Therapeutic Plasma Exchange in Patients with Severe Fever with Thrombocytopenia Syndrome: A Single Institution Experience / 대한수혈학회지

Background@#Severe fever with thrombocytopenia syndrome (SFTS) is a novel infection caused by the tick-borne SFTS virus. More than 200 patients are reported every year in Korea, but there is no established treatment. In patients with SFTS, therapeutic plasma exchange (TPE) can be applied. @*Methods@#Clinical and laboratory characteristics of patients diagnosed with SFTS who underwent TPE were analyzed. The factors that can differentiate the prognosis between the patients who recovered after TPE and those who died were analyzed. @*Results@#Ten patients were diagnosed with SFTS and treated with TPE. The mean age was 70.8 (49–85) years, with three men and seven females. The laboratory findings showed a decrease in white blood cell (WBC) count, platelet count, and serum albumin and an increase in AST, ALT, LDH, and CK levels. Patients performed an average of three (2∼4) TPE procedures at intervals of 1∼2 days, three of whom died. Compared to the results at admission, the WBC counts increased after TPE, and the platelet counts remained unchanged. The AST, LDH, and CK levels decreased by 2∼6 fold in the recovered patients and increased in those who died. Among them, the change in LDH was statistically significant between the two groups (P=0.0227). @*Conclusion@#TPE has been used as an adjuvant treatment in SFTS patients who do not have a definitive treatment to date. Additional studies, including small-scale studies such as this study, will be needed to establish the timing, interval, and predictive factors of the effect of TPE.

Therapeutic Plasma Exchange in Patients with Severe Fever with Thrombocytopenia Syndrome: A Single Institution Experience / 대한수혈학회지

Background@#Severe fever with thrombocytopenia syndrome (SFTS) is a novel infection caused by the tick-borne SFTS virus. More than 200 patients are reported every year in Korea, but there is no established treatment. In patients with SFTS, therapeutic plasma exchange (TPE) can be applied. @*Methods@#Clinical and laboratory characteristics of patients diagnosed with SFTS who underwent TPE were analyzed. The factors that can differentiate the prognosis between the patients who recovered after TPE and those who died were analyzed. @*Results@#Ten patients were diagnosed with SFTS and treated with TPE. The mean age was 70.8 (49–85) years, with three men and seven females. The laboratory findings showed a decrease in white blood cell (WBC) count, platelet count, and serum albumin and an increase in AST, ALT, LDH, and CK levels. Patients performed an average of three (2∼4) TPE procedures at intervals of 1∼2 days, three of whom died. Compared to the results at admission, the WBC counts increased after TPE, and the platelet counts remained unchanged. The AST, LDH, and CK levels decreased by 2∼6 fold in the recovered patients and increased in those who died. Among them, the change in LDH was statistically significant between the two groups (P=0.0227). @*Conclusion@#TPE has been used as an adjuvant treatment in SFTS patients who do not have a definitive treatment to date. Additional studies, including small-scale studies such as this study, will be needed to establish the timing, interval, and predictive factors of the effect of TPE.

Association of ADRβ2 Haplotypes with Coronary Artery Disease in Korean Patients

BACKGROUND: Beta₂-adrenergic receptor (ADRβ2) gene variations seem to be correlated with disease progression, prognosis, and drug response to β-blockers in cardiovascular events. In this study, we investigated the genotypes and haplotypes of ADRβ2 in Korean patients and analysed their association with coronary artery disease (CAD). METHODS: One hundred five patients diagnosed with stable angina (SA), 109 patients with acute coronary syndrome (ACS), and 88 controls were enrolled. Five single nucleotide polymorphisms (SNPs) were determined at positions 46, 79, 252, 491, and 523 nucleotides, using the polymerase chain reaction and direct sequencing analysis. The haplotype reconstruction was carried out using genotype data, and analyses of the association between the genetic variation and CAD were performed. RESULTS: There were significant differences in the allele frequencies for the 79CG SNPs among the three groups. Relative to the control group, the distribution of 79CG genotypes was significantly different in both the SA group (P=0.0003) and the ACS group (P=0.0056). Compared with the CC genotype of 79CG, subjects with CG or GG had a higher risk of CAD (adjusted odds ratio [OR], 12.851; P=0.014). The frequencies of specific ACGCA, GCACC, and GGGCC haplotypes were 6.4% vs. 0%, 8.3% vs. 0%, and 6.9% vs. 0.6%, respectively, in the ACS group and controls. The GGGCC haplotype was significantly associated with CAD (adjusted OR, 12.266; P=0.016). CONCLUSIONS: Although there are large ethnic differences in the distribution of ADRβ2 SNPs and their association with CAD, the 79G polymorphism and GGGCC haplotype in ADRβ2 might specifically contribute to CAD pathogenesis in Korean patients.

