Design and Laboratory Implementation of Web Application for Collaboratively Setting Reference Intervals

BACKGROUND: Although the same equipment and reagents can be employed for inspecting identical samples, the setting and verification methods for the corresponding reference intervals differ from each other, and such methods are not well established. To address the issues associated with establishing and validating reference intervals, a Web-based application is proposed for collaboratively setting reference intervals. METHODS: A Web application was designed for automatically providing the statistical results associated with a reference interval upon receiving the corresponding test results from participating institutions and incorporating the cumulative data. RESULTS: By employing the proposed Web-based application (www.referencerange.org), reference intervals can be collaboratively set based on objective and statistical analyses incorporating clinical chemistry results obtained from Korea Healthcare Association in the years 2016 and 2017. Cumulative data obtained from the existing input peer group associated with an inspection are updated in real time, and the current set reference interval is displayed in real time. CONCLUSIONS: In this study, a Web-based application is designed for collaboratively setting reference intervals whereby all Korean laboratories can easily participate, collectively set reference intervals, and apply the set reference intervals. Hence, the proposed application can aid in providing basic data associated with health information.

Report on the External Quality Assessment Scheme for Blood Gas (Central Laboratory and Point-of-Care Testing) and Glucose (Point-of-Care Testing) Analysis in Korea (2016–2017)

In the 2016 and 2017 programs for blood gas analysis (BGA) in central laboratory and by point-of-care testing (POCT), and glucose analysis by POCT, external quality assessment of 9, 3, and 1 analytes, respectively, was performed each year. The materials used were commercially available quality control materials, and three levels were used per trial. Based on the information and results from each participating laboratory, statistical analysis was carried out. Results were provided to each laboratory through individual and comprehensive reports. The mean response rates were 96.6%, 96.5%, and 95.6% for BGA in central laboratory, BGA (POCT), and glucose (POCT), respectively. The number of participating laboratories in BGA (central laboratory and POCT) in 2017 was not significantly different from that in 2016. However, in the glucose (POCT) program, the number of registered instruments sharply increased in 2017 as the allowable number of registered instruments was increased from 5 to 30. The coefficient of variation (CV) did not show any significant differences in pH, sodium, chloride, and ionized calcium of BGA. However, the differences of CV were found to be relative large between instruments in other analytes of BGA and glucose POCT.

A Case of Chronic Myeloid Leukemia With Rare Variant ETV6/ABL1 Rearrangement

No abstract available.

Annual Report on the External Quality Assessment Scheme for Routine Clinical Chemistry in Korea (2016)

In 2016, the clinical chemistry proficiency-testing program consisted of 21 programs, including the general chemistry program of the Korean Association of External Quality Assessment Service. The general chemistry program consisted of 28 test items and was conducted using two level control materials four times per year. Based on the information and results for each test item entered by each institution, statistical analysis data according to test method, instrument, and reagent were reported. The report comprised a general statistics report showing the characteristics of all participating institutions and a separate institutional report showing the evaluation data of individual institutions. The statistics included the number of participating institutions and the mean, standard deviation, coefficient of variation, median, minimum, and maximum values for each group. Each report was composed of a table, histogram, and Levey-Jennings chart showing the statistics for each test item. The results of each institution and the statistics for each classification are presented in the table showing the statistics, and a standard deviation index is presented together with a method classification and a classification by reagent companies. A total of 14 items, including albumin, were evaluated by more than 1,000 institutions. There was no significant difference in the distribution of the measurement methods compared with those used in the previous year. The coefficient of variation showed a tendency to increase as the concentration of the level control material decreased and as the number of participating institutions decreased for each test item. Most of them showed a coefficient of variation within 10%. These statistical data will be useful when interpreting the survey results from the institutions and selecting a test method.

Clinical Usefulness of Human Epididymis Protein 4 in Lung Cancer

Human epididymis protein 4 (HE4) has been suggested as a useful new biomarker of lung cancer; however, few relevant large-scale studies have been published. In this study, we evaluated the utility of serum HE4 for lung cancer detection. HE4 levels were measured in serum samples from 100 lung cancer patients, 57 patients with benign lung diseases, and 274 healthy controls by using a chemiluminescent immunoassay, and variations in HE4 levels were analyzed by clinical status such as lung cancer, benign lung disease, and healthy condition, Tumor, Lymph Nodes, Metastasis (TNM) stage, tumor score, and histological cancer type. Lung cancer patients had significantly higher serum HE4 levels than patients with benign lung diseases and healthy controls (P<0.0001). The area under the ROC curve for HE4 was 0.84 (95% confidence interval, 0.78–0.89; P<0.0001) between lung cancer patients and healthy controls. Serum HE4 levels were significantly higher in patients with advanced disease (according to TNM stage) than in healthy controls (P<0.0001). HE4 levels were significantly elevated in patients with tumors of all types, those of different histological subgroups, and those with the smallest tumors (P=0.002). This report supports the potential of serum HE4 as an ancillary diagnostic marker for lung cancer detection.

