| 1. |
- Andreasson, Ulf, 1968, et al.
(författare)
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Assessing the commutability of candidate reference materials for the harmonization of neurofilament light measurements in blood
- 2023
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 61:7, s. 1245-1254
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Neurofilament light chain (NfL) concentration in blood is a biomarker of neuro-axonal injury in the nervous system and there now exist several assays with high enough sensitivity to measure NfL in serum and plasma. There is a need for harmonization with the goal of creating a certified reference material (CRM) for NfL and an early step in such an effort is to determine the best matrix for the CRM. This is done in a commutability study and here the results of the first one for NfL in blood is presented.Methods Forty paired individual serum and plasma samples were analyzed for NfL on four different analytical platforms. Neat and differently spiked serum and plasma were evaluated for their suitability as a CRM using the difference in bias approach.Results The correlation between the different platforms with regards to measured NfL concentrations were very high (Spearman's rho >= 0.96). Samples spiked with cerebrospinal fluid (CSF) showed higher commutability compared to samples spiked with recombinant human NfL protein and serum seems to be a better choice than plasma as the matrix for a CRM.Conclusions The results from this first commutability study on NfL in serum/plasma showed that it is feasible to create a CRM for NfL in blood and that spiking should be done using CSF rather than with recombinant human NfL protein.
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| 2. |
- Ankarberg-Lindgren, Carina, 1963, et al.
(författare)
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Methodological considerations in determining sex steroids in children: comparison of conventional immunoassays with liquid chromatography-tandem mass spectrometry.
- 2024
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Ingår i: Clinical chemistry and laboratory medicine. - 1437-4331. ; 62:1, s. 85-96
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Tidskriftsartikel (refereegranskat)abstract
- In laboratory medicine, external quality assessment (EQA) schemes have become versatile tools for detecting analytical flaws. However, EQA schemes are lacking for pediatric sex steroid levels. We aimed to investigate the suitability of different estradiol and testosterone immunoassays in a pediatric setting in comparison with clinical liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays.The study was conducted by staff and the advisory group on endocrinology at Equalis, the Swedish provider of EQA schemes for laboratory medicine. The test material consisted of five pooled serum samples from children who were either prepubertal or in puberty. Clinical laboratories enrolled in Equalis EQA schemes for estradiol and testosterone were invited to participate, as were clinical laboratories using LC-MS/MS-assays. Samples were analyzed by either routine immunoassays (n=18) or in-house LC-MS/MS assays (n=3).For estradiol, LC-MS/MS assays showed a high degree of conformity with interlaboratory coefficients of variation (CV) below 24.2%. Reported levels were between 4.9±1.2 and 33.9±1.6pmol/L (group mean±standard deviation). The direct immunoassays had lower precision; their CVs were up to 81.4%. Reported concentrations were between 25.3±18.1 and 45.7±19.4pmol/L, an overestimation compared to LC-MS/MS. Testosterone LC-MS/MS also showed a high degree of conformity, CVs were below 13.4%, and reported concentrations were from 0.06±0.00 to 1.00±0.11nmol/L. The direct immunoassays had a larger discrepancy between results; CVs were up to 95.8%. Concentrations were between 0.12±0.11 and 0.85±0.23nmol/L.For the safe diagnosis and determination of sex steroids in children, analysis with mass spectrometry-based methods is recommended.
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| 3. |
- Arslan, Burak, 1990, et al.
(författare)
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Blood-based biomarkers in Alzheimer's disease - moving towards a new era of diagnostics
- 2024
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Ingår i: CLINICAL CHEMISTRY AND LABORATORY MEDICINE. - 1434-6621 .- 1437-4331.
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD), a primary cause of dementia globally, is traditionally diagnosed via cerebrospinal fluid (CSF) measures and positron emission tomography (PET). The invasiveness, cost, and limited accessibility of these methods have led to exploring blood-based biomarkers as a promising alternative for AD diagnosis and monitoring. Recent advancements in sensitive immunoassays have identified potential blood-based biomarkers, such as A beta 42/A beta 40 ratios and phosphorylated tau (p-tau) species. This paper briefly evaluates the clinical utility and reliability of these biomarkers across various AD stages, highlighting challenges like refining plasma A beta 42/A beta 40 assays and enhancing the precision of p-tau, particularly p-tau181, p-tau217, and p-tau231. The discussion also covers other plasma biomarkers like neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and synaptic biomarkers, assessing their significance in AD diagnostics. The need for ongoing research and development of robust assays to match the performance of CSF and PET biomarkers is underscored. In summary, blood-based biomarkers are increasingly crucial in AD diagnosis, follow-up, prognostication, treatment response evaluation, and population screening, particularly in primary care settings. These developments are set to revolutionize AD diagnostics, offering earlier and more accessible detection and management options
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| 4. |
- Arslan, Burak, 1990, et al.
