Early Life and Childhood Environmental Exposures, More Than Genetic Predisposition, Influence Age of Diagnosis in a Diverse Cohort of 2952 Patients With IBD.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) develops from a combination of genetic and environmental factors. The aim of this study was to determine the contribution of established environmental risk factors and genetic risk on age of IBD diagnosis in a diverse cohort. METHODS: IBD patients in clinic completed detailed questionnaires. Blood was drawn for genetic analysis. Environmental risk factors and age of diagnosis were analyzed by ethnicity (Hispanic/Latinx or non-Hispanic White [NHW] individuals) and IBD subtype (ulcerative colitis or Crohn's disease [CD]). Weighted genetic risk scores and environmental risk scores were developed. We examined the relationship between environmental risk scores, genetic risk scores, and age of diagnosis. RESULTS: A total of 2952 patients were included: 58.9% had CD. A total of 46.83% were of Hispanic background. Early life exposures like cesarean delivery and being born in a developed country were associated with a younger age of IBD diagnosis. Childhood exposures such as frequent plastic water bottle use and having more than 1 bathroom at home were associated with a younger age of IBD. Hispanic and NHW individuals shared similar susceptibilities to environmental exposures. Environmental factors explained 21% of the variance in age of CD diagnosis and 39% in ulcerative colitis. In models incorporating genetic risk score and environmental risk score, the environment was the only significant factor associated with younger age of IBD diagnosis in all groups. CONCLUSIONS: Early life and childhood exposures impact IBD diagnosis and influence Hispanic and NHW individuals similarly. A cumulative environmental risk score contributes more to age of IBD diagnosis than genetic risk.

Bacterial Quorum-Sensing Molecules in Serum: A Potential Tool for Crohn's Disease Management.

Crohn's disease (CD) is an idiopathic inflammatory condition of the gastrointestinal tract with the primary method of diagnosis and follow-up being colonoscopy. A disturbed host-microbiome interaction, including the presence of pathobionts, is implicated in initiation and perpetuation of inflammation. As such, we hypothesized that bacterial quorum-sensing (QS) molecules (QSMs), small molecules bacteria generate to regulate gene expression, would be elevated in patients with CD. We collected serum at the time of colonoscopy from patients with CD and healthy controls, determining through biosensors for QSMs that patients with CD had significantly elevated levels of QSMs in serum. Expansion of these studies may allow for QSM levels in serum to serve as a biomarker for intestinal inflammation in patients with CD.

Lamina Propria Phagocyte Profiling Reveals Targetable Signaling Pathways in Refractory Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Lamina propria phagocytes are key mediators of inflammatory bowel disease (IBD). We aimed to understand the transcriptomic and functional differences in these cells based on location, disease type, inflammation state, and medication use in patients with IBD. METHODS: Phagocytic immune cells in the lamina propria, as defined by the marker CD11b, were isolated from 54 unique patients (n = 111 gut mucosal biopsies). We performed flow cytometry for cell phenotyping (n = 30) and RNA sequencing with differential gene expression analysis (n = 58). We further cultured these cells in vitro and exposed them to janus kinase inhibitors to measure cytokine output (n = 27). Finally, we matched patient genomic data to our RNA sequencing data to perform candidate gene expression quantitative trait locus analysis (n = 34). RESULTS: We found distinct differences in gene expression between CD11b+ cells from the colon vs ileum, as well as in different inflammatory states and, to a lesser degree, IBD types (Crohn's disease or ulcerative colitis). These genes mapped to targetable immune pathways and metabolic and cancer pathways. We further explored the janus kinase-signal transducer and activator of transcription pathway, which was upregulated across many comparisons including in biopsies from anti-tumor necrosis factor refractory patients. We found that isolated CD11b+ cells treated with janus kinase inhibitors had decreased secretion of cytokines tumor necrosis factora and interleukin-8 (P ≤ .05). We also found 3 genetic variants acting as expression quantitative trait loci (P ≤ .1) within our CD11b+ data set. CONCLUSIONS: Lamina propria phagocytes from IBD mucosa provide pathogenetic clues on the nature of treatment refractoriness and inform new targets for therapy.

Transcriptional Behavior of Regulatory T Cells Predicts IBD Patient Responses to Vedolizumab Therapy.

