Dealmorin8149

OBJECTIVES The impact of genetic variants (single nucleotide polymorphisms [SNPs]) in the clinical heterogeneity of ulcerative colitis (UC) remains unclear. We showed that patients with UC exhibit a deficiency in MGAT5 glycogene transcription in intestinal T cells associated with a hyperimmune response. Herein, we evaluated whether MGAT5 SNPs might functionally impact on T cells glycosylation and plasma IgG glycome in patients with UC, as well as in UC clinical outcomes. METHODS Three selected MGAT5 SNPs (rs3814022, rs4953911, and rs1257220), previously associated with severity of autoimmune disease or with plasma glycome composition in healthy individuals, were functionally evaluated in patients with UC through analysis of MGAT5 mRNA levels in colonic (n = 14) and circulating (n = 24) T cells and through profiling the plasma IgG Fc glycosylation (n = 152). MGAT5 SNPs were genotyped in 931 patients with UC from 2 European cohorts and further associated with patients' prognosis. Targeted next-generation sequencing for MGAT5 coding and regulatory regions was also performed. RESULTS MGAT5 SNPs were shown to be functionally associated with low transcription levels of MGAT5 in colonic and circulating T cells from patients with UC and with agalactosylation of IgGs, often associated with a proinflammatory phenotype. The SNPs rs3814022 and rs4953911 were further associated with the need of biologics. Next-generation sequencing data further revealed a combination of MGAT5 SNPs that stratify patients with UC according to their severity. DISCUSSION Our results revealed that MGAT5 SNPs have a phenotypic impact on T cells glycosylation and in plasma IgG glycome composition associated with UC pathogenesis. MGAT5 SNPs display a tendency in the association with a worse disease course in patients with UC.INTRODUCTION The prognosis of Cronkhite-Canada syndrome (CCS) is considered poor. Despite the recent therapeutic improvements, the survival outcomes and prognostic factors have been less studied. This study aimed to investigate the long-term clinical and endoscopic outcomes of CCS. METHODS Thirty-one patients diagnosed since 1999 and followed up for over 6 months were included. Data regarding survival outcomes, clinical symptoms, endoscopic findings, and treatment were collected and analyzed. R (version 3.6.1) was used to perform the survival analyses. RESULTS The median (interquartile range) follow-up time was 42.5 (19.5-85.8) months. The 5-year overall survival (OS) was 87.4%. The maximum gastric polyp size over 2 cm was associated with worse OS (Hazard ratio [HR] 18, 95% confidence interval [CI] 1.6-210, P = 0.021). The 3-year relapse-free survival (RFS) after corticosteroid treatment was 66.8%. Age older than 60 years (HR 7.0, 95% CI 1.5-33.0, P = 0.015) and maximum gastric polyp size over 2 cm (HR 6.0, 95% CI 1.6-23.0, P = 0.009) were associated with worse RFS. Twenty-three patients received follow-up endoscopic examinations, with a median (interquartile range) follow-up time of 29.0 (14.0-53.5) months. Eight (34.8%) and 12 (52.2%) patients achieved complete remission under gastroscopy and colonoscopy, respectively. Colonic lesions showed a tendency of earlier responses compared with gastric lesions (25.0 [11.3-39.8] months vs 31.0 [21.0-39.8] months). DISCUSSION Patients with CCS usually responded well to glucocorticoids with a fairly good 5-year survival rate. Large gastric polyp was associated with worse OS and RFS, whereas age older than 60 years was another predictor for worse RFS. Diffuse gastrointestinal lesions partly or completely resolved after treatment, and colonic lesions showed a better response than gastric lesions.OBJECTIVES Obesity is a risk factor for several phenotypes such as gallstones, metabolic syndrome (MS), and nonalcoholic fatty liver disease (NAFLD). It has been suggested that cholecystectomy is a risk factor for metabolic abnormalities and NAFLD. We aimed to determine whether cholecystectomy is associated with MS or NAFLD in a Dutch population-based study. METHODS The Rotterdam Study is an ongoing prospective population-based cohort. We included participants who underwent a liver ultrasound between 2009 and 2014 to assess steatosis. The prevalence of MS and NAFLD was calculated, and we performed regression analyses relating cholecystectomy with MS and NAFLD and adjusted for age, sex, study cohort, education level, physical activity, energy intake, time since cholecystectomy, body mass index, presence of hypertension, diabetes mellitus, and steatosis/MS. RESULTS We included 4,307 participants (57.5% women, median age 66.0 years [interquartile range 58-74]). In total, 265 participants (6.2%) underwent a cholecystectomy. The median age at the time of cholecystectomy was 57.0 years (47.5-66.5), and the median time from cholecystectomy to imaging of the liver was 10.0 years (0.5-19.5). The prevalence of MS in participants with cholecystectomy was 67.2% and 51.9% in participants without cholecystectomy (P less then 0.001). selleck chemical Ultrasound diagnosed moderate/severe NAFLD was present in, respectively, 42.7% and 34.2% of the participants (P = 0.008). After multivariable adjustments for metabolic factors, cholecystectomy was no longer associated with the presence of MS or NAFLD. DISCUSSION The prevalence of MS and NAFLD is higher in participants after cholecystectomy. However, our trial shows that cholecystectomy may not be independently associated with the presence of MS and NAFLD after correction for metabolic factors.INTRODUCTION Eosinophilic esophagitis (EoE) is a T-helper 2 (Th2), eosinophilic disease associated with pathologic tissue remodeling that leads to end-organ dysfunction. During early-stage disease, inflammation and subepithelial fibrosis are coupled and reversible, but in late-stage or therapy-resistant disease, there can be uncoupling of these features with progressive esophageal rigidity and strictures contributing