Revision of Laboratory Testing Guidelines for Initial Diagnosis of Hematologic Neoplasms

Human Induced Pluripotent Stem Cells: Clinical Significance and Applications in Neurologic Diseases

The generation of human induced pluripotent stem cells (iPSCs) from somatic cells using gene transfer opens new areas for precision medicine with personalized cell therapy and encourages the discovery of essential platforms for targeted drug development. iPSCs retain the genome of the donor, may regenerate indefinitely, and undergo differentiation into virtually any cell type of interest using a range of published protocols. There has been enormous interest among researchers regarding the application of iPSC technology to regenerative medicine and human disease modeling, in particular, modeling of neurologic diseases using patient-specific iPSCs. For instance, Parkinson’s disease, Alzheimer’s disease, and spinal cord injuries may be treated with iPSC therapy or replacement tissues obtained from iPSCs. In this review, we discuss the work so far on generation and characterization of iPSCs and focus on recent advances in the use of human iPSCs in clinical setting.

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.

Development of Statistical Software for the Korean Laboratory Accreditation Program Using R Language: LaboStats

BACKGROUND: In Korea, the Korean Laboratory Accreditation Program (KLAP) has set minimum standards for verification of clinical test performance. This verification process is time-consuming and labor-intensive when performed manually. We developed a free, statistical software program for KLAP, using the R language (R Foundation for Statistical Computing, Vienna, Austria). METHODS: We used CLSI guidelines for the algorithm. We built graphic user interfaces, including data input, with Embarcadero Delphi EX4 (Embarcadero Technologies, Inc., Texas, USA). The R Base Package and MCR Package for Method Comparison Regression were used to implement statistical and graphical procedures. RESULTS: Our program LaboStats has six modules: parallel test, linearity, method comparison, precision, reference interval, and cutoff. Data can be entered into the field either manually or by copying and pasting from an MS Excel worksheet. Users can print out precise reports. CONCLUSIONS: LaboStats can be useful for evaluating clinical test performance characteristics and preparing documents requested by KLAP.

Human Induced Pluripotent Stem Cells: Clinical Significance and Applications in Neurologic Diseases

The generation of human induced pluripotent stem cells (iPSCs) from somatic cells using gene transfer opens new areas for precision medicine with personalized cell therapy and encourages the discovery of essential platforms for targeted drug development. iPSCs retain the genome of the donor, may regenerate indefinitely, and undergo differentiation into virtually any cell type of interest using a range of published protocols. There has been enormous interest among researchers regarding the application of iPSC technology to regenerative medicine and human disease modeling, in particular, modeling of neurologic diseases using patient-specific iPSCs. For instance, Parkinson’s disease, Alzheimer’s disease, and spinal cord injuries may be treated with iPSC therapy or replacement tissues obtained from iPSCs. In this review, we discuss the work so far on generation and characterization of iPSCs and focus on recent advances in the use of human iPSCs in clinical setting.

An Automated Draft Report Generator for Peripheral Blood Smear Examinations Based on Complete Blood Count Parameters

BACKGROUND: Complete blood count (CBC) results play an important role in peripheral blood smear (PBS) examinations. Many descriptions in PBS reports may simply be translated from CBC parameters. We developed a computer program that automatically generates a PBS draft report based on CBC parameters and age- and sex-matched reference ranges. METHODS: The Java programming language was used to develop a computer program that supports a graphical user interface. Four hematology analyzers from three different laboratories were tested: Sysmex XE-5000 (Sysmex, Kobe, Japan), Sysmex XN-9000 (Sysmex), DxH800 (Beckman Coulter, Brea, CA, USA), and ADVIA 2120i (Siemens Healthcare Diagnostics, Eschborn, Germany). Input data files containing 862 CBC results were generated from hematology analyzers, middlewares, or laboratory information systems. The draft reports were compared with the content of input data files. RESULTS: We developed a computer program that reads CBC results from a data file and automatically writes a draft PBS report. Age- and sex-matched reference ranges can be automatically applied. After examining PBS, users can modify the draft report based on microscopic findings. Recommendations such as suggestions for further evaluations are also provided based on morphological findings, and they can be modified by users. The program was compatible with all four hematology analyzers tested. CONCLUSIONS: Our program is expected to reduce the time required to manually incorporate CBC results into PBS reports. Systematic inclusion of CBC results could help improve the reliability and sensitivity of PBS examinations.

