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.

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.

Commutability Assessment of Processed Human Plasma Samples for Normetanephrine and Metanephrine Measurements Based on the Candidate Reference Measurement Procedure.

Background: To identify candidate external quality assessment (EQA) materials for normetanephrine and metanephrine measurements, we assessed the commutability of eight processed human plasma samples. The agreement between routine assays and the candidate reference measurement procedure (cRMP) was also evaluated. Methods: Fifty-three clinical samples and eight processed plasma samples were prepared. The processed samples included pooled and individual plasma samples spiked with pure normetanephrine and metanephrine and non-spiked pooled and individual plasma samples. The clinical and processed samples were subjected to four routine isotope dilution tandem mass spectrometry assays and cRMP. Commutability was assessed based on two approaches recommended by the CLSI and International Federation of Clinical Chemistry (IFCC). Passing-Bablok regression and Bland-Altman analysis were used to evaluate the agreement between the routine assays and cRMP. Results: The commutability results of the CLSI approach were better than those of the IFCC approach. For the CLSI approach, spiked individual plasma samples and spiked high-concentration pooled plasma samples were commutable for all routine assays for both analytes. The non-spiked pooled plasma sample was commutable for two out of four routine assays for metanephrine and three out of four routine assays for normetanephrine. The agreement between the routine assays and the cRMP was satisfactory, except for one routine assay showing significant bias. Conclusions: High-concentration spiked pooled plasma samples and spiked individual plasma samples are candidate EQA materials for normetanephrine and metanephrine measurements.

Commutability Assessment of Candidate External Quality Assessment Materials for Aminotransferase Activity Measurements Based on Different Approaches in China.

BACKGROUND: Using commutable external quality assessment (EQA) materials is important for monitoring successful harmonization efforts. We assessed the commutability of four human serum pool (HSP) preparations to identify candidate EQA materials for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity measurement. METHODS: One set each of 85 clinical samples (CSs) was collected for ALT and AST activity measurement. The 15 candidate EQA materials included four types of HSP preparations (A to D): materials A, C, and D contained human original recombinant (HOR) aminotransferases; materials B was mixed leftover samples. The CSs and 15 candidate EQA materials were analyzed using seven routine assays, and the ln-transformed results were analyzed in 21 assay pairs. Commutability was assessed using Deming regression, with a 95% prediction interval (CLSI approach) and the difference in bias with an error component model (International Federation of Clinical Chemistry and Laboratory Medicine [IFCC] approach). RESULTS: For ALT, all materials were commutable for 14-21 assay pairs according to the CLSI and IFCC approaches. For AST, B01-03 showed commutability for 14-21 assay pairs, and C01-03 and D01-03 showed commutability for no less than 10 assay pairs according to the two approaches. A01-06 were commutable for 9-16 assay pairs according to the CLSI approach, but for 6-9 assay pairs according to the IFCC approach. CONCLUSIONS: Mixed leftover samples showed desirable commutability characteristics as candidate EQA materials for routine aminotransferase activity measurements. Human serum bases supplemented with HOR were commutable for most routine ALT activity measurements.

Commutability of possible external quality assessment materials for progesterone measurement.

BACKGROUND: The commutability of control materials used for external quality assessment (EQA) programs is of great importance. Evaluating the commutability of control materials is crucial to assess their suitability for EQA programs. METHODS: Forty-eight individual patient serum samples, commercial EQA samples, human serum pools (HSPs), commercially available sterile filtered charcoal stripped serum (CS) and swine serum were analyzed using the isotope dilution liquid chromatography-tandem mass spectrometry (ID LC-MS/MS) comparative method and six immunoassays for progesterone. The commutability was assessed according to the EP14-A2 guideline and the difference in bias approach, respectively. RESULTS: According to the EP14-A2 guideline, HSPs and CS were commutable for all the tested immunoassays, while swine serum showed positive matrix effects in some assays. Based on the difference in bias approach, a large number of inconclusive and noncommutable results appeared. CONCLUSIONS: The commutability of the processed materials varied depending on which evaluation approach and criterion was applied. Noncommutability of the EQA materials was observed. And HSPs and CS were possible commutable candidate control materials according to the EP14-A2 guideline.

