Genomic Signatures from Clinical Tumor Sequencing in Patients with Breast Cancer Having Germline BRCA1/2 Mutation / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#BRCA1 and BRCA2 are among the most important genes involved in DNA repair via homologous recombination (HR). Germline BRCA1/2 (gBRCA1/2)-related cancers have specific characteristics and treatment options but conducting gBRCA1/2 testing and interpreting the genetic imprint are sometimes complicated. Here, we describe the concordance of gBRCA1/2 derived from a panel of clinical tumor tissues using next-generation sequencing (NGS) and genetic aspects of tumors harboring gBRCA1/2 pathogenic variants. @*Materials and Methods@#Targeted sequencing was performed using available tumor tissue from patients who underwent gBRCA1/2 testing. Comparative genomic analysis was performed according to gBRCA1/2 pathogenicity. @*Results@#A total of 321 patients who underwent gBRCA1/2 testing were screened, and 26 patients with gBRCA1/2 pathogenic (gBRCA1/2p) variants, eight patients with gBRCA1/2 variants of uncertain significance (VUS; gBRCA1/2v), and 43 patients with gBRCA1/2 wild-type (gBRCA1/2w) were included in analysis. Mutations in TP53 (49.4%) and PIK3CA (23.4%) were frequently detected in all samples. The number of single-nucleotide variants (SNVs) per tumor tissue was higher in the gBRCA1/2w group than that in the gBRCA1/2p group (14.81 vs. 18.86, p=0.278). Tumor mutation burden (TMB) was significantly higher in the gBRCA1/2w group than in the gBRCA1/2p group (10.21 vs. 13.47, p=0.017). Except for BRCA1/2, other HR-related genes were frequently mutated in patients with gBRCA1/2w. @*Conclusion@#We demonstrated high sensitivity of gBRCA1/2 in tumors analyzed by NGS using a panel of tumor tissues. TMB value and aberration of non-BRCA1/2 HR-related genes differed significantly according to gBRCA1/2 pathogenicity in patients with breast cancer.

Differential Impact of Serum 25-Hydroxyvitamin D3 Levels onthe Prognosis of Patients with LiverCirrhosis According to MELD andChild-Pugh Scores

Background@#Prognosis of patients with diverse chronic diseases is reportedly associated with 25-hydroxyvitamin D levels. In this study, we investigated the potential role of 25-hydroxyvitamin D3 (25[OH]D3) levels in improving the predictive power of conventional prognostic models for patients with liver cirrhosis. @*Methods@#We investigated clinical findings, including serum 25(OH)D3 levels at admission, of 155 patients with cirrhosis who were followed up for a median of 16.9 months. @*Results@#Median 25(OH)D3 levels were significantly different among patients exhibiting Child-Pugh grades A, B, and C. Mortality, including urgent transplantation, was significantly associated with 25(OH)D3 levels in univariate analysis. Severe vitamin-D deficiency (serum 25[OH]D3 level < 5.0 ng/mL) was significantly related to increased mortality, even after adjusting for Child-Pugh and Model for End-stage Liver Disease (MELD) scores. In particular, the presence of severe vitamin D deficiency clearly defined a subgroup with significantly poorer survival among patients with Child-Pugh scores of 5–10 or MELD scores ≤ 20. A new combination model of MELD score and severe vitamin D deficiency showed significantly more accurate predictive power for short- and long-term mortality than MELD scores alone. Additionally, serum 25(OH)D3 levels and new model scores were significantly associated with the development of spontaneous bacterial peritonitis, overt encephalopathy, and acute kidney injury. @*Conclusion@#Serum 25(OH)D3 level is an independent prognostic factor for patients with liver cirrhosis and has a differential impact on disease outcomes according to MELD and Child-Pugh scores.

Comparison of Biotin Interference in Second- and Third-Generation Roche Free Thyroxine Immunoassays

No abstract available.

