Insight into the status of plasma renin and aldosterone measurement: findings from 526 clinical laboratories in China.

OBJECTIVES: Accurate measurements of renin and aldosterone levels play an important role in primary aldosteronism screening, which is of great importance in the management and categorization of hypertension. The objective of this study is to investigate the current status of plasma renin and aldosterone measurements in China, which is achieved by analyzing the results of 526 clinical laboratories nationwide for three pooled fresh plasma samples derived from more than 2,000 patients. METHODS: Renin and aldosterone in three pooled plasma samples were measured four times in 526 laboratories employing various measurement systems. The inter- and intra-laboratory %CV were calculated and compared. To determine the source of the substantial inter-laboratory %CV, laboratories were categorized according to the measurement systems they are using, and both the inter- and intra-measurement-system %CV were calculated and compared. RESULTS: Regarding renin, the majority of laboratories use four primary commercial immunoassays. However, for aldosterone, in addition to commercial immunoassays, laboratory-developed liquid chromatography-tandem mass spectrometry (LC-MS) methods are also used by laboratories. The median values of intra-laboratory %CVs, intra-measurement-system %CVs, inter-laboratory %CVs, and inter-measurement systems %CVs varied between 1.6 and 2.6 %, 4.6 and 14.9 %, 8.3 and 25.7 %, and 10.0 and 34.4 % for renin, respectively. For aldosterone, these values ranged from 1.4 to 2.2 %, 2.5-14.7 %, 9.9-31.0 %, and 10.0-35.5 %, respectively. CONCLUSIONS: The precision within laboratories and measurement systems for plasma renin and aldosterone measurements is satisfactory. However, the comparability between laboratories using different measurement systems remains lacking, indicating the long way to achieve standardization and harmonization for these two analytes.

Prognostic Assessment of Colorectal Cancer Patients after Laparoscopic Surgery: A Comprehensive Evaluation of the Glasgow Prognostic Score and Fibrinogen-to-Prealbumin Ratio.

BACKGROUND Previous studies have shown that systemic inflammation and suboptimal nutritional status are associated with poor cancer prognosis. This study aims to investigate the prognostic value of preoperative Glasgow prognostic score (GPS) and fibrinogen-to-prealbumin ratio (FPR) in patients with CRC (colorectal cancer) after laparoscopic surgery. MATERIAL AND METHODS In this study, the clinical data of 112 patients with CRC who underwent laparoscopic surgery were retrospectively analyzed, and the 3-year and 5-year survival rates of these patients were evaluated. In addition, the prognostic role of preoperative FPR and GPS in CRC patients was assessed using X-tile software, Kaplan-Meier analysis, and Cox regression analysis. Receiver operating characteristic (ROC) curves were generated to assess the predictive value of FPR, GPS, and FPR-GPS for the survival of these patients. RESULTS The results revealed a significant negative correlation between high FPR, elevated GPS, and overall survival (OS) in patients with CRC. Univariate and multivariate Cox regression analyses identified GPS (HR=3.207, 95% CI: 1.746~6.126), FPR (HR=2.669, 95% CI: 1.052~6.772), and lymph node metastasis (HR=2.222, 95% CI: 1.199~4.115) as independent prognostic indicators for overall survival. The ROC analysis demonstrated that the prediction based on FPR and GPS outperformed a single indicator in accurately predicting the prognosis of CRC patients. CONCLUSIONS Combining the preoperative FPR with the GPS contributes to accurate prognosis assessment for CRC patients after laparoscopic surgery. Patients exhibiting high FPR and GPS values are associated with a worse prognosis.

Imprecision remains to be improved in the measurement of serum cystatin C with heterogeneous systems.

