Glycosylation is one of the most common posttranslational modifications of proteins and lipids. In the case of tumors, cell transformation accompanied by aberrant glycosylation results in the expression of tumor-associated glycans that promote tumor invasion. As part of the innate immunity, anti-glycan antibodies recognize tumor-associated glycans, and these antibodies can be present in the bloodstream in the early stages of cancer. Recently, anti-glycan antibody profiles have been of interest in various cancer studies. Novel advantages in the field of analytical techniques have simplified the analysis of anti-glycan antibodies and made it easier to have more comprehensive knowledge about their functions. One of the robust approaches for studying anti-glycan antibodies engages in microarray technology. The analysis of glycan microarrays can provide more expanded information to simultaneously specify or suggest the role of antibodies to a wide variety of glycans in the progression of different diseases, therefore making it possible to identify new biomarkers for diagnosing cancer and/or the state of the disease. Thus, in this review, we discuss antibodies to various glycans, their application for diagnosing cancer and one of the most promising tools for the investigation of these molecules, microarrays.

Mini Review

April 25, 2020

Detection of circulating anti-skin antibodies by indirect immunofluorescence and by ELISA: a comparative systematic review and meta-analysis

Otto Van de gaer, Petra de Haes, Xavier Bossuyt

Page range: 1623-1633

Abstract

Background Both enzyme-linked immunosorbent assays (ELISAs) and indirect immunofluorescence (IIF) are available for the diagnosis of autoimmune bullous diseases (AIBD). Many studies have reported on the performance of ELISAs and concluded that ELISAs could replace IIF. This study compares the diagnostic accuracy of ELISA and IIF for the detection of autoantibodies to desmoglein 1 (DSG1), desmoglein 3 (DSG3), bullous pemphigoid antigen 2 (BP180) and bullous pemphigoid antigen 1 (BP230) to support the diagnosis of pemphigus vulgaris (PV), pemphigus foliaceus (PF) and bullous pemphigoid (BP). Methods A literature search was performed in the PubMed database. The meta-analysis was performed using summary values and a bivariate random effect model. Results The five included studies on PV did not demonstrate significant differences between IIF and DSG3-ELISA (sensitivity 82.3% vs. 81.6%, p = 0.9284; specificity 95.6% vs. 93.9%, p = 0.5318; diagnostic odds ratio [DOR] 101.60 vs. 67.760, p = 0.6206). The three included studies on PF did not demonstrate significant differences between IIF and DSG1-ELISA (sensitivity 80.6% vs. 83.1%, p = 0.8501; specificity 97.5% vs. 93.9%, p = 0.3614; DOR 160.72 vs. 75.615, p = 0.5381). The eight included studies on BP showed that BP230-ELISA differed significantly from both IIF on monkey esophagus (MO) and BP180-ELISA with regard to DOR (11.384 vs. 68.349, p = 0.0008; 11.384 vs. 41.699, p = 0.0125, respectively) Conclusions Our meta-analysis shows that ELISA performs as well as IIF for diagnosing PV, PF and BP.

Opinion Papers

April 13, 2020

The shift of the paradigm between ageing and diseases

Francesco Salvatore

Page range: 1635-1644

Abstract

In the area of the Medical Sciences, the chronological age has always been, and still is, an indicator by which we try to understand the health status of an individual. However, besides considering people born with an already expressed disease, each human genome has sequence alterations called predisposing mutations; carriers of such genetic alterations have an increased risk of contracting diseases during their life. In addition, the exposome, i.e. the totality of environmental noxae (“hits”) to which our body is exposed throughout life (through ingestion, breathing, body surface hits, and psychosociological stress agents, etc.) contributes to increase gradually but inexorably the frailty of an organism, and this process is usually referred to as “physiological ageing”. This position paper proposes that we invert our visual angle and view the passage-of-time not as the cause of diseases, but consider the genome alterations present at birth and the noxae received during our life as the real major causes of ageing. The Biomedical Sciences are now increasingly unraveling the etiopathogenesis of most chronic degenerative diseases; thus, it will be possible to monitor and treat those that most contribute to the increased frailty of each person, which is now referred to with the misnomer “physiological ageing”. These concepts are not banal; indeed, they imply that we must try to avoid the causes of alterations that result later in chronic degenerative diseases. Thus, we should shift our attention from the cure to the prevention of alterations/diseases also to improve both the length and quality of our life. Moreover, this approach involves real personalized or individualized medicine, thus conferring a more direct benefit to each of us by finalizing either the cure or the monitoring of diseases.

