Biobank publications

Subscribe to Biobank publications feed Biobank publications
NCBI: db=pubmed; Term=biobank
Updated: 1 hour 30 min ago

Quantification of Stable Isotope Traces Close to Natural Enrichment in Human Plasma Metabolites Using Gas Chromatography-Mass Spectrometry.

Thu, 02/15/2018 - 15:29

Quantification of Stable Isotope Traces Close to Natural Enrichment in Human Plasma Metabolites Using Gas Chromatography-Mass Spectrometry.

Metabolites. 2018 Feb 14;8(1):

Authors: Krämer L, Jäger C, Trezzi JP, Jacobs DM, Hiller K

Abstract
Currently, changes in metabolic fluxes following consumption of stable isotope-enriched foods are usually limited to the analysis of postprandial kinetics of glucose. Kinetic information on a larger diversity of metabolites is often lacking, mainly due to the marginal percentage of fully isotopically enriched plant material in the administered food product, and hence, an even weaker 13C enrichment in downstream plasma metabolites. Therefore, we developed an analytical workflow to determine weak 13C enrichments of diverse plasma metabolites with conventional gas chromatography-mass spectrometry (GC-MS). The limit of quantification was increased by optimizing (1) the metabolite extraction from plasma, (2) the GC-MS measurement, and (3) most importantly, the computational data processing. We applied our workflow to study the catabolic dynamics of 13C-enriched wheat bread in three human subjects. For that purpose, we collected time-resolved human plasma samples at 16 timepoints after the consumption of 13C-labeled bread and quantified 13C enrichment of 12 metabolites (glucose, lactate, alanine, glycine, serine, citrate, glutamate, glutamine, valine, isoleucine, tyrosine, and threonine). Based on isotopomer specific analysis, we were able to distinguish catabolic profiles of starch and protein hydrolysis. More generally, our study highlights that conventional GC-MS equipment is sufficient to detect isotope traces below 1% if an appropriate data processing is integrated.

PMID: 29443915 [PubMed]

Night Shift Work, Genetic Risk, and Type 2 Diabetes in the UK Biobank.

Thu, 02/15/2018 - 15:29
Related Articles

Night Shift Work, Genetic Risk, and Type 2 Diabetes in the UK Biobank.

Diabetes Care. 2018 Feb 12;:

Authors: Vetter C, Dashti HS, Lane JM, Anderson SG, Schernhammer ES, Rutter MK, Saxena R, Scheer FAJL

Abstract
OBJECTIVE: To examine the effects of past and current night shift work and genetic type 2 diabetes vulnerability on type 2 diabetes odds.
RESEARCH DESIGN AND METHODS: In the UK Biobank, we examined associations of current (N = 272,214) and lifetime (N = 70,480) night shift work exposure with type 2 diabetes risk (6,770 and 1,191 prevalent cases, respectively). For 180,704 and 44,141 unrelated participants of European ancestry (4,002 and 726 cases, respectively) with genetic data, we assessed whether shift work exposure modified the relationship between a genetic risk score (comprising 110 single-nucleotide polymorphisms) for type 2 diabetes and prevalent diabetes.
RESULTS: Compared with day workers, all current night shift workers were at higher multivariable-adjusted odds for type 2 diabetes (none or rare night shifts: odds ratio [OR] 1.15 [95% CI 1.05-1.26]; some nights: OR 1.18 [95% CI 1.05-1.32]; and usual nights: OR 1.44 [95% CI 1.19-1.73]), except current permanent night shift workers (OR 1.09 [95% CI 0.93-1.27]). Considering a person's lifetime work schedule and compared with never shift workers, working more night shifts per month was associated with higher type 2 diabetes odds (<3/month: OR 1.24 [95% CI 0.90-1.68]; 3-8/month: OR 1.11 [95% CI 0.90-1.37]; and >8/month: OR 1.36 [95% CI 1.14-1.62]; Ptrend = 0.001). The association between genetic type 2 diabetes predisposition and type 2 diabetes odds was not modified by shift work exposure.
CONCLUSIONS: Our findings show that night shift work, especially rotating shift work including night shifts, is associated with higher type 2 diabetes odds and that the number of night shifts worked per month appears most relevant for type 2 diabetes odds. Also, shift work exposure does not modify genetic risk for type 2 diabetes, a novel finding that warrants replication.

PMID: 29440150 [PubMed - as supplied by publisher]

Associations of dyslipidaemia and lipid-lowering treatment with risk of postoperative cognitive dysfunction: a systematic review and meta-analysis.

