Volume 63, Issue 6

Poor health literacy and inappropriate test prescribing hamper the value of laboratory medicine. The disintermediation between test producers and interpreters may happen both in Point of Care Tests, where doctor mediation is provided, but laboratory expert supervision is not, and in Direct to Consumer Testing, where no medical mediation is provided at all. In these cases, the respect for patient’s autonomy must not preclude the principles of non-maleficence (as an individual concern) and justice (as a societal concern), as wrong test interpretation can generate confusion, anxiety, inappropriate social behavior, useless medical examinations and considerable cost increase. Considering how different is patient ability to understand test results (if any) and handle any physical and psychological consequence, promoting health literacy and professional laboratory mediation become crucial professional priorities. The aims of this review are 1) to describe the importance of health literacy on laboratory test interpretation, medical advice and therapeutic compliance; 2) to discuss doctor-level, patient-level and caregiver-level educational interventions in light of the four principles of the value-based framework (personal value, technical value, allocative value and societal value). Based on these premises, the authors support the need to enhance health literacy in patients, help doctors improve the communication of results and validate commercial tests under the scrutiny of scientific community.

Circulating tumor cells (CTCs) are pivotal in the distant metastasis of tumors, serving as one of the primary materials for liquid biopsy. They hold significant clinical importance in assessing prognosis, predicting efficacy, evaluating therapeutic outcomes, and studying recurrence, metastasis, and resistance mechanisms in cancer patients. Nevertheless, the rareness and heterogeneity of CTC and the complexity of metastasis make the clinical application of CTC detection confront many challenges, which may need to be settled by some practical strategies. This article will review the content mentioned above.

Malignant effusions, pleural effusion or ascites, represent a common problem in cancer patients. Pleural effusion in a cancer patient may be caused also by non-neoplastic conditions, and the diagnosis of malignant pleural effusion is established by the demonstration of tumor cells in pleural fluid. Microscopical detection of tumor cells in pleural fluid often fails, and there is an unmet medical need for more sensitive methods. New approaches, including isolation using magnetic beads coated with monoclonal antibodies targeting antigens expressed on tumor cells not only increase the diagnostic sensitivity, but also provide material for the analysis of predictive biomarkers. The advent of new technologies illustrates the incremental role of laboratory medicine in the management of patients with malignant effusions.

The presence of letrozole, an aromatase inhibitor, in an athlete’s sample constitutes one of the more frequent anti-doping rules violation. It is possible to challenge this violation but it is the athletes who have to demonstrate their innocence. The conditions to evidence/establish the absence of fault or negligence hinge on two points: 1. the athletes or their legal representatives have to present verified circumstances of contamination and the source of contamination has to be identified; and 2. there have to be verified claims by the athlete about the fact that the intake of the prohibited substance was not known, i.e. that the violation was not intentional. This corresponds to the suggested shift terminology from “contaminated product” to “unpredictable source of a prohibited substance”. In the recent years, several top athletes challenged their ADRV with a low urine letrozole concentration and requested a hair test. In three cases, letrozole concentration in segmented hair, particularly in the segment corresponding to the urine AAF was significantly lower than 1 pg/mg, which is the limit of quantification of the method. Considering that a ¼ of a 2.5 mg therapeutic dose of letrozole produces a hair concentration of approximately 30 pg/mg, it is easy to establish that the dose that entered in the body of these athletes was incidental. Nevertheless, all three athletes were sentenced a 2-years ban as the source of contamination was not identified. In that sense, the WADA dogma contradicts scientific evidence, and from a forensic perspective, this appears difficult to understand.