OBJECTIVES: Except for the large bias of some measurement systems for serum cystatin C (CysC) measurements, unacceptable imprecision has been observed for the heterogenous system. This study analyzed the external quality assessment (EQA) results in 2018-2021 to provide an insight into the imprecision of CysC assays. METHODS: Five EQA samples were sent to participating laboratories every year. Participants were divided into reagent/calibrator-based peer groups, for which the robust mean of each sample and robust coefficient of variation (CV) were calculated by Algorithm A from ISO 13528. Peers with more than 12 participants per year were selected for further analysis. The limit of CV was determined to be 4.85% based on clinical application requirements. The concentration-related effect on CVs was investigated using logarithmic curve fitting; the difference in medians and robust CVs between instrument-based subgroups was also evaluated. RESULTS: The total number of participating laboratories increased from 845 to 1,695 in four years and heterogeneous systems remained the mainstream (≥85%). Of 18 peers with ≥12 participants, those using homogeneous systems showed relatively steady and small CVs over four years, with the mean four-year CVs ranging from 3.21 to 3.68%. Some peers using heterogenous systems showed reduced CVs over four years, while 7/15 still had unacceptable CVs in 2021 (5.01-8.34%). Six peers showed larger CVs at the low or high concentrations, and some instrument-based subgroups presented greater imprecision than others. CONCLUSIONS: More efforts should be made to improve the imprecision of heterogeneous systems for CysC measurement.

Exploration of suitable external quality assessment materials for serum C-peptide measurement.

OBJECTIVES: To find suitable external quality assessment (EQA) materials for serum C-peptide, we evaluated the commutability of five types of processed materials. METHODS: Seventy-four individual serum samples and 12 processed samples including three EQA samples currently in use, frozen human serum pools (FHSP), and three other kinds of processed samples were prepared by dissolving WHO International Standard Reagent for C-peptide (WHO ISR 13/146) in three different matrixes: 0.05 % bovine serum albumin, fetal bovine serum and human serum pools. Samples were analyzed using the isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method and six widely used immunoassays. The commutabilities of processed materials were assessed according to the difference in bias approach recommended by the IFCC. And the short- and long-term stability of FHSP samples at different temperatures were also evaluated. RESULTS: Out of the five kinds of processed materials, FHSP samples were commutable on most assays. In contrast, the EQA materials currently in use were only commutable on a few immunoassays. Additionally, processed materials derived from WHO ISR 13/146 were found to be un-commutable on over half of immunoassays. The FHSP samples could be stably stored at 4 and -20 °C for at least 16 days, and at -80 °C for at least 1 year, but at room temperature only for 12 h. CONCLUSIONS: With clarified commutability and stability information, the human serum pool samples along with the developed ID-LC-MS/MS method could be used in the EQA program to promote the comparability among laboratories for C-peptide measurement in China.

Preoperative Neutrophil-Lymphocyte Ratio (NLR)-Binding Fibrinogen-Albumin Ratio (FAR) Is Superior to Platelet-Lymphocyte Ratio (PLR)-Binding Fibrinogen-Albumin Ratio (FAR) and Lymphocyte-Monocyte (LMR)-Binding Fibrinogen-Albumin Ratio (FAR) as Predictors of Survival in Surgical Patients with Colorectal Adenocarcinoma.

BACKGROUND Studies have revealed that having systemic inflammation is linked to worse survival rates across a range of malignancies. This study aimed to evaluate the predictive significance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in combination with fibrinogen-to-albumin ratio (FAR) in surgical patients with colorectal adenocarcinoma (CRC). MATERIAL AND METHODS From January 2010 to December 2016, 200 patients with CRC had their preoperative NLR, PLR, LMR, and FAR assessed. Following that, univariate and multivariate analytic techniques were used to establish the prognostic value of these 4 indicators. Plotting the receiver operating characteristic (ROC) curves allowed researchers to assess whether the NLR-FAR, PLR-FAR, and LMR-FAR could be applied to predict survival. RESULTS High preoperative NLR (≥3.9 vs <3.9, P<0.001), high preoperative PLR (≥106 vs <106, P=0.039), low preoperative LMR (≥4.2 vs <4.2, P<0.001), and high preoperative FAR (≥0.09 vs <0.09, P=0.028) were significantly associated with worse overall survival in multivariate analysis, which was also confirmed with survival curves. The prediction outcomes of the combined components outperformed those of a single index. NLR-FAR outperformed PLR-FAR and LMR-FAR as a predictor of CRC, with an area under the curve (AUC) of 97.24% (95% confidence interval (CI)=0.9535 to 0.9915, P<0.0001), 92.57% (95% CI=0.8880 to 0.9634, P<0.0001), and 90.26% (95% CI=0.8515 to 0.9538, P<0.0001). CONCLUSIONS In patients with CRC, preoperative NLR, PLR, LMR, and FAR can be utilized as independent predictors of overall survival. Additionally, in the combined detection findings, NLR and FAR performed better as predictors of CRC patients than PLR-FAR and LMR-FAR.

