Clinical Chemistry and Laboratory Medicine (CCLM)

Published by De Gruyter

Volume 60 Issue 1

Issue of Clinical Chemistry and Laboratory Medicine (CCLM)

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Contents
Journal Overview

Publicly Available November 23, 2021

Frontmatter

Page range: i-iv

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Editorials

Publicly Available November 1, 2021

EU health policy is on the brink of a spectacular own-goal that will harm patients and hamper innovation

Denis Horgan

Page range: 1-3

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Publicly Available September 17, 2021

Theranos revisited: the trial and lessons learned

Eleftherios P. Diamandis, Karl J. Lackner, Mario Plebani

Page range: 4-6

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Reviews

Publicly Available November 1, 2021

Review and evolution of guidelines for diagnosis of COVID-19 vaccine induced thrombotic thrombocytopenia (VITT)

Emmanuel J. Favaloro, Leonardo Pasalic, Giuseppe Lippi

Page range: 7-17

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Abstract

Coronavirus disease 2019 (COVID-19) is a life-threatening infectious disease caused by Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). In response to the still ongoing pandemic outbreak, a number of COVID-19 vaccines have been quickly developed and deployed. Although minor adverse events, either local (e.g., soreness, itch, redness) or systematic (fever, malaise, headache, etc.), are not uncommon following any COVID-19 vaccination, one rare vaccine-associated event can cause fatal consequences due to development of antibodies against platelet factor 4 (PF4), which trigger platelet activation, aggregation, and possible resultant thrombosis, often at unusual vascular sites. Termed thrombosis with thrombocytopenia syndrome (TTS) by reporting government agencies, the term vaccine-induced (immune) thrombotic thrombocytopenia (VITT) is more widely adopted by workers in the field. In response to increasing reports of VITT, several expert groups have formulated guidelines for diagnosis and/or management of VITT. Herein, we review some key guidelines related to diagnosis of VITT, and also provide some commentary on their development and evolution.

Publicly Available October 25, 2021

High-sensitivity cardiac troponins in pediatric population

Aldo Clerico, Alberto Aimo, Massimiliano Cantinotti

Page range: 18-32

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Abstract

Apparently healthy children often complain of chest pain, especially after physical exercise. Cardiac biomarker levels are often measured, but the clinical relevance of these assays in children is still debated, even when a cardiac disease is present. Coronary artery disease is exceedingly rare in children, but elevated circulating levels of cardiac troponin I (cTnI) and T (cTnT) in an acute setting may help detect heart failure due to an unknown cardiac disorder, or worsening heart failure, particularly in combination with other biomarkers such as B-type natriuretic peptides. However, the interpretation of biomarkers is often challenging, especially when institutions transition from conventional cTn assays to high-sensitivity (hs-cTn) methods, as well demonstrated in the emergency setting for adult patients. From a clinical perspective, the lack of established reference values in the pediatric age is the main problem limiting the use of hs-cTn methods for the diagnosis and managements of cardiac diseases in infants, children and adolescents. This review aims to discuss the possibility to use hs-cTnI and hs-cTnT to detect cardiac disease and to explore age-related differences in biomarker levels in the pediatric age. We start from some analytical and pathophysiological considerations related to hs-cTn assays. Then, after a systematic literature search, we discuss the current evidence and possible limitations of hs-cTn assay as indicators of cardiac disease in the most frequently cardiac disease in pediatric setting.

Opinion Papers

Open Access September 17, 2021

Implementation of the new EU IVD regulation – urgent initiatives are needed to avert impending crisis

Christa Cobbaert, Ettore D. Capoluongo, Florent J.L.A. Vanstapel, Patrick M.M. Bossuyt, Harjit Pal Bhattoa, Peter Henrik Nissen, Matthias Orth, Thomas Streichert, Ian S. Young, Elizabeth Macintyre, Alan G. Fraser, Michael Neumaier

