Vedolizumab and Ustekinumab Levels in Pregnant Women With Inflammatory Bowel Disease and Infants Exposed In Utero.

Background & Aims: Vedolizumab and ustekinumab pharmacokinetics in pregnancy and the infant after in utero exposure remain incompletely defined. We aim to define the antenatal stability of ustekinumab and vedolizumab levels and the time at which infant drug levels become undetectable.

Methods: This multicenter prospective observational cohort study recruited pregnant or preconception women with inflammatory bowel disease receiving vedolizumab or ustekinumab.

An Extremes of Phenotype Approach Confirms Significant Genetic Heterogeneity in Patients with Ulcerative Colitis.

Background And Aims: Ulcerative colitis [UC] is a major form of inflammatory bowel disease globally. Phenotypic heterogeneity is defined by several variables including age of onset and disease extent. The genetics of disease severity remains poorly understood.

Emu Oil Attenuates Disease Severity and Results in Fewer Large Colonic Tumors in a Mouse Model of Colitis-Associated Colorectal Cancer.

Ulcerative colitis patients have an increased risk of developing colorectal cancer (CRC). The aim of the current study was to determine whether Emu Oil (EO) could reduce the severity of colitis, thereby inhibiting colitis-associated CRC (CA-CRC) development. Female C57BL/6 mice ( = 8/group) were injected (i.

Orally administered emu oil attenuates disease in a mouse model of Crohn's-like colitis.

Crohn's disease is a severe, incurable inflammatory bowel disease. Orally administered emu oil has demonstrated anti-inflammatory properties in previous models of gastrointestinal disease. We aimed to determine whether orally administered emu oil could attenuate disease in a mouse model of Crohn's-like colitis.

Vedolizumab for ulcerative colitis: Real world outcomes from a multicenter observational cohort of Australia and Oxford.

Background: Vedolizumab (VDZ), a humanised monoclonal antibody that selectively inhibits integrins is approved for use in adult moderate to severe ulcerative colitis (UC) patients.

Aim: To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving remission.

Methods: A retrospective review of Australian and Oxford, United Kingdom data for UC patients.

The role of a plant-based diet in the pathogenesis, etiology and management of the inflammatory bowel diseases.

: Inflammatory Bowel Disease (IBD) carries a significant burden on an individual's quality-of-life and on the healthcare system. The majority of patients use dietary modifications to manage their symptoms, despite limited research to support these changes. There is emerging data that a plant-based diet will be of benefit to IBD patients.

Inflammatory bowel diseases: interrelationships between dietary vitamin D, exposure to UV radiation and the fecal microbiome.

: Environmental factors and an altered fecal microbiome are believed to be central to the pathogenesis of inflammatory bowel diseases (IBD). Vitamin D and ultraviolet radiation (UVR) are environmental factors that are associated by several pathways, including changes to the gastrointestinal microbiome, with the development and course of IBD.: This review explores the interaction of vitamin D, and UVR, with the intestinal innate and adaptive immune systems, and how they may influence the gut microbiome and the subsequent development, and progression, of IBD.

Level of UV Exposure, Skin Type, and Age Are More Important than Thiopurine Use for Keratinocyte Carcinoma Development in IBD Patients.

Background: Retrospective studies observe an increased risk of keratinocyte carcinomas (KCs) in patients with inflammatory bowel disease (IBD) on thiopurine (TP) medication. The role of traditional risk factors such as skin type and sun protection behavior has not been studied in this population. This study aimed to examine traditional KC risk factors and thiopurine use on skin cancer development in an IBD cohort.

Vitamin D metabolites are lower with active Crohn's disease and spontaneously recover with development of remission.

Background: Vitamin D deficiency is associated with active Crohn's disease (CD). However, it remains unclear if lower 25-hydroxyvitamin D [25(OH)D] concentration is the cause, or consequence, of intestinal inflammation. Existing literature has focused on circulating 25(OH)D rather than the active metabolite 1,25(OH)D, or its breakdown product, 24,25(OH)D.

Anti-TNF Therapy in Pregnant Women With Inflammatory Bowel Disease: Effects of Therapeutic Strategies on Disease Behavior and Birth Outcomes.

Background: Active inflammatory bowel disease (IBD) adversely affects pregnancy outcomes. Little is known about the risk of relapse after stopping anti-tumor necrosis factor (anti-TNF) treatment during pregnancy. We assessed the risk of relapse before delivery in women who discontinued anti-TNF treatment before gestational week (GW) 30, predictors of reduced infant birth weight, a marker associated with long-term adverse outcomes, and rates and satisfaction with counseling.

Emu Oil reduces disease severity in a mouse model of chronic ulcerative colitis.

Ulcerative colitis (UC) is characterized by mucosal inflammation and ulceration of the large intestine. Emu Oil (EO) has been reported to protect the intestine against mucositis, NSAID-enteropathy, UC-associated colorectal cancer and acute UC. We aimed to determine whether EO could reduce the severity chronic UC in mice.

Ultraviolet Irradiation of Skin Alters the Faecal Microbiome Independently of Vitamin D in Mice.

Reduced sunlight exposure has been associated with an increased incidence of Crohn's disease and ulcerative colitis. The effect of ultraviolet radiation (UVR) on the faecal microbiome and susceptibility to colitis has not been explored. C57Bl/6 female mice were fed three different vitamin D-containing diets for 24 days before half of the mice in each group were UV-irradiated (1 kJ/m²) for each of four days, followed by twice-weekly irradiation of shaved dorsal skin for 35 days.

High Dose Vitamin D supplementation alters faecal microbiome and predisposes mice to more severe colitis.

