Review Article2022-09-01 Clinical Chemistry

Review of the Use of Liquid Chromatography-Tandem Mass Spectrometry in Clinical Laboratories: Part II–Operations

Brian A. Rappold , B.S.

Ann Lab Med 2022; 42(5): 531-557

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Abstract : Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is increasingly utilized in clinical laboratories because it has advantages in terms of specificity and sensitivity over other analytical technologies. These advantages come with additional responsibilities and challenges given that many assays and platforms are not provided to laboratories as a single kit or device. The skills, staff, and assays used in LC-MS/MS are internally developed by the laboratory, with relatively few exceptions. Hence, a laboratory that deploys LC-MS/MS assays must be conscientious of the practices and procedures adopted to overcome the challenges associated with the technology. This review discusses the post-development landscape of LC-MS/MS assays, including validation, quality assurance, operations, and troubleshooting. The content knowledge of LC-MS/MS users is quite broad and deep and spans multiple scientific fields, including biology, clinical chemistry, chromatography, engineering, and MS. However, there are no formal academic programs or specific literature to train laboratory staff on the fundamentals of LC-MS/MS beyond the reports on method development. Therefore, depending on their experience level, some readers may be familiar with aspects of the laboratory practices described herein, while others may be not. This review endeavors to assemble aspects of LC-MS/MS operations in the clinical laboratory to provide a framework for the thoughtful development and execution of LC-MS/MS applications.

Review Article2023-05-01

Biomarkers in Heart Failure: From Research to Clinical Practice

Alexander E. Berezin , M.D., Ph.D. and Alexander A. Berezin , M.D.

Ann Lab Med 2023; 43(3): 225-236

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Abstract : The aim of this narrative review is to summarize contemporary evidence on the use of circulating cardiac biomarkers of heart failure (HF) and to identify a promising biomarker model for clinical use in personalized point-of-care HF management. We discuss the reported biomarkers of HF classified into clusters, including myocardial stretch and biomechanical stress; cardiac myocyte injury; systemic, adipocyte tissue, and microvascular inflammation; cardiac fibrosis and matrix remodeling; neurohumoral activation and oxidative stress; impaired endothelial function and integrity; and renal and skeletal muscle dysfunction. We focus on the benefits and drawbacks of biomarker-guided assistance in daily clinical management of patients with HF. In addition, we provide clear information on the role of alternative biomarkers and future directions with the aim of improving the predictive ability and reproducibility of multiple biomarker models and advancing genomic, transcriptomic, proteomic, and metabolomic evaluations.

Brief Communication2022-01-01 Diagnostic Immunology

Clinical Evaluation of the Rapid STANDARD Q COVID-19 Ag Test for the Screening of Severe Acute Respiratory Syndrome Coronavirus 2

Hyung Woo Kim , M.D., Mikyoung Park , M.D., Ph.D., and Jong Ho Lee , M.D.

Ann Lab Med 2022; 42(1): 100-104

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Abstract : Standard tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detect the presence of viral RNA using real-time reverse transcription (rRT)-PCR. Recently, convenient, rapid, and relatively inexpensive SARS-CoV-2 antigen (Ag) detection methods have been developed. The STANDARD Q COVID-19 Ag test (SD Biosensor, Inc., Suwon, Korea) is a rapid immunochromatography test that qualitatively detects the nucleocapsid protein of SARS-CoV-2 using gold conjugated antibodies. We evaluated its performance in comparison with that of Allplex 2019-nCoV Assay (Seegene, Seoul, Korea) in a retrospective case-control study using residual samples. The sensitivity and specificity of the STANDARD Q COVID-19 Ag test were 89.2% (58/65) and 96.0% (96/100), respectively. Cycle threshold (Ct) values for the three target SARS-CoV-2 genes (envelope, RNA-dependent RNA polymerase, and nucleocapsid genes) included in Allplex 2019-nCoV Assay were significantly lower in Ag test-positive patients than in Ag test-negative patients (P

Original Article2022-01-01 Clinical Chemistry

Comprehensive Laboratory Data Analysis to Predict the Clinical Severity of Coronavirus Disease 2019 in 1,952 Patients in Daegu, Korea

Eun-Hyung Yoo , M.D., Ph.D., Soon Hee Chang , M.D., Ph.D., Do-Young Song , M.D., Ph.D., Chae Hoon Lee , M.D., Ph.D., Gyu Young Cheong , M.D., Ph.D., Sunggyun Park , M.D., Ph.D., Jae Hee Lee , M.D., Ph.D., Sooin Lee , M.D., Ph.D., Sang-Gyu Kwak , Ph.D., Chang-Ho Jeon , M.D., Ph.D., and Kyung Eun Song , M.D., Ph.D.