Objectives This paper further explores the Sigma Metric (SM) and its application in clinical chemistry. It discusses the SM, assay stability, and control failure relationship. Content : SM is not a valid measure of assay stability or the likelihood of failure. When an out-of-control event occurs for an assay with a higher SM value, the same QC rule will have greater power to detect error than assays with a lower SM value. Thus, it is easier to prevent errors from happening for higher SM assays. This rationale encourages using more frequent QC events and more QC samples for a QC scheme of a low SM assay or simply more QC cost for low SM assays. A laboratory can have a high-precision instrument that frequently fails and a low-precision instrument that hardly ever fails. Parvin’s patient risk model presumes the bracketed continuous mode (BCM) testing workflow. If overlooked when designing QC schemes, this leads to the common misconception of the SM that one can save the cost of QC since assays with high SM require less frequent QC to ensure patient risk. There is no evidence that an assay’s precision is correlated with its failure rate. Schmidt et al., in a series of papers, showed that an assay with a higher P f or shift in probability will have a higher expected number of unacceptable results. Incorporating P f into the QC design process presents significant challenges despite the proactive quality control (PQC) methodology. Summary Unfortunately, TEa Six Sigma, as widely practiced in Clinical Chemistry, is not based on classical Six Sigma mathematical statistics. Classical Six Sigma would facilitate comparing results across activities where the principles of Six Sigma are employed.

The EN ISO 15189:2022 standard, titled “Medical laboratories – Requirements for quality and competence,” is a significant update to the regulations for medical laboratories. The revised standard was published on December 6, 2022, replacing both EN ISO 15189:2012 and EN ISO 22870:2016. Key objectives of the revision include: 1. Alignment with ISO/IEC 17025:2017, 2. Removal of unintended prescription, 3. Focus on patient interest and safety, 4. Minimization of new requirements, and 5. Improved clarity of text. Dedicating to harmonizing accreditation processes across Europe the EFLM Committee on Accreditation and ISO/CEN standards (C: A/ISO) has produced this guidance document to assist the laboratory medicine community in understanding and implementing the criteria of the EN ISO 15189 revision. Two main objectives of the guidance in educating both laboratories and accreditation bodies with their assessors as well as other stakeholders in laboratory medicine were agreed on. Firstly, to clarify the relevant changes covering all paragraphs of the standard and secondly to make an impact analysis on previous C: A/ISO guidance documents.

Objectives Accurately quantifying low-density lipoprotein cholesterol (LDL-C) is crucial for precise cardiovascular disease risk assessment and treatment decisions. The commonly used Friedewald equation (LDL-C FW ) has faced criticism for its tendency to underestimate LDL-C, particularly at high triglycerides (TG) or low LDL-C, potentially leading to undertreatment. Newer equations, such as those by Martin and Hopkins (LDL-C MH ) or Sampson (LDL-C SN ), have been proposed as alternatives. Our study aimed to assess the validity of LDL-C FW , LDL-C MH , and LDL-C SN compared to ß-quantification (LDL-C UC ), the reference method recommended by the Lipid Research Clinics. Methods Using data from three studies comprising 5,738 datasets, LDL-C was determined with the four methods in samples with TG up to 5.65 mmol/L. We calculated median and mean differences, correlations, and used the Passing and Bablok regression for comparisons. Concordance/discordance analyses were conducted. Results All equations provided generally accurate LDL-C estimations with slight differences among them. At TG<1.69 mmol/L, no clinically significant divergences were observed. As TG values increased, LDL-C FW offered the most accurate estimation, followed by LDL-C SN , while LDL-C MH exhibited increasingly strong positive bias. LDL-C FW was not inferior to LDL-C SN and LDL-C MH in terms of concordance/discordance. Conclusions LDL-C FW generally provided reliable estimates of LDL-C in most samples, showing non-inferiority to LDL-C SN or LDL-C MH , thereby confirming its legitimacy for routine use. Since current treatment recommendations are based on studies employing LDL-C FW , its replacement by alternatives is not justified.

Objectives Autoverification increases the efficiency of laboratories. Laboratories accredited according to ISO 15189:2022 need to validate their processes, including autoverification, and assess the associated risks to patient safety. The aim of this study was to propose a systematic verification algorithm for autoverification and to assess its potential risks. Methods The study was conducted using retrospective data from the Laboratory Information System (LIS). Seven laboratory medicine specialists participated. Autoverification rules were defined for analytes in serum, stool, urine and whole blood determined on Alinity ci (Abbott), Atellica 1500 (Siemens) and ABL90 FLEX (Radiometer). Criteria included internal quality control results, instrument flags, hemolysis/icteria/lipemia indices, median patient values, critical values, measurement ranges, delta checks, and reference values. Verification was performed step by step. Risk analysis was performed using Failure Modes and Effects Analysis and the Risk Priority Number (RPN) was calculated. Results During the study, 23,633 laboratory reports were generated, containing 246,579 test results for 167 biochemical tests. Of these, 198,879 (80.66 %) met the criteria for autoverification. For 2,057 results (0.83 %), the experts disagreed with the autoverification criteria (false negatives). Discrepancies were mainly associated to median and delta check values. Only 45 false positives (0.02 %) were identified, resulting in an RPN of 0 for all cases. Conclusions The autoverified and non-autoverified results showed high agreement with the expert opinions, with minimal disagreement (0.02 % and 0.83 %, respectively). The risk analysis showed that autoverification did not pose a significant risk to patient safety. This study, the first of its kind, provides step-by-step recommendations for implementing autoverification in laboratories.

