Development and Validation of a Novel Warfarin Dosing Algorithm for Korean Patients With VKORC1 1173C

BACKGROUND: Differences in the performance of suggested warfarin dosing algorithms among different ethnicities and genotypes have been reported; this necessitates the development of an algorithm with enhanced performance for specific population groups. Previous warfarin dosing algorithms underestimated warfarin doses in VKORC1 1173C carriers. We aimed to develop and validate a new warfarin dosing algorithm for Korean patients with VKORC1 1173C.METHODS: A total of 109 patients carrying VKORC1 1173CT (N=105) or 1173CC (N=4) were included in this study. Multiple regression analysis was performed to deduce a new dosing algorithm. Following literature searches for genotype-guided warfarin dosing algorithms, 21 algorithms were selected and evaluated using the correlation coefficient (ρ) of actual dose and estimated dose, mean error, and root mean square error.RESULTS: The developed algorithm is as follows: maintenance dose (mg/week)=exp [3.223−0.009×(age)+0.577×(body surface area [BSA])+0.178×(sex)−0.481×(CYP2C9 genotype)+0.227×(VKORC1 genotype)]. Integrated variables explained 44% of the variance in the maintenance dose. The predicted and actual doses showed moderate correlation (ρ=0.641) with the best performance with a mean error of −1.30 mg/week. The proportion of underestimated groups was 17%, which was lower than with the other algorithms.CONCLUSIONS: This is the first study to develop and validate a warfarin dosing algorithm based on data from VKORC1 1173C carriers; it showed superior predictive performance compared with previously published algorithms.

ary Characteristics and Needs for Community Kitchens among Young Adults of Single-person Households in Seoul according to the Cooking Attitude / 대한지역사회영양학회지

Objectives@#This study examined the dietary characteristics and needs for community kitchens among young adults of single-person households in Seoul according to the cooking attitude. @*Methods@#During April 2018, an online survey was conducted on young adults of singleperson households in their 20s and 30s residing in Seoul. The respondents were classified into the more positive cooking attitude group (More Positive Group; n=152, mean=4.11) and the less positive cooking attitude group (Less Positive Group; n=190, mean=3.03) based on the mean score (3.51) of the 4-item 5-point Likert scales measuring the cooking attitude. The responses of the two groups were compared. @*Results@#Approximately 90% of the More Positive Group had the cooking ability to prepare ordinary meals or more advanced cooking skills, whereas only 61% of the Less Positive Group had such skills. Approximately a half of the More Positive Group cooked at home three times a week or more; only 30% of the Less Positive Group did so, and more than 30% of the group seldom cooked. The More Positive Group had higher mean scores in the levels of satisfaction with dietary life and care for food safety and nutrition than the Less Positive Group. Approximately 30% of all the respondents expressed their needs for community kitchens. The most frequently answered reason for such needs was “being able to have a meal with others”. @*Conclusions@#The young adults of single-person households with a more positive cooking attitude possessed a higher cooking ability, cooked more often, and cared more about food safety and nutrition than those with a less positive cooking attitude. There were moderate needs for community kitchens among young adults of single-person households living in Seoul. Therefore, societal efforts to improve their cooking attitude would be meaningful for improving their quality of dietary life. Cooking lessons or social dining programs based on community kitchens could be an option.

Analysis of hematologic parameters of donors, patients, and granulocyte concentrates to predict successful granulocyte transfusion

BACKGROUND: Granulocyte transfusion (GTx) is performed as a supportive therapy in severe neutropenic patients caused by various conditions. The study aimed to analyze the hematologic parameters of donors, patients, and granulocyte concentrates to predict successful GTx. METHODS: This study was performed in 281 donors, with their granulocyte concentrates being collected through apheresis, and in 54 severe neutropenic patients who had various hematologic diseases. Complete blood cell counts of donors pre- and post-apheresis, granulocyte concentrates, and patients pre- and post-GTx were analyzed. Patients were divided into two groups according to survival at discharge (Group S, survival; Group D, dead) to compare various factors including age, infection status, pre- and post-GTx total white blood cell counts (TWBCC) and absolute neutrophil counts (ANC), total number of GTx, infused TWBCC and ANC per weight, and use of G-CSF during therapy. RESULTS: Overall data of patients showed that both TWBCC and ANC were significantly increased after GTx (median values at pre-GTx, TWBCC=0.40×109/L, ANC=0.14×109/L; post-GTx, TWBCC=0.57×109/L, ANC=0.29×109/L, both P<0.0001). After GTx, Group S (N=25) showed significantly higher TWBCC and ANC than Group D (N=29) (P=0.01 and P=0.04, respectively). Using different cutoff levels, post-GTx TWBCC greater than 0.5×109/L showed statistically significant difference between the two groups (P<0.01). None of the other factors showed statistically significant differences. CONCLUSION: The TWBCC and ANC after GTx were significant factors to predict patients' outcome. Therefore, follow-up of those two parameters may be helpful to select or consider other therapeutic modalities including additional GTx.