Vitamin D has been suggested as a possible adjunctive treatment to ameliorate disease severity in human inflammatory bowel disease. In this study, the effects of diets containing high (D++, 10,000 IU/kg), moderate (D+, 2,280 IU/kg) or no vitamin D (D-) on the severity of dextran sodium sulphate (DSS) colitis in female C57Bl/6 mice were investigated. The group on high dose vitamin D (D++) developed the most severe colitis as measured by blinded endoscopic (p < 0.

Nonsynonymous Polymorphism in Guanine Monophosphate Synthetase Is a Risk Factor for Unfavorable Thiopurine Metabolite Ratios in Patients With Inflammatory Bowel Disease.

Background: Up to 20% of patients with inflammatory bowel disease (IBD) who are refractory to thiopurine therapy preferentially produce 6-methylmercaptopurine (6-MMP) at the expense of 6-thioguanine nucleotides (6-TGN), resulting in a high 6-MMP:6-TGN ratio (>20). The objective of this study was to evaluate whether genetic variability in guanine monophosphate synthetase (GMPS) contributes to preferential 6-MMP metabolizer phenotype.

Methods: Exome sequencing was performed in a cohort of IBD patients with 6-MMP:6-TGN ratios of >100 to identify nonsynonymous single nucleotide polymorphisms (nsSNPs).

Anti-TNF Therapeutic Drug Monitoring in Postoperative Crohn's Disease.

Background: Anti-TNF prevents postoperative Crohn's disease recurrence in most patients but not all. This study aimed to define the relationship between adalimumab pharmacokinetics, maintenance of remission and recurrence.

Methods: As part of a study of postoperative Crohn's disease management, some patients undergoing resection received prophylactic postoperative adalimumab.

Emu Oil Improves Clinical Indicators of Disease in a Mouse Model of Colitis-Associated Colorectal Cancer.

Background/aims: Ulcerative colitis is a remitting and relapsing inflammatory bowel disorder. Current treatments are limited, and if poorly controlled, colitis may progress to colorectal cancer. Previously, Emu Oil protected the intestine in experimental models of gut damage.

Performance of risk prediction for inflammatory bowel disease based on genotyping platform and genomic risk score method.

Background: Predicting risk of disease from genotypes is being increasingly proposed for a variety of diagnostic and prognostic purposes. Genome-wide association studies (GWAS) have identified a large number of genome-wide significant susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC), two subtypes of inflammatory bowel disease (IBD). Recent studies have demonstrated that including only loci that are significantly associated with disease in the prediction model has low predictive power and that power can substantially be improved using a polygenic approach.

Fine-mapping inflammatory bowel disease loci to single-variant resolution.

Inflammatory bowel diseases are chronic gastrointestinal inflammatory disorders that affect millions of people worldwide. Genome-wide association studies have identified 200 inflammatory bowel disease-associated loci, but few have been conclusively resolved to specific functional variants. Here we report fine-mapping of 94 inflammatory bowel disease loci using high-density genotyping in 67,852 individuals.

Dysplasia and colorectal cancer surveillance in inflammatory bowel disease.

Inflammatory bowel disease (IBD) patients are at an increased risk of developing colorectal cancer (CRC), a devastating complication of which intestinal dysplasia is the precursor. Considerable progress has been made to determine CRC risk in IBD, identification & management of dysplasia and preventative methods. Traditionally, surveillance colonoscopies with random colonic biopsies was used.

Efficacy of Rectal Tacrolimus for Induction Therapy in Patients With Resistant Ulcerative Proctitis.

Background & Aims: Resistant ulcerative proctitis can be extremely difficult to manage. Topically administered tacrolimus, however, may be effective in difficult-to-treat proctitis. This was a randomized, double-blind, placebo-controlled induction trial of rectal tacrolimus in patients with active ulcerative colitis.

Serologic antibodies in relation to outcome in postoperative Crohn's disease.

Background And Aim: Disease recurs frequently after Crohn's disease resection. The role of serological antimicrobial antibodies in predicting recurrence or as a marker of recurrence has not been well defined.

Methods: A total of 169 patients (523 samples) were prospectively studied, with testing peri-operatively, and 6, 12 and 18 months postoperatively.

Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy.

Aim: To study the innate immune function in ulcerative colitis (UC) patients who fail to respond to anti-tumor necrosis factor (TNF) therapy.

Methods: Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell (PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor (TLR) expression and cytokine production post TLR stimulation was assessed in UC "responders" ( = 12) and "non-responders" ( = 12) and compared to healthy controls ( = 12).

High Vitamin D-Binding Protein Concentration, Low Albumin, and Mode of Remission Predict Relapse in Crohn's Disease.

Background: Vitamin D (25(OH)D) deficiency occurs in active Crohn's disease (CD) and may be secondary to reduced sunlight exposure and oral intake. Vitamin D-binding protein (VDBP) levels, however, fluctuate less with season and sunlight. The aim, therefore, was to examine patients with CD in remission and determine any associations between VDBP, serum 25(OH)D, and the calculated free 25(OH)D concentrations with the risk of disease flare.

Concentrations of Adalimumab and Infliximab in Mothers and Newborns, and Effects on Infection.

Background & Aims: Little is known about in utero exposure to and postnatal clearance of anti-tumor necrosis factor (anti-TNF) agents in neonates. We investigated the concentrations of adalimumab and infliximab in umbilical cord blood of newborns and rates of clearance after birth, and how these correlated with drug concentrations in mothers at birth and risk of infection during the first year of life.

Methods: We performed a prospective study of 80 pregnant women with inflammatory bowel diseases at tertiary hospitals in Denmark, Australia, and New Zealand from March 2012 through November 2014: 36 received adalimumab and 44 received infliximab; 39 received concomitant thiopurines during pregnancy.