BACKGROUND: Inflammatory bowel disease (IBD) involves chronic T cell-mediated inflammatory responses. Vedolizumab (VDZ), a monoclonal antibody against α4ß7 integrin, inhibits lymphocyte extravasation into intestinal mucosae and is effective in ulcerative colitis (UC) and Crohn's disease (CD). AIM: We sought to identify immune cell phenotypic and gene expression signatures that related to response to VDZ. METHODS: Peripheral blood (PBMC) and lamina propria mononuclear cells (LPMCs) were analyzed by flow cytometry and Cytofkit. Sorted CD4 + memory (Tmem) or regulatory T (Treg) cells from PBMC and LPMC were analyzed by RNA sequencing (RNA-seq). Clinical response (≥2-point drop in partial Mayo scores [UC] or Harvey-Bradshaw index [CD]) was assessed 14 to 22 weeks after VDZ initiation. Machine-learning models were used to infer combinatorial traits that predicted response to VDZ. RESULTS: Seventy-one patients were enrolled: 37 received VDZ and 21 patients remained on VDZ >2 years. Fourteen of 37 patients (38%; 8 UC, 6 CD) responded to VDZ. Immune cell phenotypes and CD4 + Tmem and Treg transcriptional behaviors were most divergent between the ileum and colon, irrespective of IBD subtype or inflammation status. Vedolizumab treatment had the greatest impact on Treg metabolic pathways, and response was associated with increased expression of genes involved in oxidative phosphorylation. The strongest clinical predictor of VDZ efficacy was concurrent use of thiopurines. Mucosal tissues offered the greatest number of response-predictive biomarkers, whereas PBMC Treg-expressed genes were the best predictors in combinatorial models of response. CONCLUSIONS: Mucosal and peripheral blood immune cell phenotypes and transcriptional profiles can inform VDZ efficacy and inform new opportunities for combination therapies.

Vedolizumab (VDZ) is effective in the treatment of IBD. Immunophenotyping and RNAseq of T cells were used to inform its mechanism of action. Changes in T regulatory cells in the periphery and mucosa have the greatest relationship to VDZ response.

Factores asociados al reingreso hospitalario en pacientes con trastorno bipolar en Valle del Cauca, Colombia / Factors related with hospital readmission in patients with bipolar disorder in Valle del Cauca, Colombia

RESUMEN Objetivo Identificar factores asociados con el reingreso hospitalario en pacientes con trastorno bipolar (TB) en un hospital psiquiátrico y desarrollar un modelo explicativo del riesgo de reingreso. Método Estudio observacional longitudinal retrospectivo a partir de base de datos secundaria aportada por el Hospital Psiquiátrico Departamental Universitario del Valle. Estadística: análisis de supervivencia utilizando un modelo de regresión Cox. Se definió como variable dependiente el riesgo de reingreso y como variables independientes algunas sociodemográficas y clínicas. Resultados Se obtuvo una asociación estadísticamente significativa entre el riesgo de reingreso y las variables: falta de red de apoyo al no tener acudiente HR=1,33 [IC 95% 1,02-1,72; (p=0,034)] y falta de adherencia al tratamiento HR=2,33 [IC 95% 1,87-2,90; (p=0,000)]. Conclusión Para disminuir el reingreso hospitalario por TB, se deben priorizar las intervenciones en los casos de pacientes que no tengan acudiente y haya inadecuada adherencia al tratamiento; esta última, a partir de la percepción por parte del médico especialista. Enfocarse sobre estos dos factores puede incidir sobre los reingresos.

ABSTRACT Objective To identify the factors associated with hospital readmission in patients with bipolar disorder between 2011 and 2017 in a psychiatric hospital in order to develop an explanatory model of the risk of rehospitalization. Method Retrospective longitudinal observational study based on a secondary database provided by the Hospital Psiquiátrico Departamental Universitario del Valle. Statistics: Survival analysis using a Cox regression model. The risk of readmission was defined as a dependent variable and some sociodemographic and clinical variables were defined as independent variables. Results From the multivariate model of Cox Regression, a statistically significant association was obtained between the risk of readmission and the variables: lack of support network due to lack of retentive HR=1.33 [95% CI 1.02-1.72; (p=0.034)] and not having adherence to the treatment HR=2.33 [95% CI 1.87-2.90; (p=0.000)]. Conclusion In order to reduce hospital readmission due to bipolar disorder, interven-tions should be prioritized in cases where patients do not have a guardian and there is inadequate adherence to the treatment; the latter perceived by the specialist doctor. Focusing on these two factors can influence readmissions.

Social barriers influence inflammatory bowel disease (IBD) outcomes and disproportionally affect Hispanics and non-Hispanic Blacks with IBD.

