ABSTRACT
Purpose@#Acute kidney injury (AKI) following sepsis is associated with higher mortality; however, reliable biomarkers for AKI development and recovery remain to be elucidated. @*Materials and Methods@#Patients with sepsis admitted to the medical intensive care unit (ICU) of Severance Hospital between June 2018 and May 2019 were prospectively analyzed. Patients were divided into those with and without AKI within 48 hours. Patients with septic AKI were subdivided into AKI-recovery and non-recovery groups based on whether their kidney injury recovered within 7 days. @*Results@#A total of 84 patients were enrolled. The baseline creatinine (2.9 mg/dL vs. 0.8 mg/dL vs. 1.2 mg/dL, p<0.001), Charlson Comorbidity Index (4.5 vs. 2.0 vs. 3.0, p=0.002), Sequential Organ Failure Assessment (10.0 vs. 6.5 vs. 8.0, p<0.001), and Acute Physiology and Chronic Health Evaluation II scores (32.0 vs. 21.5 vs. 30.5, p=0.004) were higher in the non-recovery AKI group compared to the non-AKI and AKI-recovery groups. The Kaplan-Meier curves revealed that non-recovery from AKI was associated with lower survival (p<0.001). High-lactate (p≤0.05) and kynurenine levels (p≤0.05) were associated with non-recovery of renal function following AKI. The areas under the curve for predicting non-recovery from AKI were 0.693 and 0.721 for lactate and kynurenine, respectively. The survival rate was lower in the high-kynurenine (p=0.040) and high-lactate (p=0.010) groups. @*Conclusion@#The mortality of patients who recovered from AKI was comparable to that of patients without AKI. Lactate and kynurenine could be useful biomarkers for the diagnosis and recovery of AKI following sepsis.
ABSTRACT
Background@#Although urine culture is considered a reference standard for the diagnosis of urinary tract infection (UTI), it is time-consuming, labor-intensive, and expensive. Here, we evaluated the performance of five recent automated urine analyzers for UTI diagnosis. @*Methods@#For the 510 specimens analyzed, the criterion for ‘significant bacteriuria’ was defined as ≥ 104 CFU/mL in the inoculated plate for all specimens or ≥ 103 CFU/mL for specimens from patients using a Foley catheter or with urinary symptoms. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of UTI were analyzed using indicators individually, in different combinations, or with various cut-off values. @*Results@#Seventy-one specimens (13.9%) exhibited ‘significant bacteriuria’. In the eceiver operating characteristics curve analysis, UF-5000 (Sysmex Corp., Japan) showed the highest area under the curve values for both males and females (0.876 and 0.846, respectively). The PPVs for specimens from males with all indicators positive increased up to 100% after adjusting the cut-off values. NPVs for specimens with all indicators negative were 94.3%– 98.2% in males and 78.1%–93.8% in females after adjusting the cut-off values. @*Conclusion@#As a rapid and accurate diagnostic tool, urine sediment analyzers can be valuable for UTI diagnosis by reducing unnecessary culture and can help clinicians determine a treatment plan.
ABSTRACT
Background@#Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is increasingly used for immunosuppressive drug tests. However, most LC-MS/MS tests are laboratory-developed and their agreement is unknown in different Korean laboratories.This interlaboratory comparison study evaluated test reproducibility and identified potential error sources. @*Methods@#Test samples containing three concentrations of tacrolimus, sirolimus, everolimus, cyclosporine, and mycophenolic acid were prepared by pooling surplus samples from patients undergoing routine therapeutic drug monitoring and tested in duplicate in the participating 10 clinical laboratories. Reconstitution and storage experiments were conducted for the commonly used commercial calibrator set. The robust estimators of reproducibility parameters were calculated. Spearman’s rank correlation coefficient (rho, ρ) was used to evaluate the correlation between drugs. Multiple linear regression was used to determine whether the experimental conditions alter the calibration curves. @*Results@#The reproducibility coefficient of variation exceeded 10% only for sirolimus concentrations 1 and 2 (10.8% and 12.5%, respectively) and everolimus concentrations 1 and 2 (12.3% and 11.4%, respectively). The percent difference values showed weak correlations between sirolimus and everolimus (ρ = 0.334, P = 0.175). The everolimus calibration curve slope was significantly altered after reconstitution following prolonged 5°C storage (P = 0.015 for 14 days; P = 0.025 for 28 days); the expected differences at 6 ng/mL were 0.598% for 14 days and 0.384% for 28 days. @*Conclusions@#LC-MS/MS test reproducibility for immunosuppressive drugs seems to be good in the Korean clinical laboratories. Continuous efforts are required to achieve test standardization and harmonization, especially for sirolimus and everolimus.
