Publications by authors named "Dong Wook Jekarl"

49 Publications

The factors influencing clinical outcomes after leukapheresis in acute leukaemia.

Sci Rep 2021 03 19;11(1):6426. Epub 2021 Mar 19.

Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.

Leukapheresis is used for the mechanical removal of leukaemic cells in hyperleukocytosis. However, the effectiveness of leukapheresis remains unclear due to selection and confounding factors in the cohorts. We compared the effectiveness of leukapheresis among the subgroups according to either the 2016 World Health Organization classification or the number of cytogenetic abnormalities with a retrospective, single-centre study from January 2009 to December 2018. Acute myeloid leukaemia (AML, n = 212) and acute lymphoblastic leukaemia (ALL, n = 97) were included. The 30-day survival rates (95% confidence interval, 95% CI) for AML and ALL were 86.3% (81.6-90.9%) and 94.8% (90.3-99.2%), respectively. For AML, 'primary AML with myelodysplasia-related changes' and 'AML with biallelic mutation of CEBPA' showed better 30-day survival outcomes (P = 0.026) than the other subgroups. A higher platelet count after leukapheresis was associated with better 30-day survival in AML patients (P = 0.029). A decrease in blast percentage count after leukapheresis was associated with better 30-day survival in ALL patients (P = 0.034). Our study suggested that prophylactic platelet transfusion to raise the platelet count to 50 × 10/L or greater might improve clinical outcome in AML patients undergoing leukapheresis.
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http://dx.doi.org/10.1038/s41598-021-85918-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979875PMC
March 2021

Immune gene expression networks in sepsis: A network biology approach.

PLoS One 2021 5;16(3):e0247669. Epub 2021 Mar 5.

Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

To study the dysregulated host immune response to infection in sepsis, gene expression profiles from the Gene Expression Omnibus (GEO) datasets GSE54514, GSE57065, GSE64456, GSE95233, GSE66099 and GSE72829 were selected. From the Kyoto Encyclopedia of Genes and Genomes (KEGG) immune system pathways, 998 unique genes were selected, and genes were classified as follows based on gene annotation from KEGG, Gene Ontology, and Reactome: adaptive immunity, antigen presentation, cytokines and chemokines, complement, hematopoiesis, innate immunity, leukocyte migration, NK cell activity, platelet activity, and signaling. After correlation matrix formation, correlation coefficient of 0.8 was selected for network generation and network analysis. Total transcriptome was analyzed for differentially expressed genes (DEG), followed by gene set enrichment analysis. The network topological structure revealed that adaptive immunity tended to form a prominent and isolated cluster in sepsis. Common genes within the cluster from the 6 datasets included CD247, CD8A, ITK, LAT, and LCK. The clustering coefficient and modularity parameters were increased in 5/6 and 4/6 datasets in the sepsis group that seemed to be associated with functional aspect of the network. GSE95233 revealed that the nonsurvivor group showed a prominent and isolated adaptive immunity cluster, whereas the survivor group had isolated complement-coagulation and platelet-related clusters. T cell receptor signaling (TCR) pathway and antigen processing and presentation pathway were down-regulated in 5/6 and 4/6 datasets, respectively. Complement and coagulation, Fc gamma, epsilon related signaling pathways were up-regulated in 5/6 datasets. Altogether, network and gene set enrichment analysis showed that adaptive-immunity-related genes along with TCR pathway were down-regulated and isolated from immune the network that seemed to be associated with unfavorable prognosis. Prominence of platelet and complement-coagulation-related genes in the immune network was associated with survival in sepsis. Complement-coagulation pathway was up-regulated in the sepsis group that was associated with favorable prognosis. Network and gene set enrichment analysis supported elucidation of sepsis pathogenesis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247669PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935325PMC
September 2021

HLA-A, -B, -C, -DRB1 allele and haplotype frequencies of the Korean population and performance characteristics of HLA typing by next-generation sequencing.

HLA 2021 03 2;97(3):188-197. Epub 2021 Feb 2.

Department of Laboratory Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.

Introduction: Human leukocyte antigen (HLA) identification at the allelic level is important for haematopoietic stem cell transplantation (HSCT). Next-generation sequencing (NGS) resolves ambiguous alleles by determining the phase of the polymorphisms. The aim of this study was to validate the software for HLA-SBT (sequence-based typing), assess Korean allele frequency, and characterise the performance of NGS-HLA typing.

Methods: From the 2009 to 2016 registry, 1293 unrelated healthy donors with a complete dataset of previously characterised HLA-A, -B, -C, and -DRB1 loci were selected and assessed for frequency, haplotype inference, and relative linkage disequilibrium. For performance characteristics of NGS-HLA, alleles included in 1293 cases and ambiguous or alleles assigned as new by SBT-HLA software, or unassigned alleles were included. A total of 91 and 41 quality control samples resulted in 1056 alleles (132 samples × 4 loci × 2 diploid) for analysis. The GenDx NGSgo kit was used for NGS-HLA typing using the Illumina MiSeq platform.

Results: A panel of 132 samples covered 231 alleles, including 53 HLA-A, 80 HLA-B, 43 HLA-C, and 55 HLA-DRB1 by HLA-SBT typing. Comparison of SBT-HLA and NGS-HLA typing showed 99.7% (1053/1056) concordance and discrepant cases were resolved by manual evaluation. Typing by NGS resulted in 67 HLA-A, 112 HLA-B, 71 HLA-C, and 72 HLA-DRB1 alleles. A total of 132 ambiguous, 4 new, and 1 unassigned alleles by HLA-SBT were resolved by NGS-HLA typing.

Conclusions: NGS-HLA typing provided robust and conclusive results without ambiguities, and its implementation could support HSCT in clinical settings.
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http://dx.doi.org/10.1111/tan.14167DOI Listing
March 2021

Transfusion of a D--phenotype patient using the Rare Blood Donor Registry of the Korean Red Cross Blood Services.

Blood Transfus 2021 01 9;19(1):91-92. Epub 2020 Oct 9.

Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, St. Mary's Hospital, Banpo-Daero, Seocho-Gu, Seoul, Republic of Korea.

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http://dx.doi.org/10.2450/2020.0264-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850921PMC
January 2021

Analytical and Clinical Evaluation of Chemiluminescent Carcinoembryonic Antigen (CEA) by HISCL-5000 Immunoanalyzer.

Ann Clin Lab Sci 2020 May;50(3):417-422

Department of Laboratory Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital.

Objective: The carcinoembryonic antigen (CEA) is coupled with a diagnosis and prognosis for cancers METHODS: The analytical performance of CEA by chemiluminescent immunoassay (HISCL-5000, Sysmex, Kobe, Japan) was evaluated on the basis of precision, linearity, trueness, and method comparison. Clinical evaluation was performed by area under the receiver operating characteristic curve (AU-ROC) curve analysis for lung, stomach and colorectal cancers.

Results: Total coefficient of variation (CV) (5.039% to 5.632%), linearity (0.5 to 982 ng/mL) and the percentage bias by trueness verification were less than desirable specifications for imprecision (6.4%) and bias (14.3%). The regression equation was y=0.354+0.957x(r=0.968) from method comparison. AUROC for lung, stomach, and colorectal cancers compared with normal healthy control ranged from 0.908 to 0.967 (cut-off 4.50 to 4.71 ng/mL), and compared with non-malignant benign disease, ranged from 0.578 to 0.721 (cut-off 8 to 20.70 ng/mL).

Conclusions: CEA by HISCL-5000 immunoassay provided reliable performance. Comorbidities should be considered for interpretation of CEA.
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May 2020

Complex interaction networks of cytokines after transarterial chemotherapy in patients with hepatocellular carcinoma.

PLoS One 2019 21;14(11):e0224318. Epub 2019 Nov 21.

Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Treating hepatocellular carcinoma with transarterial chemoembolization (TACE) induces both local inflammation in the tumor microenvironment as well as systemic inflammation. We analyzed serum cytokine response to TACE to evaluate this. Serum samples obtained from 203 HCC patients treated with TACE were analyzed for inflammatory cytokines including interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IL-22, TNF-α, IFN-γ, and C-reactive protein (CRP) levels. Cytokine concentrations were measured at day 0 (D0, baseline, n = 203), day3 (D3, n = 156), day7 (D7, n = 147), and day 60 (D60, n = 115) after TACE. Network analysis of the cytokines was performed to understand their interactive relationship. After TACE, IL-1β, -6,-9, -12, and -22 increased by D60. IL-2, -5, -10, -17A and INF-γ decreased by D60, and IL-4, -13 and TNF-α revealed stable concentration. D0 network revealed that IL-2, -4, -5, and -10 formed a module. D3 network had the highest clustering coefficient and average degree that revealed similar pattern as CRP. D7 network revealed that IL-6, -9 and CRP were isolated from the network. D60 network had the lower network heterogeneity and lower clustering coefficient, network diameter, shortest path and characteristic path length. Degree correlation revealed that assortative network turned to disassortative network by D60 indicating that the network gained scale free feature. D60 cytokine network retained inflammatory function and these parameters indicated that the systemic inflammation induced by TACE appeared to be attenuated by D60. IL-9 at D3 and D7 seemed to be related to anti-tumor effect and IL-6 at D7 and D60, and IL-22 at D60 was related to regenerative but not pro- or anti- inflammatory function. Median survival month of patient group with high and low values of cytokine with P-values were as follows: D0 CRP, 9.5 and 54.2 months (P<0.0001); D0 IL-2, 39.9 and 56.1 months (P = 0.0084); D3 CRP, 31.3 and 55.1 months (P = 0.0056); D7 CRP, 28.7 and 50.7 months (P = 0.0065), respectively. TACE is associated with systemic inflammation which appears to peak at Day 3 and resolve by D60. Among the tested cytokines, IL-6 and IL-22 appear to play a regenerative role.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224318PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874208PMC
April 2020

Diagnosis and Prognosis of Sepsis Based on Use of Cytokines, Chemokines, and Growth Factors.

Dis Markers 2019 8;2019:1089107. Epub 2019 Sep 8.

Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.

The focus of sepsis has shifted from inflammation to organ dysfunction on the basis of a recent definition based on the sequential organ failure score (SOFA). A diagnostic and prognostic marker is necessary under this definition but is currently unknown. We enrolled 80 sepsis patients consecutively admitted to an intensive care unit through the emergency department and 80 healthy control patients who received routine health check-ups from August 2018 to January 2019. SEPSIS-3 criteria were used for the diagnosis of patients based on SOFA score ≥ 2 from the baseline along with evidence of infection. Concentrations of 28 cytokines, eight chemokines, and nine growth factors were measured on the day of diagnosis. Hierarchical cluster analysis was performed for molecules. The majority of infections were pneumonia (45% of patients) and urinary tract infections (40% of patients). Most of the measured molecules were increased in patients with sepsis. Area under receiver operating characteristic curve (AUROC) values were found to be as follows: hepatic growth factor (HGF), 0.899; interleukin-1 receptor antagonist (IL-1RA), 0.893; C-C motif ligand 5 (CCL5) 5, 0.887; C-X-C motif chemokine 10 (CXCL10), 0.851; CCL2, 0.840; and IL-6, 0.830. IL-1RA, IL-6, IL-8, IL-15, and CCL11 concentrations correlated with SOFA score with statistical significance. Prognosis multivariate analysis revealed an odds ratio of 0.968 for epidermal growth factor (EGF). Three clusters were formed, of which Clusters 2 and 3 were associated with nonsurvivors. Diagnosis of sepsis was performed using cytokines, chemokines, and growth factors. HGF revealed the highest diagnostic capability, and EGF predicted favorable prognosis among the tested molecules.
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http://dx.doi.org/10.1155/2019/1089107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754872PMC
February 2020

Evaluating Diagnostic Tests for Infection Without a Reference Standard: Use of Latent Class Analysis.

