Increased synthesis and intestinal expression of IL-39 in patients with inflammatory bowel disease.

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.

Differential expression of TOB/BTG family members in patients with plaque psoriasis: cross-sectional study.

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.

The interrelation between anxiety and quality of life among patients with ulcerative colitis in remission / La interrelación entre ansiedad y calidad de vida en pacientes con colitis ulcerosa en remisión

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. (AU)

Objetivo: Determinar si la ansiedad o depresión están asociados con pobre calidad de vida en pacientes con colitis ulcerosa en remisión. Pacientes y métodos: Se incluyó a pacientes de manera consecutiva con diagnóstico establecido de colitis ulcerosa en remisión de al menos 12 meses y quienes completaron los cuestionarios de manera completa como el IBDQ-32, HAD. Las características sociodemográficas y clínicas fueron recabadas. Se utilizaron pruebas no paramétricas y se realizó correlación de HADS y IBDQ-32 con la prueba de Spearman (r). Un valor de p < 0,05 fue considerado como significativo. Resultados: De los 124 pacientes, el 65% fueron hombres con una media de 10 años de evolución (IQR: 5-79 años). La prevalencia para la ansiedad fue del 15,3% y el 2,4% para depresión. La calidad de vida global fue de 192 puntos (IQR: 175-208). La pobre calidad de vida estuvo asociada con la ansiedad (p = 0,002) y la depresión (p = 0,013). La depresión estuvo representada como pobre calidad de vida a nivel de las esferas digestiva (p = 0,04). La ansiedad se correlacionó de manera negativa con la calidad de vida (r = –0,54; p < 0,001). Conclusiones: La ansiedad es frecuente en pacientes con colitis ulcerosa en remisión; no obstante, el diagnóstico y el tratamiento oportuno debe ser implementado para mejorar la calidad de vida. (AU)

Analysis of Clinical Trial Screen Failures in Inflammatory Bowel Diseases (IBD): Real World Results from the International Organization for the study of IBD.

BACKGROUND: Recruitment for randomized controlled trials (RCTs) in IBD have substantially dropped over time. This study aimed to assess reasons why IBD patients are not included in sponsored multicenter phase IIb-III RCTs. METHODS: All IOIBD members (n=58) were invited to participate. We divided barriers to participation as follow: 1) reasons patients with active IBD were not deemed appropriate for a RCT; 2) reasons qualified patients did not wish to participate; 3) reasons for screen failure (SF) in patients agreeing to participate. We assess those 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 10 centers across the world, were included in the prospective study. A RCT has not been proposed to 65 of them (mainly due to eligibility criteria). Of the 41 patients to whom a RCT was offered, 8 refused (mainly due to reluctance to receive placebo) and 28 agreed to participate. Among these 28 patients, 5 failed their screening and 23 were finally included in a RCT. A total of 107 patients (61 male (57%), 67 CD (62.6%)), from 13 centers worldwide, were included in our retrospective study of SFs. The main reason was insufficient disease activity. CONCLUSION: This first multicenter study analyzing reasons for non-enrollment in IBD RCTs shown that we lose patients at each step. Eligibility criteria, the risk of placebo assignment and insufficient disease activity were part of the main barriers.

Development of the global inflammatory bowel disease visualization of epidemiology studies in the 21st century (GIVES-21).

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.

The interrelation between anxiety and quality of life among patients with ulcerative colitis in remission.

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.

Global Hospitalization Trends for Crohn's Disease and Ulcerative Colitis in the 21st Century: A Systematic Review With Temporal Analyses.

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.

Diagnostic Delay of Inflammatory Bowel Disease Is Significantly Higher in Public versus Private Health Care System in Mexican Patients.

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.

Association of dietary fiber consumption with disease activity in ulcerative colitis: An exploratory study in the Mexican population.

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.

INTRODUCCIÓN: La fibra dietética suplementada coadyuva en la remisión de la colitis ulcerosa crónica idiopática (CUCI). OBJETIVO: Evaluar la asociación entre la cantidad de fibra de la dieta habitual y la actividad de la enfermedad en pacientes con CUCI. MÉTODOS: Estudio transversal de una de cohorte de pacientes con CUCI. Se calculó el consumo de fibra dietética y con U de Mann-Whitney se comparó con la cantidad recomendada (14 g/1000 kcal). Con coeficiente de correlación de Spearman se analizaron el número de recaídas y la cantidad de fibra consumida, y la relación de esta con la actividad de la enfermedad mediante regresión logística. RESULTADOS: El grupo sin actividad actual de CUCI consumió más fibra dietética (RIC = 18-26, p = 0.062) y 47 % consumió más de la cantidad recomendada; el análisis de regresión logística mostró que cumplir con esta se asoció como factor protector en contra de la actividad actual de la CUCI (RM = 0.227, p = 0.032). En la fibra y el número de recaídas en el último año se observó una correlación inversamente proporcional (r = −0.399, p = 0.011). CONCLUSIONES: El consumo recomendado de fibra en la población general tuvo un efecto protector para la actividad actual de la CUCI en pacientes mexicanos.

IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis: The PROCTRIAL Consensus.

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.

