Publications by authors named "Young-Kyung Lee"

82 Publications

Factors associated with worsening oxygenation in patient with non-severe COVID-19 pneumonia.

Tuberc Respir Dis (Seoul) 2021 Jan 5. Epub 2021 Jan 5.

Department of Internal Medicine, Seoul Medical Center, Seoul, South Korea.

Background: This study aimed to determine parameters for worsening oxygenation in non-severe COVID-19 pneumonia.

Methods: This retrospective cohort study included confirmed COVID-19 pneumonia in a public hospital in South Korea. The worsening oxygenation group was defined as those with SpO2 ≤ 94%, or received oxygen or mechanical ventilation (MV) throughout the clinical course versus the non-worsening group who were without any respiratory event. Parameters were compared, and the extent of viral pneumonia from an initial chest CT were calculated using artificial intelligence (AI) and measured visually by a radiologist.

Results: We included 136 patients with 32 (23.5%) in the worsening oxygenation group, of whom two needed MV and one died. Initial vital signs and duration of symptoms showed no difference between the two groups, however, univariate logistic regression analysis revealed that a variety of parameters at admission were associated with an increased risk of a desaturation event. A subset of patients were studied to eliminate potential bias, that ferritin ≥ 280 μg/L (p=0.029), LDH ≥ 240 U/L (p=0.029), pneumonia volume (p=0.021), and extent (p=0.030) by AI, and visual severity scores (p=0.042) were the predictive parameters for worsening oxygenation in a sex-, age-, and comorbid illness-matched case-control study using propensity score (n=52).

Conclusion: Our study presents initial CT evaluated by AI or visual severity scoring as well as serum markers of inflammation at admission are significantly associated with worsening oxygenation in this COVID-19 pneumonia cohort.
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http://dx.doi.org/10.4046/trd.2020.0139DOI Listing
January 2021

Establishment of a Nationwide Korean Imaging Cohort of Coronavirus Disease 2019.

J Korean Med Sci 2020 Nov 30;35(46):e413. Epub 2020 Nov 30.

Department of Radiology, Pusan National University Hospital, Pusan National University School of Medicine and Biomedical Research Institute, Busan, Korea.

Background: The Korean Society of Thoracic Radiology (KSTR) recently constructed a nation-wide coronavirus disease 2019 (COVID-19) database and imaging repository, referred to the Korean imaging cohort of COVID-19 (KICC-19) based on the collaborative efforts of its members. The purpose of this study was to provide a summary of the clinico-epidemiological data and imaging data of the KICC-19.

Methods: The KSTR members at 17 COVID-19 referral centers retrospectively collected imaging data and clinical information of consecutive patients with reverse transcription polymerase chain reaction-proven COVID-19 in respiratory specimens from February 2020 through May 2020 who underwent diagnostic chest computed tomography (CT) or radiograph in each participating hospital.

Results: The cohort consisted of 239 men and 283 women (mean age, 52.3 years; age range, 11-97 years). Of the 522 subjects, 201 (38.5%) had an underlying disease. The most common symptoms were fever (n = 292) and cough (n = 245). The 151 patients (28.9%) had lymphocytopenia, 86 had (16.5%) thrombocytopenia, and 227 patients (43.5%) had an elevated CRP at admission. The 121 (23.4%) needed nasal oxygen therapy or mechanical ventilation (n = 38; 7.3%), and 49 patients (9.4%) were admitted to an intensive care unit. Although most patients had cured, 21 patients (4.0%) died. The 465 (89.1%) subjects underwent a low to standard-dose chest CT scan at least once during hospitalization, resulting in a total of 658 CT scans. The 497 subjects (95.2%) underwent chest radiography at least once during hospitalization, which resulted in a total of 1,475 chest radiographs.

Conclusion: The KICC-19 was successfully established and comprised of 658 CT scans and 1,475 chest radiographs of 522 hospitalized Korean COVID-19 patients. The KICC-19 will provide a more comprehensive understanding of the clinical, epidemiological, and radiologic characteristics of patients with COVID-19.
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http://dx.doi.org/10.3346/jkms.2020.35.e413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707929PMC
November 2020

Noninvasive prenatal test of single-gene disorders by linked-read direct haplotyping: application in various diseases.

Eur J Hum Genet 2020 Nov 24. Epub 2020 Nov 24.

Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

Direct haplotyping enables noninvasive prenatal testing (NIPT) without analyzing proband, which is a promising strategy for pregnancies at risk of an inherited single-gene disorder. Here, we aimed to expand the scope of single-gene disorders that NIPT using linked-read direct haplotyping would be applicable to. Three families at risk of myotonic dystrophy type 1, lipoid congenital adrenal hyperplasia, and Fukuyama congenital muscular dystrophy were recruited. All cases exhibited distinct characteristics that are often encountered as hurdles (i.e., repeat expansion, identical variants in both parents, and novel variants with retrotransposon insertion) in the universal clinical application of NIPT. Direct haplotyping of parental genomes was performed by linked-read sequencing, combined with allele-specific PCR, if necessary. Target DMPK, STAR, and FKTN genes in the maternal plasma DNA were sequenced. Posterior risk calculations and an Anderson-Darling test were performed to deduce the maternal and paternal inheritance, respectively. In all cases, we could predict the inheritance of maternal mutant allele with > 99.9% confidence, while paternal mutant alleles were not predicted to be inherited. Our study indicates that direct haplotyping and posterior risk calculation can be applied with subtle modifications to NIPT for the detection of an expanded range of diseases.
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http://dx.doi.org/10.1038/s41431-020-00759-9DOI Listing
November 2020

Establishment of sex-specific reference intervals for automated haematology analyser-delivered research parameters in healthy Korean adults: a retrospective database review.

