Search

We performed a comprehensive analysis on 3,594 Staphylococcus aureus isolates from routine culture during the last 4 years. The antimicrobial susceptibilities of the isolates were analyzed according to their origin and were compared based on the type of specimens. The proportion of methicillin-resistant Staphylococcus aureus (MRSA) in community-associated (CA), health care-associated, community onset (HACO), and health care-associated (HA) isolates were 33.0%, 54.3%, and 73.3%, respectively. The MRSA rate differed significantly between specimens, with the highest rate from urine in the CA and HACO isolates, whereas the highest rate from the respiratory tract was in the HA isolates. The monitoring of the MRSA rate in CA, HACO, and HA S aureus isolates would be valuable for surveillance. The elevated rates of MRSA in urinary specimens from CA and HCA isolates need to be addressed for infection control., (Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Respiratory viruses are the main causes of upper and lower respiratory tract diseases. Rapid and accurate detection of respiratory viruses is crucial for appropriate patient treatment and prevention of endemic spread., Objectives: We compared two multiplex polymerase chain reaction (PCR) assays for the detection of respiratory viral pathogens., Methods: A total of 245 respiratory specimens (229 sputum samples, 14 bronchoalveolar lavage samples, 6 nasal swabs, 3 throat swabs, 7 unknown) were analyzed using two multiplex assays: One-step RV real-time PCR (BioSewoom, Seoul, Korea) and Seeplex RV 12 Detection kit (Seegene, Seoul, Korea). The results were further confirmed using sequencing as a reference., Results: Among 245 samples (265 identifications including co-infections), the identification of respiratory viruses was 44.9% (119/265), 44.2% (117/265) and 45.3% (120/265) by One-step RV assay, Seeplex RV assay and sequencing, respectively. The concordance rate between One-step RV assay and sequencing was 95.5% (253/265), and that between Seeplex RV assay and sequencing was 89.8% (238/265) (P = 0.0189). The sensitivities of One-step RV and Seeplex RV assays were 94.1% [95% confidential interval (CI), 88.3%-97.6%] and 83.3% (95% CI, 75.4%-89.5%), respectively (P = 0.0002). The specificities of One-step RV and Seeplex RV assays were 96.6% (95% CI, 92.2%-98.9%) and 95.2% (95% CI, 90.3%-98.0%), respectively., Conclusion: Although the performances of One-step RV and Seeplex RV assays were overall comparable, One-step RV assay showed better sensitivity and concordance with sequencing. One-step RV assay can be a useful option for respiratory virus testing in clinical laboratories., (© 2013 John Wiley & Sons Ltd.)

There are sparse data concerning sex- and age-specific characteristics of community-acquired bacteraemia (CAB) and hospital-acquired bacteraemia (HAB). Between January 2008 and December 2012, we identified 2956 bacteraemia cases, which we classified as CAB, HAB or healthcare-associated bacteraemia (HCAB). Almost half of the pathogens were Escherichia coli in CAB patients. By contrast, Staphylococcus aureus was most frequent (16.2%) in HAB patients. HCAB showed mixed features of CAB and HAB. In CAB, E. coli was significantly more abundant in females than in males (56.9 vs 24.3%, respectively). This trend was most striking in young adults (20-39 years) (77.2% in females vs 11.4% in males). HAB cases showed greater heterogeneity in their associated pathogens. The extended-spectrum β-lactamase-positive rates of E. coli and Klebsiella pneumoniae, respectively, were 31.3 and 33.8% in HAB and 8.8 and 8.4% in CAB. The non-susceptibility rates of S. aureus to oxacillin were 37.4% in CAB and 73.0% in HAB. In conclusion, CAB and HAB showed different distributions of micro-organisms, and these distributions also differed with patient age and sex. In addition, antimicrobial susceptibility needs to be monitored separately.

