Expert opinion on medical diagnostics最新文献

Introduction: The discovery of hemochromatosis genes and the availability of molecular-genetic tests considerably modified the knowledge of the disease relative to physiopathology, penetrance, and expression, and had major impact in the diagnostic settings.

Areas covered: Hemochromatosis is a heterogenous disorder at both genetic and phenotypic level. The review discusses criteria to define patients' iron phenotype and to use molecular tests to diagnose HFE-related and non-HFE hemochromatosis. The material examined includes articles published in the journals covered by PubMed US National Library of Medicine. The author has been working in the field of iron overload diseases for several years and has contributed 18 of the papers cited in the references.

Expert opinion: Hemochromatosis genotyping is inseparable from phenotype characterization. A full clinical assessment is needed and DNA test performed when data suggest a clear indication of suspicion of being at risk for HH. HFE testing for p.Cys282Tyr mutation and p.His63Asp variant is the first molecular diagnostic step. Genotyping for rare mutations can be offered to patients with negative first-level HFE testing who have iron overload with no other explanation and should be performed in referral centers for iron overload disorders that can provide genetic advice and in-house genotyping services.

Introduction: Bipolar disorder is diagnosed on the basis of patient and/or family reports and behavioral observation. Traditionally regarded as an affective disorder involving behavioral changes, bipolar disorder has been reconceptualized as a multisystem disease associated with mood, cognitive, metabolic, autonomic and sleep/wake dysfunctions. Accordingly, recent studies have focused on the identification of biomarkers related to the pathophysiological mechanisms underlying the development, clinical presentation and course of bipolar disorder.

Areas covered: This article provides an overview of the available literature regarding circulating peripheral and neuroimaging biomarkers in bipolar disorder. Neurotrophic factors, immune parameters, oxidative stress parameters, hormones and neuroimaging findings were taken into consideration.

Expert opinion: Biomarkers research in bipolar disorder is a new field with an expanding knowledge. Current evidence suggests that a single biomarker will not be able to cover the biological and clinical complexity of bipolar disorder. Alternatively, a composite of biomarkers, including neurotrophic factors, cytokines and oxidative stress molecules, may be promising to identify altered mood states and neuroprogression in bipolar disorder.

Introduction: Femoral head avascular necrosis (FHAVN) is the result of irreversible anoxia of the subchondral bone. The death of bone cells can cause articular collapse and pain, and in turn usually leads to degenerative arthritis. FHAVN is a common disorder, affecting mainly young male adults. Reliability, accuracy and prognostic value of any classification system are important in evaluation and treatment of FHAVN.

Areas covered: Although in the past, scintigraphy and CT and more recently PET have been used for diagnosing AVN, currently the most important imaging methods included in the most widely used classification systems, consist of radiographs and magnetic resonance imaging (MRI). The latter is used in major classification systems for early detection (pre-radiographic stage) of FHAVN and for assessing lesion size and location before collapse of the articular surface occurs. The purpose of this review is to present the current data regarding the accuracy of the X-rays and MRI in diagnosing, monitoring and postoperative evaluation of FHAVN.

Expert opinion: The author's opinion is that MRI may contribute to improve staging, investigate radiologically occult collapse, depict other causes of disability and pain, assess prognosis and evaluate treatment. Newer MRI techniques, such as diffusion-weighted imaging and perfusion imaging, have not yet provided additional and clinically useful information.

Introduction: Cardiovascular disease (CVD) has been a burden on the healthcare system for decades and has increased the need for earlier diagnosis, better risk stratification and cost- effective treatment to reduce the rates of hospitalization. Biomarker research has broadened our knowledge base, shedding more light on the underlying pathophysiological mechanisms associated with the development of heart disorders. Recent technological advances have made it possible to use noninvasive and cost-effective biomarkers for identifying patients who are at risk of developing coronary heart disease and atherosclerosis.

Areas covered: In this paper the authors review the development of neutrophil gelatinase-associated lipocalin (NGAL) as a cardiac biomarker, highlighting studies that validate its use in predicting acute changes in patients with an array of cardiac disorders, and stake a case for the use of NGAL as a clinical diagnostic tool to predict outcomes in patients with CVD.

Expert opinion: The authors believe that NGAL should be used as a clinical diagnostic tool to predict outcomes in patients with CVD. Growing evidence has illustrated the biological role that neutrophils, such as NGAL, play in inflammation and atherosclerosis. Further studies are needed to determine NGAL's stability in serum and urine, and to substantiate its widespread use, but there are expanding possibilities for this biomarker in clinical practice.

Introduction: Bacterial vaginosis (BV) has been associated with pelvic inflammatory disease, adverse pregnancy outcomes, increased susceptibility to sexually transmitted infections and infertility. Diagnosis of BV should be rapid, reliable and safe. This is especially vital in pregnant women where intervention may be necessary for the well-being of both the mother and the foetus.

Areas covered: This paper consulted PUBMED, LISTA and Web of Science for point-of-care and laboratory-based tests commonly used for the diagnosis and management of BV in pregnant women. An overview of strengths and weaknesses of the methods used may partially explain why treatment plans have failed. Differences in sampling and detection methods, time of gestation, inter-examiner variability and interpretation of data, and the use of different reference tests, amongst many other factors, complicated a meta-analysis of the data.