BMJ Open 2020 10 8;10(10):e036887. Epub 2020 Oct 8.

Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, The Republic of Korea.

Objectives: Automated haematology analysers measure various parameters of relevance to clinical research along with routine complete blood count (CBC)-related components. We aimed to establish ethnicity-specific and sex-specific reference intervals for 26 research-specific parameters as well as 18 routinely reported components using a large cohort of healthy Korean adults. The necessity of requiring separate sex-specific reference intervals for each parameter was also examined.

Design: A retrospective database review.

Setting: Single tertiary-care hospital of approximately 375 physicians and 530 nurses.

Participants: This study included 1383 reference individuals (840 men and 543 women).

Primary And Secondary Outcome Measures: Following the Clinical and Laboratory Standards Institute guidelines for establishing reference intervals, routine CBCs as well as research parameters were measured using an ADVIA 2120i instrument.

Results: All the routine components except for mean platelet volume and per cent lymphocytes differed significantly between men and women. Most research parameters also differed between the sexes; the exceptions were large platelets, platelet dry mass distribution width, per cent basophil saturation, per cent peroxidase saturation and per cent abnormal peroxidase absorption. Despite these differences, separate reference intervals for men and women were required only for two research-specific parameters: 'percentage high cellular haemoglobin' and 'percentage of hyperchromic red blood cells (RBCs)'.

Conclusion: Even though most parameters showed significant differences between men and women, none of the evaluated parameters except two RBC-related factors required separate reference intervals for each sex.
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http://dx.doi.org/10.1136/bmjopen-2020-036887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545637PMC
October 2020

Four cases of coronavirus disease 2019 in the early stage of pandemic of South Korea: a single public hospital experience.

Korean J Intern Med 2020 07 1;35(4):788-792. Epub 2020 Jul 1.

Department of Laboratory Medicine, Seoul Medical Center, Seoul, Korea.

In view of this pandemic, as of February 2020, South Korea has the second highest number of confirmed cases in the world. Herein, we report four confirmed coronavirus disease 2019 (COVID-19) cases in the early stage of the pandemic in South Korea and describe the identification, diagnosis, clinical course, and management, including one patient's initial mild symptoms at presentation and their progression to pneumonia on day 21 of illness. Within 48 hours of hospitalization, all four patients underwent evaluation for initial laboratory parameters, COVID-19 polymerase chain reaction (PCR), and chest computed tomography (CT) findings. All four mild COVID-19 patients were discharged, and they were re-examined 14 days after discharge. Despite all four of them being asymptomatic, one patient was re-admitted after confirmation of COVID-19 through PCR viral nucleic acid detection. She could be discharged after 7 days with two subsequent negative COVID-19 PCR at 24-hour intervals. Patients with mild COVID-19 generally have normal follow-up chest CT scans after discharge, even if the early chest CT definitely indicates pneumonia. Re-hospitalized patients with COVID-19 PCR positive results after discharge were not related to her initial chest CT, lab, symptoms compared other three patients.
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http://dx.doi.org/10.3904/kjim.2020.079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373956PMC
July 2020

Differentiating thymoma from thymic cyst in anterior mediastinal abnormalities smaller than 3 cm.

J Thorac Dis 2020 Apr;12(4):1357-1365

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Gyeonggi-do, Korea.

Background: Computed tomography (CT) screening for lung cancer has led to frequent findings of small anterior mediastinal masses. It is very hard to distinguish small thymomas from thymic cysts. The objective of this study was to develop a clinical model for predicting small thymomas (<3 cm) in asymptomatic patients.

Methods: Patients who underwent thymectomy for anterior mediastinal masses between 2004 and 2016 were included. All preoperative CT scans (pre- and post-enhanced) were retrospectively reviewed. Size, location, contour, shape, presence of calcification, and enhancement [Hounsfield units (HU)] were evaluated. A nomogram was built based on the predictive factors. For external validation, patients undergoing thymectomy in 2017 were enrolled and thymoma prediction was computed using the proposed nomogram.

Results: The study population consisted of 43 patients with thymoma and 57 with thymic cyst. The multivariable analysis identified a lobulated contour and a large difference in HU between post- and pre-enhancement as predictive factors of thymoma. These factors were included in the nomogram, which showed 95% (19/20) power for predicting thymoma after external validation.

Conclusions: This clinical model can be used to predict thymoma in patients with small, asymptomatic thymic abnormalities on CT screening.
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http://dx.doi.org/10.21037/jtd.2020.02.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212157PMC
April 2020

Direct Haplotyping-Based Noninvasive Prenatal Test for Myotonic Dystrophy Type 1 with Large CTG Expansion.

Clin Chem 2020 04;66(4):614-615

Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

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http://dx.doi.org/10.1093/clinchem/hvaa025DOI Listing
April 2020

A Rare Episode of Extensive Bone Marrow Necrosis in a Chemotherapy-naïve Patient with Multiple Myeloma Exhibiting and Mutations.

Ann Clin Lab Sci 2020 Jan;50(1):136-139

Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea.

Bone marrow necrosis (BMN) is a rare life-threatening condition in which the marrow is replaced by necrotic material. Half of BMN occurrences are attributed to chemotherapy or granulocyte-colony stimulating factor treatment in patients with hematolymphoid malignancies. However, we present a patient diagnosed with both multiple myeloma and extensive BMN despite being treatment-naïve. Our patient exhibited a deletion, frameshift mutation, and a single nucleotide change. He is the third such patient reported, but the first to have his cytogenetic and molecular genetic profiles investigated using conventional cytogenetics, fluorescence in situ hybridization, and next-generation sequencing.
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January 2020

Chest Radiographic and CT Findings of the 2019 Novel Coronavirus Disease (COVID-19): Analysis of Nine Patients Treated in Korea.

