Search

Competing Interests: Conflicto de intereses: Los autores declaran no tener ningún conflicto de intereses.

Objectives: Urinalysis is widely used and is also frequently requested in emergency situations for screening hypovolemia, urinary tract infections, diabetes, ketoacidosis and hematuria. Our aim was to evaluate the impact of reporting urinary sediment in emergency department specimens with the Sysmex UN system., Methods: We evaluated urinalyses requested by the emergency department over a three-month period and examined red blood cell count interference, compared leukocyte esterase dipsticks to cytofluorimetric leukocyte count and nitrites to cytofluorimetric bacterial count. We then examined digital microscopy images to identify additional elements of interest or pathology., Results: We collected 532 cases, 354 with only chemical and cytofluorimetric analysis and 178 with digital microscopy. Automated erythrocyte counting showed a 7 % error rate, mainly false-positive results. Leukocyte esterase had a sensitivity of 88.22 % and specificity of 88.84 % at the lower limit, while nitrites had a sensitivity of 41.06 % and a specificity of 99.38 %. Pathological elements were detected in 126 samples by digital microscopy: 70 had casts, 36 crystals and seven cells with high pathological value., Conclusions: Evaluation of urine sediments by trained specialists can provide potentially important information even in emergency situations, whereby the pre-analytical phase must always be taken into account., Competing Interests: Competing interests: The authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Objectives: Coronavirus disease 2019 (COVID-19) is a life-threatening infectious disorder characterized by a sustained prothrombotic state. Since homocysteine is a potential biomarker of thrombotic diseases, the aim of this article is to provide an updated overview on the possible role played by hyperhomocysteinemia in influencing an unfavorable COVID-19 progression., Methods: We carried out an electronic search in Medline (PubMed interface) using the keywords ("COVID-19" OR "SARS-CoV-2") AND "homocysteine", between 2019 and the present time, with no language restrictions, to identify all articles which explored the concentration of homocysteine in COVID-19 patients with or without unfavorable disease progression., Results: Three studies, totaling 694 hospitalized COVID-19 patients, were included in our systematic review. Overall, the differences between the mean homocysteine values in non-severe vs. severe COVID-19 patients were always positive (i.e., 15.1%, 24.1% and 22.8%, generating a positive weight mean difference of 1.75 μmol/L (95%CI, 1.26-2.25 μmol/L; p=0.011), which translates into a cumulative difference of approximately ∼1.2 μmol/L., Conclusions: Despite the limited evidence that has been garnered so far, increased homocysteine ​​levels may be a potentially useful marker for predicting the risk of unfavorable progression in patients with COVID-19., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Diabetes is one of the most prevalent diseases worldwide, whereby type 1 diabetes mellitus (T1DM) alone involves nearly 15 million patients. Although T1DM and type 2 diabetes mellitus (T2DM) are the most common types, there are other forms of diabetes which may remain often under-diagnosed, or that can be misdiagnosed as being T1DM or T2DM. After an initial diagnostic step, the differential diagnosis among T1DM, T2DM, Maturity-Onset Diabetes of the Young (MODY) and others forms has important implication for both therapeutic and behavioral decisions. Although the criteria used for diagnosing diabetes mellitus are well defined by the guidelines of the American Diabetes Association (ADA), no clear indications are provided on the optimal approach to be followed for classifying diabetes, especially in children. In this circumstance, both routine and genetic blood test may play a pivotal role. Therefore, the purpose of this article is to provide, through a narrative literature review, some elements that may aid accurate diagnosis and classification of diabetes in children and young people.

Objectives: The underlying causes and mechanisms of pre-eclampsia (PE), its exact etiology remains unclear and poorly understood. Hypoxia, ischemia, and oxidative stress induced by free radicals have been associated with development of PE. Ischemia-modified albumin (IMA) is a chemically modified albumin due to oxidative stress. IMA, a serum biomarker of hypoxia, ischemia, and oxidative free radicals is a potential biomarker for PE. The aim of the current proposal was to study serum IMA as a diagnostic biomarker of pre-eclampsia (PE) in pregnant females and to evaluate the correlation between serum IMA and different markers of pre-eclampsia (BP, urinary protein, LFT, KFT, serum total protein & uric acid)., Methods: A total of 60 pregnant women aged between 21 and 35 years were recruited (30 PE cases and 30 normal pregnancy). Serum IMA was measured by spectrophotometric method developed by Bar-Or D. BP and biochemical parameters (urinary protein, LFT, KFT, serum total protein & uric acid) were also assayed and compared between two groups. Correlation analysis was done for analyzing the relationship between serum IMA and biochemical parameters., Results: The mean serum IMA was significantly higher in normotensive pregnant females (0.93 ABSU) than PE cases (0.71 ABSU). Kidney function and liver function parameters were more deranged in PE cases than in controls. Serum IMA was positively correlated with serum creatinine (r=0.322), serum uric acid (r=0.54) and urinary protein (0.376) whereas negatively correlated with total serum bilirubin (r=-0.515) and serum albumin (r=-0.380)., Conclusions: Elevated serum IMA concentrations in normotensive pregnant controls as compared to PE cases suggest that apart from ongoing ischemia and oxidative stress in placenta IMA values are influenced by many other mechanisms in pregnancy., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: The effect of radiofrequency exposure on human health and health care equipment is a matter of ongoing debate. This study was planned to investigate the influence of radiofrequency (RF) waves emitted by a commercial mobile phone on red blood cells (RBC) in vitro., Methods: The study population consisted of 16 ostensibly healthy volunteers. Two whole blood specimens were collected from each volunteer. One sample was placed in a plastic rack, 1 cm distant from the chassis of a commercial mobile phone which was activated by a remote phone call lasting 30 min. The other blood sample was placed in another plastic rack, but was kept distant from any type of RF source. The main RBC parameters including RBC count, hematocrit (Ht), hemoglobin, mean corpuscular platelet volume (MPV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and RBC distribution width (RDW-CV) were assessed with an Advia 2120., Results: The exposure of whole blood to the mobile phone call significantly increased Ht, hemoglobin, MCV and MCH, whereas the RBC count, MCHC and RDW-CV remained unchanged. A significant correlation was observed between variation of Ht and those of hemoglobin (p=0.008), MCV (p=0.009) or MCH (p=0.037), as well as between hemoglobin and MCV (p=0.048). Increased values were found in 13/16 (81%) samples for both Ht and hemoglobin, 14/16 (88%) samples for MCH and 16/16 (100%) samples for MCV., Conclusions: These results suggest that close mobile phone exposure may be an unappreciated and possibly underestimated cause of preanalytical bias in RBC testing.

