T cell-mediated oral tolerance is intact in germ-free mice

Commensal enteric bacteria stimulate innate immune cells and increase numbers of lamina propria and mesenteric lymph node (MLN) T and B lymphocytes. However, the influence of luminal bacteria on acquired immune function is not understood fully. We investigated the effects of intestinal bacterial colonization on T cell tolerogenic responses to oral antigen compared to systemic immunization. Lymphocytes specific for ovalbumin–T cell receptor (OVA–TCR Tg+) were transplanted into germ-free (GF) or specific pathogen-free (SPF) BALB/c mice. Recipient mice were fed OVA or immunized subcutaneously with OVA peptide (323–339) in complete Freund's adjuvant (CFA). Although the efficiency of transfer was less in GF recipients, similar proportions of cells from draining peripheral lymph node (LN) or MLN were proliferating 3–4 days later in vivo in GF and SPF mice. In separate experiments, mice were fed tolerogenic doses of OVA and then challenged with an immunogenic dose of OVA 4 days later. Ten days after immunization, lymphocytes were restimulated with OVA in vitro to assess antigen-specific proliferative responses. At both high and low doses of OVA, cells from both SPF and GF mice fed OVA prior to immunization had decreased proliferation compared to cells from control SPF or GF mice. In addition, secretion of interferon (IFN)-γ and interleukin (IL)-10 by OVA–TCR Tg+ lymphocytes was reduced in both SPF and GF mice fed OVA compared to control SPF or GF mice. Unlike previous reports indicating defective humoral responses to oral antigen in GF mice, our results indicate that commensal enteric bacteria do not enhance the induction of acquired, antigen-specific T cell tolerance to oral OVA

Diverticulosis Is Associated With Internal Hemorrhoids on Colonoscopy: Possible Clues to Etiology

Hemorrhoids are a common but poorly understood gastrointestinal condition. Bowel habits and fiber consumption are frequently cited as risk factors for hemorrhoids, but research has been inconclusive. Recent genome-wide association studies (GWAS) have suggested an association between diverticular disease and hemorrhoids. We sought to investigate the association between colonic diverticulosis and internal hemorrhoids to validate the prediction from the GWAS

Inflammatory Bowel Disease is Similar in Patients with Older Onset and Younger Onset

Background: As the American population is aging, the number of older people with inflammatory bowel disease is increasing. We used clinical data from the Sinai-Helmsley Alliance for Research Excellence (SHARE), a prospective cohort, to examine disease and treatment differences in older adults. Methods: We performed a cross-sectional study assessing demographics and disease behavior by age at diagnosis with univariate, bivariate, and multivariate analyses. "Older-onset" patients were diagnosed after age 60, "younger-onset" patients were diagnosed before age 60 but are older than 60 years, and the remainder were "young." Results: There were 91 older-onset, 389 younger-onset, and 3431 young patients with Crohn's disease. Older-onset patients had more ileal (37%) and colonic (27%) disease compared with younger-onset and young patients. There were no differences in disease behavior, location, or surgeries between older-onset and young patients with Crohn's disease within 5 years of diagnosis. Older-onset patients with inflammatory disease had a higher odds of being in remission. Young patients reported more anti-tumor necrosis factor and thiopurine use compared with younger-onset and older-onset patients (P < 0.01). There were 98 older-onset, 218 younger-onset, and 1702 young patients with ulcerative colitis. There were no differences in disease extent, activity index, or surgeries. Young patients with ulcerative colitis reported more anti-tumor necrosis factor use (26%) compared with younger-onset patients (17%, P < 0.01). Conclusions: Disease behavior or location was not different between younger and older adults with inflammatory bowel disease. Older patients were less likely to be treated with immunosuppression. If older patients have similar disease behavior, less frequent treatment with immunosuppressives may risk suboptimally controlled disease

Reduced impact of renal failure on the outcome of patients with alcoholic liver disease undergoing liver transplantation

Pre-transplant renal failure is commonly reported to be a poor prognostic indicator affecting survival after liver transplantation (LT). However, whether the impact of renal failure on patient outcome varies according to the etiology of the underlying liver disease is largely unknown

cMET inhibitor crizotinib impairs angiogenesis and reduces tumor burden in the C3(1)-Tag model of basal-like breast cancer

Epidemiologic studies have associated obesity with increased risk of the aggressive basal-like breast cancer (BBC) subtype. Hepatocyte growth factor (HGF) signaling through its receptor, cMET, is elevated in obesity and is a pro-tumorigenic pathway strongly associated with BBC. We previously reported that high fat diet (HFD) elevated HGF, cMET, and phospho-cMET in normal mammary gland, with accelerated tumor development, compared to low fat diet (LFD)-fed lean controls in a murine model of BBC. We also showed that weight loss resulted in a significant reversal of HFD-induced effects on latency and elevation of HGF/cMET signaling in normal mammary and cMET in normal mammary and tumors. Here, we sought to inhibit BBC tumor progression in LFD- and HFD-fed C3(1)-Tag BBC mice using a small molecule cMET inhibitor, and began crizotinib treatment (50mg/kg body weight by oral gavage) upon identification of the first palpable tumor. We next investigated if administering crizotinib in a window prior to tumor development would inhibit or delay BBC tumorigenesis. Treatment: Crizotinib significantly reduced mean tumor burden by 27.96 and 37.29%, and mean tumor vascularity by 35.04 and 33.52%, in our LFD- and HFD-fed C3(1)-Tag BBC mice, respectively. Prevention: Crizotinib significantly accelerated primary tumor progression in both diet groups but had no effect on total tumor progression or total tumor burden. In sum, cMET inhibition by crizotinib limited tumor development and microvascular density in basal-like tumor-bearing mice but did not appear to be an effective preventive agent for BBC.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-1920-3) contains supplementary material, which is available to authorized users

