Association Between High-Sensitivity C-Reactive Protein and Metabolic Syndrome Among Hispanic/Latino Participants of the Hispanic Community Health Study/Study of Latinos.

Purpose: To determine whether high-sensitivity C-reactive protein (hsCRP) is associated with incident Metabolic Syndrome (MetS) among U.S. Hispanic/Latino adults. Patients and Methods: The Hispanic Community Health Study/Study of Latinos is a longitudinal observational cohort assessing cardiovascular health among diverse U.S. Hispanic/Latino adults. hsCRP was measured at visit 1 (2008-2011) and classified as low, moderate, or high, based on the Centers for Disease Control and Prevention and American Heart Association (CDC/AHA) guidelines. All MetS components [abdominal obesity, triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure, and fasting glucose] were measured at visit 1 and visit 2 (2014-2017). MetS was defined as the presence of three or more components based on the 2005 definition from the modified Third Report of the National Cholesterol Education Program Adult Treatment Panel (modified NCEP ATP III). Participants free of MetS at visit 1 and with complete data on hsCRP and all MetS components were included (n = 6121 participants). We used Poisson regression analysis to determine whether hsCRP was associated with incident MetS after adjusting for demographic, behavioral, and clinical factors. All analyses accounted for the complex survey design of the study. Results: In fully adjusted models, moderate versus low hsCRP was associated with a 33% increased risk of MetS [incidence rate ratio (IRR): 1.33, 95% confidence interval (CI): 1.10-1.61], while high versus low hsCRP was associated with a 89% increased risk of MetS (IRR: 1.89, 95% CI: 1.58-2.25). Conclusions: Greater levels of hsCRP were associated with new onset of MetS in a diverse sample of U.S. Hispanic/Latino adults. Results suggest that hsCRP may be an independent risk factor for MetS.

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.

Vancomycin in the treatment of inflammatory bowel disease: there is a role beyond Clostridioides difficile infection.

The development of new biological agents and small molecules has revolutionized the treatment of Inflammatory Bowel Disease (IBD). However, many patients do not respond or gradually lose their response, necessitating the search for other therapeutic strategies (1). In this clinical case, we describe the evolution of a patient with difficult-to-manage Crohn's Disease (CD) who was treated with oral vancomycin.

Comparative Safety of Biologic Agents in Patients With Inflammatory Bowel Disease With Active or Recent Malignancy: A Multi-Center Cohort Study.

BACKGROUND & AIMS: Safety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer. METHODS: We conducted a multicenter retrospective cohort study of patients with IBD and either active cancer (cohort A) or recent prior cancer (within ≤5 years; cohort B) who were treated with TNFα antagonists or non-TNF biologics after their cancer diagnosis. Primary outcomes were progression-free survival (cohort A) or recurrence-free survival (cohort B). Safety was compared using inverse probability of treatment weighting with propensity scores. RESULTS: In cohort A, of 125 patients (483.8 person-years of follow-up evaluation) with active cancer (age, 54 ± 15 y, 75% solid-organ malignancy), 10 of 55 (incidence rate [IR] per 100 py, 4.4) and 9 of 40 (IR, 10.4) patients treated with TNFα antagonists and non-TNF biologics had cancer progression, respectively. There was no difference in the risk of progression-free survival between TNFα antagonists vs non-TNF biologics (hazard ratio, 0.76; 95% CI, 0.25-2.30). In cohort B, of 170 patients (513 person-years of follow-up evaluation) with recent prior cancer (age, 53 ± 15 y, 84% solid-organ malignancy; duration of remission, 19 ± 19 mo), 8 of 78 (IR, 3.4) and 5 of 66 (IR 3.7) patients treated with TNFα antagonists and non-TNF biologics had cancer recurrence, respectively. The risk of recurrence-free survival was similar between both groups (hazard ratio, 0.94; 95% CI, 0.24-3.77). CONCLUSIONS: In patients with IBD with active or recent cancer, TNFα antagonists and non-TNF biologics have comparable safety. The choice of biologic should be dictated by IBD disease severity in collaboration with an oncologist.

The Current State of Care for Black and Hispanic Inflammatory Bowel Disease Patients.

Research on the care of inflammatory bowel disease (IBD) patients has been primarily in populations of European ancestry. However, the incidence of IBD, which comprises Crohn's disease and ulcerative colitis, is increasing in different populations around the world. In this comprehensive review, we examine the epidemiology, clinical presentations, disease phenotypes, treatment outcomes, social determinants of health, and genetic and environmental factors in the pathogenesis of IBD in Black and Hispanic patients in the United States. To improve health equity of underserved minorities with IBD, we identified the following priority areas: access to care, accurate assessment of treatment outcomes, incorporation of Black and Hispanic patients in therapeutic clinical trials, and investigation of environmental factors that lead to the increase in disease incidence.

