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81.

Objective

For patients with metastatic renal cell cancer (mRCC), treatment choice is mainly based on clinical parameters. With many treatments available and the limited response to treatment and associated toxicities, there is much interest in identifying better biomarkers for personalized treatment. EuroTARGET aims to identify and characterize host- and tumor-related biomarkers for prediction of response to tyrosine kinase inhibitor therapy in mRCC. Here, we describe the EuroTARGET mRCC patient cohort.

Methods and materials

EuroTARGET is a European collaborative project designed as an observational study for which patients with mRCC were recruited prospectively in 62 centers. In addition, 462 patients with mRCC from previous studies were included. Detailed clinical information (baseline and follow-up) from all patients was entered in web-based case record forms. Blood was collected for germline DNA and pharmacokinetic/pharmacodynamic analyses and, where available, fresh-frozen tumor material was collected to perform tumor DNA, RNA, kinome, and methylome analyses.

Results

In total, 1,210 patients with mRCC were included. Of these, 920 received a tyrosine kinase inhibitor as first-line targeted treatment (sunitinib [N = 713, 78%], sorafenib [N = 41, 4%], or pazopanib [N = 166, 18%]) and had at least 6 months of outcome assessment (median follow-up 15.3 months [interquartile range: 8.5–30.2 months]). Germline DNA samples were available from 824 of these patients, fresh-frozen tumor material from 142 patients, fresh-frozen normal kidney tissue from 95 patients, and tissue microarrays created from formalin-fixed paraffin-embedded tumor material from 247 patients. Of the 920 patients, germline DNA variant chip data were successfully generated for 811 patients (Illumina HumanOmniExpress BeadChip). For 80 patients, next-generation exome sequencing of germline and tumor DNA was performed, tumor RNA sequencing was performed for 124 patients, kinome activity measured and processed for 121 patients (PamChip), and methylome data (Illumina Infinium HumanMethylation450 BeadChip) were created for 116 RCC tissues (and 23 normal kidney tissues). For 73 out of the 920 patients, all platform data types were generated. In addition, 40 patients were included in a pharmacokinetic/pharmacodynamic phase IV substudy.

Conclusions

Analysis of EuroTARGET cohort data will contribute to personalization of therapy for patients with mRCC. The extensive clinical data and multiplatform EuroTARGET data will be freely available.  相似文献   
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83.
Acid-fast bacilli (AFB) were detected in the autopsy lung tissue homogenate samples of four cows (variety Frisian cross) in a dairy farm in Bangladesh. Histopathological examination of the lung tissue demonstrated prominent granulomas, caseating necrosis and calcification indicative of tuberculosis (TB) infection. Mycobacteria could not be cultured from the tissue homogenate samples by Lowenstein-Jensen based conventional culture method though AFB were evident by Ziehl-Neelsen (ZN) staining of the smears of tissue homogenate and in paraffin embedded tissue slices. Spoligotyping performed on DNA extracts of paraffin embedded lung tissue samples confirmed the AFB as a member of the M. tuberculosis complex (MTBC) with a pattern assigned to M. africanum subtype I. This characterization by spoligotyping was confirmed by subjecting M. africanum subtype I isolates from other parts of the world to an alternative identification method based on DNA polymorphism in the gyrB gene (Hain Life Science, GmbH, Nehren, Germany). Since M. africanum is believed to be a human pathogen, general infection in cattle may be a public health threat. The presence of these bacteria in the animal reservoir most likely originated from a caretaker.  相似文献   
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85.
"Mycobacterium tilburgii" is a nontuberculous mycobacterium that cannot be cultured by current techniques. It is described as causing disseminated disease in adults. We present the first cases of disseminated disease in 2 immunocompromised children. This paper stresses the importance of molecular techniques for correct mycobacterial identification and guidance to immunological diagnosis.  相似文献   
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87.
Direct repeat spoligotyping of 85 paraffin-embedded lung biopsies was used to investigated the occurrence around Beijing of the Beijing family of Mycobacterium tuberculosis. Samples ranged in time from 1956 to 1990. Hybridization patterns were found with 49 (58%) samples, and 45 (92%) produced typical Beijing family patterns extending over the 34-year period.  相似文献   
88.
PurposeTo analyze agreement on postoperative complications after hypospadias surgery according to medical records and parents' reports.Materials & methodsIn this retrospective cohort study, data were collected from 409 children who received an initial one-stage hypospadias correction in the Radboudumc, The Netherlands.Postoperative complications according to medical records were compared with parent-reported complications in an online questionnaire. Main complications studied were wound-related complications, urinary tract infections, fistulas, stenosis, and prepuce-related complications. Agreement was determined by Cohen's kappa coefficient.ResultsSlightly less complications were mentioned in medical records (37%) compared to parents' reports (42%). Overall agreement was moderate (κ = 0.50, 95% confidence interval (CI):0.41–0.59), but poor for some specific complications. Agreement was higher for complications that needed reoperation compared to when no reoperation was performed (κ = 0.53, 95% CI: 0.43–0.62 and κ = 0.18, 95% CI: 0.06–0.31) and for patients with recent surgery (< 5 years before questionnaire completion) compared to less recent surgeries (κ = 0.69, 95% CI: 0.55–0.84 and κ = 0.43, 95% CI: 0.33–0.54).ConclusionsAgreement on complications according to medical records and parents' reports was poor to moderate, but better after reoperation and more recent surgery. Some complications mentioned in medical records were missing from parents' reports and the other way around. Better agreement will give physicians and parents a more reliable view on postoperative outcome after hypospadias surgery.Type of studyDiagnostic test.Level of evidenceLevel III.  相似文献   
89.

Background  

Preventive interventions are developed for children of parents with mental and substance use disorders (COPMI), because these children have a higher risk of developing a psychological or behavioral disorder in the future. Mental health and substance use disorders contribute significantly to the global burden of disease. Although the exact number of parents with a mental illness is unclear, the subject of mentally ill parents is gaining attention. Moreover there is a lack of interventions for COPMI-children, as well of (cost-) effectiveness studies evaluating COPMI interventions. Innovative interventions such as e-health provide a new field for exploration. There is no knowledge about the opportunities for using the internet to prevent problems in children at risk. In the current study we will focus on the (cost-) effectiveness of an online health prevention program for COPMI-children.  相似文献   
90.
International collaboration is essential for the optimal selection of unrelated hematopoietic stem cell donors. This review focuses on the benefit of a joint worldwide donor file called Bone Marrow Donors Worldwide and the experience of the Europdonor Foundation in selecting strategies to identify the best human leukocyte antigen-matched donor in the shortest time.  相似文献   
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