Wed, 02/14/2018 - 13:45

Associations of dyslipidaemia and lipid-lowering treatment with risk of postoperative cognitive dysfunction: a systematic review and meta-analysis.

J Epidemiol Community Health. 2018 Feb 02;:

Authors: Feinkohl I, Winterer G, Pischon T

Abstract
BACKGROUND: Lipid imbalance is linked to age-related cognitive impairment, but its role in postoperative cognitive dysfunction (POCD) is unknown. Here, we present a systematic review and meta-analysis on dyslipidaemia, lipid-lowering treatment and POCD risk.
METHODS: PubMed, Ovid SP and Cochrane databases were searched for longitudinal studies that reported on associations of any measure of dyslipidaemia and/or lipid-lowering treatment with POCD as relative risks (RRs) or ORs. Fixed-effects inverse variance models were used to combine effects.
RESULTS: Of 205 articles identified in the search, 17 studies on 2725 patients (grand mean age 67 years; mean age range 61-71 years) with follow-up periods of 1 day to 4 years (median 7 days; IQR 1-68 days) were included. Studies focused almost exclusively on hypercholesterolaemia as a measure of dyslipidaemia and on statins as lipid-lowering treatment. Across 12 studies on hypercholesterolaemia, we found no association with POCD risk (RR 0.93; 95% CI 0.80 to 1.08; P=0.34). Statin use before surgery was associated with a reduced POCD risk across eight studies (RR 0.81; 95% CI 0.67 to 0.98; P=0.03), but data on treatment duration were lacking.
CONCLUSION: Statin users appear to be at reduced risk of POCD although hypercholesterolaemia per se may not be associated with POCD risk. Trial studies are needed to evaluate the usefulness of statins in POCD prevention.

PMID: 29437865 [PubMed - as supplied by publisher]

MR-PheWAS: exploring the causal effect of SUA level on multiple disease outcomes by using genetic instruments in UK Biobank.

Wed, 02/14/2018 - 13:45

MR-PheWAS: exploring the causal effect of SUA level on multiple disease outcomes by using genetic instruments in UK Biobank.

Ann Rheum Dis. 2018 Feb 06;:

Authors: Li X, Meng X, Spiliopoulou A, Timofeeva M, Wei WQ, Gifford A, Shen X, He Y, Varley T, McKeigue P, Tzoulaki I, Wright AF, Joshi P, Denny JC, Campbell H, Theodoratou E

Abstract
OBJECTIVES: We aimed to investigate the role of serum uric acid (SUA) level in a broad spectrum of disease outcomes using data for 120 091 individuals from UK Biobank.
METHODS: We performed a phenome-wide association study (PheWAS) to identify disease outcomes associated with SUA genetic risk loci. We then implemented conventional Mendelian randomisation (MR) analysis to investigate the causal relevance between SUA level and disease outcomes identified from PheWAS. We next applied MR Egger analysis to detect and account for potential pleiotropy, which conventional MR analysis might mistake for causality, and used the HEIDI (heterogeneity in dependent instruments) test to remove cross-phenotype associations that were likely due to genetic linkage.
RESULTS: Our PheWAS identified 25 disease groups/outcomes associated with SUA genetic risk loci after multiple testing correction (P<8.57e-05). Our conventional MR analysis implicated a causal role of SUA level in three disease groups: inflammatory polyarthropathies (OR=1.22, 95% CI 1.11 to 1.34), hypertensive disease (OR=1.08, 95% CI 1.03 to 1.14) and disorders of metabolism (OR=1.07, 95% CI 1.01 to 1.14); and four disease outcomes: gout (OR=4.88, 95% CI 3.91 to 6.09), essential hypertension (OR=1.08, 95% CI 1.03 to 1.14), myocardial infarction (OR=1.16, 95% CI 1.03 to 1.30) and coeliac disease (OR=1.41, 95% CI 1.05 to 1.89). After balancing pleiotropic effects in MR Egger analysis, only gout and its encompassing disease group of inflammatory polyarthropathies were considered to be causally associated with SUA level. Our analysis highlighted a locus (ATXN2/S2HB3) that may influence SUA level and multiple cardiovascular and autoimmune diseases via pleiotropy.
CONCLUSIONS: Elevated SUA level is convincing to cause gout and inflammatory polyarthropathies, and might act as a marker for the wider range of diseases with which it associates. Our findings support further investigation on the clinical relevance of SUA level with cardiovascular, metabolic, autoimmune and respiratory diseases.

