146 results on '"Panteghini, Mauro"'
Search Results
2. Common reference intervals for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) in serum: results from an IFCC multicenter study
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Ceruotti, Ferruccio, Henny, Joseph, Queralto, Josep, Ziyu, Shen, Chen, Baorong, Boyd, James C., Panteghini, Mauro, Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya ve Klinik Biyokimya Anabilim Dalı., Özarda, Yeşim, and AAL-8873-2021
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Male ,Reproducibility of results ,Aspartate aminotransferase blood level ,Catalytic-activity concentrations ,Gamma glutamyl transferase blood level ,Ethnic groups ,6 Asian cities ,Turkey (republic) ,Gamma-glutamyl transferase ,Creatine kinase blood level ,Middle aged ,Alanine transaminase ,Priority journal ,37-degrees-c ,Aged, 80 and over ,Clinical Chemistry ,Thyrotropin ,Nonparametric Methods ,Multicenter study ,Enzymes ,Erythrocyte ,Cholesterol blood level ,Italy ,Female ,Alanine aminotransferase blood level ,Sex factors ,Human ,Adult ,Laboratory test ,China ,Adolescent ,Gamma glutamyltransferase ,Reference limits ,Major clinical study ,Aspartate aminotransferase ,digestive system ,Article ,Reference values ,Humans ,Creatinine blood level ,Blood chemical analysis ,Aged ,International agencies ,Healthy-subjects ,International-federation ,Questionnaire ,Reference intervals ,Gamma-glutamyltransferase ,Part ,Sex difference ,digestive system diseases ,Standardization ,Young adult ,Alanine aminotransferase ,Medical laboratory technology ,Laboratories ,Reference value ,Uric acid blood level ,Aspartate aminotransferases - Abstract
Background: Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) measurements are important for the assessment of liver damage. The aim of this study was to define the reference intervals (RIs) for these enzymes in adults, paying attention to standardization of the methods used and careful selection of the reference population. Methods: AST, ALT and GGT were measured with commercial analytical systems standardized to the IFCC-recommended reference measurement systems. Three centers (two in Italy and one in China) measured their own freshly collected samples; one of these centers also measured frozen samples from the Nordic Countries RI Project and from a Turkish center. RIs were generated using non-parametric techniques from the results of 765 individuals (411 females and 354 males, 18-85 years old) selected on the basis of the results of other laboratory tests and a specific questionnaire. Results: AST results from the four regions (Milan, Beijing, Bursa and Nordic Countries) were statistically different, but these differences were too small to be clinically relevant. Likewise, differences between the upper reference limits for genders was only 1.7 U/L (0.03 mu kat/L), allowing a single RI of 11-34 U/L (0.18-0.57 mu kat/L) to be defined. Inter-regional differences were not statistically significant for ALT, but partitioning was required due to significant gender differences. RIs for ALT were 8-41 U/L (0.13-0.68 mu kat/L) for females and 9-59 U/L (0.15-0.99 mu kat/L) for males, respectively. The upper reference limits for GGT from the Nordic Country population were higher than those from the other three regions and results from this group were excluded from final calculations. The GGT RIs were 6-40 U/L (0.11-0.66 mu kat/L) for females and 12-68 U/L (0.20-1.13 mu kat/L) for males, respectively. Conclusions: For AST and ALT, the implementation of common RIs appears to be possible, because no differences between regions were observed. However, a common RI for GGT that is applicable worldwide appears unlikely due to differences among populations. Clin Chem Lab Med 2010;48:1593-601. IFCC Abbott Laboratories Ortho-Clinical Diagnostics Inc. Sysmex Europe GmbH Binding Site Ltd.
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- 2010
3. Time to refresh and integrate the JCTLM database entries for total bilirubin: the way forward.
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Panteghini M, Miller WG, and Wielgosz R
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- 2024
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4. Adult reference intervals for serum thyroid-stimulating hormone using Abbott Alinity i measuring system.
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Stefanska A, Krintus M, Siodmiak J, Wolska A, Szternel L, Gackowska L, and Panteghini M
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- 2024
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5. The information about the metrological traceability pedigree of the in vitro diagnostic calibrators should be improved: the case of plasma ethanol.
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Capoferri A, Pasqualetti S, Borrillo F, Dolci A, and Panteghini M
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- 2024
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6. Analytical performance specifications - moving from models to practical recommendations.
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Sandberg S, Zima T, and Panteghini M
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- 2024
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7. An improved implementation of metrological traceability concepts is needed to benefit from standardization of laboratory results.
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Panteghini M
- Abstract
Non-harmonization of laboratory results represents a concrete risk for patient safety. To avoid harms, it is agreed that measurements by in vitro diagnostic medical devices (IVD-MD) on clinical samples should be traceable to higher-order references and adjusted to give the same result. However, metrological traceability is not a formal claim and has to be correctly implemented, which in practice does not happen for a non-negligible number of measurands. Stakeholders, such as higher-order reference providers, IVD manufacturers, and External Quality Assessment organizers, have major responsibilities and should improve their contribution by unambiguously and rigorously applying what is described in the International Organization for Standardization 17511:2020 standard and other documents provided by the international scientific bodies, such as Joint Committee on Traceability in Laboratory Medicine and IFCC. For their part, laboratory professionals should take responsibility to abandon non-selective methods and move to IVD-MDs displaying proper selectivity, which is one of the indispensable prerequisites for the correct implementation of metrological traceability. The practicality of metrological traceability concepts is not impossible but relevant education and appropriate training of all involved stakeholders are essential to obtain the expected benefits in terms of standardization., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)
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- 2024
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8. An outline of measurement uncertainty of total protein in urine estimated according to the ISO Technical Specification 20914.
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Borrillo F and Panteghini M
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- Humans, Uncertainty, Urinalysis methods, Urinalysis standards, Proteinuria urine, Proteinuria diagnosis
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- 2024
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9. State-of-the-art model for derivation of analytical performance specifications: how to define the highest level of analytical performance technically achievable.
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Borrillo F and Panteghini M
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- Humans, C-Reactive Protein analysis, C-Reactive Protein standards, Uncertainty, Models, Theoretical, Clinical Laboratory Techniques standards, Ferritins blood, Ferritins analysis
- Abstract
To be accurate and equivalent among assays, laboratory results should be traceable to higher-order references and their quality should fulfill maximum allowable measurement uncertainty (MU) as defined to fit the intended clinical use. Accordingly, laboratory professionals should estimate and validate MU of performed tests using appropriate analytical performance specifications (APS). Current consensus supports the derivation of APS by using one of the three models established by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Strategic Conference held in Milan in 2014. It is recognized that some models are better suited for certain measurands than for others and the attention should be primarily directed towards their biological and clinical characteristics. Among others, model 3 should reflect the state of the art of the measurements that can be defined as the best analytical performance that is technically achievable. Taking serum C-reactive protein and ferritin as examples, here we describe the theoretical premises and the experimental protocol to be used to derive APS for MU when a measurand is allocated to this model. Although the model lacks a direct relationship with clinical outcomes, useful information about the in vitro diagnostic medical device performance and the average quality of provided results may be obtained., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)
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- 2024
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10. Analytical performance specifications for combined uncertainty budget in the implementation of metrological traceability.