Background: The impact of social determinants of health in inflammatory bowel disease (IBD) remains understudied. We evaluated the impact of social barriers on IBD outcomes within a diverse cohort of patients. Methods: We performed a cross-sectional study on adult IBD patients and assessed known social determinants of health. We calculated the total prevalence of these barriers in the sample as a whole and within each ethnic group. We summed the number of barriers present for each individual to create a cumulative social barrier score (SBS), and we evaluated the relationship of each barrier and of the cumulative SBS with IBD outcomes, including disease activity and depressive symptoms. Results: A total of 316 patients were included in the study. Disparities in the prevalence of social barriers emerged by ethnicity: non-Hispanic Blacks reported the greatest number of social barriers, followed by Hispanic patients. Prevalent social barriers included financial strains (38.4%), such as food insecurity, medical care delays (~30%), and low educational attainment (26.8%). Social barriers associated with poor IBD outcomes included low educational attainment, poor health literacy, and financial insecurity. High SBS was associated with greater depressive symptoms [odds ratio (OR) 1.94, 95% confidence interval (CI) 1.21-2.9, p = 0.001] and lower reported use of medications. Greater ulcerative colitis (UC) disease activity was observed in patients with greater SBS. No associations were identified between SBS and IBD surgeries, hospitalizations, or disease location. Conclusion: Our study identifies social barriers that may impact IBD care and are disproportionately higher in non-Hispanic Blacks and Hispanics in the United States. Future studies should focus on implementing interventions to reduce these barriers and improve delivery of care.

Translation and validation of the “personal evaluation of transitions in treatment (PETIT)” scale for people with schizophrenia.

To adapt the ‘Personal Evaluation of Transitions in Treatment (PETIT)’ scale into Spanish and analyse its psychometric properties on schizophrenic population.

Traducción y validación de la escala personal evaluation of transitions in treatment (PETIT)” para población conesquizofrenia / Translation and validation of the “personal evaluation of transitions in treatment (petit)” scale for schizophrenic population

Objetivo. Adaptar al español la escala Personal Evaluation of Transitions in Treatment (PETIT) y analizar sus propiedades psicométricas en población con esquizofrenia. Metodología. Participaron 223 pacientes en tratamiento ambulatorio con diagnóstico de esquizofrenia según criterios DSM-5. Se utilizaron como gold estándar la variable cumplimiento terapéutico, DAI10 y SMAQ y se analizaron las propiedades psicométricas de la escala en tres momentos (basal, al mes y 6 meses). Resultados. La validez de apariencia (lógica) de la escala es muy elevada. En el análisis factorial exploratorio identificamos que sería necesario eliminar el ítem-7. La fiabilidad de la escala es alta con un alfa-Cronbach de 0,91 demostrando buena consistencia interna. El análisis factorial confirmatorio tras eliminar el ítem-7 obtiene 5 componentes que explican el 57,76% de la varianza. El contenido de la escala es válido para discriminar pacientes con diferente adherencia, respuesta al tratamiento y calidad de vida. El punto de corte de la escala PETIT en español se establece en 24 puntos para ambos sexos; presentando una buena sensibilidad al cambio, y una fuerza de concordancia muy buena para los tres momentos evaluados. Conclusiones. La escala PETIT tras eliminar el ítem7 y utilizando 24 como punto de corte permite detectar cambios en la adherencia al tratamiento, su respuesta y las modificaciones resultantes en la calidad de vida de los pacientes. Su uso como único instrumento que mide todo lo anterior lo hace recomendable en la práctica clínica ya que esta precisa de métodos de evaluación sencillos que no consuman grandes esfuerzos o tiempo.(AU)

Aims. To adapt the ‘Personal Evaluation of Transitions in Treatment (PETIT)’ scale into Spanish and analyse its psychometric properties on schizophrenic population. Method. 223 patients in outpatient treatment diagnosed with schizophrenia according to DSM-5 criteria participated in the study. A defined variable ‘therapeutic compliance’, DAI10 and SMAQ were used as a gold standard and the psychometric properties of the scale were analysed at three time points (baseline, 1 month and 6 months). Results. The scale has very high face (or logical) validity. Exploratory factor analysis showed it would be necessary to eliminate item 7. The reliability of the scale is high (Cronbach’s alpha = 0.91), demonstrating good internal consistency. After eliminating item 7, confirmatory factor analysis obtained 5 components that explained 57,76% of the variance. The content of the scale is valid for discriminating between patients of different treatment adherence, response and quality of life. The cut-off point of the ‘PETIT’ scale in Spanish is set at 24 points for both sexes, with good sensibility to change and very good concordance force over the three time points evaluated. Conclusions. After eliminating item 7 and using ‘24’ as cut-off point, the ‘PETIT’ scale was able to detect changes in both adherence and response to treatment as well as the resulting modifications to the quality of life of patients. Its use as a single instrument to measure all of the above makes it advisable for use in clinical practice, as the evaluationmethods it requires are relatively simple and quick to perform.(AU)

Patient Adherence to Fecal Calprotectin Testing Is Low Compared to Other Commonly Ordered Tests in Patients With Inflammatory Bowel Disease.

