Usefulness of Chromosomal Microarray in Hematologic Malignancies: A Case of Aggressive NK-cell Leukemia with 1q Abnormality

A variety of clonal cytogenetic abnormalities have been reported in aggressive natural killer (NK)-cell lymphoma and leukemia. Recent chromosomal microarray studies have shown both gain and loss of 1q and loss of 7p as recurrent abnormalities in aggressive NK-cell leukemia. Here, we report a case of aggressive NK-cell leukemia with complex chromosomal gains and losses, as confirmed by chromosomal microarray analysis. The patient showed an aggressive clinical course, which was complicated by hemophagocytic lymphohistiocytosis. Conventional cytogenetic analysis revealed trisomy 3 and 1q gain only. However, chromosomal microarray analysis detected an additional gain of 1q21.1–q24.2 and a loss of 1q24.2–q31.3. These abnormal lesions might play a role in the pathogenesis of aggressive NK-cell leukemia by inactivating tumor suppressor genes or by activating oncogenes. These results suggest that chromosomal microarray analysis may be used to provide further genetic information for patients with hematological malignancies, including aggressive NK-cell leukemia.

The Effects of Weight Control Behaviors among Korean Obese Adults / 가정의학회지

BACKGROUND: This study aimed to identify and examine the effects of weight control behaviors correlated with weight loss in obese individuals who attempted to lose weight within the past year. METHODS: In this cross-sectional study, data from 9,461 obese individuals were collected from the fifth and sixth Korean National Health and Nutrition Examination Survey (2010–2014). Three of nine verified methods of weight control suggested in the survey were selected: diet therapy (reduced food intake), exercise therapy (exercise), and medication therapy (prescribed weight loss medications). Participants were divided into one of seven groups (diet therapy alone; exercise therapy alone; drug therapy alone; combined diet and exercise therapy; combined exercise and drug therapy; combined diet and drug therapy; or combined diet, exercise, and drug therapy). Logistic regression analysis was used to determine whether the group that tried to lose weight in the past year had indeed lost weight compared to the group that did not. RESULTS: The odds ratios for weight loss (≥3 but < 6 kg vs. ≥6 but < 10 kg) for the combined therapies were 2.05 (95% confidence interval, 1.23–3.41) for combined diet and exercise therapy and 5.43 (1.74–16.92) for combined diet, exercise, and drug therapy. CONCLUSION: All levels of weight loss were significantly associated with combined diet and exercise therapy. Weight loss ≥6 kg but < 10 kg was significantly associated with combined diet and exercise therapy as well as with combined diet, exercise, and medication therapy among individuals who tried to lose weight in the past year.

Association between Breastfeeding and Prevalence of Diabetes in Korean Parous Women: The Korea National Health and Nutrition Examination Survey, 2010–2014 / 가정의학회지

BACKGROUND: It is well known that breastfeeding has a significant impact on the health of mothers and children. With the growing importance of breastfeeding, the present study aimed to investigate the relationship between breastfeeding and the prevalence of diabetes in Korean parous women. METHODS: The data of 5,448 premenopausal parous women aged 20–49 years who agreed to participate in the 5th–6th Korea National Health and Nutrition Examination Survey were analyzed in this study. Control group included women who had not breastfed. The subjects who had breastfed were classified into three groups based on the duration of breastfeeding: 0–6 months, 6–12 months, and >12 months. The variables included age, body mass index, education level, income, alcohol drinking, smoking, family history of diabetes, use of oral contraceptives, the number of pregnancies, and regular exercise. RESULTS: Among the subjects, the prevalence of diabetes was significantly lower in women who had breastfed compared to those who had not, with an odds ratio of 0.534 (95% confidence interval [CI], 0.289–0.976) in women who breastfed for 0–6 months and 0.575 (95% CI, 0.321–0.990) in women who breastfed for 6–12 months (both P < 0.05). CONCLUSION: The present study found a reduced prevalence of diabetes in women who had breastfed compared to those who had not. However, no association between the duration of breastfeeding and the prevalence of diabetes could be found.

