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  • Original Article2022-07-01
    Clinical Chemistry

    Prognostic Utility of Procalcitonin, Presepsin, and the VACO Index for Predicting 30-day Mortality in Hospitalized COVID-19 Patients

    Mikyoung Park , M.D., Ph.D, Mina Hur , M.D., Ph.D, Hanah Kim , M.D., Ph.D, Chae Hoon Lee , M.D., Ph.D, Jong Ho Lee , M.D., Hyung Woo Kim , M.D., and Minjeong Nam , M.D., Ph.D.

    Ann Lab Med 2022; 42(4): 406-414

    Abstract : Background: Biomarkers and clinical indices have been investigated for predicting mortality in patients with coronavirus disease (COVID-19). We explored the prognostic utility of procalcitonin (PCT), presepsin, and the Veterans Health Administration COVID-19 (VACO) index for predicting 30-day-mortality in COVID-19 patients. Methods: In total, 54 hospitalized COVID-19 patients were enrolled. PCT and presepsin levels were measured using the Elecsys BRAHMS PCT assay (Roche Diagnostics GmbH, Mannheim, Germany) and HISCL Presepsin assay (Sysmex, Kobe, Japan), respectively. The VACO index was calculated based on age, sex, and comorbidities. PCT and presepsin levels and the VACO index were compared using ROC curve, Kaplan–Meier method, and reclassification analysis for the 30-day mortality. Results: ROC curve analysis was used to measure PCT and presepsin levels and the VACO index to predict 30-day mortality; the optimal cut-off values were 0.138 ng/mL for PCT, 717 pg/mL for presepsin, and 12.1% for the VACO index. On Kaplan–Meier survival analysis, hazard ratios (95% confidence interval) were 15.9 (4.1-61.3) for PCT, 26.3 (6.4-108.0) for presepsin, and 6.0 (1.7-21.1) for the VACO index. On reclassification analysis, PCT and presepsin in addition to the VACO index significantly improved the prognostic value of the index. Conclusions: This study demonstrated the prognostic utility of measuring PCT and presepsin levels and the VACO index in COVID-19 patients. The biomarkers in addition to the clinical index were more useful than the index alone for predicting clinical outcomes in COVID-19 patients.

  • Brief Communication2021-01-01
    Clinical Chemistry

    A Sensitive and Specific Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Quantification of Salivary Melatonin and Cortisol: Development and Comparison With Immunoassays

    Sunghwan Shin , M.D., Hyeonju Oh , M.S., Hea Ree Park , M.D., Eun Yeon Joo , M.D., Ph.D., and Soo-Youn Lee , M.D., Ph.D.

    Ann Lab Med 2021; 41(1): 108-113

    Abstract : Melatonin and cortisol are clinically important for diagnosing sleep and mood disorders. We developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for simultaneous measurement of salivary melatonin and cortisol concentrations according to the Clinical and Laboratory Standards Institute guidelines. Additionally, we compared the LC-MS/MS assay with immunoassays, ELISA (Direct Salivary Melatonin Elisa EK-DSM, Bühlmann Laboratories AG, Schönenbuch, Switzerland) and electrochemiluminescence immunoassay (Cortisol II, Roche, Mannheim, Germany), using 121 saliva samples. The LC-MS/MS assay exhibited good performance in terms of linearity, precision, accuracy, limit of detection, lower limit of quantification, extraction recovery, carry-over, and matrix effect. The LC-MS/MS assay and immunoassays showed strong correlation (Pearson’s r=0.910 for melatonin, r=0.955 for cortisol), but demonstrated a significant mean bias of 23.2% (range 54.0–143.7%) for melatonin and 48.9% (range 59.7–184.7%) for cortisol. Our LC-MS/MS assay provided more sensitive and reliable salivary melatonin and cortisol quantification results compared with immunoassays.

  • Brief Communication2021-09-01
    Transfusion Medicine

    ABO-Incompatible Transfusion Events Reported in Written Judgments and in the Korean Hemovigilance System

    Sooin Choi , M.D., Jungwon Hyun , M.D., HongBi Yu , B.S., and Duck Cho , M.D.