Background: Colonization of multidrug-resistant microorganisms is a potential source of cross transmission and subsequent infection. Screening of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) is not yet a routine practice in most hospitals., Methods: The purpose of this study was to investigate the risk factors of fecal carriage of ESBL-E in hospitalized patients. A total of 174 samples (from 97 patients) was collected. Screening test was accomplished using commercial chromogenic medium (ChromID ESBL agar; bioMérieux, Marcy l'Etoile, France). The presence of ESBLs of grown isolates was confirmed by Clinical and Laboratory Standards Institute guidelines. Analysis of the risk factors of ESBL-E carriage was performed by multivariate logistic regression., Results: Among the risk factors, multivariate analysis demonstrated that prolonged hospitalization (≥90 days) (odds ratio [OR], 6.76; 95% confidence interval [CI]: 1.17-39.23; P = .033), prolonged intensive care unit stay (≥14 days) (OR, 4.78; 95% CI: 1.70-13.42; P = .003), and methicillin-resistant Staphylococcus aureus carriage (OR, 3.29; 95% CI: 1.20-9.01; P = .020) were found to be significantly associated with fecal carriers., Conclusion: This study clarified the characteristics and the risk factors of hospitalized patients carrying ESBL-E. In addition, the cost-benefit of routine screening in addition to methicillin-resistant Staphylococcus aureus and vancomycin-resitant Enterococci needs to be assessed., (Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Objectives: The aim of this study was to investigate the diagnostic utility of plasma neutrophil gelatinase-associated lipocalin (NGAL) as an early objective biomarker to predict acute kidney injury (AKI) in critically ill patients with suspected sepsis, for whom procalcitonin (PCT) was used for the diagnosis and staging of sepsis., Design and Methods: Plasma NGAL was measured using the Triage NGAL Test (Alere, Inc., San Diego, CA, USA) in 231 samples obtained from patients with suspected sepsis. The results of NGAL were compared with those of Elecsys BRAHMS PCT (Roche Diagnostics, Basel, Switzerland). Renal failure was assessed using the renal subscore of Sepsis-related Organ Failure Assessment (SOFA) score. AKI was defined according to the Acute Kidney Injury Network criteria., Results: The concentrations of plasma NGAL were significantly different according to the five groups of PCT concentration (P<0.0001) and the renal subscore of SOFA score (P<0.0001). Plasma NGAL was significantly increased in the patients with AKI compared with those without AKI (416.5 ng/mL vs. 181.0 ng/mL, P=0.0223)., Conclusion: Plasma NGAL seems to be a highly sensitive and objective predictor of AKI in patients with sepsis. Plasma NGAL can be added for the diagnosis and staging of renal failure in sepsis., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

We evaluated the performance of the Vitek MS for identification of Gram-positive cocci routinely isolated in clinical microbiology laboratories. With a total of 424 well-characterized isolates, the results of the Vitek MS were compared to those of conventional methods and 16S rRNA gene sequencing. The Vitek MS correctly identified 97.9 % of the isolates tested to species level. The Vitek MS correctly identified the species of 97.2 % of the staphylococci (95.9 % of coagulase-negative staphylococci), 97.8 % of the streptococci, and 100 % of the enterococci. For the identification of Gram-positive cocci isolates, the overall concordance rate between conventional identification and the Vitek MS was 94.5 %. The Vitek MS matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) system can be a reliable and rapid method for the identification of most relevant Gram-positive cocci. In addition, expanding the database of the Vitek MS, especially for coagulase-negative staphylococci, is needed to enhance the performance of the Vitek MS.

Objectives: There is sparse data on apoB dyslipoproteinemia in Asian population. The purpose of this study was to assess apoB dyslipoproteinemia and to compare the LDL-C, non-HDL and apoB for risk assessment with percentile equivalent cut off in Korean population., Methods: With 1193 Korean adult subjects, the prevalence and characteristics of different types of dyslipoproteinemias were analyzed in each age and gender group. The percentile values of direct LDL-C, calculated LDL-C, non HDL-C, HDL-C, apoAI, apoB and apoB/apoAI ratio were estimated., Results: The prevalences of normoapoB-hyperTG, hyperapoB-normoTG and hyperapoB-hyperTG dyslipoproteinemia were 6.9, 8.9 and 10.9% in men and 3.7, 6.4 and 2.8% in women. The 40th percentile of direct LDL-C, calculated LDL-C, non-HDL-C and apo B were 108, 104.2, 126 and 85 mg/dl, respectively. The individual above optimal cut off was significantly underestimated with LDL-C than with non-HDL and apoB, in groups with adverse risk factors., Conclusions: This study firstly shows the prevalence of various types of dyslipoproteinemias in Asian population. The percentile values of Korean population were similar to those of NHANES. Integration of lipid markers is needed for making clinical decisions and further research involving various populations and methodologies should be performed., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Interferon-gamma (IFN-γ) release assays (IGRAs) are in vitro immune tests that have recently been introduced as an alternative to the tuberculin skin test (TST). An increasing body of evidence supports the use of IGRAs for the diagnosis of latent tuberculosis infection (LTBI) in various clinical situations. Currently, two commercial IGRAs are available: the QuantiFERON-TB Gold In-Tube test (QFT-GIT, Cellestis Ltd, Carnegie, Australia) and the T-SPOT TB assay (T-SPOT, Oxford Immunotec Ltd., Abingdon, UK). Though the clinical performances of these two IGRAs varied widely according to the characteristics of each study, they were reported to be better than those of TST in most cases. In this concise review, the performance characteristics, the use in special clinical situations, and the guidelines of IGRAs are presented.