Performance Evaluation of Automated Chemistry Analyser for Urine Chemistry Test

BACKGROUND: Prompt and accurate urine chemistry analysis is important to provide information for diagnosis and therapy. In this study, we evaluated the overall performance and utility of an automated chemistry analyser for urine chemistry testing in accordance with Clinical and Laboratory Standards Institute guidelines. METHODS: From January 2015 to March 2015, we evaluated the precision, linearity, limits of detection, carryover, and turnaround times after automation of nine items: total protein, albumin, glucose, blood urea nitrogen, total calcium, magnesium, inorganic phosphate, creatinine, and uric acid. A Hitachi 7600-110 instrument (Hitachi Ltd., Japan) and Hitachi ID Privileged Access Manager (Hitachi Ltd.) were used for automated chemistry analysis and sample preparation, respectively. RESULTS: Regarding precision, the coefficient of variation was 3.9% to 1.6% for high levels and 3.3% to 24.1% for low levels. The linearity and coefficients of determination of all the test items were acceptable. Performance comparison revealed that the two systems were comparable, as evidenced by correlation coefficients >0.975 for most items; moreover, carryover of all items was <1%. The mean turnaround time was 59 minutes. CONCLUSIONS: Urine chemistry testing can be performed with acceptable precision, linearity, and performance by using the Hitachi 7600-110 automated chemistry analyser. The sample preparation system reduces turnaround time, which enhances the clinical utility of urine chemistry testing.

Inadvertent Transmission of a Donor's Constitutional Chromosome Abnormality after Hematopoietic Stem Cell Transplantation

A pre-transplant screening work-up of donors for allogeneic hematopoietic stem cell transplantation (HSCT) is essential. Inadvertent transmission of malignancy from donors with subclinical diseases to recipients has been reported recently in several cases. A 49-year-old male was diagnosed with acute myeloid leukemia. He underwent a course of induction chemotherapy and achieved cytogenetic complete remission (CR). He was treated with an additional cycle of consolidation chemotherapy followed by full matched sibling allogeneic HSCT due to an additional deletion in 9q known as an adverse prognostic factor. Post transplantation bone marrow biopsy revealed molecular CR, but conventional cytogenetics identified the presence of 46,XY,t(1:2)(p32:q35). A cytogenetic analysis of the donor graft specimen revealed t(1:2). We confirmed the donor origin of t(1:2). We report the first case of a person with constitutional t(1;2) serving as a stem cell donor.

First Report of Neutrophil Involvement of Exflagellated Plasmodium vivax Microgametes

No abstract available.

Pulmonary Infection Caused by Mycobacterium neoaurum: The First Case in Korea

Mycobacterium neoaurum is rapidly growing mycobacteria that can cause human infections. It commonly causes bloodstream infections in immunocompromised hosts, and unlike other mycobacteria species, it rarely causes pulmonary infections. We confirmed the first pulmonary infection case in Korea caused by M. neoaurum using full-length 16S rRNA gene sequencing.

Smartphone-based Mobile Web to Provide Laboratory Test Reference Information / 임상검사와정도관리

BACKGROUND: Majority of clinical laboratories disseminate laboratory test information through guidebooks or handouts. However, these methods cannot instantly confer information, for example, when a novel laboratory test is introduced, or a change is made to a test request procedure or type of specimen involved. To overcome these limitations, we developed a mobile web application that is a laboratory test information repository, initially for use in Korea. METHODS: We established a laboratory master database of searchable laboratory test information using a web-based framework. Information pertaining to clinical test indications, interpretation of test results, and related laboratory tests was revised; test request guidelines were also updated. Information concerning tests that are occasionally subject to change and newly introduced tests was updated promptly. RESULTS: Our mobile web-based application uses the domain name www.schlab.org and can also be accessed via a desktop browser. The information for each test includes basic details such as specimen type, container, turnaround time, and so on and an introduction in addition to a more detailed explanation of associated tests and usage recommendations. The number of monthly visitors to the site was 529 (649 page views), with visitors using the mobile web for 31 seconds per visit. CONCLUSIONS: We developed a mobile web application that provides information on laboratory tests. We improved on the existing method of transmitting such information (i.e., a laboratory request guidebook) by offering a system that provides updated test information and increased accessibility. Our method is expected to reduce instances of inaccurate or unnecessary test orders, improper specimen collection, delayed specimen arrival, and inappropriate treatment.

