Performance Evaluation of Bruker Biotyper, ASTA MicroIDSys, and VITEK-MS and Three Extraction Methods for Filamentous Fungal Identification in Clinical Laboratories.

Filamentous fungi are a major cause of life-threatening infections in immunocompromised patients; thus, rapid and accurate identification is critical. Filamentous fungal identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been demonstrated with high sensitivity and reproducibility; however, its wider application has been limited in clinical laboratories because of practical challenges such as database availability or lack of standardization. In this study, we compared the performance of the Bruker Biotyper, ASTA MicroIDSys, and Vitek MS for 84 clinical filamentous fungal isolates. Moreover, the sensitivity of three independent sample preparation methods (direct, on plate, in tube) was compared. Bruker Biotyper identified 71.43% (60/84) of isolates correctly (species, genus, or complex/group level). ASTA MicroIDSys and Vitek MS showed accuracy rates of 70.24% (59/84) and 55.95% (47/84), respectively. We found that any difference in sensitivity may be attributed to the database of the systems. In addition, the "in tube" method showed the highest sensitivity among the three methods; however, there was no statistical difference among them. For the broader application of MALDI-TOF MS for filamentous fungal identification, further studies from multiple perspectives are required.

Effects of age and gender on the cytochrome P450 2D6 activity in a Korean population.

WHAT IS KNOWN AND OBJECTIVE: Age and gender have been reported to play a crucial role in modulating the disposition of pharmacological agents, and to influence the activities of cytochrome P450 (CYP) 2D6, a drug-metabolizing enzyme involved in the disposition of clinically used drugs. In the present study, the effects of age and gender on the CYP2D6 activity were evaluated using dextromethorphan as a probe drug in humans. METHODS: Healthy young (20 < age < 30 years, n = 60) and old age (age >60 years, n = 60) subjects were enrolled and were given 15 mg dextromethorphan orally. Blood samples were collected before and 3 h after medication. Dextromethorphan and its metabolite dextrorphan were measured using HPLC-fluorescence, and dextromethorphan metabolic ratio (MR, log [dextromethorphan/dextrorphan]) was used to evaluate the CYP2D6 activity. RESULTS AND DISCUSSION: Mean (±SD) dextromethorphan MR was -2.42 ± 0.46 for the young male group, -2.28 ± 0.56 for the young female group, -2.46 ± 0.55 for the older male group and -2.34 ± 0.65 for the old female group. Based on our findings, the effects of age and gender on CYP2D6 activity were not statistically significant. WHAT IS NEW AND CONCLUSION: The results of the present study indicate that age and gender play a minor role in the modulation of CYP2D6 activity in the Korean population.

Evaluation of global laboratory methods and establishing on-therapy ranges for monitoring apixaban and rivaroxaban: Experience at a single institution.

BACKGROUND: Apixaban and rivaroxaban are approved for the prevention and treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), and embolic stroke in atrial fibrillation (AF) patients. The aim of this study was to find appropriate methods of monitoring the anticoagulant effects of are direct oral anticoagulants (DOACs) and establish on-therapy ranges using conventional tests. METHODS: A total of 184 samples were collected from 91 patients receiving DOACs. Concentrations of apixaban and rivaroxaban in plasma were accessed by an anti-factor Xa chromogenic assay. PT, APTT, antithrombin, D-dimer, dRVVT screen/confirm, FDP, and fibrinogen levels were measured. On-therapy ranges were calculated by substituting previously reported trough plasma concentrations of DOACs. RESULTS: Anti-factor Xa chromogenic assay-based DOACs levels were 26.0-279.5 (115.9 ± 56.5) ng/mL for apixaban at 2.5 mg BID, 19.9-565.1 (205.3 ± 162.4) ng/mL for apixaban at 5 mg BID, 2.3-395.3 (205.3 ± 162.4) ng/mL for rivaroxaban at 15 mg OD, 3.6-494.8 (119.6 ± 95.1) ng/mL for rivaroxaban at 20 mg OD, and 9.6-431.4 (140.8 ± 113.6) ng/mL for rivaroxaban at 15 mg BID. PT (%), antithrombin, and dRVVT confirm tests showed good correlation with plasma apixaban levels. Plasma rivaroxaban concentrations were correlated well with PT (sec), PT (%),and dRVVT confirm results. On-therapy ranges established for dRVVT confirm test by linear regression were as follows: 1.32-1.52 for apixaban 2.5 mg BID, 1.12-1.75 for apixaban 5 mg BID, 1.11-1.78 for rivaroxaban 15 mg OD, 1.09-1.64 for rivaroxaban 20 mg OD, and 1.22-1.81 for rivaroxaban 20 mg BID. CONCLUSIONS: Apixaban concentrations were well correlated with PT (%), antithrombin, and dRVVT confirm test. Rivaroxaban concentrations showed good correlation with PT (sec), PT (%), and dRVVT confirm test.

