Report on the Project for Establishment of the Standardized Korean Laboratory Terminology Database, 2015.

The National Health Information Standards Committee was established in 2004 in Korea. The practical subcommittee for laboratory test terminology was placed in charge of standardizing laboratory medicine terminology in Korean. We aimed to establish a standardized Korean laboratory terminology database, Korea-Logical Observation Identifier Names and Codes (K-LOINC) based on former products sponsored by this committee. The primary product was revised based on the opinions of specialists. Next, we mapped the electronic data interchange (EDI) codes that were revised in 2014, to the corresponding K-LOINC. We established a database of synonyms, including the laboratory codes of three reference laboratories and four tertiary hospitals in Korea. Furthermore, we supplemented the clinical microbiology section of K-LOINC using an alternative mapping strategy. We investigated other systems that utilize laboratory codes in order to investigate the compatibility of K-LOINC with statistical standards for a number of tests. A total of 48,990 laboratory codes were adopted (21,539 new and 16,330 revised). All of the LOINC synonyms were translated into Korean, and 39,347 Korean synonyms were added. Moreover, 21,773 synonyms were added from reference laboratories and tertiary hospitals. Alternative strategies were established for mapping within the microbiology domain. When we applied these to a smaller hospital, the mapping rate was successfully increased. Finally, we confirmed K-LOINC compatibility with other statistical standards, including a newly proposed EDI code system. This project successfully established an up-to-date standardized Korean laboratory terminology database, as well as an updated EDI mapping to facilitate the introduction of standard terminology into institutions.

Clinical Validation of Anyplex II HPV HR Detection Test for Cervical Cancer Screening in Korea.

CONTEXT: The Anyplex II HPV HR detection kit (Seegene Inc, Seoul, Korea) is a new, multiplex, real-time polymerase chain reaction assay to detect individual 14 high-risk (HR) human papillomavirus (HPV) types in a single tube. OBJECTIVE: To evaluate the clinical performance of the HPV HR kit in predicting high-grade squamous intraepithelial lesions and cervical intraepithelial lesions grade 2 or worse in cervical cancer screening. DESIGN: We analyzed 1137 cervical samples in Huro Path medium (CelltraZone, Seoul, Korea) from Korean women. The clinical performance of the HPV HR kit was compared with Hybrid Capture 2 (Qiagen, Valencia, California) using the noninferiority score test in a routine cervical cancer screening setting. The intralaboratory and interlaboratory agreements of HPV HR were also evaluated. RESULTS: Overall agreement between the 2 assays was 92.4% (1051 of 1137) with a κ value of 0.787. Clinical sensitivity of HPV HR for high-grade squamous intraepithelial lesions and cervical intraepithelial lesions grade 2 or worse was 94.4% (95% confidence interval [CI], 89.2-99.7) and 92.5% (95% CI, 84.3-100.0), respectively. The respective values for Hybrid Capture 2 were 93.1% (95% CI, 87.2-98.9) and 87.5% (95% CI, 77.3-99.7). Clinical sensitivity and specificity of HPV HR were not inferior to those of Hybrid Capture 2 (P = .005 and P = .04, respectively). The HPV HR showed good intralaboratory and interlaboratory reproducibility at 98.0% (κ = 0.953) and 97.4% (κ = 0.940), respectively. CONCLUSIONS: The HPV HR demonstrates comparable performance to the Hybrid Capture 2 test and can be useful for HPV-based cervical cancer screening testing.

Human bocavirus in patients with respiratory tract infection.

