Expert opinion on medical diagnostics最新文献

Introduction: Diagnosis of mitochondrial disorders is challenging, because of their highly variable clinical manifestations and age-of-onset and the shortage of specific diagnostic tools. Recent molecular studies have found that serum fibroblast growth factor 21 (FGF21) has potential to be a biomarker for muscle-manifesting mitochondrial disease, as well as for follow-up of disease progression and effect of intervention.

Areas covered: Serum FGF21 as a biomarker is compared to conventional serum diagnostic tools for mitochondrial disorders.

Expert opinion: Mitochondrial disorders are a large group of different progressive disorders, with the age-of-onset from neonatal life to late adulthood, and symptoms originating from any organ system but sharing an underlying cause of mitochondrial dysfunction. The prevalence of these disorders is about 1:2000, varying somewhat between different countries. Serum diagnostic tools include lactate, pyruvate, their ratio, creatine kinase and amino acids. However, none of these markers are both sensitive and specific. Increased levels of FGF21 cytokine were recently found in the serum of patients, who have a muscle-manifesting mitochondrial disease, thus providing a promising, novel, sensitive and specific biomarker for these disorders.

Introduction: Rapid HIV tests have been widely adopted globally as an important component of HIV prevention and control programs. The INSTI™ HIV-1/HIV-2 antibody test is a second-generation HIV antibody test, available in most countries for use from whole blood, serum, and plasma.

Areas covered: Available data on kit characteristics and current performance data on the INSTI™ HIV-1/HIV-2 antibody test are presented together with six other rapid point-of-care tests (RPOCTs) for HIV antibody. Few published data are available providing direct comparisons of INSTI™ with other RPOCTs for HIV antibody and standard laboratory-based HIV-1/HIV-2 antibody assays. Existing data showed that INSTI™ has comparable performance to other RPOCTs but detected seroconversion later than standard laboratory-based assays.

Expert opinion: The good performance of INSTI HIV-1/HIV-2 antibody test, its ease of use, the rapid availability of results (< 5 min), and the lack of specialized equipment required to use the kit make this kit a useful addition to the global market. The unique antigen and flow through technology contained in the kit make it a strong addition to HIV RPOCTs and to rapid/rapid algorithms used in many resource-limited settings.

Evidence for a causal role for vitamin D in multiple sclerosis (MS) is being gathered. Epidemiological, molecular and animal model studies have paved the way in our understanding of the effects of vitamin D in demyelinating disease. Several clinical trials have been completed and more are under way to understand the full extent and value of vitamin D supplementation on disease progression. Many questions remain unanswered however and careful study design is increasingly pertinent. Timing of exposure, dosage and transgenerational effects are some of the several important questions that need to be addressed. In this issue, Carlson and Rose highlight these points and provide a review of vitamin D and MS with an emphasis on the most recent clinical studies. Further evidence of vitamin D deficiency as a causal factor, its molecular targets in MS and its prospect as a therapeutic and preventative agent are questions that warrant further study.

Introduction: The diagnosis of gastroesophageal reflux disease (GERD) is challenging. The wide variation in symptoms is a major reason for the controversies. Since the expression of GERD varies from nonerosive reflux disease over Barrett's esophagus to chronic respiratory disease, it is clear that not one investigation technique will provide an answer in all situations.

Areas covered: Relevant literature published in PubMed and CINAHL and recent guidelines were collected and reviewed. Diagnostic tests were evaluated by the following criteria: ability to confirm a diagnosis, to exclude other diagnoses with similar presentation, to detect complications, to predict disease severity.

Expert opinion: Multiple intraluminal impedance (MII) is extensively evaluated in recent years, but other new techniques and measurements were also developed, mainly to diagnose extra-esophageal symptoms. Although evidence for a "relation" between GER and extra-esophageal symptoms is demonstrated, the "causality" between both is not proven. MII measures in a reliable reproducible way non-acid or weakly acid reflux. However, as long as medical therapeutic options are limited to anti-acid medications, MII lacks therapeutic implications, and therefore clinical impact. Since investigations for GER are invasive or cause irradiation, normal ranges cannot be established. As a consequence, the "old" techniques remain the standard diagnostic tools: barium meal for anatomy, endoscopy for esophagitis, and pH monitoring to demonstrate a time relation between (acid) GER and symptoms. MII provides more information than pH monitoring, but is more expensive and has limited therapeutic impact as long as drugs are mainly "anti-acid."

