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Background Various methods are used for the diagnosis of Clostridioides difficile infection (CDI). We systematically analyzed and investigated the performance of current laboratory diagnostic methods for CDI. Methods We performed systematic review and meta-analysis of studies in PubMed, Web of Science, Cochrane Library, and KoreaMed. The following methods were evaluated: glutamate dehydrogenase (GDH) enzyme immunoassays (GDH EIAs), toxin A and B detection by enzyme immunoassays (toxin AB EIAs), and nucleic acid amplification tests (NAATs) for C. difficile toxin genes. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each method were calculated. Results Based on 39 studies, the pooled sensitivities/specificities were 92.7%/94.6%, 57.9%/97.0%, and 90.0%/95.8% for GDH EIAs, toxin AB EIAs, and NAATs, respectively, compared with those of toxigenic culture. The pooled sensitivities of automated EIAs were significantly higher than those of non-automated EIAs for both GDH and toxins A and B. The pooled sensitivity of Xpert C. difficile was significantly higher than those of other NAATs. PPVs increased as CDI prevalence increased, and NPVs were excellent when CDI prevalence was low; at CDI prevalence of 5%, PPV=37%-65% and NPV=97%-100%; at CDI prevalence of 50%, PPV=92%-97% and NPV=65%-98%. Conclusions Toxin AB EIAs still show unsatisfactory sensitivity, whereas GDH EIAs and NAATs show relatively high sensitivity. However, toxin AB EIAs are the most specific tests. This study may provide useful information for CDI diagnosis.

Objectives The BD MAX Check-Points CPO Assay (BD MAX CPO Assay; BD, The Netherlands) is a diagnostic test designed for the rapid detection and differentiation of the bla KPC, bla NDM, bla VIM/bla IMP-1, and bla OXA-48 genes. We verified the performance of the BD MAX CPO Assay to implement it in the clinical laboratory. Methods A total of 113 bacterial isolates collected from various clinical specimens harboring carbapenemase genes as confirmed by polymerase chain reaction (PCR) and sequencing were evaluated. The results of the BD MAX CPO Assay were compared to previously confirmed results. Results All results of the BD MAX CPO Assay were concordant with previous results; 61 Klebsiella pneumoniae carbapenemase (KPC), 40 New Delhi metallo-β-lactamase (NDM), three oxacillinase-48 (OXA-48)-like, two imipenem (IMP), and four multiple carbapenemase genes (one KPC/NDM, three NDM/OXA) were detected by the BD MAX CPO Assay. Three non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae isolates were negative. Conclusions The BD MAX CPO Assay can be used to identify carbapenemase gene in bacterial isolates cultured from clinical specimens in the clinical laboratory.

Background Deficiency in DNA damage response (DDR) pathway and accumulation of DNA damage increases mutation rates resulting in genomic instability and eventually increases the risk of cancer. The aim of our study was to investigate expressions of DNA repair genes as new prognostic biomarkers in acute myeloid leukemia (AML). Methods We utilized The Cancer Genome Atlas AML project (TCGA-LAML cohort, 15 acute promyelocytic leukemia (APL) and 155 non-APL AML) for the expression data of DNA repair genes. For validation, clinical samples (Ewha study group, 9 APL and 72 non-APL AML patients) were analyzed for the expression of 22 DNA repair genes using a custom RT2 Profiler PCR Array. Results APL patients presented significantly lower expression of DNA repair genes than non-APL AML patients in both study groups. Among non-APL AML patients, high expression levels of PARP1, XRCC1, and RAD51 were associated with poor overall survival (OS) probability in both study groups. Furthermore, Cox regression analysis showed that increased expression levels of PARP1, XRCC1, RAD51, BRCA1 and MRE11A could be independent risk factors for OS in the Ewha study group. Among non-APL patients of the Ewha study group, the OS probability of DDR-overexpressed group with at least one gene or more showing Z score greater than 1.5 was poorer than that of DDR non-overexpressed group. Conclusion In the current study, the DNA repair gene expression profile of APL patients was different from that of non-APL AML patients. Overexpression of DNA repair genes could be a poor prognostic biomarker in non-APL AML.