Page range: 33-43

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Abstract

Laboratory medicine in the European Union is at the dawn of a regulatory revolution as it reaches the end of the transition from IVDD 98/79/EC (https://eur-lex.eur-opa.eu/legal-content/EN/TXT/?uri=CELEX%3A31998L0079&qid=1628781352814) to IVDR 2017/746 https://eur-lex.europa.eu/eli/reg/2017/746. Without amendments and contingency plans, implementation of the IVDR in May 2022 will lead the healthcare sector into uncharted waters due to unpreparedness of the EU regulatory infrastructure. Prospective risk analyses were not made by the European Commission, and if nothing happens it can be anticipated that the consequences will impact all stakeholders of the medical test pipeline, may seriously harm patients and may prevent caregivers from making appropriate clinical decisions due to non-availability of medical tests. Finally, it also may discourage manufacturers and academia from developing specialty tests, thereby hampering innovation in medical diagnostic care. We hereby inform laboratory professionals about the imminent diagnostic collapse using testimonies from representative stakeholders of the diagnostic supply chain and from academia developing innovative in-house tests in domains of unmet clinical needs. Steps taken by the EFLM Task Force on European Regulatory Affairs, under the umbrella of the Biomedical Alliance in Europe, will be highlighted, as well as the search for solutions through dialogue with the European Commission. Although we recognize that the IVDR promotes positive goals such as increased clinical evidence, surveillance, and transparency, we need to ensure that the capabilities of the diagnostic sector are not damaged by infrastructural unpreparedness, while at the same time being forced to submit to a growing bureaucratic and unsupportive structure that will not support its “ droit d’exister ”.

October 19, 2021

Exploration of novel biomarkers for hypertensive disorders of pregnancy by comprehensive analysis of peptide fragments in blood: their potential and technologies supporting quantification

Yoshihiko Araki, Yoshiki Miura, Hiroshi Fujiwara

Page range: 44-51

Abstract

Among the many complications associated with pregnancy, hypertensive disorders of pregnancy (HDP) constitute one of the most important. Since the pathophysiology of HDP is complex, new disease biomarkers (DBMs) are needed to serve as indicators of disease activity. However, in the current status of laboratory medicine, despite the fact that blood pressure measurement has been used for a long time, not many DBMs contribute adequately to the subsequent diagnosis and treatment. In this article, we discuss studies focusing on peptide fragments in blood identified by comprehensive quantitative methods, among the currently proposed DBM candidates. Furthermore, we describe the basic techniques of peptidomics, especially quantitative proteomics, and outline the current status and challenges of measuring peptides in blood as DBM for HDP.

General Clinical Chemistry and Laboratory Medicine

November 2, 2021

Total lab automation: sample stability of clinical chemistry parameters in an automated storage and retrieval module

Kobe Vercruysse, Stijn Lambrecht, Matthijs Oyaert

Page range: 52-59

Abstract

Objectives Automated storage and retrieval modules (SRM), as part of total lab automation (TLA) systems, offer tremendous practical and economic benefits. In contrast to manual storage systems, SRMs indicate continuous motion of samples and may leave samples prone to temperature fluctuations. This study investigates analyte stability in serum and heparin plasma within an automated storage module. Methods The stability of 28 common biochemistry analytes was investigated using 57 freshly obtained routine serum samples and 42 lithium-heparin plasma samples. Following baseline measurement, samples were stored at 2–8 °C in the automated SRM of the Accelerator a3600 TLA and reanalyzed at fixed time points (2, 4, 8, 12, 24, 48 and 72 h) on the Abbott Architect c16000 chemistry analyzer. The concentration at each time point was expressed as %-difference to the baseline value and mean results were compared to the criteria for desirable bias derived from the biological variation database. Results Nine of the analytes exceeded the bias criterion within 72 h after initial measurement in either serum samples, plasma samples or both. Lithium-heparin plasma samples showed increasing values for phosphor, potassium and lactate dehydrogenase (LDH), which were only considered stable for respectively 24, 12 and 4 h, glucose was considered stable for 8 h. Electrolyte concentrations and LDH activity significantly increased in serum samples beyond 48 h. Bicarbonate should not be performed as add-on test at all. Conclusions The presented data indicate that the conditions within an SRM have no clinical impact on sample stability and allow stable measurement of routine analytes within 72 h, comparable to manual storage facilities.

Open Access October 13, 2021

Instability of corticotropin during long-term storage – myth or reality?