Background: Whole blood viscosity (WBV) is the resistance of blood flow in blood vessels. Increased WBV may be a cardiovascular risk factor. The proper screening of WBV can help the early detection of cardiovascular disease. We investigated the performance of a new scanning capillary tube viscometer (SCTV) for the measurement of WBV., Methods: We evaluated the total precision of the SCTV for 20 days using three control viscosity materials, and the within-day precision with the whole blood samples of three different individuals. For the linearity evaluation, serial dilutions of a high concentration standard material were used. For the method comparison, the results of the SCTV method were compared to those of Brookfield rotating viscometer on 227 subjects., Results: The SCTV had good within-run and total-run coefficient of variant (CV)s at low-, medium-, and high-concentration samples, at shear rates of 1 and 300 s(-1). The within-day CVs with the three human blood samples were 6.3%, 3.7% and 3.8% at a shear rate of 1s(-1), and 3.2%, 3.0% and 4.1% at a shear rate of 300 s(-1). The SCTV method showed an excellent linearity in the range of 84.9 to 558.2 milliPoise (mP) and 28.8 to 71.0 mP at shear rates of 1 and 300 s(-1), respectively. For the comparison study, the SCTV and the rotating viscometer showed comparable results., Conclusions: The SCTV showed a stable analytical performance, and was comparable with the rotational viscometer. This new SCTV method can be used in the clinical laboratory for various needs., (Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Fourth-generation human immunodeficiency virus-1 (HIV-1) screening assays have improved sensitivity, but vary in performance characteristics. The purpose of this study was to evaluate four different fourth-generation HIV-1 assays. These assays included the AxSYM HIV Ag/Ab Combo (Abbott diagnostics, Delkenheim, Germany), ARCHITECT HIV Ag/Ab Combo (Abbott), Elecsys 2010 HIV Combi (Roche Diagnostics GmbH, Mannheim, Germany), and Elecsys HIV Combi PT (Roche). A total of 1,306 samples that included 1,225 clinical samples and 81 samples consisting of seroconversion panels, an HIV-1 p24 antigen sensitivity panel, and dilution series of HIV-1 lysates and HIV-1 antibodies were tested. All of the assays had sensitivities of 100% on clinical samples. The specificities of the AxSYM, ARCHITECT, Elecsys 2010 HIV Combi, and Elecsys HIV Combi PT were 99.6, 99.6, 99.0, and 99.5%, respectively. Of the 81 samples with different levels of HIV antigen or antibody and/or subtypes, Elecsys HIV Combi PT and ARCHITECT HIV Ag/Ab Combo showed better analytical sensitivities than the other two assays. In summary, the performance characteristics of AxSYM, ARCHITECT, and Elecsys HIV Combi PT were comparable and satisfactory for clinical samples. ARCHITECT HIV Ag/Ab Combo and Elecsys HIV Combi PT have the higher analytical sensitivities, and would be preferable for reducing the window period., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Leukocyte reduction filters are widely used for platelet transfusion therapy, and effective leukocyte removal is mandatory for transfusion safety. We evaluated both the performance of leukocyte reduction filters for platelets and the effect of filtration on platelet function., Methods: A total of 100 pooled products (eight platelet concentrates were randomly pooled for each product) were used in this study: 50 were filtered by BioP-plus (Fresenius Kabi AG, Homburg, Germany) and 50 by PXL-8 (Pall Corporation, East Hills, NY, USA). Leukocyte reduction, platelet recovery, and filtration time were evaluated in each leukocyte reduction filter. Platelet aggregation responses to thrombin receptor activation peptide stimulation were compared in pre- and post-filtration products using impedance aggregometry (Multiplate Analyzer, Dynabyte Medical, Munich, Germany)., Results: Leukocyte counts were uniformly less than 8.3×10(5) in all the post-filtration products, except one filtered by the PXL-8. Leukocyte reduction was 99.1% for BioP-plus and 99.7% for PXL-8, and platelet recovery was 84.2% for the BioP-plus and 86.7% for PXL-8. Filtration time of the BioP-plus was significantly shorter than that of PXL-8. Post-filtration platelet aggregation tended to decrease in both filters, showing no difference between them., Conclusions: Both BioP-plus and PXL-8 leukocyte reduction filters for platelets performed well with effective leukocyte reduction and satisfactory platelet recovery. Although platelet function was decreased after filtration procedures, its clinical relevance is uncertain., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A normal karyotype is usually present in cases of classic paroxysmal nocturnal hemoglobinuria (PNH), whereas chromosomal abnormalities involving chromosome bands 13q12 to 13q14 (13q12q14) are frequently found in various hematologic malignancies, including chronic lymphoblastic leukemia (CLL) and myelodysplastic syndrome (MDS). Here, we present a case of a 55-year-old male patient with PNH who had a deletion of chromosome 13q [del(13q)]. He presented with cough, fever, and pancytopenia. Flow cytometry of the patient's peripheral blood demonstrated that 21.7% and 21.5% of the erythrocytes were CD59 and CD55 deficient, respectively, and 63.5% of the granulocytes were FLAER and CD24 deficient. Examination of the bone marrow indicated that blasts were not increased but mild dyshematopoietic features were present. Conventional cytogenetic analysis and fluorescence in situ hybridization revealed a deletion of chromosome 13q (q12q14). The patient received an allogeneic hematopoietic stem cell transplantation. Whether this abnormality can be considered as an evidence of MDS in the setting of overt PNH requires an evaluation in the future.

