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En el laboratorio clínico, la calibración de los procedimientos de medición es un aspecto clave a la hora de garantizar la fiabilidad de los resultados del paciente. A lo largo de los años, se han publicado multitud de publicaciones y procedimientos para la evaluación del control de calidad y la interpretación de sus resultados. En esta publicación, nos centraremos en un aspecto crítico, la calibración, ya que no existen publicaciones o directrices claras sobre metodologías de calibración. Por lo general, solo están disponibles las recomendaciones del fabricante del reactivo o instrumento. El propósito de esta revisión es ahondar en esta deficiencia, con el fin de suscitar un debate y mejorar la situación actual.

Calibration of an analytical measurement procedure is an important basis for the reliability of patient results. Many publications and as well as procedures on how to estimate quality control and interpret those results have been become available over the years. In this publication we are focusing on the critical part of the calibration as there are no clear communication or guidelines on how to perform it. Usually only the recommendation of the reagent or instrument manufacturer is available. We would like to point out this gap to invite for a discussion and improvement of the current situation.

This article discusses the discovery of a novel variant of the thiopurine S-methyltransferase (TPMT) gene in a Malay individual. The TPMT gene is important for the metabolism of thiopurine drugs used in the treatment of various conditions. The variant, which involves an in-frame deletion and insertion event, was found to be specific to the Malay population and was not present in major genomic databases. The study highlights the importance of genetic testing in optimizing drug therapy and calls for further investigation into the variant's clinical implications. [Extracted from the article]

Reporting a measurement procedure and its analytical performance following method evaluation in a peer-reviewed journal is an important means for clinical laboratory practitioners to share their findings. It also represents an important source of evidence base to help others make informed decisions about their practice. At present, there are significant variations in the information reported in laboratory medicine journal publications describing the analytical performance of measurement procedures. These variations also challenge authors, readers, reviewers, and editors in deciding the quality of a submitted manuscript. The International Federation of Clinical Chemistry and Laboratory Medicine Working Group on Method Evaluation Protocols (IFCC WG-MEP) developed a checklist and recommends its adoption to enable a consistent approach to reporting method evaluation and analytical performance characteristics of measurement procedures in laboratory medicine journals. It is envisioned that the LEAP checklist will improve the standardisation of journal publications describing method evaluation and analytical performance characteristics, improving the quality of the evidence base that is relied upon by practitioners. [ABSTRACT FROM AUTHOR]

Emerging technology in laboratory medicine can be defined as an analytical method (including biomarkers) or device (software, applications, and algorithms) that by its stage of development, translation into broad routine clinical practice, or geographical adoption and implementation has the potential to add value to clinical diagnostics. Paediatric laboratory medicine itself may be considered an emerging area of specialisation that is established relatively recently following increased appreciation and understanding of the unique physiology and healthcare needs of the children. Through four clinical (neonatal hypoglycaemia, neonatal hyperbilirubinaemia, sickle cell disorder, congenital adrenal hyperplasia) and six technological (microassays, noninvasive testing, alternative matrices, next generation sequencing, exosome analysis, machine learning) illustrations, key takeaways of application of emerging technology for each area are summarised. Additionally, nine key considerations when applying emerging technology in paediatric laboratory medicine setting are discussed. [ABSTRACT FROM AUTHOR]

In this computer simulation study, we examine four different statistical approaches of linearity assessment, including two variants of deviation from linearity (individual (IDL) and averaged (AD)), along with detection capabilities of residuals of linear regression (individual and averaged). From the results of the simulation, the following broad suggestions are provided to laboratory practitioners when performing linearity assessment. A high imprecision can challenge linearity investigations by producing a high false positive rate or low power of detection. Therefore, the imprecision of the measurement procedure should be considered when interpreting linearity assessment results. In the presence of high imprecision, the results of linearity assessment should be interpreted with caution. Different linearity assessment approaches examined in this study performed well under different analytical scenarios. For optimal outcomes, a considered and tailored study design should be implemented. With the exception of specific scenarios, both ADL and IDL methods were suboptimal for the assessment of linearity compared. When imprecision is low (3 %), averaged residual of linear regression with triplicate measurements and a non-linearity acceptance limit of 5 % produces <5 % false positive rates and a high power for detection of non-linearity of >70 % across different types and degrees of non-linearity. Detection of departures from linearity are difficult to identify in practice and enhanced methods of detection need development. [ABSTRACT FROM AUTHOR]

Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.

Reference intervals depend on the distribution of results within a reference population and can be influenced by subclinical disease. Functional reference limits present an opportunity to derive clinically relevant reference limits from routinely collected data sources, which consist of mixed populations of unhealthy and healthy groups. Serum ferritin is a good example of the utility of functional reference limits. Several studies have identified clinically relevant reference limits through examining the relationship between serum ferritin and erythrocyte parameters. These ferritin functional limits often represent the inflection point at which erythrocyte parameters change significantly. Comparison of ferritin functional reference limits with those based on population distributional reference limits reveals that the lower reference limit may fall below the point at which patients become clinically unwell. Functional reference limits may be considered for any biomarker that exhibits a correlated relationship with other biomarkers.

