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BACKGROUND Pyoderma gangrenosum (PG) is a sterile neutrophilic dermatosis that can be associated with systemic diseases, such as ulcerative colitis, polyarthritis, diabetes mellitus, myelodysplastic syndrome, and/or myeloid leukemia, and is often misdiagnosed as a necrotizing infection. Few reports have described imaging studies of PG; however, necrotizing fasciitis (NF) exhibits distinct imaging characteristics. If deep fascial involvement is not demonstrated on magnetic resonance imaging (MRI), NF is excluded. CASE REPORT We present a case of PG mimicking NF on MRI in a 67-year-old woman with acute myeloblastic leukemia. After undergoing a second cycle of decitabine therapy, she was admitted for pain in her lower left leg. The condition was initially misdiagnosed as NF because MRI findings demonstrated signal intensity in the fascia. MRI revealed fasciitis that exhibited linear fluid signal intensity in the fascia of lower left leg. Despite broad-spectrum antibiotics, the lesion rapidly progressed to a swollen hemorrhagic patch with bullae and an ulcer. Skin biopsy results ultimately led to the diagnosis of PG, based on histopathological findings. The patient was treated with intravenous steroids and regular wound dressing. The skin lesion on the lower left leg exhibited a good response. CONCLUSIONS Despite the presence of a lesion that invaded the fascia on MRI, our patient was diagnosed with PG following a skin biopsy and completely recovered with steroid treatment. To distinguish PG from NF, it is more important to identify the characteristic clinical features than to rely solely on imaging findings.

Single nucleotide substitution in codon 140 of HLA-B*40:02:01:01 results in the novel HLA-B*40:489 allele. This article is protected by copyright. All rights reserved.

Background and purpose Rupture of the extracranial carotid artery is a rare, but potentially disastrous event. We aimed to review the clinical presentations and radiologic findings of this entity and to evaluate the efficacy of endovascular treatment with covered stent graft. Materials and methods Since January 2009, eight patients with extracranial carotid artery rupture received endovascular treatment with covered stent graft. We retrospectively reviewed their medical records and radiologic findings. Results The ruptured sites were in the common carotid artery (n = 5), cervical ICA (n = 2) and petrous ICA (n = 1), respectively. The causes of injury included spontaneous (n = 2), carotid blowout syndrome (CBS) (n = 2), iatrogenic (n = 2) and traumatic (n = 2). Technical success and immediate hemostasis were achieved in all cases. Procedure-related complications occurred in 3 patients (37.5%). In a patient, the ipsilateral angular branch of the MCA was occluded during the procedure and it was completely reopened via mechanical thrombectomy without any neurologic deficit. Minor cerebral infarction was developed in 2 patients (25%). During a mean follow-up of 334 days (range 3–2053 days), two patients died: one from recurrent CBS and the other from aspiration pneumonia. Conclusions The covered stent grafting is an effective method for the treatment of extracranial carotid artery rupture.

Although rivaroxaban has recently become widely used for thrombosis treatment, it is difficult for clinicians to make clinical decisions in critical situations, such as emergent surgery or interventions, because a specific anti-Xa assay is not available in many laboratories. This study assessed the relationships between rivaroxaban-specific anti-factor Xa activity (AXA) and unfractionated heparin (UFH)-specific AXA and determined the cutoff level for UFH-specific AXA in critical situations for patients undergoing rivaroxaban therapy.Thirty-eight blood samples were collected from patients with cancer-associated thrombosis receiving rivaroxaban therapy. All samples were assessed using both rivaroxaban-specific and UFH-specific anti-Xa assays. Routine coagulation studies, including prothrombin time (PT) and activated partial thromboplastin time, were also conducted on the samples.A positive dose-dependent correlation between rivaroxaban-specific and UFH-specific AXA was evident (R = 0.97; P .0001). Rivaroxaban-specific AXA was also positively correlated with PT (R = 0.95; P .0001) but only weakly with activated partial thromboplastin time (R = 0.67; P .0001). Patients with plasma rivaroxaban concentrations 100 ng/mL were found to have UFH-specific AXA 1.41 IU/mL and PT 17.3 seconds, with sensitivities of 100% and 93.3% and specificities of 87.0% and 95.7%, respectively.Our study demonstrates that UFH-calibrated AXA correlates strongly with plasma rivaroxaban concentration. This assay appears to be sensitive to the presence of rivaroxaban, which may be advantageous in the setting of assessing drug levels for critical events. These findings suggest that if a rivaroxaban-specific anti-Xa assay is unavailable, the chromogenic anti-Xa assay for UFH may be useful to assess the anticoagulant effects of rivaroxaban.

Rationale: Parvovirus B19 (PV) infection is usually symptomless and can cause benign, short-lived conditions. Anemia associated with PRCA is the most representative hematologic manifestation, but neutropenia and thrombocytopenia have been rarely reported. Patient concerns: Three patients were admitted to the hospital with neutropenia and thrombocytopenia. The accompanying symptoms were fever, myalgia, rash, or arthralgia, and all patients were previously healthy. Diagnosis: Patients were positive for PV PCR and diagnosed with PV infection. Before the diagnosis of PV infection, 2 patients underwent BM study and almost absence of erythroid progenitor cells in BM aspiration were a clue for the PV infection. Other BM findings were hypocellular marrow and a few hemophagocytic histiocytes. Interventions: Patients received supportive care with follow-up of CBC. Outcomes: All 3 patients spontaneously recovered from neutropenia and thrombocytopenia within 3 weeks without severe complications. Lessons: The evaluation of PV infection should be considered in situations where there is neutropenia and thrombocytopenia in healthy individuals even without anemia as a differential diagnosis.