KLF5-mediated aquaporin 3 activated autophagy to facilitate cisplatin resistance of gastric cancer.

BACKGROUND: Resistance to chemotherapeutic drugs limits the control of gastric cancer (GC) development. The study intended to probe into the mechanism of aquaporin 3 (AQP3) on the chemoresistance of GC. METHODS: Cisplatin (CDDP)-resistant cells were constructed. Parental AGS and HGC-27 cells and their respective CDDP-resistant cells were transfected with AQP3 overexpression plasmid, AQP3 short hairpin RNA (sh-AQP3) and sh-Kruppel-like factor 5 (shKLF5). The expressions of AQP3 and factors related to autophagy (LC3 I, LC3 II, Atg5, Beclin-1, p62)/epithelial-mesenchymal transition (EMT; E-cadherin and snail) were assessed by Western blot and qRT-PCR. Cell counting kit-8 assay was adopted to test cell viability and half maximal inhibitory concentration (IC 50) was determined. Transwell assay was used for the examination of cell migration and invasion. The regulatory relationship of AQP3 and KLF5 was tested by chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays. RESULTS: AQP3 was highly-expressed in GC cells and its level was even higher in CDDP-resistant GC cells. AQP3 silencing inhibited viability, autophagy and EMT in CDDP-resistant GC cells, while AQP3 overexpression had the opposite effect. KLF5 positively modulated AQP3 in GC cells resistant to CDDP. KLF5 knockdown reversed AQP3-induced autophagy, viability, migration, invasion and EMT in CDDP-resistant GC cells. CONCLUSION: KLF5-modulated AQP3 activated autophagy to facilitate the resistance of GC to CDDP.

Performance of HDL-C measurements assessed by a 4-year trueness-based EQA/PT program in China.

OBJECTIVES: A trueness-based EQA/PT program for high density lipoprotein cholesterol (HDL-C) was initiated. We analyzed the 4 year EQA/PT program to overview the measurement standardization for HDL-C in China. METHODS: Two levels of freshly frozen, commutable serum external quality assessment/proficiency testing (EQA/PT) materials were prepared and determined by reference measurement procedure each year. The samples were delivered to clinical laboratories and measured 15 times in 3 days. The precision [coefficient of variation (CV)], trueness (bias), and accuracy [total error (TE)] were calculated and used to evaluate measurement performance. The pass rates of individual laboratories and peer groups were analyzed using the acceptable performance from the National Cholesterol Education Program (NCEP) and biological variation as the evaluation criteria. RESULTS: More than 60% of laboratories use heterogeneous systems, and there was a decrease in the percentage from 2016 to 2019. About 95, 78, and 33% of laboratories met the minimum, desirable and optimum TE criteria derived from biological variation. The pass rates were 87.0% (84.7-88.8%), 58.7% (55.3-62.4%), and 97.3% (95.6-98.3%) that met the acceptable performance of TE, bias, and CV of NCEP. The homogeneous systems had higher pass rates of TE, bias, and CV than the heterogeneous groups in 2016, but they did not show apparent advantages in 2017-2019. CONCLUSIONS: The trueness-based EQA/PT program can be used to evaluate the accuracy, reproducibility, and trueness of results. For some IVD manufacturers and individual laboratories, accuracy, especially trueness, are still problems. Efforts should be made to improve the situation and achieve better HDL-C measurement standardization.

A simple method for rapid screening and diagnosis of common organic acidemias: quantitative detection of serum and urine organic acid profiles based on liquid chromatography-tandem mass spectrometry.

Organic acid (OA) analysis is a specific test for inherited metabolic disorders (IMDs); however, the previous detection methods are laborious and costly. This study aims to develop a rapid method for the simultaneous quantification of serum and urine OA profiles. The method was established based on the liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique. The specificity, sensitivity, robustness, and accuracy of the established method were validated. Fifteen healthy subjects and nine IMD patients were measured for clinical validation. OAs with their intrinsic isomers were completely separated. The LC-MS/MS analysis time was 5.5 min. Calibration curves were linear within the ranges of 27.00 µg/g for all OAs. The average correlation relationship (R) varied from 0.9891 to 0.9998. The limit of detection and limit of quantification varied from 0.003 to 0.07 µg/g and 0.006 to 0.08 µg/g, respectively. No obvious carryover was observed. The intra-assay, inter-assay, and total imprecisions were 1.22-4.14%, 0.90-5.20%, and 1.67-5.90%, respectively. The mean spiked recovery at the three levels varied from 94.31 to 106.68%. The matrix effects can be compensated for by internal standard correction. Nine IMD patients were identified. A robust LC-MS/MS method for the rapid determination of serum and urine OA profiles without derivatization or liquid-liquid extraction was developed and validated. The analysis of five common OAs can be completed in short minutes. This innovative LC-MS/MS method for OA profiles may present its potential in future rapid screening and diagnosis of IMDs.

