Citations

Objective Recent guidelines on endoscopic sampling recommend complete gastric polyp removal for solitary fundic polyps >10 mm, hyperplastic polyps >5 mm and all adenomatous polyps. We aim to describe endoscopic approach to polyps in the time period prior to the American Society of Gastrointestinal Endoscopy (ASGE) guidelines and to identify opportunities for clinical practice improvements. Design Retrospective review of the Clinical Outcome Research Initiative (CORI) database, including all oesophagogastroduodenoscopies (OGDs). Reviewers grouped interventions during procedures based on instruments used for polyp sampling by forceps or snare polypectomy. Logistic regression estimated the effect of variables of interest on method of polypectomy. Results Of 783 037 OGDs reported in the CORI database, 25 670 (3.3%) described gastric polyps and met the inclusion criteria. Mean gastric polyp size was 6.5±4.9 mm, and 46.2% and 14.5% were located in the corpus and antrum, respectively. Polyps in the forceps group were smaller than polyps in the snare group (5.7±4.0 mm vs 9.3±6.4 mm, respectively, p<0.001). We identified 1056 polyps (41.3%) >10 mm that only underwent forceps biopsy. Forceps were used more frequently in the gastric fundus. Conclusions Snare polypectomy was underused in gastric polyps, per current ASGE guidelines. Anatomical location and endoscopic features of polyps were important predictors of the approach to gastric polypectomy.

ObjectiveTo examine the association between macrophage migration inhibitory factor (MIF) promoter polymorphisms and granulomatosis with polyangiitis (GPA) in human subjects, and to assess the role of MIF in a murine model of granulomatous vasculitis.MethodsThe human study involved 1,077 patients with GPA and healthy controls whose serum was genotyped by capillary electrophoresis for the MIF −794 CATT5−8 promoter microsatellite (rs5844572). MIF promoter, CATT‐length–dependent gene expression in response to β‐glucan was assessed by gene reporter assays. In mouse studies, granulomatous disease was induced by injection of Candida albicans β‐glucan into wild‐type (WT) or Mif‐knockout (Mif‐KO) C57BL/6 mice and C57BL/6 mice transgenically overexpressing Mif in lung epithelium (Mif lung–Tg2.1). Mice were treated with a neutralizing anti‐MIF antibody and analyzed for the density of pulmonary granulomas, expression of inflammatory chemokines, and frequency of mortality.ResultsThe percentage of human subjects carrying >5 CATT repeats in each MIF allele (high genotypic MIF expressers) was 60.2% among patients with GPA and 53.9% among healthy controls (adjusted P = 0.049). In response to granulomatous stimulation, human MIF gene expression increased proportionally with CATT length. Mif lung–Tg2.1 mice exhibited more pulmonary granulomas than WT mice, which in turn showed more granulomas than Mif‐KO mice. A significantly higher percentage of Mif lung–Tg2.1 mice, compared to Mif‐KO or WT mice, died when injected with Candida albicans β‐glucan, and treatment of these mice with an anti‐MIF monoclonal antibody protected against a lethal outcome. Levels of MIF‐dependent neutrophil/macrophage chemokines were elevated in the bronchoalveolar lavage fluid or plasma of Mif lung–Tg2.1 mice.ConclusionPatients with GPA have an increased frequency of high MIF expression CATT alleles. Higher Mif expression increases the incidence of mortality and pulmonary granulomas in Mif lung–Tg2.1 mice, while anti‐MIF treatment protects these mice against death. Blockade of MIF in high genotypic MIF expressers may therefore offer a selective pharmacologic therapy for GPA.

ABSTRACTBackgroundComplications related to peritoneal dialysis (PD) in patients with autosomal‐dominant polycystic kidney disease (ADPKD), including intraperitoneal rupture of renal cyst, hernia, membrane failure and peritonitis, have been reported. However, long‐term clinical outcomes of ADPKD patients on PD remain unclear. We performed this meta‐analysis to assess the risks of death, technique failure and peritonitis in ADPKD patients on PD.MethodsA systematic review was conducted using MEDLINE, EMBASE and Cochrane databases from inception to October 2017 to identify studies that evaluated the outcomes of ADPKD patients on PD, including the risks of death, technique failure and peritonitis. Non‐ADPKD patients on PD were used as controls. Effect estimates from the individual study were extracted and combined using the random‐effect, generic inverse variance method of DerSimonian and Laird.ResultsTwelve cohort studies with a total of 14 673 patients on PD (931 ADPKD and 13 742 non‐ADPKD patients) were enrolled. Compared with non‐ADPKD status, ADPKD was associated with significantly decreased mortality risk with pooled odds ratio (OR) of 0.68 (95% confidence interval (CI), 0.53–0.86; I2 = 0). There were no associations of ADPKD with the risks of technique failure of PD and peritonitis with pooled OR of 0.93 (95% CI, 0.79–1.10; I2 = 0) and 0.88 (95% CI, 0.75–1.05; I2 = 0), respectively. We found no publication bias as assessed by Egger's regression asymmetry test, with P = 0.90, 0.28 and 0.60 for the risks of mortality, technique failure and peritonitis in ADPKD patients on PD, respectively.ConclusionCompared with non‐ADPKD patients on PD, our study demonstrates that ADPKD patients on PD have 0.68‐fold decreased mortality risk. There are no associations of ADPKD status with the risks of technique failure or peritonitis.