Objectives Mutations in the GRN gene encoded glycoprotein progranulin (PGRN), cause 5–10 % of all cases of frontotemporal lobar degeneration (FTLD). The aim of our study was to verify the analytical and clinical performance of an automated chemiluminescent immunoassay method for PGRN measurement recently developed (Chorus Evo, Diesse Diagnostica, Italy). Methods Five plasma pools and residual plasma samples (K 2 EDTA) from 25 control subjects (11 males, 62–79 years; 14 females, 54–76 years) and 151 patients (70 males, 53–81 years; 81 females, 44–82 years) with different neurodegenerative disorders (NDs), were assayed. In 61 out of 151 patients, genetic GRN screening was carried. Results Within-run imprecision (CV%) ranged from 3.8 % (11.5 pg/L) to 10.8 % (2.5 pg/L), and between-run, from 5.6 % (68.7 pg/L) to 10.7 % (2.8 pg/L). At genetic screening, 3 out of 61 patients were classified as GRN + carriers, 18 as “other mutations” and 40 as “no-mutations” carriers. The PGRN median level in GRN + carriers (15.9 pg/L) was significantly lower than that in control subjects (32.8 pg/L; p=0.006), in GRN − (27.50 pg/L; p=0.007), in other mutation carriers (24.80 pg/L; p=0.05) and in NDs patients (22.40 pg/L; p=0.05) ROC analysis, demonstrates the accuracy of progranulin levels in discriminating between “ GRN +” and “ GRN −” carriers (AUC 0.985) as well as “ GRN +” and “other mutations” carriers (AUC 0.870). Conclusions The new automated progranulin method, for robust analytical performance, is suitable for use in the clinical setting, supporting clinicians in making a differential diagnosis in patients with neurodegenerative disorder.

Objectives C-peptide is an equimolar by-product of insulin biosynthesis. It is used clinically to assess insulin secretion and differentiate types of diabetes. However, the lack of standardization across assays limits its broader application. This study aimed to examine discrepancies between the leading C-peptide measurement methods used in clinical laboratories and propose a solution to reduce them based on a complete traceability chain. Methods Two sets of serum samples were distributed to 10 manufacturers of C-peptide assays. The first set (A, n=20) was analyzed independently by each manufacturer, who then returned their results to us. Subsequently, we sent out the second set (B, n=20) along with the reference values for set A. For set B, each manufacturer provided both non-calibrated and recalibrated values for each sample. The recalibration was performed according to each manufacturer’s internal standard protocols. We assessed how recalibration affected agreement between methods and alignment with the reference method. Non-parametric statistical approaches, including Passing-Bablok regression, level of agreement, and standard deviation analysis, were applied to compare data from multiple perspectives. Results Despite most manufacturers using the same WHO C-peptide calibrator material, significant disagreement was observed between methods prior to recalibration. Recalibration with matrix-appropriate serum samples reduced the discordance among assays, bringing them closer to the reference method. Overall, recalibration reduced both systematic bias and individual assay disagreement. Conclusions These findings underscore the importance of appropriate calibration schemes to improve agreement across C-peptide assays, enhancing the accuracy of C-peptide testing for clinical practice.