Ann Lab Med 2020 Jan;40(1):68-71

Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Evaluation of diagnostic tests requires reference standards, which are often unavailable. Latent class analysis (LCA) can be used to evaluate diagnostic tests without reference standards, using a combination of observed and estimated results. Conditionally independent diagnostic tests for infection are required. We used LCA to construct a reference standard and evaluate the capability of non-invasive tests (stool antigen test and serum antibody test) to diagnose infection compared with the conventional method, where histology is the reference standard. A total of 96 healthy subjects with endoscopy histology results were enrolled from January to July 2016. Sensitivity and specificity were determined for the LCA approach (i.e., using a combination of three tests as the reference standard) and the conventional method. When LCA was used, sensitivity and specificity were 83.8% and 99.4% for histology, 80.0% and 81.9% for the stool antigen test, and 63.6% and 89.3% for the serum antibody test, respectively. When the conventional method was used, sensitivity and specificity were 75.8% and 71.1% for the stool antigen test and 77.7% and 60.7% for the serum antibody test, respectively. LCA can be applied to evaluate diagnostic tests that lack a reference standard.
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http://dx.doi.org/10.3343/alm.2020.40.1.68DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713662PMC
January 2020

Procalcitonin as a prognostic marker for sepsis based on SEPSIS-3.

J Clin Lab Anal 2019 Nov 16;33(9):e22996. Epub 2019 Aug 16.

Department of Emergency Medicine, The Catholic University of Korea, Incheon St. Mary's Hospital, Incheon, Korea.

Background: The revised definition of sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection (SEPSIS-3). The objective of this study was to evaluate procalcitonin (PCT) for the diagnosis and prognosis of sepsis using SEPSIS-3.

Methods: We enrolled 248 patients, who were admitted to the emergency department with suspected bacterial infection from June 2016 to February 2017. Definite bacterial infection was defined by proven culture results, and probable bacterial infection was based on diagnostic modalities other than culture. The sequential organ failure assessment (SOFA) score of 2 points or more from the baseline was diagnosed as sepsis. PCT was measured by the AFIAS-6 immunoassay system (Boditech Med Inc.) using whole blood. White blood cell (WBC), C-reactive protein (CRP), and erythrocyte sedimentation rate (ERS) were evaluated.

Results: The final diagnosis was sepsis in 185 patients with infection of respiratory and genitourinary tract constituted 84.6%. The area under the receiver operating characteristic curve (AUROC) with 95% confidence interval (CI) was as follows: PCT, 0.682 (0.589-0.765); CRP, 0.583 (0.487-0.673); ESR, 0.540 (0.515-0.699); and WBC, 0.611 (0.455-0.633), respectively. In multivariate analysis, age, SOFA, and PCT (log scale) predicted non-survivors with an odds ratio with 95% confidence interval of 1.055 (1.008-1.105), 1.303 (1.142-1.486), and 2.004 (1.240-3.238), respectively. Among sepsis group, initial PCT was increased in non-survivor (23.2 ng/dL) compared to survivor group (8.1 ng/dL) with statistical significance (P = .005).

Conclusions: PCT could support and predict the unfavorable prognosis of sepsis based on SEPSIS-3, whereas diagnostic potential of PCT requires further evaluations.
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http://dx.doi.org/10.1002/jcla.22996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868407PMC
November 2019

A Mutation in as a Novel Candidate Gene for Endothelial Corneal Dystrophy.

J Clin Med 2019 08 6;8(8). Epub 2019 Aug 6.

Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.

Corneal dystrophies (CDs) are a diverse group of inherited disorders with a heterogeneous genetic background. Here, we report the identification of a novel ZNF143 heterozygous missense mutation in three individuals of the same family with clinical and pathological features that are consistent with endothelial CD. Ophthalmologic examination revealed diffuse corneal clouding and edema with decreased endothelial cell density. Pathological findings showed increased corneal thickness due to edema of basal epithelial cells and stroma, and abnormal metaplastic endothelium with stratified epithelium-like changes. Patients' metaplastic corneal endothelial cells expressed predominantly cytokerain 7, cytokeratin 19, and E-cadherin. Although Sanger sequencing did not detect any mutation associated with endothelial CDs, whole exome sequencing identified the c.937G>C p.(Asp313His) mutation as a candidate gene for our patients' endothelial CD. In-vitro functional studies demonstrated that mutant promoted the mesenchymal-to-epithelial transition; it upregulated the expression of genes associated with epithelialization in human corneal endothelial cells. Additionally, proinflammatory cytokine responsive genes were significantly enriched after mutant  transfection, which may contribute to the severe phenotype of the three patients. These findings link a mutation in with endothelial CD for the first time.
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http://dx.doi.org/10.3390/jcm8081174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723187PMC
August 2019

Clinical Significance of Inflammatory Biomarkers in Acute Pediatric Diarrhea.

Pediatr Gastroenterol Hepatol Nutr 2019 Jul 18;22(4):369-376. Epub 2019 Jun 18.

Department of Laboratory Medicine, Incheon St. Mary's Hospital, School of Medicine, The Catholic University of Korea, Incheon, Korea.

Purpose: The aim of this study was to evaluate the clinical significance of inflammatory biomarkers in acute infectious diarrhea among children.

Methods: Clinical parameters including fever, bacterial and viral etiology based on stool culture and multiplex polymerase chain reaction, and nine biomarkers including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and leukocytes in blood and calprotectin, lactoferrin, myeloperoxidase, polymorphonuclear elastase, leukocytes, and occult blood in feces were evaluated in children who were hospitalized due to acute diarrhea without underlying disease.

Results: A total of 62 patients were included. Among these patients, 33 had fever, 18 showed bacterial infections, and 40 patients were infected with 43 viruses. Of all the biomarkers, CRP was significantly correlated with fever (<0.001). CRP, ESR, calprotectin, lactoferrin, myeloperoxidase, fecal leukocytes, and occult blood were significantly associated with infection with bacterial pathogens (<0.001, =0.04, =0.03, =0.003, =0.02, =0.03, =0.002, respectively). The combination of CRP and fecal lactoferrin at their best cut-off values (13.7 mg/L and 22.8 µg/mL, respectively) yielded a sensitivity of 72.2%, and a specificity of 95.5% for bacterial etiology compared with their individual use.