AbstractOsteoblast differentiation is controlled by transcription factor RUNX2 which temporally activates or represses several bone‐related genes, including those encoding extracellular matrix proteins or factors that control cell‐cell, and cell‐matrix interactions. Cell‐cell communication in the many skeletal pericellular micro‐niches is critical for bone development and involves paracrine secretion of growth factors and morphogens. This paracrine signaling is in part regulated by “A Disintegrin And Metalloproteinase” (ADAM) proteins. These cell membrane‐associated metalloproteinases support proteolytic release (“shedding”) of protein ectodomains residing at the cell surface. We analyzed microarray and RNA‐sequencing data for Adam genes and show that Adam17, Adam10, and Adam9 are stimulated during BMP2 mediated induction of osteogenic differentiation and are robustly expressed in human osteoblastic cells. ADAM17, which was initially identified as a tumor necrosis factor alpha (TNFα) converting enzyme also called (TACE), regulates TNFα‐signaling pathway, which inhibits osteoblast differentiation. We demonstrate that Adam17 expression is suppressed by RUNX2 during osteoblast differentiation through the proximal Adam17 promoter region (−0.4 kb) containing two functional RUNX2 binding motifs. Adam17 downregulation during osteoblast differentiation is paralleled by increased RUNX2 expression, cytoplasmic‐nuclear translocation and enhanced binding to the Adam17 proximal promoter. Forced expression of Adam17 reduces Runx2 and Alpl expression, indicating that Adam17 may negatively modulate osteoblast differentiation. These findings suggest a novel regulatory mechanism involving a reciprocal Runx2‐Adam17 negative feedback loop to regulate progression through osteoblast differentiation. Our results suggest that RUNX2 may control paracrine signaling through regulation of ectodomain shedding at the cell surface of osteoblasts by directly suppressing Adam17 expression.

Abstract Background Volumetric laser endomicroscopy (VLE) provides circumferential images 3 mm into the biliary and pancreatic ducts. We aimed to correlate VLE images with the normal and abnormal microstructure of these ducts. Methods: Samples from patients undergoing hepatic or pancreatic resection were evaluated. VLE images were collected using a low-profile VLE catheter inserted manually into the biliary and pancreatic ducts ex vivo. Histological correlation was assessed by two unblinded investigators. Results 25 patients (20 liver and 5 pancreatic samples) and 111 images were analyzed. VLE revealed three histological layers: epithelium, connective tissue, and parenchyma. It identified distinctive patterns for primary sclerosing cholangitis (PSC), pancreatic cysts, neuroendocrine tumor, and adenocarcinoma adjacent to the pancreatic duct or ampulla. VLE failed to identify dysplasia in a dominant stricture and inflammatory infiltrates in PSC. Reflectivity measurements of the liver parenchyma diagnosed liver cirrhosis with high sensitivity. Conclusions VLE can identify histological changes in the biliary and pancreatic ducts allowing real-time diagnosis. Further studies are needed to measure the accuracy of VLE in a larger sample and to validate our findings in vivo.

Background Reducing readmission after catheter ablation ( CA ) in atrial fibrillation (AF) is important. Methods and Results We utilized National Readmission Data ( NRD ) 2010–2014. AF was identified by International Classification of Diseases, Ninth Edition, Clinical Modification (ICD‐9‐CM) diagnostic code 427.31 in the primary field, while first CA of AF was identified via ICD‐9 ‐procedure code 37.34. Any admission within 30 or 90 days of index admission was considered a readmission. Cox proportional hazard regression was used to adjust for confounders. The primary outcomes were 30‐ and 90‐day readmissions and the secondary outcome was AF recurrence. In total, 1 128 372 patients with AF were identified from January 1, 2010 to September 30, 2014. Of which 37 360 (3.3%) underwent CA . Patients aged ≥65 years and female sex were less likely to receive CA for AF . Overall, 10.9% and 16.5% of CA patients were readmitted within 30 and 90 days post‐CA, respectively. Most common causes of readmissions were arrhythmia ( AF , atrial flutter), heart failure, pulmonary causes (pneumonia, chronic obstructive pulmonary disease) and bleeding complications (gastrointestinal bleed, intracranial hemorrhage). Patients with diabetes mellitus, heart failure, coronary artery disease ( CAD ), chronic pulmonary and kidney disease, prior stroke/transient ischemic attack (TIA), female sex, length of stay ≥2 and disposition to the facility were prone to higher 30‐ and 90‐day readmissions post ‐CA . Predictors of increase in AF recurrence post‐ CA were female sex, diabetes mellitus, chronic pulmonary disease, and length of stay ≥2. Trends of 90‐day readmission and AF recurrence were found to improve over the study period. Conclusions We identified several demographic and clinical factors associated with the use of CA in AF , and short‐term outcomes of the same, which could potentially help in the patient selection and improve outcomes.