How useful is bone marrow study as an initial investigative tool without lymph node biopsy in malignant lymphoma?: Eleven years of experience at a single institution.

BACKGROUND: Bone marrow (BM) study plays an important role as initial investigation specimen of lymphoma as well as staging lymphoma. This study aimed to investigate the utility of BM studies for classification of lymphoma and evaluate features of BM involvement by lymphoma over a period of 11 years. METHODS: A total of 1162 cases of BM studies for lymphoma evaluation were reviewed for the incidence of lymphoma subtypes, the percentage of marrow involvement, the pattern of involvement and discordance with histopathologic diagnoses of lymph nodes and other tissues. RESULTS: A total of 255 of 1162 cases underwent BM study without pathologic information, and 108 cases show lymphoma involvement. Lymph node biopsy underwent in 66 cases, and 10 cases show discordant result between BM and lymph node biopsy. Seven discordant cases were due to insufficient further studies. Lymphoma was diagnosed only by BM study in 38 cases. Abnormal lymphocytes were found in BM aspiration in 34 cases. Also, abnormal clonal lymphocytes were detected by flow cytometry in 26 cases. Four cases showed disease-related chromosomal abnormalities. FISH analysis detected abnormal findings in two cases, however, discordant with other additional studies. CONCLUSIONS: Discrepancies between the BM study and lymph node biopsy were due to insufficient further study and discordance of immunohistochemical stain result. BM study can be utilized as initial diagnosis of lymphoma by the combination of morphological feature, involvement pattern, and additional tests such as flow cytometry, chromosomal analysis, and FISH analysis. Thus, BM study with further analysis is an essential choice when lymph node biopsies are unavailable.

Detection and genomic analysis of genital group B streptococcus in pregnant Korean women.

AIM: Group B streptococcus (GBS) is a leading cause of life-threatening bacterial infections among newborns, and neonates born to heavily colonized women may be subject to vertical transmission. We sought to determine an appropriate detection method for genital GBS in pregnant women by comparing culture-based methods and real-time polymerase chain reaction (PCR). In addition, we performed molecular serotyping and multilocus sequence typing (MLST) on isolates. METHODS: A total of 150 pregnant women were enrolled and underwent vaginal-rectal swabbing at 16-40 weeks of gestation. GBS was identified by conventional culture and real-time PCR with or without enrichment. Molecular serotyping and MLST were performed on isolates. RESULTS: Overall genital GBS positive rate among the 150 study subjects was 17.3%. Direct culture identified 18 (12.0%) positive specimens, enrichment culture 22 (14.6%), direct PCR 24 (16.0%) and enrichment PCR 25 (16.6%). The sensitivity and specificity by direct and enrichment PCR were as follows: for direct PCR, 90.9% and 96.9%, respectively; and for enrichment PCR, 95.5% and 96.9%, respectively. Resistance rates to clindamycin and erythromycin were 33.3% and 19.1%, respectively. Serotype III-1 was the most common (26.3%), followed by serotype Ib (21.1%), III-3 (15.8%), V (15.8%), II (10.5%), IV (5.3%) and VI (5.3%). Most common sequence types (ST) were ST-1, ST-19 and ST-862 (15.8%), followed by ST-2 and ST-654 (10.5%). CONCLUSION: Direct real-time PCR using vaginal-rectal specimen could be used for detecting GBS in emergent conditions. Molecular serotypes III, Ib and V were most common. MLST analysis frequently presented ST-1, ST-19 and ST-862.

