Expert opinion on medical diagnostics最新文献

Introduction: Fabry disease (FD) is an X-linked disorder of glycosphingolipid metabolism caused by deficiency of the lysosomal enzyme alpha galactosidase A. Clinical features include neuropathic pain, rash, proteinuria renal failure, stroke and cardiomyopathy accompanied by a reduced life expectancy. Patients report an average delay of > 10 years between symptom onset and diagnosis. Newborn screening studies suggest a much higher prevalence than that found on population studies supporting the notion that FD is under-diagnosed.

Areas covered: Four key challenges in the diagnosis of FD and strategies to overcome them are discussed. The clinical features of FD are highly heterogeneous resulting in patients presenting to many different specialists, often with non-specific symptoms with a wide differential diagnosis. The pathophysiological mechanisms underlying this are poorly understood and the prediction of pathogenicity on the basis of gene mutation analysis can be problematic. While the availability of treatment adds an impetus to make the correct diagnosis, our understanding of when and if treatment may be required in a specific individual is incomplete.

Expert opinion: Improving diagnostic rates of FD requires a greater awareness of the disorder among physicians to whom patients may present, new strategies to determine the pathogenicity of novel mutations and a greater understanding of the natural history of FD across the phenotypic spectrum. Collaborative clinical and laboratory research is vital in furthering knowledge of the underlying mechanisms of this disorder and how they may be impacted by current or future therapies.

Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide and this burden is predicted to increase unless exposure to risk factors is addressed. Diagnosis of COPD is a challenge: COPD is underdiagnosed and frequently misdiagnosed for asthma or other respiratory conditions. Although spirometry is only one parameter for establishing a clinical diagnosis of COPD, lack of routine spirometry is a key cause of COPD misdiagnosis. Differential diagnosis from asthma is essential because the treatment strategies for, and progression and outcomes of, the two conditions vary greatly.

Areas covered: Here the authors review methods for the differential diagnosis of COPD and asthma; approaches to improve diagnosis, including case-finding and screening; the identification of specific COPD phenotypes and targeted therapy; and the potential role of exhaled biomarkers in the diagnosis of COPD.

Expert opinion: Methods to diagnose COPD, specifically differential diagnosis from asthma, have improved in recent years. To translate these into clinical practice will require the development of combined guidelines for COPD and asthma that include COPD-asthma overlap syndrome and are based on evidence from randomized controlled trials.

Introduction: The imaging evaluation of pulmonary nodules, often incidentally detected on imaging examinations performed for other clinical reasons, is a frequently encountered clinical circumstance. With advances in imaging modalities, both the detection and characterization of pulmonary nodules continue to evolve and improve.

Areas covered: This article will review the imaging modalities used to detect and diagnose benign and malignant pulmonary nodules, with a focus on computed tomography (CT), which continues to be the mainstay for evaluation. The authors discuss recent advances in the lung nodule management, and an algorithm for the management of indeterminate pulmonary nodules.

Expert opinion: There are set of criteria that define a benign nodule, the most important of which are the lack of temporal change for 2 years or more, and certain benign imaging criteria, including specific patterns of calcification or the presence of fat. Although some indeterminate pulmonary nodules are immediately actionable, generally those approaching 1 cm or larger in diameter, at which size the diagnostic accuracy of tools such as positron emission tomography (PET)/CT, single photon emission CT (SPECT) and biopsy techniques are sufficient to warrant their use. The majority of indeterminate pulmonary nodules are under 1 cm, for which serial CT examinations through at least 2 years for solid nodules and 3 years for ground-glass nodules, are used to demonstrate either benign biologic behavior or otherwise. The management of incidental pulmonary nodules involves a multidisciplinary approach in which radiology plays a pivotal role. Newer imaging and postprocessing techniques have made this a more accurate technique eliminating ambiguity and unnecessary follow-up.

Introduction: This article provides an overview of actual biomarkers with an impact on improvement of diagnosis and treatment of esophageal cancer patients.

Areas covered: Recent literature has been analyzed and provides information regarding the potential role of molecular markers as a diagnostic or prognostic factor in esophageal cancer.

Expert opinion: Until now, the role of molecular markers is far from being firmly established for routine use and is not without obstacles. However, with reliable standardized methods, established cut-off values and promising candidates in marker panels with markers of genetic, epigenetic and proteomic origin might result in a marker tool worthwhile of being validated in large, prospective, randomized trials. Novel validated marker combinations have to be clinically applied to prove their putative role in complementing clinical techniques within the development of better detection concepts of esophageal cancer, improving patients' long-term prognosis by early and purposive therapy within individualized treatment concepts.

Introduction: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with heterogeneous manifestations. Of particular importance for clinicians are the precise assessment of disease activity and the ability to make appropriate therapeutic decisions. Therefore, interest has increased in biomarkers that can be measured as indicators of pathogenic processes, disease activity and response to management.

Areas covered: This article introduces well-studied, as well as newly discovered, biomarkers related to SLE, divided into categories for diagnosis, disease activity and organ involvement.

Expert opinion: The lack of reliable biomarkers for lupus hampers the assessment of disease activity and impedes the evaluation of treatment response. Although many reports of lupus biomarkers have been published, few longitudinal and interventional studies have validated the utility of any biomarker for monitoring disease activity. Consortiums of investigators will certainly help in recruiting sufficient number of patients and facilitating the development of standardized assays. Moreover, owing to the multifactorial nature of lupus, a multiplexed approach will clearly be essential. Another promising approach is the use of high-throughput technology, including DNA and antibody microarrays, flow cytometry and proteomic techniques.

