.44). A clinical course of initial activity and then long remission for >5 years was found to be a protective factor ( p = 0.002, OR = 0.31, 95% CI = 0.14-0.67)., Conclusion: The frequency of EIM was 55.8% in our population, and the factors associated with their development were pancolitis and colectomy; meanwhile, a clinical course of initial activity and then long remission was a protector feature., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 by S. Karger AG, Basel.)

Background: Incidence of inflammatory bowel disease (IBD) is increasing in newly industrialised countries (NICs); however, data on suboptimal response to anti-tumor necrosis factor (anti-TNF) agents are limited., Objectives: To assess incidence and indicators of suboptimal response to first anti-TNF therapy in IBD patients in NICs., Methods: A chart review was conducted in ten countries from Asia-Pacific (APAC), Latin America (LatAm), and Russia and the Middle East (RME) regions among patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD), initiating anti-TNF therapy in 2010-2015. The cumulative incidence of suboptimal response to anti-TNF therapy was assessed using the following indicators: dose escalation or discontinuation, augmentation with non-biologic therapy, IBD-related hospitalization, or surgery., Results: The study included 1,674 patients (570 UC; 1,104 CD). At 24 months, 32.9% of UC (APAC: 45.1%; LatAm: 38.2%; RME: 23.8%) and 41.2% of CD patients (APAC: 54.1%; LatAm: 42.5%; RME: 29.5%) had experienced suboptimal response. The most frequent first indicator was non-biologic therapy augmentation in LatAm (41.7%), IBD-related hospitalization in RME (UC: 50.7%; CD:37.3%) and in APAC for CD (39.1%), and anti-TNF discontinuation in APAC for UC (38.3%)., Conclusion: Suboptimal response to anti-TNF agents is common in IBD patients in NICs. Observed regional differences in the incidence and indicators may reflect local practice and anti-TNF restrictions in IBD management., Nct Registration Number: NCT03090139., Competing Interests: Declaration of Competing Interests Qasim M Rana Khan, Olga Fadeeva and Dirk Demuth are employees of Takeda Pharmaceuticals Company Ltd. Morgane Guennec and Cecilia Sison are employees of IQVIA, which was funded by Takeda Pharmaceuticals Company Ltd to conduct this study. Jesús K. Yamamoto-Furusho is an advisory committee/board member for Takeda Pharmaceuticals Company Ltd; has received honoraria from AbbVie, Takeda, Janssen, Farmasa, Ferring, Alfasigma, Hospira, UCB, Danone, Almirall and Pfizer as a speaker, key opinion leader, and member of national and international advisory boards; has received research funds from Bristol, Shire, Pfizer and Takeda and former President of the Pan American Crohn's and Colitis organisation (PANCCO). Othman Al Harbi is a consultant or advisory committee/board member for AbbVie, Janssen, Pfizer and Takeda Pharmaceuticals Company Ltd. Alessandro Armuzzi is a consultant or advisory/board member for AbbVie, Allergan, Amgen, Biogen, Celgene, Celltrion, Ferring, Hospira, Janssen, Lilly, MSD, Mundipharma, Mylan, Pfizer, Roche, Samsung Bioepis, Sofar, and Takeda Pharmaceuticals Company Ltd; has received lecture fees from AbbVie, Amgen, AstraZeneca, Chiesi, Ferring, Hospira, Janssen, Medtronic, MSD, Mitsubishi Tanabe, Mundipharma, Nikkiso, Otsuka, Pfizer, Samsung Bioepis, Takeda, Tigenix, and Zambon; and research funding from MSD, Pfizer and Takeda. Webber Chan indicated no relevant financial relationships. Enrique Ponce de Leon is a consultant or advisory/board member for AbbVie, Janssen and Takeda Pharmaceuticals Company Ltd. Jiaming Qian is an advisory committee/board member for Takeda Pharmaceuticals Company Ltd. Marina Shapina is an advisory committee/board member for Takeda Pharmaceuticals Company Ltd. Murat Toruner is an advisory committee/board member for Takeda Pharmaceuticals Company Ltd; has received consulting fees from AbbVie Turkey, MSD Turkey, Janssen Turkey, Takeda Turkey and has received lecture fees from AbbVie Turkey, MSD Turkey, Janssen Turkey, Takeda Turkey, Ferring Turkey and UCB Turkey. Chia-Hung Tu is an advisory committee/board member for Takeda Pharmaceuticals Company Ltd. Byong Duk Ye has