Background Unfractionated heparin (UFH) has unstable pharmacokinetics and requires close monitoring. The activated partial thromboplastin time (aPTT) test has been used to monitor UFH therapy for decades in Korea, but its results can be affected by numerous variables. We established an aPTT heparin therapeutic range (HTR) corresponding to therapeutic anti-Xa levels for continuous intravenous UFH administration, and used appropriate monitoring to determine if an adequate dose of UFH was applied. Methods A total of 134 ex vivo samples were obtained from 71 patients with a variety of thromboembolisms. All patients received intravenous UFH therapy and were enrolled from June to September 2015 at Gyeongsang National University Hospital. All laboratory protocols were in accordance with the Clinical and Laboratory Standards Institute guidelines and the College of American Pathologist requirements for aPTT HTR. Results An aPTT range of 87.1 sec to 128.7 sec corresponded to anti-Xa levels of 0.3 IU/mL to 0.7 IU/mL for HTR under our laboratory conditions. Based on their anti-Xa levels, blood specimen distribution were as follows: less than 0.3 IU/mL, 65.7%; 0.3-0.7 IU/mL (therapeutic range), 33.6%; and more than 0.7 IU/mL, 0.7%. No evidence of recurring thromboembolism was observed. Conclusion Using the conventional aPTT target range may lead to inappropriate dosing of UFH. Transitioning from the aPTT test to the anti-Xa assay is required to avoid the laborious validation of the aPTT HTR test, even though the anti-Xa assay is more expensive.

The 5q35.2-q35.3 duplication phenotype is characterized by growth delay, microcephaly, mental retardation and delayed bone aging. However, there has been no reports on the occurrence of pancytopenia as a consequence of 5q35.2-q35.3 duplication. A 42-year-old male visited the emergency room due to multiple trauma. He had been diagnosed with mental retardation in the past. No previous history of severe bleeding symptom was also reported. Complete blood cell counts were leukocyte 3.51×109/L, neutrophil 0.19×109/L, hemoglobin 8.3 g/dL, hematocrit 25.0%, and platelet 4.0×109/L. There was no relevant history of any medication intake and there were no other haematological parameters leading to the persistent pancytopenia. A bone marrow biopsy revealed hypercellular marrow with increased trilineage hematopoiesis. The uptake of fluorodeoxyglucose was increased in multiple lymph nodes, bone and spleen in positron emission tomography–computed tomography. A biopsy of the right axillary lymph node was performed and histologic findings were unremarkable. The chromosomal microarray revealed a 3.46 Mb microduplication at the 5q35.2-q35.3 site including NSD1. The patient had distinctive features related to atypical pancytopenia. Various managements for pancytopenia had no effect on the patient. However, there were no complications such as massive bleeding or serious infection compared to the severity of pancytopenia during a follow-up of 3 months. In addition, periodic patterns of deterioration and improvement in pancytopenia appeared spontaneously. Since it is rare for these distinctive features of pancytopenia and chromosomal abnormality to coexist, it is important to investigate the association. In the current study, we describe the first case of 5q35.2-q35.3 microduplication encompassing NSD1 with unexplained pancytopenia. Keywords: Pancytopenia, Chromosomal abnormality, Microarray

Cortisol is a well-known endogenous glucocorticoid that serves as a stress indicator. It is normally released under stressful condition to warn about imminent danger and thus is critical for survival of the species. However, it is unclear how cortisol relates to cognitive process under physiological condition in high-order primates such as non-human primates (NHP). Here, we report that a slight but significant increase in blood cortisol level by mild stress is positively correlated with the cognitive function in cynomolgus monkey. We stimulated 3 groups of monkeys by viewing consecutive series of pictures of monkeys, pictures of humans, or animation still pictures. We first found that the blood cortisol level was significantly higher during the stimulation session and returned to normal after stimulation session. Among the three types of pictures, the monkeys which were stimulated with monkey pictures showed the most significant increase in cortisol level during stimulation. Furthermore, the monkeys showed significantly enhanced manipulation, suggesting that cortisol affected cognitive processes. Overall, our study demonstrates that visual stimulation both increases blood cortisol and enhances manipulating behavior. Therefore, unlike the common notion that cortisol is a stress indicator, our data supports that a mild increase of cortisol enhances cognition in NHP.

Background We determined the epidemiological characteristics of erythromycin (EM)-resistant Streptococcus pyogenes (group A streptococci, GAS) strains isolated from Korea and Japan, using emm genotyping and multilocus sequence typing (MLST). Methods Clinical isolates of GAS had been collected from 1992 to 2012 in Korea and from 2004 to 2009 in Japan. EM resistance was determined by the microdilution method, and resistance genotypes were assessed by PCR. The emm genotyping and MLST were performed by DNA sequencing. Results The emm genotypes and sequence types (STs) were concordant in 143 (85.1%) of 168 EM-resistant GAS strains from Korea. ST36/emm12 (35.1%), ST52/emm28 (22.6%), and ST49/emm75 (16.1%) were the most common types. Most of the ST36 (93.9%) and ST52 (95.8%) strains harbored erm(B), whereas strains ST49, ST42, and ST15 contained mef(A). The concordance between emm genotypes and STs was 41 (93.2%) among 44 EM-resistant GAS strains from Japan. ST36/emm12 (34.1%), ST49/emm75 (18.2%), and ST28/emm1 (15.9%) were the major types. ST36 isolates harbored either erm(B) (56.3%) or mef(A) (37.5%), whereas isolates ST28, ST49, and ST38 carried only mef(A). The proportion of erm(B) and mef(A) was 66.1% and 33.3% in Korea and 22.7% and 68.2% in Japan, respectively. Conclusions The common STs in Korea and Japan were ST36 and ST49, whereas ST52 was present only in Korea and ST28 only in Japan. Genotype erm(B) was predominant in Korea, whereas mef(A) was frequent in Japan. There were differences between Korea and Japan regarding the frequencies of emm genotypes, STs, and EM resistance genes among the EM-resistant GAS.

