Background: Although dialysis ameliorates uremia and fluid and electrolytes disorders, annual mortality rate remains high in dialysis population reflecting its shortcoming in replacing renal function. Unlike the normal kidney, dialysis causes dramatic shifts in volume and composition of body fluids and indiscriminate removal of vital solutes. Present study was undertaken to determine the impact of hemodialysis on plasma metabolites in end-stage renal disease (ESRD) patients. Read More
Center of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China. Electronic address:
Background: Measurement uncertainty (MU) is a metrological concept, which can be used for objectively estimating the quality of test results in medical laboratories. The Nordtest guide recommends an approach that uses both internal quality control (IQC) and external quality assessment (EQA) data to evaluate the MU. Bootstrap resampling is employed to simulate the unknown distribution based on the mathematical statistics method using an existing small sample of data, where the aim is to transform the small sample into a large sample. Read More
Department of Clinical Pharmacy, Oita University Hospital, Hasama-machi, Oita, Japan.
Objectives: Protein-free (unbound) drug concentrations have been reported to be better biomarker of pharmacodynamics compared with total drug concentrations. In this study, we developed and validated an assay for the quantification of total and free itraconazole and hydroxyitraconazole, a main metabolite with antifungal activity, in human plasma using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS).
Design & Methods: Plasma sample was ultra-filtrated for the measurement of free itraconazole and hydroxyitraconazole concentrations. Read More
Assay performance is dependent on the accuracy and precision of a given method. These attributes can be combined into an analytical Sigma-metric, providing a simple value for laboratorians to use in evaluating a test method's capability to meet its analytical quality requirements. Sigma-metrics were determined for 37 clinical chemistry assays, 13 immunoassays, and 3 ICT methods on the Alinity ci system. Read More
Background: Serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) are used in the diagnosis and monitoring of plasma cell dyscrasias. IFE is considered the most sensitive method for the detection of monoclonal proteins (M-proteins), but it is not quantitative. The goal of this study was to establish the analytical sensitivity and diagnostic performance of SPE on the Sebia Hydrasys using HYDRAGEL 30 PROTEIN(E) β1-β2. Read More
Objectives: Our purpose was to determine a) overall and sex-specific 99th percentile upper reference limits (URL) and b) influences of statistical methods and comorbidities on the URLs.
Methods: Heparin plasma from 838 normal subjects (423 men, 415 women) were obtained from the AACC (Universal Sample Bank). The cobas e602 measured cTnT (Roche Gen 5 assay); limit of detection (LoD), 3ng/L. Read More
Service of Clinical Pathology, La Fe University Hospital, Av Fernando Abril Martorell 106, 46026, Valencia, Spain.
Objectives: Accurate evaluation of analyzers is highly recommended before these devices are broadly introduced for routine testing. Concerning quantification of IgG subclasses (IgGSc), standardization has not yet been reached and thus different assays might lead to different results. Here we report the analytical performances of The Binding Site (TBS) SPAPLUS® human IgGSc assay and the concordance with the Siemens BNII® human IgGSc assay. Read More
Department of Biochemistry and Molecular Genetics & Core Lab (CDB), Hospital Clínic, IDIBAPS, Barcelona, Catalonia, Spain. Electronic address:
Objectives: This study is the first verification of the novel iPTH Siemens ADVIA Centaur® Intact Parathyroid Hormone (iPTHm) chemiluminescence immunoassay based on monoclonal antibodies. We also compared the iPTH results obtained using this assay with the previous ADVIA Centaur® Parathyroid Hormone assay (iPTHp) based on polyclonal antibodies.
Design And Methods: The analytical performance study of iPTHm assay included LoD, LoQ, intra- and inter-assay reproducibility, and linearity. Read More
Diazyme Laboratories, Inc., 12889 Gregg Ct., Poway, CA 92064, United States.
