OBJECTIVES:Pathological conditions may result in clinical chemical values exceeding the linearity range of laboratory methods. In clinical practice, not all tests require exact numerical values for patient management, as useful information can still be provided when results are reported to a defined cutoff. This study describes an approach to reduce unnecessary dilutions by identifying tests that can be reported above a defined threshold. METHODS:Eighty-six clinical chemistry assays on Cobas 8000 (middleware: Infinity) were reviewed at the Laboratory Medicine of the University Hospital of Padua. Fifteen analytes requiring manual dilution beyond predefined automated limits were selected. A multi-step workflow was implemented, including literature review, clinician and staff engagement, definition of upper reporting limits, middleware customisation, and retrospective and prospective performance evaluation. Key outcomes included turnaround time (TAT), auto-release rate, manual dilution frequency, estimated costs, and clinician requests for exact values. RESULTS:Literature review and clinician feedback supported the definition of upper reporting limits beyond which exact values were not routinely required, except for lactate dehydrogenase (LDH), where oncologic follow-up necessitated precise reporting. Implementation of the new rules eliminated most manual dilutions, substantially reducing costs and improving efficiency. P90 TAT decreased for samples above cutoff values in most analytes between 2023 and 2025. LDH was the only analyte for which manual dilution was not completely eliminated in 2025, with a residual rate of 3.38 per 1000 tests (vs. 7.32 per 1000 in 2023). Clinician feedback confirmed the appropriateness of the new reporting rules. CONCLUSIONS:This study shows that revising validation rules to report results above predefined thresholds provides clinically meaningful information while reducing unnecessary manual procedures. This model supports appropriate patient management and improves efficiency by enhancing process automation, consistency, and decision-making.

BACKGROUND:Chromatographic separation has become a critical analytical technique in routine laboratory medicine. Although several documents address standardisation in chromatography, they largely focus on industrial and pharmaceutical applications. Routine medical laboratories remain underserved, creating a need for guidance tailored to their specific context. This paper aims to provide technical guidance on applying ISO 15189:2022 requirements to chromatographic methods, ensuring quality and risk management across all laboratory phases. CONTENT:Building on previous work of the European Federation of Laboratory Medicine Committee on Accreditation and ISO/CEN Standards, we reviewed ISO 15189:2022 requirements and interpreted them in relation to chromatographic procedures. Key vulnerabilities inherent to chromatography - such as sample preparation variability, column performance drift, and detector calibration - were identified and mapped to relevant quality and competence clauses. SUMMARY AND OUTLOOK:The guidance highlights chromatography-specific risks and proposes structured verification, documentation, and risk management strategies. It addresses pre-analytical, analytical, and post-analytical phases, emphasizing traceability, method verification, and result of release. Special consideration is given to laboratory-developed tests using chromatographic techniques, aligning them with European in vitro diagnostic regulation. By contextualising ISO 15189:2022 within the technical realities of chromatography, this paper provides laboratories and auditors with practical tools to safeguard quality, reduce uncertainty, and ensure reliable patient results. The proposed framework advances regulatory harmonisation and supports the routine implementation of chromatography in medical laboratories.

Objectives To maximize participation in the international standardization effort, this recommendation aims to update the international guidance of the Working Group on Laboratory Errors and Patient Safety of the International Federation of Clinical Chemistry and Laboratory Medicine by identifying a limited and globally applicable panel of Essential Quality Indicators (QIs) focused on patient safety, clinical outcomes, and harmonization across medical laboratories.Methods Through a consensus meeting, experts from multiple countries reviewed the IFCC Model of Quality Indicators (MQI) to identify high-priority indicators. Selection prioritized the probability of patient harm, ease of detection, and feasibility of data collection and implementation within national contexts.Results Six essential QIs covering the total testing process were identified and ratified: (1) rate of misidentified requests (Pre-MisR) and misidentified samples (Pre-MisS); (2) rate of sample rejections (Pre-RejS); (3) rate of hemolysis detected either by automated hemolysis index (Pre-HemI) or visual inspection (Pre-HemV); (4) rate of unacceptable results in External Quality Assessment/Proficiency Testing (Intra-Unac); (5) turnaround time of cardiac troponin at the 90th percentile for the emergency room (Post-TnTAT, Post-TnTAT clin); and (6) rate of incorrect laboratory reports (Post-RectRep). Recommendations on calculation, reporting frequency, and integration into IFCC and national comparison programs are provided.Conclusions The proposed essential QI panel provides a standardized and feasible framework to support its integration into national comparison programs and the IFCC MQI platform. Its implementation will facilitate data consolidation, strengthen the development of national and global quality specifications, and contribute to continuous improvement in patient safety.