Fecal immunochemical tests (FIT) for hemoglobin are currently considered the screening investigation of choice for colorectal cancer and are worldwide recommended. Similarly, fecal calprotectin is a widely used test for monitoring intestinal inflammation. The pre-analytical issues regarding stool samples have hardly been dealt with and are difficult to solve. Currently, there are no reference analytes available which allow to correct test results for the variable water content of the stool sample. Studies on preanalytics of stool samples have generally focused on sample preparation and sample storage, but generally have paid little attention to the variability in sample hydration and sample composition. Stercobilin is a stable heme metabolite which is abundant in stool. Stercobilin concentration can be simply assayed in stool extracts using colorimetry (determination of the I index). Serum indices (H, I and L) and bilirubin concentration of fecal extracts were determined on a Atellica Platform (Siemens). The inter-individual variation of stercobilin was found to be high. Assaying stercobilin allows to correct for stool sample dilution. The median value of the I-index was used as a reference for correcting the data. Correcting fecal blood results for sample dilution resulted in a significant increase in positive tests (from 9.3 to 11.7 %). For calprotectin, correction resulted in 3.1 % extra positive results and 7.7 % negative results. Except in the case of obstructive jaundice, this correction can be applied. Correcting test results of common fecal analytes like FIT and calprotectin may result in a better tailored test interpretation. [ABSTRACT FROM AUTHOR]

Venous blood collection systems (VBCSs) are combinations of in-vitro diagnostics and medical devices, usually available as integrated set. However, purchasing and using a combination of devices from different sets is considered by clinical laboratories as an option to achieve specific sampling tasks or reduce costs. This systematic review aimed to retrieve available evidence regarding safety, efficacy, and economic aspects of VBCSs, focusing on differences between integrated and combined systems. The literature review was carried out in PubMed. Cited documents and resources made available by scientific organisations were also screened. Extracted evidence was clustered according to Quality/Efficacy/Performance, Safety, and Costs/Procurement domains and discussed in the current European regulatory framework. Twenty documents published between 2010 and 2021 were included. There was no evidence to suggest equivalence between combined and integrated VBCSs in terms of safety and efficacy. Scientific society's consensus documents and product standards report that combined VBCS can impact operators' and patients' safety. Analytical performances and overall efficacy of combined VBCSs are not guaranteed without whole system validation and verification. EU regulatory framework clearly allocates responsibilities for the validation and verification of an integrated VBCS, but not for combined VBCSs, lacking information about the management of product nonconformities and post-market surveillance. Laboratory validation of combined VBCS demands risk-benefit and cost-benefit analyses, a non-negligible organisational and economic burden, and investment in knowledge acquisition. Implications in terms of laboratory responsibility and legal liability should be part of a comprehensive assessment of safety, efficacy, and cost carried out during device procurement. [ABSTRACT FROM AUTHOR]

Objectives: There is limited information on the influence of collecting small amounts of blood on the quality of blood gas analysis. Therefore, the purpose of this study was to investigate the effects of different degrees of underfilling of syringes on test results of venous blood gas analysis., Methods: Venous blood was collected by venipuncture from 19 healthcare workers in three 1.0 mL syringes for blood gas analysis, by manually aspirating different volumes of blood (i.e., 1.0, 0.5 and 0.25 mL). Routine blood gas analysis was then immediately performed with GEM Premier 5,000. The results of the two underfilled syringes were compared with those of the reference syringe filled with appropriate blood volume., Results: The values of most assayed parameters did not differ significantly in the two underfilled syringes. Statistically significant variations were found for lactate, hematocrit and total hemoglobin, the values of which gradually increased as the fill volume diminished, as well as for sodium concentration, which decreased in both insufficiently filled blood gas syringes. The bias was clinically meaningful for lactate in syringe filled with 0.25 mL of blood, and for hematocrit, total hemoglobin and sodium in both syringes containing 0.5 and 0.25 mL of blood., Conclusions: Collection of smaller volumes of venous blood than the specified filling volume in blood gas syringes may have an effect on the quality of some test results, namely lactate, hematocrit, total hemoglobin and sodium. Specific indications must be given for standardizing the volume of blood to be collected within these syringes., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Efficient and timely transportation of clinical samples is pivotal to ensure accurate diagnoses and effective patient care. During the transportation process, preservation of sample integrity is crucial to avoid pre-analytical aberrations on laboratory results. Here, we present a comparative analysis between a two-step Tempus600 hub solution single-tube and a one-step, container-based pneumatic transport system (PTS) from Airco, for the in-house transportation of blood samples. Ten blood samples from healthy volunteers were split in 10 mL collection tubes filled at full or half capacity for transportation with the two PTS (about 250 m). To compare the impact of transportation, markers of hemolysis such as lactate dehydrogenase (LDH), potassium (K+), and the hemolysis index (HI), were determined. Additionally, differences in HI in routine samples and repeated transportation was investigated. To assess and compare the mechanistic impact profiles, we recorded the acceleration profiles of the two PTS using a shock data logger. Transportation using the Tempus600 hub solution resulted in 49 and 46 % higher HI with samples filled to total or half capacity, respectively. Routine samples transported with the Tempus600 hub solution showed a higher median HI by 23 and 33 %. Additionally, shock logger analysis showed an elevated amount of shocks (6.5 fold) and shock intensities (1.8 fold). The Tempus600 hub solution caused an increased number of unreportable LDH or K+ results based on the hemolysis index. However, it was only statistically significant for LDH (p<0.01 and p<0.08) – while the comparisons for K+ were not statistically significant (p<0.28 and p<0.56). [ABSTRACT FROM AUTHOR]