Evaluation of Analytical Performance of an Automated Glycated Hemoglobin Analyzer, HLC-723 G11

Quality Assurance of Diagnostic Immunologic Tests for Screening of Transfusion-Transmissible Infections at Korean Blood Centers / 대한수혈학회지

The Korean government previously established a national blood policy and national blood system based on basic and essential legislation. This achievement was the result of collaborative efforts between the Korean Centers for Disease Control and Prevention, the Korean Society of Blood Transfusion, the Korean Society for Laboratory Medicine, the Laboratory Medicine Foundation, and/or the Korean Association of External Quality Assessment Service. To ensure a safe and effective transfusion, a comprehensive quality assurance (QA) system to assess every process from donor selection to transfusion is mandatory. From a blood safety perspective, selection of appropriate donor blood screening tests for transfusion-transmissible infections (TTI) and the QA program is of great importance. In this article, we review legislation regarding the national blood policy and national blood system as well as the selection logic regarding diagnostic immunologic tests for TTI and quality assurance efforts for TTI of each blood center.

Effect of Irradiation on Microparticles in Red Blood Cell Concentrates

Changes in microparticles (MP) from red blood cell (RBC) concentrates in the context of irradiation have not been investigated. The aim of this study was to evaluate how irradiation affects the number of MPs within transfusion components. Twenty RBC concentrates, within 14 days after donation, were exposed to gamma rays (dose rate: 25 cGy) from a cesium-137 irradiator. Flow cytometry was used to determine the numbers of MPs derived from RBC concentrates before and 24 hr after irradiation. The mean number of MPs (±standard deviation) in RBC concentrates was 21.9×10(9)/L (±22.7×10(9)/L), and the total number of MPs ranged from 2.6×10(9)/L to 96.9×10(9)/L. The mean number of MPs increased to 22.6×10(9)/L (±31.6×10(9)/L) after irradiation. Before irradiation, the CD41-positive and CD235a-positive MPs constituted 9.5% (1.0×10(9)/L) and 2.2% (263×10(6)/L) of total MPs, respectively. After irradiation, CD41-positive MPs increased to 12.1% (1.5×10(9)/L) (P=0.014), but the CD235a-positive MPs decreased to 2.0% (214×10(6)/L) of the total MPs (P=0.369). Irradiation increases the number of CD41-positive MPs within RBC concentrates, suggesting the irradiation of RBC concentrates could be associated with thrombotic risk of circulating blood through the numerical change.

Development of Severe Hemolytic Anemia after Treatment with Anti-D Immunoglobulin in a Patient with Immune Thrombocytopenic Purpura / 대한수혈학회지

A 78-year-old female was admitted due to nasal bleeding and purpuric macules on both legs. The patient underwent renal biopsy, and a diagnosis of Henoch-Schonlein purpura nephritis was made. The patient's platelet count was 1.6x10(10)/L, and, based on results from bone marrow biopsy, the patient was diagnosed with immune thrombocytopenic purpura. Despite treatment with glucocorticoid and IV immunoglobulin, thrombocytopenia continued. The patient's blood group was Rhesus D positive and treatment with IV anti-D immunoglobulin followed. Thereafter, platelet count showed a rapid increase; however, occurrence of hemolytic anemia, hyperbilirubinemia, and hemoglobinuria consistent with intravascular hemolysis was observed.

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.

A Case of Anti-Sda Proven by Urine Neutralization Test

Anti-Sda is of no clinical significance, because it rarely causes hemolytic transfusion reactions. Even when its presence is suspected during antibody screening test, further identification of the antibody is usually not performed. We experienced a case of anti-Sda in 73 yr-old male patient showing mixed field agglutination by microcolumn agglutination. Antibody specificity could not be identified by conventional antibody identification test, and it was proven to be anti-Sda by urine neutralization test. In spite of its little clinical significance, it may give incompatible crossmatching results reacting with Sda antigen, which occurs at a high frequency in general population. When incompatible crossmatch results arising from anti-Sda are suspected, the problem may be solved by using the urine-neutralized serum of in crossmatching test.