EDTA Treatment for Overcoming the Prozone Effect and for Predicting C1q Binding in HLA Antibody Testing

The Luminex-based single antigen bead (SAB) assay is widely used to detect HLA antibody in transplant recipients. However, one limitation of the SAB assay is the prozone effect, which occurs mostly as a result of complement interference. We investigated the efficacy of EDTA treatment for overcoming the prozone effect and predicting C1q binding of HLA antibody. We subjected 27 non-treated (naïve) and EDTA-treated serum samples from highly sensitized patients to IgG-SAB assays, and we confirmed the prozone effect in 53% and 31% of class I and class II antibody tests, respectively, after EDTA treatment. When we conducted additional assays after dithiothreitol treatment and serum dilution, EDTA was the most efficacious in eliminating the prozone effect. Reducing the prozone effect by EDTA treatment strengthened the correlation between IgG mean fluorescence intensity (MFI) and C1q MFI values (ρ=0.825) as compared with the naïve sera (ρ=0.068). Although C1q positivity was dependent on the concentration of HLA antibody in EDTA-treated sera, the correlations varied individually. Overall, our results confirmed the efficacy of EDTA treatment for overcoming the prozone effect. EDTA treatment showed a positive effect on the correlation between IgG MFI and C1q MFI values.

Evaluation of Hemoglobin Trigger and Appropriateness of Perioperative Red Cell Transfusion in Surgical Departments / 대한수혈학회지

BACKGROUND: Red blood cell (RBC) transfusion is an essential practice during surgery to accommodate for bleeding. As such, there are efforts being made to allow for a safe and appropriate transfusion due to shortages of blood components and to minimize transfusion-related adverse reactions. However, a conventional transfusion decision with relatively high hemoglobin (Hb) threshold is still performed in clinical setting. In this study, we investigated the threshold of Hblevel and appropriateness of RBC transfusion in patients receiving perioperative RBC transfusion in surgical departments. METHODS: We investigated the pre-transfusion Hb level of 1,379 patients (2,170 episodes) receiving perioperative RBC transfusion in five surgical departments, including cardiothoracic surgery (CS), general surgery (GS), neurosurgery (NS), obstetrics and gynecology (OBGY), and orthopedics (OS), between June 2017 and March 2018. The appropriateness of transfusion was evaluated with two criteria: 1) pretransfusion Hb level ≤10 g/dL and 2) posttransfusion Hb level ≤10 g/dL. RESULTS: The median pretransfusion Hb level was 8.5 g/dL (interquartile range 7.7~9.4); that of each department was as follows: 8.6 g/dL (7.9~9.2) in CS, 7.9 g/dL (7.3~8.6) in GS, 9.1 g/dL (8.5~9.8) in NS, 8.5 g/dL (7.7~9.8) in OBGY, and 8.7 g/dL (7.9~9.7) in OS. With a criteria of pretransfusion of Hb level ≤10 g/dL, 85.4% of total episodes were appropriate. With criteria of post-transfusion of Hb level ≤10 g/dL, 44.7% were appropriate. CONCLUSION: This study presents a fundamental data observing the trend of RBC transfusion in a single institution. A significant proportion of inappropriate RBC transfusion are still being conducted in surgical setting. Continuous and effective education of clinicians and implementation of monitoring systems to assess the appropriateness of RBC transfusion may be necessary.

Principles of Genetic Counseling in the Era of Next-Generation Sequencing

Traditional genetic counseling has focused on the target gene and its natural progress with respect to disease risk. Next-generation sequencing (NGS) can produce information on several genetic variants simultaneously, with different functions and consequences for each. Accordingly, determining the status of the patient or consultant and interpreting sequencing results from many genes can largely increase the complexity of genetic counseling. Moreover, the current environment of big data that can be readily shared via the internet and a ubiquitous network provides many different avenues for which a consultant must handle the traditional principle of genetic counseling in different ways. Thus, further consideration and rethinking of genetic counseling principles are necessary in the era of NGS. In this review, we discuss several aspects of genetic counseling that one can encounter when faced with NGS data.