Objectives: There are two platforms for the detection of Lp-PLA2 in sera or plasmas: by its enzymatic activity (PLAC® activity test) and by its mass concentration (PLAC® mass test). It has been long recognized that these two platforms are not correlated well. The underlying cause for this is therefore investigated by the biochemical characterization of the two PLAC tests. Read More
Departments of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Canada; Family Medicine, Cumming School of Medicine, University of Calgary, Canada; Community Health Sciences, Cumming School of Medicine, University of Calgary, Canada; Calgary Laboratory Services, Calgary, Alberta, Canada. Electronic address:
Background: The Canadian Diabetes Association recommends testing most individuals with diabetes mellitus using HbA1c once every 3months. In Alberta, Canada, a provincial intervention to reduce inappropriate HbA1c test orders was implemented to align with this guideline, where only one HbA1c test request every 90days for most individuals can be processed. Here, we evaluated the provincial intervention to reduce redundant HbA1c testing in Alberta. Read More
Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Esbjerg, Denmark; Department of Clinical Biochemistry, Hospital of South West Jutland, Esbjerg, Denmark; Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Objectives: Investigation of the blood compatibility requires a number of sensitive assays to quantify the activation of the blood protein cascades and cells induced by biomaterials. A global assay measuring the blood compatibility of biomaterials could be a valuable tool in such regard. In this study, we investigated whether an enzyme-linked immunosorbent assay (ELISA), that specifically measures the electrophoretic "fast form" of α2-macroglobulin (F-α2M), could be a sensitive and global marker for activation of calcium dependent and in-dependent proteases in plasma exposed to biomaterials in vitro. Read More
Objective: To provide evidence regarding the effect of vitamin D supplementation on symptomatic knee osteoarthritis (OA).
Methods: A systematic review and meta-analysis was performed to quantitatively pool the results from randomized clinical trials. Studies were identified from a search of the Embase, MEDLINE and Web of Science databases up to January 22, 2017, and also from conference abstracts, ClinicalTrials. Read More
Background: Minor head traumatisms are a common reason for consultation in paediatric emergency departments. The diagnosis of traumatic brain injuries involves performing a cranial computed tomography (CCT), associated with a risk of cancer due to the radiation. The serum S100B is an effective biomarker used to reduce reliance on CCT. Read More
Objectives: Alzheimer's disease (AD) is the most common cause of dementia in the world. As many AD biomarkers occur at rather low abundances in CSF or blood, techniques of very high sensitivity and accuracy are important as diagnostic tools in the clinic. Here, we aimed to provide proof of concept of the use of a single molecule detection technique, Fluorescence Correlation Spectroscopy (FCS) for detection of novel candidate biomarkers for AD. Read More
Department of Chemical Pathology, The Canberra Hospital, Canberra, ACT 2605, Australia; Australian National University Medical School, Canberra, ACT 2601, Australia.
Immunoassay procedures have a wide application in clinical medicine and as such are used throughout clinical biochemistry laboratories both for urgent and routine testing. Clinicians and laboratory personnel are often presented with immunoassay results which are inconsistent with clinical findings. Without a high index of suspicion interferences will often not be suspected. Read More
Protein electrophoresis and immunofixation are subject to a variety of analytical interferences that may affect monoclonal protein diagnostics performed in the context of monoclonal gammopathies. Interferences include endogenous substances, such as hemoglobin and fibrinogen, and exogenous compounds, such as radiocontrast dyes, antibiotics, and monoclonal antibody therapies. General approaches to managing interferences begin with recognition of the problem. Read More
Low serum bilirubin concentrations are reported to be strongly associated with cardio-metabolic disease, but this relationship has not been reported among Indigenous Australian people who are known to be at high risk for diabetes and chronic kidney disease (CKD).
Hypothesis: serum bilirubin will be negatively associated with markers of chronic disease, including CKD and anaemia among Indigenous Australians.
Method: A cross-sectional analysis of 594 adult Aboriginal and Torres Strait Islander (TSI) people in good health or with diabetes and markers of CKD. Read More
Background: Atherosclerotic plaque formation is characterized by recruitment of monocytes/macrophages, which contributes to its calcification by releasing pro-osteogenic cytokines. Chemotaxis-related proteins, including netrin-1, gremlin-1 and macrophage inflammatory protein-1β (MIP-1β), regulate immune cell migration. However, their relation with the presence of subclinical atherosclerosis, assessed by measures of coronary artery calcifications (CAC) in patients without known coronary artery disease (CAD), remains unclear. Read More
Objectives: Regulatory standards mandate laboratories to perform studies to ensure accuracy and reliability of their test results. Method comparison and bias estimation are important components of these studies.
Design & Methods: We developed an interactive website for evaluating the relative performance of two analytical methods using R programming language tools. Read More
Introduction: Vitamin B12 deficiency is mostly caused by insufficient gastro-intestinal absorption and in rare conditions by Transcobalamin (TC) deficiency. Unsaturated Transcobalamin (apoTC) can be measured by a binding assay using radiolabeled cobalamin. The Active B12 test analyzes saturated Transcobalamin (holoTC) and we hypothesize that this test can be used to measure total TC by additional in vitro saturation with cobalamin. Read More
Purpose: Some blood biomarkers or histological examination by liver biopsy are used for the diagnosis of liver diseases in clinics. However, conventional blood biomarkers show poor specificity and sensitivity, and liver biopsy is highly invasiveness. Therefore, to overcome such disadvantages, specific/sensitive and noninvasive options are desirable. Read More
Objectives: Immunoassays involving sample incubation followed by a wash step prior to introduction of labeled analyte are potentially subject to both positive and negative interference (bidirectional interference) by a competing ligand. We examine this phenomenon from a theoretical standpoint using a mathematical model for sequential-step immunoassays in the presence of interferent.