Background: Limited data exist on adherence to fecal calprotectin (FCP) testing in patients with inflammatory bowel disease. Methods: Completion rates for patients who had at least one FCP test ordered (n = 3082) and a subgroup with C-reactive protein, complete blood count, and Clostridium difficile tests also ordered (n = 1563) were analyzed. Results: More patients completed blood than stool tests, with FCP having the poorest adherence of all tests analyzed. Older patients had higher FCP completion rates. No differences were noted in completion rates across age, gender, or ethnicity for blood tests. Conclusions: Further studies are needed to develop strategies that improve the uptake of FCP.

Real-World Experience With Proactive Therapeutic Drug Monitoring During Infliximab Reintroduction.

Background: Interruptions in infliximab therapy are associated with the development of antibodies to infliximab (ATI), infusion reactions (IRs), and loss of response. Despite these challenges, recent observational studies suggest that reinitiating infliximab after a drug holiday can be safe and effective. We assessed the utility of our protocol for restarting infliximab using early serum infliximab and ATI measurements. Methods: A retrospective cohort study of patients restarted on infliximab after at least a 6-month drug holiday. The cohort was divided into 2 groups: a "therapeutic drug monitoring (TDM) group," those who had serum infliximab and ATI measured 1-3 weeks after first reinduction dose, and a "non-TDM group." Outcomes included results of TDM, occurrence of immediate IR (IIR) and delayed hypersensitivity reactions, and medication persistence at 14 weeks and 1 year. Results: About 76 patients were included: 49 in the TDM group and 27 in the non-TDM group. Of 76, 67 (88%) patients tolerated the first reinduction dose without IR. Formation of ATI was seen in 17 of 49 (35%) patients and was associated with longer drug holidays. Most did not experience IR during the entire therapy course-in 26 of 32 (81%) without ATI and 20 of 27 (74%) in the non-TDM group. Infliximab persistence at 14 weeks and 1 year was 76% and 57% for the cohort, respectively. Conclusion: Infliximab can be safely and effectively restarted after a drug holiday. We suggest performing TDM with a drug-tolerant assay 1-3 weeks after the first reinduction infusion as a means to identify patients at risk for severe IIR at the second dose.

Low-Fat, High-Fiber Diet Reduces Markers of Inflammation and Dysbiosis and Improves Quality of Life in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: A high-fat diet has been associated with an increased risk of ulcerative colitis (UC). We studied the effects of a low-fat, high-fiber diet (LFD) vs an improved standard American diet (iSAD, included higher quantities of fruits, vegetables, and fiber than a typical SAD). We collected data on quality of life, markers of inflammation, and fecal markers of intestinal dysbiosis in patients with UC. METHODS: We analyzed data from a parallel-group, cross-over study of 17 patients with UC in remission or with mild disease (with a flare within the past 18 mo), from February 25, 2015, through September 11, 2018. Participants were assigned randomly to 2 groups and received a LFD (10% of calories from fat) or an iSAD (35%-40% of calories from fat) for the first 4-week period, followed by a 2-week washout period, and then switched to the other diet for 4 weeks. All diets were catered and delivered to patients' homes, and each participant served as her or his own control. Serum and stool samples were collected at baseline and week 4 of each diet and analyzed for markers of inflammation. We performed 16s ribosomal RNA sequencing and untargeted and targeted metabolomic analyses on stool samples. The primary outcome was quality of life, which was measured by the short inflammatory bowel disease (IBD) questionnaire at baseline and week 4 of the diets. Secondary outcomes included changes in the Short-Form 36 health survey, partial Mayo score, markers of inflammation, microbiome and metabolome analysis, and adherence to the diet. RESULTS: Participants' baseline diets were unhealthier than either study diet. All patients remained in remission throughout the study period. Compared with baseline, the iSAD and LFD each increased quality of life, based on the short IBD questionnaire and Short-Form 36 health survey scores (baseline short IBD questionnaire score, 4.98; iSAD, 5.55; LFD, 5.77; baseline vs iSAD, P = .02; baseline vs LFD, P = .001). Serum amyloid A decreased significantly from 7.99 mg/L at baseline to 4.50 mg/L after LFD (P = .02), but did not decrease significantly compared with iSAD (7.20 mg/L; iSAD vs LFD, P = .07). The serum level of C-reactive protein decreased numerically from 3.23 mg/L at baseline to 2.51 mg/L after LFD (P = .07). The relative abundance of Actinobacteria in fecal samples decreased from 13.69% at baseline to 7.82% after LFD (P = .017), whereas the relative abundance of Bacteroidetes increased from 14.6% at baseline to 24.02% on LFD (P = .015). The relative abundance of Faecalibacterium prausnitzii was higher after 4 weeks on the LFD (7.20%) compared with iSAD (5.37%; P = .04). Fecal levels of acetate (an anti-inflammatory metabolite) increased from a relative abundance of 40.37 at baseline to 42.52 on the iSAD and 53.98 on the LFD (baseline vs LFD, P = .05; iSAD vs LFD, P = .09). The fecal level of tryptophan decreased from a relative abundance of 1.33 at baseline to 1.08 on the iSAD (P = .43), but increased to a relative abundance of 2.27 on the LFD (baseline vs LFD, P = .04; iSAD vs LFD, P = .08); fecal levels of lauric acid decreased after LFD (baseline, 203.4; iSAD, 381.4; LFD, 29.91; baseline vs LFD, P = .04; iSAD vs LFD, P = .02). CONCLUSIONS: In a cross-over study of patients with UC in remission, we found that a catered LFD or iSAD were each well tolerated and increased quality of life. However, the LFD decreased markers of inflammation and reduced intestinal dysbiosis in fecal samples. Dietary interventions therefore might benefit patients with UC in remission. ClinicalTrials.gov no: NCT04147598.

