Clinical chemistry and laboratory medicine最新文献

Objectives: Mild traumatic brain injury (mTBI) remains challenging to diagnose effectively in the emergency department. Abbott has developed the "GFAP/UCH-L1" mTBI test, to guide the clinical decision to perform a computed tomography (CT) head scan by ruling out the presence of mTBI. We evaluated the diagnostic accuracy of the "GFAP/UCH-L1" mTBI test in a Greek cohort and established age-dependent cut-offs.

Methods: A total of 362 subjects with suspected mTBI and admitted to the Emergency department of the KAT General Hospital of Athens, Greece were recruited for the study. All subjects underwent a CT head scan to establish the diagnosis of mTBI. GFAP and UCH-L1 were measured using Alinity I (Abbott). 163 healthy subjects served as controls.

Results: Using the manufacturer's cut-offs (35 ng/L for GFAP and 400 ng/L for UCH-L1), the "GFAP/UCH-L1" mTBI test had a sensitivity of 99.1 % and a specificity of 40.6 %. However, the specificity dropped to 14.9 % in patients older than 65 years old. By defining a new cut-off of 115 ng/L for GFAP and 335 ng/L specifically for patients older than 65 years, specificity was increased up to 30.6 % without changing test sensitivity and the number of CT head scans avoided was doubled in this subgroup.

Conclusions: The "GFAP/UCH-L1" mTBI test is an efficient "rule-out test" to exclude patients suffering from mTBI. By adjusting the cut-offs in patients older than 65 years old, we could significantly increase the number of CT head scans avoided without affecting the sensitivity. These new cut-offs should be externally validated.

Important advancements have been made in understanding the pathogenetic mechanisms underlying acute and chronic lung disorders. But although a wide variety of innovative biomarkers have and are being investigated, they are not largely employed to evaluate non-neoplastic lung diseases. The current work aims to examine the use of Krebs von den Lungen-6 (KL-6), a mucin-like glycoprotein predominantly expressed on the surface of type II alveolar epithelial cells (AEC2s), to evaluate the stage, response to treatment, and prognosis in patients with non-neoplastic lung disorders. Data analysis suggests that KL-6 can be utilized as an effective diagnostic and prognostic biomarker in individuals with interstitial lung disease and as a predictor of clinical outcomes in subjects with SARS-CoV-2-related pneumonia. Moreover, KL-6 can be reliably used in routine clinical settings to diagnose and predict the outcome of patients with chronic obstructive pulmonary disease (COPD) exacerbation. The optimal cut-off points within the European population should be defined to improve KL-6's diagnostic efficacy.

The 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for chronic kidney disease (CKD) evaluation and management bring important updates, particularly for European laboratories. These guidelines emphasize the need for harmonization in CKD testing, promoting the use of regional equations. In Europe, the European Kidney Function Consortium (EKFC) equation is particularly suited for European populations, particularly compared to the CKD-EPI 2021 race-free equation. A significant focus is placed on the combined use of creatinine and cystatin C to estimate glomerular filtration rate (eGFRcr-cys), improving diagnostic accuracy. In situations where eGFR may be inaccurate or clinically insufficient, the guidelines encourage the use of measured GFR (mGFR) through exogenous markers like iohexol. These guidelines emphasize the need to standardize creatinine and cystatin C measurements, ensure traceability to international reference materials, and adopt harmonized reporting practices. The recommendations also highlight the importance of incorporating risk prediction models, such as the Kidney Failure Risk Equation (KFRE), into routine clinical practice to better tailor patient care. This article provides a European perspective on how these KDIGO updates should be implemented in clinical laboratories to enhance CKD diagnosis and management, ensuring consistency across the continent.

Although the concept of bias appears consolidated in laboratory science, some important changes in its definition and management have occurred since the introduction of metrological traceability theory in laboratory medicine. In the traceability era, medical laboratories should rely on manufacturers who must ensure traceability of their in vitro diagnostic medical devices (IVD-MD) to the highest available references, providing bias correction during the trueness transfer process to calibrators before they are marketed. However, sometimes some bias can be observed arising from an insufficient correction during the traceability implementation. This source of bias can be discovered by the IVD-MD surveillance by traceability-based external quality assessment and confirmed by ad-hoc validation experiments. The assessment of significance should be based on its impact on measurement uncertainty (MU) of results. The IVD manufacturer, appropriately warned, is responsible to take an immediate investigation and eventually fix the problem with a corrective action. Even if IVD-MD is correctly aligned in the validation steps and bias components are eliminated, during ordinary use the system may undergo systematic variations such as those caused by recalibrations and lot changes. These sources of randomly occurring bias are incorporated in the estimate of intermediate reproducibility of IVD-MD through internal quality control and can be tolerated until the estimated MU on clinical samples fulfils the predefined specifications. A readjustment of the IVD-MD by the end-user must be undertaken to try to correct the bias becoming significant. If the bias remains, the IVD manufacturer should be requested to rectify the problem.