Expert opinion: Inconsistencies found in clinical and laboratory detection methods used for the monitoring of treatment have a direct impact on success rates. With current advances in technology, the diagnosis of BV is taking on a new perspective. New information implicating specific vaginal biofilms in adverse pregnancy outcomes through the application of advanced technology promises to change the way we view the aetiology, diagnosis and management of BV.

Introduction: A few non-invasive biometrological methods are available for monitoring skin stiffening in systemic scleroderma. Among them, the Cutometer® is used for years by several clinical teams.

Objectives: To revisit the microscopic structure of the dermal fibrous networks in scleroderma and the relationship with changes in viscoelasticity.

Methods: The suction method delivered by the Cutometer® was applied following the progressive stress-vs-strain modality.

Results: The test procedure was sensitive enough to document the initial progression steps of acroscleroderma. Four stages were thus identified including i) the incipient, ii) the progressive, iii) the overt, and iv) the regressive acroscleroderma.

Conclusion: The non-invasive determination of skin biomechanical functions is relevant both in routine clinical practice and in antisclerotic drug development. It is complementary although not a substitute for the determination of selected serum biomarkers.

Introduction: Diabetes mellitus is commonly responsible for skin changes including discrete to mild xerosis.

Areas covered: This review focuses on some selected relevant bioinstrumental methods assessing diabetes xerosis. Peer-reviewed articles on objective non-invasive methods were scrutinized. The reviewed methods address i) the xerosis severity grading scale, ii) corneodynamics referring to the desquamation rate, iii) electrometric assessment of skin hydration including skin capacitance mapping and iv) implication of the imperceptible perspiration. The subjective clinical assessment often fails to disclose diabetic xerosis with confidence and precision. By contrast, a multipronged biometrological approach identifies a cluster of diabetic patients who experience alterations in the structural and functional maturation of the stratum corneum.

Expert opinion: A multipronged biometrological approach helps identifying the changes in the stratum corneum of diabetic xerosis. There is a continuum between the 'dry skin' feeling, xerosis and ichthyosiform presentations, particularly on the shins and feet of diabetic patients.

Background: Coronary heart disease (CHD) remains prevalent despite efforts to improve CHD risk assessment. The authors developed a multi-analyte immunoassay-based CHD risk assessment (CHDRA) algorithm, clinically validated in a multicenter study, to improve CHDRA in intermediate risk individuals.

Objective: Clinical laboratory validation of the CHDRA biomarker assays' analytical performance.

Methods: Multiplexed immunoassay panels developed for the seven CHDRA assays were evaluated with donor sera in a clinical laboratory. Specificity, sensitivity, interfering substances and reproducibility of the CHDRA assays, along with the effects of pre-analytical specimen processing, were evaluated.

Results: Analytical measurements of the CHDRA panel proteins (CTACK, Eotaxin, Fas Ligand, HGF, IL-16, MCP-3 and sFas) exhibited acceptable accuracy (80 - 120%), cross-reactivity (< 1%), interference (< 30% at high concentrations of bilirubin, lipids, hemoglobin and HAMA), sensitivity and reproducibility (< 20% CV across multiple runs, operators and instruments). Recoveries from donor sera subjected to typical clinical laboratory pre-analytical conditions were within 80 - 120%. The pre-analytical variables did not substantively impact the CHDRA scores.

Conclusions: The CHDRA panel analytical validation in a clinical laboratory meets or exceeds the specifications established during the clinical utility studies. Risk score reproducibility across multiple test scenarios suggests the assays are not susceptible to clinical laboratory pre-analytical and analytical variation.

Introduction: In patients with metastatic colorectal cancers, multimodal management and the use of biological agents such as monoclonal antibodies have had major positive effects on survival. The ability to predict which patients may be at 'high risk' of distant metastasis could have major implications on patient management. Histomorphological, immunohistochemical or molecular biomarkers are currently being investigated in order to test their potential value as predictors of metastasis.

Areas covered: Here, the author reviews the clinical and functional data supporting the investigation of three novel promising biomarkers for the prediction of metastasis in patients with colorectal cancer: tumor budding, Raf1 kinase inhibitor protein (RKIP) and metastasis-associated in colon cancer-1 (MACC1).

Expert opinion: The lifespan of most potential biomarkers is short as evidenced by the rare cases that have successfully made their way into daily practice such as KRAS or microsatellite instability (MSI) status. Although the three biomarkers reviewed herein have the potential to become important predictive biomarkers of metastasis, they have similar hurdles to overcome before they can be implemented into clinical management: standardization and validation in prospective patient cohorts.

INTRODUCTION: The advent of high throughput technologies capable of comprehensive analysis of genes, transcripts, proteins and other significant biological molecules has provided an unprecedented opportunity for the identification of molecular markers of disease processes. However, it has simultaneously complicated the problem of extracting meaningful molecular signatures of biological processes from these complex datasets. The process of biomarker discovery and characterization provides opportunities for more sophisticated approaches to integrating purely statistical and expert knowledge-based approaches. AREAS COVERED: In this review we will present examples of current practices for biomarker discovery from complex omic datasets and the challenges that have been encountered in deriving valid and useful signatures of disease. We will then present a high-level review of data-driven (statistical) and knowledge-based methods applied to biomarker discovery, highlighting some current efforts to combine the two distinct approaches. EXPERT OPINION: Effective, reproducible and objective tools for combining data-driven and knowledge-based approaches to identify predictive signatures of disease are key to future success in the biomarker field. We will describe our recommendations for possible approaches to this problem including metrics for the evaluation of biomarkers.