Publicly Available July 20, 2020

Managing COVID-19 outbreak in Nigeria: matters arising

Augustine Anayochukwu Onyeaghala, Isiramen Olajide

Page range: 1645-1650

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Abstract

Severe Acute Respiratory Syndrome – novel Coronavirus 2 (SARS-nCoV-2), was first reported in Wuhan, China, in December, 2019. Since the outbreak, the virus has infected more than 9,866,685 individuals, 4,983,029 treated and discharged and 495,692 deaths globally. The first Coronavirus Disease 2019 (COVID-19) in Nigeria was imported in February, 2020 and since then community transmission has been prevalent. As at the time of writing this report, Nigeria has reported about 23,298 cases of COVID-19, 8,253 treated and discharged and 554 deaths, giving a case mortality ratio of 2.4%. While responsible government agencies and international partners have been working hard to curtail the spread of the disease, we present in this report, some matters arising from managing COVID-19 pandemic in Nigeria; and proffered suggestions which could help not only in managing the current COVID-19 pandemic, but also for winning future outbreaks of public health significance with a view to curtailing global health security.

March 11, 2020

Circulating tumor DNA (ctDNA) is not a good proxy for liquid biopsies of tumor tissues for early detection

Clare Fiala, Eleftherios P. Diamandis

Page range: 1651-1653

Abstract

The important conclusion that ctDNA is a mediocre proxy for liquid biopsies of tumor tissues for early detection was reached after new data were published recently in Nature Genetics . These data have shown that most mutations found in ctDNA are not related to tumor tissues but rather to the precancerous condition clonal hematopoiesis. Previously, our group has analyzed the sensitivity of the ctDNA test for early detection of cancer and concluded that the achievable sensitivity, especially for small tumors, is not enough to have clinical value. Now, the new data have shown a serious compromise in specificity. We believe that scientists who are interested in early cancer diagnostics should be aware of the limitations of this test, in both sensitivity and specificity. Our work may prompt further work aiming to alleviate these important issues in the cancer diagnostics field.

General Clinical Chemistry and Laboratory Medicine

Publicly Available June 5, 2020

Exact time of venous blood sample collection – an unresolved issue, on behalf of the European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for Preanalytical Phase (WG-PRE)

Alexander von Meyer, Giuseppe Lippi, Ana-Maria Simundic, Janne Cadamuro

Page range: 1655-1662

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Abstract

Objectives An accurate knowledge of blood collection times is crucial for verifying the stability of laboratory analytes. We therefore aimed to (i) assess if and how this information is collected throughout Europe and (ii) provide a list of potentially available solutions. Methods A survey was issued by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group on Preanalytical Phase (WG-PRE) in 2017, aiming to collect data on preanalytical process management, including sampling time documentation, in European laboratories. A preceding pilot survey was disseminated in Austria in 2016. Additionally, preanalytical experts were surveyed on their local setting on this topic. Finally, the current scientific literature was reviewed on established possibilities of sampling time collection. Results A total number of 85 responses was collected from the pilot survey, whilst 1347 responses from 37 European countries were obtained from the final survey. A minority (i.e. ~13%) of responders to the latter declared they are unaware of the exact sampling time. The corresponding rate in Austria was ~70% in the pilot and ~30% in the final survey, respectively. Answers from 17 preanalytical experts from 16 countries revealed that sampling time collection seems to be better documented for out- than for in-patients. Eight different solutions for sample time documentation are presented. Conclusions The sample collection time seems to be documented very heterogeneously across Europe, or not at all. Here we provide some solutions to this issue and believe that laboratories should urgently aim to implement one of these.

