Scandinavian Journal of Clinical & Laboratory Investigation最新文献

Hematology laboratories routinely face analytical challenges despite automation and standardized workflows. While Six Sigma metrics are increasingly applied in clinical chemistry, their use in hematology remains limited due to variability in Total Allowable Error (TEa) standards and lack of integrated assessment tools. This study aims to evaluate analytical performance in hematology by combining sigma metrics with an innovative graphic decision tool to guide quality control (QC) planning. A retrospective study over was conducted in a tertiary hematology lab. Internal Quality Control (IQC) and External Quality Assurance Scheme (EQAS) data for five analytes-hemoglobin, WBC, RBC, hematocrit, and platelet count-were analyzed using the Six Sigma model. TEa values were selected using a hierarchical approach based on the 2014 Milan Consensus, prioritizing biological variation, CLIA, and RCPA guidelines. A novel graphic tool was used to visualize performance zones and inform QC strategies. Sigma metrics varied across parameters and TEa sources. Hemoglobin demonstrated excellent performance (σ > 6), while hematocrit and platelet count showed sigma <3 under strict TEa. Graphic tool stratification revealed actionable insights; application of TEa optimization reclassified low-performing tests, significantly improving QC efficiency. Subsequent QGI calculations identified the predominant source of error. This study introduces a first-time application of a graphic tool in hematology for sigma visualization and QC planning. The dual-framework approach enhances diagnostic accuracy and resource utilization, offering a practical, scalable model for laboratories seeking personalized, risk-based quality management.

Objective: To investigate chemiluminescence immunoassay (CLIA) in detecting anti-centromere antibodies (ACA) in primary biliary cholangitis (PBC) patients.

Methods: In this retrospective study, 165 patients diagnosed with PBC at Hangzhou Xixi Hospital between December 2020 and January 2023 were enrolled. ACA positivity was assessed using three methods: indirect immunofluorescence (IIF), line immunoassay (LIA), and CLIA. The agreement among the methods was evaluated using kappa statistics and correlation analysis. Logistic regression was used to assess the association between ACA positivity and portal hypertension. Receiver operating characteristic (ROC) curve analysis was performed to compare the predictive performance of CLIA and LIA for portal hypertension.

Results: Among the 165 PBC patients, 69 (41.8%), 68 (41.2%), and 66 (40.0%) were ACA-positive by IIF, LIA, and CLIA, respectively. CLIA showed excellent agreement with IIF (κ = 0.962) and LIA (κ = 0.975), and a strong correlation with LIA in quantitative detection (R = 0.893, p < 0.001). Logistic regression confirmed that ACA positivity was significantly associated with portal hypertension (OR = 2.726, 95% CI: 1.437-5.169, p = 0.002). CLIA demonstrated superior predictive performance over LIA for portal hypertension (AUC: 0.705 vs. 0.638, p = 0.001).

Conclusion: CLIA exhibits excellent concordance with conventional methods for detecting ACA and provides a broader linear range for quantitative assessment. ACA positivity was significantly associated with portal hypertension in PBC patients. The main advantage of CLIA lies in its precise quantification of ACA and prognostic value, highlighting its potential role in risk stratification and disease monitoring in PBC patients.

Home sampling of saliva is noninvasive, easy, and convenient, especially for multiple sampling. Such samples are therefore appropriate for the measurement of melatonin, a biomarker for circadian dysregulation. However, home sampling is restricted by access to appropriate storage conditions. This study, therefore, evaluated the effect of common storage conditions on the stability of melatonin in synthetic fiber swabs employed for home sampling. Saliva was provided by healthy volunteers during daytime, pooled and subsequently divided into fractions, each spiked with different amounts of melatonin. Synthetic fiber swabs were allowed to accumulate saliva from these fractions followed by storage at room temperature, 4 °C or -20 °C for 24, 48 or 72 h. The melatonin levels were analyzed employing a commercial ELISA assay. Differences in concentrations at each storage condition were evaluated with a two-way repeated measures ANOVA followed by a Tukey multiple comparison test. Samples were significantly more stable at -20 °C compared to room temperature and 4 °C, irrespective of the storage duration. However, no significant decrease from baseline was observed for samples stored at either 4 °C or -20 °C after 72 h. In comparison, a significant decrease was observed at room temperature after just 24 h. In conclusion, storage at -20 °C may be considered the gold standard for synthetic fiber swabs for quantification of salivary melatonin. However, storage at 4 °C ensures stability for 72 h while also ensuring convenience for home sampling. It is therefore our recommendation that such home samples are refrigerated, transported cold and centrifuged within 72 h of collection.