Is Prostate-Specific Antigen Effective for Population Screening of Prostate Cancer? A Systematic Review

BACKGROUND: The effectiveness of prostate-specific antigen (PSA) for population screening has presented controversial results in large trials and prior reviews. We investigated the effectiveness of PSA population screening in a systematic review. METHODS: The study was conducted using existing systematic reviews. We searched Ovid MEDLINE, Embase, Cochrane library, and the major Korean databases. The quality of the systematic reviews was assessed by two reviewers independently using AMSTAR. Randomized controlled trials were assessed using the risk of bias tool in the Cochrane group. Meta-analyses were conducted using Review Manager. The level of evidence of each outcome was assessed using GRADE. RESULTS: Prostate-cancer-specific mortality was not reduced based on similar prior reviews (relative risk [RR] 0.93; 95% confidence interval [CI], 0.81-1.07, P=0.31). The detection rate of stage 1 prostate cancer was not greater, with a RR of 1.67 (95% CI, 0.95-2.94) and high heterogeneity. The detection rate of all cancer stages in the screening group was high, with a RR of 1.45 (95% CI, 1.13-1.85). No difference in all-cause mortality was observed between the screening and control groups (RR, 0.99; 95% CI, 0.98-1.01, P=0.50). Prostate-cancer-specific mortality, all-cause mortality, and diagnosis of prostate cancer at stages 3-4 showed moderate levels of evidence. CONCLUSIONS: Differently from prior studies, our review included updated Norrkoping data and assessed the sole effect of PSA testing for prostate cancer screening. PSA screening alone did not increase early stage prostate cancer detection and did not lower mortality.

Simultaneous Translocation of Both TCR Loci (14q11) with Rare Partner Loci (Xq22 and 12p13) in a Case of T-lymphoblastic Leukemia

The most common recurrent cytogenetic abnormalities in T-lymphoblastic leukemia (T-acute lymphoblastic leukemia [T-ALL]) involve T-cell receptor (TCR) loci and a variety of partner genes, including HOX11, HOX11L2, MYC, and TAL1. In this report, we present a rare case involving simultaneous translocation of the TCR alpha/delta loci with different partner loci (Xq22 and 12p13); this resulted in a poor prognosis. Chromosomal analysis showed 46,Y,t(X;14)(q22;q11.2),t(12;14)(p13;q11.2) and FISH analysis by using a T-cell receptor alpha delta DNA probe, Split Signal (DakoCytomation, Denmark), showed translocations at the same TCR alpha/delta locus on both chromosomes. FISH with 2 bacterial artificial chromosome clones showed break apart signal, which suggests involvement of the IRS4 gene. To our knowledge, this is the first report of T-ALL in which both TCR alpha/delta loci were translocated with different partner loci, and 1 of the partner loci, Xq22, was a rare translocation partner locus that included IRS4 gene.

Clinical Characteristics and ALB Gene Mutation Analysis of Korean Patients with Bisalbuminemia / 대한진단검사의학회지

BACKGROUND: Bisalbuminemia is a hereditary or an acquired condition characterized by the presence of 2 albumin variants with different mobilities on serum protein electrophoresis (SPE). The clinical significance of bisalbuminemia has not been clearly established. However, some regions of the albumin variant may affect the biochemical analysis of biomolecules such as steroid or thyroid hormones by altering their albumin-binding affinities. In this study, we analyzed the clinical manifestations, genetic variations, and the albumin-binding characteristics in Korean patients with bisalbuminemia. METHODS: We performed SPE for samples from 580 Korean subjects and identified bisalbuminemia on the basis of the results of SPE. The clinical and biochemical characteristics, ALB gene mutations, and the structures of the albumin variants of patients with bisalbuminemia were analyzed. RESULTS: SPE showed bisalbuminemia in 2 patients. One patient showed a genetic variation known as Nagasaki-1 (Asp293Gly) and the other showed a hitherto unreported missense mutation (c.593A>T; Lys198Ile). In both cases, the serum concentrations of the substances with binding affinity for albumin were not affected, and the mutation sites of the albumin were not located with the protein-binding loci. CONCLUSIONS: The 2 Korean patients with bisalbuminemia showed genetic variations, including a novel missense mutation. The ALB gene analysis with 3D modeling is useful for determining the nature of bisalbuminemia and for predicting the effects on the albumin-binding affinity of other biochemical compounds.