Open Access January 13, 2020

Percentile transformation and recalibration functions allow harmonization of thyroid-stimulating hormone (TSH) immunoassay results

Andrea Padoan, Aldo Clerico, Martina Zaninotto, Tommaso Trenti, Renato Tozzoli, Rosalia Aloe, Antonio Alfano, Sara Rizzardi, Ruggero Dittadi, Marco Migliardi, Marcello Bagnasco, Mario Plebani

Page range: 1663-1672

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Abstract

Background The comparability of thyroid-stimulating hormone (TSH) results cannot be easily obtained using SI-traceable reference measurement procedures (RPMs) or reference materials, whilst harmonization is more feasible. The aim of this study was to identify and validate a new approach for the harmonization of TSH results. Methods Percentile normalization was applied to 125,419 TSH results, obtained from seven laboratories using three immunoassays (Access 3rd IS Thyrotropin, Beckman Coulter Diagnostics; Architect System, Abbott Diagnostics and Elecsys, Roche Diagnostics). Recalibration equations (RCAL) were derived by robust regressions using bootstrapped distribution. Two datasets, the first of 119 EQAs, the second of 610, 638 and 639 results from Access, Architect and Elecsys TSH results, respectively, were used to validate RCAL. A dataset of 142,821 TSH values was used to derive reference intervals (RIs) after applying RCAL. Results Access, Abbott and Elecsys TSH distributions were significantly different (p < 0.001). RCAL intercepts and slopes were −0.003 and 0.984 for Access, 0.032 and 1.041 for Architect, −0.031 and 1.003 for Elecsys, respectively. Validation using EQAs showed that before and after RCAL, the coefficients of variation (CVs) or among-assay results decreased from 10.72% to 8.16%. The second validation dataset was used to test RCALs. The median of between-assay differences ranged from −0.0053 to 0.1955 mIU/L of TSH. Elecsys recalibrated to Access (and vice-versa) showed non-significant difference. TSH RI after RCAL resulted in 0.37–5.11 mIU/L overall, 0.49–4.96 mIU/L for females and 0.40–4.92 mIU/L for males. A significant difference across age classes was identified. Conclusions Percentile normalization and robust regression are valuable tools for deriving RCALs and harmonizing TSH values.

November 29, 2019

Interference of anti-streptavidin antibodies in immunoassays: a very rare phenomenon or a more common finding?

Nick Verougstraete, Mario Berth, Mario Vaneechoutte, Joris Delanghe, Nico Callewaert

Page range: 1673-1680

Abstract

Background Anti-streptavidin antibodies (ASA) may cause analytical interference on certain immunoassay platforms. Streptavidin is purified from the non-pathogenic Streptomyces avidinii soil bacterium. In contrast to interference with biotin, ASA interference is supposed to be much rarer. In-depth studies on this topic are lacking. Therefore, we carried out an analysis toward the prevalence and the possible underlying cause of this interference. Methods Anti-streptavidin (AS)-immunoglobulin G (IgG) and AS-IgM concentrations were determined on multiple samples from two patients with ASA interference and on 500 random samples. On a subset of 100 samples, thyroid-stimulating hormone (TSH) was measured on a Cobas analyzer before and after performing a neutralization protocol which removes ASA. The relationship between the ratio of TSH after neutralization/TSH before neutralization and the ASA concentration was evaluated. Subsequently, an extract of S. avidinii colonies was analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Results A positive correlation between AS-IgM concentrations and TSH ratio was obtained. Eight samples out of 500 exceeded the calculated AS-IgM cut-off value. In comparison to the AS-IgM concentrations in the population, titers from the two described cases clearly stood out. The isolated cases represent the end of a broader spectrum as there is a continuum of AS-IgM reactivity in the general population. We could not observe any differences in the immunoblot patterns between the cases and controls, which may indicate the general presence of ASA in the population. Conclusions Interference due to ASA is more prevalent than initially thought and is caused by IgM antibodies.

Open Access April 22, 2020

Blood sampling for metanephrines comparing venipuncture vs. indwelling intravenous cannula in healthy subjects

Karin Eijkelenkamp, Eva H. van Geel, Michiel N. Kerstens, Martijn van Faassen, Ido P. Kema, Thera P. Links, Anouk N.A. van der Horst-Schrivers