The spread of delta variants (B.1.671.2) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a severe global threat. Multiplex real-time PCR is a common method for confirming SARS-CoV-2 infection, however, additional tests, such as whole genomic sequencing, are required to reveal the presence or type of viral mutation. Moreover, applying whole genomic sequencing to all SARS-CoV-2 positive samples is challenging due to time and cost constraints. Here, we report that the double or low amplification curve observed during RNA-dependent RNA polymerase (RdRp) gene/S gene amplification in the Allplex SARS-CoV-2 Assay is related to delta/alpha variants. We analyzed the RdRp/S gene amplification curve using 94 samples confirmed as SARS-CoV-2 infection by the Allplex SARS-CoV-2 Assay from January to August, 2021. These positive samples identified variant types using the Novaplex SARS-CoV-2 Variants I and IV Assays. Overall, 17 samples showing a double curve and 11 samples showing a low amplification pattern were associated with alpha-/delta-type strains with variants in the P681 region. The double or low curve shown in the RdRp gene amplification curve had 100% sensitivity and 100% specificity for diagnosing delta/alpha variants. During the SARS-CoV-2 virus diagnostic RT-PCR test using the Allplex SARS-CoV-2 Assay, we could consider the presence of delta/alpha variants in the samples with double or low amplification curve of the RdRp/S gene channel. This PCR amplification curve abnormality enables rapid and cost-effective variant type prediction during SARS-CoV-2 diagnostic testing in clinical laboratories.

The interest inIn April 2018, about 50 questions on the current status of CDI assays and details on implementation and perceptions were written, and a survey questionnaire was administered to laboratory medicine specialists in 200 institutions.One-hundred and fifty institutions responded to the questionnaire, of which 90 (60.0%) including one commercial laboratory, performed CDI assays. The toxin AB enzyme immunoassay (toxin AB EIA), nucleic acid amplification test (NAAT), andThis study provides useful evidence on the current status of CDI laboratory diagnosis in Korea as well as on items that require improvement and is thought to aid in standardizing and improving the CDI laboratory diagnosis in Korea.

In May 2015, we conducted a voluntary online survey on laboratory diagnostic assays for Clostridium difficile infection (CDI) across clinical microbiology laboratories in Korea. Responses were obtained from 66 laboratories, including 61 hospitals and five commercial laboratories. Among them, nine laboratories reported having not conducted CDI assays. The toxin AB enzyme immunoassay (toxin AB EIA), nucleic acid amplification test (NAAT), and C. difficile culture, alone or in combination with other assays, were used in 51 (89.5%), 37 (64.9%), and 37 (64.9%) of the remaining 57 laboratories, respectively, and 23 (40.4%) of the laboratories performed all three assays. Only one laboratory used the glutamate dehydrogenase assay. Nine laboratories used the toxin AB EIA as a stand-alone assay. The median (range) of examined specimens in one month for the toxin AB EIA, NAAT, and C. difficile culture was 160 (50-2,060), 70 (7-720), and 130 (9-750), respectively. These findings serve as valuable basic data regarding the current status of laboratory diagnosis of CDI in Korea, offering guidance for improved implementation.

Performances of the colistin antimicrobial susceptibility testing (AST) systems of Acinetobacter baumannii vary depending on the manufacturer, and data on colistin-resistant A. baumannii are limited. We evaluated the VITEK2 and Sensititre systems to determine colistin resistance and minimum inhibitory concentration (MIC) for A. baumannii isolated from a clinical microbiology laboratory. A total of 213 clinical A. baumannii isolates were tested, including 81 colistin-resistant A. baumannii. ASTs were performed using the VITEK2 and Sensititre systems according to the manufacturer’s instructions. Reference MICs for colistin were determined using the manual broth microdilution method (BMD). The results of the two AST methods were compared with the BMD results. VITEK2 and Sensititre systems showed category agreements of 95.3% and 99.1%, respectively. VITEK2 had a relatively high very major error (VME) rate (9.9%). Sensititre reported higher MICs than the reference method for the susceptible isolates and showed low essential agreement. In conclusion, the automated systems investigated in this study showed good category agreements for colistin AST of A. baumannii. However, VITEK2 had a high VME rate, and Sensititre had differences in MIC results. Colistin AST remains a challenging task in the clinical laboratory.