Jacquelien J. Hillebrand, Li Zhou, Marilee A. Marcinkus, Maria Datwyler, Susan H. Gawel, Frans Martens, Gerard J. Davis, Annemieke C. Heijboer

Page range: 60-65

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Abstract

Objectives Corticotropin is notorious for its instability. Whereas several studies have investigated its short-term stability in plasma following venous blood sampling, studies on long-term stability are lacking. Here we investigated the long-term storage stability of corticotropin in ethylenediaminetetraacetic acid containing plasma. Methods Specimens from healthy volunteers (neat, spiked) were stored in polypropylene microcentrifuge tubes with socket screw-caps at −20 °C and −70 °C for up to one and a half years. Corticotropin in plasma was measured using an Abbott research only immunoassay. Separately, specimens from patients were collected during diagnostic routine testing and stored in polystyrene tubes with push-caps at −20 °C for up to 6 years. In these samples corticotropin hormone was measured using the Diasorin corticotropin immunoassay. Results Storage of specimens at −20 °C or −70 °C for up to one and a half years showed minimal changes (<11%) in corticotropin levels, while storage of patient samples at −20 °C for up to 6 years showed a significant (54%) reduction in corticotropin levels. Conclusions Corticotropin levels are stable in plasma when stored at −20 °C for one and a half years using the Abbott research only assay, but with longer storage time a significant reduction in corticotropin levels can be expected. Once specimens are stored for future corticotropin measurements, one should consider storage time, storage temperature and assay differences.

October 21, 2021

External quality assessment of serum indices: Spanish SEQC-ML program

Rubén Gómez Rioja, Monserrat Ventura, María Antonia Llopis, Josep Miquel Bauça, Andrea Caballero Garralda, Mercedes Ibarz, Debora Martinez, Carolina Gómez, Paloma Salas Gómez-Pablos, Isabel García del Pino, Jose Delgado, Juan Jose Puente, Iciar Marzana

Page range: 66-73

Abstract

Objectives Serum indices included in clinical chemistry instruments are widely used by laboratories to assess the quality of samples. Instruments that report quantitative results allow an evaluation of their diagnostic performance in a similar way to other biochemical tests. The Spanish Society of Laboratory Medicine (SEQC-ML) launched a monthly External Quality program of serum indices in 2018 using three lyophilized materials of simultaneous annual distribution. We present the results of the first three years of the program. Methods The use of four different quality control materials with different concentrations in three alternate months allows an annual evaluation of the participant’s accuracy. Assigned values are established by consensus among homogeneous groups, considering necessary at least 10 participants for a comparison at instrument level. The average percentage difference results per instrument allow the assessment of bias among groups. Results The imprecision of the three indices ranges between 3 and 9%, with no major differences among instruments. Significant differences were observed in all indices among instruments with more than 10 participants (Roche Cobas, Abbott Architect, Abbott Alinity and Siemens Advia). The 90th percentile of the distribution of percentage differences was used as the analytical performance specification (APS). An improvement in performance was observed in the first three years of the program, probably due to the learning curve effect. In 2020, APS of 7.8, 12.2 and 9.7% were proposed for hemolytic, icteric and lipemic indices, respectively. Conclusions Serum indices have a great impact on the quality and the reliability of laboratory test results. Participation in proficiency testing programs for serum indices is helpful to encourage harmonization among providers and laboratories.

November 2, 2021

Comparison of two LC-MS/MS methods for the quantification of 24,25-dihydroxyvitamin D3 in patients and external quality assurance samples

Sieglinde Zelzer, Caroline Le Goff, Stéphanie Peeters, Chiara Calaprice, Andreas Meinitzer, Dietmar Enko, Walter Goessler, Markus Herrmann, Etienne Cavalier