Objectives Prompt recognition of hyperammonaemia can avoid severe consequences of delayed treatment. Strict sample transport requirements present barriers to requesting and, if not achieved, rejection by the laboratory. Evidence is sparse on in vitro ammonia stability from studies using modern techniques or based in clinical settings. Stability in hyperammonaemic samples is unknown. This study aimed to examine ammonia stability and its source in samples from hyperammonaemic patients and to determine a clinically significant change to establish acceptable sample requirements for ammonia analysis. Methods Blood samples were taken from 19 hyperammonaemic patients and placed either on ice or kept at room temperature. Plasma ammonia was measured every 10 min for 2 h. Haemolysis index (HI), full blood count, liver enzymes and amino acids were analysed. Expert physicians were surveyed on a clinically significant ammonia change. Stability was assessed using the reference change value (RCV). Results Ammonia increased with time [peak value 14.9 % (8.4–17.1), median (95 % confidence interval)], and was predominately of cellular origin. Ice did not improve stability and increased HI. Survey results found a significantly increased ammonia between 39 % (30–48) at 50 μmol/L and 21 % (15–28) at 1,000 μmol/L. Ammonia RCV was 40.8 %. Conclusions Chilling samples did not improve blood ammonia stability. The increase in blood ammonia from patients with hyperammonaemia over 2 h was lower than that considered clinically significant and the calculated RCV. Transport of samples for ammonia analysis does not require ice and laboratories should accept samples if received within 2 h of venepuncture.

Objectives Measurements of acid-base status are performed quickly after blood sampling avoiding errors. This necessitates rapid sample transport which can be problematic. This study measures blood sampled in critically ill patients over 180 min and proposes a mathematical physio-chemical model to simulate changes. Methods Eleven blood samples were taken from 30 critically ill patients and measured at baseline (2 samples) and 36, 54, 72, 90, 108, 126, 144, 162, and 180 min. A mathematical model was proposed including red blood cell metabolism, carbon dioxide diffusion, electrolyte distribution and water transport. This model was used to simulate values of plasma pH, pCO 2 , pO 2 , SO 2 , glucose, lactate, Na + and Cl − during analysis delay. Simulated and measured values were compared using Bland-Altman and correlation analysis, and goodness of model fits evaluated with chi-squared. Results The mathematical model provided a good fit to data in 29 of 30 patients with no significant differences (p>0.1) between simulated and measured plasma values. Differences were (bias±SD): pH 0.000 ± 0.012, pCO 2 0.00 ± 0.24 kPa, lactate −0.10 ± 0.23 mmol/L, glucose 0.00 ± 0.34 mmol/L, Cl −  −0.2 ± 1.21 mmol/L, Na + 0.0 ± 1.0 mmol/L, pO 2 0.0 ± 0.44 kPa, SO 2  −0.6 ± 5.5 %, with these values close to manufacturers’ measurement errors. All linear correlations had R 2 >0.86. Simulations of pH, PCO 2 , glucose and lactate could be performed from baseline values without patient specific parameters. Conclusions This paper illustrates that analysis delay can be accurately simulated with a mathematical model of physio-chemistry. While further evaluation is necessary, this may indicate a role for this model in clinical practice to simulate analysis delay.

Objectives External quality assessment (EQA) programs play a pivotal role in harmonizing laboratory practices, offering users a benchmark system to evaluate their own performance and identify areas requiring improvement. The objective of this study was to go through and analyze the UK NEQAS “Immunology, Immunochemistry and Allergy” EQA reports between 2012 and 2021 to assess the overall level of harmonization in autoimmune diagnostics and identify areas requiring improvement for future actions. Methods The EQA programs reviewed included anti-nuclear (ANA), anti-dsDNA, anti-centromere, anti-extractable nuclear antigen (ENA), anti-phospholipids, anti-neutrophil cytoplasm (ANCA), anti-proteinase 3 (PR3), anti-myeloperoxidase (MPO), anti-glomerular basement membrane (GBM), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), mitochondrial (AMA), liver-kidney-microsomal (LKM), smooth muscle (ASMA), APCA, and celiac disease antibodies. Results In the analyzed period, the number in participating laboratories showed an increase for almost all programs. Among solid phase methods, the use of ELISA techniques showed a progressive reduction, while new technologies, such as the fluoroenzymatic immunoassay, chemiluminescence immunoassay, Luminex and immunoblot showed an increased number of users. The number of results complying with the expected negative or positive target slightly increased for almost all antibodies in the last decade. A description of the most frequent causes of mistakes or misinterpretation for each specific test and method is also provided in this study. Conclusions Although numerous challenges need to be addressed in the area of autoantibody detection to enhance testing quality and attain higher harmonization, the period analyzed revealed that the ever-expanding range of autoantibodies, coupled with the introduction of new tests and methodologies and the advent of automated platforms, has brought about significant changes in autoimmune diagnostics.