Conclusion: Blood CRP is a useful diagnostic marker for both fever and bacterial etiology in acute pediatric diarrhea. The combination of CRP and fecal lactoferrin yields better diagnostic capability for bacterial etiology than their use alone for acute diarrhea in children without underlying gastrointestinal disease.
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http://dx.doi.org/10.5223/pghn.2019.22.4.369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629592PMC
July 2019

Analytical evaluation and clinical application of insulin and C-peptide by a whole blood, lateral flow, point of care (POC) assay system.

Scand J Clin Lab Invest 2019 Sep 18;79(5):347-353. Epub 2019 Jun 18.

b Laboratory for Development and Evaluation Center, The Catholic University of Korea , Seoul , Korea.

The analytical performance and clinical application of measuring insulin and connecting peptide (C-peptide) by point of care (POC) assay were evaluated. A POC assay system (SelexOn, Osang Healthcare Inc., Anyang-si, Korea) was evaluated for precision, linearity, limit of blank (LOB), and limit of detection (LOD). Method comparison was performed with the Cobas Elecsys insulin and C-peptide assay (Roche Diagnostics GmbH, Mannheim, Germany) using 215 and 201 patient specimens for insulin and C-peptide, respectively. For clinical application, insulin resistance indices were studied. Homeostasis model assessment (HOMA) 1 and 2, Quantitative insulin sensitivity check index (QUIKI), fasting insulin resistance index (FIRI), and other indices were evaluated. The coefficient of variation (CV) of imprecision for low, medium, and high concentrations was 10.8%1, 15.99%, and 12.05%, respectively, for insulin and 9.21%, 13.51%, and 13.77%, respectively, for C-peptide. The linearity was validated to 839.78 pmol/L for insulin and to 17.30 nmol/L for C-peptide. LOB and LOD were 8.05 and 9.72 pmol/L for insulin and 0.05 and 0.08 nmol/L for C-peptide, respectively. For the method comparison, the regression equation was  = 1.259 - 8.818 ( = 0.957) for insulin and  = 1.163 - 0.088 ( = 0.985) for C-peptide. The ROC value and overall accuracy were as follows: HOMA2 (C-peptide), 0.809, 79.7%; TyG, 0.788, 73.6%; CPR, 0.775, 74.8%; HOMA1, 0.725, 70.3%; QUIKI, 0.720, 70.3%; FIRI, 0.715, 70.1%; McAuley, 0.658, 65.1%; HOMA2 (Insulin), 0.645, 64.7%; Raynaud, 0.611, 61.4%, respectively. The POC assay system for insulin and C-peptide provided reliable results through a rapid and simple test that could be applied to clinical settings.
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http://dx.doi.org/10.1080/00365513.2019.1627575DOI Listing
September 2019

Enumeration of CD34-positive Stem Cells Using the ADAMII Image-based Fluorescence Cell Counter.

Ann Lab Med 2019 Jul;39(4):388-395

Laboratory Development and Evaluation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background: It is very important to accurately enumerate CD34-positive (CD34+) cells for successful hematopoietic stem cell transplantation (HSCT). We evaluated the ability of the newly developed image based-immunofluorescence cell counter ADAMII (NanoEntek, Seoul, Korea) to enumerate CD34+ cells, which was improved through simultaneous CD45 analysis.

Methods: We enumerated CD34+ cells with ADAMII using 19 peripheral blood (PB) and 91 leukapheresis samples from HSCT donors. Analytical performance, including precision and linearity, was analyzed, and sample stability during storage was evaluated. Viable CD34+ cell count (vCD34) and viable CD45+ cell count (vCD45) and the percentage of viable CD34+ cells among viable CD45+ cells (CD34/CD45) as measured by ADAMII were compared with the corresponding values from two flow cytometry assays, using regression analysis.

Results: ADAMII demonstrated acceptable precision, as CV values of vCD34 from six samples with different counts were all <10% (range: 3.49-9.51%). CV values of the vCD45 and CD34/45 ranged from 4.03% to 9.67% and from 2.48% to 10.07%, respectively. The linearity of vCD34 showed an excellent ² value (0.99) when analyzed using the intended count and flow cytometry data. The ADAMII and two flow cytometry-based assays generated very similar data for the PB and leukapheresis samples.

Conclusions: ADAMII demonstrated excellent performance for use as a routine clinical assay in terms of CD34+ cell enumeration from PB and leukapheresis samples. Moreover, it could be used as a point-of-care-test for determining mobilization time and predicting an adequate apheresis stem cell product.
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http://dx.doi.org/10.3343/alm.2019.39.4.388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400716PMC
July 2019

CDKN2B downregulation and other genetic characteristics in T-acute lymphoblastic leukemia.

Exp Mol Med 2019 01 11;51(1):1-15. Epub 2019 Jan 11.

Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

We identified principal genetic alterations in 97.1% (99/102) of patients with T-acute lymphoblastic leukemia (T-ALL) using integrative genetic analyses, including massive parallel sequencing and multiplex ligation-dependent probe amplification (MLPA). A total of 133 mutations were identified in the following genes in descending order: NOTCH1 (66.7%), FBXW7 (19.6%), PHF6 (15.7%), RUNX1 (12.7%), NRAS (10.8%), and DNMT3A (9.8%). Copy number alterations were most frequently detected in CDKN2B, CDKN2A, and genes on 9p21.3 in T-ALL (45.1%). Gene expression data demonstrated the downregulation of CDKN2B in most cases of T-ALL, whereas CDKN2A downregulation was mainly restricted to deletions. Additional quantitative methylation analysis demonstrated that CDKN2B downregulation stemmed from deletion and hypermethylation. Analysis of 64 patients with CDKN2B hypermethylation indicated an association with an older age of onset and early T cell precursor ALL, which involved very early arrest of T cell differentiation. Genes associated with methylation and myeloid neoplasms, including DNMT3A and NRAS, were more commonly mutated in T-ALL with CDKN2B hypermethylation. In particular, a CDKN2B biallelic deletion or high methylation level (≥45%), the age of onset, and the GATA3 and SH2B3 mutations were factors associated with a poor prognosis. This study clarifies that one of the most important genetic events in T-ALL, namely, CDKN2B downregulation, occurs mechanistically via deletion and hypermethylation. Different susceptible genetic backgrounds exist based on the CDKN2B downregulation mechanism.
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http://dx.doi.org/10.1038/s12276-018-0195-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329696PMC
January 2019

Cytokine and molecular networks in sepsis cases: a network biology approach.