Expression of SARS-CoV-2 Entry Molecules ACE2 and TMPRSS2 in the Gut of Patients With IBD.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have intestinal inflammation and are treated with immune-modulating medications. In the face of the coronavirus disease-19 pandemic, we do not know whether patients with IBD will be more susceptible to infection or disease. We hypothesized that the viral entry molecules angiotensin I converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are expressed in the intestine. We further hypothesized that their expression could be affected by inflammation or medication usage. METHODS: We examined the expression of Ace2 and Tmprss2 by quantitative polymerase chain reacion in animal models of IBD. Publicly available data from organoids and mucosal biopsies from patients with IBD were examined for expression of ACE2 and TMPRSS2. We conducted RNA sequencing for CD11b-enriched cells and peripheral and lamina propria T-cells from well-annotated patient samples. RESULTS: ACE2 and TMPRSS2 were abundantly expressed in the ileum and colon and had high expression in intestinal epithelial cells. In animal models, inflammation led to downregulation of epithelial Ace2. Expression of ACE2 and TMPRSS2 was not increased in samples from patients with compared with those of control patients. In CD11b-enriched cells but not T-cells, the level of expression of ACE2 and TMPRSS2 in the mucosa was comparable to other functional mucosal genes and was not affected by inflammation. Anti-tumor necrosis factor drugs, vedolizumab, ustekinumab, and steroids were linked to significantly lower expression of ACE2 in CD11b-enriched cells. CONCLUSIONS: The viral entry molecules ACE2 and TMPRSS2 are expressed in the ileum and colon. Patients with IBD do not have higher expression during inflammation; medical therapy is associated with lower levels of ACE2. These data provide reassurance for patients with IBD.

Understanding Participation in Genetic Research Among Patients With Multiple Sclerosis: The Influences of Ethnicity, Gender, Education, and Age.

This study examined reasons for participation in a genetic study of risk for multiple sclerosis (MS). Our sample consisted of 101 patients diagnosed with MS who were approached about enrolling in the Multiple Sclerosis Genetic Susceptibility Study. Participants were predominantly Hispanic (80%), female (80%), and well educated (71%), having at least some level of college education. Of these 101 individuals who were approached, 95 agreed to participate and are the focus of this report. Among enrollees, the most frequently cited reasons for participation were to find a cure for MS (56%), having MS (46%), and helping future generations (37%). Regression models comparing ethnic groups, Hispanics endorsed having MS as a reason to participate significantly more frequently than non-Hispanics (HI 52%, non-HI 19%, p = 0.015) while non-Hispanics endorsed finding new and better treatments significantly more frequently than Hispanics (Hispanic 17%, non-Hispanic 50%, p = 0.003). Among our three age groups, younger individuals endorsed finding a cure for MS significantly more frequently (74% of 18-35-year olds vs. 56% of 36-55 year olds vs. 39% of >55 year olds). Our results suggest that motivations for participation in genetic research vary by ethnicity, and that these influences need to be considered in developing more inclusive programs of disease-related genetic research. Future efforts should focus on development of standard methods for understanding participation in genetic and genomic research, especially among underrepresented groups as a catalyst for engaging all populations.