Point-of-care testing (POCT) is becoming an increasingly popular way to perform laboratory tests closer to the patient. This option has several recognized advantages, such as accessibility, portability, speed, convenience, ease of use, ever-growing test panels, lower cumulative healthcare costs when used within appropriate clinical pathways, better patient empowerment and engagement, and reduction of certain pre-analytical errors, especially those related to specimen transportation. On the other hand, POCT also poses some limitations and risks, namely the risk of lower accuracy and reliability compared to traditional laboratory tests, quality control and connectivity issues, high dependence on operators (with varying levels of expertise or training), challenges related to patient data management, higher costs per individual test, regulatory and compliance issues such as the need for appropriate validation prior to clinical use (especially for rapid diagnostic tests; RDTs), as well as additional preanalytical sources of error that may remain undetected in this type of testing, which is usually based on whole blood samples (i.e., presence of interfering substances, clotting, hemolysis, etc.). There is no doubt that POCT is a breakthrough innovation in laboratory medicine, but the discussion on its appropriate use requires further debate and initiatives. This collective opinion paper, composed of abstracts of the lectures presented at the two-day expert meeting "Point-Of-Care-Testing: State of the Art and Perspective" (Venice, April 4-5, 2024), aims to provide a thoughtful overview of the state-of-the-art in POCT, its current applications, advantages and potential limitations, as well as some interesting reflections on the future perspectives of this particular field of laboratory medicine.

ObjectivesHealthcare has a considerable environmental impact, yet it has been largely overlooked. Clinical laboratories, in particular, consume significantly more energy and water per unit area compared to standard office buildings. It is crucial to raise awareness among laboratories about the significance of embracing eco-friendly practices. Numerous energy-saving measures do not incur additional costs but necessitate a shift in organizational culture and mindset.Design & MethodsThis paper conducts a cost-benefit analysis of energy consumption at the Laboratory Medicine Unit of University Hospital of Padova, beginning with laboratory refrigerators and freezers.ResultsThe need to rationalize the existing units, especially the combined refrigerators-freezers, and reorganize the contents of the Ultra-Low Temperature freezers with an energy-saving perspective has emerged.ConclusionsBy implementing these practices, this initiative can gradually expand to encompass more green activities in the future.

In the last few decades, quality in laboratory medicine has evolved in concert with the transformation and the changes (technological, scientific and organizational) in this sector. Laboratory professionals have faced great challenges, at times being overwhelmed, yet also involved in this progress. Worldwide, laboratory professionals and scientific societies involved in laboratory medicine have raised awareness concerning the need to identify new quality assurance tools that are effective in reducing the error rate and enhancing patient safety, in addition to Internal Quality Control (IQC) procedures and the participation in the External Quality Assessment Schemes (EQAS). The use of Quality Indicators (QIs), specifically designed for laboratory medicine are effective in assessing and monitoring all critical events occurring in the different phases of Total Testing Process (TTP), in particular, in the extra-analytical phases. The Model of Quality Indicators (MQI), proposed by the Working Group "Laboratory Errors and Patient Safety " (WG-LEPS) of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and validated by experts in consensus conferences, is an important window of opportunity for the medical laboratory to demonstrate the use of an effective quality assurance tool fit for this purpose. Aim of this paper is to provide an update of the state-of-the-art concerning the most used QIs data collected in 2021 and the Quality Specifications (QSs) proposed for their evaluation. Moreover, a strategy for the future is proposed in order to improve the MQI and encourage its use in medical laboratories throughout the world.