Apixaban is effective and safe for preventing stroke, and its usage has increased exponentially in recent years. However, data concerning the therapeutic range of apixaban is limited. This study determined the trough and peak levels of apixaban-specific anti-factor Xa activity (AFXaA) in acute ischemic stroke patients with non-valvular atrial fibrillation (NVAF) in Korea. The study included 85 patients who received apixaban. Blood samples were taken to measure the trough and peak levels of AFXaA using a chromogenic anti-factor assay, as well as prothrombin time (PT) and activated partial thromboplastin time (aPTT). We also reviewed complications such as major bleeding of patients treated with apixaban. In patients given a 5.0-mg apixaban dose, the median trough and peak levels of AFXaA were 104.5 and 202.0 ng/mL. In patients given a 2.5-mg apixaban dose, the median trough and peak AFXaA levels were 76.0 and 151.0 ng/mL. The PT showed a positive correlation with increased AFXaA activity at both levels (Trough R = 0.486, Peak R = 0.592), but the aPTT had no relationship with AFXaA activity at both levels (Trough R = 0.181, Peak R = 0.129). Two cases with intracranial bleeding belonged to the highest AFXaA quartile (Trough, p = 0.176; Peak, p = 0.053). In conclusion, we determined the trough and peak levels of AFXaA in patients with NVAF while being treated with the apixaban in Korea. Our results could be used as a starting point when setting the reference ranges for laboratories using anti-Xa assay. Large-scale studies are needed to establish the reference range for AFXaA in patients with NVAF.

Resting state fMRI (rs-fMRI) using arterial spin labelling (ASL) technique was performed for the preoperative localization of the sensorimotor cortex in a patient with lymphoma and the results were compared to those of task-based (tb) and rs-fMRI studies using blood oxygenation level-dependent (BOLD) sequence. Rs-fMRI using ASL showed similar results in the regions of the sensorimotor network to those of tb- and rs-fMRI fMRI using BOLD. ASL technique has a potential in clinical practice because all of brain perfusion imaging, cerebral blood flow measurement, and rs-fMRI study can be performed at a single acquisition.

Background: Breast cancer remains a leading cause of cancer-related death in women. Numerous studies have demonstrated that mammaglobin is one of the most promising markers for diagnosis of breast cancer. However, little is known about the relationship between mammaglobin and overall survival. The small number of published studies has yielded controversial results. Objective: This study was performed to clarify the association between expression of mammaglobin in peripheral blood and prognosis in breast cancer patients. Methods: We systematically reviewed and meta-analyzed the data showing the association between expression of mammaglobin in peripheral blood and prognosis in breast cancer patients. The data were obtained from analysis of disease free survival (DFS)/event free survival (EFS) and overall survival (OS). Results: Our analysis showed that patients expressing mammaglobin in peripheral blood before the removal of the primary tumors or chemotherapy showed shorter DFS/EFS, but no change in OS. The detection of mammaglobin mRNA in peripheral blood was not associated with worse outcome for OS, but the effect size was not small. Conclusion: These data indicate that a meaningful association of mammaglobin might be found if large scale studies are performed. Large prospective studies are necessary to determine the prognostic value of the detection of mammaglobin mRNA in peripheral blood of breast cancer patients.

OBJECTIVE. Varying anatomic characteristics and clinical and radiologic manifestations are diagnostic challenges in the evaluation of the cerebral vein and of venous sinus diseases. The purpose of this article is to introduce bone subtraction CT venography and review normal variations and diseases involving the cerebral veins and venous sinuses. CONCLUSION. Knowledge of the normal variations and pathologic findings will be helpful for the accurate diagnosis of diseases involving the cerebral venous system. Bone subtraction CT venography offers complete 3D visualization of the cerebral venous system and can be useful for the evaluation of the cerebral vein and venous sinus diseases.

Little is known about the biological role of human mammaglobin (hMAM) that is considered as a promising marker for breast cancer. Here, we investigated hMAM's role related to migration and invasion of human breast cancer cells (hBCC). Compared to normal cells, hBCC have high MAM mRNA expression levels. Of the hBCC tested, MAM mRNA expression levels were higher in noninvasive than in invasive cells. Overexpression of hMAM in breast cancer cells decreased migration and invasion, whereas knockdown of hMAM increased both. Taken together, these results suggest that metastasis of hBCC could be controlled by hMAM expression levels.

The performance of the BacT/Alert FA Plus and FN Plus resin bottles was evaluated in comparison with that of standard aerobic (SA) and standard anaerobic (SN) bottles. Twenty milliliters of blood from adult patients was equally distributed into four types of bottles: FA Plus, FN Plus, SA, and SN. The detection of clinically significant organisms and the time to detection (TTD) were monitored for each bottle. Among the 3,103 blood culture sets that were requested, the blood volume of each bottle was over 4 ml in 1,481 sets (47.7%). Among these 1,481 sets, 158 cultures grew in the FA Plus and SA bottles, and 136 grew in the FN Plus and SN bottles. Growth in only one type of bottle was more commonly observed for the FA Plus ( n = 38) than for the SA ( n = 14) ( P = 0.001) bottles and for the FN Plus ( n = 27) than for the SN ( n = 10) ( P = 0.008) bottles. Gram-negative bacilli were more frequently isolated in the resin bottles ( P < 0.05). The skin contamination rate was 1.2% in the resin bottles and the standard bottles. The mean TTD was 11.1 h in the FA Plus bottles versus 13.1 h in the SA bottles ( P < 0.001) and 12.0 h in the FN Plus bottles versus 12.8 h in the SN bottles ( P = 0.083). Clinically significant bacteria, including Gram-negative bacilli, were isolated more frequently from the resin bottles than from the standard bottles. Clinically significant bacteria were detected faster using the aerobic resin bottles than using the standard aerobic bottles. This finding might not be applicable to the standard-practice 10-ml protocol for each bottle because the results from using a smaller volume (5 ml) might be less pronounced.