Report on the Project for Establishment of the Standardized Korean Laboratory Terminology Database, 2015

The National Health Information Standards Committee was established in 2004 in Korea. The practical subcommittee for laboratory test terminology was placed in charge of standardizing laboratory medicine terminology in Korean. We aimed to establish a standardized Korean laboratory terminology database, Korea-Logical Observation Identifier Names and Codes (K-LOINC) based on former products sponsored by this committee. The primary product was revised based on the opinions of specialists. Next, we mapped the electronic data interchange (EDI) codes that were revised in 2014, to the corresponding K-LOINC. We established a database of synonyms, including the laboratory codes of three reference laboratories and four tertiary hospitals in Korea. Furthermore, we supplemented the clinical microbiology section of K-LOINC using an alternative mapping strategy. We investigated other systems that utilize laboratory codes in order to investigate the compatibility of K-LOINC with statistical standards for a number of tests. A total of 48,990 laboratory codes were adopted (21,539 new and 16,330 revised). All of the LOINC synonyms were translated into Korean, and 39,347 Korean synonyms were added. Moreover, 21,773 synonyms were added from reference laboratories and tertiary hospitals. Alternative strategies were established for mapping within the microbiology domain. When we applied these to a smaller hospital, the mapping rate was successfully increased. Finally, we confirmed K-LOINC compatibility with other statistical standards, including a newly proposed EDI code system. This project successfully established an up-to-date standardized Korean laboratory terminology database, as well as an updated EDI mapping to facilitate the introduction of standard terminology into institutions.

Identification of the ABO*cis-AB04 Allele With a Unique Substitution C796A: The First Case in Korea

No abstract available.

Pseudohypoaldosteronism in a newborn male with functional polymorphisms in the mineralocorticoid receptor genes

Hyponatremia and hyperkalemia in infancy can be attributed to various causes, originating from a variety of renal and genetic disorders. Pseudohypoaldosteronism type 1 (PHA1) is one of these disorders, causing mineralocorticoid resistance that results in urinary salt wasting, failure to thrive, metabolic acidosis, and dehydration. PHA1 is heterogeneous in etiology. Inactivating mutations in the NR3C2 gene (4q31.1), which encodes the mineralocorticoid receptor, causes a less severe autosomal dominant form that is restricted to the kidney, while mutations in the amiloride-sensitive epithelial sodium channel gene (alpha subunit=SCNN1A, 12p13; beta subunit=SCNN1b, 16p12.2-p12.1; gamma subunit=SCNN1G, 16p12) causes a more severe autosomal recessive form, which has systemic effects. Here we report a neonatal case of kidney restricted PHA1 (renal type of PHA1) who first showed laboratory abnormalities before obvious PHA1 manifestations, with two functional polymorphisms in the NR3C2 gene. This is the second genetically confirmed case in Korea and the first to show functional polymorphisms that have previously been reported in the literature.

ABO*Ael03/O Genotype with ABO Discrepancy: The First Case in Korea

The Ael subgroup expresses the least amount of A antigens and could only be detected by performing the adsorption-elution test. The frequency of the Ael subgroup is about 0.001% in Koreans, and the Ael02 allele, which originates from A102, is the most frequently identified allele in the Korean population. We report a Korean family with the Ael03 allele identified by molecular genetic analysis. To the best of our knowledge, this is the first such report in Korea to date.

Therapy-Related Acute Megakaryoblastic Leukemia in a Lung Cancer Patient

No abstract available.