Laboratory diagnosis of Clostridium difficile infection: Comparison of Techlab C. diff Quik Chek Complete, Xpert C. difficile, and multistep algorithmic approach.

BACKGROUND: Clostridium difficile is a major pathogen responsible for nosocomial infectious diarrhea. We explored optimal laboratory strategies for diagnosis of C. difficile infection (CDI) in our clinical settings, a 1400-bed tertiary care hospital. METHODS: Using 191 fresh stool samples from adult patients, we evaluated the performance of Xpert C. difficile (Xpert CD), C. diff Quik Chek Complete (which simultaneously detects glutamate dehydrogenase [GDH] and C. difficile toxins [CDT]), toxigenic culture, and a two-step algorithm composed of GDH/CDT as a screening test and Xpert CD as a confirmatory test. RESULTS: Clostridium difficile was detected in 35 samples (18.3%), and all isolates were toxigenic strains. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of each assay for detecting CDI were as follows: Quik Chek Complete CDT (45.7%, 100%, 100%, 89.1%), Quik Chek Complete GDH (97.1%, 99.4%, 97.1%, 99.4%), Xpert CD (94.3%, 100%, 100%, 98.7%), and toxigenic culture (91.4%, 100%, 100%, 98.1%). A two-step algorithm performed identically with Xpert CD assay. CONCLUSION: Our data showed that most C. difficile isolates from adult patients were toxigenic. We demonstrated that a two-step algorithm based on GDH/CDT assay followed by Xpert CD assay as a confirmatory test was rapid, reliable, and cost effective for diagnosis of CDI in an adult patient setting with high prevalence of toxigenic C. difficile.

Performance evaluation of Mindray CAL 8000(BC-6800 and SC-120) hematology analyzer and slidemaker/stainer.

INTRODUCTION: The Mindray CAL 8000 is a cellular analysis line that consists of the BC-6800, an automated hematology analyzer, and the SC-120, an automated slidemaker/stainer. We evaluated the performances of the BC-6800 and the SC-120. METHODS: Four hundred and eight normal and abnormal samples were analyzed. The performance of the BC-6800 and Sysmex XE-2100 were compared, and blood films by the SC-120 and manual method were compared according to the CLSI guideline H26-A2 and H20-A2. RESULTS: Most parameters measured by the BC-6800 matched well with the XE-2100 and manual differential. The flag efficiency of the BC-6800 for blasts (95.3%) and atypical lymphocytes (92.6%) were higher while immature granulocytes (89.7%) and NRBCs (94.1%) were lower than that of the XE-2100. Additionally, the BC-6800 detected four of five samples infected with plasmodium parasites. The SC-120 showed no carry-over and expected repeatability. There was good agreement on the five-part differential including abnormal cells between blood films by the SC-120 and manually prepared blood films. The shape of the RBC was also comparable between blood films. CONCLUSION: The CAL-8000 analysis line is beneficial for precise, fast hematology work, and even more useful in malaria endemic areas.

Ahcyl2 upregulates NBCe1-B via multiple serine residues of the PEST domain-mediated association.

Inositol-1,4,5-triphosphate [IP3] receptors binding protein released with IP3 (IRBIT) was previously reported as an activator of NBCe1-B. Recent studies have characterized IRBIT homologue S-Adenosylhomocysteine hydrolase-like 2 (AHCYL2). AHCYL2 is highly homologous to IRBIT (88%) and heteromerizes with IRBIT. The two important domains in the N-terminus of AHCYL2 are a PEST domain and a coiled-coil domain which are highly comparable to those in IRBIT. Therefore, in this study, we tried to identify the role of those domains in mouse AHCYL2 (Ahcyl2), and we succeeded in identifying PEST domain of Ahcyl2 as a regulation region for NBCe1-B activity. Site directed mutagenesis and coimmunoprecipitation assay showed that NBCe1-B binds to the N-terminal Ahcyl2-PEST domain, and its binding is determined by the phosphorylation of 4 critical serine residues (Ser151, Ser154, Ser157, and Ser160) in Ahcyl2 PEST domain. Also we revealed that 4 critical serine residues in Ahcyl2 PEST domain are indispensable for the activation of NBCe1-B using measurement of intracellular pH experiment. Thus, these results suggested that the NBCe1-B is interacted with 4 critical serine residues in Ahcyl2 PEST domain, which play an important role in intracellular pH regulation through NBCe1-B.

