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Precision medicine risk prediction

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https://www.readbyqxmd.com/read/28524737/utilizing-next-generation-sequencing-in-the-management-of-multiple-myeloma
#1
Marta Lionetti, Antonino Neri
Multiple myeloma (MM) is a bone marrow plasma cell malignancy characterized by wide clinical presentation and heterogeneous genetic background. Despite the recent advances in patient outcome, new markers are needed for improving risk prediction and choice of a more appropriate therapy. In this perspective, the genetic makeup of MM cells is being better characterized by means of next-generation sequencing (NGS) technologies. Areas covered: The authors discuss how the application of NGS has improved our knowledge of MM biology by discovering its mutational landscape, identifying the operating mutational processes, and revealing the clonal composition of tumors and the dynamics of its evolution; and how this can have important clinical implications in terms of prognostication, therapeutic choices, and response assessment...
May 26, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28523274/identification-of-braf-positive-cases-based-on-whole-slide-image-analysis
#2
Vlad Popovici, Aleš Křenek, Eva Budinská
A key requirement for precision medicine is the accurate identification of patients that would respond to a specific treatment or those that represent a high-risk group, and a plethora of molecular biomarkers have been proposed for this purpose during the last decade. Their application in clinical settings, however, is not always straightforward due to relatively high costs of some tests, limited availability of the biological material and time, and procedural constraints. Hence, there is an increasing interest in constructing tissue-based surrogate biomarkers that could be applied with minimal overhead directly to histopathology images and which could be used for guiding the selection of eventual further molecular tests...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28499030/moderator-s-view-predictive-models-a-prelude-to-precision-nephrology
#3
Carmine Zoccali
Appropriate diagnosis is fundamental in medicine because it sets the basis for the prediction of disease outcome at the single patient level (prognosis) and decisions regarding the most appropriate therapy. However, given the large series of social, clinical and biological factors that determine the likelihood of an individual's future outcome, prognosis only partly depends on diagnosis and aetiology and treatment is not decided solely on the basis of the underlying diagnosis. This issue is crucial in multifactorial diseases like atherosclerosis, where the use of statins has now shifted from 'treating hypercholesterolaemia' to 'treating the risk of adverse cardiovascular events'...
May 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28497916/emerging-endotypes-of-chronic-rhinosinusitis-and-its-application-to-precision-medicine
#4
REVIEW
Dae Woo Kim, Seong H Cho
Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease with various underlying pathophysiologic mechanisms which translate to endotypes, in contrast to clinical phenotypes or histological subtypes. Defining endotypes can help clinicians predict disease prognosis, select subjects suitable for a specific therapy, and assess risks for comorbid conditions, including asthma. Therefore, with recent advancement of biologicals in CRS clinical trials, endotyping can be a breakthrough in treating recalcitrant CRS...
July 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28497027/data-based-radiation-oncology-design-of-clinical-trials-in-the-toxicity-biomarkers-era
#5
REVIEW
David Azria, Ariane Lapierre, Sophie Gourgou, Dirk De Ruysscher, Jacques Colinge, Philippe Lambin, Muriel Brengues, Tim Ward, Søren M Bentzen, Hubert Thierens, Tiziana Rancati, Christopher J Talbot, Ana Vega, Sarah L Kerns, Christian Nicolaj Andreassen, Jenny Chang-Claude, Catharine M L West, Corey M Gill, Barry S Rosenstein