    Ann Lab Med 2021; 41(5): 493-498

    Abstract : Fatal ABO-incompatible (ABOi) transfusion is one of the most common causes of transfusion-related death, but its reporting has been limited in Korea. We comprehensively reviewed ABOi transfusion events in Korea by analyzing cases reported in literature, Korean hemovigilance system (KOHEVIS) annual reports, and written judgments. Written judgments were assessed using a written judgment management system or a comprehensive legal information system. We found nine cases of ABOi transfusion events in written judgments (from 1953 to 2019), 16 in the KOHEVIS (from 2008 to 2018), and nine in published reports (from 1978 to 2019). One case was found in all three sources. Overall, we found 32 cases of ABOi transfusion events. Four cases died and 23 survived, while the outcomes for five were unavailable. ABOi transfusion errors occurred at the administration (50%, 16/32), sample (13%, 4/32), and testing (9%, 3/32) stages. The causes of errors were unavailable for nine cases (28%, 9/32). We report the status of ABOi transfusions in Korea and expect our results to contribute to the prevention of adverse reactions due to ABOi transfusion.

  • Original Article2021-09-01
    Diagnostic Genetics

    Expanding the Non-Invasive Diagnosis of Acute Rejection in Kidney Transplants Through Detection of Donor-Derived DNA in Urine: Proof-of-Concept Study

    Jieun Kim , M.D., Ph,D., Dong-Moung Kim , B.A., Yu Jin Park , M.D., Ph.D., Seung-Tae Lee , M.D., Ph,D., Hyon-Suk Kim , M.D., Ph,D., Myoung Soo Kim , M.D., Ph.D., Beom Seok Kim , M.D., Ph.D., and Jong Rak Choi , M.D., Ph.D.

    Ann Lab Med 2021; 41(5): 469-478

    Abstract : Background: Approximately 10%-20% of kidney transplant (KT) recipients suffer from acute rejection (AR); thus, sensitive and accurate monitoring of allograft status is recommended. We evaluated the clinical utility of donor-derived DNA (dd-DNA) detection in the urine of KT recipients as a non-invasive means for diagnosing AR. Methods: Urine samples serially collected from 39 KT recipients were tested for 39 single-nucleotide variant loci selected according to technical criteria (i.e., high minor allele frequency and low analytical error) using next-generation sequencing. The fraction of dd-DNA was calculated and normalized by the urine creatinine (UCr) level (%dd-DNA/UCr). The diagnostic performance of %dd-DNA/UCr for AR was assessed by ROC curve analysis. Results: There was an increasing trend of %dd-DNA/UCr in the AR group before subsequent graft injury, which occurred before (median of 52 days) histological rejection. The serum creatinine (SCr) level differed significantly between the AR and non-AR groups at two and four months of follow-up, whereas %dd-DNA/UCr differed between the groups at six months of follow-up. The combination of %dd-DNA/UCr, SCr, and spot urine protein (UPtn)/UCr showed high discriminating power, with an area under the ROC curve of 0.93 (95% confidence interval: 0.81-1.00) and a high negative predictive value of 100.0%. Conclusions: Although the dd-DNA-based test cannot eliminate the need for biopsy, the high negative predictive value of this marker could increase the prebiopsy probability of detecting treatable injury to make biopsy an even more effective diagnostic tool.

  • Original Article2021-03-01
    Diagnostic Immunology

    Relationship Between Rotavirus P[6] Infection in Korean Neonates and Histo-Blood Group Antigen: a Single-Center Study

    Su-Kyung Lee , M.S., Su Jin Oh , M.S., Seoheui Choi , M.D., Soo Han Choi , M.D., Seon-Hee Shin , M.D., Eun Jin Lee , M.D., Eun-Jung Cho , M.D., Jungwon Hyun , M.D., Hyun Soo Kim , M.D.

    Ann Lab Med 2021; 41(2): 181-189

    Abstract : Background: Rotaviruses are a major cause of pediatric gastroenteritis. The rotavirus P[6] genotype is the most prevalent genotype isolated from Korean neonates but has rarely been reported in other countries. Histo-blood group antigen (HBGA) is known to play an important role in rotavirus infection. We investigated the relationship between rotavirus genotype and HBGA-Lewis blood type in Korean children and explored the reasons for the predominance of rotavirus P[6] strain in Korean neonates. Methods: Blood and stool samples were collected from 16 rotavirus-infected patients. Rotavirus G (VP7) and P (VP4) genotyping was performed using reverse transcription-PCR and sequencing. Lewis antigen phenotypes (Lea/Leb) were tested, and HBGA-Lewis genotype was determined by sequencing the secretor (FUT2) and Lewis (FUT3) genes. Deduced amino acid sequences and three-dimensional structures of the VP8* portion of the rotavirus VP4 protein were analyzed. Results: All P[6] rotaviruses were isolated from neonates under one month of age, who were negative or weakly positive for the Leb antigen. However, 10 of the 11 non-P[6] rotaviruses were isolated from older children who were Leb antigen-positive. The VP8* amino acid sequences differed among P[6], P[4], and P[8] genotypes. Korean P[6] strains showed a unique VP8* sequence with amino acid substitutions, including Y169>L169, which differed from the sequences of P[6] strains from other countries. Conclusions: The predominance of the rotavirus P[6] genotype in Korean neonates may be related to the interaction between HBGA-Lewis antigen and the VP8* portion of the VP4 protein, and this information will be helpful in future neonatal vaccine development.

