In the era of precision medicine, pharmacogenetics has substantial potential for addressing inter-individual variability in drug responses. Although pharmacogenetics has been a research focus for many years, resulting in the establishment of several formal guidelines, its clinical implementation remains limited to several gene–drug combinations in most countries, including Korea. The main causes of delayed implementation are technical challenges in genotyping and knowledge gaps among healthcare providers; therefore, clinical laboratories play a critical role in the timely implementation of pharmacogenetics. This paper presents an update of the Clinical Pharmacogenetic Testing and Application guidelines issued by the Korean Society for Laboratory Medicine and aims to provide the necessary information for clinical laboratories planning to implement or expand their pharmacogenetic testing. Current knowledge regarding nomenclature, gene–drug relationships, genotyping technologies, testing strategies, methods for clinically relevant information delivery, QC, and reimbursements has been curated and described in this guideline.

Purpose: This study aimed to examine the clinical features and determinants of macrolideunresponsive Mycoplasma pneumoniae pneumonia (MUMP) and to assess the differences in the time to fever resolution between doxycycline (DXC), tosufloxacin (TFX) and corticosteroid (CST) as second-line treatment. Methods: We retrospectively analyzed the medical records of patients under the age of 18 who were admitted to Nowon Eulji University Hospital between July 2018 and February 2020, diagnosed with mycoplasma pneumonia. Macrolide resistance was confirmed by detecting point mutations in the 23S rRNA gene. MUMP was clinically defined by persistent fever (≥38.0°C) lasting for 72 hours or more after the initiation of macrolide treatment. In cases of MUMP, patients were treated with an addition of CST, or the initial macrolide was replaced either DXC or TFX. Results: Out of 157 cases of mycoplasma pneumonia, 83 cases (52.9%) did not respond to macrolides. Patients with MUMP exhibited significantly higher C-reactive protein (CRP) levels (3.2±3.0 vs. 2.4±2.2 mg/dL, P=0.047), more frequent lobar/segmental infiltrations or pleural effusions (56.6% vs. 27.0%, P<0.001; 6.0% vs. 0.0%, P=0.032), and a higher prevalence of 23S rRNA gene mutations (96.4% vs. 64.6%, P<0.001) when compared to those with macrolide-susceptible M. pneumoniae pneumonia. In terms of second-line treatment, 15 patients (18.1%) responded to CST, 30 (36.1%) to DXC, and 38 (45.8%) to TFX. The time to defervescence (TTD) after initiation second-line treatment was significantly shorter in the CST group compared to the DXC (10.3±12.7 vs. 19.4±17.2 hours, P=0.003) and TFX groups (10.3±12.7 vs. 25.0±20.1 hours, P=0.043), with no significant difference observed between the DXC and TFX groups (19.4±17.2 vs. 25.0±20.1 hours, P=0.262). Conclusions High CRP levels, the presence of positive 23S rRNA gene mutation, lobar or segmental lung infiltration, and pleural effusion observed in chest X-ray findings were significant factors associated with macrolide unresponsiveness. In this study, CST demonstrated a shorter TTD compared to DXC or TFX. Further, larger-scale prospective studies are needed to determine the optimal second-line treatment for MUMP.

Despite strict guidelines for coronavirus disease 2019 (COVID-19), South Korea is facing its fourth pandemic wave. In this study, by using an automated electrochemiluminescence immunoassay assay, we tracked anti-spike protein receptor-binding domain (anti-S-RBD) antibody titer from the second dose to 2 weeks after the booster dose vaccination. After the second dose, 234 participants had their anti-S-RBD antibody titers decrease over time. We also showed the booster dose (the third dose) increased antibody titer by average 14 (min–max, 2–255)-fold higher compared to the second dose among the 211-booster group participants, therefore, the booster dose could be recommended for low responders to the second dose. Our findings showed a distinct humoral response after booster doses of BNT162b2 mRNA vaccines and may provide further evidence of booster vaccination efficacy. These data will also be helpful in vaccination policy decisions that determine the need for the booster dose.

The antibody titer of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was observed in 289 healthy healthcare workers who had completed the second dose of the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine. Antibody tests were performed using both the automated electrochemiluminescence immunoassay (ECLIA) and the chromatographic lateral flow immunoassay (LFIA). All subjects had antibodies against the receptor binding domain of the spike protein of SARS-CoV-2 only one week after completing the vaccination, and the antibody titer became significantly higher after another week (P < 0.001). Since there was a large amount of antibody formation within two weeks after completion of vaccination, the less sensitive method, LFIA, also showed high sensitivity.There was no significant difference between whole blood and serum in detecting SARS-CoV-2 antibodies after vaccination. This is an early study of vaccinations among Koreans and is expected to contribute to the establishment of national guidelines on COVID-19 vaccination.