Page range: 74-81

Abstract

Objectives In-house developed liquid-chromatography mass spectrometry (LC-MS/MS) methods are used more and more frequently for the simultaneous quantification of vitamin D metabolites. Among these, 24,25-dihydroxyvitamin D3 (24,25(OH) 2 D 3 ) is of clinical interest. This study assessed the agreement of this metabolite in two validated in-house LC-MS/MS methods. Methods 24,25(OH) 2 D 3 was measured in 20 samples from the vitamin D external quality assurance (DEQAS) program and in a mixed cohort of hospital patients samples (n=195) with the LC-MS/MS method at the Medical University of Graz (LC-MS/MS 1) and at the University of Liège (LC-MS/MS 2). Results In DEQAS samples, 24,25(OH) 2 D 3 results with LC-MS/MS 1 had a proportional bias of 1.0% and a negative systemic difference of −0.05%. LC-MS/MS 2 also showed a proportional bias of 1.0% and the negative systemic bias was −0.22%. Comparing the EQA samples with both methods, no systemic bias was found (0.0%) and the slope was 1%. The mean difference of 195 serum sample measurements between the two LC-MS/MS methods was minimal (−0.2%). Both LC-MS/MS methods showed a constant bias of 0.31 nmol/L and a positive proportional bias of 0.90%, respectively. Conclusions This study is the first to assess the comparability of 24,25(OH) 2 D 3 concentrations in a mixed cohort of hospitalized patients with two fully validated in-house LC-MS/MS methods. Despite different sample preparation, chromatographic separation and ionization, both methods showed high precision measurements of 24,25(OH) 2 D 3 . Furthermore, we demonstrate the improvement of accuracy and precision measurements of 24,25(OH) 2 D 3 in serum samples and in the DEQAS program.

October 20, 2021

Isotope dilution LC-MS/MS quantification of the cystic fibrosis transmembrane conductance regulator (CFTR) modulators ivacaftor, lumacaftor, tezacaftor, elexacaftor, and their major metabolites in human serum

Katharina Habler, Anne-Sophie Kalla, Michael Rychlik, Mathias Bruegel, Daniel Teupser, Susanne Nährig, Michael Vogeser, Michael Paal

Page range: 82-91

Abstract

Objectives Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators have revolutionized the therapeutic landscape in CF treatment. These vital drugs are extensively metabolized via CYP3A, so caution must be exercised in multimodal CF therapy because of the risk of adverse drug interactions. Our goal was to develop a highly sensitive assay for the purpose of therapeutic drug monitoring (TDM) in diagnostic laboratories. Methods After protein precipitation, the CFTR modulators ivacaftor, lumacaftor, tezacaftor, elexacaftor, and their metabolites ivacaftor-M1, ivacaftor-M6, and tezacaftor-M1 were separated with a two-dimensional chromatography setup within 5 min, and quantified with stable isotope-labeled internal standards. The method was validated according to the European Medicines Agency (EMA) guideline on bioanalytical method validation and applied to CF patient samples. Results Inaccuracy was ≤7.0% and the imprecision coefficient of variation (CV) was ≤8.3% for all quality controls (QCs). The method consistently compensated for matrix effects, recovery, and process efficiency were 105–115 and 96.5–103%, respectively. Analysis of CF serum samples provided concentrations comparable to the pharmacokinetic profile data reported in the EMA assessment report for the triple combination therapy Kaftrio. Conclusions We hereby present a robust and highly selective isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) assay for the simultaneous quantification of the so far approved CFTR modulators and their metabolites in human serum. The assay is suitable for state-of-the-art pharmacovigilance of CFTR modulator therapy in CF patients, in order to maximize safety and efficacy, and also to establish dose-response relationships in clinical trials.

Hematology and Coagulation

September 17, 2021

The development of autoverification system of lymphocyte subset assays on the flow cytometry platform

Jue Shi, Run-Qing Mu, Pan Wang, Wen-Qing Geng, Yong-Jun Jiang, Min Zhao, Hong Shang, Zi-Ning Zhang

