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.

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.

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.

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.

Increased expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and MMP10, MMP23 in inflammatory bowel disease: Cross-sectional study.

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, r2  = .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.

Expression of TOB/BTG family members in patients with inflammatory bowel disease.

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.

Mental Health Factors Associated With Fatigue in Mexican Patients With Inflammatory Bowel Disease.

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.

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.

Differential Cytokine Expression in the Duodenum and Rectum of Children with Non-Immunoglobulin E-Mediated Cow's Milk Protein Allergy.

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.

Validity and reliability of the health-related questionnaire IBDQ-32 in Mexican patients with inflammatory bowel disease.

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.

Prevalence of mental disorder and impact on quality of life in inflammatory bowel disease.

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.

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.

Validity and reliability of the Inflammatory Bowel Disease Fatigue Scale in Mexican patients.

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.

INTRODUCCIÓN: La fatiga es una manifestación extraintestinal de la enfermedad inflamatoria intestinal (EII). OBJETIVO: Obtener la validez de constructo, la validez discriminante y la confiabilidad de un instrumento para evaluar una escala de fatiga para EII en pacientes mexicanos. MÉTODOS: Se incluyeron 200 pacientes con diagnóstico confirmado de EII. Se evaluaron las características demográficas y clínicas actuales del padecimiento. Cada paciente contestó la Escala de Fatiga para EII (IBD-F) y el Índice de Calidad de Sueño de Pittsburgh (PSQI), empleado para determinar la validez discriminante de la IBD-F. Se realizó un análisis factorial de cada sección de la IBD-F, se utilizó la t de Student de muestras independientes para el contraste del PSQI y la confiabilidad se evaluó mediante alfa de ZCronbach. RESULTADOS: Los reactivos de ambas secciones de la IBD-F mostraron altas cargas factoriales, que explicaron 68.3 y 38.4 % de la varianza, respectivamente. El alfa de Cronbach fue > 0.80 en ambas, las cuales discriminaron a los pacientes con mayores alteraciones en el sueño. CONCLUSIONES: La IBD-F es una escala válida y confiable para pacientes mexicanos con EII. La evaluación objetiva de la fatiga permitirá realizar intervenciones oportunas para disminuir el impacto de esta manifestación en el paciente con EII.

Gene Expression Profiling of Mediators Associated with the Inflammatory Pathways in the Intestinal Tissue from Patients with Ulcerative Colitis.

BACKGROUND: Multiple genes have been associated with IBD, and many of these can be linked to alterations in autophagy, UPR, ubiquitination, and metabolic and immune response pathways. The aim of this study was to analyze a transcriptomic panel of mediators associated with the inflammatory pathways in the colonic mucosa of UC patients. Patients and Methods. We studied a total of 100 patients with definitive diagnosis of UC (50 active and 50 in remission) and a control group (50 subjects) without endoscopic evidence of intestinal inflammation. Colonic mucosal biopsies were taken by colonoscopy and preserved in RNA later. Gene expression were measured by real-time polymerase chain reaction (RT-PCR). RESULTS: The gene expressions of XBP1, AGR2, HSPA5, UBE2L3, TNFRSF14, LAMP3, FCGR2A, LSP1, CTLA4, SOD2, TDO2, and ALDOB mRNA levels were significantly higher in the colonic mucosa from UC patients (both quiescent and active) as compared to the control group (P < 0.05). Conversely, IRGM, ORDML3, UBD, CUL2, CYLD, FOXC2, FOXO4, DOK3, and SNX20 mRNA levels were found to be significantly lower in patients with active disease, as compared to those with active disease (P < 0.05). Gene expressions of IRGM, CTLA4, FOXO4, SLC26A3, SLC39A4, SOD2, TDO2, and ALDOB were associated with clinical outcomes, such as medical treatment in response to aminosalicylates, histological remission, clinical course, and evolution. CONCLUSIONS: : The gene expressions of FOXO4, ALDOB, SOD2, TOD2, SLC26A3, and SLC39A4 were associated with the clinical course and histological activity and are of relevance since these provide the utility of new prognostic markers in IBD. Gene expression signature showed dysregulation in mediators associated with autophagy, ubiquitination, ER stress, oxidative stress, carbohydrate metabolism, solute transport, and T cell regulation in the colonic mucosa from patients with UC, suggesting that these genes could be involved in the pathogenesis of UC.

Validación de Belief Medicines Questionnaire y Self-efficacy for Appropriate Medication Use Scale para medir adherencia al tratamiento farmacológico en pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: Treatment adherence is crucial in inflammatory bowel disease (IBD) to prevent relapses and complications. In Mexico, there is not a validated tool to assess adherence in patients with IBD. OBJECTIVE: To translate the beliefs about medicines questionnaire (BMQ) and self-efficacy for appropriate medication use scale (SEAMS) instruments, as well as to determine their validity, reliability and sensitivity in IBD-diagnosed Mexican patients. METHOD: After informed consent was obtained, 149 IBD-diagnosed patients were included. The instruments were translated into Spanish and were subsequently applied during medical consultation. For SEAMS, exploratory factorial analysis and ROC curve analysis were carried out and Cronbach's alpha was determined; for the BMQ, Cohen's kappa coefficient and its predictive capacity were employed. RESULTS: Seventy-five women (50.3%) were included, with an average age of 44 years. The SEAMS scale showed a single factor that was highly reliable (Cronbach's alpha = 0.92) and a cutoff point of 33 to identify adherent patients. The "adherence" and "recall barrier" dimensions of the BMQ were adequate adherence predictors. CONCLUSIONS: The SEAMS and BMQ Spanish versions are valid for measuring self-efficacy and barriers to pharmacological treatment adherence in Mexican patients with IBD.