Relationship between Marital Status and Metabolic Syndrome in Korean Middle-Aged Women: The Sixth Korea National Health and Nutrition Examination Survey (2013–2014) / 가정의학회지

BACKGROUND: This study aimed to investigate the relationship between marital status and the incidence of metabolic syndrome in Korean middle-aged women. METHODS: Based on data from the sixth Korea National Health and Nutrition Examination Survey (2013–2014), 3,225 women aged 40–69 years were subjected to the analysis. Marital status was categorized as married, unmarried, separated, widowed, or divorced. The odds ratios (ORs) for metabolic syndrome were calculated based on marital status. After adjustment for age, income level, education level, alcohol intake, smoking status, leisure physical activity, menopause status, daily calories, and fat intake, changes in the OR for metabolic syndrome based on marital status were examined by multivariate logistic regression analysis. RESULTS: The OR for metabolic syndrome in the widowed group to the married group was 4.818 (95% confidence interval [CI], 3.861–6.002; P < 0.001) and that after adjustment of age, economic level, education level, alcohol intake, smoking status, physical activity, menopause status, total daily calories, and fat intake was 2.141 (CI, 1.432–3.199; P < 0.001), both of which were statistically significant. The OR for metabolic syndrome in the unmarried group to the married group was 0.246 (CI, 0.141–0.431; P < 0.001) after adjustment of all components. On the contrary, the ORs of the separated group and the divorced group to the married group were not significant. CONCLUSION: In comparison with the married middle-aged group, the widowed middle-aged group tended to have a higher risk of metabolic syndrome, which is speculated to be related to socioeconomic factors and health behavior.

Risk Factors for Vancomycin-Associated Nephrotoxicity in Elderly Patients

OBJECTIVE: Infection is very common in the elderly, so there is a high prevalence of antibiotics use among this population. Especially, due to the emergence of resistant bacteria, the use of vancomycin is growing. The purpose of this study was to evaluate risk factors associated with vancomycin-induced nephrotoxicity in elderly patients. METHODS: The subjects of this study were patients over 18 years old who received intravenous vancomycin in a general hospital located in Gangneung-si, Korea between August 1, 2013 and July 31, 2015. Data collection regarding vancomycin use and baseline characteristics was conducted using computerized hospital database. Logistic regression analysis was used to identify risk factors associated with vancomycin-induced nephrotoxicity. RESULTS: A total of 290 patients were finally included, and 191(66%) out of these patients were age 65 or older. The incidence of vancomycin-induced nephrotoxicity was 11.0%, 12.6%, and 7.0% in the all adult patients, the elderly patients, and the non-elderly patients, respectively. There were significant differences in comorbidities between patients with nephrotoxicity and patients without nephrotoxicity in the all adult patients, and there were significant differences in vancomycin duration, comorbidities, and number of nephrotoxic agents between patients with nephrotoxicity and patients without nephrotoxicity in the elderly patients. However, according to the logistic regression analysis, there was no significant risk factor that increases the incidence of vancomycin-induced nephrotoxicity in all three age groups. CONCLUSION: There were no differences in risk factors that increase the incidence of vancomycin-induced nephrotoxicity between all adult patients, elderly patients, and non-elderly patients. Further studies with larger sample sizes to identify risk factors associated with vancomycin-induced nephrotoxicity in the elderly to improve the outcome of pharmacotherapy are required.

A Case of Primary Anti-D Alloimmunization by RHD (c.1227G>A) DEL Red Blood Cell Transfusion / 대한수혈학회지

The Rh blood group D antigen is the most immunogenic of all antigens, next to ABO antigens. Anti-D immunization is clinically important since it may cause clinical problems, such as severe hemolytic transfusion reactions and hemolytic disease of the newborn. DEL is an extremely weak D variant that cannot be detected by basic serologic typing and is typed as D-negative without the absorption-elution techniques and RHD genotyping. Of the DEL phenotype, RHD (c.1227G>A) allelic variant is the most common in Korea. The DEL phenotype has been considered to carry only a few D antigens to induce anti-D immunization, but a few cases have reported that this allelic variant is capable of inducing anti-D immunization in a D-negative recipient, for which it is clinical significant. Herein, we present a case of primary anti-D alloimmunization in a RhD negative patient after receiving RHD (c.1227G>A) DEL red cell transfusion identified by serological and molecular tests, including RHD genotyping.

A Case of Hemolytic Disease of the Fetus and Newborn due to Anti-S Antibody: The First Case in Korea / 대한수혈학회지

A full term male infant was admitted to the neonatal intensive care unit due to jaundice and mild hemolytic anemia within the first 24 hours of his life. The total serum bilirubin level was 11.2 mg/dL at 24 hours of age. The patient was RhD positive and blood group A, and his mother was RhD positive and blood group B. The direct and indirect antiglobulin tests of the infant were all positive. On antibody screening and identification tests, anti-S antibodies were identified from both the infant and mother. The RBC phenotyping for S antigen revealed positive for infant and negative for mother. This report documents the first case of hemolytic disease of the fetus and newborn due to the anti-S antibody in Korea.