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Panteghini M
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- Uncertainty, Calibration, Humans, Reference Standards, Clinical Laboratory Techniques standards, Clinical Laboratory Techniques economics, Budgets, Quality Control
- Abstract
In addition to the correct implementation of calibration traceability, the definition and fulfillment of maximum allowable measurement uncertainty (MAU) are essential in assuring that laboratory measurements are clinically usable. Across the entire calibration hierarchy, three major contributors to the measurement uncertainty (MU) budget are identified, starting with the higher-order reference providers, extending through the in vitro diagnostic (IVD) manufacturers and their processes for assigning calibrator values, and ending with medical laboratories generating the random variability of results reported to clinicians. To understand if it is possible to achieve MAU and, consequently, to fix the possible drawbacks, the definition of combined MU budget limits across the entire calibration hierarchy has a central role. In particular, quality specifications for MU of reference and commercial calibrator materials should be defined according to the MAU on clinical samples. All involved stakeholders (i.e., higher-order reference providers, IVD manufacturers, medical laboratories) should be prepared to improve their performance whenever the clinical application of the test is made questionable by the failure to achieve MAU., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)
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- 2024
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11. What the Milan conference has taught us about analytical performance specification model definition and measurand allocation.
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Panteghini M
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- Humans, Clinical Laboratory Techniques standards, Chemistry, Clinical standards, Congresses as Topic
- Abstract
Analytical performance specifications (APS) represent the criteria that specify the quality required for laboratory test information to satisfy clinical needs. In 2014 the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) considered timely to update the topic of APS by organizing a conference in Milan in which some strategic concepts were proposed. Here I summarize the essential points representing the EFLM Strategic Conference heritage and discuss the approaches that will permit us to become more concrete, including roles and main actions expected from each of involved stakeholders for contributing a quantum leap forward in the way of practicality of Milan consensus about APS., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)
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- 2024
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12. APS calculator: a data-driven tool for setting outcome-based analytical performance specifications for measurement uncertainty using specific clinical requirements and population data.
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Çubukçu HC, Vanstapel F, Thelen M, van Schrojenstein Lantman M, Bernabeu-Andreu FA, Meško Brguljan P, Milinkovic N, Linko S, Panteghini M, and Boursier G
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- Humans, Uncertainty, Nutrition Surveys, Fasting, Clinical Laboratory Techniques methods, Laboratories
- Abstract
Objectives: According to ISO 15189:2022, analytical performance specifications (APS) should relate to intended clinical use and impact on patient care. Therefore, we aimed to develop a web application for laboratory professionals to calculate APS based on a simulation of the impact of measurement uncertainty (MU) on the outcome using the chosen decision limits, agreement thresholds, and data of the population of interest., Methods: We developed the "APS Calculator" allowing users to upload and select data of concern, specify decision limits and agreement thresholds, and conduct simulations to determine APS for MU. The simulation involved categorizing original measurand concentrations, generating measured (simulated) results by introducing different degrees of MU, and recategorizing measured concentrations based on clinical decision limits and acceptable clinical misclassification rates. The agreements between original and simulated result categories were assessed, and values that met or exceeded user-specified agreement thresholds that set goals for the between-category agreement were considered acceptable. The application generates contour plots of agreement rates and corresponding MU values. We tested the application using National Health and Nutrition Examination Survey data, with decision limits from relevant guidelines., Results: We determined APS for MU of six measurands (blood total hemoglobin, plasma fasting glucose, serum total and high-density lipoprotein cholesterol, triglycerides, and total folate) to demonstrate the potential of the application to generate APS., Conclusions: The developed data-driven web application offers a flexible tool for laboratory professionals to calculate APS for MU using their chosen decision limits and agreement thresholds, and the data of the population of interest., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)
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- 2023
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13. Analytical performance specifications for measurement uncertainty in therapeutic monitoring of immunosuppressive drugs.
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Cattaneo D and Panteghini M
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- Humans, Uncertainty, Reference Standards, Clinical Laboratory Techniques, Immunosuppressive Agents therapeutic use
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- 2023
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14. Documenting and validating metrological traceability of serum alanine aminotransferase measurements: a priority for medical laboratory community for providing high quality service in hepatology.
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Panteghini M
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- Humans, Alanine Transaminase, Reference Standards, Clinical Laboratory Techniques, Gastroenterology
- Abstract
Alanine aminotransferase (ALT) represents the first-level test to detect individuals with hepatocellular damage of any etiology. However, it has been highlighted that the lack of assay harmonization may lead to overdiagnosis and unnecessary further testing if guideline-recommended fixed cut-offs are uncritically employed. To solve the issue of ALT (dis)harmonization and improve the interpretation of its values, a series of urgent actions for documenting and validating metrological traceability of serum ALT measurements, as described in this paper, are no longer postponeable. It is time that all medical laboratory stakeholders ( in vitro diagnostic manufacturers, laboratorians, external quality assessment scheme organizers) actively co-operate to implement the ALT standardization in a concerted action following well-established theoretical assumptions and applying experimental approaches described in literature., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)
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- 2023
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15. Validation of metrological traceability of the new generation of Abbott Alinity alkaline phosphatase assay.
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Bianchi G, Frusciante E, Colombo G, Infusino I, Aloisio E, and Panteghini M
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- Humans, Serum, Calibration, Reference Standards, Alkaline Phosphatase, Clinical Enzyme Tests
- Abstract
Objectives: Recently, Abbott Diagnostics marketed a new generation of Alinity enzyme assays, introducing a multiparametric calibrator [Consolidated Chemistry Calibrator (ConCC)] in place of or in addition to factor-based calibrations. For alkaline phosphatase (ALP), both calibration options are offered, i.e., with ConCC (ALP2) and with an experimental calibration factor (ALP2F). Both options are declared traceable to the 2011 IFCC reference measurement procedure (RMP). Before to replace the old generation (ALP1) with the new one, we decided to validate the trueness of ALP2/ALP2F., Methods: Three approaches were employed: (a) preliminary comparison on 48 native frozen serum samples with ALP1, of which traceability to RMP was previously successfully verified; (b) examination of three banked serum pools (BSP) with values assigned by RMP; (c) direct comparison with RMP on a set of 24 fresh serum samples. Bias estimation and regression studies were performed, and the standard measurement uncertainty associated with ALP measurements on clinical samples (u
result ) was estimated and compared with established analytical performance specifications (APS). ConCC commutability was also assessed., Results: A positive proportional bias was found with both ALP2 and ALP2F when compared to ALP1 and RMP. This positive bias was confirmed on BSP: in average, +13.1 % for ALP2 and +10.0 % for ALP2F, respectively. uresult were 13.28 % for ALP2 and 10.04 % for ALP2F, both not fulfilling the minimum APS of 4.0 %. Furthermore, ConCC was not commutable with clinical samples., Conclusions: Our results unearth problems in the correct implementation of traceability of Alinity ALP2/ALP2F, with the risk for the new assay to be unfit for clinical purposes., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)- Published
- 2023
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16. State of the art of measurement uncertainty of serum ferritin.
