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Diener M.K.,The Surgical Center | Knebel P.,Visceral and Transplantation Surgery | Kieser M.,Institute of Medical Biometry and Informatics | Schuler P.,University of Heidelberg | And 28 more authors.
The Lancet

Background Postoperative surgical site infections are one of the most frequent complications after open abdominal surgery, and triclosan-coated sutures were developed to reduce their occurrence. The aim of the PROUD trial was to obtain reliable data for the eff ectiveness of triclosan-coated PDS Plus sutures for abdominal wall closure, compared with non-coated PDS II sutures, in the prevention of surgical site infections. Methods This multicentre, randomised controlled group-sequential superiority trial was done in 24 German hospitals. Adult patients (aged ≥18 years) who underwent elective midline abdominal laparotomy for any reason were eligible for inclusion. Exclusion criteria were impaired mental state, language problems, and participation in another intervention trial that interfered with the intervention or outcome of this trial. A central web-based randomisation tool was used to randomly assign eligible participants by permuted block randomisation with a 1:1 allocation ratio and block size 4 before mass closure to either triclosan-coated sutures (PDS Plus) or uncoated sutures (PDS II) for abdominal fascia closure. The primary endpoint was the occurrence of superfi cial or deep surgical site infection according to the Centers for Disease Control and Prevention criteria within 30 days after the operation. Patients, surgeons, and the outcome assessors were masked to group assignment. Interim and fi nal analyses were by modifi ed intention to treat. This trial is registered with the German Clinical Trials Register, number DRKS00000390. Findings Between April 7, 2010, and Oct 19, 2012, 1224 patients were randomly assigned to intervention groups (607 to PDS Plus, and 617 to PDS II), of whom 1185 (587 PDS Plus and 598 PDS II) were analysed by intention to treat. The study groups were well balanced in terms of patient and procedure characteristics. The occurrence of surgical site infections did not diff er between the PDS Plus group (87 [14.8%] of 587) and the PDS II group (96 [16.1%] of 598; OR 0.91, 95% CI 0.66-1.25; p=0.64). Serious adverse events also did not diff er between the groups-146 of 583 (25.0%) patients treated with PDS Plus had at least one serious adverse event, compared with 138 of 602 (22.9%) patients treated with PDS II; p=0.39). Interpretation Triclosan-coated PDS Plus did not reduce the occurrence of surgical site infection after elective midline laparotomy. Innovative, multifactorial strategies need to be developed and assessed in future trials to reduce surgical site infections. Funding Johnson & Johnson Medical Limited. Source

Rafnar T.,Amgen | Sulem P.,Amgen | Thorleifsson G.,Amgen | Vermeulen S.H.,Radboud University Nijmegen | And 86 more authors.
Human Molecular Genetics

Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have yielded common variants at 12 loci that associate with risk of the disease. We report here the results of a GWAS of UBC including 1670 UBC cases and 90 180 controls, followed by replication analysis in additional 5266 UBC cases and 10 456 controls. We tested a dataset containing 34.2 million variants, generated by imputation based on whole-genome sequencing of 2230 Icelanders. Several correlated variants at 20p12, represented by rs62185668, show genome-wide significant association with UBC after combining discovery and replication results (OR = 1.19, P = 1.5 × 10-11 for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately kb upstream from the JAG1 gene, an important component of the Notch signaling pathways that may be oncogenic or tumor suppressive in several forms of cancer. Our results add to the growing number of UBC risk variants discovered through GWAS. © The Author 2014. Source

Ovsiannikov D.,St. Josefs Hospital Dortmund Horde | Selinski S.,Leibniz Research Center for Working Environment and Human Factors o | Lehmann M.-L.,Leibniz Research Center for Working Environment and Human Factors o | Blaszkewicz M.,Leibniz Research Center for Working Environment and Human Factors o | And 4 more authors.
Journal of Toxicology and Environmental Health - Part A: Current Issues

In the 1990s, an uncommonly high percentage of glutathione S-transferase M1 (GSTM1) negative bladder cancer cases (70%) was reported in the greater Dortmund area. The question arose as to whether this uncommonly high percentage of GSTM1 negative bladder cancer cases was due to environmental and/or occupational exposure decades ago. Thus, 15 years later, another study on bladder cancer was performed in the same area after the coal, iron, and steel industries had finally closed in the 1990s. In total 196 bladder cancer patients from the St.-Josefs-Hospital Dortmund-Hörde and 235 controls with benign urological diseases were assessed by questionnaire and genotyped for GSTM1, glutathione S-transferase T1 (GSTT1), and the N-acetyltransferase 2 (NAT2) tag SNP rs1495741. The frequency of the GSTM1 negative genotype was 52% in bladder cancer cases and thus lower compared to a previous study performed from 1992 to 1995 in the same area (70%). NAT2 genotypes were distributed equally among cases and controls (63% slow acetylators). Fewer GSTT1 negative genotypes were present in cases (17%) than in controls (20%). Copyright © Taylor & Francis Group, LLC. Source

Ovsiannikov D.,Urologische Klinik | Stohr R.,Friedrich - Alexander - University, Erlangen - Nuremberg | Hartmann A.,Friedrich - Alexander - University, Erlangen - Nuremberg | Bottrich R.,St. Josefs Hospital Dortmund Horde | And 2 more authors.
Urologe - Ausgabe A

Bladder cancer may be caused by external factors like tobacco smoking, but may also be familial. We report on a father and son who developed this tumour at the ages of 45 and 35. Testing various genetic markers including the mismatch repair proteins MLH1, MSH2 and MSH6, whose loss is associated with a higher risk for hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome), did not point to a familial disease. Thus the heavy smoking habits of the two patients must be considered as causal. © 2011 Springer-Verlag. Source

Rafnar T.,DeCODE Genetics Inc. | Vermeulen S.H.,Biostatistics and HTA | Sulem P.,DeCODE Genetics Inc. | Thorleifsson G.,DeCODE Genetics Inc. | And 76 more authors.
Human Molecular Genetics

Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 3 10 -11. SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC. © The Author 2011. Published by Oxford University Press. All rights reserved. Source

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