We aimed to identify the presence of the measles IgG antibody (mIgG-Ab) in healthcare personnel and finding out who needs the measles vaccination. The history of measles vaccination was obtained from the national vaccine registry. A baseline mIgG-Ab test was performed, and the measles vaccine was administered to participants who tested negative or equivocal for mIgG-Abs. During the study, 2885 (87.3%) of the 3303 employees were tested for measles serostatus. The baseline seropositivity rate for mIgG-Abs was 91.9%. Among the 234 seronegative cases, 82.9% were born after 1985. The seroprevalence rate was lower in those who received the measles–mumps–rubella (MMR) vaccine &gt, 10 years before the testing time, especially if they were born after 1985 and if there was only one previous record of vaccination. Among the 234 seronegative cases, MMR vaccination was administered in 174 cases, of which serostatus was evaluated in 146 cases. After the first dose, positive seroconversion was achieved in 126 participants (86.3%). After a second dose, 15 achieved (75.0%) positive seroconversion. In healthcare personnel born after the period when measles incidence significantly decreased, it may be necessary to reassess their immune status for measles if more than 10 years have elapsed since the last vaccination.

The methods and results obtained using commercialized automation systems used for antimicrobial susceptibility testing are not entirely consistent. Therefore, we evaluated different antimicrobial susceptibility testing methods to determine vancomycin susceptibility and minimum inhibitory concentration (MIC) for Staphylococcus aureus with reduced vancomycin susceptibility (SA-RVS). A total of 128 clinical isolates of S. aureus were tested, including 99 isolates showing an MIC of ≥2 µg/mL using the VITEK2 system (VITEK2). Antimicrobial susceptibility tests were performed using the Sensititre system (Sensititre), Phoenix M50 system (Phoenix), and MicroScan WalkAway 96 Plus system (MicroScan). Vancomycin MICs were determined using the broth microdilution method (BMD) and Etest. Essential agreement and category agreement for each method were compared with BMD results as the reference method. The BMD and Etest showed complete essential agreement (100%). VITEK2, Sensititre, and Phoenix showed high essential agreement (>99%), while MicroScan showed the lowest essential agreement (92.2%). The MIC MICs determined via Etest, VITEK2, and MicroScan tended to be higher than that determined via BMD. When comparing BMD with Etest, the category agreement was 93.8% and minor errors were observed for eight isolates. VITEK2, Sensititre, and Phoenix showed category agreements of 96.1%, 96.1%, and 99.2%, respectively, while MicroScan showed the lowest category agreement of 85.2%. The determination of vancomycin susceptibility and MIC for S. aureus varied among the methods. Caution should be taken when interpreting RVS and intermediate results for S. aureus. For confirmation of SA-RVS results, it would be appropriate to test with BMD or a more reliable testing method.

Background Various methods are used for the diagnosis of Clostridioides difficile infection (CDI). We systematically analyzed and investigated the performance of current laboratory diagnostic methods for CDI. Methods We performed systematic review and meta-analysis of studies in PubMed, Web of Science, Cochrane Library, and KoreaMed. The following methods were evaluated glutamate dehydrogenase (GDH) enzyme immunoassays (GDH EIAs), toxin A and B detection by enzyme immunoassays (toxin AB EIAs), and nucleic acid amplification tests (NAATs) for C. difficile toxin genes. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each method were calculated. Results Based on 39 studies, the pooled sensitivities/specificities were 92.7%/94.6%, 57.9%/97.0%, and 90.0%/95.8% for GDH EIAs, toxin AB EIAs, and NAATs, respectively, compared with those of toxigenic culture. The pooled sensitivities of automated EIAs were significantly higher than those of non-automated EIAs for both GDH and toxins A and B. The pooled sensitivity of Xpert C. difficile was significantly higher than those of other NAATs. PPVs increased as CDI prevalence increased, and NPVs were excellent when CDI prevalence was low; at CDI prevalence of 5%, PPV = 37%-65% and NPV = 97%-100%; at CDI prevalence of 50%, PPV = 92%-97% and NPV = 65%-98%. Conclusions Toxin AB EIAs still show unsatisfactory sensitivity, whereas GDH EIAs and NAATs show relatively high sensitivity. However, toxin AB EIAs are the most specific tests. This study may provide useful information for CDI diagnosis.