Korean J Radiol 2020 04 26;21(4):494-500. Epub 2019 Feb 26.

Department of Radiology, Chonnam National University Hospital, Gwangju, Korea.

Objective: This study presents a preliminary report on the chest radiographic and computed tomography (CT) findings of the 2019 novel coronavirus disease (COVID-19) pneumonia in Korea.

Materials And Methods: As part of a multi-institutional collaboration coordinated by the Korean Society of Thoracic Radiology, we collected nine patients with COVID-19 infections who had undergone chest radiography and CT scans. We analyzed the radiographic and CT findings of COVID-19 pneumonia at baseline. Fisher's exact test was used to compare CT findings depending on the shape of pulmonary lesions.

Results: Three of the nine patients (33.3%) had parenchymal abnormalities detected by chest radiography, and most of the abnormalities were peripheral consolidations. Chest CT images showed bilateral involvement in eight of the nine patients, and a unilobar reversed halo sign in the other patient. In total, 77 pulmonary lesions were found, including patchy lesions (39%), large confluent lesions (13%), and small nodular lesions (48%). The peripheral and posterior lung fields were involved in 78% and 67% of the lesions, respectively. The lesions were typically ill-defined and were composed of mixed ground-glass opacities and consolidation or pure ground-glass opacities. Patchy to confluent lesions were primarily distributed in the lower lobes ( = 0.040) and along the pleura ( < 0.001), whereas nodular lesions were primarily distributed along the bronchovascular bundles ( = 0.006).

Conclusion: COVID-19 pneumonia in Korea primarily manifested as pure to mixed ground-glass opacities with a patchy to confluent or nodular shape in the bilateral peripheral posterior lungs. A considerable proportion of patients with COVID-19 pneumonia had normal chest radiographs.
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http://dx.doi.org/10.3348/kjr.2020.0132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082662PMC
April 2020

Immature platelet fraction: A useful marker for identifying the cause of thrombocytopenia and predicting platelet recovery.

Medicine (Baltimore) 2020 Feb;99(7):e19096

Departments of Laboratory Medicine, Hallym University Sacred Heart Hospital, Departments of Laboratory Medicine, Hallym University College of Medicine, Anyang, Republic of Korea.

Introduction: The assessment of bone marrow thrombopoietic activity in patients with thrombocytopenia is necessary to achieve an accurate diagnosis and administer effective treatment. We evaluated the discriminatory power of the immature platelet fraction (IPF) in differentiating hyperdestructive/consumptive thrombocytopenia from hypoproductive thrombocytopenia and its potential use as a predictive marker for platelet recovery.

Methods: In this observational study, platelet indices, including IPF, were measured in 105 healthy individuals, 27 patients with hyperdestructive/consumptive thrombocytopenia (all with immune thrombocytopenic purpura [ITP]), and 35 patients with hypoproductive thrombocytopenia (5 with aplastic anemia and 30 with cancer who were undergoing chemotherapy) using a Sysmex XN-3000 hematology analyzer.

Results: The platelet distribution width, mean platelet volume, platelet large cell ratio, IPF, and absolute immature platelet count (AIPC) were significantly higher in the hyperdestructive/consumptive thrombocytopenia group than in the hypoproductive thrombocytopenia group (P < .001). The IPF showed the highest difference between the two patient groups (200%). Receiver operating characteristics analysis that showed the IPF had the largest area under the curve among all the platelet indices analyzed; its cut-off value was 2.3%. The IPF decreased 3 to 4 days in advance of platelet count elevation in patients with ITP, whereas the delta AIPC increased 3 days in advance. Furthermore, the IPF and delta AIPC increased 5.5 days and 8.5 days, respectively, before platelet counts increased up to 130.0 × 10/L in cancer patients receiving chemotherapy.

Conclusion: These data demonstrated that the IPF and delta AIPC are both excellent indicators of the etiology of thrombocytopenia and predictive markers for platelet recovery.
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http://dx.doi.org/10.1097/MD.0000000000019096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035018PMC
February 2020

Novel genes exhibiting DNA methylation alterations in Korean patients with chronic lymphocytic leukaemia: a methyl-CpG-binding domain sequencing study.

Sci Rep 2020 01 23;10(1):1085. Epub 2020 Jan 23.

Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea.

Chronic lymphocytic leukaemia (CLL) exhibits differences between Asians and Caucasians in terms of incidence rate, age at onset, immunophenotype, and genetic profile. We performed genome-wide methylation profiling of CLL in an Asian cohort for the first time. Eight Korean patients without somatic immunoglobulin heavy chain gene hypermutations underwent methyl-CpG-binding domain sequencing (MBD-seq), as did five control subjects. Gene Ontology, pathway analysis, and network-based prioritization of differentially methylated genes were also performed. More regions were hypomethylated (2,062 windows) than were hypermethylated (777 windows). Promoters contained the highest proportion of differentially methylated regions (0.08%), while distal intergenic and intron regions contained the largest number of differentially methylated regions. Protein-coding genes were the most abundant, followed by long noncoding and short noncoding genes. The most significantly over-represented signalling pathways in the differentially methylated gene list included immune/cancer-related pathways and B-cell receptor signalling. Among the top 10 hub genes identified via network-based prioritization, four (UBC, GRB2, CREBBP, and GAB2) had no known relevance to CLL, while the other six (STAT3, PTPN6, SYK, STAT5B, XPO1, and ABL1) have previously been linked to CLL in Caucasians. As such, our analysis identified four novel candidate genes of potential significance to Asian patients with CLL.
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http://dx.doi.org/10.1038/s41598-020-57919-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978354PMC
January 2020

Plasma vs. serum in circulating tumor DNA measurement: characterization by DNA fragment sizing and digital droplet polymerase chain reaction.