INTRODUCTION:Despite the important diagnostic role of peripheral blood morphology, cell classification is subjective. Automated image-processing systems (AIS) provide more accurate and objective morphological evaluation. The aims of this multicenter study were the evaluation of the intra and inter-laboratory variation between different AIS in cell pre-classification and after reclassification, compared with manual optical microscopy, the reference method.METHODS:Six peripheral blood samples were included in this study, for each sample, 70 May-Grunwald and Giemsa stained PB smears were prepared from each specimen and 10 slides were delivered to the seven laboratories involved. Smears were processed by both optical microscopy (OM) and AIS. In addition, the assessment times of both methods were recorded.RESULTS:Within-laboratory Reproducibility ranged between 4.76% and 153.78%; between-laboratory Precision ranged between 2.10% and 82.2%, while Total Imprecision ranged between 5.21% and 20.60%. The relative Bland Altman bias ranged between -0.01% and 20.60%. The mean of assessment times were 326 ± 110 s and 191 ± 68 s for AIS post reclassification and OM, respectively.CONCLUSIONS:AIS can be helpful when the number of cell counted are low and can give advantages in terms of efficiency, objectivity and time saving in the morphological analysis of blood cells. They can also help in the interpretation of some morphological features and can serve as learning and investigation tools.

Abstract Serial measurements of cardiac troponin are recommended by international guidelines to diagnose myocardial infarction (MI) since 2000. However, some relevant differences exist between the three different international guidelines published between 2020 and 2021 for the management of patients with chest pain and no ST-segment elevation. In particular, there is no agreement on the cut-offs or absolute change values to diagnose non-ST-segment elevation MI (NSTEMI). Other controversial issues concern the diagnostic accuracy and cost-effectiveness of cut-off values for the most rapid algorithms (0 h/1 h or 0 h/2 h) to rule-in and rule-out NSTEMI. Finally, another important point is the possible differences between demographic and clinical characteristics of patients enrolled in multicenter trials compared to those routinely admitted to the Emergency Department in Italy. The Study Group of Cardiac Biomarkers, supported by the Italian Scientific Societies Società Italiana di Biochimica Clinica, Italian Society of the European Ligand Assay Society, and Società Italiana di Patolgia Clinica e Medicina di Laboratorio decided to revise the document previously published in 2013 about the management of patients with suspected NSTEMI, and to provide some suggestions for the use of these biomarkers in clinical practice, with a particular focus on the Italian setting.

Abstract Objectives SARS-CoV-2 serology presents an important role in several aspects of COVID-19 pandemic. Immunoassays performances have to be accurately evaluated and correlated with neutralizing antibodies. We investigated the analytical and clinical performances of a SARS-CoV-2 RBD IgG assay, automated on a high throughput platform, and the correlation of the antibodies (Ab) levels with the plaque reduction neutralization (PRNT50) Ab titers. Methods A series of 546 samples were evaluated by SARS-CoV-2 RBD IgG assay (Snibe diagnostics), including 171 negative and 168 positive SARS-CoV-2 subjects and a further group of 207 subjects of the COVID-19 family clusters follow-up cohort. Results Assay imprecision ranged from 3.98 to 12.18% being satisfactory at low and medium levels; linearity was excellent in all the measurement range. Considering specimens collected after 14 days post symptoms onset, overall sensitivity and specificity were 99.0 and 92.5%, respectively. A total of 281 leftover samples results of the PRNT50 test were available. An elevated correlation was obtained between the SARS-CoV-2 RBD IgG assay and the PRNT50 titer at univariate (ρ=0.689) and multivariate (ρ=0.712) analyses. Conclusions SARS-CoV-2 S-RBD IgG assay shows satisfactory analytical and clinical performances, and a strong correlation with sera neutralizing activity.