Inhibitor development is the most serious complication in patients with hemophilia. We investigated association of HLA genotypes with inhibitor development in Korean patients with severe hemophilia A (HA). HLA genotyping was done in 100 patients with severe HA including 27 patients with inhibitors. The allele frequencies between inhibitor-positive and inhibitor-negative patients were compared. HLA class I alleles were not associated with the inhibitor status. In HLA class II, DRB1*15 [n = 100, odds ratio (OR) 0.217, P = 0.028] and DPB1*05:01 [OR 0.461, P = 0.026] were negatively associated with inhibitor development. In a subgroup of patients with intron 22 inversion, C*07:02 was positively associated with inhibitor development [n = 30, OR 5.500, P = 0.043]. In the subgroup of patients without intron 22 inversion, the negative association between DPB1*05:01 and inhibitor development was reinforced [n = 70, OR 0.327, P = 0.010], and positive association of DRB1*13:02 and DPB1*04:01 with inhibitor development was identified [OR 3.059, P = 0.037 for both]. Previously reported risk alleles were not consistently associated with inhibitor risk in our series. This study demonstrated the profile of HLA alleles associated with inhibitor risk in Korean patients with severe HA was different from that in patients of other ethnicities, which needs to be considered in risk assessment and management.

Despite prevalence of clonal evolution in patients with aplastic anemia (AA), somatic mutation of human leukocyte antigen (HLA) gene is rarely reported. Herein, we reported a case of acquired AA (aAA) harboring a new four-base-pair deletion mutation within exon 4 of HLA-B*40:02 leading to frameshift and premature stop codon. The HLA-B*40:02 mutant allele was detected in the patient's peripheral blood sample not in patient's buccal epithelial cells. The patient received allogenic hematopoietic stem cell transplantation (HSCT) from HLA-matched sibling donor. On day 30 after HSCT, the mutant HLA allele was not detected by high-resolution sequence-based HLA typing. Serial chimerism analyses showed mixed chimeric status indicative of coexisting donor and recipient hematopoietic cells. Our data could provide additional support in view of pathophysiology of aAA that somatic mutation of HLA-B*40:02 allele is one of the possible origin of clonal escape to evade immune attack in patient with aAA.

The aim of this study was to investigate the molecular mechanisms of ertapenem resistance among Enterobacteriaceae isolates in a clinical microbiology laboratory at a tertiary university hospital. A total of 40 clinical isolates including 20 resistant and 20 intermediate isolates were collected from August 2012 to July 2013. Ertapenem susceptibility was confirmed by the broth microdilution method. PCR and sequencing analysis of carbapenemase, AmpC β-lactamase, and extended-spectrum β-lactamase (ESBL) genes were performed. Outer membrane proteins (OMPs) were examined by urea-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Molecular epidemiology studies were performed by pulsed-field gel electrophoresis (PFGE). AmpC β-lactamases and ESBLs were found in 32 (80.0%) and 20 (50.0%) of the 40 isolates with ertapenem non-susceptibility, respectively. Distributions of β-lactamase genes differed among the species. One Citrobacter freundii isolate among the 40 isolates with ertapenem non-susceptibility carrying the blaIMP-1 associated class 1 integron was detected. SDS-PAGE of OMPs showed altered or greatly diminished expression of porins in all isolates of Klebsiella pneumoniae (n=5) and Enterobacter cloacae (n=11) with ertapenem resistance. Porin alterations were less common among the isolates with intermediate susceptibility (4/19). Integration of the results of molecular analysis of β-lactamases and OMP analysis revealed that most of the isolates with ertapenem resistance exhibited β-lactamase activity and porin alteration. PFGE revealed that most isolates were epidemiologically unrelated. Ertapenem resistance in clinical Enterobacteriaceae isolates was associated with β-lactamase activity and porin alteration. Even though carbapenemase-producing Enterobacteriaceae are still rare, continuous monitoring and infection control for carbapenem-resistant Enterobacteriaceae are necessary.

BACKGROUND Glycated albumin (GA) is a better marker of short-term glycemic control than glycated hemoglobin (A1c). Dyslipidemia is the main cause of cardiovascular complications in diabetes mellitus (DM). Studies on the correlation of GA with lipid indices are sparse. We investigated the diagnostic utility of GA for DM and its relationship with serum lipid profiles compared with that of A1c. METHODS The GA enzymatic method was used to determine the diagnostic utility of GA for DM by using samples from 163 normal subjects (group 1) and 102 patients newly diagnosed with type 2 DM (T2DM; group 2). To analyze the lipid profiles, 263 patients with T2DM receiving treatment (group 3) were recruited. RESULTS GA correlated with A1c (r=0.934, P