Clin Chem Lab Med 2020 03;58(4):527-532

Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea.

Background Choosing the specimen type is the first step of the pre-analytical process. Previous reports suggested plasma as the optimal specimen for circulating tumor DNA (ctDNA) analysis. However, head-to-head comparisons between plasma and serum using platforms with high analytical sensitivity, such as droplet digital polymerase chain reaction (ddPCR), are limited, and several recent studies have supported the clinical utility of serum-derived ctDNA. This study aimed to compare the DNA profiles isolated from plasma and serum, characterize the effects of the differences between specimens on ctDNA measurement, and determine the major contributors to these differences. Methods We isolated cell-free DNA (cfDNA) from 119 matched plasma/serum samples from cancer patients and analyzed the cfDNA profiles by DNA fragment sizing. We then assessed KRAS mutations in ctDNA from matched plasma/serum using ddPCR. Results The amount of large DNA fragments was increased in serum, whereas that of cfDNA fragments (<800 bp) was similar in both specimens. ctDNA was less frequently detected in serum, and the KRAS-mutated fraction in serum was significantly lower than that in plasma. The differences in ctDNA fractions between the two specimen types correlated well with the amount of large DNA fragments and white blood cell and neutrophil counts. Conclusions Our results provided detailed insights into the differences between plasma and serum using DNA fragment sizing and ddPCR, potentially contributing to ctDNA analysis standardization. Our study also suggested that using plasma minimizes the dilution of tumor-derived DNA and optimizes the sensitivity of ctDNA analysis. So, plasma should be the preferred specimen type.
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http://dx.doi.org/10.1515/cclm-2019-0896DOI Listing
March 2020

Hepatitis virus B and C infections are associated with an increased risk of non-Hodgkin lymphoma: A nested case-control study using a national sample cohort.

J Med Virol 2020 08 19;92(8):1214-1220. Epub 2019 Dec 19.

Department of Otorhinolaryngology-Head & Neck Surgery, Hallym University College of Medicine, Anyang, Korea.

Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are suspected of being associated with non-Hodgkin lymphoma (NHL); however, persuasive data are lacking. Hence, a nested large-population case-control study was performed to investigate such associations in Koreans.

Methods: Data were collected from 929 patients with NHL and 3716 healthy subjects, who were matched 1:4 for age, sex, income, and region of residence, from the Korean Health Insurance Review and Assessment Service-National Sample Cohort. The diagnoses of NHL and HBV/HCV infection were based on the International Classification of Diseases (version 10) codes. Conditional logistic regression models were used to assess odds ratios (ORs) for NHL with respect to HBV or HCV with adjustment for the Charlson comorbidity index.

Results: HBV and HCV rates were higher in the NHL group (3.3% and 1.3%, respectively) than in the control group (0.9% and 0.3%, respectively; P < .001 for each). The adjusted OR of hepatitis infection in patients with NHL were 3.25 (95% confidence interval [CI] = 1.99-5.31) for HBV and 3.36 (95% CI = 1.51-7.46) for HCV (P < .001 for each). Subgroups categorized by age (<55 vs ≥55 years) or sex showed significantly higher adjusted ORs of HBV for NHL. Moreover, patients with NHL ≥ 55 years of age or those who were female showed significantly higher adjusted ORs of HCV; those <55 years or who were male also tended to have higher ORs of HCV.

Conclusion: Infection with either HBV or HCV is associated with NHL in Koreans.
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http://dx.doi.org/10.1002/jmv.25653DOI Listing
August 2020

Increased risk of lymphoid malignancy in patients with herpes zoster: a longitudinal follow-up study using a national cohort.

BMC Cancer 2019 Nov 27;19(1):1148. Epub 2019 Nov 27.

Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Republic of Korea.

Background: The association between herpes zoster and the risk of lymphoid neoplasms in Asian populations has not yet been established. We performed a longitudinal follow-up study using a nationwide cohort to assess the risk of lymphoid neoplasms arising after herpes zoster infection in the adult Korean population.

Methods: Data from participants ≥20 years of age who were registered in the Korean National Health Insurance Service-National Sample Cohort database between 2002 and 2013 were collected. We extracted the data of participants with herpes zoster (n = 59,495) as well as those of matched references at a ratio of 1:4 (n = 237,980) and investigated the subsequent occurrence of lymphoid neoplasms. A stratified Cox proportional hazards model was used to calculate unadjusted hazard ratios (HRs) as well as those adjusted for the Charlson comorbidity index score.

Results: The rate of lymphoid neoplasms was higher in the herpes zoster group (0.15% [90/59,495]) than in the reference group (0.08% [212/237,980], P < 0.001). The unadjusted and adjusted HRs of herpes zoster in patients with lymphoid neoplasms were 1.68 (95% confidence interval [CI] = 1.31-2.15) and 1.58 (95% CI = 1.23-2.02), respectively (P < 0.001 for both). On subgroup analyses according to age and sex, herpes zoster was associated with an increased risk of lymphoid neoplasms in all subgroups; the adjusted HRs were 1.53 (95% CI = 1.05-2.24) for patients < 60 years old, 1.58 (95% CI = 1.14-2.20) for patients ≥60 years old, 1.64 (95% CI = 1.16-2.31) for men, and 1.51 (95% CI = 1.06-2.16) for women (P < 0.05 for all). On subgroup analysis of lymphoid neoplasm subtypes, herpes zoster was associated with the risk of Hodgkin's disease (adjusted HR: 3.23 [95% CI = 1.17-8.93]) and multiple myeloma/malignant plasma cell neoplasms (adjusted HR: 2.17 [95% CI = 1.33-3.54]) (P < 0.05 for both).