Objectives: The performance of recently developed vitamin D total assays (ADVIA Centaur and Elecsys) was compared to that of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and LIASON 25-OH Vitamin D total assays., Design and Methods: A total of 157 clinical samples and standard reference material (SRM) 972 were analyzed., Results: The correlations of LC-MS/MS with the three immunoassays were acceptable. However, compared to LC-MS/MS, LIAISON and ADVIA Centaur showed negative bias, and Elecsys showed positive bias. There was a lack of agreement among the four methods with only LC-MS/MS results close to the certified values of SRM 972. The prevalence of vitamin D insufficiency (<50 nmol/L) was higher with ADVIA Centaur (51.6%) and LIAISON (52.2%) and lower with Elecsys (37.6%), compared with that of LC-MS/MS (44.6%)., Conclusion: The new, automated total vitamin D assays show acceptable correlation with LC-MS/MS, and could be used in routine laboratories. However, standardization of vitamin D assays and consideration of assay-specific decision limits should be addressed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: A higher circulating vitamin D level is inversely associated with the risk of colorectal cancer, but the association with adenoma risk is less clear., Aims: We examined the association between the circulating 25-hydroxyvitamin D(3) [25(OH)D(3)] concentration and colorectal adenoma in asymptomatic average-risk participants undergoing initial screening colonoscopy., Methods: The study subjects were comprised of 143 cases of colorectal adenomas and 143 age- and gender-matched controls with normal colonoscopy among the 586 asymptomatic average-risk subjects (median age, 58 years; range, 50-73 years) who underwent first screening colonoscopy and measurement of the serum 25(OH)D(3) between December 2009 and April 2010, consistent with winter months of the region., Results: The mean concentration of serum 25(OH)D(3) in the adenoma and control groups was 20.0 ± 11.0 ng/ml and 25.0 ± 20.0 ng/ml, respectively (P = 0.009). Using multivariate analysis, higher levels of 25(OH)D(3) were associated with a statistically significant decreased risk of colorectal adenoma after multivariable adjustment (highest vs. lowest quartile OR 0.38, 95% CI 0.18-0.80, P (trend) = 0.012). The inverse association of circulating 25(OH)D(3) with colorectal adenoma was stronger among the patients with proximal adenoma than that among the patients without proximal adenoma (highest vs. lowest quartile OR 0.29, 95% CI 0.13-0.66, P (trend) = 0.001)., Conclusions: The present study suggests that high levels of circulating vitamin D are associated with a decreased risk of colorectal adenoma, and especially adenoma located in the proximal colon.

Background: Though recent reports have indicated a higher prevalence of latent tuberculosis infection (LTBI) in laboratory personnel than in other healthcare workers, these studies included only a limited number of laboratory personnel., Methods: We have thus focused on the laboratory personnel, who had a high level of exposure to specimens from patients with TB. We recruited 173 laboratory personnel and performed QuantiFERON-TB Gold In-Tube test (QFT-G) and tuberculin skin test (TST)., Results: QFT-G was positive in 21.4% of the enrolled laboratory personnel, and TST was positive in 33.3%. The agreement between the two tests was fair (κ = 0.234). In multivariate analyses, household contactwith TBpatients (P = 0.013), the laboratory sections of microbiology (P = 0.045) and chemistry/immunology (P = 0.014) were shown to be significantly associated with positive QFT-G results., Conclusion: Our data show a high prevalence of TST and QFT-G positivity in laboratory personnel and emphasize the importance of LTBI screening for laboratory personnel. In BCG-vaccinated populations with an intermediate incidence setting, QFT-G seems to be superior to TST as a screening tool for the detection of LTBI. Further study, including results of follow-up tests will be helpful for confirmation of our findings., (© 2011 Wiley Periodicals, Inc.)