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Rovegno L, Civera E, Infusino I, and Panteghini M
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- Humans, Uncertainty, Reference Standards, Calibration, Ferritins
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- 2023
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17. Developments in reference measurement systems for C-reactive protein and the importance of maintaining currently used clinical decision-making criteria.
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Panteghini M
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- Humans, Reference Standards, Quality Control, Calibration, C-Reactive Protein, Clinical Decision-Making
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- 2023
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18. In reply to: Limitations in using the EFLM WG-A/ISO approach for assessment of reagent lot variability.
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Thelen MHM, van Schrojenstein Lantman M, Boursier G, Vanstapel F, and Panteghini M
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- Quality Control, Indicators and Reagents standards, Reagent Kits, Diagnostic
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- 2023
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19. Implementing metrological traceability of C-reactive protein measurements: consensus summary from the Joint Committee for Traceability in Laboratory Medicine Workshop.
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Miller WG, Panteghini M, and Wielgosz R
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- Humans, Reference Standards, Consensus, Calibration, Laboratories, C-Reactive Protein
- Abstract
The Joint Committee for Traceability in Laboratory Medicine (JCTLM) currently lists the secondary commutable certified reference material (CRM) ERM DA-474/IFCC (DA-474) "C-Reactive Protein in Human Serum" and two generic immunoassay-based method principles as the basis for implementing the metrological traceability of C-reactive protein (CRP) measurements by end-user measurement procedures used by medical laboratories. The current metrological traceability has produced well harmonized results for clinical samples among different end-user measurement procedures. New higher-order pure substance and secondary commutable CRMs have been nominated for listing by the JCTLM. However, the data supporting performance of these new candidate CRMs, including use of new mass spectrometry based candidate reference measurement procedures (RMPs), was not clear regarding the influence that introducing these new CRMs would have on the current well harmonized results achieved with the existing metrological traceability to DA-474. The clinically relevant CRP measurand in blood serum or plasma is a pentamer of identical subunits, which adds complexity to the application of higher-order CRMs and RMPs. The JCTLM convened a workshop in December 2022 to review the appropriate implementation of metrological traceability of CRP measurements. The workshop consensus was that the extent-of-equivalence data must include considerations about the impact of a new CRM when used for its intended purpose in the calibration hierarchies of existing end-user measuring systems; and that a new RMP must compare results with another existing well validated candidate RMP or with a globally available end-user measurement system., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)
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- 2023
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20. C-reactive protein and clinical outcome in COVID-19 patients: the importance of harmonized measurements.
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Aloisio E, Colombo G, Dolci A, and Panteghini M
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- Humans, C-Reactive Protein metabolism, Hospital Mortality, Prognosis, Biomarkers, COVID-19 diagnosis
- Abstract
C-reactive protein (CRP) is a cytokine-mediated acute phase reactant with a recognized role in inflammatory conditions and infectious disease. In coronavirus disease 2019 (COVID-19), elevated CRP concentrations in serum were frequently detected and significantly associated with poor outcome in terms of disease severity, need for intensive care, and in-hospital death. For these reasons, the marker was proposed as a powerful test for prognostic classification of COVID-19 patients. In most of available publications, there was however confounding information about how interpretative criteria for CRP in COVID-19 should be derived, including quality of employed assays and optimal cut-off definition. Assuring result harmonization and controlling measurement uncertainty in terms of performance specifications are fundamental to allow worldwide application of clinical information according to specific CRP thresholds and to avoid risk of patient misclassification., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)
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- 2023
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21. Judging the clinical suitability of analytical performance of cardiac troponin assays.
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Krintus M and Panteghini M
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- Humans, Troponin I, Biomarkers, Biological Assay, Troponin T, Myocardial Infarction diagnosis
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New millennium diagnostic criteria for acute myocardial infarction precipitated a revolutionary shift from an approach based primarily on electrocardiography and clinical symptoms to a strategy based on biomarkers, and preferably cardiac troponins (cTn) I and T. In the last 20 years, clinical recommendations have strengthened the role of cTn and led to the development of highly sensitive (hs-cTn) assays, which are now leading players in all current clinical practice guidelines. To optimize the clinical use of these hs-cTn assays, focus on their analytical aspects has become increasingly important, emphasizing the need for the establishment of suitable analytical performance by the definition and implementation of appropriate specifications. An accurate estimate of measurement uncertainty, together with the acquisition of the highest analytical quality when very low concentrations of hs-cTn are measured, are essential requirements and should represent a practical laboratory standard in assuring optimal clinical use. Additional goals for further improving the quality of laboratory information should be the establishment of robust data concerning biological variation of cTn and the resolution of practical challenges opposed to the harmonization of cTn I results obtained by differing commercial measuring systems., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)
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- 2023
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22. Current performance of C-reactive protein determination and derivation of quality specifications for its measurement uncertainty.
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Borrillo F and Panteghini M
- Subjects
- Humans, Reference Standards, Uncertainty, Reproducibility of Results, Calibration, C-Reactive Protein
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From External Quality Assessment data, current harmonization of CRP measuring systems appears to be satisfactory, the inter-assay CV being well below 10%. The inter-method variability is even better (close to 3%) when the widely used measuring systems are compared at CRP concentrations employed as cut-off for detecting sub-clinical infection (i.e., 10.0 mg/L) and measurement variability estimated, according to ISO 20914:2019 Technical Specification, from the intermediate within-lab reproducibility of 6-month consecutive measurement data. According to the state-of-the-art model (which is better suited for CRP), the maximum allowable measurement uncertainty (MAU) for CRP measurement on clinical samples with 10.0 mg/L concentrations is 3.76% (desirable quality). As measurement uncertainty (MU) of the only available reference material (ERM-DA474/IFCC) is ∼3%, to fulfil desirable MAU on clinical samples, IVD manufacturers should work to keep the contribution of remaining MU sources (commercial calibrator and intermediate within-lab reproducibility) lower than 2.3%., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)
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- 2023
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23. Redesigning the surveillance of in vitro diagnostic medical devices and of medical laboratory performance by quality control in the traceability era.
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Panteghini M
- Subjects
- Humans, Reference Standards, Quality Control, Uncertainty, Reproducibility of Results, Reagent Kits, Diagnostic, Laboratories
- Abstract
IVD manufacturers have total responsibility in terms of the traceability of marketed in vitro diagnostic medical devices (IVD-MD). This includes the provision of a quality control (QC) material as a part of the measuring system, suitable for traceability verification and alignment surveillance by end-users in daily practice. This material [to be used for the internal QC (IQC) component I as described in this paper] should have unbiased target values and an acceptability range corresponding to analytical performance specifications (APS) for suitable (expanded) measurement uncertainty (MU) on clinical samples. On the other hand, medical laboratories (by the IQC component II as described in this paper) should improve the IQC process and its judging criteria to establish a direct link between their performance, estimated as MU of provided results, and APS defined according to recommended models to apply corrective actions if the performance is worsening with the risk to jeopardize the clinical validity of test results. The participation to external quality assessment (EQA) programs that meet specific metrological criteria is also central to the evaluation of performance of IVD-MDs and of medical laboratories in terms of harmonization and clinical suitability of their measurements. In addition to the use of commutable materials, in this type of EQA it is necessary to assign values to them with selected reference procedures and to define and apply maximum allowable APS to substantiate the suitability of laboratory measurements in the clinical setting., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)
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- 2022
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24. Definition and application of performance specifications for measurement uncertainty of 23 common laboratory tests: linking theory to daily practice.
