Expert opinion on medical diagnostics最新文献

Introduction: The concept of interstitial cystitis (IC) has changed dramatically during the last decades, eventually representing a symptom complex with varying contents. To include all patients with bladder pain, the umbrella term 'bladder pain syndrome' (BPS) has been suggested, incorporating the classic presentation of IC as a separate phenotype. This change of concepts has not been uncontroversial. Bladder pain syndrome often has a profound effect on the patients' quality of life. Generally, recognition of this problem complex is hampered by insufficient familiarity in the medical community. The correct diagnosis is often delayed by several years and may be preceded by multiple medical consultations and treatment attempts. There is no doubt that an early and correct diagnosis is of great significance for the patient.

Areas covered: In this article, a critical review of methods and means to approach the diagnosis is presented including some notes of current controversies.

Expert opinion: The key to an early diagnosis is symptom recognition. We are dealing with a heterogeneous concept including various phenotypes. The successful treatment requires understanding and expedient use of objective means, such as cystoscopy, biopsy and input from the multidisciplinary team. In the literature, limited evidence exists for the management of BPS/IC, due to heterogeneity in methodology and description of the syndrome(s). A more consequent use of available methods is desirable. For the immediate future, better understanding of the aetiology, pathogenesis and presentation of various BPS/IC phenotypes is indispensable.

Introduction: Intrauterine infection is a global problem and a significant contributor to morbidity and perinatal death. The host response to infection causes an inflammatory state that acts synergistically with microbial insult to induce preterm birth and fetal damage. Prompt and accurate diagnosis of intra-amniotic infection in the asymptomatic stage of the disease is critical for improved maternal and neonatal outcomes.

Areas covered: This article provides an overview of the most recent progress, challenges, and opportunities for discovery and clinical implementation of various maternal serum, cervicovaginal, and amniotic fluid biomarkers in pregnancies complicated by intra-amniotic infection.

Expert opinion: Clinically relevant biomarkers are critical to the accurate diagnostic of intrauterine infection. Front-end implementation of such biomarkers will also translate in lower incidence of early-onset neonatal sepsis (EONS) which is an important determinant of neonatal morbidity and mortality associated with prematurity. However, of the hundreds of differentially expressed proteins, only few may have clinical utility and thus function as biomarkers. The small number of validation studies along with barriers to implementation of technological innovations in the clinical setting are current limitations.

Introduction: In the study of heart failure (HF), biomarkers have served as an important tool for diagnostic, therapeutic and prognostic assessment. Their main categories in the area of HF are markers of ventricular dysfunction, inflammation, metabolism, neurohormones, oxidative stress, myocardial injury and extracellular matrix remodeling.

Areas covered: Leptin contributes to the modulation of metabolism, respiratory control and inflammation, which are factors associated with cardiovascular disease. Serum levels of leptin in patients with HF have shown conflicting results in previous studies. Most studies have suggested that serum leptin levels may be increased in patients without cachexia. On the other hand, leptin levels are decreased in patients with advanced HF and cardiac cachexia or specific HF etiologies such as Chagas' disease. Other studies have showed that leptin levels were related to exercise intolerance. The only exception of the direct correlation of serum leptin levels with severity of CHF is present in CHF with cardiac cachexia, because patients with cardiac cachexia have plasma leptin concentrations lower than those without cardiac cachexia.

Expert opinion: These findings can make leptin an important diagnostic and prognostic marker for HF and be included in routine investigation of patients with HF.

Introduction: Hypoxia-inducible factor-1α (HIF-1α) is a key player in the signaling pathway that mediates a complex and pleiotropic range of adaptive responses to hypoxia. It serves as cellular hypoxia sensor and plays a critical role in physiologic processes including glucose metabolism, iron metabolism, erythropoiesis, angiogenesis, cell survival and apoptosis, but also, pathologic processes such as carcinogenesis, progression and metastasis of many cancers. With the recent advent of new molecular targeted therapies, there is a growing need of molecular understanding of physiology and physiopathology and increased demand of diagnosis, prognosis and follow-up markers.

Areas covered: This paper reviews the biology of regulation of HIF-1α, its physiological and physiopathological effects.

Expert opinion: The authors discuss the potential diagnosis and the prognosis significance of HIF-1α that was evaluated in recent studies.

Introduction: Pneumocystis jirovecii pneumonia (PCP) is one of the most common opportunistic infections in HIV-infected adults. Although the microscopic demonstration of the organisms in respiratory specimens is still the golden standard of its diagnosis, recent advances in the diagnostic tools have been changing the situation.

Areas covered: Colonization of Pneumocystis is highly prevalent among the general population and could be associated with the transmission and development of PCP in immunocompromised individuals. Nested or conventional polymerase chain reaction (PCR) has a high sensitivity, detecting Pneumocystis DNA in induced sputum or oropharyngeal wash, but often produces false positives. Although quantitative real-time PCR is promising for discriminating colonization from PCP, the targeted DNA sequences and the cut-off values remain to be standardized. Serum β-D-glucan is useful as an adjunctive tool for the diagnosis of PCP. High-resolution computed tomography, which typically shows diffuse ground-glass opacities, is informative for evaluation of immunocompromised patients with suspected PCP and normal chest radiography.

Expert opinion: Although these new tools have been making the diagnosis of PCP less invasive and more accurate, any one of them can not make a definitive diagnosis by itself. The diagnostic criteria based on the combination of the testing ought to be established.

