Clinical chemistry and laboratory medicine最新文献

Objectives: Qualitative faecal immunochemical tests for haemoglobin (FIT), for triaging for colorectal cancer investigations, are available for professional use. The aim was to evaluate these lateral flow tests. No previous analytical evaluations have been published.

Methods: Analytical sensitivity (AS) was assessed using samples spanning manufacturers' quoted AS, concurrently with the quantitative OC-SENSOR PLEDIA, using Hb-spiked samples in manufacturers' buffer (n≥5; ≤9-99 ng Hb/mL buffer), Hb-spiked faeces (n=6; <2-34 µg Hb/g faeces) and natural faeces (n=17; <2-82 μg/g); concentrations for 50 %/100 % Hb-detected were compared with quoted AS. Compatibility with two external quality assessment schemes (EQAS) (n=9; 3-96 μg/g) and prozone compared with manufacturers limits (n=9; 2,500-10,000,000 ng/mL) were tested. Ease-of-use by five healthcare personnel was assessed.

Results: Seven products showed lower AS (ng/mL) than manufacturers quoted using Hb-spiked aqueous samples compared with OC-SENSOR, one was equivocal; six manufacturers quoted AS in µg/g, five showed lower AS using Hb-spiked faeces. Results were similar but less consistent for natural faeces. Result lines for low concentrations can be faint and open to interpretation. Results were consistent with manufacturers quoted prozone limits. Results were consistent for seven products for two EQAS. The ease-of-use was 68.5-85.6 %; products with lower scores could be improved with better instructions and sample bottles.

Conclusions: AS was lower for seven products (aqueous samples) and five products (aqueous/faecal samples) and prozone consistent with manufacturers expected concentrations, compared with OC-SENSOR. EQAS results were mostly consistent with expected results; products can be used by healthcare professionals, though some manufacturer improvements could be made.

In the last decades, clinical laboratories have significantly advanced their technological capabilities, through the use of interconnected systems and advanced software. Laboratory Information Systems (LIS), introduced in the 1970s, have transformed into sophisticated information technology (IT) components that integrate with various digital tools, enhancing data retrieval and exchange. However, the current capabilities of LIS are not sufficient to rapidly save the extensive data, generated during the total testing process (TTP), beyond just test results. This opinion paper discusses qualitative types of TTP data, proposing how to divide laboratory-generated information into two categories, namely metadata and peridata. Being both metadata and peridata information derived from the testing process, it is proposed that the first is useful to describe the characteristics of data, while the second is for interpretation of test results. Together with standardizing preanalytical coding, the subdivision of laboratory-generated information into metadata or peridata might enhance ML studies, also by facilitating the adherence of laboratory-derived data to the Findability, Accessibility, Interoperability, and Reusability (FAIR) principles. Finally, integrating metadata and peridata into LIS can improve data usability, support clinical utility, and advance AI model development in healthcare, emphasizing the need for standardized data management practices.

Objectives: The identification of vitamin B12 (B12) deficiency in the newborn may prevent neurological damage and a delay in the normal growth. In this study we characterized the incidence of B12 deficiency in newborns, the costs associated to the clinical diagnosis and management, and the relevance to optimize the use of cobalamin biomarkers during treatment follow-up.

Methods: Starting from a continuous case series of 146,470 screened newborns (November, 1st 2021- December, 3rd 2023), the Regional Reference Laboratory for Neonatal Screening identified 87 newborns having altered levels of biomarkers of cobalamin metabolism measured by Newborn Screening. These subjects were confirmed with a nutritional B12 deficiency of maternal origin by performing the serum B12 measurements and plasma homocysteine (Hcy) both on the newborns and respective mothers. A cost analysis was performed to characterize the costs/year of identifying and managing B12 deficiency cases.

Results: At baseline, median (interquartile range) serum B12 levels of 185.0 (142.3-246.0) ng/L and threefold increased plasma Hcy concentrations above the normal level confirmed a severe condition of deficiency in the newborns. After intramuscular B12 supplementation, serum B12 measured at the first follow up visit showed a fivefold increase, and the levels of Hcy returned to normal. From the healthcare perspective, the costs for diagnosing and managing all newborns with B12 deficiency is 188,480 €/year.

Conclusions: Preventing B12 depletion in newborns lowers healthcare costs and likely improves their health outcomes. Further studies are however required to address the clinical pathway to identify, treat and monitor pregnant women with marginal and low B12 status, in order to achieve these goals.

Objectives: As thyroid disorders are common amongst the elderly, this study aims to evaluate the reference interval (RI) for thyroid stimulating hormone (TSH) in healthy adults aged 70 years and over.

Methods: A proposed RI was determined from the Australian participants of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. Participants had no history of cardiovascular disease, thyroid cancer, dementia, or life-threatening illnesses. Participants prescribed with any thyroid-related medication at baseline were excluded. TSH levels were measured using a commercial chemiluminescence microparticle immunoassay. The RI was determined using the middle 95th percentile of the logarithmic transformed data of baseline TSH. Cox proportional hazard regression models were used to validate the RI by assessing disease incidence over time.

Results: A total of 10,995 participants had baseline TSH measures. Median (IQR) age was 73.9 (71.8-77.3) years. We propose a RI of 0.34-3.75 mU/L. TSH levels did not differ by age or sex. At baseline, there was no association between symptoms associated with thyroid disease and levels of TSH. Over the follow-up period of up to 11 years, no association was seen between baseline TSH levels and relevant disease outcomes for participants within the RI.

Conclusions: From a group of initially healthy, community-dwelling adults aged >=70 years, we propose a RI of TSH to best represent euthyroidism. This concentration was not associated with an increased risk of thyroid related symptoms or outcomes, confirming its appropriateness for clinical use.