Background: CD4+CD25+ regulatory T-cells (Tregs) play a critical role in immune responses. We explored the status of Tregs in neoplastic and autoimmune hematologic diseases. We also evaluated the technical aspects of Treg measurement in terms of sample type and detection markers., Methods: A total of 68 subjects were enrolled: 11 with AML, 8 with MDS, 10 with autoimmune diseases, and 39 controls. Tregs were analyzed in peripheral blood (PB) and bone marrow (BM) samples from each subject. Flow cytometry and the Human Regulatory T cell Staining Kit (eBioscience, USA) for CD4, CD25, and FoxP3 (forkhead box P3) were used., Results: The CD4+CD25(high)/CD4 and CD4+CD25(high)FoxP3+/CD4 populations were significantly correlated (P<0.0001). The AML and high-risk MDS groups had significantly larger CD4+CD25(high)/CD4 and CD4+CD25(high)FoxP3+/CD4 populations in PB than the autoimmune (P=0.007 and 0.012, respectively) and control groups (P=0.004 and 0.006, respectively). Comparable findings were observed in BM. The CD4+CD25(high)FoxP3+/CD4 population was significantly larger in PB than in BM (P=0.0003)., Conclusions: This study provides comparison data for Tregs in AML, MDS, and autoimmune hematologic diseases, and would be helpful for understanding the different immunologic bases of various hematologic diseases. Treg measurement using CD4, CD25, and/or FoxP3 in PB rather than in BM seems to be practical for routine hematologic purposes. Large-scale analysis of the diagnostic role of Treg measurement is needed.

Background: Clostridium difficile infection (CDI) has markedly risen and is associated with hypervirulent ribotype 027 outbreaks in North America and Europe since 2003. The aims of this study were to determine the prevalence of ribotype 027 among C. difficile isolates in Korea, to characterize the ribotype 027 isolates, and to determine the clinical severity of CDI in patients infected with these isolates., Methods: A total of 1,251 isolates of C. difficile recovered from stool specimens of suspected CDI patients at two tertiary-care hospitals and one commercial laboratory between 2002 and 2009. Genes for toxin A (tcdA), toxin B (tcdB), and binary toxin (cdtA and cdtB) were detected by PCR. Mutation in the tcdC gene was detected by sequencing after PCR amplification. For molecular genotyping, we performed PCR-ribotyping, pulsed-field gel electrophoresis (PFGE), and multilocus variable-number tandem-repeat analysis (MLVA). Minimum inhibitory concentrations of moxifloxacin were determined using Etest strips (AB bioMérieux, Sweden)., Results: We identified 7 isolates as ribotype 027. These isolates had the same tcdC mutation as the epidemic strain, and 6 of them were resistant to moxifloxacin. The isolates were categorized into 3 different PFGE types and 7 different MLVA types. All the 7 cases had occurred sporadically., Conclusions: C. difficile ribotype 027 is uncommon, but it has emerged in Korea. The spread of this ribotype should be closely monitored in order to avoid an outbreak of CDI in Korea.

The therapeutic dose of warfarin is dependent upon intrinsic patient characteristics that are highly variable. We assessed the effects of CYP2C9, VKORC1 1173 C/T polymorphisms, and old age on warfarin dosing and sensitivity by measuring plasma S-/R-warfarin levels in Korean patients. INR and the plasma S-/R-warfarin concentrations were determined in 58 patients who had the VKORC1 1173C/T CYP2C9 genotypes, were on a long-term anticoagulation regimen with warfarin, and took a daily dose of warfarin. The pharmacokinetic sensitivity of warfarin was significantly higher in the CYP2C9 *1/*3 genotypes than in the CYP2C9 *1/*1 genotypes [ratio of S-warfarin concentration/dose, 0.53 vs. 0.21; p=0.01]. Pharmacodynamic sensitivity in older patients (≥ 75 years) with the CYP2C9 *1/*1 and VKORC1 1173 TT genotypes was significantly higher as compared to younger patients (<75 years) [Ratio of INR/S-warfarin concentration, 4.88 vs. 3.41; p = 0.026]. The CYP2C9*3 allele and old age (≥ 75 years) with the VKORC1 1173 T allele were also associated with increased risk of over-anticoagulation. The increase of over-anticoagulation risk and warfarin sensitivity is related to the CYP2C9*3 allele and old age with the VKORC1 1173 T allele in Korean patients with thromboembolic disease. These findings suggest that a lower initial and maintenance dose should be considered for the patients with CYP2C9 *3 allele and advanced age in this patient population. However, due to the limited number of patients in the study population, our finding needs to be confirmed by a larger, well-controlled study.

Streptococcus suis is a swine pathogen that causes meningitis, septicemia, pneumonia, and endocarditis. The first case of human S. suis infection was reported in Denmark in 1968, and since then, this infection with has been reported in many countries, especially in Southeast Asia because of the high density of pigs in this region. We report the case of a patient with septic arthritis and bacteremia caused by S. suis. Cases in which S. suis is isolated from the joint fluid are very rare, and to the best of our knowledge, this is first case report of S. suis infection in Korea. The identity of this organism was confirmed by phenotypic characterization and 16S rRNA sequence analysis. An 81-yr-old Korean woman who presented with fever, arthralgia, and headache was admitted to a secondary referral center in Korea. Culture of aspirated joint fluid and blood samples showed the growth of S. suis biotype II, which was identified by the Vitek2 GPI and API 20 Strep systems (bioMérieux, USA), and this organism was susceptible to penicillin G and vancomycin. The 16S rRNA sequences of the blood culture isolates showed 99% homology with those of S. suis subsp. suis, which are reported in GenBank. The patient's fever subsided, and blood and joint cultures were negative for bacterial growth after antibiotic therapy; however, the swelling and pain in her left knee joint persisted. She plans to undergo total knee replacement.