ABSTRACT
Procalcitonin (PCT) is a useful bacterial infection biomarker with the potential for guiding antibiotic therapy. We evaluated the concordance of three automated PCT immunoassays: Kryptor (BRAHMS GmbH, Hennigsdorf, Germany), Atellica IM 1600 (Siemens Healthcare Diagnostics, Munich, Germany), and Cobas e801 (Roche Diagnostics, Mannheim, Germany). In 119 serum samples with a PCT concentration < 5.00 μg/L, Kryptor (reference assay) was compared with the other two immunoassays by Spearman’s rank correlation, regression analysis, and concordance at two antibiotic stewardship medical decision points: 0.25 and 0.50 μg/L. The Atellica IM 1600 and Cobas e801 results showed high correlations with those of Kryptor, with correlation coefficient (ρ) values of 0.97 and 0.99, respectively. However, negative biases were observed in both immunoassays (slope/y-intercept: 0.75/–0.00 for Atellica IM 1600; 0.88/–0.01 for Cobas e801). Atellica IM 1600 and Cobas e801 demonstrated excellent concordance with Kryptor at both medical decision points, with linearly weighted κ values of 0.90 and 0.92, respectively, despite discrepancies, which were more prominent at the 0.25 μg/L medical decision point. Based on these biases and discrepancies, the alternate use of different PCT immunoassays in repeat examinations is inadvisable. Standardization is required before comparing the results of different PCT immunoassays.
ABSTRACT
Background@#Although urine culture is considered a reference standard for the diagnosis of urinary tract infection (UTI), it is time-consuming, labor-intensive, and expensive. Here, we evaluated the performance of five recent automated urine analyzers for UTI diagnosis. @*Methods@#For the 510 specimens analyzed, the criterion for ‘significant bacteriuria’ was defined as ≥ 104 CFU/mL in the inoculated plate for all specimens or ≥ 103 CFU/mL for specimens from patients using a Foley catheter or with urinary symptoms. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of UTI were analyzed using indicators individually, in different combinations, or with various cut-off values. @*Results@#Seventy-one specimens (13.9%) exhibited ‘significant bacteriuria’. In the eceiver operating characteristics curve analysis, UF-5000 (Sysmex Corp., Japan) showed the highest area under the curve values for both males and females (0.876 and 0.846, respectively). The PPVs for specimens from males with all indicators positive increased up to 100% after adjusting the cut-off values. NPVs for specimens with all indicators negative were 94.3%– 98.2% in males and 78.1%–93.8% in females after adjusting the cut-off values. @*Conclusion@#As a rapid and accurate diagnostic tool, urine sediment analyzers can be valuable for UTI diagnosis by reducing unnecessary culture and can help clinicians determine a treatment plan.
ABSTRACT
The use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) in clinical laboratories is increasing and is likely to expand into even more clinical venues in the future. Mass spectrometry is the standard method for analyte identification in the clinical chemistry field; however, differences in mass spectrometry protocols and handling affect the accuracy and reliability of these tests and prevent direct comparisons of results between laboratories. For example, the results of laboratories using LC-MS/MS methods are less likely to be reproducible than those of laboratories using conventional, automated methods. This is due to inadequate handling of the equipment and/or poor quality control after the implementation of the method, which may result in unnecessary medical expenditures or even adverse outcomes for the patients. Unfortunately, guidelines to monitor the accuracy of LC-MS/MS-based clinical tests are still lacking. In general, the quality control methods used in conventional clinical tests could also be applied to LC-MS/MS. However, additional quality control methods specific to LC-MS/MS techniques must be continuously employed to maintain the same quality level achieved during method development and verification. This report is intended to help clinical laboratories that operate LC-MS/MS improve the accuracy and reliability of their testing by providing guidance for quality assurance and improvement, based on a collection of existing guidelines and expert opinions from the literature.