Page range: 92-100

Abstract

Objectives Peripheral blood lymphocyte subsets are important parameters for monitoring immune status; however, lymphocyte subset detection is time-consuming and error-prone. This study aimed to explore a highly efficient and clinically useful autoverification system for lymphocyte subset assays performed on the flow cytometry platform. Methods A total of 94,402 lymphocyte subset test results were collected. To establish the limited-range rules, 80,427 results were first used (69,135 T lymphocyte subset tests and 11,292 NK, B, T lymphocyte tests), of which 15,000 T lymphocyte subset tests from human immunodeficiency virus (HIV) infected patients were used to set customized limited-range rules for HIV infected patients. Subsequently, 13,975 results were used for historical data validation and online test validation. Results Three key autoverification rules were established, including limited-range, delta-check, and logical rules. Guidelines for addressing the issues that trigger these rules were summarized. The historical data during the validation phase showed that the total autoverification passing rate of lymphocyte subset assays was 69.65% (6,941/9,966), with a 67.93% (5,268/7,755) passing rate for T lymphocyte subset tests and 75.67% (1,673/2,211) for NK, B, T lymphocyte tests. For online test validation, the total autoverification passing rate was 75.26% (3,017/4,009), with 73.23% (2,191/2,992) for the T lymphocyte subset test and 81.22% (826/1,017) for the NK, B, T lymphocyte test. The turnaround time (TAT) was reduced from 228 to 167 min using the autoverification system. Conclusions The autoverification system based on the laboratory information system for lymphocyte subset assays reduced TAT and the number of error reports and helped in the identification of abnormal cell populations that may offer clues for clinical interventions.

Cancer Diagnostics

Open Access October 25, 2021

Comparison of the QuikRead go^® point-of-care faecal immunochemical test for haemoglobin with the FOB Gold Wide^® laboratory analyser to diagnose colorectal cancer in symptomatic patients

William Maclean, Zahida Zahoor, Shane O’Driscoll, Carolyn Piggott, Martin B. Whyte, Timothy Rockall, Iain Jourdan, Sally C. Benton

Page range: 101-108

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Abstract

Objectives Faecal immunochemical testing for haemoglobin (FIT) is used to triage patients for colonic investigations. Point-of-care (POC) FIT devices on the market have limited data for their diagnostic accuracy for colorectal cancer (CRC). Here, a POC FIT device is compared with a laboratory-based FIT system using patient collected samples from the urgent referral pathway for suspected CRC. Methods A prospective, observational cohort study. Patients collected two samples from the same stool. These were measured by POC QuikRead go ® (Aidian Oy, Espoo, Finland) and laboratory-based FOB Gold Wide ® (Sentinel Diagnostics, Italy). Faecal haemoglobin <10 μg haemoglobin/g of faeces was considered as negative. At this threshold, comparisons between the two systems were made by calculating percentage agreement and Cohen’s kappa coefficient. Proportion of negative results were compared with Chi squared testing. Sensitivities for CRC were calculated. Results A total of 629 included patients provided paired samples for FIT to compare the QuikRead go ® and FOB Gold Wide ® . The agreement around the negative threshold was 83.0% and Cohen’s kappa coefficient was 0.54. The QuikRead go ® reported 440/629 (70.0% of samples) as negative compared to 523/629 (83.1%) for the FOB Gold Wide ® , this difference was significant (p-value<0.001). Sensitivities for CRC detection by the QuikRead go ® and FOB Gold Wide ® were 92.9% (95% confidence interval (CI): 68.5–98.7%) and 100% (CI: 78.5–100%) respectively. Conclusions Both systems were accurate in their ability to detect CRC. Whilst good agreement around the negative threshold was identified, more patients would be triaged to further colonic investigation if using the QuikRead go ® .

October 25, 2021

Evaluation of circulating Dickkopf-1 as a prognostic biomarker in ovarian cancer patients

Daniel Martin Klotz, Theresa Link, Maren Goeckenjan, Pauline Wimberger, Anna R. Poetsch, Nikolai Jaschke, Lorenz C. Hofbauer, Andy Göbel, Tilman D. Rachner, Jan Dominik Kuhlmann