Introduction: Parkinson's disease (PD) is the most common neurodegenerative disease leading to movement disorders, and is characterized neuropathologically by the progressive loss of dopaminergic neurons, intracellular α-synuclein deposition and the formation of Lewy bodies. The difficulty of making a definitive diagnosis of PD itself, as opposed to other neurodegenerative diseases associated with parkinsonism, is a central issue in clinical PD research. However, recent advances in diagnostic methods, encompassing imaging techniques, genetic testing and measurement of biological markers may permit earlier diagnosis, and thus potentially improved management of PD.

Areas covered: In addition to clinical symptoms and imaging techniques, a number of genetic and biological markers obtained from body fluids such as cerebrospinal fluids may hold promise for the early detection of PD. It is often difficult to make an accurate diagnosis and to distinguish PD from other diseases with features of parkinsonism, particularly during the early stages of the disease. In this regard, biomarkers which are specific for PD, in combination with observation of clinical symptoms, may facilitate the early diagnosis and improved management of PD.

Expert opinion: Good biomarkers for PD could be helpful for early diagnosis, management and tracking of disease progression. Furthermore, combined analysis using several kinds of biomarkers may allow the detection of preclinical PD, which in turn may facilitate a prevention of disease onset with the use of disease-modifying drugs.

Introduction: Dengue is of major concern around the world. Having no pathognomonic features that reliably distinguish it from other febrile illnesses, laboratory diagnosis is important for confirmation. Ideally, a dengue diagnostic test should be sensitive, specific and applicable from the onset of disease to 10 days post-infection.

Areas covered: In this review, the pro and cons of currently available diagnostic arrays as well as evaluations that have been conducted by numerous groups using both in-house and commercialized kits were assessed and reviewed. We also probed into the challenges and hurdles of applying these assays worldwide. This review also glimpsed at newer technologies that may be invaluable in the future of dengue diagnostics.

Expert opinion: To diagnose dengue, an understanding of the complex immune responses and the clinical features of this disease is essential. The MAC-ELISA currently remains the assay of choice but needs further evaluation and confirmation. Viral RT-PCR and NS1 have gained interest but their inconsistencies and great variability are of concern. Combinations of these tests have improved sensitivity but specificity issues still exist. Consequently, the favorable method of diagnosing dengue currently is to run multiple tests or obtain a paired sample so that more than one parameter is detected or a rising titer is demonstrated.

Making a diagnosis of pulmonary vasculitis is challenging. The most common cause of pulmonary vasculitis is small vessel anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Pulmonary involvement in other forms of vasculitis such as large vessel vasculitis is rare. Since correct and timely diagnosis is pivotal to start (immunosuppressive) therapy to avoid vasculitic damage, a complete patient history should be obtained and a physical examination performed. Initial laboratory evaluation should include inflammation markers, renal and liver function tests, and the determination of ANCA. New developments in ANCA testing result in tests with excellent predictive value for the diagnosis of AAV-related pulmonary vasculitis. Consequently, ANCA should be tested with these tests of the so-called second (capture ELISA) or third (anchor ELISA) generation. In patients who are ANCA negative, a simple algorithm is presented based on laboratory evaluation of autoantibodies and 18F-FDG-PET-CT scanning. Such an algorithm may be useful for accelerating the diagnostic process needed to make a diagnosis of pulmonary vasculitis, or alternatively, to quickly exclude such a diagnosis.

Introduction: Cross sectional imaging is important for initial evaluation of pancreatic cancer, whereas endoscopic ultrasound (EUS) will often help better visualize, differentiate and make final tissue diagnosis. It plays an important role in the multi-disciplinary evaluation and staging of pancreatic cancer as accurate staging has significant impact on treatment decisions.

Areas covered: This review will cover the yield and utility of EUS and EUS FNA for diagnosis of pancreas cancer. In addition, this article reviews the utility and diagnostic yield of the non-invasive imaging modalities, including surface ultrasound, CT scan, PET CT scan and MRI. Tumor size, histology and disease processes that mimic pancreatic cancers will also be reviewed.

Expert opinion: The accurate diagnosis and staging of pancreatic neoplasms is essential for optimal patient management. Abdominal imaging with multidetector CT or MRI is the most important initial step in the evaluation of pancreatic cancer because they are widely available and can detect most masses and/or demonstrate dilated bile or pancreatic ducts indicative of obstruction. Endoscopic ultrasound will remain important for detecting small tumors, ruling out diseases that mimic adenocarcinoma and for obtaining tissue diagnosis with fine needle aspiration.

Introduction: Translational oncology has been improved by using tissue microarrays (TMAs), which facilitate biomarker analysis of large cohorts on a single slide. This has allowed for rapid analysis and validation of potential biomarkers for prognostic and predictive value, as well as for evaluation of biomarker prevalence. Coupled with quantitative analysis of immunohistochemical (IHC) staining, objective and standardized biomarker data from tumor samples can further advance companion diagnostic approaches for the identification of drug-responsive or resistant patient subpopulations.

Areas covered: This review covers the advantages, disadvantages and applications of TMAs for biomarker research. Research literature and reviews of TMAs and quantitative image analysis methodology have been surveyed for this review (with an AQUA® analysis focus). Applications such as multi-marker diagnostic development and pathway-based biomarker subpopulation analyses are described.

Expert opinion: Tissue microarrays are a useful tool for biomarker analyses including prevalence surveys, disease progression assessment and addressing potential prognostic or predictive value. By combining quantitative image analysis with TMAs, analyses will be more objective and reproducible, allowing for more robust IHC-based diagnostic test development. Quantitative multi-biomarker IHC diagnostic tests that can predict drug response will allow for greater success of clinical trials for targeted therapies and provide more personalized clinical decision making.