Brief Communication2022-01-01
Clinical Microbiology
Ki Ho Hong 
, M.D., Ji Won In , M.D., Jaehyeon Lee , M.D., So Yeon Kim , M.D., Kyoung Ah Lee , M.T., Seunghyun Kim , M.T., Yeoungim An , M.T., Donggeun Lee , M.T., Heungsup Sung , M.D., Jae-Seok Kim , M.D., and Hyukmin Lee , M.D.
Abstract : The sensitivity of molecular diagnostics could be affected by nucleotide variants in pathogen genes, and the sites affected by such variants should be monitored. We report a single-nucleotide variant (SNV) in the nucleocapsid (N) gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), i.e., G29179T, which impairs the diagnostic sensitivity of the Xpert Xpress SARS-CoV-2 assay (Cepheid, Sunnyvale, CA, USA). We observed significant differences between the threshold cycle (Ct) values for envelope (E) and N genes and confirmed the SNV as the cause of the differences using Sanger sequencing. This SNV, G29179T, is the most prevalent in Korea and is associated with the B.1.497 virus lineage, which is dominant in Korea. Clinical laboratories should be aware of the various SNVs in the SARS-CoV-2 genome and consider their potential effects on the diagnosis of coronavirus disease 2019.
Brief Communication2021-01-01
Clinical Chemistry
Sunghwan Shin , M.D., Jongwon Oh , M.D., and Hyung-Doo Park , M.D., Ph.D.
Abstract : The Barricor tube (Becton Dickinson [BD], Sunnyvale, CA, USA) was recently developed to mechanically separate plasma by increasing the centrifugation rate. We compared the Barricor tube with existing serum- and plasma-based tubes based on 35 biochemical analytes and preanalytical turnaround time (TAT). Blood samples were collected from 30 healthy volunteers in a Barricor tube, serum separating tube (SST, Vacutainer SST II Tube 8.5 mL, #368972; BD), or plasma separating tube (PST, Vacutainer PST Tube 8.0 mL, #367964; BD) in random order. Next, 27 chemistry analytes, six immunochemistry analytes, and two cardiac markers were compared using Passing-Bablok regression and the Bland-Altman method. Preanalytical TAT was measured for each tube. The Barricor tube exhibited bias exceeding the desirable limit for nine and four analytes compared with the SST and PST, respectively. The Barricor tube lactate dehydrogenase value showed a bias of -10.29% and -9.86% compared with that of the SST and PST, respectively. The preanalytical TAT of Barricor tube was 8.8 minutes, which was the shortest among the three tubes. The clinical performance of the Barricor tube was equivalent to that of the SST and PST for most analytes, with an apparent advantage in preanalytical TAT. When using the Barricor tube, the reference range needs to be changed for some analytes that exceed the desirable bias limit.
Original Article2022-01-01
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.
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.
Review Article2022-05-01
General Laboratory Medicine
Sun Huh , M.D., Ph.D.
Abstract : Background: A bibliometric analysis of the Annals of Laboratory Medicine (ALM) was performed to understand its position in the medical laboratory technology category and to suggest a developmental strategy. Methods: Journal metrics, including the number of articles by publication type, country of authors, total citations, 2-year impact factor, country of cited authors, journals citing ALM, and Hirsch-index, were obtained from the Journal Citation Report and Web of Science Core Collection. Target data included ALM content in the Web of Science from January 1, 2012, to October 5, 2021. Bibliometric analysis was performed using Biblioshiny. Results: The impact factor increased from 1.481 in 2013 to 3.464 in 2020. Authors belonging to the USA, China, and Korea cited ALM articles the most. Plos One, Scientific Reports, and Frontiers in Microbiology most frequently cited ALM, besides ALM itself. The Hirsch-index was 34. The co-occurrence network of Keyword Plus indicated four clusters: diagnosis, identification, prevalence, and risk. The conceptual structure map of Keyword Plus based on multiple correspondence analysis showed two clusters: bacterial susceptibility at the bench and clinical courses. The co-citation network showed that ALM was in the cluster of the New England Journal of Medicine, The Lancet, JAMA, and the Annals of Internal Medicine. The collaboration network showed that Korean authors collaborated mainly with authors from the USA, Germany, and Italy. Conclusions: The journal’s promotion to an international top-tier journal has been successful. “Principles of transparency and best practice in scholarly publishing” and a preprint policy are yet to be added.
Brief Communication2021-07-01
Diagnostic Immunology
Hyunhye Kang , M.D., Jaeeun Yoo , M.D., Sang-Yoon Lee , M.T., and Eun-Jee Oh , M.D., Ph.D.