Page range: 109-117

Abstract

Objectives Dickkopf-1 (DKK1) is a secreted protein, known for suppressing the differentiation and activity of bone-building osteoblasts by acting as an inhibitor of Wnt-signalling. Soluble DKK1 (sDKK1) has been proposed as prognostic biomarker for a wide range of malignancies, however, clinical relevance of sDKK1 as potential blood-based marker for ovarian cancer is unknown. Methods sDKK1 levels were quantified in a cohort of 150 clinically documented ovarian cancer patients by a commercially available DKK1 ELISA (Biomedica, Vienna, Austria). Results Median sDKK1 level was significantly elevated at primary diagnosis of ovarian cancer compared to healthy controls (estimated difference (ED) of 7.75 ng/mL (95% CI: 3.01–12.30 ng/mL, p=0.001)). Higher levels of sDKK1 at diagnosis indicated an increased volume of intraoperative malignant ascites (ED 7.08 pmol/L, 95% CI: 1.46–13.05, p=0.02) and predicted suboptimal debulking surgery (ED 6.88 pmol/L, 95% CI: 1.73–11.87, p=0.01). sDKK1 did not correlate with CA125 and higher sDKK1 levels predicted a higher risk of recurrence and poor survival (PFS: HR=0.507, 95% CI: 0.317–0.809; p=0.004; OS: HR=0.561, 95% CI: 0.320–0.986; p=0.044). Prognostic relevance of sDKK1 was partly sustained in wt BRCA patients (PFS: HR=0.507, 95% CI: 0.317–0.809; p=0.004). Conclusions This is the first study demonstrating the prognostic relevance of sDKK1 in ovarian cancer patients, including those with wt BRCA 1/2 status. Our data encourage further evaluation of sDKK1 in ovarian cancer patients, possibly in terms of a therapy monitoring marker or a response predictor for sDKK1-directed targeted therapies.

Cardiovascular Diseases

Open Access November 1, 2021

Soluble CD40 ligand and outcome in patients with coronary artery disease undergoing percutaneous coronary intervention

Fabio Angeli, Paolo Verdecchia, Stefano Savonitto, Sara Cavallini, Andrea Santucci, Stefano Coiro, Rocco Sclafani, Clara Riccini, Stefano De Servi, Claudio Cavallini

Page range: 118-126

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Abstract

Objectives CD40 ligand (CD40L), a transmembrane glycoprotein belonging to the tumor necrosis factor family and expressed by a variety of cells, is involved in the basic mechanisms of inflammation, atherosclerosis and thrombosis. Some studies suggest that the soluble form of CD40L (sCD40L) is a predictor of major cardiovascular events and mortality in a variety of clinical settings, but data from literature are conflicting. Methods We studied consecutive patients with acute (ACS) or chronic (CCS) coronary syndrome who underwent percutaneous coronary artery intervention (PCI). Blood samples for sCD40L dosage were taken at baseline immediately before PCI. We tested the relation between sCD40L and pre-specified outcome measures consisting of new ACS, clinical restenosis and all-cause mortality. We recruited 3,841 patients (mean age 64 ± 11 years, 79% men) with ACS (n=2,383) or CCS (n=1,458). Results During a mean follow-up of two years (±0.6 years), 642 patients developed ACS, 409 developed restenosis (≥70% of at least one of the previously treated coronary segments) and 175 died. For each 1-standard deviation increase in sCD40L (0.80 ng/mL), the hazard ratios (HRs) for ACS, restenosis, and mortality were 1.11 (95% confidence interval [CI]: 1.05 to 1.18, p<0.0001), 1.10 (95% CI: 1.02 to 1.19, p=0.010), and 1.00 (95% CI: 0.86 to 1.16, p=0.983), respectively. In multivariable Cox regression models with adjustment for several potential confounders including age, acute or chronic coronary syndrome, multi-vessel disease, stent placement, diabetes, previous coronary events and dyslipidemia, sCD40L remained an independent predictor of ACS and coronary restenosis. There were no interactions between sCD40L and acute or chronic coronary syndrome or stent placement. Conclusions Among patients with ACS or CCS who undergo PCI, higher levels of sCD40L predict an increased risk of acute coronary events and coronary restenosis, but not of mortality.

Diabetes

September 6, 2021

Lot variation and inter-device differences contribute to poor analytical performance of the DCA Vantage™ HbA_1c POCT instrument in a true clinical setting

Anders Abildgaard, Cindy Søndersø Knudsen, Lise Nørkjær Bjerg, Sten Lund, Julie Støy