Anemia as a useful biomarker in patients with diffuse large B-cell lymphoma treated with R-CHOP immunochemotherapy.

The aim of the current study is to evaluate the prognostic value of anemia, an easily estimable parameter in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy. A total of 157 patients with newly diagnosed diffuse large B-cell lymphoma treated with ≥1 cycle of R-CHOP were included. Hemoglobin level without red cell transfusion within 7 days of initiation of treatment was chosen as a parameter of baseline cancer-induced anemia. To investigate the clinical significance of chemotherapy-induced anemia and its recovery after completion of treatment, 87 patients in complete remission for ≥6 months from the time of the last cycle of R-CHOP were grouped and analyzed separately. Patients with a cancer-induced anemia of hemoglobin <10 g/dL showed inferior event-free and disease-free survival compared to those with hemoglobin ≥10 g/dL. This finding was observed irrespective of the status of pre-treatment bone marrow involvement. In multivariate analysis, hemoglobin <10 g/dL was found to be an international prognostic index-independent prognostic factor. Risk of relapse was significantly higher for patients who were still anemic at 6 months after R-CHOP, compared to those who achieved complete recovery from chemotherapy-induced anemia within 6 months.

Prognostic role of serum lactate dehydrogenase beyond initial diagnosis: a retrospective analysis of patients with diffuse large B cell lymphoma.

BACKGROUND/AIMS: Baseline serum lactate dehydrogenase (LDH) level is a well-known prognostic factor in patients with non-Hodgkin's lymphoma; however, its role beyond initial diagnosis has not yet been defined. METHODS: This study was conducted as a retrospective analysis of patients with diffuse large B cell lymphoma (DLBCL) treated with R-CHOP21, who had undergone regular checks for LDH during immunochemotherapy (n = 119) and during the posttreatment follow-up period after complete remission (CR; n = 100). The 119 patients were classified into 4 groups according to their baseline and change in LDH level during treatment, and an analysis of tumor response and survival was performed. The value of LDH as a predictor for relapse was evaluated among the patients with regular follow-up visits after achieving CR. RESULTS: An increased LDH level during immunochemotherapy had no impact on tumor response or survival, and only the LDH status 'before' treatment was a prognostic marker. The sensitivity, specificity, positive predictive value and negative predictive value of serum LDH for detecting relapse after CR were 47.4, 86.5, 9.3 and 98.3%, respectively. CONCLUSION: The measurement of LDH level beyond initial diagnosis has no clear benefit in predicting disease progression or relapse in patients with DLBCL treated with R-CHOP21.

Bone marrow involvement is predictive of infusion-related reaction during rituximab administration in patients with B cell lymphoma.

PURPOSE: The purpose of this study is to evaluate risk factors for infusion-related reaction (IRR) following rituximab administration in patients with B cell non-Hodgkin lymphoma. METHODS: A retrospective analysis was conducted of patients with newly diagnosed B cell lymphoma who have received rituximab-included immunochemotherapy with appropriate premedication and commonly used schedule of infusion rate. IRRs were graded by review of the patients' electronic medical record according to the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: One hundred and sixty-nine patients were included in the analysis and most of the patients (150; 88.8 %) had diffuse large B cell lymphoma (DLBCL). Thirty-six patients (21.3 %) had any grade of IRRs: 23 patients were grade (G) 1 (13.6 %), 13 had ≥G2 IRRs (7.7 %), and only 4 had ≥G3 IRRs (2.4 %). All except one patient had IRR during the first cycle and only two had repetitive IRR thereafter. Bone marrow (BM) involvement was the strongest risk factor for IRR in multivariable analysis (odds ratio 4.06, 95 % confidence interval 1.67-9.89; p = 0.002). A subgroup analysis confined to patients with DLBCL showed very similar results when compared with the entire population, and patients with DLBCL who had ≥G2 IRR showed shorter event-free and overall survival when compared to those who did not. CONCLUSIONS: BM involvement is predictive of occurrence of IRR during rituximab administration in patients with B cell lymphoma. More intensive premedication and careful observation for IRR during rituximab administration are required for patients with B cell lymphoma who have BM involvement.