The ability to stratify patients using a set of biomarkers, which predict that toxicity risk would allow for radiotherapy (RT) modulation and serve as a valuable tool for precision medicine and personalized RT. For patients presenting with tumors with a low risk of recurrence, modifying RT schedules to avoid toxicity would be clinically advantageous. Indeed, for the patient at low risk of developing radiation-associated toxicity, use of a hypofractionated protocol could be proposed leading to treatment time reduction and a cost-utility advantage...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28493232/anthracycline-induced-cardiotoxicity-biomarkers-and-omics-technology-in-the-era-of-patient-specific-care
#6
REVIEW
Shayan Moazeni, Martin Cadeiras, Eric H Yang, Mario C Deng, Kim-Lien Nguyen
Anthracyclines are highly effective against a variety of malignancies. However, their dose-dependent cardiotoxic effects can potentially limit their use. In the past decade, serum biomarkers have been used to diagnose, monitor, predict, and prognosticate disease. Biomarkers such as cardiac troponin and natriuretic peptides have some predictive value, but still lack reliability in this patient population. Novel biomarkers such as galectin-3, soluble ST-2 proteins, myeloperoxidase, and fibrocytes are being explored as potential biomarkers to reliably predict the onset of cardiotoxicity...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28490744/precision-radiology-predicting-longevity-using-feature-engineering-and-deep-learning-methods-in-a-radiomics-framework
#7
Luke Oakden-Rayner, Gustavo Carneiro, Taryn Bessen, Jacinto C Nascimento, Andrew P Bradley, Lyle J Palmer
Precision medicine approaches rely on obtaining precise knowledge of the true state of health of an individual patient, which results from a combination of their genetic risks and environmental exposures. This approach is currently limited by the lack of effective and efficient non-invasive medical tests to define the full range of phenotypic variation associated with individual health. Such knowledge is critical for improved early intervention, for better treatment decisions, and for ameliorating the steadily worsening epidemic of chronic disease...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28456503/novel-oxytocin-receptor-variants-in-laboring-women-requiring-high-doses-of-oxytocin
#8
Erin L Reinl, Zane A Goodwin, Nandini Raghuraman, Grace Y Lee, Erin Y Jo, Beakal M Gezahegn, Meghan K Pillai, Alison G Cahill, Cristina De Guzman Strong, Sarah K England
BACKGROUND: Although oxytocin commonly is used to augment or induce labor, it is difficult to predict its effectiveness because oxytocin dose requirements vary significantly among women. One possibility is that women requiring high or low doses of oxytocin have variations in the oxytocin receptor gene. OBJECTIVES: To identify oxytocin receptor gene variants in laboring women with low and high oxytocin dosage requirements. STUDY DESIGN: Term, nulliparous women requiring oxytocin doses of ≤4 mU/min (low-dose requiring, n = 83) or ≥20 mU/min (high-dose requiring, n = 104) for labor augmentation or induction provided consent to a postpartum blood draw as a source of genomic DNA...
April 26, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28439188/next-generation-sequencing-reveals-high-prevalence-of-brca1-and-brca2-variants-of-unknown-significance-in-early-onset-breast-cancer-in-african-american-women
#9
Luisel Ricks-Santi, J Tyson McDonald, Bert Gold, Michael Dean, Nicole Thompson, Muneer Abbas, Bradford Wilson, Yasmine Kanaan, Tammey J Naab, Georgia Dunston
BACKGROUND: Variants of unknown significance (VUSs) have been identified in BRCA1 and BRCA2 and account for the majority of all identified sequence alterations. Notably, VUSs occur disproportionately in people of African descent hampering breast cancer (BCa) management and prevention efforts in the population. Our study sought to identify and characterize mutations associated with increased risk of BCa at young age. METHODS: In our study, the spectrum of mutations in BRCA1 and BRCA2 was enumerated in a cohort of 31 African American women of early age at onset breast cancer, with a family history of breast or cancer in general and/or with triple negative breast cancer...