Page range: 127-134

Abstract

Objectives The glycated haemoglobin fraction A 1c (HbA 1c ) is widely used in the management of diabetes mellitus, and the Siemens DCA Vantage™ point-of-care testing (POCT) instrument offers rapid HbA 1c results even far from a clinical laboratory. However, the analytical performance has been questioned, and not much is known about effects of changing reagent lot, instrument and operator. We therefore compared the analytical performance of the DCA Vantage™ with established routine methods (Tosoh G8/G11 ion exchange HPLC) in a true clinical setting at two Danish hospitals. Methods We extracted all routine clinical HbA 1c results incidentally drawn from the same patient within 48 h (n=960 pairs) and evaluated the effect of reagent lot, operator and instrument. We also performed a prospective method comparison in our diabetes out-patient clinic (n=97). Results The critical difference (CD) between two POCT results varied between 5.14 and 6.61 mmol/mol (0.47–0.55%), and the analytical imprecision of the DCA Vantage™ (CV A ) was >3%. Significant effect of reagent lot and inter-instrument differences were found, whereas no effect of operator was seen. Conclusions The DCA Vantage™ HbA 1c analysis does not fulfil the prevailing analytical performance specifications, but rigorous validation of new reagent lots and continuous recalibration of instruments may potentially improve the precision substantially. Our findings, therefore, clearly emphasise the necessity of a close collaboration between clinicians and laboratory professionals in the POCT field. Finally, POCT HbA 1c results should always be interpreted together with other measures of glycaemic control to avoid inappropriate change of patient treatments due to measurement uncertainty.

Infectious Diseases

Open Access October 25, 2021

Lipase elevation in serum of COVID-19 patients: frequency, extent of increase and clinical value

Simone Caruso, Elena Aloisio, Alberto Dolci, Mauro Panteghini

Page range: 135-142

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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.

Acknowledgment

Publicly Available November 5, 2021

Acknowledgment

Page range: 143-148

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Letters to the Editors

Publicly Available September 2, 2021

Presepsin value predicts the risk of developing severe/critical COVID-19 illness: results of a pooled analysis

Giuseppe Lippi, Fabian Sanchis-Gomar, Brandon M. Henry

Page range: e1-e3

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Publicly Available September 2, 2021

Measuring accuracy of the neutralizing activity of COVID-19 convalescent plasma

Massimo Franchini, Carlo Mengoli, Beatrice Caruso, Roberto Petilino, Alessia Ballotari, Claudia Glingani

Page range: e4-e6

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September 17, 2021

Evaluation of reference intervals for classical and alternative pathway functional complement assays

Sara Capiau, Joris R. Delanghe, Pieter M. De Kesel

Page range: e7-e9

August 27, 2021

Reference values for plasma neurofilament light chain in healthy Chinese children

Jianing Jin, Yiqin Cui, Yi Hong, Dongming Zhou, Ni He, Zhifeng Mao, Shanshan Mao

Page range: e10-e12

September 15, 2021

Cerebrospinal fluid neurogranin in Alzheimer’s disease studies: are immunoassay results interchangeable?

Clément Aveneau, Claire Hourregue, Emmanuel Cognat, Julien Dumurgier, Hugo Vanderstichele, Eugeen Vanmechelen, Henrik Zetterberg, Jacques Hugon, Kaj Blennow, Claire Paquet, Elodie Bouaziz-Amar

Page range: e13-e17

Open Access September 1, 2021

Pepsin pretreatment corrects underestimation of 25-hydroxyvitamin D measurement by an automated immunoassay in subjects with high vitamin D binding protein levels

Anneke C. Muller Kobold, Ido P. Kema, Janneke Dijck-Brouwer, Karin Koerts, Michiel Weening, Twan Storteboom, Jenny E. Kootstra-Ros, Martijn van Faassen, Ineke J. Riphagen

Page range: e18-e20

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September 6, 2021

A conspicuous reduced plasma creatinine: the first presenting sign of Waldenstrom macroglobulinemia

Wilma Potze, Michel J. Vos, Henk Engel, Joan Doornebal

Page range: e21-e24

September 17, 2021

Effect of non-linearity on rheumatoid factor assay in Beckman system IMMAGE800

Huaizhou Wang, Yi Zhou, Liling Lin, Rongrong Zhu, ChengWen He, Yanghua Qin

Page range: e25-e27

About this journal

Objective
Clinical Chemistry and Laboratory Medicine (CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. It is focused on basic and applied research and cutting-edge clinical laboratory medicine. CCLM is one of the leading journals in the field, with an impact factor over 8. All contributions submitted for publication in CCLM are single-blind peer reviewed by at least two experts in the field. CCLM is led by a multi-institutional editorial board. It is issued monthly, both in print and electronically. Letters to the Editor and Congress Abstracts are published online only.