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Braga F, Pasqualetti S, Borrillo F, Capoferri A, Chibireva M, Rovegno L, and Panteghini M
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- Male, Humans, Uncertainty, Cholesterol, Homocysteine, Laboratories, Serum Albumin
- Abstract
Laboratories should estimate and validate [using analytical performance specifications (APS)] the measurement uncertainty (MU) of performed tests. It is therefore essential to appropriately define APS for MU, but also to provide a perspective on suitability of the practical application of these APS. In this study, 23 commonly ordered measurands were allocated to the models defined during the 2014 EFLM Strategic Conference to derive APS for MU. Then, we checked if the performance of commercial measuring systems used in our laboratory may achieve them. Most measurands (serum alkaline phosphatase, aspartate aminotransferase, creatine kinase, γ-glutamyltransferase, lactate dehydrogenase, pancreatic amylase, total proteins, immunoglobulin G, A, M, magnesium, urate, and prostate-specific antigen, plasma homocysteine, and blood red and white cells) were allocated to the biological variation (BV) model and desirable APS were defined accordingly (2.65%, 4.75%, 7.25%, 4.45%, 2.60%, 3.15%, 1.30%, 2.20%, 2.50%, 2.95%, 1.44%, 4.16%, 3.40%, 3.52%, 1.55%, and 5.65%, respectively). Desirable APS for serum total cholesterol (3.00%) and urine albumin (9.00%) were derived using outcome-based model. Lacking outcome-based information, serum albumin, high-density lipoprotein cholesterol, triglycerides, and blood platelets were temporarily reallocated to BV model, the corresponding desirable APS being 1.25%, 2.84%, 9.90%, and 4.85%, respectively. A mix between the two previous models was employed for serum digoxin, with a 6.00% desirable APS. In daily practice by using our laboratory systems, 16 tests fulfilled desirable and five minimum APS, while two (serum albumin and plasma homocysteine) exceeded goals, needing improvements., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)
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- 2022
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25. Pursuing appropriateness of laboratory tests: a 15-year experience in an academic medical institution.
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Panteghini M, Dolci A, Birindelli S, Szoke D, Aloisio E, and Caruso S
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- Academic Medical Centers, Bilirubin, C-Reactive Protein, Homocysteine, Humans, Magnesium, Natriuretic Peptide, Brain, Procalcitonin, Prostate-Specific Antigen, Transaminases, Vitamins, Diagnostic Tests, Routine, Unnecessary Procedures
- Abstract
Appropriateness in Laboratory Medicine has been the object of various types of interventions. From published experiences, it is now clear that to effectively manage the laboratory test demand it is recommended to activate evidence-based preventative strategies stopping inappropriate requests before they can reach the laboratory. To guarantee appropriate laboratory test utilization, healthcare institutions should implement and optimize a computerized provider order entry (CPOE), exploiting the potential of electronic requesting as "enabling factor" for reinforcing appropriateness and sustaining its effects over time. In our academic institution, over the last 15 years, our medical laboratory has enforced various interventions to improve test appropriateness, all directly or indirectly based on CPOE use. The following types of intervention were implemented: (1) applying specific recommendations supported by monitoring by CPOE as well as a continuous consultation with clinicians (tumour markers); (2) removing outdated tests and avoiding redundant duplications (cardiac markers, pancreatic enzymes); (3) order restraints to selected wards and gating policy (procalcitonin, B-type natriuretic peptide, homocysteine); (4) reflex testing (bilirubin fractions, free prostate-specific antigen, aminotransferases, magnesium in hypocalcemia); and (5) minimum retesting interval (D-Dimer, vitamin B
12 , C-reactive protein, γ-glutamyltranspeptidase). In this paper, we reviewed these interventions and summarized their outcomes primarily related to the changes in total test volumes and cost savings, without neglecting patient safety. Our experience confirmed that laboratory professionals have an irreplaceable role as "stewards" in designing, implementing, evaluating, and maintaining interventions focused to improving test appropriateness., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)- Published
- 2022
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26. Alignment of the new generation of Abbott Alinity γ-glutamyltransferase assay to the IFCC reference measurement system should be improved.
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Bianchi G, Colombo G, Pasqualetti S, and Panteghini M
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- Biological Assay, Humans, Reference Standards, Clinical Enzyme Tests, gamma-Glutamyltransferase
- Published
- 2022
- Full Text
- View/download PDF
27. The simple reproducibility of a measurement result does not equal its overall measurement uncertainty.
- Author
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Panteghini M
- Subjects
- Calibration, Humans, Reference Standards, Reproducibility of Results, Uncertainty
- Published
- 2022
- Full Text
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28. Reply to Westgard et al.: 'Keep your eyes wide … as the present now will later be past'.
- Author
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Panteghini M
- Subjects
- Humans, Quality Control, Eye, Laboratories
- Published
- 2022
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29. 'Penelope test': a practical instrument for checking appropriateness of laboratory tests.
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Caruso S, Szoke D, and Panteghini M
- Subjects
- Humans, Retrospective Studies, Laboratories
- Abstract
In medical laboratories, the appropriateness challenge directly revolves around the laboratory test and its proper selection, data analysis, and result reporting. However, laboratories have also a role in the appropriate management of those phases of total testing process (TTP) that traditionally are not under their direct control. So that, the laboratory obligation to act along the entire TTP is now widely accepted in order to achieve better care management. Because of the large number of variables involved in the overall TTP structure, it is difficult to monitor appropriateness in real time. However, it is possible to retrospectively reconstruct the body of the clinical process involved in the management of a specific laboratory test to track key passages that may be defective or incomplete in terms of appropriateness. Here we proposed an appropriateness check-list scheme along the TTP chain to be potentially applied to any laboratory test. This scheme consists of a series of questions that healthcare professionals should answer to achieve laboratory test appropriateness. In the system, even a single lacking answer may compromise the integrity of all appropriateness evaluation process as the inability to answer may involve a significant deviation from the optimal trajectory, which compromise the test appropriateness and the quality of subsequent steps. Using two examples of the check-list application, we showed that the proposed instrument may offer an objective help to avoid inappropriate use of laboratory tests in an integrated way involving both laboratory professionals and user clinicians., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)
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- 2022
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30. Biological variation of serum cholinesterase catalytic concentrations.
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Altilia M, Braga F, Capoferri A, and Panteghini M
- Subjects
- Humans, Cholinesterases
- Published
- 2022
- Full Text
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31. Improving D-dimer testing appropriateness by controlling periodicity of retesting: prevention is better than cure.