Introduction: Malignant pleural effusion (MPE) is a frequent problem faced by clinicians, but tumor pleural involvement can be seen without effusion.

Areas covered: Imaging, pleural fluid analysis, biomarkers for MPE, needle pleural biopsy and thoracoscopy. To prepare this review, we performed a search using keywords: 'diagnosis' + 'malignant' + 'pleural' + 'effusion' (all fields) in PubMed, and found 4106 articles overall (until 16 January 2013, 881 in the last 5 years).

Expert opinion: Ultrasound techniques will stay as valuable tools for pleural effusions. Biomarkers in pleural fluid do not currently provide an acceptable yield for MPE. In subjects with past history of asbestos exposure, some serum or plasma markers (soluble mesothelin, fibulin) might help in selecting cases for close follow-up, to detect mesothelioma early. Needle pleural biopsy is justified only if used with image-techniques (ultrasound or CT) guidance, and thoracoscopy is better for both diagnosis and immediate palliative treatment (pleurodesis). Animal models of MPE and 'spheroids' are promising for research involving both pathophysiology and therapy. Considering the possibility of direct pleural delivery of nanotechnology-developed compounds-fit to both diagnosis and therapy purposes ('theranostics')-MPE and mesothelioma in particular are likely to benefit sooner than later from this exciting perspective.

Introduction: Despite the effectiveness of multidrug therapy, leprosy still represents a significant global health problem: transmission of Mycobacterium leprae (M. leprae) is not sufficiently reduced as witnessed by unwavering new case rates in leprosy-endemic countries. Early detection of M. leprae infection (before clinical manifestations occur) is vital to reduction of transmission. Current diagnosis relies on detection of clinical signs since there are no tests available to detect asymptomatic M. leprae infection or predict progression to leprosy.

Areas covered: Identification of risk factors (immunological or genetic biomarkers) for disease development and/or onset of leprosy reactions is imperative for efficient diagnosis. Tests simultaneously detecting biomarkers specific for cellular and humoral immunity are well suited for diagnosis of different clinical outcomes of leprosy. This review describes the challenges of discovery of biomarkers for M. leprae infection and their implementation in field-friendly tests.

Expert opinion: In view of the complicated nature of M. leprae infections, it is essential to invest in longitudinal studies allowing intra-individual comparison of immune and genetic biomarkers in various leprosy-endemic areas. Furthermore, the effect of co-infections on biomarker profiles should also be taken into account. Diagnostic tests based on such biomarkers can contribute significantly to early detection of leprosy (reactions) thus helping reduce nerve damage.

Introduction: Medical diagnostics is a critical element of effective medical treatment. However, many modern and emerging diagnostic technologies are not affordable or compatible with the needs and conditions found in low- and middle-income countries. Resource-poor countries require low-cost, robust, easy-to-use, and portable diagnostic devices compatible with telemedicine that can be adapted to meet diverse medical needs.

Areas covered: The most suitable devices are likely those that will be based on optical technologies, which are used for many types of biological analyses. This manuscript describes several prototypes of low-cost optical technologies and their application developed at the FDA's Office of Science and Engineering laboratories including a webcam-based multiwavelength fluorescence plate reader, a webcam-based fluorescence microscope demonstrated for colonic mucosa tissue pathology analysis, a lens-free optical detector used for the detection of Botulinum A neurotoxin activity, and a lab-on-a-chip which enables the performance of enzyme-linked immunosorbent assay and other immunological or enzymatic assays without the need of dedicated laboratories and complex equipment demonstrated for the detection of the toxin staphylococcal enterotoxin B.