Diabetes mellitus affected more than 500 million of people globally, with an annual mortality of 1.5 million directly attributable to diabetic complications. Oxidative stress, in particularly in post-prandial state, plays a vital role in the pathogenesis of the diabetic complications. However, oxidative status marker is generally poorly characterized and their mechanisms of action are not well understood. In this work, we proposed a new framework for deep characterization of oxidative stress in erythrocytes (and in urine) using home-built micro-scale NMR system. The dynamic of post-prandial oxidative status (against a wide variety of nutritional load) in individual was assessed based on the proposed oxidative status of the red blood cells, with respect to the traditional risk-factors such as urinary isoprostane, reveals new insights into our understanding of diabetes. This new method can be potentially important in drafting guidelines for sub-stratification of diabetes mellitus for clinical care and management. [ABSTRACT FROM AUTHOR]

Calibration of an analytical measurement procedure is an important basis for the reliability of patient results. Many publications and as well as procedures on how to estimate quality control and interpret those results have been become available over the years. In this publication we are focusing on the critical part of the calibration as there are no clear communication or guidelines on how to perform it. Usually only the recommendation of the reagent or instrument manufacturer is available. We would like to point out this gap to invite for a discussion and improvement of the current situation. [ABSTRACT FROM AUTHOR]

Background: Plasma copeptin measurement is useful for the differential diagnoses of polyuria-polydipsia syndrome. It has also been proposed as a prognostic marker for cardiovascular diseases. However, limited information is available about the within- (CVI) and between-subject (CVG) biological variation (BV). This study presents BV estimates for copeptin in healthy individuals. Methods: Samples were collected weekly from 41 healthy subjects over 5 weeks and analyzed using the BRAHMS Copeptin proAVP KRYPTOR assay after at least 8 h of food and fluid abstinence. Outlier detection, variance homogeneity, and trend analysis were performed followed by CV-ANOVA for BV and analytical variation (CVA) estimation with 95% confidence intervals. Reference change values (RCVs), index of individuality (II), and analytical performance specification (APS) were also calculated. Results: The analysis included 178 results from 20 males and 202 values from 21 females. Copeptin concentrations were significantly higher in males than in females (mean 8.5 vs 5.2 pmol/L, P < 0.0001). CVI estimates were 18.0% (95% CI, 15.4%–21.6%) and 19.0% (95% CI, 16.4%–22.6%), for males and females, respectively; RCVs were −35% (decreasing value) and 54% (increasing value). There was marked individuality for copeptin. No result exceeded the diagnostic threshold (>21.4 pmol/L) for arginine vasopressin resistance. Conclusions: The availability of BV data allows for refined APS and associated II, and RCVs applicable as aids in the serial monitoring of patients with specific diseases such as heart failure. The BV estimates are only applicable in subjects who abstained from oral intake due to the rapid and marked effects of fluids on copeptin physiology. [ABSTRACT FROM AUTHOR]

Interference from isomeric steroids is a potential cause of disparity between mass spectrometry-based 17-hydroxyprogesterone (17OHP) results. We aimed to assess the proficiency of mass spectrometry laboratories to report 17OHP in the presence of known isomeric steroids. A series of five samples were prepared using a previously demonstrated commutable approach. These samples included a control (spiked to 15.0 nmol/L 17OHP) and four challenge samples further enriched with equimolar concentrations of 17OHP isomers (11α-hydroxyprogesterone, 11β-hydroxyprogesterone, 16α-hydroxyprogesterone or 21-hydroxyprogesterone). These samples were distributed to 38 participating laboratories that reported serum 17OHP results using mass spectrometry in two external quality assurance programs. The result for each challenge sample was compared to the control sample submitted by each participant. Twenty-six laboratories (68 % of distribution) across three continents returned results. Twenty-five laboratories used liquid chromatography-tandem mass spectrometry (LC-MS/MS), and one used gas chromatography-tandem mass spectrometry to measure 17OHP. The all-method median of the control sample was 14.3 nmol/L, ranging from 12.4 to 17.6 nmol/L. One laboratory had results that approached the lower limit of tolerance (minus 17.7 % of the control sample), suggesting the isomeric steroid caused an irregular result. Most participating laboratories demonstrated their ability to reliably measure 17OHP in the presence of the four clinically relevant isomeric steroids. The performance of the 12 (32 %) laboratories that did not engage in this activity remains unclear. We recommend that all laboratories offering LC-MS/MS analysis of 17OHP in serum, plasma, or dried bloodspots determine that the isomeric steroids are appropriately separated. [ABSTRACT FROM AUTHOR]

Monoclonal gammopathy (MG) is a spectrum of diseases ranging from the benign asymptomatic monoclonal gammopathy of undetermined significance to the malignant multiple myeloma. Clinical guidelines and laboratory recommendations have been developed to inform best practices in the diagnosis, monitoring, and management of MG. In this review, the pathophysiology, relevant laboratory testing recommended in clinical practice guidelines and laboratory recommendations related to MG testing and reporting are examined. The clinical guidelines recommend serum protein electrophoresis, serum immunofixation and serum free light chain measurement as initial screening. The laboratory recommendations omit serum immunofixation as it offers limited additional diagnostic value. The laboratory recommendations offer guidance on reporting findings beyond monoclonal protein, which was not required by the clinical guidelines. The clinical guidelines suggested monitoring total IgA concentration by turbidimetry or nephelometry method if the monoclonal protein migrates in the non-gamma region, whereas the laboratory recommendations make allowance for involved IgM and IgG. Additionally, several external quality assurance programs for MG protein electrophoresis and free light chain testing are also appraised. The external quality assurance programs show varied assessment criteria for protein electrophoresis reporting and unit of measurement. There is also significant disparity in reported monoclonal protein concentrations with wide inter-method analytical variation noted for both monoclonal protein quantification and serum free light chain measurement, however this variation appears smaller when the same method was used. Greater harmonization among laboratory recommendations and reporting format may improve clinical interpretation of MG testing. [ABSTRACT FROM AUTHOR]