Therapeutic Plasma Exchange for a Patient with Severe Cold Agglutinin Disease Naery Yang, Sholhui Park, Hae-Sun Chung, Yeung Chul Mun, Shinae Yu, Min-Jung Kwon, Hee-Yeon Woo, Sukjoong Oh, Miae Lee Departments of Laboratory Medicine, Internal Medicine, Ewha Womans University School of Medicine, Departments of Laboratory Medicine, Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Coagulase-negative staphylococci (CoNS) are reported to be the leading cause of nosocomial bloodstream infections. Staphylococcus pettenkoferi is a novel member of CoNS that was first isolated from the human blood and bursitis wound in 2002. We have reported cases of 6 S. pettenkoferi strains isolated from blood specimens, including one pathogen and 5 contaminants and catheter colonizers. Brucker Biotyper (Brucker Daltonics, Bremen, Germany) and molecular typing with 16S rRNA gene sequencing confirmed the 6 isolates as S. pettenkoferi. The conventional phenotypic identification of these isolates is not reliable owing to their inconsistent biochemical characteristics. Five of the 6 isolates were found to be resistant to oxacillin, and all isolates showed susceptibility to vancomycin and linezolid. For accurate identification of this novel species, advanced methods by using Brucker Biotyper or molecular methods such as 16S rRNA gene sequencing are required.

The clinical performance of three human papillomavirus (HPV) DNA commercial assays for cervical cancer screening was evaluated; the AdvanSure HPV Screening Real-Time PCR (AdvanSure PCR; LG Life Sciences) that was developed recently for the detection of both high-risk and low-risk genotypes, the Abbott RealTime High-Risk HPV Test (Abbott PCR; Abbott Molecular) and the Hybrid Capture High-Risk HPV DNA test (HC2; Qiagen). The three different HPV DNA tests were compared using cytology samples obtained from 619 women who underwent routine cervical cancer screening. The gold-standard assay was histopathological confirmation of cervical intraepithelial neoplasia of grade 2 or worse. The clinical sensitivities of the AdvanSure PCR, the Abbott PCR and the HC2 for the detection of cervical intraepithelial neoplasia of grade 2 or worse were 95.5%, 95.5% and 100%, respectively, while the clinical specificities were 61.6%, 86.4% and 83.3%, respectively. There were no significant differences in the clinical sensitivities of the Abbott PCR and the AdvanSure PCR compared to the HC2. The clinical specificities of the Abbott PCR and the AdvanSure PCR for the detection of HPV types 16/18 were 97.8% and 98.5%, respectively. For cervical cancer screening, all three tests showed relatively good clinical sensitivities, but the AdvanSure PCR had lower clinical specificity than the Abbott PCR and the HC2. The AdvanSure PCR and the Abbott PCR assays have the advantage of being automated and the ability to distinguish between HPV types 16/18 and other HPV types. The two real-time PCR assays could be useful tools in HPV testing for cervical cancer screening.

We report a case of CTX-M-55-type extended-spectrum β-lactamase (ESBL)-producing Shigella sonnei infection in a 27-year-old Korean woman who had traveled to China. The patient was admitted to the hospital due to abdominal pain, watery diarrhea, and fever (39.3℃). S. sonnei was isolated from her stool specimens, and the pathogen was found to be resistant to cefotaxime due to CTX-M-55-type ESBL. Insertion sequence (IS)Ecp1 was found upstream of the blaCTX-M-55 gene. The blaCTX-M-55 gene was transferred from the S. sonnei isolate to an Escherichia coli J53 recipient by conjugation. Pulsed-field gel electrophoresis and Southern blotting revealed that the blaCTX-M-55 gene was located on a plasmid of approximately 130 kb.

Trimethoprim-sulfamethoxazole is the first-line antimicrobial combination for Stenotrophomonas maltophilia infections. However, allergy or intolerance and increasing resistance limit the use of trimethoprim-sulfamethoxazole. Quinolones can be used as an alternative therapeutic option, but resistance can emerge rapidly during therapy. We analyzed the contribution of SmeABC and SmeDEF efflux pumps to levofloxacin resistance in clinical isolates of S. maltophilia. Nonduplicate clinical isolates of S. maltophilia were collected in 2010 from 11 university hospitals (n = 102). Fifty-five levofloxacin nonsusceptible (minimum inhibitory concentration [MIC] ≥4 μg/ml) and 47 susceptible (MIC ≤2 μg/ml) isolates were tested for efflux pump overexpression. Real-time reverse transcription-PCR was performed for amplification and quantification of smeB, smeC, smeD, and smeF mRNA. To determine which antimicrobials were affected by smeD overexpression, the growth rates of a levofloxacin-susceptible S. maltophilia isolate were compared by measuring absorbance of antimicrobial-supplemented Luria-Bertani broth (LB) cultures with or without triclosan. Significant relationships between sme gene overexpression and resistance were observed for smeD against levofloxacin, smeC and smeF against ceftazidime, and smeC against ticarcillin-clavulanate. The mean MICs of moxifloxacin and tigecycline did not significantly differ for isolates with or without overexpression of smeB, smeC, and smeF, but were significantly higher for isolates with smeD overexpression. The mean MICs of amikacin were significantly higher for smeC or smeF overexpressing isolates. Increased growth of a levofloxacin-susceptible isolate was observed in LB with 1/2 MIC levofloxacin in the presence of triclosan. These data suggest that the expression of smeD plays a role in levofloxacin resistance in S. maltophilia.