The antibody titer of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was observed in 289 healthy healthcare workers who had completed the second dose of the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine. Antibody tests were performed using both the automated electrochemiluminescence immunoassay (ECLIA) and the chromatographic lateral flow immunoassay (LFIA). All subjects had antibodies against the receptor binding domain of the spike protein of SARS-CoV-2 only one week after completing the vaccination, and the antibody titer became significantly higher after another week (P < 0.001). Since there was a large amount of antibody formation within two weeks after completion of vaccination, the less sensitive method, LFIA, also showed high sensitivity.There was no significant difference between whole blood and serum in detecting SARS-CoV-2 antibodies after vaccination. This is an early study of vaccinations among Koreans and is expected to contribute to the establishment of national guidelines on COVID-19 vaccination.

Background: Clinical specimens are valuable materials that require a traceable management system. Maintenance of temperature and loss prevention during transport are important for the reliability of the clinical test results. Current transportation systems can suffer from temperature changes and agitation. Quality improvement in this pre-analytic phase is required. This study acquired preliminary data from a newly developed specimen transportation system adopting a real-time temperature monitoring during transportation using temperature sensor and global positioning system to establish appropriate guidelines. Methods: Temperature preservation performance was compared between two transportation boxes (newly developed one [A] and conventional one [B]) at exterior temperatures of 35℃ and ?18℃, reflecting the extreme temperature range in Korea. Influences of the temperatures on analytical results of whole blood, serum, plasma, and urine specimens were investigated, as were the effects of vibration. Results: The interior temperature of box A measured at multiple sites was maintained within 1.0?9.0℃ at both exterior temperatures. The interior temperature of box B was outside of this range. The analyzed parameters varied comparably with the variations occurring at the recommended and published storage temperature. Vibration affected nonspecific enolase and lactate dehydrogenase. Conclusions Temperature preservation and real-time monitoring during specimen transportation are important. The present data highlight the importance of transportation conditions and indicate that laboratories should know the characteristics of temperature changes in their transportation system.

Mixed-species malaria infections are often unrecognized or underestimated. We hereby report the first described case of mixed infection with Plasmodium falciparum and Plasmodium ovale malaria in a returned traveller in Korea. In August 2016, a 25-year-old returned traveller from Cameroon and Democratic Republic of Congo presented with fever. He was diagnosed as P. falciparum malaria and successfully treated with artesunate. And 5 weeks after the completion of treatment, he presented with fever and diagnosed as P. ovale infection. P. ovale infection is a rare cause of malaria and often shows delayed presentation due to its dormant liver stage as hypnozoites. At re-presentation, the immunochromatographic test and microscopic examinations of our patient did not reveal P. ovale, which was only detected via polymerase chain reaction (PCR) assay. This case highlights the importance of considering malaria infection even in persons who have previously received malaria treatment. It also shows the usefulness of PCR testing for diagnosing P. ovale infections, which often present with a low level of parasitaemia.
Adult ; Cameroon ; Coinfection* ; Congo ; Fever ; Humans ; Korea* ; Liver ; Malaria ; Plasmodium falciparum* ; Plasmodium ovale* ; Plasmodium* ; Polymerase Chain Reaction

BACKGROUND: For correct interpretation of the high-density lipoprotein cholesterol (HDL-C) data from the Korea National Health and Nutrition Examination Survey (KNHANES), the values should be comparable to reference values. We aimed to suggest a way to calibrate KNHANES HDL-C data from 2008 to 2015 to the Centers for Disease Control and Prevention (CDC) reference method values. METHODS: We derived three calibration equations based on comparisons between the HDL-C values of the KNHANES laboratory and the CDC reference method values in 2009, 2012, and 2015 using commutable frozen serum samples. The selection of calibration equation for correcting KNHANES HDL-C in each year was determined by the accuracy-based external quality assurance results of the KNHANES laboratory. RESULTS: Significant positive biases of HDL-C values were observed in all years (2.85-9.40%). We created the following calibration equations: standard HDL-C=0.872×[original KNHANES HDL-C]+2.460 for 2008, 2009, and 2010; standard HDL-C=0.952×[original KNHANES HDL-C]+1.096 for 2012, 2013, and 2014; and standard HDL-C=1.01×[original KNHANES HDL-C]-3.172 for 2011 and 2015. We calibrated the biases of KNHANES HDL-C data using the calibration equations. CONCLUSIONS: Since the KNHANES HDL-C values (2008-2015) showed substantial positive biases compared with the CDC reference method values, we suggested using calibration equations to correct KNHANES data from these years. Since the necessity for correcting the biases depends on the characteristics of research topics, each researcher should determine whether to calibrate KNHANES HDL-C data or not for each study.
Algorithms ; Calibration ; Cholesterol, HDL/*blood/standards ; Humans ; *Nutrition Surveys ; Reference Values ; Republic of Korea