Diagnostic Utility of Serum Cytokeratin Fragment 21-1 in Patients with Lung Cancer

BACKGROUND: Lung cancer is the most lethal malignant neoplasm in the world. Serum cytokeratin fragment 21-1 (Cyfra 21-1) is a valuable tumor marker for detection of lung cancer, and it has good sensitivity and specificity. The aim of this study was to investigate the diagnostic value of Cyfra 21-1 levels in patients with lung cancer. METHODS: We retrospectively reviewed 814 samples from 169 patients with lung cancer, 124 patients with benign pulmonary diseases, and 521 normal controls from health check-up clinic. Serum Cyfra 21-1 levels were determined with Architect CYFRA 21-1 kit (Abbott, USA) using Architect i2000 analyzer. RESULTS: Median levels and interquartile ranges for Cyfra 21-1 in patients with lung cancer (non-small cell lung cancer: 3.16 [1.98, 9.00] ng/mL, small cell lung cancer: 3.32 [2.07, 5.20] ng/mL) were higher than those in patients with benign pulmonary diseases (1.50 [1.17, 2.17] ng/mL; P<0.01) and in normal controls (1.26 [0.93, 1.75] ng/mL; P<0.01). Sensitivity, specificity, positive predictive value, and negative predictive value for Cyfra 21-1 were 70.4%, 81.2%, 49.6%, and 91.3%, respectively. The area under the curve for Cyfra 21-1 was 0.839 (95% confidence interval, 0.802-0.877). CONCLUSIONS: We concluded that Cyfra 21-1 may be useful in the diagnosis of lung cancer.

Performance Evaluation of the ARKRAY ADAMS A1c HA-8180

The hemoglobin A1c (Hb A1c) test is widely used to diagnose diabetes mellitus and monitor glycemic control in patients with diabetes. We evaluated the performance of the ARKRAY ADAMS A1c HA-8180 (ARKRAY KDK, Japan), an automated, HPLC-based Hb A1c analyzer. The ARKRAY ADAMS A1c HA-8180 was evaluated for its linearity and precision and compared to the HLC-723 G7 (Tosoh Corporation, Japan), according to the Clinical and Laboratory Standards Institute's guidelines. The coefficients of variation (CVs) for within-run precision at low and high levels were 0.6% and 0.3%, respectively, and the total CVs at low and high levels were 0.8% and 0.6%, respectively. The coefficient of determination (R2) was 0.9975, with linearity in the range of 3.0-18.5%. A comparison between the ARKRAY ADAMS A1c HA-8180 and HLC-723 G7 revealed a good correlation (r=0.9955) in the range of 4.8-14.6%. The runtime was 57 s per sample. The ARKRAY ADAMS A1c HA-8180 showed good analytical performance and high throughput. Therefore, it is suitable for routine use for clinical measurements of Hb A1c.

Quantitative PCR for Etiologic Diagnosis of Methicillin-Resistant Staphylococcus aureus Pneumonia in Intensive Care Unit / 결핵및호흡기질환

BACKGROUND: Ventilator-associated pneumonia (VAP) requires prompt and appropriate treatment. Since methicillin-resistant Staphylococcus aureus (MRSA) is a frequent pathogen in VAP, rapid identification of it, is pivotal. Our aim was to evaluate the utility of quantitative polymerase chain reaction (qPCR) as a useful method for etiologic diagnoses of MRSA pneumonia. METHODS: We performed qPCR for mecA, S. aureus-specific femA-SA, and S. epidermidis-specific femA-SE genes from bronchoalveolar lavage or bronchial washing samples obtained from clinically-suspected VAP. Molecular identification of MRSA was based on the presence of the mecA and femA-SA gene, with the absence of the femA-SE gene. To compensate for the experimental and clinical conditions, we spiked an internal control in the course of DNA extraction. We estimated number of colony-forming units per mL (CFU/mL) of MRSA samples through a standard curve of a serially-diluted reference MRSA strain. We compared the threshold cycle (Ct) value with the microbiologic results of MRSA. RESULTS: We obtained the mecA gene standard curve, which showed the detection limit of the mecA gene to be 100 fg, which corresponds to a copy number of 30. We chose cut-off Ct values of 27.94 (equivalent to 1x10(4) CFU/mL) and 21.78 (equivalent to 1x10(5) CFU/mL). The sensitivity and specificity of our assay were 88.9% and 88.9% respectively, when compared with quantitative cultures. CONCLUSION: Our results were valuable for diagnosing and identifying pathogens involved in VAP. We believe our modified qPCR is an appropriate tool for the rapid diagnosis of clinical pathogens regarding patients in the intensive care unit.

