Pharmacogenetics is a rapidly evolving field and the number of pharmacogenetic tests for clinical use is steadily increasing. However, incorrect or inadequate implementation of pharmacogenetic tests in clinical practice may result in a rise in medical costs and adverse outcomes in patients. This document suggests guidelines for the clinical application, interpretation, and reporting of pharmacogenetic test results based on a literature review and the collection of evidence-based expert opinions. The clinical laboratory practice guidelines encompass the clinical pharmacogenetic tests covered by public medical insurance in Korea. Technical, ethical, and regulatory issues related to clinical pharmacogenetic tests have also been addressed. In particular, this document comprises the following pharmacogenetic tests: CYP2C9 and VKORC1 for warfarin, CYP2C19 for clopidogrel, CYP2D6 for tricyclic antidepressants, codeine, tamoxifen, and atomoxetine, NAT2 for isoniazid, UGT1A1 for irinotecan, TPMT for thiopurines, EGFR for tyrosine kinase inhibitors, ERBB2 (HER2) for erb-b2 receptor tyrosine kinase 2-targeted therapy, and KRAS for anti-epidermal growth factor receptor drugs. These guidelines would help improve the usefulness of pharmacogenetic tests in routine clinical settings.
Antidepressive Agents, Tricyclic ; Atomoxetine Hydrochloride ; Clinical Laboratory Services ; Codeine ; Cytochrome P-450 CYP2C19 ; Cytochrome P-450 CYP2C9 ; Cytochrome P-450 CYP2D6 ; Expert Testimony ; Genetic Testing ; Humans ; Insurance ; Isoniazid ; Korea ; Pharmacogenetics ; Protein-Tyrosine Kinases ; Tamoxifen ; Warfarin

BACKGROUND: The purpose of this study is to investigate the positive rates of screening tests for inherited metabolic disorders, set cutoff values, and report the actual status of internal quality controls in LabGenomics Clinical Laboratories by using LC-MS/MS system. METHODS: We use Agilent 1260 Infinity HPLC System (Agilent Technologies, USA) for liquid chromatography, and API 2000 (AB Sciex, Canada) for MS/MS system. We set up screening tests for 55 diseases, which include metabolic disorders of 25 amino acids, 16 organic acids, and 14 fatty acids. RESULTS: We determined the analyte cutoff values as 99.9 or 0.1 percentiles in 15,000 newborn samples. The total number of samples tested from January 2012 to September 2014 was 119,948; of these, 6,681 were repeated. Of the repeated samples, 713 were presumed to be positive in the screening tests. Repeat screening with newly obtained dried blood spot specimens was recommended for these 713 samples and 600 specimens were obtained. Thus, the recall rate was 0.5% (600/119,948) for all samples and 84.2% (600/713) for the samples presumed to be positive in the screening tests. About 70 samples, that is, 0.06% of the total samples and 11.7% of the "reobtained" samples, again tested positive; we recommended confirmatory tests for these samples. CONCLUSIONS: We have presented data on the status of neonatal screening tests for inherited metabolic disorders using LC-MS/MS, including positive rates and recall rates of screening tests, set up cutoff values and reported the actual status of internal quality controls in a clinical laboratory in Korea.
Amino Acids ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Fatty Acids ; Humans ; Infant, Newborn ; Korea* ; Mass Screening ; Neonatal Screening* ; Quality Control ; Tandem Mass Spectrometry*