BACKGROUND: B-type natriuretic peptide (BNP) levels are elevated in various conditions unrelated to heart failure, such as acute coronary syndrome, and cardiac troponin (cTn) levels may also be elevated in several non-ischemic conditions. This study aimed to evaluate the clinical usefulness of combined cardiac marker testing (BNP and cTnI) with point-of-care devices in patients who presented to the emergency department (ED). METHODS: Two thousand six hundred and seventy-four consecutive patients who visited the ED from March to August 2013 were included in this study. Cardiac marker testing was performed using the Triage Cardio3 panel (Alere, USA). Electronic medical records were collected on August 2014. RESULTS: We found that 22.2% patients had elevated BNP and/or cTnI (12.8% with only elevated BNP, 4.4% with only elevated cTnI, and 5.0% with both elevations). Patients with elevations in both marker levels showed significantly higher admission rate (78.5% vs. 62.7%, P=0.006) and longer length of hospital stay (11 vs. 6 days, P=0.001) than those with only elevated cTnI. Patients with elevations in both marker levels also showed higher admission rate (78.5% vs. 67.3%, P=0.016) and higher BNP levels (430 vs. 194 pg/mL, P<0.001) than those with only elevated BNP. CONCLUSIONS: Concurrent elevation of BNP and cTnI may be associated with inferior clinical outcome and combined testing of cTnI and BNP levels with high sensitivity would provide important information for assisting management decisions at the ED.
Acute Coronary Syndrome ; Electronic Health Records ; Emergencies* ; Emergency Service, Hospital* ; Heart Failure ; Humans ; Length of Stay ; Natriuretic Peptide, Brain ; Point-of-Care Systems* ; Triage ; Troponin ; Troponin I

BACKGROUND: A newborn screening (NBS) program has been utilized to detect asymptomatic newborns with inherited metabolic diseases (IMDs). There have been some bottlenecks such as false-positives and imprecision in the current NBS tests. To overcome these issues, we developed a multigene panel for IMD testing and investigated the utility of our integrated screening model in a routine NBS environment. We also evaluated the genetic epidemiologic characteristics of IMDs in a Korean population. METHODS: In total, 269 dried blood spots with positive results from current NBS tests were collected from 120,700 consecutive newborns. We screened 97 genes related to NBS in Korea and detected IMDs, using an integrated screening model based on biochemical tests and next-generation sequencing (NGS) called NewbornSeq. Haplotype analysis was conducted to detect founder effects. RESULTS: The overall positive rate of IMDs was 20%. We identified 10 additional newborns with preventable IMDs that would not have been detected prior to the implementation of our NGS-based platform NewbornSeq. The incidence of IMDs was approximately 1 in 2,235 births. Haplotype analysis demonstrated founder effects in p.Y138X in DUOXA2, p.R885Q in DUOX2, p.Y439C in PCCB, p.R285Pfs*2 in SLC25A13, and p.R224Q in GALT. CONCLUSIONS: Through a population-based study in the NBS environment, we highlight the screening and epidemiological implications of NGS. The integrated screening model will effectively contribute to public health by enabling faster and more accurate IMD detection through NBS. This study suggested founder mutations as an explanation for recurrent IMD-causing mutations in the Korean population.
Computational Biology ; DNA/chemistry/isolation & purification/metabolism ; Dried Blood Spot Testing ; Galactokinase ; Genomics ; Haplotypes ; High-Throughput Nucleotide Sequencing ; Humans ; Incidence ; Infant, Newborn ; Membrane Proteins/genetics ; Metabolic Diseases/*diagnosis/epidemiology/genetics ; Metabolism, Inborn Errors/diagnosis/epidemiology/genetics ; Mitochondrial Membrane Transport Proteins/genetics ; Neonatal Screening ; Polymorphism, Genetic ; Republic of Korea/epidemiology ; Sequence Analysis, DNA