BACKGROUND: Human bocavirus (HBoV) is a newly identified viral pathogen, and its clinical epidemiology and significance in respiratory infections have not yet been completely elucidated. We investigated the prevalence of HBoV infection and the association between viral (HBoV) load and clinical features of the infection in patients of all age-groups. METHODS: Nasopharyngeal aspirates from patients with symptoms of respiratory infection were tested for presence of HBoV by using real-time polymerase chain reaction. HBoV-positive patients were categorized into low- and high-viral-load groups using 1.0×10(6) copies/mL as the threshold value of viral load. RESULTS: Detection rate of HBoV was 4.8% (N=93) in a total of 1,926 samples with peak incidence of infection being observed in patients aged 6-12 months. HBoV infection was more frequently observed in young children, especially, in children aged less than 5 yr, and the HBoV load decreased with increase in age. HBoV was codetected with other respiratory viruses in 17 (18.3%) of the 93 HBoV-positive patients and 15 patients (88.2%) belonged to the low-viral-load group. Patients infected with HBoV alone showed a higher viral load than those patients in whom HBoV was codetected with other respiratory viruses (median load, 3.78×10(5) copies/mL vs. 1.94×10(4) copies/mL, P=0.014). Higher pulse rate (P=0.007) and respiratory rate (P=0.021) were observed in patients with a high-viral-load. CONCLUSIONS: Our results suggest that HBoV may be the causative agent of respiratory infection in the high-viral-load group.

A case of therapy-related acute lymphoblastic leukemia with t(11;19)(q23;p13.3) and MLL/MLLT1 gene rearrangement.

Therapy-related ALL (t-ALL) is a rare secondary leukemia that develops after chemotherapy and/or radiotherapy for primary malignancies. Chromosomal 11q23 abnormalities are the most common karyotypic alterations in t-ALL. The t(11;19)(q23;p13) aberration is extremely rare and has not been confirmed at the molecular genetic level. Here, we report a case of t-ALL with t(11;19)(q23;p13.3) and MLL-MLLT1 (alias ENL) gene rearrangement confirmed by cytogenetic analysis, multiplex reverse transcription-PCR (multiplex RT-PCR), and DNA sequencing in a patient who had undergone treatment for breast cancer. A 40-yr-old woman developed acute leukemia 15 months after undergoing 6 cycles of adjuvant chemotherapy (doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m²), radiation therapy (dose, 5,900 cGy), and anticancer endocrine therapy with tamoxifen. The complete blood cell counts and bone marrow examination showed increased blasts and the blasts showed B lineage immunophenotype (positive for CD19, CD34, and cytoplasmic CD79a). Cytogenetic analysis revealed the karyotype 47,XX,+X,t(11;19)(q23;p13.3)[4]/46,XX[16]. FISH analyses, multiplex RT-PCR, and DNA sequencing confirmed the MLL-MLLT1 gene rearrangement. The patient underwent induction chemotherapy with fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) and achieved complete remission. Subsequently, she underwent consolidation chemotherapy, but died of brain ischemia in the pons and the region of the middle cerebral artery. To our knowledge, this is the first case report of t-ALL with t(11;19)(q23;p13.3) and the MLL-MLLT1 gene rearrangement.

[Evaluation of various formulae for glomerular filtration rate estimation and proposal of new formulae for the Korean population].

BACKGROUND: Some researchers have questioned the necessity of adjusting glomerular filtration rate (GFR) by body surface area (BSA). We compared the relationship between estimated GFR (eGFR) and radionuclide GFR (rGFR) with or without BSA adjustment by comparing the results obtained using various formulae with those obtained using 2 new proposed formulae. METHODS: A retrospective study was performed using 204 Korean individuals whose GFR had been estimated by the (99m)Tc-diethylenetriaminepentaacetic acid method between March 2004 and July 2008. We used the modification of diet in renal disease (MDRD) II formula, Mayo clinic quadratic (MCQ) formula, Cockcroft-Gault (CG) formula, and lean body mass-adjusted CG formula. Two new formulae, skeletal muscle mass index (SMI)-adjusted CG formula and SMI × 3.4/SCr, were proposed by us. We analyzed each parameter with Pearson's correlation coefficient and also obtained the bias values. RESULTS: BSA did not satisfy the fundamental prerequisites of an adjustment factor for rGFR. MDRD II and MCQ GFR estimates demonstrated higher Pearson's correlation coefficient with BSA-unadjusted rGFR than they did with BSA-adjusted rGFR. The other GFR formulae estimates showed better correlation with rGFR and more favorable bias (P<0.001) when both GFR estimates and rGFR values were BSA-unadjusted. SMI-adjusted CG and SMI × 3.4/SCr GFR estimates demonstrated correlation with rGFR and bias values similar to those of the MDRD II and CG GFR estimates. CONCLUSIONS: We suggest that absolute, non-corrected GFR and GFR estimate be preferred in daily practice. The absolute, non-corrected GFR and GFR estimate are considered helpful for patients with eGFR ≤ 60 mL/min/1.73 m(2). We also recommend the clinical use of the new formulae, SMI-adjusted CG and SMI × 3.4/SCr (BSA-unadjusted).