PMID: 29437585 [PubMed - as supplied by publisher]

Number of incident cases of the main eye diseases of ageing in the UK Biobank cohort, projected over a 25-year period from time of recruitment.

Wed, 02/14/2018 - 13:45

Number of incident cases of the main eye diseases of ageing in the UK Biobank cohort, projected over a 25-year period from time of recruitment.

Br J Ophthalmol. 2018 Feb 06;:

Authors: Desai P, Minassian DC, Reidy A, Allen N, Sudlow C

Abstract
OBJECTIVES: To estimate the number of new cases of age-related macular degeneration, cataract and glaucoma accruing in the UK Biobank cohort, over a period of 25 years from time of recruitment. Our secondary objective was to assess the statistical power of nested case-control studies of these eye diseases. We aimed to provide quantitative information relevant to UK Biobank's eye disease case ascertainment efforts and to the potential for UK Biobank-based research into the causes of eye disease.
METHODS: We constructed a Markov discrete-time state transition model to simulate the population dynamics of the eye disorders within the UK Biobank cohort, using prevalence data from population-based epidemiological studies to derive incidence, and Office for National Statistics data on mortality and migration overseas.
RESULTS: By 2023, >900 new cases of each of 'wet' (neovascular) and 'dry' age-related macular degeneration, >1200 cases of primary open angle glaucoma and almost 15 000 cases of cataracts are expected to have accrued in the subcohort of 68 500 participants who had ocular assessment at baseline, with around seven times as many cases of each disease in the whole cohort of 500 000 participants. These predicted incident case numbers generate good or substantial statistical power for a range of nested case-control studies of potential genetic, lifestyle and environmental determinants of disease.
CONCLUSIONS: Over the next few years, UK Biobank is expected to generate sufficient numbers of new cases for statistically well-powered studies of the determinants of the major causes of sight loss: age-related macular degeneration, vision-impairing cataract and glaucoma.

PMID: 29437582 [PubMed - as supplied by publisher]

A Stepwise Procedure to Define a Data Collection Framework for a Clinical Biobank.

Wed, 02/14/2018 - 13:45

A Stepwise Procedure to Define a Data Collection Framework for a Clinical Biobank.

Biopreserv Biobank. 2018 Feb 13;:

Authors: Manders P, Peters TMA, Siezen AE, van Rooij IALM, Snijder R, Swinkels DW, Zielhuis GA

Abstract
INTRODUCTION: Current guidelines for clinical biobanking have a strong focus on obtaining, handling, and storage of biospecimens. However, to allow for research tying biomarker analysis to clinical decision making, there should be more focus on collection of data on donor characteristics. Therefore, our aim was to develop a stepwise procedure to define a framework as a tool to help start the data collection process in clinical biobanking.
MATERIALS AND METHODS: The Radboud Biobank (RB) is a central clinical biobanking facility designed in accordance with the standards set by the Parelsnoer Institute, a Dutch national biobank originally initiated with eight different disease cohorts. To organize the information of these cohorts, we used our experience and knowledge in the field of biobanking and translational research to identify research domains and information categories to classify data. We extended this classification system to a stepwise procedure for defining a data collection framework and examined its utility for existing RB biobanks.
RESULTS: Our approach resulted in the definition of a three-step procedure: (1) Identification of research domains and relevant questions within the field that may benefit from biobank samples. (2) Identification of information categories and accompanying subcategories that are relevant for answering questions in identified research domains. (3) Reduction to an efficient framework based on essentiality and quality criteria. We showed the utility of the procedure for three existing RB biobanks.
DISCUSSION: We developed guidelines for the definition of a framework that supports the standardization of the biobank data collection process. Connecting the biobank database to pertinent information collected from the electronic health record will improve data quality and efficiency for both care and research. This is crucial when using the corresponding biospecimens for scientific research. Further, it also facilitates the combination of different clinical biobanks for a specific disease.

PMID: 29437488 [PubMed - as supplied by publisher]

A novel variant in GLIS3 is associated with osteoarthritis.

Wed, 02/14/2018 - 13:45

A novel variant in GLIS3 is associated with osteoarthritis.