BACKGROUND: The XN-series (Sysmex, Japan) is the new hematology analyzer from Sysmex, with new channels to improve the accuracy of differential leukocyte count and platelet count in the low cell count range. We evaluated the analytical performance and low white blood cell (WBC) mode of the XN-2000. METHODS: Precision, linearity, and carryover were evaluated for the analyzer. We analyzed the accordance of complete blood count (CBC), reticulocyte count, and differential leukocyte count between the XN-2000 and XE-2100 (Sysmex), using 200 samples from normal controls and patients. For 80 samples with a WBC count <1.5x10(9) cells/L, the low WBC mode was evaluated by comparing the automated count with a manual differential count as the reference. RESULTS: The coefficients of variation of precision were <5% for most CBC parameters and <10% for differential leukocyte count. All results obtained with the XN-2000 showed good correlation with those obtained with the XE-2100. The correlation coefficients (r) were >0.9800 for all CBC parameters except mean corpuscular hemoglobin concentration, mean platelet volume, and platelet distribution width, and >0.9900 for differential leukocyte count except monocytes and basophils. The low WBC mode provided accurate counts for neutrophils and lymphocytes, with r>0.9300 for samples with a WBC count of 0.1-1.5x10(9) cells/L. CONCLUSIONS: The XN-2000 showed good analytical performance and correlation with the existing model, the XE-2100. The XN-2000 provided accurate results for differential leukocyte count in samples with a WBC count of 0.1-1.5x10(9) cells/L, and reduced manual slide reviews.
Basophils ; Blood Cell Count ; Blood Platelets ; Cell Count ; Erythrocyte Indices ; Hematology* ; Humans ; Leukocyte Count* ; Leukocytes ; Lymphocytes ; Mean Platelet Volume ; Monocytes ; Neutrophils ; Platelet Count ; Reticulocyte Count

In the past decade, clinical microbiology underwent revolutionary changes in methods used to identify microorganisms, a transition from slow and traditional microbial identification algorithms to rapid molecular methods and mass spectrometry (MS). Earlier, MS was clinically used as a highly complex method that was adapted for protein-centered analysis of samples in chemistry laboratories. Recently, a paradigm-shift happened when matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) MS was implemented to be used in microbiology laboratories for rapid and robust methods for accurate microbial identification. Two instrument platforms, marketed by well-established manufacturers, are beginning to displace automated phenotypic identification instruments and in some cases even genetic sequence-based identification practices. This review summarizes the current role of MALDI-TOF MS in clinical research, in diagnostic clinical microbiology laboratories, and serves as an introduction to MALDI-TOF MS, highlighting research associated with sample preparation, algorithms, interpretations, and limitations. Currently available MALDI-TOF MS instruments as well as software platforms that support the use of MALDI-TOF with direct specimens have been discussed in this review. Finally, clinical laboratories are consistently striving to extend the potential of these new methods, often in partnership with developmental scientists, resulting in novel technologies, such as MALDI-TOF MS, which could shape and define the diagnostic landscape for years to come.
Chemistry ; Mass Spectrometry

Newborn screening (NBS) has been effective for detecting asymptomatic newborns with inherited metabolic diseases and has facilitated early clinical intervention, which has resulted in significant decreases in the rates of morbidity and mortality caused by these diseases. The outcome of the NBS program heavily depends on technological advances. Since Dr. Robert Guthrie developed a bacterial inhibition assay to screen for metabolic diseases in the early 1960s, use of the NBS program has spread to many countries. Tandem mass spectrometry (TMS) was a second major technological breakthrough that has allowed screening to be extended to disorders of fatty acid and organic acid metabolism as well as to those of amino acid metabolism, and recently screening has also been expanded to include lysosomal storage diseases. TMS can detect multiple analytes rapidly and simultaneously and is currently applied to nearly 80% of the newborn population in Korea. Next-generation sequencing (NGS) technology could be another major breakthrough to improve the current NBS program. To integrate NGS into the NBS program, various considerations about its analytical validity, clinical validity, clinical utility, and ethical, legal, and social implications should be addressed on the basis of population screening. Here, the authors review population screening criteria, the current status of NBS, and recent advances in NGS. In addition, we discuss the practical and ethical issues, opportunities, and challenges regarding the implementation of NGS in NBS.
Ethics ; Humans ; Infant, Newborn* ; Korea ; Lysosomal Storage Diseases ; Mass Screening* ; Metabolic Diseases ; Metabolism ; Mortality ; Tandem Mass Spectrometry

No abstract available.