Objectives To compare a new ready-to-use monotest immunoassay, CHORUS Promonitor, for the quantification of serum biological drug levels and anti-drug antibodies of anti-TNF agents, against the reference batch-based ELISA test, Promonitor. Methods Blood samples were collected from patients treated with anti-TNF agents, infliximab (IFX) or adalimumab (ADL). IFX and ADL levels, as well as anti-IFX and anti-ADL antibodies were quantified and compared between the standard ELISA reference test, Promonitor, and the automated monotest ELISA assay, CHORUS Promonitor. Data analysis included both qualitative and quantitative comparison between both tests. For the qualitative comparison, overall percent agreement (OPA) was calculated. For the quantitative comparison, Passing-Bablok regression analysis and Bland–Altman analysis were used. Results For IFX and ADL levels, the qualitative overall agreement between methods was 100 % (Cohen’s coefficient=1). For anti-IFX and anti-ADL antibodies, OPA was 98.8 % and 97.3 %, respectively. Quantitative comparison indicated a very strong correlation between both assays: IFX (r=0.97, n=74), ADL (r=0.95, n=54), anti-IFX (r=0.93, n=72), and anti-ADL (r=0.97, n=61). The regression analysis determined an excellent comparability of drug levels between methods. Bland–Altman analysis showed a bias difference between assays of 6 % for IFX, 0 % for ADL, 24 % for anti-IFX, and 14 % for anti-ADL. Conclusions Monotest CHORUS Promonitor was a reliable assay to quantify IFX, ADL, anti-IFX and anti-ADL in samples with comparable results to those obtained with the reference batch-based ELISA technique.

Objectives Careful consideration of the pre-analytical process for urine examination is essential to avoid errors and support accurate results and decision-making. Our objective was to assess the impact of various pre-analytical factors on urine test strip and quantitative chemistry results, including stability, tube type, fill volume, and centrifugation. Methods Residual random urine specimens were identified. Stability of 10 urine test strips and 13 quantitative chemistry parameters were assessed at eight time points (2, 4, 6, 8, 24, 48, 72, and 96 h) at room temperature (RT) and 2–8 °C (n=10–20 samples). The effect of additional pre-analytical variables was assessed, including using preservative tubes for urine chemistry as well as preservative tube underfilling and centrifugation on urine test strip results (n=10 samples). Results Seven of the ten urine tests strips evaluated met the minimal agreement criteria for stability (Cohen’s kappa >0.70) across all conditions. A Cohen’s kappa value of <0.70 was observed for pH (48 h), glucose (72 h), and protein (96 h) at RT. All 13 urine chemistry analytes remained stable at defined time points and conditions. Underfilling preservative tubes for urine test strips and centrifugation demonstrated no significant effect. The impact of using preservative tubes for urine chemistry was negligible with the exception of sodium and osmolality. Conclusions These findings highlight the pre-analytical factors that impact urine specimen evaluation and may be useful in informing clinical laboratory practices. Acceptable stability window for urine test strips should be considered in the context of the proportion of pathological samples evaluated.

Objectives We evaluated the performance of a novel flow cell morphology analyzer AUTION EYE AI-4510 for counting particles in urine. Methods Analytical performance was assessed according to the EFLM European Urinalysis Guideline 2023. Trueness was compared by analyzing 1.012 fresh urine samples with the AUTION EYE AI-4510 (ARKRAY, Inc., Kyoto, Japan) against phase-contrast visual microscopy. Poisson statistics were utilized in assessment of imprecision of particle counts both with quality control material and patient specimens. Results Relative imprecision against theoretical Poisson imprecision, R(CV), was estimated to be 1.1 for red blood cells (RBC), 1.0 for white blood cells (WBC), 0.9 for squamous epithelial cells (SEC) and 1.1 for bacteria. The agreement with visual microscopy (Cohen’s weighted kappa) was 0.93 for RBC, 0.95 for WBC, 0.90 for SEC, 0.79 for non-squamous epithelial cells (NSEC), 0.67 for combined casts, 0.90 for crystals and 0.88 for bacteria. No clinically significant bias was observed. Limits of quantitation at CV=30 % reached 4 × 10 6 /L for RBC and 5 × 10 6 /L for WBC. Differentiation of urinary crystals was improved as compared to previous data on digital cuvette imaging. Conclusions The ARKRAY AUTION EYE AI-4510 provided a desirable imprecision, met the criteria for linearity, LoQ and carry-over, and showed an optimum comparison to visual microscopy for RBC, WBC, SEC and crystals as defined in the EFLM European Urinalysis Guideline 2023. The identification of kidney damage is recommended to be improved by using user-defined review rules. Performance of bacteria counting needs to be confirmed against urine bacterial cultures.