JAK2 V617F and MPL W515L/K Mutations in Korean Patients with Essential Thrombocythemia / 대한진단검사의학회지

JAK2 V617F and MPL W515L/K mutations have been reported in approximately 50% and 5% of the patients with essential thrombocythemia (ET), respectively. We investigated the frequency of MPL W515L/K mutations in a series of consecutive patients with ET and post-essential thrombocythemia myelofibrosis (post-ET MF). The study subjects were 63 patients diagnosed either with ET (N=59) or post-ET MF (N=4) at our institution between June 2006 and February 2010. Among them, 35 (55.6%) had the JAK2 V617F mutation. MPL W515L/K mutations were detected by direct sequencing analyses of exon 10, and 2 patients were found to harbor the following MPL mutations: W515L in 1 patient with ET and W515K in 1 patient with post-ET MF. Neither of the patients had the JAK2 V617F mutation. The frequencies of the MPL W515L/K and JAK2 V617F-negative mutations in our subjects with ET/post-ET MF were 3.2% (2/63) and 7.1% (2/28), respectively. This is the first study to report the frequency of JAK2 V617F and MPL W515L/K mutations in Korean patients with ET/post-ET MF.

A Case of Resistance to Thyroid Hormone with Thyroid Cancer

Resistance to thyroid hormone (RTH) is an autosomal dominant hereditary disorder that is difficult to diagnose because of its rarity and variable clinical features. The magnitude of RTH is caused by mutations in the thyroid hormone receptor beta (TRbeta) gene. We recently treated a 38-yr-old woman with RTH who had incidental papillary thyroid carcinoma. She presented with goiter and displayed elevated thyroid hormone levels with an unsuppressed TSH. She was determined to harbor a missense mutation of M310T in exon 9 of the TRbeta gene, and diagnosed with generalized RTH. This mutation has not yet been reported in Korea. RTH is very rare and easily overlooked, but should be considered in patients who present with goiter and elevated thyroid hormone levels with an unsuppressed TSH. The association between thyroid cancer and RTH needs further study.

ERRATUM / 대한진단검사의학회지

No abstract available.

Frequent CD7 Antigen Loss in Aggressive Natural Killer-Cell Leukemia: A Useful Diagnostic Marker / 대한진단검사의학회지

BACKGROUND: Aggressive natural killer-cell leukemia (ANKL) is a rare neoplasm characterized by systemic proliferation of NK cells. However, the differential diagnosis of NK lymphoproliferative disorders is difficult because of the absence of a distinct diagnostic hallmark. Therefore, to identify diagnostic markers for ANKL, we analyzed the clinical data and laboratory findings obtained for 20 patients with ANKL. METHODS: From January 2000 to July 2007, 20 patients were diagnosed with ANKL on the basis of bone marrow studies. We retrospectively analyzed the clinical features and laboratory findings, including the complete blood count, Epstein-Barr virus status, immunophenotype, and the cytogenetic results. RESULTS: The subjects included 6 women and 14 men (median age, 44 yr; range, 2-70 yr). Cytogenetic studies were performed in 18 patients, and karyotypic abnormalities were observed in 9 patients (50%). None of the cytogenetic abnormalities were constantly observed in all the patients. However, 6q abnormalities were observed in 4 patients (4/18, 22%). The immunophenotype of the leukemic NK-cells was cytoplasmic CD3+, surface CD3-, CD16/56+, CD2+, and CD5-. Notably, the CD7 antigen was absent in 10 patients (50%). When the CD7 loss was combined with cytogenetic abnormalities, clonal markers could be identified in 75% of the ANKL cases. CONCLUSIONS: The CD7 antigen loss was frequently observed in our series of ANKL patients. In conjunction with the cytogenetic findings, this characteristic immunophenotypic finding can serve as a reliable marker for the timely diagnosis of ANKL. Therefore, immunophenotypic analysis of CD7 expression should be included in the diagnosis of NK cell neoplasms.

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.

Evaluation of COSMOsensor Glucose Monitoring System / 대한진단검사의학회지

BACKGROUND: Glucometer is a most widely-used point-of-care testing (POCT) analyzer and plays an important role in diabetes management. We evaluated the performance of the recently developed glucometer, COSMOsensor (Cosmogenome Inc., Seoul, Korea), comparing it with three foreign-made glucometers. METHODS: COSMOsensor was evaluated for linearity, precision, comparison of method and analysing time as well as the effect of operator. Other glucometers, Accu-Chek inform (Roche Diagnostics LTD., Mannheim, Germany), Precision(TM)PCx (Abbott Laboratories, Bedford, MA, USA), and Sure- Step.Flexx (LifeScan Inc., Milpitas, CA, USA) were evaluated for the same categories according to NCCLS guidelines. RESULTS: All four glucometers showed a good linearity (r> or =0.9814) and the within-run and total-run coefficients of variation (CVs) were within 3.5%. A high correlation (r> or =0.9659) was also found between the glucometers and Hitachi 7600 (Hitachi Co., Tokyo, Japan) in the central laboratory. Although differences with the reference method were within an allowable range, all glucometers showed variable bias compared with the reference method. CONCLUSIONS: The COSMOsensor showed a good analytical performance in linearity, precision, and correlation with the reference method, when compared with other foreign-made glucometers. Its rapid turnaround time and easy operation are appropriate for diabetes management and a rapid POCT analyzer. All glucometers showed variable biases, which might be due to different calibration status.