Background Delayed entry of blood culture bottles is inevitable when microbiological laboratories do not operate for 24 hr. There are few studies reported for prestorage of these bottles. The growth dynamics of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were investigated with respect to various preincubation conditions. Methods Fifteen or 150 colony-forming units (CFU) of bacteria were inoculated into standard aerobic or anaerobic blood culture bottles. Bottles were preincubated at 25℃ or 37℃ for 0, 2, 4, 8, 12, 24, or 48 hr. The time to detection (TTD) then was monitored using the BacT/Alert 3D system (bioMerieux Inc., USA). Results Significant difference in TTD was observed following preincubation for 8 hr at 25℃ vs. 4 hr at 37℃ for S. aureus, 4 hr at 25℃ vs. 4 hr at 37℃ for E. coli, 12 hr at 25℃ vs. 4 hr at 37℃ for P. aeruginosa, compared to no preincubation (P

We analyzed the relation between platelet aggregation measured by light transmittance aggregometry (LTA) and platelet reactivity index (PRI) measured by vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay.It has been suggested that LTA and VASP-P assay correlate differently according to the level of P2Y12 receptor blockade by thienopyridines.We simultaneously measured platelet function by LTA and VASP-P assay in 466 East Asians undergoing elective percutaneous coronary intervention after a 600-mg clopidogrel loading. High on-clopidogrel platelet reactivity (HPR) was defined by published consensus criteria.The degree of correlation between LTA and the VASP-P assay was different according to PRI levels. The correlation was lower in patients with poor responsiveness (PRI60%) (n = 216) (0.035 ≤ r(2) ≤ 0.047), which was greater in responsive patients (PRI ≤60%) (n = 250) (0.315 ≤ r(2) ≤ 0.526). Despite a 600-mg loading, East Asians had a high prevalence of HPR (40.1%-63.5%), and the prevalence of HPR also differed between LTA and VASP-P assay. A PRI cutoff of58% (area under curve, 0.829; 95% confidence intervals, 0.792-0.862; P.001) corresponded to the published HPR cutoff by 5-μM adenosine diphosphate-induced maximal platelet aggregation46%.This is the largest study correlating platelet reactivity measured by LTA and VASP-P assay in a percutaneous coronary intervention-treated cohort. The correlation is dependent on the level of responsiveness. Future investigations are needed to better define the optimal cutoffs of HPR measured by LTA and VASP-P assay for personalized antiplatelet therapy.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Compared with standard dual antiplatelet therapy, adjunctive cilostazol to dual antiplatelet therapy ('triple antiplatelet therapy’) has a potential to reduce ischemic event occurrence after percutaneous coronary intervention. • The pharmacokinetic and pharmacodynamic effects of clopidogrel have been significantly influenced by the enzyme activity of the ABCB1 C3435T and the CYP2C19 system. • For the pharmacokinetics of cilostazol, genetic polymorphisms of the CYP3A5 and CYP2C19 have been associated with the substantial interindividual variability in healthy volunteers. WHAT THIS STUDY ADDS • Loss-of-function polymorphism of the CYP2C19 gene, but not the ABCB1 C3435T and CYP3A5*3 genes, affects the antiplatelet effect of triple antiplatelet therapy. • Most of extensive and intermediate East Asian metabolizers (0 or 1 CYP2C19 loss-of-function allele) show adequate platelet inhibition when treated with triple antiplatelet therapy after percutaneous coronary intervention. • However, carriage of 2 CYP2C19 loss-of-function alleles is still associated with the risk of high platelet reactivity (defined by by 5 µM ADP-induced maximal platelet aggregation >46%), which clinical impact needs to be validated in future clinical trials. AIMS Although adjunctive cilostazol to dual antiplatelet therapy can reduce the risks of clinical events after percutaneous coronary intervention (PCI), whether genetic polymorphism can influence the pharmacodynamics of this regimen has not been evaluated. METHODS One hundred and twenty-seven patients treated with PCI and taking triple antiplatelet therapy (≥1 month) were enrolled. Platelet reactivity was assessed by conventional aggregometry and the VerifyNow P2Y12 assay. High on-treatment platelet reactivity (HPR) was defined as 5 µm ADP-induced maximal platelet reactivity (Aggmax) >46%. CYP3A5*3, CYP2C19*2/*3 and ABCB1 3435C > T were genotyped. RESULTSCYP3A5*3 and ABCB1 3435C > T variants did not affect the antiplatelet effect of triple antiplatelet therapy. For non-carriers, one and two carriers of the CYP2C19 loss-of-function (LOF) allele, Aggmax consecutively increased after the addition of 5 µm[mean (95% confidence intervals): 24.6% (20.8 to 28.5%) vs. 28.7% (25.4 to 32.0%) vs. 32.3% (25.8 to 38.7%), P = 0.062, respectively] and 20 µm ADP [34.2% (29.3 to 39.0%) vs. 41.7% (37.8 to 45.6%) vs. 44.9% (37.9 to 51.9%), P = 0.007, respectively]. Likewise, late platelet reactivity and P2Y12 reaction units proportionally changed according to the number of CYP2C19 LOF alleles. HPRs were observed in 9.2% of subjects: 6.3%, 7.4% and 20.0% with 0, 1 and 2 carriers of CYP2C19 LOF allele(s) (P = 0.099). In multivariate analysis, carriage of two CYP2C19 LOF alleles was a significant predictor for the prevalence of HPR (odds ratio 5.78, 95% CI 1.21, 27.78, P = 0.028). CONCLUSION Among PCI-treated patients, the effect of triple antiplatelet therapy is influenced by the CYP2C19 LOF allele. Its clinical benefit needs to be validated according to the CYP2C19 metabolic phenotype in future clinical trials. [Adjunctive Cilostazol Versus High Maintenance dose ClopidogrEL in Acute Myocardial Infarction Patients According to CYP2C19 Polymorphism (ACCEL-AMI-2C19), NCT00915733 and Adjunctive Cilostazol Versus High Maintenance-dose Clopidogrel According to Cytochrome 2C19 Polymorphism (ACCEL-2C19), NCT01012193].