Microbial Signatures and Innate Immune Gene Expression in Lamina Propria Phagocytes of Inflammatory Bowel Disease Patients.

BACKGROUND & AIMS: The interaction between intestinal microbiota and the immune system plays a vital role in inflammatory bowel disease (IBD). Although numerous deep-sequencing studies have suggested dysbiosis in IBD, identifying specific bacteria from the stool or mucosa that are responsible for disease susceptibility or severity has remained a challenge. Lamina propria phagocytes ideally are localized to interact with bacteria that are in close proximity to, or have invaded, the tissue. Thus, we examined the microbial populations associated with the lamina propria phagocytes in 20 Crohn's disease and 12 ulcerative colitis patients. Specifically, we aimed to address whether the phagocyte-associated microbiota differed from the mucosa-associated microbiota and whether this varied based on IBD type or the state of inflammation. METHODS: 16S ribosomal RNA gene sequencing and innate immune gene expression profiling was done on CD11b+ lamina propria phagocytes isolated from the biopsies obtained from IBD patients. RESULTS: Phagocyte-associated microbiota was enriched in bacterial species belonging to phylum Proteobacteria, whereas species belonging to phylum Bacteroidetes were enriched in the mucosal microbiota of IBD patients. Disease type was the most influential factor in driving differences in the microbiota of both the mucosa and the lamina propria phagocytes, irrespective of inflammation state o`r anatomic location. Crohn's disease and ulcerative colitis specimens showed similar patterns of increased inflammatory gene expression in phagocytes isolated from inflamed areas compared with those isolated from uninflamed regions. CONCLUSIONS: This pilot study shows the feasibility of using lamina propria phagocytes to characterize the microbiota in IBD patients. The approach used in this study can narrow the spectrum of potentially dysbiotic bacterial populations and clinically relevant gene expression signatures in IBD patients.

Inflammatory Cytokine Profile in Crohn's Disease Nonresponders to Optimal Antitumor Necrosis Factor Therapy.

BACKGROUND: A significant number of patients receiving therapy with antitumor necrosis factor (TNF) agents for Crohn's disease experience primary or secondary nonresponse. The aim of this study was to assess whether patients with nonresponse to anti-TNF agents have increased expression of alternative cytokine pathways. METHODS: We designed a prospective, cross-sectional study that included patients with Crohn's disease receiving anti-TNF undergoing colonoscopy with adequate serum trough drug levels (≥8 µg/mL) and without anti-drug antibodies. Inflammatory cytokines and cell adhesions markers measured included intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1, interleukin (IL)-8, IL-1ß, and IL-6. The primary outcome was the presence of active endoscopic inflammation defined as the presence of at least 1 ulceration ≥5 mm. RESULTS: In total, 47 patients were included. Patients with active inflammation had significantly higher levels of ICAM-1 and IL-1ß when compared with those without intestinal inflammation (45.9 vs. 35.8 ng/mL, P<0.0001 and 3.2 vs. 1.5 pg/mL, P=0.002, respectively). There were no significant differences in the other study variables. Using receiving operating curves, ICAM and IL-1ß had a good correlation (receiver operating characteristic ≥0.8) with inflammation in this cohort of patients with "anti-TNF resistance." The results were similar in the group of patients with previous anti-TNF exposure. CONCLUSION: Our study suggests that patients who have active inflammation with seemingly adequate serum anti-TNF levels have increased levels of specific inflammatory pathways that may serve as biomarkers of nonresponse as well as potential targets of therapy in anti-TNF nonresponders.

Hispanics Coming to the US Adopt US Cultural Behaviors and Eat Less Healthy: Implications for Development of Inflammatory Bowel Disease.