received a research grant from Celltrion and Pfizer Korea; is a consultant or advisory/board member for AbbVie Korea, Celltrion, Chong Kun Dang Pharm., Daewoong Pharma., Ferring Korea, Janssen Korea, Kangstem Biotech, Kuhnil Pharm., Medtronic Korea, Shire Korea, Takeda Korea, IQVIA, Cornerstones Health, Robarts Clinical Trials Inc. and Takeda; has received lecture fees from AbbVie Korea, Celltrion, Ferring Korea, Janssen Korea, Shire Korea, Takeda Korea, and IQVIA., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The Wnt signaling pathway is a crucial regulator of the intestinal epithelium homeostasis and is altered in most colon cancers. While the role of aberrant canonical, β-catenin-dependent Wnt signaling has been well established in colon cancer promotion, much less is known about the role played by noncanonical, β-catenin-independent Wnt signaling in this type of cancer. This work aimed to characterize the noncanonical signal transduction pathway in colon cancer cells. To this end, we used the prototype noncanonical ligand, Wnt5a, in comparison with Wnt3a, the prototype of a canonical β-catenin activating ligand. The analysis of the expression profile of Wnt receptors in colon cancer cell lines showed a clear increase in both level expression and variety of Frizzled receptor types expressed in colon cancer cells compared with non-malignant cells. We found that Wnt5a activates a typical Wnt/Ca++ - noncanonical signaling pathway in colon malignant cells, inducing the hyperphosphorylation of Dvl1, Dvl2 and Dvl3, promoting Ca++ mobilization as a result of phospholipase C (PLC) activation via pertussis toxin-sensitive G-protein, and inducing PLC-dependent cell migration. We also found that while the co-receptor Ror2 tyrosine kinase activity is not required for Ca++ mobilization-induced by Wnt5a, it is required for the inhibitory effects of Wnt5a on the β-catenin-dependent transcriptional activity. Unexpectedly, we found that although the prototype canonical Wnt3a ligand was unique in stimulating the β-catenin-dependent transcriptional activity, it also simultaneously activated PLC, promoted Ca++ mobilization, and induced Rho kinase and PLC-dependent cell migration. Our data indicate, therefore, that a Wnt ligand can activate at the same time the so-called Wnt canonical and noncanonical pathways inducing the formation of complex signaling networks to integrate both pathways in colon cancer cells., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Incidence of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is increasing worldwide; nevertheless, it is still unknown if this is the case in Mexico. Thus, the aim of this study was to analyze the distribution and trends of hospital discharges (HD) (for the period between 2004 and 2015) and deaths (for the period between 2004 and 2013) reported for UC and CD in Mexico., Methods: Quantitative cross-sectional study was performed. Secondary data sources analysis was performed through Dynamic Cubes of the General Direction of Health Information; variables were categorized by diagnosis, age, sex, and state. The Mann-Whitney U test was used to analyze the differences between the first and last years that were studied. Statistical analysis was performed in SPSS v.24., Results: The number of HD increased by 98.9% between 2004 and 2015 (IBD: p =0.033, CD: p =0.009, UC: p =0.051); it was more frequent, for both sexes and diagnoses, between 15 and 44 years, with a second peak for men with UC (between 45 and 64 years). Deaths increased by 96.2% from 2004 to 2011 (IBD: p =0.056, CD: p =0.064, UC: p =0.04). UC is three times more frequent than CD. Mexico City has the highest number of HD (4,179; 22.7%) while the state of Veracruz has the highest number of deaths (273; 38.2%)., Conclusions: HD for IBD in Mexico is increasing significantly; the number of deaths increased until 2011, but from then on, they are apparently decreasing. IBD affects Mexican people without any gender predominance, often affecting patients between 15 and 44 years of age. UC is three times more frequent than CD., Competing Interests: The authors declare they have no conflicts of interest., (Copyright © 2020 Andrea Sarmiento-Aguilar et al.)