Background— Among patients treated with clopidogrel, carriers of the cytochrome P450 ( CYP ) 2C19 loss-of-function allele have shown increased platelet reactivity and higher rates of ischemic events. Although adjunctive cilostazol to dual antiplatelet therapy (or “triple antiplatelet therapy”) intensifies platelet inhibition, it remains unknown whether triple antiplatelet therapy after percutaneous coronary intervention can achieve adequate platelet inhibition in patients with the CYP2C19 mutant allele. Methods and Results— CYP2C19 genotyping for * 1 , * 2 , and * 3 was performed in 134 high-risk patients undergoing elective percutaneous coronary intervention. After measurement of preprocedural platelet reactivity, patients were randomly assigned to receive either adjunctive cilostazol 100 mg twice daily (triple group; n=69) or high maintenance-dose (MD) clopidogrel of 150 mg daily (high-MD group; n=65). Using light transmittance aggregometry and the VerifyNow P2Y 12 assay, platelet reactivity was assessed before the index procedure and at 30-day follow-up. The primary end point was absolute change in maximal platelet aggregation (ΔAgg max ) according to CYP2C19 genotyping. High posttreatment platelet reactivity was defined as 5 μmol/L ADP–induced maximal platelet aggregation >50%. In noncarriers of the CYP2C19*2/*3 mutant allele, ΔAgg max values after 5 and 20 μmol/L ADP stimuli did not differ significantly between the triple (n=22) versus the high-MD group (n=22) (23.6±21.6% versus 16.6±15.4%, P =0.224 and 26.4±22.2% versus 18.6±14.9%, P =0.174, respectively). Absolute changes in late platelet aggregation and P2Y 12 reaction unit were not different between the groups. The rate of high posttreatment platelet reactivity at 30-day follow-up also was comparable between the triple versus the high-MD group (4.5% versus 13.6%, P =0.607). In carriers of at least 1 CYP2C19 *2/*3 mutant allele, the triple group (n=47) showed greater values of ΔAgg max after addition of 5 μmol/L (25.8±16.8% versus 11.1±19.8%, P P 12 reaction unit were consistently greater in the triple versus the high-MD group. Fewer patients in the triple group met the criteria of high posttreatment platelet reactivity at 30-day follow-up compared with the high-MD group (6.4% versus 37.2%, P Conclusions— Among high-risk patients undergoing elective percutaneous coronary intervention, adjunctive cilostazol can achieve consistently intensified platelet inhibition and reduce the risk of high posttreatment platelet reactivity irrespective of CYP2C19 genotyping. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01012193.

Background: Group A streptococcus (GAS) is the most common cause of bacterial pharyngitis in children. Antibiotic resistance rates and emm genotypes of GAS isolated from patients with acute pharyngitis were studied in 2009. Methods: Throat cultures were taken from 499 children with acute pharyngitis in Jinju, Korea, in 2008-2009. A total of 174 strains (34.9%) of GAS were isolated, and antimicrobial susceptibility testing was performed using the disk diffusion method. The phenotypes of macrolide resistance and macrolide resistance genes were determined. The emm genotypes were identified using PCR and sequencing. The data were compared with those acquired in 2002 in the same region. Data on the annual macrolide production were collected between 1999 and 2008. Results: The resistance rates of GAS to erythromycin, clindamycin, and tetracycline were 4.6%, 2.9%, and 2.3%, respectively. The constitutive resistance rate was 62.5% for the erm(B) gene and 37.5% for the M phenotype of the mef(A) gene. emm4 was most frequently detected (28.2%), followed by emm89 (20.1%). Most of the erythromycin resistant strains had the emm28 genotype. We noted a gradual increase in macrolide production during the study period. Conclusions: The erythromycin resistance rate of GAS isolated from children with acute pharyngitis was significantly lower in 2009 (4.6%) than in 2002 (44.8%). We observed a remarkable change in the distribution of emm genotypes during the 7-yr period. The significant decline in erythromycin resistance in 2009 might be associated with a prominent decrease in the resistant genotype emm12 (3.4% in 2009 vs. 28.0% in 2002) rather than restriction of macrolide use. (Korean J Lab Med 2010; 30:485-90)

Background : T antigens and emm genotypes are useful markers for epidemiologic investigation of Streptococcus pyogenes infections. Epidemiologic studies of S. pyogenes were performed on a large scale in Jinju. This was the third study being carried out in the same area over the past 10 years. Methods : A total of 328 S. pyogenes were isolated from throat cultures obtained from asymptomatic schoolchildren in the Jinju area in 2004. T typing was performed by a slide agglutination, and emm genotyping by PCR and DNA sequencing. We compared the results of this study with those of the previous ones performed in 1995 and 2002. Results : T5/27/44 were the most prevalent, accounting for 29.6% of all isolates; T12 and T6 were 13.4% and 10.7%, respectively, and T nontypeable was 3.4%. The emm44/61 type was the most prevalent accounting for 29.3%, and emm6 and emm1 were 11.6% and 9.8%, respectively. Conclusions : Newly recognized T5/27/44 and emm44/61 were the most prevalent, accounting for about 30% of all isolates, while T12 and emm12 were significantly decreased in 2004 compared to the results of previous years. This study demonstrated divergent features of S. pyogenes epidemiology over the past 10 years in the Jinju area.

The M protein and streptococcus pyrogenic exotoxin (SPE A) are important virulence factors in group A streptococci (GAS) infections. The emm types of GAS strains isolated from patients with sepsis were determined by sequencing the 5' N-terminus of the emm gene, encoding the M protein, and clonality analysis using pulsed-field gel electrophoresis. The presence of speA and production of SPE A were also examined. There were no predominant GAS clones. The emm genotypes were variable, and the most common genotype was emm13 (17.9%). The production prevalence of SPE A was 21.4%. The low mortality rate (7.1%) of GAS sepsis might be attributable to the low incidence of virulent strains such as emm1 (10.7%) and emm3 (7.1%), as well as to low production rate of SPE A.