2017: Ethnicity & Disease
https://www.readbyqxmd.com/read/28432351/early-measurement-of-il-10-predicts-the-outcomes-of-patients-with-acute-respiratory-distress-syndrome-receiving-extracorporeal-membrane-oxygenation
#10
Chia-Hsiung Liu, Shuenn-Wen Kuo, Wen-Je Ko, Pi-Ru Tsai, Shu-Wei Wu, Chien-Heng Lai, Chih-Hsien Wang, Yih-Sharng Chen, Pei-Lung Chen, Tze-Tze Liu, Shu-Chien Huang, Tzuu-Shuh Jou
Patients diagnosed with acute respiratory distress syndrome are generally severely distressed and associated with high morbidity and mortality despite aggressive treatments such as extracorporeal membrane oxygenation (ECMO) support. To identify potential biomarker of predicting value for appropriate use of this intensive care resource, plasma interleukin-10 along with relevant inflammatory cytokines and immune cell populations were examined during the early and subsequent disease courses of 51 critically ill patients who received ECMO support...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28430339/characterization-of-a-rare-nonpathogenic-sequence-variant-c-1905c-t-of-the-dihydropyrimidine-dehydrogenase-gene-dpyd
#11
Raffaele Palmirotta, Domenica Lovero, Erica Silvestris, Claudia Carella, Claudia Felici, Davide Quaresmini, Paola Cafforio, Franco Silvestris
BACKGROUND: In the era of precision medicine, the suitability of fluoropyrimidine therapies in clinical oncology can be checked by pharmacogenetic investigations of single patients, thus optimizing resources and indicating the appropriate drugs to personalize their chemotherapy. For example, the presence of dihydropyrimidine dehydrogenase gene (DPYD) polymorphisms in cancer patients may lead to adverse effects when adopting fluoropyrimidine-based therapies. METHODS: We detected in a cancer patient a rare germline synonymous heterozygous variant of DPYD (c...
April 11, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28408460/can-histologic-transformation-of-follicular-lymphoma-be-predicted-and-prevented
#12
Robert Kridel, Laurie H Sehn, Randy D Gascoyne
Transformation to aggressive lymphoma is a critical event in the clinical course of follicular lymphoma patients. Yet, it is a challenge to reliably predict transformation at the time of diagnosis. Understanding the risk of transformation would be useful to guide and monitor patients, as well as for evaluation of novel treatment strategies that could potentially prevent transformation. Herein, we review the contribution of clinical, pathological and genetic risk factors to transformation. Patients with multiple clinical high-risk factors are at elevated risk of transformation but we are currently lacking a prognostic index that would specifically address transformation rather than disease progression or overall survival...
April 13, 2017: Blood
https://www.readbyqxmd.com/read/28390881/safe-selection-of-outpatient-joint-arthroplasty-patients-with-medical-risk-stratification-the-outpatient-arthroplasty-risk-assessment-score
#13
R Michael Meneghini, Mary Ziemba-Davis, Marshall K Ishmael, Alexander L Kuzma, Peter Caccavallo
BACKGROUND: Current patient selection criteria and medical risk stratification methods for outpatient primary total joint arthroplasty (TJA) surgery are unproven. This study assessed the predictive ability of a medically based risk assessment score in selecting patients for outpatient and short stay surgery. METHODS: A retrospective review of 1120 consecutive primary TJAs in an early discharge program was performed. An Outpatient Arthroplasty Risk Assessment ("OARA") score was developed by a high-volume arthroplasty surgeon and perioperative internal medicine specialist to stratify patients as "low-moderate risk (≤59)" and "not appropriate" (≥60) for early discharge...
March 14, 2017: Journal of Arthroplasty
https://www.readbyqxmd.com/read/28283684/pharmacogenetics-in-type-2-diabetes-precision-medicine-or-discovery-tool
#14
REVIEW
Jose C Florez
In recent years, technological and analytical advances have led to an explosion in the discovery of genetic loci associated with type 2 diabetes. However, their ability to improve prediction of disease outcomes beyond standard clinical risk factors has been limited. On the other hand, genetic effects on drug response may be stronger than those commonly seen for disease incidence. Pharmacogenetic findings may aid in identifying new drug targets, elucidate pathophysiology, unravel disease heterogeneity, help prioritise specific genes in regions of genetic association, and contribute to personalised or precision treatment...