INTRODUCTION: The incidence of inflammatory bowel disease (IBD) among US Hispanics is rising. Adoption of an American diet and/or US acculturation may help explain this rise. AIMS: To measure changes in diet occurring with immigration to the USA in IBD patients and controls, and to compare US acculturation between Hispanics with versus without IBD. Last, we examine the current diet of Hispanics with IBD compared to the diet of Hispanic controls. METHODS: This was a cross-sectional study of Hispanic immigrants with and without IBD. Participants were recruited from a university-based GI clinic. All participants completed an abbreviated version of the Stephenson Multi-Group Acculturation Scale and a 24-h diet recall (the ASA-24). Diet quality was calculated using the Healthy Eating Index (HEI-2010). RESULTS: We included 58 participants: 29 controls and 29 IBD patients. Most participants were Cuban or Colombian. Most participants, particularly those with IBD, reported changing their diet after immigration (72% of IBD and 57% of controls). IBD participants and controls scored similarly on US and Hispanic acculturation measures. IBD patients and controls scored equally poorly on the HEI-2010, although they differed on specific measures of poor intake. IBD patients reported a higher intake of refined grains and lower consumption of fruits, whereas controls reported higher intake of empty calories (derived from fat and alcohol). CONCLUSION: The majority of Hispanics change their diet upon immigration to the USA and eat poorly irrespective of the presence of IBD. Future studies should examine gene-diet interactions to better understand underlying causes of IBD in Hispanics.

Genetic Characterization and Influence on Inflammatory Bowel Disease Expression in a Diverse Hispanic South Florida Cohort.

OBJECTIVES: Hispanics represent an understudied inflammatory bowel disease (IBD) population. Prior studies examining genetic predisposition to IBD in Hispanics are limited. In this study, we examined whether European-derived IBD variants confer risk in Hispanics and their influence on IBD phenotype in Hispanics compared to non-Hispanic whites (NHW). METHODS: Self-identified Hispanics and NHWs with IBD were included. Hispanic controls were included for our genetic analyses. We performed single-variant testing at previously identified Crohn's disease (CD) and ulcerative colitis (UC) IBD variants in Hispanic cases and controls. These risk variants were used to compute individual genetic risk scores. Genetic risk scores and phenotype associations were compared between Hispanic and NHW. RESULTS: A total of 1,115 participants were included: 698 controls and 417 IBD patients (230 Hispanics). We found evidence of association within our Hispanic cohort at 22 IBD risk loci, with ~76% of the risk loci demonstrating over-representation of the European risk allele; these included loci corresponding to IL23R and NOD2 genes. CD genetic risk score for Hispanics (199.67) was similar to the score for NHW (200.33), P=0.51; the same was true in UC. Genetic risk scores did not predict IBD phenotype or complications in Hispanics or NHW except for a younger age of CD onset in Hispanics (P=0.04). CONCLUSIONS: This study highlights the fundamental importance of these loci in IBD pathogenesis including in our diverse Hispanic population. Future studies looking at non-genetic mechanisms of disease are needed to explain differences in age of presentation and phenotype between Hispanics and NHW.

Psychopathological profile and prevalence of dual pathology on patients with alcoholic dependence undergoing outpatient treatment.

AIMS: Assess the prevalence of dual pathology in patients with alcohol dependence and describe the psychopathological profile of mental disorders, impulsiveness, ADHD presence and craving. METHOD: It is a cross-sectional study about dual pathology, carried out on 102 patients undergoing outpatient treatment. The presence of dual pathology is established by means of the MINI-5 interview and the MCMI-III test; DSM-IV being used as the alcohol abuse criteria. Impulsiveness, ADHD presence, craving and quality of life were measured through SIS, ASRSv1, MACS and SF-36. RESULTS: The prevalence of dual pathology ranges from 45.1% to 80.4% according to MCMI-III and MINI-5, respectively. The most frequent pathologies are current major depressive episodes, followed by current generalized anxiety disorders, suicide risk and current dysthymia disorders; 73.2% of dual patients present a moderate and intense global score according to MACS, 56.1% got a meaningful score in impulsiveness according to SIS and 41.5% has highly consistent symptoms with ADHD. As regards quality of life, 53.7% of the sample had bad mental health. In the case of dual patients consuming other substances, 30% had a history of bipolar disorders and 10% had a high suicide risk. CONCLUSIONS: The prevalence of psychiatric comorbidity in patients with alcohol dependence undergoing outpatient treatment varies depending on the detection method, MINI being the one identifying a greater number of cases. More than half of dual patients present impulsive behavior, a bad mental health state and high craving levels. Special attention should be paid to dual patients consuming other substances.