Ann Lab Med 2022; 42(1): 24-35

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Abstract : Background: Laboratory parameter abnormalities are commonly observed in COVID-19 patients; however, their clinical significance remains controversial. We assessed the prevalence, characteristics, and clinical impact of laboratory parameters in COVID-19 patients hospitalized in Daegu, Korea. Methods: We investigated the clinical and laboratory parameters of 1,952 COVID-19 patients on admission in nine hospitals in Daegu, Korea. The average patient age was 58.1 years, and 700 (35.9%) patients were men. The patients were classified into mild (N=1,612), moderate (N=294), and severe (N=46) disease groups based on clinical severity scores. We used chi-square test, multiple comparison analysis, and multinomial logistic regression to evaluate the correlation between laboratory parameters and disease severity. Results: Laboratory parameters on admission in the three disease groups were significantly different in terms of hematologic (Hb, Hct, white blood cell count, lymphocyte%, and platelet count), coagulation (prothrombin time and activated partial thromboplastin time), biochemical (albumin, aspartate aminotransferase, alanine aminotransferase, lactate, blood urea nitrogen, creatinine, and electrolytes), inflammatory (C-reactive protein and procalcitonin), cardiac (creatinine kinase MB isoenzyme and troponin I), and molecular virologic (Ct value of SARS-CoV-2 RdRP gene) parameters. Relative lymphopenia, prothrombin time prolongation, and hypoalbuminemia were significant indicators of COVID-19 severity. Patients with both hypoalbuminemia and lymphopenia had a higher risk of severe COVID-19. Conclusions: Laboratory parameter abnormalities on admission are common, are significantly associated with clinical severity, and can serve as independent predictors of COVID-19 severity. Monitoring the laboratory parameters, including albumin and lymphocyte count, is crucial for timely treatment of COVID-19.

Original Article2022-01-01 General Laboratory Medicine

Economic Evaluation of Total Laboratory Automation in the Clinical Laboratory of a Tertiary Care Hospital

KyungYi Kim , M.S., Sang-Guk Lee , M.D., Ph.D., Tae Hyun Kim , Ph.D., and Sang Gyu Lee , M.D., Ph.D., M.B.A.

Ann Lab Med 2022; 42(1): 89-95

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Abstract : Background: Total laboratory automation (TLA) is an innovation in laboratory technology; however, the high up-front costs restrict its widespread adoption. To examine whether the capital investment for TLA is worthwhile, we analyzed its clinical- and cost-effectiveness for the expected payback period. Methods: Clinical chemistry tests and immunoassays performed in the clinical laboratory of a tertiary care hospital were divided into a post-TLA group, including 1,182,419 tests performed during December 2019, and a pre-TLA group, including 1,151,501 tests performed during December 2018. Laboratory information system data were used to measure clinical effectiveness, and depreciation data were used to calculate TLA costs. Results: Laboratory performance improved after TLA adoption in all four key performance indicators: mean turn-around time (TAT), representing the timeliness of result reporting, decreased by 6.1%; the 99th percentile of TAT, representing the outlier rate, decreased by 13.3%; the TAT CV, representing predictability, decreased by 70.0%; and weighted tube touch moment (wTTM), representing staff safety, improved by 77.6%. Based on these effectiveness results, economic evaluation was performed using two approaches. First, the incremental cost-effectiveness ratio and wTTM were used as the most cost-effective performance indicators. Second, the expected payback period was calculated. Considering only staff cost reduction, it was anticipated that 4.75 yrs would be needed to payback the initial investment. Conclusions: TLA can significantly enhance laboratory performance, has a relatively quick payback period, and can reduce total hospital expenses in the long term. Therefore, the capital investment for TLA adoption is considered to be worthwhile.

Brief Communication2022-01-01 Transfusion Medicine

Choice of ABO Group for Blood Component Transfusion in ABO-Incompatible Solid Organ Transplantation: A Questionnaire Survey in Korea and Guideline Proposal

Yousun Chung , M.D., Dae-Hyun Ko , M.D., Ph.D., Jihyang Lim , M.D., Ph.D., Kyeong-Hee Kim , M.D., Ph.D., and Hyungsuk Kim , M.D.

