NSAIDs, statins, low-dose aspirin and PPIs, and the risk of oesophageal adenocarcinoma among patients with Barrett's oesophagus: A populationbased case-control study

Objectives: Non-steroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), low-dose aspirin and statins may decrease the risk of oesophageal adenocarcinoma (OAC) among patients with Barrett's oesophagus (BO). However, previous studies did not adequately address bias and confounding. Our objective was to estimate the risk of OAC among patients with BO exposed to NSAIDs, statins and PPIs. Design: Case-control study nested within a BO cohort. Setting: Two primary care databases (the UK and the Netherlands (NL)). Participants: Cases were adults ≥18 years of age with OAC or high-grade dysplasia (HGD) diagnosis ≥1 year after BO diagnosis. Controls were matched on age, sex, year of BO diagnosis and database. Exposure: Drug use was assessed from BO diagnosis until matching date. Outcome measure: Adjusted ORs with 95% CI were calculated by conditional logistic regression. Results: Within the BO cohort (n=15 134), 45 OAC (UK: 40, NL: 5) and 12 HGD cases (NL: 12) were identified. ORa for OAC during NSAID use was 1.2 (95% CI 0.6 to 2.5) and during statin use for <3 years 0.5 (95% CI 0.1 to 1.7). When including HGD cases (n=57), ORa for NSAID use was 0.9 (95% CI 0.5 to 1.8) and for statin use <3 years 0.5 (95% CI 0.1 to 1.7). Higher doses of statins showed lower estimates for OAC and HGD, though not statistically significant. Low-dose aspirin and PPIs did not significantly decrease the risk of OAC and HGD. Conclusions: In this population-based nested case- control study, use of NSAIDs, PPIs, low-dose aspirin or statins did not reduce the risk of HGD and OAC among patients with BO. These findings indicate that for an unselected group of patients with BO chemoprevention by use of drugs to reduce progression to HGD and OAC should not be directly considered as routine care

Роль русского языка и литературы в формировании межкультурной компетенции иностранных студентов-филологов

Contains fulltext : 176878.pdf (publisher's version ) (Open Access)Orally ingested bacteria interact with intestinal mucosa and may impact immunity. However, insights in mechanisms involved are limited. In this randomized placebo-controlled cross-over trial, healthy human subjects were given Lactobacillus plantarum supplementation (strain TIFN101, CIP104448, or WCFS1) or placebo for 7 days. To determine whether L. plantarum can enhance immune response, we compared the effects of three stains on systemic and gut mucosal immunity, by among others assessing memory responses against tetanus toxoid (TT)-antigen, and mucosal gene transcription, in human volunteers during induction of mild immune stressor in the intestine, by giving a commonly used enteropathic drug, indomethacin [non-steroidal anti-inflammatory drug (NSAID)]. Systemic effects of the interventions were studies in peripheral blood samples. NSAID was found to induce a reduction in serum CD4+/Foxp3 regulatory cells, which was prevented by L. plantarum TIFN101. T-cell polarization experiments showed L. plantarum TIFN101 to enhance responses against TT-antigen, which indicates stimulation of memory responses by this strain. Cell extracts of the specific L. plantarum strains provoked responses after WCFS1 and TIFN101 consumption, indicating stimulation of immune responses against the specific bacteria. Mucosal immunomodulatory effects were studied in duodenal biopsies. In small intestinal mucosa, TIFN101 upregulated genes associated with maintenance of T- and B-cell function and antigen presentation. Furthermore, L. plantarum TIFN101 and WCFS1 downregulated immunological pathways involved in antigen presentation and shared downregulation of snoRNAs, which may suggest cellular destabilization, but may also be an indicator of tissue repair. Full sequencing of the L. plantarum strains revealed possible gene clusters that might be responsible for the differential biological effects of the bacteria on host immunity. In conclusion, the impact of oral consumption L. plantarum on host immunity is strain dependent and involves responses against bacterial cell components. Some strains may enhance specific responses against pathogens by enhancing antigen presentation and leukocyte maintenance in mucosa. In future studies and clinical settings, caution should be taken in selecting beneficial bacteria as closely related strains can have different effects. Our data show that specific bacterial strains can prevent immune stress induced by commonly consumed painkillers such as NSAID and can have enhancing beneficial effects on immunity of consumers by stimulating antigen presentation and memory responses

Endoscopic Diagnosis and Response Evaluation in Patients with Eosinophilic Esophagitis