This study aimed to investigate the effect of obesity on angiogenesis and its relationship with liver steatosis in obese children and adolescents. The study ıncluded 81 obese ın chıldren and 30 healthy controls. Obese subjects were subdıvıded by ultrasound ınto three groups: no steatosıs, grade 1 lıver steatosıs (NAFL), and grade 2 NAFL. Obese individuals, regardless of the presence of NAFL, exhibited significant insulin resistance (p < .01) compared to their lean counterparts. All obese subjects showed elevated serum ALT, wıth a sıgnıfıcantly greater ın those wıth NAFL. Marked dyslipidemia by decreased high-density lipoprotein (HDL) levels and elevated triglycerides, was observed in obese individuals with NAFL. The serum levels of angiopoietin-1 (Ang-1) and vascular endothelial growth factor-165b (VEGF165b) were measured as anti-angiogenic markers, while vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor-2 (FGF-2) and P-selectin were assessed as pro-angiogenic factors. Compared to normal-weight children (5558 ± 674 pg/mL), Ang-1 levels were significantly elevated in all obese subgroups (8861 ± 1026; 8105 ± 615; 7388 ± 924, respectıvely). However, no significant differences in Ang-1 levels were observed among the obese subgroups. Ang-1 and VEGF165b levels were significantly higher in insulin-resistant individuals (7575 ± 747 pg/mL and 293 ± 44.4 pg/mL, respectively) compared to insulin-sensitive subjects (6143 ± 557 pg/mL and 179 ± 31.4 pg/mL, respectively). These findings suggest that insulin resistance in obese children is associated with altered angiogenic signaling. However, no significant differences in the serum levels of angiogenic factors were observed between obese groups with and without NAFL.

The aim of this study was to validate the blood glucose point-of-care system, cobas^® pulse (Roche Diagnostics GmbH), which is the successor to the Accu-Chek^® Inform II system (Roche Diagnostics GmbH). Since the cobas^® pulse device is intended to replace an existing device from the same manufacturer, we found it highly relevant to perform an industry-independent validation regarding accuracy and comparability with existing glucose measurement systems. From 40 randomly selected, non-fasting adults capillary and venous blood was drawn simultaneously. Correlation and agreement was evaluated by comparing capillary blood glucose on cobas^® pulse to plasma glucose on cobas^® 8000 (Roche Diagnostics GmbH) and capillary blood glucose on ABL800 Flex (Radiometer, Denmark), respectively. The cobas^® pulse generally showed good agreement with both comparison methods, although the agreement between cobas^® pulse and ABL800 Flex was better (bias -0.01 mmol/L) than between cobas^® pulse and cobas^® 8000 (bias 0.61 mmol/L). Differences between measurements of low blood glucose levels (range 0.5 to 4.8 mmol/L) and higher blood glucose levels (range 9.7 to 15.3 mmol/L) when comparing cobas^® pulse to ABL800 Flex was also within allowable limits. Altogether, the validation study demonstrated a clinically satisfactory performance of the cobas^® pulse point-of-care device.

The aim was to assess and compare the analytical performance of the FUS-200 and its new upgrade, the MUS-3600 urine autoanalyzers, and to compare performance with manual microscopy. First morning, void urine samples were randomly collected, and suitable samples were analyzed on both autoanalyzers. In addition, concurrent manual microscopic examinations were performed for all suitable urine samples. Carry-over, linearity and imprecision analysis were performed to assess analytical and diagnostic performance of both urine autoanalyzers according to Clinical and Laboratory Standards Institute (CLSI) EP15-A2, and the study was conducted in accordance with CLSI GP16-A3 Urinalysis; Approved Guideline. A total of 518 samples were collected, and of these, 494 (95.4%) were suitable for analysis and were included in the study. Sensitivity and positive likelihood ratio (LR+) values for WBC and squamous epithelium (SqEC) counts for both autoanalyzers were >90% and >10%, respectively. Specificity and LR+ values obtained from MUS-3600 were better compared to the FUS-200 (respectively 92.8 vs. 84.7; 5.5 vs. 10.1). One group agreement between the MUS-3600 and manual microscopy was >90%. Both analyzers displayed comparable performance for RBC and WBC counts, which were moderately correlated with each other. These results show the diagnostic performance of the MUS-3600 and FUS-200 was satisfactory for urine sediment analysis and was compatible with manual microscopy findings. However, random urine samples are sub-optimal for evaluating diagnostic performance, particularly for bacterial, cast, crystal and yeast analysis. Thus, we recommend using more appropriate urine samples for this comparison, such as from patients with suspected urinary tract infections.