Methods: Detection of H. pylori infection was performed by a 13C-urea breath test in 31 patients with UC. In each patient, a serum sample was drawn to measure IL-10 by the ELISA technique. Based on the primary breath test result, two groups were formed and serum IL-10 was measured., Results: Serological IL-10 levels in patients with UC and negative 13C-urea breath test was 10.28 pg/ml whereas in patients with UC and positive 13C-urea breath test was 5.5 pg/ml ( P = 0.035). IL-10 levels were higher in the inflammatory endoscopic and histological active groups which tested positive in the 13C-urea breath tests for H. pylori ( P < 0.05)., Conclusions: The role of IL-10 secretion in patients with UC in determining the clinicopathological outcome of infection merits further study. This study suggests an association between serum IL-10 and disease severity in patients with UC and HP infection., Competing Interests: The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2020 Jesús K. Yamamoto-Furusho et al.)

Introduction and Aims: There is no systematized information for determining/monitoring the burden of inflammatory bowel disease in Mexico. The aim of the present study was to estimate the annual burden of inflammatory bowel disease on the Mexican National Healthcare System, by number of patients seen, hospitalizations, and specific deaths, stratified into age groups., Materials and Methods: Utilizing specific databases of the Mexican National Healthcare System registries coded as ICD-10: K50 and K51, we retrieved and analyzed the data corresponding to the patients seen and hospitalized in 2015, stratified by age group, as well as the specific deaths. Treatment trends among physicians were also examined., Results: In 2015, 5,009 women (8.1) and 4,944 men (8.4) with Crohn's disease received medical attention (prevalence of cases seen) and 35.1% of those patients were ≥50years of age. In that same period, 17,177 women (27.7) and 15,883 men (26.9) with ulcerative colitis were seen and 31.6% of those patients were ≥50years of age. The hospitalized cases (prevalence of hospitalized cases) were 1,097 patients (0.91) with Crohn's disease and 43.7% of those patients were ≥50years of age; and 5,345 patients (4.42) with ulcerative colitis and 47.6% of those patients were ≥50years of age. Deaths (specific mortality rate) were: 32 women (0.52) and 36 men (0.50) due to Crohn's disease, and 267 women (4.31) and 186 men (3.15) due to ulcerative colitis., Conclusions: Inflammatory bowel disease is a burden on the health of Mexican adults and the Mexican National Healthcare System, and it is expected to increase over the next 15years., (Copyright © 2020 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.)

So far, available evidence suggests that patients with inflammatory bowel disease (IBD) are not at greater risk for developing COVID-19 infection. In regard to patients with IBD remission: 5-aminosalycylates (5-ASAs) do not increase the risk for infection and should be continued. There is no need to suspend them or lower the dose. Immunomodulating drugs, such as thiopurines and methotrexate, should be continued, without modifying doses (even in patients with positive SARS-CoV-2 infection). No type of biologic therapy should be suspended, unless there are signs of COVID-19. Regarding patients with IBD activity: the oral and/or topical 5-ASA dose should be optimized in cases of disease relapse. Budesonide MMX should be considered in cases of mild-to-moderate activity, to avoid systemic steroid use. Systemic steroids should be avoided whenever possible because doses above 20mg per day have an immunosuppressive effect, which could increase susceptibility to any type of infection, including COVID-19. The combined use of thiopurines with steroids and/or tumor necrosis factor (TNF) monoclonal antibodies should also be avoided because those combinations can increase the risk for infections, including COVID-19. Finally, biologic treatment with anti-TNF-alpha agents or any other mechanism of action, such as anti-integrins or anti-interleukins, should be suspended if patients become infected with SARS-CoV-2. The drugs can be restarted once the infectious process is resolved., (Copyright © 2020 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.)