Introduction: IgA nephropathy, the most prevalent glomerular disease in the world, requires a renal biopsy for diagnosis. Reliable biomarkers are needed for the non-invasive diagnosis of this disease and to more fully delineate its natural history and risk for progression.

Areas covered: In this review, the authors examine serum levels of galactose-deficient IgA1 (Gd-IgA1) and glycan-specific IgG and IgA autoantibodies that are integral to pathogenesis of IgA nephropathy. They also explore biomarkers related to alternative and lectin pathways of complement activation and serum and urinary peptide biomarkers detected by mass spectrometric methods. The literature search included review of all publications having IgA nephropathy in the title that were cited in PubMed and Scopus over the past 10 years and a non-systematic review of abstracts published for the annual meetings of the American Society of Nephrology and the International Symposia on IgA Nephropathy.

Expert opinion: Serum Gd-IgA1 level and glycan-specific autoantibody levels are prime candidates to become diagnostic biomarkers for IgA nephropathy because of their central role in the earliest stages of disease pathogenesis. Assays for serum levels of complement proteins C3 and factor H are readily available in clinical practice and deserve continued study, either alone or in tandem with total serum IgA or serum Gd-IgA1 levels, as prognostic biomarkers for patients with IgA nephropathy. Urinary peptidomic data are also reviewed because this approach can successfully differentiate patients with IgA nephropathy from healthy controls and from patients with other forms of renal disease.

Introduction: Coeliac disease is an autoimmune condition resulting from an abnormal reaction to dietary gluten leading to small bowel villous atrophy. International prevalence studies suggest that coeliac disease affects 1% of the adult population. However, despite its high prevalence, large numbers of patients go undiagnosed. One method of increasing detection rates would be to introduce a quick screening test in the form of a finger-prick blood test.

Areas covered: There are currently four available point-of-care tests (POCTs) available for use by health professionals. This diagnostic evaluation will review the evidence for the use of POCTs in coeliac disease including Simtomax a novel test for deamidated gliadin peptides and total IgA level.

Expert opinion: An accurate POCT has the potential to increase the rates of diagnosis of coeliac disease if used effectively as part of a case finding approach in primary or secondary care. Evidence for the use of Simtomax is currently fairly limited only drawing comparison with laboratory serology rather than the gold standard of histology and it has only been trialled in high-risk populations. However, results to date are encouraging and further research into this area is required.

Introduction: High-throughput molecular profiling is transforming long-standing conceptions of diffuse gliomas, the most common primary brain tumors. Indeed, comprehensive genomic, transcriptomic and epigenomic analyses have not only provided striking mechanistic insights into the pathogenesis of diffuse gliomas but also greatly enriched the pool of potential biomarkers for prognostic and predictive patient stratification.

Areas covered: This article summarizes significant recent developments in the molecular characterization of diffuse gliomas, focusing on implications for biomarker development and application. In doing so, we will also address relevant high-throughput molecular profiling technologies and both the opportunities and challenges implicit in their widespread incorporation into disease management workflows.

Expert opinion: Although the number of validated biomarkers guiding diffuse glioma management is currently quite small, rapidly progressing molecular annotation continues to provide a steady stream of clinically relevant candidates, many of which show promise for predictive capabilities in the context of specific targeted therapeutics. Such potential now requires rigorous validation in well-designed clinical trials supported by robust molecular profiling assays operative from standard clinical material.

Introduction: Kaposi's sarcoma (KS) is a vascular neoplasm with distinct clinical-epidemiological subtypes and varied clinical presentations. While the association of KS with human herpesvirus-8 (HHV8, KSHV) infection is well known, additional factors are needed for tumorigenesis. The precise sequence of events involved in KS development, progression and regression continues to be investigated. The discovery of KSHV biomarkers is helpful for diagnostic purposes, for understanding KS pathogenesis and for identifying potential druggable targets.

Areas covered: This article reviews a number of key biomarkers relevant for the diagnosis of KS and HHV8-related pathogenesis. New developments in KS, potential therapeutic targets and the challenges involved in their discovery are highlighted.

Expert opinion: Although there is currently no cure for KS, continued research devoted to uncovering biomarkers and understanding their pathogenic roles remains encouraging. The hope is that sometime soon one of these candidate targets will provide a curative therapy for this enigmatic sarcoma.

Introduction: Skeletal muscle channelopathies are rare disorders of muscle membrane excitability. Their episodic nature may result in diagnostic difficulty and delays in diagnosis. Advances in diagnostic clinical electrophysiology combined with DNA-based diagnosis have improved diagnostic accuracy and efficiency. Ascribing pathogenic status to identified genetic variants in muscle channel genes may be complex and functional analysis, including molecular expression, may help with this. Accurate clinical and genetic diagnosis enables genetic counselling, advice regarding prognosis and aids treatment selection.

Areas covered: An approach to accurate and efficient diagnosis is outlined. The importance of detailed clinical evaluation including careful history, examination and family history is emphasised. The role of specialised electrodiagnostics combined with DNA testing and molecular expression is considered. New potential biomarkers including muscle MRI using MRC Centre protocols are discussed.

Expert opinion: A combined diagnostic approach using careful clinical assessment, specialised neurophysiology and DNA testing will now achieve a clear diagnosis in most patients with muscle channelopathies. An accurate diagnosis enables genetic counselling and provides information regarding prognosis and treatment selection. Genetic analysis often identifies new variants of uncertain significance. In this situation, functional expression studies as part of a diagnostic service will enable determination of pathogenic status of novel genetic variants.