(författare)
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Neurofilament light chain as neuronal injury marker - what is needed to facilitate implementation in clinical laboratory practice?
- 2023
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 61:7, s. 1140-1149
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Tidskriftsartikel (refereegranskat)abstract
- Neurobiomarkers have attracted significant attention over the last ten years. One promising biomarker is the neurofilament light chain protein (NfL). Since the introduction of ultrasensitive assays, NfL has been developed into a widely used axonal damage marker of relevance to the diagnosis, prognostication, follow-up, and treatment monitoring of a range of neurological disorders, including multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. The marker is increasingly used clinically, as well as in clinical trials. Even if we have validated precise, sensitive, and specific assays for NfL quantification in both cerebrospinal fluid and blood, there are analytical, as well as pre- and post-analytical aspects of the total NfL testing process, including biomarker interpretation, to consider. Although the biomarker is already in use in specialised clinical laboratory settings, a more general use requires some further work. In this review, we provide brief basic information and opinions on NfL as a biomarker of axonal injury in neurological diseases and pinpoint additional work needed to facilitate biomarker implementation in clinical practice.
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| 5. |
- Blennow, Kaj, 1958, et al.
(författare)
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Second-generation Elecsys cerebrospinal fluid immunoassays aid diagnosis of early Alzheimer's disease.
- 2023
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Ingår i: Clinical chemistry and laboratory medicine. - : Walter de Gruyter GmbH. - 1437-4331 .- 1434-6621. ; 61:2, s. 234-244
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Tidskriftsartikel (refereegranskat)abstract
- Timely diagnosis of Alzheimer's disease (AD) is critical for appropriate treatment/patient management. Cerebrospinal fluid (CSF) biomarker analysis is often used to aid diagnosis. We assessed analytical performance of second-generation (Gen II) Elecsys® CSF immunoassays (Roche Diagnostics International Ltd), and adjusted existing cut-offs, to evaluate their potential utility in clinical routine.Analytical performance was assessed using CSF samples measured with Elecsys CSF Gen II immunoassays on cobas e analyzers. Aβ42 Gen I/Gen II immunoassay method comparisons were performed (Passing-Bablok regression). Cut-off values were adjusted using estimated bias in biomarker levels between BioFINDER protocol aliquots/Gen I immunoassays and Gen II protocol aliquots/immunoassays. Distribution of Gen II immunoassay values was evaluated in AD, mild cognitive impairment (MCI), and cognitively normal cohorts; percentage observations outside the measuring range were derived.The Gen II immunoassays demonstrated good analytical performance, including repeatability, intermediate precision, lot-to-lot agreement (Pearson's r:≥0.999), and platform agreement (Pearson's r:≥0.995). Aβ42 Gen I/Gen II immunoassay measurements were strongly correlated (Pearson's r: 0.985-0.999). Aβ42 Gen II immunoassay cut-offs were adjusted to 1,030 and 800ng/L, and pTau181/Aβ42 ratio cut-offs to 0.023 and 0.029, for Gen II and I protocols, respectively. No observations were below the lower limit of the measuring range; above the upper limit, there were none from the AD cohort, and 2.6 and 6.8% from the MCI and cognitively normal cohorts, respectively.Our findings suggest that the Gen II immunoassays have potential utility in clinical routine to aid diagnosis of AD.
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| 6. |
- Bonroy, Carolien, et al.
(författare)
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Detection of antinuclear antibodies : recommendations from EFLM, EASI and ICAP
- 2023
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 61:7, s. 1167-1198
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Antinuclear antibodies (ANA) are important for the diagnosis of various autoimmune diseases. ANA are usually detected by indirect immunofluorescence assay (IFA) using HEp-2 cells (HEp-2 IFA). There are many variables influencing HEp-2 IFA results, such as subjective visual reading, serum screening dilution, substrate manufacturing, microscope components and conjugate. Newer developments on ANA testing that offer novel features adopted by some clinical laboratories include automated computer-assisted diagnosis (CAD) systems and solid phase assays (SPA).Methods: A group of experts reviewed current literature and established recommendations on methodological aspects of ANA testing. This process was supported by a two round Delphi exercise. International expert groups that participated in this initiative included (i) the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group “Autoimmunity Testing”; (ii) the European Autoimmune Standardization Initiative (EASI); and (iii) the International Consensus on ANA Patterns (ICAP).Results: In total, 35 recommendations/statements related to (i) ANA testing and reporting by HEp-2 IFA; (ii) HEp-2 IFA methodological aspects including substrate/conjugate selection and the application of CAD systems; (iii) quality assurance; (iv) HEp-2 IFA validation/verification approaches and (v) SPA were formulated. Globally, 95% of all submitted scores in the final Delphi round were above 6 (moderately agree, agree or strongly agree) and 85% above 7 (agree and strongly agree), indicating strong international support for the proposed recommendations.Conclusions: These recommendations are an important step to achieve high quality ANA testing.