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Caruso S, Szoke D, Birindelli S, Falvella FS, Dolci A, and Panteghini M
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- Humans, Fibrin Fibrinogen Degradation Products
- Published
- 2022
- Full Text
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32. An approach for determining allowable between reagent lot variation.
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van Schrojenstein Lantman M, Çubukçu HC, Boursier G, Panteghini M, Bernabeu-Andreu FA, Milinkovic N, Mesko Brguljan P, Linko S, Brugnoni D, O'Kelly R, Kroupis C, Lohmander M, Šprongl L, Vanstapel F, and Thelen M
- Subjects
- Calibration, Humans, Indicators and Reagents, Quality Control, Uncertainty, Laboratories
- Abstract
Clinicians trust medical laboratories to provide reliable results on which they rely for clinical decisions. Laboratories fulfil their responsibility for accurate and consistent results by utilizing an arsenal of approaches, ranging from validation and verification experiments to daily quality control procedures. All these procedures verify, on different moments, that the results of a certain examination procedure have analytical performance characteristics (APC) that meet analytical performance specifications (APS) set for a particular intended use. The APC can in part be determined by estimating the measurement uncertainty component under conditions of within-laboratory precision ( u
Rw ), which comprises all components influencing the measurement uncertainty of random sources. To maintain the adequacy of their measurement procedures, laboratories need to distinguish aspects that are manageable vs. those that are not. One of the aspects that may influence uRw is the momentary significant bias caused by shifts in reagent and/or calibrator lots, which, when accepted or unnoticed, become a factor of the APC. In this paper, we postulate a model for allocating a part of allowable uRw to between-reagent lot variation, based on the need for long-term consistency of the measurement variability for that specific measurand. The allocation manages the ratio between short-term and long-term variation and indicates laboratories when to reject or correct certain variations due to reagent lots., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)- Published
- 2022
- Full Text
- View/download PDF
33. A step towards optimal efficiency of HbA 1c measurement as a first-line laboratory test: the TOP-HOLE (Towards OPtimal glycoHemOgLobin tEsting) project.
- Author
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Pasqualetti S, Carnevale A, Dolci A, and Panteghini M
- Subjects
- Humans, Uncertainty, Automation, Laboratory, Hematologic Tests
- Abstract
Objectives: The TOP-HOLE (Towards OPtimal glycoHemOgLobin tEsting) project aimed to validate the HbA
1c enzymatic method on the Abbott Alinity c platform and to implement the HbA1c testing process on the total laboratory automation (TLA) system of our institution., Methods: Three different measuring systems were employed: Architect c4000 stand-alone (s-a), Alinity c s-a, and Alinity c TLA. Eight frozen whole blood samples, IFCC value-assigned, were used for checking trueness. A comparison study testing transferability of HbA1c results from Architect to Alinity was also performed. The alignment of Alinity TLA vs. s-a was verified and the measurement uncertainty (MU) estimated according to ISO 20914:2019. Turnaround time (TAT) and full time equivalent (FTE) were used as efficiency indicators., Results: For HbA1c concentrations covering cut-offs adopted in clinical setting, the bias for both Architect and Alinity s-a was negligible. When compared with Architect, Alinity showed a mean positive bias of 0.54 mmol/mol, corresponding to a mean difference of 0.87%. A perfect alignment of Alinity TLA to the Alinity s-a was shown, and a MU of 1.58% was obtained, widely fulfilling the desirable 3.0% goal. After the full automation of HbA1c testing, 90% of results were released with a maximum TAT of 1 h, 0.30 FTE resource was also saved., Conclusions: The traceability of Alinity HbA1c enzymatic assay to the IFCC reference system was correctly implemented. We successfully completed the integration of the HbA1c testing on our TLA system, without worsening the optimal analytical performance. The shift of HbA1c testing from s-a mode to TLA significantly decreased TAT., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)- Published
- 2022
- Full Text
- View/download PDF
34. Lipase elevation in serum of COVID-19 patients: frequency, extent of increase and clinical value.
- Author
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Caruso S, Aloisio E, Dolci A, and Panteghini M
- Subjects
- Acute Disease, Biomarkers blood, Humans, Intensive Care Units, Retrospective Studies, COVID-19 blood, COVID-19 diagnosis, Lipase blood
- Abstract
Objectives: Previous studies reported lipase elevations in serum of COVID-19 patients trying to establish a causal link between SARS-CoV-2 infection and pancreatic damage. However, the degree and prevalence of hyperlipasemia was not uniform across studies., Methods: We retrospectively evaluated 1,092 hospitalized patients with COVID-19 and at least one available lipase result. The number and frequency of patients with lipase above the upper reference limit (URL), >3 URL, and >6 URL were estimated. Correlations between lipase values and other biomarkers of organ or tissue damage were performed to identify possible extra-pancreatic sources of lipase release. The potential prognostic role of lipase to predict death and intensive care unit (ICU) admission during hospitalization was also evaluated., Results: Lipase was >URL in 344 (31.5%) of COVID-19 patients. Among them, 65 (5.9%) and 25 (2.3%) had a peak lipase >3 URL and >6 URL, respectively. In the latter group, three patients had acute pancreatitis of gallstone or drug-induced etiology. In others, the etiology of lipase elevations appeared multifactorial and could not be directly related to SARS-CoV-2 infection. No correlation was found between lipase and other tested biomarkers of organ and tissue damage. Lipase concentrations were not different between survivors and non-survivors; however, lipase was significantly increased (p<0.001) in patients admitted to the ICU, even if the odds ratio for lipase as predictor of ICU admission was not significant., Conclusions: Lipase was elevated in ∼1/3 of COVID-19 patients, but the clinical significance of this finding is unclear and irrelevant to patient prognosis during hospitalization., (© 2021 Simone Caruso et al., published by De Gruyter, Berlin/Boston.)
- Published
- 2021
- Full Text
- View/download PDF
35. Pancreatic lipase: why laboratory community does not take enough care of this clinically important test?
- Author
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Pasqualetti S, Borrillo F, Rovegno L, and Panteghini M
- Subjects
- Acute Disease, Humans, Laboratories, Reference Standards, Lipase blood, Pancreatic Function Tests, Pancreatitis diagnosis
- Abstract
Although being the recommended laboratory test to diagnose acute pancreatitis, serum pancreatic lipase (LIP) is among the poorly standardized laboratory tests, and laboratory stakeholders often appear to not take enough care of the quality of its measurements. Here we discuss some important issues that, if not correctly managed and solved, make misdiagnosis of acute pancreatitis by using serum LIP a real possibility. First, the current unavailability of a suitable higher-order reference material to be used as common calibrator should be filled up to definitively improve the inter-method bias. Second, knowledge of the analytical characteristics that may explain the defective performance of LIP assays should be deepened. IVD manufacturers should be more explicit in providing this information, including description of their internal protocol for transferring LIP values from internal references to commercial calibrators. Third, recommended models for accurately estimating measurement uncertainty and reliably defining analytical performance specifications for LIP measurements should be applied. Finally, investments considering alternative options for measuring LIP (e.g., targeted to the development of automated LIP immunoassays) should be warranted. All involved stakeholders (standardization bodies, higher-order reference providers, in vitro diagnostics manufacturers, and laboratory professionals) should contribute to fill the existing gap., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)