Design & Methods: Competitive binding to antibody between analyte and interferent was modeled for sequential-step immunoassays. Read More
Background: Storage of blood samples after centrifugation, decapping and initial sampling allows ordering of additional blood tests. The pre-analytic stability of biochemistry and immunochemistry analytes has been studied in detail, but little is known about the post-analytical stability in incurred samples.
Methods: We examined the stability of 23 routine analytes on the Dimension Vista® (Siemens Healthineers, Denmark): 42-60 routine samples in lithium-heparin gel tubes (Vacutainer, BD, USA) were centrifuged at 3000×g for 10min. Read More
Objectives: Determination of cardiac troponin (cTn) is central in the emergency department (ED) for the diagnosis of myocardial infarction. In view of adverse effects of long waiting time on patient outcome, implementation of point-of-care-testing (POCT) is suggested if the turn-around-time is longer than 60min. The present study aimed to determine the 99th percentile and imprecision of two POCT in a healthy population measuring cTnI and cTnT and compare these analytical characteristics against three central laboratory test (CLT) for cTnI. Read More
Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, PR China; Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, PR China. Electronic address:
Objective: To evaluate how thyroglobulin (Tg) and thyroglobulin antibody (TgAb) results compare among different chemiluminescence methods.
Methods: Serum specimens from 153 patients with thyroiditis and 127 apparently healthy individuals were collected at the Peking Union Medical College Hospital from September 2014 to December 2014. TgAb and Tg levels were analyzed by using three different platforms manufactured by Roche, Beckman, and Siemens. Read More
Department of Modern Sciences & Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;; Division of Applied Medicine, Medical School, University of Aberdeen, Foresterhill, Aberdeen, UK.. Electronic address:
Ischaemic stroke, which is mostly caused by atherosclerosis, is one of the most widely causes of mortality and morbidity. One of the most important enzymatic activities of paraoxonase-1 (PON1) in association with high-density lipoprotein (HDL) is the prevention of low-density lipoprotein (LDL) oxidation, which gives it an anti-atherogenic activity. PON1 expression and activity is influenced by various factors; the most important of which is genetic polymorphism, mainly single nucleotide polymorphisms (SNPs). Read More
Background: Since plasma oxalate (POx) concentrations increase at lower glomerular filtration rate (GFR) levels, even among those without enteric (EH) or primary hyperoxaluria (PH), the appropriate thresholds for considering a disorder of oxalate metabolism are poorly defined. The current study was completed to establish relationships between POx, GFR, and urine oxalate excretion (UOx) among patients with PH, EH, and routine urinary stone disease (USD).
Methods: The most recent POx measurement on all Mayo Clinic patients between 2005 and 2015 were electronically pulled from the Lab Information System together with the closest serum creatinine within 14days and 24h urine study within 60days. Read More
Although uric acid is not part of any definition of metabolic syndrome, a number of studies have shown strong associations between the concentration of uric acid and metabolic syndrome or its components. The purpose of this systematic review with meta-analysis was to evaluate, using prospective interventional studies, the effects of allopurinol therapy and uric acid normalization on serum concentrations of triacylglycerol, total-cholesterol, LDL-cholesterol and HDL-cholesterol in hyperuricemic subjects. A systematic search of the PubMed and Scopus databases was performed following the guidelines described in the PRISMA statement. Read More
Department of Adult Cardiology, Deutsches Herzzentrum München, Technische Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
Background: CUB and zona pellucida-like domain-containing protein 1 (CUZD1) was identified as a pancreas-specific protein and was proposed as a candidate biomarker for pancreatic related disorders. CUZD1 protein levels in tissues and biological fluids have not been extensively examined. The purpose of the present study was to generate specific antibodies targeting CUZD1 to assess CUZD1 expression within tissues and biological fluids. Read More
Cachexia is a complex multifactorial syndrome, characterized by loss of skeletal muscle and fat mass, which affects the majority of advanced cancer patients and is associated with poor prognosis. Interestingly, reversing muscle loss in animal models of cancer cachexia leads to prolong survival. Therefore, detecting cachexia and maintaining muscle mass represent a major goal in the care of cancer patients. Read More
Graduate Program in Endocrinology, Universidade Federal do Rio Grande do Sul (UFRGS), Zip Code 90040-341 Porto Alegre, Brazil; Endocrinology Division, Hospital de Clínicas de Porto Alegre, Zip Code 90035-903 Porto Alegre, Brazil. Electronic address:
Background: Glycated hemoglobin (HbA1c) is an alternative test used for the diagnosis and monitoring of diabetes in kidney transplant recipients. Immunosuppressive drugs are the most important risk factors related with changes in the glucose metabolism after transplant. It is still unknown if they impact on the variability of HbA1c. Read More
Zsigmondy Vilmos Harkány SPA Hospital, 7815 Harkány, Zsigmondy sétány 1, Hungary; Heart Institute, University of Pécs, 7624 Pécs, Ifjúság u. 13, Hungary.