Identification of a Novel Splicing Mutation in the ARSA Gene in a Patient with Late-infantile Form of Metachromatic Leukodystrophy / 대한진단검사의학회지

Metachromatic leukodystrophy (MLD; MIM 250100), a severe neurodegenerative disorder inherited as an autosomal recessive trait, is caused by mutations in the arylsulfatase A (ARSA) gene. Although several germ line ARSA mutations have been identified in patients with MLD of various ethnic backgrounds elsewhere in the world, no genetically confirmed cases of MLD have been reported in Korea. Recently, we identified a mutation in the ARSA gene of a Korean male with MLD. A male infant with late-infantile form of MLD had been admitted to our hospital for further examination. His neuromuscular symptoms, which included inability to walk at the age of 12 months, gradually worsened, even after allograft bone marrow transplantation; he died at the age of 9 yr. His elder brother had also been diagnosed with MLD. To confirm the presence of a genetic abnormality, all the coding exons of the ARSA gene and the flanking introns were amplified by PCR. A molecular analysis of the ARSA gene revealed both a novel heterozygous splicing mutation (c.1101+1G>T) in intron 6 and a heterozygous missense mutation in exon 2 (c.296G>A; Gly99Asp). The patient's elder brother who had MLD is believed to have had the same mutation, which may be correlated with a rapidly deteriorating clinical course. This study identified a novel mutation in the ARSA gene, related to a late-infantile form of MLD with a lethal clinical course and suggested that molecular diagnosis of patients may be useful in early diagnosis and for deciding intervention measures for their family members.

Annual Report on External Quality Assessment in Diagnostic Genetics in Korea (2008) / 임상검사와정도관리

The quality control for genetic tests would be of great importance as the test volume and clinical demands increase dramatically. Diagnostic genetics subcommitee of KSQACP performed two trials for cytogenetic study in 2008. A total of 41 laboratories participated in the cytogenetic surveys, and most of them showed acceptable results. However, some laboratories showed unacceptable results for the karyotype nomenclature and detection of complex cytogenetic abnormalities in hematologic neoplasias. The molecular genetics surveys included various tests: M. tuberculosis detection, hepatitis B (HBV) and C virus (HCV) detection and quantification, human papilloma virus (HPV) genotyping, gene rearrangement tests for leukemias and lymphomas, apolipoprotein E (APOE) genotyping, methylenetetrahydrofolate reductase (MTHFR) genotyping, hereditary breast and ovarian cancer genes (BRCA1 and BRCA2), and genetic tests for hereditary disorders such as spinal muscular atrophy (SMA), Huntington disease (HD), spinocerebellar ataxia (SCA), Prader-Willi/Angelman syndrome (PWS/AS), mitochondrial encephalopathy with lactic acidosis and strokelike episodes (MELAS), myoclonic epilepsy ragged red fiber (MERRF), wilson disease (ATP7B) and cancer-associated genes (KRAS). Molecular genetic surveys showed excellent results in most of the participants. External quality assessment program for genetic analysis in 2008 was proved to be helpful in continuous education and evaluation of quality improvement.

Diagnostic Usefulness of SD Malaria Antigen and Antibody Kits for Differential Diagnosis of vivax Malaria in Patients with Fever of Unknown Origin / 대한진단검사의학회지

BACKGROUND: Examination of peripheral blood smear (PBS) is the gold standard for the diagnosis of malaria; however, its diagnostic utility will be dependent on the examiner's microscopic experience, the quality of the smear, and the degree of parasitemia. Therefore, it is essential to have available a rapid and simple test that is as sensitive and specific as PBS, at a small-middle range medical center, a health care center, and a military hospital in a malaria endemic area. METHODS: Malaria antigen and antibody tests were performed on 120 febrile patients who were requested for complete blood count (CBC) and PBS at two military hospitals from May 2004 to August 2005. RESULTS: Of the 45 patients who were diagnosed with malaria by examination of peripheral blood smears, 42 were positive on both malaria antigen and antibody tests, and 2 were positive on either antigen or antibody test. Only 1 patient was negative on the both test. Furthermore, all 75 patients with negative microscopic examinations also had negative malaria antigen and antibody tests. CONCLUSIONS: The results of this study show that a rapid differential diagnosis of malaria can be made by performing malaria antigen and antibody tests on febrile patients at hospitals in malaria endemic areas. Moreover, the test is simple and convenient enough to be performed without any special equipment or experience.