Factors Affecting the Freshness of Transfused Packed Red Blood Cells / 대한수혈학회지

BACKGROUND: The relationship between the storage age of packed red blood cells (pRBCs) and clinical outcomes is controversial. However, no systematic study regarding how fresh pRBCs were transfused to patients have been available so far. Therefore, we newly defined concepts for supply age (period from blood collection to supply to hospital), storage age (period from supply to transfusion to patient), and transfusion age (supply age plus storage age) and investigated them. The factors affecting each age were also analyzed. METHODS: A retrospective analysis for three ages of pRBCs was performed for patients who were transfused > or =1 pRBCs unit at three university hospitals between January 2009 and December 2013. Inventory age (period from blood collection to inventory check point at each blood bank) was prospectively checked on a daily basis for 30 days. Four blood centers and blood groups of transfused pRBCs were included. RESULTS: The mean supply, storage, and transfusion ages of pRBCs were 6.2, 6.0, and 12.0 days, respectively. 58%, 61%, and 66% of total transfused pRBCs were in a fresh category of supply, storage, and transfusion ages correspondingly. Storage and transfusion ages were affected by ABO blood group, hospitals, and years in listing orders. Inventory age was mainly affected by ABO blood group and hospitals. CONCLUSION: The freshness of transfused pRBCs was affected by hospitals and blood centers. Therefore, using the supply, storage, transfusion, and inventory ages as new norms can be useful to establishment of inventory and supply policies of hospitals and blood centers.

Epidemiologic Features of Parainfluenza Virus Type 1, 2 and 3 Infection in Seoul and a Neighboring Area, 2008-2011 / 대한임상미생물학회지

BACKGROUND: Parainfluenza virus (PIV) is a significant cause of acute respiratory infections. Epidemiological information on PIV infection could be very helpful for patient management. The aim of this study was to investigate the epidemiology of PIV infection in Seoul and a neighboring area with regard to PIV type. METHODS: The diagnosis of PIV infection was made by virus isolation. The R-mix Too cell system (Diagnostic Hybrids, Inc., Athens, OH, USA) and D3 Ultra DFA Respiratory Virus Screening & ID kits (Diagnostic Hybrids, Inc.) were used for virus culture and identification. The medical records of patients with positive virus cultures were reviewed retrospectively. RESULTS: Seven hundred and ten PIV viruses (5.6%) were isolated from 12,723 specimens. The number of subjects with PIV type III, I and II was 357, 304 and 49, respectively. PIV infection showed a peak incidence in the first year of life regardless of subtypes. The most common diagnosis among all PIV subtypes was pneumonia. Lower respiratory tract infections constituted the majority (76.3%) of PIV infections. The most common diagnosis of PIV type I and II was croup and that of PIV type III was pneumonia. A difference in seasonal variation between subtypes was observed. PIV I (62.2%) was mainly isolated from July to September while PIV type III (86.8%) was isolated from April to July. CONCLUSION: Lower respiratory infection was most commonly found in hospitalized patients with PIV infection. Clinical features of PIV infection were similar those seen in Western PIV reports, with the exception of the seasonal outbreak pattern.

A Case of Atypical Chronic Myeloid Leukemia with the JAK2V617F Mutation

Atypical chronic myeloid leukemia (aCML) is a rare leukemic disorder that shows myelodysplastic and myeloproliferative features simultaneously. The Janus kinase 2 gene V617F mutation (JAK2V617F) in aCML has been the source of much controversy. Some JAK2V617F positive cases have been reported but others observed no JAK2V617F mutation in aCML as defined by WHO classification. Recently, we experienced a case of aCML with JAK2V617F mutation with typical myelodysplastic/myeloproliferative features in peripheral blood and bone marrow aspirates. The karyotype was normal and no BCR/ABL1, PDGFRA or PDGFRB gene rearrangement was noted with FISH analysis. JAK2V617F mutation of the case was identified with amplification refractory mutation system PCR and direct sequencing. We also studied JAK2V617F mutation status in 3 additional cases of previously diagnosed aCML in our institution, but no mutation was identified.