  • Original Article2022-11-01
    Transfusion and Cell Therapy

    Natural Killer Cell Expansion and Cytotoxicity Differ Depending on the Culture Medium Used

    Seung Kwon Koh , B.S., Jeehun Park , Ph.D., Seong-Eun Kim , B.S., Yuree Lim , M.S., Minh-Trang Thi Phan , Ph.D., Jinho Kim , B.S., Ilwoong Hwang , M.D., Yong-Oon Ahn , Ph.D., Sue Shin , M.D., Junsang Doh , Ph.D., and Duck Cho , M.D.

    Ann Lab Med 2022; 42(6): 638-649

    Abstract : Background: Adoptive cell therapy using umbilical cord blood (UCB)-derived allogeneic natural killer (NK) cells has shown encouraging results. However, because of the insufficient availability of NK cells and limited UCB volume, more effective culture methods are required. NK cell expansion and functionality are largely affected by the culture medium. While human serum is a major affecting component in culture media, the way it regulates NK cell functionality remains elusive. We elucidated the effects of different culture media and human serum supplementation on UCB NK cell expansion and functionality. Methods: UCB NK cells were cultured under stimulation with K562-OX40L-mbIL-18/21 feeder cells and IL-2 and IL-15 in serum-containing and serum-free culture media. The effects of the culture media and human serum supplementation on NK cell expansion and cytotoxicity were evaluated by analyzing the expansion rate, activating and inhibitory receptor levels, and the cytotoxicity of the UCB NK cells. Results: The optimal medium for NK cell expansion was Dulbecco’s modified Eagle’s medium/Ham’s F12 with supplements and that for cytotoxicity was AIM V supplemented with Immune Cell Serum Replacement. Shifting media is an advantageous strategy for obtaining several highly functional UCB NK cells. Live cell imaging and killing time measurement revealed that human serum enhanced NK cell proliferation but delayed target recognition, resulting in reduced cytotoxicity. Conclusions: Culture medium supplementation with human serum strongly affects UCB NK cell expansion and functionality. Thus, culture media should be carefully selected to ensure both NK cell quantity and quality for adoptive cell therapy.

  • Original Article2022-01-01
    Diagnostic Genetics

    Clinical Utility of Methylation-Specific Multiplex Ligation-Dependent Probe Amplification for the Diagnosis of Prader–Willi Syndrome and Angelman Syndrome

    Boram Kim , M.D., Yongsook Park , M.T., Sung Im Cho , M.T., Man Jin Kim , M.D., Jong-Hee Chae , M.D., Ph.D., Ji Yeon Kim , M.D., Ph.D., Moon-Woo Seong , M.D., Ph.D., and Sung Sup Park , M.D., Ph.D.

    Ann Lab Med 2022; 42(1): 79-88

    Abstract : Background: Prader–Willi syndrome (PWS) and Angelman syndrome (AS) are genomic imprinting disorders that are mainly caused by a deletion on 15q11-q13, the uniparental disomy of chromosome 15, or an imprinting defect. We evaluated the utility of methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as a diagnostic tool and for demonstrating the relationship between molecular mechanisms and clinical presentation. Methods: We performed MS-MLPA using DNA samples from 93 subjects (45 PWS, 24 AS, and 24 non-PWS/AS controls) who had previously undergone MS-PCR for the diagnosis of PWS/AS. We compared the results of both assays, and patients’ clinical phenotypes were reviewed retrospectively. Results: MS-MLPA showed a 100% concordance rate with MS-PCR. Among the 45 PWS patients, 26 (57.8%) had a deletion of 15q11-q13, and the others (42.2%) had uniparental disomy 15 or an imprinting defect. Among the 24 AS patients, 16 (66.7%) had a deletion of 15q11-q13, 7 AS patients (29.2%) had uniparental disomy 15 or an imprinting defect, and one AS patient (4.2%) showed an imprinting center deletion. Conclusions: MS-MLPA has clinical utility for the diagnosis of PWS/AS, and it is superior to MS-PCR in that it can identify the molecular mechanism underlying the disease.