Ann Lab Med 2022; 42(1): 105-109

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Abstract : The number of ABO-incompatible solid organ transplantations (ABOi SOTs) has markedly increased worldwide since the early 2000s. We investigated the choice of ABO group for blood component transfusion in ABOi SOT. We conducted a survey by e-mailing a questionnaire to blood bank specialists at 77 major hospitals in Korea, among whom 34 responded to the survey. In major ABOi SOT, for red blood cells (RBCs), the recipient’s type (70.6%) was the most common choice, followed by group O (29.4%); for platelets, group AB (50.0%) was the most common choice, followed by the donor type (38.2%); for plasma, group AB (55.9%) was the most common choice, followed by the donor type (32.4%). In bidirectional ABOi SOT, for RBCs, the recipient’s type (55.9%) was the most common choice, followed by group O (44.1%); for platelets and plasma, group AB was the most common choice (94.1% and 97.1%, respectively). The policies for transfusion in ABOi SOT were diverse. We suggest a guideline on the choice of ABO group for transfusion in ABOi SOT to secure patient health and enable an efficient use of blood components.

Original Article2022-03-01 Clinical Microbiology

Virulence Factors Associated With Escherichia coli Bacteremia and Urinary Tract Infection

Bongyoung Kim , M.D., Ph.D., Jin-Hong Kim , M.D., and Yangsoon Lee , M.D., Ph.D.

Ann Lab Med 2022; 42(2): 203-212

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Abstract : Background: Extraintestinal pathogenic Escherichia coli (ExPEC) causes various infections, including urinary tract infection (UTI), sepsis, and neonatal meningitis. ExPEC strains have virulence factors (VFs) that facilitate infection by allowing bacterial cells to migrate into and multiply within the host. We compared the microbiological characteristics of ExPEC isolates from blood and urine specimens from UTI patients. Methods: We conducted a single-center, prospective study in an 855-bed tertiary-care hospital in Korea. We consecutively recruited 80 hospitalized UTI patients with E. coli isolates, which were isolated from blood and/or urine, and urine alone between March 2019 and May 2020. We evaluated the 80 E. coli isolates for the presence of bacterial genes encoding the sequence types (STs), antimicrobial resistance, and VFs using whole-genome sequencing (WGS). Results: We found no significant differences in STs, antimicrobial resistance patterns, or VFs between isolates from blood and urine specimens. ST131, a pandemic multidrug-resistant clone present in both blood and urine, was the most frequent ST (N=19/80, 24%), and ST131 isolates carried more virulence genes, especially, tsh and espC, than non-ST131 isolates. The virulence scores of the ST131 group and the ST69, ST95, and ST1193 groups differed significantly (P

Original Article2022-01-01 Diagnostic Immunology

Performance Comparison of Five SARS-CoV-2 Antibody Assays for Seroprevalence Studies

Younhee Park , M.D., Ki Ho Hong , M.D., Su-Kyung Lee , M.S., Jungwon Hyun , M.D., Eun-Jee Oh , M.D., Jaehyeon Lee , M.D., Hyukmin Lee , M.D., Sang Hoon Song , M.D., Seung-Jung Kee , M.D., Gye Cheol Kwon , M.D., Su Hwan Kim , B.S., Hyeon-Nam Do , M.S., Ah-Ra Kim , M.S., June-Woo Lee , Ph.D., Sung Soon Kim , Ph.D., and Hyun Soo Kim , M.D., Ph.D.

Ann Lab Med 2022; 42(1): 71-78

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Abstract : Background: Seroprevalence studies of coronavirus disease 2019 (COVID-19) cases, including asymptomatic and past infections, are important to estimate the scale of the disease outbreak and to establish quarantine measures. We evaluated the clinical performance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays available in Korea for use in seroprevalence studies. Methods: The sensitivity, specificity, cross-reactivity, and interference of five SARS-CoV-2 antibody assays were evaluated using the following: 398 serum samples from confirmed COVID-19 patients, 510 negative control samples from before 2018 (pre-pandemic), 163 serum samples from patients with SARS, Middle East respiratory syndrome (MERS), and other viral infections, and five samples for the interference study. Results: The sensitivities of the five assays ranged from 92.2% to 98%, and their specificities, including cross-reactivity and interference, ranged from 97.5% to 100%. The agreement rates were excellent (kappa >0.9). Adjustment of the cutoff values could be considered through ROC curve analysis. The positive predictive values of the individual assays varied from 3.5% to 100% at a 0.1% prevalence but were as high as ≥95% when two assays were combined. Conclusions: The prevalence of COVID-19 in Korea is considered to be exceptionally low at present; thus, we recommend using a combination of two or more SARS-CoV-2 antibody assays rather than a single assay. These results could help select SARS-CoV-2 antibody assays for COVID-19 seroprevalence studies in Korea.