A Case of Concomitant Inv(3)(q21q26) and Cryptic BCR/ABL1 Rearrangement in the Blast Crisis of Chronic Myeloid Leukemia

Structural abnormalities of the long arm of chromosome 3 (3q) have been associated with elevated platelet count and hyperplasia of megakaryocytes with dysplasia in various hematological malignancies. Some cases of chronic myeloid leukemia (CML) may acquire inv(3) (q21q26) or t(3;3)(q21;q26), and such a finding usually indicates accelerated or blast phase of their disease. We report a case of concomitant inv(3) (q21q26) and cryptic BCR/ABL1 rearrangement in the blast crisis of CML. The patient was 17-year-old male and showed marked leukocytosis and thrombocytosis at admission. Leukocyte differentials showed eosinophilia, basophilia and increased blasts. The bone marrow was hypercellular with granulocytic hyperplasia, and dysmorphic megakaryocytes were frequently observed. Conventional cytogenetic analysis revealed only an inv(3)(q21q26) and no Philadelphia chromosome was observed. FISH and RT-PCR analyses confirmed cryptic BCR/ABL1 rearrangement. The patient responded poorly with imatinib and induction chemotherapy, and expired during the course of 2nd chemotherapy with increased dose of imatinib.

Clinical Characteristics and Comparison of the Various Methods Used for the Diagnosis of the New Influenza A Pandemic in Korea

BACKGROUND: Laboratory diagnosis of new influenza A (H1N1) is crucial for managing patients and establishing control and prevention measures. We compared the diagnostic accuracies of the real time RT-PCR (rRT-PCR) test recommended for the confirmation of the new flu and the viral culture method used conventionally for viral disease with that of the rapid antigen test (RAT). METHODS: We performed RAT, R-mix culture, and real-time PCR by using 861 respiratory samples collected from December 2009 to January 2010 and evaluated the abilities of these methods to detect new influenza A. The relationship among the positive rates of RAT, grades of culture, and the cycle threshold (Ct) values of rRT-PCR was also evaluated. RESULTS: Of the 861 patients, 308 (35.8%) were diagnosed with new influenza A. The sensitivities, specificities, positive predictive values, and negative predictive values of the tests were respectively as follows: 59.7%, 99.5%, 98.4%, and 81.6% for RAT; 93.2%, 100%, 100%, and 96.3% for R-mix culture; and 95.8%, 100%, 100%, and 97.7% for rRT-PCR. Samples with weak positive grade in culture and those with Ct values of 30-37 in rRT-PCR showed positivities as low as 25.3% and 2.3% in RAT, respectively. The hospitalization rate and death rate of the confirmed patients were 3.2% and 0.3%, respectively, and gastrointestinal symptoms were observed in 7.2% of the patients. CONCLUSIONS: R-mix culture and rRT-PCR tests showed excellent reliability in the diagnosis of new influenza A and could be very useful, especially for samples with low viral load.

A Case of Therapy-related Acute Lymphoblastic Leukemia with t(11;19)(q23;p13.3) and MLL/MLLT1 Gene Rearrangement / 대한진단검사의학회지

Therapy-related ALL (t-ALL) is a rare secondary leukemia that develops after chemotherapy and/or radiotherapy for primary malignancies. Chromosomal 11q23 abnormalities are the most common karyotypic alterations in t-ALL. The t(11;19)(q23;p13) aberration is extremely rare and has not been confirmed at the molecular genetic level. Here, we report a case of t-ALL with t(11;19)(q23;p13.3) and MLL-MLLT1 (alias ENL) gene rearrangement confirmed by cytogenetic analysis, multiplex reverse transcription-PCR (multiplex RT-PCR), and DNA sequencing in a patient who had undergone treatment for breast cancer. A 40-yr-old woman developed acute leukemia 15 months after undergoing 6 cycles of adjuvant chemotherapy (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2), radiation therapy (dose, 5,900 cGy), and anticancer endocrine therapy with tamoxifen. The complete blood cell counts and bone marrow examination showed increased blasts and the blasts showed B lineage immunophenotype (positive for CD19, CD34, and cytoplasmic CD79a). Cytogenetic analysis revealed the karyotype 47,XX,+X,t(11;19)(q23;p13.3)[4]/46,XX[16]. FISH analyses, multiplex RT-PCR, and DNA sequencing confirmed the MLL-MLLT1 gene rearrangement. The patient underwent induction chemotherapy with fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) and achieved complete remission. Subsequently, she underwent consolidation chemotherapy, but died of brain ischemia in the pons and the region of the middle cerebral artery. To our knowledge, this is the first case report of t-ALL with t(11;19)(q23;p13.3) and the MLL-MLLT1 gene rearrangement.

