Biomarkers in Sepsis

There is much enthusiasm and interest in sepsis biomarkers, particularly because sepsis is a highly lethal condition, its diagnosis is challenging, and even simple treatment with antibiotics has led to serious adverse consequences such as emergence of resistant pathogens. Yet development of a sepsis biomarker requires many more steps than simply finding an association between a particular molecule and a clinical state or outcome. Demonstration of improvement of therapeutic practice using receiver-operating characteristic and other analyses is important. Validation in independent, prospective and, preferably, multicenter trials is essential. Many promising candidate sepsis biomarkers have recently been proposed. While procalcitonin (PCT) is currently the most studied sepsis biomarker, evidence of potential value has been found for a wide array of blood biomarkers including proteins, mRNA expression in whole blood or leukocytes, micro-RNAs (miRNA), pathogen and host DNA, pathogen and host genetic variants and metabolomic panels, and even in the novel use of currently available clinical data. While the most common early reports link putative sepsis biomarker levels to severity of illness and outcome (prognostic), this is not anticipated to be their primary use. More important is the distinction between infection and noninfectious inflammatory responses (diagnostic) and the use of sepsis biomarkers to direct therapy (predictive).     

Heart Failure Biomarkers

Biomarker testing in patients with heart failure (HF) is rapidly expanding. With high-quality research indicating its diagnostic and prognostic capabilities, biomarkers are excellent adjuncts to manage patients with HF. Their superiority lies mainly in their reflection of ongoing pathophysiological events at a cellular level. Monitoring biomarker levels has been shown to provide incremental information on the progression of disease, thus allowing to better tailor treatment and management. Several biomarkers have gained attention in the past decade and continuing research demonstrates the specificity of each biomarker to be used on its own or in combination to improve diagnostic accuracy. This review will provide an insight into the role of such biomarkers, which are widely studied in the setting of HF so as to delineate their role in diagnosing, prognosticating, and titrating HF therapy.     

Biomarkers in spondyloarthritis

In spondyloarthritis, in particular ankylosing spondylitis (AS), a need exists for clinically meaningful biomarkers, both for diagnosis and prognosis. Earlier diagnosis has become an imperative since the advent of biologic therapy, which has proved effective in controlling axial inflammation. Presently, however, there are no biomarkers that reliably distinguish inflammatory back pain from the far more prevalent mechanical back pain. The target sites in AS—sacroiliac joints and the spine—are relatively inaccessible to the investigator and clinician, so defining markers associated with or predictive of axial inflammation remains an important goal. Cytokines, metalloproteinases, and cartilage catabolic products are all candidates for the important role of biomarker in spondyloarthritis.     

Biomarkers in COPD

Although there is increasing interest in using pulmonary biomarkers for a more complete and clinically relevant assessment of COPD and a plethora of biomarkers are becoming available, there is little information regarding their reproducibility and correlation with other outcome measurements in COPD. The lack of well-validated biomarkers that can be used for monitoring disease activity, predicting future clinical outcomes and the effect of therapeutic interventions highlights the factual need to identify new biomarkers in COPD. It is likely that, using what is called ‘integrative functional informatics’, which is a novel direction in the interfacing and integration of different technologies (genomics, proteomics, metabolomics and metabonomics, pharmacogenetics, and integrative approaches) for collection and analysis of data on biomarkers, we will be able to identify robust, reliable, and reproducible biomarkers in COPD.     

结核病生物标记物研究进展

结核病是由结核分枝杆菌复合群所致的以呼吸系统感染为主的慢性传染病,传统的检测方法检出率低、漏诊率高,导致结核菌继续传播和病人治疗延误。因此,迫切需要发现新的结核病诊断标志物以建立快速、敏感、高效的结核病诊断方法,而生物标记物正可以达到此目的。结核病中的某些生物标记物还具有治疗的作用,有些生物标记物可用于研制TB疫苗。对生物标记物不断深入的研究将有利于理解结核病的发生发展过程。本文就结核病中的生物标记物作一综述。     

Biomarkers of aging

This article presents a conceptual discussion of some aspects involved in biomarkers of aging. A biomarker of aging is a biological parameter of an organism that either alone or in some multivariate composite will, in the absence of disease, better predict functional capability at some late age than will chronological age. The reasons for undertaking biomarker research, criteria for putative biomarkers, measurement and assessment of putative biomarkers, and the new initiative by the National Institute on Aging in biomarker research are discussed.     

Biomarkers in Spondyloarthritis

Key challenges in the management of spondyloarthritis focus on the lack of availability of measures of disease activity and the inability to predict joint damage or response to treatment, which is expensive and associated with potentially serious toxicity. Recent studies have focused on the possible contribution of soluble biomarkers, which have been selected based on current understanding of their role in inflammation and/or their association with turnover of joint matrix. Emerging candidates for disease activity markers include interleukin-6 and soluble cytotoxic T lymphocyte associated molecule-4. Potential predictors of damage include metalloproteinase-3 and sclerostin. Acute-phase reactants C-reactive protein and serum amyloid A and interleukin-6 are currently the best predictors of treatment response. Significant study limitations are small sample size and the lack of multivariate analyses that can determine whether the biomarker contributes information that is independent of other clinical and laboratory variables used in routine care.     