Background Therapy-related myeloid neoplasm after treatment for acute promyelocytic leukemia (APL) is a relatively infrequent but severe complication. Most therapy-related myeloid neoplasms after treatment for APL are classified as therapy-related myelodysplastic syndrome or therapy-related acute myeloid leukemia. Translocation of 5q31-33, PDGFRB occur rarely in therapy-related myeloid neoplasm and there has been two identified PDGFRB partner genes located at 14q32, TRIP11 and KIAA1509. Results The TRIP11-PDGFRB fusion was identified in a patient with therapy-related myeloid neoplasm with t(5;14)(q33;q32) after treatment of APL using conventional cytogenetics, fluorescence in situ hybridization (FISH) and molecular methods. Cytogenetic analysis of the bone marrow aspirate revealed 46, XY, t(5;14)(q33;q32) in all 20 analyzed cells. No other cytogenetic abnormalities were observed. Break-apart FISH analysis demonstrated that rearrangement of PDGFRB at 5q33 was positive in 460 of 500 cells analyzed, while the PML-RARA rearrangement remained undetectable by RT-PCR. Sequencing of RT-PCR products revealed fusion between exon 16 of TRIP11 and exon 11 of PDGFRB. However, the KIAA1509-PDGFRB fusion was not detected by RT-PCR. Conclusion We firstly demonstrated that therapy-related myeloid neoplasm with TRIP11-PDGFRB fusion was identified after treatment of APL.

OBJECTIVE To determine the effect of adding cilostazol (100 mg b.i.d.) to standard-dose clopidogrel (75 mg/d) (TRIPLE) compared with double-dose clopidogrel (150 mg/d) (DOUBLE) and the influence of the cytochrome P450 (CYP2C19*2/*3, CYP3A5*3)and ATP-binding cassette subfamily B1(ABCB1 C3435T) genetic polymorphisms in type 2 diabetes (T2DM) patients. RESEARCH DESIGN AND METHODS T2DM patients were treated with TRIPLE (n = 41) or DOUBLE (n = 39) after percutaneous coronary intervention. Conventional aggregometry and VerifyNow were performed at baseline and at 30 days. The primary end point was absolute change in 20-μM ADP-induced maximal platelet aggregation (ΔMPA20) between baseline and switching values. RESULTS TRIPLE versus DOUBLE showed greater ΔMPA20 (22.9 ± 11.6 vs.12.7 ± 15.5%; difference, 10.2% [95% CI 4.2–16.3]; P < 0.001). Carriage of one (β coefficient, −5.4%; P = 0.162) and two CYP2C19 loss-of-function allele(s) (−8.3%; P = 0.007) were associated with lower ΔMPA20 in DOUBLE–treated patients, but not in TRIPLE-treated patients. CONCLUSIONS Among T2DM patients, adding cilostazol achieves greater platelet inhibition compared with clopidogrel (150 mg/d), which is not influenced by genetic polymorphisms.

ObjectivesThe aim of this study was to assess the degree of platelet inhibition by adjunctive cilostazol in patients with acute myocardial infarction (AMI) according to hepatic cytochrome P450 2C19 (CYP2C19) genotype.BackgroundAlthough adjunctive cilostazol intensifies platelet inhibition in AMI patients, it is not established whether this regimen can be free from the effect of CYP2C19 loss-of-function variants (*2/*3).MethodsWe randomly assigned 126 AMI patients with available CYP2C19 genotyping to receive adjunctive cilostazol (triple group; n = 64) or high maintenance-dose (MD) clopidogrel of 150 mg/day (high-MD group; n = 62). Using conventional aggregometry and VerifyNow (Accumetrics Inc., San Diego, California), platelet reactivity was measured at pre-discharge and 30-day follow-up. Primary endpoint was change in maximal platelet aggregation (ΔAggmax) between pre-discharge and 30-day follow-up. High on-treatment platelet reactivity (HPR) was defined as 20 μmol/l adenosine diphosphate–induced maximal platelet aggregation (Aggmax) >59%.ResultsIn noncarriers, despite numerically greater inhibition by adjunctive cilostazol, changes in platelet measures and the rate of HPR did not significantly differ between the 2 groups. In carriers, ΔAggmax after 5 and 20 μmol/l adenosine diphosphate stimuli was significantly higher in the triple (n = 39) versus high-MD group (n = 38) (21.8 ± 13.9% vs. 9.0 ± 13.3%, p < 0.001, and 24.2 ± 17.2% vs. 7.7 ± 15.5%, p < 0.001, respectively). Likewise, changes in late platelet aggregation and P2Y12 reaction unit were consistently greater in the triple versus high-MD group. Fewer patients in the triple group met the criteria of HPR at 30-day follow-up than in the high-MD group (15.4% vs. 44.7%, p = 0.005).ConclusionsCompared with high-MD clopidogrel, adjunctive cilostazol significantly enhances platelet inhibition and reduces the rate of HPR, especially in AMI patients with CYP2C19 loss-of-function variants. (Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel in Acute Myocardial Infarction (AMI) Patients According to CYP2C19 Polymorphism [ACCELAMI2C19]; NCT00915733)

Pyogenic intraventricular empyema (PIE) is a potentially fatal CNS infection. However, it is sometimes difficult to diagnose PIE on the basis of clinical and conventional MRI findings. Diffusion-weighted imaging (DWI) has been accepted as a useful MR sequence for the diagnosis of various intracranial infections. The purpose of this study was to determine the DWI characteristics of PIE and the role of DWI in the diagnosis of PIE.Eight patients with PIE underwent MRI including DWI. We assessed the presence and signal characteristics of PIE. In seven patients, the signal intensities of the PIE and cerebrospinal fluid (CSF) were measured and the contrast-to-noise ratio (CNR) percentage was calculated. ADC values of the PIE, CSF, and white matter were also determined.PIE was detected in all patients by DWI, in five (63%) by FLAIR imaging, and in two (25%) by T1- and T2-weighted imaging. The CNR percentages of the PIEs in relation to the CSF were highest for DWI, followed by FLAIR, T1-, and T2-weighted imaging. There were statistically significant differences between the images of each sequence. In all patients, PIE showed hyperintensities on DWI and hypointensities to the CSF and hypo- or isointensities to the white matter on ADC maps. The ADC values (mean+/-SD) of the PIE, CSF, and white matter were 0.60+/-0.27, 2.81+/-0.04, and 0.79+/-0.08 (x10(-3) mm(2)/s). There was a statistically significant difference between PIE and the CSF.PIE shows a bright intensity on DWI, and DWI is a sensitive MR sequence for the diagnosis of PIE.