Objectives: To provide age- and sex-specific paediatric reference intervals (RIs) for 13 haematological parameters analysed on Sysmex XN-9000 and compare different methods for estimating RIs after indirect sampling.

Methods: Via the Danish Laboratory Information System, we conducted a population-based study. We identified samples from children aged 0-18 years analysed at Aarhus University Hospital from 2019 to 2023, including samples from general practitioners only. Information about all parameters were available for all samples via linkage to the local laboratory middleware. Then, we applied two different methods. First, we excluded potential pathological samples by predefined criteria: if the child had other abnormal blood measurements at date of request, or had a blood sample of any type analysed in the period two months before to two months after. We estimated RIs stratified by age- and sex using the non-parametric percentile method. Second, we used refineR (an open source automated algorithm) to exclude pathological samples and for RI estimation. Finally, we compared our data to results from a study using the direct method.

Results: We identified 22,786 samples. After exclusion by predefined criteria, the population comprised 10,199 samples from 8,736 children (57 % of samples were from females and median age was 13 years). We estimated RIs for red blood cell, white blood cell and platelet indices. The two different methods showed agreement. Furthermore, our data provided results comparable to direct sampling.

Conclusions: Our study provided age- and sex-specific paediatric RIs for 13 haematology parameters useful for laboratories worldwide. RIs were robust using different methods in the framework of indirect sampling. Finally, our data showed agreement with the direct method, indicating that indirect sampling could be useful for establishing RIs on haematology parameters in the future.

The presented guidelines are an update of the position paper, endorsed by the International Osteoporosis Foundation (IOF), on nomenclature of bone markers published over 2 decades ago. Novel insight into bone biology and pathophysiology of bone disorders has highlighted the increasing relevance of new and known mediators implicated in various aspects of bone metabolism. This updated guideline proposes the nomenclature Bone Status Indices (BSI) as the comprehensive classification rather than bone turnover markers, bone markers, metabolic markers of bone turnover or metabolic markers of bone turnover, that are currently in use for the implicated molecules. On behalf of the IFCC Committee on Bone Metabolism and the Joint IOF Working Group and IFCC Committee on Bone Metabolism, the authors propose standardized nomenclature, abbreviations and measurement units for the bone status indices.

Objectives: Expanded carrier screening (ECS) is a preventive genetic test that enables couples to know their risk of having a child affected by certain monogenetic diseases. This study aimed to evaluate the carrier frequency for rare monogenic diseases in the general Chinese population and the impacts of ECS on their reproductive decisions and pregnancy outcomes.

Methods: This single-center study was conducted between September 2022 and April 2023. An ECS panel containing 224 recessive genes was offered to 1,499 Chinese couples from the general population who were at early gestational ages or planned to conceive.

Results: Overall, 55.0 % of the individuals carried for at least one recessive condition. There were 16 autosomal recessive (AR) genes with a carrier frequency of ≥1/100 and 22 AR genes with a carrier frequency of <1/100 to ≥1/200. The most common AR and X-linked diseases were GJB2-related non-syndromic hearing loss, and hemolytic anemia, respectively. Fifty-five couples (3.67 %; 1 in 27.3) were at increased risk of having an affected child with 19 pregnant at the time of testing. Of these, 10 opted for amniocentesis, and four affected pregnancies were identified, with three of them being terminated.

Conclusions: This study not only provides valuable information about the recessive genetic landscape, but also establishes a solid foundation for couple-based ECS in a real clinical setting.

Objectives: CD34+ hematopoietic stem cell (HSC) enumeration, crucial for HSC transplantation, is performed by flow cytometry to guide clinical decisions. Variability in enumeration arises from biological factors, assay components, and technology. External quality assurance schemes (EQAS) train participants to minimize inter-laboratory variations. The goal is to estimate total error (TE) values for CD34 cell enumeration using state-of-the-art (SOTA) methods with EQA data and to define quality specifications by comparing TE using different cutoffs.

Methods: A total of 3,994 results from 40 laboratories were collected over 11 years (2011-2022) as part of the IC-2 Stem Cells Scheme of the GECLID Program that includes absolute numbers of CD34 cells. The data were analyzed in two periods: 2011-2016 and 2017-2022. The TE value achieved by at least 60 %, 70 %, 80 %, and 90  % of laboratories was calculated across the two different periods and at various levels of CD34 cell counts: above 25, 25 to 15, and under 15 cells/μL.

Results: A decrease in the SOTA-based TE for CD34 cell enumeration was observed in the most recent period in 2017-2021 compared with 2012-2016. A significant increase of P75 TE values in the low CD34 range (<15 cells/μL) levels was found (p<0.001).

Conclusions: Technical advancements contribute to the decrease TE over time. The TE of CD34 cell FC counts is measure-dependent, making it responsive to precision enhancement strategies. The TE measured by EQAS in this study may serve as a quality specification for implementing ISO 15189 standards in clinical laboratories for CD34 cell enumeration.