Original Article2022-01-01 Diagnostic Immunology

Clinical Performance of Two Automated Immunoassays, EliA CTD Screen and QUANTA Flash CTD Screen Plus, for Antinuclear Antibody Screening

Sumi Yoon , M.D., Hee-Won Moon , M.D., Ph.D., Hanah Kim , M.D., Ph.D., Mina Hur , M.D., Ph.D., and Yeo-Min Yun , M.D., Ph.D.

Ann Lab Med 2022; 42(1): 63-70

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Abstract : Background: Recently, two fully automated immunoassays for antinuclear antibody (ANA) screening were introduced: EliA CTD Screen (Thermo Fisher Scientific, Freiburg, Germany) and QUANTA Flash CTD Screen Plus (Inova Diagnostics, San Diego, USA). We evaluated their clinical performance in comparison with the indirect immunofluorescence assay (IIFA) and analyzed samples with discrepant results. Methods: In total, 406 serum samples (206 from patients undergoing routine checkups and 200 from rheumatology clinic patients) were assayed using EliA, QUANTA Flash, and IIFA. We evaluated assay concordance and agreement and confirmed the presence of anti-extractable nuclear antigen (ENA) antibodies in samples with discrepant automated immunoassay and IIFA results. Additionally, we compared the clinical performance of each assay in diagnosing ANA-associated rheumatic disease (AARD) and adjusted the cut-off values. Results: In rheumatology clinic samples, the concordance and agreement were 91.5% and strong between EliA and QUANTA Flash, 79.0% and weak between EliA and IIFA, and 80.5% and moderate between QUANTA Flash and IIFA, respectively. In automated immunoassay-positive, IIFA-negative samples (N=15), all anti-ENA antibodies detected (6/15) were anti-Sjögren’s syndrome antigen A/Ro (Ro60) antibodies. The automated immunoassays and IIFA showed high accuracy for diagnosing AARD, and adjusted cut-off values improved their sensitivities (EliA with 0.56 ratio, 82.9% sensitivity; QUANTA Flash with 9.7 chemiluminescent units, 87.8% sensitivity). Conclusions: The two automated immunoassays showed reliable performance compared with IIFA and can be efficiently used with the IIFA in clinical immunology laboratories. Clinical cut-off values can be adjusted according to the workflow in each laboratory.

Guideline2022-07-01 Clinical Microbiology

Update of Guidelines for Laboratory Diagnosis of COVID-19 in Korea

Ki Ho Hong , M.D., Gab Jung Kim , Ph.D., Kyoung Ho Roh , M.D., Heungsup Sung , M.D., Jaehyeon Lee , M.D., So Yeon Kim , M.D., Taek Soo Kim , M.D., Jae-Sun Park , Ph.D., Hee Jae Huh , M.D., Younhee Park , M.D., Jae-Seok Kim , M.D., Hyun Soo Kim , M.D., Moon-Woo Seong , M.D., Nam Hee Ryoo , M.D., Sang Hoon Song , M.D., Hyukmin Lee , M.D., Gye Cheol Kwon , M.D., and Cheon Kwon Yoo , Ph.D.

Ann Lab Med 2022; 42(4): 391-397

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Abstract : Korean Society for Laboratory Medicine and the Korea Disease Prevention and Control Agency have announced guidelines for diagnosing coronavirus disease (COVID-19) in clinical laboratories in Korea. With the ongoing pandemic, we propose an update of the previous guidelines based on new scientific data. This update includes recommendations for tests that were not included in the previous guidelines, including the rapid molecular test, antigen test, antibody test, and self-collected specimens, and a revision of the previous recommendations. This update will aid clinical laboratories in performing laboratory tests for diagnosing COVID-19.