Variants of t(8;21)(q22;q22) account for approximately 3% of all t(8;21) in acute myeloid leukemia (AML). We report a 63-year-old female patient with AML, who showed a 3-way novel variant of t(8;21), t(1;21;8)(q21;q22;q22). She presented with gastric discomfort and splenomegaly, and her complete blood count was: white blood cell count 7.96 × 10(9)/l, with 7% blasts; hemoglobin 8.3 g/dl, and platelets 66 × 10(9)/l. Her bone marrow showed increased blasts (32.5%) with a basophilic cytoplasm, salmon-pink granules and Auer rods. Cytogenetic analysis revealed a karyotype of 46,XX,t(1;21;8)(q21;q22;q22), and fluorescence in situ hybridization confirmed a RUNX1-RUNX1T1 fusion signal on the derivative chromosome 8. After induction chemotherapy, the patient achieved complete remission and has been stable for 6 months. To the best of our knowledge, this is the first report on the novel variant of t(8;21) involving the breakpoint 1q21 and the third case with a translocation among chromosomes 1, 21 and 8. Although the clinical relevance of variant t(8;21) is still unclear, a review of 24 such cases in the literature does not imply a poorer prognosis of variant t(8;21) than of the classic t(8;21)., (Copyright © 2011 S. Karger AG, Basel.)

In this study, we estimated the reference intervals of the serum homocysteine (Hcy) level using two automated immunoassays, and we demonstrated the effects of various factors on the Hcy level in a Korean population. We calculated the gender- and assay-specific reference intervals using the data from 809 healthy Koreans, and we assessed the effects of physiologic and lifestyle factors on the Hcy level. The upper limit was higher in males (19.21 and 19.76 μmol/l) than that in females (14.99 μmol/l and 15.16 μmol/l, AxSym and ADVIA centaur, respectively); the upper limits were comparable between the two assays. Smokers, vitamin nonusers, and persons without regular exercise showed a lower folate level and a higher Hcy level. The risk of hyperhomocysteinemia was significantly associated with the male gender (adjusted OR: 5.705, P-value: 0.008) and with the low folate level group (adjusted OR: 10.412, P-value: 0.002) on the multivariate analysis. The Hcy level was significantly different according to various factors, especially in the gender and folate level. The reference interval should be determined for each ethnic population and for each assay. The appropriate cutoff for assessing the risk for cardiovascular disease or stroke should also be validated in each population., (© 2011 Wiley-Liss, Inc.)

Background: Insulin assays are affected by varying degrees of interference from anti-insulin antibodies (IAs) and by cross-reactivity with recombinant insulin analogues. We evaluated the usefulness of the E170 insulin assay by assessing IA effects and cross-reactivity with 2 analogues., Methods: Sera were obtained from 59 type 2 diabetes patients receiving continuous subcutaneous insulin infusion and 18 healthy controls. Insulin levels were determined using an E170 analyzer. To investigate the effects of IAs, we performed IA radioimmunoassays, and analyzed the differences between directly measured insulin (direct insulin) and polyethylene glycol (PEG)-treated insulins (free, IA-unbound; total, IA-bound and unbound insulin). We performed in-vitro cross-reactivity tests with insulin aspart and insulin glulisine., Results: In IA-positive patients, E170 free insulin levels measured using the E170 analyzer were significantly lower than the direct insulin levels. The mean value of the direct/free insulin ratio and IA-bound insulin, which were calculated as the difference between total and free insulin, increased significantly as endogenous IA levels increased. The E170 insulin assay showed low cross-reactivities with both analogues (< 0.7%)., Conclusions: IAs interfered with E170 insulin assay, and the extent of interference correlated with the IA levels, which may be attributable to the increase in IA-bound insulin, and not to an error in the assay. The E170 insulin assay may measure only endogenous insulin since cross-reactivity is low. Our results suggest that the measurement of free insulin after PEG pre-treatment could be useful for beta cell function assessment in diabetic patients undergoing insulin therapy.