Conclusion: Herpes zoster is associated with lymphoid neoplasm development in the Korean population irrespective of age and sex. The risks of Hodgkin's disease and plasma cell neoplasms are significantly elevated in patients with herpes zoster.
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http://dx.doi.org/10.1186/s12885-019-6349-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882027PMC
November 2019

Circulating tumor DNA as a prognostic indicator in resectable pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.

Sci Rep 2019 11 18;9(1):16971. Epub 2019 Nov 18.

Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea.

Circulating tumor DNA (ctDNA) is a promising prognostic biomarker in various cancers. Due to the high recurrence rate of resectable pancreatic ductal adenocarcinoma (PDAC), effective strategies for prognostic stratification are necessary. Yet, for resectable PDAC, prognostic impact of ctDNA lacks systemic evidence. We sought to investigate the prognostic significance of baseline ctDNA and postoperative ctDNA in patients with resectable PDAC. PubMed, EMBASE, and the Cochrane library were searched up to March 2019. Five studies met the inclusion criteria, and 375 patients were pooled for the meta-analysis. Positive ctDNA significantly indicated poor overall survival (at baseline, hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.13-4.56; postoperative, HR 3.66, 95% CI 1.45-9.28). Patients with detectable ctDNA showed the trend to have higher risk for disease recurrence than those without detectable ctDNA (at baseline, HR 1.96, 95% CI 0.65-5.87; postoperative, HR 2.20, 95% CI 0.99-4.87). The results were consistent regardless of pre- or post-operative ctDNA. There was no significant heterogeneity among the included studies. In conclusion, our meta-analysis revealed that ctDNA, either at baseline or postoperative, might be a useful prognostic biomarker for stratifying risk of death and recurrence in resectable PDAC.
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http://dx.doi.org/10.1038/s41598-019-53271-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861312PMC
November 2019

A Novel Pathogenic CALR Exon 9 Mutation in a Patient with Essential Thrombocythemia.

Lab Med 2020 May;51(3):306-309

Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Anyang, South Korea.

The clinical phenotypes and prognoses of CALR-mutant myeloproliferative neoplasms depend on the mutation type. The 2 most common mutations, type 1 (52-bp deletion) and type 2 (5-bp insertion), account for 85% of CALR-mutated neoplasms. The former confers a myelofibrotic phenotype, and the latter is associated with a low risk of thrombosis and an indolent clinical course. Individual case reports for patients with novel pathogenic CALR mutations are rare. Herein, we present the first case in the literature, to our knowledge, of a 63-year old ethnic Korean man with essential thrombocythemia who was diagnosed with a novel +1-bp frameshift mutation in CALR, which was predicted to exhibit a type 2-like phenotype.
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http://dx.doi.org/10.1093/labmed/lmz064DOI Listing
May 2020

The risk of herpes zoster virus infection in patients with depression: A longitudinal follow-up study using a national sample cohort.

Medicine (Baltimore) 2019 Oct;98(40):e17430

Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Republic of Korea.

The features of herpes zoster share some commonalities with depression, including decreased cellular immunity, a close correlation with nutritional status, and a higher prevalence in the elderly population. We aimed to assess the association between herpes zoster infection and depression in the Korean population.We performed a longitudinal follow-up study of a nationwide sample cohort derived from the Korean National Health Insurance Service database. Individuals diagnosed with depression between 2002 and 2013 (n = 58,278) as well as matched controls (n = 233,112), with both groups comprising 34.3% male and 65.7% female subjects, were extracted and analyzed for the presence of herpes zoster infection. Depression was diagnosed based on the International Classification of Diseases tenth revision (ICD-10) codes F31-F39, while herpes zoster was diagnosed as ICD-10 B02.The rate of herpes zoster infection was higher in the depressed group (6.8% [3967/58,278]) than in the control group (6.3% [14,689/233,122], P < .001). The adjusted hazard ratio (HR) for herpes zoster infection was 1.09 (95% CI: 1.05-1.13) in the depressed group (P < .001). Subgroup analyses revealed that the adjusted HRs for herpes zoster infection were higher only in women younger than 60 years among participants with depression. These HRs were 1.13 (95% CI: 1.02-1.25; P = .016) in women younger than 40 years and 1.11 (95% CI: 1.04-1.17; P < .001) in women aged 40-59 years.Depression is a predictor of herpes zoster infection in Korean women younger than 60 years.
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http://dx.doi.org/10.1097/MD.0000000000017430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783196PMC
October 2019

Mortality and cause of death in South Korean patients with Parkinson's disease: a longitudinal follow-up study using a national sample cohort.

BMJ Open 2019 09 17;9(9):e029776. Epub 2019 Sep 17.

Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea

Objective: The incidence rate of Parkinson's disease (PD) is growing rapidly owing to the ageing population. We investigated the mortality rates and causes of death in South Korean patients with PD.

Design: We investigated a national cohort using the nationwide insurance database.

Setting: Korean Health Insurance Review and Assessment Service-National Sample Cohort database.

Participants: We included 3510 participants ≥60 years of age who were diagnosed with PD between 2002 and 2013, as well as 14 040 matched controls.