ABSTRACT
Background@#The rapid antimicrobial susceptibility testing (AST) performed on urine samples would guide the adequate choice of antibiotics for obtaining better treatment outcomes in patients. Our study aimed to evaluate the performance of the modified-EUCAST (European Committee on Antimicrobial Susceptibility Testing) rapid direct AST on urine samples. @*Methods@#From >2,000 urine samples, a total of 128 urine samples containing bacterial counts of ≥2 × 10 4 CFU/mL with a uniform bacterial shape were initially included based on flow cytometry (Sysmex UF-1000i, Japan) and Gram staining, respectively. A total of 103 samples showing the presence of Enterobacteriaceae were finally selected in this study. The urine samples were directly inoculated on Mueller-Hinton agar, which was used in the current EUCAST rapid direct AST on blood samples. The size of the growth inhibition zones around antimicrobial disks was measured using a digital scanner (BIOMIC vision analyzer, Giles scientific, USA) and further confirmed by visualization with naked eyes after incubation for 4, 6, and 8 hours. The AST interpretations were compared to those of the conventional VITEK 2 AST system (bioMérieux, France) and the discrepancies between both tests were confirmed with the E-test. @*Results@#The antibiotics, namely ampicillin, cefazolin, aztreonam, ceftazidime, cefotaxime, cefoxitin, cefepime, gentamicin, ciprofloxacin, and cotrimoxazole showed excellent correlations with modified-EUCAST rapid direct test and conventional ASTs with >0.75 weighted kappa values. The categorical agreement of the rapid direct AST was 1,442 (93.3%), with 76 (4.9%) minor error, 9 (0.6%) major error and 18 (1.2%) very major error, implicating the reliability of this method for clinical application. @*Conclusion@#Performing the modified-EUCAST rapid direct AST on urine samples can predict reliable AST results within 8 hours. The rapid direct AST can help the physicians to initiate adequate antimicrobial treatment for urinary tract infections.
ABSTRACT
Subject(s)
Humans , Immunoassay , Indicators and Reagents , Mass Spectrometry , Methods , Pathology, Molecular , Spectrum AnalysisABSTRACT
Appropriate reference intervals of serum insulin-like growth factor I (IGF-I) is important for diagnosing and monitoring patients with growth hormone-related diseases. To establish reference intervals, adult individuals (n=1,334, 680 men and 654 women) were divided into six age groups (20–29, 30–39, 40–49, 50–59, 60–69, ≥70). Serum IGF-I was measured by chemiluminescence immunoassay (Liaison). Concordance of patient classification based on reference intervals, manufacturer’s intervals, and standard deviation score (SDS) was evaluated. New reference intervals had higher upper and lower limits than those specified by the manufacturer. The agreement between classification using new reference interval and the manufacturer’s reference interval, and that using new reference interval and SDS was 75.0% (weighted kappa, 0.17), 91.9% (weighted kappa, 0.51) in men and 91.0% (weighted kappa, 0.41), 92.5% (weighted kappa, 0.53) in women, respectively. Reference intervals should be established not only based on age and sex, but also on ethnicity and assay method.
ABSTRACT
BACKGROUND: Automated cellular analyzers are expected to improve the analytical performance in body fluid (BF) analysis. We evaluated the analytical performance of three automated cellular analyzers and established optimum reflex analysis guidelines. METHODS: A total of 542 BF samples (88 cerebrospinal fluid [CSF] samples and 454 non-CSF samples) were examined using manual counting and three automated cellular analyzers: UniCel DxH 800 (Beckman Coulter), XN-350 (Sysmex), and UF-5000 (Sysmex). Additionally, 2,779 BF analysis results were retrospectively reviewed. For malignant cell analysis, the receiver operating characteristic (ROC) curve was used, and the detection of high fluorescence-BF cells (HF-BFs) using the XN-350 analyzer was compared with cytology results. RESULTS: All three analyzers showed good agreement for total nucleated cell (TNC) and red blood cell (RBC) counts, except for the RBC count in CSF samples using the UniCel DxH 800. However, variable degrees of differences were observed during differential cell counting. For malignant cell analysis, the area under the curve was 0.63 for the XN-350 analyzer and 0.76 for manual counting. We established our own reflex analysis guidelines as follows: HF-BFs 83.4/100 WBCs or eosinophils >3.8% are the criteria for mandatory double check confirmation with 1,000× magnification examination. CONCLUSIONS: The three automated analyzers showed good analytical performances. Application of reflex analysis guidelines is recommended for eosinophils and HF-BFs, and manual confirmation is warranted.