Effect of GI endoscopy nurse experience on screening colonoscopy outcomes

The effect of gastrointestinal endoscopy nursing experience on colonoscopy outcomes is unknown

Depression is associated with more aggressive inflammatory bowel disease

OBJECTIVES: Depression is prevalent in inflammatory bowel disease (IBD) patients. The impact of depression on IBD is not well-studied. It is unknown how providers should assess depression. METHODS: We used data from the Sinai-Helmsley Alliance for Research Excellence cohort, to assess methods of diagnosing depression and effects of baseline depression on disease activity at follow-up. A patient health questionnaire (PHQ-8) score ≥5 was consistent with mild depression. Relapse was defined as a modified Harvey-Bradshaw Index ≥5 or Simple Clinical Colitis Activity Index >2. We performed binomial regression to calculate adjusted risk ratios (RRs). RESULTS: We included 2,798 Crohn's disease (CD) patients with 22-month mean follow-up and 1,516 ulcerative colitis (UC) patients with 24-month mean follow-up. A total of 64% of CD patients and 45% of UC patients were in remission at baseline. By self-report, 20% of CD and 14% of UC patients were depressed. By PHQ-8, 38% of CD and 32% of UC patients were depressed ( P <0.01). Adjusted for sex, remission, and disease activity, CD patients with baseline depression were at an increased risk for relapse (RR: 2.3; 95% confidence interval (CI): 1.9-2.8), surgery, or hospitalization (RR: 1.3 95% CI: 1.1-1.6) at follow-up. UC patients with baseline depression were also at increased risk for relapse (RR: 1.3; 95% CI: 0.9-1.7), surgery, or hospitalization (RR: 1.3; 95% CI: 1.1-1.5) at follow-up. CONCLUSIONS: Baseline depression is associated with a higher risk for aggressive IBD at follow-up. A single question is not a sensitive method of assessing depression. Providers should consider administering the PHQ-8 to capture those at greater risk for aggressive disease

Nucleotide excision repair gene polymorphisms, meat intake and colon cancer risk

Much of the DNA damage from colon cancer-related carcinogens, including heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH) from red meat cooked at high temperature, are repaired by the nucleotide excision repair (NER) pathway. Thus, we examined whether NER non-synonymous single nucleotide polymorphisms (nsSNPs) modified the association between red meat intake and colon cancer risk

A High-Fiber Diet Does Not Protect Against Asymptomatic Diverticulosis

The complications of diverticulosis cause considerable morbidity in the United States; health care expenditures for this disorder are estimated to be $2.5 billion per year. Many physicians and patients believe that a high-fiber diet and frequent bowel movements prevent the development of diverticulosis. Evidence for these associations is poor. We sought to determine whether low-fiber or high-fat diets, diets that include large quantities of red meat, constipation, or physical inactivity increase risk for asymptomatic diverticulosis

Rapid Recurrence of Eosinophilic Esophagitis Activity After Successful Treatment in the Observation Phase of a Randomized, Double-Blind, Double-Dummy Trial

Background & Aims: Eosinophilic esophagitis (EoE) is chronic and recurs if treatment is discontinued. We aimed to determine rates of recurrence, and whether initial treatment with oral viscous budesonide (OVB) resulted in less recurrence than fluticasone from a multidose inhaler (MDI). Methods: This was the observation phase of a randomized, double-blind, double-dummy trial comparing OVB with MDI for initial EoE treatment. Subjects with a histologic response (<15 eosinophils/high-power field) in the trial entered an observation phase in which treatment was discontinued and symptoms were monitored. Patients underwent an endoscopy or a biopsy when symptoms recurred or at 1 year. We analyzed time to symptom recurrence and assessed endoscopic severity and histologic relapse (≥15 eosinophils/high-power field) at follow-up endoscopy. Results: Thirty-three of the 58 subjects (57%) had symptom recurrence before 1 year. The overall median time to symptom recurrence was 244 days. There was no difference in the rate of symptom recurrence for subjects treated with OVB vs MDI (hazard ratio, 1.04; 95% CI, 0.52–2.08). At symptom recurrence, 78% of patients had histologic relapse. The patients had significant increases in mean Dysphagia Symptom Questionnaire score (3.8 vs 8.7; P < .001), and the EoE Endoscopic Reference Score (1.3 vs 4.6; P < .001) compared with end of treatment. Conclusions: EoE disease activity recurred rapidly after initial histologic response to topical steroids (either OVB or MDI). Because most subjects had recurrent endoscopic and histologic signs not reliably detected by symptoms, maintenance therapy should be recommended in EoE patients achieving histologic response to topical steroids. Clinicaltrials.gov no: NCT02019758