Elevated triglyceride (TG) levels, common in hypertriglyceridemia, can significantly interfere with electrolyte analysis, particularly by the indirect ion-selective electrode (ISE) method. However, comprehensive data on the concentration-dependent measurement differences for potassium, sodium and chloride, along with validated corrective algorithms, are lacking. This study assessed the discrepancies in these electrolytes between direct and indirect ISE methods in serum samples with high TGs, while developing correction formulas for the indirect ISE. A total of 154 serum samples with high TGs and 50 control serum samples were analyzed in this retrospective cross-sectional study. Triglycerides were measured using colorimetric methods on the Roche Cobas 8000 analyzer (Roche Laboratories, Basel, Switzerland). Sodium, potassium and chloride were measured with direct ISE (Vitros 5600 Integrated System; Ortho-Clinical Diagnostics, Inc., Raritan, NJ) and indirect ISE (Roche Cobas 8000 analyzer). Our results revealed significant negative biases in the indirect ISE, particularly in samples with TG >20.00 mmol/L. For TG levels between 20.01 and 30.00 mmol/L, the negative biases for sodium, potassium and chloride were -2.31%, -3.86% and -4.58%, respectively. Notably, in the subgroup with TG >60.00 mmol/L, the negative biases reached their maximum values: -12.05% for potassium, -6.88% for sodium, and -10.59% for chloride. Additionally, linear correction formulas that aligned indirect results with direct measurements were developed and validated. Post-correction, differences fell within clinical thresholds (Diff_Na of |4| mmol/L, Diff_Cl of |4| mmol/L, Diff_K of |0.5| mmol/L). Collectively, high TGs impact electrolyte measurements by indirect ISE, but the correction formulas might mitigate the discrepancies. These correction formulas were platform-specific, and their generalizability to other analytical systems requires further investigation.

Familial hypocalciuric hypercalcemia (FHH) is a genetically heterogeneous autosomal dominant disorder of calcium homeostasis, which is usually asymptomatic and characterized by low or normal phosphorus, inappropriately normal or elevated PTH, and low fractional excretion of calcium (FECa) in addition to hypercalcemia. Loss-of-function mutations in the G protein subunit alpha 11 (GNA11) gene, an important downstream signaling partner of the Calcium-sensing receptor (CaSR), cause FHH type 2. We reviewed the GNA11 gene-associated FHH type 2. A 14-year-old male was referred due to hypercalcemia (2.89 mmol/L). Slightly elevated PTH (7.95 pmol/L), but normal phosphorus (1.19 mmol/L), alkaline phosphatase (271 U/L), magnesium (0.95 mmol/L), and albumin (43 g/L) levels were detected. The FECa was found to be low when serum calcium was high (FECa was <0.01%, and <0.01% on two separate tests). A homozygous c.301T > C, p.Y101H variant was detected in the GNA11 gene. The same variant was detected heterozygous for both parents. While the calcium levels of the mother and father were normal, their spot urinary FECa was found low (Ca: 2.47 mmol/L, FECa: <0.01%, and Ca: 2.45 mmol/L, FECa: 0.01%, respectively). Hypocalciuria without hypercalcemia can be detected in cases heterozygous for the GNA11 gene mutation. Severe hypercalcemia may not occur in homozygous cases.

As neuroblastoma is a highly heterogeneous pediatric solid tumor, it is essential to select appropriate reference genes to compare the concentration of circulating free DNA (cfDNA) between patients with neuroblastoma and healthy individuals. cfDNA was extracted from peripheral blood and quantified using quantitative Polymerase Chain Reaction (qPCR). The stability of candidate reference genes (RGs) was analyzed using the ΔCt method, geNorm, NormFinder, and BestKeeper. The results from these four algorithms were integrated using the RefFinder tool to generate a comprehensive stability ranking and assess the stability of these candidate RGs across different sample groups. Alpha hemoglobin stabilizing protein (AHSP) and Hypoxanthine-Guanine Phosphoribosyltransferase 1 (HPRT1) exhibited the highest stability, whereas Beta-2-microglobulin(B2M) and HBS1-like protein(HBS1L) demonstrated the lowest stability. qPCR of cfDNA from patients with neuroblastoma revealed differences in the stability of various reference genes. Prioritizing reference genes with better stability may facilitate more accurate detection of intergroup differences in the samples.

Cystatin C was identified as a marker of glomerular filtration rate (GFR) in 1979, and the parallel analysis of cystatin C and creatinine led to the identification of shrunken pore syndrome (SPS) - a new kidney disorder - in 2015. Since then, it has been shown that cystatin C in many aspects is superior to creatinine as a marker of GFR and cardiovascular risk. SPS, an entity within the selective glomerular hypofiltration syndromes (SGHS), has been demonstrated to be associated with a strong increase in morbidity and mortality in several populations. Despite the seriousness of SPS and SGHS, and the availability of potential treatments, many patients with these conditions remain undiagnosed, due to the limitations of the international Kidney Disease Improving Global Outcomes Organization (KDIGO) guidelines. Given the significant clinical advantages of cystatin C in diagnosing and treating kidney disorders, there is a need to expand the KDIGO guidelines to include cystatin C measurements alongside creatinine at least in the initial patient evaluation but also in follow-up evaluations. This would improve the early detection and management of patients with kidney diseases, ultimately enhancing patient outcomes. The present discourse summarizes the development of this understanding from the original observations in 1979 and 2015 to the latest findings.