Evaluation of Plasmodium vivax ELISA for the blood screen.

Plasmodium vivax malaria is the indigenous strain in the Republic of Korea (ROK). Plasmodium vivax can be transmitted through the transfusions of various blood components, which became a severe problem with the safety of blood transfusions and blood-related products in ROK. We evaluated a P. vivax-specific enzyme-linked immunosorbent assay (Genedia Malaria Ab ELISA 2.0, Green Cross, ROK) with blood samples from four groups: 251 samples from P. vivax-infected patients, 39 samples from post-treatment patients upon follow-up, 200 samples from healthy volunteers and 421 samples from domestic travellers to and from high endemic areas of ROK. The positive cases from the ELISA test were confirmed by both Giemsa microscopic and polymerase chain reaction methods. The clinical sensitivity and specificity of detecting P. vivax with ELISA test were 94.4% and 99.0%, respectively. Thirteen of 421 domestic travellers (3.0%) to endemic areas tested positive. The results indicate the effectiveness of detecting antibodies against P. vivax in blood with Genedia Malaria Ab ELISA 2.0 test in a large blood screen setting.

Acute myeloid leukemia (AML-M2) associated with variant t(8;21): report of three cases.

Variants of the t(8;21)(q22;q22) involving chromosome 8, 21, and other chromosomes account for approximately 3% of all t(8;21)(q22;q22) found in patients with acute myeloid leukemia (AML). The clinicopathologic features of AML with the variant t(8;21) have not been well established. We report three cases of AML with variants of t(8;21) characterized, respectively, by derivative 8 with the interstitial inverted insertion of 21q and concurrent monosomy 21, t(8;18;21)(p22;q11.3;q22), and t(2;21;8)(q11.2;q22;q22). Fluorescence in situ hybridization or reverse transcriptase-polymerase chain reaction assay confirmed the presence of RUNX1-RUNX1T1 gene (previously AML1-ETO) rearrangements. Among these cases, three-way breakpoints 18p11.3 and 2q11.2 have not been previously reported. The present report deals with the results of hematologic, immunophenotypic, cytogenetic, fluorescence in situ hybridization, and molecular analyses of these variants. The possible role of the genes in this region in leukemogenesis, response to treatment, and clinical implications are discussed.

The implementation and effects of a clinical laboratory accreditation program in Korea from 1999 to 2006.

BACKGROUND: The Korean Laboratory Accreditation Program (KLAP) by the Korean Society of Laboratory Medicine (KSLM) was started in 1999. We summarized history and achievement of KLAP for the last 8 yr. METHODS: We analyzed 8 yr data (1999-2006) of historical events, trends of participating laboratories, and scores according to the impact of the question to the outcome of the tests. Inspection check lists are for 'laboratory management', 'clinical chemistry', 'diagnostic hematology', 'clinical microbiology', 'diagnostic immunology', 'transfusion medicine', 'cytogenetics', 'molecular genetics', 'histocompatibility', 'flow cytometry', and 'comprehensive laboratory test verification report'. The laboratories with score 90 or higher got 2-yr certificate and laboratories with score between 60 and 89 got 1-yr certificate. The laboratories with score below 60 failed accreditation. RESULTS: The number of accredited laboratories was 2.4 times higher in 2006 (n=227) than in 1999 (n=96). Inspection check lists have been revised 5 times till 2006. The average accreditation rate was 99.6% during these periods and the 2-yr accreditation rate was 32.4% in 2000, 45.6% in 2001, 53.3% in 2002, 47.3% in 2003, 68.5% in 2004, 37.7% in 2005, and 47.7% in 2006. Number of participants in inspector training workshops increased from 89 in 2000 to 766 in 2006. CONCLUSIONS: The KLAP has been in place successfully and stabilized over the past 8 yr. It seemed to enhance the laboratory quality. Efforts for improvement of quality control and inspector training workshops appeared to be in the main contributing factors.