Page range: 1681-1686

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Abstract

Background To diagnose pheochromocytoma or sympathetic paraganglioma, guidelines recommend blood sampling after at least 30 min of supine rest and using an indwelling intravenous cannula is preferred. Although blood sampling by venipuncture is more convenient and cost-effective, it is unknown whether venipuncture affects plasma concentrations of free metanephrines (MNs). We therefore investigated whether there is a difference in plasma concentrations of free MNs collected by venipuncture or by an intravenous cannula. Methods We included 22 healthy participants (12 men and 10 women, median age 26 years). We collected blood using an indwelling cannula and venipuncture to determine plasma concentrations of free MNs and catecholamines, and calculated the median of the individually calculated absolute and relative differences. Results Plasma concentrations of free MN, normetanephrine (NMN) and epinephrine were higher with blood sampling using venipuncture compared to that when using an indwelling cannula. The median (interquartile range [IQR]) difference was MN 0.020 (−0.004 to 0.040) nmol/L, median percentage difference 20.5% (−2.4 to 35.2%), NMN 0.019 (−0.004 to 0.077) nmol/L, median percentage difference 4.6% (−1.1 to 25.4%) and epinephrine 0.022 (0.007–0.079) nmol/L, median percentage difference 24.9% (7.8–83.3%). When the two sampling conditions were compared, plasma-free 3-methoxytyramine (3-MT), norepinephrine and dopamine concentrations did not differ. Conclusions Blood sampling by venipuncture resulted in statistically significant higher concentrations of MN, NMN and epinephrine compared to sampling by means of an indwelling cannula. However, differences were small. For most patients it seems justifiable to collect blood via venipuncture.

Open Access May 15, 2020

Volumetric absorptive microsampling and dried blood spot microsampling vs. conventional venous sampling for tacrolimus trough concentration monitoring

Herman Veenhof, Remco A. Koster, Lenneke A.T. Junier, Stefan P. Berger, Stephan J.L. Bakker, Daan J. Touw

Page range: 1687-1695

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Abstract

Objectives Monitoring tacrolimus blood concentrations is important for preventing allograft rejection in transplant patients. Our hospital offers dried blood spot (DBS) sampling, giving patients the opportunity to sample a drop of blood from a fingerprick at home, which can be sent to the laboratory by mail. In this study, both a volumetric absorptive microsampling (VAMS) device and DBS sampling were compared to venous whole blood (WB) sampling. Methods A total of 130 matched fingerprick VAMS, fingerprick DBS and venous WB samples were obtained from 107 different kidney transplant patients by trained phlebotomists for method comparison using Passing-Bablok regression. Bias was assessed using Bland-Altman. A multidisciplinary team pre-defined an acceptance limit requiring >80% of all matched samples within 15% of the mean of both samples. Sampling quality was evaluated for both VAMS and DBS samples. Results 32.3% of the VAMS samples and 6.2% of the DBS samples were of insufficient quality, leading to 88 matched samples fit for analysis. Passing-Bablok regression showed a significant difference between VAMS and WB, with a slope of 0.88 (95% CI 0.81–0.97) but not for DBS (slope 1.00; 95% CI 0.95–1.04). Both VAMS (after correction for the slope) and DBS showed no significant bias in Bland-Altman analysis. For VAMS and DBS, the acceptance limit was met for 83.0% and 96.6% of the samples, respectively. Conclusions VAMS sampling can replace WB sampling for tacrolimus trough concentration monitoring, but VAMS sampling is currently inferior to DBS sampling, both regarding sample quality and agreement with WB tacrolimus concentrations.

Open Access January 11, 2020

Trueness evaluation and verification of inter-assay agreement of serum folate measuring systems

Federica Braga, Erika Frusciante, Simona Ferraro, Mauro Panteghini

Page range: 1697-1705

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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.

April 10, 2020

Effects of endurance exercise on serum concentration of calcitonin gene-related peptide (CGRP): a potential link between exercise intensity and headache

Cantor Tarperi, Fabian Sanchis-Gomar, Martina Montagnana, Elisa Danese, Gian Luca Salvagno, Matteo Gelati, Kristina Skroce, Federico Schena, Giuseppe Lippi

Page range: 1707-1712

Abstract

Background Calcitonin gene-related peptide (CGRP) is a powerful neuropeptide that is strongly involved in headache pain pathogenesis by triggering vasodilation, mast cell degranulation and neurogenic inflammation. This evidence has prompted us to investigate the acute influence of endurance exercise on CGRP concentration in blood. Methods The study population consisted of 48 male amateur runners, who ran a half-marathon distance at 75%–85% of maximal oxygen uptake. Blood was drawn before the run (pre-run) and immediately after each runner ended his trial (post-run). The serum concentration of CGRP was measured with a commercial enzyme-linked immunosorbent assay (ELISA) technique. Results Overall, 22/48 subjects (45.8%) reported suffering from headache, three of whom (6.2%) had an exertional headache, whilst 26/48 (54.2%) subjects did not report at least one headache episode during the previous 6 months (i.e. headache-free). All 48 athletes successfully covered the 21.1 km distance. Serum concentration of CGRP significantly increased by 1.5-fold in the entire group, as well as in the headache-positive and headache-free cohorts. Univariate Spearman’s correlation revealed that post-run variation of serum CGRP was significantly and inversely associated with running time (r = −0.30; p = 0.036). Conclusions The serum concentration of CGRP is significantly enhanced by medium-distance endurance exercise and the post-exercise increase is dependent on running intensity. Accordingly, high-exercise intensity might be directly related to triggering both exertional headache and/or migraine episodes.