Background: By varying the collected blood volume and storage temperature of the blood culture bottles prior to entry in an automated blood culture system, growth of organisms will be affected. Methods: Blood culture bottles with a 20 mL blood volume per set were stored at 37 o C (1 st period) and room temperature (RT, 2nd period) upon arrival at the laboratory after working hours compared to baseline period (10 mL, RT). The time to detection (TTD) for all strains and the number of days until the final report after bottle entry were compared among the three periods. Results: The median TTD for all strains was 13.5 h, 10.6 h, and 11.3 h in the baseline (N=268), 1st (N=454), and 2 nd period (N=370), respectively (P＜0.001). The final identification report was available within two days of bottle entry for 12.3%, 30.6% and 15.1% of bottles in the three different periods, respectively (P＜0.001). Conclusion: Collecting an adequate blood volume is critical to reduce TTD. The preincubation of blood culture bottles at 37 o C during the night shift might enable earlier final reports than storage at RT for samples with the same collected blood volume. (Ann Clin Microbiol 2014;17:14-19)

Background: This study compared the growth of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Haemophilus influenzae in blood culture bottles containing anticoagulants, sodium polyanethol sulfonate (SPS) and sodium citrate. Methods: One hundred and fifty colony forming units of five different bacterial species were inoculated into standard aerobic (SA) and standard anaerobic (SN) bottles and were combined with 5 mL of human blood in solution with SPS or sodium citrate. Time to detection (TTD) was then monitored using the BacT/ Alert 3D system (bioMerieux Inc.). Results: Compared to the bacteria-only controls, cultures containing S. aureus, E. coli, P. aeruginosa, and S. pneumoniae plus SPS blood or citrated blood trended toward reduced TTD in both SA and SN bottles; however, there was no significant difference in TTD between SPS and sodium citrate anticoagulant. Although H. influenzae showed a remarkable difference in TTD between SPS (SA 14.8 h, SN 15.0 h) and sodium citrate (SA 23.5 h, SN 18.3 h), this difference was not statistically significant (P=0.10). Conclusion: Addition of blood enhanced growth of bacteria. All experimental bacteria except H. influenzae showed similar TTD in SPS blood and citrated blood. These results support the usefulness of sodium citrate anticoagulant for artificial inoculation in blood culture bottles. (Ann Clin Microbiol 2013;16: 168-173)

Background: Blood culture is essential for the diagnosis and management of bloodstream infections. Blood volume is a key parameter determining the success of blood cultures. Studies comparing compliance between physicians and phlebotomists regarding optimal blood culture procedure are very rare in Korea. Methods: After educating physicians (interns) and phlebotomists about the correct procedure for blood culturing, the blood volumes of forty-three percent of randomly selected aerobic and anaerobic culture sets for adult patients (≥18 years old) were compared between these two groups over a period of three months. Physicians obtained blood from all admitted patients except those in the emergency department, where phlebotomists performed blood collection. Results: The numbers of blood culture sets requested during the study period were 3,238 and 2,136 for the physician and phlebotomist groups, respectively. The blood volumes of blood culture sets were significantly higher for the phlebotomists (16.7 mL) than for the physicians (9.2 mL). The positive rate of blood culture was also higher for the phlebotomist group (10.3% vs. 7.9%). The contamination rates (0.8%) were the same for both groups. Conclusion: Although the patients' medical conditions, antibiotics prescriptions, or duration of hospitalization may have affected the positive rate of blood cultures, this rate might also have been influenced by the blood volume. The compliance of phlebotomists was greater than that of physicians regarding the blood volume collected for blood cultures. (Ann Clin Microbiol 2013;16:81-86)

Background: A central venous catheter (CVC) is commonly used for administering chemotherapy to cancer patients. The institutional guideline of the Gyeongsang National University Hospital (GNUH) for blood culture analysis of indwelling CVC patients recommended 6 sets (2 from the periphery and 4 from ...

Department of Laboratory Madicine, Seoul National University College of Medicine, Seoul, Gyeongsang National University School of Medicine, Jinju, Hanyang University College of Medicine, Seoul, Hallym University College of Medicine, Chuncheon, Inje University College of Medicine, Busan, Sungkyunkwan University School of Medicine, Seoul, University of Ulsan College of Medicine, Ulsan, Wonkwang University Medical School, Iksan, Pusan National University School of Medicine, Yangsan, Jeju National University School of Medicine, Jeju, Korea