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| 7. |
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| 8. |
- Bäcklund, Nils, et al.
(författare)
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Salivary cortisol and cortisone in diagnosis of Cushing's syndrome - a comparison of six different analytical methods
- 2023
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 61:10, s. 1780-1791
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Salivary cortisol and cortisone at late night and after dexamethasone suppression test (DST) are increasingly used for screening of Cushing's syndrome (CS). We aimed to establish reference intervals for salivary cortisol and cortisone with three liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques and for salivary cortisol with three immunoassays (IAs), and evaluate their diagnostic accuracy for CS.Methods: Salivary samples at 08:00 h, 23:00 h and 08:00 h after a 1-mg DST were collected from a reference population (n=155) and patients with CS (n=22). Sample aliquots were analyzed by three LC-MS/MS and three IA methods. After establishing reference intervals, the upper reference limit (URL) for each method was used to calculate sensitivity and specificity for CS. Diagnostic accuracy was evaluated by comparing ROC curves.Results: URLs for salivary cortisol at 23:00 h were similar for the LC-MS/MS methods (3.4-3.9 nmol/L), but varied between IAs: Roche (5.8 nmol/L), Salimetrics (4.3 nmol/L), Cisbio (21.6 nmol/L). Corresponding URLs after DST were 0.7-1.0, and 2.4, 4.0 and 5.4 nmol/L, respectively. Salivary cortisone URLs were 13.5-16.6 nmol/L at 23:00 h and 3.0-3.5 nmol/L at 08:00 h after DST. All methods had ROC AUCs =0.96.Conclusions: We present robust reference intervals for salivary cortisol and cortisone at 08:00 h, 23:00 h and 08:00 h after DST for several clinically used methods. The similarities between LC-MS/MS methods allows for direct comparison of absolute values. Diagnostic accuracy for CS was high for all salivary cortisol and cortisone LC-MS/MS methods and salivary cortisol IAs evaluated.
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| 9. |
- Cadamuro, Janne, et al.
(författare)
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Preanalytical quality improvement - an interdisciplinary journey, on behalf of the European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for Preanalytical Phase (WG-PRE)
- 2022
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 60:5, s. 662-668
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Tidskriftsartikel (refereegranskat)abstract
- Since the beginning of laboratory medicine, the main focus was to provide high quality analytics. Over time the importance of the extra-analytical phases and their contribution to the overall quality became evident. However, as the initial preanalytical processes take place outside of the laboratory and mostly without its supervision, all professions participating in these process steps, from test selection to sample collection and transport, need to engage accordingly. Focusing solely on intra-laboratory processes will not be sufficient to achieve the best possible preanalytical quality. The Working Group for the Preanalytical Phase (WG-PRE) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has provided several recommendations, opinion papers and scientific evidence over the past years, aiming to standardize the preanalytical phase across Europe. One of its strategies to reach this goal are educational efforts. As such, the WG-PRE has organized five conferences in the past decade with the sole focus on preanalytical quality. This year's conference mainly aims to depict the views of different professions on preanalytical processes in order to acquire common ground as basis for further improvements. This article summarizes the content of this 6th preanalytical conference.
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| 10. |
- Clarin, M., et al.
(författare)
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Detection of subarachnoid haemorrhage with spectrophotometry of cerebrospinal fluid - a comparison of two methods
- 2022
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 60:7, s. 1053-1057
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Spectrophotometric absorption curve analysis of cerebrospinal fluid (CSF) for oxyhaemoglobin and bilirubin is necessary to accurately diagnose subarachnoid haemorrhage (SAH) in patients with typical symptoms but with negative findings on X-ray examinations. In this study, we evaluated the performance of two methods for interpreting absorption curves; one method from the United Kingdom National External Quality Assessment Service (UK-NEQAS) and the other from the national quality assurance programme in Sweden (Equalis). Methods Consecutive absorbance curves (n=336) were interpreted with two different methods, and their performance was compared to the diagnosis as stated in the patient records. Results The UK-NEQAS method displayed equal sensitivity to the Equalis method, but the specificity of the UK-NEQAS method was significantly higher than the Equalis method resulting in fewer false positive results. For UK-NEQAS, a positive predictive value (PPV) of 84.6% and a negative predictive value (NPV) of 99.7% were observed, whereas the Equalis method had a PPV of 27.5% and an NPV of 99.7%. Conclusions The semi-automated method based on the guidelines from UK-NEQAS provides an efficient and correct interpretation of absorbance curves with short turn-around times. We propose using this method for the routine interpretation of CSF spectrophotometric curves.
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