Open Access October 4, 2019

Comprehensive characterization and resolution of discrepant spectrophotometric bilirubin results in patients on eltrombopag therapy

Timothy H.T. Cheng, Teresa K.C. Tsui, Jeffrey S.S. Kwok, Lydia C.W. Lit, Elaine Y.L. Wong, Richard K.T. Kam, Denis Grote-Koska, Antje Staaden, Hitoshi Okada, Noriko Fuke, Raymond S.M. Wong, Chi-Kong Li, Michael H.M. Chan

Page range: 1713-1723

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Abstract

Background Eltrombopag is a thrombopoietin receptor agonist used for the treatment of thrombocytopenic conditions. It can cause pH-dependent discoloration of plasma/serum. Eltrombopag is potentially hepatotoxic. It can affect the assessment of hyperbilirubinemia because of its (i) absorbance at ~450 nm (bilirubin), (ii) absorbance at ~550 nm (diazo-bilirubin) and (iii) it can cause yellowish discoloration of the eyes at normal circulating bilirubin levels. Methods We collected 66 samples from patients on a range of eltrombopag dosages up to 150 mg daily. Bilirubin was measured using multiple routine spectrophotometric analyzers, the Doumas reference method and high-performance liquid chromatography (HPLC). Plasma/serum eltrombopag concentrations were determined using liquid chromatography tandem mass spectrometry (LC-MS/MS). Spike-in and admixture experiments delineated the effects of eltrombopag and its metabolites. Results Forty-nine of 52 samples from patients on ≥50 mg daily eltrombopag therapy showed significantly discrepant inter-analyzer total bilirubin results, a difference up to 64 μmol/L (3.7 mg/dL). In one sample, total bilirubin varied from 8 to 65 μmol/L (0.4–3.8 mg/dL) by different routine analyzers, with direct bilirubin ≤4 μmol/L (0.2 mg/dL). There was a positive correlation between total bilirubin difference and plasma eltrombopag concentration (r = 0.679), and spike-in experiments demonstrated that Beckman AU and Doumas reference methods were susceptible to positive interference. HPLC can quantify bilirubin after separating eltrombopag, and results suggest different analyzers are affected to varying degrees by eltrombopag and its metabolites. Conclusions Eltrombopag and its metabolites can cause positive interference to the spectrophotometric measurements of total bilirubin. Accurate measurements of total bilirubin may improve our understanding of the prevalence of hyperbilirubinemia in patients on eltrombopag therapy.

February 14, 2020

Influence of pancreatic status on circulating plasma sterols in patients with cystic fibrosis

Monica Gelzo, Paola Iacotucci, Concetta Sica, Renato Liguori, Marika Comegna, Vincenzo Carnovale, Antonio Dello Russo, Gaetano Corso, Giuseppe Castaldo

Page range: 1725-1730

Abstract

Background Patients with cystic fibrosis (CF) have a reduced intestinal absorption of cholesterol and in a preliminary study we observed differences in plasma sterol profile between patients with pancreatic sufficiency (PS) and those with pancreatic insufficiency (PI). Therefore, we hypothesized that the sterol analysis may contribute to study the digestion and absorption state of lipids in patients with CF. To this aim we evaluated plasma sterols in a significant number of adult patients with CF in relation to the pancreatic status. Methods Beside cholesterol, we measured phytosterols and lathosterol as markers of intestinal absorption and hepatic biosynthesis, respectively, by gas-chromatography in plasma of adult CF patients with pancreatic sufficiency (PS-CF, n = 57), insufficiency (PI-CF, n = 97) and healthy subjects (control group, CT, n = 71). Results PI-CF patients had cholesterol and phytosterols levels significantly lower than PS-CF and CT (p < 5 × 10 −10 ) suggesting a reduced intestinal absorption of sterols related to PI. Instead, lathosterol was significantly higher in PI-CF patients than PS-CF and CT (p < 0.0003) indicating an enhanced cholesterol biosynthesis. In PI-CF patients, phytosterols positively correlate with vitamin E (p = 0.004). Both the classes of molecules need cholesterol esterase for the intestinal digestion, thus the reduced levels of such lipids in serum from PI-CF patients may depend on a reduced enzyme activity, despite the pancreatic enzyme supplementation in all PI-CF patients. Conclusions A plasma sterols profile may be useful to evaluate the metabolic status of lipids in adult patients with CF and could help to manage the pancreatic enzyme supplementation therapy.