  • Letter to the Editor2022-03-01
    Diagnostic Immunology

    Clinical Significance of Elevated Serum Caspase-1 Levels in Patients With Ankylosing Spondylitis

    Sang-Hyon Kim , M.D., Ph.D., Ji-Hyun Lee , M.S., Hye-Jin Jeong , M.D., Ji-Min Kim , M.D., Ph.D., Won-Ki Baek , M.D., Ph.D., Tae-Hwan Kim , M.D., Ph.D., Jae-Bum Jun , M.D., Ph.D., and Chang-Nam Son , M.D., Ph.D.

    Ann Lab Med 2022; 42(2): 293-295
  • Original Article2021-01-01
    Diagnostic Genetics

    Detection of Spinal Muscular Atrophy Using a Duplexed Real-Time PCR Approach With Locked Nucleic Acid-Modified Primers

    Jianyan Pan , Ph.D., Chunhua Zhang , Ph.D., Yanling Teng , M.S., Sijing Zeng , M.S., Siyi Chen , Ph.D., Desheng Liang , M.D., Ph.D., Zhuo Li , Ph.D., and Lingqian Wu , M.D., Ph.D.

    Ann Lab Med 2021; 41(1): 101-107

    Abstract : Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder mainly caused by homozygous deletions that include exon 7 of the survival motor neuron 1 (SMN1) gene. A nearby paralog gene, SMN2, obstructs the specific detection of SMN1. We optimized a duplexed real-time PCR approach using locked nucleic acid (LNA)-modified primers to specifically detect SMN1. Methods: An LNA-modified primer pair with 3´ ends targeting SMN1 specific sites c.835-44g and c.840C was designed, and its specificity was examined by real-time PCR and Sanger Sequencing. A duplexed real-time PCR approach for amplifying SMN1 and control gene albumin (ALB) was developed. A randomized double-blind trial with 97 fresh peripheral blood samples and 25 dried blood spots (DBS) was conducted to evaluate the clinical efficacy of the duplexed approach. This new approach was then used to screen 753 newborn DBS. Results: The LNA-modified primers exhibited enhanced specificity and 6.8% increased efficiency for SMN1 amplification, compared with conventional primers. After stabilizing the SMN1 test by optimizing the duplexed real-time PCR approach, a clinical trial validated that the sensitivity and specificity of our new approach for detecting SMA patients and carriers was 100%. Using this new approach, 15 of the screened 753 newborns were identified as carriers via DBS, while the rest were identified as normal individuals. These data reveal a carrier rate of 1.99% in Hunan province, South Central China. Conclusions: We have developed a novel, specific SMN1 detection approach utilizing real-time PCR with LNA-modified primers, which could be applied to both prenatal carrier and newborn screening.

  • Original Article2021-07-01

    Recent Epidemiological Changes in Group B Streptococcus Among Pregnant Korean Women

    Seong Jin Choi , M.D., Jieun Kang , M.D., and Young Uh , M.D.

    Ann Lab Med 2021; 41(4): 380-385

    Abstract : Background: Although group B Streptococcus (GBS) colonization rate among pregnant Korean women is lower than that among women from many Western countries, recent data show an upward trend. We investigated recent epidemiological changes in GBS among pregnant Korean women in terms of colonization rate, antimicrobial susceptibility, serotype, and resistance genotype. Methods: Vaginal and anorectal swab specimens from 379 pregnant Korean women were cultured on Strep B Carrot Broth with GBS Detect (Hardy Diagnostics, USA), selective Todd-Hewitt broth (Becton Dickinson, USA), and Granada agar plate medium (Becton Dickinson). The antimicrobial susceptibility, serotypes, and macrolide-lincosamide-streptogramin B (MLSB) resistance genes of the GBS isolates were tested. Results: The GBS colonization rate among pregnant Korean women was 19.8% (75/379). Colonization rates using Strep B Carrot Broth with GBS Detect, selective Todd-Hewitt broth, and Granada agar plate medium cultures were 19.5%, 19.3%, and 15.0%, respectively. Six pregnant women were colonized by non-beta-hemolytic GBS and were detected only in Strep B Carrot Broth with GBS Detect. Resistance rates of GBS to clindamycin, erythromycin, and tetracycline were 16.0%, 28.0%, and 42.7%, respectively. The most common GBS serotypes were V (22.7%), VIII (20.0%), and III (20.0%). The frequency of MLSB resistance genes erm(B) and erm(TR) were 63.6% and 36.4%, respectively. Conclusions: The GBS colonization rate among pregnant Korean women has risen to levels observed in Western countries. To accurately evaluate GBS epidemiology among pregnant Korean women, periodic studies in multiple centers, including primary clinics, are necessary.

Journal Information March, 2023
Vol.43 No.2
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