The impact of seven hemoglobin variants (Hb Q-Thailand, Hb G-Honolulu, Hb Ube-2, Hb New York, Hb J-Bangkok, Hb G-Coushatta, and Hb E) on the outcome of HbA1c was investigated for six methods by comparing with liquid chromatography-tandem mass spectrometry (LC/MS/MS) reference method. Twenty-nine normal and 112 variant samples were measured by LC/MS/MS, Sebia Capillarys 3 TERA, Intelligene Biosystems QuanTOF, Premier Hb9210, Arkray HA-8190V, Bio-Rad D-100, and Tosoh G11, then evaluated for correlation, consistency, and mean relative bias among six methods. The lowest biological variation bias of ±2.8 % was an acceptable standard. All methods showed poor correlation and consistency with LC/MS/MS for Hb E. The unacceptable biases were observed for Capillarys 3 TERA (−14.4 to −3.7 % for Hb Q-Thailand, Hb Ube-2, Hb New York, Hb J-Bangkok and Hb E), QuanTOF (−8.3 to −2.9 % for Hb Ube-2, Hb New York and Hb G-Coushatta), Premier Hb9210 (−18.3 to −3.6 % for Hb Q-Thailand, Hb Ube-2, Hb New York, Hb J-Bangkok and Hb E), HA-8190V variant mode (−17.3 to 6.6 % for Hb G-Honolulu, Hb Ube-2, Hb New York, Hb G-Coushatta and Hb E). All variant samples showed larger biases than ±2.8 % comparing HA-8190V fast mode, D-100, and G11 with LC/MS/MS. The accuracy of different HbA1c methods was influenced by some Hb variants, especially Hb Ube-2 and Hb New York. Thus, laboratories need to choose appropriate methods to measure HbA1c with different Hb variants. [ABSTRACT FROM AUTHOR]

Objectives: The measurement of fasting glucose is a common practice for lowering the risk of hyperglycemia before an oral glucose tolerance test (OGTT). In this study we analyze advantages and limitations of near-patient measurement of capillary fasting glucose with a portable glucometer or blood sampling and measurement of plasma glucose with laboratory instrumentation., Methods: The final study population consisted of 241 subjects (mean age: 36 ± 8 years; 97.9 % pregnant women) referred to our local phlebotomy center for an OGTT. Fasting glucose was measured in capillary blood using a near-patient glucometer (glucometer-based strategy) and in plasma with laboratory instrumentation using the hexokinase reference assay (laboratory-based strategy)., Results: The mean turnaround time from sample collection to obtaining the glucose value was longer with the laboratory-based strategy (32 min 8 vs. 8 s). The imprecision of the glucometer was higher than that of the laboratory assay (3.4 vs. 0.8 %). A negative bias of -3.3 % in fasting glucose was found with the glucometer compared to the laboratory measurement. The diagnostic accuracy, sensitivity and specificity of the glucometer for detecting fasting glucose values ≥7.0 mmol/L were 99.2 , 50.0 and 100.0 % compared to the laboratory assay. The glucometer-based strategy had an incremental cost of 0.17€ per patient compared to the laboratory-based strategy., Conclusions: Screening fasting glucose in capillary blood with a near-patient glucometer instead of measuring fasting plasma glucose with laboratory instrumentation allows faster patient management in the phlebotomy center but is associated with higher imprecision, inaccuracy, costs and avoidable finger pricks., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

There is limited information on the influence of collecting small amounts of blood on the quality of blood gas analysis. Therefore, the purpose of this study was to investigate the effects of different degrees of underfilling of syringes on test results of venous blood gas analysis. Venous blood was collected by venipuncture from 19 healthcare workers in three 1.0 mL syringes for blood gas analysis, by manually aspirating different volumes of blood (i.e., 1.0, 0.5 and 0.25 mL). Routine blood gas analysis was then immediately performed with GEM Premier 5,000. The results of the two underfilled syringes were compared with those of the reference syringe filled with appropriate blood volume. The values of most assayed parameters did not differ significantly in the two underfilled syringes. Statistically significant variations were found for lactate, hematocrit and total hemoglobin, the values of which gradually increased as the fill volume diminished, as well as for sodium concentration, which decreased in both insufficiently filled blood gas syringes. The bias was clinically meaningful for lactate in syringe filled with 0.25 mL of blood, and for hematocrit, total hemoglobin and sodium in both syringes containing 0.5 and 0.25 mL of blood. Collection of smaller volumes of venous blood than the specified filling volume in blood gas syringes may have an effect on the quality of some test results, namely lactate, hematocrit, total hemoglobin and sodium. Specific indications must be given for standardizing the volume of blood to be collected within these syringes. [ABSTRACT FROM AUTHOR]

Because there is little published evidence on the effects of incomplete filling of K2EDTA evacuated blood tubes on routine hematological testing, this original study aimed to provide updated information on this preanalytical aspect. The study population consisted of 17 ostensibly healthy volunteers. Blood was drawn by venipuncture with a 10 mL syringe and dispensed in varying amounts (0.2, 0.5, 1.0, 2.0, and 3.0 mL) into 3.0 mL blood tubes containing spray-dried 5.4 mg K2EDTA. All tubes were gently mixed and used to perform routine hematology tests on the Sysmex XN-10. Clinically significant variations were defined when the limits of desirable specifications of bias derived from biologic variation were exceeded. The desirable bias was exceeded in 33 % filled tubes (1.0 mL) for hematocrit and MCV (increased values) and for MCHC (decreased values), while it was exceeded in 17 % filled tubes (0.5 mL) for hemoglobin, hematocrit and MCV (increased values), and for MCHC (decreased values). Finally, the variation of values was higher than the desirable bias for RBC, hemoglobin, hematocrit and MCV (increase), and for MCHC and MPV (decrease) in 7 % filled tubes (0.2 mL). No clinically significant variations were observed in tubes filled up to 67 % of their nominal volume (i.e., 2.0 mL). Consideration should be given to reject spray-dried K2EDTA blood tubes that contain a blood volume <67 % of the nominal fill volume, as biased laboratory data in these samples may interfere with clinical decision making and care management. [ABSTRACT FROM AUTHOR]

In vivo hemolysis is associated with thromboembolism. Although an increased Hemolysis Index (HI) can be due to in vitro as well as in vivo hemolysis, both reflects a more fragile erythrocyte population. We therefore hypothesized that HI above upper reference limit would be associated with an increased risk of cardiovascular disease (CVD). We identified persons with two elevated HI (HI+) from blood samples analyzed at a university hospital laboratory from 2012 to 2017. We compared their risk of CVD with the risk in matched comparators with normal HI and from the general population. HI+ persons and comparators were followed from start date (date of the second elevated HI) until the first of the main outcome: CVD, emigration, death, or end of observation time on December 31, 2018. In 43,102 unique HI+ persons, the risk of developing CVD was 40% higher compared with the general population and 13% higher compared with the matched blood sample cohort. HI+ was associated with a significantly increased cumulative incidence of both arterial and venous CVD compared with the matched blood sample cohort and the general population (respectively 47 and 14% for arterial CVD; 78 and 24% for venous CVD). Moreover, overall mortality risk was significantly higher in patients with HI+ than in the two comparator groups. Elevated HI is associated with increased risk of arterial and venous CVD and with increased mortality. Our findings imply that HI may contribute as a CVD risk biomarker. [ABSTRACT FROM AUTHOR]