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.

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.

Using Genotyping to Identify an A1B(weak) Blood Group / 대한수혈학회지

Since an exact ABO blood type match is essential for transfusion therapy, any ABO discrepancies should be resolved prior to the issuing of blood. The authors confirmed the ABO blood group of a 50-year-old male using genotyping. On a routine blood group test, the cell type was A+; however, anti-B was undetected in his serum. To determine the cause of this ABO discrepancy, an adsorption elution test and saliva test were performed. The presence of a weak B substance was suspected despite no evidence of the B antigen on red blood cells. Polymerase-chain-reaction restriction-fragment-length-polymorphism (PCR-RFLP) and sequencing analysis of exons 6 and 7 demonstrated that his blood type was A1Bweak (the A allele tested as the A105 subtype, while the B allele was most similar to the B302 subtype). Again, using genotyping, we subsequently confirmed the A1Bweak blood type in a leukemic patient who was in complete remission.

Clinical Evaluation of SD CHECK GOLD as Point-of-care Glucose Meter / 임상검사와정도관리

BACKGROUND: Self-monitoring devices for blood glucose are widely used as a point-of-care testing (POCT) in the management of diabetic patients. In the present study, we evaluated the performance of SD CHECK GOLD Blood Glucose Testing System (SD diagnostic, Korea) using electrochemical detection technique. METHODS: SD CHECK GOLD was tested for linearity, precision and comparison of method. Other glucometers including ACCU CHEK ACTIVE (Roche Diagnostics Ltd., Germany) and ONE TOUCH ULTRA (Lifescan Inc., USA) were compared for the same categories according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: SD CHECK GOLD revealed good linearity in glucose concentration ranging from 50 mg/dL to 550 mg/dL (r(2)=0.9931). In the precision study, within-run precision and total-run precision (CV)s were within 10%. Excellent correlation was found between SD CHECK GOLD and Toshiba 200FR (Toshiba, Japan) (y=0.9212x, r=0.9756). CONCLUSIONS: SD CHECK GOLD showed good linearity, precision, and correlation with the reference method. No significant effect of testing procedure or operator was found. SD CHECK GOLD provided rapid and reliable results for blood glucose and seemed to be appropriate for the clinical useful in the management of diabetic patients.

An Experience with Unexpected Antibody Screening Tests using a Panel That Included Di(a) Cells in Koreans / 대한수혈학회지

BACKGROUND: In Korea, a screening panel of cells from abroad without Di(a) positive cells has been commonly used when a patient has an unexpected antibody screening test. It has been reported that Di(a) occurs with a frequency of 6.14 to 14.5% among Koreans. However, the current popular antibody screening panels contain no Di(a) positive cells. In this study, we evaluate the clinical usefulness of the Di(a) Cell Panel (Diagnostic Grifols, Barcelona, Spain) for Koreans. METHODS: A total of 3,372 pretransfusion samples were employed for unexpected antibody screening testing using panels of cells by the DG Gel microtube column agglutination system, including additional Di(a) cells (Diagnostic Grifols, Barcelona, Spain). The positive cases in this system were confirmed again with DiaMed Di(a) antigen positive panel cells (DiaMed Ag, Cresssier, Morat, Switzerland) and this was followed by sequence- based Diego genotyping. RESULTS: The positive detection rate of an unexpected antibody screening test using SeraScan Diana I and II was 1.07% (36/3372), and seven samples were reactive (1+~2+) with the SeraScan Di(a) panel cells (0.21%). However, among the 5 available genotyped samples, two cases were typed as Di(a-b+). CONCLUSION: Even though there is discrepancy between the genotype and the two antibody screening kits, the addition of Di(a) positive cells as unexpected antibody screening panel cells is recommended.