Objectives The knowledge of the measurement uncertainty (MU) of a diagnostic laboratory test is essential to keep the reliability of laboratory results under control, is requested by regulatory bodies, and for the clinician to be aware of the grey zone of variability around the reported values. The calculation of the percent allowable total error (%aTE) defines the levels of acceptable and optimal MU for each measurand. The CD34+ hemopoietic precursor cell level in blood, as a flow cytometric measurand, still lacks reliable MU and %aTE indicators. Methods %aTE of the absolute count of CD34+ cells in stabilized peripheral blood has been evaluated using a UKNEQAS database of 69,294 valid results entries from the Stem Cell Enumeration EQA/PT Programme over the last 20 years. The state-of-the-art (SOTA) desirable performance achievable by 80 % of participants and the optimal performance by the best laboratories were calculated at four levels of absolute CD34+ cell counts, from 0 to 10 to >50 cells/μL. Results Double platform users displayed worse %aTE as compared to single platform users in both periods, with a general trend to improvement with time. Single platform users in the 2014–2024 decade performed best, with a flat %aTE trend over the years. The SOTA-based %aTE were calculated for each method and every decision-making cell level, showing relatively narrow ranges. Conclusions Our EQA/PT study with stabilized peripheral blood CD34+ cell suspensions reliably estimated the %aTE of the absolute CD34+ cell count, mostly related to the purely analytical variability and devoid of the preanalytical interferences caused by the decay of fresh samples.

Objectives This study utilized large-scale health examination data to explore gender– and age–specific reference intervals (RIs) for serum uric acid (UA) using indirect methods and assessed the consistency of different approaches. Methods UA data were collected from a hospital in Zhejiang Province, China. The test set covered January 2019 to December 2023, with a validation set from January to June 2024. Various methods – EP28 nonparametric (EP28-NP), parametric (EP28-P), TMC, refineR, and Kosmic – were used to establish gender– and age–specific RIs. Continuous age-based RIs were derived using the Generalized Additive Model for Location Scale and Shape (GAMLSS). Validation rates were calculated for each method using the validation set. Results Using EP28-NP as the benchmark, other methods showed similar UA RIs (bias ratios ≤0.375, except for one group), with Kosmic, refineR, and TMC yielding slightly higher values than EP28-NP and EP28-P. For males, UA RIs varied by age: 19–42 years (256–537 μmol/L), 43–66 years (235–513 μmol/L) and ≥67 years (214–515 μmol/L), with validation rates ranging from 94.05 to 96.50 %. Male continuous RIs declined from ages 20–79 and then gradually increased after age 80. For females, UA RIs were age-dependent: 19–48 years (169–374 μmol/L), 49–74 years (178–405 μmol/L), and ≥75 years (186–470 μmol/L), with validation rates ranging from 92.70 to 96.80 %. Female continuous RIs decreased from ages 20–48, then increased significantly from age 49 onward. Conclusions Three indirect methods and two EP28 methods demonstrated good consistency in establishing UA RIs. Males had higher RIs than females, and RIs showed a non-linear correlation with age.