Purpose of review The aim of this review is to provide practical guidance for clinicians to support the optimal use of endoscopy in both the diagnosis and the evaluation of treat- ment response in patients with eosinophilic esophagitis (EoE). Recent findings The systematic and high-quality assessment and grading of EoE endoscopic features improves EoE detection. Fibrotic complications of EoE that negatively impact patients’ symptoms and quality of life can be detected and treated through endoscopy. The correlation between endoscopic features of EoE and histological activity remains chal- lenging. However, assessment of endoscopic activity is fast and reliable in the evaluation of treatment response and, therefore, is supported by current guidelines. New modalities such as FLIP panometry and molecular markers for diagnosis and monitoring of EoE are promising, but whether they may replace endoscopy in guiding treatment of EoE needs to be ascertained

Reduced risk of Barrett’s esophagus in statin users: case–control study and meta-analysis

Background: Use of statins has been associated with a reduced incidence of esophageal adenocarcinoma in population-based studies. However there are few studies examining statin use and the development of Barrett’s esophagus. Aim: The purpose of this study was to examine the association between statin use and the presence of Barrett’s esophagus in patients having their first gastroscopy. Methods: We have performed a case–control study comparing statin use between patients with, and without, an incident diagnosis of non-dysplastic Barrett’s esophagus. Male Barrett’s cases (134) were compared to 268 male age-matched controls in each of two control groups (erosive gastro-esophageal reflux and dyspepsia without significant upper gastrointestinal disease). Risk factor and drug exposure were established using standardised interviews. Logistic regression was used to compare statin exposure and correct for confounding factors. We performed a meta-analysis pooling our results with three other case–control studies. Results: Regular statin use was associated with a significantly lower incidence of Barrett’s esophagus compared to the combined control groups [adjusted OR 0.62 (95 % confidence intervals 0.37–0.93)]. This effect was more marked in combined statin plus aspirin users [adjusted OR 0.43 (95 % CI 0.21–0.89)]. The inverse association between statin or statin plus aspirin use and risk of Barrett’s was significantly greater with longer duration of use. Meta-analysis of pooled data (1098 Barrett’s, 2085 controls) showed that statin use was significantly associated with a reduced risk of Barrett’s esophagus [pooled adjusted OR 0.63 (95 % CI 0.51–0.77)]. Conclusions: Statin use is associated with a reduced incidence of a new diagnosis of Barrett’s esophagus

Effects of Non-Steroidal Anti-Inflammatory Drugs on the Gastrointestinal and Cardiovascular System

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used for pain relief and antiinflammatory purposes. They are often combined with proton pump inhibitors (PPIs), the most potent blockers of gastric acid secretion to reduce gastroduodenal complications of NSAID use. This thesis studied the use and safety of NSAIDs and PPIs

Effect of obesity on the expression of nutrient receptors and satiety hormones in the human colon

Background: Receptors located on enteroendocrine cells (EECs) of the colon can detect nutrients in the lumen. These receptors regulate appetite through a variety of mechanisms, including hormonal and neuronal signals. We assessed the effect of obesity on the expression of these G-protein coupled receptors (GPCRs) and hormones at both mRNA and protein level. Methods: qPCR and immunohistochemistry were used to examine colonic tissue from cohorts of patients from the Netherlands (proximal and sigmoid tissue) and the United Kingdom (tissue from across the colon) and patients were grouped by body mass index (BMI) value (BMI < 25 and BMI ≥ 25). Results: The mRNA expression of the hormones/signaling molecules serotonin, glucagon, peptide YY (PYY), CCK and somatostatin were not significantly different between BMI groups. GPR40 mRNA expression was significantly increased in sigmoid colon samples in the BMI ≥ 25 group, but not proximal colon. GPR41, GPR109a, GPR43, GPR120, GPRC6A, and CaSR mRNA expression were unaltered between low and high BMI. At the protein level, serotonin and PYY containing cell numbers were similar in high and low BMI groups. Enterochromaffin cells (EC) showed high degree of co-expression with amino acid sensing receptor, CaSR while co-expression with PYY containing L-cells was limited, regardless of BMI. Conclusions: While expression of medium/long chain fatty acid receptor GPR40 was increased in the sigmoid colon of the high BMI group, expression of other nutrient sensing GPCRs, and expression profiles of EECs involved in peripheral mechanisms of appetite regulation were unchanged. Collectively, these data suggest that in human colonic tissue, EEC and nutrient-sensing receptor expression profiles are not affected despite changes to BMI