Subject(s)
Body Fluids , Cell Count , Cerebrospinal Fluid , Eosinophils , Erythrocytes , Leukocytes , Reflex , Retrospective Studies , ROC CurveABSTRACT
Appropriate reference intervals of serum insulin-like growth factor I (IGF-I) is important for diagnosing and monitoring patients with growth hormone-related diseases. To establish reference intervals, adult individuals (n=1,334, 680 men and 654 women) were divided into six age groups (20–29, 30–39, 40–49, 50–59, 60–69, ≥70). Serum IGF-I was measured by chemiluminescence immunoassay (Liaison). Concordance of patient classification based on reference intervals, manufacturer’s intervals, and standard deviation score (SDS) was evaluated. New reference intervals had higher upper and lower limits than those specified by the manufacturer. The agreement between classification using new reference interval and the manufacturer’s reference interval, and that using new reference interval and SDS was 75.0% (weighted kappa, 0.17), 91.9% (weighted kappa, 0.51) in men and 91.0% (weighted kappa, 0.41), 92.5% (weighted kappa, 0.53) in women, respectively. Reference intervals should be established not only based on age and sex, but also on ethnicity and assay method.
ABSTRACT
BACKGROUND: Recently, a new automated chemistry analyzer, Atellica CH930 (Siemens, Germany), was introduced. It automatically measures internal quality control (QC) materials according to a pre-determined schedule. For this purpose, the instrument has space for storage of QC materials. We evaluated the analytical performance of chemistry items by using the Atellica system. METHODS: The precision of 29 items was evaluated with three levels of QC materials with two storage methods. We stored the QC materials in the dedicated storage space in the instrument during the precision evaluation period. In addition, we aliquoted and stored the materials in the refrigerator, and then loaded the material in a timely manner. Linearity, carry-over, and agreement with current methods were also evaluated. RESULTS: The within-laboratory coefficient of variation (CV) of most items, except for total CO2 (tCO2), was within 5.0% in both QC storage methods without significant differences in CV between storage methods. The CV of tCO2 was 5.2%, 5.8%, and 5.1% at three different levels when the QC materials were stored in a dedicated space in the instrument. The linearity was acceptable, showing <5% nonlinearity. Although good agreement was observed for most items, some items, such as calcium, total bilirubin, aspartate transaminase, and chloride, showed unequivalent results. CONCLUSIONS: Atellica CH930 showed acceptable precision, linearity, and agreement in routine chemistry items. The automatic QC function using the storage device has no problem with stability or precision. It can reduce the manual process, allowing technicians to focus on reviewing the QC results and reporting reliable results.
Subject(s)
Appointments and Schedules , Aspartate Aminotransferases , Bilirubin , Calcium , Chemistry , Quality ControlABSTRACT
The Clinical Mass Spectrometry Research Committee (CMSRC), in affiliation with the Korean Society of Clinical Chemistry (KSCC), conducted a questionnaire survey on opinions about the general status of clinical mass spectrometric analysis in Korea. As a result, we understand that this field has passed through the introductory stage and is settled as a field of clinical laboratory testing in Korea, with the number of new laboratories performing mass spectrometric analysis being low. In spite of the many difficulties in introducing and operating clinical mass spectrometric analysis, there is a strong interest in this field, and even though further expansion is expected, there are still many issues to be resolved. In the future, it will be necessary to make concrete and thorough efforts to further develop the laboratory tests using clinical mass spectrometric analysis in Korea, centering on the CMSRC affiliated with the KSCC.