Clinical Application of Enteral Nutrition Combined with Microbial Preparation for Intestinal Preparation in Elderly Patients with Colorectal Cancer.

BACKGROUND The purpose of this study was to determine the safety and efficacy of enteral nutrition in combination with microbial preparations for bowel preparation in elderly patients with colorectal cancer. MATERIAL AND METHODS Were divided 160 patients diagnosed with colorectal cancer into a control group (n=80) and an experimental group (n=80) by random number table method. The control group took the traditional intestinal preparation, and the experimental group took oral enteral nutrition combined with microbial preparations. Both groups were treated by the same medical team. The postoperative recovery, complications, nutritional status, inflammation, and other indicators of the 2 groups were compared. RESULTS The nutritional status of the experimental group was significantly better than that of the control group, the incidence of tissue inflammation and postoperative complications was significantly lower than that of the control group, and the stool test results of patients with postoperative diarrhea were better than those of the control group, and the difference between groups was statistically significant. CONCLUSIONS The intestinal preparation using enteral nutrition combined with microbial preparations can alleviate the systemic inflammatory response in elderly patients, improve the nutritional status, reduce the occurrence of postoperative complications, and facilitate rapid postoperative recovery.

The consistency of aminotransferase analysis in China: a comparison of six mainstream aminotransferase routine methods and recalibration using human pooled serum preparations supplemented with human recombinant aminotransferases.

Background: To evaluate the consistency of six mainstream homogeneous systems for aminotransferase measurements and improve the consistency of measurements by applying uniform calibrators.Methods: 200 individual samples were grouped into four sets for assays with and without pyridoxal-5-phosphate (P-5'-P) for Alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Routine assays for the P-5'-P group were compared with a reference measurement procedure (RMP). In the non-P-5'-P group, four routine assays were analyzed in a pairwise method across six method pairs. Recalibration was performed using human serum pools (HSPs) supplemented with human original recombinant aminotransferases (HOR). Data were analyzed by Passing-Bablok regression and Bland-Altman plots.Results: In the P-5'-P group, the mean biases for Ortho and Dimension assays for ALT were 17.0% and -25.4%, respectively; for AST, the mean biases were -9.5% and -9.6%, respectively. In the non-P-5'-P group, the mean deviations ranged from -5.9% to 5.9% for ALT. For AST, the relative deviations ranged from -19.1% to 6.5%. After recalibration, in the P-5'-P group, the relative biases were reduced to -12.2% to 7.7% for ALT and -6.9% to 0.8% for AST. The mean deviations for the non-P-5'-P AST group were reduced remarkably (-3.0% to 3.3%).Conclusion: Assays supplemented with P-5'-P exhibited poor performance against RMP for both ALT and AST. For assays without P-5'-P, AST results showed non-satisfactory comparability for almost all method pairs. Uniform calibrators such as HSPs supplemented with HOR could improve consistency among the mainstream homogeneous systems for the measurement of aminotransferase activity, particularly for AST measurement.

A candidate reference method and multiple commutable control materials for serum 25-hydroxyvitamin D measurement.