In November 2010, NDM-1-producing Klebsiella pneumoniae (NDMKP) was identified for the first time in South Korea from four patients with no history of traveling abroad who stayed for 21 to 205 days in a tertiary care hospital. All were sequence type (ST) 340 and had nearly identical XbaI pulsed-field gel electrophoresis (PFGE) patterns. The bla NDM-1 -carrying plasmids were in the IncN group, with sizes ranging from 50 to 200 kb. These findings suggest that NDMKP had already been introduced into South Korea before this clustering was found.

The flanking genetic structure of qnrA1 in Korean Enterobacter loacae was identical to that of the Chinese Escherichia coli strain, the first qnrA1-carrying strain reported in Asia. Analysis of restriction enzyme sites and Southern blot hybridization results showed that qnrA1 was transferred between E. cloacae and E. coli via Inc HI2 type plasmid.

Glanzmann thrombasthenia (GT) is an autosomal recessive bleeding disorder caused by defective glycoprotein, αIIb and β3, encoded by ITGA2B and ITGB3 genes, respectively. We herein describe four unrelated Korean patients with genetically confirmed GT. Two patients were homozygous for c.1913+5G>T (IVS11+5G>T) mutation of ITGB3 with a signature of founder effect. The other two patients were compound heterozygous for two mutations of ITGA2B: c.[2333A>C];[2975delA] (p.[Q778P];[E992Gfs*30]) and c.[1750C>T];[2333A>C] (p.[R584X];[Q778P]). The c.2975delA mutation was a novel frameshift mutation of ITGA2B. Although from a limited number of patients, these results suggests c.1913+5G>T of ITGB3 is a recurrent mutation in Korean patients with GT. Pediatr Blood Cancer 2012;59:335–338. © 2011 Wiley Periodicals, Inc.

Background: Clopidogrel has been widely used to prevent recurrent ischemia in patients with acute coronary syndrome (ACS). However, inter-individual variability in response to clopidogrel has been a problem in the clinical setting. The aim of the present study was to investigate the frequency of clopidogrel resistance and to determine the clinical, pharmacokinetic, and pharmacogenetic factors for clopidogrel resistance in Korean patients with ACS. Methods: Clinical information, such as the underlying diseases and concurrent medications, of 114 patients with ACS who received clopidogrel therapy was studied. The degree of inhibition of platelets was assessed using the VerifyNow assay (Accumetrics, USA). The patients who showed less than 20% inhibition of platelets were defined as non-responders to clopidogrel treatment. Steady state plasma concentrations of clopidogrel were measured using HPLC/tandem mass spectrometry. CYP2C19 genotyping was also performed. Results: A wide inter-individual variability was observed in platelet inhibition (0–76%); 56 patients (49%) showed less than 20% inhibition. There were no differences between the patients ’ history of diabetes mellitus and concurrent medications as well as the plasma concentrations of clopidogrel of the responders and non-responders. CYP2C19 variants, including CYP2C19*2 and CYP2C19*3, were more commonly observed in the non-responders than in the responders (P value < 0.0001). Conclusions: The response to clopidogrel was highly variable in Korean patients with ACS. The results of the present study confirmed that the genetic polymorphism of CYP2C19 could be important in clopidogrel response. However, further studies are required to investigate other likely factors involved in clopidogrel resistance.

This study explores experiences of housewives with infants' Pumasi child rearing community(i.e, communal child rearing community). A concrete context of pumasi child rearing of housewives with Infants was found. Results were as follows: The backgrounds of participation in pumasi child rearing community are isolated condition of child rearing and housewives' needs to find way of communication with others. Pumasi child rearing communities give meaningful experiences. They meet the developmental needs of both mothers and children and also provide various parenting models and skills, give a high value to individual child rearing, develop an everyday life community and strengthen the health of communities.