Adiponectin/leptin ratio (ALR) is a promising novel marker of cardio-metabolic risk in patients with metabolic syndrome. Our aim was to study the association of adiponectin-leptin ratio with markers of obesity and adiposity and also to assess its usefulness as a marker of increased cardiometabolic risk (CMR) in Indian children and youth with type 1 diabetes mellitus. This observational study included 79 children and youth with type 1 diabetes (T1DM) (10–21 years) having disease duration>6 months. Demographic data and laboratory findings were obtained from patients' records. Patients with ALR<1 were categorised as having increased CMR and those with ALR>1 were categorised as having no CMR. ALR showed a significant negative correlation with body mass index (BMI), waist and hip circumference and body fat percentage (p<0.05). Body fat percentage was the single most important predictor of ALR. Children and youth with increased CMR had higher weight, BMI, waist and hip circumferences and body fat percentage as compared to those with no CMR (p<0.05). In T1DM children with dyslipidemia, ALR was significantly lower as compared to those without dyslipidemia (p<0.05). ALR may be a useful marker for adiposity and increased cardiometabolic risk in Indian children and youth with type 1 diabetes mellitus. [ABSTRACT FROM AUTHOR]

This article provides a critical literature review and pooled analysis of diagnostic accuracy of the fully-automated Siemens SARS-CoV-2 Antigen (CoV2Ag) chemiluminescent immunoassay for diagnosis of acute SARS-CoV-2 infections. An electronic search was conducted in Scopus, PubMed and medRxiv using the keywords ["Siemens AND CoV2Ag"] OR ["Siemens AND SARS-CoV-2 AND antigen"] for capturing studies that investigated the accuracy of Siemens CoV2Ag for diagnosing acute SARS-CoV-2 infection against a reference SARS-CoV-2 molecular test. The retrieved information was used for constructing a 2 × 2 table and for calculating pooled diagnostic sensitivity, specificity, Summary Receiver Operating Characteristic Curve (SROC) and Agreement. This study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting checklist. Four studies totalling 1,310 respiratory samples (612 with high viral load) were finally included in our analysis. The cumulative area under the curve, accuracy, sensitivity, specificity, were 0.964 (95% CI, 0.957–0.971), 86.9% (95% CI, 84.9–88.7%), 0.79 (95% CI, 0.76–0.82) and 0.98 (95% CI, 0.96–0.99), respectively. The negative (NPV) and positive (PPV) predictive values were 0.77 (0.74–0.79) and 0.98 (95% CI, 0.96–99), respectively. The diagnostic sensitivity in samples with high viral load (i.e., Ct<29–30) was 0.95 (95% CI, 0.93–0.97). The Siemens CoV2Ag fully-automated and high-throughput immunoassay approximates the minimum performance criteria for general SARS-CoV-2 antigen testing and displays excellent performance in samples with high viral load, thus representing a valuable screening solution for risk assessment in COVID-19 and for limiting viral spread. [ABSTRACT FROM AUTHOR]

Liquichek control sample was stable for 13 weeks for hemolysis and icteria, while sample for L-index exceeded acceptability criteria at week 9 (16%) (Figure 1A). Stability of commercial control samples and in-house sample pools is comparable for hemolysis and icteria, but stability of in-house sample pool is significantly shorter for measurement of L index. Keywords: hemolysis; icteria; internal quality assessment; lipemia; stability EN hemolysis icteria internal quality assessment lipemia stability e74 e77 4 04/25/23 20230515 NES 230515 To the Editor, Measurement of hemolysis (H), icteria (I) and lipemia (L) indices is crucial for assessment of appropriate sample quality for analysis. [Extracted from the article]

This study investigated the effect of appropriate pre-phlebotomy instructions on patients' awareness of the need to fast, their fasting status at phlebotomy, and the measurement of specific biochemical analytes and indices. While booking their phlebotomy appointments, two-hundred outpatients, with a wide range of pre-existing medical conditions, were recruited and randomly assigned to either control or intervention groups. The control group received no instructions while the intervention group was verbally instructed to fast for precisely 12 h prior to their appointment. Serum samples were collected from participants to quantify common biochemical analytes and serum indices, some of which were known to be influenced by fasting status, such as triglyceride and the lipaemic index. At the same appointment, participants completed a survey assessing their perception of, and adherence to, fasting requirements. In the intervention group, 99% responded that they had fasted before phlebotomy vs. 16% of controls. Subjects stated they fasted for 12 h in 51% of the intervention group and 7% of the controls. Median concentrations for potassium and total bilirubin were statistically, but not clinically, significantly different. In the study, a single patient in the intervention group was found to have a lipaemic sample. Without instruction, it appears few patients will fast appropriately prior to blood collection. This study suggests that most patients recall and adhere to verbal instructions regarding fasting. Though many in the control group stated they did not fast, triglyceride concentration and lipaemia were not significantly different from the intervention group, and biochemical analyses appear unaffected by fasting status. [ABSTRACT FROM AUTHOR]

On the occasion of the 60th anniversary of Clinical Chemistry and Laboratory Medicine (CCLM) we present a review of recent developments in the discipline of laboratory hematology as these are reflected by papers published in CCLM in the period 2012–2022. Since data on CCLM publications from 1963 to 2012 are also available, we were able to make a comparison between the two periods. This interestingly revealed that the share of laboratory hematology papers has steadily increased and reached now 16% of all papers published in CCLM. It also became evident that blood coagulation and fibrinolysis, erythrocytes, platelets and instrument and method evaluation constituted the 'hottest' topics with regard to number of publications. Some traditional, characteristic CCLM categories like reference intervals, standardization and harmonization, were more stable and probably will remain so in the future. With the advent of important newer topics, like new coagulation assays and drugs and cell population data generated by hematology analyzers, laboratory hematology is anticipated to remain a significant discipline in CCLM publications. [ABSTRACT FROM AUTHOR]