OBJECTIVES: The aim of the current study was to establish a reliable candidate reference method for serum 25-hydroxyvitamin D [25(OH)D] measurement and to assess the commutability of multiple control materials among liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. METHODS: Serum 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] together with spiked internal standards were extracted with a one-step approach and then analyzed by LC-MS/MS. The commutability assessment for 25(OH)D was conducted according to the Clinical and Laboratory Standards Institute (CLSI) EP14-A3 protocol. 25(OH)D concentrations in 5 levels of unprocessed serum pools, 7 levels of serum pools spiked with 25(OH)D3 or 25(OH)D2, 3 levels of commercial control materials, 2 levels of spiked bovine serum, and 4 levels of external quality assessment (EQA) materials were measured along with 30 single-donor samples using the candidate reference method and two routine LC-MS/MS methods. RESULTS: The candidate reference method could separate 25(OH)D2 and 25(OH)D3 from 14 potential interfering compounds completely within a 9-min analysis time. Good method precision was obtained, and measurement results on certified reference material NIST SRM 972a were within the uncertainty of the certified values. All candidate materials were assessed commutable for LC-MS/MS methods. CONCLUSIONS: The candidate reference method for serum 25(OH)D measurement is precise, accurate, and robust against interferences and can provide an accuracy base for routine methods. The multiple alternative control materials with commutability among LC-MS/MS methods will facilitate the further standardization for serum 25(OH)D measurement.

Measurement of serum 17-hydroxyprogesterone using isotope dilution liquid chromatography-tandem mass spectrometry candidate reference method and evaluation of the performance for three routine methods.

OBJECTIVES: Accurate measurements of serum 17-hydroxyprogesterone (17OHP) are essential for diagnosis and treatment monitoring for congenital adrenal hyperplasia patients. The performance of serum 17OHP routine methods remains highly variable that calls for a candidate reference measurement procedure (cRMP) to improve the standardization of serum 17OHP measurements. METHODS: Serum samples spiked with internal standards were extracted with a combination of solid-phase extraction and liquid-liquid extraction. The 17OHP was quantified by the isotope dilution coupled with liquid chromatography/tandem mass spectrometry (ID-LC/MS/MS) with electrospray ionization in positive ion mode. Nine structural analogs of 17OHP were evaluated for interferences. The precision and analytical recovery were assessed. Twenty native and 40 spiked serum for performance evaluation were measured by the cRMP and two clinical LC/MS routine methods. RESULTS: No apparent interferences were found with the 17OHP measurement. The within-run, between-run, and total precision for our method were 0.4-0.8%, 0.6-2.0%, and 1.0-2.1% for four pooled serum (2.46-102.72 nmol/L), respectively. The recoveries of added 17OHP were 100.0-100.2%. For the performance of two LC/MS routine methods, they showed relative deviation ranges of -22.1 to 1.1% and -6.7 to 12.8%, respectively. CONCLUSIONS: We developed and validated a reliable serum 17OHP method using ID-LC/MS/MS. The desirable accuracy and precision of this method enable it to serve as a promising cRMP to improve the standardization for serum 17OHP routine measurements.

Quantitation of plasma metanephrines using isotope dilution liquid chromatography tandem mass spectrometry (ID-LC/MS/MS): a candidate reference measurement procedure and its application to evaluating routine ID-LC/MS/MS methods.

Accurate measurement of plasma metanephrines (MNs) including metanephrine (MN) and normetanephrine (NMN) is crucial for the screening and diagnosis in pheochromocytomas and paragangliomas (PPGLs). Although the number of laboratories using liquid chromatography tandem mass spectrometry (LC-MS/MS) method to measure MNs has been increasing rapidly, those laboratory-developed assays showed incomparable results. There are no reference measurement procedures (RMPs) or reference materials (RMs) for MNs in Joint Committee for Traceability in Laboratory Medicine (JCTLM), which hindered the standardization of MNs measurement. We established a candidate RMP (cRMP) based on isotope dilution liquid chromatography tandem mass spectrometry (ID-LC/MS/MS) method for plasma MNs measurement. Plasma samples were spiked with MN-D3 and NMN-D3 as internal standards; protein precipitation and ion-exchange solid phase extraction (SPE) were performed to extract samples, eventually analyzed by LC-MS/MS. The cRMP was applied to evaluate two routine ID-LC/MS/MS methods through split-sample comparisons. Fifty-three individual patient samples were determined by cRMP and two routine ID-LC/MS/MS methods; results were analyzed by ordinary linear regression and Bland-Altman plots. The cRMP exhibited desirable imprecision, with intra-run and total imprecision (coefficient variation, CV) for MN being 0.79-1.36% and 1.53-1.87% and for NMN being 1.10-1.34% and 1.15-1.64%. The analytical recoveries of MN and NMN ranged from 98.3 to 101.7% and from 98.5 to 101.9%, respectively. Significant calibrator biases and sample-specific deviations were observed in method comparison. An accurate, precise, and reliable cRMP for plasma MNs was developed, and RMs with value assigned following the cRMP would help minimize the calibration bias and improve the comparability of different measuring systems.

