Letter to the Editor2022-05-01 Diagnostic Genetics
Youngeun Lee 
, M.D., Hyun Jin Park , M.D., Hyoung Jin Kang , M.D., Ph.D., Jung Min Ko , M.D., Ph.D., Boram Kim , M.D., Yoon Hwan Chang , M.D., Ph.D., Hyun Kyung Kim , M.D., Ph.D., Jee-Soo Lee , M.D., Man Jin Kim , M.D., Sung Sup Park , M.D., Ph.D., and Moon-Woo Seong , M.D., Ph.D.
Editorial2022-11-01
Haeil Park , M.D., Ph.D.
Letter to the Editor2021-11-01 Diagnostic Genetics
Philippe Colson , Pharm, D., Ph.D., Céline Boschi , Jessica Grace Bengone-Abogourin , Ludivine Brechard , Anne Motte , M.D., and Isabelle Allemand , M.D.
Letter to the Editor2023-01-01 Clinical Microbiology
Kuenyoul Park , M.D., Heungsup Sung , M.D., and Mi-Na Kim , M.D.
Original Article2022-09-01 Clinical Chemistry
Yuhang Deng , M.D., Qingxiang Liu , M.S., Zhenni Liu , M.D., Haijian Zhao , M.D., Weiyan Zhou , M.D., and Chuanbao Zhang , M.D.
Abstract : Background: To identify candidate external quality assessment (EQA) materials for normetanephrine and metanephrine measurements, we assessed the commutability of eight processed human plasma samples. The agreement between routine assays and the candidate reference measurement procedure (cRMP) was also evaluated. Methods: Fifty-three clinical samples and eight processed plasma samples were prepared. The processed samples included pooled and individual plasma samples spiked with pure normetanephrine and metanephrine and non-spiked pooled and individual plasma samples. The clinical and processed samples were subjected to four routine isotope dilution tandem mass spectrometry assays and cRMP. Commutability was assessed based on two approaches recommended by the CLSI and International Federation of Clinical Chemistry (IFCC). Passing–Bablok regression and Bland–Altman analysis were used to evaluate the agreement between the routine assays and cRMP. Results: The commutability results of the CLSI approach were better than those of the IFCC approach. For the CLSI approach, spiked individual plasma samples and spiked high-concentration pooled plasma samples were commutable for all routine assays for both analytes. The non-spiked pooled plasma sample was commutable for two out of four routine assays for metanephrine and three out of four routine assays for normetanephrine. The agreement between the routine assays and the cRMP was satisfactory, except for one routine assay showing significant bias. Conclusions: High-concentration spiked pooled plasma samples and spiked individual plasma samples are candidate EQA materials for normetanephrine and metanephrine measurements.
Original Article2023-05-01 Diagnostic Genetics
Man Jin Kim , M.D., Soo Yeon Kim , M.D., Jin Sook Lee , M.D., Sanggoo Kang , M.B.A., Lae-Jeong Park , Ph.D., Wooyong Choi , B.S., Ju Yeol Jung , M.S., Taehyung Kim , M.S., Sung Sup Park , M.D., Jung Min Ko , M.D., Moon-Woo Seong , M.D., Ph.D., and Jong Hee Chae , M.D., Ph.D.
Abstract : Background: New genome sequencing technologies with enhanced diagnostic efficiency have emerged. Rapid and timely diagnosis of treatable rare genetic diseases can alter their medical management and clinical course. However, multiple factors, including ethical issues, must be considered. We designed a targeted sequencing platform to avoid ethical issues and reduce the turnaround time. Methods: We designed an automated sequencing platform using dried blood spot samples and a NEOseq_ACTION panel comprising 254 genes associated with Mendelian diseases having curable or manageable treatment options. Retrospective validation was performed using data from 24 genetically and biochemically confirmed patients. Prospective validation was performed using data from 111 patients with suspected actionable genetic diseases. Results: In prospective clinical validation, 13.5% patients presented with medically actionable diseases, including short- or medium-chain acyl-CoA dehydrogenase deficiencies (N=6), hyperphenylalaninemia (N=2), mucopolysaccharidosis type IVA (N=1), alpha thalassemia (N=1), 3-methylcrotonyl-CoA carboxylase 2 deficiency (N=1), propionic acidemia (N=1), glycogen storage disease, type IX(a) (N=1), congenital myasthenic syndrome (N=1), and citrullinemia, type II (N=1). Using the automated analytic pipeline, the turnaround time from blood collection to result reporting was
Original Article2023-05-01 Clinical Chemistry
Jonna A. van der Stam , M.Sc., Sjoerd Bouwmeester , M.D., Saskia L. M. van Loon , Ph.D., Natal A. W. van Riel , Ph.D., Lukas R. Dekker , Ph.D., Arjen-Kars Boer , Ph.D., Patrick Houthuizen , Ph.D., and Volkher Scharnhorst , Ph.D.