This review is an integral part of the special issue for the 60 years of the journal Clinical Chemistry and Laboratory Medicine (CCLM). The aim of the review is to highlight the role of the clinical laboratory since the emergence of the "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), which causes Coronavirus disease 2019 (COVID-19), with special focus on the contribution of the journal in generating knowledge in SARS-CoV-2 diagnosis. As of October 30, 2022, a total of 186 CCLM publications were dedicated to COVID-19. Of importance, major International Federation of Clinical Chemistry (IFCC) guidelines related to the diagnosis of COVID-19 were published in CCLM. Between early-2020 and late October 2022, COVID-19 publications represented around 27% of all articles in CCLM, highlighting the willingness of the editorial board to help the field in order to better describe and diagnose this new emerging disease. First launched in 1963 under the name "Zeitschrift für Klinische Chemie", the Journal was entirely devoted to clinical chemistry in the strict sense. The various topics published in relation to COVID-19 including its diagnosis, its impact on biochemical or hematological measures, as well as biosafety measures, is the perfect example that shows that the journal has greatly diversified over time. [ABSTRACT FROM AUTHOR]

Since its discovery in the late 1960s, HbA1c has proven to be a major biomarker of diabetes mellitus survey and diagnosis. Other biomarkers have also been described using classical laboratory methods or more innovative, non-invasive ones. All biomarkers of diabetes, including the historical glucose assay, have well-controlled strengths and limitations, determining their indications in clinical use. They all request high quality preanalytical and analytical methodologies, necessitating a strict evaluation of their performances by external quality control assessment trials. Specific requirements are needed for point-of-care testing technologies. This general overview, which describes how old and new tools of diabetes mellitus biological survey have evolved over the last decade, has been built through the prism of papers published in Clinical Chemistry and Laboratory Medicine during this period. [ABSTRACT FROM AUTHOR]

The platelet function analyser (PFA) is a prevalent platelet function screening instrument, and comes in two models–the original PFA-100 and the contemporary PFA-200. The instruments have 'identical' output, being a 'closure time' (CT). Moreover, normal reference ranges provided by the manufacturer, for the specific test cartridges, are the same for both models. There are three different types of test cartridge: collagen/epinephrine (C/Epi), collagen/adenosine diphosphate (C/ADP), and "Innovance PFA P2Y" (only available in certain geographical locations). The PFA-100 was released in the mid 1990s, and so is approaching 50 years of age. The PFA-200, released in some locations in the mid 2010s, is destined to eventually replace the PFA-100, but is not yet available in the USA. The test system is highly sensitive to von Willebrand disease (VWD; C/Epi and C/ADP) and to aspirin therapy (C/Epi only), but only has moderate sensitivity to defects in platelet function and/or deficiencies in platelet number. Accordingly, recommendations for use for screening platelet function vary according to user experience. Some workers have alternatively used the PFA to assess thrombosis risk or pre-operative bleeding risk. In this review, we provide an overview of the history of PFA, and summarise its current clinical utility. [ABSTRACT FROM AUTHOR]

Identifying the cause of pleural effusion is challenging for pulmonologists. Imaging, biopsy, microbiology and biochemical analyses are routinely used for diagnosing pleural effusion. Among these diagnostic tools, biochemical analyses are promising because they have the advantages of low cost, minimal invasiveness, observer independence and short turn-around time. Here, we reviewed the past, present and future of pleural fluid biochemical analysis. We reviewed the history of Light's criteria and its modifications and the current status of biomarkers for heart failure, malignant pleural effusion, tuberculosis pleural effusion and parapneumonic pleural effusion. In addition, we anticipate the future of pleural fluid biochemical analysis, including the utility of machine learning, molecular diagnosis and high-throughput technologies. Clinical Chemistry and Laboratory Medicine (CCLM) should address the topic of pleural fluid biochemical analysis in the future to promote specific knowledge in the laboratory professional community. [ABSTRACT FROM AUTHOR]

Clinical laboratories play a vital role in the healthcare system. Objective medical data provided by clinical laboratories supports approximately 60–70% of clinical decisions, however, evidence supporting this claim is poorly documented and laboratories still lack visibility, despite their indisputable impact on patient care and public health. The International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on Outcome Studies in Laboratory Medicine (TF-OSLM) was recently developed to support directed research evaluating the role of laboratory medicine on clinical outcomes. Establishing and documenting this evidence is key to enhance visibility of the field in the eye of the public and other healthcare professionals together with optimizing patient outcomes and health care system operations. In this review, we discuss four areas that exemplify the contribution of laboratory medicine directly to patient care. This includes high-sensitivity cardiac troponin (hs-cTn) and N-terminal pro-B-type natriuretic peptide/B-type natriuretic peptides (NT-proBNP/BNP) for the diagnosis and prognosis of myocardial infarction and heart failure, respectively, and procalcitonin for the management of sepsis and antibiotic stewardship. Emerging markers of traumatic brain injury and the role of laboratory medicine in the fight against the COVID-19 pandemic are discussed along with an introduction to plans of IFCC TF-OSLM. [ABSTRACT FROM AUTHOR]

Therapy failure caused by complex population-drug-drug (PDDI) interactions including CYP3A4 can be predicted using mechanistic physiologically-based pharmacokinetic (PBPK) modeling. A synergy between ritonavir-boosted lopinavir (LPVr), ivermectin, and chloroquine was suggested to improve COVID-19 treatment. This work aimed to study the PDDI of the two CYP3A4 substrates (ivermectin and chloroquine) with LPVr in mild-to-moderate COVID-19 adults, geriatrics, and pregnancy populations. The PDDI of LPVr with ivermectin or chloroquine was investigated. Pearson's correlations between plasma, saliva, and lung interstitial fluid (ISF) levels were evaluated. Target site (lung epithelial lining fluid [ELF]) levels of ivermectin and chloroquine were estimated. Upon LPVr coadministration, while the chloroquine plasma levels were reduced by 30, 40, and 20%, the ivermectin plasma levels were increased by a minimum of 425, 234, and 453% in adults, geriatrics, and pregnancy populations, respectively. The established correlation equations can be useful in therapeutic drug monitoring (TDM) and dosing regimen optimization. Neither chloroquine nor ivermectin reached therapeutic ELF levels in the presence of LPVr despite reaching toxic ivermectin plasma levels. PBPK modeling, guided with TDM in saliva, can be advantageous to evaluate the probability of reaching therapeutic ELF levels in the presence of PDDI, especially in home-treated patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the comparison of between 10 and 15 minutes centrifugation time for immunochemcial and chemical assays and the impact on the hospital laboratory turnaround time.