The relationship between iron parameters and platelet parameters in women with iron deficiency anemia and thrombocytosis.

Changes of platelet count (PLT) and platelet parameters have been reported in iron deficiency anemia (IDA). However, the relationship between iron metabolism and thrombopoiesis is not yet fully known. We studied the relationship between iron and platelet parameters in women with IDA and thrombocytosis. Forty-one adult women with IDA and thrombocytosis were enrolled. The relationship between iron parameters (such as serum iron, serum ferritin, total iron-binding capacity (TIBC)C, and transferrin saturation (Tfsat)), and platelet parameters (PLT, platelet crit (PCT), mean platelet volume (MPV), mean platelet component (MPC), mean platelet mass, platelet distribution width, and large platelet (LPLT)), which measured with CBC on ADVIA, were investigated. In addition, the difference in platelet and iron parameters between severe IDA (Hb < 7 g/dl) and non-severe IDA were compared. PLT inversely correlated with serum iron and Tfsat (p < 0.05). Serum iron and TIBC revealed no significant relationships with any platelet parameters. PLT, PCT, and MPV inversely correlated with mean corpuscular hemoglobin concentration (MCHC) but MPC exhibited linear correlation with Hb, hematocrit, and MCHC (p < 0.05). PCT had linear correlation with PLT and MPV (p < 0.001), whereas PCT, MPV, and LPLT (p < 0.001 for two formers, p < 0.05) inversely correlated with MPC. In this study, the important iron parameters affecting PLT were serum iron and Tfsat. In addition, patients with more severe and hypochromic anemia had higher PLT, PCT, and MPV.

Short-Term (6 Weeks) Experience of a Modular Workcell for Hemostasis Testing Including an Intelligent Data Manager at a Tertiary Care Hospital.

OBJECTIVE: Modular workcells could be a better solution than total laboratory automation (TLA) in hemostasis laboratories. Here, we evaluated the impact of implementing a modular workcell (HemoCell) with an intelligent data management facility (HemoHub). METHODS: We compared the turnaround times (TATs), numbers of rerun samples, and rerun times pre- and postimplementation of the HemoCell at Gil Medical Center. Prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, and fibrinogen were evaluated. RESULTS: The TAT standard deviations (SDs) and maximum TAT values decreased after HemoCell implementation, although the mean TATs for PT, aPTT, and D-dimer were increased. Numbers of rerun samples were increased (18.1/day vs 44.7/day). However, rerun times were reduced, and SDs were decreased during the post-HemoCell period compared with pre-HemoCell. Additionally, technologists needed smaller working space and less labor. CONCLUSION: The modular workcell could improve quality and efficiency by providing more consistent TATs and shorter rerun times in the hemostasis laboratory.

Role of FDG-PET/CT in detecting lymphomatous bone marrow involvement in patients with newly diagnosed diffuse large B-cell lymphoma.

To evaluate the role of FDG-PET/CT in detecting bone marrow (BM) involvement, pre-treatment bilateral bone marrow biopsies (BMBs) and FDG-PET/CT scans of 89 patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-CHOP were reviewed and analyzed. Fourteen patients (15.7%) had lymphomatous involvement based on BMB (BMB+), and 17 patients (19.1%) had the possibility of BM involvement on FDG-PET/CT (FDG-PET/CT+). Seventy-two patients (80.8%) had concordant results between BMB and FDG-PET/CT (seven patients were positive for both, and 65 patients were negative for both), but 17 patients (19.2%) had a discordant interpretation (seven patients were BMB+ and FDG-PET/CT-, and ten were BMB- and FDG-PET/CT+). Although BMB+ patients had an inferior 2-year EFS (37.0% vs. 79.8%, p < 0.001) and OS (36.3% vs. 81.0%, p < 0.001) compared to BMB- patients, no differences in EFS (62.6% vs. 72.7%, p = 0.185) and OS (59.4% vs. 78.0%, p = 0.146) were shown between FDG-PET/CT+ and FDG-PET/CT- patients. Whereas six of seven patients with diffuse hypermetabolism were BMB+, only one of ten patients with focal hypermetabolism was BMB+. The results suggest that FDG-PET/CT had a limited value to detect BM involvement in patients with DLBCL. Focal hypermetabolism of hematopoietic BM in FDG-PET/CT had no impact on survival.