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.

Commutability of external quality assessment materials for serum sodium and potassium measurements.

Background The commutability of electrolyte trueness verification materials (ETVs) and commercial general chemistry materials (GCs) was evaluated to investigate their suitability for use in an external quality assessment (EQA) program for serum sodium and potassium measurements. Methods Eighty fresh individual human samples (40 for sodium measurements and 40 for potassium measurements), six ETVs and three GCs were analyzed by five routine methods (validated methods) and by inductively coupled plasma mass spectrometry reference methods (comparative methods) for the determination of sodium and potassium. The commutability was analyzed according to Clinical and Laboratory Standards Institute (CLSI) EP14-A3 protocol and difference in bias approach, respectively. The linearity, bias and imprecision of the routine methods were also assessed according to CLSI guidelines. Results According to EP14-A3 protocol, ETVs were commutable for all assays, and GCs were commutable for 3/5 assays for sodium. ETVs were commutable in most assays except Cobas C501, while GCs showed no commutability except in case of AU5821 for potassium. According to a difference in bias approach, the commutability of ETVs was inconclusive for most routine assays for both sodium and potassium, and GCs were inconclusive for sodium and non-commutable for potassium in most routine assays. The routine methods exhibited excellent linearities and precisions. The majority and minority of relative biases between the routine and reference methods were beyond the bias limits for sodium and potassium, respectively. Conclusions Superiority in the commutability of ETVs over GCs was observed among the sodium and potassium assays whichever evaluation approach was applied.

Quality assessment of interpretative commenting and competency comparison of comment providers in China.

Background This study aimed to evaluate the ability of comment providers who were responsible for interpreting results in clinical laboratories in China and to improve the quality of interpretative comments. Methods Basic information and interpretative comments for five cases of 1912 routine chemistry External Quality Assessment (EQA) participant laboratories were collected by web-based EQA system in May 2018. EQA organizers assigned scores to each key phrase of comments based on predetermined marking scale and calculated total scores for each participant's answer. Final scores and ranking were calculated according to scores of cases. Finally, we comprehensively analyzed the type of hospital and the professional title of participants. Results In total, 772 clinical laboratories, 1472 participants, from different Chinese provinces submitted interpretative comments. Median scores, interquartile ranges and score ranges of the five cases were 13 (11-15, 1-20), 13 (10-16, 0-20), 15 (12-17, 0-21), 7 (5-9, -2 to 14) and 12 (10-13, -2 to 18). The final scores and ranking of participants that came from tertiary hospitals were higher than those from secondary and other hospitals; however, there were no significant differences (0.774). When grouped by professional title, we found that although no significant variability existed among senior, intermediate, junior and others (0.699), it existed between laboratory physicians and technicians, as the median final scores of the former were higher than the latter. Conclusions Practice and quality of interpretative comments are indeed different among different laboratories and participants in China. Laboratories should train and assess the interpretative ability of personnel. EQA organizers should also improve the scoring method and establish peer assessors team through this survey.

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.

Commutability of control materials for external quality assessment of serum apolipoprotein A-I measurement.

BACKGROUND: The aim of the current study was to evaluate the commutability of commercial control materials and human serum pools and to investigate the suitability of the materials for the external quality assessment (EQA) of serum apolipoprotein A-I (apo A-I) measurement. METHODS: The Clinical and Laboratory Standards Institute (CLSI) EP14-A3 protocol was used for the commutability study. Apo A-I concentrations in two levels of commercial control materials used in EQA program, two fresh-frozen human serum pools (FSPs) and two frozen human serum pools prepared from residual clinical specimens (RSPs) were measured along with 50 individual samples using nine commercial assays. Measurement results of the 50 individual samples obtained with different assays were pairwise analyzed by Deming regression, and 95% prediction intervals (PIs) were calculated. The commutability of the processed materials was evaluated by comparing the measurement results of the materials with the limits of the PIs. RESULTS: The FSP-1 was commutable for all the 36 assay pairs, and FSP-2 was commutable for 30 pairs; RSP-1 and RSP-2 showed commutability for 27/36 and 22/36 assay pairs, respectively, whereas the two EQA materials were commutable only for 4/36 and 5/36 assay pairs, respectively. CONCLUSIONS: Non-commutability of the tested EQA materials has been observed among current apo A-I assays. EQA programs need either to take into account the commutability-related biases in the interpretation of the EQA results or to use more commutable materials. Frozen human serum pools were commutable for most of the assays.