Background The use of alternative sample matrices may be an advantageous perspective when the laboratory falls short of serum or lithium-heparin plasma for performing clinical chemistry and/or immunochemistry testing. This study was aimed at exploring whether some tests may be performed in citrate plasma as an alternative to lithium-heparin plasma. Methods Paired lithium-heparin and citrate plasma samples collected from 55 inpatients were analyzed on Roche Cobas 8000 for 28 different clinical chemistry and immunochemistry parameters. Data obtained in citrate plasma were adjusted for either the dilution factor or using an equation corresponding to the linear regression calculated by comparing unadjusted lithium-heparin and citrate plasma values. Results Except for magnesium (+17%) and sodium (+11%), unadjusted values of all remaining analytes were significantly lower in citrate than in lithium-heparin plasma, with bias ranging between -6.4% and -25.9%. The correlation between lithium-heparin and citrate plasma values was generally excellent (i.e. >0.90). The adjustment of citrate plasma values for the dilution factor (i.e. 1.1) was only effective in harmonizing the results of albumin and lipase, whilst the concentration of all other analytes remained significantly different between the two sample matrices. The adjustment of plasma citrate values using corrective formulas was instead effective in harmonizing all parameters, with no results remaining statistically different between the two sample matrices. Conclusions Citrate plasma may be used in exceptional circumstances for clinical chemistry and immunochemistry testing as a replacement for lithium-heparin plasma, provided that citrate plasma values are adjusted by using validated corrective equations.

Background Plasma glucose levels provide the cornerstone of diabetes evaluation, and so it is crucial that clinical laboratories provide accurate and reliable plasma glucose results. To prevent in vitro glycolysis, citrate is used. Here, we present the first study on the 75-g oral glucose tolerance test (OGTT) using the currently available new citrate-containing tubes in liquid and granular forms and the previous sodium fluoride (NaF) for the diagnosis of carbohydrate metabolism disorders and gestational diabetes mellitus (GDM) according to the American Diabetes Association (ADA) guidelines. Methods The 75-g OGTT was performed in 147 volunteers, 83 of whom were pregnant women. Blood was collected in NaF/K3 ethylenediaminetetraacetic acid (EDTA) and NaF/Na2EDTA/citrate in liquid form in tubes in Brescia and in NaF/K2Ox and NaF/Na2EDTA/citrate in granular form in Vicenza. Glucose was measured within 3-4 h from the OGTT. The mean biases were calculated and compared with the desirable bias (<± 2.1%). Results OGTT glucose concentrations were higher in citrate tubes when compared to NaF-containing tubes. When citrate tubes were used, GDM increased to 12.5 and 11.7% in Brescia and Vicenza, respectively. Impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes mellitus (DM) increased to 36.7, 6.7 and 3.4%, respectively, in Brescia. In Vicenza, an increase of 47 and 1.9% in IFG and IGT, respectively, was found. Conclusions OGTT glucose measurement in citrate-containing tubes was shown to be more effective than those containing only NaF in diagnosing carbohydrate disorders. This new glycolysis inhibitor seems to be a necessary preanalytical tool for accurate and reliable plasma glucose results.

It has been well documented over recent years that the preanalytical phase is a leading contributor to errors in the total testing process (TTP). There has however been great progress made in recent years due to the exponential growth of working groups specialising in the field. Patient safety is clearly at the forefront of any healthcare system and any reduction in errors at any stage will improve patient safety. Venous blood collection is a key step in the TTP, and here we review the key errors that occur in venous phlebotomy process and summarise the evidence around their significance to patient safety. Recent studies have identified that patient identification and tube labelling are the steps that carry the highest risk with regard to patient safety. Other studies have shown that in 16.1% of cases, patient identification is incorrectly performed and that 56% of patient identification errors are due to poor labelling practice. We recommend that patient identification must be done using open questions and ideally three separate pieces of information. Labelling of the tube or linking the identity of the patient to the tube label electronically must be done in the presence of the patient whether it is before or after sampling. Combined this will minimise any chance of patient misidentification.

Several lines of evidence now confirm that the vast majority of errors in laboratory medicine occur in the extra-analytical phases of the total testing processing, especially in the preanalytical phase. Most importantly, the collection of unsuitable specimens for testing (either due to inappropriate volume or quality) is by far the most frequent source of all laboratory errors, thus calling for urgent strategies for improving blood sample quality and managing data potentially generated measuring unsuitable specimens. A comprehensive overview of scientific literature leads us to conclude that hemolyzed samples are the most frequent cause of specimen non-conformity in clinical laboratories (40-70%), followed by insufficient or inappropriate sample volume (10-20%), biological samples collected in the wrong container (5-15%) and undue clotting (5-10%). Less frequent causes of impaired sample quality include contamination by infusion fluids (i.e. most often saline or glucose solutions), cross-contamination of blood tubes additives, inappropriate sample storage conditions or repeated freezing-thawing cycles. Therefore, this article is aimed to summarize the current evidence about the most frequent types of unsuitable blood samples, along with tentative recommendations on how to prevent or manage these preanalytical non-conformities.

The rapid, accurate and safe detection of SARS-CoV-2 is the key to improving surveillance and infection containment. The aim of the present study was to ascertain whether, after heat/chemical inactivation, SARS-CoV-2 N antigen chemiluminescence (CLEIA) assay in saliva remains a valid alternative to molecular testing. In 2022, 139 COVID-19 inpatients and 467 healthcare workers were enrolled. In 606 self-collected saliva samples (Salivette), SARS-CoV-2 was detected by molecular (TaqPath rRT-PCR) and chemiluminescent Ag assays (Lumipulse G). The effect of sample pre-treatment (extraction solution-ES or heating) on antigen recovery was verified. Salivary SARS-CoV-2 antigen assay was highly accurate (AUC=0.959, 95% CI: 0.943–0.974), with 90% sensitivity and 92% specificity. Of the 254 antigen positive samples, 29 were false positives. We demonstrated that heterophilic antibodies could be a cause of false positive results. A significant antigen concentration decrease was observed after ES treatment (p=0.0026), with misclassification of 43 samples. Heat had a minimal impact, after treatment the correct classification of cases was maintained. CLEIA SARS-CoV-2 salivary antigen provides accurate, timely and high-throughput results that remain accurate also after heat inactivation, thus ensuring a safer work environment. This supports the use of salivary antigen detection by CLEIA in surveillance programs. [ABSTRACT FROM AUTHOR]