- Published
- 2021
- Full Text
- View/download PDF
36. Impact of optimizing pre-analytical phase on the diagnosis of gestational diabetes and related outcomes.
- Author
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Szoke D, Borille S, Cardellicchio M, Spadaccini G, Taricco E, Vignali M, Cetin I, Birindelli S, and Panteghini M
- Subjects
- Blood Glucose, Female, Gestational Age, Glucose Tolerance Test, Humans, Infant, Newborn, Pre-Analytical Phase methods, Pregnancy, Pregnancy Outcome epidemiology, Diabetes, Gestational diagnosis
- Abstract
Objectives: Pre-analytical plasma glucose (PG) sampling methodology may significantly affect gestational diabetes mellitus (GDM) incidence, but no studies directly examined the impact on perinatal outcomes. We compared the effect on oral glucose tolerance test (OGTT) results of using for blood sampling the traditional sodium fluoride (NaF) tubes, batched at controlled temperature, and the more effective citrate-buffered tubes, in terms of GDM diagnosis and related outcomes., Methods: We evaluated 578 pregnant women performing OGTT between 24- and 28-weeks' gestation. Paired NaF and citrate blood samples were drawn and analyzed for PG. GDM diagnosis was made by applying the 'one-step' American Diabetes Association strategy. Data on perinatal outcomes were collected in a subset of 330 women who delivered in our hospital network., Results: Using the standard NaF approach, 69 (11.9%) GDM women were detected. Using citrate PG values, 90 women were additionally identified as GDM, increasing the GDM prevalence to 27.5%. Perinatal outcomes were analyzed according to the different diagnostic allocation (NaF-diagnosed GDM, additional citrate-diagnosed GDM, and no GDM). NaF-diagnosed GDM showed a higher incidence of large for gestational age (LGA) (p=0.034), and of cesarean and preterm delivery (p<0.01) vs. no GDM. The only outcome remaining more frequent in the additional citrate diagnosed GDM when compared with no GDM group was LGA (17.2 vs. 6.8%, p=0.025)., Conclusions: If a health care system plans to use citrate tubes for GDM diagnosis, considerations about clinical implications are mandatory by balancing higher sensitivity in detecting a poor glycemic control with effects on outcomes to avoid "overdiagnosis"., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)
- Published
- 2021
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- View/download PDF
37. Prognostic role of Krebs von den Lungen-6 (KL-6) measurement in idiopathic pulmonary fibrosis: a systematic review and meta-analysis.
- Author
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Aloisio E, Braga F, Puricelli C, and Panteghini M
- Subjects
- Biomarkers, Humans, Mucin-1, Odds Ratio, Prognosis, Proportional Hazards Models, Idiopathic Pulmonary Fibrosis diagnosis
- Abstract
Objectives: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial disease with limited therapeutic options. The measurement of Krebs von den Lungen-6 (KL-6) glycoprotein has been proposed for evaluating the risk of IPF progression and predicting patient prognosis, but the robustness of available evidence is unclear., Methods: We searched Medline and Embase databases for peer-reviewed literature from inception to April 2020. Original articles investigating KL-6 as prognostic marker for IPF were retrieved. Considered outcomes were the risk of developing acute exacerbation (AE) and patient survival. Meta-analysis of selected studies was conducted, and quantitative data were uniformed as odds ratio (OR) or hazard ratio (HR) estimates, with corresponding 95% confidence intervals (CI)., Results: Twenty-six studies were included in the systematic review and 14 were finally meta-analysed. For AE development, the pooled OR (seven studies) for KL-6 was 2.72 (CI 1.22-6.06; p=0.015). However, a high degree of heterogeneity (I
2 =85.6%) was found among selected studies. Using data from three studies reporting binary data, a pooled sensitivity of 72% (CI 60-82%) and a specificity of 60% (CI 52-68%) were found for KL-6 measurement in detecting insurgence of AE in IPF patients. Pooled HR (seven studies) for mortality prediction was 1.009 (CI 0.983-1.036; p=0.505)., Conclusions: Although our meta-analysis suggested that IPF patients with increased KL-6 concentrations had a significant increased risk of developing AE, the detection power of the evaluated biomarker is limited. Furthermore, no relationship between biomarker concentrations and mortality was found. Caution is also needed when extending obtained results to non-Asian populations., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)- Published
- 2021
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- View/download PDF
38. Performance specifications for measurement uncertainty of common biochemical measurands according to Milan models.
- Author
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Braga F and Panteghini M
- Abstract
Objectives: Definition and fullfillment of analytical performance specifications (APS) for measurement uncertainty (MU) allow to make laboratory determinations clinically usable. The 2014 Milan Strategic Conference have proposed models to objectively derive APS based on: (a) the effect of analytical performance on clinical outcome; (b) biological variation components; and (3) the state of the art of the measurement, defined as the highest level of analytical performance technically achievable. Using these models appropriately, we present here a proposal for defining APS for standard MU for some common biochemical measurands., Methods: We allocated a group of 13 measurands selected among the most commonly laboratory requested tests to each of the three Milan models on the basis of their biological and clinical characteristics. Both minimum and desirable levels of quality of APS for standard MU of clinical samples were defined by using information obtained from available studies., Results: Blood total hemoglobin, plasma glucose, blood glycated hemoglobin, and serum 25-hydroxyvitamin D3 were allocated to the model 1 and the corresponding desirable APS were 2.80, 2.00, 3.00, and 10.0%, respectively. Plasma potassium, sodium, chloride, total calcium, alanine aminotransferase, creatinine, urea, and total bilirubin were allocated to the model 2 and the corresponding desirable APS were 1.96, 0.27, 0.49, 0.91, 4.65, 2.20, 7.05, and 10.5%, respectively. For C-reactive protein, allocated to the model 3, a desirable MU of 3.76% was defined., Conclusions: APS for MU of clinical samples derived in this study are essential to objectively evaluate the reliability of results provided by medical laboratories., (© 2021 Federica Braga and Mauro Panteghini, published by De Gruyter, Berlin/Boston.)
- Published
- 2021
- Full Text
- View/download PDF
39. Use of Neurosoft expert system improves turnaround time in a laboratory section specialized in protein diagnostics: a two-year experience.
- Author
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Borrillo F, Infusino I, Birindelli S, and Panteghini M
- Subjects
- Humans, Time Factors, Expert Systems, Laboratories, Hospital
- Published
- 2021
- Full Text
- View/download PDF
40. SARS-CoV-2 serologic tests: do not forget the good laboratory practice.
- Author
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Aloisio E, Falvella FS, Carnevale A, and Panteghini M
- Subjects
- Humans, SARS-CoV-2, Uncertainty, COVID-19 diagnosis, COVID-19 Serological Testing statistics & numerical data, Immunoassay statistics & numerical data
- Published
- 2020
- Full Text
- View/download PDF
41. Searching for a role of procalcitonin determination in COVID-19: a study on a selected cohort of hospitalized patients.