Nowadays, Klebsiella oxytoca is described as a causative organism for antibiotic-associated hemorrhagic colitis (AAHC). Here we report two cases of pediatric AAHC, from which K. oxytoca was cultured after starting amoxicillin-clavulanate or amoxicillin treatment. The patients developed severe abdominal pain and a large amount of bloody diarrhea. K. oxytoca was obtained in intestinal fluid culture of a boy through the colonoscopy. On the other hand, colonic tissue culture and intestinal fluid culture were negative of the other patient. K. oxytoca was detected in stool culture when he was admitted. These cases showed characteristic endoscopic findings of segmental hemorrhagic colitis, and both boys recovered spontaneously within 2–3 days after they stopped taking the antibiotics. Therefore, in children who develop relatively large amount of bloody diarrhea after antibiotic treatment, we should consider AAHC caused by K. oxytoca.

Background Familial hemophagocytic lymphohistiocytosis is a fatal disease characterized by immune dysregulation from defective function of cytotoxic lymphocytes. Three causative genes have been identified for this autosomal recessive disorder ( PRF1 , UNC13D , and STX11 ). We investigated the molecular genetics of familial hemophagocytic lymphohistiocytosis in Korea. Design and Methods Pediatric patients who fulfilled the HLH-2004 criteria were recruited from the Korean Registry for Histiocytosis. Molecular genetic studies were performed on the patients’ DNA samples by direct sequencing of all coding exons and flanking sequences of PRF1 , UNC13D , and STX11 . Results Forty patients were studied and familial hemophagocytic lymphohistiocytosis mutations were identified in nine; eight patients had UNC13D mutations (89%) and one had a mutation in PRF1 . No patient had a STX11 mutation. Notably, four patients had only one UNC13D mutant allele, suggesting that the other mutation was missed by conventional direct sequencing. All UNC13D mutations were deleterious in nature. One known splicing mutation, c.754-1G>C, was recurrent, accounting for 58% of all the mutant alleles (7/12). Five UNC13D mutations were novel (p.Gln98X, p.Glu565SerfsX7, c.1993-2A>G, c.2367+1G>A, and c.2954+5G>A). The one patient with PRF1 mutation was homozygous for a frameshift mutation (p.Leu364GlufsX93), which was previously reported to be the most frequent PRF1 mutation in Japan. Conclusions This is the first investigation on the molecular genetics of familial hemophagocytic lymphohistiocytosis in Korea. The data showed that UNC13D is the predominant causative gene in the Korean population. The identification of mutations missed by conventional sequencing would better delineate the mutation spectrum and help to establish the optimal molecular diagnostic strategy for familial hemophagocytic lymphohistiocytosis in Korea, which might need an RNA-based screening strategy.

Background The importance and usefulness of therapeutic drug monitoring (TDM) have been emphasized, and analysis of drugs has been increased in clinical laboratories. We evaluated the analytical performance and clinical usefulness of a recently introduced enzyme multiplied immunoassay instrument, Viva-E Drug Testing System (Dade Behring Inc., USA). Methods Using patients' samples and quality control material, we evaluated the analytical performance of Viva-E for a total of 11 drugs (cyclosporine, tacrolimus, mycophenolic acid, valproic acid, digoxin, theophylline, carbamazepine, phenytoin, phenobarbital, vancomycin, and gentamicin) with respect to linearity, precision, and correlations with other methods according to CLSI guidelines. Cobas Integra 800 (Roche Diagnostics, Switzerland) and API 4000 LC-MS/MS System (Applied Biosystems, USA) were used to make a comparison. In addition, we analyzed analysis time. Results Viva-E showed a good linearity (r2 >or= 0.97) for all items. Within-run CVs were within 5% and total CVs were within 10% for all drugs except for tacrolimus and digoxin at low concentrations. The system correlated well with the other methods (r=0.9283-0.9778). The time required for reporting the first sample was 11 min and the analysis time was 1.1 min. Conclusions Since Viva-E showed a good analytical performance required for TDM in its linearity, precision, and accuracy with its wide drug menus including cyclosporine, tacrolimus, and mycophenolic acid, stat and random accessing functions, and the consolidation to a single workstation, it could be very useful in the clinical laboratory for various needs.