Eur Cytokine Netw 2018 Sep;29(3):103-111

Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Laboratory for Development and Evaluation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea.

Sepsis is a life-threatening condition of organ dysfunction caused by a dysregulated host immune response to infection. We performed network analysis of cytokine molecules and compared network structures between a systematic inflammatory response syndrome (SIRS) or normal control (NC) group and a sepsis group. We recruited SIRS (n = 33) and sepsis (n = 89) patients from electronic medical records (EMR) according to whether data on PCT, CRP, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-17, IL-22, TNF-α, and IFN-γ levels were available. From the public GEO dataset, GSE66099, GSE9960, GSE95233, GSE57065 were downloaded. Genes corresponding to 15 molecules were extracted from an expression array. A correlation matrix was formed for the 15 molecules and statistically significant molecular pairs were used as pairs for network analysis of coexpression. The number of molecular or gene expression pairs significantly correlated among the SIRS or control and sepsis groups are as follows for datasets: EMR, 15 and 15; GEO66099-1, 13 and 15; GEO9960, 13 and 11; GSE95233, 13 and 8; GSE66099-2, 15 and 14; GSE57065, 14 and 13, respectively. Network analysis revealed that network diameter, number of nodes and shortest path were equal to or lower in the sepsis group. The coexpression network in sepsis patients was relatively small sized and had lower shortest paths compared with the SIRS group or healthy control group. Cytokines with one degree (k = 1) are increased in sepsis group compared with SIRS or healthy control group. IL-9 and IL-2 were not included in network of sepsis group indicating that these cytokines showed no correlation with other cytokines. These data might imply that cytokines tend to be dysregulated in the sepsis group compared to that of SIRS or normal control groups.
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http://dx.doi.org/10.1684/ecn.2018.0414DOI Listing
September 2018

Diagnosis of Liver Fibrosis With Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein (WFA-M2BP) Among Chronic Hepatitis B Patients.

Ann Lab Med 2018 Jul;38(4):348-354

Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background: Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA-M2BP) is a protein with altered glycosylation that reacts with lectin, and was recently identified as a useful non-invasive biomarker for the diagnosis of liver fibrosis in patients with hepatitis C virus infection.This study aimed to evaluate the diagnostic efficacy of WFA-M2BP for liver fibrosis in the context of hepatitis B virus (HBV).

Methods: We enrolled 151 patients infected with HBV. Liver biopsy and elastography (Fibroscan) were performed during the initial visit. Fibrosis was graded according to the Knodell histologic activity index (F0-3). WFA-M2BP levels were determined with an automated immunoassay analyzer (M2BPGi, HISCL-5000, Sysmex, Japan). The diagnostic efficacy of WFA-M2BP was compared with those of various conventional or composite biomarkers, including enhanced liver fibrosis (ELF) score, Fibroscan, aspartate transaminase (AST)-to-platelet ratio index (APRI), and FIB-4, based on the area under the ROC curve (AUC) value.

Results: The majority of patients were at fibrosis stages F1 and F2. The F2 and F3 AUC values for WFA-M2BP were similar to those for FIB-4, APRI, ELF, and Fibroscan, although the latter showed the best diagnostic efficacy. The diagnostic accuracy of all tested biomarkers for F2 and F3 was 60-70%. In multivariate analysis, WFA-M2BP, ELF, and platelet count significantly predicted stage ≥F2, whereas only platelet count significantly predicted F3.

Conclusions: WFA-M2BP can support a diagnosis of liver fibrosis with similar diagnostic efficacy to other biomarkers, and predicted liver fibrosis stage ≥2 among patients with chronic hepatitis B.
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http://dx.doi.org/10.3343/alm.2018.38.4.348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895864PMC
July 2018

Ubiquitin C decrement plays a pivotal role in replicative senescence of bone marrow mesenchymal stromal cells.

Cell Death Dis 2018 01 30;9(2):139. Epub 2018 Jan 30.

Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.

Human bone marrow-mesenchymal stromal cells (hBM-MSCs) undergo cellular senescence during in vitro culture. In this study, we defined this replicative senescence as impaired proliferation, deterioration in representative cell characteristics, accumulated DNA damage, and decreased telomere length and telomerase activity with or without genomic abnormalities. The UBC gene expression gradually decreased during passaging along with the reduction in series of molecules including hub genes; CDK1, CCNA2, MCM10, E2F1, BRCA1, HIST1H1A and HIST1H3B. UBC knockdown in hBM-MSCs induced impaired proliferation in dose-dependent manner and showed replicative senescence-like phenomenon. Gene expression changes after UBC knockdown were similar to late passage hBM-MSCs. Additionally, UBC overexpession improved the proliferation activity of hBM-MSCs accompanied by increased expression of the hub genes. Consequently, UBC worked in higher-order through regulation of the hub genes controlling cell cycle and proliferation. These results indicate that the decrement of UBC expression plays a pivotal role in replicative senescence of hBM-MSCs.
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http://dx.doi.org/10.1038/s41419-017-0032-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833785PMC
January 2018

Passage-dependent accumulation of somatic mutations in mesenchymal stromal cells during in vitro culture revealed by whole genome sequencing.

Sci Rep 2017 11 6;7(1):14508. Epub 2017 Nov 6.

Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Human mesenchymal stromal cells (MSCs) have served as a major cellular resource for cell-based immunomodulatory and regenerative therapies. However, genomic instability may accumulate during ex vivo expansion of MSCs, thereby increasing the potential of malignant transformation. Here, we performed whole genome sequencing of two peripheral blood-derived MSC lines (MSC1 and MSC2) at various passages (passage 1 [P1] to P9). The majority of single-nucleotide variations (SNVs) occurred in later passages; specifically, 90% and 70% of all SNVs in MSC1 and MSC2 were observed in P9 and P7/P9, respectively. These late-occurring SNVs were enriched with C > A transversions and were overrepresented in intronic regions compared to intergenic regions, suggesting that the mutational forces are not constant across the passages. Clonality analyses also distinguished early-occurring, subclonal SNVs from late-occurring, clonally fixed SNVs. In addition, MSCs were largely devoid of copy number alterations (CNAs) (i.e., 0-2 CNAs per passage), with one exception (MSC2-P3) harboring 29 passage-specific CNAs. Our findings suggest that the SNVs found to be abundant at later passages likely resulted from the accumulation of replication stress, which can be associated with proliferation activity. Thus, the genomic instability associated with proliferation records should be considered for clinical applications of MSCs.
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http://dx.doi.org/10.1038/s41598-017-15155-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674020PMC
November 2017

Considerations when using next-generation sequencing for genetic diagnosis of long-QT syndrome in the clinical testing laboratory.

Clin Chim Acta 2017 Jan 18;464:128-135. Epub 2016 Nov 18.

Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: Congenital long-QT syndrome (LQTS) is a potentially lethal cardiac electrophysiologic disorder characterized by QT interval prolongation and T-wave abnormalities. At least 13 LQTS-associated genes have been reported, but the high cost and low throughput of conventional Sanger sequencing has hampered the multi-gene-based LQTS diagnosis in clinical laboratories.

Methods: We developed an NGS (next-generation sequencing)-based targeted gene panel for 13 LQTS genes using the Ion PGM platform, and a cohort of 36 LQTS patients were studied for characterization of analytical performance specifications.

Results: This panel efficiently explored 212 of all 221 coding exons in 13 LQTS-associated genes. And for those genomic regions covered by the design of the NGS panel, the analytical sensitivity and analytical specificity for all potentially pathogenic variants were both 100% and showed 100% concordance with clinically validated Sanger sequencing results in five major LQTS genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2).

Conclusion: This is the first description of an NGS panel targeting a multi-gene panel of 13 LQTS-associated genes. We developed and validated this robust, high-throughput NGS test and informatics pipeline for LQTS diagnosis suitable for the clinical testing laboratory.
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http://dx.doi.org/10.1016/j.cca.2016.11.013DOI Listing
January 2017

Combined Group I and III ABO Discrepancies in Multiple Myeloma with IgG-Lambda Type: A Case Report.

Med Princ Pract 2017 5;26(1):90-92. Epub 2016 Sep 5.

Department of Laboratory Medicine, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea.

Objective: To report a case with unusual ABO discrepancies caused by coexistence of the loss of anti-B isoagglutinin and rouleau formation.

Clinical Presentation And Intervention: A 79-year-old female diagnosed as having multiple myeloma (MM) with monoclonal IgG-λ type showed rouleau formation in peripheral blood smear. The ABO and Rh blood type before the diagnosis of MM was A+, but the following ABO grouping was interpreted as AB+. The ABO genotype revealed the subtypes A102 and O101, which confirmed her ABO phenotype as A+.

Conclusion: This was a case of combined group I and III ABO discrepancies mimicking blood group AB.
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http://dx.doi.org/10.1159/000450579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588301PMC
September 2017

Genetic-pathologic characterization of myeloproliferative neoplasms.

Exp Mol Med 2016 07 22;48:e247. Epub 2016 Jul 22.

Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the proliferation of one or more myeloid lineages. The current study demonstrates that three driver mutations were detected in 82.6% of 407 MPNs with a mutation distribution of JAK2 in 275 (67.6%), CALR in 55 (13.5%) and MPL in 6 (1.5%). The mutations were mutually exclusive in principle except in one patient with both CALR and MPL mutations. The driver mutation directed the pathologic features of MPNs, including lineage hyperplasia, laboratory findings and clinical presentation. JAK2-mutated MPN showed erythroid, granulocytic and/or megakaryocytic hyperplasia whereas CALR- and MPL-mutated MPNs displayed granulocytic and/or megakaryocytic hyperplasia. The lineage hyperplasia was closely associated with a higher mutant allele burden and peripheral cytosis. These findings corroborated that the lineage hyperplasia consisted of clonal proliferation of each hematopoietic lineage acquiring driver mutations. Our study has also demonstrated that bone marrow (BM) fibrosis was associated with disease progression. Patients with overt fibrosis (grade ⩾2) presented an increased mutant allele burden (P<0.001), an increase in chromosomal abnormalities (P<0.001) and a poor prognosis (P<0.001). Moreover, among patients with overt fibrosis, all patients with wild-type JAK2/CALR/MPL (triple-negative) showed genomic alterations by genome-wide microarray study and revealed the poorest overall survival, followed by JAK2-mutated MPNs. The genetic-pathologic characteristics provided the information for understanding disease pathogenesis and the progression of MPNs. The prognostic significance of the driver mutation and BM fibrosis suggests the necessity of a prospective therapeutic strategy to improve the clinical outcome.
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http://dx.doi.org/10.1038/emm.2016.55DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973314PMC
July 2016

Tissue-specific Differentiation Potency of Mesenchymal Stromal Cells from Perinatal Tissues.

Sci Rep 2016 Apr 5;6:23544. Epub 2016 Apr 5.

Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Human perinatal tissue is an abundant source of mesenchymal stromal cells(MSCs) and lacks the ethical concerns. Perinatal MSCs can be obtained from various tissues as like amnion, chorion, and umbilical cord. Still, little is known of the distinct nature of each MSC type. In this study, we successfully isolated and cultured MSCs from amnion(AMSCs), chorion(CMSCs), and umbilical cord(UC-MSCs). Proliferation potential was different among them, that AMSCs revealed the lowest proliferation rate due to increased Annexin V and senescence-associated β-galactosidase positive cells. We demonstrated distinct characteristic gene expression according to the source of the original tissue using microarray. In particular, genes associated with apoptosis and senescence including CDKN2A were up-regulated in AMSCs. In CMSCs, genes associated with heart morphogenesis and blood circulation including HTR2B were up-regulated. Genes associated with neurological system processes including NPY were up-regulated in UC-MSCs. Quantitative RT-PCR confirmed the gene expression data. And in vitro differentiation of MSCs demonstrated that CMSCs and UC-MSCs had a more pronounced ability to differentiate into cardiomyocyte and neural cells, respectively. This study firstly demonstrated the innate tissue-specific differentiation potency of perinatal MSCs which can be helpful in choosing more adequate cell sources for better outcome in a specific disease.
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http://dx.doi.org/10.1038/srep23544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820697PMC
April 2016

Are prognostic scores and biomarkers such as procalcitonin the appropriate prognostic precursors for elderly patients with sepsis in the emergency department?

Aging Clin Exp Res 2016 Oct 7;28(5):917-24. Epub 2015 Dec 7.

Department of Laboratory Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: The mortality of patients with severe sepsis and septic shock is still high, and the prognosis of elderly patients tends to be particularly poor. Therefore, this study sought to conduct a comparative analysis of the abbreviated mortality in emergency department sepsis (abbMEDS) score, sequential organ failure assessment (SOFA) score, infection probability score (IPS), initial procalcitonin (PCT), and cytokine levels to investigate the effectiveness of each index in predicting the prognosis of elderly patients with sepsis in the emergency department (ED).

Methods: This was a single-center prospective study, and classified 55 patients (≥65 years of age) with systemic inflammatory response syndrome (SIRS) from January 2013 to December 2013 in the ED. A total of 36 elderly patients were diagnosed with sepsis. The prediction of prognosis using the prognostic scores (abbMEDS, SOFA, IPS) was analyzed. An early blood examination (WBC count, C-reactive protein, PCT, and cytokines) was conducted within the first 2 h of the patient's arrival at the ED.

Results: The median (IQR) age of subjects was 76.5 (70.5-81.5). After 28 days, 27 subjects (75 %) had survived, and 9 (25 %) had died. Fifteen (41.7 %) were sent to intensive care units (ICUs). The SOFA score and abbMEDS showed higher median (IQR) values of 9.5 (7.0-11.0) and 13.5 (12.0-15.0), respectively, in the ICU group than in the general ward group (p < 0.001). Analysis of the levels of PCT, IL-10, IL-6, and IL-5 had a significantly better ability to predict ICU admission (p = 0.001, p = 0.023, p = 0.030, p = 0.001). The prediction of mortality in the first 28 days via SOFA and the abbMEDS resulted in scores of 11.0 (8.0-11.0) and 14.0 (12.5-15.5) (p = 0.004, p = 0.003), respectively. However, levels of IPS, PCT, and cytokines did not show significant differences.

Conclusions: In predicting ICU admission and the death of elderly sepsis patients in ED, SOFA and abbMEDS scores were effective. Of the various biomarkers, PCT, IL-10, IL-6, and IL-5 were effective in predicting ICU admission, but were not effective in predicting the death of elderly sepsis patients.
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http://dx.doi.org/10.1007/s40520-015-0500-7DOI Listing
October 2016

Novel FLG null mutations in Korean patients with atopic dermatitis and comparison of the mutational spectra in Asian populations.

J Dermatol 2015 Sep 21;42(9):867-73. Epub 2015 May 21.

Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Filaggrin is essential for the development of the skin barrier. Mutations in the gene encoding filaggrin have been identified as major predisposing factors for atopic disorders. Molecular analysis of the FLG gene in this study showed nine null and one unclassified mutation in 13 of 81 Korean patients with atopic dermatitis (AD): five novel null mutations (i.e. p.S1405*, c.5671_5672delinsTA, p.W1947*, p.G2025* and p.E3070*); four reported null mutations (i.e. c.3321delA, p.S1515*, p.S3296* and p.K4022*); and one unclassified mutation (i.e. c.306delAAAGCACAG). These variants are nonsense, premature termination codon or in-frame deletion expected to cause loss-of-function of FLG. Genotype-phenotype correlation is not obvious in Korean AD patients with FLG null mutations. According to a review of the mutational spectra of the FLG gene in the Asian populations, FLG null mutations appeared to be unique in each population but some mutations such as p.R501*, c.3321delA, p.S1515*, p.S3296* and p.K4022* were commonly found in at least two of the selected Asian populations including Korean, Japanese, Chinese, Singaporean Chinese or Taiwanese. Further investigations on a larger group of Korean AD would be necessary to elucidate its clinical pathogenesis and mutational spectrum related to specific FLG null mutations for AD.
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http://dx.doi.org/10.1111/1346-8138.12935DOI Listing
September 2015

Genetic and epigenetic alterations of bone marrow stromal cells in myelodysplastic syndrome and acute myeloid leukemia patients.

Stem Cell Res 2015 Mar 24;14(2):177-84. Epub 2015 Jan 24.

Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address:

We evaluated the characteristics of bone marrow stromal cells (BMSCs) and hematopoietic cells (HCs) from patients of myelodysplastic syndrome (MDS, n=21) and acute myeloid leukemia (AML, n=58), and compared the results with control BMSCs derived from healthy donors (n=8). The patient BMSCs had lower proliferative activity than that of the controls due to increased senescence. This retarded proliferation induced failure to obtain enough metaphase cells for karyotyping in patient BMSCs (10%). Patient BMSCs were genetically altered which was demonstrated by chromosome abnormalities in 5% of the patients (one MDS and three AML), whereas no clonal abnormalities were detected in the controls. The most common abnormality of the BMSCs was an extra chromosome 5, followed by an extra chromosome 7 and balanced translocations. The proportion of the abnormal metaphase cells was low (17.8%). We also analyzed the epigenetic changes of long interspersed nucleotide element 1 (LINE-1) repetitive element and CDKN2B using pyrosequencing. The quantitative measurement of global LINE-1 methylation demonstrated that patient BMSCs revealed global hypomethylation (68.2±3.8) compared with controls (72.9±3.4, P<0.001) and that the global hypomethylation of BMSCs were more significant in AML than in MDS patients (67.9±3.8, 69.4±4.2, respectively). These findings seem worthy of further evaluation of their association with ineffective hematopoiesis and leukemogenesis.
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http://dx.doi.org/10.1016/j.scr.2015.01.004DOI Listing
March 2015

Identification of compound heterozygous mutations in the BBS7 gene in a Korean family with Bardet-Biedl syndrome.