INTRODUCCIÓN: La adherencia terapéutica es crucial en la enfermedad inflamatoria intestinal (EII) para evitar recaídas y complicaciones. En México no se dispone de una herramienta validada para evaluar adherencia en pacientes con EII. OBJETIVO: Traducir los instrumentos Belief Medicines Questionnaire (BMQ) y Self-Efficacy for Appropriate Medication Use Scale (SEAMS), y determinar su validez, fiabilidad y sensibilidad en pacientes mexicanos con diagnóstico de EII. MÉTODO: Se incluyeron 149 pacientes con diagnóstico de EII, previo consentimiento informado. Se tradujeron los instrumentos al español y posteriormente fueron aplicados durante la consulta médica. Para la SEAMS se realizó análisis factorial exploratorio, análisis de curva ROC y determinación del alpha de Cronbach; para el BMQ se empleó el coeficiente kappa de Cohen y su capacidad predictiva. RESULTADOS: Se incluyeron 75 mujeres (50.3 %) con edad promedio de 44 años. La escala SEAMS mostró un único factor altamente confiable (alfa de Cronbach = 0.92) y un punto de corte de 33 para identificar a los pacientes adherentes. Las dimensiones "adherencia" y "barrera de recuerdo" del BMQ fueron adecuados predictores de adherencia. CONCLUSIONES: Las versiones en español SEAMS y BMQ son válidas para medir autoeficacia y barreras para la adherencia al tratamiento farmacológico en pacientes mexicanos con EII.

Inflammatory bowel disease therapy: blockade of cytokines and cytokine signaling pathways.

PURPOSE OF REVIEW: Treatment of inflammatory bowel disease (IBD) patients can vary depending on the degree of response, lack of response or intolerance to conventional or biological agents aimed at blocking various cytokines or integrins. Recent therapies targeting several cytokines were reviewed to evaluate efficacy in IBD patients. RECENT FINDINGS: Ustekinumab is an interleukin inhibitor which blocks the p40 subunit of IL-12 and IL-23 axis and is already approved for the treatment of Crohn's disease patients, specially those who had inadequate response or intolerance to conventional treatment with anti-TNF-α agents. Several treatments have been developed that are focused on the blockade of specific cytokines such as IL-6, IL-12, IL-13, IL-17, IL-23 and a chemokine named IFN-γ-inducible protein-10 as well as some oral small-molecule inhibitors of intracellular cytoplasmic tyrosine kinases like tofacitinib, filgotinib and upadacitinib. SUMMARY: Several biologics blocking different and specific cytokines and oral small molecule agents have been and are being evaluated in IBD patients. A comprehensive understanding of the underlying immunological mechanisms will allow to develop effective and safe agents that inhibit one or more cytokines to improve the outcome in patients with IBD.

The Transient Receptor Potential Vanilloid 1 Is Associated with Active Inflammation in Ulcerative Colitis.

The transient receptor potential vanilloid 1 (TRPV1) may play a role in the pathogenesis of ulcerative colitis (UC). The aim of the study was to determine the gene and protein expression of TRPV1 in UC patients and noninflamed controls. Gene expression was performed by RT-PCR, and protein expression was performed by immunohistochemistry. The gene expression of TRPV1 was significantly increased in the remission UC group compared to active UC patients (P = 0.002), and an upregulation of the TRPV1 gene was associated with clinical outcomes such as age at diagnosis (<40 years) (P = 0.02) and clinical disease course characterized by relapsing and continuous activity (P = 0.07). TRPV1 immunoreactive cells were conspicuously higher in all intestinal layers from active UC patients compared with noninflamed control tissue. These findings suggest that TRPV1 might be involved in UC pathogenesis.

Hospital Anxiety and Depression Scale (HADS): Validation in Mexican Patients with Inflammatory Bowel Disease. / Escala de Ansiedad y Depresión Hospitalaria (HADS): Validación en pacientes mexicanos con enfermedad inflamatoria intestinal.

INTRODUCTION: The Hospital Anxiety and Depression Scale (HADS) is a self-administered instrument for outpatients, but its behaviour differs according to the clinical population to which it is applied. In Mexico it is not validated in patients with Inflammatory Bowel Disease (IBD). OBJECTIVES: To validate the HADS scale in the Mexican population with IBD. METHODS: 112 patients with IBD from the "Salvador Zubirán" National Institute of Medical Sciences and Nutrition were included, to whom the HADS was applied and some demographic and clinical characteristics of the disease were evaluated. An exploratory factor analysis was performed and factorial congruence was calculated to determine the construct validity of the HADS, while reliability was evaluated using Cronbach's alpha. RESULTS: The result of the varimax rotation of the 14 items of the HADS explained 50.1% of the variance, having two main factors. Ten items showed high factor loading for the dimensions originally proposed. The internal consistency of the HADS was high (alpha=0.88) with high values for the congruence coefficients. CONCLUSIONS: The HADS scale is a valid instrument to detect possible cases of Anxiety and Depression in Mexican patients with IBD. The validation of this instrument allows its routine use for the integral evaluation of the patient and their timely referral to mental health.