A Patient with Fatal Septicemia Caused by a Rare Pathogen Dermabacter Hominis

Dermabacter hominis (D. hominis) is a recently discovered gram-positive bacterial species, and it is usually recognized as an opportunistic human pathogen. Very few documented cases of severe infections caused by Dermabacter hominis have been published. In this report, we describe a case of fatal septicemia caused by Dermabacter hominis.

Immune Hemolytic Anemia after ABO-mismatched Liver Transplantation: A Case Report / 대한수혈학회지

Limitations due to lack of appropriate available donors for liver transplantation necessitates the use of ABO-mismatched donors. Transplantation of ABO-mismatched solid organs is sometimes associated with the development of immune hemolytic anemia, which is caused by production of antibodies by the donor B lymphocytes in a primary or secondary immune response against the recipient's red blood cell antigens. This condition is referred to as Passenger Lymphocyte Syndrome (PLS). PLS is more frequent in heart and lung transplants than in liver and kidney transplants with incidence of PLS in liver transplantation at 30~40%. When present, PLS typically manifests 1~3 weeks after transplantation, and subsides within 3 months after symptoms are first detected. In most patients, PLS is self-limiting and exhibits mild symptoms, but in some cases PLS can be life-threatening. We report a case of immune hemolytic anemia after an ABO-mismatched liver transplantation involving a blood group O donor and a blood group A recipient, and successful treatment of the resulting PLS symptoms by transfusion of gamma-irradiated group O Red Blood Cells (RBCs) accompanied by administration of 60 mg/day of methylprednisolone for 1 week.

Evaluation of Various Formulae for Glomerular Filtration Rate Estimation and Proposal of New Formulae for the Korean Population / 대한진단검사의학회지

BACKGROUND: Some researchers have questioned the necessity of adjusting glomerular filtration rate (GFR) by body surface area (BSA). We compared the relationship between estimated GFR (eGFR) and radionuclide GFR (rGFR) with or without BSA adjustment by comparing the results obtained using various formulae with those obtained using 2 new proposed formulae. METHODS: A retrospective study was performed using 204 Korean individuals whose GFR had been estimated by the (99m)Tc-diethylenetriaminepentaacetic acid method between March 2004 and July 2008. We used the modification of diet in renal disease (MDRD) II formula, Mayo clinic quadratic (MCQ) formula, Cockcroft-Gault (CG) formula, and lean body mass-adjusted CG formula. Two new formulae, skeletal muscle mass index (SMI)-adjusted CG formula and SMIx3.4/SCr, were proposed by us. We analyzed each parameter with Pearson's correlation coefficient and also obtained the bias values. RESULTS: BSA did not satisfy the fundamental prerequisites of an adjustment factor for rGFR. MDRD II and MCQ GFR estimates demonstrated higher Pearson's correlation coefficient with BSA-unadjusted rGFR than they did with BSA-adjusted rGFR. The other GFR formulae estimates showed better correlation with rGFR and more favorable bias (P<0.001) when both GFR estimates and rGFR values were BSA-unadjusted. SMI-adjusted CG and SMIx3.4/SCr GFR estimates demonstrated correlation with rGFR and bias values similar to those of the MDRD II and CG GFR estimates. CONCLUSIONS: We suggest that absolute, non-corrected GFR and GFR estimate be preferred in daily practice. The absolute, non-corrected GFR and GFR estimate are considered helpful for patients with eGFR< or =60 mL/min/1.73 m2. We also recommend the clinical use of the new formulae, SMI-adjusted CG and SMIx3.4/SCr (BSA-unadjusted).