Biomarkers for mesothelioma

PURPOSE OF REVIEW: Mesothelioma is an incurable cancer and its global incidence continues to increase. There has been strong interest in the search for a biomarker that would be of value for the diagnosis, prognosis and disease monitoring of mesothelioma. Large series evaluating the use of novel candidate markers have recently been published. RECENT FINDINGS: To date, global gene profiling studies have failed to find a molecule that reliably captures all subtypes of mesothelioma, and differentiates it from benign pathologies and metastatic carcinomas. Soluble mesothelin-related peptide (SMRP), osteopontin and megakaryocyte potentiating factor have been assessed as markers. SMRP testing is clinically available and provides reasonable diagnostic sensitivity and specificity when applied to serum or pleural fluid. Elevated SMRP levels can occur in metastatic, especially ovarian and pancreatic, adenocarcinomas. False negatives are common with sarcomatoid mesothelioma. SMRP levels may reflect tumor load and disease progression. The role of SMRP in predicting mesothelioma development in subjects exposed to asbestos has raised interest. Osteopontin lacks specificity as a diagnostic marker for mesothelioma but may have value in disease monitoring. SUMMARY: The proposed markers have insufficient accuracy to replace cytohistology as the gold standard for diagnosis for mesothelioma. Elevated SMRP levels raise suspicion of mesothelioma although negative values do not exclude disease. Its role in disease monitoring in patients and in predicting disease development in at-risk individuals warrant further study.     

Biomarkers in osteoarthritis

PURPOSE OF REVIEW: Biomarker discovery and validation for osteoarthritis have accelerated over the past several years, coincident with an evolving understanding of joint tissue molecules and their complex interactions, and the compelling need for improved osteoarthritis outcome measures in clinical trials. This review highlights advances in osteoarthritis-related biomarker research within the past year. RECENT FINDINGS: The studies in the past year involving biochemical markers in humans can be assigned to one of four categories: new approaches and new biomarkers, exploratory studies in specialized disease subsets, large cross-sectional validation studies, and longitudinal studies, with and without an intervention. SUMMARY: Most these studies have examined the association of a biomarker with some aspect of the natural history of osteoarthritis. As illustrated by the six studies reviewed here that included therapeutic interventions, however, several biomarkers are emerging that display credible association with disease modification. The expanding pool of informative osteoarthritis-related biomarkers is expected to positively impact the development of therapeutics for this disease and, it is hoped, ultimately clinical care.     

Biomarkers in osteoarthritis

PURPOSE OF REVIEW: Osteoarthritis is a chronic disease characterized by progressive destruction of articular cartilage and subchondral bone, and synovial reaction. Clinical and radiologic findings that form the basis of the diagnosis of osteoarthritis are poorly sensitive for monitoring the progression of the disease. Biologic markers reflecting quantitative and dynamic changes of joint tissue turnover represent promising adjunct tools. RECENT FINDINGS: New tissue-specific markers have been developed and include assays for type II collagen synthesis and degradation and synovitis. Prospective studies indicate that increased or decreased levels of some of these markers are associated with rapid progression of joint destruction in patients with knee osteoarthritis. Because progression of joint damage is likely to result primarily from an imbalance between degradation and reparative processes, a combination of markers reflecting these two components appears promising. For example, combining two new markers for type II collagen synthesis and degradation in an uncoupling index of cartilage turnover was more effective in predicting 1-year radiologic progression in knee osteoarthritis than the measurement of a single marker. Preliminary data in rheumatoid arthritis show a rapid response of a marker of type II collagen degradation under disease-modifying antirheumatic drugs, with early changes of this marker being predictive of long-term radiologic progression. SUMMARY: Recent evidence suggests that the combination of some biologic markers will be useful for identifying patients at risk for rapid joint destruction in osteoarthritis. Because of their rapid changes under treatment, biologic markers will play an important role in the development and monitoring of new structure-modifying therapies for osteoarthritis.     

Biomarkers by gender

Regressions were determined for age-related human biological functions containing information for both genders. Their intercept T₀ on the age axis (x) was used as a measure of the aging rate. The peak of the frequency distribution of T₀ was consistent with earlier estimates. The frequency distribution of the ratio R of T₀(women)/T₀(men) peaked at unity. However, when the T₀-values were divided into two groups, namely those relating to functions involving musculature vs. the rest, respectively, the ratio of R for musculature was <1 and that for the latter significantly >1. This suggests that men are the stronger gender when musculature is involved, but, more broadly, women are “biologically stronger”.     

Cross-Disciplinary Biomarkers Research: Lessons Learned by the CKD Biomarkers Consortium

Significant advances are needed to improve the diagnosis, prognosis, and management of persons with CKD. Discovery of new biomarkers and improvements in currently available biomarkers for CKD hold great promise to achieve these necessary advances. Interest in identification and evaluation of biomarkers for CKD has increased substantially over the past decade. In 2009, the National Institute of Diabetes and Digestive and Kidney Diseases established the CKD Biomarkers Consortium (http://www.ckdbiomarkersconsortium.org/), a multidisciplinary, collaborative study group located at over a dozen academic medical centers. The main objective of the consortium was to evaluate new biomarkers for purposes related to CKD in established prospective cohorts, including those enriched for CKD. During the first 5 years of the consortium, many insights into collaborative biomarker research were gained that may be useful to other investigators involved in biomarkers research. These lessons learned are outlined in this Special Feature and include a wide range of issues related to biospecimen collection, storage, and retrieval, and the internal and external quality assessment of laboratories that performed the assays. The authors propose that investigations involving biomarker discovery and validation are greatly enhanced by establishing and following explicit quality control metrics, including the use of blind replicate and proficiency samples, by carefully considering the conditions under which specimens are collected, handled, and stored, and by conducting pilot and feasibility studies when there are concerns about the condition of the specimens or the accuracy or reproducibility of the assays.