Objectives Although existing cytopathological examination is considered essential for the diagnosis of malignant serous effusions, its accuracy is pretty low. Tumor specific protein 70 (SP70), which is highly expressed on human tumor cell membrane, was identified in our previous study. This study aimed to explore whether SP70 targeted tumor cell isolation technology with immunomagnetic beads can improve the accuracy of cytopathological examination. Methods Cytopathological analysis with SP70 targeted tumor cell isolation technology was used in this study. In total, 255 cases were enrolled. Serous effusions were analyzed by both existing cytopathological examination and the new cytopathological analysis concurrently. Results The sensitivities of existing cytopathological examination and the new cytopathological analysis were 51.26 % and 85.43 %, respectively, while the specificities were 100 % for both. This new cytopathological analysis demonstrated a higher interobserver agreement with malignant diagnosis than the existing cytopathological examination (kappa coefficient: 0.720 vs . 0.316, p<0.001). In addition, it achieved superior diagnostic efficacy for malignancy differentiation compared to existing cytopathological examination (AUC: 0.927 vs . 0.756, p<0.001). The follow-up results showed that 74 malignant cases with final clinical diagnosis were positive only with the new cytopathological analysis. Among these cases, there were 58 negative and 16 atypical by the existing cytopathological examination. In these malignant cases, 74.3 % (55/74) had been confirmed to have serosa metastasis based on radiographic evidence, and 73.7 % (28/38) harbored tumor hotspot mutations. Conclusions As illustrated in this work, cytopathological analysis with SP70 targeted tumor cell isolation technology can improve the accuracy of existing cytopathological examination prominently.

Objectives We examined the 0- and 2-h diagnostic performance of the Mindray high-sensitivity cardiac troponin I (hs-cTnI) assay using two predefined sex-specific 99th percentile upper reference limits (URL) in patients with normal electrocardiograms to aid in the diagnosis of myocardial infarction (MI). Methods Consecutive emergency department patients undergoing serial high-sensitivity cardiac troponin I (hs-cTnI) testing on clinical indication were studied in the ‘Mindray hs-cTnI Assay Analytical and Clinical Evaluation for the Diagnosis and RIsk Assessment of Myocardial InfarctIon’ (MERITnI) trial (NCT05853042). Plasma hs-cTnI testing was performed using Mindray CL1200i (investigational) and Abbott Alinity (clinical) assays. Results In 1,556 patients (60.7 % male, 43.3 % White, 45.8 % Black, 34.8 % chest pain), 2.7 % had type 1 MI, 2.7 % type 2 MI, and 21.5 % non-MI myocardial injury. At 0 h for all MIs (n=86), using package insert URLs and Universal Sample Bank (USB) URLs, sensitivities were 83.7 and 93.0 %. At 0/2 h for all MIs with package insert and USB URLs, sensitivities were higher with serial testing, at 95.3 and 97.7 %. Negative predictive value (NPVs) were excellent and similar for both URLs, ranging from 98 to 100 %. Substantial hs-cTnI concentration differences were observed between sex and injury types. Alinity hs-cTnI diagnostic observations were similar for both package insert and USB URLs. Conclusions The Mindray CL1200i hs-cTnI assay provides the relevant clinical diagnostic information to enable clinicians to deliver cost-effective care for patients to aid in the diagnosis of MI predicated on 0- and 2-h serial testing based on sex-specific 99th percentiles. Novel observations were observed for findings based on different URLs and for females and MI types.

Objectives Recently, four publications have applied Sigma metrics to infectious disease serology testing. Three studies applied Sigma metrics to assays in a blood bank setting, whereas one used anti-toxoplasma testing in a diagnostic laboratory. One of the four studies applied the approach to microtitre plate enzyme immunoassays, whereas the other three were on fully automated chemiluminescent assay. The approaches used by each study differed in the approach used to calculate imprecision, measured as a percentage coefficient of variation, and bias. All four studies used the difference between the mean of the quality control result and the assay cut-off to describe the total allowable error. Methods This paper compares and critically reviews the methods used to calculate the Sigma value for each assay in the four studies and provides an evidence-based assessment of these approaches using real-world quality control data obtained from the National Serology Reference Laboratory, Australia (NRL) QConnect™ quality control program. Results The assessment found that there was a lack of standardisation in the application of Sigma metrics for infectious disease testing, including examples of inappropriate assumptions being used. Westgard Sigma Rules suggest that assays found to have a Sigma value of six or greater can be monitored using two quality control measures and applying a single mean ± three standard deviation rule. Conclusions Although this approach will significantly reduce the number of false rejections generated by using the full range of Westgard rules, we provide evidence that even this approach can potentially cause true errors to be missed.