Background: The Streptococcus pneumoniae urinary antigen test (SPUAT) (Binax Now, USA) was developed for detecting polysaccharide C in urine samples for rapid diagnosis of pneumococcal pneumonia, the most common cause of community-acquired pneumonia (CAP). To validate positive results of these tests, we retrospectively investigated all positive results obtained from the emergency room of a Korean university hospital among patients with suspected CAP. Methods: One hundred twenty-three positive SPUAT results were abstracted and analyzed from the authors' laboratory information system among the SPUAT results performed from 1,143 pneumonic patients admitted from the emergency room of a university hospital between 2007 and 2008. Medical records, including conventional microbiologic analysis results, were reviewed in detail for all positive test results. Results: Among 123 patients with the positive SPUAT results, 24 patients were excluded due to hospitalization history during the preceding month. Nine of 99 patients (9.1%) with suspected CAP had confirmed pneumococcal pneumonia upon conventional sputum or blood culture. Thirty-five positive results (35.4%) showed other microorganisms upon conventional methods, which might be due to possible cross-reactivity. Among those, 23 positive results were considered bacterial pneumonic agents, and 12 positive results were regarded as urinary tract infection strains or contaminating agents. Fifty-five positive SPUAT results (55.6%) showed negative conventional microbiologic growth, and some positive SPUAT results might be caused by true pneumococcal infection although without cultural evidence. Conclusion: Our retrospective study demonstrated that a positive SPUAT result typically does not agree well with conventional culture methods, suggesting that the value of a positive SPUAT result in etiology determination may be limited under practical conditions in a university hospital. (Korean J Clin Microbiol 2010;13:14-18)

Background: Ureaplasma urealyticum and Mycoplasma hominis are associated with an increased risk of pregnancy complications, such as preterm birth and premature membrane rupture. The purpose of this study was to determine the isolation rates and antimicrobial susceptibilities of genital mycoplasma in a sample of pregnant women from Jinju, Korea. Methods: Vaginal swabs were obtained from 258 pregnant women between 2004 and 2008 and tested for the presence of U. urealyticum and M. hominis at Gyeongsang National University Hospital. The identification and antimicrobial susceptibilities of U. urealyticum and M. hominis were determined with a commercially available kit, the Mycoplasma IST2 Kit (bioMe rieux, Marcy-l’Etoile, France), and evaluated according to standards set by the Clinical and Laboratory Standards Institute (CLSI). Results: U. urealyticum only was detected in 105 specimens (38.6%), while M. hominis only was detected only in 2 specimens (1.8%). Seven specimens (6.7%) were positive both for U. urealyticum and M. hominis. Susceptibilities of U. urealyticum to azithromycin, erythromycin, clarithromycin, and doxycycline were 75.2%, 82.9%, 88.6%, and 88.6%, respectively, while almost all of the isolates were susceptible to josamycin (99.0%) and pristinamycin (100%). The susceptibility of U. urealyticum to ofloxacin and ciprofloxacin was 56.2% and 15.2%, respectively. Conclusion: The rate of isolation of genital mycoplasma in pregnant women was 44.2% in Jinju; most of the mycoplasma were U. urealyticum. U. urealyticum and M. hominis were highly resistant to quinolones, but susceptible to josamycin. Therefore, empirical treatment without prior identification and determination of the antimicrobial susceptibility of genital mycoplasma will fail in many cases. (Korean J Clin Microbiol 2009;12:159-162)

Background: Streptococcus pyogenes is the most common cause of bacterial pharyngitis. T antigens and emm genotypes are essential markers for an epidemiological study of S. pyogenes. Macrolide resistance of S. pyogenes is a serious obstracle to successfully treating a sore throat. Methods: One-hundred forty-seven strains of S. pyogenes isolated from healthy school children in 2006 were subjected to T typing and emm genotyping. A disk diffusion method was applied for several antibiotics. A double disk diffusion test was performed to evaluate the phenotype distribution of macrolide resistance. Results: Among T antigens and emm genotypes, T11 (19.7%) and emm78 (16.7%), respectively, were the most common in 2006. Both T5/27/44 (2.3%) and emm44/61 (9.1%) declined to a great extent from about 29% in 2004. The rate of resistance to antibiotics were 11.6% to erythromycin, 4.8% to clindamycin, 21.8% to tetracycline, and 7.5% to ofloxacin. M and cMLSB phenotypes were 52.9% and 41.2% respectively. Conclusion: T typing and emm genotyping proved a dynamic change in their distribution in 2006 compared to the results of 2004. Erythromycin and clindamycin resistance remained low as in 2004, whereas ofloxacin resistance increased slightly. M and cMLSB phenotypes were equivalent in 2006, whereas cMLSB was predominant in 2004. (Korean J Clin Microbiol 2009;12:6-10)

Background: Group A streptococci (GAS) are the most common cause of pharyngitis in children. The streptococci in throat cultures from healthy elementary school children in Jinju were compared with previous results. Methods: Throat cultures were taken from 1,402 healthy school children in 2006. β-hemolytic streptococci (BHS) were identified with a bacitracin disk (0.04 U) and latex agglutination test (Seroiden Strepto Kit, Eiken, Tokyo, Japan). Results: Two-hundred sixteen (15.4%) and 149 (10.6%) cultures grew BHS and GAS, respectively. The isolation rate of GAS was significantly lower than in 2004 (16.0%) or 2002 (16.9%) (P＜0.05). Among BHS, the prevalence of group A strains (69.0%) decreased significantly compared with 2004 (84.9%) and 2002 (83.8%) (P＜0.05). None of the 1 st -grade children yielded BHS or GAS. Conclusion: The isolation rates of BHS and GAS from healthy school children were lower in 2006 than in previous years. Natural immunization against the common serotypes or improvement in individual hygiene might have played roles in the reduction of isolations of GAS. (Korean J Clin Microbiol 2008;11: 1-4)

α-hemolytic streptococci (AHS) are common normal oropharyngeal flora that can transfer antibiotic-resistance genes to Streptococcus pneumoniae. Reports on antibiotic resistance in AHS from throats are rare in Korea. A total of 333 healthy school children were subjected to recovery of AHS from the throat, and antibiotic susceptibility tests were screened with the disk diffusion method. The rate of resistance to erythromycin was 22.2%, to clindamycin 12.0%, and to cefotaxime 3.0%. Whereas the resistance rate of S. pneumoniae to erythromycin exceeds 70% in Korea, pharyngeal AHS showed low resistance rates. (Korean J Clin Microbiol 2008;11:69-70)