Introduction: TRPVs are a group of receptors with a channel activity predominantly permeable to Ca 2+ . This subfamily is involved in the development of gastrointestinal diseases such as ulcerative colitis (UC). The aim of the study was to characterize the gene and protein expression of the TRPV subfamily in UC patients and controls., Methods: We determined by quantitative PCR the gene expression of TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6 in 45 UC patients (29 active UC and 16 remission UC) and 26 noninflamed controls. Protein expression was evaluated in 5  μ m thick sections of formalin-fixed, paraffin-embedded tissue from 5 customized severe active UC patients and 5 control surgical specimens., Results: TRPV2 gene expression was increased in the control group compared with active UC and remission patients ( P = 0.002 and P = 0.05, respectively). TRPV3 gene expression was significantly higher in controls than in active UC patients ( P = 0.002). The gene expression of TRPV4 was significantly higher in colonic tissue from patients with remission UC compared with active UC patients ( P = 0.05) and controls ( P = 0.005). TRPV5 had significantly higher mRNA levels in a control group compared with active UC patients ( P = 0.02). The gene expression of TRPV6 was significantly higher in the colonic tissue from patients with active UC compared with the control group ( P = 0.05). The protein expression of TRPV2 was upregulated in the mucosa and submucosa from the controls compared with the UC patients ( P ≤ 0.003). The protein expression of TRPV3 and TRPV4 was upregulated in all intestinal layers from the controls compared with the UC patients ( P < 0.001). TRPV5 was upregulated in the submucosa and serosa from the controls vs. UC patients ( P < 0.001). TRPV6 was upregulated in all intestinal layers from the UC patients vs. controls ( P ≤ 0.001)., Conclusion: The TRPV subfamily clearly showed a differential expression in the UC patients compared with the controls, suggesting their role in the pathophysiology of UC., Competing Interests: The authors declare they have no competing interests., (Copyright © 2020 Joel J. Toledo Mauriño et al.)

Background: Ulcerative colitis (UC) is a chronic disease characterized by periods of activity and remission. The platelet, one of the main activators of neutrophils, contains Interleukin 8 (IL-8), a potent neutrophil chemo-attractant and P-selectin that induces excretion of superoxide in the neutrophils, forming platelet-neutrophil aggregates that are increased in individuals with active UC, hence an index of both cells could produce a monitoring tool. No previous studies have evaluated this ratio in UC., Goal: To evaluate the clinical utility of the Neutrophil-Platelet (NeuPla) ratio in patients with UC., Study: A total of 158 patients with a diagnosis of UC. This index was based on the ratio between platelets and the neutrophil differential in blood count. The activity was classified using Mayo endoscopic sub-score, histological (Riley score) and for clinical was used the Truelove-Witts, Montreal, Mayo and Yamamoto-Furusho scores., Results: The correlation of the NeuPla ratio with activity scales were significant (P <0.05). An optimal cut-off point to classify patients with clinical activity was 14.94 with a sensitivity 87.95% and specificity 63.5 and endoscopy activity with a cut-off 14.64 with a sensibility of 70.5% and specificity of 61.8%., Conclusions: The NeuPla ratio showed an adequate diagnostic utility to identify UC patients with clinical and endoscopy activity without the use of invasive studies like a colonoscopy or expensive fecal biomarkers such as calprotectin and have a better diagnostic performance in comparison to other serum biomarkers (C reactive protein, erythrocyte sedimentation rate and albumin)., Competing Interests: The authors have declared that no competing interests exist.