Abstract : Background: Heart failure (HF) biomarkers have prognostic value. The aim of this study was to combine HF biomarkers into an objective classification system for risk stratification of patients with HF. Methods: HF biomarkers were analyzed in a population of HF outpatients and expressed relative to their cut-off values (N-terminal pro-B-type natriuretic peptide [NT-proBNP] >1,000 pg/mL, soluble suppression of tumorigenesis-2 [ST2] >35 ng/mL, growth differentiation factor-15 [GDF-15] >2,000 pg/mL, and fibroblast growth factor-23 [FGF-23] >95.4 pg/mL). Biomarkers that remained significant in multivariable analysis were combined to devise the Heartmarker score. The performance of the Heartmarker score was compared to the widely used New York Heart Association (NYHA) classification based on symptoms during ordinary activity. Results: HF biomarkers of 245 patients were analyzed, 45 (18%) of whom experienced the composite endpoint of HF hospitalization, appropriate implantable cardioverter-defibrillator shock, or death. HF biomarkers were elevated more often in patients that reached the composite endpoint than in patients that did not reach the endpoint. NT-proBNP, ST2, and GDF-15 were independent predictors of the composite endpoint and were thus combined as the Heartmarker score. The event-free survival and distance covered in 6 minutes of walking decreased with an increasing Heartmarker score. Compared with the NYHA classification, the Heartmarker score was better at discriminating between different risk classes and had a comparable relationship to functional capacity. Conclusions: The Heartmarker score is a reproducible and intuitive model for risk stratification of outpatients with HF, using routine biomarker measurements.
Original Article2023-03-01 Clinical Microbiology
Son Young Jun , Ph.D., Young Ah Kim , M.D., Ph.D., Suk-Jun Lee , Ph.D., Woon-Won Jung , Ph.D., Hyun-Sook Kim , Ph.D., Sung-Soo Kim , Ph.D., Hyunsoo Kim , M.D., Dongeun Yong , M.D., and Kyungwon Lee , M.D.
Abstract : Background: Development of an accessible method to routinely evaluate the clonality of strains is needed in microbiology laboratories. We compared the discriminatory power of the Fourier-transform infrared (FTIR) spectroscopy–based IR Biotyper (Bruker Daltonics GmbH, Bremen, Germany) to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), using whole-genome sequencing (WGS) as the reference method. Methods: Eighty-three extended-spectrum β-lactamase–producing Escherichia coli isolates were tested using WGS, MALDI-TOF MS, and IR Biotyper. Simpson’s diversity index (SDI), a statistical analysis for testing the homogeneity of a dendrogram, and the adjusted Rand index (aRI) were used to compare the discriminatory ability between typing tests. Results: The SDI (95% confidence interval) was 0.969 (0.952–0.985) for WGS, 0.865 (0.807–0.924) for MALDI-TOF MS, and 0.974 (0.965–0.983) for IR Biotyper. Compared with WGS, IR Biotyper showed compatible diversity, whereas MALDI-TOF MS did not. The concordance and aRI improved from 66.3% to 84.3% and from 0.173 to 0.538, respectively, for IR Biotyper versus MALDI-TOF MS with WGS as the reference method. IR Biotyper showed substantially improved performance in strain typing compared with MALDI-TOF MS. Conclusions: IR Biotyper is useful for diversity analysis with improved discriminatory power over MALDI-TOF MS in comparison with WGS as a reference method. IR Biotyper is an accessible method to evaluate the clonality of strains and could be applied in epidemiological analysis during an outbreak of a health care facility, as well as for research on the transmission of resistant bacteria in community settings.
Editorial2022-11-01
Seokho Kim , Ph.D.
Brief Communication2022-09-01 Diagnostic Hematology
Young Eun Lee , M.S., Ha Jin Lim , M.D., Ju Heon Park , M.D., Hye Ran Kim , Ph.D., Min-Gu Kang , M.D., Ph.D., Young Kuk Cho , Ph.D., Jong Hee Shin , M.D., Ph.D., and Myung Geun Shin , M.D., Ph.D.
Abstract : Cytogenetically normal acute myeloid leukemia (CN-AML) accounts for 40%–50% of all AML cases. Despite advances in understanding the molecular pathophysiology of CN-AML, its clinical outcome remains unsatisfactory and unpredictable. To investigate its clinical implication in CN-AML, we measured the expression of prohibitin 2 (PHB2) using immunohistochemical staining (IHCS) of paraffin-embedded bone marrow sections from 134 CN-AML patients. IHCS results were semi-quantitatively scored. Clinical outcome was analyzed in comparison with other prognostic markers, including NPM1 polymorphism and FLT3 internal tandem duplication, and WT1 and BAALC mRNA expression. Except for BAALC mRNA expression, the known molecular markers showed no prognostic effect in the CN-AML patients. PHB2 protein overexpression was significantly associated with adverse prognosis in CN-AML patients. The PHB2 protein expression status may serve as an independent prognostic indicator in CN-AML.
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