Interventions: None PRIMARY AND SECONDARY OUTCOME MEASURES: A stratified Cox proportional hazards model was used to evaluate patients with PD who were matched 1:4 with non-PD control subjects adjusted for age, sex, income and region of residence. The causes of death were grouped into 12 classifications.

Results: The adjusted HR for mortality in the PD group was 2.09 (95% CI 1.94 to 2.24, p<0.001). Subgroup analysis according to age (<70 years, 70-79 years, and ≥80 years) and sex revealed that patients with PD showed higher adjusted HRs for mortality across all subgroups. Mortalities caused by metabolic, mental, neurologic, circulatory, respiratory, and genitourinary diseases, as well as trauma, were more common in the PD group than in the control group, with the highest OR observed in patients with neurologic disease.

Conclusions: We demonstrated that PD in South Korean patients ≥60 years of age was associated with increased mortality in both sexes regardless of age.
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http://dx.doi.org/10.1136/bmjopen-2019-029776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756321PMC
September 2019

Mixed Phenotype Acute Leukemia that Evolved from Myelodysplastic Syndrome with Excess Blasts.

Lab Med 2020 May;51(3):288-295

Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Anyang, South Korea.

Myelodysplastic syndrome (MDS) that evolves into acute leukemia with blasts of mixed phenotypes has rarely been reported and has no distinct diagnostic category. Herein, we describe a 79-year-old Korean female patient with MDS-excess blasts (MDS-EB) that evolved into acute leukemia; the blasts simultaneously expressed B-lymphoid and myeloid antigens. The patient was diagnosed with MDS-EB with blasts of myeloid lineage coexpressing a few B-lymphoid antigens with 7q and 20q abnormalities. The disease progressed to acute leukemia with blasts carrying more B-lymphoid antigens, which was immunophenotypically compatible with B-lymphoid/myeloid acute leukemia. Unlike previously reported patients whose blast populations are bilineal, our patient is the first with biphenotypic acute leukemia that progressed from MDS. The diagnosis of our patient introduces the possibility that many other types of biphenotypic acute leukemia may have gone undiagnosed and encourages hematologists to designate a specific diagnostic category for this type of disease, so that it can more readily be detected and studied in the future.
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http://dx.doi.org/10.1093/labmed/lmz054DOI Listing
May 2020

Dosimetric comparison of two treatment planning systems for spine SBRT.

Med Dosim 2020 Spring;45(1):77-84. Epub 2019 Aug 1.

Department of Medical Physics, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, ON M4N 3M5, Canada.

Two commonly used treatment planning systems (TPS) are compared for the planning of spine stereotactic body radiotherapy (SBRT). The main purpose is to highlight relative advantages and disadvantages of each system and propose a methodologic approach for comparisons. Twenty clinical plans were inversely planned with step-and-shoot intensity-modulated radiotherapy (IMRT) each using 9 to 11 beams, referred to as IMRT_P. The prescription dose was 24 Gy in 2 fractions, and the plans were generated following our institutional protocol using the Pinnacle v9.2. Each case was replanned using a 2-arc volumetric modulated arc therapy (VMAT) approach, referred as VMAT_P. CT and structure sets were DICOM exported to Monaco v5.10 and planned in 2 different ways: IMRT (IMRT_M) and VMAT (VMAT_M) using the same prescription dose. Dose volume histograms (DVH) and other dose statistics of planning target volumes (PTV) and organ-at-risk (OAR) were analyzed and compared between plans. The gradient index (GI = ratio of 50% isodose volume to prescribed isodose volume) was used to measure dose fall-off outside of the PTV. Another metric - Gradient Index Inner (GI = the rate (in Gy/mm) - at which the dose changes from the level of the spinal cord/thecal sac toward the prescription dose) was developed and compared. All plans were considered clinically acceptable by institutional guidelines and achieved all of the OAR dose constraints. VMAT_M and IMRT_M showed comparable dose statistics for the PTV when compared to VMAT_P and IMRT_P, respectively. For IMRT plans, the median GI was 1.88 Gy/mm vs 1.52 Gy/mm for IMRT_M and IMRT_P respectively (p< 0.001). All other IMRT metrics were statistically similar except for the PTV maximum dose (D), which was higher for IMRT_M than IMRT_P (median 30.7 Gy vs 29.0 Gy, p< 0.001). For VMAT plans, only PTV D showed a statistical different between VMAT_M and VMAT_P of median 12.7 Gy vs 9.7 Gy (p< 0.001). In terms of beam sequencing parameters, the number of monitor units was statistically higher for VMAT_P compared to VMAT_M (median = 6764 vs 5376) whereas the number of segments for IMRT_M was statistically greater than IMRT_P (median = 155 vs 73). We were able to generate clinically acceptable plans for different types of spine SBRT using 2 different TPS. We used an evaluation strategy involving coverage, conformity, and dose gradient that can compared between TPS.
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http://dx.doi.org/10.1016/j.meddos.2019.07.001DOI Listing
December 2020

Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumor DNA.

Mol Oncol 2019 08 30;13(8):1623-1650. Epub 2019 Jul 30.

Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.

Reliable biomarkers are required to evaluate and manage pancreatic ductal adenocarcinoma. Circulating tumor cells and circulating tumor DNA are shed into blood and can be relatively easily obtained from minimally invasive liquid biopsies for serial assays and characterization, thereby providing a unique potential for early diagnosis, forecasting disease prognosis, and monitoring of therapeutic response. In this review, we provide an overview of current technologies used to detect circulating tumor cells and circulating tumor DNA and describe recent advances regarding the multiple clinical applications of liquid biopsy in pancreatic ductal adenocarcinoma.
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http://dx.doi.org/10.1002/1878-0261.12537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6670020PMC
August 2019

First Report of a Patient With Natural Killer-Lymphoblastic Leukemia/Lymphoma in Korea.