Abstract : Pretransplant crossmatch (XM) testing is widely used for detecting preformed donor-specific antibodies (DSAs) against human leukocyte antigen (HLA). However, in some cases, there is a positive XM result in the absence of HLA-DSAs, the cause of which was rarely identified. We reviewed the causes of sequential positive XM results at a single center and analyzed the presence of non-HLA antibodies in patients with an unexplained positive pretransplant XM result. Among 251 patients with T-cell/B-cell complement-dependent cytotoxicity (CDC) or flow cytometric crossmatch (FCXM) positivity, HLA-DSAs were confirmed in 88 (35.1%) by a single antigen bead (SAB) assay, 150 (59.8%) used rituximab (anti-CD20), and 13 (5.2%) had neither HLA-DSAs nor a desensitization history. Anti-angiotensin II type 1 receptor IgG and 33 non-HLA antibodies were tested in the 13 patients with an unexplained positive pretransplant XM result, and more than one non-HLA antibody were revealed in all these patients; 11 patients had non-HLA antibodies reported to be associated with graft rejection, and two patients experienced rejection episode after kidney transplantation. Our study suggests considering non-HLA antibodies testing when a CDC or FCXM test is positive without a definite cause. Assessing non-HLA antibodies might be useful for interpreting XM results and evaluating immunologic risk in transplant recipients.
Original Article2021-05-01
Hyun-Ki Kim , M.D., Hyung-Doo Park , M.D., Sang-Guk Lee , M.D., Hyojin Chae , M.D., Sang Hoon Song , M.D., Yong-Wha Lee , M.D., Yeo-Min Yun , M.D., Sunhyun Ahn , M.D., Serim Kim , M.D., Sun Min Lee , M.D., Soo-Youn Lee , M.D., and Sail Chun , M.D.; on behalf of the Clinical Mass Spectrometry Research Committee of the Korean Society of Clinical Chemistry
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.
Original Article2021-01-01
Yutong Zou , B.S., Danchen Wang , M.S., Xinqi Cheng , M.S., Chaochao Ma , B.S., Songbai Lin , Ph.D., Yingying Hu , B.S., Songlin Yu , M.S., Liangyu Xia , M.S., Honglei Li , B.S., Yicong Yin , M.S., Huaicheng Liu , B.S., Dianxi Zhang , B.S., Kui Zhang , B.S., Xiaolan Lian , Ph.D., Tengda Xu , Ph.D., and Ling Qiu , M.S.
Abstract : Background: Thyroid diseases are highly prevalent worldwide, but their diagnosis remains a challenge. We established reference intervals (RIs) for thyroid-associated hormones and evaluated the prevalence of thyroid diseases in China. Methods: After excluding outliers based on the results of ultrasound screening, thyroid antibody tests, and the Tukey method, the medical records of 20,303 euthyroid adults, who visited the Department of Health Care at Peking Union Medical College Hospital from January 2014 to December 2018, were analyzed. Thyroid-associated hormones were measured by the Siemens Advia Centaur XP analyzer. The RIs for thyroid-associated hormones were calculated according to the CLSI C28-A3 guidelines, and were compared with the RIs provided by Siemens. The prevalence of thyroid diseases over the five years was evaluated and compared using the chi-square test. Results: The RIs for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were 0.71–4.92 mIU/L, 12.2–20.1 pmol/L, 3.9–6.0 pmol/L, 65.6–135.1 nmol/L, and 1.2–2.2 nmol/L, respectively. The RIs of all hormones except TT4 differed significantly between males and females. The RIs of TSH increased with increasing age. The prevalence of overt hypothyroidism, overt hyperthyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism was 0.5% and 0.8%, 0.2% and 0.6%, 3.8% and 6.1%, and 3.3% and 4.7% in males and females, respectively, which differed from those provided by Siemens. Conclusions: Sex-specific RIs were established for thyroid-associated hormones, and the prevalence of thyroid diseases was determined in the Chinese population.
Original Article2021-05-01
Young Ah Kim , M.D., Hyunsoo Kim , M.D., Young Hee Seo , B.D., Go Eun Park , B.D., Hyukmin Lee , M.D., and Kyungwon Lee , M.D.