Subject(s)
Chemistry, Clinical , Korea , Mass SpectrometryABSTRACT
The accuracy-based lipid (ABL) proficiency testing (PT) program was started in 2016 by the Korean External Quality Assessment Service to minimize the matrix effect. We analyzed 3 years of the program. We made or purchased six kinds of commutable frozen sera based on the Clinical and Laboratory Standards Institute 37A guideline and distributed it in two rounds per year from 2016 to 2018. We obtained reference values for levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), total glycerides, and triglycerides in each fresh frozen pool at the reference-measurement laboratories. We evaluated the average percent bias of the participating laboratories based on the National Cholesterol Education Program (NCEP) bias limit. The number of participating laboratories evaluating TC, HDLC, LDLC, total glycerides, and triglycerides increased from 164 to 223, 163 to 223, 158 to 214, 98 to 139, and 61 to 82, respectively. The average percent bias of all participating laboratories for TC, HDLC, LDLC, total glycerides, and triglycerides was +0.14%, −0.54%, +2.9%, −1.08%, and −1.32%, respectively. The average percent bias exceeded the NCEP bias limit only once or twice for TC, HDLC, and total glycerides but frequently for LDLC (eight out of 18 pools). The manufacturer-specific bias estimation report seemed useful for traceability. Although the average percent bias of participating laboratories for TC, HDLC, LDLC, total glycerides, and triglycerides was mostly within the bias limit provided by NCEP, cases of bias limit exceeding the NCEP bias limit occurred occasionally, especially for LDLC during the 3 years of the ABL PT program in Korea, suggesting that ABL PT can be used to keep maintaining traceability.
Subject(s)
Bias , Cholesterol , Education , Glycerides , Korea , Laboratory Proficiency Testing , Lipoproteins , Reference Values , TriglyceridesABSTRACT
BACKGROUND: In Korea, the Korean Laboratory Accreditation Program (KLAP) has set minimum standards for verification of clinical test performance. This verification process is time-consuming and labor-intensive when performed manually. We developed a free, statistical software program for KLAP, using the R language (R Foundation for Statistical Computing, Vienna, Austria). METHODS: We used CLSI guidelines for the algorithm. We built graphic user interfaces, including data input, with Embarcadero Delphi EX4 (Embarcadero Technologies, Inc., Texas, USA). The R Base Package and MCR Package for Method Comparison Regression were used to implement statistical and graphical procedures. RESULTS: Our program LaboStats has six modules: parallel test, linearity, method comparison, precision, reference interval, and cutoff. Data can be entered into the field either manually or by copying and pasting from an MS Excel worksheet. Users can print out precise reports. CONCLUSIONS: LaboStats can be useful for evaluating clinical test performance characteristics and preparing documents requested by KLAP.
Subject(s)
Accreditation , Korea , Mathematical Computing , Methods , TexasABSTRACT
BACKGROUND: It is known that the blood collection tube used can cause fluctuations in laboratory test results. We compared test results obtained when blood was collected in V-tube (AB Medical, Korea), BD Vacutainer Tubes (BD, USA), and Greiner Vacuette Tubes (Greiner, USA) in clinical chemistry and thyroid hormone assays. METHODS: One hundred volunteers from three hospitals were recruited and the peripheral blood samples were collected in each of the three serum separation tubes (SSTs). These samples were used for 28 routine clinical chemistry assays and three thyroid hormone assays. The results were analyzed by the Student paired t-test and the Bland-Altman plot. For stability tests, the initial results were compared with the day 1 (24±2 hours), day 3 (72±2 hours), and day 7 (168±2 hours) results, respectively. RESULTS: The difference in the test results obtained from the samples in each tube (V-Tube vs. BD-Tube, V-Tube vs. Greiner-Tube, and BD-Tube vs. Greiner-Tube) were satisfied with the Clinical Laboratory Improvement Amendments of 1988 allowable difference ranges. Except for four analytes (low-density lipoprotein cholesterol, magnesium, potassium, and thyroid-stimulating hormone), all analytes were within the allowable critical difference range based on biological variability. The paired t-test revealed significant differences between the results of nine assays for samples in V-Tube vs. BD-Tube and seven assays for samples in V-Tube vs. Greiner-Tube, but each set of results showed good correlations. The test results on different days showed a significant difference in several assays, but they were within the allowable difference range. CONCLUSIONS: The assay results for blood samples collected in SST V-Tubes were comparable to those obtained when blood was collected in BD Tubes and Greiner Tubes, and the blood collected in V-Tubes also showed excellent results in the stability tests.