D-dimer, a universally unique marker for fibrin degradation, is generated through the enzymatic interplay of thrombin, factor XIIIa, and plasmin. The emergence of D-dimer-containing fibrin molecules occurs in both intravascular and extravascular spaces during pivotal physiological processes like haemostasis, thrombosis, and tissue repair. Given the inherently physiological nature of fibrin formation and fibrinolysis, basal levels of D-dimer fragments are present in plasma. Beyond its role as a marker of routine physiological processes, aberrations in D-dimer levels are indicative of a spectrum of conditions, both non-pathological and pathological. The clinical utility of D-dimer has been firmly established, particularly in scenarios like venous thromboembolism (VTE), pulmonary embolism (PE), deep vein thrombosis (DVT), and disseminated intravascular coagulation (DIC). Additionally, recent applications have extended to assess the prognosis of COVID-19. While D-dimer is commonly associated with thrombotic conditions, its elevation is not confined to these conditions alone. Elevated D-dimer levels are observed across various diseases, where its significance extends beyond diagnostic indicators to prognostic implications., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Keywords: antigen; COVID-19; diagnosis; immunoassay; SARS-CoV-2 EN antigen COVID-19 diagnosis immunoassay SARS-CoV-2 e165 e167 3 07/18/23 20230801 NES 230801 To the Editor, More than three years after the abrupt emergence of the still ongoing coronavirus disease 2019 (COVID-19) pandemic, the diagnostic approach to suspected SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) acute infection remains almost entirely based on laboratory testing, as extensively reviewed elsewhere [[1]]. Table 1: Main advantages and limitations of SARS-CoV-2 antigen rapid diagnostic tests (RDTs) and laboratory-based SARS-CoV-2 antigen immunoassays. [Extracted from the article]

Biological variation (BV) data obtained in a standardized way is valuable to assess the analytical requirements and the utility of a reference interval. Our study aimed to determine the short-term BV of thrombophilia (protein S, protein C, activated protein C resistance (APCR) and factor VIII) and hemophilia (factors VIII, IX and XI) parameters in plasma. Coagulation factors V and XII were also evaluated. Based on the obtained data, we assessed analytical performance specifications for the parameters. Finally, we intended to provide a robust tool for comparison of serial measurements of factors V, VIII, IX and XI. A blood draw was performed weekly in 19 apparently healthy Caucasian adults for five weeks at Saint-Luc University Hospital (Brussels, Belgium). Parameters were measured in duplicate. BV components were calculated with a nested analysis of variance after exclusion of outliers. The analytical coefficient of variation (CV) varied from 1.5 to 4.6%, the within-subject CV from 1.6 to 8.9% and the between-subject CV from 3.8 to 24.1%. All parameters showed high individuality. For most parameters, the analytical goal was met with our assays. Reference change values (RCV) of −16.7% to +20.0%, −20.7% to +26.0%, −15.3% to +18.1% and −13.1% to +15.1% were obtained for factors V, VIII, IX and XI respectively. All studied parameters were highly individualized. The assessment of BV data can guide setting analytical goal specifications. Comparison of serial measurements in the follow-up of patients suffering from hepatic failure or mild hemophilia is facilitated by evaluation of the RCV. [ABSTRACT FROM AUTHOR]

Antigen tests are an essential part of SARS-CoV-2 testing strategies. Rapid antigen tests are easy to use but less sensitive compared to nucleic acid amplification tests (NAT) and less suitable for large-scale testing. In contrast, laboratory-based antigen tests are suitable for high-throughput immunoanalyzers. Here we evaluated the diagnostic performance of the laboratory-based Siemens Healthineers SARS-CoV-2 Antigen (CoV2Ag) assay. In a public test center, from 447 individuals anterior nasal swab specimens as well as nasopharyngeal swab specimens were collected. The nasal swab specimens were collected in sample inactivation medium and measured using the CoV2Ag assay. The nasopharyngeal swab specimens were measured by RT-PCR. Additionally, 9,046 swab specimens obtained for screening purposes in a tertiary care hospital were analyzed and positive CoV2Ag results confirmed by NAT. In total, 234/447 (52.3%) participants of the public test center were positive for SARS-CoV-2-RNA. Viral lineage B1.1.529 was dominant during the study. Sensitivity and specificity of the CoV2Ag assay were 88.5% (95%CI: 83.7–91.9%) and 99.5% (97.4–99.9%), respectively. Sensitivity increased to 93.7% (97.4–99.9%) and 98.7% (97.4–99.9%) for swab specimens with cycle threshold values <30 and <25, respectively. Out of 9,046 CoV2Ag screening tests from hospitalized patients, 21 (0.2%) swab specimens were determined as false-positive by confirmatory NAT. Using sample tubes containing inactivation medium the laboratory-based high-throughput CoV2Ag assay is a very specific and highly sensitive assay for detection of SARS-CoV-2 antigen in nasal swab specimens including the B1.1.529 variant. In low prevalence settings confirmation of positive CoV2Ag results by SARS-CoV-2-RNA testing is recommended. [ABSTRACT FROM AUTHOR]

High risk of SARS-CoV-2 infection (symptomatic patients) The diagnosis of high-risk patients (i.e., those presenting signs and symptoms suggestive for SARS-CoV-2 infection) should still be carried out with laboratory-based molecular assays, using upper or lower respiratory tracts samples. Keywords: COVID-19; diagnosis; SARS-CoV-2; sequencing; variants EN COVID-19 diagnosis SARS-CoV-2 sequencing variants 975 981 7 05/26/22 20220601 NES 220601 Test indications in specific settings This document, endorsed by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) "Working Group on SARS-CoV-2 Variants", aims to update previous indications for diagnosing acute SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, taking into consideration the evidence emerged after origin and spread of new lineages and sub-lineages of the virus characterized by mutated genetic, biochemical, biological and clinical characteristics [[1]]. 21 Lippi, G, Henry, BM, Plebani, M. LumiraDX SARS-CoV-2 antigen test for diagnosing acute SARS-CoV-2 infection: critical literature review and meta-analysis. [Extracted from the article]