Background: Carbohydrate-deficient transferrin (CDT) levels have rarely been determined in an Asian population. We evaluated the analytical performance of a test for measuring CDT levels by using capillary electrophoresis (EP)., Methods: We determined the precision of CDT measurement by using capillary EP and nephelometry and compared the CDT values obtained using both the methods. We included healthy control subjects, abstinent patients with liver disease, and individuals consuming varying amounts of alcohol., Results: The CDT measurement by using capillary EP were correlated well with those CDT measurement by using nephelometry, N Latex CDT assay, Y=0.5706X+1.581, R=0.930. The results obtained from both methods showed good qualitative agreement with each other (κ coefficient=0.61). Genetic variants of transferrin isoforms were detected in 4.1% of the tested population. Both the CDT and γ-glutamyl transpeptidase (GGT) levels in the abstinent patients with liver disease were significantly higher than those in healthy abstinent individuals (0.9% vs. 0.5%, 109.5 mg/dL vs. 28.5 mg/dL, respectively), but the difference in CDT values in the 2 groups was less pronounced for the CDT values. Individuals who had a mean daily alcohol intake of more than 60 g/day showed significantly higher CDT levels than those who had a mean daily alcohol intake of less than 60 g/day (1.9% vs. 0.7%, P=0.03)., Conclusions: The CDT test using capillary EP showed good performance, and this method has several advantages such as automation and detection of variant forms. Thus, CDT can be a more useful marker than GGT for monitoring alcohol abstinence, especially in patients with liver disease.

ALL with MLL gene rearrangement secondary to chemotherapy has been rarely reported. We report a case of therapy-related ALL (t-ALL) with MLL gene rearrangement in a patient who had undergone treatment for breast cancer. A 60-yr-old woman with breast cancer underwent breast-conserving surgery followed by 6 cycles of adjuvant chemotherapy (cyclophosphamide, epirubicin, and fluorouracil) and radiation therapy (dose, 5,040 cGy to the left breast and a 1,000 cGy boost to the tumor bed). A follow-up examination performed 14 months after the chemotherapy revealed no evidence of breast malignancy. However, the patient's complete blood cell count indicated acute leukemia: white blood cell count, 174.1 x 10(9)/L with 88% blasts; Hb level, 12.5 g/dL; and platelet count, 103.0 x 10(9)/L. Examination of the bone marrow aspirate smear revealed a high percentage of blasts (85.1% of all nucleated cells); the blasts showed a pro-B immunophenotype and were positive for CD19, CD79a, HLA-DR, CD34, and terminal deoxynucleotidyl transferase (TdT). Cytogenetic and FISH analyses revealed t(4;11)(q21;q23) and MLL gene rearrangement, respectively. The patient received induction chemotherapy with cyclophosphamide, vincristine, doxorubicin, and dexamethasone and achieved complete remission. Following consolidation chemotherapy, she underwent allogenic peripheral blood stem cell transplantation and has been clinically stable. To our knowledge, this is the first reported case of t-ALL with MLL gene rearrangement following treatment of breast cancer in Korea.

Background: Despite the diagnostic utility of immunophenotyping for myelodysplastic syndromes (MDS), it has not been widely performed, and reports on this are absent in Korea. We aimed to evaluate the immunophenotypic features of non-blastic granulocytes, monocytes, and blasts in patients with MDS and non-clonal disorders using routine flow cytometry (FCM). Moreover, we evaluated the phenotypic abnormalities of mature cells in leukemic patients., Methods: Marrow aspirates from 60 patients, including 18 with MDS, 18 with leukemia, and 24 with non-clonal disorders (control group), were analyzed using FCM. Blasts, non-blast myeloid cells, and monocytes were gated based on CD45 expression and side scatter (SSC). The phenotypes were then compared among the 3 groups., Results: Compared to non-clonal disorders, the granulocytic lineages of MDS showed decreased SSC (P=0.005), increased CD45 intensity (P=0.020), decreased CD10-positive granulocytes (P= 0.030), and a higher CD56-positive rate (P=0.005). It is noteworthy that similar results were obtained in the leukemia group, and these findings were not related to the phenotypes of the leukemic cells. Using blast and monocytic gating, useful parameters for generating a differential diagnosis were not found., Conclusions: Gating the granulocytic region is a relatively easy method for MDS immunophenotyping. Among the parameters studied, SSC, CD10, and CD56 were the most useful for differentiating MDS from non-clonal disorders. While immunophenotypic changes in MDS appear to be useful for differentiating MDS from non-clonal disorders, these changes were also noted in the mature cells of leukemic patients.