Background: Urinary biomarkers might provide non-invasive tool for monitoring of systemic processes. We aimed to investigate the time-course of urinary orosomucoid (u-ORM) excretion after cardiac surgery hypothesizing that u-ORM is an early and sensitive marker of systemic inflammatory activation.
Methods: During a 5-day follow-up study we monitored u-ORM levels in cardiovascular patients who underwent on-pump cardiac surgery (n=38). Read More
Introduction: Lactic acidosis represents the pathologic accumulation of lactate and hydrogen ions. It is important to efficiently diagnose lactic acidosis as delayed treatment will lead to poor patient outcomes. As plasma lactate levels may not be rapidly available, some physicians may use elevated anion gaps to test for the need to measure lactate. Read More
Royal College of Pathologists of Australasia Quality Assurance Programs Pty Ltd, Sydney, Australia. Electronic address:
Introduction: Diabetes is a major health problem for Australia's Aboriginal and Torres Strait Islander peoples. Point-of-care testing for haemoglobin A1c (HbA1c) has been the cornerstone of a long-standing program (QAAMS) to manage glycaemic control in Indigenous people with diabetes and recently, to diagnose diabetes.
Methods: The QAAMS quality management framework includes monthly testing of quality control (QC) and external quality assurance (EQA) samples. Read More
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada. Electronic address:
Objective: To statistically compare and evaluate commonly used methods of estimating reference intervals and to determine which method is best based on characteristics of the distribution of various data sets.
Design And Methods: Three approaches for estimating reference intervals, i.e. Read More
The aim of this study was to perform a systematic review of the published literature to determine the available serum/plasma steroid reference intervals generated by mass spectrometry (MS) methods across all age groups in healthy subjects and to suggest recommendations to achieve common MS based reference intervals for serum steroids. MEDLINE, EMBASE and PubMed databases were used to conduct a comprehensive search for English language, MS-based reference interval studies for serum/plasma steroids. Selection of steroids to include was based on those listed in the Royal College of Pathologists of Australasia Quality Assurance Programs, Chemical Pathology, Endocrine Program. Read More
Gaining a better understanding of Quality Control (QC) processes is a key requirement to improving performance and reducing patient risk. Detecting analytical error is dependent on a QC strategy that reliably detects a critical shift in a result away from the true value. Recently the concept of Six Sigma has been used by diagnostic laboratories to assess the performance of assays and to assist in the selection of QC rules. Read More
Pathology and Laboratory Medicine, London Health Sciences Centre & St. Joseph's Health Care London, London, Ontario, Canada; Western University, Department of Pathology and Laboratory Medicine, London, Ontario, Canada. Electronic address:
Acute pancreatitis is a rapid onset of inflammation of the pancreas causing mild to severe life threatening conditions [1, 2]. In Canada, acute pancreatitis is the 5th most expensive digestive disease in Canada with a considerable economic burden on the health care system . The diagnosis of acute pancreatitis is usually based on the presence of abdominal pain and elevated levels of serum amylase and/or lipase. Read More
Clinical Institute, Faculty of Health Sciences, University of Southern Denmark, J. B. Winsløws Vej 19, 5000 Odense C, Denmark; Hans Christian Andersen Children's Hospital, Odense University Hospital, Kløvervænget 25, 5000 Odense C, Denmark. Electronic address:
Background: Analysis of serum 25-hydroxyvitamin D (s-25(OH)D) may be complicated by the less active or in-active vitamin D metabolite C3-epi-25(OH)D3 (C3-epimer). We aimed to explore the relationship between s-C3-epimer and s-25(OH)D and other determinants and describe the longitudinal course of the C3-epimer fraction in paired mother-child samples.
Method: S-25(OH)D and s-C3-epimer were estimated by liquid chromatography mass spectrometry in 290 mother-infant pairs from the population-based Odense Child Cohort. Read More