Ann Rheum Dis. 2018 Feb 07;:

Authors: Casalone E, Tachmazidou I, Zengini E, Hatzikotoulas K, Hackinger S, Suveges D, Steinberg J, Rayner NW, Consortium A, Wilkinson JM, Panoutsopoulou K, Zeggini E

Abstract
OBJECTIVES: Osteoarthritis (OA) is a complex disease, but its genetic aetiology remains poorly characterised. To identify novel susceptibility loci for OA, we carried out a genome-wide association study (GWAS) in individuals from the largest UK-based OA collections to date.
METHODS: We carried out a discovery GWAS in 5414 OA individuals with knee and/or hip total joint replacement (TJR) and 9939 population-based controls. We followed-up prioritised variants in OA subjects from the interim release of the UK Biobank resource (up to 12 658 cases and 50 898 controls) and our lead finding in operated OA subjects from the full release of UK Biobank (17 894 cases and 89 470 controls). We investigated its functional implications in methylation, gene expression and proteomics data in primary chondrocytes from 12 pairs of intact and degraded cartilage samples from patients undergoing TJR.
RESULTS: We detect a genome-wide significant association at rs10116772 with TJR (P=3.7×10-8; for allele A: OR (95% CI) 0.97 (0.96 to 0.98)), an intronic variant in GLIS3, which is expressed in cartilage. Variants in strong correlation with rs10116772 have been associated with elevated plasma glucose levels and diabetes.
CONCLUSIONS: We identify a novel susceptibility locus for OA that has been previously implicated in diabetes and glycaemic traits.

PMID: 29436472 [PubMed - as supplied by publisher]

Healthy living and cancer: evidence from UK Biobank.

Tue, 02/13/2018 - 21:30

Healthy living and cancer: evidence from UK Biobank.

Ecancermedicalscience. 2018;12:792

Authors: Elwood PC, Whitmarsh A, Gallacher J, Bayer A, Adams R, Heslop L, Pickering J, Morgan G, Galante J, Dolwani S, Longley M, Roberts ZE

Abstract
Context: UK Biobank is a prospective study of half a million subjects, almost all aged 40-69 years, identified in 22 centres across the UK during 2006-2010.
Objective: A healthy lifestyle has been described as 'better than any pill, and no side effects [5]. We therefore examined the relationships between healthy behaviours: low alcohol intake, non-smoking, healthy BMI, physical activity and a healthy diet, and the risk of all cancers, colon, breast and prostate cancers in a large dataset.
Method: Data on lifestyle behaviours were provided by 343,150 subjects, and height and weight were measured at recruitment. 14,285 subjects were diagnosed with cancer during a median of 5.1 years of follow-up.
Results: Compared with subjects who followed none or a single healthy behaviour, a healthy lifestyle based on all five behaviours was associated with a reduction of about one-third in incident cancer (hazard ratio [HR] 0.68; 95% confidence intervals [CI] 0.63-0.74). Colorectal cancer was reduced in subjects following the five behaviours by about one-quarter (HR 0.75; 95% CI 0.58-0.97), and breast cancer by about one-third (HR 0.65; 95% CI 0.52-0.83). The association between a healthy lifestyle and prostate cancer suggested a significant increase in risk, but this can be attributed to bias consequent on inequalities in the uptake of the prostate specific antigen screening test.
Conclusions: Taken together with reported reductions in diabetes, vascular disease and dementia, it is clearly important that every effort is taken to promote healthy lifestyles throughout the population, and it is pointed out that cancer and other screening clinics afford 'teachable moments' for the promotion of a healthy lifestyle.

PMID: 29434658 [PubMed]

Correction: Long-term intra-individual reproducibility of heart rate dynamics during exercise and recovery in the UK Biobank cohort.

Tue, 02/13/2018 - 21:30

Correction: Long-term intra-individual reproducibility of heart rate dynamics during exercise and recovery in the UK Biobank cohort.

PLoS One. 2018;13(2):e0193039

Authors: Orini M, Tinker A, Munroe PB, Lambiase PD

Abstract
[This corrects the article DOI: 10.1371/journal.pone.0183732.].

PMID: 29432496 [PubMed - in process]

The Japanese Society of Pathology Guidelines on the handling of pathological tissue samples for genomic research: Standard operating procedures based on empirical analyses.

Tue, 02/13/2018 - 21:30

The Japanese Society of Pathology Guidelines on the handling of pathological tissue samples for genomic research: Standard operating procedures based on empirical analyses.