Ann Lab Med 2019 Sep;39(5):493-495

Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea.

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http://dx.doi.org/10.3343/alm.2019.39.5.493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502956PMC
September 2019

Mean Platelet Volume and Platelet Distribution Width Indicate that Platelets Remain Small for Most of Their Lifespans in Patients with Essential Thrombocythemia.

Clin Lab 2019 Apr;65(4)

Background: Platelets are large when young and immature and shrink as they age. The mean platelet volume (MPV) and platelet distribution width (PDW) reflect the volume and distribution of platelets, respectively. We compared the MPVs and PDWs of patients with immune thrombocytopenic purpura (ITP) or essential thrombocythemia (ET) to those of healthy individuals to test whether these values can reflect the pathomechanisms of these diseases.

Methods: Platelet counts, MPVs, and PDWs were measured in 153 healthy individuals and in 20 and 34 patients with ITP and ET, respectively, using an XN-3000 instrument.

Results: The MPVs and PDWs were significantly higher in ITP patients than in healthy individuals or ET patients. The MPVs were significantly lower in ET patients than in both ITP patients and healthy individuals; however, the PDWs in ET patients were similar to those in healthy individuals. The MPVs and PDWs did not correlate with platelet count in ITP or ET patients.

Conclusions: Our data suggested an increased production of young, large platelets and nondiscriminatory destruction of circulating platelets irrespective of their ages in ITP. Decreased MPVs and unelevated PDWs in ET suggest that clonal process-produced platelets remain small throughout their lifespans.
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http://dx.doi.org/10.7754/Clin.Lab.2018.180938DOI Listing
April 2019

Recent progress in laboratory diagnosis of thalassemia and hemoglobinopathy: a study by the Korean Red Blood Cell Disorder Working Party of the Korean Society of Hematology.

Blood Res 2019 Mar 21;54(1):17-22. Epub 2019 Mar 21.

Department of Laboratory Medicine, Dong-A University College of Medicine, Busan, Korea.

Genetic hemoglobin disorders are caused by mutations and/or deletions in the α-globin or β-globin genes. Thalassemia is caused by quantitative defects and hemoglobinopathies by structural defect of hemoglobin. The incidence of thalassemia and hemoglobinopathy is increased in Korea with rapid influx of people from endemic areas. Thus, the awareness of the disease is needed. α-thalassemias are caused by deletions in α-globin gene, while β-thalassemias are associated with decreased synthesis of β-globin due to β-globin gene mutations. Hemoglobinopathies involve structural defects in hemoglobin due to altered amino acid sequence in the α- or β-globin chains. When the patient is suspected with thalassemia/hemoglobinopathy from abnormal complete blood count findings and/or family history, the next step is detecting hemoglobin abnormality using electrophoresis methods including high performance liquid chromatography and mass spectrometry. The development of novel molecular genetic technologies, such as massively parallel sequencing, facilitates a more precise molecular diagnosis of thalassemia/hemoglobinopathy. Moreover, prenatal diagnosis using genetic testing enables the prevention of thalassemia birth and pregnancy complications. We aimed to review the spectrum and classification of thalassemia/hemoglobinopathy diseases and the diagnostic strategies including screening tests, molecular genetic tests, and prenatal diagnosis.
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http://dx.doi.org/10.5045/br.2019.54.1.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439293PMC
March 2019

A Myelodysplastic Syndrome with Concurrent Basophilia and Eosinophilia Lacking Oncogenic Mutations in 54 Relevant Genes.

Clin Lab 2019 Jan;65(1)

Myelodysplastic syndromes (MDS) with basophilia or eosinophilia are very rare and portend poor prognoses. We present a rare patient who had MDS with excess blasts as well as peripheral basophilia and concurrent bone marrow (BM) basophilia/eosinophilia. She had a complex karyotype including 5q and 7q deletions; however, no oncogenic mutations were observed on next-generation sequencing of 54 genes known to be frequently mutated in acute myeloid leukemia/MDS. Peripheral basophilia resolved after decitabine treatment. Ours is the first report to describe a genome-wide analysis and the use of decitabine to successfully treat basophilia in an MDS patient with concurrent BM basophilia/eosinophilia.
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http://dx.doi.org/10.7754/Clin.Lab.2018.180729DOI Listing
January 2019

Mean Platelet Volume, Platelet Distribution Width, and Platelet Count, in Connection with Immune Thrombocytopenic Purpura and Essential Thrombocytopenia.

Lab Med 2019 Jul;50(3):279-285

Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea.

Objective: To examine the kinetic characteristics of platelet (PLT) destruction and thrombopoiesis by using mean platelet volume (MPV) and platelet distribution width (PDW).

Methods: Using the ADVIA2120i instrument, we measured PLT counts, MPV, and PDW in 153 healthy individuals, 35 patients with immune thrombocytopenic purpura (ITP), and 48 patients with essential thrombocytopenia (ET).

Results: In the ITP group, the MPV and PDW were higher than those values in healthy individuals. In the ET group, the MPV was lower than in the ITP group and in healthy individuals, and the PDW was lower than in the ITP group. When the ITP group was subdivided (PLT counts <45 × 103/µL vs ≥ 45 × 103/µL), the MPV and PDW tended to be higher in patients with PLT counts less than 45 × 103 per µL. When patients with ET were subdivided (PLT counts <770 × 103/µL vs ≥770 × 103/µL), the MPV and PDW were lower in patients with PLT count of 770 or greater × 103 per µL.