Objectives: Serum cystatin C (CysC) is a reliable and ideal endogenous marker for accurately assessing early changes in glomerular filtration rate (GFR), surpassing the limitations of creatinine-based estimated GFR. To improve the precision of GFR calculation, the development of strategies for accurately measuring serum CysC is crucial.

Methods: In this study, the full-length CysC pure product and fully recombinant ¹⁵N-labeled CysC internal standard were subjected to protein cleavage. Subsequently, an LC-MS/MS method was developed for the absolute quantification of serum CysC. The traceability of the method was assigned calibrator using the amino acid reference measurement procedure (RMP). It involved calibrating the instrument using an amino acid reference material with known amino acid concentrations for calibration and comparison purposes.

Results: The total imprecision of the method was determined to be ≤8.2 %, and a lower functional limit of quantification (LLoQ) was achieved. The recoveries ranged from 97.36 to 103.26 %. The relative bias between this candidate RMP for measurement of ERM-DA471-IFCC and the target value was 1.74 %. The linearity response was observed within the concentration range of 0.21-10.13 mg/L, with a high R² value of 0.999. The results obtained using our method was consistent with those obtained using other certified RMPs.

Conclusions: With the establishment of this highly selective and accurate serum CysC measurement method, it is now possible to assess the correlation between immunoassay results of serum CysC and the intended target when discrepancies are suspected in the clinical setting.

Objectives: The COVID-19 pandemic has exposed a number of key challenges that need to be urgently addressed. Mass spectrometric studies of blood plasma proteomics provide a deep understanding of the relationship between the severe course of infection and activation of specific pathophysiological pathways. Analysis of plasma proteins in whole blood may also be relevant for the pandemic as it requires minimal sample preparation.

Methods: The frozen whole blood samples were used to analyze 203 plasma proteins using multiple reaction monitoring (MRM) mass spectrometry and stable isotope-labeled peptide standards (SIS). A total of 131 samples (FRCC, Russia) from patients with mild (n=41), moderate (n=39) and severe (n=19) COVID-19 infection and healthy controls (n=32) were analyzed.

Results: Levels of 94 proteins were quantified and compared. Significant differences between all of the groups were revealed for 44 proteins. Changes in the levels of 61 reproducible COVID-19 markers (SERPINA3, SERPING1, ORM1, HRG, LBP, APOA1, AHSG, AFM, ITIH2, etc.) were consistent with studies performed with serum/plasma samples. The best-performing classifier built with 10 proteins achieved the best combination of ROC-AUC (0.97-0.98) and accuracy (0.90-0.93) metrics and distinguished patients from controls, as well as patients by severity.

Conclusions: Here, for the first time, frozen whole blood samples were used for proteomic analysis and assessment of the status of patients with COVID-19. The results obtained with frozen whole blood samples are consistent with those from plasma and serum.

Objectives: The performance of synovial fluid biomarker D-lactate to diagnose septic arthritis (SA) and differentiate it from crystal-induced arthritis (CA), other non-infectious rheumatic joint diseases (RD) and osteoarthrosis (OA) was evaluated.

Methods: Consecutive adult patients undergoing synovial fluid aspiration due to joint pain were prospectively included in different German and Swiss centers. Synovial fluid was collected for culture, leukocyte count and differentiation, detection of crystals, and D-lactate concentration. Youden's J statistic was used to determine optimal D-lactate cut-off value on the receiver operating characteristic (ROC) curve by maximizing sensitivity and specificity.

Results: In total 231 patients were included. Thirty-nine patients had SA and 192 aseptic arthritis (56 patients with OA, 68 with CA, and 68 with RD). The median concentration of synovial fluid D-lactate was significantly higher in patients with SA than in those with OA, CA, and RD (p<0.0001, p<0.0001 and p<0.0001, respectively). The optimal cut-off of synovial fluid D-lactate to diagnose SA was 0.033 mmol/L with a sensitivity of 92.3 % and specificity of 85.4 % independent of previous antimicrobial treatment. Sensitivity and specificity of synovial fluid leukocyte count at a cut-off of 20,000 cells/µL was 81.1 % and 80.8 %, respectively.

Conclusions: Synovial fluid D-lactate showed a high performance for diagnosing SA which was superior to synovial fluid leukocyte count. Given its high sensitivity and specificity, it serves as both an effective screening tool for SA and a differentiator between SA and RD, especially CA.

Objectives: A smear review is typically made in flagged differential counts performed with hematology analyzers although the clinical value of such reviews is uncertain. Therefore, we evaluated the differences in differential counts between Sysmex XN-9000 and a smear review in flagged samples. Furthermore, the clinical value of blasts identified was investigated.

Methods: Data on all differential counts performed in a two-year period were identified at two laboratories. In patients with blasts, the electronic health record was reviewed. Agreement between automated and manual differential counts was evaluated by Bland-Altman plots. Concordance between the two methods categorized according to reference intervals was evaluated and adjusted for irrelevant non-concordance caused by random analytical error.

Results: In total, 5,500 flagged differential counts were identified from 4,092 patients. A good agreement between the automated and manual differential count was found for all cell types (-0.480 × 10⁹/L to 0.297 × 10⁹/L). The concordance between the two methods was excellent for all cell types, except for monocytes (82 %) where the automated estimates were higher than the manual in 19 % of samples. Blasts were identified in 241 (1 %) of smear reviews. Acute leukemia was diagnosed in 13 (5 %) patients, and only in one patient contributed the detection of blasts to the suspicion of acute leukemia.

Conclusions: Our findings indicate that routine smear review of all flagged samples do not contribute with additional, significant information. After local validation and dialogue with clinical departments, such reviews may potentially be omitted to increase cost-effectiveness and reduce turn-around-time.