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Topics

clinical biochemistry
clinical genomics and molecular biology
clinical haematology and coagulation
clinical immunology and autoimmunity
clinical microbiology
drug monitoring and analysis
evaluation of diagnostic biomarkers
disease-oriented topics (cardiovascular disease, cancer diagnostics, diabetes)
new reagents, instrumentation and technologies
new methodologies
reference materials and methods
reference values and decision limits
quality and safety in laboratory medicine
translational laboratory medicine
clinical metrology

Article formats
Research Articles, Reviews, Mini Reviews and Opinion Papers on all aspects of clinical chemistry and laboratory medicine, Guidelines and Recommendations, Point/Counterpoint Articles, Letters to the Editor, Editorials

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Volume 60 Issue 1

Issue of Clinical Chemistry and Laboratory Medicine (CCLM)

Frontmatter

EU health policy is on the brink of a spectacular own-goal that will harm patients and hamper innovation

Theranos revisited: the trial and lessons learned

Review and evolution of guidelines for diagnosis of COVID-19 vaccine induced thrombotic thrombocytopenia (VITT)

Abstract

High-sensitivity cardiac troponins in pediatric population

Abstract

Implementation of the new EU IVD regulation – urgent initiatives are needed to avert impending crisis

Abstract

Exploration of novel biomarkers for hypertensive disorders of pregnancy by comprehensive analysis of peptide fragments in blood: their potential and technologies supporting quantification

Abstract

Total lab automation: sample stability of clinical chemistry parameters in an automated storage and retrieval module

Abstract

Instability of corticotropin during long-term storage – myth or reality?

Abstract

External quality assessment of serum indices: Spanish SEQC-ML program

Abstract

Comparison of two LC-MS/MS methods for the quantification of 24,25-dihydroxyvitamin D3 in patients and external quality assurance samples

Abstract

Isotope dilution LC-MS/MS quantification of the cystic fibrosis transmembrane conductance regulator (CFTR) modulators ivacaftor, lumacaftor, tezacaftor, elexacaftor, and their major metabolites in human serum

Abstract

The development of autoverification system of lymphocyte subset assays on the flow cytometry platform

Abstract

Comparison of the QuikRead go® point-of-care faecal immunochemical test for haemoglobin with the FOB Gold Wide® laboratory analyser to diagnose colorectal cancer in symptomatic patients

Abstract

Evaluation of circulating Dickkopf-1 as a prognostic biomarker in ovarian cancer patients

Abstract

Soluble CD40 ligand and outcome in patients with coronary artery disease undergoing percutaneous coronary intervention

Abstract

Lot variation and inter-device differences contribute to poor analytical performance of the DCA Vantage™ HbA1c POCT instrument in a true clinical setting

Abstract

Lipase elevation in serum of COVID-19 patients: frequency, extent of increase and clinical value

Abstract

Acknowledgment

Presepsin value predicts the risk of developing severe/critical COVID-19 illness: results of a pooled analysis

Measuring accuracy of the neutralizing activity of COVID-19 convalescent plasma

Evaluation of reference intervals for classical and alternative pathway functional complement assays

Reference values for plasma neurofilament light chain in healthy Chinese children

Cerebrospinal fluid neurogranin in Alzheimer’s disease studies: are immunoassay results interchangeable?

Pepsin pretreatment corrects underestimation of 25-hydroxyvitamin D measurement by an automated immunoassay in subjects with high vitamin D binding protein levels

A conspicuous reduced plasma creatinine: the first presenting sign of Waldenstrom macroglobulinemia

Effect of non-linearity on rheumatoid factor assay in Beckman system IMMAGE800

Comparison of the QuikRead go^® point-of-care faecal immunochemical test for haemoglobin with the FOB Gold Wide^® laboratory analyser to diagnose colorectal cancer in symptomatic patients

Lot variation and inter-device differences contribute to poor analytical performance of the DCA Vantage™ HbA_1c POCT instrument in a true clinical setting