Characterization of a functional recombinant human creatine kinase-MB isoenzyme prepared by tandem affinity purification from Escherichia coli.

Creatine kinase isoform CK-MB has been widely applied as a biomarker of myocardial injury. While a variety of methods have been used to measure CK-MB activity or mass in clinical laboratories, a CK-MB standard is needed to eliminate between-method bias. Because the in vitro expression of human creatine kinase generates three isoenzymes, CK-MM, CK-MB, and CK-BB, it is important to establish an effective method to purify the isoform CK-MB from the mixture. In this study, we aimed at using tandem affinity purification (TAP) to purify recombinant CK-MB protein and evaluate its value in clinical laboratories. After the optimized sequence coding CK-M and CK-B were synthesized, they were combined with TAP tags (6His and SBP) and inserted into a pRSFDuet vector; then, the constructed 6His-CK-M-SBP-CK-B-pRSF plasmid was transformed into Escherichia coli BL21 (DE3) for expression. After TAP, we obtained purified CK-MB protein. We also did recovery testing using the engineered CK-MB and standard CK-MB (Randox) at different concentrations, and the results suggested that the engineered CK-MB could be used as the reference material. Moreover, the stability study of recombinant CK-MB showed high stability during long-term storage at -80 °C. In conclusion, the TAP-purified recombinant CK-MB protein may be a much better and cheaper standard or reference material for clinical laboratories.

Assessment of enzyme measurement procedures in China through a trueness verification program.

BACKGROUND: Since 2003, the National Center for Clinical Laboratories (NCCL) has organized a network of reference laboratories and several survey programs to improve standardization in China. METHODS: We analyzed the 2015 trueness verification program to assess the status of enzyme measurement standardization. Commutable serum-based materials were prepared and sent to 10 reference laboratories to assign target values for 2 enzymes (alanine aminotransferase-pyridoxal phosphate [ALT-pp] and γ-glutamyltransferase [GGT]) using IFCC reference measurement procedures. RESULTS: Analytical performance was assessed for compliance to 3 indexes: trueness (bias), imprecision (CV), and accuracy (total error). Of the 250 participating laboratories, about half (≥124) used heterogeneous systems. More laboratories met the tolerance limit of imprecision than of trueness or accuracy. Except at the lowest concentration, the CV pass rates were >90% for the 2 enzymes. The optimal performance criterion derived from biological variation yielded pass rates for total error (ALT 77%, GGT 80%) that were higher than for bias (ALT 63%, GGT 73%). CONCLUSIONS: PT/EQA results for commutable samples can be used to assess trueness against reference measurement procedures. Despite global and national standardization programs, bias remains a critical limitation of current enzyme measurement procedures in China.

Status of External Quality Assessment on Tumor Markers in China.

BACKGROUND: The nationwide external quality assessment (EQA) of tumor markers in China has been launched for years. The quality of the performance of Chinese clinical laboratories on tumor markers is partly reflected through analysis of EQA results. This report presents an 8-year EQA result of the six most common tumor markers from 2006 to 2013. METHODS: Ten freeze-dried EQA samples were distributed to participants every year. Satisfactory performance was defined as scores of more than 80% of acceptable responses with the evaluation criterion of ± 25%. The robust coefficient of variability (CV) between laboratories and percentage difference against the target value of each sample were also calculated by year. RESULTS: A total number of 1154 laboratories submitted results in 2013, which was more than threefold of 2006. The proportion of laboratories with satisfactory performance showed an overall rising trend over the years and was up to 95% for the second survey in 2013. The overall decrease of robust CV was observed for all analytes including alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), total prostate specific antigen (t-PSA), cancer antigen 125 (CA 125), cancer antigen 15-3 (CA 15-3), and cancer antigen 19-9 (CA 19-9) except for CEA, which exhibited a rise followed by a flat trend. The percentage difference narrowed gradually and was less than 2% in 2013. CONCLUSIONS: The 8-year EQA results showed a significant enhancement of degree of harmonization of tumor markers in China. However, standardization among various testing systems and improvement of harmonization has yet to be achieved.