Background: Ovarian cancer (OC) is the second most common gynecological cancer and the first cause of death from gynecological malignancy in Western Europe and the USA. While human epididymis-specific protein 4 (HE4) has been reported as a predictive diagnostic index, it has not been widely accepted because of inconsistent conclusions. The aim of this study was to evaluate the diagnostic value of HE4 systematically for ovarian cancer. Methods: All relevant original studies about HE4 in the diagnosis of ovarian cancer published from January 1974 to May 2011 were retrieved. By measuring methodological qualities, 12 papers were selected for this study, while 531 articles were searched. The overall diagnostic sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-), and area under the receiver operating characteristic curve (AUC-ROC) were used to evaluate the diagnostic value of HE4 for ovarian cancer using the Meta-DiSc statistical software. Results: There were 2607 subjects included in this meta-analysis. The sensitivity, specificity, LR+ and LR- (95% confidence interval) of HE4 was 0.800 (0.770-0.827), 0.916 (0.902-0.929), 10.271 (6.982-15.109) and 0.228 (0.181-0.287), respectively. The area under the summary receiver operating characteristic (sROC) curve of HE4 was 0.946. The index of Q* was 0.885. Conclusions: HE4 was found to be better than CA125 as an auxiliary indicator for the diagnosis of ovarian cancer in terms of better sensitivity, specificity, LR+ and LR-. [ABSTRACT FROM AUTHOR]

The advent of modern instrumentation, with associated improvements in test performance and reliability, together with appropriate internal quality control (IQC) and external quality assurance (EQA) measures, has led to substantial reductions in analytical errors within hemostasis laboratories. Unfortunately, the reporting of incorrect or inappropriate test results still occurs, perhaps even as frequently as in the past. Many of these cases arise due to a variety of events largely outside the control of the laboratories performing the tests. These events are primarily preanalytical, related to sample collection and processing, but can also include post-analytical events related to the reporting and interpretation of test results. The current report provides an overview of these events, as well as guidance for prevention or minimization. In particular, we propose several strategies for the post-analytical reporting of hemostasis assays, and how this may provide the final opportunity to prevent serious clinical errors in diagnosis. This report should be of interest to both the laboratory scientists working in hemostasis and clinicians that request and attempt to interpret the test results. Laboratory scientists are ultimately responsible for these test results, and there is a duty to provide both accurate and precise results to enable clinicians to manage patients appropriately and to avoid the need to recollect and retest. Also, clinicians will not be in a position to best diagnose and manage their patient unless they gain an appreciation of these issues. Clin Chem Lab Med 2010;48:309–21. [ABSTRACT FROM AUTHOR]

Hemolysis is associated with erroneous or delayed results. Objectives of the study were to compare four different methods for obtaining hemolysis in vitro on three different analyzers. Hemolysis was prepared with addition of pure hemoglobin into serum pool, osmotic shock, aspiration through blood collection needle, freezing/thawing of whole blood. Biochemistry parameters were measured in duplicate at Architect c8000 (Abbott, Abbott Park, USA), Beckman Coulter AU680 (Beckman Coulter, Brea, USA) and Cobas 6000 c501 (Roche, Mannheim, Germany), according to manufacturers' declarations. Cut-off value was defined as the highest value of H index with corresponding bias lower than acceptance criteria. We were not able to obtain results with freezing protocol. On all three platforms, lowest number of analytes were sensitive to hemolysis at H=0.5 using method of adding free hemoglobin. When osmotic shock was used, cut-off values for the most analytes were generally met at lower values. Hemolysis significantly interfered with measurement of potassium and lactate dehydrogenase (LD) at H=0.5 on all platforms. The most of the tested analytes had the lowest acceptable H index when aspiration method was used. At the low level of hemolysis (H=0.8) glucose, sodium, potassium, chloride, phosphate, and LD were affected on all analyzers, with some additional analytes depending on the manufacturer. Hemolysis interference differs on different analyzers and according to protocol for obtaining hemolysis. Aspiration method was generally the most sensitive to hemolysis interference, while addition of free Hb was the most resistant. [ABSTRACT FROM AUTHOR]

An effective vaccine against SARS-CoV-2 is essential to mitigate the COVID-19 pandemic. In these several months, a number of groups have started to report humoral responses and side effects after BNT162b2 vaccinations. Although these reports demonstrate the safety and efficacy, further studies are warranted to verify these findings. Here we examined the levels of SARS-CoV-2 antibodies in Japanese healthy volunteers who underwent BNT162b2 vaccine, to assess the humoral responses and side effects. Forty-one healthy volunteers' samples were used for the measurement of SARS-CoV-2 antibodies with chemiluminescent assays against the Receptor Binding Domain (RBD) of the virus. We also measured the side effects of the vaccination. Although the levels of IgM varied, all participants were seronegative for IgM and IgG before vaccination, and both IgM and IgG were significantly increased after the vaccinations. We further analyzed the humoral responses in relation to age, and found that the IgG levels for 14 days and 35 days, and IgM levels for 14 days after vaccination showed clear declining trends with age. Commonly reported side effects in the participants were sore arm/pain (90.0%) after the first dose, and generalized weakness/fatigue (70.0%), fever (57.5%), and sore arm/pain (90.0%) after the second dose. BNT162b2 vaccination generates sufficient production of IgG especially after the second dose, though the response decreases age-dependently. The high frequencies of generalized weakness/fatigue, fever, and sore arm/pain were not negligible, especially after the second dose. This may be associated with the age characteristics of the population. [ABSTRACT FROM AUTHOR]

BV estimates in athletes vs. the general population Different BV estimates may be expected in athletes considering the continuous high-endurance exercise, compared to a general, more sedate population. BV estimates derived from athletes in this study could help to set APS in both clinical laboratories providing health services to athletes, the accredited laboratories of the World Anti-doping Agency (WADA) network and the organizations that audit these laboratories [[42]]. Keywords: athletes; biological variation; endurance exercise; long-term period; routine laboratory measurands EN athletes biological variation endurance exercise long-term period routine laboratory measurands 618 628 11 03/11/22 20220301 NES 220301 Introduction Biological variation (BV) describes the fluctuation of a measurand around its homeostatic set point in steady-state conditions and is known as the within-subject BV (CV SB I sb ), whereas the variations between the homeostatic set points of different individuals is denoted the between-subject BV (CV SB G sb ). Further study of our data, for these in homogeneously distributed as well as for the other measurands, by e.g. Bayesian models, which provide individual within-participant BV estimates, would be helpful to better understand the effect of exercise in athletes and its potential effect on the derived BV estimates [[26]]. [Extracted from the article]