Mycobacterium wolinskyi infection confirmed by rpoB gene sequencing.

Identification of rapidly growing mycobacteria (RGM) is problematic because there are many taxonomic changes. 16S rRNA gene is commonly used to identify Mycobacterium species, but alternative gene targets have been introduced for more accurate identification. We report a rare case of a prosthetic knee infection due to Mycobacterium wolinskyi. The isolate was not identified by 16S rRNA gene sequencing alone and substantially confirmed by rpoB gene sequencing. The identification was delayed because our laboratory did not routinely identify RGM to the species level. Simultaneous sequencing of both 16S rRNA and rpoB genes will allow rapid and accurate identification of M. wolinskyi isolates.

Frequencies of glycosylphosphatidylinositol (GPI)-deficient cells using high-sensitivity flow cytometry as per the 2018 ICCS/ESCCA consensus guideline in patients with hematologic malignancy, aplastic anemia, or cytopenia.

OBJECTIVES: We examined the frequencies and sizes of glycosylphosphatidylinositol (GPI)-deficient cells as per the International Clinical Cytometry Society/European Society for Clinical Cell Analysis (ICCS/ESCCA) consensus guidelines for the high-sensitivity detection of GPI-deficient cells. METHODS: In 2018, the ICCS/ESCCA guidelines for the high-sensitivity detection of GPI-deficient cells were published. We evaluated frequencies and sizes of GPI-deficient red blood cells (RBCs), neutrophils, and monocytes as determined using the ICCS/ESCCA guidelines and Clinical and Laboratory Standards Institute (CLSI) guidelines in patients with a hematologic malignancy, aplastic anemia, or cytopenia. RESULTS: A total of 106 (38.7%) patients exhibited GPI deficiency in at least one blood cell lineage. GPI-deficient cells of one or more lineages were found in 62.7% of patients with a hematologic malignancy, 51.1% of patients with aplastic anemia, and 23.4% of patients with cytopenia. GPI-deficient monocytes were most frequently detected in all three groups. By population size, GPI-deficient clones (>1%) in monocytes were mostly detected in patients with a hematologic malignancy or aplastic anemia. Rare cells with GPI deficiency (<0.1%) in monocytes were most common among patients with cytopenia. CONCLUSION: High-sensitive flow cytometry analysis including monocytes may be necessary for patients with a hematologic disorder.

Guidelines for Mobile Laboratories for Molecular Diagnostic Testing of COVID-19.

With the rapid spread of the coronavirus disease (COVID-19), the need for rapid testing and diagnosis and consequently, the demand for mobile laboratories have increased. Despite this need, there are no clear guidelines for the operation, maintenance, or quality control of mobile laboratories. We provide guidelines for the operation, management, and quality control of mobile laboratories, and specifically for the implementation and execution of COVID-19 molecular diagnostic testing. These practical guidelines are primarily based on expert opinions and a laboratory accreditation inspection checklist. The scope of these guidelines includes the facility, preoperative evaluation, PCR testing, internal and external quality control, sample handling, reporting, laboratory personnel, biosafety level, and laboratory safety management. These guidelines are useful for the maintenance and operation of mobile laboratories not only in normal circumstances but also during public health crises and emergencies.

Genotypic and Phenotypic Characteristics of Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Korean Patients.

BACKGROUND: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant cancer predisposition syndrome. HLRCC is characterized by the development of cutaneous leiomyomas, early-onset uterine leiomyomas, and HLRCC-associated renal cell cancer (RCC) and caused by germline fumarate hydratase (FH) deficiency. We investigated the genotypic and phenotypic characteristics of Korean patients with HLRCC. METHODS: We performed direct sequencing analysis of FH in 13 patients with suspected HLRCC and their family members. A chromosomal microarray test was performed in female patients with negative sequencing results but highly suspected HLRCC. In addition, we analyzed the clinical characteristics and evaluated the genotype-phenotype correlations in Korean patients with HLRCC. RESULTS: We identified six different pathogenic or likely pathogenic FH variants in six of the 13 patients (46.2%). The variants included two nonsense variants, two splicing variants, one frameshift variant, and one missense variant. Of the six variants, two (33.3%) were novel (c.132+1G>C, and c.243dup). RCC and early-onset uterine leiomyoma were frequently observed in families with HLRCC, while cutaneous leiomyoma was less common. No significant genotype-phenotype correlation was observed. CONCLUSIONS: We describe the genotypic and phenotypic spectrum in a small series of Korean patients with HLRCC. Our data reveal the unique characteristics of Korean patients with HLRCC and suggest a need for establishing an optimal diagnostic approach for them.