Standardization of terminology in laboratory medicine II.

Standardization of medical terminology is essential in data transmission between health care institutes and in maximizing the benefits of information technology. The purpose of this study was to standardize medical terms for laboratory observations. During the second year of the study, a standard database of concept names for laboratory terms that covered those used in tertiary health care institutes and reference laboratories was developed. The laboratory terms in the Logical Observation Identifier Names and Codes (LOINC) database were adopted and matched with the electronic data interchange (EDI) codes in Korea. A public hearing and a workshop for clinical pathologists were held to collect the opinions of experts. The Korean standard laboratory terminology database containing six axial concept names, components, property, time aspect, system (specimen), scale type, and method type, was established for 29,340 test observations. Short names and mapping tables for EDI codes and UMLS were added. Synonym tables were prepared to help match concept names to common terms used in the fields. We herein described the Korean standard laboratory terminology database for test names, result description terms, and result units encompassing most of the laboratory tests in Korea.

Enhanced detection of respiratory viruses using cryopreserved R-Mix ReadyCells.

BACKGROUND: R-Mix, which contains a fresh mixture of two cell lines, Mv1Lu (mink lung cells) and A549 cells, has shown good sensitivity and specificity for respiratory virus culture. However, it has until recently only been available in North America, in part due to the shipping constraints associated with cell aging and the difficulty in providing these cells to hard to reach regions. Recently, cryopreserved R-Mix ReadyCells for longer storage were developed. These cells, which are shipped on dry ice and have a shelf life as long as 6 months from date of manufacture, can be thawed and used as needed with minimal addition of refeeding media. OBJECTIVE: Assess the potential for cryopreserved R-Mix ReadyCells to replace conventional culture. STUDY DESIGN: Two hundred and twenty-three nasopharyngeal aspirates confirmed as respiratory virus-positive by conventional culture were inoculated into cryopreserved R-Mix ReadyCells and re-inoculated into conventional culture cells simultaneously. After 1 and 3 days of incubation cryopreserved R-Mix ReadyCells and conventional culture cells were screened using a respiratory virus fluorescent antibody pool for the detection of seven major respiratory viruses (influenza A and B viruses, parainfluenza 1, 2 and 3 viruses, respiratory syncytial virus and adenovirus). Positive pool results were further differentiated with specific monoclonal antibodies against the individual viruses. RESULTS: After 1 day of incubation detection rates for conventional culture were 25%, 39%, 39%, 49%, and 10% for influenza A virus, influenza B virus, parainfluenza viruses, respiratory syncytial virus, and adenovirus, respectively. Corresponding detection rates for cryopreserved R-Mix ReadyCells were 78%, 91%, 72%, 81%, and 65%. Average detection rates of cryopreserved R-Mix ReadyCells for all respiratory viruses were 80% after 1 day incubation and 95% after 3 days incubation, compared to 35% and 70% by conventional culture. CONCLUSION: The cryopreserved R-Mix ReadyCells system offers a highly sensitive and rapid method for detection of respiratory viruses that may allow it to replace conventional cell culture systems.

Evaluation of the Roche CoaguChek XS handheld coagulation analyzer in a cardiac outpatient clinic.

This study evaluated the performance of a handheld coagulation analyzer for measurements of capillary blood specimens of 93 outpatient cardiology patients with atrial fibrillation who were receiving oral anti-coagulant therapy. The international normalized ratio (INR) results of the CoaguChek XS system (Roche Diagnostics) were compared with those obtained in the central laboratory with citrated venous blood specimens using the ACL9000 coagulation analyzer (Instrumentation Laboratory). The INR results for prothrombin time by the CoaguChek XS analyzer were closely correlated with the central laboratory's results in the INR range of 0.96 approximately 8.53 (r = 0.964). A statistically significant difference was noted between 2 lots of test strips, but the difference was miniscule (mean +/- 95% confidence interval: 0.04+/-0.02). The CV of 8 replicate assays with the CoaguChek XS for a blood specimen with high INR value (INR=3.9) was 1.4%; for a blood specimen with medium INR value (INR=1.3), the CV of 8 replicate assays was <0.1%. This study shows that the CoaguChek XS analyzer is precise and reliable for assessment of INR results at clinically significant ranges in cardiac outpatients.