Subject(s)
Humans , Chemistry , Chemistry, Clinical , Cholesterol , Lipoproteins , Magnesium , Potassium , Thyroid Gland , Vacuum , VolunteersABSTRACT
BACKGROUND: With the advent of sodium glucose co-transporter 2 inhibitors to control glucose and treat diabetes, laboratory data aided by either timed or spot glucose levels in the urine could be used as an alternative marker of drug response. The aim of this study was to assess the agreement between overnight urinary glucose excretion (UGE) and morning spot urinary glucose-to-creatinine ratio (UGCR). METHODS: In this prospective cross-sectional study, we enrolled a total of 215 participants with either normal glucose tolerance (NGT), pre-diabetes, or type 2 diabetes mellitus (T2DM). To exclude external factors such as food intake and physical activity, urine samples collected overnight at an 8-hr interval and the first-voided morning spot urine were collected and compared. RESULTS: The median values of overnight 8-hr UGE in participants with NGT (N=14), pre-diabetes (N=41), and T2DM (N=160) were 35.0 mg, 35.6 mg, and 653.4 mg, respectively. In participants with T2DM, the median values of overnight 8-hr UGCR and first-voided morning spot UGCR (M-UGCR) were 1.37 mg/mg and 0.16 mg/mg, respectively. Quantitative analyses using an intraclass correlation coefficient (ICC) demonstrated a good reliability of measurement of the overnight 8-hr UGCR and M-UGCR (ICC=0.943, P<0.001). The M-UGCR was also significantly related to the overnight 8-hr UGE (r=0.828, P<0.001). CONCLUSIONS: M-UGCR and overnight 8-hr UGCR showed good agreement, suggesting that M-UGCR be used as a simple index for estimating overnight amounts of UGE in patients with T2DM.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Blood Glucose/analysis , Creatinine/urine , Cross-Sectional Studies , Diabetes Mellitus, Type 2/pathology , Glucose/analysis , Linear Models , Prospective Studies , UrinalysisABSTRACT
BACKGROUND: Hemoglobin A1c (HbA1c) is considered a marker useful for the follow-up and diagnosis of diabetes and implies the importance of reliable assay methods that are traceable to a reference method. We evaluated analytical performance of a new high-performance liquid chromatography system for the HbA1c assay: D-100 from Bio-Rad Laboratories (USA). METHODS: We evaluated precision, linearity, and carry-over of D-100, according to the Clinical and Laboratory Standards Institute's guidelines. Comparative analysis of D-100 with Integra 800 (Roche Diagnostics, Germany) and Capillarys 3 (Sebia, France) was conducted. Additionally, we evaluated the throughput of the three instruments. RESULTS: Precision of low- and high-concentration controls in D-100 showed a CV of less than 1%. The linearity was excellent (R²=0.999) in the range of 3.51-18.7%, and carry-over was not observed. HbA1c results of D-100 (n=144) showed good correlation with those of Integra 800 (r=0.993) and Capillarys 3 (r=0.996). The % bias between D-100 and Integra 800 or Capillarys 3 was within the allowable range at all 3 medical decision levels (5.7%, 6.5%, and 10.0%). Elapsed time in the analysis of the first sample by D-100 was shorter than that of Integra 800 (2.4 vs. 11.1 minutes), but subsequent samples took more time (0.8 vs. 0.3 minutes per sample). CONCLUSIONS: D-100 showed reliable analytical performance with good precision and linearity, minimal carry-over, and acceptable comparative characteristics relative to other instruments. D-100 is expected to be useful for clinical measurements of HbA1c for diabetes diagnosis and theranostics.