to clinical dysphagia and food impactions. No current pharmacotherapeutic interventions directly target esophageal fibrosis. Based on the ability of the thiazolidinediones (TZD) to regulate intestinal and hepatic fibrosis, we tested the antifibrotic effects of the TZDs, rosiglitazone and pioglitazone, in preclinical studies using primary human esophageal fibroblasts. METHODS Primary fibroblasts isolated from normal or EoE esophagi were treated with transforming growth factor (TGF)-β1 in the absence or presence of TZDs and, in some experiments, without or with budesonide and analyzed by quantitative real-time PCR and immunoblotting. Immunohistochemical analysis of human esophageal biopsies was performed. RESULTS EoE esophageal biopsies and esophageal fibroblasts expressed higher levels of the TZD receptor, peroxisome proliferator-activated receptor-γ (PPAR-γ), than normal controls. PPAR-γ was inducible by the Th2 cytokine, interleukin 4 (IL-4). TZD significantly reduced TGF-β1-induced myofibroblast and fibrotic gene and protein expression preferentially in EoE, but not normal esophageal fibroblasts. In esophageal fibroblasts, TGF-β1 increased phosphorylated Smad2/3 and p38, but TZDs preferentially inhibited p38 phosphorylation, suggesting signaling pathway-specific effects. The TZDs were more potent than budesonide at decreasing collagen-1α1 expression. DISCUSSION The TZDs preferentially exert antifibrotic effects in TGF-β1-activated EoE fibroblasts and provide a preclinical foundation for further investigation of the potential of the TZDs in EoE pathologic remodeling.OBJECTIVES Strong evidence links obesity to esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), and pancreatic cancer (PC). However, national-level studies testing the link between obesity and recent temporal trends in the incidence of these cancers are lacking. METHODS We queried the Surveillance, Epidemiology, and End Results (SEER) to identify the incidence of EC, GC, CRC, and PC. Cancer surgeries stratified by obesity (body mass index ≥30 kg/m) were obtained from the National Inpatient Sample (NIS). We quantified trends in cancer incidence and resections in 2002-2013, across age groups, using the average annual percent change (AAPC). RESULTS The incidence of CRC and GC increased in the 20-49 year age group (AAPC +1.5% and +0.7%, respectively, P less then 0.001) and across all ages for PC. Conversely, the incidence of CRC and GC decreased in patients 50 years or older and all adults for EC. According to the NIS, the number of patients with obesity undergoing CRC resections increased in all ages (highest AAPC was +15.3% in the 18-49 year age group with rectal cancer, P = 0.047). This trend was opposite to a general decrease in nonobese patients undergoing CRC resections. Furthermore, EC, GC, and PC resections only increased in adults 50 years or older with obesity. DISCUSSION Despite a temporal rise in young-onset CRC, GC, and PC, we only identify a corresponding increase in young adults with obesity undergoing CRC resections. These data support a hypothesis that the early onset of obesity may be shifting the risk of CRC to a younger age.INTRODUCTION Data about the efficacy of palliative double stenting for malignant duodenal and biliary obstruction are limited. METHODS A systematic literature search was performed to assess the feasibility and optimal method of double stenting for malignant duodenobiliary obstruction compared with surgical double bypass in terms of technical and clinical success, adverse events, reinterventions, and survival. Event rates with 95% confidence intervals were calculated. RESULTS Seventy-two retrospective and 8 prospective studies published until July 2018 were included. Technical and clinical success rates of double stenting were 97% (95%-99%) and 92% (89%-95%), respectively. Clinical success of endoscopic biliary stenting was higher than that of surgery (97% [94%-99%] vs 86% [78%-92%]). Double stenting was associated with less adverse events (13% [8%-19%] vs 28% [19%-38%]) but more frequent need for reintervention (21% [16%-27%] vs 10% [4%-19%]) than double bypass. No significant difference was found between technical and clinical success and reintervention rate of endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic drainage, and endoscopic ultrasound-guided biliary drainage. ERCP was associated with the least adverse events (3% [1%-6%]), followed by percutaneous transhepatic drainage (10% [0%-37%]) and endoscopic ultrasound-guided biliary drainage (23% [15%-33%]). DISCUSSION Substantially high technical and clinical success can be achieved with double stenting. Based on the adverse event profile, ERCP can be recommended as the first choice for biliary stenting as part of double stenting, if feasible. Prospective comparative studies with well-defined outcomes and cohorts are needed.INTRODUCTION Colonoscopy is an imperfect gold standard for detecting colorectal neoplasms because some proportion of adenomas may be missed, mainly small lesions. This proportion is expected to be higher in case of inadequate bowel cleansing, which is frequently seen in routine practice. We estimated the proportions of neoplasms that are in principle detectable by colonoscopy but might be missed in case of incomplete bowel preparation. METHODS For 8,193 participants of screening colonoscopy in South-Western Germany, recruited between 2005 and 2016, the prevalence and numbers of different findings were extracted from colonoscopy reports and compared according to the reported bowel preparation quality. RESULTS Bowel preparation quality was reported as good, poor, or was unspecified in 30.3%, 11.1%, and 58.6% of colonoscopy records. Reported prevalences of nonadvanced adenomas (NAAs) were similar among participants with poor and unspecified bowel preparation quality but substantially lower than among participants with good bowel preparation (adjusted prevalence rate ratio [RR] 0.