July 22, 2020

Influence of isotopically labeled internal standards on quantification of serum/plasma 17α-hydroxyprogesterone (17OHP) by liquid chromatography mass spectrometry

Tze Ping Loh, Chung Shun Ho, Michaela F. Hartmann, Rosita Zakaria, Clara Wai Shan Lo, Sjoerd van den Berg, Yolanda B. de Rijke, Brian R. Cooke, Kirsten Hoad, Peter Graham, Stephen R. Davies, Lindsey G. Mackay, Stefan A. Wudy, Ronda F. Greaves

Page range: 1731-1739

Abstract

Objectives Our recent survey of 44 mass spectrometry laboratories across 17 countries identified variation in internal standard (IS) choice for the measurement of serum/plasma 17α-hydroxyprogesterone (17OHP) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The choice of IS may contribute to inter-method variations. This study evaluated the effect of two common isotopically labeled IS on the quantification of 17OHP by LC-MS/MS. Methods Three collaborating LC-MS/MS laboratories from Asia, Europe and Australia, who routinely measure serum 17OHP, compared two IS, (1) IsoSciences carbon-13 labeled 17OHP-[2,3,4- 13 C 3 ], and (2) IsoSciences deuterated 17OHP-[2,2,4,6,6,21,21,21- 2 H]. This was performed as part of their routine patient runs using their respective laboratory standard operating procedure. Results The three laboratories measured 99, 89, 95 independent samples, respectively (up to 100 nmol/L) using the 13 C- and 2 H-labeled IS. The slopes of the Passing-Bablok regression ranged 0.98–1.00 (all 95% confidence interval [CI] estimates included the line of identity), and intercept of <0.1 nmol/L. Average percentage differences of −0.04% to −5.4% were observed between the two IS materials, which were less than the optimal bias specification of 7% determined by biological variation, indicating no clinically significant difference. The results of 12 Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) proficiency samples (1–40 nmol/L) measured by the laboratories were all within the RCPAQAP analytical performance specifications for both IS. Conclusions Overall, the comparison between the results of 13 C- and 2 H-labeled IS for 17OHP showed good agreement, and show no clinically significant bias when incorporated into the LC-MS/MS methods employed in the collaborating laboratories.

Reference Values and Biological Variations

Publicly Available April 17, 2020

The European Biological Variation Study (EuBIVAS): weekly biological variation of cardiac troponin I estimated by the use of two different high-sensitivity cardiac troponin I assays

Ferruccio Ceriotti, Jorge Díaz-Garzón Marco, Pilar Fernández-Calle, Alessio Maregnani, Aasne K. Aarsand, Abdurrahman Coskun, Niels Jonker, Sverre Sandberg, Anna Carobene, on behalf of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group on Biological Variation

Page range: 1741-1747

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Abstract

Background Cardiac troponins (cTn) are specific markers for cardiac damage and acute coronary syndromes. The availability of new high-sensitivity assays allows cTn detection in healthy people, thus permitting the estimation of biological variation (BV) of cTn. The knowledge of BV is important to define analytical performance specifications (APS) and reference change values (RCVs). The aim of this study was to estimate the within- and between-subject weekly BV (CV I , CV G ) of cTnI applying two high-sensitivity cTnI assays, using European Biological Variation Study (EuBIVAS) specimens. Methods Thirty-eight men and 53 women underwent weekly fasting blood drawings for 10 consecutive weeks. Duplicate measurements were performed with Singulex Clarity (Singulex, USA) and Siemens Atellica (Siemens Healthineers, Germany). Results cTnI was measurable in 99.4% and 74.3% of the samples with Singulex and Atellica assays, respectively. Concentrations were significantly higher in men than in women with both methods. The CV I estimates with 95% confidence interval (CI) were for Singulex 16.6% (15.6–17.7) and for Atellica 13.8% (12.7–15.0), with the observed difference likely being caused by the different number of measurable samples. No significant CV I differences were observed between men and women. The CV G estimates for women were 40.3% and 36.3%, and for men 65.3% and 36.5% for Singulex and Atellica, respectively. The resulting APS and RCVs were similar for the two methods. Conclusions This is the first study able to estimate cTnI BV for such a large cohort of well-characterized healthy individuals deriving objective APS and RCV values for detecting significant variations in cTnI serial measurements, even within the 99th percentile.