Analysis of Clinical Features and Hepatitis B Virus DNA Level in the Concomitant Cases of Hepatitis B Surface Antigen and Antibody / 대한임상미생물학회지

BACKGROUND: After an infection with HBV, HBsAg is the first virologic marker detectable in the serum. If anti-HBs against 'a'determinant of HBsAg appears, HBsAg will disappear and the patients will recover from the HBV infection in most cases. However, we encounter not infrequently concomitant cases of HBsAg and anti-HBs. In this study we evaluated HBV DNA levels in concomitant cases to aid in the interpretation of these serologic results. METHODS: This study included 36 cases with positivity for both HBsAg and anti-HBs in an electrochemiluminescent immunoassay as well as a radioimmunoassay. They were tested for HBeAg, anti-HBe, and HBV DNA levels. RESULTS: Chronic viral hepatitis was the most frequent diagnosis (15/36 : 41.7%) and AST and ALT levels were normal in 17 (47.2%) and 20 (55.6%) cases, respectively, among total 36 concomitant cases. HBeAg was positive in 24 and anti-HBe in 17 cases. HBV DNA was positive in 33 cases (91.7%). including all 24 HBeAg positive cases and 9 (75%) of 12 HBeAg negative cases; 6 (50%) of 12 HBeAg negative cases had HBV DNA levels higher than 105 copy/mL. CONCLUSIONS: This study showed that viral replication still exists in most cases of concomitant HBsAg and anti-HBs, and even in some HBeAg negative cases. So in the concomitant cases, HBV DNA quantitation may aid in the interpretation of clinical significance of these cases.

Experience of Bloodless Medicine and Surgery in Soonchunhyang University / 대한진단검사의학회지

BACKGROUND: We established a bloodless center at Soonchunhyang University Hospital (SCH) in 1996 and have provided medical and surgical care for Jehovah's Witness patients. In this study, we evaluated their outcomes to provide the basis of bloodless medicine and surgery in Korea. METHODS: A retropective review of the medical records of 757 Jehovah's Witness patients admitted in the SCH Bloodless Center from December 1996 to July 2003 was performed. RESULTS: Among 757 patients, 19 (2.5%) expired during treatment and 4 of them died of cardiopul-monary dysfunction secondary to anemia. As alternatives to blood transfusion, 85 (11.2%) patients were treated with iron, 81 (10.7%) with erythropoietin, 49 (6.5%) with aprotinin, 31 (4.1%) with hemodilution and 28 (3.7%) with cell saver. Four hundreds fifteen (54.8%) of 757 patients underwent surgery. The most frequently involved cinical department was Obstetric/Gynecology (23.8%). The ratio of female and the percentage of cases treated with alternatives to blood transfusion were higher in surgery group than non-surgery group patients.(Chi-square test, P<0.01) CONCLUSIONS: Most Jehovah's Witness patients were treated successfully in our bloodless center with various alternatives to blood transfusion, such as erythropoietin, intraoperative autotransfusion, acute normovolemic hemodilution etc. Collaboration and good communication among surgeons, anesthesiologists, hematologists and blood bank physicians are very important to provide qualified medical or surgical treatment to the patients who have a religious objection to receiving blood or blood-related products.

Virus Genotype and Lamivudine Resistant Mutation in Chronic B-Viral Hepatitis and Correlation with Pathologic Findings / 대한진단검사의학회지

BACKGROUND: Despite significant progress in vaccine and therapeutic regimen, hepatitis B virus (HBV) infection remains one of the major diseases. Long-term use of lamivudine can induce the emergence of drug resistance. TRUGENE(TM) HBV Genotyping (Visible Genetics Inc., Ga, USA) is an assay that reports the viral genotype and mutations likely to confer resistance to antiviral therapy. In this study, we analyzed HBV genotype and mutations and correlated them with the histologic grade and stage of the liver disease to provide the useful information about the therapy of chronic liver disease. METHODS: HBV DNA was isolated from 86 patients with HBV-associated chronic liver diseases and analyzed by TRUGENE(TM) HBV Genotyping. Histologic grade and stage were correlated with RESULTS: HBV genotypes of 86 patients were all C (100%). Mutations associated with lamivudine resistance were detected in 10 patients (11.6%) and M204I (YIDD) mutant was the most common. Unknown mutation such as L180F was also detected. Statistical analysis showed that the number of coding changes at HBsAg region was significantly correlated with the lobular activity (P=0.01). CONCLUSIONS: All patients were genotype C and lamivudine resistant mutations were detected in 11.6%. L180F mutation, not known previously, was detected in one case. Number of coding changes at HBsAg region was significantly correlated with the lobular activity. It was considered that follow-up studies about the clinical significance of coding changes in HBsAg are needed, and that a further study such as in vitro transfection is necessary to confirm the possibility of a novel mutation of L180F.