Development of a designated comparison method for alkaline phosphatase measurements and its application to evaluating routine methods.

The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) published the reference measurement procedure (RMP) for ALP measurement in 2011. However, the RMP is of high requirements for laboratories, complicated, time-consuming and high cost of reagents. Many manufacturers do not trace results to the higher procedure. And there is currently no designated comparison method (DCM) for ALP measurement. Thus, the standardization of ALP measurement is hindered. Automatic biochemical analyzers are easy to operate and widely used in clinical laboratories. Therefore, according to the RMP, establishing a DCM based on an automatic biochemical analyzer will be a practical way to establish traceability to the accuracy base and promote the standardization of ALP measurement. On the basis of conforming to the RMP recommended by IFCC as far as possible, the DCM was established based on a Thermo Indiko automatic biochemical analyzer. Performances of the method were validated. The DCM repeatability and within laboratory imprecision was <1% and <2.5%, respectively. For evaluation of trueness, the biases were within the equivalent limits. Measurement procedure comparisons and biases estimation were carried out between the DCM, the RMP, and the six routine methods using a panel of 40 individual human serum samples. The comparisons between the DCM and the RMP gave satisfying results. Compared with the DCM, the relative biases of some routine methods failed to meet the bias limit derived from biological variation.

Trends of incidence and prognosis of gastric neuroendocrine neoplasms: a study based on SEER and our multicenter research.

BACKGROUND: To investigate the recent epidemiological trends of gastric neuroendocrine neoplasms (GNENs) and establish a new tool to estimate the prognosis of gastric neuroendocrine carcinoma (GNEC) and gastric neuroendocrine tumor (GNET). METHODS: Nomograms were established based on a retrospective study on patients diagnosed with GNENs from 1975 to 2016 in Surveillance, Epidemiology and End Results database. External validation was performed among 246 GNENs patients in Jiangsu province to verify the discrimination and calibration of the nomograms. RESULTS: The age-adjusted incidence of GNENs has increased from 0.309 to 6.149 per 1,000,000 persons in the past 4 decades. Multivariate analysis indicated independent prognostic factors for both GNEC and GNET including age, distant metastasis and surgical intervention (P < 0.05). In addition, T, N staging and grade were significantly associated with survival of GNEC, while size was a predictor for GNET (P < 0.05). The C-indexes of the nomograms were 0.840 for GNEC and 0.718 for GNET, which were higher than those of the 8th AJCC staging system (0.773 and 0.599). Excellent discrimination was observed in the validation cohorts (C-index of nomogram vs AJCC staging for GNEC: 0.743 vs 0.714; GNET: 0.945 vs 0.927). Survival rates predicted by nomograms were close to the actual survival rates in the calibration plots in both training and validation sets. CONCLUSIONS: The incidence of the GNENs is increasing steadily in the past 40 years. We established more excellent nomograms to predict the prognosis of GNENs than traditional staging system, helping clinicians to make tailored decisions.

Effects of calcium dobesilate (CaD) interference on serum creatinine measurements: a national External Quality Assessment (EQA)-based educational survey of drug-laboratory test interactions.

Objectives: Drug-laboratory test interactions (DLTIs) are one of the major sources of laboratory errors. Calcium dobesilate (CaD) interference on serum creatinine testing is a widespread problem that has long been ignored in China. A national EQA-based survey was launched to investigate the current status of CaD interference on creatinine routine methods used in China and enhance the education of CaD interference in clinical laboratories. Methods: A descriptive survey was developed to characterize the status quo of Chinese laboratory professionals' cognition to CaD interference. Four of survey samples which were spiked with/without interference additive were shipped to 175 participant laboratories. The target reference values from a reference measurement procedure were compared against the results from participating laboratories to evaluate the CaD interference on serum creatinine measurements using enzymatic method or Jaffé method. Results: The lack of knowledge of DLTIs and the barriers to collect information from pharmacological and laboratory data systems had become the main problems on implementing DLTIs education in China. A significant negative influence of CaD on enzymatic method was observed regardless of measurement platforms. Jaffé method was generally free from interaction with CaD but showed poor precision and accuracy at low creatinine concentrations. Conclusions: More efforts should be made to enhance the education of DLTIs in clinical laboratories in China.