Background: Procalcitonin (PCT) is a relatively new marker for bacterial infections, and its diagnostic utility has been variable across the studies. We investigated the diagnostic utility of PCT for the patients with blood culture-positive sepsis, and compared it with that of C-reactive protein (CRP)., Methods: In 1,270 consecutive blood samples, PCT and CRP were simultaneously measured and results were compared according to the five categories of PCT concentrations (<0.05 ng/mL; 0.05-0.49 ng/mL; 0.5-1.99 ng/mL; 2-9.99 ng/mL; > or = 10 ng/mL). In 506 samples, they were further analyzed according to the result of blood culture. PCT and CRP were measured using enzyme-linked fluorescent assay (bioMerieux Co., France) and rate nephelometry (Beckman Coulter Co., USA), respectively. Their diagnostic utilities were compared using ROC curves., Results: The mean concentrations of CRP in five categories of PCT were 15.4 mg/L, 42.1 mg/L, 101.2 mg/L, 125.0 mg/L, 167.1 mg/L, respectively (P<0.0001). Both PCT and CRP showed significant differences between the two positive and negative groups of blood culture (PCT, 8.47 vs 2.44 ng/mL, P=0.0133; CRP, 110.48 vs 59.78 mg/L, P<0.0001). The areas under the ROC curves (95% confidence interval) for PCT and CRP were 0.720 (0.644-0.788) and 0.558 (0.478-0.636), respectively, and showed a significant difference (P=0.005)., Conclusions: The diagnostic utility of PCT is superior to that of CRP for the patients with blood culture-positive sepsis. PCT seems to be reliable for sepsis diagnosis, and may provide useful information for the critically ill patients.

Due to an extreme shortage of cadaveric kidneys, many centers in Japan successfully performed ABO-incompatible kidney transplantations using plasmapheresis, splenectomy and immunosuppression. Recently, a protocol including anti-CD20 monoclonal antibody (rituximab) and antigen-selective immunoadsorption has been used for ABO-incompatible transplantation in Europe. In Korea, ABO-incompatible kidney transplantation has been rarely performed. We report an experience of successful ABO-incompatible kidney transplantation using plasmapheresis and rituximab. The patient was a 32-yr-old female suffering from chronic renal failure, and her blood type was O, Rh+. The donor was her husband, and his blood type was B, Rh+. A combination therapy including 5 times of plasmapheresis starting from 10 days before transplantation with 2-day interval, intravenous gammaglobulin, rituximab at 2 weeks before transplantation and potent immunosuppression successfully decreased the titers of anti-A and anti-B antibodies to 1:2 and 1:1, respectively. The kidney transplantation was successful without any sign of hyperacute or acute rejection.

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism and DNA methylation. Studies on MTHFR polymorphism in leukemia have largely focused on the protective role of MTHFR polymorphism in acute lymphoblastic leukemia (ALL). We evaluated the C677T and A1298C polymorphisms using the TaqMan allelic discrimination assay in various malignancies. The study population included 115 subjects with chronic myelogenous leukemia (CML), 200 with acute myelogenous leukemia (AML), 196 with multiple myeloma (MM) and 434 healthy control subjects. The frequency of 1298CC was statistically significantly higher in subjects with CML than that of the controls (OR=5.12, 95% CI: 1.75-14.9, P-value=.003). Of note, the frequencies of 677CC/1298CC genotype were statistically significantly higher in subjects with CML, AML and MM than that of the controls (OR=8.8, 3.5, 3.83, P-value=.002, 0.036, 0.023, respectively). Our results demonstrate that the MTHFR 1298CC homozygote variant is strongly associated with an increased risk of CML, while MTHFR C677T does not significantly affect the risk of CML. Moreover, we demonstrated that MTHFR 677CC and 1298CC genotype might have combined effect on risk of CML, AML and MM and it is inferred that the A1298C may play a different role in carcinogenesis, depending on the types of organs involved, the types of disease entities and the genotype of C677T.

Background: NAD(P)H:quinone oxidoreductase 1 (NQO1) is an important enzyme in the metabolism of xenobiotics. NQO1 (609)C --> T (NQO1*2) has been reported to be associated with reduced enzyme activity, benzene-induced hematotoxicity, and acute leukemia. Incidences of multiple myeloma show interethnic variation and exposure to asbestos, petroleum products, and diesel exhaust is a risk factor for multiple myeloma. We studied the associations of NQO1 polymorphism with multiple myeloma risk, stage, and prognostic factors (hemoglobin, calcium, beta(2)-microglobulin, M-protein and creatinine)., Methods: The frequency of NQO1 polymorphism was investigated in 117 myeloma patients and 166 controls. NQO1 genetic polymorphism was determined by TaqMan allelic discrimination assay. Prognostic factors were obtained from the patients' medical records., Results: The frequencies of the NQO1*1/*1, *1/*2, and *2/*2 genotypes were 31.6%, 63.2%, and 5.1% in the patients, whereas the respective figures in the controls were 31.9%, 48.3%, and 19,9%. The frequency of NQO1*2/*2 was significantly lower in patients than in controls and the odds ratio (OR) was 0.24 (95% confidence interval: 0.01-0.68) to NQO1*1/*1 genotype, indicating a decreased risk for multiple myeloma. There were no significant differences in tumor stages and other prognostic factors among NQO1 genotypes., Conclusions: A risk for multiple myeloma decreased in NQO1*2/*2 genotype in Koreans. We report, for the first time, that NQO1 polymorphism is associated with multiple myeloma risk.