Performance of the Elecsys HIV combi PT Assay Compared to the ARCHITECT HIV Ag/Ab Combo Assay

BACKGROUND: The aim of this study was to compare the analytical sensitivity and specificity of the recently updated 4th generation Elecsys HIV combi PT assay (Roche Diagnostics GmbH, Germany) to those of the ARCHITECT HIV Ag/Ab Combo assay (Abbott Laboratories, Germany). METHODS: A total of 2,003 fresh random clinical samples, 4 HIV seroconversion panels, a WHO International Standard p24 antigen sensitivity panel, 5 HIV-1 subtype viral lysates, and 5 HIV-1 subtype antibodies were tested in comparative studies with the Elecsys HIV combi PT and ARCHITECT HIV Ag/Ab Combo assays. Samples were assayed with both tests on the same day. The MP Diagnostics HIV Western Blot 2.2 Assay, the Elecsys HIV p24 Ag Test and Confirmatory Test, and the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test were performed as supplementary tests. RESULTS: Both the Elecsys and ARCHITECT assays detected viral antigens in all four seroconversion panels on the same bleed days, and had lower limits of detection of <1 IU/mL with the p24 antigen sensitivity panel. The ARCHITECT assay showed slightly higher sensitivity in detecting viral antigens with some HIV-1 subtype viral lysates, while the Elecsys assay was more sensitive in detecting each of the 5 HIV-1 subtype antibodies. Both assays detected 5/5 HIV+ clinical samples correctly. The analytical specificities of the Elecsys and ARCHITECT assays were 99.90% and 99.80%, respectively. CONCLUSIONS: The Elecsys HIV combi PT assay performed comparably to the ARCHITECT HIV Ag/Ab Combo assay. Thus, the Elecsys HIV combi PT assay is suitable for diagnostic testing in university hospital settings.

Evaluation of the Wisecheck Glucose Monitoring System

BACKGROUND: Glucometers are widely used for self-monitoring and point-of-care testing in diabetes management. We evaluated the performance of the recently developed Wisecheck Glucose Monitoring System (Wisemeditech, Korea) compared to that of 2 other well-known glucometer systems. METHODS: The Wisecheck glucometer was evaluated for precision, linearity, and carryover rate. One-hundred fifty samples samples were tested, and the results obtained from the Wisecheck glucometer, ACCU-CHEK Performa (Roche Diagnostics, Germany) and SD GlucoLink (SD Diagnostics, Korea) were compared to those obtained using the laboratory reference method from the Toshiba 200FR (Toshiba, Japan), according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: The coefficient of variation (CV) values for within-run imprecision at low, middle, and high levels were 2.06%, 1.02%, and 2.02%, respectively, and the CV values for total-run imprecision at low, middle, and high levels were 2.98%, 2.41%, and 1.88%, respectively. In the linearity test, the coefficient of determination (R2) was 0.9985 in glucose concentration ranging from 48.6 mg/dL to 428 mg/dL (P<0.0001). The results obtained using the Wisecheck glucometer were well correlated with those obtained using the Toshiba 200FR (R2=0.980, P<0.0001). The carryover rate was 0.12%. CONCLUSIONS: The Wisecheck glucometer showed good precision, linearity, and correlation with the reference method. It provided rapid and reliable measurements of blood glucose levels and seemed appropriate for use in diabetes management.

Chromosomal Abnormalities in Myelodysplastic Syndrome with Near-tetraploidy: A Case Report

Massive hyperdiploidy and tetraploidy are rare cytogenetic abnormalities in myelocytic malignancies, especially in myelodysplastic syndrome (MDS). These abnormalities are known to be associated with leukemogenesis, leukemic transformation and poor prognosis. We report here the first case of MDS with near-tetraploid cytogenetic abnormality in Korea. A 80-yr-old male was diagnosed with refractory anemia with excess blasts-2 (RAEB-2). Bone marrow aspiration smear showed 16% of blasts, which were large sized myeloid blasts with irregular margins and cytoplasmic vacuolation. Cytogenetic analysis of bone marrow cells revealed numercal and structural cytogenetic abnormalities including near-tetraploidy in 8 of 20 metaphases: 45,XY,add(1)(p36.1),del(10)(p11.2),del(11)(q13),-12,-16,der(17)t(11;17) (q13;q21),add(20)(q13.1),+mar[8]/85~90,idemx2[cp8]/46,XY[4]. After chemotherapy with decitabine, he showed pancytopenia during follow-up period and died of sepsis 14 months after the diagnosis.