Cardiovascular Diseases

Publicly Available July 6, 2020

Comparison of the diagnostic performance with whole blood and plasma of four rapid antibody tests for SARS-CoV-2

Bram Decru, Jan Van Elslande, Matthias Weemaes, Els Houben, Ine Empsen, Emmanuel André, Marc Van Ranst, Katrien Lagrou, Pieter Vermeersch

Page range: e197-e199

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Infectious Diseases

July 10, 2020

Exploring the possibilities of infrared spectroscopy for urine sediment examination and detection of pathogenic bacteria in urinary tract infections

Mieke Steenbeke, Sander De Bruyne, Jerina Boelens, Matthijs Oyaert, Griet Glorieux, Wim Van Biesen, Jere Linjala, Joris R. Delanghe, Marijn M. Speeckaert

Page range: 1759-1767

Abstract

Objectives In this study, the possibilities of Fourier-transformed infrared spectroscopy (FTIR) for analysis of urine sediments and for detection of bacteria causing urinary tract infections (UTIs) were investigated. Methods Dried urine specimens of control subjects and patients presenting with various nephrological and urological conditions were analysed using mid-infrared spectroscopy (4,000–400 cm −1 ). Urine samples from patients with a UTI were inoculated on a blood agar plate. After drying of the pure bacterial colonies, FTIR was applied and compared with the results obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Chemometric data analysis was used to classify the different species. Results Due to the typical molecular assignments of lipids, proteins, nucleic acids and carbohydrates, FTIR was able to identify bacteria and showed promising results in the detection of proteins, lipids, white and red blood cells, as well as in the identification of crystals. Principal component analysis (PCA) allowed to differentiate between Gram-negative and Gram-positive species and soft independent modelling of class analogy (SIMCA) revealed promising classification ratios between the different pathogens. Conclusions FTIR can be considered as a supplementary method for urine sediment examination and for detection of pathogenic bacteria in UTI.

Letters to the Editors

Open Access July 3, 2020

Towards the rational utilization of SARS-CoV-2 serological tests in clinical practice

Mario Plebani, Andrea Padoan, Laura Sciacovelli, Daniela Basso

Page range: e189-e191

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Publicly Available July 8, 2020

Response of anti-SARS-CoV-2 total antibodies to nucleocapsid antigen in COVID-19 patients: a longitudinal study

Julien Favresse, Christine Eucher, Marc Elsen, Kim Laffineur, Jean-Michel Dogné, Jonathan Douxfils

Page range: e193-e196

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February 7, 2020

Development, optimization and validation of an absolute specific assay for active myeloperoxidase (MPO) and its application in a clinical context: role of MPO specific activity in coronary artery disease

Alessandro Trentini, Valentina Rosta, Savino Spadaro, Tiziana Bellini, Paola Rizzo, Francesco Vieceli Dalla Sega, Angelina Passaro, Giovanni Zuliani, Valentina Gentili, Gianluca Campo, Carlo Cervellati