In this comprehensive review, we examine the epidemiology, clinical presentations, disease phenotypes, treatment outcomes, social determinants of health, and genetic and environment factors in the pathogenesis of IBD in Black and Hispanic patients in the United States.

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.

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility.

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.

Combining Pentoxifylline With Vedolizumab for Crohn's Disease: Results of a Randomised, Placebo-controlled Pilot Study.

BACKGROUND AND AIMS: The efficacy of current biologics may be limited by targeting only one pathway. Pentoxifylline [PTX] interferes with tumour necrosis factor [TNF] gene expression. We performed a randomised, placebo-controlled pilot study to determine if PTX plus vedolizumab [VDZ] in patients with Crohn's disease [CD] is safe and improves response compared with VDZ monotherapy. METHODS: Thirty adult patients with active CD were randomised to VDZ/PTX or VDZ/placebo and followed for 24 weeks. Endoscopic activity and inflammatory cytokines were measured at baseline and Week 24. Descriptive statistics were used to determine estimates of effect. RESULTS: Demographics were similar but baseline disease activity was higher in the VDZ/PTX group. There was no difference in clinical remission at Week 14 (60.0% vs 66.67%, odds ratio [OR] 0.76, 95% confidence interval [CI] 0.16, 3.51) or steroid-free clinical remission at Week 24 in patients receiving VDZ/PTX. Improved clinical response was noted in the VDZ/PTX group at Weeks 6, 14, and 24 [Week 6: 20% vs 6.67%, Week 14: 26.67% vs 6.67%, Week 24: 40% vs 20%]. The rate of endoscopic remission was similar between the groups [40% vs 33.33%], with a greater mean decrease in Simple Endoscopic Score-CD [SES-CD] and C-reactive protein [CRP] with VDZ/PTX [SES-CD -3.17 vs -0.15, CRP -5.56 vs 0.46]. An increase in serum TNF-α concentration was observed with VDZ/placebo group; PTX mitigated this effect. No serious adverse events occurred. CONCLUSIONS: VDZ/PTX did not provide benefit over VDZ monotherapy in clinical or endoscopic remission but appeared to improve clinical response and was safe. These data should inform a fully powered study.

Diet as a treatment for inflammatory bowel disease: is it ready for prime time?

PURPOSE OF REVIEW: Diet remains an important topic for patients with inflammatory bowel disease (IBD), yet few guidelines for dietary recommendations exist. There is a growing interest in the use of diet as treatment or adjuvant therapy for both ulcerative colitis and Crohn's disease. Here, we highlight the latest evidence on the use of diet for treatment of symptoms, active disease and maintenance of remission in ulcerative colitis and Crohn's disease. RECENT FINDINGS: The Crohn's Disease Exclusion Diet (CDED) and the Specific Carbohydrate Diet (SCD) are studied diets that have gained popularity, but there is growing interest in the use and efficacy of less restrictive diets such as the Mediterranean diet. Recent data suggest healthful dietary patterns alone, with an emphasis on whole foods that are high in vegetable fibre and that promote less consumption of ultra-processed foods may also help achieve remission in patients with ulcerative colitis and Crohn's disease. SUMMARY: In this review, we summarize the literature on diet as treatment for IBD. We highlight the latest clinical dietary studies, randomized clinical trials, as well as new and emerging diets for the treatment of IBD.

Recommendations on the Appropriate Management of Steroids and Discharge Planning During and After Hospital Admission for Moderate-Severe Ulcerative Colitis: Results of a RAND Appropriateness Panel.

INTRODUCTION: Limited guidance exists for the postdischarge care of patients with ulcerative colitis hospitalized for moderate-severe flares. METHODS: RAND methodology was used to establish appropriateness of inpatient and postdischarge steroid dosing, discharge criteria, follow-up, and postdischarge biologic or small molecule initiation. A literature review informed on the panel's voting, which occurred anonymously during 2 rounds before and after a moderated virtual session. RESULTS: Methylprednisolone 40-60 mg intravenous every 24 hours or hydrocortisone 100 mg intravenous 3 times daily is appropriate for inpatient management, with methylprednisolone 40 mg being appropriate if intolerant of higher doses. It is appropriate to discharge patients once rectal bleeding has resolved (Mayo subscore 0-1) and/or stool frequency has returned to baseline frequency and form (Mayo subscore 0-1). It is appropriate to discharge patients on 40 mg of prednisone after observing patients for 24 hours in hospital to ensure stability before discharge. For patients being discharged on steroids without in-hospital biologic or small molecule therapy initiation, it is appropriate to start antitumor necrosis factor (TNF) therapy after discharge for anti-TNF-naive patients. For anti-TNF-exposed patients, it is appropriate to start vedolizumab or ustekinumab for all patients and tofacitinib for those with a low risk of adverse events. It is appropriate to follow up patients clinically within 2 weeks and with lower endoscopy within 4-6 months after discharge. DISCUSSION: We provide recommendations on the inpatient and postdischarge management of patients with ulcerative colitis hospitalized for moderate-severe flares.