Pathol Int. 2018 Feb;68(2):63-90

Authors: Kanai Y, Nishihara H, Miyagi Y, Tsuruyama T, Taguchi K, Katoh H, Takeuchi T, Gotoh M, Kuramoto J, Arai E, Ojima H, Shibuya A, Yoshida T, Akahane T, Kasajima R, Morita KI, Inazawa J, Sasaki T, Fukayama M, Oda Y

Abstract
Genome research using appropriately collected pathological tissue samples is expected to yield breakthroughs in the development of biomarkers and identification of therapeutic targets for diseases such as cancers. In this connection, the Japanese Society of Pathology (JSP) has developed "The JSP Guidelines on the Handling of Pathological Tissue Samples for Genomic Research" based on an abundance of data from empirical analyses of tissue samples collected and stored under various conditions. Tissue samples should be collected from appropriate sites within surgically resected specimens, without disturbing the features on which pathological diagnosis is based, while avoiding bleeding or necrotic foci. They should be collected as soon as possible after resection: at the latest within about 3 h of storage at 4°C. Preferably, snap-frozen samples should be stored in liquid nitrogen (about -180°C) until use. When intending to use genomic DNA extracted from formalin-fixed paraffin-embedded tissue, 10% neutral buffered formalin should be used. Insufficient fixation and overfixation must both be avoided. We hope that pathologists, clinicians, clinical laboratory technicians and biobank operators will come to master the handling of pathological tissue samples based on the standard operating procedures in these Guidelines to yield results that will assist in the realization of genomic medicine.

PMID: 29431262 [PubMed - in process]

Dietary assessment in UK Biobank: an evaluation of the performance of the touchscreen dietary questionnaire.

Tue, 02/13/2018 - 21:30

Dietary assessment in UK Biobank: an evaluation of the performance of the touchscreen dietary questionnaire.

J Nutr Sci. 2018;7:e6

Authors: Bradbury KE, Young HJ, Guo W, Key TJ

Abstract
UK Biobank is an open access prospective cohort of 500 000 men and women. Information on the frequency of consumption of main foods was collected at recruitment with a touchscreen questionnaire; prior to examining the associations between diet and disease, it is essential to evaluate the performance of the dietary touchscreen questionnaire. The objectives of the present paper are to: describe the repeatability of the touchscreen questionnaire in participants (n 20 348) who repeated the assessment centre visit approximately 4 years after recruitment, and compare the dietary touchscreen variables with mean intakes from participants (n 140 080) who completed at least one of the four web-based 24-h dietary assessments post-recruitment. For fish and meat items, 90 % or more of participants reported the same or adjacent category of intake at the repeat assessment visit; for vegetables and fruit, and for a derived partial fibre score (in fifths), 70 % or more of participants were classified into the same or adjacent category of intake (κweighted > 0·50 for all). Participants were also categorised based on their responses to the dietary touchscreen questionnaire at recruitment, and within each category the group mean intake of the same food group or nutrient from participants who had completed at least one web-based 24-h dietary assessment was calculated. The comparison showed that the dietary touchscreen variables, available on the full cohort, reliably rank participants according to intakes of the main food groups.

PMID: 29430297 [PubMed]

Transformation of Summary Statistics from Linear Mixed Model Association on All-or-None Traits to Odds Ratio.

Tue, 02/13/2018 - 21:30

Transformation of Summary Statistics from Linear Mixed Model Association on All-or-None Traits to Odds Ratio.

Genetics. 2018 Feb 02;:

Authors: Lloyd-Jones LR, Robinson MR, Yang J, Visscher PM

Abstract
Genome-wide association studies (GWAS) have identified thousands of loci that are robustly associated with complex diseases. The use of linear mixed model (LMM) methodology for GWAS is becoming more prevalent due to its ability to control for population structure and cryptic relatedness and increase power. The odds ratio (OR) is a common measure of the association of a disease with an exposure (e.g., a genetic variant) and is readably available from logistic regression. However, when the LMM is applied to all-or-none traits it provides estimates of genetic effects on the observed 0-1 scale, a different scale to that in logistic regression. This limits the comparability of results across studies, for example in a meta-analysis, and makes the interpretation of the magnitude of an effect from an LMM GWAS difficult. In this study, we derived transformations from the genetic effects estimated under the LMM to the OR that only rely on summary statistics. To test the proposed transformations, we used real genotypes from two large publicly available data sets to simulate all-or-none phenotypes for a set of scenarios that differ in underlying model, disease prevalence and heritability. Furthermore, we applied these transformations to GWAS summary statistics for type 2 diabetes generated from 108,042 individuals in the UK Biobank. In both simulation and real data application, we observed very high concordance between the transformed OR from the LMM and either the simulated truth or estimates from logistic regression. The transformations derived and validated in this study improve the comparability of results from prospective and already performed LMM GWAS on complex diseases by providing a reliable transformation to a common comparative scale for the genetic effects.