Expert opinion: Sensitive and effective optical detection devices can be developed using readily available consumer electronics components such as webcams, charge-coupled device cameras, and LEDs. There are challenges in developing devices with sufficient sensitivity and specificity. Several optical and computational approaches were developed to overcome these challenges to create optical detectors that can serve as low-cost medical diagnostics in resource-poor settings.

Introduction: Vitamin D has attracted a lot of attention in relation to multiple sclerosis (MS) and many other disorders; however, the evidence for a major role(s) for vitamin D in MS is compelling and multifactorial involving results from epidemiology, immunology, genetics, biochemistry and translational medicine.

Areas covered: Multiple studies that illustrate that insufficient levels of vitamin D not only contribute to the risk of getting MS but may also worsen disease progression for MS patients are discussed. Genetic evidence also implicates vitamin D as being important in MS since individuals are at greater risk of getting MS if they harbor a mutation in a gene responsible for vitamin D synthesis (25-hydroxylase). Other modifiers of MS disease appear to interact with the vitamin D receptor. The Epstein-Barr virus (EBV) is a risk factor for MS and may in part worsen disease through the interactions between one of its gene products (EBNA-3) and the vitamin D receptor to attenuate vitamin D-regulated genes. Retrospective studies have shown that higher vitamin D levels are associated with a significant improvement of clinical and magnetic resonance imaging outcomes. Increasing clinical observations are also indicating adverse effects of low vitamin D in MS.

Expert opinion: Mounting evidence from epidemiology, genetic, retrospective clinical studies and emerging basic science studies support a strong rationale for how vitamin D could be an important modifier of MS disease. Well-designed clinical trials are now ongoing and will provide further insight on how vitamin D supplementation may impact MS.

Introduction: The World Health Organization has classified myalgic encephalomyelitis (ME) as a neurological disease since 1969 considering chronic fatigue syndrome (CFS) as a synonym used interchangeably for ME since 1969. ME and CFS are considered to be neuro-immune disorders, characterized by specific symptom profiles and a neuro-immune pathophysiology. However, there is controversy as to which criteria should be used to classify patients with "chronic fatigue syndrome."

Areas covered: The Centers for Disease Control and Prevention (CDC) criteria consider chronic fatigue (CF) to be distinctive for CFS, whereas the International Consensus Criteria (ICC) stresses the presence of post-exertion malaise (PEM) as the hallmark feature of ME. These case definitions have not been subjected to rigorous external validation methods, for example, pattern recognition analyses, instead being based on clinical insights and consensus.

Expert opinion: Pattern recognition methods showed the existence of three qualitatively different categories: (a) CF, where CF evident, but not satisfying full CDC syndrome criteria. (b) CFS, satisfying CDC criteria but without PEM. (c) ME, where PEM is evident in CFS. Future research on this "chronic fatigue spectrum" should, therefore, use the above-mentioned validated categories and novel tailored algorithms to classify patients into ME, CFS, or CF.

Introduction: Identification of periprosthetic joint infection (PJI) is critical, as the treatment between infected and non-infected arthroplasties is fundamentally different and missing the diagnosis may lead to a delay in diagnosis and the potential for a decreased rate of treatment success. Yet in the absence of a true gold standard, the diagnosis of PJI can be elusive. Given the rising incidence of this PJI and the growing infection burden anticipated in coming years, much effort is being put toward improving diagnostic tests for PJI.

Areas covered: The best current practice for diagnosis of PJI is to follow an algorithmic approach. Emerging technology such as advanced imaging modalities, increasing availability of serum markers, synovial fluid biomarker analysis and new point-of-care modalities offer the potential to greatly enhance our ability to identify PJI in the future.

Expert opinion: As there has been more focus on the diagnosis of PJI in recent years, new tests have been developed. These new tests will need to be rigorously evaluated before being incorporated into the diagnostic algorithm. Synovial fluid biomarker analysis and greater access to point-of-care testing may allow the biggest improvements in the diagnosis of PJI in the near future.