Perfil psicopatológico y prevalencia de patología dual de los pacientes con dependencia alcohólica en tratamiento ambulatorio / Psychopathological profile and prevalence of dual pathology on patients with alcoholic dependence undergoing outpatient treatment

Objetivo. Estimar la prevalencia de patología dual (PD) en pacientes con dependencia alcohólica y describir el perfil psicopatológico de los trastornos mentales, su impulsividad, hiperactividad y craving. Metodología. Estudio transversal sobre PD de 102 pacientes en tratamiento ambulatorio. Se determina la presencia de PD mediante la entrevista MINI-5 y el test MCMI-III, utilizando como criterio de abuso o dependencia de alcohol el DSM-IV. Se emplearon además la EIE (impulsividad), ASRSv1 (hiperactividad), EMCA (craving) y SF-36 (calidad de vida). Resultados. La prevalencia de PD varía del 45,1% (MCMI-III) al 80,4% (MINI-5) dependiendo del instrumento utilizado. Predominan el episodio depresivo mayor actual y recidivante, seguido por el trastorno de ansiedad generalizada actual, el riesgo de suicidio y el trastorno distímico actual; el 73,2% de los pacientes duales presenta una puntuación global moderada-intensa en EMCA, un 56,1% tiene conducta impulsiva y un 41,5% síntomas altamente consistentes con el TDAH. Respecto a la calidad de vida, el 53,7% tenía un mal estado de salud mental. Un 30% de los pacientes con PD y consumo añadido de drogas tenía antecedentes de trastorno bipolar y un 10% riesgo de suicidio alto. Conclusiones. La prevalencia de comorbilidad psiquiátrica en pacientes con dependencia alcohólica en tratamiento ambulatorio varía dependiendo del método de detección, siendo la MINI la que identifica un mayor número de casos. Más de la mitad de los pacientes con PD tiene conducta impulsiva, mala calidad de salud mental y altos niveles de craving. Requieren especial atención los PD con consumo de otras sustancias

Aims. Assess the prevalence of dual pathology in patients with alcohol dependence and describe the psychopathological profile of mental disorders, impulsiveness, ADHD presence and craving. Method. It is a cross-sectional study about dual pathology, carried out on 102 patients undergoing outpatient treatment. The presence of dual pathology is established by means of the MINI-5 interview and the MCMI-III test; DSM-IV being used as the alcohol abuse criteria. Impulsiveness, ADHD presence, craving and quality of life were measured through SIS, ASRSv1, MACS and SF-36. Results. The prevalence of dual pathology ranges from 45.1% to 80.4% according to MCMI-III and MINI-5, respectively. The most frequent pathologies are current major depressive episodes, followed by current generalized anxiety disorders, suicide risk and current dysthymia disorders; 73.2% of dual patients present a moderate and intense global score according to MACS, 56.1% got a meaningful score in impulsiveness according to SIS and 41.5% has highly consistent symptoms with ADHD. As regards quality of life, 53.7% of the sample had bad mental health. In the case of dual patients consuming other substances, 30% had a history of bipolar disorders and 10% had a high suicide risk. Conclusions. The prevalence of psychiatric comorbidity in patients with alcohol dependence undergoing outpatient treatment varies depending on the detection method, MINI being the one identifying a greater number of cases. More than half of dual patients present impulsive behavior, a bad mental health state and high craving levels. Special attention should be paid to dual patients consuming other substances

Serum Amyloid A as a Surrogate Marker for Mucosal and Histologic Inflammation in Patients with Crohn's Disease.

BACKGROUND: Serum amyloid A (SAA) is an acute-phase protein, but its role as a biomarker of disease activity in Crohn's disease is unclear. The aim of the study was to assess the correlation between SAA, inflammatory cytokines, and mucosal inflammation in patients with Crohn's disease and to investigate whether this marker might be useful in patients who do not have elevated C-reactive protein (CRP) levels despite having active disease. METHODS: Cross-sectional study including patients with Crohn's disease who underwent colonoscopies for assessment of disease activity. Predictive variables were recorded at the time of the procedure and included demographics, phenotype of disease, medications, and collection of serum for cytokine analysis (SAA, CRP, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukins 8, 1ß, and 6). The primary outcome was the presence of mucosal healing (MH) (absence of macroscopic and microscopic inflammation). RESULTS: Ninety-four patients were included. Sixty-eight (72.3%) had not achieved MH. SAA, CRP, intercellular adhesion molecule, and interleukin-6 levels were significantly lower in those patients with MH. SAA was the only test that performed well in the sensitivity/specificity analysis (receiver operating characteristic: 0.81, P = 0.046). A high SAA was able to identify 70% of the patients with a normal CRP but active inflammation. CONCLUSIONS: High circulating SAA levels can correlate with lack of MH and may be used as a surrogate marker for disease activity, even in those patients in whom CRP levels do not correlate with disease activity.