Important advances achieved in pharmacological cancer treatment have led progressively to a reduction in mortality from many forms of cancer, and increasing numbers of previously incurable patients can now hope to become cancer-free. Yet, to achieve these improved outcomes a high price has been paid in terms of untoward side effects associated with treatment, cardio-toxicity in particular. Several recent studies have reported that cardiac troponin assay using high-sensitivity methods (hscTn) can enable the early detection of myocardial injury related to chemotherapy or abuse of drugs that are potentially cardiotoxic. Several authors have recently suggested that changes in hs- cTn values enable the early diagnosis of cardiac injury from chemotherapy, thus potentially benefitting cancer patients with increased troponin values by initiating early cardioprotective therapy. However, large randomised clinical trials are needed in order to evaluate the cost/benefit ratio of standardised protocols for the early detection of cardiotoxicity using the hs- cTn assay in patients treated with chemotherapy.

The recent pandemic outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and associated with the pathology called COVID-19 (coronavirus disease 2019), has now become one of the most strenuous health care challenges since the emergence of the three pandemics caused by influenza viruses during the past century. Throughout the clinical decision-making of COVID-19, laboratory tests are essential for supporting the screening, diagnosis, prognostication and therapeutic monitoring of this severe infectious disease. Serological testing, that reflects the humoral immune response developing after interaction between the host and the virus (or its components), enables to garner a vast array of clinical information which can be especially used in seroprevalence or seroconversion studies. To this end, the Task Force on COVID-19 of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) has endorsed a series of technical, practical and clinical ad interim recommendations, aimed at facilitating and optimizing the introduction, clinical usage and governance of SARS-CoV-2 serological immunoassays in routine practice.

AbstractBackgroundSARS-CoV-2 serology presents an important role in understanding the virus epidemiology, in vaccine prioritization strategies and in convalescent plasma therapy. Immunoassays performances have to be accurately evaluated and correlated with neutralizing antibodies to be used as a surrogate measure of neutralizing activity. We investigate the analytical and clinical performance of a SARS-CoV-2 RBD IgG assay, automated on a high throughput platform, and the correlation of the antibodies (Ab) levels with the plaque reduction neutralization (PRNT50) Ab titers.MethodsA series of 546 samples were evaluated by SARS-CoV-2 RBD IgG assay (Snibe diagnostics), including 171 negative and 168 positive SARS-CoV-2 subjects and a further group of 207 subjects of the COVID-19 family clusters follow-up cohort.ResultsAssay precision was acceptable at low and medium levels; linearity was excellent in all the measurement range. Considering specimens collected after 14 days post symptoms onset, overall sensitivity and specificity were 99.0% and 92.5%, respectively. A total of 281 leftover samples results of the PRNT50 test were available. An elevated correlation was obtained between the SARS-CoV-2 RBD IgG assay and the PRNT50 titer at univariate (rho = 0.689) and multivariate (rho = 0.712) analyses.ConclusionsSARS-CoV-2 S-RBD IgG assay achieves elevated analytical and clinical performances, and a strong correlation with sera neutralization activity.

Article Kinetics and biological characteristics of humoral response developing after SARS-CoV-2 infection: implications for vaccination was published on July 1, 2021 in the journal Clinical Chemistry and Laboratory Medicine (CCLM) (volume 59, issue 8).

Introduction: D-Dimer assessment represents a cornerstone in the diagnostic approach to several thrombotic disorders. Recent literature has highlighted the role of D-Dimer also in the diagnostic pathway of coronavirus infection (COVID-19) and the importance of harmonized reporting [D-dimer unit (DDU) or fibrinogen equivalent unit (FEU);unit of measure;cut-off] in order to guarantee the correct interpretation of the results. Methods: D-Dimer data from 100 EQA participants and the inter-laboratory variability (CV%) of the last 7 years for the most used analytical systems: Werfen, HemosIL HS;Werfen, HemosIL HS-500;Auto D-D, Sclavo;Innovance, Siemens;VIDAS, bioMerieux and STA Liatest, Stago have been evaluated. Results: Concerning the results expression in DDU or FEU, we observed a prevalence of FEU (55.1%) over DDU (44.9%);the value was confirmed in the last 7 years (average FEU = 55.6%), differently from data obtained in the survey conducted in 2014 at a national level. The units used are: ng/mL (67.8%), μg/L (29.0%) and mg/L (3.2%) for D-Dimer DDU;ng/mL (57.9%), μg/mL (21.0%), μg/L (15.8%) and mg/L (5.3%) for D-Dimer FEU. Inter-laboratory variability (mean CV%) calculated on a total of 72 controls is lower for all diagnostic systems at pathological levels than the one observed for concentrations below the cut-off. Discussion: This study demonstrates that the reporting of D-Dimer results does not comply with the 2014 SIBioC consensus document which recommended the use of μg/L FEU, and highlights 8 different types of information. Data reported in this study call for the harmonization of D-Dimer reporting in order to guarantee the correct interpretation of the information, both in the case of COVID-19 and in all the diseases already known where this analyte has a clinical relevance.