Commutability of possible external quality assessment materials for cardiac troponin measurement.

BACKGROUND: The measurement of cardiac troponin is crucial in the diagnosis of myocardial infarction. The performance of troponin measurement is most conveniently monitored by external quality assessment (EQA) programs. The commutability of EQA samples is often unknown and the effectiveness of EQA programs is limited. METHODS: Commutability of possible EQA materials was evaluated. Commercial control materials used in an EQA program, human serum pools prepared from patient samples, purified analyte preparations, swine sera from model animals and a set of patient samples were measured for cTnI with 4 assays including Abbott Architect, Beckman Access, Ortho Vitros and Siemens Centaur. The measurement results were logarithm-transformed, and the transformed data for patient samples were pairwise analyzed with Deming regression and 95% prediction intervals were calculated for each pair of assays. The commutability of the materials was evaluated by comparing the logarithmic results of the materials with the limits of the intervals. Matrix-related biases were estimated for noncommutable materials. The impact of matrix-related bias on EQA was analyzed and a possible correction for the bias was proposed. RESULTS: Human serum pools were commutable for all assays; purified analyte preparations were commutable for 2 of the 6 assay pairs; commercial control materials and swine sera were all noncommutable; swine sera showed no reactivity to Vitros assay. The matrix-related biases for noncommutable materials ranged from -83% to 944%. Matrix-related biases of the EQA materials caused major abnormal between-assay variations in the EQA program and correction of the biases normalized the variations. CONCLUSION: Commutability of materials has major impact on the effectiveness of EQA programs for cTnI measurement. Human serum pools prepared from patient samples are commutable and other materials are mostly noncommutable. EQA programs should include at least one human serum pool to allow proper interpretation of EQA results.

[National external quality assessment and comparability of assays for tumor markers measurements].

OBJECTIVE: To evaluate the performance of tumor markers (TM) measurements in clinical laboratories by external quality assessment (EQA) and investigate the comparability of assays for TM. METHODS: Ten quality control sera specimens were distributed to 586 laboratories by global Express Mail Services (EMS) in March 2008 and tested twice with 5 specimens each time. Analytes were total prostate specific antigen (PSA), free PSA, carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), human chorionic gonadotrophin (HCG), beta-HCG, carbohydrate antigen 19-9 (CA19-9), cancer antigen 15-3 (CA 15-3), cancer antigen 125 (CA125), beta-2-microglobulin and ferritin. The collected data were divided into peer groups according to analyzers or methods and the median of peer group was adopted as the target value (TV) separately after outlier removal. Two standard deviations of the median were set as the limit of difference. RESULTS: The first TM EQA results of 2008 showed that the pass percentage of all participating laboratories ranged from 87.3% (CA125) to 95.5% (beta-2-microglobulin). And the second batch ranged from 83.5% (HCG) to 94.0% (beta-2-microglobulin). The coefficient variances (CVs) of intra-group values determined by automatic analyzers were lesser than 15% for each test of every specimen. The CVs of radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) were over 20% and 50% respectively. The inter-group medians of 9 tests showed CVs>20% with HCG 13.4% and ferritin 15.7%. The CV of paired medians of some automatic analyzers was small and showed no statistical significance (all Z<1.890, all P>0.05). CONCLUSION: The analytical performance of automatic analyzers is superior to RIA and ELISA. There is an excellent comparability within automatic analyzers for TM measurements and a lack of comparability within RIA and ELISA. Noncomparability is found in over 80% of TM assays.