Asociación del consumo de fibra dietética con la actividad de la colitis ulcerosa crónica idiopática. Estudio exploratorio en población mexicana / Association of dietary fiber consumption with disease activity in ulcerative colitis. An exploratory study in the Mexican population

Resumen Introducción: La fibra dietética suplementada coadyuva en la remisión de la colitis ulcerosa crónica idiopática (CUCI). Objetivo: Evaluar la asociación entre la cantidad de fibra de la dieta habitual y la actividad de la enfermedad en pacientes con CUCI. Métodos: Estudio transversal de una de cohorte de pacientes con CUCI. Se calculó el consumo de fibra dietética y con U de Mann-Whitney se comparó con la cantidad recomendada (14 g/1000 kcal). Con coeficiente de correlación de Spearman se analizaron el número de recaídas y la cantidad de fibra consumida, y la relación de esta con la actividad de la enfermedad mediante regresión logística. Resultados: El grupo sin actividad actual de CUCI consumió más fibra dietética (RIC = 18-26, p = 0.062) y 47 % consumió más de la cantidad recomendada; el análisis de regresión logística mostró que cumplir con esta se asoció como factor protector en contra de la actividad actual de la CUCI (RM = 0.227, p = 0.032). En la fibra y el número de recaídas en el último año se observó una correlación inversamente proporcional (r = −0.399, p = 0.011). Conclusiones: El consumo recomendado de fibra en la población general tuvo un efecto protector para la actividad actual de la CUCI en pacientes mexicanos.

Abstract 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.

Clinical differentiation of inflammatory bowel disease (IBD) in Latin America and the Caribbean.

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.

Validity and reliability of the health-related questionnaire IBDQ-32 in Mexican patients with inflammatory bowel disease / Validez y confiabilidad del cuestionario relacionado con la salud IBDQ-32 en pacientes mexicanos con enfermedad inflamatoria intestinal

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.(AU)

Antecedentes: La enfermedad inflamatoria intestinal comprende dos afecciones: colitis ulcerosa y enfermedad de Crohn. El Cuestionario de enfermedad inflamatoria intestinal 32 (IBDQ-32) es un cuestionario específico que ha sido traducido del inglés al español y validado. En los países de habla hispana de América no ha sido validado. El objetivo fue determinar las propiedades psicométricas, validez y confiabilidad de la versión mexicana del cuestionario IBDQ-32. Métodos: Participaron en el estudio un total de 316 pacientes con enfermedad inflamatoria intestinal y 100 controles sanos. Los cuestionarios IBDQ-32 y SF-36 se aplicaron en dos ocasiones (separadas por 15 días). Se determinaron las propiedades psicométricas de la versión mexicana del cuestionario IBDQ-32. Resultados: Los pacientes con enfermedad inflamatoria intestinal tenían una calidad de vida deteriorada, en comparación con los controles sanos. No hubo diferencias en las puntuaciones totales de IBDQ-32 y sus dominios entre la colitis ulcerosa y la enfermedad de Crohn. La confiabilidad de la consistencia interna fue buena. El coeficiente intraclase mostró buena confiabilidad (medición repetida) para la escala total y las cuatro subescalas. La varianza explicada del análisis factorial es superior al 50%, por lo que se considera adecuada/aceptable. La correlación entre IBDQ-32 y SF-36 mostró una asociación satisfactoria. El dominio social es el único que presentó un efecto techo. Conclusiones: La versión mexicana del cuestionario de calidad de vida IBDQ-32 es válida y confiable. Esta muestra incluyó todo el espectro de la enfermedad inflamatoria (remisión y actividad) y fue comparable al evaluar la calidad de vida con el cuestionario genérico SF-36.(AU)

Depression and Anxiety Disorders Impact in the Quality of Life of Patients with Inflammatory Bowel Disease.

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.

ABCC7/CFTR Expression Is Associated with the Clinical Course of Ulcerative Colitis Patients.

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.

Changes in chronic idiopathic ulcerative colitis epidemiological pattern in Mexico in a tertiary care hospital.

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.

ANTECEDENTES: La colitis ulcerosa crónica idiopática (CUCI) es una enfermedad con inflamación crónica de la mucosa del colon de origen multifactorial. El objetivo de este trabajo es identificar posibles cambios en el comportamiento de la CUCI en un hospital de referencia. MÉTODOS: Se incluyeron nuevos casos de CUCI confirmados por histopatología de enero del 2007 a diciembre del 2014. RESULTADOS: Se incluyeron un total de 189 pacientes. La media de nuevos casos anuales de CUCI fue de 23.6. Este estudio incorpora 95 pacientes de sexo masculino (50 %) y 94 de sexo femenino (50 %), con una edad promedio al diagnóstico de 44.6 años. La frecuencia de pancolitis fue del 77 %, en comparación con el 59 % en el periodo anterior. Las manifestaciones extraintestinales (MEI) estuvieron presentes en el 55.8 % y las colectomías en el 5.2 %. CONCLUSIÓN: Algunas características de la enfermedad han cambiado con el tiempo: aumento de la frecuencia de pancolitis y MEI, así como disminución de la tasa de colectomías.

AKAP12/Gravin is over-expressed in patients with ulcerative colitis.

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.

Gene expression profiling of inflammatory cytokines in esophageal biopsies of different phenotypes of gastroesophageal reflux disease: a cross-sectional study.

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.