OBJECTIVES:Numerous analytical systems, rapidly made available on the market throughout the SARS-CoV-2 pandemic, aim to detect COVID-19, and to continuously update and improve the same systems. Medical laboratory professionals have also developed in-house analytical procedures in order to satisfy the enormous volume of requests for tests. These developments have highlighted the need control the analytical procedures used in order to guarantee patient safety. The External Quality Assessment (EQA) Scheme, an important quality assurance tool, aims to guarantee high standard performance for laboratory and analytical procedures. The aim of the present study was to report on the results collected in an experimental EQA scheme for the serological diagnosis of SARS-CoV-2. METHODS:All qualitative results collected in the different EQA surveys were summarized in order to identify the percentage of laboratory results in relation to typology of antibodies, results and samples. RESULTS:A total of 4,867 data sets were collected. The analysis of EQA data made, demonstrates a better agreement among laboratories results for total Ig than single immunoglobulins (IgG, IgM, IgA) in the case samples positive for SARS-CoV-2, and a wide divergence between IgM results for positive samples (only 34.9% were correct). Results for negative controls and specificity controls demonstrated a better overall agreement than results for positive samples. CONCLUSIONS:Working in collaboration with the IVD manufacturers, laboratory professionals must strive to achieve harmonization of results, and to develop well-defined protocols complying with the ISO 15189 requirements.

Article Towards the rational utilization of SARS-CoV-2 serological tests in clinical practice was published on October 1, 2020 in the journal Clinical Chemistry and Laboratory Medicine (CCLM) (volume 58, issue 10).

Background: The evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibody (Ab) assay performances is of the utmost importance in establishing and monitoring virus spread in the community. In this study focusing on IgG antibodies, we compare reliability of three chemiluminescent (CLIA) and two enzyme linked immunosorbent (ELISA) assays. Methods: Sera from a total of 271 subjects, including 64 reverse transcription-polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 patients were tested for specific Ab using Maglumi (Snibe), Liaison (Diasorin), iFlash (Yhlo), Euroimmun (Medizinische Labordiagnostika AG) and Wantai (Wantai Biological Pharmacy) assays. Diagnostic sensitivity and specificity, positive and negative likelihood ratios were evaluated using manufacturers' and optimized thresholds. Results: Optimized thresholds (Maglumi 2 kAU/L, Liaison 6.2 kAU/L and iFlash 15.0 kAU/L) allowed us to achieve a negative likelihood ratio and an accuracy of: 0.06 and 93.5% for Maglumi; 0.03 and 93.1% for Liaison; 0.03 and 91% for iFlash. Diagnostic sensitivities and specificities were above 93.8% and 85.9%, respectively for all CLIA assays. Overall agreement was 90.3% (Cohen's kappa = 0.805 and SE = 0.041) for CLIA, and 98.4% (Cohen's kappa = 0.962 and SE = 0.126) for ELISA. Conclusions: The results obtained indicate that, for CLIA assays, it might be possible to define thresholds that improve the negative likelihood ratio. Thus, a negative test result enables the identification of subjects at risk of being infected, who should then be closely monitored over time with a view to preventing further viral spread. Redefined thresholds, in addition, improved the overall inter-assay agreement, paving the way to a better harmonization of serologic tests.