- Author
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Dolci A, Robbiano C, Aloisio E, Chibireva M, Serafini L, Falvella FS, Pasqualetti S, and Panteghini M
- Subjects
- Aged, Bacterial Infections blood, Bacterial Infections diagnosis, Bacterial Infections mortality, Biomarkers blood, COVID-19 blood, COVID-19 mortality, Coinfection blood, Coinfection mortality, Female, Hospital Mortality, Humans, Male, Middle Aged, Multivariate Analysis, ROC Curve, Regression Analysis, Retrospective Studies, SARS-CoV-2, COVID-19 diagnosis, Coinfection diagnosis, Procalcitonin blood
- Abstract
Objectives: Procalcitonin (PCT) has been proposed for differentiating viral vs. bacterial infections. In COVID-19, some preliminary results have shown that PCT testing could act as a predictor of bacterial co-infection and be a useful marker for assessment of disease severity., Methods: We studied 83 COVID-19 hospitalized patients in whom PCT was specifically ordered by attending physicians. PCT results were evaluated according to the ability to accurately predict bacterial co-infections and death in comparison with other known biomarkers of infection and with major laboratory predictors of COVID-19 severity., Results: Thirty-three (39.8%) patients suffered an in-hospital bacterial co-infection and 44 (53.0%) patients died. In predicting bacterial co-infection, PCT showed a relatively low accuracy (area under receiver-operating characteristic [ROC] curve [AUC]: 0.757; 95% confidence interval [CI]: 0.651-0.845), with a strength for detecting the outcome not significantly different from that of white blood cell count and C-reactive protein (CRP). In predicting patient death, PCT showed an AUC of 0.815 (CI: 0.714-0.892), not better than those of other more common laboratory tests, such as blood lymphocyte percentage (AUC: 0.874, p=0.19), serum lactate dehydrogenase (AUC: 0.860, p=0.47), blood neutrophil count (AUC: 0.845, p=0.59), and serum albumin (AUC: 0.839, p=0.73)., Conclusions: Procalcitonin (PCT) testing, even when appropriately ordered, did not provide a significant added value in COVID-19 patients when compared with more consolidated biomarkers of infection and poor clinical outcome. The major application of PCT in COVID-19 is its ability, associated with a negative predictive value >90%, to exclude a bacterial co-infection when a rule-out cut-off (<0.25 μg/L) is applied.
- Published
- 2020
- Full Text
- View/download PDF
42. Hypoalbuminemia and elevated D-dimer in COVID-19 patients: a call for result harmonization.
- Author
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Aloisio E, Serafini L, Chibireva M, Dolci A, and Panteghini M
- Subjects
- Betacoronavirus, COVID-19, Fibrin Fibrinogen Degradation Products, Humans, SARS-CoV-2, Coronavirus Infections, Hypoalbuminemia diagnosis, Pandemics, Pneumonia, Viral, Vascular Diseases
- Published
- 2020
- Full Text
- View/download PDF
43. Derivation of performance specifications for uncertainty of serum C-reactive protein measurement according to the Milan model 3 (state of the art).
- Author
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Braga F and Panteghini M
- Subjects
- Blood Chemical Analysis standards, C-Reactive Protein standards, Calibration, Humans, Models, Chemical, Reference Standards, Uncertainty, C-Reactive Protein analysis
- Published
- 2020
- Full Text
- View/download PDF
44. Laboratory-related issues in the measurement of cardiac troponins with highly sensitive assays.
- Author
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Krintus M and Panteghini M
- Subjects
- Biomarkers blood, Blood Chemical Analysis methods, False Negative Reactions, False Positive Reactions, Humans, Laboratories standards, Sensitivity and Specificity, Time Factors, Troponin I blood, Troponin T blood
- Abstract
A number of assay-related issues can affect the performance of cardiac troponin (cTn) measurement in everyday practice. In this respect, it is vital that all information on cTn assays is known and that the performance characteristics of assays are objectively assessed and adequately described. The advent of the latest generation of more sensitive cTn assays has heralded a new wave of information about low concentrations of cTn in blood. These recent generation assays have improved analytical sensitivity and corresponding performance at low cTn concentrations when compared to their predecessors, providing a convincing goal for laboratory medicine in helping clinicians in the diagnosis of acute myocardial infarction. Crucial to the clinical utility of highly sensitive cTn assays is the laboratorians' role in closely scrutinizing proposed assays and defining their value in relation to available evidence. Analytical, as well as pre-analytical and post-analytical, aspects must be documented. In this review, we describe what laboratory professionals should know about their cTn assay performance characteristics and the pre-analytical prerequisites for robustness to ensure optimal post-analytical reporting.
- Published
- 2020
- Full Text
- View/download PDF
45. Improving measurement uncertainty of plasma electrolytes: a complex but not impossible task.
- Author
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Pasqualetti S, Chibireva M, Borrillo F, Braga F, and Panteghini M
- Subjects
- Calibration, Humans, Reference Standards, Uncertainty, Electrolytes blood, Potassium
- Published
- 2020
- Full Text
- View/download PDF
46. Trueness evaluation and verification of inter-assay agreement of serum folate measuring systems.
- Author
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Braga F, Frusciante E, Ferraro S, and Panteghini M
- Subjects
- Folic Acid standards, Humans, Reference Values, Reproducibility of Results, Diagnostic Tests, Routine methods, Folic Acid blood
- Abstract
Background Definitive data to establish if the use of the WHO International Standard (IS) 03/178 as a common calibrator of commercial measuring systems (MSs) has improved the harmonization of serum total folate (tFOL) measurements to a clinically suitable level are lacking. Here, we report the results of an intercomparison study aimed to verify if the current inter-assay variability is acceptable for clinical application of tFOL testing. Methods After confirming their commutability, the IS 03/178 and National Institute for Standards and Technology SRM 3949 L1 were used for evaluating the correctness of traceability implementation by manufacturers and the MSs trueness, respectively. The inter-assay agreement was verified using 20 patient pools. The measurement uncertainty (U) of tFOL measurements on clinical samples was also estimated. An outcome-based model for defining desirable performance specifications for bias and imprecision for serum tFOL measurements was applied. Results The majority of evaluated MSs overestimated the WHO IS value of +5% or more with the risk to produce an unacceptably high number of false-negative results in clinical practice. The mean inter-assay CV on all pools and on those with tFOL values >3.0 μg/L (n = 15) was 12.5% and 7.1%, respectively. In neither case the goal of 3.0% was fulfilled. The residual bias resulted in an excessive U of tFOL measurement on clinical samples. Conclusions The implementation of traceability of tFOL MSs to the WHO IS 03/178 is currently inadequate, resulting in an inter-assay variability that does not permit the use of a common threshold for detecting folate deficiency.