PMID: 29429966 [PubMed - as supplied by publisher]

[The biological rationale for immunotherapy in cancer].

Tue, 02/13/2018 - 21:30

[The biological rationale for immunotherapy in cancer].

Rev Mal Respir. 2018 Feb 07;:

Authors: Benzaquen J, Marquette CH, Glaichenhaus N, Leroy S, Hofman P, Ilié M

Abstract
INTRODUCTION: Immunotherapy aims to promote the immune system's activity against malignant cells by stimulating the response to several tumor antigens.
STATE OF THE ART: Immunosurveillance may adjust the immunogenicity of tumors. To be effective, immunity must induce the specific activation of CD4+ and CD8+ T lymphocytes, as well as activation of innate immunity. Activator and inhibitory costimulatory molecules regulate T lymphocyte activation at immunity checkpoints such as PD-1/PD-L1 and CTLA-4. Adaptive immune resistance confers tumour resistance to immunosurveillance through these immune checkpoints.
PERSPECTIVES: Approaches involving the combination of several immunotherapies with each other or with chemotherapy and radiotherapy and antibodies against other molecules of costimulation are under development. The development of biomarkers, which can select a targeted population and predict therapeutic response, represents a major challenge. Tumour high-throughput sequencing could refine "immunoscore". Intratumoral T cell receptor seems to represent a promising biomarker.
CONCLUSIONS: Numerous challenges still remain in developing research approaches for the development of immunotherapies.

PMID: 29428191 [PubMed - as supplied by publisher]

Risk Assessment for Venous Thromboembolism in Chemotherapy-Treated Ambulatory Cancer Patients.

Tue, 02/13/2018 - 21:30
Related Articles

Risk Assessment for Venous Thromboembolism in Chemotherapy-Treated Ambulatory Cancer Patients.

Med Decis Making. 2017 Feb;37(2):234-242

Authors: Ferroni P, Zanzotto FM, Scarpato N, Riondino S, Nanni U, Roselli M, Guadagni F

Abstract
OBJECTIVE: To design a precision medicine approach aimed at exploiting significant patterns in data, in order to produce venous thromboembolism (VTE) risk predictors for cancer outpatients that might be of advantage over the currently recommended model (Khorana score).
DESIGN: Multiple kernel learning (MKL) based on support vector machines and random optimization (RO) models were used to produce VTE risk predictors (referred to as machine learning [ML]-RO) yielding the best classification performance over a training (3-fold cross-validation) and testing set.
RESULTS: Attributes of the patient data set ( n = 1179) were clustered into 9 groups according to clinical significance. Our analysis produced 6 ML-RO models in the training set, which yielded better likelihood ratios (LRs) than baseline models. Of interest, the most significant LRs were observed in 2 ML-RO approaches not including the Khorana score (ML-RO-2: positive likelihood ratio [+LR] = 1.68, negative likelihood ratio [-LR] = 0.24; ML-RO-3: +LR = 1.64, -LR = 0.37). The enhanced performance of ML-RO approaches over the Khorana score was further confirmed by the analysis of the areas under the Precision-Recall curve (AUCPR), and the approaches were superior in the ML-RO approaches (best performances: ML-RO-2: AUCPR = 0.212; ML-RO-3-K: AUCPR = 0.146) compared with the Khorana score (AUCPR = 0.096). Of interest, the best-fitting model was ML-RO-2, in which blood lipids and body mass index/performance status retained the strongest weights, with a weaker association with tumor site/stage and drugs.
CONCLUSIONS: Although the monocentric validation of the presented predictors might represent a limitation, these results demonstrate that a model based on MKL and RO may represent a novel methodological approach to derive VTE risk classifiers. Moreover, this study highlights the advantages of optimizing the relative importance of groups of clinical attributes in the selection of VTE risk predictors.

PMID: 27491558 [PubMed - indexed for MEDLINE]

Combined CD44, c-MET, and EGFR expression in p16-positive and p16-negative head and neck squamous cell carcinomas.

Tue, 02/13/2018 - 21:30
Related Articles

Combined CD44, c-MET, and EGFR expression in p16-positive and p16-negative head and neck squamous cell carcinomas.