Abstract : Background: One health is a flexible concept with many facets, including the environment, community, and the nosocomial super-bacteria resistance network. We investigated the molecular prevalence of extended-spectrum-β-lactamase-producing Escherichia coli (ESBL-EC) in workers, livestock, and the farm environment in Korea. Methods: ESBL-EC isolates were obtained from samples from 19 swine farms, 35 retail stores, seven slaughterhouses, and 45 related workers throughout Korea from August 2017 to July 2018, using ChromID ESBL (BioMérieux, Marcy l’Etoile, France) agar and enrichment broth. The presence of ESBL and mobilized colistin resistance (mcr) genes and antimicrobial resistance were determined. Clonality was evaluated with pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Results: In total, 232 ESBL-EC isolates were obtained from 1,614 non-duplicated samples (14.4% positive rate). The ESBL-EC isolates showed regional and source-related differences. blaCTX-M-55 (N=100), blaCTX-M-14 (N=65), blaCTX-M-15 (N=33), and blaCTX-M-65 (N=23) were common ESBL types. The ESBL-EC isolates showed high resistance rates for various antimicrobial classes; however, all isolates were susceptible to carbapenem. One swine-originating colistin-resistant isolate did not carry any known mcr gene. PFGE was successful for 197 of the 232 isolates, and most PFGE types were heterogeneous, except for some dominant PFGE types (O, R, T, U, and V). MLST of 88 isolates was performed for representative PFGE types; however, no dominant sequence type was observed. Conclusions: The proportion of ESBL-EC in swine industry-related samples was significant, and the isolates harbored common clinical ESBL gene types. These molecular epidemiologic data could provide important evidence for antimicrobial-resistance control through a one health approach.
Original Article2021-05-01
Xiang Sun , M.S., Bo Zhang , M.S., Guangjian Xu , M.S., Junwen Chen , M.S., Yongpeng Shang , Ph.D., Zhiwei Lin , Ph.D., Zhijian Yu , M.D., Jinxin Zheng , M.D., and Bing Bai , M.D.
Abstract : Background: Tigecycline, eravacycline, and omadacycline are recently developed tetracyclines. Susceptibility of microbes to these tetracyclines and their molecular mechanisms have not been well elucidated. We investigated the susceptibility of Moraxella catarrhalis to tigecycline, eravacycline, and omadacycline and its resistance mechanisms against these tetracyclines. Methods: A total of 207 non-duplicate M. catarrhalis isolates were collected from different inpatients. The minimum inhibitory concentrations (MICs) of the tetracyclines were determined by broth microdilution. Tigecycline-, eravacycline-, or omadacycline-resistant isolates were induced under in vitro pressure. The tet genes and mutations in the 16S rRNA was detected by PCR and sequencing. Results: Eravacycline had a lower MIC50 (0.06 mg/L) than tigecycline (0.125 mg/L) or omadacycline (0.125 mg/L) against M. catarrhalis isolates. We found that 136 isolates (65.7%) had the tetB gene, and 15 (7.2%) isolates were positive for tetL; however, their presence was not correlated with high tigecycline, eravacycline, or omadacycline (≥1 mg/L) MICs. Compared with the initial MIC after 160 days of induction, the MICs of tigecycline or eravacycline against three M. catarrhalis isolates increased ≥eight-fold, while those of omadacycline against two M. catarrhalis isolates increased 64-fold. Mutations in the 16S rRNA genes (C1036T and/or G460A) were observed in omadacycline-induced resistant isolates, and increased RR (the genes encoding 16SrRNA (four copies, RR1-RR4) copy number of 16S rRNA genes with mutations was associated with increased resistance to omadacycline. Conclusions: Tigecycline, eravacycline, and omadacycline exhibited robust antimicrobial effects against M. catarrhalis. Mutations in the 16S rRNA genes contributed to omadacycline resistance in M. catarrhalis.
Brief Communication2021-05-01
Sung Hoon Kim , M.D., Eun Song Song , M.D., Somy Yoon , Ph.D., Gwang Hyeon Eom , Ph.D., Gaeun Kang , M.D., and Young Kuk Cho , M.D.
Abstract : Diagnosis of Kawasaki disease (KD) is occasionally delayed because it is solely based on clinical symptoms. Previous studies have attempted to identify diagnostic biomarkers for KD. Recently, patients with KD were reported to have elevated serum ferritin levels. We investigated the usefulness of the serum ferritin level as a diagnostic biomarker for distinguishing KD from other acute febrile illnesses. Blood samples were obtained from pediatric patients with KD (N=77) and those with other acute febrile illnesses (N=32) between December 2007 and June 2011 for measuring various laboratory parameters, including serum ferritin levels. In patients with KD, laboratory tests were performed at diagnosis and repeated at 2, 14, and 56 days after intravenous immunoglobulin treatment. At the time of diagnosis, serum ferritin levels in patients with KD (188.8 μg/L) were significantly higher than those in patients with other acute febrile illnesses (106.8 μg/L, P=0.003). The serum ferritin cut-off value of 120.8 μg/L effectively distinguished patients with KD from those with other acute febrile illnesses, with a sensitivity and specificity of 74.5% and 83.3%, respectively. Serum ferritin may be a useful biomarker to distinguish KD from other acute febrile illnesses.
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