Intrachromosomal amplification of chromosome 21 in Korean pediatric patients with B-cell precursor acute lymphoblastic leukemia in a single institution

BACKGROUND: Intrachromosomal amplification of chromosome 21 (iAMP21), defined as the presence of three or more RUNX1 signals on one marker chromosome, is a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) that is known to have a poor prognosis when treated with standard therapy. The aim of this study was to evaluate the clinical characteristics of Korean children with iAMP21. METHODS: The cytogenetic data from BCP-ALL children were reviewed. The ETV6/RUNX1 ES Dual Color Probe was used for fluorescence in situ hybridization (FISH). RESULTS: In total, 295 children were included. Of these, 10 patients (3.4%) had iAMP21. The median age of iAMP21 patients was 9 years, and the median value of white blood cell count was 5.09×10⁹/L. Slow early treatment response was observed more in iAMP21 patients. Patients with iAMP21 had a higher incidence of relapse and worse survival rates. In patients with iAMP21, the estimated 10-year cumulative incidence of relapse was 53.3%. The estimated 10-year event-free survival and overall survival rate were 46.7% and 64.8%, respectively. Most cases of leukemic relapse developed in the late period (median, 43 mo). In multivariate analysis, high risk group was the only factor that had a significant impact on death. CONCLUSION: The existence of iAMP21 was related to delayed treatment response and was likely to affect increased relapse and death in the late period. Further studies are needed to reveal its effect on BCP-ALL treatment outcomes and its role as an independent prognostic factor.

Novel Pathogenic Variant (c.580C>T) in the CPS1 Gene in a Newborn With Carbamoyl Phosphate Synthetase 1 Deficiency Identified by Whole Exome Sequencing

Diagnosis of the urea cycle disorder (USD) carbamoyl-phosphate synthetase 1 (CPS1) deficiency (CPS1D) based on only the measurements of biochemical intermediary metabolites is not sufficient to properly exclude other UCDs with similar symptoms. We report the first Korean CPS1D patient using whole exome sequencing (WES). A four-day-old female neonate presented with respiratory failure due to severe metabolic encephalopathy with hyperammonemia (1,690 µmol/L; reference range, 11.2-48.2 µmol/L). Plasma amino acid analysis revealed markedly elevated levels of alanine (2,923 µmol/L; reference range, 131-710 µmol/L) and glutamine (5,777 µmol/L; reference range, 376-709 µmol/L), whereas that of citrulline was decreased (2 µmol/L; reference range, 10-45 µmol/L). WES revealed compound heterozygous pathogenic variants in the CPS1 gene: one novel nonsense pathogenic variant of c.580C>T (p.Gln194*) and one known pathogenic frameshift pathogenic variant of c.1547delG (p.Gly516Alafs*5), which was previously reported in Japanese patients with CPS1D. We successfully applied WES to molecularly diagnose the first Korean patient with CPS1D in a clinical setting. This result supports the clinical applicability of WES for cost-effective molecular diagnosis of UCDs.

Laboratory Identification of Leptotrichia Species Isolated From Bacteremia Patients at a Single Institution

We describe the laboratory identification of Leptotrichia species from clinical isolates collected over a six-year period. Five isolates from blood cultures were identified as Leptotrichia species. Gram stain showed large, fusiform, gram-negative or -variable bacilli. Identification based on biochemical testing was unsuccessful; however, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry proved to be a useful tool for identifying Leptotrichia species to the genus level. Species level identification was successfully achieved by using 16S ribosomal RNA gene sequencing.

Identification of Mucorales From Clinical Specimens: A 4-Year Experience in a Single Institution

Mucormycosis, a fatal opportunistic infection in immunocompromised hosts, is caused by fungi belonging to the order Mucorales. Early diagnosis based on exact identification and multidisciplinary treatments is critical. However, identification of Mucorales fungi is difficult and often delayed, resulting in poor prognosis. This study aimed to compare the results of phenotypic and molecular identification of 12 Mucorales isolates collected from 4-yr-accumulated data. All isolates were identified on the basis of phenotypic characteristics such as growth rate, colony morphology, and reproductive structures. PCR and direct sequencing were performed to target internal transcribed spacer (ITS) and/or D1/D2 regions. Target DNA sequencing identified five Lichtheimia isolates, two Rhizopus microsporus isolates, two Rhizomucor pusillus isolates, one Cunninghamella bertholletiae isolate, one Mucor fragilis isolate, and one Syncephalastrum racemosum isolate. Five of the 12 (41.7%) isolates were incorrectly identified on the basis of phenotypic identification. DNA sequencing showed that of these five isolates, two were Lichtheimia isolates, one was Mucor isolate, one was Rhizomucor isolate, and one was Rhizopus microspores. All the isolates were identified at the species level by ITS and/or D1/D2 analyses. Phenotypic differentiation and identification of Mucorales is difficult because different Mucorales share similar morphology. Our results indicate that the molecular methods employed in this study are valuable for identifying Mucorales.