J Oral Pathol Med. 2017 Mar;46(3):208-213

Authors: Baschnagel AM, Tonlaar N, Eskandari M, Kumar T, Williams L, Hanna A, Pruetz BL, Wilson GD

Abstract
PURPOSE/OBJECTIVE(S): To examine the association between CD44 and c-MET expression in relation to p16 and EGFR in patients with head and neck squamous cell carcinoma (HNSCC).
MATERIALS/METHODS: Immunohistochemical staining of CD44, p16, EGFR, and c-MET was performed on 105 locally advanced HNSCC patients treated with chemoradiation. CD44 expression was correlated with c-MET, EGFR, and p16, locoregional control (LRC), distant metastases (DM), disease-free survival (DFS) and overall survival (OS).
RESULTS: High CD44 expression was present in 33% of patients and was associated with non-oropharynx primaries (P < 0.001), high c-MET expression (P < 0.001), p16-negative (P < 0.001) and EGFR-positive tumors (P < 0.001). Fifty-seven percent of CD44 high expressing tumors had high c-MET expression compared to 21% of CD44 low expressing tumors (P < 0.001). High CD44 expression predicted for worse LRC (HR: 2.44; 95% CI: 1.16-5.13; P = 0.018), DFS (HR: 2.61; 95% CI: 1.46-4.67; P = 0.001), and OS (HR: 2.52; 95% CI: 1.30-4.92; P = 0.007) but not DM (P = 0.57) on univariate analysis. Patients with both high CD44 and c-MET expression had a poor prognosis with a 2-year DFS of 30% compared to 70% in the rest of the cohort (P = 0.003). On multivariable analysis, after adjusting for site, T-stage, smoking history, and EGFR status, high c-MET (P = 0.039) and negative p16 status (P = 0.034) predicted for worse DFS, while high CD44 expression did not (P = 0.43).
CONCLUSIONS: High CD44 expression is associated with high c-MET expression, p16-negative tumors, and EGFR-positive tumors. The combination of these markers predicts for poor prognosis in HNSCC patients treated with chemoradiation.

PMID: 27442811 [PubMed - indexed for MEDLINE]

Frequent reconstitution of IDH2(R140Q) mutant clonal multilineage hematopoiesis following chemotherapy for acute myeloid leukemia.

Tue, 02/13/2018 - 21:30
Related Articles

Frequent reconstitution of IDH2(R140Q) mutant clonal multilineage hematopoiesis following chemotherapy for acute myeloid leukemia.

Leukemia. 2016 09;30(9):1946-50

Authors: Wiseman DH, Williams EL, Wilks DP, Sun Leong H, Somerville TD, Dennis MW, Struys EA, Bakkali A, Salomons GS, Somervaille TC

PMID: 27118404 [PubMed - indexed for MEDLINE]

Dasatinib, a Src inhibitor, sensitizes liver metastatic colorectal carcinoma to oxaliplatin in tumors with high levels of phospho-Src.

Tue, 02/13/2018 - 21:30
Related Articles

Dasatinib, a Src inhibitor, sensitizes liver metastatic colorectal carcinoma to oxaliplatin in tumors with high levels of phospho-Src.

Oncotarget. 2016 May 31;7(22):33111-24

Authors: Perez M, Lucena-Cacace A, Marín-Gómez LM, Padillo-Ruiz J, Robles-Frias MJ, Saez C, Garcia-Carbonero R, Carnero A

Abstract
Despite the development of new antineoplastic agents for the treatment of colorectal cancer (CRC), oxaliplatin and fluoropyrimidines remain the most commonly employed drugs for the treatment of both early and advanced disease. Intrinsic or acquired resistance is, however, an important limitation to pharmacological therapy, and the development of chemosensitization strategies constitute a major goal with important clinical implications. In the present work, we determined that high levels of activated Src kinase, measured as phospho-Src at the Tyr419 residue in CRC cell lines, can promote colorectal carcinoma cell resistance to oxaliplatin, but not to 5-fluorouracil (5FU), and that inhibition of this protein restores sensitivity to oxaliplatin. Similar results were observed with in vivo patient-derived xenograft (PDX) models that were orthotopically grown in murine livers. In PDX tumor lines derived from human CRC liver metastasis, dasatinib, a Src inhibitor, increases sensitivity to oxaliplatin only in tumors with high p-Src. However, dasatinib did not modify sensitivity to 5FU in any of the models. Our data suggest that chemoresistance induced by p-Src is specific to oxaliplatin, and that p-Src levels can be used to identify patients who may benefit from this combination therapy. These results are relevant for clinicians as they identify a novel biomarker of drug resistance that is suitable to pharmacological manipulation.