High diagnostic accuracy of antigen microarray for sensitive detection of hepatitis C virus infection.

BACKGROUND: Hepatitis C virus (HCV) can be transmitted through blood transfusion. Screening ELISA, the most widely used method for HCV diagnosis, sometimes yields false-positive and false-negative results, so a confirmatory test is used. This secondary testing is labor-intensive and expensive, and thus is impractical for massive blood bank screening. Therefore, a new massive screening method with high accuracy is needed for sensitive and specific detection of HCV. METHODS: With sol-gel material, we designed novel antigen microarray in 96-well plates for HCV detection. Each individual well was spotted with 4 different HCV antigens. We used this new system to test 154 patient serum samples previously tested for HCV by ELISA (87 HCV positive and 67 HCV negative) (HCV EIA3.0, ABBOTT). We assessed the detection limit of our microarray system with the use of serial 10-fold dilutions of an HCV-positive sample. RESULTS: Our microarray assay was reproducible and displayed higher diagnostic accuracy (specificity) (98.78%) than did the ELISA (81.71%). Our method yielded significantly fewer false-positive results than did the ELISA. The detection limit of our assay was 1000 times more sensitive than that of the ELISA. In addition, we found this novel assay technology to be compatible with the currently employed automated methods used for ELISA. CONCLUSION: We successfully applied the sol-gel-based protein microarray technology to a screening assay for HCV diagnosis with confirmatory test-level accuracy. This new, inexpensive method will improve the specificity and sensitivity of massive sample diagnosis.

[Survey results of medical insurance reimbursement system for independent medical laboratories in Korea].

BACKGROUND: A questionnaire survey was performed to perceive the problem of the current medical insurance reimbursement system for laboratory tests referred to independent medical laboratories; then, we intended to find a way to improve the reimbursement system. METHODS: Questionnaires were distributed to 220 independent medical laboratories and 700 laboratory physicians from July through October 2005. Frequency analysis was used to analyse the replies from 109 respondents to 25 questionnaire items regarding the current medical insurance reimbursement system for referral tests, problems with the system, and suggestions for the improvement of the system. RESULTS: Among the 109 respondents to this survey, 49 (45.8%) considered the current reimbursement system to be unsatisfactory, while only 16 (15.0%) answered satisfactory. The problem was that the referral clinics-not the laboratories that performed the tests--would first receive their reimbursement for the laboratory tests from Health Insurance Review Agency (HIRA) and then give a portion of the laboratory test fees to the independent medical laboratories after the deduction of administrative fees. They (62.5% of the respondents) would prefer a separated reimbursement system by which the referral clinic-as well as the independent medical laboratory-would receive their reimbursement directly from HIRA through an Electronic Data Interchange (EDI) system. In this new system, 34% of the respondents expected the quality of the laboratory tests to be improved; however, 41.6% answered that the income of the referral clinic is expected to decrease. CONCLUSIONS: For the improvement of the medical insurance reimbursement system, the administrative fee for the referral clinic and the test fee for the independent medical laboratory should be reimbursed directly to the respective organizations. These changes could be made possible with the proper analysis of medical costs and the development of an effective EDI reimbursement system.

[Standardization of terminology in laboratory medicine I].

BACKGROUND: Standardization of medical terminology is essential for data transmission between health-care institutions or clinical laboratories and for maximizing the benefits of information technology. Purpose of our study was to standardize the medical terms used in the clinical laboratory, such as test names, units, terms used in result descriptions, etc. During the first year of the study, we developed a standard database of concept names for laboratory terms, which covered the terms used in government health care centers, their branch offices, and primary health care units. METHODS: Laboratory terms were collected from the electronic data interchange (EDI) codes from National Health Insurance Corporation (NHIC), Logical Observation Identifier Names and Codes (LOINC) database, community health centers and their branch offices, and clinical laboratories of representative university medical centers. For standard expression, we referred to the English-Korean/ Korean-English medical dictionary of Korean Medical Association and the rules for foreign language translation. Programs for mapping between LOINC DB and EDI code and for translating English to Korean were developed. RESULTS: A Korean standard laboratory terminology database containing six axial concept names such as components, property, time aspect, system (specimen), scale type, and method type was established for 7,508 test observations. Short names and a mapping table for EDI codes and Unified Medical Language System (UMLS) were added. Synonym tables for concept names, words used in the database, and six axial terms were prepared to make it easier to find the standard terminology with common terms used in the field of laboratory medicine. CONCLUSIONS: Here we report for the first time a Korean standard laboratory terminology database for test names, result description terms, result units covering most laboratory tests in primary healthcare centers.