Ann Lab Med 2015 Jan 8;35(1):181-4. Epub 2014 Dec 8.

Department of Laboratory Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

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http://dx.doi.org/10.3343/alm.2015.35.1.181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272959PMC
January 2015

Clinical Significance of Fecal Lactoferrin and Multiplex Polymerase Chain Reaction in Patients with Acute Diarrhea.

Gut Liver 2015 Sep;9(5):636-40

Department of Internal Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Incheon, Korea.

Background/aims: The diagnostic yield of fecal leukocyte and stool cultures is unsatisfactory in patients with acute diarrhea. This study was performed to evaluate the clinical significance of the fecal lactoferrin test and fecal multiplex polymerase chain reaction (PCR) in patients with acute diarrhea.

Methods: Clinical parameters and laboratory findings, including fecal leukocytes, fecal lactoferrin, stool cultures and stool multiplex PCR for bacteria and viruses, were evaluated prospectively for patients who were hospitalized due to acute diarrhea.

Results: A total of 54 patients were included (male, 23; median age, 42.5 years). Fecal leukocytes and fecal lactoferrin were positive in 33 (61.1%) and 14 (25.4%) patients, respectively. Among the 31 patients who were available for fecal pathogen evaluation, fecal multiplex PCR detected bacterial pathogens in 21 patients, whereas conventional stool cultures were positive in only one patient (67.7% vs 3.2%, p=0.000). Positive fecal lactoferrin was associated with presence of moderate to severe dehydration and detection of bacterial pathogens by multiplex PCR (21.4% vs 2.5%, p=0.049; 100% vs 56.5%, p=0.032, respectively).

Conclusions: Fecal lactoferrin is a useful marker for more severe dehydration and bacterial etiology in patients with acute diarrhea. Fecal multiplex PCR can detect more causative organisms than conventional stool cultures in patients with acute diarrhea.
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http://dx.doi.org/10.5009/gnl14106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562781PMC
September 2015

Fragmented Red Cell as a Possible Favorable Prognostic Marker of Hematopoietic Stem Cell Transplantation Associated Thrombotic Microangiopathy.

J Clin Lab Anal 2015 Nov 10;29(6):444-50. Epub 2014 Nov 10.

Division of Hematology, Department of Internal Medicine, Catholic Hematopoietic Stem Cell Transplantation Center, Seoul St. Mary's Hospital, Catholic University of Korea, Seoul, Korea.

Background: Fragmented red cell (FRC) by automated hematologic analyzer is known to detect schistocyte. In this study, it is noted that FRC might be a favorable prognostic marker of hematopoietic stem cell transplantation associated thrombotic microangiopathy (TA-TMA).

Methods: The peripheral blood samples and clinical data of 89 patients were collected. The diagnosis of TA-TMA was defined by the Blood and Marrow Transplant Clinical Trials Network's criteria and schistocyte or both schistocyte- and FRC-positive cases and other parameters fulfilled are regarded as TA-TMA.

Results: Schistocyte and FRC displayed a correlation coefficient of 0.461 (P < 0.001) by Spearman's method. The diagnostic concordance of TA-TMA using schistocyte and FRC was 92.1% with kappa index of 0.531 (P < 0.001). The number of diagnosed patients and mean survival month were as follows: TA-TMA by schistocyte, 8 (8.9%), 13.5 month; TA-TMA by schistocyte and FRC, 7 (7.8%), 40.4 month; No TMA, 74 (83.1%), 38.3 month, respectively. Kaplan-Meier survival analysis by log-rank method of the patient with TA-TMA by schistocyte and rest of the group showed statistical significance (P < 0.01).

Conclusion: As evidenced by the data, FRC might be a favorable prognostic marker for TA-TMA, but additional studies with larger patients groups are required for validation of clinical applications.
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http://dx.doi.org/10.1002/jcla.21792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6807144PMC
November 2015

Clonal spread of catalase-negative ST5/SCCmec II Staphylococcus aureus carrying the staphylococcal enterotoxin A (sea), staphylococcal enterotoxin b (seb), and toxic shock toxin (tst) virulence genes.

Ann Clin Lab Sci 2014 ;44(4):394-8

Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul

17 catalase-negative methicillin-resistant Staphylococcus aureus (MRSA) isolates were recovered from respiratory specimens of patients at a 700-bed hospital in Korea. The goal of this study was to determine the molecular characteristics of catalase-negative MRSA strains in Korea for the first time. Characteristics that we explored included kat A gene mutation sequence, sequence type, staphylococcal cassette chromosome (SCC) mec subtype classification, and toxin gene profiles. All 17 isolates showed similar pulsed field gel electrophoresis (PFGE) pattern. Four mutations were identified in the kat A gene of a representative catalase-negative MRSA strain: A602G causing a histidine 201 to arginine change, A695T causing a glutamic acid 232 to valine change, T778A causing a tryptophan 260 to arginine change, and G1438A causing a glycine 480 to serine change. Previous studies suggest that the A695T and T778A mutations may have strong effects on the catalase activity of catalase-negative MRSA. The sequence type (ST) and SCCmec type of this isolate were ST 5 and SCCmec type II, respectively. All 17 isolates harbored toxic shock toxin (tst), staphylococcal enterotoxin A (sea), and staphylococcal enterotoxin B (seb) virulence genes. The mortality rate of the present study was 11.8%, suggesting that the clinical relevance of catalase-negative MRSA requires further study in the future.
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June 2015
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