Conclusions: In ITP, the overall PLT composition varies, and PLT sequestration is nondiscriminatory. In ET, PLTs quickly shrink and remain small, resulting in a high proportion of small-sized PLTs.
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http://dx.doi.org/10.1093/labmed/lmy082DOI Listing
July 2019

Association Between Prolonged Closure Time on the Platelet Function Analyzer-200 and Risk of Perioperative Blood Transfusion.

Ann Lab Med 2019 May;39(3):330-332

Department of Laboratory Medicine, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea.

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http://dx.doi.org/10.3343/alm.2019.39.3.330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340840PMC
May 2019

Reclassification of and variants of uncertain significance: a multifactorial analysis of multicentre prospective cohort.

J Med Genet 2018 12 10;55(12):794-802. Epub 2018 Nov 10.

Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: and () variants classified ambiguously as variants of uncertain significance (VUS) are a major challenge for clinical genetic testing in breast cancer; their relevance to the cancer risk is unclear and the association with the response to specific -targeted agents is uncertain. To minimise the proportion of VUS in , we performed the multifactorial likelihood analysis and validated this method using an independent cohort of patients with breast cancer.

Methods: We used a data set of 2115 patients with breast cancer from the nationwide multicentre prospective Korean Hereditary Breast Cancer study. In total, 83 VUSs (, n=26; , n=57) were analysed. The multifactorial probability was estimated by combining the prior probability with the overall likelihood ratio derived from co-occurrence of each VUS with pathogenic variants, personal and family history, and tumour characteristics. The classification was compared with the interpretation according to the American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG/AMP) guidelines. An external validation was conducted using independent data set of 810 patients.

Results: We were able to redefine 38 VUSs (, n=10; , n=28). The revised classification was highly correlated with the ACMG/AMP guideline-based interpretation (, p for trend=0.015; , p=0.001). Our approach reduced the proportion of VUS from 19% (154/810) to 8.9% (72/810) in the retrospective validation data set.

Conclusion: The classification in this study would minimise the 'uncertainty' in clinical interpretation, and this validated multifactorial model can be used for the reliable annotation of VUSs.
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http://dx.doi.org/10.1136/jmedgenet-2018-105565DOI Listing
December 2018

Association between the Urinary N-acetyl-β-D-Glucosaminidase/Creatinine Ratio and Factors of the Metabolic Syndrome.

Ann Clin Lab Sci 2018 Sep;48(5):627-633

Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Gyeonggi-do, Korea

Urinary N-acetyl-β-D-glucosaminidase (NAG) is an early marker for kidney injury. To explore the utility of urinary NAG in assessing kidney damage associated with metabolic syndrome (MetS), we investigated associations between urinary NAG levels and MetS factors. The study included 95 healthy controls, 51 hypertension (HTN) outpatients, 96 with type 2 diabetes mellitus (DM), and 80 with comorbidity of HTN and DM. We measured the NAG/creatinine (Cr), albumin/Cr, and protein/Cr ratios in urine, and collected data for MetS factors from the medical records. The urinary NAG/Cr ratio showed a significant increase in the HTN and DM groups than in the control (3.8, 3.6, and 2.8 IU/g·Cr, respectively). The urinary NAG/Cr ratio was significantly higher in normoalbuminuric DM patients (3.8 IU/g·Cr) than in the control (2.8 IU/g·Cr). Among MetS factors, high blood pressure, high fasting blood glucose, and low HDL-cholesterol were associated with high urinary NAG/Cr ratio in study subjects. Moreover, the subjects with 3 or 4 factors exhibited a higher urinary NAG/Cr ratio than those with less than 3 factors (7.4 vs. 3.3 IU/g·Cr). These results suggest that the urinary NAG/Cr ratio is a sensitive indicator for early injury of the kidney in association with MetS including DM.
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September 2018

A comparison of complete blood count reference intervals in healthy elderly vs. younger Korean adults: a large population study.

Clin Chem Lab Med 2019 04;57(5):716-729

Department of Laboratory Medicine, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea.

Background The use of laboratory reference intervals based on younger populations is of questionable validity in older populations. We established reference intervals for 16 complete blood count (CBC) parameters in healthy elderly Koreans aged ≥60 years and compared them to those of individuals aged 20-59 years. Methods Among 64,532 individuals (39,609 men and 24,923 women) aged ≥20 years who underwent medical checkups, 8151 healthy subjects (12.6%, 5270 men and 2881 women, including 675 and 511, respectively, who were ≥60 years of age) were enrolled based on stringent criteria including laboratory, imaging and endoscopy results; previous medical history; and medication history. CBC parameters were measured using an Advia2120i instrument. Results Overall, healthy individuals aged ≥60 years did not require separate reference intervals from those aged <60 years except for red cell distribution width (RDW) and mean corpuscular hemoglobin (MCH) in women. However, subjects aged ≥60 years still required sex-specific reference intervals for red blood cell count, hemoglobin, hematocrit, MCH, monocytes and eosinophils. Separate reference intervals were required for MCH, eosinophils and basophils for certain age subgroups of men aged ≥60 years, and for MCH and RDW in certain age subgroups of women aged ≥60 years, compared to counterparts <60 years of age. Conclusions Healthy elderly Koreans can use the same reference intervals as younger populations. Thus, abnormal CBC results may not necessarily be attributable to physiologic changes but possible underlying diseases that should be investigated.
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http://dx.doi.org/10.1515/cclm-2018-0649DOI Listing
April 2019