Evaluation of the Automated Instrument QWALYS-3 for Unexpected Antibody Screening / 대한수혈학회지

BACKGROUND: The use of automated techniques reduces the impact of human errors in blood banking and it improves the standardization and the quality of the achieved results. Erythrocyte Magnetized Technology (EMT) is now being widely used due to its simplicity and efficiency for detecting alloantibody. We evaluated the antibody screening test of the QWALYS-3 (DIAGAST, Loos Cedex, France). METHODS: The evaluation focused on antibody screening using the QWALYS-3 as compared to the standard manual tube method and the Ortho BioVue system in clinical samples (n=100) and frozen stored samples (n=64), which had RBC alloantibody. RESULTS: Using the manual tube method, the sensitivity of antibody screening was 100% by the QWALYS-3 and 42.8% by the Ortho BioVue in the clinical samples (n=7) and 2 results were discrepant by the QWALYS-3 for negative samples. For the known antibodies from the frozen stored samples (n=64) this correspondence rate amounted to 93.7% (n=60). CONCLUSION: The QWALYS-3 system displayed a good match rate with the Ortho BioVue system (92%). It also showed reliable results for the general accuracy when compared to the manual method (concordance rate: 98%). The QWALYS-3 system will facilitate the automation of routine antibody screening with high reliability, sensitivity and specificity compared to the standard manual methods.

Evaluation of the LG Advansure(TM) Malaria P.f./P.v. real-time QPCR for the Diagnosis of Malaria

BACKGROUND: Malaria is a problematic disease in Korea, and microscopic examination of Giemsa-stained blood smear has been used as the gold standard for its diagnosis. However, this technique is time-consuming and has low sensitivity in samples with low numbers of malarial parasites (<20 parasites/microL). Here, we evaluated the performance characteristics of the LG Advansure(TM) Malaria P.f./P.v. real-time QPCR (LG life sciences, Korea). METHODS: Blood samples from 173 persons who visited Korea University Ansan Hospital were evaluated. QPCR was performed in 73 malaria patients and 100 healthy subjects by using the LG Advansure Malaria P.f./P.v. real-time QPCRR kit, and the results were compared with those of microscopy. The detection limit of this kit was determined by serial dilution of Plasmodium-infected blood with normal blood (blood not infected with Plasmodium). RESULTS: Among the 73 patients that were microscopically confirmed to have malaria (Plasmodium vivax infection, N=70, P. falciparum infection, N=3), 69 patients were diagnosed with P. vivax infection and 3 were diagnosed with P. falciparum infection by LG Advansure(TM) Malaria P.f./P.v. real-time QPCR. Both the tests indicated absence of infection in the 100 healthy subjects. The detection limit of LG Advansure(TM) Malaria P.f./P.v. real-time QPCR was 0.1 parasite/microL. CONCLUSIONS: LG Advansure(TM) Malaria P.f./P.v. real-time QPCR is a very sensitive and specific technique and can be used as a confirmatory test for malaria.

A Case of Hemophagocytic Lymphohistiocytosis with Clonal Karyotype Abnormalities

There have been a few reports of hemophagocytic lymphohistiocytosis (HLH) with chromosomal abnormalities. Clonal chromosomal abnormalities in HLH patients are usually found in association with hematologic malignancies and rarely with epstein-barr virus (EBV) infection. Here, we report a fatal case of HLH with clonal karyotype abnormalities. A 75-yr-old man was admitted with persistent anorexia and high fever. Laboratory data revealed pancytopenia, hypofibrinogenemia, hyperferritinemia, prolonged prothrombin time and activated partial thromboplastin time, and marked elevated level of serum transaminases. In real time-PCR using whole blood, EBV DNA was not detected but cytomegalovirus (CMV) DNA was detected. The bone marrow aspiration smear showed hyperplasia of mature histiocytes with prominent hemophagocytosis. In chromosomal analysis of bone marrow aspirates, complex chromosomal abnormalities were found. In spite of steroid pulse therapy and antibiotic treatment, he died of disseminated intravascular coagulopathy.