Performance of Copeptin for Early Diagnosis of Acute Myocardial Infarction in an Emergency Department Setting.

BACKGROUND: Rapid and accurate diagnosis of acute myocardial infarction (AMI) is critical for initiating effective treatment and achieving better prognosis. We investigated the performance of copeptin for early diagnosis of AMI, in comparison with creatine kinase myocardial band (CK-MB) and troponin I (TnI). METHODS: We prospectively enrolled 271 patients presenting with chest pain (within six hours of onset), suggestive of acute coronary syndrome, at an emergency department (ED). Serum CK-MB, TnI, and copeptin levels were measured. The diagnostic performance of CK-MB, TnI, and copeptin, alone and in combination, for AMI was assessed by ROC curve analysis by comparing the area under the curve (AUC). Sensitivity, specificity, negative predictive value, and positive predictive value of each marker were obtained, and the characteristics of each marker were analyzed. RESULTS: The patients were diagnosed as having ST elevation myocardial infarction (STEMI; N=43), non-ST elevation myocardial infarction (NSTEMI; N=25), unstable angina (N=78), or other diseases (N=125). AUC comparisons showed copeptin had significantly better diagnostic performance than TnI in patients with chest pain within two hours of onset (AMI: P=0.022, ≤1 hour; STEMI: P=0.017, ≤1 hour and P=0.010, ≤2 hours). In addition, TnI and copeptin in combination exhibited significantly better diagnostic performance than CK-MB plus TnI in AMI and STEMI patients. CONCLUSIONS: The combination of TnI and copeptin improves AMI diagnostic performance in patients with early-onset chest pain in an ED setting.

Vascular events in Korean patients with myeloproliferative neoplasms and their relationship to JAK2 mutation.

Evaluation of the Janus kinase 2 (JAK2) V617F mutation has been widely used for the diagnosis of myeloproliferative neoplasms (MPN). However, its prognostic relevance to clinical outcome is not completely understood. We investigated the association of JAK2 V617F with vascular events in Korean patients with myeloproliferative neoplasms (MPN). We studied 283 patients from 15 centers, who were diagnosed with MPN. The JAK2 V617F status was evaluated by allele-specific polymerase chain reaction (PCR) and sequencing. The patients' diagnoses were essential thrombocythemia (ET n = 146), polycythemia vera (PV n = 120), primary myelofibrosis (n = 12), and unclassifiable MPN (MPNu n = 5). JAK2 V617F was detected in 89 (61%) patients with ET, 103 (86%) with PV, four (33%) with myelofibrosis, and four (80%) with MPNu. A higher number of leukocytes, haemoglobin levels and BM cellularity as well as an older age, lower platelet counts, and diagnosis of PV were significantly correlated with JAK2 V617F. Eighty-three and 43 episodes of thrombosis and bleeding occurred in 100 patients each before and after the diagnosis. Vascular events more frequently occurred in 37% of patients with JAK2 V617F than in 29% of those without the mutation (p = 0.045). Among 175 patients whose samples were available for sequencing, 28 patients with homozygous JAK2 V617F had vascular events more frequently (57%) than those who were heterozygotes (39%) or had the wild type (27%) (p = 0.03). The multivariate analysis showed that a JAK2 homozygous mutation, hypercholesterolemia and older age were independent risk factors for a vascular event. The results of this study showed that Korean patients with MPN had a similar JAK2 mutation rate and frequency of vascular events when compared to Western patients. The presence of V617F was significantly related to vascular events. Therefore, initial evaluation for the JAK2 mutation and careful monitoring for vascular events should be performed in MPN patients.