Phenotypes and genotypes of macrolide-resistant Streptococcus pyogenes isolated in Seoul, Korea.

The mechanisms of resistance to macrolides in 51 erythromycin-resistant clinical isolates of Streptococcus pyogenes collected from 1997 through 2003 in Seoul, Korea were evaluated. They were characterized by their antimicrobial susceptibility, phenotype (using triple-disc and induction tests), resistance genotype, emm genotyping (M typing) and phylogenetic analysis. Erythromycin resistance was observed in 23% of isolates. Inducible phenotype was the most common (iMLS, 51%, 26 strains), followed by the constitutive phenotype (cMLS, 31%, 16 strains) and the M phenotype (18%, 9 strains). Eight of twenty-six iMLS isolates exhibited the iMLS-C phenotype. The remaining 18 isolates gave small inhibition zones (<12 mm) around all three discs, and mild blunting of the spiramycin and clindamycin zones of inhibition proximal to the erythromycin disc. They showed remarkable inducibility in erythromycin and clindamycin resistance. The MIC90 of erythromycin and clindamycin rose from 8 to >128 microg ml-1 and from 0.5 to >128 microg ml-1, respectively. Their resistance characteristics did not fit into any known iMLS subtype reported so far in the literature. So, it was named as an iMLS-D, new subtype. All of these iMLS-D strains harboured the erm(B) gene, demonstrated the emm12 genotype, except one, and formed a tight cluster in a phylogenetic tree, with 89.2 to 100% sequence homology, suggesting that they are closely related. Nine of sixteen cMLS strains had the emm28 genotype, which had been reported to be associated with multiple drug resistance.

Improved sensitivity and physical properties of sol-gel protein chips using large-scale material screening and selection.

Protein chips are a powerful emerging technology with extensive biomedical applications. However, the development of optimal, economical surface materials capable of maintaining the activity of embedded proteins is a challenge. Here, we introduce a new optimized, low-cost, sol-gel biomaterial for use in protein chips with femtogram-level sensitivity. A novel protein chip material with significantly improved physical properties and sensitivity was produced using unique screening and selection methods. Using this platform, the sensitive, specific detection of the interactions between an HIV antigen and its antibody and between a cyclin-kinase protein pair was observed. This study is the first to demonstrate the detection of protein-protein interactions on sol-gel microarrays and describes an important improvement in the physical properties of sol-gel-derived protein chip materials for biomedical research.

Decrease in plasma adiponectin concentrations in patients with variant angina pectoris.

BACKGROUND: Plasma adiponectin is decreased in patients with coronary artery diseases, especially in patients with acute coronary syndrome (ACS). However, the correlation between plasma adiponectin and variant angina pectoris (VAP) has not been verified. Plasma adiponectin concentrations between VAP and other coronary artery diseases was compared in the present study. The association between plasma adiponectin concentration and VAP was also investigated. METHODS AND RESULTS: Plasma adiponectin concentrations in the VAP group (n=101) were compared with those of the ACS group (n=117), the stable angina pectoris group (n=108), and the normal coronary group (n=81). Plasma adiponectin concentrations in VAP and ACS were significantly lower than that of the normal coronary group (6.6+/-5.4 vs 5.2+/-4.0 vs 9.0 +/-6.2 microg/ml, p<0.001, respectively). Multivariate analysis indicated that plasma adiponectin (odds ratio (OR) 0.735, 95% confidence interval (CI) 0.621-0.855, p=0.011), smoking (OR 2.012, 95% CI 1.210-3.880, p=0.020), and age (OR 0.976, 95% CI 0.957-0.997, p=0.022) correlated independently with the development of VAP. CONCLUSIONS: Our results suggest that a decrease in plasma adiponectin concentration might be associated with the development of VAP.