Development and validation of a candidate reference method for serum cortisol by isotope dilution liquid chromatography-tandem mass spectrometry combined with dextran sulfate-Mg2+ precipitation.

Accurate and precise cortisol measurements are requisite for ensuring appropriate diagnosis and management of diseases related with adrenal or pituitary gland disorders. Prompted by the needs in characterization of certified reference materials and quality assurance for serum cortisol measurements, we developed and evaluated a highly reliable measurement procedure based on isotope dilution liquid chromatography-tandem mass spectrometry (ID LC-MS/MS) combined with dextran sulfate-Mg2+ precipitation as the sample pretreatment. An appropriate amount of serum was accurately weighed and spiked with the isotope labelled internal standard. After precipitation, massive lipids and lipoproteins were removed from serum matrix. The clear supernatant was transferred and extracted with ethyl acetate-hexane solution. The cortisol was analyzed with LC-MS/MS in positive electrospray ionization mode. The within-run and total coefficient of variations (CVs) ranged from 0.3 to 0.6% and 0.7 to 1.2%, respectively, for a concentration range of 76.30 to 768.04 nmol/L. A regression comparison of the results obtained by the present method and the certified values of ERM-DA451 showed agreement with no statistical difference (Y = 1.0092 X-0.7455; 95% CI for the slope, 0.9940 to 1.0212; 95% CI for the intercept, - 3.6575 to 2.6390, r2 = 0.999). All structural analogs of cortisol tested were well resolved from cortisol in 12 min on a phenyl ligand column under an isocratic elution. The limit of quantification was estimated to 5 pg cortisol in absolute amount. This method is accurate and simple and can be served as a candidate reference measurement procedure in establishment of serum cortisol reference system.

Commutability of reference materials for alkaline phosphatase measurements.

Commutability is a prerequisite when using a candidate reference materials (CanRMs) for calibration and trueness control of routine methods or for value transfer from the reference method to end-user calibrators of routine methods through a calibration hierarchy. The CanRMs include commercial general chemistry materials (GCs), enzyme trueness verification materials (ETVs), and secondary reference materials (SRMs). The commutability of CanRMs was evaluated based on the difference in bias and EP14-A3 to investigate their suitability for ALP measurement. A total of 44 fresh individual clinical samples (CSs) and the CanRMs were analyzed by six routine methods (validated methods) and by IFCC primary reference method (comparative method) for the determination of Alkaline Phosphatase (ALP). The commutability was performed based on IFCC working group recommendations for assessing commutability and analyzed according to EP14-A3 guide and difference in bias approach, respectively. The bias of the routine methods was assessed according to CLSI guidelines. The result of commutable materials obtained from the two evaluation approaches are not significantly different. It was observed that the routine methods with lower bias were associated with more commutable CanRMs. None of the CanRMs were suitable for use as commutable RMs. The findings of this study have a number of important implications for future practice.

Analysis and evaluation of the external quality assessment results of quality indicators in laboratory medicine all over China from 2015 to 2018.

Background This study aimed to comprehensively evaluate laboratory quality in China and explore factors affecting laboratory errors through analyzing the external quality assessment (EQA) results of quality indicators (QIs). Methods According to model 3 (interpretive) of the proficiency testing scheme, the National Center for Clinical Laboratories of China (CNCCL) developed a questionnaire for 15 QIs. Clinical laboratories from different provinces of China participated in the EQA program of QIs annually and submitted data via an online reporting system named Clinet-EQA. The results of QIs were expressed in percentage and sigma value or minute. Three levels of quality specifications (QSs) were defined based on percentile values. Furthermore, the QIs were analyzed by disciplines, hospital scales and information construction levels of participant laboratories. Results A total of 3450 laboratories nationwide continuously attended the EQA program and submitted complete data from 2015 to 2018. The performance of most QIs has improved year by year. QIs in post-analytical gained the best performance with sigma values that varied from 5.3σ to 6.0σ. The comparison of results among different disciplines showed significant differences for five QIs. More than half of QIs had statistical differences among different hospital scales measured by hospital grades and number of hospital beds. The performance of nine QIs were influenced by information construction levels of participant laboratories. Conclusions The overall laboratory quality in China has improved since the initiation of EQA program for QIs, but the performance of some QIs was still unsatisfactory. Therefore, laboratories should make efforts for continuous quality improvement based on information provided by QSs.