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.

Trends in the epidemiology of inflammatory bowel disease in Colombia by demographics and region using a nationally representative claims database and characterization of inflammatory bowel disease phenotype in a case series of Colombian patients.

ABSTRACT: The incidence of inflammatory bowel disease (IBD) is on the rise in Latin America. The aims of this study were to examine epidemiologic trends of IBD in Colombia by demographics, region, urbanicity, and to describe the IBD phenotype in a large well-characterized Colombian cohort.We used a national database of 33 million adults encompassing 97.6% of the Colombian population in order to obtain epidemiologic trends of IBD using International Classification of Diseases 10codes for adults with ulcerative colitis (UC) and Crohn disease (CD). We calculated the incidence and prevalence of UC and CD from 2010-2017 and examined epidemiologic trends by urbanicity, demographics, and region. We then examined the IBD phenotype (using Montreal Classification), prevalence of IBD-related surgeries, and types of IBD-medications prescribed to adult patients attending a regional IBD clinic in Medellin, Colombia between 2001 and 2017.The incidence of UC increased from 5.59/100,000 in 2010 to 6.3/100,000 in 2017 (relative risk [RR] 1.12, confidence interval (CI) (1.09-1.18), P < .0001). While CD incidence did not increase, the prevalence increased within this period. The Andes region had the highest incidence of IBD (5.56/100,000 in 2017). IBD was seen less in rural regions in Colombia (RR=.95, CI (0.92-0.97), p < .01). An increased risk of IBD was present in women, even after adjusting for age and diagnosis year (RR 1.06 (1.02-1.08), P = .0003). The highest IBD risk occurred in patients 40 to 59 years of age. In the clinic cohort, there were 649 IBD patients: 73.7% UC and 24.5% CD. Mean age of diagnosis in CD was 41.0 years and 39.9 years in UC. UC patients developed mostly pancolitis (43%). CD patients developed mostly ileocolonic disease and greater than a third of patients had an inflammatory, non-fistulizing phenotype (37.7%). A total of 16.7% of CD patients had perianal disease. CD patients received more biologics than UC patients (odds ratio: 3.20, 95% CI 2.19-4.69 P < .001).Using both a national representative sample and a regional clinic cohort, we find that UC is more common in Colombia and is on the rise in urban regions; especially occurring in an older age cohort when compared to Western countries. Future studies are warranted to understand evolving environmental factors explaining this rise.

Ethnicity Influences Risk of Inflammatory Bowel Disease (IBD)-Associated Colon Cancer: A Cross-sectional Analysis of Dysplasia Prevalence and Risk Factors in Hispanics and Non-Hispanic Whites With IBD.

Background: Inflammatory bowel disease (IBD) is an emerging disease in Hispanics. In this study, we examine the prevalence of IBD-related colon dysplasia (IBD-dys) in Hispanics versus non-Hispanic whites (NHWs) and compare differences in established clinical and environmental risk factors. Methods: We performed a cross-sectional analysis on adult Hispanics and NHWs with IBD who met criteria for colorectal cancer surveillance and were followed at our center between 2008 and 2018. Clinical variables and IBD phenotype were recorded. Lifestyle IBD-dys risk factors were examined, including smoking and lack of physical activity. Using multivariable regression, we compared the prevalence of IBD-dys in Hispanics versus NHW, using relevant covariates. Receiver operating characteristic and area under the curve were performed to find the best fitting model. Results: A total of 445 IBD patients were included (148 Hispanics and 297 NHWs). IBD phenotype was similar between groups, except that Hispanics had shorter disease duration, a lower frequency of Crohn's disease-related complications, and lower reported use of steroids. Frequency of surveillance colonoscopies was similar between Hispanics and NHW. There were no differences in median body mass index between Hispanics and NHW [26.5 (IQR 6.0) vs 25.0 (IQR 6.0), P = 0.40]. Hispanics were less likely than NHW to consume alcohol but smoking history was similar between groups. Three out of 148 Hispanic patients had IBD-dys (2.02%) compared to 29 out of 297 NHWs (9.76%). Adjusting for disease duration, primary sclerosing cholangitis, family history of colon cancer, and smoking, Hispanics had a lower prevalence of IBD-dys compared to NHW [ORadjusted = 0.207 (95% CI 0.046-0.938), P = 0.008]. Conclusions: Hispanics with IBD undergoing surveillance had a lower prevalence of IBD-dys than their NHW counterparts, despite similar risk factors. Future studies should examine dietary and microbial factors that may explain differences in risk.

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.