PMID: 27105527 [PubMed - indexed for MEDLINE]

Association of benign prostatic hyperplasia and subsequent risk of bladder cancer: an Asian population cohort study.

Sun, 02/11/2018 - 14:37

Association of benign prostatic hyperplasia and subsequent risk of bladder cancer: an Asian population cohort study.

World J Urol. 2018 Feb 09;:

Authors: Fang CW, Liao CH, Wu SC, Muo CH

Abstract
OBJECTIVES: Few studies discussed the link between benign prostatic hyperplasia (BPH) and bladder cancer. We performed this cohort study to investigate whether there is an association between BPH and subsequent risk of bladder cancer.
METHODS: We identified 35,092 study subjects including 17546 BPH patients and 17546 comparisons from the National Health Insurance database. The comparison cohort was frequency matched with age and index-year. We measured subsequent bladder cancer rates (per 1000 person-years) in two cohorts. Attributable risks (ARs) was calculated based on the bladder cancer rates in two cohorts. The hazard ratios (HRs) and 95% confidence intervals (CIs) for bladder cancer were estimated via Cox proportional hazard regression.
RESULTS: BPH patients had a higher bladder cancer rate than comparisons (AR = 0.81 per 1000 person-years) and exhibited 4.69- and 4.11-fold increases in bladder cancer risk in the crude and adjusted Cox models, respectively (95% CIs = 4.15-6.99 and 2.70-6.26). The AR was highest in patients aged 65-74 years old (AR = 1.33). BPH patients with chronic kidney disease were at an elevated bladder cancer risk. Regarding the association between bladder cancer and transurethral prostatectomy (TURP), BPH patients who underwent TURP were at a higher risk of bladder cancer (AR = 1.69; HR = 6.17, 95% CI = 3.68-10.3) than those who did not (AR = 0.69; HR = 3.73, 95% CI = 2.43-5.74).
CONCLUSIONS: In this study, BPH patients were found to have an increased risk of subsequent bladder cancer. Based on the limitations of retrospective nature, further studies are needed.

PMID: 29427001 [PubMed - as supplied by publisher]

Correction: Phenome-wide heritability analysis of the UK Biobank.

Sat, 02/10/2018 - 13:46

Correction: Phenome-wide heritability analysis of the UK Biobank.

PLoS Genet. 2018 Feb;14(2):e1007228

Authors: Ge T, Chen CY, Neale BM, Sabuncu MR, Smoller JW

Abstract
[This corrects the article DOI: 10.1371/journal.pgen.1006711.].

PMID: 29425192 [PubMed - in process]

IL8 and IL16 levels indicate serum and plasma quality.

Sat, 02/10/2018 - 13:46

IL8 and IL16 levels indicate serum and plasma quality.

Clin Chem Lab Med. 2018 Feb 09;:

Authors: Kofanova O, Henry E, Quesada RA, Bulla A, Linares HN, Lescuyer P, Shea K, Stone M, Tybring G, Bellora C, Betsou F

Abstract
BACKGROUND: Longer pre-centrifugation times alter the quality of serum and plasma samples. Markers for such delays in sample processing and hence for the sample quality, have been identified.
METHODS: Twenty cytokines in serum, EDTA plasma and citrate plasma samples were screened for changes in concentration induced by extended blood pre-centrifugation delays at room temperature. The two cytokines that showed the largest changes were further validated for their "diagnostic performance" in identifying serum or plasma samples with extended pre-centrifugation times.
RESULTS: In this study, using R&D Systems ELISA kits, EDTA plasma samples and serum samples with a pre-centrifugation delay longer than 24 h had an IL16 concentration higher than 313 pg/mL, and an IL8 concentration higher than 125 pg/mL, respectively. EDTA plasma samples with a pre-centrifugation delay longer than 48 h had an IL16 concentration higher than 897 pg/mL, citrate plasma samples had an IL8 concentration higher than 21.5 pg/mL and serum samples had an IL8 concentration higher than 528 pg/mL.
CONCLUSIONS: These robust and accurate tools, based on simple and commercially available ELISA assays can greatly facilitate qualification of serum and plasma legacy collections with undocumented pre-analytics.

PMID: 29425105 [PubMed - as supplied by publisher]