Evaluation of ABO Antibody Titration Using Tube and Column Agglutination Techniques

BACKGROUND: ABO antibody titration is useful for the evaluation of ABO-incompatible bone marrow or solid organ transplantations, yet the results quite vary between different test methods used. We compared the results of microcolumn agglutination and tube methods. METHODS: Anti-A and anti-B isoagglutionin titers were determined in 63 healthy individuals (23 O, 20 A, and 20 B blood groups) using 4 different methods: immediate spin tube (tube), microcolumn agglutination without anti-human globulin (AHG) (CAT), tube with AHG (tube-AHG) and microcolumn agglutination with AHG (CAT-AHG). RESULTS: The median (range) titers of anti-A and anti-B in group O individuals by tube, CAT, tube-AHG, and CAT-AHG methods were 64 (8-512), 64 (8-512), 128 (8-2,048), and 128 (16-2,048); 64 (16-128), 128 (16-256), 128 (16-512), and 256 (16-512), respectively. The median (range) titers of anti-A in group B and anti-B in group A individuals by the four methods were 64 (16-128), 128 (8-128), 128 (8-256), and 256 (8-256); 64 (8-128), 64 (8-128), 32 (8-128), and 64 (8-256), respectively. The isoagglutinin titer measured by CAT-AHGmethod was the highest. The titers measured by CAT and CAT-AHG methods were 0-1 titer higher than those by tube and tube-AHG methods, respectively. Whatever method was used, the isoagglutinin titers were higher in women than in men. CONCLUSIONS: CAT-AHG was the most sensitive method among the four methods tested. Since AHG titer values are critical for the clinical management and CAT has less manual procedures than tube method, CAT-AHG method could be used for the standardization of ABO antibody titration in different institutions.

The Frequency of Unexpected Antibodies by Using Two Micro-column Agglutination Systems: DiaMed-ID and Ortho BioVue Systems / 대한수혈학회지

BACKGROUND: Unexpected antibody screening and identification tests are very important for safe blood transfusion. The micro-column agglutination test (MCAT) is widely used due to its simplicity and efficiency for detecting alloantibodies. We analyzed the frequency of unexpected antibodies at three university hospital blood banks, which use two different MCAT systems. METHODS: From February 2002 to December 2009, a total of 295,876 unexpected antibody screening tests were performed at three university hospital blood banks. Two hospital blood banks (Anam and Ansan Hospitals) used the DiaMed-ID system (DiaMed Ag, Switzerland) and the other (Guro Hospital) used the Ortho BioVue system (Ortho-Clinical Diagnostics, USA) for antibody screening and identification tests. RESULTS: The rates of detecting unexpected antibodies on screening test based on the 'tests performed' and the 'persons tested' were 1.16% per test and 0.96% per person in Korea University Guro Hospital, 0.65% and 0.41% in Korea University Anam Hospital and 0.76% and 0.57% in Korea University Ansan hospital, respectively. There were significant differences in the frequencies based on the two different systems (P<0.001). Among the warm antibodies, Rh antibodies were more frequently detected by the DiaMed-ID system, and Lewis antibodies were most frequently detected by the Ortho BioVue System. CONCLUSION: We should carefully interpretate the frequency of unexpected antibodies in the Korean population because the frequencies of unexpected antibodies are different according to different employed micro-column agglutination systems.

Characteristics of Intron 6 Nucleotide Sequences of cis-AB in Koreans / 대한수혈학회지

BACKGROUND: The cis-AB is a very rare phenotype in the ABO blood group system. It corresponds to a special ABO allele that encodes glycosyltransferase that is capable of synthesizing both A and B antigens. Until now, the exon 6 and 7 gene sequences of cis-AB alleles are well known. In this study, we report on the intron 6 sequence structure of the cis-AB allele. METHODS: Standard serologic tests for the ABO blood group phenotypes were performed in four cis-AB samples. Allele-separation by cloning and subsequent sequencing was carried out. RESULTS: The results showed that intron 6 of cis-AB is almost identical to the A101 allele except for three single nucleotide polymorphisms at nucleotide positions 163, 179 and 662, where the nucleotides of the A101 replace those of B101. CONCLUSION: The intron 6 sequences of cis-AB in Koreans have both A101 and B101 blood group sequences.