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- Apweiler, Rolf, et al.
(författare)
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Approaching clinical proteomics : current state and future fields of application in fluid proteomics
- 2009
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 47:6, s. 724-744
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Forskningsöversikt (refereegranskat)abstract
- The field of clinical proteomics offers opportunities to identify new disease biomarkers in body fluids, cells and tissues. These biomarkers can be used in clinical applications for diagnosis, stratification of patients for specific treatment, or therapy monitoring. New protein array formats and improved spectrometry technologies have brought these analyses to a level with potential for use in clinical diagnostics. The nature of the human body fluid proteome with its large dynamic range of protein concentrations presents problems with quantitation. The extreme complexity of the proteome in body fluids presents enormous challenges and requires the establishment of standard operating procedures for handling of specimens, increasing sensitivity for detection and bioinformatical tools for distribution of proteomic data into the public domain. From studies of in vitro diagnostics, especially in clinical chemistry, it is evident that most errors occur in the preanalytical phase and during implementation of the diagnostic strategy. This is also true for clinical proteomics, and especially for fluid proteomics because of the multiple pretreatment processes. These processes include depletion of high-abundance proteins from plasma or enrichment processes for urine where biological variation or differences in proteolytic activities in the sample along with preanalytical variables such as inter- and intra-assay variability will likely influence the results of proteomics studies. However, before proteomic analysis can be introduced at a broader level into the clinical setting, standardization of the preanalytical phase including patient preparation, sample collection, sample preparation, sample storage, measurement and data analysis needs to be improved. In this review, we discuss the recent technological advances and applications that fulfil the criteria for clinical proteomics, with the focus on fluid proteomics. These advances relate to preanalytical factors, analytical standardization and quality-control measures required for effective implementation into routine laboratory testing in order to generate clinically useful information. With new disease biomarker candidates, it will be crucial to design and perform clinical studies that can identify novel diagnostic strategies based on these techniques, and to validate their impact on clinical decision-making.
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| 2. |
- Arsov, Stefan, et al.
(författare)
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Advanced glycation end-products and skin autofluorescence in end-stage renal disease : a review
- 2014
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 52:1, SI, s. 11-20
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Forskningsöversikt (refereegranskat)abstract
- Chronic kidney disease (CKD), especially in its end stage, is marked by extremely high cardiovascular rates of morbidity and mortality; hemodialysis patients have a five-fold shorter life expectancy than healthy subjects of the same age. In CKD the metabolic products that accumulate in the body are so-called uremic toxins. These include advanced glycation end-products (AGE). AGE levels are markedly increased in CKD patients not only because of impaired excretion but also because of increased production. AGE formation has initially been described as a non-enzymatic reaction between proteins and glucose in the so-called Maillard reaction, but they are also more rapidly formed during oxidative stress and subsequent formation of reactive carbonyl compounds like (methyl) glyoxal. AGE accumulate in tissue where they cross-link with proteins, e. g., collagen, inducing tissue stiffening of blood vessels and skin. They may also interact with receptor of AGE (RAGE) and other receptors, which lead to activation of intracellular transduction mechanisms resulting in cytokine release and further tissue damage in CKD. The accumulation of AGE in the skin can be measured non-invasively using autofluorescence. The skin autofluorescence is a strong marker of cardiovascular mortality in CKD. The focus of this review is on the role of tissue and plasma AGE, and of skin autofluorescence as a proxy of tissue AGE accumulation, in the increase in cardiovascular disease in end stage renal disease (ESRD). This review will also present the possibility of reducing the AGE accumulation in ESRD patients using the following five methods: 1) use of low AGE peritoneal dialysis solutions; 2) use of advanced hemodialysis techniques; 3) use of AGE reducing drugs; 4) optimizing the nutrition of hemodialysis patients; and 5) renal transplantation.
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| 3. |
- Lindahl, Bertil
(författare)
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Acute coronary syndrome : the present and future role of biomarkers
- 2013
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 51:9, s. 1699-1706
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Forskningsöversikt (refereegranskat)abstract
- Over the past two decades there have been dramatic changes in the diagnosis, treatment and prognosis of acute coronary syndrome (ACS). Several new treatment modalities have been added and the prognosis has improved dramatically. Biomarkers play a crucial role in the management of ACS. At present, cardiac troponin is the biomarker of choice for diagnosis of acute myocardial infarction (AMI). Currently, there are no other biomarkers, which can compete, neither regarding specificity nor regarding early sensitivity. However, there is still a clinical need of a biomarker able to reliably rule-in or rule-out AMI immediately on admission. MicroRNAs seem to be promising new candidates for diagnostic purposes. The optimal combination of biomarkers and new imaging techniques is another important area for research. The list of biomarkers associated with an adverse prognosis in ACS is long. However, for most of them it has been very difficult to prove an added clinical value. Only cardiac troponin, and to some degree also B-type natriuretic peptides, is widely used in clinical practice for risk assessment. Among new markers, growth differentiation factor 15 and the mid-regional part of the prohormone of adrenomedullin, have shown some promising results. Since the renal function is assessed in clinical routine, also markers of the renal function have gained increasing interest. Cardiac troponin has been proven useful for selection of antithrombotic, antiplatelet and invasive treatment. Besides cardiac troponin, no other markers have consistently been shown to be useful for selection of specific treatments.
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| 4. |
- Theodorsson, Elvar
(författare)
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Issues in assessing analytical performance specifications in healthcare systems assembling multiple laboratories and measuring systems
- 2024
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : WALTER DE GRUYTER GMBH. - 1434-6621 .- 1437-4331.
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Forskningsöversikt (refereegranskat)abstract
- Analytical performance specifications (APS) are usually compared to the intermediate reproducibility uncertainty of measuring a particular measurand using a single in vitro diagnostic medical device (IVD MD). Healthcare systems assembling multiple laboratories that include several IVD MDs and cater to patients suffering from long-term disease conditions mean that samples from a patient are analyzed using a few IVD MDs, sometimes from different manufacturers, but rarely all IVD MDs in the healthcare system. The reproducibility uncertainty for results of a measurand measured within a healthcare system and the components of this measurement uncertainty is useful in strategies to minimize bias and overall measurement uncertainty within the healthcare system. The root mean squares deviation (RMSD) calculated as the sample standard deviation (SD) and relative SD includes both imprecision and bias and is appropriate for expressing such uncertainties. Results from commutable stabilized internal and external control samples, from measuring split natural patient samples or using big-data techniques, are essential in monitoring bias and measurement uncertainties in healthcare systems. Variance component analysis (VCA) can be employed to quantify the relative contributions of the most influential factors causing measurement uncertainty. Such results represent invaluable information for minimizing measurement uncertainty in the interest of the healthcare system's patients.
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