The aim of this study was to evaluate the performances of MicroScan (Siemens Healthcare, USA) and Phoenix (Becton Dickinson Diagnostic Systems, USA) automated systems for the detection of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae. ESBL-producers were detected from 18 E. coli strains and 26 K. pneumoniae strains using MicroScan, Phoenix, and double-disk synergy test (DDST). The ESBL types were determined by PCR direct sequencing. ESBL genes were detected in 38 (86.4%) of the 44 test strains. The sensitivities of MicroScan, Phoenix, and DDST were 94.6%, 79%, and 89.5%, respectively. Both MicroScan and Phoenix provided acceptable results for the examination of clinical isolates.
beta-Lactamases ; Delivery of Health Care ; Escherichia ; Escherichia coli ; Klebsiella ; Klebsiella pneumoniae ; Pneumonia ; Polymerase Chain Reaction

In Korea, the majority of imported malaria cases are Plasmodium vivax and P. falciparum, but Plasmodium ovale cases are rarely reported. We describe an imported case of P. ovale that was confirmed by peripheral blood smear and nested PCR targeting the small subunit ribosomal RNA (SSU rRNA) gene. A 37-yr-old male had visited the Republic of Ghana in tropical West Africa 3 months ago, and suffered from fever and headache since 2 weeks after his return to Korea. The results of rapid malaria test using SD Malaria Antigen/Antibody Kit (Standard Diagnostics, Korea) were negative, but Plasmodium species was observed in Wright-Giemsa-stained peripheral blood smear. For the evaluation of possible mixed infection and identification of species, we performed a nested PCR targeting the SSU rRNA gene. P. ovale single infection was confirmed by PCR. The sequence analysis of the P. ovale SSU rRNA gene showed that our isolate was P. ovale classic type. We should confirm P. ovale infection for an accurate diagnosis and treatment of imported malaria cases in Korea because the number of travelers to P. ovale-endemic regions has recently increased.
Africa, Western ; Coinfection ; Fever ; Genes, rRNA ; Ghana ; Headache ; Humans ; Korea ; Malaria ; Male ; Plasmodium ; Plasmodium ovale ; Plasmodium vivax ; Polymerase Chain Reaction ; RNA, Ribosomal ; Sequence Analysis

Massive hyperdiploidy and tetraploidy are rare cytogenetic abnormalities in myelocytic malignancies, especially in myelodysplastic syndrome (MDS). These abnormalities are known to be associated with leukemogenesis, leukemic transformation and poor prognosis. We report here the first case of MDS with near-tetraploid cytogenetic abnormality in Korea. A 80-yr-old male was diagnosed with refractory anemia with excess blasts-2 (RAEB-2). Bone marrow aspiration smear showed 16% of blasts, which were large sized myeloid blasts with irregular margins and cytoplasmic vacuolation. Cytogenetic analysis of bone marrow cells revealed numercal and structural cytogenetic abnormalities including near-tetraploidy in 8 of 20 metaphases: 45,XY,add(1)(p36.1),del(10)(p11.2),del(11)(q13),-12,-16,der(17)t(11;17) (q13;q21),add(20)(q13.1),+mar[8]/85~90,idemx2[cp8]/46,XY[4]. After chemotherapy with decitabine, he showed pancytopenia during follow-up period and died of sepsis 14 months after the diagnosis.
Anemia, Refractory ; Azacitidine ; Bone Marrow ; Bone Marrow Cells ; Chromosome Aberrations ; Cytogenetic Analysis ; Cytoplasm ; Follow-Up Studies ; Humans ; Korea ; Male ; Myelodysplastic Syndromes ; Pancytopenia ; Prognosis ; Sepsis ; Tetraploidy

Here, we report two cases of identified anti-Di(b) antibodies with rare Di(a+b−) blood types from two different hospitals in Korea. Di(b) mismatched transfusion could cause a hemolytic transfusion reaction. However, it is extremely difficult to find compatible blood for patients with such a rare blood type. In this regard, we concluded that national level rare donor registry program, wherein rare blood types are indexed, needs to be established. Moreover, laboratory medicine specialists at each hospital should encourage donor registration and family testing through education for helping patients with rare blood types. These efforts will help establish a system that guarantees safe blood transfusion for patients.
Antibodies ; Blood Donors* ; Blood Transfusion ; Education ; Humans ; Korea* ; Phenotype* ; Specialization ; Tissue Donors ; Transfusion Reaction