March 10, 2017: Diabetologia
https://www.readbyqxmd.com/read/28281838/diagnostic-function-of-the-neuroinflammatory-biomarker-ykl-40-in-alzheimer-s-disease-and-other-neurodegenerative-diseases
#15
Filippo Baldacci, Simone Lista, Enrica Cavedo, Ubaldo Bonuccelli, Harald Hampel
Neuroinflammation is a crucial mechanism in the pathophysiology of neurodegenerative diseases pathophysiology. Cerebrospinal fluid (CSF) YKL-40 - an indicator of microglial activation - has recently been identified by proteomic studies as a candidate biomarker for Alzheimer's disease (AD). Areas covered: We review the impact of CSF YKL-40 as a pathophysiological biomarker for AD and other neurodegenerative diseases. CSF YKL-40 concentrations have been shown to predict progression from prodromal mild cognitive impairment to AD dementia...
March 20, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28273476/predicting-polygenic-obesity-using-genetic-information
#16
REVIEW
Ruth J F Loos, A Cecile J W Janssens
Except in rare cases, obesity tends to be a consequence of both an unhealthy lifestyle and a genetic susceptibility to gain weight. With more than 200 common genetic variants identified, there is a growing interest in developing personalized preventive and treatment strategies to predict an individual's obesity risk. We review the literature on the prediction of obesity and show that models based on the established genetic variants have poorer predictive ability than traditional predictors, such as family history of obesity and childhood obesity...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28261156/a-decision-tree-analysis-of-diabetic-foot-amputation-risk-in-indian-patients
#17
Prasad Umesh Kasbekar, Pranay Goel, Shailaja Prakash Jadhav
AIM: The aim of this study is to create an evidence-based tool that guides the risk of amputation in diabetic foot patients. MATERIALS AND METHODS: Hospital records of 301 diabetic foot patients were examined retrospectively for explanatory variables of foot amputation decisions. The study included all patients with a lower limb ulcer with a known history of diabetes mellitus or those diagnosed post-admission. The dataset was analyzed, and a risk scoring system was constructed using the decision tree algorithm, C5...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28245528/corrected-roc-analysis-for-misclassified-binary-outcomes
#18
Matthew Zawistowski, Jeremy B Sussman, Timothy P Hofer, Douglas Bentley, Rodney A Hayward, Wyndy L Wiitala
Creating accurate risk prediction models from Big Data resources such as Electronic Health Records (EHRs) is a critical step toward achieving precision medicine. A major challenge in developing these tools is accounting for imperfect aspects of EHR data, particularly the potential for misclassified outcomes. Misclassification, the swapping of case and control outcome labels, is well known to bias effect size estimates for regression prediction models. In this paper, we study the effect of misclassification on accuracy assessment for risk prediction models and find that it leads to bias in the area under the curve (AUC) metric from standard ROC analysis...
June 15, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28155639/inferring-new-indications-for-approved-drugs-via-random-walk-on-drug-disease-heterogenous-networks
#19
Hui Liu, Yinglong Song, Jihong Guan, Libo Luo, Ziheng Zhuang
BACKGROUND: Since traditional drug research and development is often time-consuming and high-risk, there is an increasing interest in establishing new medical indications for approved drugs, referred to as drug repositioning, which provides a relatively low-cost and high-efficiency approach for drug discovery. With the explosive growth of large-scale biochemical and phenotypic data, drug repositioning holds great potential for precision medicine in the post-genomic era. It is urgent to develop rational and systematic approaches to predict new indications for approved drugs on a large scale...
December 23, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28152863/breast-oncology-precision-medicine-genomic-testing-and-treatment-at-the-population-level
#20
Yun Li, Allison W Kurian, Steven J Katz
288 Background: The 21-gene assay used to estimate breast cancer recurrence and tailor chemotherapy (chemo) receipt has demonstrated predictive validity and clinical utility. Yet it is unclear how involved patients are in the decision to perform the test, or how oncologists use results to recommend systemic chemo. We examined the patient experience with assay testing, physician recommendations, and chemo receipt based on test results. METHODS: The iCanCare study surveyed a weighted random sample of newly diagnosed patients with early-stage breast cancer who were treated in 2013-14, identified through the population-based SEER registries of Los Angeles and Georgia about 3 months after surgical treatment, and merged with SEER data (N=2632, RR=70%)...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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