- Published
- 2020
- Full Text
- View/download PDF
47. Lactate dehydrogenase: an old enzyme reborn as a COVID-19 marker (and not only).
- Author
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Panteghini M
- Subjects
- Biomarkers blood, COVID-19, Coronavirus Infections diagnosis, Coronavirus Infections enzymology, Coronavirus Infections epidemiology, Disease-Free Survival, Humans, Pandemics, Pneumonia, Viral diagnosis, Pneumonia, Viral enzymology, Pneumonia, Viral epidemiology, Coronavirus Infections blood, L-Lactate Dehydrogenase blood, Pneumonia, Viral blood
- Abstract
Background Historically, the lactate dehydrogenase (LDH) measurement was introduced into Laboratory Medicine as component (together with creatine kinase (CK) and aspartate aminotransferase) of the classical enzyme triad employed for the diagnosis of myocardial infarction, which was subsequently replaced by CK-MB, and more recently by cardiac troponins. Afterwards, for many years, the clinical application of serum LDH measurement has been limited to the evaluation of anemias and to as a rough prognostic tool for certain tumors. Content In the last few years, significant changes have happened. First, the test has been confirmed as a robust predictor of poor outcomes in many neoplastic conditions. Furthermore, in the Revised International Staging System adopted in the 2015 by the International Myeloma Working Group, LDH acts as determinant of disease biology in differentiating myeloma stages. Finally, in the last few months, LDH is definitively reborn given its proven significant contribution in defining the COVID-19 severity. Conclusions This increased clinical role calls for an improvement of LDH assay standardization through the implementation of traceability of results of clinical samples to the available reference measurement system.
- Published
- 2020
- Full Text
- View/download PDF
48. Implementation of metrological traceability in laboratory medicine: where we are and what is missing.
- Author
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Panteghini M and Braga F
- Subjects
- Calibration, Chromatography, Liquid, Clinical Laboratory Information Systems, Gas Chromatography-Mass Spectrometry, Humans, Laboratories organization & administration, Quality Control, Reproducibility of Results, Uncertainty, Laboratories standards
- Abstract
Background The Joint Committee on Traceability in Laboratory Medicine (JCTLM) has recently created the Task Force on Reference Measurement System Implementation (TF-RMSI) for providing guidance on traceability implementation to in vitro diagnostics (IVD) manufacturers. Using serum creatinine (sCr) as an example, a preliminary exercise was carried out by checking what type of information is available in the JCTLM database and comparing this against derived analytical performance specifications (APS) for measurement uncertainty (MU) of sCr. Content APS for standard MU of sCr measurements were established as a fraction (≤0.75, minimum quality; ≤0.50, desirable quality; and ≤0.25, optimum quality) of the intra-individual biological variation of the measurand (4.4%). By allowing no more than one third of the total MU budget for patient samples to be derived from higher-order references, two out of the four JCTLM reference materials (RMs) at least allow minimum APS to be achieved for the MU of patient samples. Commutability was explicitly assessed for one of the JCTLM-listed matrixed RMs, which was produced in compliance with ISO 15194:2009 standard, whereas the remaining three RMs were assessed against the ISO 15194:2002 version of the standard, which only required the extent of commutability testing to be reported. Regarding the three listed reference methods, the MU associated with isotopic dilution-mass spectrometry coupled to gas chromatography (ID/GC/MS) and isotopic dilution-mass spectrometry coupled to liquid chromatography (ID/LC/MS) would allow APS to be fulfilled, while the isotope dilution surface-enhanced Raman scattering (ID/SERS) method displays higher MU. Summary The most recently listed RM for sCr in the JCTLM database meets the ISO 15194:2009 requirements with MU that would allow APS to be fulfilled and has had commutability demonstrated for use as a common calibrator in implementing traceability of sCr measurements. Splitting clinical samples with a laboratory performing ID/GC/MS or ID/LC/MS provides an alternative but would also require all components of uncertainty of these materials to be assessed. Outlook Using appropriately derived APS to judge whether reference measurement system components are fit for purpose represents a novel approach. The TF-RMSI is planning to review a greater number of measurands to provide more robust information about the state of the art of available reference measurement systems and their impact on the ability of clinical measurements to meet APS.
- Published
- 2020
- Full Text
- View/download PDF
49. Traceability validation of six enzyme measurements on the Abbott Alinity c analytical system.
- Author
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Aloisio E, Frusciante E, Pasqualetti S, Infusino I, Krintus M, Sypniewska G, and Panteghini M
- Subjects
- Calibration, Enzymes standards, Humans, Laboratory Personnel, Reference Values, Uncertainty, Enzymes blood, Laboratories organization & administration
- Abstract
Background Laboratory professionals should independently verify the correct implementation of metrological traceability of commercial measuring systems and determine if their performance is fit for purpose. We evaluated the trueness, uncertainty of measurements, and transferability of six clinically important enzyme measurements (alanine aminotransferase [ALT], alkaline phosphatase [ALP], aspartate aminotransferase [AST], creatine kinase [CK], γ-glutamyltransferase [γGT], and lactate dehydrogenase [LDH]) performed on the Abbott Alinity c analytical system. Methods Target values and associated uncertainties were assigned to three pools for each enzyme by using the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference measurement procedures (RMPs) and the pools were then measured on the Alinity system. Bias estimation and regression studies were performed, and the uncertainty associated with Alinity measurements was also estimated, using analytical performance specifications (APS) derived from biological variability of measurands as goals. Finally, to validate the transferability of the obtained results, a comparison study between two Alinity systems located in Milan, Italy, and Bydgoszcz, Poland, was carried out. Results Correct implementation of traceability to the IFCC RMPs and acceptable measurement uncertainty fulfilling desirable (ALP, AST, LDH) or optimal APS (ALT, CK, γGT) was verified for all evaluated enzymes. An optimal alignment between the two Alinity systems located in Milan and Bydgoszcz was also found for all enzyme measurements. Conclusions We confirmed that measurements of ALT, ALP, AST, CK, γGT, and LDH performed on the Alinity c analytical system are correctly standardized to the IFCC reference measurement systems and the system alignment is consistent between different platforms.
- Published
- 2020
- Full Text
- View/download PDF
50. The internal quality control in the traceability era.
- Author
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Braga F, Pasqualetti S, Aloisio E, and Panteghini M
- Subjects
- Calibration, Clinical Laboratory Techniques, Diagnostic Techniques and Procedures, Humans, Reference Standards, Reproducibility of Results, Uncertainty, Quality Control
- Abstract
To be accurate and equivalent, laboratory results should be traceable to higher-order references. Furthermore, their quality should fulfill acceptable measurement uncertainty (MU) as defined to fit the intended clinical use. With this aim, in vitro diagnostics (IVD) manufacturers should define a calibration hierarchy to assign traceable values to their system calibrators. Medical laboratories should know and verify how manufacturers have implemented the traceability of their calibrators and estimate the corresponding MU on clinical samples. Accordingly, the internal quality control (IQC) program should be redesigned to permit IVD traceability surveillance through the verification by medical laboratories that control materials, provided by the manufacturer as a part of measuring systems, are in the clinically suitable validation range (IQC component I). Separately, laboratories should also monitor the reliability of employed IVD measuring systems through the IQC component II, devoted to estimation of MU due to random effects and to obtaining MU of provided results, in order to apply prompt corrective actions if the performance is worsening when compared to appropriate analytical specifications, thus jeopardizing the clinical validity of test results.
- Published
- 2020
- Full Text
- View/download PDF
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