Page range: 1749-1758

Abstract

Background Myeloperoxidase (MPO) is an enzyme with a recognized prognostic role in coronary artery disease (CAD), which is also emerging as a promising biomarker for cardiac risk stratification. However, the lack of a consensus method for its quantification has hindered its implementation in clinical practice. The aim of our work was to optimize an absolute sensitive assay for active MPO without external standards, to validate the method in the clinical context of CAD patients, and to estimate the enzyme specific activity. Methods In order to determine the MPO concentration using fluorescence readings, this ELISA assay exploits the activity of the enzyme recognized by specific antibodies. The assay was validated in a small cohort of patients that included: healthy subjects (n=60); patients with acute myocardial infarction (AMI, n=25); patients with stable CAD (SCAD, n=25) and a concomitant chronic obstructive pulmonary disease (COPD). Then, total MPO concentration and specific activity (activity/total MPO) were determined. Results The assay showed an intra- and inter-assay coefficient of variation of 5.8% and 10.4%, respectively, with a limit of detection (LoD) of 0.074 μU. Both AMI and SCAD patients had higher active and total MPO than controls (p<0.0001 and p<0.01, respectively). The specific activity of MPO was higher in SCAD patients compared to both controls and AMI (p<0.0001). Conclusions The study presents a robust and sensitive method for assaying MPO activity in biological fluids with low variability. Moreover, the determination of the specific activity could provide novel insight into the role of MPO in cardiovascular diseases (CVDs).

Publicly Available July 8, 2020

The early antibody response to SARS-Cov-2 infection

Ruggero Dittadi, Haleh Afshar, Paolo Carraro

Page range: e201-e203

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Publicly Available July 16, 2020

Laboratory work safety rules and guidelines during COVID-19 pandemic in Polish clinical laboratories – do our laboratories work according to a recent IFCC Taskforce Recommendations?

Milena Małecka, Kinga Ogrodzińska, Gabriela Salczyńska, Olga Ciepiela

Page range: e205-e208

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Publicly Available July 20, 2020

Serum prealbumin deserves more significance in the early triage of COVID-19 patients

Xiao-long Guo, Yan Zhang, Yu-hua Zeng, Feng-ya Zhao, Wei-ping Liu, Li Xiao, Ming-gang Yin, Cheng-li Zhang

Page range: e209-e211

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February 17, 2020

Reference intervals for clinically reportable platelet parameters on the Mindray BC-6800Plus hematology analyzer

Hanah Kim, Mina Hur, Seung-Wan Kim, Hee-Won Moon, Yeo-Min Yun

Page range: e213-e215

March 7, 2020

A new method for monitoring harmonization of laboratory results within EQA schemes

Wim Coucke, Jelena Vlašić Tanasković, Ana Hećimović, Lorena Honović, Snježana Hrabrić Vlah, Goran Ferenčak, Jadranka Vuković Rodríguez, Jasna Leniček Krleža

Page range: e217-e219

March 5, 2020

Potential serum magnesium under request in primary care. Laboratory interventions to identify patients with hypomagnesemia

Maria Salinas, Emilio Flores, Maite López-Garrigós, Francisco Pomares, Rosa Carbonell, Carlos Leiva-Salinas, on behalf of the PRIMLAB working group

Page range: e221-e223

March 11, 2020

Interference from immunocomplexes on a high-sensitivity cardiac troponin T immunoassay

Luca Dalle Carbonare, Michela Pizzini, Valentina Micheletti, Claudia Lo Cascio, Chiara Bovo, Domenico Girelli, Giuseppe Lippi

Page range: e225-e227

January 11, 2020

Interleukin-6 chemiluminescent immunoassay on Lumipulse G600 II: analytical evaluation and comparison with three other laboratory analyzers

Ludovic Glady, Thomas Lavaux, Rim Charchour, Jean-Marc Lacorte, Jean-Marc Lessinger

Page range: e229-e231

November 12, 2019

Detection of Hb Phnom Penh by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry during the measurement of glycated hemoglobin

Anping Xu, Yajun Wang, Jie Li, Weijie Xie, Weidong Chen, Ling Ji

Page range: e233-e235

January 13, 2020

Persistently increased vitamin B12 concentration due to cobalamin macrocomplexes: a case report and review of the literature

José A. Delgado Rodríguez, María I. Pastor García, Josep Miquel Bauça, Ramón Vidal Mullor, Antònia Barceló

Page range: e237-e239

January 11, 2020

Antidepressant use limits serotonin as a marker for neuroendocrine tumor disease activity by lowering of circulating serotonin concentrations

Huub H. van Rossum, Jocelyn Spruit, Catharina M. Korse, Froukje E. de Vries, Margot E.T. Tesselaar

Page range: e241-e243

May 9, 2020

Limitations of rapid diagnostic testing in the work-up of dengue infection – a case report

Shaun S. Tan, Sharon Saw, Gabriel Yan, Ai Teng Chong, Zhixin Yang, Ai Ping Tan, Anantharaman Vathsala, Sunil K. Sethi

Page range: e245-e246

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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